Enhancement of Mn2+, Fe2+ and NH4+-N removal by biochar synergistic strains combined with activated sludge in real wastewater treatment.

Acinetobacter sp. AL-6 combining with biochar was adapted in activated sludge (AS & co-system) to decontaminate Mn2+, Fe2+ and NH4+-N, and treat activated sludge (AS) for its activity and settling performance improvement. Specifically, the co-system promoted the growth of bacteria in the activated sludge, thus increasing its ability to nitrify and adsorb Mn2+ and Fe2+, resulting in the removal of high concentrations of NH4+-N, Mn2+, Fe2+ and COD in the reactor by 100%, 100%, 100%, and 96.8%, respectively. And the pH of wastewater was increased from 4 to 8.5 by co-system also facilitated the precipitation of Mn2+ and Fe2+. The MLVSS/MLSS ratio increased from 0.64 to 0.95 and SVI30 decreased from 92.54 to 1.54 after the addition of co-system, which indicated that biochar helped to improve the activity and settling performance of activated sludge and prevented it from being damaged by the compound Mn2+ and Fe2+. In addition, biochar promoted the increase of the tyrosine-like protein substance and humic acid-like organic matter in the sludge EPS, thus enhanced the ability of sludge to adsorb Mn2+ and Fe2+. Concretely, compared with AS group, the proteins content and polysaccharides content of the AS & co-system group were increased by 13.14 times and 6.30 times respectively. Further, microbial diversity analysis showed that more resistant bacteria and dominant bacteria Acinetobacter sp. AL-6 in sludge enhanced the nitrification and adsorption of manganese and iron under the promotion of biochar. Pre-eminently, the more effective AS & co-system were applied to the removal of actual electrolytic manganese slag leachate taken from the contaminated site, and the removal of NH4+-N, Mn2+, Fe2+ and COD remained high at 100%, 100%, 71.82% and 94.72%, respectively, revealing advanced value for high engineering applications of AS & co-system.

DNA Damage-Induced Apoptosis Suppressor Triggers Progression and Stemness of Glioma by Enhancing Lymphoid Enhancer-Binding Factor 1 Expression.

Background: DNA damage-induced apoptosis suppressor (DDIAS) has recently been discovered to induce cancer progression, but its functions and mechanisms in glioma have not been well studied. Methods: DDIAS expression in glioma tissues was analyzed by the Gene Expression Profiling Interactive Analysis server (GEPIA) and the Gene Expression database of Normal and Tumor tissue 2 (GENT2) databases. The role of DDIAS in glioma progression was studied by short hairpin RNA (shRNA) targeting DDIAS. The effects of DDIAS on glioma cell viability, cell proliferation, invasion, migration, and tumor sphere formation were determined by cell counting kit-8 (CCK-8), EdU, Transwell, tumor spheroid formation, extreme limiting dilution analysis assays in vitro and xenograft model construction in vivo. In addition, RNA sequencing and further functional experiments were used to analyze the DDIAS regulatory mechanism in glioma. Results: We found that DDIAS was highly expressed in glioma and that upregulated DDIAS indicated poor prognosis. Functionally, DDIAS knockdown inhibited glioma cell viability, cell proliferation, invasion and migration in vitro and tumor growth in vivo. In addition, lymphoid enhancer-binding factor 1 (LEF1) was identified as the downstream effector of DDIAS by RNA sequencing. DDIAS downregulation inhibited LEF1 mRNA and protein expression. The expression of DDIAS and LEF1 was positively correlated, and LEF1 overexpression rescued the inhibitory phenotype induced by DDIAS downregulation. We further showed that DDIAS downregulation inhibited cyclin A1, vimentin and the stemness-related factor CD133 and decreased the sphere formation capability, but these features were rescued by upregulation of LEF1. Conclusion: Taken together, these findings suggest that DDIAS promotes glioma progression and stemness by inducing LEF1 expression, proving that DDIAS may be a potential target for the treatment of glioma.

In vitro fermentation characteristics of polysaccharides from coix seed and its effects on the gut microbiota.

