Clinicopathological characteristics and typing of multilocular cystic renal neoplasm of low malignant potential.

BACKGROUND: Up until now, no research has been reported on the association between the clinical growth rate of multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) and computed tomography (CT) imaging characteristics. Our study sought to examine the correlation between them, with the objective of distinguishing unique features of MCRNLMP from renal cysts and exploring effective management strategies. AIM: To investigate optimal management strategies of MCRNLMP. METHODS: We retrospectively collected and analyzed data from 1520 patients, comprising 1444 with renal cysts and 76 with MCRNLMP, who underwent renal cyst decompression, radical nephrectomy, or nephron-sparing surgery for renal cystic disease between January 2013 and December 2021 at our institution. Detection of MCRNLMP utilized the Bosniak classification for imaging and the 2016 World Health Organization criteria for clinical pathology. RESULTS: Our meticulous exploration has revealed compelling findings on the occurrence of MCRNLMP. Precisely, it comprises 1.48% of all cases involving simple renal cysts, 5.26% of those with complex renal cysts, and a noteworthy 12.11% of renal tumors coexisting with renal cysts, indicating a statistically significant difference (P = 0.001). Moreover, MCRNLMP constituted a significant 22.37% of the patient population whose cysts demonstrated a rapid growth rate of ≥ 2.0 cm/year, whereas it only represented 0.66% among those with a growth rate below 2.0 cm/year. Of the 76 MCRNLMP cases studied, none of the nine patients who underwent subsequent nephron-sparing surgery or radical nephrectomy following renal cyst decompression experienced recurrence or metastasis. In the remaining 67 patients, who were actively monitored over a 3-year postoperative period, only one showed suspicious recurrence on CT scans. CONCLUSION: MCRNLMP can be tentatively identified and categorized into three types based on CT scanning and growth rate indicators. In treating MCRNLMP, partial nephrectomy is preferred, while radical nephrectomy should be minimized. After surgery, active monitoring is advisable to prevent unnecessary nephrectomy.

Serum tRF-33-RZYQHQ9M739P0J as a novel biomarker for auxiliary diagnosis and disease course monitoring of hepatocellular carcinoma.

Objective: In most cases, patients with hepatocellular carcinoma (HCC) develop advanced disease when diagnosed. Finding new molecules to combine with traditional biomarkers is crucial for HCC early diagnosis. In cancer development, tRNA-derived small RNAs (tsRNA) play a crucial role. Here, we aimed to identify a novel biomarker among tsRNAs that can facilitate HCC diagnosis and monitor its prognosis. Methods: We screened candidate tsRNAs in 3 pairs of HCC and adjacent tissues through high-throughput sequencing. tRF-33-RZYQQ9M739P0J was screened in tissues, sera, and cells through quantitative real-time polymerase chain reaction (qRT-PCR) for further analysis. tRF-33-RZYQHQ9M739P0J was characterized using agarose gel electrophoresis, Sanger sequencing, and nuclear and cytoplasmic RNA isolation. Experiments at room temperature and repeated freeze-thaw cycles were conducted to evaluate the detection performance of tRF-33-RZYQHQ9M739P0J. We measured the levels of differential expression of tRF-33-RZYQHQ9M739P0J in sera using qRT-PCR. We applied the chi-square test to evaluate the correlation between tRF-33-RZYQHQ9M739P0J expression levels and clinicopathological features, and assessed its prognostic value by plotting Kaplan-Meier curves. The diagnostic efficacy of tRF-33-RZYQHQ9M739P0J was evaluated using the receiver operating characteristic (ROC) curve. Finally, the downstream genes related to tRF-33-RZYQHQ9M739P0J were explored through bioinformatics prediction. Results: tRF-33-RZYQHQ9M739P0J was highly expressed in HCC tissues and sera, and its expression was correlated with metastasis, TNM stage, BCLC stage, and vein invasion. Expression of tRF-33-RZYQHQ9M739P0J were decreased after surgery in patients with HCC. High serum tRF-33-RZYQHQ9M739P0J levels are associated with low survival rates, and they can predict survival times in patients with HCC according to the Kaplan-Meier analysis. Combining tRF-33-RZYQHQ9M739P0J with serum alpha-fetoprotein and prothrombin induced by vitamin K absence II can improve the diagnostic efficiency of HCC, suggesting its potential as a biomarker for HCC. Conclusion: tRF-33-RZYQHQ9M739P0J may not only be a promising non-invasive marker for early diagnosis, but also a predictor of liver cancer progression.

Single-Atom-Based Nanoenzyme in Tissue Repair.

