The mediating role of synovitis in meniscus pathology and knee osteoarthritis radiographic progression.

Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between meniscus pathologies and KOA radiographic progression remains unclear. We conducted an observational study in the Osteoarthritis Initiative (OAI) cohort, with a 48-month follow-up. Meniscus pathology and synovitis were measured by MRI osteoarthritis knee score (MOAKS) at baseline and 24 months, and a comprehensive synovitis score was calculated using effusion and Hoffa synovitis scores. The knee osteoarthritis radiographic progression was considered that Kellgren-Lawrence (KL) grade and joint space narrowing (JSN) grade at 48 months were increased compared to those at baseline. This study included a total of 589 participants, with KL grades mainly being KL1 (26.5%), KL2 (34.1%), and KL3 (30.2%) at baseline, while JSN grades were mostly 0 at baseline. A logistic regression model was used to analyze the relationship between meniscus pathology, synovitis, and KOA progression. Mediation analysis was used to evaluate the mediation effect of synovitis. The average age of the participants was 61 years old, 62% of which were female. The medial meniscus extrusion was longitudinally correlated with the progression of KL (odds ratio [OR]: 2.271, 95% confidence interval [CI]: 1.412-3.694) and medial JSN (OR: 3.211, 95% CI: 2.040-5.054). Additionally, the longitudinal correlation between medial meniscus damage and progression of KOA (OR: 1.853, 95% CI: 1.177-2.941) and medial JSN (OR: 1.655, 95% CI: 1.053-2.602) was significant. Synovitis was found to mediate the relationship between medial meniscus extrusion and KL and medial JSN progression at baseline (ß: 0.029, 95% CI: 0.010-0.053; ß: 0.022, 95% CI: 0.005-0.046) and beyond 24 months (ß: 0.039, 95% CI: 0.016-0.068; ß: 0.047, 95% CI: 0.020-0.078). However, we did not find evidence of synovitis mediating the relationship between meniscal damage and KOA progression. Synovitis mediates the relationship between medial meniscus extrusion (rather than meniscus damage) and KOA progression.

MyoD Over-Expression Rescues GST-bFGF Repressed Myogenesis.

During embryogenesis, basic fibroblast growth factor (bFGF) is released from neural tube and myotome to promote myogenic fate in the somite, and is routinely used for the culture of adult skeletal muscle (SKM) stem cells (MuSC, called satellite cells). However, the mechanism employed by bFGF to promote SKM lineage and MuSC proliferation has not been analyzed in detail. Furthermore, the question of if the post-translational modification (PTM) of bFGF is important to its stemness-promoting effect has not been answered. In this study, GST-bFGF was expressed and purified from E.coli, which lacks the PTM system in eukaryotes. We found that both GST-bFGF and commercially available bFGF activated the Akt-Erk pathway and had strong cell proliferation effect on C2C12 myoblasts and MuSC. GST-bFGF reversibly compromised the myogenesis of C2C12 myoblasts and MuSC, and it increased the expression of Myf5, Pax3/7, and Cyclin D1 but strongly repressed that of MyoD, suggesting the maintenance of myogenic stemness amid repressed MyoD expression. The proliferation effect of GST-bFGF was conserved in C2C12 over-expressed with MyoD (C2C12-tTA-MyoD), implying its independence of the down-regulation of MyoD. In addition, the repressive effect of GST-bFGF on myogenic differentiation was almost totally rescued by the over-expression of MyoD. Together, these evidences suggest that (1) GST-bFGF and bFGF have similar effects on myogenic cell proliferation and differentiation, and (2) GST-bFGF can promote MuSC stemness and proliferation by differentially regulating MRFs and Pax3/7, (3) MyoD repression by GST-bFGF is reversible and independent of the proliferation effect, and (4) GST-bFGF can be a good substitute for bFGF in sustaining MuSC stemness and proliferation.

Development of a multifunctional bioreactor to evaluate the promotion effects of cyclic stretching and electrical stimulation on muscle differentiation.

