Association between the atherogenic index of plasma and coronary collateral circulation in patients with chronic total occlusion.

BACKGROUND: The atherogenic index of plasma (AIP) is considered an independent risk factor for coronary artery disease (CAD). The present study investigated whether AIP correlates with the formation of coronary collateral circulation (CCC) in CAD patients with chronic total occlusion (CTO). METHODS: This retrospective study included 1093 CAD patients with CTO confirmed by coronary angiography from January 2020 to December 2020 at Beijing Anzhen Hospital. Based on the Rentrop scoring system, the patients were divided into the good CCC group and the poor CCC group. AIP was calculated by log (triglyceride/high-density lipoprotein cholesterol). Meanwhile, the study population was further divided into four groups according to the quartiles of AIP. RESULTS: Patients in the poor CCC group exhibited significantly higher AIP compared to those in the good CCC group (0.31 ± 0.27 vs. 0.14 ± 0.24, p < 0.001). Multivariate logistic regression analysis revealed an independent association between AIP and poor CCC, regardless of whether AIP was treated as a continuous or categorical variable (p < 0.001), after adjusting for confounding factors. Besides, this association remained consistent across most subgroups. The incorporation of AIP into the baseline model significantly enhanced the accuracy of identifying poor CCC [area under the curve (AUC): baseline model, 0.661 vs. baseline model + AIP, 0.721, p for comparison < 0.001]. CONCLUSIONS: Elevated AIP is independently associated with an increased risk of poor CCC in CAD patients with CTO, and AIP may improve the ability to identify poor CCC in clinical practice.

A QTL GN1.1, encoding FT-L1, regulates grain number and yield by modulating polar auxin transport in rice.

Rice grain number is a crucial agronomic trait impacting yield. In this study, we characterized a quantitative trait locus (QTL), GRAIN NUMBER 1.1 (GN1.1), which encodes a Flowering Locus T-like1 (FT-L1) protein and acts as a negative regulator of grain number in rice. The elite allele GN1.1B, derived from the Oryza indica variety, BF3-104, exhibits a 14.6% increase in grain yield compared with the O. japonica variety, Nipponbare, based on plot yield tests. We demonstrated that GN1.1 interacted with and enhanced the stability of ADP-ribosylation factor (Arf)-GTPase-activating protein (Gap), OsZAC. Loss of function of OsZAC results in increased grain number. Based on our data, we propose that GN1.1B facilitates the elevation of auxin content in young rice panicles by affecting polar auxin transport (PAT) through interaction with OsZAC. Our study unveils the pivotal role of the GN1.1 locus in rice panicle development and presents a novel, promising allele for enhancing rice grain yield through genetic improvement.

Oncolytic adenovirus carrying SPAG9-shRNA enhanced the efficacy of docetaxel for advanced prostate cancer.

Sperm-associated antigen 9 (SPAG9) is closely related to the growth and metastasis of advanced prostate cancer. Docetaxel (DTX) is the gold standard for chemotherapy of prostate cancer, but its side effects decrease the life quality of patients. Therefore, it is urgent to develop combination therapy to increase chemotherapy efficacy for advanced prostate cancer. Oncolytic adenovirus carrying a short hairpin RNA (shRNA) targeting SPAG9 (ZD55-shSPAG9) was applied alone or in combination with docetaxel in prostate cancer cells. Cells were analyzed by cell counting kit-8, Hocehst-33258, transwell and western blot analysis. For in vivo experiments, nude mice were loaded with prostate cancer cells. ZD55-shSPAG9 effectively silenced the expression of SPAG9 in prostate cancer cells in vitro and in vivo. The replication of ZD55-shSPAG9 in prostate cancer cells was not affected by docetaxel, but the combined use of ZD55-shSAPAG9 and docetaxel has a better inhibitory effect on tumor growth and invasion in vitro and in vivo. Our study showed that the combined use of ZD55-shSPAG9 and docetaxel may be a new approach to the treatment of advanced prostate cancer.

[Family-centered psychological support helps improve illness cognition and quality of life in patients with advanced prostate cancer].

