High Breakthrough Pressure in Hydrogels Enabled Ultrastable Treatment of Hypersaline Wastewaters.

Surface effects of low-surface-tension contaminants accumulating at the evaporation surface easily induce wetting in membrane distillation, especially in hypersaline scenarios. Herein, we propose a novel strategy to eliminate the surface effect and redistribute contaminants at the evaporation interface simply by incorporating a layer of hydrogel. The as-fabricated composite membrane exhibits remarkable stability, even when exposed to solution with salt concentration of 5 M and surfactant concentration of 8 mM. Breakthrough pressure of the membrane reaches 20 bar in the presence of surfactants, surpassing commercial hydrophobic membranes by one to two magnitudes. Density functional theory and molecular dynamics simulations reveal the important role of the hydrogel-surfactant interaction in suppressing the surface effect. As a proof of concept, we demonstrate the membrane in stably processing synthetic wastewater containing 144 mg L-1 surfactants, 1 g L-1 mineral oils, and 192 g L-1 NaCl, showing its potential in addressing challenges of hypersaline water treatment.

HER2 phosphorylation induced by TGF-ß promotes mammary morphogenesis and breast cancer progression.

Transforming growth factor ß (TGF-ß) and HER2 signaling collaborate to promote breast cancer progression. However, their molecular interplay is largely unclear. TGF-ß can activate mitogen-activated protein kinase (MAPK) and AKT, but the underlying mechanism is not fully understood. In this study, we report that TGF-ß enhances HER2 activation, leading to the activation of MAPK and AKT. This process depends on the TGF-ß type I receptor TßRI kinase activity. TßRI phosphorylates HER2 at Ser779, promoting Y1248 phosphorylation and HER2 activation. Mice with HER2 S779A mutation display impaired mammary morphogenesis, reduced ductal elongation, and branching. Furthermore, wild-type HER2, but not S779A mutant, promotes TGF-ß-induced epithelial-mesenchymal transition, cell migration, and lung metastasis of breast cells. Increased HER2 S779 phosphorylation is observed in human breast cancers and positively correlated with the activation of HER2, MAPK, and AKT. Our findings demonstrate the crucial role of TGF-ß-induced S779 phosphorylation in HER2 activation, mammary gland development, and the pro-oncogenic function of TGF-ß in breast cancer progression.

A growth factor-reduced culture system for colorectal cancer organoids.

Although organoids derived from tumor tissues have been widely used in cancer research, it is a great challenge for cultured organoids to retain the characteristics of the original tumor tissues due to their heterogeneity. In this study, we explore organoid culture recipes to capture tumor features of colorectal cancers. We find that the activation of Wnt and EGF signaling and inhibition of BMP signaling are non-essential for the survival of most colorectal cancer organoids (CRCOs). We design a growth factor-reduced culture medium containing FGF10, A83-01 (TGF-ß type I receptor inhibitor), SB202190 (p38 MAPK inhibitor), gastrin, and nicotinamide. Using this medium, we can maintain tumor features in long-term CRCO cultivation, as evidenced by histopathology, genetic stability, tumorigenicity, and response of clinical treatments. Our findings offer a reliable and economical strategy for CRCO culture, facilitating the utilization of organoids in colorectal cancer research and treatment.

Mesenchymal Stem Cell Derived Exosomes Repair Uterine Injury by Targeting Transforming Growth Factor-ß Signaling.

Intrauterine adhesions (IUA) refer to adhesions within the uterine cavity and cervix caused by injuries from uterine surgery. They are a significant cause of female infertility. Exosomes derived from mesenchymal stem cells (MSCs) play an active role in the treatment of IUA. However, the mechanism by which they reduce fibrosis in the damaged endometrium remains unclear. In this paper, we demonstrate that exosomes derived from placental mesenchymal stem cells (PMSCs) can restore uterine functions and improve the fertility rate of injured animals. This is achieved by promoting cell proliferation, increasing endometrial thickness, and reversing fibrosis. Regarding the molecular mechanism behind these therapeutic effects, we identify three specific miRNAs, namely, miR-125b-5p, miR-30c-5p, and miR-23a-3p, enriched in PMSC-exosomes, as the key players in the treatment of IUA. Specifically, miR-125b-5p/miR-30c-5p and miR-23a-3p inhibit the expression of smad2 and smad3 by targeting their 3'-untranslated regions, resulting in the downregulation of the transforming growth factor-ß (TGF-ß)/smad signaling pathway and the reversal of fibrosis. Notably, the safety of PMSC-exosomes in intrauterine treatment was also been confirmed. In conclusion, we illustrate that exosomes derived from PMSCs possess the capability to repair endometrial damage and enhance fertility in injured animals by regulating the TGF-ß/smad pathway via miR-125b-5p, miR-30c-5p, and miR-23a-3p. This provides insights into the precision treatment of IUA through exosome-based cell-free therapy.

