A Chinese patient with Rothmund-Thomson syndrome.

INTRODUCTION: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder that has been reported in all ethnicities, with several identifiable pathogenic variants. There have been reported cases indicating that RTS may lead to low birth weight in fetuses, but specific data on the fetal period are lacking. Genetic testing for RTS II is currently carried out by identifying pathogenic variants in RECQL4. METHODS: In order to determine the cause, we performed whole-genome sequencing (WGS) analysis on the patient and his parents. Variants detected by WGS were confirmed by Sanger sequencing and examined in family members. RESULTS: After analyzing the WGS data, we found a heterozygous nonsense mutation c.2752G>T (p.Glu918Ter) and a novel frameshift insertion mutation c.1547dupC (p.Leu517AlafsTer23) of RECQL4, which is a known pathogenic/disease-causing variant of RTS. Further validation indicated these were compound heterozygous mutations from parents. CONCLUSION: Our study expands the mutational spectrum of the RECQL4 gene and enriches the phenotype spectrum of Chinese RTS patients. Our information can assist the patient's parents in making informed decisions regarding their future pregnancies. This case offers a new perspective for clinicians to consider whether to perform prenatal diagnosis.

Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia.

Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.

Coupled sorptive and oxidative antimony(III) removal by iron-modified biochar: Mechanisms of electron-donating capacity and reactive Fe species.

Sorption and oxidation are two potential pathways for the decontamination of trivalent antimony (Sb(III))-bearing water, using iron (Fe)-modified biochar (FeBC). Here we investigated the sorption and oxidation behavior of FeBC for Sb(III) in aqueous solutions. Results revealed that Sb(III) removal by FeBC was significantly improved showing the maximum Sb(III) sorption (64.0 mg g-1). Density functional theory (DFT) calculations indicated that magnetite (Fe3O4) in FeBC offered a sorption energy of -0.22 eV, which is 5 times that of non-modified biochar. With the addition of peroxymonosulfate (PMS), the sorption of Sb(III) on FeBC was 7 times higher than that on BC, indicating the sorption capacity of FeBC for Sb(III) could be substantially increased by adding oxidizing agents. Electrochemical analysis showed that Fe modification imparted FeBC higher electron-donating capacity than that of BC (0.045 v. s. 0.023 mmol e- (g biochar)-1), which might be the reason for the strong Sb(III) oxidation (63.6%) on the surface of FeBC. This study provides new information that is key for the development of effective biochar-based composite materials for the removal of Sb(III) from drinking water and wastewater. The findings from this study have important implications for protecting human health and agriculture.

Biochar Derived from Urban Green Waste Can Enhance the Removal of Cd from Water and Reduce Soil Cd Bioavailability.

The beneficial utilization of potentially increasing urban green waste (UGW) is critical for sustainable urban development in China. In this study, UGW was pyrolyzed at different temperatures, and the resulting biochar was used to amend Cd-contaminated soils to grow cabbage. Our results showed that the Cd adsorption capacity of UGW-biochar was positively correlated with the surface area, O/C, and (O+N)/C value of biochar. Furthermore, UGW-biochar was incorporated into three Cd-contaminated soils, including one acidic soil and two neutral soils, to assess its impact on the availability of Cd. The most substantial reduction in the concentration of available Cd was observed in the acidic soil, of the three tested soils. In the neutral soils, a more substantial reduction was found in the heavily Cd-contaminated soil compared to the lightly Cd-contaminated soil. UGW-biochar amendments to the three Cd-contaminated soils resulted in an increase in the cabbage biomass in acidic soil, whereas in neutral soils, it increased in lightly contaminated soils but decreased in heavily contaminated soils. Additionally, the Cd bioaccumulation factor (BCF), translocation factor (TF), and removal efficiency (RE), as impacted by the biochar application, were calculated in the lightly Cd-contaminated soil-cabbage system. The BCF decreased from 5.84 to 3.80 as the dosage of the UGW-biochar increased from 0% to 3%, indicating that the UGW-biochar immobilized Cd and reduced its bioaccumulation in cabbage roots. Based on our investigations, UGW-biochar effectively immobilizes Cd by reducing its mobility and bioavailability in a lightly contaminated environment matrix.

Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome.

The placenta is important for fetal development in mammals, and spatial transcriptomic profiling of placenta helps to resolve its structure and function. In this study, we described the landscape of spatial transcriptome of human placental villi obtained from two pregnant women at the first trimester using the modified Stereo-seq method applied for paraformaldehyde (PFA) fixation samples. The PFA fixation of human placenta villi was better than fresh villi embedded in optimum cutting temperature (OCT) compound, since it greatly improved tissue morphology and the specificity of RNA signals. The main cell types in chorionic villi such as syncytiotrophoblasts (SCT), villous cytotrophoblasts (VCT), fibroblasts (FB), and extravillous trophoblasts (EVT) were identified with the spatial transcriptome data, whereas the minor cell types of Hofbauer cells (HB) and endothelial cells (Endo) were spatially located by deconvolution of scRNA-seq data. We demonstrated that the Stereo-seq data of human villi could be used for sophisticated analyses such as spatial cell-communication and regulatory activity. We found that the SCT and VCT exhibited the most ligand-receptor pairs that could increase differentiation of the SCT, and that the spatial localization of specific regulons in different cell types was associated with the pathways related to hormones transport and secretion, regulation of mitotic cell cycle, and nutrient transport pathway in SCT. In EVT, regulatory pathways such as the epithelial to mesenchyme transition, epithelial development and differentiation, and extracellular matrix organization were identified. Finally, viral receptors and drug transporters were identified in villi according to the pathway analysis, which could help to explain the vertical transmission of several infectious diseases and drug metabolism efficacy. Our study provides a valuable resource for further investigation of the placenta development, physiology and pathology in a spatial context.

Clinical and Genetic Characteristics of a Cohort with Distal Vaginal Atresia.

Distal vaginal atresia is a rare abnormality of female reproductive tract in which the vagina is closed or absent. The distal vagina may be replaced by fibrous tissue and the condition is often not diagnosed until a girl fails to begin having periods at puberty. Although it is a congenital disorder, potential genetic causes of distal vaginal atresia are still unknown. We recruited a cohort of 39 patients with distal vaginal atresia and analyzed their phenotypic and genetic features. In addition to the complaint of distal vaginal atresia, approximately 17.9% (7/39) of the patients had other Müllerian anomalies, and 17.9% (7/39) of the patients had other structural abnormalities, including renal-tract, skeletal and cardiac anomalies. Using genome sequencing, we identified two fragment duplications on 17q12 encompassing HNF1B and LHX1, two dosage-sensitive genes with candidate pathogenic variants, in two unrelated patients. A large fragment of uniparental disomy was detected in another patient, affecting genes involved in cell morphogenesis and connective tissue development. Additionally, we reported two variants on TBX3 and AXL, leading to distal vaginal atresia in mutated mouse model, in our clinical subjects for the first time. Essential biological functions of these detected genes with pathogenic variants included regulating reproductive development and cell fate and patterning during embryogenesis. We displayed the comprehensive clinical and genetic characteristic of a cohort with distal vaginal atresia and they were highly heterogeneous both phenotypically and genetically. The duplication of 17q12 in our cohort could help to expand its phenotypic spectrum and potential contribution to the distal vaginal atresia. Our findings of pathogenic genetic variants and associated phenotypes in our cohort could provide evidence and new insight for further research attempting to reveal genetic causes of distal vaginal atresia.

Polyadenylation ligation-mediated sequencing (PALM-Seq) characterizes cell-free coding and non-coding RNAs in human biofluids.

