Three-Dimensional Simulation of Whole-Genome Structuring Through the Transition from Anaphase to Interphase.

In order to analyze the three-dimensional genome architecture, it is important to simulate how the genome is structured through the cell cycle progression. In this chapter, we present the usage of our computation codes for simulating how the human genome is formed as the cell transforms from anaphase to interphase. We do not use the global Hi-C data as an input into the genome simulation but represent all chromosomes as linear polymers annotated by the neighboring region contact index (NCI), which classifies the A/B type of each local chromatin region. The simulated mitotic chromosomes heterogeneously expand upon entry to the G1 phase, which induces phase separation of A and B chromatin regions, establishing chromosome territories, compartments, and lamina and nucleolus associations in the interphase nucleus. When the appropriate one-dimensional chromosomal annotation is possible, using the protocol of this chapter, one can quantitatively simulate the three-dimensional genome structure and dynamics of human cells of interest.

lncRNA PVT1 silencing inhibits gastric cancer cells' progression via enhancing chemosensitivity to paclitaxel.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide because of its high morbidity and the absence of effective therapies. Even though paclitaxel is a powerful anticancer chemotherapy drug, recent studies have indicated its ineffectiveness against GC cells. Long non-coding RNA (lncRNA) PVT1 has a high expression in GC cells and increases the progression of tumors via inducing drug resistance. In the present study, the effects of the siRNA-mediated lncRNA PVT1 gene silencing along with paclitaxel treatment on the rate of apoptosis, growth, and migration of AGS GC cells were investigated. AGS cells were cultured and then transfected with siRNA PVT1 using electroporation. The MTT test was used to examine the effect of treatments on the viability of cultured cells. Furthermore, the flow cytometry method was used to evaluate the impact of treatments on the cell cycle process and apoptosis induction in GC cells. Finally, the mRNA expression of target genes was assessed using the qRT-PCR method. The results showed that lncRNA PVT1 gene suppression, along with paclitaxel treatment, reduces the viability of cancer cells and significantly increases the apoptosis rate of cancer cells and the number of cells arrested in the G2/M phase compared to the control group. Based on the results of qRT-PCR, combined treatment significantly decreased the expression of MMP3, MMP9, MDR1, MRP1, Bcl-2, k-Ras, and c-Myc genes and increased the expression of the Bax gene compared to the control group. The results of our study showed that lncRNA PVT1 gene targeting, together with paclitaxel treatment, induces apoptosis, inhibits growth, alleviates drug resistance, and reduces the migratory capability of GC cells. Therefore, there is a need for further investigations to evaluate the feasibility and effectiveness of this approach in vivo in animal models.

Ti3+/Ti4+ and Co2+/Co3+ redox couples in Ce-doped Co-Ce/TiO2 for enhancing photothermocatalytic toluene oxidation.

Cerium and cobalt loaded Co-Ce/TiO2 catalyst prepared by impregnation method was investigated for photothermal catalytic toluene oxidation. Based on catalyst characterizations (XPS, EPR and H2-TPR), redox cycle between Co and TiO2 (Co2+ + Ti4+ ↔ Co3+ + Ti3+) results in the formation of Co3+, Ti3+ and oxygen vacancies, which play important roles in toluene catalytic oxidation reaction. The introduction of Ce brings in the dual redox cycles (Co2+ + Ti4+ ↔ Co3+ + Ti3+, Co2+ + Ce4+ ↔ Co3+ + Ce3+), further promoting the elevation of reaction sites amount. Under full spectrum irradiation with light intensity of 580 mW/cm2, Co-Ce/TiO2 catalyst achieved 96% of toluene conversion and 73% of CO2 yield, obviously higher than Co/P25 and Co/TiO2. Co-Ce/TiO2 efficiently maintains 10-hour stability test under water vapor conditions and exhibits better photothermal catalytic performance than counterparts under different wavelengths illumination. Photothermal catalytic reaction displays improved activities compared with thermal catalysis, which is attributed to the promotional effect of light including photocatalysis and light activation of reactive oxygen species.

Nitrogen-cycling processes under long-term compound heavy metal(loids) pressure around a gold mine: Stimulation of nitrite reduction.