OBJECTIVE: To explore the effect of family-centered psychological support (FCPS) on illness cognition and quality of life in patients with advanced prostate cancer (PCa). METHODS: Using a randomized controlled study design, we divided 84 advanced PCa patients into an intervention group and a control group, all provided with PCa-related knowledge and answers to their questions, while the former group with FCPS in addition. Before, immediately after and at 1 and 3 months after intervention, we evaluated the effectiveness using the Illness Cognition Questionnaire (ICQ) and Functional Assessment of Cancer Therapy － Prostate (FACT-P). RESULTS: Totally, 78 of the patients completed the whole intervention procedure, 38 in the intervention and 40 in the control group. There were statistically significant differences between the intervention and control groups in the scores on the three factors of ICQ acceptance (17.89 ± 3.86 vs 15.20 ± 2.83, t = 3.528, P < 0.05), perceived benefits (18.68 ± 3.02 vs 17.08 ± 2.74, t = 2.465, P < 0.05) and helplessness (13.37 ± 3.00 vs 15.63 ± 3.11, t = －3.259, P < 0.05) immediately after intervention, and so were there at 1 and 3 months after intervention (P < 0.05). The patients in the intervention group showed remarkably higher quality of life scores than the controls immediately after (100.59 ± 11.66 vs 92.20 ± 9.54, t = 7.943, P < 0.05) and at 1 month (93.03 ± 13.33 vs83.55 ± 14.29, t = 3.481, P < 0.05) and 3 months after intervention (85.66 ± 17.39 vs 75.95 ± 16.66, t = 3.025, P < 0.05). The covariance analysis found that, excluding the time effect, FCPS significantly improved the positive illness cognition of the patients (P < 0.05). CONCLUSIONS: Family-centered psychological support contributes to the positive illness cognition of the patients with advanced PCa and helps improve their quality of life, and therefore deserves to be popularized in clinical practice.

The impact of female sex hormones on cardiovascular disease: from mechanisms to hormone therapy.

Cardiovascular disease remains the leading cause of mortality in women, yet it has not raised the awareness from the public. The pathogenesis of cardiovascular disease differs significantly between females and males concerning the effect of sex hormones. Estrogen and progestogen impact cardiovascular system through genomic and non-genomic effects. Before menopause, cardiovascular protective effects of estrogens have been well described. Progestogens were often used in combination with estrogens in hormone therapy. Fluctuations in sex hormone levels, particularly estrogen deficiency, were considered the specific risk factor in women's cardiovascular disease. However, considerable heterogeneity in the impact of hormone therapy was observed in clinical trials. The heterogeneity is likely closely associated with factors such as the initial time, administration route, dosage, and formulation of hormone therapy. This review will delve into the pathogenesis and hormone therapy, summarizing the effect of female sex hormones on hypertension, pre-eclampsia, coronary heart disease, heart failure with preserved ejection fraction, and cardiovascular risk factors specific to women.

Dysfunction of duplicated pair rice histone acetyltransferases causes segregation distortion and an interspecific reproductive barrier.

Postzygotic reproductive isolation, which results in the irreversible divergence of species, is commonly accompanied by hybrid sterility, necrosis/weakness, or lethality in the F1 or other offspring generations. Here we show that the loss of function of HWS1 and HWS2, a couple of duplicated paralogs, together confer complete interspecific incompatibility between Asian and African rice. Both of these non-Mendelian determinants encode the putative Esa1-associated factor 6 (EAF6) protein, which functions as a characteristic subunit of the histone H4 acetyltransferase complex regulating transcriptional activation via genome-wide histone modification. The proliferating tapetum and inappropriate polar nuclei arrangement cause defective pollen and seeds in F2 hybrid offspring due to the recombinant HWS1/2-mediated misregulation of vitamin (biotin and thiamine) metabolism and lipid synthesis. Evolutionary analysis of HWS1/2 suggests that this gene pair has undergone incomplete lineage sorting (ILS) and multiple gene duplication events during speciation. Our findings have not only uncovered a pair of speciation genes that control hybrid breakdown but also illustrate a passive mechanism that could be scaled up and used in the guidance and optimization of hybrid breeding applications for distant hybridization.

The molecular basis of heat stress responses in plants.

