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.

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).

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.

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.

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).

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.

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.

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.

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.

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.

Contributions of SGK3 to transporter-related diseases.

Serum- and glucocorticoid-induced kinase 3 (SGK3), which is ubiquitously expressed in mammals, is regulated by estrogens and androgens. SGK3 is activated by insulin and growth factors through signaling pathways involving phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent kinase-1 (PDK-1), and mammalian target of rapamycin complex 2 (mTORC2). Activated SGK3 can activate ion channels (TRPV5/6, SOC, Kv1.3, Kv1.5, Kv7.1, BKCa, Kir2.1, Kir2.2, ENaC, Nav1.5, ClC-2, and ClC Ka), carriers and receptors (Npt2a, Npt2b, NHE3, GluR1, GluR6, SN1, EAAT1, EAAT2, EAAT4, EAAT5, SGLT1, SLC1A5, SLC6A19, SLC6A8, and NaDC1), and Na+/K+-ATPase, promoting the transportation of calcium, phosphorus, sodium, glucose, and neutral amino acids in the kidney and intestine, the absorption of potassium and neutral amino acids in the renal tubules, the transportation of glutamate and glutamine in the nervous system, and the transportation of creatine. SGK3-sensitive transporters contribute to a variety of physiological and pathophysiological processes, such as maintaining calcium and phosphorus homeostasis, hydro-salinity balance and acid-base balance, cell proliferation, muscle action potential, cardiac and neural electrophysiological disturbances, bone density, intestinal nutrition absorption, immune function, and multiple substance metabolism. These processes are related to kidney stones, hypophosphorous rickets, multiple syndromes, arrhythmia, hypertension, heart failure, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, glaucoma, ataxia idiopathic deafness, and other diseases.

The Effect of Prebiotics and Oral Anti-Diabetic Agents on Gut Microbiome in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

Background: Nutritional interventions such as the use of prebiotics can promote eubiosis of gut microbiome and maintain glucose homeostasis in patients with type 2 diabetes (T2D). However, it would appear that results of the effects of prebiotics on the community of microbes in the gut are not consistent. Aim: To examine the effect of prebiotics and oral antidiabetic agents on gut microbiome in patients with T2D. Methods: The PRISMA Extension Statement for Systematic Reviews and Network Meta-analyses was used to conduct this review. Searches were carried out in EMBASE, EBSCO-host databases, Google Scholar and the reference lists of articles for studies that are relevant to the research question, from database inception to 15 August 2022. The search strategy was based on PICOS framework. Network Meta-analysis which allows the estimation of relative treatment effects by combing both direct trial evidence (e.g., treatment A vs. treatment B) and indirect evidence was conducted. Furthermore, pairwise meta-analysis was also carried out to estimate effect sizes based on head-to-head comparisons of treatments and/or control conditions. Results: Findings of the Network meta-analysis revealed that prebiotics significantly reduced HbA1c compared with control and the SMD was −0.43 [95% CI, −0.77, −0.08; p = 0.02], whereas there was no significant difference (p > 0.05) between the other treatments and control. In addition, anti-diabetic agents including glipizide and metformin also reduced HbA1C, although these were not significantly different (p > 0.05) from control. While prebiotics promoted Bifidobacterium and Akkermansia, the improvements were not significantly different (p > 0.05) from control. On the other hand, metformin decreased the relative abundance of Bifidobacterium, but increased Lactobacillus and Akkermansia, although the differences were not significant (p > 0.05) compared with control. With respect to fasting blood glucose and BMI, the effects of prebiotics and oral antidiabetic agents did not differ significantly (p > 0.05) from controls. Conclusions: The findings of the systematic review and Network meta-analysis demonstrated prebiotics were significantly (p < 0.05) more effective in reducing HbA1c than control in patients with T2D. However, the effects of prebiotics and oral antidiabetic agents did not differ significantly (p > 0.05) from the controls in relation to fasting blood glucose, post-prandial blood glucose, body mass index and the genera of gut bacteria examined. More studies are required to fully investigate the effects of prebiotics and oral antidiabetic agents in patients with T2D

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.

Greater Protection of Lower Dietary Carbohydrate to Fiber Ratio (CFR) against Poor Blood Pressure Control in Patients with Essential Hypertension: A Cross-Sectional Study.

(1) Background: Carbohydrate combined with dietary fiber (DF) applied as a surrogate marker of overall carbohydrate quality is a more essential determinant of cardiometabolic health. However, to date, no studies have applied this metric to analyze its associations with poor blood pressure control in hypertensive patients. (2) Methods: A cross-sectional design was implemented in one tertiary hospital and one community hospital in China. Using Feihua Nutrition Software to analyze participants' two-day dietary log, the quantity of carbohydrate and fiber was obtained and the carbohydrate to fiber ratio (CFR) was calculated. The participants were divided into Q1, Q2, Q3, and Q4 groups by quartile method, from low to high according to CFR. The poor systolic and diastolic blood pressure (SBP and DBP) controls were defined as ≥140 mmHg and ≥90 mmHg, respectively. (3) Results: A convenience sample of 459 participants was included and the mean CFR was 29.6. Taking Q1 as reference, after adjusting for covariates, the CFR in Q4 was associated with higher poor SBP-controlled rate (OR, 4.374; 95% CI, 2.236-8.559). Taking Q2 as reference, after adjusting for covariates, the CFRs in Q3 and Q4 were associated with higher poor DBP-controlled rates [(OR = 1.964, 95% CI: 1.016-3.795) and (OR = 4.219, 95% CI: 2.132-8.637), respectively]. The CFR was the stronger protective determinant of SBP and DBP than DF or carbohydrate alone. (4) Conclusions: A higher CFR is a stronger risk factor for blood pressure (BP) control, and low CFR foods or a combination of corresponding food components, should be recommended in the dietary management of hypertensive patients.

