Long noncoding RNA MALAT-1: A versatile regulator in cancer progression, metastasis, immunity, and therapeutic resistance.

Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that do not code for proteins but have been linked to cancer development and metastasis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) influences crucial cancer hallmarks through intricate molecular mechanisms, including proliferation, invasion, angiogenesis, apoptosis, and the epithelial-mesenchymal transition (EMT). The current article highlights the involvement of MALAT-1 in drug resistance, making it a potential target to overcome chemotherapy refractoriness. It discusses the impact of MALAT-1 on immunomodulatory molecules, such as major histocompatibility complex (MHC) proteins and PD-L1, leading to immune evasion and hindering anti-tumor immune responses. MALAT-1 also plays a significant role in cancer immunology by regulating diverse immune cell populations. In summary, MALAT-1 is a versatile cancer regulator, influencing tumorigenesis, chemoresistance, and immunotherapy responses. Understanding its precise molecular mechanisms is crucial for developing targeted therapies, and therapeutic strategies targeting MALAT-1 show promise for improving cancer treatment outcomes. However, further research is needed to fully uncover the role of MALAT-1 in cancer biology and translate these findings into clinical applications.

The recent advances in cell delivery approaches, biochemical and engineering procedures of cell therapy applied to coronary heart disease.

Cell therapy is an important topic in the field of regeneration medicine that is gaining attention within the scientific community. However, its potential for treatment in coronary heart disease (CHD) has yet to be established. Several various strategies, types of cells, routes of distribution, and supporting procedures have been tried and refined to trigger heart rejuvenation in CHD. However, only a few of them result in a real considerable promise for clinical usage. In this review, we give an update on techniques and clinical studies of cell treatment as used to cure CHD that are now ongoing or have been completed in the previous five years. We also highlight the emerging efficacy of stem cell treatment for CHD. We specifically examine and comment on current breakthroughs in cell treatment applied to CHD, including the most effective types of cells, transport modalities, engineering, and biochemical approaches used in this context. We believe the current review will be helpful for the researcher to distill this information and design future studies to overcome the challenges faced by this revolutionary approach for CHD.

Status and Future Directions of Therapeutics and Prognosis of Cardiac Amyloidosis.

Accumulation of aberrant proteins in the heart causes cardiac amyloidosis, an uncommon and complicated illness. It can be classified into two main types: light chain (AL) and transthyretin (ATTR). The diagnosis of cardiac amyloidosis is challenging due to its non-specific clinical presentation and lack of definitive diagnostic tests. Diagnostic accuracy has increased with the advent of modern imaging methods, including cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Depending on the severity of cardiac amyloidosis, a number of treatments may be attempted and specified according to the subtype of amyloidosis and the presence of complications. However, there are still significant challenges in treating this condition due to its complexity and lack of effective treatments. The prognosis for patients with cardiac amyloidosis is poor. Despite recent advances in diagnosis and treatment, there is still a need for more effective treatments to improve outcomes for patients with this condition. Therefore, we aim to review the current and future therapeutics reported in the literature and among ongoing clinical trials recruiting patients with CA.

Detection of sulfur mustard simulants using the microwave atmospheric pressure plasma optical emission spectroscopy method.

Sulfur mustard (SM) is one kind of highly toxic chemical warfare agent and easy to spread, while existing detection methods cannot fulfill the requirement of rapid response, good portability, and cost competitiveness at the same time. In this work, the microwave atmospheric pressure plasma optical emission spectroscopy (MW-APP-OES) method, taking the advantage of non-thermal equilibrium, high reactivity, and high purity of MW plasma, is developed to detect three kinds of SM simulants, i.e., 2-chloroethyl ethyl sulfide, dipropyl disulfide, and ethanethiol. Characteristic OES from both atom lines (C I and Cl I) and radical bands (CS, CH, and C2) is identified, confirming MW-APP-OES can preserve more information about target agents without full atomization. Gas flow rate and MW power are optimized to achieve the best analytical results. Good linearity is obtained from the calibration curve for the CS band (linear coefficients R 2 > 0.995) over a wide range of concentrations, and a limit of detection down to sub-ppm is achieved with response time on the order of second. With SM simulants as examples, the analytical results in this work indicate that MW-APP-OES is a promising method for real-time and in-site detection of chemical warfare agents.

