Prognostic Value of Sublingual Microcirculation in Sepsis: A Systematic Review and Meta-analysis.

Objectives: To investigate the relationship between sublingual microcirculation and the prognosis of sepsis. Data sources: The PubMed, Web of Science, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies published from January 2003 to November 2023. Study selection: Clinical studies examining sublingual microcirculation and the prognosis of sepsis were included. Data extraction: Sublingual microcirculation indices included the microvascular blood index (MFI), total vascular density (TVD), perfusion vascular density (PVD), perfusion vascular vessel (PPV), and heterogeneity index (HI). Prognostic outcomes included mortality and severity. Funnel plots and Egger's test were used to detect publication bias. The ability of the small vessel PPV (PPVs) to predict sepsis-related mortality was analyzed based on the summary receiver operating characteristic (SROC) curve, pooled sensitivity, and pooled specificity. Data synthesis: Twenty-five studies involving 1750 subjects were included. The TVD (95% CI 0.11-0.39), PVD (95% CI 0.42-0.88), PPV (95% CI 6.63-13.83), and MFI (95% CI 0.13-0.6) of the survival group were greater than those of the nonsurvival group. The HI in the survival group was lower than that in the nonsurvival group (95% CI -0.49 to -0.03). The TVD (95% CI 0.41-0.83), PVD (95% CI 0.83-1.17), PPV (95% CI 14.49-24.9), and MFI (95% CI 0.25-0.66) of the nonsevere group were greater than those of the severe group. Subgroup analysis revealed no significant difference in TVD between the survival group and the nonsurvival group in the small vessel subgroup. The area under the SROC curve (AUC) was 0.88. Conclusions: Sublingual microcirculation was worse among patients who died and patients with severe sepsis than among patients who survived and patients with nonsevere sepsis. PPV has a good predictive value for the mortality of sepsis patients. This study was recorded in PROSPERO (registration number: CRD42023486349).

The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis.

BACKGROUND: Platelet-rich plasma (PRP) is a therapeutic approach that is gaining attention for its potential in the treatment of poor ovarian response. This meta-analysis aimed to systematically review and analyze clinical studies to evaluate the impact of PRP on poor responders undergoing ovarian stimulation for IVF. METHODS: A comprehensive search was conducted in electronic databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify relevant studies published in English. The pooled data, such as pregnancy outcome, number of MII oocytes, number of transferable embryos, and ovarian reserve markers were analyzed using R version 4.2.3. RESULTS: A total of 10 trials were enrolled in the present meta-analysis. Following PRP treatment, live birth rate was found to be 16.6% (95% CI 8.8%-26.1%), while clinical pregnancy rate was observed to be 25.4% (95% CI 13.1%-39.9%). PRP pretreatment resulted in a higher number of MII oocytes (MD 1.073, 95% CI 0.720 to 1.427), a higher number of embryos (MD 0.946, 95% CI 0.569 to 1.323), a higher antral follicle count (MD 1.117; 95% CI 0.689 to 1.544), and the change of hormone levels. CONCLUSIONS: Among the studies evaluated in this review, PRP showed promising results in poor responder. Further research is required to clarify the potential role of PRP in female reproductive health.

What is the context? The incidence of poor ovarian response following ovarian stimulation ranges globally from 5.6% to 35.1%.Although various interventions have been implemented in patients with POR, there is a lack of empirical evidence demonstrating the superiority of any of these therapies over one another.Platelet-rich plasma, which is rich in growth factors that have been implicated in cellular growth, differentiation, angiogenesis, and tissue repair, is emerging as a promising therapeutic modality.Limited data determines the viability of PRP as an alternative therapy for POR patients, but further evidence is needed to quantify this effect.What is new? To the best of our knowledge, this is the first systematic review and meta-analysis that investigated the efficacy of PRP on women with POR, including ten trials and 876 patients.This review provides a comprehensive overview of the existing evidence on the utilization of PRP in poor responders, while also emphasizing the primary limitations in the literature and the necessity for future research based on evidence.What is the impact? Among the studies evaluated in this review, PRP showed a potential positive impact on the regulation of sex hormone levels, ovarian response, and pregnancy outcomes.

