Chinese herb ultrafine powder supplementation improves egg nutritional value and quality in laying hens.

This study evaluates the effects of dietary Chinese herb ultrafine powder (CHUP) supplementation in late-phase laying hens on the quality and nutritional values of eggs. A total of 576 Xinyang black-feather laying hens (300-day-old) were randomly allocated into eight groups for a 120-day feeding trial. Each group contained eight replicates with nine hens per replicate. The experimental groups included the control (basal diet) and different levels of CHUP groups (details in 'Materials and methods'). The results showed that the eggshell strength was increased (p < 0.05) in the L, LF, L-LF, L-T, and LF-T groups on day 60 of the trial. In addition, the plasma estradiol level in the L-LF, LF-T, and L-LF-T groups and unsaturated fatty acids concentrations in egg yolk of the CHUP groups (except LF-T group) were increased, whereas total cholesterol (T, L-LF, L-T, and L-LF-T groups) in egg yolk and the atherogenicity (T, L-T, and L-LF-T groups) and thrombogenicity (T, L-LF, L-T, and L-LF-T groups) indexes were decreased (p < 0.05) on day 60 of the trial compared with the control group. Moreover, bitter amino acids in egg albumen were decreased (p < 0.05) in the L-LF group on day 60 and the L-LF-T group on day 120 of the trial. Collectively, these findings indicate that dietary CHUP supplementation could improve eggshell quality and increase plasma reproductive hormone, fatty acid and amino acid composition, and nutritional values of eggs, especially L-LF and L-LF-T.

Identification of MACC1 as a potential biomarker for pulmonary arterial hypertension based on bioinformatics and machine learning.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by abnormal early activation of pulmonary arterial smooth muscle cells (PASMCs), yet the underlying mechanisms remain to be elucidated. METHODS: Normal and PAH gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database and analyzed using gene set enrichment analysis (GSEA) to uncover the underlying mechanisms. Weighted gene co-expression network analysis (WGCNA) and machine learning methods were deployed to further filter hub genes. A number of immune infiltration analysis methods were applied to explore the immune landscape of PAH. Enzyme-linked immunosorbent assay (ELISA) was employed to compare MACC1 levels between PAH and normal subjects. The important role of MACC1 in the progression of PAH was verified through Western blot and real-time qPCR, among others. RESULTS: 39 up-regulated and 7 down-regulated genes were identified by 'limma' and 'RRA' packages. WGCNA and machine learning further narrowed down the list to 4 hub genes, with MACC1 showing strong diagnostic capacity. In vivo and in vitro experiments revealed that MACC1 was highsly associated with malignant features of PASMCs in PAH. CONCLUSIONS: These findings suggest that targeting MACC1 may offer a promising therapeutic strategy for treating PAH, and further clinical studies are warranted to evaluate its efficacy.

Genomic evolution and insights into agronomic trait innovations of Sesamum species.

Sesame is an ancient oilseed crop with high oil content and quality. However, the evolutionary history and genetic mechanisms of its valuable agronomic traits remain unclear. Here, we report chromosome-scale genomes of cultivated sesame (Sesamum indicum L.) and six wild Sesamum species, representing all three karyotypes within this genus. Karyotyping and genome-based phylogenic analysis revealed the evolutionary route of Sesamum species from n = 13 to n = 16 and revealed that allotetraploidization occurred in the wild species Sesamum radiatum. Early divergence of the Sesamum genus (48.5-19.7 million years ago) during the Tertiary period and its ancient phylogenic position within eudicots were observed. Pan-genome analysis revealed 9164 core gene families in the 7 Sesamum species. These families are significantly enriched in various metabolic pathways, including fatty acid (FA) metabolism and FA biosynthesis. Structural variations in SiPT1 and SiDT1 within the phosphatidyl ethanolamine-binding protein gene family lead to the genomic evolution of plant-architecture and inflorescence-development phenotypes in Sesamum. A genome-wide association study (GWAS) of an interspecific population and genome comparisons revealed a long terminal repeat insertion and a sequence deletion in DIR genes of wild Sesamum angustifolium and cultivated sesame, respectively; both variations independently cause high susceptibility to Fusarium wilt disease. A GWAS of 560 sesame accessions combined with an overexpression study confirmed that the NAC1 and PPO genes play an important role in upregulating oil content of sesame. Our study provides high-quality genomic resources for cultivated and wild Sesamum species and insights that can improve molecular breeding strategies for sesame and other oilseed crops.