A multifunctional bioreactor was fabricated in this study to investigate the facilitation efficiency of electrical and mechanical stimulations on myogenic differentiation. This bioreactor consisted of a highly stretchable conductive membrane prepared by depositing polypyrrole (PPy) on a flexible polydimethylsiloxane (PDMS) film. The tensile deformation of the PPy/PDMS membrane can be tuned by adjusting the channel depth. In addition, PPy/PDMS maintained its electrical conductivity under continuous cyclic stretching in the strain range of 6.5%-13% for 24 h. This device can be used to individually or simultaneously perform cyclic stretching and electrical stimulation. The results of single stimulation showed that either cyclic stretching or electrical stimulation upregulated myogenic gene expression and promoted myotube formation, where electrical stimulation improved better than cyclic stretching. However, only cyclic stretching can align C2C12 cells perpendicular to the stretching direction, and electrical stimulation did not affect cell morphology. Myosin heavy chain (MHC) immunostaining demonstrated that oriented cells under cyclic stretching resulted in parallel myotubes. The combination of these two stimuli exhibited synergetic effects on both myogenic gene regulation and myotube formation, and the incorporated electrical field did not affect the orientation effect of the cyclic stretching. These results suggested that these two treatments likely influenced cells through different pathways. Overall, the simultaneous application of cyclic stretching and electrical stimulation preserved both stimuli's advantages, so myo-differentiation can be highly improved to obtain abundant parallel myotubes, suggesting that our developed multifunctional bioreactor should benefit muscle tissue engineering applications.

Post-transcriptional regulation of myogenic transcription factors during muscle development and pathogenesis.

The transcriptional regulation of skeletal muscle (SKM) development (myogenesis) has been documented for over 3 decades and served as a paradigm for tissue-specific cell type determination and differentiation. Myogenic stem cells (MuSC) in embryos and adult SKM are regulated by the transcription factors Pax3 and Pax7 for their stem cell characteristics, while their lineage determination and terminal differentiation are both dictated by the myogenic regulatory factors (MRF) that comprise Mrf4, Myf5, Myogenin, and MyoD. The myocyte enhancer factor Mef2c is activated by MRF during terminal differentiation and collaborates with them to promote myoblast fusion and differentiation. Recent studies have found critical regulation of these myogenic transcription factors at mRNA level, including subcellular localization, stability, and translational regulation. Therefore, the regulation of Pax3/7, MRFs and Mef2c mRNAs by RNA-binding factors and non-coding RNAs (ncRNA), including microRNAs and long non-coding RNAs (lncRNA), will be the focus of this review and the impact of this regulation on myogenesis will be further addressed. Interestingly, the stem cell characteristics of MuSC has been found to be critically regulated by ncRNAs, implying the involvement of ncRNAs in SKM homeostasis and regeneration. Current studies have further identified that some ncRNAs are implicated in the etiology of some SKM diseases and can serve as valuable tools/indicators for prediction of prognosis. The roles of ncRNAs in the MuSC biology and SKM disease etiology will also be discussed in this review.

Knee arthroscopy has limited effects on relieving local symptoms of knee osteoarthritis: an analysis of data from the Osteoarthritis Initiative.

