Gibberellins regulate masculinization through the SpGAI-SpSTM module in dioecious spinach.

The sex of dioecious plants is mainly determined by genetic factors, but it can also be converted by environmental cues such as exogenous phytohormones. Gibberellic acids (GAs) are well-known inducers of flowering and sexual development, yet the pathway of gibberellin-induced sex conversion in dioecious spinach (Spinacia oleracea L.) remains elusive. Based on sex detection before and after GA3 application using T11A and SSR19 molecular markers, we confirmed and elevated the masculinization effect of GA on a single female plant through exogenous applications of GA3, showing complete conversion and functional stamens. Silencing of GIBBERELLIC ACID INSENSITIVE (SpGAI), a single DELLA family protein that is a central GA signaling repressor, results in similar masculinization. We also show that SpGAI can physically interact with the spinach KNOX transcription factor SHOOT MERISTEMLESS (SpSTM), which is a homolog of the flower meristem identity regulator STM in Arabidopsis. The silencing of SpSTM also masculinized female flowers in spinach. Furthermore, SpSTM could directly bind the intron of SpPI to repress SpPI expression in developing female flowers. Overall, our results suggest that GA induces a female masculinization process through the SpGAI-SpSTM-SpPI regulatory module in spinach. These insights may help to clarify the molecular mechanism underlying the sex conversion system in dioecious plants while also elucidating the physiological basis for the generation of unisexual flowers so as to establish dioecy in plants.

Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma.

Hepatocellular carcinoma is the third leading cause of deaths from cancer worldwide. Infection with the hepatitis B virus is one of the leading risk factors for developing hepatocellular carcinoma, particularly in East Asia1. Although surgical treatment may be effective in the early stages, the five-year overall rate of survival after developing this cancer is only 50-70%2. Here, using proteomic and phospho-proteomic profiling, we characterize 110 paired tumour and non-tumour tissues of clinical early-stage hepatocellular carcinoma related to hepatitis B virus infection. Our quantitative proteomic data highlight heterogeneity in early-stage hepatocellular carcinoma: we used this to stratify the cohort into the subtypes S-I, S-II and S-III, each of which has a different clinical outcome. S-III, which is characterized by disrupted cholesterol homeostasis, is associated with the lowest overall rate of survival and the greatest risk of a poor prognosis after first-line surgery. The knockdown of sterol O-acyltransferase 1 (SOAT1)-high expression of which is a signature specific to the S-III subtype-alters the distribution of cellular cholesterol, and effectively suppresses the proliferation and migration of hepatocellular carcinoma. Finally, on the basis of a patient-derived tumour xenograft mouse model of hepatocellular carcinoma, we found that treatment with avasimibe, an inhibitor of SOAT1, markedly reduced the size of tumours that had high levels of SOAT1 expression. The proteomic stratification of early-stage hepatocellular carcinoma presented in this study provides insight into the tumour biology of this cancer, and suggests opportunities for personalized therapies that target it.

Chromosome-level genome assembly of Hippophae tibetana provides insights into high-altitude adaptation and flavonoid biosynthesis.

BACKGROUND: As an endemic shrub of the Qinghai-Tibetan Plateau (QTP), the distribution of Hippophae tibetana Schlecht. ranges between 2800 and 5200 m above sea level. As the most basal branch of the Hippophae genus, H. tibetana has an extensive evolutionary history. The H. tibetana is a valuable tree for studying the ecological evolution of species under extreme conditions. RESULTS: Here, we generated a high-quality chromosome-level genome of H. tibetana. The total size of the assembly genome is 917 Mb. The phylogenomic analysis of 1064 single-copy genes showed a divergence between 3.4 and 12.8 Mya for H. tibetana. Multiple gene families associated with DNA repair and disease resistance were significantly expanded in H. tibetana. We also identified many genes related to DNA repair with signs of positive selection. These results showed expansion and positive selection likely play important roles in H. tibetana's adaptation to comprehensive extreme environments in the QTP. A comprehensive genomic and transcriptomic analysis identified 49 genes involved in the flavonoid biosynthesis pathway in H. tibetana. We generated transgenic sea buckthorn hairy root producing high levels of flavonoid. CONCLUSIONS: Taken together, this H. tibetana high-quality genome provides insights into the plant adaptation mechanisms of plant under extreme environments and lay foundation for the functional genomic research and molecular breeding of H. tibetana.