Mining and tailings deposition can cause serious heavy metal(loids) pollution to the surrounding soil environment. Soil microorganisms adapt their metabolism to such conditions, driving alterations in soil function. This study aims to elucidate the response patterns of nitrogen-cycling microorganisms under long-term heavy metal(loids) exposure. The results showed that the diversity and abundance of nitrogen-cycling microorganisms showed negative feedback to heavy metal(loids) concentrations. Denitrifying microorganisms were shown to be the dominant microorganisms with over 60% of relative abundance and a complex community structure including 27 phyla. Further, the key bacterial species in the denitrification process were calculated using a random forest model, where the top three key species (Pseudomonas stutzei, Sphingobium japonicum and Leifsonia rubra) were found to play a prominent role in nitrite reduction. Functional gene analysis and qPCR revealed that nirK, which is involved in nitrite reduction, significantly accumulated in the most metal-rich soil with the increase of absolute abundance of 63.86%. The experimental results confirmed that the activity of nitrite reductase (Nir) encoded by nirK in the soil was increased at high concentrations of heavy metal(loids). Partial least squares-path model identified three potential modes of nitrite reduction processes being stimulated by heavy metal(loids), the most prominent of which contributed to enhanced nirK abundance and soil Nir activity through positive stimulation of key species. The results provide new insights and preliminary evidence on the stimulation of nitrite reduction processes by heavy metal(loids).

The role of sulfur cycle in new particle formation: Cycloaddition reaction of SO3 to H2S.

The chemistry of sulfur cycle contributes significantly to the atmospheric nucleation process, which is the first step of new particle formation (NPF). In the present study, cycloaddition reaction mechanism of sulfur trioxide (SO3) to hydrogen sulfide (H2S) which is a typical air pollutant and toxic gas detrimental to the environment were comprehensively investigate through theoretical calculations and Atmospheric Cluster Dynamic Code simulations. Gas-phase stability and nucleation potential of the product thiosulfuric acid (H2S2O3, TSA) were further analyzed to evaluate its atmospheric impact. Without any catalysts, the H2S + SO3 reaction is infeasible with a barrier of 24.2 kcal/mol. Atmospheric nucleation precursors formic acid (FA), sulfuric acid (SA), and water (H2O) could effectively lower the reaction barriers as catalysts, even to a barrierless reaction with the efficiency of cis-SA > trans-FA > trans-SA > H2O. Subsequently, the gas-phase stability of TSA was investigated. A hydrolysis reaction barrier of up to 61.4 kcal/mol alone with an endothermic isomerization reaction barrier of 5.1 kcal/mol under the catalytic effect of SA demonstrates the sufficient stability of TSA. Furthermore, topological and kinetic analysis were conducted to determine the nucleation potential of TSA. Atmospheric clusters formed by TSA and atmospheric nucleation precursors (SA, ammonia NH3, and dimethylamine DMA) were thermodynamically stable. Moreover, the gradually decreasing evaporation coefficients for TSA-base clusters, particularly for TSA-DMA, suggests that TSA may participate in NPF where the concentration of base molecules are relatively higher. The present new reaction mechanism may contributes to a better understanding of atmospheric sulfur cycle and NPF.

Carbon emissions in China's steel industry from a life cycle perspective: Carbon footprint insights.

China is the most important steel producer in the world, and its steel industry is one of the most carbon-intensive industries in China. Consequently, research on carbon emissions from the steel industry is crucial for China to achieve carbon neutrality and meet its sustainable global development goals. We constructed a carbon dioxide (CO2) emission model for China's iron and steel industry from a life cycle perspective, conducted an empirical analysis based on data from 2019, and calculated the CO2 emissions of the industry throughout its life cycle. Key emission reduction factors were identified using sensitivity analysis. The results demonstrated that the CO2 emission intensity of the steel industry was 2.33 ton CO2/ton, and the production and manufacturing stages were the main sources of CO2 emissions, accounting for 89.84% of the total steel life-cycle emissions. Notably, fossil fuel combustion had the highest sensitivity to steel CO2 emissions, with a sensitivity coefficient of 0.68, reducing the amount of fossil fuel combustion by 20% and carbon emissions by 13.60%. The sensitivities of power structure optimization and scrap consumption were similar, while that of the transportation structure adjustment was the lowest, with a sensitivity coefficient of less than 0.1. Given the current strategic goals of peak carbon and carbon neutrality, it is in the best interest of the Chinese government to actively promote energy-saving and low-carbon technologies, increase the ratio of scrap steel to steelmaking, and build a new power system.

Dynamical robustness of a Boolean model for the human gonadal sex determination.

