EGFR signaling controls directionality of epithelial multilayer formation upon loss of cell polarity.

Apical-basal polarity is maintained by distinct protein complexes that reside in membrane junctions, and polarity loss in monolayered epithelial cells can lead to formation of multilayers, cell extrusion, and/or malignant overgrowth. Yet, how polarity loss cooperates with intrinsic signals to control directional invasion toward neighboring epithelial cells remains elusive. Using the Drosophila ovarian follicular epithelium as a model, we found that posterior follicle cells with loss of lethal giant larvae (lgl) or Discs large (Dlg) accumulate apically toward germline cells, whereas cells with loss of Bazooka (Baz) or atypical protein kinase C (aPKC) expand toward the basal side of wildtype neighbors. Further studies revealed that these distinct multilayering patterns in the follicular epithelium were determined by epidermal growth factor receptor (EGFR) signaling and its downstream target Pointed, a zinc-finger transcription factor. Additionally, we identified Rho kinase as a Pointed target that regulates formation of distinct multilayering patterns. These findings provide insight into how cell polarity genes and receptor tyrosine kinase signaling interact to govern epithelial cell organization and directional growth that contribute to epithelial tumor formation.

The strength, position, and width changes of the intertropical convergence zone since the Last Glacial Maximum.

The intertropical convergence zone (ITCZ) plays a key role in regulating tropical hydroclimate and global water cycle through changes in its convection strength, latitudinal position, and width. The long-term variability of the ITCZ, along with the corresponding driving mechanisms, however, remains obscure, mainly because it is difficult to separate different ITCZ variables in paleoclimate proxy records. Here, we report a speleothem oxygen isotope (δ18O) record from southwestern Sulawesi, Indonesia, and compile it with other speleothem records from the Maritime Continent. Using the spatial gradient of speleothem δ18O along a transect across the ITCZ, we constrain ITCZ variabilities over the Maritime Continent during the past 30,000 y. We find that ITCZ convection strength overall intensified from the last glacial period to the Holocene, following changes in climate boundary conditions. The mean position of the regional ITCZ has moved latitudinally no more than 3° in the past 30,000 y, consistent with the deduction from the atmospheric energy framework. However, different from modern observations and model simulations for future warming, the ITCZ appeared narrower during both the late Holocene and most part of the last glacial period, and its expansion occurred during Heinrich stadials and the early-to-mid Holocene. We also find that during the last glacial and deglacial period, prominent millennial-scale ITCZ changes were closely tied to the variability of the Atlantic meridional overturning circulation (AMOC), whereas during the Holocene, they were predominantly modulated by the long-term variability of the Walker circulation.

Boundary exchange completes the marine Pb cycle jigsaw.

Material fluxes at the land-ocean interface impact seawater composition and global cycling of elements. However, most attention has been focused on the fluvial dissolved fluxes. For elements like lead (Pb), whose fluvial particulate flux into the ocean is two orders of magnitude higher than the dissolved counterpart, the role of particulates in elemental cycling is potentially important but currently less appreciated. Using both chemical analyses on samples collected from around equatorial Southeast Asia and model simulations, we show that particulate-dissolved exchange is an important mechanism controlling the concentration and isotopic composition of dissolved Pb in the ocean. Our model indicates that Pb contributed from particulate-dissolved exchange at ocean boundaries is larger than, or at least comparable to, other major Pb sources to the seawater before the Anthropocene, when the anthropogenic Pb was absent. Our work highlights the importance of boundary exchange in understanding marine element cycling and weathering-climate feedback.

Hepatic LGR4 aggravates cholestasis-induced liver injury in mice.

