High-sensitivity C-reactive protein predicts microalbuminuria progression in essential hypertensive patients: a 3-year follow-up study.

OBJECTIVES: To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period. METHODS AND RESULTS: Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ±â€…9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group (n = 99, 50%), the group with baseline hs-CRP above the median (n = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) (P = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes (ß = 0.342; P < 0.001), baseline SBP (ß = 0.148; P = 0.02), and baseline log-transformed hs-CRP (ß = 0.169; P = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) (ß = -0.163; P = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes (ß = 0.359; P < 0.001) and baseline log-transformed hs-CRP (ß = 0.190; P = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups. CONCLUSION: Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria.

A TrmBL2-like transcription factor mediates the growth phase-dependent expression of halolysin SptA in a concentration-dependent manner in Natrinema gari J7-2.

To cope with a high-salinity environment, haloarchaea generally employ the twin-arginine translocation (Tat) pathway to transport secretory proteins across the cytoplasm membrane in a folded state, including Tat-dependent extracellular subtilases (halolysins) capable of autocatalytic activation. Some halolysins, such as SptA of Natrinema gari J7-2, are produced at late-log phase to prevent premature enzyme activation and proteolytic damage of cellular proteins in haloarchaea; however, the regulation mechanism for growth phase-dependent expression of halolysins remains largely unknown. In this study, a DNA-protein pull-down assay was performed to identify the proteins binding to the 5'-flanking sequence of sptA encoding halolysin SptA in strain J7-2, revealing a TrmBL2-like transcription factor (NgTrmBL2). The ΔtrmBL2 mutant of strain J7-2 showed a sharp decrease in the production of SptA, suggesting that NgTrmBL2 positively regulates sptA expression. The purified recombinant NgTrmBL2 mainly existed as a dimer although monomeric and higher-order oligomeric forms were detected by native-PAGE analysis. The results of electrophoretic mobility shift assays (EMSAs) showed that NgTrmBL2 binds to the 5'-flanking sequence of sptA in a non-specific and concentration-dependent manner and exhibits an increased DNA-binding affinity with the increase in KCl concentration. Moreover, we found that a distal cis-regulatory element embedded in the neighboring upstream gene negatively regulates trmBL2 expression and thus participates in the growth phase-dependent biosynthesis of halolysin SptA. IMPORTANCE: Extracellular proteases play important roles in nutrient metabolism, processing of functional proteins, and antagonism of haloarchaea, but no transcription factor involved in regulating the expression of haloaechaeal extracellular protease has been reported yet. Here we report that a TrmBL2-like transcription factor (NgTrmBL2) mediates the growth phase-dependent expression of an extracellular protease, halolysin SptA, of haloarchaeon Natrinema gari J7-2. In contrast to its hyperthermophilic archaeal homologs, which are generally considered to be global transcription repressors, NgTrmBL2 functions as a positive regulator for sptA expression. This study provides new clues about the transcriptional regulation mechanism of extracellular protease in haloarchaea and the functional diversity of archaeal TrmBL2.

Genome-Wide Methylation Analysis Reveals a KCNK3-Prominent Causal Cascade on Hypertension.

BACKGROUND: Despite advances in understanding hypertension's genetic structure, how noncoding genetic variants influence it remains unclear. Studying their interaction with DNA methylation is crucial to deciphering this complex disease's genetic mechanisms. METHODS: We investigated the genetic and epigenetic interplay in hypertension using whole-genome bisulfite sequencing. Methylation profiling in 918 males revealed allele-specific methylation and methylation quantitative trait loci. We engineered rs1275988T/C mutant mice using CRISPR/Cas9, bred them for homozygosity, and subjected them to a high-salt diet. Telemetry captured their cardiovascular metrics. Protein-DNA interactions were elucidated using DNA pull-downs, mass spectrometry, and Western blots. A wire myograph assessed vascular function, and analysis of the Kcnk3 gene methylation highlighted the mutation's role in hypertension. RESULTS: We discovered that DNA methylation-associated genetic effects, especially in non-CpG island and noncoding distal regulatory regions, significantly contribute to hypertension predisposition. We identified distinct methylation quantitative trait locus patterns in the hypertensive population and observed that the onset of hypertension is influenced by the transmission of genetic effects through the demethylation process. By evidence-driven prioritization and in vivo experiments, we unearthed rs1275988 in a cell type-specific enhancer as a notable hypertension causal variant, intensifying hypertension through the modulation of local DNA methylation and consequential alterations in Kcnk3 gene expression and vascular remodeling. When exposed to a high-salt diet, mice with the rs1275988C/C genotype exhibited exacerbated hypertension and significant vascular remodeling, underscored by increased aortic wall thickness. The C allele of rs1275988 was associated with elevated DNA methylation levels, driving down the expression of the Kcnk3 gene by attenuating Nr2f2 binding at the enhancer locus. CONCLUSIONS: Our research reveals new insights into the complex interplay between genetic variations and DNA methylation in hypertension. We underscore hypomethylation's potential in hypertension onset and identify rs1275988 as a causal variant in vascular remodeling. This work advances our understanding of hypertension's molecular mechanisms and encourages personalized health care strategies.

