Trends in cardiovascular health among US adults by glycemic status based on Life's Essential 8.

OBJECTIVE: We aimed to assess the secular trends in cardiovascular health (CVH) among U.S. adults with different glycemic statuses based on the Life's Essential 8 (LE8). METHODS: This cross-sectional study used nationally representative data from 6 cycles of the National Health and Nutrition Examination Surveys between 2007 and 2018. Survey-weighted linear models were used to assess time trends in LE8 scores. Stratified analyses and sensitivity analyses were conducted to validate the stability of the results. RESULTS: A total of 23,616 participants were included in this study. From 2007 to 2018, there was no significant improvement in overall CVH and the proportion of ideal CVH among participants with diabetes and prediabetes. We observed an opposite trend between health behavior and health factors in the diabetes group, mainly in increasing physical activity scores and sleep scores (P for trend<0.001), and declining BMI scores [difference, -6.81 (95% CI, -12.82 to -0.80)] and blood glucose scores [difference, -6.41 (95% CI, -9.86 to -2.96)]. Dietary health remained at a consistently low level among participants with different glycemic status. The blood lipid scores in the prediabetes group improved but were still at a lower level than other groups. Education/income differences persist in the CVH of participants with diabetes or prediabetes, especially in health behavior factors. Sensitivity analyses of the absolute difference and change in proportion showed a consistent trend. CONCLUSIONS: Trends in CVH among participants with diabetes or prediabetes were suboptimal from 2007 to 2018, with persistent education/income disparities.

Multiparametric cardiac magnetic resonance reveals persistent myocardial inflammation in patients with exertional heat illness.

OBJECTIVES: To explore the clinical potential of multiparametric cardiac magnetic resonance (CMR) in evaluating myocardial inflammation in patients with exertional heat illness (EHI). METHODS: This prospective study enrolled 28 males with EHI (18 patients with exertional heat exhaustion (EHE) and 10 with exertional heat stroke (EHS)) and 18 age-matched male healthy controls (HC). All subjects underwent multiparametric CMR, and 9 patients had follow-up CMR measurements 3 months after recovery from EHI. CMR-derived left ventricular geometry, function, strain, native T1, extracellular volume (ECV), T2, T2*, and late gadolinium enhancement (LGE) were obtained and compared among different groups. RESULTS: Compared with HC, EHI patients showed increased global ECV, T2, and T2* values (22.6% ± 4.1 vs. 19.7% ± 1.7; 46.8 ms ± 3.4 vs. 45.1 ms ± 1.2; 25.5 ms ± 2.2 vs. 23.8 ms ± 1.7; all p < 0.05). Subgroup analysis showed that ECV was higher in the EHS patients than those in EHE and HC groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). Repeated CMR measurements at 3 months after baseline CMR showed persistently higher ECV than HC (p = 0.042). CONCLUSIONS: With multiparametric CMR, EHI patients demonstrated increased global ECV, T2, and persistent myocardial inflammation at 3-month follow-up after EHI episode. Therefore, multiparametric CMR might be an effective method in evaluating myocardial inflammation in patients with EHI. CLINICAL RELEVANCE STATEMENT: This study showed persistent myocardial inflammation after an exertional heat illness (EHI) episode demonstrated by multiparametric CMR, which is a potential promising method to evaluate the severity of myocardial inflammation and guide return to work, play, or duty in EHI patients. KEY POINTS: • EHI patients showed an increased global extracellular volume (ECV), late gadolinium enhancement, and T2 value, indicating myocardial edema and fibrosis. • ECV was higher in the exertional heat stroke patients than exertional heat exhaustion and healthy control groups (24.7% ± 4.9 vs. 21.4% ± 3.2, 24.7% ± 4.9 vs. 19.7% ± 1.7; both p < 0.05). • EHI patients showed persistent myocardial inflammation with higher ECV than healthy controls 3 months after index CMR (22.3% ± 2.4 vs. 19.7% ± 1.7, p = 0.042).