Global warming impacts crop production and threatens food security. Elevated temperatures are sensed by different cell components. Temperature increases are classified as either mild warm temperatures or excessively hot temperatures, which are perceived by distinct signaling pathways in plants. Warm temperatures induce thermomorphogenesis, while high-temperature stress triggers heat acclimation and has destructive effects on plant growth and development. In this review, we systematically summarize the heat-responsive genetic networks in Arabidopsis and crop plants based on recent studies. In addition, we highlight the strategies used to improve grain yield under heat stress from a source-sink perspective. We also discuss the remaining issues regarding the characteristics of thermosensors and the urgency required to explore the basis of acclimation under multifactorial stress combination.

Effect of Body Mass Index on the Prognostic Value of Atherogenic Index of Plasma in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

(1) Background: The aim of this study was to investigate whether the prognostic value of the atherogenic index of plasma (AIP) for adverse cardiovascular events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) varied across different BMI groups. (2) Methods: This study was a retrospective analysis of a prospective registry involving 1725 ACS patients undergoing PCI. The primary endpoint was a composite of all-cause death, non-fatal ischemic stroke, non-fatal spontaneous myocardial infarction (MI), and unplanned repeat revascularization. (3) Results: The study population finally consisted of 526 patients with BMI < 24 kg/m2 (age 62 ± 10 years; male 64.3%), 827 patients with 24 kg/m2 ≤ BMI < 28 kg/m2 (age 60 ± 10 years; male 81.8%), and 372 patients with BMI ≥ 28 kg/m2 (age 57 ± 11 years; male 81.2%). The AIP as a continuous variable increased the risk for the primary endpoint in ACS patients undergoing PCI with BMI < 24 kg/m2 (HR 2.506; 95% CI 1.285-4.885; p = 0.007), while it did not increase the risk in patients with BMI ≥ 24 kg/m2 (hazard ratio [HR]: 1.747; 95% CI 0.921-3.316; p = 0.088 for patients with 24 kg/m2 ≤ BMI < 28 kg/m2; and HR: 2.096; 95% CI 0.835-5.261; p = 0.115 for patients with BMI ≥ 28 kg/m2, respectively). Compared with the lowest AIP tertile, the top AIP tertile was associated with a significantly increased risk of the primary endpoint in BMI < 24 kg/m2 group (HR: 1.772, 95% CI: 1.110 to 2.828, p = 0.016). (4) Conclusions: The AIP was significantly associated with an increased risk of adverse cardiovascular events in ACS patients undergoing PCI with BMI < 24 kg/m2, but not in the patients with BMI ≥ 24 kg/m2.

Neoadjuvant androgen deprivation therapy combined with abiraterone acetate in patients with locally advanced or metastatic prostate cancer: When to perform radical prostatectomy?

The surgical timing after neoadjuvant androgen-deprivation therapy (ADT) plus abiraterone acetate (AA) for patients with locally advanced or metastatic prostate cancer (PCa) is unknown. We divided patients with locally advanced or metastatic PCa into three groups according to prostate-specific antigen (PSA) nadir after neoadjuvant ADT plus AA: group 1 (PSA ≤ 0.2 ng/ml), group 2 (0.2 < PSA ≤ 4.0 ng/ml), and group 3 (PSA > 4.0 ng/ml).The median PSA baseline levels in groups 1, 2, 3 were 118.42 (32.03-457.78), 143.48 (17.7-8100.16), and153.35 (46.44-423.31) ng/ml, respectively. The median times of progression to CRPC in groups 1, 2,and 3 were 30, 26, and 26 months, respectively. Compared to patients with PSA nadir >0.2 ng/ml, patients with PSA nadir <0.2 ng/ml presented with longer PFS (p = 0.048).Our results suggested that, in patients with locally advanced or metastatic PCa, the time to progression to CRPC was longer after radical prostatectomy when PSA decreased below 0.2 ng/ml using neoadjuvant ADT plus AA.

Current status and progress of the development of prostate cancer vaccines.

At present, common treatments of prostate cancer mainly include surgery, radiotherapy, chemotherapy and hormone therapy. However, patients have high recurrence rate after treatment, and are prone to castration-resistant prostate cancer. Tumor vaccine is based on tumor specific antigen (TSA) and tumor associated antigen (TAA) to activate specific immune response of the body to cancer cells. With continuous maturity of tumor vaccine technology, different forms of prostate cancer vaccines have been developed, such as cellular vaccines, extracellular-based anti-tumor vaccines, polypeptide vaccines, and nucleic acid vaccines. In this review, we summarize current status and progress in the development of prostate cancer vaccines.