MicroRNA-21 promotes head and neck squamous cell carcinoma (HNSCC) induced transition of bone marrow mesenchymal stem cells to cancer-associated fibroblasts.

BACKGROUND: Most patients diagnosed with head and neck tumor will present with locally advanced disease, requiring multimodality therapy. Bone marrow-derived mesenchymal stromal cells (BMSCs) respond to a variety of tumor cell-derived signals, such as inflammatory cytokines and growth factors. As a result, the inflammatory tumor microenvironment may lead to the recruitment of BMSCs. Whether BMSCs in the tumor environment are more likely to promote tumor growth or tumor suppression is still controversial. We aimed to determine whether microRNA-21(miR-21) would play a vital role in HNSCC induced transition of human bone marrow mesenchymal stem cells (hBMSCs) to cancer-associated fibroblasts (CAFs). METHODS: In this study, we used electron microscope to observed exosomes collected from human tissue and two cell lines. We co-cultured hBMSCs with exosomes from FaDu and Cal-27 cells with miR-21 inhibited or not, then assessed cell cycle changes of hBMSCs with flow cytometry and determined expression level of α-SMA and FAP through qRT-PCR and Western blot. RESULTS: We observed an up-regulation of miR-21 expression in HNSCC tissue and FaDu and Cal-27 cells. Importantly, the exosomes derived from both cells induced CAFs-like characteristics in hBMSCs. while treatment with a miR-21 inhibitor effectively suppressed the transition of hBMSCs to CAFs and reversed the changes in the cell cycle distribution. This suggests that miR-21 plays a crucial role in facilitating the transition of hBMSCs to CAFs and modulating the cell cycle dynamics. CONCLUSION: Our findings highlight the significance of miR-21 in mediating the communication between HNSCC cells and hBMSCs through exosomes, leading to the promotion of CAFs-like features and alterations in the cell cycle of hBMSCs.

Dietary supplementation with Chinese herb ultrafine powder improves intestinal morphology and physical barrier function by altering jejunal microbiota in laying hens.

Introduction: Chinese medicinal herbs play important roles in anti-inflammatory, antioxidant, and antibacterial activities. However, the effects of Chinese herb ultrafine powder (CHUP) on laying hens still need to be elucidated. Therefore, this study aimed to evaluate the effects of dietary CHUP supplementation on jejunal morphology, physical barrier function, and microbiota in laying hens. Methods: A total of 576 Xinyang black-feather laying hens (300 days old) were randomly assigned into eight groups, with eight replicates per group and nine hens per replicate. The hens were fed a basal diet (control group) and a basal diet supplemented with 0.5% Leonuri herba (LH group), 0.25% Ligustri lucidi fructus (LF group), 0.25% Taraxaci herba (TH group), 0.5% LH + 0.25% LF (LH-LF group), 0.5% LH + 0.25% TH (LH-TH group), 0.25% LF + 0.25% TH (LF-TH group), and 0.5% LH + 0.25% LF + 0.25% TH (LH-LF-TH group), respectively, for 120 days. Results: The results showed that dietary LH-LF and LH-LF-TH supplementation increased (p < 0.05) the jejunal villus height to crypt depth ratio of laying hens. Dietary LF-TH supplementation up-regulated jejunal claudin-5 expression, while LH supplementation up-regulated jejunal claudin-1 expression and increased the jejunal abundances of potentially beneficial bacteria related to short-chain fatty acids and bacteriocins production, such as Blautia, Carnobacterium, Clostridiales, and Erysipelotrichales (p < 0.05). In addition, dietary LH supplementation enriched (p < 0.05) the tetracycline biosynthesis, butirosin/neomycin biosynthesis, and D-arginine/D-ornithine metabolism, whereas steroid biosynthesis and limonene/pinene degradation were enriched (p < 0.05) in the LH-LF and LH-LF-TH groups. Moreover, Spearman's correlation analysis revealed the potential correlation between the abundance of the jejunal microbiota and jejunal morphology and the physical barrier function of laying hens. Discussion: Collectively, these findings suggest that dietary CHUP supplementation could enhance the beneficial bacteria abundance, physical barrier function, and metabolic function associated with short-chain fatty acids and bacteriocins production. Moreover, combined supplementation of dietary CHUP showed better effects than the sole CHUP supplementation.