BACKGROUND: Cell-free messenger RNA (cf-mRNA) and long non-coding RNA (cf-lncRNA) are becoming increasingly important in liquid biopsy by providing biomarkers for disease prediction, diagnosis and prognosis, but the simultaneous characterization of coding and non-coding RNAs in human biofluids remains challenging. METHODS: Here, we developed polyadenylation ligation-mediated sequencing (PALM-Seq), an RNA sequencing strategy employing treatment of RNA with T4 polynucleotide kinase to generate cell-free RNA (cfRNA) fragments with 5' phosphate and 3' hydroxyl and RNase H to deplete abundant RNAs, achieving simultaneous quantification and characterization of cfRNAs. RESULTS: Using PALM-Seq, we successfully identified well-known differentially abundant mRNA, lncRNA and microRNA in the blood plasma of pregnant women. We further characterized cfRNAs in blood plasma, saliva, urine, seminal plasma and amniotic fluid and found that the detected numbers of different RNA biotypes varied with body fluids. The profiles of cf-mRNA reflected the function of originated tissues, and immune cells significantly contributed RNA to blood plasma and saliva. Short fragments (<50 nt) of mRNA and lncRNA were major in biofluids, whereas seminal plasma and amniotic fluid tended to retain long RNA. Body fluids showed distinct preferences of pyrimidine at the 3' end and adenine at the 5' end of cf-mRNA and cf-lncRNA, which were correlated with the proportions of short fragments. CONCLUSION: Together, PALM-Seq enables a simultaneous characterization of cf-mRNA and cf-lncRNA, contributing to elucidating the biology and promoting the application of cfRNAs.

Gut microbiota in gastrointestinal diseases during pregnancy.

Gut microbiota (GM) is a micro-ecosystem composed of all microorganisms in the human intestine. The interaction between GM and the host plays an important role in maintaining normal physiological functions in the host. Dysbiosis of the GM may cause various diseases. GM has been demonstrated to be associated with human health and disease, and changes during individual development and disease. Pregnancy is a complicated physiological process. Hormones, the immune system, metabolism, and GM undergo drastic changes during pregnancy. Gastrointestinal diseases during pregnancy, such as hepatitis, intrahepatic cholestasis of pregnancy, and pre-eclampsia, can affect both maternal and fetal health. The dysregulation of GM during pregnancy may lead to a variety of diseases, including gastrointestinal diseases. Herein, we review recent research articles on GM in pregnancy-related gastrointestinal diseases, discuss the interaction of the GM with the host under normal physiological conditions, gastrointestinal diseases, and pregnancy-specific disorders. As more attention is paid to reproductive health, the pathogenic mechanism of GM in gastrointestinal diseases during pregnancy will be further studied to provide a theoretical basis for the use of probiotics to treat these diseases.

Peripheral Blood Transcripts Predict Preoperative Obstructive Total Anomalous Pulmonary Venous Connection.

The lack of accessible noninvasive tools to examine the molecular alterations limits our understanding of the causes of total anomalous pulmonary venous connection (TAPVC), as well as the identification of effective operational strategies. Here, we consecutively enrolled peripheral leukocyte transcripts of 26 preoperative obstructive and 22 non-obstructive patients with TAPVC. Two-hundred and fifty six differentially expressed mRNA and 27 differentially expressed long noncoding RNA transcripts were dysregulated. The up-regulated mRNA was enriched in the hydrogen peroxide catabolic process, response to mechanical stimulus, neutrophil degranulation, hemostasis, response to bacterium, and the NABA CORE MATRISOME pathway, all of which are associated with the development of fibrosis. Furthermore, we constructed predictive models using multiple machine-learning algorithms and tested the performance in the validation set. The mRNA NR3C2 and lncRNA MEG3 were screened based on multiple iterations. The random forest prediction model can predict preoperative obstruction patients in the validation set with high accuracy (area under curve = 1; sensitivity = 1). These data highlight the potential of peripheral leukocyte transcripts to evaluate obstructive-related pathophysiological alterations, leading to precision healthcare solutions that could improve patient survival after surgery. It also provides a novel direction for the study of preoperative obstructive TAPVC.