Coix seed polysaccharides had received increasing attention due to their diverse biological activities. In this study, a homogeneous polysaccharide (CSPW) was extracted and purified from coix seed. Furthermore, the saliva-gastrointestinal digestion and fecal fermentation behavior of CSPW were simulated in vitro. The results showed that CSPW was mainly composed of glucose. It cannot be degraded by the simulated salivary and intestinal digestive system, but can be degraded by the simulated gastric digestive system. After fermentation for 24 h, CSPW promoted the production of short-chain fatty acids (SCFAs), with acetic acid, propionic acid and n-butyric acid being the main metabolites. In addition, CSPW could significantly regulate the composition and microbial diversity of gut microbiota by increasing the relative abundance of beneficial bacteria, such as Limosilicactobacillus, Bifidobacterium and Collinsella. Finally, further analysis of functional prediction revealed that amino acid metabolism, nucleotide metabolism and carbohydrate metabolism were the most important pathways for CSPW to promote health. In summary, our findings suggested that CSPW could potentially be used as a good source of prebiotics because it can be used by gut microbiota to produce SCFAs and regulate the gut microbiota.

Vision-driven metasurfaces for perception enhancement.

Metasurfaces have exhibited unprecedented degree of freedom in manipulating electromagnetic (EM) waves and thus provide fantastic front-end interfaces for smart systems. Here we show a framework for perception enhancement based on vision-driven metasurface. Human's eye movements are matched with microwave radiations to extend the humans' perception spectrum. By this means, our eyes can "sense" visual information and invisible microwave information. Several experimental demonstrations are given for specific implementations, including a physiological-signal-monitoring system, an "X-ray-glasses" system, a "glimpse-and-forget" tracking system and a speech reception system for deaf people. Both the simulation and experiment results verify evident advantages in perception enhancement effects and improving information acquisition efficiency. This framework can be readily integrated into healthcare systems to monitor physiological signals and to offer assistance for people with disabilities. This work provides an alternative framework for perception enhancement and may find wide applications in healthcare, wearable devices, search-and-rescue and others.

Enhanced activation of persulfate by modified red mud biochar for degradation of dye pollutant: Resource utilization and non-radical activation.

The substantial development of the dyeing and printing industry has resulted in an increased discharge of dye wastewater containing a large amount of recalcitrant organic pollutants. Furthermore, the landfill disposal of red mud has led to significant environmental pollution such as soil erosion and groundwater contamination. Therefore, this study aimed to promote the resource utilization of red mud by preparing advanced oxidation catalyst, resulting in effective treatment of dye wastewater, and the primary reaction mechanism was revealed. In this study, biochar-loading red mud (RBC) was applied to activate persulfate (PDS) for the degradation of acid orange 7 (AO7) with the initial concentration of 50 mg L-1. The maximum removal rate of 2.45 mg L·min-1 was achieved in 20 min and corresponding with the removal ratio of 98.0% under the PDS concentration of 20 mM (4.76 g L-1). Eventually, the removal ratio of 99.2% was attained within 60 min. The high catalytic efficiency was probably ascribed to the singlet oxygen (1O2) dominant non-radical pathway and RBC-mediated electron transfer mechanism. It was found that Fe(II), specific surface areas and functional groups on the catalyst were highly related to its catalytic efficiency and passivation. RBC had better reusability due to the loading of biochar and the reduction of zero-valent iron. The non-radical pathway mechanism and electron transfer mechanism were proposed for the activation of PDS, and non-radical pathway played a dominant role. Besides, the degradation pathways and toxicity assessment were analyzed. This research proposed a new electron transfer mechanism for activation process of PDS, which can provide a theoretical support for further studies. Overall, this study demonstrated that catalysts synthesized from red mud and biomass exhibit highly efficient activation in degrading the model pollutant AO7 through PDS activation. The catalyst displayed promising reusability and practical applicability, offering potential advancements in both the resource utilization and reduction of red mud.

[Identification of Nitrate Source and Transformation Process in Shallow Groundwater Around Dianchi Lake].