FUT8-Mediated Core Fucosylation Promotes the Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disease with unclear underlying molecular mechanisms and limited therapeutic options. This study aimed to explore the role of core fucosylation and the only glycosyltransferase FUT8 in PAH. We observed increased core fucosylation in a monocrotaline (MCT)-induced PAH rat model and isolated rat pulmonary artery smooth muscle cells (PASMCs) treated with platelet-derived growth factor-BB (PDGF-BB). We found that 2-fluorofucose (2FF), a drug used to inhibit core fucosylation, improved hemodynamics and pulmonary vascular remodeling in MCT-induced PAH rats. In vitro, 2FF effectively restrains the proliferation, migration, and phenotypic switching of PASMCs and promotes apoptosis. Compared with controls, serum FUT8 concentration in PAH patients and MCT-induced rats was significantly elevated. FUT8 expression appeared increased in the lung tissues of PAH rats, and the co-localization of FUT8 with α-SMA was also observed. SiRNA was used to knockdown FUT8 in PASMCs (siFUT8). After effectively silencing FUT8 expression, phenotypic changes induced in PASMCs by PDGF-BB stimulation were alleviated. FUT8 activated the AKT pathway, while the admission of AKT activator SC79 could partially counteract the negative effect of siFUT8 on the proliferation, apoptotic resistance, and phenotypic switching of PASMCs, which may be involved in the core fucosylation of vascular endothelial growth factor receptor (VEGFR). Our research confirmed the critical role of FUT8 and its mediated core fucosylation in pulmonary vascular remodeling in PAH, providing a potential novel therapeutic target for PAH.

Excitation-Wavelength-Dependent Emission Behavior in (NH4)2SnCl6 via Sb3+ Dopant.

With high photoluminescence efficiency and a simple solution synthesis method, lead halide perovskites are expected to be a promising material for display and illumination. However, the toxicity and environmental sensitivity of lead hinder its potential applications. Here, we introduced Sb3+ ions into the lead-free perovskites derivative (NH4)2SnCl6 via a doping strategy. For the first time we synthesis the excitation-dependent perovskite with dynamically tunable fluorescence from yellow to near-infrared (NIR) emission by varying the UV excitation from 360 to 390 nm at room temperature. The DFT calculations are highly consistent no matter whether the coordination number of Sb3+ is 5 or 6. In contrasting to the early report of Sb triplet emission in the Sb doped perovskite, this material give a mixed self-trapped exciton (STE) emission. The 590 nm emission band is derived from the STE of SbCl5, and the 734 nm NIR emission band is attributed to the Sb-Sn mixed STE, which is supported by DFT calculations and spectral results. This study provides guidance for the design of perovskite phosphors with high efficiency and excitation-dependent properties.

Evolutionary analysis of Omicron variant BF.7 and BA.5.2 pandemic in China.

On December 7, 2022, China adjusted public health control measures, there have been widespread of SARS-CoV-2 infections in Chinese mainland. As the number of infected people increased, the mutation probability of SARS-CoV-2 is also raised. Therefore, it is of great importance to monitor SARS-CoV-2 variants and its mutations in China. In this current study, 665 SARS-CoV-2 genomes from China deposited in the public database were used to analyze the proportion of different variants; to determine the composition of variants in China across different provinces; and analyze specific mutation frequency, focusing on 12 immune escape residues. The results showed that no new mutations were generated on the 12 immune escape residues. The evolutionary analysis of the BF.7 variant circulating in China showed that there is an independent evolutionary branch with unique mutation sites, officially named BF.7.14 by PANGO. This variant may have been imported from Russia to Inner Mongolia at the end of September 2022 and continued its spread in China. The evolutionary analysis of BA.5.2 variant shows that the variant is composed of two sub-variants, named BA.5.2.48 and BA.5.2.49 by PANGO, respectively. This variant may have been imported from abroad to Beijing at the beginning of September 2022 and formed two sub-variants after domestic transmission. Finally, this study showed that current epidemic variants in China were already circulating in other countries, and there were no additional mutations on immune escape residues that could pose a threat to other countries.

