Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics.

Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs are also capable of promoting tissue regeneration through the secretion of various cytokines, factors, and extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate a range of biomolecules. These EVs have been found to mediate the therapeutic activities of donor cells by promoting the proliferation and migration of effector cells, facilitating angiogenesis, modulating immunity, and performing other specific functions in different tissues. Compared to the donor cells themselves, ADSC-EVs offer advantages such as fewer safety concerns and more convenient transportation and storage for clinical application. As a result, these EVs have received significant attention as cell-free therapeutic agents with potential future application in regenerative medicine. In this review, we focus on recent research progress regarding regenerative medical use of ADSC-EVs across various medical conditions, including wound healing, chronic limb ischemia, angiogenesis, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage regeneration, tendinopathy and tendon healing, peripheral nerve regeneration, and acute lung injury, among others. We also discuss the underlying mechanisms responsible for inducing these therapeutic effects. We believe that deciphering the biological properties, therapeutic effects, and underlying mechanisms associated with ADSC-EVs will provide a foundation for developing a novel therapeutic approach in regenerative medicine.

Automated segmentation and volume prediction in pediatric Wilms' tumor CT using nnu-net.

BACKGROUND: Radiologic volumetric evaluation of Wilms' tumor (WT) is an important indicator to guide treatment decisions. However, due to the heterogeneity of the tumors, radiologists have main-guard differences in diagnosis that can lead to misdiagnosis and poor treatment. The aim of this study was to explore whether CT-based outlining of WT foci can be automated using deep learning. METHODS: We included CT intravenous phase images of 105 patients with WT and double-blind outlining of lesions by two radiologists. Then, we trained an automatic segmentation model using nnUnet. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95) were used to assess the performance. Next, we optimized the automatic segmentation results based on the ratio of the three-dimensional diameter of the lesion to improve the performance of volumetric assessment. RESULTS: The DSC and HD95 was 0.83 ± 0.22 and 10.50 ± 8.98 mm. The absolute difference and percentage difference in tumor size was 72.27 ± 134.84 cm3 and 21.08% ± 30.46%. After optimization according to our method, it decreased to 40.22 ± 96.06 cm3 and 10.16% ± 9.70%. CONCLUSION: We introduce a novel method that enhances the accuracy of predicting WT volume by integrating AI automated outlining and 3D tumor diameters. This approach surpasses the accuracy of using AI outcomes alone and has the potential to enhance the clinical evaluation of pediatric patients with WT. By intertwining AI outcomes with clinical data, this method becomes more interpretive and offers promising applications beyond Wilms tumor, extending to other pediatric diseases.

The role of the gut microbiota in depressive-like behavior induced by chlorpyrifos in mice.

Chlorpyrifos (CPF) is associated with depression, cognitive dysfunction, and other neurological disorders. Increasing evidence has suggested that the gut microbiota plays a vital role in regulating the development of depression. However, it is unknown whether gut microbiota is associated with CPF-related depression. This study aimed to explore the effect of CPF on depressive-like behavior in mice and investigated the role of gut microbiota in this behavior. In our study, we selected fifty male C57BL/6 J mice for the model and subjected them to CPF poisoning by gavage for 14 days. The depressive-like behaviors of mice were assessed by the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Furthermore, we selected the high-dose group (CPF10) with obvious changes in depressive-like behaviors for the hippocampus and colon histopathological analysis, examined the changes in the gut microbiota by 16 S rRNA sequencing, screened the different microbiota among groups by linear discriminant analysis effect size (LEfSe), analyzed the correlation between intestinal bacteria and depression-like behavior indicators by Spearman analysis, and evaluated the predictive ability of different bacteria to CPF-induced depressive-like behavior using the receiver operator characteristic (ROC) curve. The results showed that CPF caused depressive-like behaviors with pathological changes in the hippocampus and colon. CPF induced changes in gut microbiota, including 49 differential bacteria. Among the top 10 abundant bacteria, Actinobacteria and Deferribacteres were increased, and Cyanobacteria, Patescibacteria and Verrucomicrobia were decreased at the phylum level. Muribaculum, Ruminococcaceae.UCG.014 and uncultured Bacteroides bacterium were decreased at the genus level. Correlation analysis demonstrated that 18 differentially abundant bacteria were correlated with CPF-induced depression. ROC curves revealed that Deferribacteres, Mucispirillum, Rikenella and GCA900066575 are potential biomarkers for depression caused by CPF. These findings will provide an experimental basis for the neurological health of the pesticide-exposed population.