BACKGROUND: Knee arthroscopy's efficacy in symptom improvement for knee osteoarthritis remains debated. In this study, we analyzed a multicenter database to investigate local symptom improvement. METHODS: We extracted and analyzed the data of 163 patients from the Osteoarthritis Initiative cohort who underwent unilateral knee arthroscopy (UKA) and were followed up for at least 24 months. UKA patients were matched to non-UKA patients (n = 163) according to sex, age, abdominal circumference, and Kellgren-Lawrence grade. The verified KOOS questionnaires (knee catching, locking, grinding, or clicking) and common local symptoms (frequent knee pain, aching, or stiffness) were set as outcomes. Furthermore, we built a binary logistic regression model to examine the relationship between UKA and local symptom improvement and new-onset symptoms, adjusting for conservative therapeutic covariables (injection of steroids or transparent acid into the knee joint, oral chondroitin sulfate, amino glucose, or analgesics). RESULT: Analysis showed that the UKA and non-UKA groups showed no obvious difference in the three knee symptoms, but the probability of new-onset grinding or clicking, and frequent knee pain, aching, or stiffness symptoms in the UKA group were respectively 5.82 and 5.65-fold higher than that in the non-UKA group. After analyzing conservative treatment data using a multiple imputation method, the results were consistent with previous regression analyses. CONCLUSION: Compared to the non-UKA group, the UKA group showed no noticeable differences in the improvement of the three knee symptoms and showed an increased the probability of new-onset grinding or clicking and frequent knee pain, aching, or stiffness symptoms. Key Points • Knee arthroscopy may increase the probability of new-onset grinding or clicking and frequent knee pain, aching, or stiffness symptoms. • We found no difference in the improvement of local knee symptoms (knee catching, locking, grinding, clicking or frequent pain, aching, or stiffness) improvement between the two groups with or without knee arthroscopy.

Anterior knee pain as a potential risk factor for falls in older adults: insights from the osteoarthritis initiative data.

BACKGROUND: Knee joint pain has been demonstrated to be a separate risk factor for falling. A common pain site in the knee, anterior knee pain(AKP), is believed to be associated with early knee osteoarthritis (KOA).This study investigated the relationship between falls and AKP in people with or at risk for KOA. METHODS: Four years of follow-up data from the Osteoarthritis Initiative cohort trial, a large-scale, multicenter observational investigation, were analyzed in this study. A patellar quadriceps tenderness/tendinitis knee exam was performed to evaluate AKP. Falls were self-reported. The associations between falls (recurrent falls: ≥2 falls/year; any falls: ≥1 fall(s)/year) and AKP were analyzed using the generalized estimation equation of repeated logistic regression and adjusted for confounding variables. RESULTS: The study analyzed data from 3,318 participants, split into two groups: those with AKP (720 participants) and those without AKP (2,598 participants). The primary outcome of the study, which focused on repeated falls, revealed that participants with AKP were 1.27 times more likely to experience repeated falls compared to those without AKP (95% CI: 1.07-1.52, P = 0.007). However, when considering any falls experienced by an individual as an additional outcome, it is important to note that our findings did not indicate a significant predictive effect of AKP on any falls investigated. Sensitivity analyses, which excluded knee arthroplasty cases, yielded consistent results with the aforementioned findings. CONCLUSIONS: Older adults with AKP experience a higher frequency of falls compared to those without AKP in individuals diagnosed with KOA or at a high risk of developing KOA.

Reciprocal Regulation of Peroxisome Biogenesis and Myogenic Factors Is Critical for Myogenesis.

Mitochondria (MITO) and peroxisomes (PEXO) are the major organelles involved in the oxidative metabolism of cells, but detailed examination of their dynamics and functional adaptations during skeletal muscle (SKM) development (myogenesis) is still lacking. In this study, we found that during myogenesis, MITO DNA, ROS level, and redox ratio increased in myotubes, but the membrane potential (Δψm) and ATP content reduced, implying that the MITO efficiency might reduce during myogenesis. The PEXO number and density both increased during myogenesis, which probably resulted from the accumulation and increased biogenesis of PEXO. The expression of PEXO biogenesis factors was induced during myogenesis in vitro and in utero, and their promoters were also activated by MyoD. Knockdown of the biogenesis factors Pex3 repressed not only the PEXO density and functions but also the levels of MITO genes and functions, suggesting a close coupling between PEXO biogenesis and MITO functions. Surprisingly, Pex3 knockdown by the CRISPRi system repressed myogenic differentiation, indicating critical involvement of PEXO biogenesis in myogenesis. Taken together, these observations suggest that the dynamics and functions of both MITO and PEXO are coupled with each other and with the metabolic changes that occur during myogenesis, and these metabolic couplings are critical to myogenesis.