Simulated depolarization ratios for dust and smoke at laser wavelengths: implications for lidar application.

Polarization measurements have been widely used to detect aerosol properties by remote sensing in recent decades. To better understand the polarization characteristics of aerosols by lidar, the numerically exact T-matrix method was used to simulate the depolarization ratio (DR) of dust and smoke aerosols at typical laser wavelengths in this study. The results show that the DRs of dust and smoke aerosols have obviously different spectral dependences. Moreover, the ratio of DRs at two wavelengths has an obvious linear relationship with the microphysical properties of aerosols, including aspect ratio, effective radius and complex refractive index. At short wavelengths, we can use it to invert the absorption characteristics of particles, further improving the detection ability of lidar. Comparing the simulation results of different channels, DR, (color ratio) CR and (lidar ratio) LR have a good logarithmic fitting relationship at 532 nm and 1064 nm, which helps to classify the aerosol types. On this basis, a new inversion algorithm, "1ß+1α+2δ", was presented. By this algorithm, the backscattering coefficient (ß), extinction coefficient (α), DR (δ) at 532 nm and 1064 nm can be used to expand the range of inversion and compare lidar data with different configurations to obtain more extensive optical characteristics of aerosols. Our study enhances the application of laser remote sensing in aerosol observations more accurately.

Method for retrieving range-resolved aerosol microphysical properties from polarization lidar measurements.

Aerosol microphysical properties, such as volume concentration (VC) and effective radius (ER), are of great importance to evaluate their radiative forcing and impacts on climate change. However, range-resolved aerosol VC and ER still cannot be obtained by remote sensing currently except for the column-integrated one from sun-photometer observation. In this study, a retrieval method of range-resolved aerosol VC and ER is firstly proposed based on the partial least squares regression (PLSR) and deep neural networks (DNN), combining polarization lidar and collocated AERONET (AErosol RObotic NETwork) sun-photometer observations. The results show that the measurement of widely-used polarization lidar can be reasonably used to derive the aerosol VC and ER, with the determination coefficient (R2) of 0.89 (0.77) for VC (ER) by use of the DNN method. Moreover, it is proven that the lidar-based height-resolved VC and ER at near-surface are well consistent with independent observations of collocated Aerodynamic Particle Sizer (APS). Additionally, we found that there are significant diurnal and seasonal variations of aerosol VC and ER in the atmosphere at Semi-Arid Climate and Environment Observatory of Lanzhou University (SACOL). Compared with columnar ones from the sun-photometer observation, this study provides a reliable and practical way to obtain full-day range-resolved aerosol VC and ER from widely-used polarization lidar observation, even under cloud conditions. Moreover, this study also can be applied to long-term observations by current ground-based lidar networks and spaceborne CALIPSO lidar, aiming to further evaluate aerosol climatic effects more accurately.

Curcumin ameliorates focal segmental glomerulosclerosis by inhibiting apoptosis and oxidative stress in podocytes.

Focal segmental glomerulosclerosis (FSGS), a podocyte disease, is the leading cause of end-stage renal disease (ESRD). Nevertheless, the current effective treatment for FSGS is deficient. Curcumin (CUR) is a principal curcuminoid of turmeric, which is a member of the ginger family. Previous studies have shown that CUR has renoprotective effects. However, the mechanism of CUR in anti-FSGS is not clear. This study aimed to explore the mechanism of CUR against FSGS through a combination of network pharmacological methods and verification of experiments. The analysis identified 98 shared targets of CUR against FSGS, and these 98 targets formed a network of protein-protein interactions (PPI). Of these 98 targets, AKT1, TNF, IL-6, VEGFA, STAT3, MAPK3, HIF1A, CASP3, IL1B, and JUN were identified as the hub targets. Molecular docking suggested that the best binding to CUR is MAPK3 and AKT1. Apoptotic process and cell proliferation were identified as the main biological processes of CUR against FSGS by gene ontology (GO) analysis. The most enriched signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was the PI3K-AKT signaling pathway. Western blots and flow cytometry showed that CUR could inhibit adriamycin (ADR) induced apoptosis, oxidative stress damage, and attenuate podocyte epithelial-mesenchymal transition (EMT) by repressing the AKT signaling pathway. Collectively, our study demonstrates that CUR can attenuate apoptosis, oxidative stress damage, and EMT in FSGS in vitro. These results supply a compelling basis for future studies of CUR for the clinical treatment of FSGS.

