Insight into the mechanism of chlorinated nitroaromatic compounds anaerobic reduction with mackinawite (FeS) nanoparticles.

Anaerobic biotechnology for wastewaters treatment can nowadays be considered as state of the art methods. Nonetheless, this technology exhibits certain inherent limitations when employed for industrial wastewater treatment, encompassing elevated substrate consumption, diminished electron transfer efficiency, and compromised system stability. To address the above issues, increasing interest is being given to the potential of using conductive non-biological materials, e,g., iron sulfide (FeS), as a readily accessible electron donor and electron shuttle in the biological decontamination process. In this study, Mackinawite nanoparticles (FeS NPs) were studied for their ability to serve as electron donors for p-chloronitrobenzene (p-CNB) anaerobic reduction within a coupled system. This coupled system achieved an impressive p-CNB removal efficiency of 78.3 ± 2.9% at a FeS NPs dosage of 1 mg/L, surpassing the efficiencies of 62.1 ± 1.5% of abiotic and 30.6 ± 1.6% of biotic control systems, respectively. Notably, the coupled system exhibited exclusive formation of aniline (AN), indicating the partial dechlorination of p-CNB. The improvements observed in the coupled system were attributed to the increased activity in the electron transport system (ETS), which enhanced the sludge conductivity and nitroaromatic reductases activity. The analysis of equivalent electron donors confirmed that the S2- ions dominated the anaerobic reduction of p-CNB in the coupled system. However, the anaerobic reduction of p-CNB would be adversely inhibited when the FeS NPs dosage exceeded 5 g/L. In a continuous operation, the p-CNB concentration and HRT were optimized as 125 mg/L and 40 h, respectively, resulting in an outstanding p-CNB removal efficiency exceeding 94.0% after 160 days. During the anaerobic reduction process, as contributed by the predominant bacterium of Thiobacillus with a 6.6% relative abundance, a mass of p-chloroaniline (p-CAN) and AN were generated. Additionally, Desulfomonile was emerged with abundances ranging from 0.3 to 0.7%, which was also beneficial for the reduction of p-CNB to AN. The long-term stable performance of the coupled system highlighted that anaerobic technology mediated by FeS NPs has a promising potential for the treatment of wastewater containing chlorinated nitroaromatic compounds, especially without the aid of organic co-substrates.

Butylparaben induced zebrafish (Danio rerio) kidney injury by down-regulating the PI3K-AKT pathway.

Butylparaben, a common endocrine disruptor in the environment, is known to be toxic to the reproductive system, heart, and intestines, but its nephrotoxicity has rarely been reported. In order to study the nephrotoxicity and mechanism of butylparaben, we examined the acute and chronic effects on human embryonic kidney cells (HEK293T) and zebrafish. Additionally, we assessed the potential remedial effects of salidroside against butylparaben-induced nephrotoxicity. Our in vitro findings demonstrated oxidative stress and cytotoxicity to HEK293T cells caused by butylparaben. In the zebrafish model, the concentration of butylparaben exposure ranged from 0.5 to 15 µM. An assortment of experimental techniques was employed, including the assessment of kidney tissue morphology using Hematoxylin-Eosin staining, kidney function analysis via fluorescent dextran injection, and gene expression studies related to kidney injury, development, and function. Additionally, butylparaben caused lipid peroxidation in the kidney, thereby damaging glomeruli and renal tubules, which resulted from the downregulation of the PI3K-AKT signaling pathway. Furthermore, salidroside ameliorated butylparaben-induced nephrotoxicity through the PI3K-AKT signaling pathway. This study reveals the seldom-reported kidney toxicity of butylparaben and the protective effect of salidroside against toxicological reactions related to nephrotoxicity. It offers valuable insights into the risks to kidney health posed by environmental toxins.

Adjuvant activity of cordycepin, a natural derivative of adenosine from Cordyceps militaris, on an inactivated rabies vaccine in an animal model.