Pd 4d Orbital Overlapping Modulation on Au@Pd Nanowires for Efficient H2O2 Production.

Isolating Pd atoms has been shown to be crucial for the design of a Pd-based electrocatalyst toward 2e- oxygen reduction reaction (ORR). However, there are limited studies focusing on the systematic compositional design that leads to an optimal balance between activity and selectivity. Herein, we design a series of Au@Pd core@shell structures to investigate the influence of the Pd 4d orbital overlapping degree on 2e- ORR performance. Density functional theory (DFT) calculations indicate that enhanced H2O2 selectivity and activity are achieved at Pdn clusters with n ≤ 3, and Pd clusters larger than Pd3 should be active for 4e- ORR. However, experimental results show that Au@Pd nanowires (NWs) with Pd4 as the primary structure exhibit the optimal H2O2 performance in an acidic electrolyte with a high mass activity (7.05 A mg-1 at 0.4 V) and H2O2 selectivity (nearly 95%). Thus, we report that Pd4, instead of Pd3, is the upper threshold of Pd cluster size for an ideal 2e- ORR. It results from the oxygen coverage on the catalyst surface during the ORR process, and such an oxygen coverage phenomenon causes electron redistribution and weakened *OOH binding strength on active sites, leading to enhanced activity of Pd4 with only 0.06 V overpotential in acidic media.

Glycolytic enzyme Enolase-1 regulates insulin gene expression in pancreatic ß-cell.

Enolase-1 (Eno1) plays a critical role in regulating glucose metabolism; however, its specific impact on pancreatic islet ß-cells remains elusive. This study aimed to provide a preliminary exploration of Eno1 function in pancreatic islet ß-cells. The findings revealed that the expression of ENO1 mRNA in type 2 diabetes donors was significantly increased and positively correlated with HbA1C and negatively correlated with insulin gene expression. A high level of Eno1 in human insulin-secreting rat INS-1832/13 cells with co-localization with intracellular insulin proteins was accordingly observed. Silencing of Eno1 using siRNA or inhibiting Eno1 protein activity with an Eno1 antagonist significantly reduced insulin secretion and insulin content in ß-cells, while the proinsulin/insulin content ratio remained unchanged. This reduction in ß-cells function was accompanied by a notable decrease in intracellular ATP and mitochondrial cytochrome C levels. Overall, our findings confirm that Eno1 regulates the insulin secretion process, particularly glucose metabolism and ATP production in the ß-cells. The mechanism primarily involves its influence on insulin production, suggesting that Eno1 represents a potential target for ß-cell protection and diabetes treatment.

Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy.

Despite the success of immune checkpoint inhibitors (ICIs) in treating solid tumors, lots of patients remain unresponsive to this therapy. Microwave ablation (MWA) stimulates systemic adaptive immunity against tumor cells by releasing tumor antigens. Additionally, IL-21 has demonstrated importance in stimulating T-cell effector function. The combination of these three therapies-MWA, IL-21, and anti-PD-1 monoclonal antibodies (mAbs)-has yet to be explored in the context of cancer treatment.In this study, we explored the impact of thermal ablation on IL-21R expression in tumor-infiltrating lymphocytes (TILs). Subsequently, we assessed alterations in the tumor microenvironment (TME) and peripheral lymphoid organs. Additionally, we conducted a thorough examination of tumor-infiltrating CD45+ immune cells across various treatment groups using single-cell RNA sequencing (scRNA-seq). Moreover, we determined the potential anti-tumor effects of the triple combination involving MWA, IL-21, and anti-PD-1 mAbs.Our findings revealed that MWA upregulated the expression of IL-21R on various immune cells in the untreated tumors. The combination of MWA with IL-21 exhibited a robust abscopal anti-tumor effect, enhancing the effector function of CD8+ T cells and facilitating dendritic cells' maturation and antigen presentation in the untreated tumor. Notably, the observed abscopal anti-tumor effect resulting from the combination is contingent upon T-cell recirculation, indicating the reliance of systemic adaptive immunity for this treatment regimen. Additionally, the combination of MWA, IL-21, and PD-1 mAbs demonstrated profound abscopal anti-tumor efficacy. Our findings provide support for further clinical investigation into a triple combination therapy involving MWA, IL-21, and ICIs for the treatment of metastatic cancer.

