Comprehensive analysis and prognostic assessment of senescence-associated genes in bladder cancer.

BACKGROUND: The prevalence and mortality of bladder cancer (BLCA) present a significant medical challenge. While the function of senescence-related genes in tumor development is recognized, their prognostic significance in BLCA has not been thoroughly explored. METHODS: BLCA transcriptome datasets were sourced from the TCGA and GEO repositories. Gene groupings were determined through differential gene expression and non-negative matrix factorization (NMF) methodologies. Key senescence-linked genes were isolated using singular and multivariate Cox regression analyses, combined with lasso regression. Validation was undertaken with GEO database information. Predictive models, or nomograms, were developed by merging risk metrics with clinical records, and their efficacy was gauged using ROC curve methodologies. The immune response's dependency on the risk metric was assessed through the immune phenomenon score (IPS). Additionally, we estimated IC50 metrics for potential chemotherapeutic agents. RESULTS: Reviewing 406 neoplastic and 19 standard tissue specimens from the TCGA repository facilitated the bifurcation of subjects into two unique clusters (C1 and C2) according to senescence-related gene expression. After a stringent statistical evaluation, a set of ten pivotal genes was discerned and applied for risk stratification. Validity tests for the devised nomograms in forecasting 1, 3, and 5-year survival probabilities for BLCA patients were executed via ROC and calibration plots. IC50 estimations highlighted a heightened responsiveness in the low-risk category to agents like cisplatin, cyclopamine, and sorafenib. CONCLUSIONS: In summation, our research emphasizes the prospective utility of risk assessments rooted in senescence-related gene signatures for enhancing BLCA clinical oversight.

Comparing the gut microbiota of Sichuan golden monkeys across multiple captive and wild settings: roles of anthropogenic activities and host factors.

BACKGROUND: Captivity and artificial food provision are common conservation strategies for the endangered golden snub-nosed monkey (Rhinopithecus roxellana). Anthropogenic activities have been reported to impact the fitness of R. roxellana by altering their gut microbiota, a crucial indicator of animal health. Nevertheless, the degree of divergence in gut microbiota between different anthropogenically-disturbed (AD) R. roxellana and their counterparts in the wild has yet to be elucidated. Here, we conducted a comparative analysis of the gut microbiota across nine populations of R. roxellana spanning China, which included seven captive populations, one wild population, and another wild population subject to artificial food provision. RESULTS: Both captivity and food provision significantly altered the gut microbiota. AD populations exhibited common variations, such as increased Bacteroidetes and decreased Firmicutes (e.g., Ruminococcus), Actinobacteria (e.g., Parvibacter), Verrucomicrobia (e.g., Akkermansia), and Tenericutes. Additionally, a reduced Firmicutes/Bacteroidetes ratiosuggested diminished capacity for complex carbohydrate degradation in captive individuals. The results of microbial functional prediction suggested that AD populations displayed heightened microbial genes linked to vitamin and amino acid metabolism, alongside decreased genes associated antibiotics biosynthesis (e.g., penicillin, cephalosporin, macrolides, and clavulanic acid) and secondary metabolite degradation (e.g., naphthalene and atrazine). These microbial alterations implied potential disparities in the health status between AD and wild individuals. AD populations exhibited varying degrees of microbial changes compared to the wild group, implying that the extent of these variations might serve as a metric for assessing the health status of AD populations. Furthermore, utilizing the individual information of captive individuals, we identified associations between variations in the gut microbiota of R. roxellana and host age, as well as pedigree. Older individuals exhibited higher microbial diversity, while a closer genetic relatedness reflected a more similar gut microbiota. CONCLUSIONS: Our aim was to assess how anthropogenic activities and host factors influence the gut microbiota of R. roxellana. Anthropogenic activities led to consistent changes in gut microbial diversity and function, while host age and genetic relatedness contributed to interindividual variations in the gut microbiota. These findings may contribute to the establishment of health assessment standards and the optimization of breeding conditions for captive R. roxellana populations.

Simultaneous separation and analysis of multiple doxorubicin hydrochloride liposomes forms in serum by circular nonuniform electric field gel electrophoresis.