Vaccination is the most feasible way of preventing rabies, an ancient zoonosis that remains a major public health concern globally. However, administration of inactivated rabies vaccination without adjuvants is always inefficient and necessitates four to five injections. In the current study, we explored the adjuvant characteristics of cordycepin, a major bioactive component of Cordyceps militaris, to boost immune responses against a commercially available rabies vaccine. We found that cordycepin could stimulate stronger phenotypic and functional maturation of dendritic cells (DCs). For animal experiments, mice were immunized 3 times with rabies vaccine in the presence or absence of cordycepin at 1-week interval. Analysis of T cell differentiation and serum antibody isotypes showed that humoral immunity was dominant with a Th2 biased immune response. These results were also supported by the raised ratio of follicular helper T cells (TFH) and germinal center B cells (GCB). Thus, titer of rabies virus neutralizing antibody (RVNAb) and rabies virus-specific memory B cells were both raised as a result. Furthermore, administration of cordycepin did not cause pathological phenomena or body weight loss. The findings indicate that cordycepin could be used as a promising adjuvant for rabies vaccines to get a higher range of protection without any side effects.

ETS2 overexpression ameliorates cartilage injury in osteoarthritis by the ETS2/miR-155/STAT1/DNMT1 feedback loop pathway.

Osteoarthritis (OA) is the most common irreversible chronic joint dysfunction disease, which is pathologically characterized by disturbance of articular cartilage homeostasis leading to subsequent inflammatory response and cartilage extracellular matrix (ECM) degradation. Increasing evidence has demonstrated the dysregulation of transcription factors play crucial roles in the occurrence and development of osteoarthritis (OA), but the potential functions and mechanism of most transcription factors in OA has not been completely illuminated. In this study, we identified that transcription factor V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) was significantly down-regulated in OA cartilage and IL-1ß-induced OA chondrocytes. Functional experiments in vitro demonstrated that the overexpressed ETS2 strikingly enhanced proliferation, outstandingly suppressed apoptosis, and dramatically reduced inflammation and ECM degradation in IL-1ß-induced OA chondrocytes, whereas the knockdown of ETS2 led to the opposite effects. Further in vivo studies have shown that up-regulated ETS2 dramatically ameliorates cartilage injury in DMM-induced OA mice. Mechanical studies have disclosed that DNMT1-mediated downregulation of ETS2 dramatically promotes STAT1 by inhibiting miR-155 transcription, and increased STAT1 initiates a feedback loop that may enhance DNMT1-mediated hypermethylation of ETS2 to inhibit ETS2 expression, thus forming a DNMT1/ETS2/miR-155/STAT1 feedback loop that inhibits MAPK signaling pathways and aggravates OA cartilage injury. In all, our results revealed that overexpression of ETS2 markedly ameliorated OA cartilage injury through the ETS2/miR-155/STAT1/DNMT1 feedback loop, providing a new perspective on the pathogenesis and therapeutic strategies for OA.

Design of multi-axis micromotion system in TERS and its nonlinearity and crosstalk correction method.

Tip-Enhanced Raman Spectroscopy (TERS) is an advanced analytical measurement technology combining Raman spectroscopy with Scanning Probe Microscopy, which can detect the molecular structure and chemical composition in micro-nano-scale. As an indispensable part, the micromotion system directly determines TERS spatial resolution. The existing multi-axis system is often composed of several single-axis nonlinear systems, which solves whole problems with a superposition idea of single-axis part. But the multi-axis crosstalk under an overall idea is not fully considered and will cause system uncooperative and even oscillational. Therefore, a multi-axis micromotion system in TERS and its correction method are proposed. The improved Duhem model, simple calculation without inversion, accurate matching and fast response, has been built for nonlinearity. And the feedforward decoupling method is designed for crosstalk, having a favorable multi-axis coordination, good error tracking and simplified controllers. Experimental results show that it can greatly correct the nonlinearity and crosstalk of multi-axis system simultaneously.

Advances in the Biological Functions and Mechanisms of miRNAs in the Development of Osteosarcoma.

Osteosarcoma is one of the most common primary malignant bone tumors, mainly occurring in children and adolescents, and is characterized by high morbidity and poor prognosis. MicroRNAs, a class of noncoding RNAs consisting of 19 to 25 nucleotides, are involved in cell proliferation, invasion, metastasis, and apoptosis to regulate the development and progression of osteosarcoma. Studies have found that microRNAs are closely related to the diagnosis, treatment, and prognosis of osteosarcoma patients and have an important role in improving drug resistance in osteosarcoma. This paper reviews the role of microRNAs in the pathogenesis of osteosarcoma and their clinical value, aiming to provide a new research direction for diagnosing and treating osteosarcoma and achieving a better prognosis.