Epigenetic regulation of high light-induced anthocyanin biosynthesis by histone demethylase IBM1 in Arabidopsis.

In plant species, anthocyanin accumulation is specifically regulated by light signaling. Although the CONSTITUTIVELY PHOTOMORPHOGENIC1/SUPPRESSOR OF PHYA-105 (COP1/SPA) complex is known to control anthocyanin biosynthesis in response to light, the precise mechanism underlying this process remains largely unknown. Here, we report that Increase in BONSAI Methylation 1 (IBM1), a JmjC domain-containing histone demethylase, participates in the regulation of light-induced anthocyanin biosynthesis in Arabidopsis. The expression of IBM1 was induced by high light (HL) stress, and loss-of-function mutations in IBM1 led to accelerated anthocyanin accumulation under HL conditions. We further identified that IBM1 is directly associated with SPA1/3/4 chromatin in vivo to establish a hypomethylation status on H3K9 and DNA non-CG at these loci under HL, thereby releasing their expression. Genetic analysis showed that quadruple mutants of IBM1 and SPA1/3/4 resemble spa134 mutants. Overexpression of SPA1 in ibm1 mutants complements the mutant phenotype. Our results elucidate the significance and mechanism of IBM1 histone demethylase in the epigenetic regulation of anthocyanin biosynthesis in Arabidopsis under HL conditions.

Degradation of Bisphenol A by Nitrogen-Rich ZIF-8-Derived Carbon Materials-Activated Peroxymonosulfate.

Bisphenol A (BPA), representing a class of organic pollutants, finds extensive applications in the pharmaceutical industry. However, its widespread use poses a significant hazard to both ecosystem integrity and human health. Advanced oxidation processes (AOPs) based on peroxymonosulfate (PMS) via heterogeneous catalysts are frequently proposed for treating persistent pollutants. In this study, the degradation performance of BPA in an oxidation system of PMS activated by transition metal sites anchored nitrogen-doped carbonaceous substrate (M-N-C) materials was investigated. As heterogeneous catalysts targeting the activation of peroxymonosulfate (PMS), M-N-C materials emerge as promising contenders poised to overcome the limitations encountered with traditional carbon materials, which often exhibit insufficient activity in the PMS activation process. Nevertheless, the amalgamation of metal sites during the synthesis process presents a formidable challenge to the structural design of M-N-C. Herein, employing ZIF-8 as the precursor of carbonaceous support, metal ions can readily penetrate the cage structure of the substrate, and the N-rich linkers serve as effective ligands for anchoring metal cations, thereby overcoming the awkward limitation. The research results of this study indicate BPA in water matrix can be effectively removed in the M-N-C/PMS system, in which the obtained nitrogen-rich ZIF-8-derived Cu-N-C presented excellent activity and stability on the PMS activation, as well as the outstanding resistance towards the variation of environmental factors. Moreover, the biological toxicity of BPA and its degradation intermediates were investigated via the Toxicity Estimation Software Tool (T.E.S.T.) based on the ECOSAR system.

Synergistic adsorption and photocatalysis study of TiO2 and activated carbon composite.