BACKGROUND: Liposomal formulations have traditionally been considered the most therapeutically effective drug delivery systems (DDS). However, their pharmacokinetics study and efficacy assessment are still challenging given size heterogeneity and unknown forms in vivo. The pharmacodynamic evaluation that solely analyzes total drug concentration is unfit for the liposomal formulation study. Hence, it is crucial to develop effective strategies for the separation and analysis of different forms of liposomal formulations in order to contribute to the study of pharmacokinetic profiles associated with both liposome-incorporated and non-liposomal drugs. (84) RESULTS: A laboratory-built circular nonuniform electric field gel electrophoresis (CNEFGE) system was developed in this study for simultaneous separation and analysis of various forms of doxorubicin hydrochloride (DOX•HCl) liposomes. Liposomes were effectively fractionized based on their size and higher concentration in situ in the concentration zone, obtaining liposome recovery >95 % and a 3.04 concentration factor. It was found that the technique could be used to evaluate not only the size distribution of liposomes but also the drug loading capacity related to size. The charge-to-size-based separation mechanism has also allowed the simultaneous separation of liposome-entrapped drugs, protein-bound drugs, and free drugs in various forms, and the technique has been successfully employed in serum. Moreover, the quantification analysis of liposomes incubated with serum for 72 h showed that the proportion of the ratio of DOX•HCl in liposome-entrapped drugs, protein-bound drugs, and free drugs is approximately 97:2:1. (143) SIGNIFICANCE: Using the separation principle of gel electrophoresis and the electrification characteristics of drug carriers, this study developed and implemented an efficient approach for the simultaneous separation and concentration of multiple forms of drug liposomes in vivo. This approach offers a wide range of applications in the pharmacokinetics, efficacy, and safety evaluation of drug carriers and liposomes. (56).

Mesenchymal Stem Cell Transplantation: Neuroprotection and Nerve Regeneration After Spinal Cord Injury.

Spinal Cord Injury (SCI), with its morbidity characteristics of high disability rate and high mortality rate, is a disease that is highly destructive to both the physiology and psychology of the patient, and for which there is still a lack of effective treatment. Following spinal cord injury, a cascade of secondary injury reactions known as ischemia, peripheral inflammatory cell infiltration, oxidative stress, etc. create a microenvironment that is unfavorable to neural recovery and ultimately results in apoptosis and necrosis of neurons and glial cells. Mesenchymal stem cell (MSC) transplantation has emerged as a more promising therapeutic options in recent years. MSC can promote spinal cord injury repair through a variety of mechanisms, including immunomodulation, neuroprotection, and nerve regeneration, giving patients with spinal cord injury hope. In this paper, it is discussed the neuroprotection and nerve regeneration components of MSCs' therapeutic method for treating spinal cord injuries.

Advances in the study of macrophage polarization in inflammatory immune skin diseases.

When exposed to various microenvironmental stimuli, macrophages are highly plastic and primarily polarized into the pro-inflammatory M1-type and the anti-inflammatory M2-type, both of which perform almost entirely opposing functions. Due to this characteristic, macrophages perform different functions at different stages of immunity and inflammation. Inflammatory immune skin diseases usually show an imbalance in the M1/M2 macrophage ratio, and altering the macrophage polarization phenotype can either make the symptoms worse or better. Therefore, this review presents the mechanisms of macrophage polarization, inflammation-related signaling pathways (JAK/STAT, NF-κB, and PI3K/Akt), and the role of both in inflammatory immune skin diseases (psoriasis, AD, SLE, BD, etc.) to provide new directions for basic and clinical research of related diseases.

The role and mechanisms of mesenchymal stem cells regulating macrophage plasticity in spinal cord injury.

