Constructing lactylation-related genes prognostic model to effectively predict the disease-free survival and treatment responsiveness in prostate cancer based on machine learning.

Background: Prostate cancer (PCa) is one of the most common malignancies in men with a poor prognosis. It is therefore of great clinical importance to find reliable prognostic indicators for PCa. Many studies have revealed the pivotal role of protein lactylation in tumor development and progression. This research aims to analyze the effect of lactylation-related genes on PCa prognosis. Methods: By downloading mRNA-Seq data of TCGA PCa, we obtained the differential genes related to lactylation in PCa. Five machine learning algorithms were used to screen for lactylation-related key genes for PCa, then the five overlapping key genes were used to construct a survival prognostic model by lasso cox regression analysis. Furthermore, the relationships between the model and related pathways, tumor mutation and immune cell subpopulations, and drug sensitivity were explored. Moreover, two risk groups were established according to the risk score calculated by the five lactylation-related genes (LRGs). Subsequently, a nomogram scoring system was established to predict disease-free survival (DFS) of patients by combining clinicopathological features and lactylation-related risk scores. In addition, the mRNA expression levels of five genes were verified in PCa cell lines by qPCR. Results: We identified 5 key LRGs (ALDOA, DDX39A, H2AX, KIF2C, RACGAP1) and constructed the LRGs prognostic model. The AUC values for 1 -, 3 -, and 5-year DFS in the TCGA dataset were 0.762, 0.745, and 0.709, respectively. The risk score was found a better predictor of DFS than traditional clinicopathological features in PCa. A nomogram that combined the risk score with clinical variables accurately predicted the outcome of the patients. The PCa patients in the high-risk group have a higher proportion of regulatory T cells and M2 macrophage, a higher tumor mutation burden, and a worse prognosis than those in the low-risk group. The high-risk group had a lower IC50 for certain chemotherapeutic drugs, such as Docetaxel, and Paclitaxel than the low-risk group. Furthermore, five key LRGs were found to be highly expressed in castration-resistant PCa cells. Conclusion: The lactylation-related genes prognostic model can effectively predict the DFS and therapeutic responses in patients with PCa.

Identification a novel Ganoderma FIP gene from Ganoderma capense and its functional expression in Pichia pastoris.

Ganoderma capense is a precious medicinal fungus in China. In this study, a novel fungal immunomodulatory protein gene, named as FIP-gca, was cloned from G. capense by homologous cloning. Sequencing analysis indicated that FIP-gca was composed of 336 bp, which encoded a polypeptide of 110 amino acids. Protein sequence blasting and phylogenetic analysis showed that FIP-gca shared homology with other Ganoderma FIPs. FIP-gca was effectively expressed in Pichia pastoris GS115 at an expression level of 166.8 mg/L and purified using HisTrap™ fast-flow prepack columns. The immunomodulation capacity of rFIP-gca was demonstrated by that rFIP-gca could obviously stimulate cell proliferation and increase IL-2 secretion of murine spleen lymphocytes. Besides, antitumor activity of rFIP-gca towards human stomach cancer AGS cell line was evaluated in vitro. Cell wound scratch assay proved that rFIP-gca could inhibit migration of AGS cells. And flow cytometry assay revealed that rFIP-gca could significantly induce apoptosis of AGS cells. rFIP-gca was able to induce 18.12% and 22.29% cell apoptosis at 0.3 µM and 0.6 µM, respectively. Conclusively, the novel FIP-gca gene from G. capense has been functionally expressed in Pichia and rFIP-gca exhibited ideal immunomodulation and anti-tumour activities, which implies its potential application and study in future.

Heterologous expression of MirMAN enhances root development and salt tolerance in Arabidopsis.