The discharge of organic pollutants by the textile and dyeing industries presents an escalating threat to aquatic environments, necessitating the development of effective remediation strategies. This study introduces the utilization of graphite-like structured activated carbon (AC), derived from highland barley straw-a biomass unique to the Plateau regions of China, including Tibet, Qinghai, and Gansu-as a support material for the TiO2 catalyst. TiO2/AC composites with different TiO2 loadings were synthesized by ultrasonic impregnation. The TiO2/AC composites were found to be polycrystalline materials composed of anatase and rutile phases. The TiO2 nanoparticles are well-dispersed over the surface of the AC. The photocatalytic activity of these composites was evaluated through their capacity to degrade a methylene blue (MB) solution upon irradiation. It was observed that the inclusion of TiO2 increases the number of adsorption sites and active sites for methylene blue, with the photocatalytic activity being notably higher at a 3-wt% TiO2 loading, achieving a remarkable 99.6 % degradation efficiency for 100 mg/L MB within 100 min. The experimental kinetic data for the photocatalytic process follow the pseudo-first-order kinetic model. Furthermore, TiO2/AC retains high photocatalytic activity after five reaction cycles. This research provides valuable insights into the application of biomass-derived materials for the purification of water, offering a sustainable solution to both pollution and agricultural waste challenges in Plateau areas of China.

Photoionization and Dissociative Photoionization of Acetaldehyde in the 10.0-13.7†eV Range by Synchrotron Photoelectron Photoion Coincidence Spectroscopy.

Photoionization and dissociative photoionization of acetaldehyde (CH3CHO) in the 10.0-13.7 eV energy range are studied by using synchrotron radiation double imaging photoelectron photoion coincidence spectroscopy (i2PEPICO). The X2A' and A2A" electronic states of CH3CHO+ as well as the Franck-Condon gap region between these two states have been populated with several vibrational sequences and assigned in the high-resolution slow photoelectron spectrum (SPES). The adiabatic ionization energies (AIEs) of the X2A' and A2A" states are measured at 10.228±0.006 and 12.52±0.05 eV, respectively. The present results show that the X2A' state is a stable state while the A2A" state is fully dissociative to produce CH3CO+, CHO+ and CH4 + fragment ions. The 0 K appearance energies (AE0K) of CH3CO+ and CHO+ fragment ions are determined through the modeling of the breakdown diagram, i. e., AE0K(CH3CO+)=10.89±0.01 eV (including a reverse barrier of ~0.19 eV) and AE0K(CHO+)=11.54±0.05 eV. In addition, the dissociation mechanisms of CH3CHO+ including statistical dissociation, direct bond breaking and isomerization are discussed with the support of the calculated dissociation limits and transition state energies.

Intelligent Assist Office Blood Pressures (IOBP) versus awake ambulatory monitoring and conventional auscultatory office readings in Chinese primary medical institutions.

To practice standardized office blood pressure (OBP) measurement guidelines pragmatically, we developed an intelligent assisted OBP (IOBP) measurement system in the Chinese community, which can automatically obtain two or three BP values after a 5-min rest before the patients visit the doctor and transfer values to the community medical network in real time. We conducted a comparative study to investigate the agreement among IOBP, awake ambulatory BP (ABP), and conventional auscultatory OBP at different BP levels. Participants were divided into three groups according to BP, with 120/80 mmHg and 160/100 mmHg as the cut-off points. Attended IOBP, unattended IOBP, and auscultatory OBP were randomly measured before ABP monitoring. In total, 245 participants were included in the analysis. The mean systolic attended/unattended IOBP, auscultatory OBP, and awake ABP were 135.0, 136.7, 135.6, and 136.2 mmHg, respectively. Bland-Altman analysis revealed a bias of -1.1 and 0.5 mmHg for systolic attended/unattended IOBP compared with awake ABP in the overall sample. For auscultatory OBP, the bias was -0.4 (attended) and 1.2 mmHg (unattended). The discrepancy between the systolic attended/unattended IOBP and awake ABP was inconsistent at different BP levels. In Group 1 the values were -8.4 and -6.9 mmHg, whereas in Group 3, the values were 9.4 and 10.0 mmHg. BP measured using the IOBP measurement system was in accordance with awake ABP and conventional OBP, and can be a good choice in the Chinese community.

Feruloyl Glyceride Mitigates Tomato Postharvest Rot by Inhibiting Penicillium expansum Spore Germination and Enhancing Suberin Accumulation.