Realizing High-Efficiency Yellow Emission of Organic Antimony Halides via Rational Structural Design.

Zero-dimensional (0D) organic metal halides have captured extensive attention for their various structures and distinguished optical characteristics. However, achieving efficient emission through rational crystal structure design remains a great challenge, and how the crystal structure affects the photophysical properties of 0D metal halides is currently unclear. Herein, a rational crystal structure regulation strategy in 0D Sb(III)-based metal halides is proposed to realize near-unity photoluminescence quantum yield (PLQY). Specifically, two 0D organic Sb(III)-based compounds with different coordination configurations, namely, (C25H22P)2SbCl5 and (C25H22P)SbCl4 (C25H22P+ = benzyltriphenylphosphonium), were successfully obtained by precisely controlling the ratio of the initial raw materials. (C25H22P)2SbCl5 adopts an octahedral coordination geometry and shows highly efficient broadband yellow emission with a PLQY of 98.6%, while (C25H22P)SbCl4 exhibits a seesaw-shaped [SbCl4]- cluster and does not emit light under photoexcitation. Theoretical calculations reveal that, by rationally controlling the coordination structure, the indirect bandgap of (C25H22P)SbCl4 can be converted to the direct bandgap of (C25H22P)2SbCl5, thus ultimately boosting the emission intensity. Together with efficient emission and outstanding stability of (C25H22P)2SbCl5, a high-performance white-light emitting diode (WLED) with a high luminous efficiency of 31.2 lm W-1 is demonstrated. Our findings provide a novel strategy to regulate the coordination structure of the crystals, so as to rationally optimize the luminescence properties of organic metal halides.

Green Triplet Self-Trapped Exciton Emission in Layered Rb3Cd2Cl7:Sb3+ Perovskite: Comparison with RbCdCl3:Sb3.

Metal halide materials have recently sparked intense research because of their excellent photophysical properties and chemical stability. For example, RbCdCl3:Sb3+ exhibits broad emission at about 600 nm with a high photoluminescence quantum yield (PLQY) over 91% and double emission bands with bright white color. Herein, we obtained a novel Rb and Cd layered perovskite Rb3Cd2Cl7 doped with Sb3+, which gives luminescence at 525 nm with a large Stokes shift of 200 nm, originating from a self-trapped exciton (STE). Its PLQY is 57.47%, but its low-temperature PLQY becomes much higher at the same wavelength. When Rb3Cd2Cl7:Sb3+ and RbCdCl3:Sb3+ were compared, the two classes of quantum confinement effects by Rb and Cd ions in the lattice were identified to describe their electronic states and different optical properties. These results suggest that properties of Sb-doped cadmium halides could be modified by the structure type and local atomic confinement to find applications as promising luminescent materials for optoelectronic devices.

"Mutation blacklist" and "mutation whitelist" of SARS-CoV-2.

Over the past two years, scientists throughout the world have completed more than 6 million SARS-CoV-2 genome sequences. Today, the number of SARS-CoV-2 genomes exceeds the total number of all other viral genomes. These genomes are a record of the evolution of SARS-CoV-2 in the human host, and provide information on the emergence of mutations. In this study, analysis of these sequenced genomes identified 296,728 de novo mutations (DNMs), and found that six types of base substitutions reached saturation in the sequenced genome population. Based on this analysis, a "mutation blacklist" of SARS-CoV-2 was compiled. The loci on the "mutation blacklist" are highly conserved, and these mutations likely have detrimental effects on virus survival, replication, and transmission. This information is valuable for SARS-CoV-2 research on gene function, vaccine design, and drug development. Through association analysis of DNMs and viral transmission rates, we identified 185 DNMs that positively correlated with the SARS-CoV-2 transmission rate, and these DNMs where classified as the "mutation whitelist" of SARS-CoV-2. The mutations on the "mutation whitelist" are beneficial for SARS-CoV-2 transmission and could therefore be used to evaluate the transmissibility of new variants. The occurrence of mutations and the evolution of viruses are dynamic processes. To more effectively monitor the mutations and variants of SARS-CoV-2, we built a SARS-CoV-2 mutation and variant monitoring and pre-warning system (MVMPS), which can monitor the occurrence and development of mutations and variants of SARS-CoV-2, as well as provide pre-warning for the prevention and control of SARS-CoV-2 (https://www.omicx.cn/). Additionally, this system could be used in real-time to update the "mutation whitelist" and "mutation blacklist" of SARS-CoV-2.

