Fibrotic Matrix Induces Mesenchymal Transformation of Epithelial Cells in Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.

Variation and correlation between water retention capacity and gas permeability of compacted loess overburden during wetting-drying cycles.

Landfill gases can have numerous detrimental effects on the global climate and urban ecological environment. The protective efficacy of the final cover layer against landfill gases, following exposure to periodic natural meteorological changes during long-term service, remains unclear. This study conducted centrifuge tests and gas permeability tests on compacted loess. The experiments examined the impact and relationship of wetting-drying cycles and dry density on the soil water characteristic curve (SWCC) and gas permeability of compacted loess. Research findings reveal that during the dehumidification process of compacted loess, the gas permeability increases non-linearly, varying the gas permeability of soil with different densities to different extents under wetting-drying cycles. Two models were introduced to describe the impact of wetting-drying cycles on gas permeability of loess with various dry densities, where fitting parameters increased with the number of wetting-drying cycles. Sensitivity analysis of the parameters in the Parker-Van Genuchten-Mualem (P-VG-M) model suggests that parameter γ's accuracy should be ensured in practical applications. Finally, from a microstructural perspective, wetting-drying cycles cause dispersed clay and other binding materials coalesce to fill minuscule pores, leading to an increase in the effective pores responsible for the gas permeability of the soil. These research results offer valuable guidance for designing water retention and gas permeability in compacted loess cover layers under wetting-drying cycles.

Study on hydraulic conductivity of dredged sediment-attapulgite vertical cutoff walls under confining pressure.

Landfills require effective containment systems to prevent the leakage of leachate into the underground environment. Cutoff walls are commonly employed for this purpose, with options including rigid and flexible designs. In areas where structural strength is not a primary concern, flexible cutoff walls offer lower permeability and environmental benefits due to their lack of cement content, thereby reducing CO2 emissions. This study investigates the use of dredged sediment and attapulgite as materials for flexible cutoff walls. Through analyses of bound water content, free water content, hydraulic conductivity, and scanning electron microscopy, we explore the impact of confining pressures on cutoff wall permeability. Our findings reveal that the consolidation induced by confining pressure does not significantly alter the bound water content within the cutoff wall. Instead, changes in water content are predominantly attributed to variations in free water content. Under identical confining pressures, we observe a positive correlation between permeability and hydraulic gradient, with permeability increasing as the hydraulic gradient rises, and anti-permeability decreasing accordingly. Additionally, when holding the hydraulic gradient constant, increasing confining pressure leads to a continuous decrease in permeability. Microscopic analyses highlight that high confining pressure not only compresses pore diameter but also alters pore morphology, thereby influencing permeability. This study contributes to the understanding of cutoff wall behavior under different conditions. Our results demonstrate that increasing confining pressure during soil consolidation effectively reduces cutoff wall permeability to meet design standards. However, the influence of high leachate head on permeability should also be considered. These findings provide a more environmentally friendly and lower permeability option for landfill sites, which is significant for the design and enhancement of containment systems in landfill sites.

Study on semi-dynamic leaching and microstructure characteristics of MSWI fly ash solidified sediment.

municipal solid waste incineration (MSWI) fly ash partially replaces cement to solidify sediment, and then can be used as intermediate cover materials in landfill as one of the resources utilization ways of MSWI fly ash and sediment. The strength and the semi-dynamic leaching characteristics of MSWI fly ash solidified sediment under hydrochloric acid attack at different pH were studied by means of unconfined compressive strength (UCS), semi-dynamic leaching, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and Thermogravimetric analysis (TGA). Results revealed that the UCS strength increased as the curing age and cement content increased. When the curing content is 50% and the replacement ratio of MSWI fly ash is 75% and 80%, the UCS of 7 d can be greater than 50 kPa. The primary contribution to the strength development was from silicic acid gels such as calcium silicate hydrate (C-S-H) and carbonates. Notably, the leaching behavior of Zn and Cu within the solidified sediment underwent substantial alterations. The leaching amount of heavy metals in a strong acidic environment (pH = 2) is significantly greater than that in a weak acidic (pH = 4) and neutral (pH = 7) environment. Conversely, minimal disparities were observed in the leaching characteristics of Zn and Cu between the weakly acidic and neutral environments. Ca(OH)2, C-S-H and carbonate exhibits a remarkable acid-resistant buffering capacity in the solidified sediment. The obvious diffusion coefficient (Dobs) was less than 10-9 m2/s in semi-dynamic leaching tests. Moreover, the mobility of Zn and Cu surpassing 12.5, coupled with a leaching index exceeding 8, further attests to the favorable S/S outcome achieved. Based on these findings, the solidified material is confidently recommended to be used as suitable landfill middle soil cover material.