Spinal Cord Injury (SCI) is a devastating neurological disorder comprising primary mechanical injury and secondary inflammatory response-mediated injury for which an effective treatment is still unavailable. It is well known that secondary inflammatory responses are a significant cause of difficulties in neurological recovery. An immune imbalance between M1/M2 macrophages at the sites of injury is involved in developing and progressing the secondary inflammatory response. Recently, Mesenchymal Stem Cells (MSCs) have shown significant therapeutic potential in tissue engineering and regenerative medicine due to their potential multidirectional differentiation and immunomodulatory properties. Accumulating evidence shows that MSCs can regulate the balance of M1/M2 macrophage polarization, suppress downstream inflammatory responses, facilitate tissue repair and regeneration, and improve the prognosis of SCI. This article briefly overviews the impact of macrophages and MSCs on SCI and repair. It discusses the mechanisms by which MSCs regulate macrophage plasticity, including paracrine action, release of exosomes and apoptotic bodies, and metabolic reprogramming. Additionally, the article summarizes the relevant signaling pathways of MSCs that regulate macrophage polarization.

Mechanism of M2 macrophages modulating astrocyte polarization through the TGF-ß/PI3K/Akt pathway.

Recent studies have revealed that activated astrocytes (AS) are divided into two distinct types, termed A1 and A2. A2 astrocytes are neuroprotective and promote tissue repair and regeneration following spinal cord injury. Whereas, the specific mechanism for the formation of the A2 phenotype remains unclear. This study focused on the PI3K/Akt pathway and examined whether TGF-ß secreted by M2 macrophages could mediate A2 polarization by activating this pathway. In this study, we revealed that both M2 macrophages and their conditioned medium (M2-CM) could facilitate the secretion of IL-10, IL-13 and TGF-ß from AS, and this effect was significantly reversed after the administration of SB431542 (a TGF-ß receptor inhibitor) or LY294002 (a PI3K inhibitor). Moreover, immunofluorescence results demonstrated that TGF-ß secreted by M2 macrophages could facilitate the expression of A2 biomarker S100A10 in AS; combined with the results of western blot, it was found that this effect was closely related to the activation of PI3K/Akt pathway in AS. In conclusion, TGF-ß secreted by M2 macrophages may induce the conversion of AS to the A2 phenotype through the activation of the PI3K/Akt pathway.

Advances in the role of STAT3 in macrophage polarization.

The physiological processes of cell growth, proliferation, differentiation, and apoptosis are closely related to STAT3, and it has been demonstrated that aberrant STAT3 expression has an impact on the onset and progression of a number of inflammatory immunological disorders, fibrotic diseases, and malignancies. In order to produce the necessary biological effects, macrophages (M0) can be polarized into pro-inflammatory (M1) and anti-inflammatory (M2) types in response to various microenvironmental stimuli. STAT3 signaling is involved in macrophage polarization, and the research of the effect of STAT3 on macrophage polarization has gained attention in recent years. In order to provide references for the treatment and investigation of disorders related to macrophage polarization, this review compiles the pertinent signaling pathways associated with STAT3 and macrophage polarization from many fundamental studies.

Changes in the Microbiota and their Roles in Patients with Type 2 Diabetes Mellitus.

An association between type 2 diabetes mellitus (T2DM) and gut microbiota is well established, but the results of related studies are inconsistent. The purpose of this investigation is to elucidate the characteristics of the gut microbiota in T2DM and non-diabetic subjects. Forty-five subjects were recruited for this study, including 29 T2DM patients and 16 non-diabetic subjects. Biochemical parameters, including body mass index (BMI), fasting plasma glucose (FPG), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and hemoglobin A1c (HbA1c), were analyzed and correlated with the gut microbiota. Bacterial community composition and diversity were detected in fecal samples using direct smear, sequencing, and real-time polymerase chain reaction (PCR). In this study, it was observed that indicators such as BMI, FPG, HbA1c, TC, and TG in T2DM patients were on the rise, concurrent with dysbiosis of the microbiota. We observed an increase in Enterococci and a decrease in Bacteroides, Bifidobacteria, and Lactobacilli in patients with T2DM. Meanwhile, total short-chain fatty acids (SCFAs) and D-lactate concentrations were decreased in the T2DM group. In addition, FPG was positively correlated with Enterococcus and negatively correlated with Bifidobacteria, Bacteroides, and Lactobacilli. This study reveals that microbiota dysbiosis is associated with disease severity in patients with T2DM. The limitation of this study is that only common bacteria were noted in this study, and more in-depth related studies are urgently needed.

