Modulating the tumoral SPARC content to enhance albumin-based drug delivery for cancer therapy.

Insufficient delivery of therapeutic agents into solid tumors by systemic administration remains a major challenge in cancer treatment. Secreted protein acidic and rich in cysteine (SPARC) has high binding affinity to albumin and has been shown to enhance the penetration and uptake of albumin-based drug carriers in tumors. Here, we developed a strategy to alter the tumor microenvironment (TME) by upregulating SPARC to enhance the delivery efficiency of albumin-based drug carriers into tumors. We prepared albumin nanoparticles encapsulating an NF-κB controllable CRISPR activation system (SP-NPs). SP-NPs achieved tumor-selective SPARC upregulation by responding to the highly activated NF-κB in tumor cells. Whereas a single dose of SP-NPs only modestly upregulated SPARC expression, serial administration of SP-NPs created a positive feedback loop that induced progressive increases in SPARC expression as well as tumor cell uptake and tumor penetration of the nanoparticles in vitro, in organoids, and in subcutaneous tumors in vivo. Additionally, pre-treatment with SP-NPs significantly enhanced the anti-tumor efficacy of Abraxane, a commercialized albumin-bound paclitaxel nanoformulation. Our data provide evidence that modulating SPARC in the TME can enhance the efficiency of albumin-based drug delivery to solid tumors, which may result in new strategies to increase the efficacy of nanoparticle-based cancer drugs.

Engineering redirected NF-κB/OIP5 expression programs to enhance tumor responses to chemotherapy in bladder cancer.

Nuclear factor kappa-B (NF-κB), a pivotal transcriptional regulator, plays a crucial role in modulating downstream genes implicated in tumor drug resistance. We establish a programmable system within bladder cancer cells to tailor drug responses by employing a synthetic clustered regularly interspaced short palindromic repeats (CRISPR)-based expression strategy that emulates natural transcriptional regulators. Our investigation uncovers the functional significance of Opa-interacting protein 5 (OIP5), upregulated upon NF-κB activation, as a key regulator governing drug-resistance to vincristine (VCR) treatment in bladder cancer. Through engineered guide RNAs (sgRNAs) targeting OIP5 to integrate NF-κB aptamers, we construct a modular scaffold RNA that encodes both the target locus and regulatory functionality. This engineered CRISPR scaffold RNA effectively responds to VCR stimulus by binding with activated NF-κB. Intriguingly, it redirects NF-κB to attenuate OIP5 expression-a reversal of its original role-while concurrently obstructing multiple NF-κB-mediated drug resistance pathways. This dual action thwarts drug resistance development. Further enhancing therapeutic potential, we develop a versatile nanoparticle system capable of co-delivering CRISPR scaffold RNAs and VCR. This synergistic approach demonstrates potent anti-tumor effects in both in vitro and in vivo settings. Our nanoparticle-mediated combination presents a compelling proof-of-concept, showcasing the utility of engineered CRISPR-based synthetic expression programs to reconfigure cellular drug responses and heighten tumor cell susceptibility to chemotherapy.

Prognostic impact of lymphovascular and perineural invasion in squamous cell carcinoma of the tongue.

This study aimed to investigate the prognostic impact of lymphovascular and perineural invasions in patients with squamous cell carcinoma of the tongue who received surgery-based treatment at our institution between January 2013 and December 2020. Patients were divided into four groups based on the presence of perineural (P-/P +) and lymphovascular invasions (V-/V +): P-V-, P-V + , P + V-, and P + V + . Log-rank and Cox proportional hazard models were used to evaluate the association between perineural /lymphovascular invasion and overall survival (OS). Altogether, 127 patients were included, and 95 (74.8%), 8 (6.3%), 18 (14.2%), and 6 (4.7%) cases were classified as P-V-, P-V + , P + V-, and P + V + , respectively. Pathologic N stage (pN stage), tumor stage, histological grade, lymphovascular invasion, perineural invasion, and postoperative radiotherapy were significantly associated with OS (p < 0.05). OS was significantly different among the four groups (p < 0.05). Significant between-group differences in OS were detected for node-positive (p < 0.05) and stage III-IV (p < 0.05) cases. OS was the worst in the P + V + group. Lymphovascular and perineural invasions are independent negative prognostic factors for squamous cell carcinoma of the tongue. Patients with lymphovascular and/or perineural invasion may have significantly poorer overall survival than those without neurovascular involvement.