Impacts of hydraulic conditions on microplastics biofilm development, shear stresses distribution, and microbial community structures in drinking water distribution pipes.

Both microplastic and biofilm are contamination sources in drinking water, but their integrated impacts on water quality have been rarely studied, especially in drinking water distribution pipes with complex hydraulic conditions. This study explored the impacts of hydraulic conditions (0-2 m/s) on microplastic biofilm (MP-BM) development, shear stresses distribution, and microbial community structures. The research was conducted for two weeks using a pilot test device to simulate practical water pipes. The following were the primary conclusions: (1) According to morphology analysis, clusters (>5 µm) significantly increased in the plastisphere when the flow velocity ranged from 0.55 m/s to 0.95 m/s, and average size of clusters decreased when the flow velocity ranged from 1.14 m/s to 1.40 m/s (2) Characteristics of MP-BM impact shear stress on both plastisphere and pipe wall biofilm. Shear stresses were positively correlated with flow velocity, number of MP-BM, and size of MP-BM, while negatively correlated with diameters of pipes. (3) 31 genera changed strictly and monotonously with the fluid velocity, accounting for 15.42%. Opportunistic pathogens in MP-BM such as Sediminibacterium, Curvibacter, and Flavobacterium were more sensitive to hydraulic conditions. Moreover, microplastics (<100 µm) deserve more attention to avoid human ingestion and to prevent mechanical damage and bio-chemical risks.

[Mechanism of Atractylodes macrocephala against Alzheimer's disease via regulating lysophagy based on LKB1-AMPK-TFEB pathway].

Myloid beta(Aß) is produced by cleavage of amyloid precursor protein(APP), which is a main reason for Alzheimer's disease(AD) occurrence and development. This study preliminarily investigated the mechanism of Atractylodes macrocephala(AM) against AD based on LKB1-AMPK-TFEB pathway. The effect of AM on memory ability of AD transgenic Caenorhabditis elegans CL2241 was detected, and then the APP plasmid was transiently transferred to mouse neuroblastoma(N2 a) cells in vitro. The mice were divided into the blank control group, APP group(model group), positive control group(100 µmol·L~(-1) rapamycin), and AM low-, medium-and high-dose groups(100, 200 and 300 µg·mL~(-1)). The content of Aß_(1-42) in cell medium, the protein level of APP, the fluorescence intensity of APP, the transcriptional activity of transcription factor EB(TFEB), the activity of lysosomes in autophagy, and autophagy flux were determined by enzyme-linked immunosorbent assay(ELISA), Western blot, fluorescence microscope, luciferase reporter gene assay, RLuc-LC3 wt/RLuc-LC3 G120 A, and mRFP-GFP-LC3, respectively. The protein expression of TFEB, LC3Ⅱ, LC3Ⅰ, LAMP2, Beclin1, LKB1, p-AMPK and p-ACC was detected by Western blot. Immunofluorescence and reverse transcription-polymerase chain reaction(RT-PCR) were used to detect the fluorescence intensity of TFEB and the mRNA expression of TFEB and downstream target genes, respectively. The results showed that AM reduced the chemotactic index of transgenic C. elegans CL2241, and decreased the content of Aß in the supernatant of cell culture medium at different concentrations. In addition, AM lowered the protein level of APP and the fluorescence intensity of APP in a dose-dependent manner. Transcriptional activity of TFEB and fluorescence intensity of mRFP-GFP-LC3 plasmid were enhanced after AM treatment, and the value of RLuc-LC3 wt/RLuc-LC3 G120 A was reduced. AM promoted the protein levels of TFEB, LAMP2 and Beclin1 at different concentrations, and increased the protein expression ratio of LC3Ⅱ/LC3Ⅰ in a dose-dependent manner. Immunofluorescence results revealed that AM improved the fluorescence intensity and nuclear expression of TFEB, and RT-PCR results indicated that AM of various concentrations elevated the mRNA expression of TFEB in APP transfected N2 a cells and promoted the transcription level of LAMP2 in a dose-dependent manner, and high-concentration AM also increased the mRNA levels of LC3 and P62. The protein levels of LKB1, p-AMPK and p-ACC were elevated by AM of different concentrations. In summary, AM regulating lysophagy and degrading APP are related to the activation of LKB1-AMPK-TFEB pathway.