Targeted Modulation of Redox and Immune Homeostasis in Acute Lung Injury Using a Thioether-Functionalized Dendrimer.

Acute lung injury (ALI) is the pathophysiological precursor of acute respiratory distress syndrome. It is characterized by increased oxidative stress and exaggerated inflammatory response that disrupts redox reactions and immune homeostasis in the lungs, thereby posing significant clinical challenges. In this study, an internally functionalized thioether-enriched dendrimer Sr-G4-PEG is developed, to scavenge both proinflammatory cytokines and reactive oxygen species (ROS) and restore homeostasis during ALI treatment. The dendrimers are synthesized using an efficient and orthogonal thiol-ene "click" chemistry approach that involves incorporating thioether moieties within the dendritic architectures to neutralize the ROS. The ROS scavenging of Sr-G4-PEG manifests in its capacity to sequester proinflammatory cytokines. The synergistic effects of scavenging ROS and sequestering inflammatory cytokines by Sr-G4-PEG contribute to redox remodeling and immune homeostasis, along with the modulation of the NLRP3-pyroptosis pathway. Treatment with Sr-G4-PEG enhances the therapeutic efficacy of ALIs by alleviating alveolar bleeding, reducing inflammatory cell infiltration, and suppressing the release of inflammatory cytokines. These results suggest that Sr-G4-PEG is a potent nanotechnological candidate for remodeling redox and immune homeostasis in the treatment of ALIs, demonstrating the great potential of dendrimer-based nanomedicine for the treatment of respiratory pathologies.

Association of long-term triglyceride-glucose index patterns with the incidence of chronic kidney disease among non-diabetic population: evidence from a functional community cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance and previous studies have confirmed the association of TyG index with incident chronic kidney disease (CKD). However, the impact of longitudinal patterns of TyG index on CKD risk among non-diabetic population is still unknown. Therefore, this study aimed to investigate the association of longitudinal patterns of TyG index with incident CKD among non-diabetic population. METHODS: A total of 5484 non-diabetic participants who underwent one health examination per year from 2015 to 2017 were included in this prospective study. TyG index variability and cumulative TyG index were calculated to assess the longitudinal patterns of TyG index. Cox proportional hazard models were performed to estimate the association of TyG index variability or cumulative TyG index with incident CKD. RESULTS: During a median of 3.82 years follow-up, 879 participants developed CKD. Compared with participants in the lowest quartile, the hazard ratio (HR) and 95% confidence interval (CI) of incident CKD were 1.772 (95% CI: 1.453, 2.162) for the highest TyG index variability quartile and 2.091 (95% CI: 1.646, 2.655) for the highest cumulative TyG index quartile in the fully adjusted models. The best discrimination and reclassification improvement were observed after adding baseline TyG, TyG index variability and cumulative TyG index to the clinical risk model for CKD. CONCLUSIONS: Both TyG index variability and cumulative TyG index can independently predict incident CKD among non-diabetic population. Monitoring longitudinal patterns of TyG index may assist with prediction and prevention of incident CKD.

A SARS-CoV-2 Mpro fluorescent sensor for exploring pharmacodynamic substances from traditional Chinese medicine.

The main protease of SARS-CoV-2 (SARS-CoV-2 Mpro) plays a critical role in the replication and life cycle of the virus. Currently, how to screen SARS-CoV-2 Mpro inhibitors from complex traditional Chinese medicine (TCM) is the bottleneck for exploring the pharmacodynamic substances of TCM against SARS-CoV-2. In this study, a simple, cost-effective, rapid, and selective fluorescent sensor (TPE-S-TLG sensor) was designed with an AIE (aggregation-induced emission) probe (TPE-Ph-In) and the SARS-CoV-2 Mpro substrate (S-TLG). The TPE-S-TLG sensor was characterized using UV-Vis absorption spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential, and Fourier transform infrared (FTIR) spectroscopy techniques. The limit of detection of this method to detect SARS-CoV-2 Mpro was measured to be 5 ng mL-1. Furthermore, the TPE-S-TLG sensor was also successfully applied to screen Mpro inhibitors from Xuebijing injection using the separation and collection of the HPLC-fully automatic partial fraction collector (HPLC-FC). Six active compounds, including protocatechualdehyde, chlorogenic acid, hydroxysafflower yellow A, caffeic acid, isoquercetin, and pentagalloylglucose, were identified using UHPLC-Q-TOF/MS that could achieve 90% of the Mpro inhibition rate for the Xuebijing injection. Accordingly, the strategy can be broadly applied in the detection of disease-related proteases as well as screening active substances from TCM.