The cyclooxygenase-expressing mesenchyme resists intestinal epithelial injury by paracrine signaling.

Paracrine signals play pivotal roles in organ homeostasis. Mesenchymal stromal cells (MSCs) play a key role in regulating epithelium homeostasis in the intestine while their paracrine effects are poorly characterized. Here, we identified prostaglandin E2 (PGE2) secreted by cyclooxygenase (COX)-expressing MSCs as a vital factor to maintain the intestinal mucosal barrier. We found that MSCs-induced organoid swelling through paracrine effect in vitro, a process due to enhanced water adsorption and is mediated by the COX-PGE2-EP4 axis. To further explore the regulatory effect of this axis on the intestinal epithelial barrier in vivo, we established the conditional knockout mouse model to specifically delete COX in MSCs and found that PGE2 reduction downregulated the gene Muc2 and induced a gastric metaplasia-like phenotype. Moreover, PGE2 defects increased the susceptibility of intestinal epithelium to colitis. Our study uncovers the paracrine signaling of COX-expressing MSCs in intestinal mucosal barrier maintenance, providing a basis for understanding the role of mesenchymal cells in the pathophysiological function of the intestine.

Transforming Growth Factor Beta Promotes Inflammation and Tumorigenesis in Smad4-Deficient Intestinal Epithelium in a YAP-Dependent Manner.

Transforming growth factor beta (TGF-ß), a multifunctional cytokine, plays critical roles in immune responses. However, the precise role of TGF-ß in colitis and colitis-associated cancer remains poorly defined. Here, it is demonstrated that TGF-ß promotes the colonic inflammation and related tumorigenesis in the absence of Smad family member 4 (Smad4). Smad4 loss in intestinal epithelium aggravates colitis and colitis-associated neoplasia induced by dextran sulfate sodium (DSS) and azoxymethane/dextran sulfate sodium (AOM/DSS), leading to over-activated immune responses and increased TGF-ß1 levels. In Smad4-deficient organoids, TGF-ß1 stimulates spheroid formation and impairs intestinal stem cell proliferation and lineage specification. YAP, whose expression is directly upregulated by TGF-ß1 after Smad4 deletion, mediates the effect of TGF-ß1 by interacting with Smad2/3. Attenuation of YAP/TAZ prevents TGF-ß1-induced spheroid formation in Smad4-/- organoids and alleviates colitis and colitis-associated cancer in Smad4-deficient mice. Collectively, these results highlight an integral role of the TGF-ß/Smad4 axis in restraining intestinal inflammation and tumorigenesis and suggest TGF-ß or YAP signaling as therapeutic targets for these gastrointestinal diseases intervention.

Programmable microfluidics for dynamic multiband camouflage.

Achieving multiband camouflage covering both visible and infrared regions is challenging due to the broad bandwidth and differentiated regulation demand in diverse regions. In this work, we propose a programmable microfluidic strategy that uses dye molecules in layered fluids to manipulate visible light- and infrared-semitransparent solvent to manipulate infrared light. With three primary fluid inputs, we achieve 64 chromaticity values and 8 emissivities from 0.42 to 0.90. In view of the wide tuning range, we demonstrate that the microfluidic film can dynamically change its surface reflectance to blend into varying backgrounds in both visible and infrared images. Moreover, we fabricate the microfluidic device in a textile form and demonstrate its ability to match exactly with the colors of natural leaves of different seasons in the full hyperspectrum range. Considering the broadband modulation and ease of operation, the programmable microfluidic strategy provides a feasible approach for smart optical surfaces in long-span optical spectra.

Corrigendum: Role of non-coding RNA in the pathophysiology and treatment of intrauterine adhesion.

[This corrects the article DOI: 10.3389/fgene.2022.948628.].

Token Sparsification for Faster Medical Image Segmentation.