Integrative analyses of ferroptosis and immune related biomarkers and the osteosarcoma associated mechanisms.

Osteosarcoma (OS) is the most common primary malignant bone tumor with high metastatic potential and relapse risk. To study the regulatory mechanism of the OS microenvironment, a complex regulatory network involving the ferroptosis- and immune response-related genes remains to be established. In the present study, we determined the effect of a comprehensive evaluation system established on the basis of ferroptosis- and immune-related genes on the immune status, related biomarkers, prognosis, and the potential regulatory networks underlying OS based on the TARGET and Gene Expression Omnibus databases that contain information on OS patients by bioinformatics analyses. We first characterized individual ferroptosis scores and immune scores through gene set variation analysis (GSVA) against TARGET-OS datasets. We then identified differentially expressed genes by score groups. Weighted gene co-expression network analysis was performed to identify the most relevant ferroptosis-related and immune-related gene modules, which facilitated the identification of 327 ferroptosis gene and 306 immune gene candidates. A 4-gene (WAS, CORT, WNT16, and GLB1L2) signature was constructed and valuation using the least absolute shrinkage and selection operator-Cox regression models to effectively predict OS prognosis. The prediction efficiency was further validated by GSE39055. We stratified patients based on the prognostic scoring systems. Eight hub genes (namely CD3D, CD8A, CD3E, IL2, CD2, MYH6, MYH7, and MYL2) were identified, and TF-miRNA target regulatory networks were constructed. Furthermore, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and GSVA were used to determine the signature's potential pathways and biological functions, which showed that the hub genes were enriched in ferroptosis-associated biological functions and immune-associated molecular mechanisms. Thereafter, we investigated the proportion and infiltration extent of 22 infiltrating immune cells by using CIBERSORT, which revealed significant subgroup differences in CD8 + T cells, M0 macrophages, and M2 macrophages. In conclusion, we determined a new ferroptosis-related and immune-related gene signature for predicting OS patients' prognosis and further explored the ferroptosis and immunity interactions during OS development, which provides insights into the exploration of molecular mechanisms and targeted therapies in patients with OS.

Manipulating the Dynamic Self-Reconstruction of CoP Electrocatalyst Driven by Charge Transport and Ion Leaching.

Surface reconstruction of electrocatalysts is very important to clarify the structure-component-activity relationship. In this work, in situ Raman and ex situ technologies are used to capture the surface structure evolution of F-Fe-CoP during the oxygen evolution reaction (OER). The results reveal that the leaching of F accelerates the dynamic reconstruction response of CoP to rapidly convert into active (oxy)hydroxide species. The further introduction of Fe can accelerate the charge transfer rate and alleviate the structural stacking caused by insufficient kinetics. The introduction of F and Fe increases the electron occupation states of cobalt sites and promotes the adsorption of OH- ions on the CoP catalyst, which significantly improves the OER performance. F-Fe-CoP exhibits excellent OER performance with an overpotential of 259 mV at 20 mA cm-2 . This finding enriches the OER mechanism associated with the surface reconstruction of CoP and provides a reference for the rational design of efficient electrocatalysts.

Ultrasound-Guided Radiofrequency and Microwave Ablation for the Management of Patients With Benign Thyroid Nodules: Systematic Review and Meta-Analysis.

ABSTRACT: Ultrasound-guided thermal ablation has been shown to considerably reduce nodule-related discomfort and cosmetic problems. Hence, this review was done to determine the effectiveness of ultrasound-guided radiofrequency or microwave ablation in the management of benign thyroid nodules. Searches were done in EMBASE, SCOPUS, PubMed Central, Cochrane library, MEDLINE, Google Scholar, ScienceDirect, and Clinicaltrials.gov until August 2022. Meta-analysis was carried out using random-effects model. With 95% confidence intervals (CIs), pooled standardized mean differences, mean differences, and/or odds ratio reported. In total, we analyzed 16 studies, most of them had high risk of bias. The pooled standardized mean difference for symptom score was -1.01 (95% CI, -1.83 to -0.19; I2 = 94.2%), for cosmetic relief was -1.26 (95% CI, -2.27 to -0.24; I2 = 96%), for postoperative nodule volume was -1.77 (95% CI, -3.06 to -0.48; I2 = 94%), for hospital stay was -3.88 (95% CI, -4.58 to -3.18; I2 = 91.1%), for operation time was -3.30 (95% CI, -3.95 to -2.64; I2 = 93.4%). The pooled odds ratio for postoperative pain was 0.04 (95% CI, 0.00-0.35; I2 = 95.1%), for postoperative hypothyroidism was 0.04 (95% CI, 0.01-0.11; I2 = 0%), for postoperative hoarseness was 0.56 (95% CI, 0.22-1.47; I2 = 0%), for postoperative hematoma was 0.57 (95% CI, 0.15-2.22; I2 = 0%). Ultrasound-guided radiofrequency and microwave ablation had better efficacy and safety profile in terms of symptoms, cosmetic relief, complication rate, duration of stay, and operation time when compared with conventional surgery or observation without treatment for patients with benign thyroid nodules.

