Small non-coding RNAome changes during human chondrocyte senescence as potential epigenetic targets in age-related osteoarthritis.

Chondrocyte senescence is a decisive component of age-related osteoarthritis, however, the function of small noncoding RNAs (sncRNAs) in chondrocyte senescence remains underexplored. Human hip joint cartilage chondrocytes were cultivated up to passage 4 to induce senescence. RNA samples were extracted and then analyzed using small RNA sequencing and qPCR. ß-galactosidase staining was used to detect the effect of sncRNA on chondrocyte aging. Results of small RNA sequencing showed that 279 miRNAs, 136 snoRNAs, 30 snRNAs, 102 piRNAs, and 5 rasiRNAs were differentially expressed in senescent chondrocytes. The differential expression of 150 sncRNAs was further validated by qPCR. Transfection of sncRNAs and ß-galactosidase staining were also performed to further revealed that hsa-miR-135b-5p, SNORA80B-201, and RNU5E-1-201 have the function to restrain chondrocyte senescence, while has-piR-019102 has the function to promote chondrocyte senescence. Our data suggest that sncRNAs have therapeutic potential as novel epigenetic targets in age-related osteoarthritis.

Label-Free Proteomic Analysis of Exosomes Secreted from THP-1-Derived Macrophages Treated with IFN-α Identifies Antiviral Proteins Enriched in Exosomes.

Exosomes are extracellular vesicles that function in intercellular communication. We have previously reported that exosomes play an important role in the transmission of antiviral molecules during interferon-α (IFN-α) treatment. In this study, the protein profiles of THP-1-derived macrophages with or without interferon-α treatment and the exosomes secreted from these cells were analyzed by label-free liquid chromatography-tandem mass spectrometry quantitation technologies. A total of 1845 and 1550 protein groups were identified in the THP-1 macrophages and the corresponding exosomes, respectively. Treating the cells with IFN-α resulted in the differential abundance of 94 proteins in cells and 67 proteins in exosomes (greater than 2.0-fold), among which 23 proteins were up-regulated in both the IFN-α treated cells and corresponding exosomes, while 14 proteins were specifically up-regulated in exosomes but not in the donor cells. GO and KEGG analysis of the identified proteins suggested that IFN-α promoted the abundance of proteins involved in the "defense response to virus" and "type I interferon signaling pathway" in both exosomes and cells. Functional analysis further indicated that exosomes from IFN-α-treated cells exhibited potent antiviral activity that restored the impaired antiviral response of IFN-α in hepatitis B virus-replicating hepatocytes. These results have deepened the understanding of the exosome-mediated transfer of IFN-α-induced antiviral molecules and may provide a new basis for therapeutic strategies to control viral infection.

MicroRNA-215 suppresses cell proliferation, migration and invasion of colon cancer by repressing Yin-Yang 1.

Colorectal cancer is one of the most common malignant tumors worldwide with rising incidence. MicroRNAs are small non-coding RNAs that implicate in multiple physiological or pathological processes. The aberrant expression of miRNA-215 (miR-215) has been illustrated in various types of cancers. However, the expression of miR-215 in human colon cancer and the biological roles of it remain largely unknown. We conducted this study to explore the expression and the function of miR-215 in human colon cancer. The results showed that miR-215 was remarkably downregulated in colon cancer tissues and cell lines. Overexpression of miR-215 by miR-215 mimic significantly inhibited colon cancer cell proliferation, migration and invasion while knockdown of miR-215 by miR-215 inhibitor exerted reverse effects. Furthermore, we newly identified Yin-Yang 1(YY1) as a direct target of miR-215 which could rescue the effects of miR-215 on colon cancer cells. In summary, our investigation revealed that miR-215 was downregulated in colon cancer and it suppressed colon cancer cell proliferation, migration and invasion by directly targeting YY1.

Clinical significance of serum lactate dehydrogenase combined with a multivariate model for predicting the near-term outcome of primary nasopharyngeal carcinoma.