Can we use sparse tokens for dense prediction, e.g., segmentation? Although token sparsification has been applied to Vision Transformers (ViT) to accelerate classification, it is still unknown how to perform segmentation from sparse tokens. To this end, we reformulate segmentation as a sparse encoding → token completion → dense decoding (SCD) pipeline. We first empirically show that naïvely applying existing approaches from classification token pruning and masked image modeling (MIM) leads to failure and inefficient training caused by inappropriate sampling algorithms and the low quality of the restored dense features. In this paper, we propose Soft-topK Token Pruning (STP) and Multi-layer Token Assembly (MTA) to address these problems. In sparse encoding, STP predicts token importance scores with a lightweight sub-network and samples the topK tokens. The intractable topK gradients are approximated through a continuous perturbed score distribution. In token completion, MTA restores a full token sequence by assembling both sparse output tokens and pruned multi-layer intermediate ones. The last dense decoding stage is compatible with existing segmentation decoders, e.g., UNETR. Experiments show SCD pipelines equipped with STP and MTA are much faster than baselines without token pruning in both training (up to 120% higher throughput) and inference (up to 60.6% higher throughput) while maintaining segmentation quality. Code is available here: https://github.com/cvlab-stonybrook/TokenSparse-for-MedSeg.

Role of noncoding RNA in the pathophysiology and treatment of intrauterine adhesion.

Intrauterine adhesion (IUA) is one of the most common diseases of the reproductive system in women. It is often accompanied by serious clinical problems that damage reproductive function, such as menstrual disorder, infertility, or recurrent abortion. The clinical effect of routine treatment is not ideal, and the postoperative recurrence rate is still very high. Therefore, exploring the pathological mechanism of IUA and finding new strategies for the effective prevention and treatment of IUA are needed. The main pathological mechanism of IUA is endometrial fibrosis and scar formation. Noncoding RNA (ncRNA) plays an important role in the fibrosis process, which is one of the latest research advances in the pathophysiology of IUA. Moreover, the exosomal miRNAs derived from mesenchymal stem cells can be used to improve IUA. This paper reviewed the role of ncRNAs in IUA pathogenesis, summarized the core pathways of endometrial fibrosis regulated by ncRNAs, and finally introduced the potential of ncRNAs as a therapeutic target.

Conversion of Harmful Fly Ash Residue to Zeolites: Innovative Processes Focusing on Maximum Activation, Extraction, and Utilization of Aluminosilicate.

Reuse of the solid residue from coal fly ash alumina extraction (FAAE) by acid leaching is problematic. Conversion of this solid residue into aluminum-rich zeolite (13X) and silicon-rich zeolite (ZSM-5) was investigated in this research. The FAAE residue was activated by alkali roasting with Na2CO3 powder (110% mass fraction) at 890 °C for 60 min. Silicon and aluminum were mainly present as two mineral phases, Na2SiO3 and NaAlSiO4, respectively, in the product obtained after roasting. The roasted product was dissolved in water (liquid/solid ratio of 2) after 20 min at 100 °C. The water-leaching liquor was investigated for total conversion to aluminosilicate zeolites without external aluminum or silicon addition. Hydrothermal synthesis of aluminum-rich zeolite 13X was successful after fine tuning of the conditions, although the filtrate had an unusually high SiO2/Al2O3 molar ratio. Production of 13X consumed a large amount of aluminum, which increased the Si/Al ratio to a level suitable for synthesis of ZSM-5. The synthesis of ZSM-5 from the mother liquor of 13X was proved feasible. The FAAE residue was transformed into high-value zeolite products by nearly 100%. Additionally, the tail liquid of this process, mainly containing Na2CO3, was completely recycled. This process could be used to realize high-efficiency and high-value utilization of similar aluminosilicate solid wastes.

Deep learning for survival analysis in breast cancer with whole slide image data.

MOTIVATION: Whole slide tissue images contain detailed data on the sub-cellular structure of cancer. Quantitative analyses of this data can lead to novel biomarkers for better cancer diagnosis and prognosis and can improve our understanding of cancer mechanisms. Such analyses are challenging to execute because of the sizes and complexity of whole slide image data and relatively limited volume of training data for machine learning methods. RESULTS: We propose and experimentally evaluate a multi-resolution deep learning method for breast cancer survival analysis. The proposed method integrates image data at multiple resolutions and tumor, lymphocyte and nuclear segmentation results from deep learning models. Our results show that this approach can significantly improve the deep learning model performance compared to using only the original image data. The proposed approach achieves a c-index value of 0.706 compared to a c-index value of 0.551 from an approach that uses only color image data at the highest image resolution. Furthermore, when clinical features (sex, age and cancer stage) are combined with image data, the proposed approach achieves a c-index of 0.773. AVAILABILITY AND IMPLEMENTATION: https://github.com/SBU-BMI/deep_survival_analysis.

The Interplay Between TGF-ß Signaling and Cell Metabolism.