Current therapy for hepatic injury induced by the accumulation of bile acids is limited. Leucine-rich repeat G protein-coupled receptor 4 (LGR4), also known as GPR48, is critical for cytoprotection and cell proliferation. Here, we reported a novel function for the LGR4 in cholestatic liver injury. In the bile duct ligation (BDL)-induced liver injury model, hepatic LGR4 expression was significantly downregulated. Deficiency of LGR4 in hepatocytes (Lgr4LKO) notably decreased BDL-induced liver injury measured by hepatic necrosis, fibrosis, and circulating liver enzymes and total bilirubin. Levels of total bile acids in plasma and liver were markedly reduced in these mice. However, deficiency of LGR4 in macrophages (Lyz2-Lgr4MKO) demonstrated no significant effect on liver injury induced by BDL. Deficiency of LGR4 in hepatocytes significantly attenuated S1PR2 and the phosphorylation of protein kinase B (AKT) induced by BDL. Recombinant Rspo1 and Rspo3 potentiated the taurocholic acid (TCA)-induced upregulation in S1PR2 and phosphorylation of AKT in hepatocytes. Inhibition of S1PR2-AKT signaling by specific AKT or S1PR2 inhibitors blocked the increase of bile acid secretion induced by Rspo1/3 in hepatocytes. Our studies indicate that the R-spondins (Rspos)-LGR4 signaling in hepatocytes aggravates the cholestatic liver injury by potentiating the production of bile acids in a S1PR2-AKT-dependent manner.NEW & NOTEWORTHY Deficiency of LGR4 in hepatocytes alleviates BDL-induced liver injury. LGR4 in macrophages demonstrates no effect on BDL-induced liver injury. Rspos-LGR4 increases bile acid synthesis and transport via potentiating S1PR2-AKT signaling in hepatocytes.

MiR-214_L-1R+4 regulate gossypol-induced immune response through MyD88-dependent signaling pathway in Cyprinus carpio.

MicroRNAs (miRNAs) have been demonstrated to act as crucial modulators with considerable impacts on the immune system. Cottonseed meal is often used as a protein source in aqua feed, cottonseed meal contains gossypol, which is harmful to animals. However, there is a lack of research on the role of miRNAs in fish exposed to gossypol stress. To determine the regulatory effects of miRNAs on gossypol toxicity, Cyprinus carpio were given to oral administration of 20 mg/kg gossypol for 7 days, and the gossypol concentration in the tissues was tested. Then, we detected spleen index, histology, immune enzyme activities of fish induced by gossypol. The results of miRNA sequencing revealed 8 differentially expressed miRNAs in gossypol group, and miR-214_L-1R+4 was found involved in immune response induced by gossypol. The potential targets of miR-214_L-1R+4 were predicted, and found a putative miR-214_L-1R+4 binding site in the 3'UTR of MyD88a. Furthermore, dual-luciferase reporter assays displayed miR-214_L-1R+4 decreased MyD88a expression through binding to the 3'UTR of MyD88a. Moreover, miR-214_L-1R+4 antagomir were intraperitoneally administered to C. carpio, down-regulated miR-214_L-1R+4 could increase MyD88a expression, as well as inflammatory cytokines and anti-inflammatory cytokines expression. These findings revealed that miR-214_L-1R+4 via the MyD88-dependent signaling pathway modulate the immune response to gossypol in C. carpio spleen.

Two-Dimensional Nanofibrous Networks by Superspreading-Based Phase Inversion for High-Efficiency Separation.

Two-dimensional (2D) nanomaterials have been widely applied as building blocks of nanoporous materials for high-precision separations. However, most existing 2D nanomaterials suffer from poor continuity and a lack of interior linking, resulting in deteriorated performance when assembled into macroscopic bulk structures. Here, a unique superspreading-based phase inversion technique is proposed to directly construct 2D nanofibrous networks (NFNs) from a polymer solution. By tailoring capillary behavior, polymer solution droplets evolve into ultrathin liquid films through superspreading; manipulating phase instability, subsequently, enables the liquid film to phase invert into continuous nanostructured networks. The assembled single-layered NFNs possess integrated structural superiorities of 1D nanoscale fiber diameter (∼40 nm) and 2D lateral infinity, exhibiting a weblike nanoarchitecture with extremely small through-pores (∼100 nm). Our NFNs show remarkable performances in air filtration (PM0.3 removal) and water purification (microfiltration level). This creation of such attractive 2D fibrous nanomaterials can pave the way for versatile high-performance separation applications.

High-Performance Waterproof, Breathable, and Radiative Cooling Membranes Based on Nanoarchitectured Fiber/Meshworks.