Elucidating the main sources and transformation process of nitrate for the prevention and control of groundwater nitrogen pollution and the development and utilization of groundwater resources has great significance. To explore the current situation and source of nitrate pollution in shallow groundwater around the Dianchi Lake, 73 shallow groundwater samples were collected in the rainy season in 2020(October) and dry season in 2021(April). Using the hydrochemistry and nitrogen and oxygen isotopes(δ15N-NO3- and δ18O-NO3-), the spatial distribution, source, and transformation process of nitrate in shallow groundwater were identified. The contribution of nitrogen from different sources to nitrate in shallow groundwater was quantitatively evaluated using the isotope mixing model(SIAR). The results showed that in nearly 40.5% of sampling points in the shallow groundwater in the dry season, ρ(NO3--N) exceeded the 20 mg·L-1 specified in the Class Ⅲ water quality standard for groundwater(GB/T 14848), and in more than 47.2% of sampling points in the rainy season, ρ (NO3--N) exceeded 20 mg·L-1. The analysis results of nitrogen and oxygen isotopes and SIAR model showed that soil organic nitrogen, chemical fertilizer nitrogen, and manure and sewage nitrogen were the main sources of nitrate in shallow groundwater; these nitrogen sources contributed 13.9%, 11.8%, and 66.5% to nitrate in shallow groundwater in the dry season and 33.7%, 31.1%, and 25.9% in the rainy season, respectively. However, the contribution rate of atmospheric nitrogen deposition was only 8.5%, which contributed little to the source of nitrate in shallow groundwater in the study area. Nitrification was the leading process of nitrate transformation in shallow groundwater in the dry season, denitrification was the dominant process in the rainy season, and denitrification was more noticeable in the rainy season than that in the dry season.

Advances in Neuroimaging and Multiple Post-Processing Techniques for Epileptogenic Zone Detection of Drug-Resistant Epilepsy.

Among the approximately 20 million patients with drug-resistant epilepsy (DRE) worldwide, the vast majority can benefit from surgery to minimize seizure reduction and neurological impairment. Precise preoperative localization of epileptogenic zone (EZ) and complete resection of the lesions can influence the postoperative prognosis. However, precise localization of EZ is difficult, and the structural and functional alterations in the brain caused by DRE vary by etiology. Neuroimaging has emerged as an approach to identify the seizure-inducing structural and functional changes in the brain, and magnetic resonance imaging (MRI) and positron emission tomography (PET) have become routine noninvasive imaging tools for preoperative evaluation of DRE in many epilepsy treatment centers. Multimodal neuroimaging offers unique advantages in detecting EZ, especially in improving the detection rate of patients with negative MRI or PET findings. This approach can characterize the brain imaging characteristics of patients with DRE caused by different etiologies, serving as a bridge between clinical and pathological findings and providing a basis for individualized clinical treatment plans. In addition to the integration of multimodal imaging modalities and the development of special scanning sequences and image post-processing techniques for early and precise localization of EZ, the application of deep machine learning for extracting image features and deep learning-based artificial intelligence have gradually improved diagnostic efficiency and accuracy. These improvements can provide clinical assistance for precisely outlining the scope of EZ and indicating the relationship between EZ and functional brain areas, thereby enabling standardized and precise surgery and ensuring good prognosis. However, most existing studies have limitations imposed by factors such as their small sample sizes or hypothesis-based study designs. Therefore, we believe that the application of neuroimaging and post-processing techniques in DRE requires further development and that more efficient and accurate imaging techniques are urgently needed in clinical practice. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Efficient rhodamine B dye degradation by red mud-grapefruit peel biochar catalysts activated persulfate in water.

The continuous and rapid development of textile industry intensifies rhodamine B dye (RhB) wastewater pollution. Meanwhile, massive red mud (RM) solid waste generated by the industrial alumina production process poses detrimental effects to the environment after leaching. For resource utilization and to reduce the expansion of RhB pollution, RM and peel red mud-biochar composite (RMBC) catalyst were synthesized in activating peroxydisulfate (PDS) for RhB degradation. Firstly, characterization results showed that compared to RM, RMBC had a higher content of catalytically active metals (Fe, Al, Ti) (higher than 0.92-4.18%), smaller pore size, and larger specific surface area (10 times), which verified RMBC had more potential catalytic oxidation activity. Secondly, under optimal dosage (catalyst, PDS), pH 4.6, and 20 mg L-1 RhB, it was found that the RhB degradation ratio of RM was 76.70%, which was reduced to 41% after three cycles, while that of RMBC was 89.98% and 67%, respectively. The results indicated that the performance of RMBC was significantly superior to that of RM. Furthermore, the quenching experiments, electron paramagnetic resonance spectroscopy tests, FTIR, and XPS analysis showed the function of O-H, C=O, C-O, Fe-O, and Fe-OH functional groups, which converted the PDS to the active state and hydrolyzed it to produce free radicals ([Formula: see text], 1O2, [Formula: see text]) for RhB degradation. And, Q Exactive Plus MS test obtained that RhB was degraded to CO2, H2O, and intermediate products. This study aimed to raise a new insight to the resource utilization of RM and the control of dye pollution.