Introduction: ß-Mannanase is a plant cell wall remodeling enzyme involved in the breakdown of hemicellulose and plays an important role in growth by hydrolyzing the mannan-like polysaccharide, but its function in adaptation to salt stress has been less studied. Methods: Based on cloned the mannanase (MAN) gene from Mirabilis jalapa L., the study was carried out by heterologously expressing the gene in Arabidopsis thaliana, and then observing the plant phenotypes and measuring relevant physiological and biochemical indicators under 150 mM salt treatment. Results and discussion: The results indicate that MirMAN is a protein with a glycohydrolase-specific structural domain located in the cell wall. We first found that MirMAN reduced the susceptibility of transgenic Arabidopsis thaliana to high salt stress and increased the survival rate of plants by 38%. This was corroborated by the following significant changes, including the reduction in reactive oxygen species (ROS) levels, increase in antioxidant enzyme activity, accumulation of soluble sugars and increase of the expression level of RD29 in transgenic plants. We also found thatthe heterologous expression of MirMAN promoted root growth mainly by elongating the primary roots and increasing the density of lateral roots. Meanwhile, the expression of ARF7, ARF19, LBD16 and LBD29 was up-regulated in the transgenic plants, and the concentration of IAA in the roots was increased. Those results indicate that MirMAN is involved in the initiation of lateral root primordia in transgenic plants through the IAA-ARF signalling pathway. In conclusion, MirMAN improves plant salt tolerance not only by regulating ROS homeostasis, but also by promoting the development of lateral roots. Reflecting the potential of the MirMAN to promote root plastic development in adaptation to salt stress adversity.

Molecular characterization and expression analysis of the remorin genes in tomato (Solanum lycopersicum L.).

Remorin (REMs) are plant-specific and plasma membrane-associated proteins that play an essential role in the growth and development of plants and adaptations to adverse environments. To our knowledge, a genome-scale investigation of the REM genes in tomato has never been systematically studied. In this study, a total of 17 SlREM genes were identified in the tomato genome using bioinformatics methods. Our results demonstrated that the 17 members of SlREM were classified into 6 groups based on phylogenetic analysis and unevenly distributed on the eight chromosomes of tomato. There were 15 REM homologous gene pairs between tomato and Arabidopsis. The SlREM gene structures and motif compositions were similar. Promoter sequence analysis showed that the SlREM gene promoters contained some tissue-specific, hormones and stress-related cis-regulatory elements. Expression analysis based on qRT-PCR (Real-time quantitative PCR) analysis showed that SlREM family genes were were differentially expressed in different tissues, and they responded to ABA, MeJA, SA, low-temperature, drought and NaCl treatments. These results potentially provide relevant information for further research on the biological functions of SlREM family genes.

A New Signature That Predicts Progression-Free Survival of Clear Cell Renal Cell Carcinoma with Anti-PD-1 Therapy.

Immunotherapy has greatly improved the survival time and quality of life of patients with renal cell carcinoma, but the benefits are limited to a small portion of patients. There are too few new biomarkers that can be used to identify molecular subtypes of renal clear cell carcinoma and predict survival time with anti-PD-1 treatment. Single-cell RNA data of clear cell renal cell carcinoma (ccRCC) treated with anti-PD-1 were obtained from public databases, then 27,707 high-quality CD4 + T and CD8 + T cells were obtained for subsequent analysis. Firstly, genes set variation analysis and CellChat algorithm were used to explore potential molecular pathway differences and intercellular communication between the responder and non-responder groups. Additionally, differentially expressed genes (DEGs) between the responder and non-responder groups were obtained using the "edgeR" package, and ccRCC samples from TCGA-KIRC (n = 533) and ICGA-KIRC (n = 91) were analyzed by the unsupervised clustering algorithm to recognize molecular subtypes with different immune characteristics. Finally, using univariate Cox analysis, least absolute shrinkage and selection operator (Lasso) regression, and multivariate Cox regression, the prognosis model of immunotherapy was established and verified to predict the progression-free survival of ccRCC patients treated with anti-PD-1. At the single cell level, there are different signal pathways and cell communication between the immunotherapy responder and non-responder groups. In addition, our research also confirms that the expression level of PDCD1/PD-1 is not an effective marker for predicting the response to immune checkpoint inhibitors (ICIs). The new prognostic immune signature (PIS) enabled the classification of ccRCC patients with anti-PD-1 therapy into high- and low-risk groups, and the progression-free survival times (PFS) and immunotherapy responses were significantly different between these two groups. In the training group, the area under the ROC curve (AUC) for predicting 1-, 2- and 3-year progression-free survival was 0.940 (95% CI: 0.894-0.985), 0.981 (95% CI: 0.960-1.000), and 0.969 (95% CI: 0.937-1.000), respectively. Validation sets confirm the robustness of the signature. This study revealed the heterogeneity between the anti-PD-1 responder and non-responder groups from different angles and established a robust PIS to predict the progression-free survival of ccRCC patients receiving immune checkpoint inhibitors.