Smart membranes with protection and thermal-wet comfort are highly demanded in various fields. Nevertheless, the existing membranes suffer from a tradeoff dilemma of liquid resistance and moisture permeability, as well as poor thermoregulating ability. Herein, a novel strategy, based on the synchronous occurrence of humidity-induced electrospinning and electromeshing, is developed to synthesize a dual-network structured nanofiber/mesh for personal comfort management. Manipulating the ejection, deformation, and phase separation of spinning jets and charged droplets enables the creation of nanofibrous membranes composed of radiative cooling nanofibers and 2D nanostructured meshworks. With a combination of a true-nanoscale fiber (∼70 nm) in 2D meshworks, a small pore size (0.84 µm), and a superhydrophobic surface (151.9°), the smart membranes present high liquid repellency (95.6 kPa), improved breathability (4.05 kg m-2 d-1), and remarkable cooling performance (7.9 °C cooler than commercial cotton fabrics). This strategy opens up a pathway to the design of advanced smart textiles for personal protection.

Polyploidy in development and tumor models in Drosophila.

Polyploidy, a cell status defined as more than two sets of genomic DNA, is a conserved strategy across species that can increase cell size and biosynthetic production, but the functional aspects of polyploidy are nuanced and vary across cell types. Throughout Drosophila developmental stages (embryo, larva, pupa and adult), polyploid cells are present in numerous organs and help orchestrate development while contributing to normal growth, well-being and homeostasis of the organism. Conversely, increasing evidence has shown that polyploid cells are prevalent in Drosophila tumors and play important roles in tumor growth and invasiveness. Here, we summarize the genes and pathways involved in polyploidy during normal and tumorigenic development, the mechanisms underlying polyploidization, and the functional aspects of polyploidy in development, homeostasis and tumorigenesis in the Drosophila model.

A single-cell atlas of adult Drosophila ovary identifies transcriptional programs and somatic cell lineage regulating oogenesis.

Oogenesis is a complex developmental process that involves spatiotemporally regulated coordination between the germline and supporting, somatic cell populations. This process has been modeled extensively using the Drosophila ovary. Although different ovarian cell types have been identified through traditional means, the large-scale expression profiles underlying each cell type remain unknown. Using single-cell RNA sequencing technology, we have built a transcriptomic data set for the adult Drosophila ovary and connected tissues. Using this data set, we identified the transcriptional trajectory of the entire follicle-cell population over the course of their development from stem cells to the oogenesis-to-ovulation transition. We further identify expression patterns during essential developmental events that take place in somatic and germline cell types such as differentiation, cell-cycle switching, migration, symmetry breaking, nurse-cell engulfment, egg-shell formation, and corpus luteum signaling. Extensive experimental validation of unique expression patterns in both ovarian and nearby, nonovarian cells also led to the identification of many new cell type-and stage-specific markers. The inclusion of several nearby tissue types in this data set also led to our identification of functional convergence in expression between distantly related cell types such as the immune-related genes that were similarly expressed in immune cells (hemocytes) and ovarian somatic cells (stretched cells) during their brief phagocytic role in nurse-cell engulfment. Taken together, these findings provide new insight into the temporal regulation of genes in a cell-type specific manner during oogenesis and begin to reveal the relatedness in expression between cell and tissues types.

A Fiber Sliding-Orientation Based Micromechanics Failure Model for Melt-Blown Nonwovens.

The mechanical model of melt-blown nonwovens (MNs) serves as the foundation for performance optimization, which can offer helpful guidance for product material selection, structural design, and cost control. However, it is challenging to describe the micromechanics failure mechanism of MNs using the traditional mechanical model, which aims to match the model curve with the experimental result at the macrolevel. Herein, a micromechanics failure model for MNs based on sliding-orientation competition is developed. Through in situ observations of fiber position changes and the fluctuation of stress-strain curves, fiber sliding and orientation are introduced into the failure process of MNs. Due to fiber bonding and static friction, only orientation happens during the first stage of stretching. In dramatic contrast, the fibers will slide and orient in the second stage of stretching to change their positions in response to the external force. Sliding friction, fiber bonding, and static friction make up the stress of MNs, and the conflict of fiber sliding and orientation causes variations in the stress. The model has been successfully applied to polylactic acid (PLA) MNs, which proves the effectiveness of the model in MNs.