Enhanced sorption of trivalent antimony by chitosan-loaded biochar in aqueous solutions: Characterization, performance and mechanisms.

Contamination of aquatic systems by antimony (Sb) is a worldwide issue due to its risks to eco-environment and human health. Batch sorption experiments were conducted to assess the equilibrium, kinetics and thermodynamics of antimonite [Sb(III)] sorption by pristine biochar (BC) and chitosan-loaded biochar (CHBC) derived from branches of Ficus microcarpa. Results showed the successful loading of chitosan onto biochar surface, exhibiting more functional groups (e.g., CO, -NH2, and -OH). Langmuir model well described the Sb(III) sorption isotherm experimental data, and the maximum sorption capacity of Sb(III) by CH1BC (biochar loaded with chitosan at a ratio of 1:1) was 168 mg g-1, whereas for the BC it was only 10 mg g-1. X-ray photoelectron spectroscopy demonstrated that CH1BC oxidized 86% of Sb(III) to Sb(V), while BC oxidized 71% of Sb(III). Density functional theory calculations suggested that the synergistic effect of exogenous hydroxyl and inherent carbonyl contributed to the enhanced removal efficiency of Sb(III) by CHBC. Key mechanisms for Sb(III) sorption onto CHBCs included electrostatic interaction, chelation, surface complexation, π-π interaction, and hydrogen bonding. Overall, this study implies that CHBC can be a new, viable sorbent for the removal of Sb(III) from aquatic systems aiding their safe and sustainable management.

Biochar protects hydrophilic dissolved organic matter against mineralization and enhances its microbial carbon use efficiency.

A combination of biochar with exogenous organic material in soils is often used in practical farmland management. The objective of this study was to determine how biochar affects organic matter decomposition by studying the decomposition of 13C-labelled hydrophilic (Hi-) and hydrophobic (Ho-) dissolved organic matter (DOM) in acid and neutral soils during a 60-day incubation experiment. The proportions of carbon (C) mineralization in Hi-DOM with or without biochar addition were 32.6% or 34.5% in acid soil (P > 0.05) and 15.4% or 22.3% in neutral soil (P < 0.05), respectively. In contrast, those proportions of Ho-DOM-C mineralization with or without biochar addition were 20.0% or 21.4% in acid soil and 19.0% or 20.5% in neutral soil (P > 0.05), respectively. These results showed that biochar could protect Hi-DOM against mineralization in neutral soil but exhibited less effect on Ho-DOM mineralization in both acid and neutral soils. Additionally, biochar did not affect microbial incorporation of Hi- or Ho-DOM in acid and neutral soils. However, biochar notably improved the microbial carbon use efficiency (CUE) of Hi-DOM while it significantly reduced the CUE of Ho-DOM in neutral soil (P < 0.05), indicating that the effect of biochar on microbial CUE was related to organic matter type and soil pH. This study suggests that Hi-DOM can outperform Ho-DOM to decrease C loss and improve microbial CUE in neutral soil with biochar addition. This phenomenon could be due mainly to the different chemical compositions of Hi-DOM and Ho-DOM and their distinct microbial preference. These findings can provide references for biochar's ability to regulate the decomposition of organic matter.

Fractionation of Heavy Metals in Multi-Contaminated Soil Treated with Biochar Using the Sequential Extraction Procedure.