Modified ß-cyclodextrin microspheres towards the application in intumescent fire resistance and smoke-suppressing of bio-based poly(L-lactic acid).

In this work, the ß-cyclodextrin (ß-CD) was modified by a phosphazene compound to prepare a novel amorphous derivate (ß-CDCP), which was combined with the ammonium polyphosphate (APP) as a synergistic flame retardant (FR) of the bio-based poly(L-lactic acid) (PLA). The effects of the APP/ß-CDCP on the thermal stability, combustion behavior, pyrolysis process, fire resistance performance and crystallizability of the PLA were investigated comprehensively and in depth by thermogravimetric (TG) analysis, limited oxygen index (LOI) analysis, UL-94 test, cone calorimetry measurement, TG-infrared (TG-IR), scanning electron microscopy-energy dispersive spectrometer, Raman spectroscopy, pyrolysis-gas chromatography/mass spectrometry and differential scanning calorimetry. The PLA/5%APP/10%ß-CDCP showed a highest LOI of 33.2 %, passed V-0 rating and exhibited self-extinguish phenomenon in the UL-94 test. Also, it presented a lowest peak of heat release rate, total heat release, peak of smoke production rate and total smoke release, and a highest char yield treated by cone calorimetry analysis. In addition, the 5%APP/10%ß-CDCP shortened significantly crystallization time and enhanced crystallization rate of the PLA. Gas phase and intumescent condensed phase fire proofing mechanisms are proposed to elucidate enhanced fire resistance in this system in detail.

A novel prognostic system combining carbonic anhydrase II and preoperative CA19-9 for intrahepatic cholangiocarcinoma after curative resection.

BACKGROUND: The role of carbonic anhydrase II (CAII) in intrahepatic cholangiocarcinoma (ICC) was investigated and a novel prognostic system combining CAII and preoperative carbohydrate antigen 19-9 (CA19-9) was established to predict the survival of patients with ICC after curative resection. METHODS: A total of 110 patients who underwent curative-intent resection for ICC between 2012 and 2020 were retrospectively analyzed. CAII in tumor and peritumor regions was examined by immunohistochemistry, and the relationships between clinicopathological factors and the prognostic value of CAII and CA19-9 were analyzed. RESULTS: CAII was frequently downregulated in ICC tissues (p < .001). Multivariate analyses indicated that showed that both low CAII expression level and preoperative CA19-9 ≥236 U/ml were independent risk factors for overall survival (OS) and recurrence-free survival (RFS) in patients with ICC after radical resection. Survival analysis revealed that patients with high CAII and low CA19-9 were significantly associated with a better OS and RFS (p < .001). The time-dependent receiver operating characteristic curves showed that CAII + CA19-9 had better prognostic predictive ability than CAII or CA19-9 alone. The nomogram constructed on independent factors including T stage, lymph node metastasis, CA19-9 (continuous variable), and CAII achieved C-indexes of 0.754 (95% CI, 0.701-0.807) and 0.730 (0.674-0.785) for OS and RFS, respectively. The calibration curve revealed acceptable agreement between actual and predicted OS and RFS. CONCLUSIONS: The combination of CAII and preoperative CA19-9 is a novel and useful prognostic tool for predicting the survival of patients with ICC after curative resection and guiding clinical decisions. PLAIN LANGUAGE SUMMARY: Carbonic anhydrase II (CAII) was frequently downregulated in intrahepatic cholangiocarcinoma (ICC) tissues. Survival analysis revealed that CAII is a novel independent factor for prognosis in patients with ICC after curative resection. CAII could be a useful prognostic marker for patients with ICC after surgery. The combination of CAII and preoperative carbohydrate antigen 19-9 is a novel and useful prognostic tool for predicting the survival of patients with ICC after curative resection and guiding clinical decisions.

Hybrid Micelles of Carbon Quantum Dot-Doxorubicin Conjugates as Nanotheranostics for Tumor Therapy and Turn-On Fluorescence Imaging: Impact of Conjugated Structures and On-Off-On Mechanism.