BACKGROUND AND OBJECTIVES: This investigation explores the clinical significance of integrating serum lactate dehydrogenase (LDH) with a multivariate model for assessing the short-term prognosis of primary nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) quantification is a crucial prognostic indicator in NPC cases, but not all patients with NPC test positive for EBV. Furthermore, widespread adoption of EBV-DNA quantification remains challenging due to its high cost. Consequently, it is imperative to incorporate additional convenient and cost-effective prognostic markers to comprehensively evaluate patient outcomes. METHODS: This retrospective analysis included 203 newly diagnosed NPC cases treated at the Affiliated Qingyuan Hospital of Guangzhou Medical University between January 2018 and March 2022. The dataset included personal information and clinical data, and the treatment protocols followed the CSCO guidelines. Efficacy assessments were based on the RECIST 1.1 criteria and were conducted after induction chemotherapy and one week and three months after radiotherapy. RESULTS: A noteworthy correlation emerged between baseline serum LDH levels and treatment efficacy at one week after radiotherapy (P = 0.03) and at three months after radiotherapy (P < 0.01). Additionally, a prognostic model that incorporates age (P = 0.010), LDH (P < 0.001), C-reactive protein (P = 0.010), and alkaline phosphatase (P = 0.005) demonstrated robust predictive accuracy and clinical applicability. CONCLUSION: This investigation substantiates the significant correlation between baseline serum LDH levels and NPC outcomes. Furthermore, we introduce a refined prognostic model that holds promise for informing personalized treatment strategies, thereby contributing to the advancement of the diagnosis of NPC.

Lactate transported by MCT1 plays an active role in promoting mitochondrial biogenesis and enhancing TCA flux in skeletal muscle.

Once considered as a "metabolic waste," lactate is now recognized as a major fuel for tricarboxylic acid (TCA) cycle. Our metabolic flux analysis reveals that skeletal muscle mainly uses lactate to fuel TCA cycle. Lactate is transported through the cell membrane via monocarboxylate transporters (MCTs) in which MCT1 is highly expressed in the muscle. We analyzed how MCT1 affects muscle functions using mice with specific deletion of MCT1 in skeletal muscle. MCT1 deletion enhances running performance, increases oxidative fibers while decreasing glycolytic fibers, and enhances flux of glucose to TCA cycle. MCT1 deficiency increases the expression of mitochondrial proteins, augments cell respiration rate, and elevates mitochondrial activity in the muscle. Mechanistically, the protein level of PGC-1α, a master regulator of mitochondrial biogenesis, is elevated upon loss of MCT1 via increases in cellular NAD+ level and SIRT1 activity. Collectively, these results demonstrate that MCT1-mediated lactate shuttle plays a key role in regulating muscle functions by modulating mitochondrial biogenesis and TCA flux.

Effects of the Taste Substances and Metal Cations in Green Tea Infusion on the Turbidity of EGCG-Mucin Mixtures.

Astringency has an important impact on the taste quality of tea infusion, a process which occurs when polyphenols complex with salivary proteins to form an impermeable membrane. (-)-Epigallocatechin gallate (EGCG) is the main astringent compound found in green tea and mucin is the main protein present in saliva. Determining the turbidity of EGCG-mucin mixtures is an effective method to quantify the astringency intensity of EGCG solutions. In this study, the effects of taste-related, substances present during green tea infusion, on the turbidity of EGCG-mucin mixtures was investigated under the reacting conditions of a pH value of 5.0, at 37 °C, and for 30 min. The results showed that epicatechins, caffeic acid, chlorogenic acid, and gallic acid reduced the turbidity of EGCG-mucin mixtures, while rutin increased turbidity. Metal ions increased the turbidity of EGCG-mucin mixtures. These can be arranged by effectiveness as Al3+ > K+ > Mg2+ > Ca2+. Caffeine, theanine, and sodium glutamate all decreased the turbidity values of EGCG-mucin mixtures, but sucrose had a weak effect. Further experiments confirmed that the turbidity of green tea infusion-mucin mixture indicated the astringent intensity of green tea infusion, and that the turbidity was significantly correlated with the contents of tea polyphenols and EGCG.