The transforming growth factor-ß (TGF-ß) signaling plays a critical role in the development and tissue homeostasis in metazoans, and deregulation of TGF-ß signaling leads to many pathological conditions. Mounting evidence suggests that TGF-ß signaling can actively alter metabolism in diverse cell types. Furthermore, metabolic pathways, beyond simply regarded as biochemical reactions, are closely intertwined with signal transduction. Here, we discuss the role of TGF-ß in glucose, lipid, amino acid, redox and polyamine metabolism with an emphasis on how TGF-ß can act as a metabolic modulator and how metabolic changes can influence TGF-ß signaling. We also describe how interplay between TGF-ß signaling and cell metabolism regulates cellular homeostasis as well as the progression of multiple diseases, including cancer.

Broadband light management in hydrogel glass for energy efficient windows.

Windows are critically important components in building envelopes that have a significant effect on the integral energy budget. For energy saving, here we propose a novel design of hydrogel-glass which consists of a layer of hydrogel and a layer of normal glass. Compared with traditional glass, the hydrogel-glass possesses a higher level of visible light transmission, stronger near-infrared light blocking, and higher mid-infrared thermal emittance. With these properties, hydrogel-glass based windows can enhance indoor illumination and reduce the temperature, reducing energy use for both lighting and cooling. Energy savings ranging from 2.37 to 10.45 MJ/m2 per year can be achieved for typical school buildings located in different cities around the world according to our simulations. With broadband light management covering the visible and thermal infrared regions of the spectrum, hydrogel-glass shows great potential for application in energy-saving windows.

GRMT: Generative Reconstruction of Mutation Tree From Scratch Using Single-Cell Sequencing Data.

Single-cell sequencing (SCS) now promises the landscape of genetic diversity at single cell level, and is particularly useful to reconstruct the evolutionary history of tumor. There are multiple types of noise that make the SCS data notoriously error-prone, and significantly complicate tumor tree reconstruction. Existing methods for tumor phylogeny estimation suffer from either high computational intensity or low-resolution indication of clonal architecture, giving a necessity of developing new methods for efficient and accurate reconstruction of tumor trees. We introduce GRMT (Generative Reconstruction of Mutation Tree from scratch), a method for inferring tumor mutation tree from SCS data. GRMT exploits the k-Dollo parsimony model to allow each mutation to be gained once and lost at most k times. Under this constraint on mutation evolution, GRMT searches for mutation tree structures from a perspective of tree generation from scratch, and implements it to an iterative process that gradually increases the tree size by introducing a new mutation per time until a complete tree structure that contains all mutations is obtained. This enables GRMT to efficiently recover the chronological order of mutations and scale well to large datasets. Extensive evaluations on simulated and real datasets suggest GRMT outperforms the state-of-the-arts in multiple performance metrics. The GRMT software is freely available at https://github.com/qasimyu/grmt.

Preparation of porous biochar based on pharmaceutical sludge activated by NaOH and its application in the adsorption of tetracycline.

In this study, two different kinds of pharmaceutical sludge activated by NaOH were used to prepare biochar. The characteristics of biochar prepared by impregnation method and dry mixing method were analyzed, including N2 adsorption-desorption isotherms, surface functional group analysis and micromorphological observation. The results showed that the biochar prepared by impregnation method had more micropores, while that prepared by dry mixing activation method had more mesopores. The adsorption reaction of tetracycline on the two different kind of biochar was investigated. Several important factors such as solution initial pH, tetracycline concentration and reaction time on adsorption reaction were investigated. The results show that both kinds of biochar have high tetracycline adsorption efficiency and excellent pH adaptability. The biochar manufactured by dry mixing activation method had better adsorption performance (379.78 mg/g, 25 °C). Regeneration experiments showed that the adsorbent had stable performance in absorbing tetracycline. Direct dry mixing activation method is a simple and effective method used to prepare porous biochar, which can be used for the resourceful utilization of pharmaceutical sludge. This work provides extensive information on the use of biochar derived from pharmaceutical sludge for the removal of TC from hospital and pharmaceutical production wastewater.

The characteristics of pharmaceutical sludge-derived biochar and its application for the adsorption of tetracycline.

In this study, the specific surface area, pore structure, surface functional groups and microstructure of the biochar derived from the pyrolysis of pharmaceutical sludge are analyzed. The results showed that the pyrolysis temperature had a great influence on the properties of sludge-based biochar (SBB), and the specific surface area of the SBB first increased and then decreased with an increase in the pyrolysis temperature. The maximum specific surface area was 214.97 m2/g at 600 °C, while the pore volume increased with an increase in the pyrolysis temperature. The pickling process removed impurities in the SBB and increased the specific surface area of the material (319.80 m2/g). The effects of pyrolysis temperature, pH, adsorption time, and initial pollutant concentration on the adsorption process were also studied. The results showed that the adsorbents had good pH adaptability, and biochar produced at 600 °C had the best adsorption capacity (94.69 mg/g). Pickling increased the adsorption capacity to 157.38 mg/g. The results showed that pharmaceutical sludge has great potential as a raw material for the preparation of adsorbent. These benefits can compensate for the cost of sludge pyrolysis treatment.