Anserine bursa palpation tenderness is a risk factor for knee osteoarthritis progression and arthroplasty: data from the Osteoarthritis Initiative.

OBJECTIVE: Anserine bursa pain (ABP) is defined as the presence of palpation tenderness medially below the joint line, which is 2 cm from the tibial tuberosity. This study aimed to determine a link between ABP and three knee outcomes: frequent pain, joint space narrowing (JSN) progression, and total knee arthroplasty (TKA). METHODS: Participants from the Osteoarthritis Initiative cohort were included in this study. Frequent ABP was defined as presenting thrice at four-time points. The Chi-square test and binary logistic regression analyses examined the associations between ABP and the three knee outcomes. Furthermore, Cox Proportional Hazards Model explored the association between ABP and TKA. RESULTS: Baseline ABP was linked to a higher risk of frequent pain (odds ratio (OR): 2.28, 95% confidence interval (CI): 1.76-2.97, P < 0 .001) and TKA (OR: 1.54, 95% CI 1.01-2.36, P = 0 .044) after adjusting for gender, baseline age, body mass index (BMI), and Kellgren-Lawrence (KL) grade. In the frequent ABP group from baseline to the 4-year follow-up (≥ 3 of four-time points), frequent pain (OR: 3.14, 95% CI: 2.34-4.22, P < 0 .001) and TKA (OR: 1.79, 95% CI: 1.11-2.90, P = 0 .017) had a high association with ABP after adjusting for gender, baseline age, BMI, and KL grade. CONCLUSION: This study highlights the association between ABP and knee outcomes; therefore, clinicians should pay closer attention during the physical examination, especially in middle-aged and older female patients. Moreover, understanding ABP cause aids in better diagnosis and treatment. Key Points • This is the first study to identify an association between anserine bursa palpation tenderness and symptomatic knee osteoarthritis. • As opposed to most studies, which focus on intra-articular symptoms and signs, this study focused on extra-articular symptoms and signs. • Clinically, anserine bursa palpation tenderness can be utilized to determine patients at risk for the progression of knee osteoarthritis, thereby aiding in providing early therapeutic intervention.

Spatiotemporal dynamics of suspended particulate matter in the Bohai Sea, China over the past decade from the space perspective.

Suspended particulate matter (SPM) concentration is an important biogeochemical parameter for water quality assessment and morphodynamic studies. In this study, the four recent SPM retrieval models developed for Bohai Sea were evaluated using in situ datasets, and the best performing model was selected to investigate the spatiotemporal dynamics of SPM in Bohai Sea from 2011 to 2021 based on 1164 satellite imageries. The results indicated that the satellite-derived SPM concentrations had a high accuracy (R2 = 0.86, relative percentage difference = 33.71 %). The SPM concentrations in the Bohai Sea demonstrated a significant decadal decreasing trend (0.503 mg/L/yr), and the distribution area with low SPM (<30 mg/L) increased by 3.29 % annually. The southern Bohai Sea declined observably, involving the Bohai Bay (2.07 mg/L/yr), Laizhou Bay (1.916 mg/L/yr), and central Bohai Sea (-0.661 mg/L/yr). Monthly SPM was characterized by significant seasonality. The SPM circulation pattern in the Bohai Strait was generally northerly inflow and southerly outflow. Significant wave heights (Hs) dominated the SPM variations and explained 58.9 % of monthly SPM changes in the Bohai Sea. The strong waves reduction was the main reason for the decadal decline of SPM concentrations. Wind waves associated with monsoons controlled seasonal variations of SPM and promoted the output in winter through the southern Bohai Strait. Storms could cause a sharp increase in SPM concentrations, especially in Bohai Bay and Laizhou Bay which were highly sensitive to northerly winds and strong waves. After the storm ended, the effects of short-duration storm might fade away within a few hours, while that of long-duration storm could last for 2-3 days. High sediment transport from Yellow River (>500 × 104 t/M) controlled 74.8 % of monthly SPM variations within 3-km area off the estuary, 45 % of that within 5-km area, and 28.4 % of that within 10-km area.