F, N neutralizing effect induced Co-P-O cleaving endows CoP nanosheets with superior HER and OER performances.

Electrochemical water splitting, the most direct and clean method used for the production of hydrogen, requires highly efficient bifunctional electrocatalysts that can accelerate hydrogen evolution reactions (HER) and oxygen evolution reactions (OER) by overcoming their kinetics barriers. Herein, self-supported F, N codoping CoP nanosheets (denoted as FN-CoP NS) are prepared as efficient and stable bifunctional electrocatalysts. Codoping of F and N neutralizes the electronegativity of surface P-O by cleaving the Co-P-O of non-metallic P sites on the surface (O derived from the surface oxidation). This contributes to an increased Co2+ content with considerable adjustable electronegativity and also optimizes HER and OER processes. As a result, FN-CoP NS requires 66 and 241 mV overpotentials to deliver the current density of 10 mA cm-2 during HER and OER, respectively. A full water electrolyzer equipped FN-CoP NS as both cathode and anode only require 1.57 V to drive the current density of 10 mA cm-2 and to sustain 50 mA cm-2 for 48 h. This work adjusts the electronic structure of metal phosphides by a double anion codoping strategy, which provides a reference value for the rational design of efficient bifunctional electrocatalysts.

Three-dimensional cross-linked Co-MoS2 catalyst on carbon cloth for efficient hydrogen evolution reaction.

MoS2-Based materials are promising hydrogen evolution reaction (HER) electrocatalysts. However, their HER activities are restrained by the poor population of HER activated edge centers, the large area exposed HER inert basal planes, and low conductivity. Fixing these problems on one system is an effective strategy, but it remains a challenge due to the harsh synthetic conditions. Herein, cobalt carbonate hydroxide (CoCH) nanosheets were used as the substrate for preparing a three-dimensional self-supported cross-linked (3DSC) Co-MoS2 nanostructured HER catalyst, which possesses abundant active centers and fast electronic transfer ability. In addition, Co activates the basal-plane sulfur atom in MoS2 to be the HER reactive center effectively. Benefiting from these advantages, 3DSC Co-MoS2 electrode integrated on carbon cloth (CC) shows that it can drive the current density of 10 and 100 mA cm-2 with only 40 and 119 mV overpotentials, respectively, which is superior to other MoS2-based HER catalysts reported recently. This research provides a facile strategy for the improvement of efficient HER electrocatalysts.

Identification of TAPBPL as a novel negative regulator of T-cell function.

T cell stimulatory and inhibitory molecules are critical for the regulation of immune responses. In this study, we identify a novel T cell co-inhibitory molecule TAPBPL, whose amino acid sequence shares homology with known B7 family members. TAPBPL protein is expressed on resting and activated T cells, B cells, monocytes, and dendritic cells (DCs), as well as on some tumor tissues. The putative TAPBPL receptor is expressed on activated CD4 and CD8 T cells. A soluble recombinant human TAPBPL-IgG Fc (hTAPBPL-Ig) fusion protein inhibits the proliferation, activation, and cytokine production of both mouse and human T cells in vitro. In vivo administration of hTAPBPL-Ig protein attenuates experimental autoimmune encephalomyelitis (EAE) in mice. Furthermore, an anti-TAPBPL monoclonal antibody neutralizes the inhibitory activity of hTAPBPL-Ig on T cells, enhances antitumor immunity, and inhibits tumor growth in animal models. Our results suggest that therapeutic intervention of the TAPBPL inhibitory pathway may represent a new strategy to modulate T cell-mediated immunity for the treatment of cancer, infections, autoimmune diseases, and transplant rejection.