A new method for determination of heavy metal adsorption parameters in compacted clay by batch tests.

Evaluation of adsorption properties of pollutants on artificial or natural clay strata is normally considered in investigations of soil and groundwater pollution. Batch adsorption tests can be used to obtain the adsorption parameters of clay particles; however, the results from these tests are usually very different from the adsorption of actual clay strata. If the adsorption parameters obtained by batch tests are used to directly evaluate the properties of adsorption of pollutants onto compacted clay, the predicted groundwater and soil pollution will be unsafe. Although the column diffusion tests are closer to the actual situation, they may require much more time, and diffusion and adsorption occur simultaneously in tests, making it difficult to accurately determine the adsorption parameters. To solve this problem, batch adsorption and column diffusion tests were conducted using three kinds of clay materials to investigate the mechanism of the differences in adsorption properties of heavy metal on clay particles and in compacted clay. The amount of adsorption per unit particle surface area of clay particles was found to be equal to that per unit pore surface area of compacted clay. A new simplified method was proposed to determine the adsorption parameters in compacted clay. It is easy to use and provide a reference for prediction and evaluation of soil and groundwater pollution.

Studies on the chemical compatibility of soil-bentonite cut-off walls for landfills.

Leachate contains composite contaminants, and the chemical compatibility of soil-bentonite cut-off walls is unclear. To better understand the issue, Fujian standard sand is used to represent a sandy soil stratum. Two clays were used as additive to examine the chemical compatibility of the soil-bentonite model backfills under the condition of composite contaminants. The results indicate that there is a representative cation when the backfills are permeated with NaCl, CaCl2, and ZnCl2 solutions and an NaCl-CaCl2-ZnCl2 mixed solution of the same ionic strength. Ca2+ has the highest maximum ionic strength among all cations from leachates. Moreover, the change in hydraulic conductivity, bound water content and effective porosity of sand-bentonite with the Ca2+ concentration or chemical oxygen demand (COD) exhibit a concentration threshold; i.e., when the concentration is smaller than the threshold, the hydraulic conductivity and effective porosity significantly increase, whereas the bound water content rapidly decreases; when the concentration is higher than the threshold, the hydraulic conductivity, bound water content and effective porosity tend to stabilize. In addition, under the condition of composite contaminants, the threshold is observed, while the hydraulic conductivity, bound water content and effective porosity vary with the COD. Thus, both the type and concentration of chemicals can change the effective porosity and affect hydraulic conductivity. Furthermore, there is a power function relationship between permeability and the effective pore.

Effect of the leachate head on the key pollutant indicator in a municipal solid waste landfill barrier system.

In previous studies of municipal solid waste (MSW) landfill barrier systems, chemical oxygen demand has been found to be the key pollutant indicator when estimating the breakthrough time for. However, the leachate head in a municipal solid waste landfill can be very high (>10 m in some Chinese landfills). The key pollutant indicator could be different at different leachate heads. The leachate head will continuously change during the use of a landfill. Different pollutants have different transport characteristics in the leachate, so it is necessary to determine whether changes in the leachate head change the key pollutant indicator for identifying breakthrough in a landfill barrier system. In this study, numerical models were used to investigate transport of common leachate pollutants through four typical landfill barrier systems with different leachate heads. Chemical oxygen demand reached the breakthrough threshold before the other pollutants, irrespective of (1) the leachate head and (2) changes in the leachate head. It was therefore clear that the leachate head did not affect the selection of the key pollutant indicator for identifying breakthrough in a landfill barrier system.

Optimizing sludge dewatering efficiency with ultrasonic Treatment: Insights into Parameters, Effects, and microstructural changes.