Regional assemblages shaped by historical and contemporary factors: Evidence from a species-rich insect group.

Understanding diversity patterns requires accounting for the roles of both historical and contemporary factors in the assembly of communities. Here, we compared diversity patterns of two moth assemblages sampled from Taihang and Yanshan mountains in Northern China and performed ancestral range reconstructions using the Multi-State Speciation and Extinction model, to track the origins of these patterns. Further, we estimated diversification rates of the two moth assemblages and explored the effects of contemporary ecological factors. From 7,788 specimens we identified 835 species belonging to 23 families, using both DNA barcode analysis and morphology. Moths in Yanshan mountains showed higher species diversity than in Taihang mountains. Ancestral range analysis indicated Yanshan as the origin, with significant historical dispersals from Yanshan to Taihang. Asymmetrical diversification, population expansion, along with frequent and considerable gene flow were detected between communities. Moreover, dispersal limitation or the joint effect of environment filtering and dispersal limitation were inferred as main driving forces shaping current diversity patterns. In summary, we demonstrate that a multiscale (community, population and species level) analysis incorporating both historical and contemporary factors can be useful in delineating factors contributing to community assembly and patterning in diversity.

The impact of dietary fiber and probiotics in infectious diseases.

Although antibiotics are commonly used to treat infectious diseases, emergence of antibiotic resistant strains highlights the necessity for developing novel alternative approaches. Meanwhile, clinically, antibiotics can destroy the gut microbes balance, which is not conducive to the recovery of infectious disorders. As a result, recent studies have begun to explore potential prevention and treatment methods for infectious diseases, starting with more readily available dietary fiber and probiotics. Moreover, researches have shown the personalized nature of host responses to dietary fiber intervention, with outcomes being dependent on individual pre-treatment gut microbes. In this review, we will focus on the roles of dietary fiber and probiotics on infectious diseases, how probiotics and dietary fiber work on infectious diseases and then explore their mechanisms, so as to guide clinical consideration of new therapies for infectious diseases.

Functional Teas from the Stems of Penthorum chinense Pursh.: Phenolic Constituents, Antioxidant and Hepatoprotective Activity.

Penthorum chinense Pursh (PCP), a medicinal and edible plant, is traditionally used for liver protection and treatment of liver diseases. In this study, we compared the differences of composition and activity of flowers, stems and leaves of PCP to select a bioactive part. The stems of PCP with stronger antioxidant activity (6.25-100 µg/mL) and lower cytotoxicity (25-200 µg/mL) than the flowers and leaves were a better bioactive part. Then the chemical composition and hepatoprotective effects of an aqueous extract and an 70% ethanolic extract made with stems of PCP were investigated. We found that the 70% ethanolic extract enriched more polyphenols and flavonoids and possessed significantly stronger hepatoprotective activity than the aqueous extract in the dose range of 25-200 µg/mL, which indicated that 70% ethanol is the better solvent of PCP in extraction technology. Moreover, ethyl acetate extract of stems of PCP (PSE) was used to evaluate the hepatoprotective ability of PCP against oxidative damage using an in vitro model of a normal rat's liver cell (BRL-3A). Besides, 12 phenolic compounds were identified from PSE by ultra-performance liquid chromatography followed by electrospray ionization mass spectrometry (UPLC-ESI-MS). Obtained results strongly support the traditional use of PCP and prove stems of PCP to be an important source of bioactive compounds associated with hepatoprotective activity.

Comparative Study of Graphene Hydrogels and Aerogels Reveals the Important Role of Buried Water in Pollutant Adsorption.