Fabrication of ionic liquid-mesoporous silica/platinum electrode with high hydroelectric stability for electric-field-assisted particle separation.

Surface chemistry of electrodes plays a critical role in the fields of electrochemistry and electric-field-assisted separation. In this study, making ingenious use of the ordered mesoporous structure of silica materials and the electrochemical stability of ionic liquids (ILs) when integrated with polyvinylpyrrolidone (PVP), the PVP-modified IL-mesoporous silica/platinum wire (Pt/PVP@meso-SiO2@IL) was fabricated to increase hydroelectric stability and avoid the problem of electrode polarization. The effect of different amounts of mesoporous silica material used to modify the surface of the Pt electrode was systematically investigated. As a result, we successfully obtained a highly ordered mesoporous Pt/PVP@meso-SiO2 material with smooth surface. Because pentyl triethylamine bis(trifluoromethylsulfonyl) imide exhibits a wide electrochemical window between -3 to 3 V, this IL was chosen to modify mesopores under vacuum. Even after repeatedly applying electric field on Pt/PVP@meso-SiO2@IL 100 times, this working electrode remained stable and showed high hydroelectric stability. After verifying the feasibility of this method, it was successfully applied in the electric-field-assisted separation of 2.0 and 3.0 µm polystyrene particles without any impediment from electrode polarization problems. This work provides a brand-new insight for resolving the problem of electrode polarization by developing a versatile tool for the electroseparation of micro-objects.

Multiple strategies enhance the efficacy of MSCs transplantation for spinal cord injury.

Spinal cord injury (SCI) is a serious complication of the central nervous system (CNS) after spine injury, often resulting in severe sensory, motor, and autonomic dysfunction below the level of injury. To date, there is no effective treatment strategy for SCI. Recently, stem cell therapy has brought hope to patients with neurological diseases. Mesenchymal stem cells (MSCs) are considered to be the most promising source of cellular therapy after SCI due to their immunomodulatory, neuroprotective and angiogenic potential. Considering the limited therapeutic effect of MSCs due to the complex pathophysiological environment following SCI, this paper not only reviews the specific mechanism of MSCs to facilitate SCI repair, but also further discusses the research status of these pluripotent stem cells combined with other therapeutic approaches to promote anatomical and functional recovery post-SCI.

Antioxidant mechanisms of mesenchymal stem cells and their therapeutic potential in vitiligo.

Vitiligo is a skin pigmentation disorder caused by melanocyte damage or abnormal function. Reac-tive oxygen species Reactive oxygen species can cause oxidative stress damage to melanocytes, which in turn induces vitiligo. Traditional treatments such as phototherapy, drugs, and other methods of treatment are long and result in frequent recurrences. Currently, mesenchymal stem cells (MSCs) are widely used in the research of various disease treatments due to their excellent paracrine effects, making them a promising immunoregulatory and tissue repair strategy. Furthermore, an increasing body of evi-dence suggests that utilizing the paracrine functions of MSCs can downregulate oxidative stress in the testes, liver, kidneys, and other affected organs in animal models of certain diseases. Addition-ally, MSCs can help create a microenvironment that promotes tissue repair and regeneration in are-as with oxidative stress damage, improving the disordered state of the injured site. In this article, we review the pathogenesis of oxidative stress in vitiligo and promising strategies for its treatment.

RNAi-mediated knockdown of juvenile hormone acid O-methyltransferase disrupts larval development in the oriental fruit fly, Bactrocera dorsalis (Hendel).