Sludge dewatering plays a critical role in the efficient and cost-effective management of wastewater treatment plants. Ultrasonic treatment has emerged as a promising technique for improving dewatering processes. This study aims to evaluate the impact of ultrasonic treatment on sludge dewatering characteristics. A series of experiments were conducted to evaluate the dewatering characteristics of sludge under ultrasonic treatment. Experimental data was collected, and the effects of ultrasonic parameters on dewatering efficiency were analyzed. Ultrasound has the capacity to disintegrate sludge flocs, liberate tightly bound water, and enhance sludge dewatering capabilities. The application of ultrasound leads to the breakdown of sludge flocs, which facilitates a substantial amount of organic acids or carbonates. This, in turn, modifies the pH value of the sludge. Additionally, ultrasound induces instantaneous high temperature and pressure within the liquid phase, consequently elevating the temperature of the sludge slurry. Optimum ultrasound energy density and duration of ultrasound treatment exist. For the sludge samples analyzed in this investigation, it was determined that the optimal ultrasonic energy density is 9.8 W, while the optimal duration of ultrasound treatment is 30 s. Excessively escalating the sound energy density or prolonging the duration of ultrasound may yield unfavorable outcomes in terms of sludge dewatering effectiveness. To enhance sludge dewatering, it is crucial to select appropriate ultrasonic energy density and duration of ultrasonic treatment. This study demonstrates the positive impact of ultrasonic treatment on the dewatering characteristics of sludge. The findings provide valuable insights into the potential of ultrasonic technology for enhancing sludge dewatering.

Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles.

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury. Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues. These proteins initiate inflammatory dysfunction, such as neurogenic heterotopic ossification. This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies. Accordingly, a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues. Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis. The relationships among brain-derived extracellular vesicles, fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo. The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury. Brain-derived extracellular vesicles (BEVs) are released after traumatic brain injury. These BEVs contain pathogens and participate in interorgan communication to initiate secondary injury in distal tissues. After achillotenotomy, the phagocytosis of BEVs by fibroblasts induces pyroptosis, which is a highly inflammatory form of lytic programmed cell death, in the injured tendon. Fibroblast pyroptosis leads to an increase in calcium and phosphorus concentrations and creates a microenvironment that promotes osteogenesis. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk suppressed fibroblast pyroptosis and effectively prevented the onset of heterotopic ossification after neuronal injury. The use of a pyroptosis inhibitor represents a potential strategy for the treatment of neurogenic heterotopic ossification.

Calcified apoptotic vesicles from PROCR+ fibroblasts initiate heterotopic ossification.

Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single-cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV-releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification.

CMOS Scaling for the 5 nm Node and Beyond: Device, Process and Technology.

After more than five decades, Moore's Law for transistors is approaching the end of the international technology roadmap of semiconductors (ITRS). The fate of complementary metal oxide semiconductor (CMOS) architecture has become increasingly unknown. In this era, 3D transistors in the form of gate-all-around (GAA) transistors are being considered as an excellent solution to scaling down beyond the 5 nm technology node, which solves the difficulties of carrier transport in the channel region which are mainly rooted in short channel effects (SCEs). In parallel to Moore, during the last two decades, transistors with a fully depleted SOI (FDSOI) design have also been processed for low-power electronics. Among all the possible designs, there are also tunneling field-effect transistors (TFETs), which offer very low power consumption and decent electrical characteristics. This review article presents new transistor designs, along with the integration of electronics and photonics, simulation methods, and continuation of CMOS process technology to the 5 nm technology node and beyond. The content highlights the innovative methods, challenges, and difficulties in device processing and design, as well as how to apply suitable metrology techniques as a tool to find out the imperfections and lattice distortions, strain status, and composition in the device structures.

New insight into the additives in preparation and reduction of shield slurry.

In the preparation of the slurry in the slurry shield (SSS) and subsequent reduction of the waste slurry produced by the slurry shield (WSSS), the additives in SSS improve the quality of filtration cake on the excavation surface, but they may also remain in WSSS, which have a negative impact on the reduction efficiency of WSSS. Therefore, it is valuable to establish the relationship between SSS and WSSS with additives as a link. Given this, this paper prepared WSSS with different dosages of additives and studied the influence of residual additives on the reduction. The residual additives made the reduction efficiency of WSSS worse, and the specific resistance to filtration increased by one to two orders of magnitude. The residual additives change the content of bound water or reduce the available sites of the soil particles that can be adsorbed by flocculants, leading to worse reduction results. To reduce the difficulty of reduction, combining polymer and bentonite as additives are recommended to prepare SSS. Polyaluminium chloride (PAC) acts by reducing bound water content through the interaction with residual bentonite, simultaneously augmenting PAM flocculation, which is recommended for reducing WSSS. This paper provides a reference for selecting materials used to prepare SSS and the subsequent reduction of WSSS.