Prognostic differences in sepsis caused by gram-negative bacteria and gram-positive bacteria: a systematic review and meta-analysis.

BACKGROUND: Bacteria are the main pathogens that cause sepsis. The pathogenic mechanisms of sepsis caused by gram-negative and gram-positive bacteria are completely different, and their prognostic differences in sepsis remain unclear. METHODS: The PubMed, Web of Science, Cochrane Library, and Embase databases were searched for Chinese and English studies (January 2003 to September 2023). Observational studies involving gram-negative (G (-))/gram-positive (G (+)) bacterial infection and the prognosis of sepsis were included. The stability of the results was evaluated by sensitivity analysis. Funnel plots and Egger tests were used to check whether there was publication bias. A meta-regression analysis was conducted on the results with high heterogeneity to identify the source of heterogeneity. A total of 6949 articles were retrieved from the database, and 45 studies involving 5586 subjects were included after screening according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-seven high-quality studies and 18 moderate-quality studies were identified according to the Newcastle‒Ottawa Scale score. There was no significant difference in the survival rate of sepsis caused by G (-) bacteria and G (+) bacteria (OR 0.95, 95% CI 0.70-1.28). Subgroup analysis according to survival follow-up time showed no significant difference. The serum concentrations of C-reactive protein (CRP) (SMD = 0.39, 95% CI 0.02-0.76), procalcitonin (SMD = 1.95, 95% CI 1.32-2.59) and tumor necrosis factor-alpha (TNF-α) (MD = 0.31, 95% CI 0.25-0.38) in the G (-) bacterial infection group were significantly higher than those in the G (+) bacterial infection group, but there was no significant difference in IL-6 (SMD = 1.33, 95% CI - 0.18-2.84) and WBC count (MD = - 0.15, 95% CI - 0.96-00.66). There were no significant differences between G (-) and G (+) bacteria in D dimer level, activated partial thromboplastin time, thrombin time, international normalized ratio, platelet count, length of stay or length of ICU stay. Sensitivity analysis of the above results indicated that the results were stable. CONCLUSION: The incidence of severe sepsis and the concentrations of inflammatory factors (CRP, PCT, TNF-α) in sepsis caused by G (-) bacteria were higher than those caused by G (+) bacteria. The two groups had no significant difference in survival rate, coagulation function, or hospital stay. The study was registered with PROSPERO (registration number: CRD42023465051).

Peripapillary vessel density correlates with visual field mean sensitivity in highly myopic eyes.