Carbon quantum dots (CDs) have attracted more and more attention in the field of biological imaging, while their applications are restricted due to their nonspecific fluorescence and small particle size. Herein, two pH-responsive carbon quantum dot-doxorubicin (DOX) conjugates were designed with maleic acid (MA, cis-butenedioic acid) and fumaric acid (FA, trans-butenedioic acid) as linker, respectively, which could self-assemble into unique hybrid micelles as tumor-specific carrier-free nanotheranostics. Owing to the acid-labile covalent modification with conjugated groups and the interaction with the surrounding DOX molecules, the fluorescence of CDs was completely quenched, while it could be recovered in the tumor intracellular microenvironment by acid-triggered cleavage of the fluorophore-drug conjugates, showing excellent turn-on fluorescence for effective cellular imaging. Especially, the trans conjugate with FA as linker possessed higher drug content, better drug release behavior and stronger inhibition of tumor cells than the cis one with MA as linker, demonstrating its promising potential as carrier-free nanotheranostics for future tumor treatment.

Triclosan to Improve the Antimicrobial Performance of Universal Adhesives.

To solve the proble ms of composite restoration failure caused by secondary caries, this study reports a light curable antibacterial triclosan derivative (TCS-IH), which was synthesized and added to the existing commercial universal adhesive to achieve a long-term antibacterial effect The effect of mixing different mass percentages of TCS-IH on the bond strength of dentin was also investigated.TCS-IH was synthesized by solution polymerization and characterized by nuclear magnetic resonance hydrogen spectroscopy (1H NMR) and Fourier transform infrared (FTIR) spectroscopy. Two commercial universal adhesives, Single Bond Universal and All Bond Universal, were selected and used as the control group, and universal adhesives with different mass percentages (1 wt%, 3 wt%, 5 wt% and 7 wt%) of TCS-IH were used as the experimental group. The antibacterial properties were analysed by means of colony count experiments, biofilm formation detection, plotting of growth curves, biofilm metabolic activity detection, insoluble extracellular polysaccharide measurements and observations by confocal laser scanning microscopy and scanning electron microscopy (SEM). The effect of adhesives on biofilm formation, metabolism, extracellular matrix production, distribution of live and dead bacteria, and bacterial morphology of Streptococcus mutans (S. mutans) was analysed. The mechanical properties were evaluated by the degree of conversion and microtensile bonding strength under different conditions. Its biosafety was tested. We found that the addition of TCS-IH significantly improved the antibacterial performance of the universal adhesive, with the 5 wt% and 7 wt% groups showing the best antibacterial effect and effectively inhibiting the formation of biofilm. In addition, the adhesive strength test results showed that there was no statistical difference (p < 0.05) in the microtensile bond strength measured under various factors in all experimental groups except for the 7 wt% group in the self-etch bonding mode, and all of them had good biosafety. In summary, the 5 wt% group of antibacterial monomer TCS-IH was selected as the optimum addition to the universal adhesive to ensure the antimicrobial properties of the universal adhesive and the stability and durability of the adhesive interface. This study provides a reference for the clinical application of adhesives with antimicrobial activity to improve the stability and durability of adhesive restorations.

[Evaluation of fluid responsiveness in patients with septic shock by critical ultrasound with small dose fluid challenge].