Abnormal tapetum development in hermaphrodites of an androdioecious tree, Tapiscia sinensis.

Tapiscia sinensis Oliv. (Tapisciaceae) has been proven to be a functional androdioecious species with both male and hermaphroditic individuals, and the pollen viability of males is far higher than that of hermaphrodites. To better understand the causes of the low pollen viability in hermaphroditic flowers, different stages of anther development were observed. We found that hermaphroditic flowers exhibit abnormal tapetum development, resulting in low pollen viability. To clarify the underlying molecular mechanism of abnormal tapetum development in hermaphrodites, quantitative real-time PCR analyses were performed. The results revealed that the expression levels of an important transcription factor for tapetum development and function, T. sinensis DYSFUNCTIONAL TAPETUM1 (TsDYT1), and its potential downstream regulatory genes T. sinensis DEFECTIVE in TAPETAL DEVELOPMENT and FUNCTION1 (TsTDF1), T. sinensis ABORTED MICROSPORE (TsAMS) and T. sinensis MALE STERILITY 1 (TsMS1) were all significantly downregulated in hermaphrodites compared with males at some key stages of anther development. The amino acid sequence similarity, expression pattern, gene structure and subcellular localization of these genes were analyzed, and the results indicated functional conservation between T. sinensis and homologues in Arabidopsis thaliana. Next, rapid amplification of cDNA end and thermal asymmetric interlaced PCR were employed to clone the full-length cDNA and promoter sequences of these genes, respectively. In addition, results of yeast two-hybrid analysis showed that TsDYT1 can form heterodimers with TsAMS, and yeast one-hybrid analysis demonstrated that TsDYT1 directly binds to the promoter regions of TsTDF1 and TsMS1. TsTDF1 can directly regulate expression of TsAMS, suggesting that a functionally conserved pathway exists between A. thaliana and T. sinensis to regulate tapetum development. In conclusion, the results suggest that abnormal expression of core transcription factors for tapetum development, including TsDYT1, TsTDF1, TsAMS and TsMS1, plays an important role in the abnormal development of the tapetum in T. sinensis hermaphrodites. Furthermore, a hermaphroditic tapetum with abnormal function causes the low pollen viability of hermaphroditic trees. Our results provide new insight into our understanding of the underlying mechanism of why pollen viability is much higher in males than hermaphrodites of the androdioecious tree T. sinensis.

The ethylene receptor regulates Typha angustifolia leaf aerenchyma morphogenesis and cell fate.

MAIN CONCLUSION: Ethylene receptor is crucial for PCD and aerenchyma formation in Typha angustifolia leaves. Not only does it receive and deliver the ethylene signal, but it probably can determine the cell fate during aerenchyma morphogenesis, which is due to the receptor expression quantity. Aquatic plant oxygen delivery relies on aerenchyma, which is formed by a programmed cell death (PCD) procedure. However, cells in the outer edge of the aerenchyma (palisade cells and septum cells) remain intact, and the mechanism is unclear. Here, we offer a hypothesis: cells that have a higher content of ethylene receptors do not undergo PCD. In this study, we investigated the leaf aerenchyma of the aquatic plant Typha angustifolia. Ethephon and pyrazinamide (PZA, an inhibitor of ACC oxidase) were used to confirm that ethylene is an essential hormone for PCD of leaf aerenchyma cells in T. angustifolia. That the ethylene receptor was an indispensable factor in this PCD was confirmed by 1-MCP (an inhibitor of the ethylene receptor) treatment. Although PCD can be avoided by blocking the ethylene receptor, excessive ethylene receptors also protect cells from PCD. TaETR1, TaETR2 and TaEIN4 in the T. angustifolia leaf were detected by immunofluorescence (IF) using polyclonal antibodies. The result showed that the content of ethylene receptors in PCD-unsusceptible cells was 4-14 times higher than that one in PCD-susceptible cells, suggesting that PCD-susceptible cells undergo the PCD programme, while PCD-unsusceptible cells do not due to the content difference in the ethylene receptor in different cells. A higher level of ethylene receptor content makes the cells insensitive to ethylene, thereby avoiding cell death and degradation.