Optimization of rice panicle architecture by specifically suppressing ligand-receptor pairs.

Rice panicle architecture determines the grain number per panicle and therefore impacts grain yield. The OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway shapes panicle architecture by regulating cytokinin metabolism. However, the specific upstream ligands perceived by the OsER1 receptor are unknown. Here, we report that the EPIDERMAL PATTERNING FACTOR (EPF)/EPF-LIKE (EPFL) small secreted peptide family members OsEPFL6, OsEPFL7, OsEPFL8, and OsEPFL9 synergistically contribute to rice panicle morphogenesis by recognizing the OsER1 receptor and activating the mitogen-activated protein kinase cascade. Notably, OsEPFL6, OsEPFL7, OsEPFL8, and OsEPFL9 negatively regulate spikelet number per panicle, but OsEPFL8 also controls rice spikelet fertility. A osepfl6 osepfl7 osepfl9 triple mutant had significantly enhanced grain yield without affecting spikelet fertility, suggesting that specifically suppressing the OsEPFL6-OsER1, OsEPFL7-OsER1, and OsEPFL9-OsER1 ligand-receptor pairs can optimize rice panicle architecture. These findings provide a framework for fundamental understanding of the role of ligand-receptor signaling in rice panicle development and demonstrate a potential method to overcome the trade-off between spikelet number and fertility.

Conjugated polymer and gold nanoparticle co-loaded PLGA nanocomposites with eccentric internal nanostructure for dual-modal targeted cellular imaging.

Herein is reported the one-step synthesis of an integrated nanocomposite with eccentrically loaded 5 nm gold nanoparticles (Au NPs) and conjugated polymer of poly[9,9-bis(6'-N,N,N-trimethylammonium)hexyl)fluorenyldivinylene-alt-4,7-(2,1,3,- benzothiadiazole) dibromide] (PFVBT). The nanocomposite is generated with surface-functionalized folic acid groups due to the matrix polymer of PLGA-PEG(2000) -folate used for encapsulation. The nanocomposite shows far-red fluorescence from PFVBT and scattering signal from Au NPs. Although Au NPs have been widely reported to quench the fluorescence of conjugated polymers, the PFVBT fluorescence is well maintained in the nanocomposite due to the eccentric location of Au NPs. The folic acid groups at the nanocomposite surface favor its cellular uptake by MCF-7 breast cancer cells, which have overexpressed folate receptors on the cell membranes. In conjugation with its low cytotoxicity, the folic-acid-functionalized nanocomposite has been successfully utilized for fluorescence and dark-field dual-modal targeted cellular imaging.

Hyperbranched conjugated polyelectrolyte for dual-modality fluorescence and magnetic resonance cancer imaging.

Herein is reported the synthesis of gadolinium ion (Gd(III))-chelated hyperbranched conjugated polyelectrolyte (HCPE-Gd) and its application in fluorescence and magnetic resonance (MR) dual imaging in live animals. The synthesized HCPE-Gd forms nanospheres with an average diameter of ∼42 nm measured by laser light scattering and a quantum yield of 10% in aqueous solution. The absorption spectrum of HCPE-Gd has two maxima at 318 and 417 nm, and its photoluminescence maximum centers at 591 nm. Confocal laser scanning microscopy studies indicate that the HCPE-Gd is internalized in MCF-7 cancer cell cytoplasm with good photostability and low cytotoxicity. Further fluorescence and MR imaging studies on hepatoma H22 tumor-bearing mouse model reveal that HCPE-Gd can serve as an efficient optical/MR dual-modal imaging nanoprobe for in vivo cancer diagnosis.

Glycosylated star-shaped conjugated oligomers for targeted two-photon fluorescence imaging.