Solvent-Induced In(III)-MOFs with Controllable Interpenetration Degree Performing High-Efficiency Separation of CO2/N2 and CO2/CH4.

Herein, three In(III)-based metal-organic frameworks (In-MOFs) with different degrees of interpenetration (DOI), namely In-MOF-1, In-MOF-2, and In-MOF-3, constructed by In3+ and Y-shaped ligands 4,4',4″-s-triazine-2,4,6-triyltribenzoate (H3TATB), are successfully synthesized through the ionothermal/solvothermal method. Subsequently, three novel In-MOFs, including noninterpenetration polycatenation, 2-fold interpenetrated, and 4-fold interpenetrated structure, are employed as the platform for systematically investigating the separation efficiency of CO2/N2, CO2/CH4, and CO2/CH4/N2 mixture gas system. Among them, In-MOF-2 shows the highest CO2 uptake capacities at 298 K and simultaneously possesses the low adsorption enthalpy of CO2 (26.4 kJ/mol at low coverage), a feature desirable for low-energy-cost adsorbent regeneration. The CO2/N2 (v: v = 15/85) selectivity of In-MOF-2 reaches 37.6 (at 298 K and 1 bar), also revealing outstanding selective separation ability from flue gases and purifying natural gas, affording a unique robust separation material as it has moderate DOI and pore size. In-MOF-2 shows exceptional stability and feasibility to achieve reproducibility. Aperture adjustment makes In-MOF-2 a versatile platform for selectively capturing CO2 from flue gases or purifying natural gas.

Influence of Iron Substitution and Solution Composition on Brucite Carbonation.

Carbon neutral or negative mining can potentially be achieved by integrating carbon mineralization processes into the mine design, operations, and closure plans. Brucite [Mg(OH)2] is a highly reactive mineral present in some ultramafic mine tailings with the potential to be rapidly carbonated and can contain significant amounts of ferrous iron [Fe(II)] substituted for Mg; however, the influence of this substitution on carbon mineralization reaction products and efficiency has not been thoroughly constrained. To better assess the efficiency of carbon storage in brucite-bearing tailings, we performed carbonation experiments using synthetic Fe(II)-substituted brucite (0, 6, 23, and 44 mol % Fe) slurries in oxic and anoxic conditions with 10% CO2. Additionally, the carbonation process was evaluated using different background electrolytes (NaCl, Na2SO4, and Na4SiO4). Our results indicate that carbonation efficiency decreases with increasing Fe(II) substitution. In oxic conditions, precipitation of ferrihydrite [Fe10IIIO14(OH)2] and layered double hydroxides {e.g., pyroaurite [Mg6Fe2III(OH)16CO3·4H2O]} limited carbonation efficiency. Carbonation in anoxic environments led to the formation of Fe(II)-substituted nesquehonite (MgCO3·3H2O) and dypingite [Mg5(CO3)4(OH)2·âˆ¼5H2O], as well as chukanovite [Fe2IICO3(OH)2] in the case of 23 and 44 mol % Fe(II)-brucite carbonation. Carbonation efficiencies were consistent between chloride- and sulfate-rich solutions but declined in the presence of dissolved Si due to the formation of amorphous SiO2·nH2O and Fe-Mg silicates. Overall, our results indicate that carbonation efficiency and the long-term fate of stored CO2 may depend on the amount of substituted Fe(II) in both feedstock minerals and carbonate products.

Rare Earth Element Adsorption to Clay Minerals: Mechanistic Insights and Implications for Recovery from Secondary Sources.