Insights into the Correlation between Microbial Community Succession and Pericarp Degradation during Pepper (Piper nigrum L.) Peeling Process via Retting.

White pepper, used both as a seasoning in people's daily diets and as a medicinal herb, is typically produced by removing the pericarp of green pepper through the retting process. However, the mechanism of the retting process for peeling remains unclear. Therefore, this study aimed to investigate the changes in physicochemical factors, microbial community succession effects, and metabolites of the pepper pericarp during the pepper peeling process. The findings indicated that pre-treatment involving physical friction before the retting process effectively reduced the production time of white pepper. During the retting process, the pectinase activity increased, leading to a decrease in the pectin content in the pepper pericarp. There was a significant correlation observed between the changes in pH, pectin content, and peeling rate and the Shannon diversity index of bacteria and fungi. Prevotella, Lactococcus, and Candida were the dominant microbial genera during the retting. The functional predictions suggested that the monosaccharides degraded from the pepper pericarp could have been utilized by microbes through sugar metabolism pathways. Metabolomic analysis showed that the metabolic pathways of carbohydrates and amino acids were the main pathways altered during the pepper peeling process. The verification experiment demonstrated that the degradation of pectin into galacturonic acid by polygalacturonase was identified as the key enzyme in shortening the pepper peeling time. The structure of the pepper pericarp collapsed after losing the support of pectin, as revealed by scanning electron microscopy. These results suggest that the decomposition of the pepper pericarp was driven by key microbiota. The succession of microbial communities was influenced by the metabolites of the pepper pericarp during retting. These findings provide new insights into the retting process and serve as an important reference for the industrial production of white pepper.

Advances in the study of aerobic glycolytic effects in resistance to radiotherapy in malignant tumors.

Aerobic glycolysis is a metabolic mode of tumor cells different from normal cells that plays an important role in tumor proliferation and distant metastasis. Radiotherapy has now become a routine and effective treatment for many malignancies, however, resistance to radiotherapy remains a major challenge in the treatment of malignant tumors. Recent studies have found that the abnormal activity of the aerobic glycolysis process in tumor cells is most likely involved in regulating chemoresistance and radiation therapy resistance in malignant tumors. However, research on the functions and mechanisms of aerobic glycolysis in the molecular mechanisms of resistance to radiotherapy in malignant tumors is still in its early stages. This review collects recent studies on the effects of aerobic glycolysis and radiation therapy resistance in malignant tumors, to further understand the progress in this area. This research may more effectively guide the clinical development of more powerful treatment plans for radiation therapy resistant subtypes of cancer patients, and take an important step to improve the disease control rate of radiation therapy resistant subtypes of cancer patients.

A Preliminary Experimental Study of Polydimethylsiloxane (PDMS)-To-PDMS Bonding Using Oxygen Plasma Treatment Incorporating Isopropyl Alcohol.

Polydimethylsiloxane (PDMS) is a widely used material for soft lithography and microfabrication. PDMS exhibits some promising properties suitable for building microfluidic devices; however, bonding PDMS to PDMS and PDMS to other materials for multilayer structures in microfluidic devices is still challenging due to the hydrophobic nature of the surface of PDMS. This paper presents a simple yet effective method to increase the bonding strength for PDMS-to-PDMS using isopropyl alcohol (IPA). The experiment was carried out to evaluate the bonding strength for both the natural-cured and the heat-cured PDMS layer. The results show the effectiveness of our approach in terms of the improved irreversible bonding strength, up to 3.060 MPa, for the natural-cured PDMS and 1.373 MPa for the heat-cured PDMS, while the best bonding strength with the existing method in literature is 1.9 MPa. The work is preliminary because the underlying mechanism is only speculative and open for future research.

Peptide-Appended Nanosonosensitizers Targeting Tumor Glycolysis for Synergistic Sonodynamic-Immunometabolic Therapy of Spinal-Metastasized Tumors.