The cooperation of cis-elements during M-cadherin promoter activation.

M-cadherin is a skeletal muscle-specific transmembrane protein mediating the cell-cell adhesion of myoblasts during myogenesis. It is expressed in the proliferating satellite cells and highly induced by myogenic regulatory factors (MRFs) during terminal myogenic differentiation. Several conserved cis-elements, including 5 E-boxes, 2 GC boxes, and 1 conserved downstream element (CDE) were identified in the M-cadherin proximal promoter. We found that E-box-3 and -4 close to the transcription initiation site (TIS) mediated most of its transactivation by MyoD, the strongest myogenic MRF. Including of any one of the other E-boxes restored the full activation by MyoD, suggesting an essential collaboration between E-boxes. Stronger activation of M-cadherin promoter than that of muscle creatine kinase (MCK) by MyoD was observed regardless of culture conditions and the presence of E47. Furthermore, MyoD/E47 heterodimer and MyoD ∼ E47 fusion protein achieved similar levels of activation in differentiation medium (DM), suggesting high affinity of MyoD/E47 to E-boxes 3/4 under DM. We also found that GC boxes and CDE positively affected MyoD mediated activation. The CDE element was predicted to be the target of the chromatin-modifying factor Meis1/Pbx1 heterodimer. Knockdown of Pbx1 significantly reduced the expression level of M-cadherin, but increased that of N-cadherin. Using ChIP assay, we further found significant reduction in MyoD recruitment to M-cadherin promoter when CDE was deleted. Taken together, these observations suggest that the chromatin-modifying function of Pbx1/Meis1 is critical to M-cadherin promoter activation before MyoD is recruited to E-boxes to trigger transcription.

Human impact on suspended particulate matter in the Yellow River Estuary, China: Evidence from remote sensing data fusion using an improved spatiotemporal fusion method.

Transport of suspended particulate matter (SPM) in estuarine waters plays an important role in regulating erosion-accretion and biogeochemical processes. In the Yellow River Estuary (YRE), artificial water and sediment regulation scheme (WSRS) and coastal engineering structures are the 2 typical anthropogenic activities affecting the spatiotemporal dynamics of estuarine SPM. The monitoring of SPM transport affected by such human activities requires SPM mapping at both high spatial and high temporal resolutions. In this study, we presented an improved Flexible Spatiotemporal Data Fusion (FSDAF) strategy with consideration of highly dynamic SPM variations in estuarine waters, and generated 30-m hourly SPM concentrations based on Landsat 8 OLI and GOCI datasets. The new strategy produced higher SPM estimation accuracy than the original FSDAF, with the relative percentage difference (RPD) decreasing from 29.75% to 5.31% using GOCI-derived hourly SPM as reference. With in situ SPM measurements as reference, the fused SPM concentrations had an RMSE of 12.09 mg/L and an RPD of 27.17%. Investigation of interday SPM variations before, during, and after the WSRS in 2018 revealed that the first WSRS significantly increased the SPM concentration and plume extent; new wetland with an area of 12.56 km2 was formed due to sediment accretion near the river mouth. The two groins offshore from the coastlines on the north and south sides of YRE exhibited obvious sediment trapping effects in that higher SPM concentrations on one side of each groin were found regardless of the turbidity modes and diurnal SPM variations; the trapping effects were associated with the number of groins and groin length. Intraday variations of SPM were influenced by tidal currents, with plume direction following the ebb and flooding tidal current direction. The inter- and intraday characteristics of the 30-m hourly SPM dynamics facilitate the detailed analysis of the sediment transport associated with human activities.

Di-(2-ethylhexyl) phthalate limits the pleiotropic effects of statins in chronic kidney disease patients undergoing dialysis and endothelial cells.