OBJECTIVE: To explore the value of critical ultrasound in evaluating the fluid responsiveness of small dose volume challenge in patients with septic shock. METHODS: Thirty-six patients with septic shock admitted to the Third People's Hospital of Datong from January 2021 to December 2021 were enrolled, and the patients were randomly divided into control group and observation group, with 18 patients in each group. The control group was treated with traditional fluid challenge (500 mL of crystalloid injected within 30 minutes); the observation group received a small dose fluid challenge (100 mL of crystalloid injected within 1 minute). The hemodynamic indexes [central venous pressure (CVP), invasive mean arterial pressure (MAP), velocity-time integra (VTI)] and bilateral lung ultrasound scores were measured by critical ultrasound in both groups. The outcome related indicators of patients in the two groups were observed. The correlation between the above indexes and the fluid challenge was evaluated. RESULTS: Compared with the control group, the heart rate (HR) and CVP of patients in the observation group after the challenge were significantly lower than those in the control group [HR (times/min): 99.74±3.22 vs. 107.65±3.14, CVP (mmHg, 1 mmHg ≈ 0.133 kPa): 7.55±0.22 vs. 10.26±0.52, both P < 0.05], invasive MAP and VTI were significantly higher than those in the control group [invasive MAP (mmHg): 77.36±2.14 vs. 69.81±2.56, VTI (cm/s): 68.85±1.26 vs. 44.71±1.28, both P < 0.05]. The ultrasonic score of the observation group was significantly better than those of the control group (all P < 0.05). In terms of outcome, the length of intensive care unit (ICU) stay, mechanical ventilation time and the time for urine volume more than 0.5 mL×kg-1×h-1 of the observation group were significantly shorter than those in the control group [the length of ICU stay (hours): 138.26±1.25 vs. 205.73±1.26, mechanical ventilation time (hours): 36.80±0.25 vs. 47.65±0.36, time to reach urine volume more than 0.5 mL×kg-1×h-1 (hours): 27.38±1.25 vs. 38.61±1.30, all P < 0.05], The dosage of norepinephrine was significantly decreased in the observation group compared with the control group (mg: 45.26±1.85 vs. 53.73±1.92, P < 0.05), and the amount of resuscitation crystalloid was significantly reduced compared with the control group (mL: 1 532.62±12.38 vs. 1 755.52 ± 12.30, P < 0.05). Correlation analysis showed that the volume of crystalloid was highly consistent with M-BLUE pulmonary ultrasound (zone 2, 4 and 5), mechanical ventilation time, norepinephrine dose, time to reach the standard of urine volume and ΔVTI (all P < 0.05). CONCLUSIONS: Small dose fluid challenge evaluated by critical ultrasound in septic shock patients has a high value for fluid responsiveness, which can better reduce the risk of obvious tissue edema caused by fluid overload, organ damage and even life-threatening, make fluid challenge more reasonable and appropriate, thereby improving the success of treatment.

Effect of Co-culture of mesenchymal stem cell and glomerulus endothelial cell to promote endothelialization under optimized perfusion flow rate in whole renal ECM scaffold.

In recent era, many researches on implantable bio-artificial organs has been increased owing to large gap between donors and receivers. Comprehensive organ based researches on perfusion culture for cell injury using different flow rate have not been conducted at the cellular level. The present study investigated the co-culture of rat glomerulus endothelial cell (rGEC) and rat bone marrow mesenchymal stem cells (rBMSC) to develop micro vascularization in the kidney scaffolds culturing by bioreactor system. To obtain kidney scaffold, extracted rat kidneys were decellularized by 1% sodium dodecyl sulfate (SDS), 1% triton X-100, and distilled water. Expanded rGECs were injected through decellularized kidney scaffold artery and cultured using bioreactor system. Vascular endothelial cells adhered and proliferated on the renal ECM scaffold in the bioreactor system for 3, 7 and 14 days. Static, 1 â€‹ml/min and 2 â€‹ml/min flow rates (FR) were tested and among them, 1 â€‹ml/min flow rate was selected based on cell viability, glomerulus character, inflammation/endothelialization proteins expression level. However, the flow injury was still existed on primary cell cultured at vessel in kidney scaffold. Therefore, co-culture of rGEC â€‹+ â€‹rBMSC found suitable to possibly solve this problem and resulted increased cell proliferation and micro-vascularization in the glomerulus, reducing inflammation and cell death which induced by flow injury. The optimized perfusion rate under rGEC â€‹+ â€‹rBMSC co-culture conditions resulted in enhanced endocellularization to make ECM derived implantable renal scaffold and might be useful as a way of treatment of the acute renal failure.

Biomimetic Mineralized Hydrophilic Polyurethane Primers for Inducing Dentin Tubule Fillings.