PURPOSE: To identify the global and regional distribution of peripapillary vessel density (pVD) and try to find out the relationships between pVD and the visual field mean sensitivity (VFMS) in healthy myopic eyes. DESIGN: Prospective cross-sectional study. METHODS: Two hundred and twenty-two participants (393 eyes) with myopia (myopic refractive error < - 0.5 diopters) from two clinical centers were recruited in this study and were divided into 4 groups according to the spherical equivalent (SE): Group1:- 0.5D ≥ SE > - 6.00D, Group2: - 6.00D ≥ SE > - 8.00D, Group3:- 8.00D ≥ SE > - 10.00D, Group4:SE ≤ -10.00D.The pVD assessed with optical coherence tomography angiography (OCTA) was quantified in 8 sectors. Peripapillary retinal nerve fibre layer (pRNFL) imaging was performed with SD-OCT. Visual field (VF) tests were performed with the 30-2 SITA standard program on the Humphrey 750i Visual Field Analyzer and were grouped into 8 regions that matched the structure. RESULTS: The pRNFL had no significant difference in all groups (p = 0.422). The average pVD were significantly lower in group 4 (47.61 ± 6.58) than in group 2 and 3 (51.49 ± 3.21, 50.48 ± 3.43 respectively) (p < 0.05). While both pVD in group2 and 3 were statistically lower than group1 (52.77 ± 2.86). The average VFMS was significantly lower in group 4 (901.85 ± 386.54) than other three groups (1169.15 ± 328.94, 1081.77 ± 338.83, 1076.89 ± 358.18, for group1,2,3 respectively). The pVD and VFMS were positively correlated in group3 (r = 0.184) and group4 (r = 0.476) (p < 0.05). Linear regression analysis demonstrated that VFMS were positively associated with pVD especially in temporal and nasal quadrants in myopic eyes. CONCLUSIONS: The pVD shows a significant positive correlation with VFMS in highly myopic eyes with SE ≤ - 8.00D. We suggest that pVD measurement by OCTA could be a sensitive and useful method for monitoring myopic functional change.

Classification of atmospheric aerosols and clouds by use of dual-polarization lidar measurements.

Accurate identification of aerosols and cloud from remote sensing observations is of importance for quantitatively evaluating their radiative forcing and related impacts. Even though polarization lidar has exhibited a unique advantage of classifying atmospheric aerosols and clouds over the past several decades, polarization measurements are often achieved at one wavelength (UV or VIS) using laser remote sensing. To better identify the types of aerosols and clouds, we developed a ground-based dual-polarization lidar system that can simultaneously detect polarization measurements at wavelengths of 355 nm and 532 nm. Our results show that the volume depolarization ratios (VDRs) at 355 nm and 532 nm markedly differ for typical types of aerosols and clouds in the atmosphere. For non-spherical particles, the ratio of VDRs at 532 nm and 355 nm are 2.87 ± 1.35 for ice cloud and 1.51 ± 0.29 for dust-dominated aerosols, respectively. However, for spherical particles, the ratios are 0.43 ± 0.26 for water cloud and 0.56 ± 0.05 for air pollutants. Consequently, we proposed a simple reliable method for classifying atmospheric aerosols and clouds from polarization measurements observed by the developed lidar system. The proposed method first distinguishes clouds from aerosols using a combination of the color ratio (CR, 532 nm/355 nm) and attenuated backscattering coefficients (ABC) at 532 nm. Then, subtypes of clouds and aerosols are identified based on the ratio of VDRs at 532 nm and 355 nm. The results showed that dual-polarization lidar measurements can remarkably improve the classification of atmospheric aerosols and clouds, compared with results using a traditional method. This study illustrates that more information on atmospheric aerosols and clouds can be obtained from polarization measurements at multiple wavelengths by active remote sensing.

Enhancing bile tolerance of Lactobacilli is involved in the hypolipidemic effects of liraglutide.

Liraglutide is an analog of human glucagon-like peptide-1 which play essential roles in regulation of glycolipid metabolism. To investigate role of lactic acid bacteria (LAB) in lipid-lowering effect of liraglutide, 40 mice were divided into normal food diet (NFD), high-fat food (HFD), 10.0 mg/kg/d simvastatin-treated HFD (SIM + HFD), 200 and 400 µg/kg/d liraglutide-treated HFD (LL + HFD and HL + HFD) groups for 5 weeks. We found that liraglutide could upregulate cholesterol 7α-hydroxylase (CYP7A1) and LDL-receptor (LDLR), whereas downregulate 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). Besides, liraglutide enhance abundance of lactobacillaceae in gut of hyperlipidemic mice and increase bile tolerance ability of LAB by upregulating bile salt hydrolases, and the lysate of liraglutide-sensitive LAB could also directly downregulate HMGCR, the key enzyme in cholesterol synthesis, and inhibit hepatocyte steatosis. These findings might provide new theoretical guidance for clinical application of liraglutide and research and development of antiobesity, hypolipidemic, and cholesterol-lowering drugs or functional foods.