Since the discovery of ferromagnetic nanoparticles Fe3O4 that exhibit enzyme-like activity in 2007, the research on nanoenzymes has made significant progress. With the in-depth study of various nanoenzymes and the rapid development of related nanotechnology, nanoenzymes have emerged as a promising alternative to natural enzymes. Within nanozymes, there is a category of metal-based single-atom nanozymes that has been rapidly developed due to low cast, convenient preparation, long storage, less immunogenicity, and especially higher efficiency. More importantly, single-atom nanozymes possess the capacity to scavenge reactive oxygen species through various mechanisms, which is beneficial in the tissue repair process. Herein, this paper systemically highlights the types of metal single-atom nanozymes, their catalytic mechanisms, and their recent applications in tissue repair. The existing challenges are identified and the prospects of future research on nanozymes composed of metallic nanomaterials are proposed. We hope this review will illuminate the potential of single-atom nanozymes in tissue repair, encouraging their sequential clinical translation.

A Voltage-Assist 16-Channel Electrochemical Biosensor with Linearity Compensation.

Large capacitive loading of electrodes induces massive error current and imperfect settling in the electrochemical signal acquisition process, leading to inaccurate acquisition results. To efficiently mitigate this inaccuracy, this paper presents a current-and-voltage dual-mode acquisition technique in which a voltage front-end (VFE) is employed to acquire the electrode voltage error and compensate the nonlinearity induced by the electrode capacitive loading. Therefore, the gain and bandwidth requirements of the current front end (CFE) can be relaxed to reduce the complexity and power consumption. With a relieved gain requirement, an inverter-based capacitive trans-impedance amplifier (IB-CTIA) is adopted to boost the input transconductance for low-noise design. By reusing the supply current, the IB-CTIA effectively achieves a low input-referred current noise of 3.9 pArms and a dynamic range (DR) of 126 dB with only 18-µW static power. The prototype chip is fabricated in a 180-nm CMOS process. Interleukin-6 immunoassays (IL-6) are implemented to verify the chip's performance. With the proposed nonlinear error compensation, the correlation coefficient of the detection result is improved from 0.951 to 0.980 and the limit of detection (LoD) is reduced from 8.31 pg/mL to 6.90 pg/mL.

Circulating cell-free DNA methylation-based multi-omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor-originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA-based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer-specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation-based model significantly. Moreover, the combination of the methylation-based model with carbohydrate antigen 19-9 (CA19-9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation-based and integrated liquid biopsy assays hold promise as non-invasive tools for detection of PDAC.

Effects of CICARE model combined with traditional Chinese medicine encapsulation on muscle strength and depression levels in hemiplegic patients with sequelae of cerebrovascular disease.

OBJECTIVE: To investigate the impact of the combination of CICARE (C - Connect, I - Introduce, C - Communicate, A - Ask, R - Respond, E - Exit) communication model and traditional Chinese medicine (TCM) poultice on muscle strength and depression levels in patients. METHODS: Patients were divided into three groups: basic treatment group, basic treatment + TCM poultice group, and combined treatment group. Conventional rehabilitation therapy, TCM poultice external application, and the combination of both with the CICARE communication model were applied in the respective groups. Muscle strength (AMA muscle strength grading scale), self-care abilities (Barthel Index), depression symptoms (Hamilton Depression Rating Scale), neurological deficit status (NIHSS score) and serum inflammatory factor levels were assessed at admission, 3 weeks, and 8 weeks of treatment. RESULTS: After 3 and 8 weeks of treatment, the combined treatment group had higher AMA muscle strength scores and improved Barthel Index scores compared to other groups (P < 0.05). Depressive symptoms also improved significantly in the combined treatment group, with lower HDRS scores at 3 and 8 weeks (P < 0.05). After 8 weeks, IL-1, IL-6, and hs-CRP levels decreased in all groups, with the combined treatment group showing the lowest levels (P < 0.05). NIHSS scores decreased significantly in all groups post-intervention, with the combined treatment group showing the greatest improvement (P < 0.05). CONCLUSION: The integration of CICARE communication model with TCM poultice shows notable benefits in enhancing muscle strength, daily living self-care abilities, reducing depression, neurological impairment, and inflammatory factors in post-stroke hemiplegia patients.

Global, regional and national epidemiology of allergic disorders in children from 1990 to 2019: findings from the Global Burden of Disease study 2019.