Salvage Surgery for Advanced Lung Adenocarcinoma After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment.

BACKGROUND: No published studies to date have evaluated the detailed pathologic and genetic features of lung adenocarcinoma after epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy and salvage surgery. We aimed to evaluate the pathologic and genetic changes of tumors in patients with advanced lung adenocarcinoma treated with EGFR TKI therapy and salvage surgery. METHODS: This study retrospectively collected data from 29 advanced lung adenocarcinoma patients who underwent EGFR TKI therapy, followed by salvage operation, between January 2010 and December 2018. All patients had partial response or stable disease without evidence of progressive disease. Next-generation sequencing was used to determine whether acquired resistant mutations in morphologically treatment-sensitive and morphologically treatment-resistant regions of tumor existed. RESULTS: There were 3, 22, and 4 patients with clinical stage IIIB, IVA, and IVB, respectively. After a mean TKI treatment duration of 134 days, 27 patients had partial response, 2 had stable disease, and 27.6% of patients were downstaged before salvage surgery. All patients had residual viable tumor cells in their tumor bed; 5 patients (17.2%) had a major pathologic response. Acquired T790M mutations (n = 4), histologic transformations (n = 2), and acquired T790M mutation with histologic transformation (n = 1) were identified in the morphologically treatment-resistant regions of tumors. The 3-year overall survival was 75.9%. CONCLUSIONS: The presence of morphologically treatment-resistant tumor regions with acquired T790M mutations and histologic transformations demonstrate the existence of resistant subclones in TKI-treated tumors before disease progression. Salvage surgery performed in selected patients before disease progression may improve survival by removing TKI-resistant subclones.

Identification and validation of a lipid metabolism gene signature for predicting biochemical recurrence of prostate cancer after radical prostatectomy.

Background: Pro5state cancer is one of the most commonly diagnosed cancers in men worldwide and biochemical recurrence occurs in approximately 25% of patients after radical prostatectomy. Current decisions regarding biochemical recurrence after radical prostatectomy are largely dependent on clinicopathological parameters, which are less accurate. A growing body of research suggests that lipid metabolism influences tumor development and treatment, and that prostate cancer is not only a malignancy but also a lipid metabolism disease. Therefore, this study aimed to identify the prognostic value of lipid metabolism-related gene signaling disease to better predict biochemical recurrence and contribute to clinical decision-making. Methods: Expression data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) database and the MSKCC database. Candidate modules closely associated with BCR were screened by univariate and LASSOcox regression analyses, and multivariate Cox regression analyses were performed to construct gene signatures. Kaplan-Meier (KM) survival analysis, time-dependent subject operating curves (ROC), independent prognostic analysis, and Nomogram were also used to assess the prognostic value of the signatures. In addition, Gene Ontology Analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to explore potential biological pathways. Results: A 6-gene lipid metabolism-related gene signature was successfully constructed and validated to predict biochemical recurrence in prostate cancer patients. In addition, we identified the 6-gene signature as an independent risk factor. Functional analysis showed that lipid metabolism-related genes were closely associated with arachidonic acid metabolism, PPAR transduction signaling pathway, fatty acid metabolism, peroxisome, and glycerophospholipid metabolism. Prognostic models were associated with immune cell infiltration. Conclusion: We have successfully developed a novel lipid metabolism-related gene signature that is highly effective in predicting BCR in patients with limited prostate cancer after RP and created a prognostic Nomogram. Furthermore, the signature may help clinicians to select high-risk subpopulations, predict patient survival, and facilitate more personalized treatment than traditional clinical factors.