Investigation of aerosol absorption with dual-polarization lidar observations.

Polarization lidar has been widely used in recent decades to observe the vertical structures of aerosols and clouds in the atmosphere. We developed a dual-polarization lidar system that can detect polarization measurements simultaneously at 355 nm and 532 nm. Dust events and haze episodes over northern China in 2014 were observed by the developed lidar. The results showed that the dust-dominated aerosol depolarization ratios at 532 nm were larger than those at 355 nm, but those of the air pollutants were smaller, indicating that this tool could provide a more accurate classification of aerosols. Moreover, we found a good relationship between the absorption coefficient of aerosols and the ratio of depolarization ratios at 532 nm and 355 nm for dust aerosols. Our results imply that aerosol absorption from polarization measurements may be determined by lidar at the ultraviolet and visible wavelengths.

Comparison of transthoracic echocardiography with computed tomography in evaluation of pulmonary veins.

BACKGROUND: Transesophageal echocardiography may be used to assess pulmonary veins for atrial fibrillation ablation. No study focused on the role of transthoracic echocardiography (TTE) in evaluating the diameter and anatomy of pulmonary veins. METHODS: Among 142 atrial fibrillation patients (57.7% men; mean age, 60.5) hospitalised for catheter ablation, we assessed pulmonary veins and compared the measurements by TTE with cardiac computed tomography (CT) before ablation. Among 17 patients who had follow-up examinations, the second measurements were also studied. RESULTS: TTE identified and determined the diameters of 140 (98.6%) right and 140 (98.6%) left superior PVs, and 136 (95.7%) right and 135 (95.1%) left inferior PVs. A separate middle PV ostia was identified in 14 out of the 22 patients (63.6%) for the right side and in 2 out of 4 (50.0%) for the left side. The PV diameters before ablation assessed by CT vs. TTE were 17.96 vs. 18.07 mm for right superior, 15.92 vs. 15.51 mm for right inferior, 18.54 vs. 18.42 mm for left superior, and 15.56 vs. 15.45 mm for left inferior vein. The paired differences between the assessments of CT and TTE were not significant (P ≥ 0.31) except for the right inferior vein with a CT-minus-TTE difference of 0.41 mm (P = 0.018). The follow-up PV diameters by both CT (P ≥ 0.069) and TTE (P ≥ 0.093) were not different from baseline measurements in the 17 patients who had follow-up measurements. CONCLUSIONS: With a better understanding of PV anatomy in TTE imaging, assessing PV diameters by non-invasive TTE is feasible. However, the clear identification of anatomic variation might still be challenging.

Evaluation of left atrial volume and function using single-beat real-time three-dimensional echocardiography in atrial fibrillation patients.

BACKGROUND: This study was aimed to evaluate the feasibility and accuracy of real-time three-dimensional echocardiography (RT-3DE) measurement of left atrial (LA) volume and function in comparison with two-dimensional echocardiography (2DE) measurements in atrial fibrillation (AF) patients. METHODS: A total of 50 pairs of AF patients and healthy controls were enrolled in this study. Indexed LA end-diastole volume (ILAEDV) and indexed LA end-systolic volume (ILAESV), as well as LA function indices such as segmental LA ejection fraction (LAEF), were assessed using 2DE Simpson's method and the RT-3DE method. RESULTS: The images showed that regional LA volume-time curves and LAEF were disordered in AF patients. ILAEDV and ILAESV were markedly increased and global LAEF was significantly decreased in AF patients compared with those in healthy controls (P < 0.01). No significant differences were found in ILAEDV, ILAESV, and LAEF levels as determined by the RT-3DE method or 2DE Simpson's method. Bland-Altman analysis showed that the two methods agreed well for measuring ILAEDV, ILAESV, and segmental LAEF. CONCLUSION: The RT-3DE method may be a feasible and accurate method for evaluating LA volume and function of AF patients in clinical practice.