The energy transition will have significant mineral demands and there is growing interest in recovering critical metals, including rare earth elements (REE), from secondary sources in aqueous and sedimentary environments. However, the role of clays in REE transport and deposition in these settings remains understudied. This work investigated REE adsorption to the clay minerals illite and kaolinite through pH adsorption experiments and extended X-ray absorption fine structure (EXAFS). Clay type, pH, and ionic strength (IS) affected adsorption, with decreased adsorption under acidic pH and elevated IS. Illite had a higher adsorption capacity than kaolinite; however, >95% adsorption was achieved at pH ∼7.5 regardless of IS or clay. These results were used to develop a surface complexation model with the derived binding constants used to predict REE speciation in the presence of competing sorbents. This demonstrated that clays become increasingly important as pH increases, and EXAFS modeling showed that REE can exist as both inner- and outer-sphere complexes. Together, this indicated that clays can be an important control on the transport and enrichment of REE in sedimentary systems. These findings can be applied to identify settings to target for resource extraction or to predict REE transport and fate as a contaminant.

Association between diabetes mellitus and postoperative urinary retention after cerebral angiography.

AIMS: The aim of this study is to examine the association between diabetes mellitus and postoperative urinary retention on cerebral angiography (including intravascular interventional therapy). METHODS: We collected data on the demographic characteristics and comorbidities, imaging and routine laboratory data, surgical information, and medications of patients who underwent cerebral angiography. Multivariate logistic regression was used to explore the correlation between diabetes and the incidence of postoperative urinary retention. RESULTS: A total of 932 patients were included, with a mean age of 59.7 years (74.1% men). Postoperative urinary retention occurred in 40.8% of the diabetes mellitus group and 30.3% of the group without diabetes. Compared with the group without diabetes, those with diabetes were more likely to experience postoperative urinary retention. Patients with higher glycosylated hemoglobin A1c levels had a higher risk of developing postoperative urinary retention. CONCLUSIONS: Diabetes was independently linked to postoperative urinary retention following cerebral angiography and patients with glycosylated hemoglobin A1c levels > 6% were more likely to experience postoperative urinary retention. Therefore, clinically regulating blood glucose levels may help to reduce the likelihood of postoperative urinary retention after cerebral angiography.

A tungsten-based metamaterial emitter for solar thermophotovoltaic systems.

Solar thermophotovoltaic systems are capable of showing efficient photoelectric conversion and are expected to surpass the Shockley-Queisser limit, owing to the spectrum-selective functionality of metamaterial selective emitters. Generally, metamaterial emitters are manufactured from multifarious materials, which also makes their manufacturing process complicated. Here, we propose a tungsten-only emitter composed of two rectangular bars with different widths and heights arranged in a cruciform structure, featuring a rectangular cavity at the top. Results from the simulations reveal that the emissivity of the metamaterial emitter exceeds 90% at the wavelength of 950-1590 nm and drops below 20% for wavelengths exceeding 2025 nm, which can effectively match GaSb photovoltaic cells. The outstanding emission performance is attributed to the coupling effect of surface plasmon resonance, cavity resonance and guided mode resonance, as evidenced by the analysis of electric and magnetic fields. We also explored the radiation spectrum in the 500-2500 K temperature range and found that it performed best at 1400 K. It is concluded that the emission performance is slightly affected by structural parameters and angles. This study presents a meaningful exploration of efficient solar utilization.

Associations of sex-related and thyroid-related hormones with risk of metabolic dysfunction-associated fatty liver disease in T2DM patients.

BACKGROUND: We aimed to examine sex-specific associations between sex- and thyroid-related hormones and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: Cross-sectional analyses of baseline information from an ongoing cohort of 432 T2DM patients (185 women and 247 men) in Xiamen, China were conducted. Plasma sex-related hormones, including estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone, and total testosterone (TT), and thyroid-related hormones, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and parathyroid hormone (PTH), were measured using chemiluminescent immunoassays. MAFLD was defined as the presence of hepatic steatosis (diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score > 60) since all subjects had T2DM in the present study. RESULTS: Prevalence of MAFLD was 65.6% in men and 61.1% in women with T2DM (P = 0.335). For men, those with MAFLD showed significantly decreased levels of FSH (median (interquartile range (IQR)):7.2 (4.9-11.1) vs. 9.8 (7.1-12.4) mIU/ml) and TT (13.2 (10.4-16.5) vs. 16.7 (12.8-21.6) nmol/L) as well as increased level of FT3 (mean ± standard deviation (SD):4.63 ± 0.68 vs. 4.39 ± 0.85 pmol/L) than those without MAFLD (all p-values < 0.05). After adjusting for potential confounding factors, FSH and LH were negative, while progesterone was positively associated with the risk of MAFLD in men, and the adjusted odds ratios (ORs) (95% confidence intervals (CIs)) were 0.919 (0.856-0.986), 0.888 (0.802-0.983), and 8.069 (2.019-32.258) (all p-values < 0.05), respectively. In women, there was no statistically significant association between sex- or thyroid-related hormones and the risk of MAFLD. CONCLUSION: FSH and LH levels were negative, whereas progesterone was positively associated with the risk of MAFLD in men with T2DM. Screening for MAFLD and monitoring sex-related hormones are important for T2DM patients, especially in men.