Genome-wide association study reveals the genetic basis of brace root angle and diameter in maize.

Brace roots are the main organ to support the above-ground part of maize plant. It involves in plant growth and development by water absorption and lodging resistance. The bracing root angle (BRA) and diameter (BRD) are important components of brace root traits. Illuminating the genetic basis of BRA and BRD will contribute the improvement for mechanized harvest and increasing production. A GWAS of BRA and BRD was conducted using an associated panel composed of 508 inbred lines of maize. The broad-sense heritability of BRA and BRD was estimated to be respectively 71% ± 0.19 and 52% ± 0.14. The phenotypic variation of BRA and BRD in the non-stiff stalk subgroup (NSS) and the stiff stalk subgroup (SS) subgroups are significantly higher than that in the tropical/subtropical subgroup (TST) subgroups. In addition, BRA and BRD are significantly positive with plant height (PH), ear length (EL), and kernel number per row (KNPR). GWAS revealed 27 candidate genes within the threshold of p < 1.84 × 10-6 by both MLM and BLINK models. Among them, three genes, GRMZM2G174736, GRMZM2G445169 and GRMZM2G479243 were involved in cell wall function, and GRMZM2G038073 encoded the NAC transcription factor family proteins. These results provide theoretical support for clarifying the genetic basis of brace roots traits.

Generation of 2D Airy beams with switchable metasurfaces.

Airy beams exhibit intriguing characteristics, such as diffraction-free propagation, self-acceleration, and self-healing, which have aroused great research interest. However, the spatial light modulator that generates Airy beams has problems such as narrow operational bandwidth, high cost, poor phase discretization, and single realization function. In the visible region (λ∼532 nm), we proposed a switchable all-dielectric metasurface for generating transmissive and reflective two-dimensional (2D) Airy beams. The metasurface was mainly composed of titanium dioxide nanopillars and vanadium dioxide substrate. Based on the Pancharatnam-Berry phase principle, a high-efficient Airy beam can be generated by controlling the phase transition of vanadium dioxide and changing the polarization state of the incident light. The optimized optical intensity conversion efficiencies of the transmissive and reflective metasurfaces were as high as 97% and 70%, respectively. In the field of biomedical and applied physics, our designed switchable metasurface is expected to offer the possibility of creating compact optical and photonic platforms for efficient generation and dynamic modulation of optical beams and open up a novel path for the application of high-resolution optical imaging systems.

A Novel Mutation in the FYCO1 Gene Causing Congenital Cataract: Case Study of a Chinese Family.

Congenital cataract is the most important global cause of visual impairment in children. Autosomal dominant and autosomal recessive inheritance account for the majority of the hereditary nonsyndromic congenital cataract. The function of FYCO1 gene is to guide the transport of the microtubule-directed vesicles. Mutations in the FYCO1 gene may cause cataracts. We reported a novel nonsense mutation in FYCO1 (c.1411C > T, P. R471 ∗), which could cause nonsyndrome autosomal recessive congenital cataract. We underwent an ophthalmology examination of all participants and collected blood samples from all participants and extracted genomic DNAs. By whole exome sequencing, we found that this family carried an unreported mutation in the FYCO1 gene: c.1411C > T, P. R471 ∗. Sanger sequencing was performed to verify the mutation. We used ITASSER and PYMOL to predict and compare the structure and function of the mutated proteins. Using SIFT software and referring to the relevant guidelines of ACMG, the mutation was determined to be pathogenic. The models suggested that the nonsense mutation p.R471∗ resulted in a profound disruption of the FYCO1 protein structure. This report expands the locus information of the FYCO1 mutations.