Ratiometric intracellular pH sensors based on nitrogen-doped graphene oxide quantum dots.

Intracellular pH (pHi) is very essential for the function of cells and organisms. Thus, it is of great scientific and technical significance to develop nanosensors for probing pHi. In this work, nitrogen-doped graphene oxide quantum dots (N-GOQDs) with fluorescent efficiency of 54% are prepared. The fluorescent spectrum excited at 340 nm contains two remarkable bands at 430 and 520 nm. Interestingly, when pH value increases from 3.6 to 10.5, the blue band at 430 nm slightly changes, while the green band at 520 nm significantly quenches. The change of fluorescent intensities also can be reflected by the variation of fluorescent color. The dual-emissive N-GOQDs are developed as ratiometric fluorescent probes for pHi, which can avoid the influence of several deviations, such as probe concentration, optical path length, and detector efficiency. As a proof of concept, pHi of Hela cells is monitored successfully. This work demonstrates the construction of nano-biosensors based on N-GOQDs with bright fluorescence, high-stability, and good biocompatibility.

Novel Immunotherapies for Osteosarcoma.

Osteosarcoma (OS) is the most common primary malignant bone sarcoma mainly affecting adolescents and young adults, which often progresses to pulmonary metastasis and leads to the death of OS patients. OS is characterized as a highly heterogeneous cancer type and the underlying pathologic mechanisms triggering tumor progress and metastasis are incompletely recognized. Surgery combined with neoadjuvant and postoperative chemotherapy has elevated 5-year survival to over 70% for patients with localized OS tumors, as opposed to only 20% of patients with recurrence and/or metastasis. Therefore, novel therapeutic strategies are needed to overcome the drawbacks of conventional treatments. Immunotherapy is gaining momentum for the treatment of OS with an increasing number of FDA-approved therapies for malignancies resistant to conventional therapies. Here, we review the OS tumor microenvironment and appraise the promising immunotherapies available in the management of OS.

Bone remodeling following mandibular reconstruction using fibula free flap.

To investigate bone remodelling responses to mandibulectomy, a joint external and internal remodelling algorithm is developed here by incorporating patient-specific longitudinal data. The primary aim of this study is to simulate bone remodelling activity in the conjunction region with a fibula free flap (FFF) reconstruction by correlating with a 28-month clinical follow-up. The secondary goal of this study is to compare the long-term outcomes of different designs of fixation plate with specific screw positioning. The results indicated that the overall bone density decreased over time, except for the Docking Site (namely DS1, a region of interest in mandibular symphysis with the conjunction of the bone union), in which the decrease of bone density ceased later and was followed by bone apposition. A negligible influence on bone remodeling outcome was found for different screw positioning. This study is believed to be the first of its kind for computationally simulating the bone turn-over process after FFF maxillofacial reconstruction by correlating with patient-specific follow-up.

Epigenetic Inactivation of Acetyl-CoA Acetyltransferase 1 Promotes the Proliferation and Metastasis in Nasopharyngeal Carcinoma by Blocking Ketogenesis.

The dysregulation of epigenetic modification and energy metabolism cooperatively contribute to the tumorigenesis of nasopharyngeal carcinoma (NPC). However, the detailed mechanisms underlying their joint contribution to NPC development and progression remain unclear. Here, we investigate the role of Acy1 Coenzyme A Acyltransferases1 (ACAT1), a key enzyme in the metabolic pathway of ketone bodies, in the proliferation and metastasis of NPC and to elucidate the underlying molecular mechanisms. Ketogenesis, plays a critical role in tumorigenesis. Previously, we reported two enzymes involved in ketone body metabolism mediate epigenetic silencing and act as tumor suppressor genes in NPC. Here, we identify another key enzyme, Acetyl-CoA acetyltransferase 1 (ACAT1), and show that its transcriptional inactivation in NPC is due to promoter hypermethylation. Ectopic overexpression of ACAT1 significantly suppressed the proliferation and colony formation of NPC cells in vitro. The migratory and invasive capacity of NPC cells was inhibited by ACAT1. The tumorigenesis of NPC cells overexpressing ACAT1 was decreased in vivo. Elevated ACAT1 in NPC cells was accompanied by an elevated expression of CDH1 and a reduced expression of vimentin and SPARC, strongly indicating that ACAT1 is involved in regulating epithelial-mesenchymal transition (EMT). We also found that ACAT1 contributes to increased intracellular levels of ß-hydroxybutyrate (ß-HB). Exogenously supplied ß-HB significantly inhibits the growth of NPC cells in a dose-dependent manner. In summary, ACAT1 may function as a tumor suppressor via modulation of ketogenesis and could thus serve as a potential therapeutic target in NPC. In summary, our data suggest that regulation of ketogenesis may serve as adjuvant therapy in NPC.