[Investigation of Virulence Variation of Enterovirus 71 Strains during Thermal Adaptive Evolution].

Objective: To study the virulence variation of enterovirus 71 (EV71) during thermal adaptive evolution, providing references for the prevention and control of the EV71-related hand, foot and mouth disease. Methods: Parental strains and thermal-adapted strains originating from EV71 sibling strains (lineage #100 and #101) were used for plaque assay validation, CCK-8 cytotoxicity experiment, and host proteomics studies after Vero cell infection. Plaque morphology and cell inhibition rate of the viral strains were obtained. Mass spectrometry was used to examine and analyze the functions of proteins that were differential expressed in the host cells. Results: Plaque morphology variation was found only in the heat-adapted strain of lineage #101. Increase in cell inhibition rate was observed in all the thermal-adapted strains, but the amount of increase varied in different strains. According to the results of clustering analysis and principal component analysis, after infection of Vero cells, the host cell protein profile of the heat-adapted strains was similar to that of the parental strains and the host cell protein profile of cold-adapted strains was similar to that of cell-adapted strains. It showed that 500 kinds of proteins presented inter-group difference in their expression, with 239 kinds being up-regulated proteins and 261 being down-regulated. The function of the up-regulated proteins were related to post-translational protein modification, while the functions of the down-regulated proteins were related to SRP-dependent cotranslational protein translocation/targeting to membrane and retrograde protein transport. Conclusion: Virulence variations of enterovirus 71 may accompany thermal adaptive evolution, but its mechanism of action still awaits further investigation.

Physiological characteristics and cold tolerance of overwintering eggs in Gomphocerus sibiricus L. (Orthoptera: Acrididae).

Gomphocerus sibiricus L., the dominant insect species in the alpine and subalpine grassland, overwinters with diapause at egg stage. In this study, cold tolerance and related cryoprotectants of G. sibiricus eggs were investigated. In particular, the supercooling point (SCP), water content, carbohydrates (trehalose, glucose, fructose, glycogen), polyols (glycerol, inositol, sorbitol), fat, and amino acids contents were evaluated at different developmental stages of G. sibiricus eggs collected under natural conditions. The SCPs of eggs were very low (-32.83 to -22.61°C) at mid-diapause. Water content gradually increased during development. The fructose, glycerol, and sorbitol contents were significantly higher in diapausing eggs than in early embryogenesis stage and post-diapause development stage. Glycogen content was high throughout the whole developmental period. The trehalose, glucose, and inositol contents were low during diapause compared to that in early embryogenesis stage and post-diapause development stage. There were no significant differences in the fat content of eggs among all development stages. The total amino acid contents in eggs in the early embryogenesis and at the start of diapause were higher than that in post-diapause eggs. The contents of Glu, Asp, Leu, Pro and Arg during diapause were significantly higher than those during post-diapause development. Results indicate that G. sibiricus eggs have a high supercooling capacity. Successful overwintering can be attributed to the accumulation of glycerol, fructose, sorbitol, and amino acids (Glu, Asp, Leu, Pro and Arg). These findings provide insight into the mechanisms underlying the adaptation of G. sibiricus to cold conditions.

Noninvasive detection of fetal subchromosomal abnormalities by semiconductor sequencing of maternal plasma DNA.