Water as the universal solvent has well-demonstrated its ability to dissolve many substances, but buried water inside different nanoporous materials always exhibits some unusual behaviors. Herein, 3D porous graphene hydrogel (GH) is developed as a super-adsorbent to remove different pollutants (antibiotics, dyes, and heavy ions) for water purification. Due to its highly porous structure and high content of water, GH also demonstrated its super adsorption capacity for adsorbing and removing different pollutants (antibiotics, dyes, and heavy ions) as compared to conventional graphene aerogel (GA). More fundamentally, the buried-water enhanced adsorption mechanism was proposed and demonstrated, such that buried water in GH plays the combinatorial roles as (1) supporting media, (2) transport nanochannels, and (3) hydrogen bondings in promoting pollutant adsorption. In parallel, molecular dynamics simulations further confirm that buried water in GH has the stronger interaction with pollutants via hydrogen bonds than other buried alcohols. GH integrates the merit of both graphene (e.g., fine chemical resistance and excellent mechanical property) and hydrogel (e.g., high water content, porous structure, and simple solution-based processability and scalability), giving it promising potential for environmental applications.

HSCCC Separation of the Two Iridoid Glycosides and Three Phenolic Compounds from Veronica ciliata and Their in Vitro Antioxidant and Anti-Hepatocarcinoma Activities.

Five main compounds, including two iridoid glycosides (catalposide, verproside) and three phenolic compounds (luteolin, 4-hydroxy benzoic acid, 3,4-dihydroxy benzoic acid), were separated and prepared from the crude extract of Veronica ciliata by high-speed countercurrent chromatography. n-Hexane/n-butanol/water (1.5:5:5, v/v/v) was used for the separation of catalposide and verproside. n-Hexane/n-butanol/water (3:2:5, v/v/v) was used for the separation of luteolin, 4-hydroxy benzoic acid and 3,4-dihydroxy benzoic acid. The head-to-tail elution mode was used with a flow rate of 5.0 mL/min and a rotary speed of 800 rpm. Finally, a total of 1.28 mg luteolin, 6 mg 4-hydroxy benzoic acid, 2 mg 3,4-dihydroxy benzoic acid, 2 mg verproside and 10 mg catalposide with purities of 98%, 99.1%, 99.5%, 99.8% and 99%, respectively, were obtained from 200 mg of crude extract. In addition, their structure was identified using MS, ¹H-NMR and (13)C-NMR. To the best of our knowledge, this is the first report of the separation and purification of iridoid glycosides and phenolic compounds from V. ciliata by high-speed countercurrent chromatography (HSCCC). Among these compounds, luteolin, 4-hydroxy benzoic acid and 3,4-dihydroxy benzoic acid were separated from V. ciliata Fisch. for the first time. The results of the antioxidant activity show that protocatechuic acid and luteolin have strong antioxidant activity compared to 2,6-di-tert-butyl-4-methylphenol (BHT) and vitamin C (Vc). Five compounds also exhibited strong anti-hepatocarcinoma activities.

An unexpected fluctuating reactivity for odd and even carbon numbers in the TiO2-based photocatalytic decarboxylation of C2-C6 dicarboxylic acids.

The degradation behaviours of five straight-chain dicarboxylic acids (from ethanedioic acid to hexanedioic acid) were compared in aqueous TiO2-based photocatalysis. When all other conditions were identical, the degradation rates were found to fluctuate regularly with the parity of the number of carbon atoms. Dicarboxylic acids with an even number of carbon atoms (e-DAs) always degraded more slowly than those acids with an odd number of carbon atoms (o-DAs). This unusual fluctuation in the reactivity for the degradation of dicarboxylic acids by TiO2-based photocatalysis is very closely related to the different pre-coordination modes of the acids with the photocatalyst. Attenuated total reflection FTIR (ATR-FTIR) of e-DAs labelled with (13)C showed that both carboxyl groups of the acid coordinate to TiO2 through bidentate chelating forms. In contrast, only one carboxyl group of the o-DAs coordinated to TiO2 in a bidentate chelating manner, whereas the other formed a monodentate binding linkage. The bidentate chelating form with bilateral symmetric coordination did not favour degradation. Isotope-labelling experiments were performed with (18)O2 to observe the different ways in which incorporated oxygen entered the initial decarboxylated products of e- and o-DAs. For the degradation of butanedioic acid, (45.9±0.5) % of the oxygen in the formed propanedioic acid came from H2O, whereas for pentanedioic acid, (97.4±0.2) % of the oxygen in the formed butanedioic acid came from H2O. Our results demonstrate that in TiO2-based photocatalysis, the reactivity of active species, such as ·OH/h(vb)(+), is far from non-selective and that the attacks of these active species on organic substrates are significantly affected by the coordination patterns of the substrates on the TiO2 surface.