Organic Nanobowls Modified Thin Film Composite Membrane for Enhanced Purification Performance toward Different Water Resources.

The structure and composition of nanofillers have a significant influence on polyamide nanofiltration (NF) membranes. In this work, an asymmetric organic nanobowl containing a concave cavity was synthesized and incorporated into a polyamide layer to prepare thin film nanocomposite (TFN) membranes via an interfacial polymerization process. Benefiting from the hydrophilicity, hollow cavity and charge property of the compatible organic nanobowls, the separation performance of the developed TFN membrane was significantly improved. The corresponding water fluxes increased to 119.44 ± 5.56, 141.82 ± 3.24 and 130.27 ± 2.05 L/(m2·h) toward Na2SO4, MgCl2 and NaCl solutions, respectively, with higher rejections, compared with the control thin film composite (TFC) and commercial (CM) membranes. Besides this, the modified TFN membrane presented a satisfying purification performance toward tap water, municipal effluent and heavy metal wastewater. More importantly, a better antifouling property of the TFN membrane than TFC and CM membranes was achieved with the assistance of organic nanobowls. These results indicate that the separation performance of the TFN membrane can be elevated by the incorporation of organic nanobowls.

Sequential Ultrafiltration-Catalysis Membrane for Excellent Removal of Multiple Pollutants in Water.

Clean water production calls for highly efficient and less energy-intensive technologies. Herein, a novel concept of a sequential ultrafiltration-catalysis membrane is developed by loading Co3O4/C@SiO2 yolk-shell nanoreactors into the fingerlike channels of a polymeric ultrafiltration membrane. Such a sequenced structure design successfully integrates selective separation with peroxymonosulfate-based catalysis to prepare a functionalized molecular sieve membrane, which exhibits excellent decontamination performance toward multipollutants by filtering the water matrices containing humic acid (HA) and bisphenol A (BPA). In this study, 100% rejection of HA and 95% catalytic degradation of BPA were achieved under a low pressure of 0.14 MPa and an ultrahigh flux of 229 L m-2 h-1, corresponding to a retention time of 3.1 s. Notably, the removal performance of multiple pollutants essentially depends on the ordered arrangement of ultrafiltration and catalysis. Moreover, the flow-through process demonstrated significant enhancement of BPA degradation kinetics, which is 21.9 times higher than that of a conventional batch reactor. This study provides a novel strategy for excellent removal of multiple pollutants in water.

Enhancing nanofiltration performance by incorporating tannic acid modified metal-organic frameworks into thin-film nanocomposite membrane.

Nanofiltration (NF) is an advanced environmental technology in water treatment. To thin film nanocomposite (TFN) membrane, good compatibility between nanofillers and polyamide (PA) layer is the guarantee of remarkable performance. Herein, tannic acid (TA) was employed as modifier of UIO-66-NH2 prior to the interfacial polymerization (IP). With TA modification, more interaction can be formed so that the compatibility between nanofillers and PA layer can be promoted at the molecular level. Characterizations demonstrated the coating of TA on UIO-66-NH2, together with successful introducing of nanofillers in TFN membranes. Compared to pristine thin film composite (TFC) membrane, both UIO-incorporated TFN (TFN-U) and TA modified UIO-incorporated TFN (TFN-TU) membranes showed higher permeance (111.2% and 93% enhancement, respectively). However, under the same nanofillers dose, TFN-TU exhibited slightly lower permeance and higher rejection than TFN-U since the bridging effect of TA healed non-selective voids in skin layer. With the increasing of nanofiller dose in IP, TFN-TU remained reasonable selectivity while TFN-U failed to. Moreover, TFN-TU showed better anti-fouling property due to TA modification. Introducing TA modified MOFs into IP can serve as an ingenious strategy for TFN membrane to achieve high-quality environmental applications.