Gonadal sex determination (GSD) is a complex but poorly understood process in the early stages of embryonic development. This process determines whether the bipotential gonadal primordium (BGP) will differentiate into testes or ovaries through the activation of genetic factors related to Sertoli or Granulosa cells, respectively. The study of this developmental process remains challenging due to experimental limitations and the complexity of the underlying genetic interactions. Boolean Networks (BNs) are binary networks that simulate genetic behavior and are commonly used for modeling gene regulatory networks (GRNs) due to their simplicity when dealing with a high number of gene interactions. Reported BNs usually use a synchronous (parallel) update scheme, which means that all the nodes (representing genes) update their values simultaneously. However, the use of this update scheme has been criticized because it cannot represent biological systems that are highly regulated at a temporal scale. Asynchronous and block-sequential updating schemes appear as an alternative to tackle this issue. In the first case, the updating scheme follows a random behavior while, in the second case, the set of network nodes is partitioned into blocks such that the nodes within a block are updated simultaneously, and the blocks are considered in a specific order sequence. To assess the impact of different updating approaches in a GRN associated to GSD we first made a node reduction without losing the main dynamics of the original network which are related to the formation of testes and ovaries. Then, we tested the effect of perturbations given by the inactivation of genes on the network attractors, specifically the SRY and WNT4 genes, since the former is only present in the Y chromosome and the latter is of importance in early embryo development. We found that both genes were crucial, but WNT4 alone showed a higher percentage of attractors towards a phenotype than the SRY alone. Finally, we found that using asynchronous and block-sequential updating schemes, the attraction basins - i.e., the set of configurations that reach an attractor - remain with similar percentages to those of the original network, which supports the robustness of the model.

Expression of the apelin system in the porcine pituitary during the oestrous cycle and early pregnancy and the effect of apelin on LH and FSH secretion.

Reproductive success requires considerable energy investment. Research has shown that some adipokines, i.e. the hormones produced in adipose tissue, affect reproductive functions by influencing all structures of the hypothalamic-pituitary-ovarian axis. Apelin is a recently identified member of the adipokine family. To the best of the authors' knowledge, this is the first study to investigate the gene and protein expression of the apelin system (the apelin hormone and the apelin receptor, APJ) in the anterior (AP) and posterior (PP) pituitary lobes of the domestic pig during different phases of the oestrous cycle (days 2 to 3, 10 to 12, 14 to 16, and 17 to 19) and in early pregnancy (days 10 to 11, 12 to 13, 15 to 16, and 27 to 28). It was also assumed that apelin participates in the regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion and influences Akt, MAPK/Erk1/2, and AMPK signalling pathways in the AP during the oestrous cycle. Apelin, APJ mRNAs and proteins were detected in both pituitary lobes. Apelin was identified in gonadotropes, somatotropes, lactotropes, and thyrotropes. The study also revealed that apelin and APJ mRNA/protein levels fluctuate during the oestrous cycle and early gestation. Apelin affects basal, GnRH- and/or insulin-stimulated gonadotropin secretion in some phases of the cycle, as well as the phosphorylation of Akt, MAPK/Erk1/2, and AMPK proteins in AP cells. These findings suggest that apelin may be produced locally in the pituitary and that this gland is receptive to apelin's action. The study also suggest that apelin may influence female reproductive functions by controlling the release of LH and FSH from AP cells, and that it affects Akt, MAPK/Erk1/2, and AMPK signalling pathways.

TRIM40 interacts with ROCK1 directly and inhibits colorectal cancer cell proliferation through the c-Myc/p21 axis.

BACKGROUND: Colorectal cancer (CRC) is the most common malignancy of the digestive tract, and to date, morbidity and mortality rates remain high. While existing therapeutic methods have achieved certain effective outcomes, there are still many problems in treating this disease. Therefore, it is still urgent to constantly find new therapeutic targets in CRC that could lead to new therapeutics. METHODS: Immunohistochemistry, Real-time PCR and Western Blot were employed to measure mRNA and protein levels of the target protein, respectively. The proliferation ability of CRC cells was evaluated using ATP assay, Soft agar assay, and nude mouse subcutaneous tumorigenesis assay. Protein Degradation Assay was conducted to determine protein degradation rate, while Ubiquitination assay was used to assess the ubiquitination modification level of target proteins. Immunoprecipitation assay was used to study protein interactions, and pull-down assay was employed to investigate direct interactions between proteins. RESULTS: TRIM40 was significantly down-regulated in CRC tissues, with its expression levels positively correlating with disease prognosis. Using both in vitro and in vivo approaches, it was demonstrated that TRIM40 could significantly inhibit the proliferation of CRC cells. Molecular mechanism studies showed that TRIM40 directly binds to and ubiquitinates ROCK1 protein, accelerating its degradation and subsequently reducing the stability of c-Myc protein. This cascade of events results in the release of transcriptional inhibition of p21 by c-Myc, leading to increased p21 expression and G0/G1 phase arrest in CRC cells. CONCLUSION: This research suggests that TRIM40 could be a valuable therapeutic target for the treatment of CRC.