Postharvest rot, caused by Penicillium expansum, in tomatoes poses significant economic and health risks. Traditional control methods, such as the use of fungicides, raise concerns about pathogen resistance, food safety, and environmental impact. In search of sustainable alternatives, plant secondary metabolites, particularly phenolic compounds and their derivatives, have emerged as promising natural antimicrobials. Among these, feruloyl glyceride (FG), a water-soluble derivative of ferulic acid, stands out due to its antioxidant properties, antibacterial properties, and improved solubility. In this study, we provide evidence demonstrating FG is capable of inhibiting the spore germination of P. expansum and effectively reducing the incidence rate of Penicillium rot of tomatoes, without compromising quality. Electron microscopy observations combined with metabolite and transcriptomic analyses revealed that FG treatments resulted in enhanced suberin accumulation through promoting the expression of suberin synthesis related genes and, consequently, inhibited the growth and expansion of P. expansum on the fruits. This work sheds light on the mechanisms underlying FG's inhibitory effects, allowing its potential application as a natural and safe alternative to replace chemical fungicides for postharvest preservation.

Online quantification of nicotine in e-cigarette aerosols by vacuum ultraviolet photoionization mass spectrometry.

The growing popularity of e-cigarettes and the associated risks of nicotine addiction present a new challenge to global public health security. Measuring the nicotine levels in e-cigarette aerosols is essential to assess the safety of e-cigarettes. In this study, a rapid in situ method was developed for online quantification of nicotine in e-cigarette aerosols by using a homemade vacuum ultraviolet photoionization aerosol mass spectrometer (VUV-AMS). E-cigarette liquids with different nicotine concentrations were prepared to generate aerosols containing different levels of nicotine, which were employed as the calibration sources for nicotine quantification by VUV-AMS. The results showed that the mass concentration of nicotine in e-cigarette aerosols has a good linear relationship with its signal intensity in the mass spectrum, and the limits of detection and quantitation of nicotine by VUV-AMS were found to be 2.0 and 6.2 µg per puff respectively. Then the online method was utilized to measure five commercial e-cigarettes, and their nicotine yields were determined to be between 31 and 188 µg per puff with the nicotine fluxes from 7.7 to 70 µg s-1, agreeing with the results of the gas chromatography with a flame ionization detector (GC-FID). This study demonstrated the feasibility and advantages of VUV-AMS for quick quantification of nicotine in e-cigarette aerosols within seconds.

Structural and functional analyses of an L-asparaginase from Geobacillus thermopakistaniensis.

Genome sequence of Geobacillus thermopakistaniensis contains an open reading frame annotated as a type II L-asparaginase (ASNaseGt). Critical structural analysis disclosed that ASNaseGt might be a type I L-asparaginase. In order to determine whether it is a type I or type II L-asparaginase, we have performed the structural-functional characterization of the recombinant protein as well as analyzed the localization of ASNaseGt in G. thermopakistaniensis. ASNaseGt exhibited optimal activity at 52 °C and pH 9.5. There was a > 3-fold increase in activity in the presence of ß-mercaptoethanol. Apparent Vmax and Km values were 2735 U/mg and 0.35 mM, respectively. ASNaseGt displayed high thermostability with >80 % residual activity even after 6 h of incubation at 55 °C. Recombinant ASNaseGt existed in oligomeric form. Addition of ß-mercaptoethanol lowered the degree of oligomerization and displayed that tetrameric form was the most active, with a specific activity of 4300 U/mg. Under physiological conditions, ASNaseGt displayed >50 % of the optimal activity. Localization studies in G. thermopakistaniensis revealed that ASNaseGt is a cytosolic protein. Structural and functional characterization, and localization in G. thermopakistaniensis displayed that ASNaseGt is not a type II but a type I L-asparaginase.

Sustainable Electrochemical Activation of Self-Generated Persulfate for the Degradation of Endocrine Disruptors: Kinetics, Performances, and Mechanisms.