Despite recent advancements in cancer immunotherapy, challenges have yet to be surmounted to achieve two major goals of magnifying antitumor immunity and remodeling the immunosuppressive tumor microenvironment. Here, a nanosystem (ODM-R) that integrates oxygen-deficient molybdenum oxide (ODM) nanosonosensitizers and R7 peptides with tumor metabolism regulation effects is designed and fabricated for synergistic sonodynamic-immunometabolic therapy of spinal-metastasized tumors. The ODM generates reactive oxygen species upon ultrasound irradiation to implement sonodynamic therapy (SDT), inducing cancer cell apoptosis and immunogenic cell death. The R7 attached on ODM markedly inhibits the uptake of glucose and excretion of lactic acid in cancer cells by perturbing the glycolysis process. The combination of SDT and tumor glycolysis obstruction by ODM-R guarantees satisfactory efficacy in synergizing with PD-L1 antibody to eradicate spinal-metastasized tumors, achieving concurrent sonodynamic-triggered immune activation and immunosuppressive tumor microenvironment remodeling. This work provides a proof-of-concept of nanosonosensitizers for boosting cancer immunotherapy by SDT and tumor metabolic regulation.

Multifunctional Janus Nanoplatform for Efficiently Synergistic Theranostics of Rheumatoid Arthritis.

Progress has been made in the application of nanomedicine in rheumatoid arthritis (RA) treatment. However, the whole process of monitoring and treatment of RA remains a formidable challenge due to the complexity of the chronic autoimmune disease. In this study, we develop a Janus nanoplatform (denoted as Janus-CPS) composed of CeO2-Pt nanozyme subunit on one side and periodic mesoporous organosilica (PMO) subunit on another side for simultaneous early diagnosis and synergistic therapy of RA. The Janus nanostructure, which enables more active sites to be exposed, enhances the reactive oxygen species scavenging capability of CeO2-Pt nanozyme subunit as compared to their core-shell counterpart. Furthermore, micheliolide (MCL), an extracted compound from natural plants with anti-osteoclastogenesis effects, is loaded into the mesopores of PMO subunit to synergize with the anti-inflammation effect of nanozymes for efficient RA treatment, which has been demonstrated by in vitro cellular experiments and in vivo collagen-induced arthritis (CIA) model. In addition, by taking advantage of the second near-infrared window (NIR-II) fluorescent imaging, indocyanine green (ICG)-loaded Janus-CPS exhibits desirable effectiveness in detecting RA lesions at a very early stage. It is anticipated that such a Janus nanoplatform may offer an alternative strategy of functional integration for versatile theranostics.

The Additive Manufacturing Approach to Polydimethylsiloxane (PDMS) Microfluidic Devices: Review and Future Directions.

This paper presents a comprehensive review of the literature for fabricating PDMS microfluidic devices by employing additive manufacturing (AM) processes. AM processes for PDMS microfluidic devices are first classified into (i) the direct printing approach and (ii) the indirect printing approach. The scope of the review covers both approaches, though the focus is on the printed mold approach, which is a kind of the so-called replica mold approach or soft lithography approach. This approach is, in essence, casting PDMS materials with the mold which is printed. The paper also includes our on-going effort on the printed mold approach. The main contribution of this paper is the identification of knowledge gaps and elaboration of future work toward closing the knowledge gaps in fabrication of PDMS microfluidic devices. The second contribution is the development of a novel classification of AM processes from design thinking. There is also a contribution in clarifying confusion in the literature regarding the soft lithography technique; this classification has provided a consistent ontology in the sub-field of the fabrication of microfluidic devices involving AM processes.

Characterization of avian influenza A (H4N2) viruses isolated from wild birds in Shanghai during 2019 to 2021.