[An improved software design of ultrasound bone densitometer].

In order to meet the requirements of ultrasound bone density measurement, we proposed a software solution to improve the accuracy and speed of measurement of bone mineral density of the ultrasound bone densitometer. We used a high-speed USB interface chip FT232H, along with a high-speed AD converter chip to calculate speed of sound (SOS), broadband ultrasound attenuation (BUA ) and other bone density parameters in the PC software. This solution improved the accuracy of the measurement data, reduced the measurement time and increased the quality of the displayed image. It is well concluded that the new software can greatly improve the accuracy and transmission speed of bone density measurement data through a high-speed USB interface and a software data processing technology.

Tumor Cell-Derived Exosomal Hybrid Nanosystems Loaded with Rhubarbic Acid and Tanshinone IIA for Sepsis Treatment.

Background: Sepsis continues to exert a significant impact on morbidity and mortality in clinical settings, with immunosuppression, multi-organ failure, and disruptions in gut microbiota being key features. Although rheinic acid and tanshinone IIA show promise in mitigating macrophage apoptosis in sepsis treatment, their precise targeting of macrophages remains limited. Additionally, the evaluation of intestinal flora changes following treatment, which plays a significant role in subsequent cytokine storms, has been overlooked. Leveraging the innate inflammation chemotaxis of tumor cell-derived exosomes allows for their rapid recognition and uptake by activated macrophages, facilitating phenotypic changes and harnessing anti-inflammatory effects. Methods: We extracted exosomes from H1299 cells using a precipitation method. Then we developed a tumor cell-derived exosomal hybrid nanosystem loaded with rhubarbic acid and tanshinone IIA (R+T/Lipo/EXO) for sepsis treatment. In vitro studies, we verify the anti-inflammatory effect and the mechanism of inhibiting cell apoptosis of nano drug delivery system. The anti-inflammatory effects, safety, and modulation of intestinal microbiota by the nanoformulations were further validated in the in vivo study. Results: Nanoformulation demonstrated enhanced macrophage internalization, reduced TNF-α expression, inhibited apoptosis, modulated intestinal flora, and alleviated immunosuppression. Conclusion: R+T/Lipo/EXO presents a promising approach using exosomal hybrid nanosystems for treating sepsis.

Nano-Proteolysis Targeting Chimeras (Nano-PROTACs) in Cancer Therapy.

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have the capability to induce specific protein degradation. While playing a revolutionary role in effectively degrading the protein of interest (POI), PROTACs encounter certain limitations that impede their clinical translation. These limitations encompass off-target effects, inadequate cell membrane permeability, and the hook effect. The advent of nanotechnology presents a promising avenue to surmount the challenges associated with conventional PROTACs. The utilization of nano-proteolysis targeting chimeras (nano-PROTACs) holds the potential to enhance specific tissue accumulation, augment membrane permeability, and enable controlled release. Consequently, this approach has the capacity to significantly enhance the controllable degradation of target proteins. Additionally, they enable a synergistic effect by combining with other therapeutic strategies. This review comprehensively summarizes the structural basis, advantages, and limitations of PROTACs. Furthermore, it highlights the latest advancements in nanosystems engineered for delivering PROTACs, as well as the development of nano-sized PROTACs employing nanocarriers as linkers. Moreover, it delves into the underlying principles of nanotechnology tailored specifically for PROTACs, alongside the current prospects of clinical research. In conclusion, the integration of nanotechnology into PROTACs harbors vast potential in enhancing the anti-tumor treatment response and expediting clinical translation.

SGK3 promotes vascular calcification via Pit-1 in chronic kidney disease.