This study presents an electrolysis system utilizing a novel self-circulation process of sulfate (SO42-) and persulfate (S2O82-) ions based on a boron-doped diamond (BDD) anode and an activated carbon fiber (ACF) cathode, which is designed to enable electrochemical remediation of environmental contaminants with reduced use of chemical reagents and minimized residues. The production of S2O82- and hydrogen peroxide (H2O2) on the BDD anode and ACF cathode, respectively, is identified as the source of active radicals for the contaminant degradation. The initiator, sulfate, is identified by comparing the degradation efficiency in NaSO4 and NaNO3 electrolytes. Quenching experiments and electron paramagnetic resonance (EPR) spectroscopy confirmed that the SO4-· and ·OH generated on the ACF cathode are the main reactive radicals. A comparison of the degradation efficiency and the generated S2O82-/H2O2 of the divided/undivided electrolysis system is used to demonstrate the superiority of the synergistic effect between the BDD anode and ACF cathode. This work provides evidence of the effectiveness of the philosophy of "catalysis in lieu of supplementary chemical agents" and sheds light on the mechanism of the generation and transmission of reactive species in the BDD and ACF electrolysis system, thereby offering new perspectives for the design and optimization of electrolysis systems.

HtrAs are essential for the survival of the haloarchaeon Natrinema gari J7-2 in response to heat, high salinity, and toxic substances.

Bacterial and eukaryotic HtrAs can act as an extracytoplasmic protein quality control (PQC) system to help cells survive in stress conditions, but the functions of archaeal HtrAs remain unknown. Particularly, haloarchaea route most secretory proteins to the Tat pathway, enabling them to fold properly in well-controlled cytoplasm with cytosolic PQC systems before secretion. It is unclear whether HtrAs are required for haloarchaeal survival and stress response. The haloarchaeon Natrinema gari J7-2 encodes three Tat signal peptide-bearing HtrAs (NgHtrA, NgHtrB, and NgHtrC), and the signal peptides of NgHtrA and NgHtrC contain a lipobox. Here, the in vitro analysis reveals that the three HtrAs show different profiles of temperature-, salinity-, and metal ion-dependent proteolytic activities and could exhibit chaperone-like activities to prevent the aggregation of reduced lysozyme when their proteolytic activities are inhibited at low temperatures or the active site is disrupted. The gene deletion and complementation assays reveal that NgHtrA and NgHtrC are essential for the survival of strain J7-2 at elevated temperature and/or high salinity and contribute to the resistance of this haloarchaeon to zinc and inhibitory substances generated from tryptone. Mutational analysis shows that the lipobox mediates membrane anchoring of NgHtrA or NgHtrC, and both the membrane-anchored and free extracellular forms of the two enzymes are involved in the stress resistance of strain J7-2, depending on the stress conditions. Deletion of the gene encoding NgHtrB in strain J7-2 causes no obvious growth defect, but NgHtrB can functionally substitute for NgHtrA or NgHtrC under some conditions.IMPORTANCEHtrA-mediated protein quality control plays an important role in the removal of aberrant proteins in the extracytoplasmic space of living cells, and the action mechanisms of HtrAs have been extensively studied in bacteria and eukaryotes; however, information about the function of archaeal HtrAs is scarce. Our results demonstrate that three HtrAs of the haloarchaeon Natrinema gari J7-2 possess both proteolytic and chaperone-like activities, confirming that the bifunctional nature of HtrAs is conserved across all three domains of life. Moreover, we found that NgHtrA and NgHtrC are essential for the survival of strain J7-2 under stress conditions, while NgHtrB can serve as a substitute for the other two HtrAs under certain circumstances. This study provides the first biochemical and genetic evidence of the importance of HtrAs for the survival of haloarchaea in response to stresses.

Rational Design of Conjugated Acetylenic Polymers Enables a Two-Electron Water Oxidation Pathway for Enhanced Photosynthetic Hydrogen Peroxide Generation.

Herein, the design of conjugated acetylenic polymers (CAPs) featuring diverse spatial arrangements and intramolecular spacers of diacetylene moieties (─C≡C─C≡C─) for photocatalytic hydrogen peroxide (H2 O2 ) production from water and O2 , without the need for sacrificial agents, is presented. It is shown that the linear configuration of diacetylene moieties within conjugated acetylenic polymers (CAPs) induces a pronounced polarization of electron distribution, which imparts enhanced charge-carrier mobility when compared to CAPs' networks featuring cross-linked arrangements. Moreover, optimizing the intramolecular spacer between diacetylene moieties within the linear structure leads to the exceptional modulation of the band structures, specifically resulting in a downshifted valence band (VB) and rendering the two-electron water oxidation pathway thermodynamically feasible for H2 O2 production. Consequently, the optimized CAPs with a linear configuration (LCAP-2), featuring spatially separated reduction centers (benzene rings) and oxidation centers (diacetylene moieties), exhibit a remarkable H2 O2 yield rate of 920.1 µmol g-1 h-1 , superior than that of the linear LCAP-1 (593.2 µmol g-1 h-1 ) and the cross-linked CCAP (433.4 µmol g-1 h-1 ). The apparent quantum efficiency (AQE) and solar-to-chemical energy conversion (SCC) efficiency of LCAP-2 are calculated to be 9.1% (λ = 420 nm) and 0.59%, respectively, surpassing the performance of most previously reported conjugated polymers.