Blending phosphogypsum to mitigate radionuclide leaching for sustainable road base applications.

Production of phosphoric acid generates a calcium sulfate byproduct known as phosphogypsum (PG). PG is not considered a suitable standalone road base material because of concerns such as strength and presence of radionuclides. This paper investigates the latter, specifically the influence of blending PG with common alkaline road base aggregates - limerock (LR) and recycled concrete aggregate (RCA) - on radionuclide leaching. Radionuclide leaching from several PG sources was assessed for gross alpha, gross beta, uranium, and combined radium (226 + 228). Solution pH affected Ra226 leaching, with minimum mobility exhibited at a pH in the range of 6-8. Mobile Ra226 concentrations in RCA blends decreased compared to original PG; Ra226 mobility initially increased at low LR replacements but decreased with increasing mass of LR (50 %-75 %). The data suggest an additional mechanism beyond pH alone impacted Ra226 mobility from the blends, possibly the binding or substitution of radium by elevated concentrations of Ba, Sr, or Ca. Blending with RCA resulted in radionuclide concentrations below respective drinking water thresholds, mitigating leaching concern from PG-RCA road base blends. PG-LR blends can meet regulatory limits when incorporating appropriate PG sources, providing an avenue for PG-amended road base materials. The blending approach reduced Ra226 mobility from PG-amended base, accommodating more PG use and serve as an alternative scenario to end-of-life stacking.

Chromium cycle in Red Soil Critical Zone constrained by chromium isotopes.

Chromium (Cr) isotopic system has been used to trace Cr pollution in the modern surface environment and redox change in the paleoenvironment. However, the transformation mechanism of Cr in soil and the accompanied Cr isotopic fractionation have not been clarified clearly. Here we measured Cr isotopic compositions (δ53Cr) of two paddy field profiles from the Red Soil Critical Zone Observatory in South China. The δ53Cr values of the young paddy fields, which have been cultivated for about 20 years, range from -0.34 ‰ to -0.22 ‰. The old paddy fields have been cultivated for >100 years and have more positive Cr isotopic compositions than the young paddy fields, from -0.20 ‰ to -0.06 ‰. The results of three-step leaching experiments show that iron and manganese oxides are enriched in heavy Cr isotopes, while organic matters have much lower Cr isotopic compositions, likely resulting from back reduction of Cr(VI). Our results suggest that Cr isotopic fractionation during the oxidation of Cr(III) is not the only reason for the depletion of heavy isotopes during oxidative weathering, and the partial back-reduction of generated Cr(VI) by organic matter plays an important role in Cr isotopic fractionation during weathering. Comparison between the old and young paddy fields further indicates that cultivation can significantly affect the Cr cycle in red soils. Paddy fields could be a potential sink for the Cr(VI) contaminant, and soils with a long history of cultivation would be more susceptible.

KDM4B Histone Demethylase Inhibition Attenuates Tumorigenicity of Malignant Melanoma Cells by Overriding the p53-Mediated Tumor Suppressor Pathway.