Integrated Bioinformatic Analysis Reveals TXNRD1 as a Novel Biomarker and Potential Therapeutic Target in Idiopathic Pulmonary Arterial Hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is a life-threatening cardiopulmonary disease lacking specific diagnostic markers and targeted therapy, and its mechanism of development remains to be elucidated. The present study aimed to explore novel diagnostic biomarkers and therapeutic targets in IPAH by integrated bioinformatics analysis. Four eligible datasets (GSE117261, GSE15197, GSE53408, GSE48149) was firstly downloaded from GEO database and subsequently integrated by Robust rank aggregation (RRA) method to screen robust differentially expressed genes (DEGs). Then functional annotation of robust DEGs was performed by GO and KEGG enrichment analysis. The protein-protein interaction (PPI) network was constructed followed by using MCODE and CytoHubba plug-in to identify hub genes. Finally, 10 hub genes were screened including ENO1, TALDO1, TXNRD1, SHMT2, IDH1, TKT, PGD, CXCL10, CXCL9, and CCL5. The GSE113439 dataset was used as a validation cohort to appraise these hub genes and TXNRD1 was selected for verification at the protein level. The experiment results confirmed that serum TXNRD1 concentration was lower in IPAH patients and the level of TXNRD1 had great predictive efficiency (AUC:0.795) as well as presents negative correlation with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). Consistently, the expression of TXNRD1 was proved to be inhibited in animal and cellular model of PAH. In addition, GSEA analysis was performed to explore the functions of TXNRD1 and the results revealed that TXNRD1 was closely correlated with mTOR signaling pathway, MYC targets, and unfolded protein response. Finally, knockdown of TXNRD1 was shown to exacerbate proliferative disorder, migration and apoptosis resistance in PASMCs. In conclusion, our study demonstrates that TXNRD1 is a promising candidate biomarker for diagnosis of IPAH and plays an important role in PAH pathogenesis, although further research is necessary.

Efficient Yellow Self-Trapped Exciton Emission in Sb3+-Doped RbCdCl3 Metal Halides.

Metal halide perovskites have flexible crystal and electronic structures and adjustable emission characteristics, which have very broad applications in the optoelectronic field. Among them, all-inorganic perovskites have attracted more attention than others in recent years because of their characteristics of large diffusion length, high luminescence efficiency, and good stability. In this work, Sb3+-doped RbCdCl3 crystalline powder was synthesized by a simple hydrothermal method, and its luminescence properties were studied, which showed a broad emission band with a large Stokes shift and efficient yellow light emission at about 596 nm at room temperature with a photoluminescence quantum yield of 91.7%. The emission came from the transition of the self-trapped exciton 1 (STE1) out of 3Pn (n = 0, 1, and 2) to S0 due to strong electron-phonon coupling, which scaled with increasing temperature. Moreover, its emission color became white at low temperatures due to the occurrence of transition of other self-trapped exciton 0 (STE0) state emission out of the 1S states of Sb ions to S0 in the lattice. These emission color changes may be used for temperature sensing, and this Sb3+-doped RbCdCl3 material expands the knowledge of the efficient luminescent inorganic material family for further applications of all-inorganic perovskites.

Origin and evolutionary analysis of the SARS-CoV-2 Omicron variant.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved rapidly into new variants throughout the pandemic. The Omicron variant has more than 50 mutations when compared with the original wild-type strain and has been identified globally in numerous countries. In this report, we analyzed the mutational profiles of several variants, including the per-site mutation rate, to determine evolutionary relationships. The Omicron variant was found to have a unique mutation profile when compared with that of other SARS-CoV-2 variants, containing mutations that are rare in clinical samples. Moreover, the presence of five mouse-adapted mutation sites suggests that Omicron may have evolved in a mouse host. Mutations in the Omicron receptor-binding domain (RBD) region, in particular, have potential implications for the ongoing pandemic.