Adjuvant Chemotherapy for Pathological Node-Positive Disease in Squamous Cell Carcinoma of the Esophagus after Neoadjuvant Chemoradiotherapy Plus Surgery.

Purpose: The purpose of the present study is to determine the impact on survival using adjuvant chemotherapy on patients with locally advanced esophageal cancer. Materials and Methods: From 2007 to 2016, we enrolled 127 locally advanced esophageal squamous cell carcinoma patients treated with combined neoadjuvant chemoradiotherapy (nCRT) and surgery. For patients with the pathological residual primary disease (pT+) and/or residual node disease (pN+) after nCRT, adjuvant chemotherapy was also given after consideration of the toxicity of nCRT, patient performance, and/or comorbidity. The regimen of adjuvant chemotherapy was cisplatin 20 mg/m2/day and 5-fluorouracil 800 mg/m2/day on days 1 through 4 and 22 through 25. The primary endpoint was overall survival (OS). Results: From a total of 127 patients, 26 of them (20.5%) received adjuvant chemotherapy. In the multivariate analysis, pN+ diseases were independently associated with poor OS (hazard ratio (HR): 4.117, 95% confidence interval (CI): 1.366-12.404; p = 0.012). For those with pN+ diseases, their 5-year OS was 36.4% in the follow-up arm compared with 45.8% in the adjuvant chemotherapy arm (p = 0.094). Conclusions: Pathologic node-positive disease is associated with poor OS in locally advanced esophagus cancer patients after combined treatments with nCRT and surgery. Adjuvant chemotherapy appeared to have improved OS in pathologic node-positive diseases.

Biodegradation of polybutylene adipate-co-terephthalate by Priestia megaterium, Pseudomonas mendocina, and Pseudomonas pseudoalcaligenes following incubation in the soil.

Soil that contained polybutylene adipate-co-terephthalate (PBAT) was incubated with Priestia megaterium, Pseudomonas mendocina, and Pseudomonas pseudoalcaligenes to improve the biodegradative process of this polymer. The mixture of Pr. megaterium and Ps. mendocina was highly effective at biodegrading the PBAT, and after eight weeks of soil incubation, approximately 84% of the PBAT film weight was lost. Mixtures of the other two species also positively affected the synergistic degradation of PBAT film in the soil, but the mixture of three species had a negative effect. The residual PBAT film microstructure clearly demonstrated the degradation of PBAT, and the degree of degradation was related to the different species. Cleavage of the PBAT film ester bond after soil microbial action affected its properties. The incubation of PBAT in soil that contained these species affected soil dehydrogenase and soil lipase in particular. The secretion of lipase by these species could play an important role in the degradation of PBAT in the soil.

Screening of early-staged colorectal neoplasia by clonal hematopoiesis-based liquid biopsy and machine-learning.

Liquid biopsy test has a better uptake for colorectal cancer (CRC) screening. However, suboptimal detection of early-staged colorectal neoplasia (CRN) limits its application. Here, we established an early-staged CRN blood test using error-corrected sequencing by comparing clonal hematopoiesis (CH) of 63 CRN patients and that of 32 controls. We identified 1,446 variants and classified the uniqueness in CRN patients. There was no significance difference in the amount of variant between CRNs and controls, but the uniqueness of variants with defective DNA mismatch repair-related mutational signature was addressed from peripheral blood in early-staged CRN patients. By machine learning approach, the early-staged CRNs was discriminated from controls with an AUC of 0.959 and an accuracy of 0.937 (95% CI, 0.863 to 0.968). The CRN predictive model was further validated by additional 20 CRNs and 10 controls and showed the accuracy, sensitivity, specificity, positive prediction value (PPV) and negative prediction value (NPV) of 0.933 (95% CI: 0.779 to 0.992), 0.95, 0.90, 0.95 and 0.90, respectively. In summary, we develop a CH-based liquid biopsy test with machine learning approach, which not only increase screening uptake but also improve the detection rate of early-staged CRN.