The acceleration of aerobic sludge granulation by alternating organic loading rate: Performance and mechanism.

As a highly promising treatment technology for wastewater, long start-up time is one of the bottlenecks hindering the widespread application of aerobic granular sludge (AGS). This study focused on exploring the possibility of alternating organic loading rate (OLR) in promoting AGS granulation. Under alternating OLR (3.6-14.4 kgCOD/m3·d), AGS granulation was significantly accelerated. The mean granule size under alternating load reached 234.6 µm at 17 d, while under constant OLR (7.2 kgCOD/m3·d), the mean granule size was only 179.2 µm. Moreover, the granule size maintained continuous growth even when the alternating OLR was changed to constant OLR. Alternating load significantly increased the content of extracellular polymeric substances (EPS), especially proteins (PN) in tightly bound EPS (TB-EPS), which was likely the main reason for accelerating AGS granulation. Moreover, alternating load reduced the hydrophilicity of EPS and promoted the content of proteins secondary structures that favored aggregation in TB-EPS, which were also beneficial for granulation. Microbial community results showed that alternating load might promote the enrichment of EPS producing bacteria, such as Thauera, Brevundimonas and Shinella. Meanwhile, the content of enzymes that regulated amino acids metabolism also increased under alternating load, which might be related to the increase of PN in EPS. These results further demonstrated that alternating load promoted granulation through EPS.

The influence of different nitrate concentrations on aerobic sludge granulation and the role of extracellular polymeric substances.

This study investigated the influence of nitrate on aerobic granular sludge (AGS) granulation. The introduction of nitrate at 5, 15 and 20 mg L-1 promoted AGS granulation, and the promoting effect was positively correlated with nitrate concentrations. Meanwhile, exogenous nitrate significantly increased denitrification rate in the AGS system. However, granular disintegration appeared at a long-term addition of nitrate. An in-deep analysis showed that nitrate stimulated the secretion of extracellular polymeric substances (EPS), especially the content of proteins, which might be the main reason for the AGS granulation. However, the rapid and excessive increase in EPS might cause granular disintegration, as excessive EPS blocked the transmission of substrates, leading to the increase of dead cells in the granules. Besides, nitrate also altered the hydrophobicity of EPS and the content of α-helix, 3-turned helix and polymeric chain that favored aggregation, which also affected AGS granulation. From the microbial community level, nitrate induced the enrichment of denitrifying bacteria, including those that also functioned as EPS producers, such as Micropruina and Flavobacterium, resulting in the rapid increase of functional enzymes associated with amino acid synthesis, thereby promoting the secretion of proteins in EPS. Conversely, disintegration caused by mass transfer blockage might lead to the loss of EPS producing bacteria and subsequent decrease in EPS content, further accelerating granular disintegration.

Acid-modified red mud biochar for the degradation of tetracycline: Synergistic effect of adsorption and nonradical activation.

In this study, a novel acid-modified red mud biochar catalyst (MMBC) was synthesized by industrial waste red mud (RM) and peanut shell (PSL) to activate peroxodisulfate (PDS) for the degradation of TC. Meanwhile, MMBC exhibited remarkable adsorption capacity, reaching a 60% removal ratio of TC within 60 min (equilibrium adsorption capacity = 12 mg/g). After adding PDS, MMBC/PDS system achieved a 93.8% removal ratio of TC within 60 min. Quenching experiments and electron paramagnetic resonance (EPR) results showed that 1O2 played a dominant role in the degradation of TC and O2•- was the mainly precursor for the production of 1O2 in the MMBC/PDS system. X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) analysis showed that the surface Fe(II), -OH and -COOH provided the active sites for the activation of PDS by MMBC. In addition, acid modification optimised the surface structure of the catalyst and enhanced the conversion of Fe (mainly Fe(III) to Fe(II)), thereby improving the adsorption and catalytic efficiency of MMBC. This study confirmed that modified red mud biochar is an efficient composite with both adsorption and catalysis, providing new ideas for the practical treatment of antibiotic wastewater and the resource utilization of red mud.