Association between systemic immune inflammatory/inflammatory response index and hypertension: A cohort study of functional community.

BACKGROUND AND AIMS: In prospective studies, there is limited evidence of the association between inflammation and hypertension. We aimed to explore the relationship between systemic immune inflammatory index (SII)/systemic inflammatory response index (SIRI) and hypertension in a prospective cohort study to identify the best inflammatory cell markers that predict hypertension. METHODS AND RESULTS: This study was conducted in a functional community cohort in Beijing. In 2015, a total of 6003 individuals without hypertension were recruited and followed up until 2021. Using a restriction cubic spline with baseline SII/SIRI as a continuous variable, the dose-response relationship between hypertension and SII/SIRI was explored. Logistic regression was used to analyze the correlation between hypertension and SII/SIRI trajectory groups. At a mean follow-up of 6 years, 970 participants developed hypertension. SII showed a significant nonlinear dose-response relationship with hypertension (P < 0.05). Higher SII/SIRI was associated with an increased risk of hypertension (SII: RR = 1.003, 95%CI: 1.001-1.004; SIRI: RR = 1.228, 95%CI: 1.015-1.486). Both SII and SIRI were more predictive in males than females (SII: 0.698 vs. 0.695; SIRI: 0.686 vs. 0.678). CONCLUSION: Both systemic immune inflammatory index (SII) and systemic inflammatory response Index (SIRI) independently increased the risk of hypertension, and both were effective inflammatory cell indicators that predict the risk of hypertension.

Prognostic Assessment of Colorectal Cancer Patients after Laparoscopic Surgery: A Comprehensive Evaluation of the Glasgow Prognostic Score and Fibrinogen-to-Prealbumin Ratio.

BACKGROUND Previous studies have shown that systemic inflammation and suboptimal nutritional status are associated with poor cancer prognosis. This study aims to investigate the prognostic value of preoperative Glasgow prognostic score (GPS) and fibrinogen-to-prealbumin ratio (FPR) in patients with CRC (colorectal cancer) after laparoscopic surgery. MATERIAL AND METHODS In this study, the clinical data of 112 patients with CRC who underwent laparoscopic surgery were retrospectively analyzed, and the 3-year and 5-year survival rates of these patients were evaluated. In addition, the prognostic role of preoperative FPR and GPS in CRC patients was assessed using X-tile software, Kaplan-Meier analysis, and Cox regression analysis. Receiver operating characteristic (ROC) curves were generated to assess the predictive value of FPR, GPS, and FPR-GPS for the survival of these patients. RESULTS The results revealed a significant negative correlation between high FPR, elevated GPS, and overall survival (OS) in patients with CRC. Univariate and multivariate Cox regression analyses identified GPS (HR=3.207, 95% CI: 1.746~6.126), FPR (HR=2.669, 95% CI: 1.052~6.772), and lymph node metastasis (HR=2.222, 95% CI: 1.199~4.115) as independent prognostic indicators for overall survival. The ROC analysis demonstrated that the prediction based on FPR and GPS outperformed a single indicator in accurately predicting the prognosis of CRC patients. CONCLUSIONS Combining the preoperative FPR with the GPS contributes to accurate prognosis assessment for CRC patients after laparoscopic surgery. Patients exhibiting high FPR and GPS values are associated with a worse prognosis.

Two zinc finger proteins, VdZFP1 and VdZFP2, interact with VdCmr1 to promote melanized microsclerotia development and stress tolerance in Verticillium dahliae.

