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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A rice QTL GS3.1 regulates grain size through metabolic-flux distribution between flavonoid and lignin metabolons without affecting stress tolerance.

Grain size is a key component trait of grain weight and yield. Numbers of quantitative trait loci (QTLs) have been identified in various bioprocesses, but there is still little known about how metabolism-related QTLs influence grain size and yield. The current study report GS3.1, a QTL that regulates rice grain size via metabolic flux allocation between two branches of phenylpropanoid metabolism. GS3.1 encodes a MATE (multidrug and toxic compounds extrusion) transporter that regulates grain size by directing the transport of p-coumaric acid from the p-coumaric acid biosynthetic metabolon to the flavonoid biosynthetic metabolon. A natural allele of GS3.1 was identified from an African rice with enlarged grains, reduced flavonoid content and increased lignin content in the panicles. Notably, the natural allele of GS3.1 caused no alterations in other tissues and did not affect stress tolerance, revealing an ideal candidate for breeding efforts. This study uncovers insights into the regulation of grain size though metabolic-flux distribution. In this way, it supports a strategy of enhancing crop yield without introducing deleterious side effects on stress tolerance mechanisms.

Emerging Roles of Long Non-coding RNAs as Novel Biomarkers in the Diagnosis and Prognosis of Prostate Cancer.

New biomarkers for early diagnosis and prognosis are important in improving the diagnosis of metastatic or recurrent prostate cancer. Recent studies have shown important roles of long non-coding RNAs (lncRNAs) in tumorigenesis. Here we provide a comprehensive review of lncRNAs implicated in prostate cancer and discuss their potential as novel biomarkers and therapeutic targets for prostate cancer. In particular, we focus on lncRNAs associated with the androgen/androgen receptor pathway and the epithelial-to-mesenchymal transition. Notably, several lncRNAs such as PCA3, PCAT18, HOTAIR, and CCAT2 are prostate cancer-specific in that they are only upregulated in prostate cancer, and consequently they are promising biomarkers for use in clinical practice.

[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.

UDP-glucosyltransferase regulates grain size and abiotic stress tolerance associated with metabolic flux redirection in rice.

Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. Here, we characterize GSA1, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops.

Combination Therapy of Prostate Cancer by Oncolytic Adenovirus Harboring Interleukin 24 and Ionizing Radiation.

Prostate cancer is a common malignant tumor and the second leading cause of cancer-related death in men. Radiation therapy is a curative treatment for localized prostate cancer and has a limited effect for castration-resistant prostate cancer (CRPC). Interleukin 24 (IL-24) has a radiosensitizing effect in cancer cells. Our previous studies showed that ZD55-IL-24, an oncolytic adenovirus harboring IL-24, had better anti-tumor effect with no toxicity to normal cells. In this study, we evaluated the synergistic anti-tumor effect of oncolytic adenovirus ZD55-IL-24 combined with radiotherapy in prostate cancer. In Vitro and In Vivo experiments showed that the combined therapy significantly inhibited the growth of prostate cancer and provoked apoptosis of prostate cancer cells. In conclusion, the combination of ionizing radiation and oncolytic adenovirus expressing IL24 could achieve synergistic anti-tumor effect on prostate cancer, and is a promising strategy for prostate cancer therapy.

Translational Regulation of Plant Response to High Temperature by a Dual-Function tRNAHis Guanylyltransferase in Rice.

As sessile organisms, plants have evolved numerous strategies to acclimate to changes in environmental temperature. However, the molecular basis of this acclimation remains largely unclear. In this study we identified a tRNAHis guanylyltransferase, AET1, which contributes to the modification of pre-tRNAHis and is required for normal growth under high-temperature conditions in rice. Interestingly, AET1 possibly interacts with both RACK1A and eIF3h in the endoplasmic reticulum. Notably, AET1 can directly bind to OsARF mRNAs including the uORFs of OsARF19 and OsARF23, indicating that AET1 is associated with translation regulation. Furthermore, polysome profiling assays suggest that the translational status remains unaffected in the aet1 mutant, but that the translational efficiency of OsARF19 and OsARF23 is reduced; moreover, OsARF23 protein levels are obviously decreased in the aet1 mutant under high temperature, implying that AET1 regulates auxin signaling in response to high temperature. Our findings provide new insights into the molecular mechanisms whereby AET1 regulates the environmental temperature response in rice by playing a dual role in tRNA modification and translational control.

Studying the Polarization Switching in Polycrystalline BiFeO3 Films by 2D Piezoresponse Force Microscopy.

For rhombohedral multiferroelectrics, non-180° ferroelectric domain switching may induce ferroelastic and/or (anti-)ferromagnetic effect. So the determination and control of ferroelectric domain switching angles is crucial for nonvolatile information storage and exchange-coupled magnetoelectric devices. We try to study the intrinsic characters of polarization switching in BiFeO3 by introducing a special data processing method to determine the switching angle from 2D PFM (Piezoresponse Force Microscopy) images of randomly oriented samples. The response surface of BiFeO3 is first plotted using the piezoelectric tensor got from first principles calculations. Then from the normalized 2D PFM signals before and after switching, the switching angles of randomly oriented BiFeO3 grains can be determined through numerical calculations. In the polycrystalline BiFeO3 films, up to 34% of all switched area is that with original out-of-plane (OP) polarization parallel to the poling field. 71° polarization switching is more favorable, with the area percentages of 71°, 109° and 180° domain switching being about 42%, 29% and 29%, respectively. Our analysis further reveals that IP stress and charge migration have comparable effect on switching, and they are sensitive to the geometric arrangements. This work helps exploring a route to control polarization switching in BiFeO3, so as to realize desirable magnetoelectric coupling.

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.

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.