Despite significant advances in the treatment of cutaneous melanoma (hereafter melanoma), the prognosis remains less favorable due to therapeutic resistance, which is presumably linked to epigenetic dysregulation. We hypothesized that the histone lysine demethylase KDM4B could play a pivotal role in controlling therapy-resistant melanoma. To validate our hypothesis, we retrieved RNA sequencing data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) program and observed upregulation of KDM4B in both primary and metastatic melanoma, which was associated with poor survival. To explore its role, we used murine B16, human SK-MEL-5, and G-361 melanoma cells as in vitro models of melanoma. We found that KDM4B inhibition using NCGC00244536 increased global levels of H3K9me3 and downregulated the expressions of cell cycle progression-related genes Cdk1, Cdk4, Ccnb1, and Ccnd1. Moreover, genetic ablation of KDM4B or its chemical inhibition using NCGC00244536 reduced p53 production by upregulating MDM2, which enhances the proteolytic degradation of p53. Interestingly, despite the reduction of p53, these interventions augmented apoptosis and senescence-induced cell death by activating pathways downstream of p53, as evidenced by reduced levels of pro-survival Bcl-2 and Bcl-xL proteins and increased production of pro-apoptotic cleaved caspase-3, caspase-7, Bax, and the senescence inducer Cdkn1a. Compared to the FDA-approved anti-melanoma agent dacarbazine, NCGC00244536 exhibited more pronounced cytotoxic and antiproliferative effects in melanoma cells. Importantly, NCGC00244536 demonstrated minimal cytotoxicity to low Kdm4b-expressing mouse embryonic fibroblasts. In conclusion, our findings suggest that KDM4B inhibition can override the antitumor effect of p53, and potentially serve as a therapeutic strategy for melanoma.

Immunohistochemical markers in predicting behavior of bladder urothelial carcinoma.

Background: Bladder cancer is the 5th most prevalent cancer among Iranian men. Finding prognostic markers to predict behavior of this cancer can help us to choose the best treatment for patients from the first place. We aimed to evaluate the correlation of immunohistochemical markers with tumor stage, grade and prognosis of disease. Methods: In this study, we reassessed the specs of proven UC among Iranian patients. Sixty specimens were collected, contained of 30 low grade and 30 high grade urothelial carcinomas. All slides were assessed by immunohistochemistry study for p21, p27, Her-2/neu, E-cadherin, and CD10. Data were analyzed by SPSS 18.0 and a p-value < 0.05 was considered significant. Results: We evaluated 60 patients in this study with mean age of 66±11 years and majority of them are men. High expression of p27 showed significant correlation with LGUC (P=0.030). HGUC related with high expression of Her-2/neu, CD10 and aberrant expression of E-Cadherin (P<0.0001). Aberrant E-Cadherin and high expression of CD10 are associated with higher tumor stage (P=0.000). CD10 intensity was the only immunohistochemical markers to predict prognosis (P=0.010). Conclusion: In the present study, CD10 intensity is the only marker that directly predicts the prognosis. The higher intensity leads to poor prognosis (recurrence or metastasis). More studies must be done in this aspect to resolve the controversies and clarify the role of immunohistochemical markers in predicting BC behaviors.

Discovery of GJC1 as a prognostic biomarker in glioma cells: insights into its cell-cycle relationship and differential expression in non-neuronal cells.

Background: Gliomas, originating from the most common non-neuronal cells in the brain (glial cells), are the most common brain tumors and are associated with high mortality and poor prognosis. Glioma cells exhibit a tendency to disrupt normal cell-cycle regulation, leading to abnormal proliferation and malignant growth. This study investigated the predictive potential of GJC1 in gliomas and explored its relationship with the cell cycle. Methods: Retrospective analysis of RNA-seq and single-cell sequencing data was conducted using the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The differential expression of GJC1 in gliomas with various pathological features and in different non-neuronal cell groups was analyzed. Functional data were examined using gene set variation analysis (GSVA). Furthermore, CellMiner was used to evaluate the relationship between GJC1 expression and predicted treatment response across these databases. Results: GJC1 expression was enriched in high-grade gliomas and 1p/19q non-codeletion gliomas. GJC1 enrichment was observed in classical and mesenchymal subtypes within the TCGA glioma subtype group. In single-cell subgroup analysis, GJC1 expression was higher in glioma tissues compared to other non-neuronal cells. Additionally, the TCGA classical subtype of glioma cells exhibited more GJC1 expression than the other subgroups. GJC1 emerged as an independent prognostic factor for overall survival in glioma. GSVA unveiled potential mechanisms by which GJC1 may impact cell-cycle regulation in glioma. Finally, a significant correlation was observed between GJC1 expression and the sensitivity of multiple anti-cancer drugs. Conclusion: These findings confirmed GJC1 as a novel biomarker and provided insights into the differential gene expression in non-neuronal cells and the impact of the cell cycle on gliomas. Consequently, GJC1 may be used to predict glioma prognosis and has potential therapeutic value.

Metabolic Reprogramming of Klebsiella pneumoniae Exposed to Serum and Its Potential Implications in Host Immune System Evasion and Resistance.