The level of di-(2-ethylhexyl) phthalate (DEHP) is elevated in chronic kidney disease patients undergoing dialysis. However, statins are unable to reduce the cardiovascular events in chronic dialysis patients. In this study, we investigated the effects of DEHP on statin-conferred pleiotropic effects and the underlying molecular mechanism in peritoneal dialysis (PD) patients and endothelial cells (ECs). In PD patients with serum DEHP level ≥0.0687 µg/mL, statin treatment was not associated with lower risk of cardiovascular disease. In ECs, exposure to DEHP abrogated the simvastatin-induced NO bioavailability and EC-related functions. Additionally, DEHP abolished the anti-inflammatory effect of simvastatin on the tumor necrosis factor α-induced upregulation of adhesion molecules and monocyte adhesion to ECs. Mechanistically, DEHP blunted the activation of transient receptor potential vanilloid type 1 (TRPV1), which is required for NO production by simvastatin in ECs. Notably, DEHP increased the activity and expression of protein phosphatase 2B (PP2B), a negative regulator of TRPV1 activity. The effect of DEHP on PP2B activation was mediated by the activation of the NADPH oxidase/reactive oxygen species (NOX-ROS) pathway. Inhibition of PP2B activity by pharmacological antagonists prevented the inhibitory effects of DEHP on simvastatin-induced Ca2+ influx, NO bioavailability, and EC migration, proliferation, tube formation, and anti-inflammatory action. Collectively, DEHP activates the NOX-ROS-PP2B pathway, which in turns inhibits TRPV1/Ca2+-dependent signaling and abrogates the statin-conferred pleiotropic protection in ECs.

Phthalate exposure causes browning-like effects on adipocytes in vitro and in vivo.

Mono(2-ethylhexyl)phthalate (MEHP) promotes adipogenesis via PPARγ. PPARγ agonists, e.g., rosiglitazone (RSG), enhance adipocyte browning. However, scientific evidence regarding MEHP as a browning chemical is lacking. This study combined 3T3-L1 adipocytes and C57BL/6J mice to examine the potential roles of MEHP in browning. MEHP and the browning agent RSG caused similar energy metabolism in adipocytes. Both MEHP and RSG caused transcriptional changes involved in browning-associated thermogenesis, energy homeostasis, inflammatory response, and glucose uptake. MEHP-treated adipocytes exhibited brown adipocyte-like characteristics, i.e., increased mitochondrial proton leak, triiodothyronine-induced Bmp8b expression, decreased inflammation, and smaller lipid droplets. Increased PDK4 and PEPCK1 in MEHP/RSG-treated adipocytes could block glucose utilization for mitochondrial respiration. Mitochondrial/peroxisomal biogenesis and fatty acid ß-oxidation in MEHP-treated adipocytes were enhanced. Candidate genes in promoting browning of MEHP-treated adipocytes were highlighted. In di(2-ethylhexyl)phthalate (DEHP)-treated mice, transcriptional changes in white adipose tissue (WAT) were associated with adipocyte differentiation, lipid synthesis, carbohydrate uptake, and WAT/brown adipose tissue (BAT) quantity. PPARγ and NR4A1 were predicted as the top two upstream regulators in orchestrating transcriptional changes. DEHP-treated mice exhibited actively expressed browning marker genes (i.e., Pparg, Adrb1, Adrb3, Ppargc1a, and Ucp1) in WAT, increased blood FGF21 levels, and higher amounts of BAT, supporting the browning-like effects in vivo.

MEHP interferes with mitochondrial functions and homeostasis in skeletal muscle cells.

Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer frequently leached out from polyvinyl chloride (PVC) products and is quickly metabolized to its monoester equivalent mono(2-ethylhexyl) phthalate (MEHP) once enters organisms. Exposure to DEHP/MEHP through food chain intake has been shown to modified metabolism but its effect on the development of metabolic myopathy of skeletal muscle (SKM) has not been revealed so far. Here, we found that MEHP repressed myogenic terminal differentiation of proliferating myoblasts (PMB) and confluent myoblasts (CMB) but had weak effect on this process once it had been initiated. The transition of mitochondria (MITO) morphology from high efficient filamentary network to low efficient vesicles was triggered by MEHP, implying its negative effects on MITO functions. The impaired MITO functions was further demonstrated by reduced MITO DNA (mtDNA) level and SDH enzyme activity as well as highly increased reactive oxygen species (ROS) in cells after MEHP treatment. The expression of metabolic genes, including PDK4, CPT1b, UCP2, and HO1, was highly increased by MEHP and the promoters of PDK4 and CPT1b were also activated by MEHP. Additionally, the stability of some subunits in the oxidative phosphorylation system (OXPHOS) complexes was found to be reduced by MEHP, implying defective oxidative metabolism in MITO and which was confirmed by repressed palmitic acid oxidation in MEHP-treated cells. Besides, MEHP also blocked insulin-induced glucose uptake. Taken together, our results suggest that MEHP is inhibitory to myogenesis and is harmful to MITO functions in SKM, so its exposure should be avoided or limited.

Effect of using different proportions of inoculum during bioleaching on sludge dewaterability.

Bioleaching, the addition of bacteria to geological materials, has been applied to sludge to remove metals and improve upon sludge dewaterability. This paper investigates the effect of using different quantities of inoculum (bacteria) during bioleaching on sludge dewaterability. The analysis was based on bioleaching experiments conducted in a 20 L bio-reactor using different quantities of inoculum (20%, 10%, 5%, 2%, 0%). Changes in pH, oxidation reduction potential (ORP), capillary suction time (CST), specific resistance to filtration (SRF) and extracellular polymeric substances (EPS) were determined to gauge sludge dewatering. Results indicate that sludge dewaterability during the 2%, 10%, and 20% inoculum experiments declined through time. Decreased dewaterability is attributed to increases in the quantity of proteins and polysaccharides in slime EPS. Dewaterability improved during the 5% inoculum experiment, and reached a maximum when pH was 2.3. During this latter experiment, CST and SRF were reduced by 74% and 62%, respectively, in comparison to control conditions, while total EPS content decreased by 71%. The decrease in total EPS was primarily due to a decrease in proteins associated with tightly bound EPS (TB-EPS). Thus, changes in the amount of proteins in TB-EPS and sludge pH played a crucial role in sludge dewaterability.

Monitoring tidal flat dynamics affected by human activities along an eroded coast in the Yellow River Delta, China.

The coast of the northern Yellow River Delta (YRD) has experienced significant erosion since 1976 due to avulsion and consequent lack of sediment supply. Moreover, massive reclamation activity, expansion of the oil industry, and sea-level rise have jointly contributed to the rapid change of tidal flats over recent decades. Therefore, accurate reporting of the coast spatial extent and stability status is urgently required. We presented a method using remotely sensed waterlines to map tidal flats and monitor their spatiotemporal dynamics. The empirical results show that the area of the intertidal zone west of Tiao River Mouth (TRM) appeared to be decreasing. Despite intense hydrodynamic force, the intertidal zone to the east of TRM has expanded due to law prohibiting land reclamation in nature reserve. However, this trend weakened due to the expansion of oil industry after 2007. The movement of the mean high-tide line is the main cause for the increase-decrease patterns of the intertidal zone area. To achieve and maintain land equilibrium in this area, we suggest that a 554-m buffer must be preserved for mean high-tide line retreat. Unfortunately, the shrink crisis of the tidal flats has been extremely severe. Future reclamation and oil projects must be supplemented by studies that evaluate the complexities and dynamics of tidal flats so as to prevent the loss of this unique ecosystem.

Fractal properties of shoreline changes on a storm-exposed island.