Radioactive stent insertion for inoperable hilar cholangiocarcinoma: a prospective randomized controlled trial.

Introduction: Hilar cholangiocarcinoma (HC) is the leading cause of hilar biliary obstruction. Radioactive stent insertion has been utilized extensively for inoperable HC patients. Aim: To assess the relative clinical outcomes of inoperable HC patients who underwent either normal or radioactive stent insertion. Material and methods: This single-center, prospective, randomized, open-label study enrolled 90 inoperable HC patients from April 2021 to March 2022 and randomly assigned them to normal or radioactive stent groups (n = 45/group), with clinical data then being compared between these groups. Results: Technical success rates in the normal and radioactive stent insertion groups were 93.3% and 97.9%, respectively (p = 1.000), and clinical success rates were similarly consistent in both groups (95.3% vs. 97.7%, p = 0.983). Individuals in the radioactive stent group exhibited significantly longer median stent patency as compared to the normal stent group (195 days vs. 115 days, p < 0.001), and median overall survival (OS) was also significantly increased in the normal stent group (242 days vs. 125 days, p = 0.002). In the normal stent insertion group, 6 (14.3%) and 5 (11.9%) patients experienced early and late postoperative complications, respectively. Additionally, early and late postoperative complications impacted 7 (16.3%) and 8 (18.6%) patients in the radioactive stent insertion group, respectively. Complication rates were comparable in these 2 patient groups. Conclusions: Radioactive stent insertion represents a safe and effective strategy for patients with inoperable HC, potentially contributing to prolonged stent patency and OS relative to normal stent insertion.

Bioflocculation characteristics of bound extracellular polymers substances from Pseudomonas sp. XD-3 and behavior of polysaccharides.

This study aimed to investigate the bioflocculation characteristics of bound extracellular polymers substances (B-EPS), which were extracted from Pseudomonas sp. XD-3. The flocculation efficiency of B-EPS achieved about 80%- 95% with an initial pH of 4-7, kaolin concentrations of 3-7 g L-1, temperature of 25-100 â„ƒ and B-EPS dosage of 9-105 mg L-1. The bioflocculation process of B-EPS conformed to pseudo-second-order kinetic mode, suggesting that the bioflocculation belonged to chemical adsorption process. Enzymatic hydrolysis experiments demonstrated that both polysaccharides and proteins were active components for bioflocculation. The polysaccharides were irregular aggregates with rough and porous surfaces and contained hydroxyl and carboxyl groups, which helped to promote bridging effect. Ribose, glucose and galactose were the main monosaccharides of polysaccharides. The molecular weight of the polysaccharides was relatively small, but the relatively loose configuration exposed more ion bridging sites, thus promoting the bioflocculation. Optimizing the ingredients of culture medium and culture time for B-EPS were effective strategies to increase the yield of flocculation active components. When the conditions were 10% of 2 g L-1 KH2PO4 + 5 g L-1 K2HPO4, 0.05% of Tween-80, citrate as carbon source and 32-48 h of culture time, both proteins and polysaccharides in B-EPS were significantly improved. This study gives an in-deep understanding on the flocculation characteristics of a novel bioflocculant from Pseudomonas sp. XD-3, which is conducive to the widespread application of bioflocculation.

Identification of major depression patients using machine learning models based on heart rate variability during sleep stages for pre-hospital screening.