[The synergistic effect of lidamycin and rituximab on human B cell lymphoma].

This study aimed to investigate the synergistic effect of lidamycin (LDM) and rituximab on human B cell lymphoma Ramos cells. Cell proliferation was measured using MTS assay, cell apoptosis was analyzed by Annexin V-FITC/PI assay, the expression of apoptosis related proteins was analyzed by Western blotting, and the in vivo lymphoma inhibition was verified using BALB/c mice inoculated via tail vein using Ramos cells which stably expressed pEGFP-N1 plasmid. The results showed that, after the pretreatment with rituximab for 48 h, rituximab and LDM showed significantly synergistic effects on cell proliferation. Cells in combined treatment group had a higher apoptosis rate than that in LDM treatment group. Compared with the LDM treatment group, the expression of apoptosis-related proteins such as Cleaved caspase-3, Cleaved caspase-7, Cleaved caspase-9 and Cleaved PARP in combined treatment groups increased, and expression of cIAP-2 and Bcl-2 decreased. The result of in vivo experiment showed that, in the combined treatment group, the survival time of BALB/c mice was significantly longer than the mice in control group and LDM treatment group, and the degree of tumor accumulation and metastasis to lymph nodes and spleen was lower.

Progress about the fibro-adipose vascular anomaly: A review.

Fibro-adipose vascular anomaly (FAVA) is a rare and complex vascular malformation associated with persistent pain, limb contracture, and even restriction of activity. However, the pathophysiology of FAVA remains unclear. Although FAVA is a benign vascular malformation, it is highly misdiagnosed and often thus undergoing repeated surgical resection and interventional sclerotherapy, resulting in worsening of symptoms and irreversible dysfunction. Therefore, aggressive diagnosis and treatment are essential. There are several different treatment options for FAVA, including surgical resection, sclerotherapy, cryoablation, drug therapy, and physical therapy. This article reviews the clinical manifestations, pathological features, pathogenesis, and treatment methods of FAVA.

Aloe-emodin alleviates cerebral ischemia-reperfusion injury by regulating microglial polarization and pyroptosis through inhibition of NLRP3 inflammasome activation.

BACKGROUND: Microglial activation plays a crucial role in injury and repair after cerebral ischemia, and microglial pyroptosis exacerbates ischemic injury. NOD-like receptor protein 3 (NLRP3) inflammasome activation has an important role in microglial polarization and pyroptosis. Aloe-emodin (AE) is a natural anthraquinone compound originated from rhubarb and aloe. It exerts antioxidative and anti-apoptotic effects during cerebral ischemia/reperfusion (I/R) injury. However, whether AE affects microglial polarization, pyroptosis, and NLRP3 inflammasome activation remains unknown. PURPOSE: This study aimed to explore the effects of AE on microglial polarization, pyroptosis, and NLRP3 inflammasome activation in the cerebral infarction area after I/R. METHODS: The transient middle cerebral artery occlusion (tMCAO) and oxygen-glucose deprivation/re-oxygenation (OGD/R) methods were used to create cerebral I/R models in vivo and in vitro, respectively. Neurological scores and triphenyl tetrazolium chloride and Nissl staining were used to assess the neuroprotective effects of AE. Immunofluorescence staining, quantitative polymerase chain reaction and western blot were applied to detect NLRP3 inflammasome activation and microglial polarization and pyroptosis levels after tMCAO or OGD/R. Cell viability and levels of interleukin (IL)-18 and IL-1ß were measured. Finally, MCC950 (an NLRP3-specific inhibitor) was used to evaluate whether AE affected microglial polarization and pyroptosis by regulating the activation of the NLRP3 inflammasome. RESULTS: AE improved neurological function scores and reduced the infarct area, brain edema rate, and Nissl-positive cell rate following I/R injury. It also showed a protective effect on BV-2 cells after OGD/R. AE inhibited microglial pyroptosis and induced M1 to M2 phenotype transformation and suppressed microglial NLRP3 inflammasome activation after tMCAO or OGD/R. The combined administration of AE and MCC950 had a synergistic effect on the inhibition of tMCAO- or OGD/R-induced NLRP3 inflammasome activation, which subsequently suppressed microglial pyroptosis and induced microglial phenotype transformation. CONCLUSION: AE exerts neuroprotective effects by regulating microglial polarization and pyroptosis through the inhibition of NLRP3 inflammasome activation after tMCAO or OGD/R. These findings provide new evidence of the molecular mechanisms underlying the neuroprotective effects of AE and may support the exploration of novel therapeutic strategies for cerebral ischemia.