Regulation of aureofuscin production by the PAS-LuxR family regulator AurJ3M.

aurJ3M(GenBank:EU697915.1), a 579 bp gene, whose deduced product (192 amino acid) was found to have amino acid sequence homology with some bacterial regulatory proteins. Computer-assisted analysis showed that AurJ3M is PAS-LuxR family regulatory protein, it combines a PAS domain with a helix-turn-helix (HTH) motif of the LuxR type. Gene deletion of aurJ3M from the S.aureofuscus SYAU0709 through gene replacement with the apramycin resistance gene aac (3) IV and the DNA fragment of the replication initiation site sequence OriT resulted in complete loss of aureofuscin production, indicating that AurJ3M is a positive regulator during the aureofuscin biosynthesis. Gene expression analyses in S.aureofuscus SYAU0709 and S.aureofuscus ΔaurJ3M by reverse transcriptase PCR (RT-PCR) indicated there no transcripts for the genes B、C、G、F、S0、S1、D in S.aureofuscus ΔaurJ3M, maintains some transcription of these genes although the levels is low. Transcription was also significantly reduced for gene A, and no difference in the transcription pattern was observed for the genes R、E and H, a similar transcription pattern was also observed for AurJ3M, A and B showed a different transcription pattern, while transcription of gene A in S.aureofuscus ΔaurJ3M when compared to the parental strain, no transcripts could be detected for gene B in the mutant; This result indicates that the deletion of aurJ3M gene doesn't have a polar effect on the transcription of genes located downstream from aurJ3M. In the ΔaurJ3M knockout mutant, except for the transcription of E、H、M and R, the transcription of other genes in the cluster was down-regulated, HPLC shows there no secondary metabolites was produced,aurJ3M has a pathway-specific regulation effect on the biosynthesis of aureofuscin. Aureofuscin had broad application prospects in food preservation, and enriched the resource pool of anti-fungal antibiotics of tetraphenyl macrolide in China.

Odometer Velocity and Acceleration Estimation Based on Tracking Differentiator Filter for 3D-Reduced Inertial Sensor System.

Velocity information from the odometer is the key information in a reduced inertial sensor system (RISS), and is prone to noise corruption. In order to improve the navigation accuracy and reliability of a 3D RISS, a method based on a tracking differentiator (TD) filter was proposed to track odometer velocity and acceleration. With the TD filter, an input signal and its differential signal are estimated fast and accurately to avoid the noise amplification that is brought by the conventional differential method. The TD filter does not depend on an object model, and has less computational complexity. Moreover, the filter phase lag is decreased by the prediction process with the differential signal of the TD filter. In this study, the numerical simulation experiments indicate that the TD filter can achieve a better performance on random noises and outliers than traditional numerical differentiation. The effectiveness of the TD filter on a 3D RISS is demonstrated using a group of offline data that were obtained from an actual vehicle experiment. We conclude that the TD filter can not only quickly and correctly filter velocity and estimate acceleration from the odometer velocity for a 3D RISS, but can also improve the reliability of the 3D RISS.

Expression of SIRT3 in various glial cell types in the periventricular white matter in the neonatal rat brain after hypoxia.

Sirtuin 3 (SIRT3) mediates cellular resistance toward various forms of stress. SIRT3 expression in the developing brain, especially its localization in various glial cell types, has not been fully explored. This study aimed to determine SIRT3 expression in the brain of neonatal rats subjected to hypoxia. By immunohistochemistry, immunofluorescence and Western blotting, we show here that SIRT3 expression in the periventricular white matter was up-regulated in hypoxia group compared with the control group at the corresponding time points. Intense SIRT3 expression was detected in microglia at early time points after hypoxia whose cell number was increased with reduced ramifications in hypoxia group compared with the control group. Furthermore, SIRT3 immunoreactivity was obviously enhanced at 24 h, 3 and 7d, but was declined at 14d after hypoxia so that SIRT3 expression between the two groups was comparable. SIRT3 immunofluorescence was also localized in astrocytes labeled with GFAP which was augmented at different time points in hypoxia group. GPAP positive astrocytes exhibited long extending processes being most pronounced at 3d. SIRT3 was moderately expressed at 24 h, 3 and 7d, but was markedly increased at 14d after hypoxia. Moderate SIRT3 expression was also localized in oligodendrocytes labeled with CNPase in the control group. The incidence of CNPase positive oligodendrocytes showing colocalization of SIRT3 increased significantly at 24 h, 3 and 7d after hypoxia. In conclusion, SIRT3 expression was differentially up-regulated in all three major glial cell types following hypoxia. It is suggested that increased SIRT3 expression in the respective glial cell types following hypoxia is involved in different signaling pathways that protect against hypoxic stress in the developing brain.