Structural basis of transcription recognition of a hydrophobic unnatural base pair by T7 RNA polymerase.

Bacteriophage T7 RNA polymerase (T7 RNAP) is widely used for synthesizing RNA molecules with synthetic modifications and unnatural base pairs (UBPs) for a variety of biotechnical and therapeutic applications. However, the molecular basis of transcription recognition of UBPs by T7 RNAP remains poorly understood. Here we focused on a representative UBP, 7-(2-thienyl)-imidazo[4,5-b]pyridine (Ds) and pyrrole 2-carbaldehyde (Pa), and investigated how the hydrophobic Ds-Pa pair is recognized by T7 RNAP. Our kinetic assays revealed that T7 RNAP selectively recognizes the Ds or Pa base in the templates and preferentially incorporates their cognate unnatural base nucleotide substrate (PaTP or DsTP) over natural NTPs. Our structural studies reveal that T7 RNAP recognizes the unnatural substrates at the pre-insertion state in a distinct manner compared to natural substrates. These results provide mechanistic insights into transcription recognition of UBP by T7 RNAP and provide valuable information for designing the next generation of UBPs.

Effect of acidic erosion on properties of solidified sewage sludge.

Solidified sludge can be regarded as a new type of earth cover material for domestic waste landfill. But the acidic environment result from the leachate in landfill is a potential threat to cement-based material. In order to evaluate the deterioration risk of solidified sludge in acidic environment, the leaching process of solidified sludge components under different pH conditions was investigated by taking Ni and Cr as the indexes of semi-dynamic leaching test. Under strongly acid environment (pH = 2), the leaching rate of Cr is significantly higher than that in the weakly acid environment or nearly neutral environment, and the diffusion coefficient increased by an order of magnitudes. The leaching and diffusion coefficients of Ni undergo a small influence from the adding amount of cement and pH value. Both Ni and Cr have relatively low migration ratio.

Macrophage-Derived Extracellular DNA Initiates Heterotopic Ossification.

Heterotopic ossification (HO) severely affects people's lives; however, its pathological mechanism remains poorly understood. Although extracellular DNA (ecDNA) has been shown to play important roles in pathological calcification, its effects in HO development and progression remain unknown. The in vivo rat Achilles tendon injury model and in vitro collagen I calcification model were used to evaluate the effects of ecDNA in the ectopic calcifications and the main cell types involved in those pathological process. Histology, immunofluorescent staining, reverse transcriptase-polymerase chain reaction analysis and micro-computed tomography were used to identify the distribution of macrophage-derived ecDNA and elucidate their roles in HO. The results showed that the amount of ecDNA and ectopic calcification increased significantly and exhibited a strong correlation in the injured tendons of HO model compared with those of the controls, which was accompanied by a significantly increased number of M2 macrophages in the injured tendon. During in vitro co-culture experiments, M2 macrophages calcified the reconstituted type I collagen and ectopic bone collected from the injured tendons of HO rats, while those effects were inhibited by deoxyribonuclease. More importantly, deoxyribonuclease reversed the pathological calcification in the injured rat tendon HO model. The present study showed that ecDNA from M2 macrophages initiates pathological calcification in HO, and the elimination of ecDNA might be developed into a clinical strategy to prevent ectopic mineralization diseases. The use of deoxyribonuclease for the targeted degradation of ecDNA at affected tissue sites provides a potential solution to treat diseases associated with ectopic mineralization.