This experiment aimed to synthesize a biomimetic mineralized hydrophilic polyurethane dentin primer containing DDDEEKC peptide (DDDEEKC-PU) to fill dentin tubules and induce mineralization. The degree of conversion (DC) was tested. Dentin samples were acid-etched and treated with DDDEEKC-PU. They were immersed in stimulated human fluid (SBF) for 7, 14 and 28 days. Dentin permeability, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and Vickers hardness were measured. After 28 days, regenerated minerals were deposited on resin tags which were confirmed to be hydroxyapatite (HAp). The minerals reduced the dentin permeability and improved the microhardness. DDDEEKC-PU was able to fill dental tubules immediately and induce mineralization simultaneously.

Clinical M2 Macrophage-Related Genes Can Serve as a Reliable Predictor of Lung Adenocarcinoma.

Background: Numerous studies have found that infiltrating M2 macrophages play an important role in the tumor progression of lung adenocarcinoma (LUAD). However, the roles of M2 macrophage infiltration and M2 macrophage-related genes in immunotherapy and clinical outcomes remain obscure. Methods: Sample information was extracted from TCGA and GEO databases. The TIME landscape was revealed using the CIBERSORT algorithm. Weighted gene co-expression network analysis (WGCNA) was used to find M2 macrophage-related gene modules. Through univariate Cox regression, lasso regression analysis, and multivariate Cox regression, the genes strongly associated with the prognosis of LUAD were screened out. Risk score (RS) was calculated, and all samples were divided into high-risk group (HRG) and low-risk group (LRG) according to the median RS. External validation of RS was performed using GSE68571 data information. Prognostic nomogram based on risk signatures and other clinical information were constructed and validated with calibration curves. Potential associations of tumor mutational burden (TMB) and risk signatures were analyzed. Finally, the potential association of risk signatures with chemotherapy efficacy was investigated using the pRRophetic algorithm. Results: Based on 504 samples extracted from TCGA database, 183 core genes were identified using WGCNA. Through a series of screening, two M2 macrophage-related genes (GRIA1 and CLEC3B) strongly correlated with LUAD prognosis were finally selected. RS was calculated, and prognostic risk nomogram including gender, age, T, N, M stage, clinical stage, and RS were constructed. The calibration curve shows that our constructed model has good performance. HRG patients were suitable for new ICI immunotherapy, while LRG was more suitable for CTLA4-immunosuppressive therapy alone. The half-maximal inhibitory concentrations (IC50) of the four chemotherapeutic drugs (metformin, cisplatin, paclitaxel, and gemcitabine) showed significant differences in HRG/LRG. Conclusions: In conclusion, a comprehensive analysis of the role of M2 macrophages in tumor progression will help predict prognosis and facilitate the advancement of therapeutic techniques.

Clinical Eosinophil-Associated Genes can Serve as a Reliable Predictor of Bladder Urothelial Cancer.

Background: Numerous studies have shown that infiltrating eosinophils play a key role in the tumor progression of bladder urothelial carcinoma (BLCA). However, the roles of eosinophils and associated hub genes in clinical outcomes and immunotherapy are not well known. Methods: BLCA patient data were extracted from the TCGA database. The tumor immune microenvironment (TIME) was revealed by the CIBERSORT algorithm. Candidate modules and hub genes associated with eosinophils were identified by weighted gene co-expression network analysis (WGCNA). The external GEO database was applied to validate the above results. TIME-related genes with prognostic significance were screened by univariate Cox regression analysis, lasso regression, and multivariate Cox regression analysis. The patient's risk score (RS) was calculated and divided subjects into high-risk group (HRG) and low-risk group (LRG). The nomogram was developed based on the risk signature. Models were validated via receiver operating characteristic (ROC) curves and calibration curves. Differences between HRG and LRG in clinical features and tumor mutational burden (TMB) were compared. The Immune Phenomenon Score (IPS) was calculated to estimate the immunotherapeutic significance of RS. Half-maximal inhibitory concentrations (IC50s) of chemotherapeutic drugs were predicted by the pRRophetic algorithm. Results: 313 eosinophil-related genes were identified by WGCNA. Subsequently, a risk signature containing 9 eosinophil-related genes (AGXT, B3GALT2, CCDC62, CLEC1B, CLEC2D, CYP19A1, DNM3, SLC5A9, SLC26A8) was finally developed via multiplex analysis and screening. Age (p < 0.001), grade (p < 0.001), and RS (p < 0.001) were independent predictors of survival in BLCA patients. Based on the calibration curve, our risk signature nomogram was confirmed as a good predictor of BLCA patients' prognosis at 1, 3, and 5 years. The association analysis of RS and immunotherapy indicated that low-risk patients were more credible for novel immune checkpoint inhibitors (ICI) immunotherapy. The chemotherapeutic drug model suggests that RS has an effect on the drug sensitivity of patients. Conclusions: In conclusion, the eosinophil-based RS can be used as a reliable clinical predictor and provide insights into the precise treatment of BLCA.