Angiogenin-mediated tsRNAs control inflammation and metabolic disorder by regulating NLRP3 inflammasome.

The cellular stress response system in immune cells plays a crucial role in regulating the development of inflammatory diseases. In response to cellular damage or microbial infection, the assembly of the NLRP3 inflammasome induces pyroptosis and the release of inflammatory cytokines. Meanwhile, Angiogenin (Ang)-mediated transfer RNA-derived small RNAs (tsRNAs) promote cell survival under stressful conditions. While both tsRNAs and inflammasomes are induced under stress conditions, the interplay between these two systems and their implications in regulating inflammatory diseases remains poorly understood. In this study, it was demonstrated that Ang deficiency exacerbated sodium arsenite-induced activation of NLRP3 inflammasome and pyroptosis. Moreover, Ang-induced 5'-tsRNAs inhibited NLRP3 inflammasome activation and pyroptosis. Mechanistically, 5'-tsRNAs recruit DDX3X protein into stress granules (SGs), consequently inhibiting the interaction between DDX3X and NLRP3, thus leading to the suppression of NLRP3 inflammasome activation. Furthermore, in vivo results showed that Ang deficiency led to the downregulation of tsRNAs, ultimately leading to an exacerbation of NLRP3 inflammasome-dependent inflammation, including lipopolysaccharide-induced systemic inflammation and type-2 diabetes-related inflammation. Altogether, our study sheds a new light on the role of Ang-induced 5'-tsRNAs in regulating NLRP3 inflammasome activation via SGs, and highlights tsRNAs as a promising target for the treatment of NLRP3 inflammasome-related diseases.

Influential Signs of Dry Eye-Related Ocular Symptoms in Participants With Unstable Tear Film.

PURPOSE: The aim of this study was to investigate the factors influencing dry eye disease (DED)-related ocular symptoms in participants with short fluorescein tear break-up time (FTBUT). METHODS: This cross-sectional study included 82 participants with short FTBUT (<10 seconds). Examinations included Ocular Surface Disease Index (OSDI), FTBUT, average noninvasive tear break-up time (NIBUTave), lid wiper epitheliopathy, lipid layer thickness, blink rate, partial blink, tear meniscus height, and meibomian gland (MG) evaluation which included ratio of residual MG area (RMGA) and MG grade in tarsal plates. One-way analysis of variance was used to detect differences between symptomatic tear film instability group (FTBUT <5 s, OSDI ≥13), asymptomatic tear film instability group (FTBUT <5 s, OSDI <13), and control group (FTBUT ≥5 s, OSDI <13). A bivariate correlation, partial correlation, and multiple linear regression analyses were used to identify major factors. Only the right eye was included. RESULTS: Among the participants with FTBUT <5 seconds, symptomatic group showed less upper RMGA ( P < 0.001) and NIBUTave ( P = 0.010). OSDI was negatively associated with upper RMGA ( r = -0.450, P < 0.001) and NIBUTave ( r = -0.414, P = 0.001), and positively associated with upper MG grade ( r = 0.277, P = 0.027). Linear regression analysis showed that the upper RMGA significantly affected OSDI (B = -41.895, P = 0.001), while not significantly correlated with age, upper MG grade, and NIBUTave. CONCLUSIONS: The upper RMGA might be the main factor affecting DED-related discomfort in participants with unstable tear film, indicating an early ocular change in DED.