A glucopyranose functionalized star-shaped oligomer, N-tris{4,4',4''-[(1E)-2-(2-{(E)-2-[4-(benzo[d]thiazol-2-yl)phenyl]vinyl}-9,9-bis(6-2-amido-2-deoxy-1-thio-ß-D-glucopyranose-hexyl)-9H-fluoren-7-yl)vinyl]phenyl}phenylamine (TVFVBN-S-NH(2)), is synthesized for two-photon fluorescence imaging. In water, TVFVBN-S-NH(2) self-assembles into nanoparticles with an average diameter of ∼49 nm and shows a fluorescence quantum yield of 0.21. Two-photon fluorescence measurements reveal that TVFVBN-S-NH(2) has a two-photon absorption cross-section of ∼1100 GM at 780 nm in water. The active amine group on the glucopyranose moiety allows further functionalization of TVFVBN-S-NH(2) with folic acid to yield TVFVBN-S-NH(2) FA with similar optical and physical properties as those for TVFVBN-S-NH(2). Cellular imaging studies reveal that TVFVBN-S-NH(2) FA has increased uptake by MCF-7 cells relative to that for TVFVBN-S-NH(2), due to specific interactions between folic acid and folate receptors on the MCF-7 cell membrane. This study demonstrates the effectiveness of glycosylation as a molecular engineering strategy to yield water-soluble materials with a large two-photon absorption (TPA) cross-section for targeted cancer-cell imaging.

Fluorescence and visual detection of single nucleotide polymorphism using cationic conjugated polyelectrolyte.

We report a simple assay for visual detection of single nucleotide polymorphisms (SNPs) with good sensitivity and selectivity. The selectivity is determined by Escherichia coli (E. coli) DNA ligase mediated circular formation upon recognition of the point mutation on DNA targets. Rolling cycle amplification (RCA) of the perfect-matched DNA target is then initiated using the in situ formed circular template in the presence of Phi29 enzyme. Due to amplification of the DNA target, the RCA product has a tandem-repeated sequence, which is significantly longer than that for the SNP strand. Direct addition of a cationic conjugated polymer of poly[9,9'-bis(6'-(N,N,N-trimethylammonium)hexyl)fluorene-co-9,9'-bis(2-(2-(2-(N,N,N-trimethylammonium)ethoxyl)-ethoxy)-ethyl)fluorene tetrabromide] containing 20 mol% 2,1,3-benzothiadiazole (PFBT(20)) into the RCA solution leads to blue-whitish fluorescent color for SNP strand and yellowish fluorescent color for amplified DNA, due to PFBT(20)/DNA complexation induced intrachain/interchain energy transfer. To further improve the contrast for visual detection, FAM-labeled peptide nucleic acid (PNA) was hybridized to each amplified sequence, which is followed by the addition of poly{2,7-[9,9-bis(6'-N,N,N-trimethylammoniumhexyl)]fluorene-co-2,5-difluoro-1,4-phenylene dibromide} (PFP). The PNA/DNA hybridization brings PFP and FAM-PNA into close proximity for energy transfer, and the solution fluorescent color appears green in the presence of target DNA with a detection limit of 1 nM, which is significantly improved as compared to that for most reported visual SNP assay.

Annealing temperature and ultraviolet irradiation effect on the ferroelectric properties of Bi(3.25)La(0.75)Ti3O12 thin films.

Bi(3.25)La(0.75)Ti3O12 thin films were prepared on Pt/Ti/SiO2/Si substrates by the metal organic decomposition method. The structural characterizations and the surface morphology observations were carried out applying X-ray diffraction and atomic force microscope, respectively. The annealing temperature and the ultraviolet irradiation effect on the ferroelectric properties were studied. It was found that the remnant polarization (Pr) and the coercive field (Ec) increased with the increase of the applied electric field (E) for all films. With the annealing temperature increasing from 670 degrees C to 750 degrees C, the increase tendency of Pr(E) and Ec (E) got enhanced from 670 degrees C to 720 degrees C, followed by weakened from 720 degrees C at 750 degrees C. These phenomena could be well explained by the different internal strain in films. The remnant polarization and the coercive field showed an obvious decrease when the top electrodes of the thin films were illuminated with UV light due to the screening effect of trapped charge carries.

Bacillus Calmette-Guerin for the Treatment of Non-muscle Invasive Bladder Cancer: History and Current Status.