Rationale: Vascular calcification (VC) is a life-threatening complication in patients with chronic kidney disease (CKD) caused mainly by hyperphosphatemia. However, the regulation of VC remains unclear despite extensive research. Although serum- and glucocorticoid-induced kinase 3 (SGK3) regulate the sodium-dependent phosphate cotransporters in the intestine and kidney, its effect on VC in CKD remains unknown. Additionally, type III sodium-dependent phosphate cotransporter-1 (Pit-1) plays a significant role in VC development induced by high phosphate in vascular smooth muscle cells (VSMCs). However, it remains unclear whether SGK3 regulates Pit-1 and how exactly SGK3 promotes VC in CKD via Pit-1 at the molecular level. Thus, we investigated the role of SGK3 in the certified outflow vein of arteriovenous fistulas (AVF) and aortas of uremic mice. Methods and Results: In our study, using uremic mice, we observed a significant upregulation of SGK3 and calcium deposition in certified outflow veins of the AVF and aortas, and the increase expression of SGK3 was positively correlated with calcium deposition in uremic aortas. In vitro, the downregulation of SGK3 reversed VSMCs calcification and phenotype switching induced by high phosphate. Mechanistically, SGK3 activation enhanced the mRNA transcription of Pit-1 through NF-κB, downregulated the ubiquitin-proteasome mediated degradation of Pit-1 via inhibiting the activity of neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2), an E3 ubiquitin ligase. Moreover, under high phosphate stimulation, the enhanced phosphate uptake induced by SGK3 activation was independent of the increased protein expression of Pit-1. Our co-immunoprecipitation and in vitro kinase assays confirmed that SGK3 interacts with Pit-1 through Thr468 in loop7, leading to enhanced phosphate uptake. Conclusion: Thus, it is justifiable to conclude that SGK3 promotes VC in CKD by enhancing the expression and activities of Pit-1, which indicate that SGK3 could be a therapeutic target for VC in CKD.

Gas-particle two-phase adsorption of toluene and ultrafine particles on activated carbon studied by molecular simulation.

Adsorption is regarded as the most reliable technology for gaseous pollutant removal. Activated carbon is a widely used adsorbent due to its good adsorption capacity and low price. However, substantial ultrafine particles (UFPs) in the air cannot be effectively removed even if a high-efficiency particulate air filter is located before the adsorption stage. The adhesion of UFPs to the porous surface of activated carbon affects the removal of gaseous pollutants and shortens its service life. So, we adopted molecular simulation to explore the gas-particle two-phase adsorption and analyze the effects of the properties of UFPs such as concentration, shape, size and chemical composition on the toluene adsorption. The parameters of equilibrium capacity, diffusion coefficient, adsorption site, radial distribution function, adsorption heat and energy distribution were used to evaluate the gas adsorption performance. The results showed that the equilibrium capacity of toluene was decreased by 16.51 % compared to that of only toluene adsorption at the toluene concentration of 1 ppb and UFPs concentration of 1.81 × 10-5/cm3. Compared with cubic and cylindrical particles, the particles in spheres were more likely to hinder the pore channels from reducing gas capacity. Larger UFPs in the selected particle size range (1-3 nm) had a greater impact. Carbon black UFPs themselves could adsorb toluene, so the amount of toluene adsorbed was not significantly decreased.

Exploring ß-glucan as a micro-nano system for oral delivery targeted the colon.

The critical role of oral colon-specific delivery systems (OCDDS) is important for delivering active agents to the colon and rectum specifically via the oral route. The use of micro/nanostructured OCDDS further improves drug stability, bioavailability, and retention time, leading to enhanced therapeutic effects. However, designing micro/nanoscale OCDDSs is challenging due to pH changes, enzymatic degradation, and systemic absorption and metabolism. Biodegradable natural polysaccharides are a promising solution to these problems, and ß-glucan is one of the most promising natural polysaccharides due to its unique structural features, conformational flexibility, and specific processing properties. This review covers the diverse chemical structures of ß-glucan, its benefits (biocompatibility, easy modification, and colon-specific degradation), and various ß-glucan-based micro/nanosized OCDDSs, as well as their drawbacks. The potential of ß-glucan offers exciting new opportunities for colon-specific drug delivery.