A biomaterial-based therapy using a sodium hyaluronate/bioglass composite hydrogel for the treatment of oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant oral disorder. Its pathophysiology is extremely complex, including excessive collagen deposition, massive inflammatory infiltration, and capillary atrophy. However, the existing clinical treatment methods do not fully take into account all the pathophysiological processes of OSF, so they are generally low effective and have many side effects. In the present study, we developed an injectable sodium hyaluronate/45S5 bioglass composite hydrogel (BG/HA), which significantly relieved mucosal pallor and restricted mouth opening in OSF rats without any obvious side effects. The core mechanism of BG/HA in the treatment of OSF is the release of biologically active silicate ions, which inhibit collagen deposition and inflammation, and promote angiogenesis and epithelial regeneration. Most interestingly, silicate ions can overall regulate the physiological environment of OSF by down-regulating α-smooth muscle actin (α-SMA) and CD68 and up-regulating CD31 expression, as well as regulating the expression of pro-fibrotic factors [transforming growth factor-ß1 (TGF-ß1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and tissue inhibitors of metalloproteinase-1 (TIMP-1)] and anti-fibrotic factors [interleukin-1ß (IL-1ß)] in macrophage. In conclusion, our study shows that BG/HA has great potential in the clinical treatment of OSF, which provides an important theoretical basis for the subsequent development of new anti-fibrotic clinical preparations. STATEMENT OF SIGNIFICANCE: : Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant mucosal disease with significant impact on the quality of patients' life. However, the existing clinical treatments have limited efficacy and many side effects. There is an urgent need for development of specific drugs for OSF treatment. In the present study, bioglass (BG) composited with sodium hyaluronate solution (HA) was used to treat OSF in an arecoline-induced rat model. BG/HA can significantly inhibit collagen deposition, regulate inflammatory response, promote angiogenesis and repair damaged mucosal epithelial cells, and thereby mitigate the development of fibrosis in vivo.

The permeability of dredged material-bentonite backfills.

Extensive attention has been paid to the treatment and disposal of dredged material, and there is a need to clarify the feasibility of recycling dredged material by using it as backfill in soil-bentonite vertical cutoff walls. By setting the dredged material in the Baimao storage yard of Meiliang Bay in Taihu Lake and bentonite as the research objects, this paper studied the influences of bentonite content, confining pressure and pore size distribution on the permeability of dredged material-bentonite backfills. According to the test results, from the perspective of medium-term and short-term permeability, it is feasible to recycle dredged material by using it as backfill in a vertical cutoff wall. The permeability of the dredged material-bentonite soil mixture decreases with increasing bentonite content, but the degree of decrease is not significant. At the same time, the higher the confining pressure is, the smaller the variation in hydraulic conductivity with bentonite content. The permeability of the soil mixture decreases with increasing confining pressure, and the range of reduction is within a certain order of magnitude. Moreover, the confining pressure has a similar impact on the decrease in the permeability of the soil mixtures with different bentonite contents. The hydraulic conductivity of the dredged material-bentonite mixture decreases because the addition of bentonite changes the pore size distribution and reduces the porosity and characteristic pore size D50 of the soil mixture.

The Lnc RNA SPRY4-IT1 Modulates Trophoblast Cell Invasion and Migration by Affecting the Epithelial-Mesenchymal Transition.

Preeclampsia is a common, pregnancy-specific disease and a major contributor to maternal and foetal morbidity and mortality. Some placental abnormalities, including deficient implantation, abnormal trophoblast cell function, and improper placental vascular development, are believed to lead to preeclampsia. The long noncoding RNA SPRY4-IT1 is more highly expressed in preeclamptic human placentas than in normal placentas. We assessed the role of epithelial-mesenchymal transition (EMT)-associated invasion and migration in HTR-8/SVneo trophoblast cells. Overexpression of SPRY4-IT1 suppressed trophoblast cell migration and invasion, whereas reduced expression of SPRY4-IT1 prevented the EMT process. Mechanistically, an RNA immunoprecipitation experiment showed that SPRY4-IT1 bound directly to HuR and mediated the ß-catenin expression associated with EMT in HTR-8/SVneo cells. Moreover, the expression levels of genes in the WNT family, such as WNT3 and WNT5B, were changed after transfection of HTR-8/SVneo with SPRY4-IT1. Together, our results highlight the roles of SPRY4-IT1 in causing trophoblast cell dysfunction by acting through the Wnt/ß-catenin pathway, and consequently in impairing spiral artery remodelling. These results suggest a new potential therapeutic target for intervention against preeclampsia.