The oriental fruit fly, Bactrocera dorsalis (Hendel), is a notoriously agricultural pest that causes serious economic losses to fruits and vegetables. Widespread insecticide resistance in B. dorsalis is a major obstacle in successful control. Therefore, new pest control strategies, such as those targeting specific genes that can block pest development, are urgently needed. In the current study, the function of JHAMT in B. dorsalis was systematically investigated. A methyltransferase gene in B. dorsalis (BdJHAMT) that is homologous to JHAMT of Drosophila melanogaster was cloned firstly. The subsequently spatiotemporal expression analysis indicated that BdJHAMT mRNA was continuously present in the larval stage, declined sharply immediately before pupation, and then increased in the adult. Subcellular localization showed that BdJHAMT was localized in the adult corpora allata and larval intestinal wall cells. The JH III titer in B. dorsalis was closely related to the transcription level of BdJHAMT in different developmental stages. The dsBdJHAMT feeding-based RNAi resulted in a greatly decreased JH III titer that disrupted fly development. The slow growth caused by BdJHAMT silencing was partially rescued by application of the JH mimic, methoprene. These results demonstrated that BdJHAMT was crucial for JH biosynthesis and thus regulated larval development in B. dorsalis, indicating it may serve as a prospective target for the development of novel control strategies against this pest.

Circular Nonuniform Electric Field Gel Electrophoresis for the Separation and Concentration of Nanoparticles.

A circular nonuniform electric field strategy coupled with gel electrophoresis was proposed to control the precise separation and efficient concentration of nano- and microparticles. The circular nonuniform electric field has the feature of exponential increase in the electric field intensity along the radius, working with three functional zones of migration, acceleration, and concentration. The distribution form of electric field lines is regulated in functional zones to control the migration behaviors of particles for separation and concentration by altering the relative position of the ring electrode (outside) and rodlike electrode (inner). The circular nonuniform electric field promotes the target-type and high-precision separation of nanoparticles based on the difference in charge-to-size ratio. The concentration multiple of nanoparticles is also controlled randomly with the alternation of radius, taking advantage of vertical extrusion and concentric converging of the migration path. This work provides a brand new insight into the simultaneous separation and concentration of particles and is promising for developing a versatile tool for the separation and preparation of various samples instead of conventional methods.

Microstructured PVDF Film with Improved Performance as Flexible Infrared Sensor.

Polyvinylidene fluoride (PVDF) is a very promising material for fabricating flexible infrared sensors due to its ferroelectricity as well as excellent flexibility and low fabrication cost. This work focuses on improving PVDF's pyroelectric performance by creating microstructures in the film. Simulation results suggest that the pyroelectric response of PVDF film can be improved if micro groove, square-pit or sinusoidal patterns are created on the film surface, with the grooved film showing the best pyroelectric performance. Suggested by the simulation results, flexible PVDF samples with groove structure are prepared by casting the precursor solution on the mold with designed patterns. Measurement results demonstrate that the optimal microstructured PVDF film can improve its pyroelectric performance by as high as 146%, which is in good agreement with the simulations. This work provides an innovative way of achieving flexible infrared sensor devices with promoted performance based on pyroelectric polymers.

RNA interference of Argonaute-1 delays ovarian development in the oriental fruit fly, Bactrocera dorsalis (Hendel).

BACKGROUND: With the development of rapid resistance, new modes of action for pesticides are needed for insect control, such as RNAi-based biopesticides targeting essential genes. To explore the function of Argonaute-1 (Ago-1) and potential miRNAs in ovarian development of Bactrocera dorsalis, an important agricultural pest, and to develop a novel control strategy for the pest, BdAgo-1 was first identified in B. dorsalis. RESULTS: Spatiotemporal expression analysis indicated that BdAgo-1 had a relatively high transcriptional level in the ovarian tissues of adult female B. dorsalis during the sexual maturation period. RNA interference (RNAi) experiment showed that BdAgo-1 knockdown significantly decreased the expression levels of ovarian development-related genes and delayed ovarian development. Although RNAi-mediated silencing of Ago-1 led to a reduced ovary surface area, a subsequent oviposition assay revealed that the influence was minimal over a longer time period. Small RNA libraries were constructed and sequenced from different ovarian developmental stages of B. dorsalis adults. Among 161 identified miRNAs, 84 miRNAs were differentially expressed during the three developmental stages of the B. dorsalis ovary. BdAgo-1 silencing caused significant down-regulation of seven differentially expressed miRNAs (DEMs) showing relatively high expression levels (>1000 TPM (Transcripts per kilobase of exon model per million mapped reads)). The expression patterns of these seven core DEMs and their putative target genes were analyzed in the ovaries of B. dorsalis. CONCLUSION: The results indicate that Ago-1 and Ago-1-dependent miRNAs are indispensable for normal ovarian development in B. dorsalis and help identify miRNA targets useful for control of this pest.