OBJECTIVE: This modelling study aimed to estimate the burden for allergic diseases in children during a period of 30 years. DESIGN: Population-based observational study. MAIN OUTCOMES AND MEASURES: The data on the incidence, mortality and disability-adjusted life years (DALYs) for childhood allergic diseases, such as atopic dermatitis (AD) and asthma, were retrieved from the Global Burden of Disease study 2019 online database. This data set spans various groups, including different regions, ages, genders and Socio-Demographic Indices (SDI), covering the period from 1990 to 2019. RESULTS: In 2019, there were approximately 81 million children with asthma and 5.6 million children with AD worldwide. The global incidence of asthma in children was 20 million. Age-standardised incidence rates showed a decrease of 4.17% for asthma, from 1075.14 (95% uncertainty intervals (UI), 724.63 to 1504.93) per 100 000 population in 1990 to 1030.33 (95% UI, 683.66 to 1449.53) in 2019. Similarly, the rates for AD decreased by 5.46%, from 594.05 (95% UI, 547.98 to 642.88) per 100 000 population in 1990 to 561.61 (95% UI, 519.03 to 608.29) in 2019. The incidence of both asthma and AD was highest in children under 5 years of age, gradually decreasing with age. Interestingly, an increase in SDI was associated with a rise in the incidence of both conditions. However, the mortality rate and DALYs for asthma showed a contrasting trend. CONCLUSIONS: Over the past three decades, there has been a worldwide increase in new asthma and AD cases, even though mortality rates have significantly declined. However, the prevalence of these allergic diseases among children varies considerably across regions, countries and age groups. This variation highlights the need for precise prevalence assessments. These assessments are vital in formulating effective strategies for prevention and treatment.

High-speed generation of non-Rayleigh speckle.

Speckle with non-Rayleigh amplitude distribution has significant research value in imaging and measurement using structured illumination. However, existing speckle customizing schemes have been limited in generation speed due to the refresh rate of spatial light modulators (SLMs). In this work, we proposed a method to rapidly generate non-Rayleigh distributed speckle fields using a digital micro-mirror device (DMD). In contrast to SLMs that allow for gray-scale phase modulation, DMD is limited to binary amplitude control. To solve this limitation, we design a Gerchberg-Saxton-like algorithm based on super-pixel method, this algorithm enables the customization of non-Rayleigh speckle with arbitrary intensity probability density function. Statistical analyses of experimental results have demonstrated that the customized speckles exhibit excellent stability in their lateral statistical properties, while also maintaining consistent propagation characteristics with Rayleigh speckle in the longitudinal direction. This method provides a new approach for high-speed and arbitrary intensity speckle customization, holding potential applications in imaging, measurement, and encryption fields.

KAT2A-mediated succinylation modification of notch1 promotes the proliferation and differentiation of dental pulp stem cells by activating notch pathway.

BACKGROUND: Dental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs. METHODS: DPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins. RESULTS: The specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation. CONCLUSION: KAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.

Interaction between Oligodendrocytes and Interneurons in Brain Development and Related Neuropsychiatric Disorders.

A variety of neurological and psychiatric disorders have recently been shown to be highly associated with the abnormal development and function of oligodendrocytes (OLs) and interneurons. OLs are the myelin-forming cells in the central nervous system (CNS), while interneurons are important neural types gating the function of excitatory neurons. These two types of cells are of great significance for the establishment and function of neural circuits, and they share similar developmental origins and transcriptional architectures, and interact with each other in multiple ways during development. In this review, we compare the similarities and differences in these two cell types, providing an important reference and further revealing the pathogenesis of related brain disorders.

Remote sensing image information extraction based on Compensated Fuzzy Neural Network and big data analytics.

Medical imaging AI systems and big data analytics have attracted much attention from researchers of industry and academia. The application of medical imaging AI systems and big data analytics play an important role in the technology of content based remote sensing (CBRS) development. Environmental data, information, and analysis have been produced promptly using remote sensing (RS). The method for creating a useful digital map from an image data set is called image information extraction. Image information extraction depends on target recognition (shape and color). For low-level image attributes like texture, Classifier-based Retrieval(CR) techniques are ineffective since they categorize the input images and only return images from the determined classes of RS. The issues mentioned earlier cannot be handled by the existing expertise based on a keyword/metadata remote sensing data service model. To get over these restrictions, Fuzzy Class Membership-based Image Extraction (FCMIE), a technology developed for Content-Based Remote Sensing (CBRS), is suggested. The compensation fuzzy neural network (CFNN) is used to calculate the category label and fuzzy category membership of the query image. Use a basic and balanced weighted distance metric. Feature information extraction (FIE) enhances remote sensing image processing and autonomous information retrieval of visual content based on time-frequency meaning, such as color, texture and shape attributes of images. Hierarchical nested structure and cyclic similarity measure produce faster queries when searching. The experiment's findings indicate that applying the proposed model can have favorable outcomes for assessment measures, including Ratio of Coverage, average means precision, recall, and efficiency retrieval that are attained more effectively than the existing CR model. In the areas of feature tracking, climate forecasting, background noise reduction, and simulating nonlinear functional behaviors, CFNN has a wide range of RS applications. The proposed method CFNN-FCMIE achieves a minimum range of 4-5% for all three feature vectors, sample mean and comparison precision-recall ratio, which gives better results than the existing classifier-based retrieval model. This work provides an important reference for medical imaging artificial intelligence system and big data analysis.