With the COVID-19 pandemic causing challenges in hospital admissions globally, the role of home health monitoring in aiding the diagnosis of mental health disorders has become increasingly important. This paper proposes an interpretable machine learning solution to optimise initial screening for major depressive disorder (MDD) in both male and female patients. The data is from the Stanford Technical Analysis and Sleep Genome Study (STAGES). We analyzed 5-min short-term electrocardiogram (ECG) signals during nighttime sleep stages of 40 MDD patients and 40 healthy controls, with a 1:1 gender ratio. After preprocessing, we calculated the time-frequency parameters of heart rate variability (HRV) based on the ECG signals and used common machine learning algorithms for classification, along with feature importance analysis for global decision analysis. Ultimately, the Bayesian optimised extremely randomized trees classifier (BO-ERTC) showed the best performance on this dataset (accuracy 86.32%, specificity 86.49%, sensitivity 85.85%, F1-score 0.86). By using feature importance analysis on the cases confirmed by BO-ERTC, we found that gender is one of the most important factors affecting the prediction of the model, which should not be overlooked in our assisted diagnosis. This method can be embedded in portable ECG monitoring systems and is consistent with the literature results.

Food Insecurity Is Common in the Orthopedic Trauma Population at a Rural Academic Trauma Center.

Background: Food insecurity is an increasingly recognized public health issue. Identifying risk factors for food insecurity would support public health initiatives to provide targeted nutrition interventions to high-risk individuals. Food insecurity has not been investigated in the orthopedic trauma population. Methods: From April 27, 2021 to June 23, 2021, we surveyed patients within six months of operative pelvic and/or extremity fracture fixation at a single institution. Food insecurity was assessed using the validated United States Department of Agriculture Household Food Insecurity questionnaire generating a food security score of 0 to 10. Patients with a food security score ≥ 3 were classified as Food Insecure (FI) and patients with a food security score < 3 were classified as Food Secure (FS). Patients also completed surveys for demographic information and food consumption. Differences between FI and FS for continuous and categorical variables were evaluated using the Wilcoxon sum rank test and Fisher's exact test, respectively. Spearman's correlation was used to describe the relationship between food security score and participant characteristics. Logistic regression was used to determine the relationship between patient demographics and odds of FI. Results: We enrolled 158 patients (48% female) with a mean age of 45.5 ± 20.3 years. Twenty-one patients (13.3%) screened positive for food insecurity (High security: n=124, 78.5%; Marginal security: n=13, 8.2%; Low security: n=12, 7.6%; Very Low security: n=9, 5.7%). Those with a household income level of ≤ $15,000 were 5.7 times more likely to be FI (95% CI 1.8-18.1). Widowed/single/divorced patients were 10.2 times more likely to be FI (95% CI 2.3-45.6). Median time to the nearest full-service grocery store was significantly longer for FI patients (t=10 minutes) than for FS patients (t=7 minutes, p=0.0202). Age (r= -0.08, p=0.327) and hours working (r= -0.10, p=0.429) demonstrated weak to no correlation with food security score. Conclusion: Food insecurity is common in the orthopedic trauma population at our rural academic trauma center. Those with lower household income and those living alone are more likely to be FI. Multicenter studies are warranted to evaluate the incidence and risk factors for food insecurity in a more diverse trauma population and to better understand its impact on patient outcomes. Level of Evidence: III.

Characteristics and Long-Term Outcome of Surgically Managed High-Grade Extremity Chondrosarcoma.