The H4 subtype of avian influenza viruses has been widely distributed among wild birds. During the surveillance of the avian influenza virus in Shanghai from 2019 to 2021, a total of 4,451 samples were collected from wild birds, among which 46 H4 subtypes of avian influenza viruses were identified, accounting for 7.40% of the total positive samples. The H4 subtype viruses have a wide range of hosts, including the spot-billed duck, common teal, and other wild birds in Anseriformes. Among all H4 subtypes, the most abundant are the H4N2 viruses. To clarify the genetic characteristics of H4N2 viruses, the whole genome sequences of 20 H4N2 viruses were analyzed. Phylogenetical analysis showed that all 8 genes of these viruses belonged to the Eurasian lineage and closely clustered with low pathogenic avian influenza viruses from countries along the East Asia-Australia migratory route. However, the PB1 gene of 1 H4N2 virus (NH21920) might provide its internal gene for highly pathogenic avian influenza H5N8 viruses in Korea and Japan. At least 10 genotypes were identified in these viruses, indicating that they underwent multiple complex recombination events. Our study has provided a better epidemiological understanding of the H4N2 viruses in wild birds. Considering the mutational potential, comprehensive surveillance of the H4N2 virus in both poultry and wild birds is imperative.

Metal recovery and heavy metal migration characteristics of ferritic stainless steel pickling sludge reduced by municipal sludge.

A new method for recovering metals from ferritic stainless steel pickling sludge using municipal sludge as a reducing agent is proposed. The effects of temperature, municipal sludge blending ratio, and reaction atmosphere on the recovery characteristics were studied. The migration characteristics of heavy metals (HMs) at different temperatures were also investigated. The results showed that municipal sludge can be used as a reducing agent for metal recovery from pickling sludge. Under optimized conditions (temperature of 650 °C and blending ratio of 5%), the recovery fractions of Fe, Cr, and Ni were 70.1, 53.7, and 60.3%, respectively. The CO2 atmosphere was beneficial for increasing the recovery fraction of the pickling sludge. The migration fractions of Cr, Mn, and Ni were approximately 10%. The migration fractions of Zn, Cu, and Pb, which are semi-volatile HMs, varied significantly with temperature. The migration fractions of Cd and As, which are volatile HMs, could exceed 70%.

A targeted and nontargeted metabolomics study on the oral processing of epicatechins from green tea.

Oral processing (OP), referring to the whole process of food digestion in human mouth, has a major influence on food flavor perception. This study focused on the compositional changes of the four green tea epicatechins (viz., EC, EGC, ECG, EGCG) during OP, based on targeted and nontargeted metabolomics. It was found that the four epicatechins were all extensively lost through transformation undergoing OP, among which EC was the most stable one, whereas EGCG the least. EGCG was further revealed to be susceptible to human oral cavity in the simulated OP in vitro. It could be converted physically by precipitating with mucin in saliva, and chemically through hydrolysis and dimerization, mediated mainly by the neutral pH condition. The OP of epicatechins also caused salivary composition changes possibly involving health benefits of green tea. These findings could raise awareness of the interactions between epicatechins, or any other food materials, with human mouth.

[Effect and Mechanism of Foliar Application Nano-MnO2 on Cadmium Enrichment of Rice].

Cadmium (Cd) is easily enriched in rice, resulting in an excessive Cd content in the grain, which seriously threatens human health. Manganese (Mn) is an essential element of plants. In a field experiment on Cd-contaminated acid soils, we investigated the effectiveness and mechanism of Mn in minimizing Cd accumulation in rice via foliar spraying using 0.1%, 0.3%, and 0.5% nano-MnO2 solutions at an early stage of heading. Compared with a control treatment, foliar spraying effectively reduced the Cd content of rice leaves, husks, and brown rice; increased the Mn content of all rice organs; but had no effect on rice yield. Foliar application of nano-MnO2 alleviated the plant stress induced by Cd by improving leaf photosynthesis, inhibiting lipid peroxidation, and increasing the content of the oxidative stress protein kinase. In addition, foliar application of nano-MnO2 limited the absorption of Cd by roots by increasing the content of iron-manganese plaque on the surfaces of rice roots and strengthening its adsorption/co-precipitation of Cd. Therefore, foliar application of nano-MnO2 during the early stages of rice heading is an effective measure to increase the Mn content and reduce the Cd content of brown rice.