Phenotypic variation and genome-wide association studies of main culm panicle node number, maximum node production rate, and degree-days to heading in rice.

BACKGROUND: Grain yield is a complex trait that results from interaction between underlying phenotypic traits and climatic, edaphic, and biotic variables. In rice, main culm panicle node number (MCPNN; the node number on which the panicle is borne) and maximum node production rate (MNPR; the number of leaves that emerge per degree-day > 10°C) are primary phenotypic plant traits that have significant positive direct effects on yield-related traits. Degree-days to heading (DDTH), which has a significant positive effect on grain yield, is influenced by the interaction between MCPNN and MNPR. The objective of this research is to assess the phenotypic variation of MCPNN, MNPR, and DDTH in a panel of diverse rice accessions, determine regions in the rice genome associated with these traits using genome-wide association studies (GWAS), and identify putative candidate genes that control these traits. RESULTS: Considerable variation was observed for the three traits in a 220-genotype diverse rice population. MCPNN ranged from 8.1 to 20.9 nodes in 2018 and from 9.9 to 21.0 nodes in 2019. MNPR ranged from 0.0097 to 0.0214 nodes/degree day > 10°C in 2018 and from 0.0108 to 0.0193 nodes/degree-day > 10°C in 2019. DDTH ranged from 713 to 2,345 degree-days > 10°C in 2018 and from 778 to 2,404 degree-days > 10°C in 2019. Thirteen significant (P < 2.91 x 10-7) trait-single nucleotide polymorphism (SNP) associations were identified using the multilocus mixed linear model for GWAS. Significant associations between MCPNN and three SNPs in chromosome 2 (S02_12032235, S02_11971745, and S02_12030176) were detected with both the 2018 and best linear unbiased prediction (BLUP) datasets. Nine SNPs in chromosome 6 (S06_1970442, S06_2310856, S06_2550351, S06_1968653, S06_2296852, S06_1968680, S06_1968681, S06_1970597, and S06_1970602) were significantly associated with MNPR in the 2019 dataset. One SNP in chromosome 11 (S11_29358169) was significantly associated with the DDTH in the BLUP dataset. CONCLUSIONS: This study identifies SNP markers that are putatively associated with MCPNN, MNPR, and DDTH. Some of these SNPs were located within or near gene models, which identify possible candidate genes involved in these traits. Validation of the putative candidate genes through expression and gene editing analyses are necessary to confirm their roles in regulating MCPNN, MNPR, and DDTH. Identifying the underlying genetic basis for primary phenotypic traits MCPNN and MNPR could lead to the development of fast and efficient approaches for their estimation, such as marker-assisted selection and gene editing, which is essential in increasing breeding efficiency and enhancing grain yield in rice. On the other hand, DDTH is a resultant variable that is highly affected by nitrogen and water management, plant density, and several other factors.

A trait-based model ensemble approach to design rice plant types for future climate.

Crop models are powerful tools to support breeding because of their capability to explore genotype × environment×management interactions that can help design promising plant types under climate change. However, relationships between plant traits and model parameters are often model specific and not necessarily direct, depending on how models formulate plant morphological and physiological features. This hinders model application in plant breeding. We developed a novel trait-based multi-model ensemble approach to improve the design of rice plant types for future climate projections. We conducted multi-model simulations targeting enhanced productivity, and aggregated results into model-ensemble sets of phenotypic traits as defined by breeders rather than by model parameters. This allowed to overcome the limitations due to ambiguities in trait-parameter mapping from single modelling approaches. Breeders' knowledge and perspective were integrated to provide clear mapping from designed plant types to breeding traits. Nine crop models from the AgMIP-Rice Project and sensitivity analysis techniques were used to explore trait responses under different climate and management scenarios at four sites. The method demonstrated the potential of yield improvement that ranged from 15.8% to 41.5% compared to the current cultivars under mid-century climate projections. These results highlight the primary role of phenological traits to improve crop adaptation to climate change, as well as traits involved with canopy development and structure. The variability of plant types derived with different models supported model ensembles to handle related uncertainty. Nevertheless, the models agreed in capturing the effect of the heterogeneity in climate conditions across sites on key traits, highlighting the need for context-specific breeding programmes to improve crop adaptation to climate change. Although further improvement is needed for crop models to fully support breeding programmes, a trait-based ensemble approach represents a major step towards the integration of crop modelling and breeding to address climate change challenges and develop adaptation options.