In the past decades, the bacillus Calmette-Guerin (BCG) treatment for non-muscle invasive bladder cancer, especially for intermediate and high-risk groups, is increasingly accepted by multiple guidelines. Currently, the front-line setting for the high-risk group is still intravesical BCG instillation. However, the BCG mechanism, usage, adverse events, and the definition of BCG failure are not yet fully understood or defined. In addition, despite BCG being generally efficacious, a number of bladder cancer patients are unresponsive to the BCG immunotherapy. In this review, we summarize the history and current status of BCG immunotherapy, and highlight recent developments in designing novel strategies for the treatment of BCG-unresponsive patients.

TT2 controls rice thermotolerance through SCT1-dependent alteration of wax biosynthesis.

Global warming threatens crop production. G proteins mediate plant responses to multiple abiotic stresses. Here we identified a natural quantitative trait locus, TT2 (THEROMOTOLERANCE 2), encoding a Gγ subunit, that confers thermotolerance in rice during both vegetative and reproductive growth without a yield penalty. A natural allele with loss of TT2 function was associated with greater retention of wax at high temperatures and increased thermotolerance. Mechanistically, we found that a transcription factor, SCT1 (Sensing Ca2+ Transcription factor 1), functions to decode Ca2+ through Ca2+-enhanced interaction with calmodulin and acts as a negative regulator of its target genes (for example, Wax Synthesis Regulatory 2 (OsWR2)). The calmodulin-SCT1 interaction was attenuated by reduced heat-triggered Ca2+ caused by disrupted TT2, thus explaining the observed heat-induced changes in wax content. Beyond establishing a bridge linking G protein, Ca2+ sensing and wax metabolism, our study illustrates innovative approaches for developing potentially yield-penalty-free thermotolerant crop varieties.

An α/ß hydrolase family member negatively regulates salt tolerance but promotes flowering through three distinct functions in rice.

Ongoing soil salinization drastically threatens crop growth, development, and yield worldwide. It is therefore crucial that we improve salt tolerance in rice by exploiting natural genetic variation. However, many salt-responsive genes confer undesirable phenotypes and therefore cannot be effectively applied to practical agricultural production. In this study, we identified a quantitative trait locus for salt tolerance from the African rice species Oryza glaberrima and named it as Salt Tolerance and Heading Date 1 (STH1). We found that STH1 regulates fatty acid metabolic homeostasis, probably by catalyzing the hydrolytic degradation of fatty acids, which contributes to salt tolerance. Meanwhile, we demonstrated that STH1 forms a protein complex with D3 and a vital regulatory factor in salt tolerance, OsHAL3, to regulate the protein abundance of OsHAL3 via the 26S proteasome pathway. Furthermore, we revealed that STH1 also serves as a co-activator with the floral integrator gene Heading date 1 to balance the expression of the florigen gene Heading date 3a under different circumstances, thus coordinating the regulation of salt tolerance and heading date. Notably, the allele of STH1 associated with enhanced salt tolerance and high yield is found in some African rice accessions but barely in Asian cultivars. Introgression of the STH1HP46 allele from African rice into modern rice cultivars is a desirable approach for boosting grain yield under salt stress. Collectively, our discoveries not only provide conceptual advances on the mechanisms of salt tolerance and synergetic regulation between salt tolerance and flowering time but also offer potential strategies to overcome the challenges resulted from increasingly serious soil salinization that many crops are facing.

A genetic module at one locus in rice protects chloroplasts to enhance thermotolerance.

How the plasma membrane senses external heat-stress signals to communicate with chloroplasts to orchestrate thermotolerance remains elusive. We identified a quantitative trait locus, Thermo-tolerance 3 (TT3), consisting of two genes, TT3.1 and TT3.2, that interact together to enhance rice thermotolerance and reduce grain-yield losses caused by heat stress. Upon heat stress, plasma membrane-localized E3 ligase TT3.1 translocates to the endosomes, on which TT3.1 ubiquitinates chloroplast precursor protein TT3.2 for vacuolar degradation, implying that TT3.1 might serve as a potential thermosensor. Lesser accumulated, mature TT3.2 proteins in chloroplasts are essential for protecting thylakoids from heat stress. Our findings not only reveal a TT3.1-TT3.2 genetic module at one locus that transduces heat signals from plasma membrane to chloroplasts but also provide the strategy for breeding highly thermotolerant crops.