Graphene Oxide Wrapped CuV2O6 Nanobelts as High-Capacity and Long-Life Cathode Materials of Aqueous Zinc-Ion Batteries.

Rechargeable aqueous zinc-ion batteries are considered as a promising alternative of lithium-ion batteries for stationary energy storage because of their economical and high safety quality. However, their widespread application is still impeded by the development of cathode materials with poor energy density and limited long-term stability. Herein, we report a high-performance CuV2O6 cathode material for aqueous zinc-ion batteries and elucidate the zinc-storage mechanism. The reversible phase transformation between CuV2O6 and ZnV2O6, accompanied by zinc ion insertion/extraction and the reduction/oxidation of metallic Cu nanoparticles, all contribute to excellent battery performance: an impressively high specific capacity of 427 mA h g-1 at current density of 0.1 A g-1, long-term cycling stability with minor capacity loss (0.7%) after 3000 cycles at a high current density of 5 A g-1, and a high energy density of 317 Wh kg-1 at a power density of 210 W kg-1. Furthermore, graphene oxide wrapped CuV2O6 nanocomposites are successfully fabricated, which demonstrates the significantly enhanced specific capacity (at least 30% improvement). This work provides an intriguing cathode material and expands available options of transition metal vanadate materials for zinc-ion batteries.

CuFeS2 Quantum Dots Anchored in Carbon Frame: Superior Lithium Storage Performance and the Study of Electrochemical Mechanism.

Herein, we report a simple and quick synthetic route to prepare the pure CuFeS2 quantum dots (QDs) @C composites with the unique structure of CuFeS2 QDs encapsulated in the carbon frame. When tested as anode materials for the lithium ion battery, the CuFeS2 QDs @C composites based electrodes exhibit excellent electrochemical performances. When charge-discharge occurred with a current density of 0.5 A g-1, the electrodes exhibit a high reversible capacity (760 mA h g-1) for as long as 700 cycles, which indicates the superior cycling life. Detailed investigations of the morphological and structural changes of CuFeS2 QDs by ex situ XRD, ex situ Raman, and ex situ TEM reveal an interesting electrochemical reaction mechanism, a hybrid of a lithium-copper iron sulfide battery and lithium-sulfur battery. The direct observation of orthorhombic FeS2 by HRTEM and the existence of Li2FeS2 detected by Raman support our assertion. We believe such an electrochemical mechanism would attract more attention to the CuFeS2 nanomaterials as lithium ion battery anode materials. The excellent electrochemical properties would be derived from the unique structure, which include CuFeS2 QDs encapsulated in the carbon frame.

Fast and Universal Approach to Encapsulating Transition Bimetal Oxide Nanoparticles in Amorphous Carbon Nanotubes under an Atmospheric Environment Based on the Marangoni Effect.

Transition metal oxide nanoparticles capsuled in amorphous carbon nanotubes (ACNTs) are attractive anode materials of lithium-ion batteries (LIBs). Here, we first designed a fast and universal method with a hydromechanics conception which is called Marangoni flow to fabricate transition bimetal oxides (TBOs) in the ACNT composite with a better electrochemistry performance. Marangoni flows can produce a liquid column with several centimeters of height in a tube with one side immersed in the liquid. The key point to induce a Marangoni flow is to make a gradient of the surface tension between the surface and the inside of the solution. With our research, we control the gradient of the surface tension by controlling the viscosity of a solution. To show how our method could be generally used, we synthesize two anode materials such as (a) CoFe2O4@ACNTs, and (b) NiFe2O4@ACNTs. All of these have a similar morphology which is ∼20 µm length with a diameter of 80-100 nm for the ACNTs, and the particles (inside the ACNTs) are smaller than 5 nm. In particular, there are amorphous carbons between the nanoparticles. All of the composite materials showed an outstanding electrochemistry performance which includes a high capacity and cycling stability so that after 600 cycles the capacity changed by less than 3%.