Analysis of the Related Influencing Factors of Hepatic Abscess Associated with Hepatobiliary Ischemic Necrosis after Cholangiocarcinoma Operation.

To investigate related factors of liver abscess associated with hepatobiliary ischemic necrosis after cholangiocarcinoma surgery, 100 patients with cholangiocarcinoma requiring surgical resection were collected and divided into a test group (53 patients with liver abscess) and a control group (47 patients without liver abscess) according to presence or absence of liver abscess. Related factors were compared: gender, age, body mass index (BMI), body temperature at admission, duration of medical history, presence or absence of a history of diabetes, time of medical history, presence or absence of hepatolithiasis, absolute neutrophil count, absolute lymphocyte count (ALC), C-reactive protein, serum albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), direct bilirubin (DBIL), serum creatine, and presence or absence of anemia. Univariate analysis showed that BMI, age, gender, absolute lymphocyte count, serum ALB, AST, and time of medical history were significantly different between the two (P<0.05). Multivariate logistic regression analysis of the above influencing factors showed that independent influencing factors of postoperative liver abscess formation were: ALC<1.1*10^9/L (P<0.001, OR=23.459, 95% CI=8.529-64.576), AST≥40 U/L (P=0.012, OR=3.946, 95% CI=1.355-11.487), time of medical history≥21 days (P=0.010, OR=4.028, 95% CI=1.389-11.681). Decreased ALC, increased AST, and occurrence of acute biliary tract infection were independent factors for hepatobiliary ischemic necrosis-related liver abscess. Abnormal nutritional status, age, and gender were also the influencing factors of liver abscess.

Hydroclimate changes across the Amazon lowlands over the past 45,000 years.

Reconstructing the history of tropical hydroclimates has been difficult, particularly for the Amazon basin-one of Earth's major centres of deep atmospheric convection. For example, whether the Amazon basin was substantially drier or remained wet during glacial times has been controversial, largely because most study sites have been located on the periphery of the basin, and because interpretations can be complicated by sediment preservation, uncertainties in chronology, and topographical setting. Here we show that rainfall in the basin responds closely to changes in glacial boundary conditions in terms of temperature and atmospheric concentrations of carbon dioxide. Our results are based on a decadally resolved, uranium/thorium-dated, oxygen isotopic record for much of the past 45,000 years, obtained using speleothems from Paraíso Cave in eastern Amazonia; we interpret the record as being broadly related to precipitation. Relative to modern levels, precipitation in the region was about 58% during the Last Glacial Maximum (around 21,000 years ago) and 142% during the mid-Holocene epoch (about 6,000 years ago). We find that, as compared with cave records from the western edge of the lowlands, the Amazon was widely drier during the last glacial period, with much less recycling of water and probably reduced plant transpiration, although the rainforest persisted throughout this time.

Two machine learning approaches for predicting cyanobacteria abundance in aquaculture ponds.

Cyanobacteria blooms in aquaculture ponds harm the harvesting of aquatic animals and threaten human health. Therefore, it is crucial to identify key drivers and develop methods to predict cyanobacteria blooms in aquaculture water management. In this study, we analyzed monitoring data from 331 aquaculture ponds in central China and developed two machine learning models - the least absolute shrinkage and selection operator (LASSO) regression model and the random forest (RF) model - to predict cyanobacterial abundance by identifying the key drivers. Simulation results demonstrated that both machine learning models are feasible for predicting cyanobacterial abundance in aquaculture ponds. The LASSO model (R2 = 0.918, MSE = 0.354) outperformed the RF model (R2 = 0.798, MSE = 0.875) in predicting cyanobacteria abundance. Farmers with well-equipped aquaculture ponds that have abundant water monitoring data can use the nine environmental variables identified by the LASSO model as an operational solution to accurately predict cyanobacteria abundance. For crude ponds with limited monitoring data, the three environmental variables identified by the RF model provide a convenient solution for useful cyanobacteria prediction. Our findings revealed that chemical oxygen demand (COD) and total organic carbon (TOC) were the two most important predictors in both models, indicating that organic carbon concentration had a close relationship with cyanobacteria growth and should be considered a key metric in water monitoring and pond management of these aquaculture ponds. We suggest that monitoring of organic carbon coupled with phosphorus reduction in feed usage can be an effective management approach for cyanobacteria prevention and to maintain a healthy ecological state in aquaculture ponds.