The role of the SGK3/TOPK signaling pathway in the transition from acute kidney injury to chronic kidney disease.

Introduction: Profibrotic phenotype of renal tubular epithelial cells (TECs) featured with epithelial to mesenchymal transition (EMT) and profibrotic factors secretion, and aberrant accumulation of CD206+ M2 macrophages are the key points in the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). Nevertheless, the underlying mechanisms involved remain incompletely understood. Serum and glucocorticoid-inducible kinase (SGK) is a serine/threonine protein kinase, required for intestinal nutrient transport and ion channels modulation. T-LAK-cell-originated protein kinase (TOPK) is a member of the mitogen activated protein kinase family, linked to cell cycle regulation. However, little is known about their roles in AKI-CKD transition. Methods: In this study, three models were constructed in C57BL/6 mice: low dose and multiple intraperitoneal injection of cisplatin, 5/6 nephrectomy and unilateral ureteral obstruction model. Rat renal tubular epithelial cells (NRK-52E) were dealt with cisplatin to induce profibrotic phenotype, while a mouse monocytic cell line (RAW264.7) were cultured with cisplatin or TGF-ß1 to induce M1 or M2 macrophage polarization respectively. And co-cultured NRK-52E and RAW264.7 through transwell plate to explore the interaction between them. The expression of SGK3 and TOPK phosphorylation were detected by immunohistochemistry, immunofluorescence and western blot analysis. Results: In vivo, the expression of SGK3 and p-TOPK were gradually inhibited in TECs, but enhanced in CD206+ M2 macrophages. In vitro, SGK3 inhibition aggravated epithelial to mesenchymal transition through reducing the phosphorylation state of TOPK, and controlling TGF-ß1 synthesis and secretion in TECs. However, SGK3/TOPK axis activation promoted CD206+ M2 macrophage polarization, which caused kidney fibrosis by mediating macrophage to myofibroblast transition (MMT). When co-cultured, the TGF-ß1 from profibrotic TECs evoked CD206+ M2 macrophage polarization and MMT, which could be attenuated by SGK3/TOPK axis inhibition in macrophages. Conversely, SGK3/TOPK signaling pathway activation in TECs could reverse CD206+ M2 macrophages aggravated EMT. Discussion: We revealed for the first time that SGK3 regulated TOPK phosphorylation to mediate TECs profibrotic phenotype, macrophage plasticity and the crosstalk between TECs and macrophages during AKI-CKD transition. Our results demonstrated the inverse effect of SGK3/TOPK signaling pathway in profibrotic TECs and CD206+ M2 macrophages polarization during the AKI-CKD transition.

Influence of the thermal-fluid behavior on the microstructure evolution during the process of selective laser melting of Ti6Al4V.

To account for the microstructure evolution corresponding to the changed scanning speed, the thermal-fluid dynamic model of the meltpool during the selective laser melting (SLM) process of Ti6Al4V was established by numerical method to study the thermal characteristics and the melt flow behavior. Results showed that increasing the laser scanning speed would result in a lower peak temperature but a higher heating and cooling rate on the specimen. Both the meltpool size and its duration were reduced with the increased laser scanning velocity. Typically, a waved solid/liquid interface was observed at the bottom of the rear part of the meltpool as the time elapsed, especially for a larger scanning velocity. The melt flow velocity had a magnitude of hundreds of millimeters per second and showed almost a linear decrease with the increased scanning speed. Except for the change in cooling rate, the variation in flow velocities of the liquid metal consequent to different laser scanning speeds may be another possible reason for the observed microstructure change. The final result suggests that the scanning velocity must be carefully tailored to obtain the optimized combination of process parameters for industrial application, allowing for its adverse influence on the microstructure morphology and thermal stress/deformation caused by higher values.