Noninvasive prenatal testing (NIPT) using sequencing of fetal cell-free DNA from maternal plasma has enabled accurate prenatal diagnosis of aneuploidy and become increasingly accepted in clinical practice. We investigated whether NIPT using semiconductor sequencing platform (SSP) could reliably detect subchromosomal deletions/duplications in women carrying high-risk fetuses. We first showed that increasing concentration of abnormal DNA and sequencing depth improved detection. Subsequently, we analyzed plasma from 1,456 pregnant women to develop a method for estimating fetal DNA concentration based on the size distribution of DNA fragments. Finally, we collected plasma from 1,476 pregnant women with fetal structural abnormalities detected on ultrasound who also underwent an invasive diagnostic procedure. We used SSP of maternal plasma DNA to detect subchromosomal abnormalities and validated our results with array comparative genomic hybridization (aCGH). With 3.5 million reads, SSP detected 56 of 78 (71.8%) subchromosomal abnormalities detected by aCGH. With increased sequencing depth up to 10 million reads and restriction of the size of abnormalities to more than 1 Mb, sensitivity improved to 69 of 73 (94.5%). Of 55 false-positive samples, 35 were caused by deletions/duplications present in maternal DNA, indicating the necessity of a validation test to exclude maternal karyotype abnormalities. This study shows that detection of fetal subchromosomal abnormalities is a viable extension of NIPT based on SSP. Although we focused on the application of cell-free DNA sequencing for NIPT, we believe that this method has broader applications for genetic diagnosis, such as analysis of circulating tumor DNA for detection of cancer.

Analysis of silent information regulator 1 (SIRT1) gene polymorphisms in antituberculosis- drug-induced hepatotoxicity in a prospective cohort study.

OBJECTIVE: Antituberculosisdrug-induced hepatotoxicity (ATDH) is a common and sometimes serious side effect related to tuberculosis (TB) treatment. A number of risk factors and host genetics contribute to the development of ATDH. However, genetic factors of ATDH remain to be identified. Silent Information Regulator 1 (SIRT1), an essential metabolism gene, was proved to be involved in ATDH in mice. The aim of this investigation was to study the association between ATDH and tag-single nucleotide polymorphisms (tag-SNPs) of the SIRT1 gene in a prospective cohort study in patients with TB. METHODS: 280 newly diagnosed TB patients were recruited in this study before starting first line anti-TB treatment and were followed up for 3 months after initiating anti-TB therapy. The tag-SNPs were selected by using Haploview 4.2 based on the HapMap database of Han Chinese Beijing. Genotyping was performed by polymerase chain reaction (PCR) and the Sequenom MassARRAY iPLEX platform. RESULTS: 24 (9.8%) of the 245 patients included in the final analysis developed hepatotoxicity during the following up period. No significant differences in the allele, genotype, or haplotype frequency distributions of the tag- SNPs (rs7069102, rs2273773, rs4746720) of the SIRT1 gene were identified between the ATDH and non-ATDH groups (all p > 0.05). CONCLUSIONS: The SIRT1 gene may not contribute to the risk for developing hepatotoxicity during anti-TB treatment in the Han Chinese population.

Mechanism and deterioration pattern of sandstone surrounding rock voiding at bottom of heavy-haul railway tunnel.

This study combines laboratory experiments and discrete element simulation methods to analyze the mechanism and deterioration patterns of sandstone surrounding rock voiding the bottom of a heavy-haul railway tunnel. It is based on previously acquired measurement data from optical fiber grating sensors installed in the Taihangshan Mountain Tunnel of the Wari Railway. By incorporating rock particle wastage rate results, a method for calculating the peak strength and elastic modulus attenuation of surrounding rock is proposed. Research indicates that the operation of heavy-haul trains leads to an instantaneous increase in the dynamic water pressure on the bottom rock ranging 144.4-390.0%, resulting in high-speed water flow eroding the rock. After 1-2 years of operation, the bottom water and soil pressures increase by 526.5% and 390.0%, respectively. Focusing on sandstone surrounding rock with high observability, laboratory experiments were conducted to monitor the degradation stages of infiltration, particle loss, and voiding of rock under the action of dynamic water flow. The impact of water flow on the "cone-shaped" bottom rock deformation was also clarified. The extent of rock deterioration and voiding was determined using miniature water and soil pressure sensors in conjunction with discrete element numerical simulations. The measured rock particle loss was used as a criterion. Finally, a fitting approach is derived to calculate the peak strength and elastic modulus attenuation of surrounding rock, gaining insight into and providing a reference for the maintenance and disposal measures for the bottom operation of heavy-haul railway tunnels.