Value of cognitive fusion targeted and standard systematic transrectal prostate biopsy for prostate cancer diagnosis.

ABSTRACT: The aim of this study was to compare the accuracies of cognitive fusion-guided targeted biopsy (TB), systematic biopsy (SB), and combined TB+SB for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in males with lesions detected by magnetic resonance imaging (MRI). We conducted a retrospective analysis of individuals who underwent prostate biopsy at Peking University People's Hospital (Beijing, China), with an emphasis on patients with both transrectal TB and SB. The main objective was to determine the precisions of SB, TB, and TB+SB for diagnosing PCa and csPCa. We also evaluated the detection rates of TB, SB, TB+ipsilateral-SB (ipsi-SB), TB+contralateral-SB (contra-SB), and TB+SB for PCa and csPCa in patients with unilateral MRI lesions. We compared the diagnostic yields of the various biopsy schemes using the McNemar's test. A total of 180 patients were enrolled. The rates of PCa detection using TB, SB, and TB+SB were 52.8%, 62.2%, and 66.7%, respectively, and the corresponding rates for csPCa were 46.1%, 56.7%, and 58.3%, respectively. Among patients with unilateral MRI lesions, the PCa detection rates for TB, SB, TB+ipsi-SB, TB+contra-SB, and TB+SB were 53.3%, 64.8%, 65.6%, 61.5%, and 68.0%, respectively. TB+ipsi-SB detected 96.4% of PCa and 95.9% of csPCa cases. These findings suggest that the combination of TB+SB has better diagnostic accuracy compared with SB or TB alone. For patients with unilateral MRI lesions, the combination of TB+ipsi-SB may be suitable in clinical settings.

Polypyrrole-coated sodium manganate microspheres cathode for superior performance Sodium-ion batteries.

P2-Na0.67Mn0.67Ni0.33O2 is a promising cathode material for sodium ion batteries (SIBs) due to its low cost, high theoretical capacity, and non-toxicity. However, it still suffers from unsatisfactory cycling stability mainly incurred by the Jahn-Teller effect of Mn3+ and electrolyte decomposition on the electrode/electrolyte interface. Herein, the P2-Na0.67Ni0.33Mn0.67O2@PPy (NNMO@PPy) composite applied as cathode materials for SIBs is obtained by introducing conductive polypyrrole (PPy) as coating layer on the P2-Na0.67Ni0.33Mn0.67O2 (NNMO) microspheres. Numerous physical characterization methods indicate that the PPy layer was uniformly coated on the surface of NNMO microspheres without change in phase structure and morphology. The PPy coating layer can alleviate Mn dissolution and effectively suppress the side reactions between the electrolyte and electrode during cycling. The optimal NNMO@PPy-9 with 9 wt% PPy delivers a high capacity of 127.4 mAh/g at the current density at 150 mA g-1, an excellent cyclic stability with high capacity retention of 80.5 % after 300 cycles, and enhanced rate performance (169.3 mAh/g at 15 mA g-1 while 89.8 mAh/g at 600 mA g-1). Furthermore, hard carbon (-)//NNMO@PPy-9 (+) full cell delivers a high energy density of 305.1 Wh kg-1 and superior cycling stability with 88.2 % capacity retention after 150 cycles. In-situ X-ray diffraction experiment and electrochemical characterization verify the highly reversible structure evolution and robust P2-type phase structure of NNMO@PPy-9 for fast and stable Na+ diffusion. This effective strategy of using conductive PPy as a coating layer may provide a new insight to modify NNMO surface, improving the cycling stability and rate capability.

Alisol B regulates AMPK/mTOR/SREBPs via directly targeting VDAC1 to alleviate hyperlipidemia.