Corrigendum: Integrated bioinformatic analysis reveals TXNRD1 as a novel biomarker and potential therapeutic target in idiopathic pulmonary arterial hypertension.

[This corrects the article DOI: 10.3389/fmed.2022.894584.].

Massive-scale genomic analysis reveals SARS-CoV-2 mutation characteristics and evolutionary trends.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in significant societal costs. Hence, an in-depth understanding of SARS-CoV-2 virus mutation and its evolution will help determine the direction of the COVID-19 pandemic. In this study, we identified 296,728 de novo mutations in more than 2,800,000 high-quality SARS-CoV-2 genomes. All possible factors affecting the mutation frequency of SARS-CoV-2 in human hosts were analyzed, including zinc finger antiviral proteins, sequence context, amino acid change, and translation efficiency. As a result, we proposed that when adenine (A) and tyrosine (T) bases are in the context of AM (M stands for adenine or cytosine) or TA motif, A or T base has lower mutation frequency. Furthermore, we hypothesized that translation efficiency can affect the mutation frequency of the third position of the codon by the selection, which explains why SARS-CoV-2 prefers AT3 codons usage. In addition, we found a host-specific asymmetric dinucleotide mutation frequency in the SARS-CoV-2 genome, which provides a new basis for determining the origin of the SARS-CoV-2. Finally, we summarize all possible factors affecting mutation frequency and provide insights into the mutation characteristics and evolutionary trends of SARS-CoV-2.

Association of cardiac injury with hypertension in hospitalized patients with COVID-19 in China.

Outbreak of global pandemic Coronavirus disease 2019 (COVID-19) has so far caused countless morbidity and mortality. However, a detailed report on the impact of COVID-19 on hypertension (HTN) and ensuing cardiac injury is unknown. Herein, we have evaluated the association between HTN and cardiac injury in 388 COVID-19 (47.5 ± 15.2 years) including 75 HTN and 313 normotension. Demographic data, cardiac injury markers, other laboratory findings, and comorbidity details were collected and analyzed. Compared to patients without HTN, hypertensive-COVID-19 patients were older, exhibited higher C-reactive protein (CRP), erythrocyte sedimentation rate, and comorbidities such as diabetes, coronary heart disease, cerebrovascular disease and chronic kidney disease. Further, these hypertensive-COVID-19 patients presented more severe disease with longer hospitalization time, and a concomitant higher rate of bilateral pneumonia, electrolyte disorder, hypoproteinemia and acute respiratory distress syndrome. In addition, cardiac injury markers such as creatine kinase (CK), myoglobin, lactic dehydrogenase (LDH), and N-terminal pro brain natriuretic peptide were significantly increased in these patients. Correlation analysis revealed that systolic blood pressure correlated significantly with the levels of CK, and LDH. Further, HTN was associated with increased LDH and CK-MB in COVID- 19 after adjusting essential variables. We also noticed that patients with elevated either high sensitivity-CRP or CRP demonstrated a significant high level of LDH along with a moderate increase in CK (p = 0.07) and CK-MB (p = 0.09). Our investigation suggested that hypertensive patients presented higher risk of cardiac injury and severe disease phenotype in COVID-19, effectively control blood pressure in HTN patients might improve the prognosis of COVID-19 patients.

Serum Anion Gap Is Associated with All-Cause Mortality among Critically Ill Patients with Congestive Heart Failure.

BACKGROUND: Congestive heart failure (CHF) is a complex clinical syndrome, with high morbidity and mortality. Serum anion gap (SAG) is associated with the severity of various cardiovascular diseases. However, the role of SAG indicators in CHF is unclear. METHODS AND RESULTS: A retrospective analysis of data from Multiparameter Intelligent Monitoring in Intensive Care III version 1.4 was conducted in critically ill patients with CHF. The clinical information of each patient, including demographic data, comorbidities, vital signs, scores, and laboratory indicators, were successfully obtained. Cox proportional hazards models were used to determine the relationship between SAG and mortality in patients with CHF, the consistency of which was further verified by subgroup analysis. RESULTS: A total of 7426 subjects met the inclusion criteria. Multivariate analysis showed that after adjusting for age, gender, ethnicity, and other potential confounders, increased SAG was significantly related to an increase in 30- and 90-day all-cause mortalities of critically ill patients with CHF compared with decreased SAG (tertile 3 versus tertile 1: adjusted hazard ratio, 95% confidence interval: 1.74, 1.46-2.08; 1.53, 1.32-1.77). Subgroup analysis indicated that the association between SAG and all-cause mortality presented similarities in most strata. CONCLUSION: SAG at admission could be a promising predictor of all-cause mortality in critically ill patients with CHF.