[Effect of abnormal lipid metabolism on immune microenvironment in tumors].

The abnormality in lipid metabolism is an indication for malignant tumors and closely related to anti-tumor immune response. This abnormality is characterized by aberrant changes in metabolic signals, lipid transporters, metabolic substrates, metabolic enzymes and metabolites in lipid metabolism, which are mainly manifested as abnormal lipid accumulationin tumor cells. Aberrant lipid accumulation in the tumor microenvironment (TME) can affect both the phenotype and function of tumor infiltrating immune cells, which helps to construct an immunosuppressive tumor microenvironment and leads to immune escape of tumor cells. The anti-tumor immunotherapy can be improved by regulating the function of immune cells through targeting the abnormal molecules or pathways in lipid metabolism.

Chlorogenic Acids Inhibit Adipogenesis: Implications of Wnt/ß-Catenin Signaling Pathway.

In our previous in vitro study, we found that chlorogenic acid (CGA) inhibited adipocyte differentiation and triglyceride (TG) accumulation, but the underlying mechanism is still unclear. Accumulative genetic evidence supports that canonical Wnt signaling is a key modulator on adipogenesis. Methods. In this study, 3T3-L1 cells were induced adipogenic differentiation and then treated with CGA. We investigate the effect of CGA in inhibiting adipogenesis and evaluate its role in modulating Wnt10b (wingless integration1 10b), ß-catenin, glycogen synthase kinase-3ß (GSK-3ß), and peroxisome proliferator-activated receptor γ (PPAR-γ) involved in the Wnt (wingless integration1)/ß-catenin signaling pathway. Results. The result showed that after CGA treatment, lipid accumulation and TG level decreased significantly in 3T3-L1 cells, indicating that CGA could inhibit adipogenesis. In addition, CGA repressed the induction of adipocyte differentiation biomarkers as PPAR-γ, adipocyte protein 2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL), and the secretion of GSK-3ß in a dose-dependent manner upregulated the expression of ß-catenin and Wnt10b both in gene and protein levels. Moreover, CGA induced phosphorylation of GSK-3ß and promoted the accumulation of free cytosolic ß-catenin in 3T3-L1 adipocytes. Conclusion. Overall, these findings gave us the implications that CGA inhibits adipogenesis via the canonical Wnt signaling pathway.

Permissive action of H2O2 mediated ClUGT75 expression for auxin glycosylation and Al3+- tolerance in watermelon.

Although Al3+-toxicity is one of the limiting factors for crop production in acidic soils, little is known about the Al3+-tolerance mechanism in watermelon, a fairly acid-tolerant crop. This work aimed to identify the interaction between the H2O2 scavenging pathway and auxin glycosylation relevant to watermelon Al3+-tolerance. By analyzing expressions of hormone-related ClUGTs and antioxidant enzyme genes in Al3+-tolerant (ZJ) and Al3+-sensitive (NBT) cultivars, we identified ClUGT75s (B1, B2, and D1) and ClSOD1-2-ClCAT as crucial components associated with Al3+-tolerance. Al3+-stress significantly increased H2O2 content by 92.7% in NBT and 42.3% in ZJ, accompanied by less Al3+-, auxin (IAA and IBA), and MDA contents in ZJ than NBT. These findings coincided with significant ClSOD1-2 expression and stable dismutation activity in NBT than ZJ. Hence, higher H2O2 content in the root apex of NBT than ZJ correlated with a significant increase in auxin content and ClSOD1-2 up-regulation. Moreover, Al3+-activated ClUGT75D1 and ClUGT75B2 in ZJ coincided with no considerable change in IBA content, suggesting that glycosylation-mediated changes in IBA content might be relevant to Al3+-tolerance in watermelon. Furthermore, exogenous H2O2 and IBA indicated ClUGT75D1 modulating IBA is likely dependent on H2O2 background. We hypothesize that a higher H2O2 level in NBT represses ClUGT75, resulting in increased auxin than those in ZJ roots. Thus, excess in both H2O2 and auxin aggravated the inhibition of root elongation under Al3+-stress. Our findings provide insights on the permissive action of H2O2 in the mediation of auxin glycosylation by ClUGT75 in root apex for Al3+-tolerance in watermelon.