Defect-engineered UiO-66-NH2 modified thin film nanocomposite membrane with enhanced nanofiltration performance.

Defect-engineered UiO-66-NH2 was introduced into a polyamide layer to form a thin film nanocomposite (TFN) membrane. Simultaneous enhancements in permeance and selectivity to Na2SO4 solution were achieved.

Low pressure operated ultrafiltration membrane with integration of hollow mesoporous carbon nanospheres for effective removal of micropollutants.

An effective way to remove micropollutants is desirable for water purification. In this work, a dual-functional ultrafiltration (DFUF) membrane was fabricated by loading hollow mesoporous carbon nanospheres (HMCNs) into the finger-like support layer pores of the polymeric ultrafiltration (UF) membrane. The designed DFUF membrane combines the high selectivity of ultrafiltration that removes macromolecules based on size exclusion mechanism, and excellent adsorption capacity of HMCNs towards micropollutants in water. When tetracycline (TCN) and 17ß-Estradiol (E2) were selected as model micropollutants, corresponding 97 % and 94 % removal were achieved at a low pressure less than 0.15 bar and a flux of 50 and 64 L h-1 m-2 (estimated residence time less than 6 s), respectively. Moreover, simultaneous removal of multiple pollutants was demonstrated by filtering a mixture containing TCN and polyethylene glycols (PEG) 600 kDa macromolecules. Over a long filtration period (more than 60 h) that produced 3180 L/m2 of permeate, the TCN concentration reduced from 100 µg/L in the feed to less than 10 µg/L in the permeate. The above results indicate that the DFUF membrane is capable of removing the small molecular and macromolecular pollutants simultaneously at low pressure, and hence offers remarkable potential in water treatment applications.

Selective MMP-13 Inhibitors: Promising Agents for the Therapy of Osteoarthritis.

Osteoarthritis (OA) is an age-related degenerative disease, which is characterized by chronic joint pain, inflammation and the damage of joint cartilage. At present, steroidal drugs and nonsteroidal anti-inflammatory drugs (NSAIDS), selective cyclooxygenase-2 (COX-2) inhibitors, are the first-line drugs for the treatment of OA. However, these drugs could lead to some cardiovascular side effects. Therefore, it is urgent to develop novel agents for the treatment of OA. Matrix metalloproteinase-13 (MMP-13), an important member of matrix metalloproteinases (MMPs) family, plays a vital role by degrading type II collagen in articular cartilage and bone in OA. It is noted that MMP-13 is specially expressed in the OA patients, and not in normal adults. In addition, broadspectrum MMP inhibitors could result in some painful and joint-stiffening side effects, called musculoskeletal syndrome (MSS) in the clinical trials. Thus, developing selective MMP-13 inhibitors is a potential strategy for the therapy of OA. In this review, we summarize the recent progress of selective MMP-13 inhibitors including two subfamilies, namely zinc-binding and non-zinc-binding selective MMP-13 inhibitors.

Effects of buccal thickness augmentation on bone remodeling after maxillary anterior implantation.

The biomechanics associated with buccal bone thickness (BBT) augmentation remains poorly understood, as there is no consistent agreement in the adequate BBT to avoid over-loading resorption or over-augmenting surgical difficulty. This study utilizes longitudinal clinical image data to establish a self-validating time-dependent finite element (FE)-based remodeling procedure to explore the effects of different buccal bone thicknesses on long-term bone remodeling outcomes in silico. Based upon the clinical computed tomography (CT) scans, a patient-specific heterogeneous FE model was constructed to enable virtual BBT augmentation at four different levels (0.5, 1.0, 1.5, and 2.0 mm), followed by investigation into the bone remodeling behavior of the different case scenarios. The findings indicated that although peri-implant bone resorption decreased with increasing initial BBT from 0.5 to 2 mm, different levels of the reduction in bone loss were associated with the amount of bone augmentation. In the case of 0.5 mm BBT, overloading resorption was triggered during the first 18 months, but such bone resorption was delayed when the BBT increased to 1.5 mm. It was found that when the BBT reached a threshold thickness of 1.5 mm, the bone volume can be better preserved. This finding agrees with the consensus in dental clinic, in which 1.5 mm BBT is considered clinically justifiable for surgical requirement of bone graft. In conclusion, this study introduced a self-validating bone remodeling algorithm in silico, and it divulged that the initial BBT affects the bone remodeling outcome significantly, and a sufficient initial BBT is considered essential to assure long-term stability and success of implant treatment.