First molecular detection and genetic characterization of porcine circovirus 4 in the Gansu Province of China.

Since its initial discovery in the Hunan province of China, genomic DNA of porcine circovirus 4 (PCV4) has been detected in pigs across multiple provinces in China, as well as in South Korea. However, the prevalence of porcine circovirus type 4 in Gansu Province, China, remains unknown. To address this gap, we undertook an extensive study where we gathered 121 clinical samples displaying diverse clinical manifestations from pig farms in Gansu Province between 2022 and 2023. Employing a real-time fluorescence quantification method, we identified the presence of PCV4 genome. Out of the 121 clinical samples analyzed, 13 samples tested positive for PCV4, resulting in a positive rate of 10.74% (13/121). This finding confirms the presence of PCV4 in pig farms within Gansu Province, China. Furthermore, we successfully sequenced and analyzed the complete genomes of two distinct PCV4 strains, comparing them with 60 reference sequences archived in the GenBank database. The results revealed a high nucleotide homology (98.2-98.8%) between the strains obtained in this study and the PCV4 reference strains, indicating a relatively low evolutionary rate of the PCV4 genome. Phylogenetic analysis revealed that two strains in this study belong to PCV4a and PCV4c. As far as we know, this study marks the inaugural report on the molecular identification and genomic attributes of PCV4 in Gansu Province, China, offering valuable insights for devising preventive and control strategies against this emerging virus.

A vacuolar processing enzyme RsVPE1 gene of radish is involved in floral bud abortion under heat stress.

Radish floral bud abortion (FBA) is an adverse biological phenomenon that occurs during reproduction. Although FBA is a frequent occurrence, its molecular mechanism remains unknown. A transcript-derived fragment (TDF72), which was obtained by cDNA amplified fragment length polymorphism (cDNA-AFLP), was up-regulated in the aborted buds and exhibited 89% sequence homology with the AtγVPE gene. In this study, TDF72 was used to clarify the role of VPE in FBA by isolation of the VPE gene RsVPE1 from radish flower buds. The full-length genomic DNA was 2346 bp including nine exons and eight introns. The full-length cDNA was 1825 bp, containing a complete open reading frame (ORF) of 1470 bp, which encoded a predicted protein containing 489 amino acid residues, with a calculated molecular mass of 53.735 kDa. Expression analysis demonstrated that RsVPE1 was expressed in all tested organs of radish at different levels. Highest expression was detected in aborted flower buds, suggesting that RsVPE1 has a role in FBA. In order to analyze the role of RsVPE1 in FBA, RsVPE1 was overexpressed in transgenic Arabidopsis thaliana plants. Aborted flower buds appeared in transgenic plants subjected to heat stress. In addition, RsVPE1 expression in the transgenic plants reached a maximum when subjected to heat stress for 24 h and increased by 2.1-fold to 2.8-fold in three homozygous transgenic lines. These results indicated that RsVPE1 led to FBA when its expression levels exceeded a particular threshold, and provided evidence for the involvement of RsVPE1 in promoting FBA under heat stress.

Characterization and bioactivity of polysaccharides obtained from pine cones of Pinus koraiensis by graded ethanol precipitation.