Sugarcane Aphid (Hemiptera: Aphididae) on Sorghum. I. Population Characteristics and Dispersion Patterns in Relation to Different Sample Unit Sizes.

The sugarcane aphid, Melanaphis sacchari (Zehntner), has emerged as a serious pest of sorghum in the United States. Field trials were conducted in Louisiana and South Carolina in 2016-2018 to investigate its population characteristics and distribution patterns in relation to four sample unit sizes (three circular and one leaf based). Sugarcane aphid populations usually progressed through a phase of rapid rise followed by a phase of rapid decline within a span of 5-6 wk, with peak density determined by sorghum cultivars and climatic conditions. Peak population densities for susceptible cultivars were 1.9-14.9× that for resistant cultivars on a per plant basis. Melanaphis sacchari tended to concentrate on the lower green leaf nodes early in the infestation, with the distribution shifting toward higher green leaf nodes as the infestation progressed. Aphid densities per cm2 at the basal and middle sections were about twice as high as at the distal section of leaves. The proportions of infested sample units were fitted to the Wilson-Room binomial model that incorporates the effect of density on clumping pattern. For a specific sample unit size, clumping patterns were similar across cultivars, years, and leaf positions, but varied across infestation stages. For a fixed aphid density per sample unit, the proportion of infested sample units decreased with increasing sample unit size. For a fixed aphid density per cm2, proportion infested increased with increasing sample unit size, indicating less clumping with a larger sample unit size. Field sampling time and efficiency between samplers were quantified.

Serum lipid levels correlate to the progression of gastric cancer with neuroendocrine immunophenotypes: A multicenter retrospective study.

PURPOSE: Dyslipidemia was associated with gastric adenocarcinoma or neuroendocrine tumors, but its role in a more malignant entity, gastric cancer with neuroendocrine immunophenotypes (GCNEI), was unclarified. This study sought to explore the relationship between serum lipid levels and the biological behaviors of gastric cancer with neuroendocrine immunophenotypes (GCNEI). METHODS: Patients with neuroendocrine carcinoma (NEC), GC with NEC components (GC-NEC), or GC expressing NE marker(s) but no NE morphology (GC-NENM) were enrolled from three centers. Their preoperative serum lipid levels, demographic, and clinicopathological information were analyzed and compared with those of patients with pure adenocarcinoma (PAC) or a background population selected from 10,061 health-check people by propensity-score matching. RESULTS: A total of 342 GCNEI patients were enrolled. Compared with the background population, total cholesterol (TCHO) and high-density lipoprotein cholesterol (HDL-C) levels were lower in GCNEI. Compared with PAC, GC-NENM and GC-NEC showed lower triglyceride (TG) levels, while, carcinoma with NE morphology showed higher low-density lipoprotein cholesterol (LDL-C) levels. Among GCNEI subtypes, GC-NEC differed from the others by higher LDL-C and non-HDL-C levels. A higher LDL-C level and(or) lower TG, HDL-C levels correlated to higher stages or large tumor sizes in GC-NENM, and a lower HDL-C level correlated to large tumor sizes in GC-NEC. A higher LDL-C level, lower TG, HDL-C, and non-HDL levels increased the risk of GC-NEC, and lower TG, and HDL-C levels increased the risk of GC-NENM and NEC. CONCLUSION: GCNEI had distinct and heterogeneous serum lipid patterns, which correlated to tumor development and progression.