Heavy metals (HMs) toxicity represents a global problem depending on the soil environment's geochemical forms. Biochar addition safely reduces HMs mobile forms, thus, reducing their toxicity to plants. While several studies have shown that biochar could significantly stabilize HMs in contaminated soils, the study of the relationship of soil properties to potential mechanisms still needs further clarification; hence the importance of assessing a naturally contaminated soil amended, in this case with Paulownia biochar (PB) and Bamboo biochar (BB) to fractionate Pb, Cd, Zn, and Cu using short sequential fractionation plans. The relationship of soil pH and organic matter and its effect on the redistribution of these metals were estimated. The results indicated that the acid-soluble metals decreased while the fraction bound to organic matter increased compared to untreated pots. The increase in the organic matter metal-bound was mostly at the expense of the decrease in the acid extractable and Fe/Mn bound ones. The highest application of PB increased the organically bound fraction of Pb, Cd, Zn, and Cu (62, 61, 34, and 61%, respectively), while the BB increased them (61, 49, 42, and 22%, respectively) over the control. Meanwhile, Fe/Mn oxides bound represents the large portion associated with zinc and copper. Concerning soil organic matter (SOM) and soil pH, as potential tools to reduce the risk of the target metals, a significant positive correlation was observed with acid-soluble extractable metal, while a negative correlation was obtained with organic matter-bound metal. The principal component analysis (PCA) shows that the total variance represents 89.7% for the TCPL-extractable and HMs forms and their relation to pH and SOM, which confirms the positive effect of the pH and SOM under PB and BB treatments on reducing the risk of the studied metals. The mobility and bioavailability of these metals and their geochemical forms widely varied according to pH, soil organic matter, biochar types, and application rates. As an environmentally friendly and economical material, biochar emphasizes its importance as a tool that makes the soil more suitable for safe cultivation in the short term and its long-term sustainability. This study proves that it reduces the mobility of HMs, their environmental risks and contributes to food safety. It also confirms that performing more controlled experiments, such as a pot, is a disciplined and effective way to assess the suitability of different types of biochar as soil modifications to restore HMs contaminated soil via controlling the mobilization of these minerals.

Influence of biochar and soil properties on soil and plant tissue concentrations of Cd and Pb: A meta-analysis.

The application of biochar to soils contaminated with potentially toxic elements (PTEs) has received particular attention due to its ability to reduce PTE uptake by the plants. Therefore, we conducted a meta-analysis to identify Cd and Pb concentrations in plant shoots and roots in response to biochar application and soil properties. We collected data from 65 peer-reviewed journal articles published from 2009 to 2020 in which 66% of manuscripts were published from 2015 to 2020. The data were processed using OpenMEE software. The results pinpointed that addition of biochar to soil caused a significant decrease in shoot and root Cd and Pb concentrations as compared to untreated soils with biochar (control), and the reduction rate was affected by plant types and both biochar and soil properties. The biochar size less than 2 mm, biochar pH higher than 10, pyrolysis temperature of 401-600 °C, and the application rate higher than 2% appeared to be effective in reducing shoot and root Cd and Pb concentration. Soil properties such as pH, SOC, and texture influenced the efficiency of biochar for reducing plant Cd and Pb uptake. Biochar application increased SOC (54.3%), CEC (48.0%), pH (0.08), and EC (59.4%), and reduced soil extractable Cd (42.1%) and Pb (47.1%) concentration in comparison to control. A detailed study on the rhizosphere chemistry and uptake mechanism will help to underpin the biochar application rates and their efficiency reducing PTE mobility and plant uptake.

Kindlin-2 promotes rear focal adhesion disassembly and directional persistence during cell migration.

Cell migration involves front-to-rear asymmetric focal adhesion (FA) dynamics, which facilitates trailing edge detachment and directional persistence. Here, we show that kindlin-2 is crucial for FA sliding and disassembly in migrating cells. Loss of kindlin-2 markedly reduced FA number and selectively impaired rear FA sliding and disassembly, resulting in defective rear retraction and reduced directional persistence during cell migration. Kindlin-2-deficient cells failed to develop serum-induced actomyosin-dependent tension at FAs. At the molecular level, kindlin-2 directly interacted with myosin light chain kinase (MYLK, hereafter referred to as MLCK), which was enhanced in response to serum stimulation. Serum deprivation inhibited rear FA disassembly, which was released in response to serum stimulation. Overexpression of the MLCK-binding kindlin-2 F0F1 fragment (amino acid residues 1-167), which inhibits the interaction of endogenous kindlin-2 with MLCK, phenocopied kindlin-2 deficiency-induced migration defects. Inhibition of MLCK, like loss of kindlin-2, also impaired trailing-edge detachment, rear FA disassembly and directional persistence. These results suggest a role of kindlin-2 in promoting actomyosin contractility at FAs, leading to increased rear FA sliding and disassembly, and directional persistence during cell migration.

Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that specifically occurs in pregnancy. Elevated levels of liver transaminases aspartate aminotransferase, alanine aminotransferase and serum bilirubin levels are common biochemical characteristics in ICP. The disorder is associated with an increased risk of premature delivery and stillbirth. The characterization of the potential microbiota in ICP could go a long way in the prevention and treatment of this pregnancy disease. METHODS: A total of 58 patients were recruited for our study: 27 ICP patients and 31 healthy pregnant subjects with no ICP. The V3 and V4 regions of the 16S rDNA collected from fecal samples of both diseased and control groups were amplified. 16S rRNA gene amplicon sequencing was then performed on gut microbiota. Sequencing data were analyzed and the correlation between components of microbiota and patient ICP status was found. Related metabolic pathways, relative abundance and significantly different operational taxonomic units (OTUs) between ICP and controls were also identified. RESULTS: Elevated levels of total bile acid, ALT, AST, Dbil and Tbil were recorded or observed in ICP subjects as compared to the control. Gut microbiota in pregnant women was dominated by four major phyla and 27 core genera. PCoA analysis results indicated that there was no significant clustering in Bray-Curtis distance matrices. Our results showed that there was a correlation between specific OTUs and measured clinical parameters of pregnant women. Comparison at the different taxonomy levels revealed high levels of abundance of Blautia and Citrobacter in ICP patients. At the family level, Enterobacteriaceae and Leuconostocaceae were higher in ICP patients. 638 KEGG Orthologs and 138 pathways significantly differed in the two groups. PLS-DA model with VIP plots indicated a total of eight genera and seven species were key taxa in ICP and control groups. CONCLUSIONS: Our research indicated that although there was no significant clustering by PCoA analysis, patients with ICP have increased rare bacteria at different phylogenetic levels. Our results also illustrated that all 638 KEGG Orthologs and 136 in 138 KEGG pathways were less abundant in ICP patients compared to the controls.

Facile synthesis of polyoxometalate-modified metal organic frameworks for eliminating tetrabromobisphenol-A from water.

Removal of tetrabromobisphenol-A (TBBPA) from wastewater is of significance to protect the aquatic life. The present study reports the facile preparation of polyoxometalate-modified metal-organic framework (MOFs) materials for TBBPA removal from water. The polyoxometalate-modified MOFs exhibited significantly higher affinity towards TBBPA than the control MOFs. The experimental data were fitted with the Langmuir, Freundlich and Dubinin-Radushkevich models. The TBBPA adsorption onto modified MOFs fitted the pseudo-second-order kinetic model. The equilibrium adsorption isotherms showed that the adsorption of TBBPA can be fitted by the Langmuir model. The maximum adsorption capacity of adsorbent composites reached 3.65 mg/g, with 95 % removal of TBBPA. The thermodynamic parameters indicated that adsorption was spontaneous. A blue shift of phosphorus peaks obtained from XPS spectra implied the formation of intrinsic chemical bonding between TBBPA and MOFs composites. Moreover, response surface methodology was employed to characterize the TBBPA adsorption in the co-existence of different factors. BPA had strong competition for TBBPA adsorption in a wide range of pH, but not at the middle level of Ca2+ concentration. Polyoxometalate-modified MOFs can easily be recycled using a simple organic solvent washing. This study provides a novel strategy for developing cost effective adsorbents to remove TBBPA from contaminated water.

The ratio of H/C is a useful parameter to predict adsorption of the herbicide metolachlor to biochars.