The aim of this study was to identify, using proteomics, the molecular alterations caused by human serum exposure to Klebsiella pneumoniae ACH2. The analysis was performed under two different conditions, native serum from healthy donors and heat-inactivated serum (to inactivate the complement system), and at two different times, after 1 and 4 h of serum exposure. More than 1,000 bacterial proteins were identified at each time point. Enterobactin, a siderophore involved in iron uptake, and proteins involved in translation were upregulated at 1 h, while the chaperone ProQ and the glyoxylate cycle were identified after 4 h. Enzymes involved in the stress response were downregulated, and the SOD activity was validated using an enzymatic assay. In addition, an intricate metabolic adaptation was observed, with pyruvate and thiamine possibly involved in survival and virulence in the first hour of serum exposure. The addition of exogenous thiamine contributes to bacterial growth in human serum, corroborating this result. During 4 h of serum exposure, the glyoxylate cycle (GC) probably plays a central role, and the addition of exogenous succinate suppresses the GC, inducing a decrease in serum resistance. Therefore, serum exposure causes important changes in iron acquisition, the expression of virulence factors, and metabolic reprogramming, which could contribute to bacterial serum resistance.

Identification of novel biomarkers, shared molecular signatures and immune cell infiltration in heart and kidney failure by transcriptomics.

Introduction: Heart failure (HF) and kidney failure (KF) are closely related conditions that often coexist, posing a complex clinical challenge. Understanding the shared mechanisms between these two conditions is crucial for developing effective therapies. Methods: This study employed transcriptomic analysis to unveil molecular signatures and novel biomarkers for both HF and KF. A total of 2869 shared differentially expressed genes (DEGs) were identified in patients with HF and KF compared to healthy controls. Functional enrichment analysis was performed to explore the common mechanisms underlying these conditions. A protein-protein interaction (PPI) network was constructed, and machine learning algorithms, including Random Forest (RF), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), were used to identify key signature genes. These genes were further analyzed using Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA), with their diagnostic values validated in both training and validation sets. Molecular docking studies were conducted. Additionally, immune cell infiltration and correlation analyses were performed to assess the relationship between immune responses and the identified biomarkers. Results: The functional enrichment analysis indicated that the common mechanisms are associated with cellular homeostasis, cell communication, cellular replication, inflammation, and extracellular matrix (ECM) production, with the PI3K-Akt signaling pathway being notably enriched. The PPI network revealed two key protein clusters related to the cell cycle and inflammation. CDK2 and CCND1 were identified as signature genes for both HF and KF. Their diagnostic value was validated in both training and validation sets. Additionally, docking studies with CDK2 and CCND1 were performed to evaluate potential drug candidates. Immune cell infiltration and correlation analyses highlighted the immune microenvironment, and that CDK2 and CCND1 are associated with immune responses in HF and KF. Discussion: This study identifies CDK2 and CCND1 as novel biomarkers linking cell cycle regulation and inflammation in heart and kidney failure. These findings offer new insights into the molecular mechanisms of HF and KF and present potential targets for diagnosis and therapy.

The overexpression of R-spondin 3 affects hair morphogenesis and hair development along with the formation and maturation of the hair follicle stem cells.

Mice hair follicles (HFs) are a valuable model for studying various aspects of hair biology, including morphogenesis, development, and regeneration due to their easily observable phenotype and genetic manipulability. The initiation and progression of hair follicle morphogenesis, as well as the hair follicle cycle, are regulated by various signaling pathways, of which the main role is played by the Wingless-type MMTV integration site family (Wnt) and the Bone Morphogenic Protein (BMP). During the hair follicle cycle, the BMP pathway maintains hair follicle stem cells (HFSCs) in a dormant state while the Wnt pathway activates them for hair growth. Given the pivotal role of the Wnt pathway in hair biology and HFSCs regulation, we investigated the influence of the Wnt modulator - R-spondin 3 (Rspo3), in these processes. For this purpose, we developed a transgenic mice model with the overexpression of Rspo3 (Rspo3GOF) in the whole ectoderm and its derivatives, starting from early morphogenesis. Rspo3GOF mice exhibited a distinct phenotype with sparse hair and visible bald areas, caused by reduced proliferation and increased apoptosis of hair matrix progenitor cells, which resulted in a premature anagen-to-catagen transition with a shortened growth phase and decreased overall length of all hair types. In addition, Rspo3GOF promoted induction of auchene and awl, canonical Wnt-dependent hair type during morphogenesis, but the overall hair amount remained reduced. We also discovered a delay in the pre-bulge formation during morphogenesis and prolonged immaturity of the HFSC population in the bulge region postnatally, which further impaired proper hair regeneration throughout the mice's lifespan. Our data supported that Rspo3 function observed in our model works in HFSCs' formation of pre-bulge during morphogenesis via enhancing activation of the canonical Wnt pathway, whereas in contrast, in the postnatal immature bulge, activation of canonical Wnt signaling was attenuated. In vitro studies on keratinocytes revealed changes in proliferation, migration, and colony formation, highlighting the inhibitory effect of constitutive overexpression of Rspo3 on these cellular processes. Our research provides novel insights into the role of Rspo3 in the regulation of hair morphogenesis and development, along with the formation and maturation of the HFSCs, which affect hair regeneration.