Synthesis of a Triangle-Fused Six-Pointed Star and Its Electrocatalytic CO2 Reduction Activity.

As electrocatalysts, molecular catalysts with large aromatic systems (such as terpyridine, porphyrin, or phthalocyanine) have been widely applied in the CO2 reduction reaction (CO2RR). However, these monomeric catalysts tend to aggregate due to strong π-π interactions, resulting in limited accessibility of the active site. In light of these challenges, we present a novel strategy of active site isolation for enhancing the CO2RR. Six Ru(Tpy)2 were integrated into the skeleton of a metallo-organic supramolecule by stepwise self-assembly in order to form a rhombus-fused six-pointed star R1 with active site isolation. The turnover frequency (TOF) of R1 was as high as 10.73 s-1 at -0.6 V versus reversible hydrogen electrode (vs RHE), which is the best reported value so far at the same potential to our knowledge. Furthermore, by increasing the connector density on R1's skeleton, a more stable triangle-fused six-pointed star T1 was successfully synthesized. T1 exhibits exceptional stability up to 126 h at -0.4 V vs RHE and excellent TOF values of CO. The strategy of active site isolation and connector density increment significantly enhanced the catalytic activity by increasing the exposure of the active site. This work provides a starting point for the design of molecular catalysts and facilitates the development of a new generation of catalysts with a high catalytic performance.

Demonstration Study of Reflector-Based Volumetric Speed-of-Sound Imaging With Linear Ultrasound Arrays.

Conventional B-mode ultrasound imaging has difficulty in delineating homogeneous soft tissues with similar acoustic impedances, as the reflectivity depends on the acoustic impedance at the interface. As a quantitative imaging biomarker sensitive to alteration of biomechanical properties, speed-of-sound (SoS) holds promising potential for tissue and disease differentiation such as delineation of different breast tissue types with similar acoustic impedance. Compared to two-dimensional (2D) SoS images, three-dimensional (3D) volumetric SoS images achieved through a full-angle ultrasound scan can reveal more intricate morphological structures of tissues; however, they generally require a ring transducer. In this study, we introduce a 3D SoS reconstruction system that utilizes hand-held linear arrays instead. This system employs a passive reflector positioned opposite the linear arrays, serving as an echogenic reference for time-of-flight (ToF) measurements, and a high-definition camera to track the location corresponding to each group of transmit-receive data. To merge these two streams of ToF measurements and location tracking, a voxel-based reconstruction algorithm is implemented. Experimental results with gelatin phantom and ex vivo tissue have demonstrated the stability of our proposed method. Moreover, the results underscore the potential of this system as a complementary diagnostic modality, particularly in the context of diseases such as breast cancer.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Exploring the functional role of tRF-39-8HM2OSRNLNKSEKH9 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is associated with high morbidity and mortality globally. tRNA-derived small RNAs (tsRNAs) have emerged as potential targets for cancer treatment. However, the specific impact of tsRNAs on HCC remains undiscovered. In this study, we aimed to investigate the biological significance of tsRNAs in HCC. First, we screened the differentially expressed tsRNAs in HCC tissues and normal tissues adjacent to the tumor (NAT) using high-throughput sequencing and the results showed that tRF-39-8HM2OSRNLNKSEKH9 was more highly expressed in HCC tissues than NATs. Agarose gel electrophoresis (AGE), nuclear-cytoplasmic separation assays and fluorescence in situ hybridization (FISH) were employed to assess the characterization of tRF-39-8HM2OSRNLNKSEKH9. The relationship between the expression of tRF-39-8HM2OSRNLNKSEKH9 and clinicopathological parameters was evaluated and we found that it was positively associated with tumor size. The cell counting kit-8 (CCK8) assay, colony formation assay and EdU staining assay were employed to investigate the role of tRF-39-8HM2OSRNLNKSEKH9 in the proliferation of HCC cells. Additionally, transwell assays demonstrated that overexpression of tRF-39-8HM2OSRNLNKSEKH9 could accelerate cell migration capability. Taken together, tRF-39-8HM2OSRNLNKSEKH9 was highly expressed in HCC cells, serum and tissues, and it may play an oncogenic role in HCC cells through interacting with downstream mRNA targets.