A Compact High-Speed Image-Based Method for Measuring the Longitudinal Motion of Living Tissues.

Intraoperative imaging of living tissue at the cell level by endomicroscopy might help surgeons optimize surgical procedures and provide individualized treatments. However, the resolution of the microscopic image is limited by the motion of living tissue caused by heartbeat and respiration. An active motion compensation (AMC) strategy has been recognized as an effective way to reduce, or even eliminate, the influence of tissue movement for intravital fluorescence microscopy (IVM). To realize the AMC system, a high-speed sensor for measuring the motion of tissues is needed. At present, state-of-the-art commercialized displacement sensors are not suitable to apply in minimally invasive imaging instruments to measure the motion of living tissues because of the size problem, range of measurement or the update rate. In this study, a compact high-speed image-based method for measuring the longitudinal motion of living tissues is proposed. The complexity of the proposed method is the same as that of the traditional wide-field fluorescent microscopy (WFFM) system, which makes it easy to be miniaturized and integrated into a minimally invasive imaging instrument. Experimental results reveal that the maximum indication error, range of measurement and the sensitivity of the laboratory-built experimental prototype is 150 µm, 6 mm and -211.46 mm-1 respectively. Experimental results indicate that the proposed optical method is expected to be used in minimally invasive imaging instruments to build an AMC system.

LINC00619 restricts gastric cancer progression by preventing microRNA-224-5p-mediated inhibition of OPCML.

Several long intergenic noncoding RNAs (lincRNAs) have been linked to carcinogenesis; however, little is known about the role of LINC00619 in gastric cancer (GC). LINC00619 was identified among differentially expressed lncRNAs linked to gastric cancer based on microarray analysis and its relationships with miR-224-5p and opioid binding protein/cell adhesion molecule-like gene (OPCML) were investigated. LINC00619, miR-224-5p, and OPCML expression were measured in GC tissues and cells. Ectopic expression and depletion experiments were conducted to assess the effects of LINC00619, miR-224-5p and OPCML on cell proliferation, invasion, migration and apoptosis as well as their effects on the expression of apoptosis- and metastasis-related genes (Bcl-2, Bax, MMP-2 and MMP-9). Tumorigenicity in the nude mice was also examined. Gastric cancer was characterized by downregulation of LINC00619 and OPCML and upregulation of miR-224-5p. Additionally, we found that miR-224-5p could interact with both LINC00619 and OPCML. Upregulation of LINC00619, which binds to miR-224-5p, led to decreased miR-224-5p expression while increasing the expression of OPCML, a target gene of miR-224-5p. Overexpression of LINC00619 or OPCML or downregulation of miR-224-5p suppressed cell proliferation, invasion, migration and tumorigenicity while promoting apoptosis in GC. Our results indicated that LINC00619 functions as a tumor suppressor in GC by impairing miR-224-5p-mediated inhibition of OPCML.

Physicochemical properties, microstructures, nutritional components, and free amino acids of Pleurotus eryngii as affected by different drying methods.

In this study, we determined the influences of different drying techniques such as natural air (ND), hot-air (HD), vacuum (VD), infrared (ID), microwave (MD), and freeze drying (FD) methods on the color, shrinkage ratio (SR), rehydration ratio (RR), firmness, crispness, microstructures, nutritional components, and free amino acids of Pleurotus eryngii. The results showed that these parameters were markedly influenced by different drying techniques. Among them, FD was the most effective drying method which retained the main characteristics of the fresh P. eryngii in above mentioned indexes, followed by ND and HD at 40 °C. Finally, despite the least drying time, MD treatment was not suitable to the drying process of P. eryngii slices since it damaged physicochemical properties and caused massive losses of the main nutrients and free amino acids. The results will provide a theoretical basis for industrial processing of P. eryngii.