Pinus koraiensis polysaccharides (PKP) were extracted by hot water from P. koraiensis pine cones. Five polysaccharide fractions named PKP-A, PKP-B, PKP-C, PKP-D and PKP-E were successfully separated at final ethanol concentrations of 30%, 50%, 60%, 70% and 80%, respectively. HPLC, FT-IR, GC-MS and automatic amino-acid analysis were applied to investigate their chemical characteristics. Monosaccharide component analysis indicated that the five fractions were all composed of D-ribose, L-rhamnose, L-arabinose, D-xylose, D-mannose, D-glucose and D-galactose, but their molar ratios were quite different. HPLC results revealed that the polysaccharides precipitated by higher concentrations of ethanol solution had lower molecular masses. Moreover, the antioxidant activities of the five fractions were studied on the basis of hydroxyl radical and ABTS radical scavenging tests. The five graded polysaccharide fractions exhibited good inhibitory power, and MTT tests in vitro showed the IC50 of PKP-A and PKP-E were 1,072.5 and 2,070.0 µg · mL-1, respectively. These results demonstrated that the PKP could be a potential source of natural antioxidants or dietary supplements.

Application of magnetic resonance imaging (MRI) technology in the characterization of microstructure and moisture content of young Moso bamboo.

Bamboo nodes play a key role in the hollow structure and the rapid growth of bamboo culm. Studying on the anatomical structure of bamboo is helpful to understand its growth mechanism. Taking the noninvasive, high-resolution and accurate technical advantages of magnetic resonance imaging (MRI), we conducted cross-sectional high-resolution MRI scanning on the tip of young Moso bamboo culm (removed shoot sheath) and extracted the gray value of the MRIs by using MATLAB software to explore the differences of water distribution in nodes, proximal nodes, and internodes. The results showed that numerous vascular bundles were repeatedly twisted and rotated horizontally at the nodal diaphragms and inner wall near the nodal diaphragms of the young bamboo, forming an intricate and highly connected network. The structure protected important tissues from mechanical stress by allocating axial loads, and enabled to laterally transport water and nutrients, which was an important basis for the rapid growth of Moso bamboo in relatively short term. The signal value (also known as brightness value) of MRIs indicated that water content of vascular bundles in young bamboo culm was much higher than that of surrounding parenchyma tissues. The mean value and standard deviation of water content between pixels of internodes were significantly higher than that of nodes, and the values of that in the proximal nodes were intermediate. The development of MRI would play a significant role in the studies of bamboo anatomy, physiology, and biochemistry.

Chemical composition and antioxidant activities of three polysaccharide fractions from pine cones.

The traditional method of gas chromatography-mass spectrometry for monosaccharide component analysis with pretreatment of acetylation is described with slight modifications and verified in detail in this paper. It was then successfully applied to the quantitative analysis of component monosaccharides in polysaccharides extracted from the pine cones. The results demonstrated that the three pine cone polysaccharides all consisted of ribose, rhamnose, arabinose, xylose, mannose, glucose and galactose in different molar ratios. According to the recovery experiment, the described method was proved accurate and practical for the analysis of pine cone polysaccharides, meeting the need in the field of chemical analysis of Pinus plants. Furthermore; the chemical characteristics, such as neutral sugar, uronic acids, amino acids, molecular weights, and antioxidant activities of the polysaccharides were investigated by chemical and instrumental methods. The results showed that the chemical compositions of the polysaccharides differed from each other, especially in the content of neutral sugar and uronic acid. In the antioxidant assays, the polysaccharide fractions exhibited effective scavenging activities on ABTS radical and hydroxyl radical, with their antioxidant capabilities decreasing in the order of PKP > PAP > PSP. Therefore, although the polysaccharide fractions had little effect on superoxide radical scavenging, they still have potential to be developed as natural antioxidant agents in functional foods or medicine.

Comparison of pharmaceutical removal in two membrane bioreactors with/without powdered activated carbon addition.