BACKGROUND: Melanin plays important roles in morphological development, survival, host-pathogen interactions and in the virulence of phytopathogenic fungi. In Verticillum dahliae, increases in melanin are recognized as markers of maturation of microsclerotia which ensures the long-term survival and stress tolerance, while decreases in melanin are correlated with increased hyphal growth in the host. The conserved upstream components of the VdCmr1-regulated pathway controlling melanin production in V. dahliae have been extensively identified, but the direct activators of this pathway are still unclear. RESULTS: We identified two genes encoding conserved C2H2-type zinc finger proteins VdZFP1 and VdZFP2 adjacent to VdPKS9, a gene encoding a negative regulator of both melanin biosynthesis and microsclerotia formation in V. dahliae. Both VdZFP1 and VdZFP2 were induced during microsclerotia development and were involved in melanin deposition. Their localization changed from cytoplasmic to nuclear in response to osmotic pressure. VdZFP1 and VdZFP2 act as modulators of microsclerotia melanization in V. dahliae, as confirmed by melanin biosynthesis inhibition and supplementation with the melanin pathway intermediate scytalone in albino strains. The results indicate that VdZFP1 and VdZFP2 participate in melanin biosynthesis by positively regulating VdCmr1. Based on the results obtained with yeast one- and two-hybrid (Y1H and Y2H) and bimolecular fluorescence complementation (BiFC) systems, we determined the melanin biosynthesis relies on the direct interactions among VdZFP1, VdZFP2 and VdCmr1, and these interactions occur on the cell walls of microsclerotia. Additionally, VdZFP1 and/or VdZFP2 mutants displayed increased sensitivity to stress factors rather than alterations in pathogenicity, reflecting the importance of melanin in stress tolerance of V. dahliae. CONCLUSIONS: Our results revealed that VdZFP1 and VdZFP2 positively regulate VdCmr1 to promote melanin deposition during microsclerotia development, providing novel insight into the regulation of melanin biosynthesis in V. dahliae.

Predictive model for treatment outcomes of peripheral T-cell lymphoma, not otherwise specified, in Taiwanese patients.

PURPOSE: We aimed to explore the clinical outcomes and prognostic factors for PTCL-NOS patients in the real world. METHODS: Clinical data were retrospectively collected from adult patients with PTCL-NOS treated at a single center in Taiwan. RESULTS: 104 PTCL-NOS patients with a median age of 53.0 years were enrolled. Patients with the International Prognostic Index (IPI) or prognostic index for peripheral T-cell lymphoma (PIT) scores of zero had a longer overall survival (OS) and progression free survival (PFS), while patients with IPI or PIT scores ≥1 did poorly. For patients who are eligible for transplantation, the use of pralatrexate as salvage chemotherapy has shown better OS (2-year OS 83.3% vs. 24.4%, P = 0.011) compared to patients who did not. By multivariate analysis, age >60 years, male, B symptoms, ECOG >1, lung involvement, and thrombocytopenia were independent adverse factors for OS. Incorporating factors in multivariate analysis, we established a novel predictive index for PTCL-NOS which efficiently stratifies patients into low (0-1 factor), intermediate-1 (2 factors), intermediate-2 (3 factors), and high risk (4-6 factors) groups with 2-year OS rates of 81.5%, 32.9%, 8.8%, and 0%, respectively (P < 0.001). CONCLUSION: PTCL-NOS patients have a dismal prognosis in Taiwan. Novel agents may improve the outcomes of PTCL-NOS patients. The usefulness of the novel prognostic index for PTCL-NOS needs further validation.

Y(OTf)3-Salazin-Catalyzed Asymmetric Aldol Condensation.

The chiral aziridine-containing vicinal iminophenol tridentate ligands (named salazins) are a class of readily prepared chiral ligands from enantiopure aziridines and salicylaldehydes. Their scandium and yttrium triflate complexes show excellent reactivity and enantioselectivities in the catalytic asymmetric aldol condensation of electron-deficient aromatic aldehydes and ketones, including acetone and cycloalkanones. The stereoselectivity is rationalized to the strong π-stacking interaction between aromatic aldehydes and the vicinal iminophenol group in the chiral ligands.