Integration of Janus Wettability and Heat Conduction in Hierarchically Designed Textiles for All-Day Personal Radiative Cooling.

Personal cooling textiles are a promising energy-free pathway for confronting serious heat-related public health threats and improving industrial worker productivity. Current cooling strategies mainly focus on passive daytime radiation, and there is a lack of research on all-day cooling methods which utilize synergistic radiative, conductive, and evaporative heat dissipation. Herein, we demonstrate a hierarchical polyurethane/silicon nitride fibrous membrane with Janus wettability fabricated via a scalable electrospinning method followed by single-side hydrophilic plasma treatment. High angular-dependent solar reflectance (91%) and human body infrared emittance (93%) allow for a temperature drop of ∼21.9 °C under direct sunlight and ∼2.8 °C at night compared with traditional cotton. The innovative integration of Janus wettability and heat conduction in hierarchically designed textiles ensures a minimum sweat consumption of 0.5 mL h-1, avoiding harmfully excessive perspiration. The excellent all-day cooling performance of this hierarchical textile presents great advantages for smart textile, energy-saving, and personal cooling applications.

Developmental Neurotoxicity of Trichlorfon in Zebrafish Larvae.

Trichlorfon is an organophosphorus pesticide widely used in aquaculture and has potential neurotoxicity, but the underlying mechanism remains unclear. In the present study, zebrafish embryos were exposed to trichlorfon at concentrations (0, 0.1, 2 and 5 mg/L) used in aquaculture from 2 to 144 h post fertilization. Trichlorfon exposure reduced the survival rate, hatching rate, heartbeat and body length and increased the malformation rate of zebrafish larvae. The locomotor activity of larvae was significantly reduced. The results of molecular docking revealed that trichlorfon could bind to acetylcholinesterase (AChE). Furthermore, trichlorfon significantly inhibited AChE activity, accompanied by decreased acetylcholine, dopamine and serotonin content in larvae. The transcription patterns of genes related to acetylcholine (e.g., ache, chrna7, chata, hact and vacht), dopamine (e.g., drd4a and drd4b) and serotonin systems (e.g., tph1, tph2, tphr, serta, sertb, htrlaa and htrlab) were consistent with the changes in acetylcholine, dopamine, serotonin content and AChE activity. The genes related to the central nervous system (CNS) (e.g., a1-tubulin, mbp, syn2a, shha and gap-43) were downregulated. Our results indicate that the developmental neurotoxicity of trichlorfon might be attributed to disorders of cholinergic, dopaminergic and serotonergic signaling and the development of the CNS.

A dual-signal sensing strategy based on ratiometric fluorescence and colorimetry for determination of Cu2+ and glyphosate.

Herein, a dual-signal sensing strategy based on ratiometric fluorescence and colorimetry for Cu2+ and glyphosate determination was constructed. Fluorescence silicon nanoparticles (SiNPs) were prepared by hydrothermal reaction, which has maximum fluorescence intensity under the excitation of 355 nm. o-Phenylenediamine (OPD) was oxidized through Cu2+ to generate 2,3-diaminophenazine (oxOPD). The obtained oxOPD showed a strong absorption peak at 417 nm and quenched the fluorescence of SiNPs at 446 nm due to fluorescence resonance energy transfer (FRET). Meanwhile, oxOPD produced a new fluorescence emission at 556 nm forming a ratiometric state. With increasing Cu2+, the original solution changed from colorless to yellow. When glyphosate was present, the interaction between Cu2+ and the functional groups of glyphosate could reduce the oxidation of oxOPD, resulting in the enhancement of fluorescence at 446 nm and the decrease of fluorescence at 556 nm. Furthermore, the addition of glyphosate changed yellow solution to colorless. Under the optimal conditions of OPD (1 mM), 20 mM Tris-HCl buffer (pH 7.5), and incubation time (4 h), the ratiometric fluorescence sensor had good selectivity and showed a wide linear range of 0.025-20 µM with the LOD of 0.008 µM for Cu2+ and 0.15-1.5 µg/mL with the LOD of 0.003 µg/mL for glyphosate, respectively. Besides, it is worth mentioning that this developed sensing system showed good performance in real samples, providing a simple and reliable dual-signal detection strategy.