BACKGROUND: The occurrence of hyperlipidemia is significantly influenced by lipid synthesis, which is regulated by sterol regulatory element binding proteins (SREBPs), thus the development of drugs that inhibit lipid synthesis has become a popular treatment strategy for hyperlipidemia. Alisol B (ALB), a triterpenoid compound extracted from Alisma, has been reported to ameliorate no-nalcoholic steatohepatitis (NASH) and slow obesity. However, the effect of ALB on hyperlipidemia and mechanism are unclear. PURPOSE: To examine the therapeutic impact of ALB on hyperlipidemia whether it inhibits SREBPs to reduce lipid synthesis. STUDY DESIGN: HepG2, HL7702 cells, and C57BL/6J mice were used to explore the effect of ALB on hyperlipidemia and the molecular mechanism in vivo and in vitro. METHODS: Hyperlipidemia models were established using western diet (WD)-fed mice in vivo and oleic acid (OA)-induced hepatocytes in vitro. Western blot, real-time PCR and other biological methods verified that ALB regulated AMPK/mTOR/SREBPs to inhibit lipid synthesis. Cellular thermal shift assay (CETSA), molecular dynamics (MD), and ultrafiltration-LC/MS analysis were used to evaluate the binding of ALB to voltage-dependent anion channel protein-1 (VDAC1). RESULTS: ALB decreased TC, TG, LDL-c, and increased HDL-c in blood, thereby ameliorating liver damage. Gene set enrichment analysis (GSEA) indicated that ALB inhibited the biosynthesis of cholesterol and fatty acids. Consistently, ALB inhibited the protein expression of n-SREBPs and downstream genes. Mechanistically, the impact of ALB on SREBPs was dependent on the regulation of AMPK/mTOR, thereby impeding the transportation of SREBPs from endoplasmic reticulum (ER) to golgi apparatus (GA). Further investigations indicated that the activation of AMPK by ALB was independent on classical upstream CAMKK2 and LKB1. Instead, ALB resulted in a decrease in ATP levels and an increase in the ratios of ADP/ATP and AMP/ATP. CETSA, MD, and ultrafiltration-LC/MS analysis indicated that ALB interacted with VDAC1. Molecular docking revealed that ALB directly bound to VDAC1 by forming hydrogen bonds at the amino acid sites S196 and H184 in the ATP-binding region. Importantly, the thermal stabilization of ALB on VDAC1 was compromised when VDAC1 was mutated at S196 and H184, suggesting that these amino acids played a crucial role in the interaction. CONCLUSION: Our findings reveal that VDAC1 serves as the target of ALB, leading to the inhibition of lipid synthesis, presents potential target and candidate drugs for hyperlipidemia.

Exploring the anti-ferroptosis mechanism of Kai-Xin-San against Alzheimer's disease through integrating network pharmacology, bioinformatics, and experimental validation strategy in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai Xin San (KXS), first proposed by Sun Simiao during the Tang Dynasty, has been utilized to treat dementia by tonifying qi and dispersing phlegm. AIM OF THE STUDY: This study aimed to elucidate the mechanism by which KXS exerts its therapeutic effects on Alzheimer's disease (AD) by targeting ferroptosis, using a combination of network pharmacology, bioinformatics, and experimental validation strategies. MATERIALS AND METHODS: The active target sites and the further potential mechanisms of KXS in protecting against AD were investigated through molecular docking, molecular dynamics simulation, and network pharmacology, and combined with the validation of animal experiments. RESULTS: Computational and experimental findings provide the first indication that KXS significantly improves learning and memory defects and inhibits neuronal ferroptosis by repairing mitochondria damage and upregulating the protein expression of ferroptosis suppressor protein 1 (FSP1) in vivo APP/PS1 mice AD model. According to bioinformatics analysis, the mechanism by which KXS inhibits ferroptosis may involve SIRT1. KXS notably upregulated the mRNA and protein expression of SIRT1 in both vivo APP/PS1 mice and in vitro APP-overexpressed HT22 cells. Additionally, KXS inhibited ferroptosis induced by APP-overexpression in HT22 cells through activating the SIRT1-FSP1 signal pathway. CONCLUSIONS: Collectively, our findings suggest that KXS may inhibit neuronal ferroptosis through activating the SIRT1/FSP1 signaling pathway. This study reveals the scientific basis and underlying modern theory of replenishing qi and eliminating phlegm, which involves the inhibition of ferroptosis. Moreover, it highlights the potential application of SIRT1 or FSP1 activators in the treatment of AD and other ferroptosis-related diseases.