Knockdown Rab11-FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling.

Rab11 family interacting protein 2 (Rab11-FIP2) is a conserved protein and effector molecule for the small GTPase Rab11. By interacting with Rab11 and MYO5B, Rab11-FIP2 regulates endosome trafficking of plasma membrane proteins, promoting cellular motility. The endosomal trafficking system in nasopharyngeal carcinoma (NPC) remains unclear. Here, an outlier analysis using the Oncomine database suggested that Rab11-FIP2 but not Rab11 and MYO5B was overexpressed in NPC. We confirmed that the transcription of Rab11-FIP2 was upregulated in NPC cell lines and primary tumor tissues as compared with a normal nasopharyngeal epithelial cell line and normal nasopharynx tissues. We further confirmed the elevated protein expression level of Rab11-FIP2 in NPC biopsies. Instead of regulating the epithelial-mesenchymal transition or Akt signaling pathway, knockdown of Rab11-FIP2 inhibited the migration and invasion ability of NPC cell lines by decreasing the expression of Rac and Cdc42. In summary, Rab11-FIP2 could be an oncogene in NPC, mainly contributing to metastatic capacity by activating Rho GTPase signaling.

Inactivation of 3-hydroxybutyrate dehydrogenase type 2 promotes proliferation and metastasis of nasopharyngeal carcinoma by iron retention.

BACKGROUND: 3-Hydroxybutyrate dehydrogenase type 2 (BDH2) is known to catalyse a rate-limiting step in the biogenesis of the mammalian siderophore and regulate intracellular iron metabolism. Here we aim to explore the expression and possible function of BDH2 in nasopharyngeal carcinoma (NPC). METHODS: The transcription and protein expression of BDH2 in NPC were determined by both real-time RT-PCR and immunohistochemistry staining assays. Cell proliferation, migration and invasion were evaluated by MTT assay, wound-healing assay and Transwell assay, respectively. The profile of genes regulated by restoring BDH2 expression in NPC cells was analysed by cDNA microarray. The level of iron in NPC cells was detected by iron colorimetric assay. RESULTS: The expression of BDH2 was significantly downregulated in NPC. Ectopic expression of BDH2 inhibited NPC cell proliferation and colony formation. Meanwhile, BDH2 suppressed the migration and invasion of NPC cells by reversing the epithelial-mesenchymal transition (EMT). In addition, a higher level of BDH2 decreased the growth and metastasis of NPC cells via reducing intracellular iron level. CONCLUSIONS: Our findings suggest that BDH2 may be a candidate tumour-suppressor gene in NPC. Decreasing intracellular iron could be an effective therapeutic approach for NPC.

A new xanthene-based fluorescent probe with a red light emission for selectively detecting glutathione and imaging in living cells.

Glutathione (GSH) is the most abundant low-molecular-weight cysteine-containing thiol in cells, which plays an essential role in many biological processes. Most reported fluorescent probes towards GSH possess short excitation and emission wavelength, which could result in low tissue penetration, high background fluorescence and photodamage to biological samples. Herein, a novel turn-on fluorescent probe (ADS) with the xanthene skeleton for GSH detection was developed based on a fluorophore, ACF-NH2. The probe had a red light emission (λem = 630 nm) and exhibited a good linear relationship for exogenous GSH (1-6 mM) and a good limit of detection (LOD: 13.1 µM, based on S/N = 3), which implied that it was possible to detect the change of GSH in the living cells (0.5-10 mM) by further structural modification. The probe displayed excellent selectivity for GSH over other analytes and good anti-interference ability. Moreover, cell viability assay indicated that ADS was biocompatible and exhibited very low cytotoxicity. A combination of mass spectrum analysis and density functional theory calculation was performed to explain the sensing mechanism of the probe. In addition, it was applied to image GSH in living cells successfully.