Combination of Dichloroacetate and Atorvastatin Regulates Excessive Proliferation and Oxidative Stress in Pulmonary Arterial Hypertension Development via p38 Signaling.

Pulmonary arterial hypertension (PAH) is a lethal disease generally characterized by pulmonary artery remodeling. Mitochondrial metabolic disorders have been implicated as a critical regulator of excessively proliferative- and apoptosis-resistant phenotypes in pulmonary artery smooth muscle cells (PASMCs). Dichloroacetate (DCA) is an emerging drug that targets aerobic glycolysis in tumor cells. Atorvastatin (ATO) is widely used for hyperlipemia in various cardiovascular diseases. Considering that DCA and ATO regulate glucose and lipid metabolism, respectively, we hypothesized that the combination of DCA and ATO could be a potential treatment for PAH. A notable decrease in the right ventricular systolic pressure accompanied by reduced right heart hypertrophy was observed in the DCA/ATO combination treatment group compared with the monocrotaline treatment group. The DCA/ATO combination treatment alleviated vascular remodeling, thereby suppressing excessive PASMC proliferation and macrophage infiltration. In vitro, both DCA and ATO alone reduced PASMC viability by upregulating oxidative stress and lowering mitochondrial membrane potential. Surprisingly, when combined, DCA/ATO was able to decrease the levels of reactive oxygen species and cell apoptosis without compromising PASMC proliferation. Furthermore, suppression of the p38 pathway through the specific inhibitor SB203580 attenuated cell death and oxidative stress at a level consistent with that of DCA/ATO combination treatment. These observations suggested a complementary effect of DCA and ATO on rescuing PASMCs from a PAH phenotype through p38 activation via the regulation of mitochondrial-related cell death and oxidative stress. DCA in combination with ATO may represent a novel therapeutic strategy for PAH treatment.

Functional polymorphism of PIN1 rs2233679 is associated with the progression of CIN to early cervical cancer in Hunan Chinese.

OBJECTIVE: Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) involves alteration of the structure, function, intracellular localization and/or stability of the phosphorylated protein on serine or threonine residues which relates to inflammation and tumorigenesis. Association between PIN1 promoter polymorphisms and cancer risk were reported in several cancers. We intend to study the relationship between the polymorphism of PIN1 promoter and cervical cancer initiation and development. MATERIALS AND METHODS: We genotyped two common single nucleotide polymorphisms (SNPs) (rs2233678 and rs2233679) in the promoter of the PIN1 gene in healthy controls, patients with CIN or cervical cancer. We used polymerase chain reaction and DNA sequencing methods to analyze these two SNPs in 179 patients and 223 healthy controls. Luciferase activity assay was used to detect PIN1 expression driven by the rs2233679. RESULTS: The results revealed that the carriers of rs2233679 genotypes CT/TT had a significantly increased risk of cervical cancer in patients with CIN compared with genotype CC (odds ration [OR] = 2.924, 95% confidence interval [CI] = 1.093-7.819, P = 0.033). Luciferase activity assay results revealed that PIN1 expression driven by the rs2233679 genotype TT was higher than the genotype CC (P < 0.05). On the other hand, no significant correlation between the healthy controls and patients was found for PIN1 rs2233678 which showed that rs2233678 genotypes CG/GG is 95% in healthy controls and 100% in patients. CONCLUSION: PIN1 rs2233679 genotype CT/TT may be a risk factor of early cervical cancer compared with genotype CC in Hunan populations. Our findings suggest that PIN1 rs2233679 genotype CT/TT might involve in the progression of the precancerous stage developing to early cancer by enhancing PIN1 expression.