Background: Dedifferentiated chondrosarcoma (DCS) is a highly malignant variant that portends a poor prognosis. Although factors such as clinico-pathological characteristics, surgical margin, and adjuvant modalities likely play a role in overall survival, debate continues with varying results on the importance of these indicators. The purpose of this study is (1) To delineate the characteristics, local recurrence (LR), and survival of patients with intermediate (IGCS), high (HGCS) and dedifferentiated (DCS) chondrosarcoma of the extremity by utilizing detailed cases at one tertiary institution. (2) To assess survival between high grade chondrosarcoma and DCS utilizing a less detailed but large cohort from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Twenty-six cases of high-grade (conventional FNCLCC grades 2 and 3, dedifferentiated) chondrosarcoma were identified from an ongoing prospective cohort of 630 sarcoma patients managed surgically at a tertiary referral university hospital between 9/1/2010-12/30/2019. A retrospective review of demographics, tumor characteristics, surgical procedure, treatment course, and survival data was performed to determine prognostic factors for survival. An additional 516 cases of chondrosarcoma were identified from the SEER database. Using the Kaplan-Meier method, both the large database and case series were evaluated, and estimated cause-specific survival was calculated at 1, 2, and 5 years. Results: There were 12 IGCS, 5 HGCS, and 9 DCS patients in the single institution cohort. DCS had a higher stage at diagnosis (p=0.04). Limb salvage was the most common procedure performed in every group (11/12 IGCS, 5/5 HGCS, and 7/9 DCS; p=0.56). Margins included 8/12 wide and 3/12 intralesional for IGCS. For HGCS, there were 3/5 wide, 1/5 marginal, and 1/5 intralesional. A majority of DCS margins were wide (8/9) with only 1 marginal. There was no difference of associated margins between the groups (p=0.85), however there was a difference when margins were classified based on numerical measurement (IGCS: 0.125cm (0.1-0.35); HGCS: 0cm (0-0.1); DCS: 0.2cm (0.1-0.5); p=0.03). The overall median follow-up was 26 months (IQR:16.1-70.8). The time interval from resection to death was lower in DCS (11.5 months (10.7-12.2)), followed by IGCS (30.3 months (16.2-78.2)), and HGCS (55.1 months (32.0-78.2; p=0.047). LR occurred in 5/9 DCS, 1/5 HGCS, and 1/14 IGCS patients. Of the DCS patients only 2/6 who received systemic therapy had LR, while all 3/3 who did not receive systemic therapy had LR. Overall systemic therapy and radiation did not impact incidence of LR (p=0.67; p=0.34). However, patients who had LR were 17.5 times more likely to die within one year (HR=17.5, 95%CI (1.01-303.7), p=0.049), after adjusting for the age at the surgery. There was no correlation with the utilization of systemic therapy, radiation therapy, or margin and overall survival (p=0.63, p=0.52, p=0.74). In the SEER patient cohort, 149 cases (28.9%) were DCS and 367 (71.1%) were HGCS. At final follow-up, 49.6% (n=256) of the cohort had a cause of death due to chondrosarcoma. HGCS was associated with higher chance of 1-year survial (p<0.001), 2-year survival (p<0.001), 5-year survival (p<0.001), and overall survival (p<0.001). Additionally, decreased survival was associated with metastatic disease at presentation (p=0.01). Overall limb salvage was most utilized for both HGCS (76.5%) and DCS (74.3%). In regard to limb salvage vs. amputation, there was no difference in survival at 1 year (p=0.10) or 2 year (p=0.13) between the groups, however those who underwent limb salvage procedure had a significantly better chance of survival at 5 years when compared to amputation (HR=1.49 (1.11-1.99); p=0.002). Conclusion: High-grade chondrosarcoma remains a fatal disease in many patients, particularly if associated with dedifferentiated subtype. Interestingly, all (100%) DCS patients who did not receive systemic therapy had LR. However, chemotherapy and radiation did not significantly increase survival. In this case series and large database study, HGCS had the smallest surgical margin, but with the longest time interval for both LR and death. Additionally, using the SEER database, DCS and amputation had worse prognosis at the 5-year survival time. Further studies on valuable prognostic influences as well as earlier identification of this rare disease may help in developing better management options. Level of Evidence: III.

CircRRAS2 promotes myogenic differentiation of bovine MuSCs and is a novel regulatory molecule of muscle development.

The proliferation and myogenic differentiation of muscle stem cells (MuSCs) are important factors affecting muscle development and beef quality. There is increasing evidence that circRNAs can regulate myogenesis. We found a novel circRNA, named circRRAS2 that is significantly upregulated in the differentiation phase of bovine MuSCs. Here, we aimed to determine its roles in the proliferation and myogenic differentiation of these cells. The results showed that circRRAS2 was expressed in several bovine tissues. CircRRAS2 inhibited MuSCs proliferation and promoted myoblast differentiation. In addition, chromatin isolation by using RNA purification and mass spectrometry in differentiated muscle cells identified 52 RNA-binding proteins that could potentially bind to circRRAS2, in order to regulate their differentiation. The results suggest that circRRAS2 could be a specific regulator of myogenesis in bovine muscle.HighlightsCircRRAS2 expression is higher in DM cells than in GM cells.CircRRAS2 could significantly inhibit the proliferation and apoptosis of bovine MuSCs.CircRRAS2 promotes the differentiation of bovine MuSCs into myotubes.CircRRAS2 may exert regulatory effects through multiple RNA binding proteins.