The Asian monsoon over the past 640,000 years and ice age terminations.

Oxygen isotope records from Chinese caves characterize changes in both the Asian monsoon and global climate. Here, using our new speleothem data, we extend the Chinese record to cover the full uranium/thorium dating range, that is, the past 640,000 years. The record's length and temporal precision allow us to test the idea that insolation changes caused by the Earth's precession drove the terminations of each of the last seven ice ages as well as the millennia-long intervals of reduced monsoon rainfall associated with each of the terminations. On the basis of our record's timing, the terminations are separated by four or five precession cycles, supporting the idea that the '100,000-year' ice age cycle is an average of discrete numbers of precession cycles. Furthermore, the suborbital component of monsoon rainfall variability exhibits power in both the precession and obliquity bands, and is nearly in anti-phase with summer boreal insolation. These observations indicate that insolation, in part, sets the pace of the occurrence of millennial-scale events, including those associated with terminations and 'unfinished terminations'.

Neuroprotective Effects of Tetrahydroxystilbene Glucoside against Rotenone-Induced Toxicity in PC12 Cells.

To investigate the mechanism of the protective effect of tetrahydroxystilbene glucoside (TSG) on nerve cells, an injury model induced by rotenone in PC12 cells was constructed. Cell viability was detected by using cell counting kit-8 (CCK8) assay. Apoptosis was detected by using flow cytometry. The mitochondrial membrane potential (MMP) was detected by using the fluorescent probe JC-1. Generation of reactive oxygen species (ROS) in PC12 cells was determined using the 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester (CM-H2DCFDA) probe. Protein expression in PC12 cells was detected using Western blotting. The results showed that TSG (20-100 µM) attenuated the cytotoxic effects of rotenone on PC12 cells. TSG pretreatment attenuated the apoptosis rate, the degradation of poly(ADP-ribose)polymerase (PARP) and the activation of cleaved caspase 3, which was induced by rotenone. TSG can significantly reduce the effect of rotenone on the reduction of MMP and the expression of cytoC in the cytosolic fraction. TSG attenuated rotenone-induced de-phosphorylation and mitochondrial translocation of cofilin, as well as rotenone-induced accumulation of ROS. The Western blot results showed that ROT could decrease the expression level of phosphorylated (p)-Glycogen synthase kinase-3ß (GSK)-3ß and p-AKT, and TSG could weaken these effects of rotenone. In addition, TSG increased the expression level of nuclear factor-E2-related factor 2 (Nrf2) in the nuclear fraction. These results suggest that TSG could protect PC12 cells against rotenone through multiple pathways. Thus, TSG has the potential to become a novel neuroprotective agent.

Neuroprotective effect of leptin on a primate model of cerebral ischemia.

The purpose of this study was to evaluate the neuroprotective effect of leptin on a non-human primate model of cerebral ischemia. A total of 39 Guangxi macaques were used to establish the primate cerebral-ischemia model. HE staining was used to evaluated the pathological changes. Moreover, magnetic resonance imaging was used for the detection of embolic area. The measurements of behavior observation and cerebral infarction area were also performed. They all received autologous thrombus operation. Furthermore, western blot and RT-PCR were also used to detect the protein and mRNA expression levels of apoptosis-related factors. Our results showed that leptin could reduce the volume of cerebral infarction by about 35%. Behavioral defects can be significantly improved. In addition, mid-term and long-term behavioral deficiencies had been significantly improved by leptin. Moreover, leptin significantly decreased the expression levels of caspase-3 and Bax, and increased the expression levels of Bcl-2. In conclusion, leptin has neuroprotective effects on cerebral ischemia by effectively reducing the volume of cerebral infarction.