A novel dual polarization multiplexing RoF system integrating optical fiber and FSO channel with AMI downlink signals.

Using dual polarization multiplexing alternate mark inversion (AMI) downlink signals, a novel radio over fiber (RoF) system integrating optical fiber and FSO channel is designed to adapt to applications in mountainous areas and other complex terrain areas. Optical heterodyne technology and self-mixing homodyne detection method are used to realize high sensitivity detection of the received signals after 25.1 km channel (including 1 km single-mode fiber and 100 m free space link) transmission. Moreover, polarization multiplexing technology is introduced to exponentially increase the transmission capacity of downlink signals. This scheme not only can be compatible with traditional optical fiber transmission systems, but also support the wireless optical access application of millimeter wave signals in RoF systems.

Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA. These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium. In this study, we found that phosphoglycerate mutase 5 (PGAM5) significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models. To address the role of PGAM5 in macrophages in OA, we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo. Mechanistically, we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways, whereas inhibited M2 polarization via STAT6-PPARγ pathway in murine bone marrow-derived macrophages. Furthermore, we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2 (DVL2) which resulted in the inhibition of ß-catenin and repolarization of M2 macrophages into M1 macrophages. Conditional knockout of both PGAM5 and ß-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice. Motivated by these findings, we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection, which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis. Collectively, these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

Melatonin serves as a novel treatment in bladder fibrosis through TGF-ß1/Smad and EMT.

BACKGROUND: Melatonin (MEL) is an indole amine molecule primarily produced in the pineal gland. Melatonin has been shown in numerous studies to have antifibrotic effects on the kidney, liver, and other organs. However, it is still unclear how melatonin works in bladder fibrosis. We explored how melatonin affects animals with bladder fibrosis and the underlying mechanisms. MATERIALS AND METHODS: MEL was used to treat human bladder smooth muscle cells (HBdSMCs) after they were stimulated with transforming growth factor-ß1 (TGF-ß1) in vitro. Proteomic analysis and bioinformatic analysis of the altered expression of these proteins were subsequently performed on HBdSMCs from the different processing methods. To construct an in vivo bladder fibrosis model, we injected protamine sulfate (PS) and lipopolysaccharide (LPS) twice a week into the rat bladder for six weeks. After two weeks of PS/LPS treatment, the mice in the treatment group were treated with MEL (20 mg/kg/d) for 4 weeks. Finally, we detected the expression of fibrosis markers from different perspectives. The TGF-ß1/Smad pathway and epithelial-mesenchymal transition (EMT) in cell and bladder tissues were also identified. Further proteomic analysis was also performed. RESULTS: In vitro, we found that TGF-ß1 treatment enhanced the expression of the fibrosis markers collagen III and α-SMA in HBdSMCs. E-cadherin expression decreased while the TGF-ß1/Smad pathway was activated. Vimentin and N-cadherin expression was also elevated at the same time. Similar findings were observed in the LPS group. After MEL treatment, the expression of collagen III and α-SMA decreased, the expression of E-cadherin increased, and the expression of vimentin and N-cadherin also decreased. According to our quantitative proteomics analysis, CCN1 and SQLE may be important proteins involved in the development of bladder fibrosis. MEL decreased the expression of these genes, leading to the relief of bladder fibrosis. Bioinformatics analysis revealed that the extracellular space structure related to metabolic pathways, actin filament binding, and stress fibers can serve as a pivotal focus in the management of fibrosis. CONCLUSION: Melatonin attenuates bladder fibrosis by blocking the TGF-ß1/Smad pathway and EMT. CCN1 appears to be a possible therapeutic target for bladder fibrosis.

The regulation of the pedunculopontine tegmental nucleus in sleep-wake states.

The pedunculopontine tegmental nucleus (PPTg) plays a vital role in sleep/wake states. There are three main kinds of heterogeneous neurons involved: cholinergic, glutamatergic, and gamma-aminobutyric acidergic (GABAergic) neurons. However, the precise roles of cholinergic, glutamatergic and GABAergic PPTg cell groups in regulating sleep-wake are unknown. Recent work suggests that the cholinergic, glutamatergic, and GABAergic neurons of the PPTg may activate the main arousal-promoting nucleus, thus exerting their wakefulness effects. We review the related projection pathways and functions of various neurons of the PPTg, especially the mechanisms of the PPTg in sleep-wake, thus providing new perspectives for research of sleep-wake mechanisms.