Extreme storm events and their consequent shoreline changes are of great importance for understanding coastal evolution and assessing storm hazards. This work investigates the fractal properties of the spatial distributions of shoreline changes caused by storms. Wavelet analysis and upper-truncated power law (UTPL) fitting are used to study the power spectra of shoreline changes and to evaluate the upper limits of the cross-shore erosion and accretion. During a period affected by storms, the alongshore shoreline change patterns are strong on the 15 km scale but are weak with lower spectral power on the 20 km scale. The areas adjacent to the eroded shoreline are usually accrete, and the cross-shore extent of erosion is larger than that of accretion when the coast is affected by storms. The fractal properties of shoreline changes due to storms are found to be temporally continuous: the effects of later storms build on the preceding shoreline conditions, including both the effects of previous storms and the subsequent shoreline recoveries. This work provides a new perspective on the various scales of the spatial variations of the morphodynamics of storm-affected shorelines.

Thyroid hormone suppresses hepatocarcinogenesis via DAPK2 and SQSTM1-dependent selective autophagy.

Recent studies have demonstrated a critical association between disruption of cellular thyroid hormone (TH) signaling and the incidence of hepatocellular carcinoma (HCC), but the underlying mechanisms remain largely elusive. Here, we showed that disruption of TH production results in a marked increase in progression of diethylnitrosamine (DEN)-induced HCC in a murine model, and conversely, TH administration suppresses the carcinogenic process via activation of autophagy. Inhibition of autophagy via treatment with chloroquine (CQ) or knockdown of ATG7 (autophagy-related 7) via adeno-associated virus (AAV) vectors, suppressed the protective effects of TH against DEN-induced hepatic damage and development of HCC. The involvement of autophagy in TH-mediated protection was further supported by data showing transcriptional activation of DAPK2 (death-associated protein kinase 2; a serine/threonine protein kinase), which enhanced the phosphorylation of SQSTM1/p62 (sequestosome 1) to promote selective autophagic clearance of protein aggregates. Ectopic expression of DAPK2 further attenuated DEN-induced hepatoxicity and DNA damage though enhanced autophagy, whereas, knockdown of DAPK2 displayed the opposite effect. The pathological significance of the TH-mediated hepatoprotective effect by DAPK2 was confirmed by the concomitant decrease in the expression of THRs and DAPK2 in matched HCC tumor tissues. Taken together, these findings indicate that TH promotes selective autophagy via induction of DAPK2-SQSTM1 cascade, which in turn protects hepatocytes from DEN-induced hepatotoxicity or carcinogenesis.

Chemotherapy resistance and metastasis-promoting effects of thyroid hormone in hepatocarcinoma cells are mediated by suppression of FoxO1 and Bim pathway.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, and systemic chemotherapy is the major treatment strategy for late-stage HCC patients. Poor prognosis following chemotherapy is the general outcome owing to recurrent resistance. Recent studies have suggested that in addition to cytotoxic effects on tumor cells, chemotherapy can induce an alternative cascade that supports tumor growth and metastasis. In the present investigation, we showed that thyroid hormone (TH), a potent hormone-mediating cellular differentiation and metabolism, acts as an antiapoptosis factor upon challenge of thyroid hormone receptor (TR)-expressing HCC cells with cancer therapy drugs, including cisplatin, doxorubicin and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TH/TR signaling promoted chemotherapy resistance through negatively regulating the pro-apoptotic protein, Bim, resulting in doxorubicin-induced metastasis of chemotherapy-resistant HCC cells. Ectopic expression of Bim in hepatoma cells challenged with chemotherapeutic drugs abolished TH/TR-triggered apoptosis resistance and metastasis. Furthermore, Bim expression was directly transactivated by Forkhead box protein O1 (FoxO1), which was negatively regulated by TH/TR. TH/TR suppressed FoxO1 activity through both transcriptional downregulation and nuclear exclusion of FoxO1 triggered by Akt-mediated phosphorylation. Ectopic expression of the constitutively active FoxO1 mutant, FoxO1-AAA, but not FoxO1-wt, diminished the suppressive effect of TH/TR on Bim. Our findings collectively suggest that expression of Bim is mediated by FoxO1 and indirectly downregulated by TH/TR, leading to chemotherapy resistance and doxorubicin-promoted metastasis of hepatoma cells.