The present study investigates the removal of six selected pharmaceuticals from municipal wastewater in two membrane bioreactors (MBRs) with and without powdered activated carbon (PAC) addition. Two approaches were carried out for obtaining different carbon dosages related to the influent: (1) with a fixed solids retention time (SRT) and varying PAC concentrations; (2) with varying SRTs and a fixed PAC concentration. The results reveal that a PAC dosage related to influent of 21 mg L-1 and SRT of 20 d are optimal. The first approach achieved a better removal performance than the second. The removal of amidotrizoic acid (up to 46%), bezafibrate (>92%) and iopromide (around 85%) were mainly caused by biological process, but were also enhanced by PAC addition. Efficient removal (>95%) of sulfamethoxazole, carbamazepine and diclofenac were highly dependent on the PAC dosage. However, carbamazepine shows re-metabolization properties during biological processing. Decreasing the SRT as done in the second approach, not only increased the PAC amount, but also decreased the mass of activated sludge and reduced the capability to degrade complex organic matter. Consequently, biodegradability and adsorbability played decisive roles in the removal of each compound.

Diagnosis of Cardiac Amyloidosis Using a Radiomics Approach Applied to Late Gadolinium-Enhanced Cardiac Magnetic Resonance Images: A Retrospective, Multicohort, Diagnostic Study.

Objectives: To assess the potential of a radiomics approach of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) in the diagnosis of cardiac amyloidosis (CA). Materials and Methods: This retrospective study included 200 patients with biopsy-proven light-chain (AL) amyloidosis. CA was diagnosed on the basis of systemic amyloidosis confirmed with evidence of cardiac involvement by imaging and clinical biomarkers. A total of 139 patients [54 ± 8 years, 75 (54%) men] in our institution were divided into training cohort [n = 97, mean age of 53 ± 8 years, 54 (56%) men] and internal validation cohort [n = 42, mean age: 56 ± 8 years, 21 (50%) men] with a ratio of 7:3, while 61 patients [mean age: 60 ± 9 years, 42 (69%) men] from the other two institutions were enrolled for external validation. Radiomics features were extracted from global (all short-axis images from base-to-apex) left ventricular (LV) myocardium and three different segments (basal, midventricular, and apex) on short-axis LGE images using the phase-sensitive reconstruction (PSIR) sequence. The Boruta algorithm was used to select the radiomics features. This model was built using the XGBoost algorithm. The two readers performed qualitative and semiquantitative assessment of the LGE images based on the visual LGE patterns, while the quantitative assessment was measured using a dedicated semi-automatic CMR software. The diagnostic performance of the radiomics and other qualitative and quantitative parameters were compared by a receiver operating characteristic (ROC) curve analysis. A correlation between radiomics and the degree of myocardial involvement by amyloidosis was tested. Results: A total of 1,906 radiomics features were extracted for each LV section. No statistical significance was indicated between any two slices for diagnosing CA, and the highest area under the curve (AUC) was found in basal section {0.92 [95% confidence interval (CI), 0.86-0.97] in the LGE images in the training set, 0.89 (95% CI, 0.79-1.00) in the internal validation set, and 0.92 (95% CI, 0.85-0.99) in the external validation set}, which was superior to the visual assessment and quantitative LGE parameters. Moderate correlations between global or basal radiomics scores (Rad-scores) and Mayo stage in all patients were reported (Spearman's Rho = 0.61, 0.62; all p < 0.01). Conclusion: A radiomics analysis of the LGE images provides incremental information compared with the visual assessment and quantitative parameters on CMR to diagnose CA. Radiomics was moderately correlated with the severity of CA. Further studies are needed to assess the prognostic significance of radiomics in patients with CA.

Robust high-bandwidth control of nano-positioning stages with Kalman filter based extended state observer and H∞ control.