Ganoderma immunomodulatory proteins: mushrooming functional FIPs.

Fungal immunomodulatory protein (FIP) is a novel functional protein family with specific immunomodulatory activity identified from several macro-fungi. A variety of biological activities of FIPs have been reported, such as anti-allergy, anti-tumor, mitogenic activity, and immunomodulation. Among all known FIPs, the firstly discovered FIP was isolated from Ganoderma lucidum, and most FIP members were from Ganoderma genus. Compared with other FIPs, Ganoderma FIPs possess some advantageous bioactivities, like stronger anti-tumor activity. Therein, gene sequences, protein structural features, biofunctions, and recombinant expression of Ganoderma FIPs were summarized and addressed, focusing on elucidating their anti-tumor activity and molecular mechanisms. Combined with current advances, development potential and application of Ganoderma FIPs were also prospected. KEY POINTS: • More than a dozen of reported FIPs are identified from Ganoderma species. • Ganoderma immunomodulatory proteins have superior anti-tumor activity with promising prospects and application. • Current review comprehensively addresses characterization, biofunctions, and anti-tumor mechanisms of Ganoderma FIPs.

Investigating early progression of Hodgkin lymphoma in a two-center analysis.

BACKGROUND/PURPOSE: The early progression of disease (POD) of Hodgkin lymphoma (HL) leads to a poor prognosis. To identify risk factors for early POD, this retrospective two-center cohort analysis was conducted. METHODS: Medical records of HL patients between 1998 and 2020 from two referral centers were reviewed. RESULTS: Two-hundred and sixty-nine patients were analyzed. The distribution of early vs. advanced stages was 51.1 vs. 48.9%, respectively. The 5-year progression free survival (PFS) was 63%, and the overall survival (OS) was 87% with a median follow-up of 52.0 months. The complete remission (CR) rate was 85.7%. Disease progression or relapsed disease occurred in 33.9% (n = 85) of patients while 17.0% of this cohort had early POD within 12 months of induction therapy. Patients with early POD had a worse median OS than those without (p < 0.001). Failure to achieve post-induction CR and high international prognostic score (IPS, 3-7) were independent risk factors for early POD. Compared with chemotherapy alone, consolidative radiotherapy after induction chemotherapy was associated with a lower risk of early POD (21.3% vs. 6.2%, p = 0.006). CONCLUSION: High IPS was an independent risk factor for early POD, which was less observed in those with consolidative radiotherapy.

COVID-19 inhibits spermatogenesis in the testes by inducing cellular senescence.

Introduction: COVID-19 (SARS-CoV-2) has been linked to organ damage in humans since its worldwide outbreak. It can also induce severe sperm damage, according to research conducted at numerous clinical institutions. However, the exact mechanism of damage is still unknown. Methods: In this study, testicular bulk-RNA-seq Data were downloaded from three COVID-19 patients and three uninfected controls from GEO to evaluate the effect of COVID-19 infection on spermatogenesis. Relative expression of each pathway and the correlation between genes or pathways were analyzed by bioinformatic methods. Results: By detecting the relative expression of each pathway and the correlation between genes or pathways, we found that COVID-19 could induce testicular cell senescence through MAPK signaling pathway. Cellular senescence was synergistic with MAPK pathway, which further affected the normal synthesis of cholesterol and androgen, inhibited the normal synthesis of lactate and pyruvate, and ultimately affected spermatogenesis. The medications targeting MAPK signaling pathway, especially MAPK1 and MAPK14, are expected to be effective therapeutic medications for reducing COVID-19 damage to spermatogenesis. Conclusion: These results give us a new understanding of how COVID-19 inhibits spermatogenesis and provide a possible solution to alleviate this damage.

Novel biomarkers predict prognosis and drug-induced neuroendocrine differentiation in patients with prostate cancer.