Evaluation of anthocyanins in Aronia melanocarpa/BSA binding by spectroscopic studies.

The interaction between Anthocyanins in Aronia melanocarpa (AMA) and bovine serum albumin (BSA) were studied in this paper by multispectral technology, such as fluorescence quenching titration, circular dichroism (CD) spectroscopy and Fourier transform infrared spectroscopy (FTIR). The results of the fluorescence titration revealed that AMA could strongly quench the intrinsic fluorescence of BSA by static quenching. The apparent binding constants KSV and number of binding sites n of AMA with BSA were obtained by fluorescence quenching method. The thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS), were calculated to be 18.45 kJ mol-1 > 0 and 149.72 J mol-1 K-1 > 0, respectively, which indicated that the interaction of AMA with BSA was driven mainly by hydrophobic forces. The binding process was a spontaneous process of Gibbs free energy change. Based on Förster's non-radiative energy transfer theory, the distance r between the donor (BSA) and the receptor (AMA) was calculated to be 3.88 nm. Their conformations were analyzed using infrared spectroscopy and CD. The results of multispectral technology showed that the binding of AMA to BSA induced the conformational change of BSA.

Anthocyanins Delay Ageing-Related Degenerative Changes in the Liver.

Liver ageing is a significant risk factor for chronic liver diseases. Anthocyanin is a food additive that has previously shown efficacy in increasing longevity. Here, we tested whether anthocyanins could protect young mice from accelerated ageing of the liver. Kunming mice were injected with D-galactose to accelerate ageing and were given 20 or 40 mg/kg anthocyanins as an intervention. After eight weeks, whole liver function and structure were evaluated, and the expression levels of genes involved in the DNA damage signalling pathway were assessed by Western blot analysis. Anthocyanins delayed the reduction of the liver index (p < 0.05), hepatic tissue injury and fibrosis. Anthocyanins also maintained the stability of the redox system (GSH-PX, T-SOD and MDA) in plasma and liver structures (p < 0.001) and reduced the levels of inflammatory factors (IL-1, IL-6 and TNF-α) in the liver (p < 0.05). Moreover, the expression levels of sensors (ATM and ATR), mediators (H2AX and γ-H2AX) and effectors (Chk1, Chk2, p53 and p-p53) in the DNA damage signalling pathway were all reduced. Anthocyanins could be widely used in the field of health products to slow ageing-related deterioration of liver function and structure by inhibiting DNA damage.

Anthocyanins from Black Chokeberry (Aroniamelanocarpa Elliot) Delayed Aging-Related Degenerative Changes of Brain.

Aging is the greatest risk factor for most neurodegenerative diseases, which is associated with decreasing cognitive function and significantly affecting life quality in the elderly. Computational analysis suggested that 4 anthocyanins from chokeberry fruit increased Klotho (aging-suppressor) structural stability, so we hypothesized that chokeberry anthocyanins could antiaging. To explore the effects of anthocyanins treatment on brain aging, mice treated with 15 or 30 mg/kg anthocyanins by gavage and injected D-galactose accelerated aging per day. After 8 weeks, cognitive and noncognitive components of behavior were determined. Our studies showed that anthocyanins blocked age-associated cognitive decline and response capacity in senescence accelerated mice. Furthermore, mice treated with anthocyanins-supplemented showed better balance of redox systems (SOD, GSH-PX, and MDA) in all age tests. Three major monoamines were norepinephrine, dopamine, and 5-hydroxytryptamine, and their levels were significantly increased; the levels of inflammatory cytokines (COX2, TGF-ß1, and IL-1) transcription and DNA damage were decreased significantly in brains of anthocyanins treated mice compared to aged models. The DNA damage signaling pathway was also regulated with anthocyanins. Our results suggested that anthocyanins was a potential approach for maintaining thinking and memory in aging mice, possibly by regulating the balance of redox system and reducing inflammation accumulation, and the most important factor was inhibiting DNA damage.