The achievable performance of the piezo-actuated nano-positioning stages is severely limited by the intrinsic nonlinearities of the actuators, the lightly damped resonant mode of the flexure-hinge mechanism, and the external disturbances. To overcome all these limitations, this paper presents a novel robust dual-loop control scheme with a Kalman filter-based extended state observer and H∞ control for nano-positioning stages to implement high-bandwidth tracking operations. In this scheme, the extended state observer (ESO) is first developed and assisted by the identified system model to estimate both the system states and total disturbances, where the estimated disturbance is compensated by the direct feedback. In particular, to further improve the estimation performance, the Kalman filter is thus incorporated into the ESO to optimize the observer gain. Then, the state-feedback-based inner-loop controller is designed via the pole-placement method to damp the resonant mode of nano-positioning stages. Finally, a H∞ robust controller is adopted in the outer-loop to eliminate the influence resulting from the external disturbances, nonlinearities, and unmodeled dynamics on tracking operations. To validate the effectiveness of the proposed approach, comparative experiments are conducted on a piezo-actuated nano-positioning stage. Experimental results demonstrate that the proposed control scheme improves the control bandwidth of the system from 3.6 kHz (the stand-alone H∞ controller) to 5.52 kHz, which is 93.5% of the first resonant frequency of the original system. Moreover, it shows excellent robustness against the variation of system dynamics due to the change in the mounted mass and the external disturbances.

Development and Validation of a Nomogram for Predicting Prognosis to Immune Checkpoint Inhibitors Plus Chemotherapy in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) plus chemotherapy improved the prognosis of patients with non-small cell lung cancer (NSCLC); however, reliable prognostic biomarkers are lacking. We explored factors associated with prognosis and developed a predictive model. METHODS: We retrospectively analyzed 130 consecutive stage IIIA-IVB NSCLC patients treated with ICIs combined with chemotherapy. Cox univariate and multivariate proportional hazards regression analyses were used to identify prognostic factors associated with progression-free survival (PFS). A nomogram was developed based on key factors in the training cohort (n = 86) and evaluated in the validation cohort (n = 44). According to the nomogram-based total point scores, we divided patients into low- and high-risk groups. RESULTS: In the training cohort, bone metastases (p = 0.017) and an increased derived neutrophil-to-lymphocyte ratio (p = 0.018) were significantly associated with poor PFS, while smoking (p = 0.007) and programmed death-ligand 1 (PD-L1) ≥50% (p = 0.001) were associated with improved PFS. A nomogram based on these factors was developed to predict PFS at 3, 6, and 12 months. The C-index of the nomogram to predict PFS was 0.725 (95% CI: 0.711-0.739) in the training cohort and 0.688 (95% CI: 0.665-0.711) in the validation cohort. The area under the curve (AUC) exhibited an acceptable discriminative ability, and calibration curves demonstrated a consistency between the actual results and predictions. In the training cohort, the median PFS (mPFS) was 12.3 and 5.7 months in the low- and high-risk groups, respectively (p < 0.001). In the validation cohort, the mPFS was 12.6 and 6.2 months in the low- and high-risk groups, respectively (p = 0.021). CONCLUSIONS: A predictive nomogram was developed to help clinicians assess prognosis early for advanced NSCLC patients who received ICI plus chemotherapy.

[Recent advances in the study of accelerated blood clearance phenomenon of PEGylated liposomes].

It is generally believed that liposomes modified with polyethylene glycol (PEG) have no or lower immunogenicity. However, based on many recent literatures, when the PEGylated liposomes were repeatedly applied to the same animal, the immune responses occurred. The first injection of PEGylated liposomes resulted in a reduction in the circulation time and an increase in hepatic and splenic accumulation of the second dose of PEGylated liposomes in a time-interval, which was called "accelerated blood clearance (ABC)" phenomenon. Such immunogenicity of PEGylated liposomes presents a barrier in the research of liposomal formulations and their use in the clinics. This review focused on the definition, the method of verification, the development of the reason for ABC phenomenon, influencing factors of ABC phenomenon, and discussed if other PEGylated nanocarriers also induce ABC phenomenon.

Protective effect of hsa-miR-570-3p targeting CD274 on triple negative breast cancer by blocking PI3K/AKT/mTOR signaling pathway.