The Renshen Chishao Decoction Could Ameliorate the Acute Lung Injury but Could Not Reduce the Neutrophil Extracellular Traps Formation.

The acute lung injury (ALI) causes severe pulmonary diseases, leading to a high mortality rate. The Renshen and Chishao have protective and anti-inflammatory effects against the ALI. To explore the protective effects of the Renshen Chishao (RC) decoction against the ALI, we established the lipopolysaccharide-indued ALI model and randomly divided the mice into seven groups: control group, ALI group, high-dose RC group, middle-dose RC group, low-dose RC group, middle-dose RC group + CXCR2 antagonist group, and ALI + CXCR2 antagonist group. We estimated the lung injury by the hematoxylin and eosin staining, the neutrophil extracellular traps (NETs) formations by the immunofluorescence colocalization and enzyme-linked immunosorbent assay (ELISA), and the CXCR2/CXCL2 pathway by the flow cytometry, ELISA, and real-time polymerase chain reaction. We conducted the high-throughput sequencing and enrichment analyses to explore the potential mechanisms. The results showed that the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung injury and inflammatory response but failed to reduce the circulating and lung tissue NETs formation and the blood neutrophil percent. The high-dose RC decoction increased the plasma CXCL2 level, but the RC decoction had no effects on the neutrophilic CXCR2 levels. Under the inhibition of the CXCR2, the middle-dose RC decoction still decreased the lung injury score but as yet had unobvious influence on the NETs formation. Other potential mechanisms of the RC decoction against the ALI involved the pathways of ribosome and coronavirus disease 2019 (COVID-19); the target genes of inflammatory factors, such as Ccl17, Cxcl17, Cd163, Cxcr5, and Il31ra, and lncRNAs; and the regulations of the respiratory cilia. In conclusion, the RC decoction pathologically ameliorated the lipopolysaccharide-induced lung inflammatory injury via upregulating the CXCL2/CXCR2 pathway but could not reduce the circulating or lung tissue NETs formation.

TOPK Activation Exerts Protective Effects on Cisplatin-induced Acute Kidney Injury.

OBJECTIVE: T-LAK-cell-originated protein kinase (TOPK), a PSD95-Disc large-ZO1 (PDZ) binding kinase (PBK), is a novel member of the mitogen-activated protein kinase (MAPK) family. Studies have shown that TOPK plays a critical role in the function of tumor cells, including apoptosis and mitosis. However, little is known on the effect of TOPK in cisplatin-induced acute kidney injury (CP-AKI). This study aimed to investigate the role and mechanism of TOPK in CP-AKI. METHODS: Cisplatin was administered to C57BL/6 mice and cultured kidney tubular epithelial cells (TECs) to establish the CP-AKI murine or cellular models. TECs were then stimulated with the specific inhibitor of TOPK OTS514 or transfected with the recombinant-activated plasmid TOPK-T9E to inhibit or activate TOPK. The TECs were treated with AKT inhibitor VIII following stimulation with OTS514 or cisplatin. Western blotting and flow cytometry were used to evaluate the cell cycle and apoptosis of TECs. RESULTS: The analysis revealed that the TOPK activity was significantly suppressed by cisplatin, both in vivo and in vitro. Furthermore, the pharmacological inhibition of TOPK by OTS514, a specific inhibitor of TOPK, exacerbated the cisplatin-induced cell cycle arrest in the G2/M phase and apoptosis of cultured TECs. Moreover, the TOPK activation via the TOPK-T9E plasmid transfection could partially reverse the cell cycle arrest at the G2/M phase and apoptosis of cisplatin-treated TECs. In addition, AKT/protein kinase B (PKB), as a TOPK target protein, was inhibited by cisplatin in cultured TECs. The pharmaceutical inhibition of AKT further aggravated the apoptosis of TECs induced by cisplatin or TOPK inhibition. TOPK systematically mediated the apoptosis via the AKT pathway in the CP-AKI cell model. CONCLUSION: These results indicate that TOPK activation protects against CP-AKI by ameliorating the G2/M cell cycle arrest and cell apoptosis.

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.

Identification of the key biochemical component contributing to disinfection byproducts in chlorinating algogenic organic matter.

Disinfection byproducts (DBPs) remains an ongoing issue because of their widespread occurrence and toxicity. Various organic substances in Algogenic organic matter (AOM) can produce DBPs in the chlorination process. To provide specific suggestions for the targeted removal of DBP precursors in AOM, the main biochemical components in AOM were qualitatively and quantitatively analyzed. An accurate model for predicting the DBP formation potentials (DBPFPs) of AOM was herein developed based on the dissolved organic carbon of the five main biochemical components in AOM and the DBPFPs of their corresponding surrogates. The contributions of each biochemical component to the three DBP species were evaluated, and the key components were identified. The results showed that lipids, proteins, carbohydrates, humic acid-like substances, and fulvic acid-like substances were the main biochemical components in AOM. Thereof, proteins (71.2 ± 2.1%) and carbohydrates (53.1 ± 2.1%) were the major contributor to the carbon content in intracellular organic matter and extracellular organic matter, respectively. The contribution results of biochemical components to the formation of DBPs showed that proteins were the key contributor to DBPs, suggesting that the targeted removal of proteins before the chlorination process would effectively reduce DBPs from AOM.