Atomically Dispersed Fe-N4 Site as a Conductive Bridge Enables Efficient and Stable Activation of Peroxymonosulfate: Active Site Renewal, Anti-Oxidative Capacity, and Pathway Alternation Mechanism.

Atomically dispersed metal sites anchored on nitrogen-doped carbonaceous substrates (M-NCs) have emerged as promising alternatives to conventional peroxymonosulfate (PMS) activators; however, the exact contribution of each site still remains elusive. Herein, isolated Fe-N4 active site-decorated three-dimensional NC substrates (FeSA-NC) via a micropore confinement strategy are fabricated to initiate PMS oxidation reaction, achieving a specific activity of 5.16 × 103 L·min-1·g-1 for the degradation of bisphenol A (BPA), which outperforms most of the state-of-the-art single-atom (SA) catalysts. Mechanism inquiry reveals enhanced chemisorption and electron transfer between PMS and FeSA-NC, enabling an inner electron shuttle mechanism in which Fe-N4 serves as a conductive bridge. The Fe-N4 sites reduce the energy barrier for the formation of SO5* and H*, thereby transforming the reaction pathway from directly adjacent electron transfer into reactive oxygen species (ROS)-dominated oxidation. Theoretical calculations and dynamic simulations reveal that the Fe-N4 sites induce facilitated desorption of reaction intermediates (PMS*/BPA*), which collectively contribute to the renewal of active sites and eventually enhance the catalytic durability. This work offers a reasonable interpretation for the important role of the Fe-N4 moiety in altering the activation mechanism and enhancing the antioxidative capacity of NC materials, which fundamentally furnishes theoretical support for SA material design.

Incidence, mortality and survival of transitional cell carcinoma in the urinary system: A population-based analysis.

The goal of this study is exploring the disparity of incidence, mortality and survival outcome among transitional cell carcinomas (TCCs) in the 4 parts of urinary system. This study comprehensively evaluates these disparities using the Surveillance, Epidemiology, and End Results (SEER) (2000-2018) database. According to the SEER database, the urinary tract is divided into 4 parts: urinary bladder, renal pelvis, ureter, and urethra. The joinpoint regression was used to analyze the secular trend of incidence and incidence-based mortality (IBM). The Kaplan-Meier method with the log-rank test is performed to evaluate survival outcomes. The bladder TCC has the highest age-adjusted incidence and mortality rate compared with TCC in other 3 locations. A slight decrease in incidence is shown in the both bladder and urethra TCCs during 2000-2018. The age-adjusted mortality rate similarly presents an initial increase among 4 locations TCCs at the beginning of study period. The survival curves demonstrate that patients with bladder TCCs have better overall survival (OS) and cancer-specific survival (CSS), whereas those with renal pelvis TCCs have the worse OS and CSS. In addition, patients with bladder TCC have the highest 1-year, 3-year, 5-year relative survival rate, and those with renal pelvis TCC have the lowest. These disparities are especially essential when we explore tumor characteristics and treatment, extrapolated from the literature on bladder TCC for upper tract urothelial carcinoma (UTUC). Notably, patients with bladder TCC especially for localized stage have better survival outcomes than those with UTUC.

Beam smoothing by introducing spatial dispersion for high-peak-power laser pulse compression.

Post-compression can effectively further improve the peak power of laser pulses by shortening the pulse duration. Which has been investigated in various ranges of energy and central wavelength. However, the spatial intensity profile of high-peak-power laser pulses is generally inhomogeneous due to pump lasers, imperfect optical components, and dust in the optical layout. In post-compression, the B-integral is proportional to intensity, and wavefront distortions are induced in the spectral broadening stage, leading to a decrease in focusing intensity. Moreover, the beam intensity may be strongly modulated and beam inhomogeneity will be intensified in this process, causing damage to optical components and limiting the achievement of high peak power enhancement. In this study, to address these challenges, the laser pulse is first smoothed by introducing spatial dispersion using prism pairs or asymmetric four-grating compressors, and then the smoothed pulse is used for post-compression. The simulation results indicate that this method can effectively remove hot spots from laser pulses and maintain high peak power enhancement in post-compression.