To find out the role of hsa-miR-570-3p targeting CD274 in triple negative breast cancer (TNBC) via PI3K/AKT/mTOR signaling pathway. Hsa-miR-570-3p and CD274 expressions in 175 TNBC patients were detected by qRT-PCR and immunohistochemistry respectively. The human TNBC cell lines (MDA-MB-468 and MDA-MB-231) were used to verify the targeting relationship between hsa-miR-570-3p and CD274 via dual-luciferase reporter gene assay. Then, MDA-MB-468 and MDA-MB-231 cells were divided into Blank, miR-NC, miR-570-3p mimics, NC siRNA, CD274 siRNA, and miR-570-3p inhibitors + CD274 siRNA groups. Next, the biological activities of cells were detected by MTT, Cell-Light EdU, Annexin-V-FITC/PI, wound healing and Transwell invasion assays. Western blotting was conducted to detect protein expressions.MiR-570-3p expression was lower in tumor tissues than that in adjacent normal tissues, which was more obvious in CD274-positive TNBC patients, which targeted CD274 in TNBC cell lines. MiR-570-3p inhibited cell proliferation, invasion and migration, but induced cell apoptosis accompanying the upregulation of apoptotic proteins and downregulation of anti-apoptotic protein. CD274 siRNA had the similar results of miR-570-3p mimics, which could be reversed by miR-570-3p inhibitors. Besides, both miR-570-3p mimics and CD274 siRNA blocked PI3K/AKT/mTOR signaling pathway in TNBC cell lines. Hsa-miR-570-3p was downregulated and CD274 was upregulated in TNBC patients. Besides, hsa-miR-570-3p targeted CD274 to inhibit cell proliferation, invasion, migration, and induce cell apoptosis, which may be related to the suppression of PI3K/AKT/mTOR pathway.

Estrogen suppresses uterine epithelial apoptosis by inducing birc1 expression.

The decision whether or not a cell undergoes apoptosis is determined by the opposing forces of pro- and antiapoptotic effectors. Here we demonstrate genetically that estrogen can tip this balance toward cell survival in uterine epithelial cells by inducing the expression of baculoviral inhibitors of apoptosis repeat-containing 1 (Birc1), a family of antiapoptotic proteins. In neonatal mice, both 17beta-estradiol and the potent synthetic estrogen diethylstilbestrol strongly suppress uterine epithelial apoptosis while markedly elevating Birc1 transcript level in an estrogen receptor-alpha-dependent manner. The induction of Birc1 before any effect on apoptosis suppression and failure of diethylstilbestrol to completely inhibit apoptosis in Birc1a-deficient uterine epithelium indicate a functional role for Birc1a in estrogen-mediated apoptosis suppression. In ovariectomized adult mice, expression of Birc1 is also induced by ovarian hormones, suggesting a role for these proteins in normal uterine physiology. We propose that by binding to active caspases, Birc1 proteins can eliminate them through proteasome degradation. These results for the first time establish Birc1 proteins as functional targets of estrogen in suppressing apoptosis in the uterus.

Polyamine analogue QMA attenuated ischemic injury in MCAO rats via ERK and Akt activated Nrf2/HO-1 signaling pathway.

Previous research showed N1-(quinolin-2-ylmethy) butane-1, 4-diamine (QMA), a polyamine analogue, was efficacious in the prevention of oxidative injury in models of cerebral ischemia. The present study manifested that pretreatment with QMA attenuated ischemic damage accompanying up regulation of Nuclear factor erythroid 2­related factor (Nrf2), Heme oxygenase­1 (HO­1), p-ERK and p-Akt in cerebral cortex tissues of middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation (OGD)-treated PC12 cells. Further more, treatment with LY294002 (specific PI3K inhibitor), PD98059 (specific ERK inhibitor), brusatol (specific Nrf2 inhibitor) and SnPP (specific HO-1 inhibitor) deprived almost all the effects of QMA in MCAO rats and OGD-treated PC12 cells. These data suggested that the protective actions of QMA on the cerebral ischemia may be related to activation of endogenous cytoprotective mechanism via ERK and Akt activated Nrf2/HO-1 signaling pathway.