Reversibly crosslinked polyurethane fibres from sugar-based 5-chloromethylfurfural: Synthesis, fibre-spinning and fibre-to-fibre recycling.

The development of recyclable crosslinked thermosetting fibres is a challenging research topic. In the present work, we have designed and synthesized polyurethane fibres from fructose-derived 5-chloromethylfurfural (CMF) and lignin-derived monomeric phenols. The greenhouse gas emissions associated with the production of CMF showed comparable results to that of 5-hydroxymethylfurfural (HMF), a high potential sugar-based platform molecule. The wet-spun biobased polyurethane fibres produced could be conveniently crosslinked using Diels-Alder chemistry to effectively enhance the glass transition temperature and mechanical properties. At a mildly elevated temperature (140 °C), the chemically crosslinked fibres could be effectively de-crosslinked, which enabled complete separation from a mixture with poly(ethylene terephthalate) (PET) and cotton fibres. These results outline a potential strategy to design and fabricate new biobased fibres with reversible crosslinking, which may enable fibre-to-fibre recycling.

De Novo Biosynthesis of L-Azetidine-2-Carboxylic Acid in Escherichia coli Strains for Powdery Mildew Treatment.

L-Azetidine-2-carboxylic acid (L-Aze), a natural nonproteinogenic amino acid found widely in plants, has recently been identified as an environmentally friendly agent for controlling powdery mildew with low toxicity. In this study, a biological route for L-Aze production via the methionine salvage pathway (Yang Cycle) was first in silico designed for Escherichia coli. Subsequently, systematic engineering strategies were employed to enhance the production efficiency, including the enhancement of the 5-phosphoribosyl 1-pyrophosphate (PRPP) supply, construction of the ATP-adenine cycle, and engineering of the strain's resistance to L-Aze. The final strain produced L-Aze from glucose with a titer of 568.5 mg/L. The antifungal activity of the produced L-Aze in the fermentation broth was also confirmed for treating powdery mildew in cucurbits. This approach not only provides a sustainable and green route for pesticide production to control powdery mildew but also expands our understanding of the exogenous construction of the Yang Cycle in E. coli.

Reclamation alters evapotranspiration and its biophysical controls in a meadow grassland on the Mongolian Plateau.

Global grasslands were constantly being replaced and reclaimed for cropland, and such reclamations may profoundly affect ecological such as water cycles. However, the long-term effects of this conversion on evapotranspiration (ET) processes remain underexplored. To discern changes in ET from grassland to reclaimed cropland and among different crop rotations, a four-year study (2018-2021) was conducted using the eddy covariance system in a Hulunber grassland and a neighboring reclaimed cropland. The ET in reclaimed cropland (248 mm) was 49% higher than the grassland (166 mm) during the growing season (crop growth period), whereas the ET in the grassland (134 mm) exceeded that in the cropland (128 mm) by 6% in the non-growing season. The croplands experienced a 19% increase in precipitation, primarily due to artificial irrigation during the growing season. Meanwhile, the increase in ET in reclaimed cropland might also be influenced by changes in vegetation type and crop growth characteristics, as well as by rational tillage practices that increase the cover of vegetation and biomass. Notably, potato cultivation most closely matched the water balance of grasslands. In addition, irrigation directly increased soil water content (SWC), and that enhancing the sensitivity of ET to SWC. Overall, this study highlighted the importance of understanding ET variations due to grassland conversion to cropland and different crop rotations, emphasizing the role of irrigation and tillage practices.