The ratio of alpha-calcitonin gene-related peptide to substance P is associated with the transition of bone metabolic states during aging and healing.

Alpha-calcitonin gene-related peptide (αCGRP) and substance P (SP) are functionally correlated sensory neuropeptides deeply involved in bone homeostasis. However, they are usually studied individually rather than as an organic whole. To figure out whether they are interdependent, we firstly recorded the real-time αCGRP and SP levels in aging bone and healing fracture, which revealed a moderate to high level of αCGRP coupled with a low αCGRP/SP ratio in an anabolic state, and a high level of αCGRP coupled with a high αCGRP/SP ratio in a catabolic state, suggesting the importance of αCGRP/SP ratio in driving aging and healing scenarios. During facture healing, increase in αCGRP/SP ratio by adding αCGRP led to better callus formation and faster callus remodeling, while simultaneous addition of αCGRP and SP resulted in hypertrophic callus and delayed remodeling. The characteristics in inflammation and osteoclast activation further confirmed the importance of high αCGRP/SP ratio during catabolic bone remodeling. In vitro assays using different mixtures of αCGRP-SP proved that the osteogenic potential of the mixtures depended mostly on αCGRP, while their effects on osteoclasts and neutrophils relied on both peptides. These results demonstrated that αCGRP and SP were spatiotemporally interdependent. The αCGRP/SP ratio may be more important than the dose of a single neuropeptide in managing age-related and trauma-related bone diseases.

A liquid chromatography-tandem mass spectrometry method for comprehensive determination of metabolites in the purine pathway of rat plasma and its application in anti-gout effects of Lycium ruthenicum Murr.

It has been proved that purine metabolites are implicated in various biological syndromes and disorders. Therefore, the realization of panoramic detection of purine metabolites will be of great significance to the pathogenesis of purine metabolic disorders. In the present study, an ultra-high performance liquid chromatography with tandem mass spectrometry method was developed for the comprehensive quantification of purine metabolites in rat plasma. The 17 purine metabolites were separated and quantified in the short running time of 15 min. The proposed method was strictly validated by applying SeraSub solution as a matrix and proved to be linear (R2 ≥ 0.9944), accurate (the recoveries of all analytes ranged from 85.3% to 103.0%, with relative standard deviation values ≤ 9.3%), and precise (the intra- and inter-day precisions were less than 10.8% and 12.4%, respectively). The method was then successfully applied to the qualification of the endogenous purine metabolites in acute gouty arthritis rats, as well as colchicine and anthocyanin-intervened rats. Results showed that uric acid, xanthine, hypoxanthine, and xanthine were considered the key factors of acute gouty arthritis. The established method and measurement of purines in rat plasma might help the investigation of the action mechanisms between purine disorders and related diseases.

Nanoclay Drug-Delivery System Loading Potassium Iodide Promotes Endocytosis and Targeted Therapy in Anaplastic Thyroid Cancer.

The rapid proliferative biological behavior of primary foci of anaplastic thyroid cancer (ATC) makes it a lethal tumor. According to the specific iodine uptake capacity of thyroid cells and enhanced endocytosis of ATC cells, we designed a kind of nanoclay drug-loading system and showed a promising treatment strategy for ATC. Introducing potassium iodide (KI) improves the homoaggregation of clay nanoparticles and then affects the distribution of nanoparticles in vivo, which makes KI@DOX-KaolinMeOH enriched almost exclusively in thyroid tissue. Simultaneously, the improvement of dispersibility of KI@DOX-KaolinMeOH changes the target uptake of ATC cells by improving the endocytosis and nanoparticle-induced autophagy, which regulate the production of autolysosomes and autophagy-enhanced chemotherapy, eventually contributing to a tumor inhibition rate of more than 90% in the primary foci of ATC. Therefore, this facile strategy to improve the homoaggregation of nanoclay by introducing KI has the potential to become an advanced drug delivery vehicle in ATC treatment.