Biochar adsorbent was produced by pyrolyzing traditional Chinese medicinal herb residue at 300, 500 and 750 °C (referred to as biochar-300, biochar-500 and biochar-750). Basic physical and chemical analyses, Fourier transform infrared spectroscopy (FT-IR), and thermodynamic analyses were performed to elucidate adsorption and properties of biochar. Biochar adsorption capacity of herbicide metolochlor, as measured by batch-type adsorption experiments by Freundlich constant Kf (mg1-n Ln kg-1), followed the order: biochar-750 > biochar-300 > biochar-500. Thermodynamic analysis suggested that adsorption of metolachlor on biochar was a spontaneous process. The adsorption isotherm for the biochar produced at the highest pyrolysis temperature was characteristic for adsorption process driven by a high surface area of biochar (85.30 m2 g-1), while the adsorption process for the biochar produced at the lowest temperature was controlled by its higher content of organic matter (39.06%) and abundant functional groups. The FT-IR spectra also showed that the biochar prepared at the lowest temperature had the highest number of surface groups. In general, pore-filling induced by the large surface area of the biochar was the dominant adsorption mechanism. When the H/C value was >0.5, the adsorption mechanism of biochar was dominated by surface chemical bond, while pore-filling played a major role when the H/C value was <0.5.

Kindlin-2 regulates mesenchymal stem cell differentiation through control of YAP1/TAZ.

Precise control of mesenchymal stem cell (MSC) differentiation is critical for tissue development and regeneration. We show here that kindlin-2 is a key determinant of MSC fate decision. Depletion of kindlin-2 in MSCs is sufficient to induce adipogenesis and inhibit osteogenesis in vitro and in vivo. Mechanistically, kindlin-2 regulates MSC differentiation through controlling YAP1/TAZ at both the transcript and protein levels. Kindlin-2 physically associates with myosin light-chain kinase in response to mechanical cues of cell microenvironment and intracellular signaling events and promotes myosin light-chain phosphorylation. Loss of kindlin-2 inhibits RhoA activation and reduces myosin light-chain phosphorylation, stress fiber formation, and focal adhesion assembly, resulting in increased Ser127 phosphorylation, nuclear exclusion, and ubiquitin ligase atrophin-1 interacting protein 4-mediated degradation of YAP1/TAZ. Our findings reveal a novel kindlin-2 signaling axis that senses the mechanical cues of cell microenvironment and controls MSC fate decision, and they suggest a new strategy to regulate MSC differentiation, tissue repair, and regeneration.

Kindlin-2 Association with Rho GDP-Dissociation Inhibitor α Suppresses Rac1 Activation and Podocyte Injury.

Alteration of podocyte behavior is critically involved in the development and progression of many forms of human glomerular diseases. The molecular mechanisms that control podocyte behavior, however, are not well understood. Here, we investigated the role of Kindlin-2, a component of cell-matrix adhesions, in podocyte behavior in vivo Ablation of Kindlin-2 in podocytes resulted in alteration of actin cytoskeletal organization, reduction of the levels of slit diaphragm proteins, effacement of podocyte foot processes, and ultimately massive proteinuria and death due to kidney failure. Through proteomic analyses and in vitro coimmunoprecipitation experiments, we identified Rho GDP-dissociation inhibitor α (RhoGDIα) as a Kindlin-2-associated protein. Loss of Kindlin-2 in podocytes significantly reduced the expression of RhoGDIα and resulted in the dissociation of Rac1 from RhoGDIα, leading to Rac1 hyperactivation and increased motility of podocytes. Inhibition of Rac1 activation effectively suppressed podocyte motility and alleviated the podocyte defects and proteinuria induced by the loss of Kindlin-2 in vivo Our results identify a novel Kindlin-2-RhoGDIα-Rac1 signaling axis that is critical for regulation of podocyte structure and function in vivo and provide evidence that it may serve as a useful target for therapeutic control of podocyte injury and associated glomerular diseases.