Insight into the effect of nitrate on AGS granulation: Granular characteristics, microbial community and metabolomics response.

As a promising wastewater treatment technology, aerobic granular sludge (AGS) process is still hindered by slow granule formation and easy disintegration in the application. While nitrate, one of the target pollutants in wastewater, showed a potential effect on AGS granulation process. Herein, this study attempted to reveal the role of nitrate in AGS granulation. By adding exogenous nitrate (10 mg L-1), the AGS formation was markedly improved and accomplished at 63 d, while the control group achieved AGS formation at 87 d. However, a disintegration was observed under a long-term nitrate feeding. A positive correlation was observed among granule size, extracellular polymeric substances (EPS) and intracellular c-di-GMP level in both formation and disintegration phases. The subsequent static biofilm assays indicated that nitrate might upregulate c-di-GMP via denitrification-derived NO, and c-di-GMP further upregulated EPS, thereby promoting AGS formation. However, excessive NO probably caused disintegration by downregulating c-di-GMP and EPS. Microbial community showed that nitrate favored the enrichment of denitrifiers and EPS producing microbes, which were responsible for the regulation of NO, c-di-GMP and EPS. Metabolomics analysis showed that amino acid metabolism was the most affected metabolism by nitrate. Some amino acids, such as Arg, His and Asp, were upregulated in the granule formation phase and downregulated in the disintegration phase, indicating the potential contribution to EPS biosynthesis. This study provides metabolic insight into how nitrate promotes/inhibits granulation, which may contribute to unwrapping the mystery of granulation and overcoming the limitations of AGS application.

Electrotaxis of alveolar epithelial cells in direct-current electric fields.

PURPOSE: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury. METHODS: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis. RESULTS: The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11. CONCLUSION: EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.

Redefining the Incidence and Profile of Fluoropyrimidine-Associated Cardiotoxicity in Cancer Patients: A Systematic Review and Meta-Analysis.

AIM: The cardiac toxicity that occurs during administration of anti-tumor agents has attracted increasing concern. Fluoropyrimidines have been used for more than half a century, but their cardiotoxicity has not been well clarified. In this study, we aimed to assess the incidence and profile of fluoropyrimidine-associated cardiotoxicity (FAC) comprehensively based on literature data. METHODS: A systematic literature search was performed using PubMed, Embase, Medline, Web of Science, and Cochrane library databases and clinical trials on studies investigating FAC. The main outcome was a pooled incidence of FAC, and the secondary outcome was specific treatment-related cardiac AEs. Random or fixed effects modeling was used for pooled meta-analyses according to the heterogeneity assessment. PROSPERO registration number: (CRD42021282155). RESULTS: A total of 211 studies involving 63,186 patients were included, covering 31 countries or regions in the world. The pooled incidence of FAC, by meta-analytic, was 5.04% for all grades and 1.5% for grade 3 or higher. A total of 0.29% of patients died due to severe cardiotoxicities. More than 38 cardiac AEs were identified, with cardiac ischemia (2.24%) and arrhythmia (1.85%) being the most frequent. We further performed the subgroup analyses and meta-regression to explore the source of heterogeneity, and compare the cardiotoxicity among different study-level characteristics, finding that the incidence of FAC varied significantly among different publication decades, country/regions, and genders. Patients with esophagus cancer had the highest risk of FAC (10.53%), while breast cancer patients had the lowest (3.66%). The treatment attribute, regimen, and dosage were significantly related to FAC. When compared with chemotherapeutic drugs or targeted agents, such a risk was remarkably increased (χ2 = 10.15, p < 0.01; χ2 = 10.77, p < 0.01). The continuous 5-FU infusion for 3-5 consecutive days with a high dosage produced the highest FAC incidence (7.3%) compared with other low-dose administration patterns. CONCLUSIONS: Our study provides comprehensive global data on the incidence and profile of FAC. Different cancer types and treatment appear to have varying cardiotoxicities. Combination therapy, high cumulative dose, addition of anthracyclines, and pre-existing heart disease potentially increase the risk of FAC.