Background: A huge focus is being placed on the development of novel signatures in the form of new combinatorial regimens to distinguish the neuroendocrine (NE) characteristics from castration resistant prostate cancer (CRPC) timely and accurately, as well as predict the disease-free survival (DFS) and progression-free survival (PFS) of prostate cancer (PCa) patients. Methods: Single cell data of 4 normal samples, 3 CRPC samples and 3 CRPC-NE samples were obtained from GEO database, and CellChatDB was used for potential intercellular communication, Secondly, using the "limma" package (v3.52.0), we obtained the differential expressed genes between CRPC and CRPC-NE both in single-cell RNA seq and bulk RNA seq samples, and discovered 12 differential genes characterized by CRPC-NE. Then, on the one hand, the diagnosis model of CRPC-NE is developed by random forest algorithm and artificial neural network (ANN) through Cbioportal database; On the other hand, using the data in Cbioportal and GEO database, the DFS and PFS prognostic model of PCa was established and verified through univariate Cox analysis, least absolute shrinkage and selection operator (Lasso) regression and multivariate Cox regression in R software. Finally, somatic mutation and immune infiltration were also discussed. Results: Our research shows that there exists specific intercellular communication in classified clusters. Secondly, a CRPC-NE diagnostic model of six genes (HMGN2, MLLT11, SOX4, PCSK1N, RGS16 and PTMA) has been established and verified, the area under the ROC curve (AUC) is as high as 0.952 (95% CI: 0.882-0.994). The mutation landscape shows that these six genes are rarely mutated in the CRPC and NEPC samples. In addition, NE-DFS signature (STMN1 and PCSK1N) and NE-PFS signature (STMN1, UBE2S and HMGN2) are good predictors of DFS and PFS in PCa patients and better than other clinical features. Lastly, the infiltration levels of plasma cells, T cells CD4 naive, Eosinophils and Monocytes were significantly different between the CRPC and NEPC groups. Conclusions: This study revealed the heterogeneity between CRPC and CRPC-NE from different perspectives, and developed a reliable diagnostic model of CRPC-NE and robust prognostic models for PCa.

Good prediction of treatment responses to neoadjuvant chemoradiotherapy for esophageal cancer based on preoperative inflammatory status and tumor glucose metabolism.

To develop a tool for predicting pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (neoCRT) in patients with esophageal cancer by combining inflammatory status and tumor glucose metabolic activity. This study included 127 patients with locally advanced esophageal cancer who had received neoCRT followed by esophagectomy from 2007 to 2016. We collected their neutrophil-lymphocyte ratio (NLR) and standardized uptake value (SUV) obtained from fluorodeoxyglucose positron emission tomography (PET/CT) before and after neoCRT. Univariate and multivariate logistic regression analyses were performed to identify potential predictive factors for pCR. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of predictors were calculated. Between pCR and non-pCR groups, there were no statistically significant differences in patient characteristics, such as sex, age, site, and clinical T/N stage. Multivariate analyses identified four independent predictors for pCR, including pre-OP NLR < 5.4 [OR 11.179; 95% CI 8.385-13.495; p = 0.003], NLR change (ΔNLR) < 3 [OR 4.891; 95% CI 2.274-9.180; p = 0.005], changes in SUV (ΔSUV) > 7.2 [OR 3.033; 95% CI 1.354-6.791; p = 0.007], and SUV changes ratio (ΔSUV ratio) > 58% [OR 3.585; 95% CI 1.576-8.152; p = 0.002]. ΔNLR had the highest accuracy and NPV (84.3% and 90.3%, respectively). Combined factors of ΔNLR < 3 and ΔSUV ratio > 58% had the best PPV for pCR (84.8%). Inflammatory status (ΔNLR) and tumor glucose metabolic activity (ΔSUV ratio), when considered together, constitute a promising low-invasive tool with high efficacy for prediction of treatment response before surgery.

Biological compatibility, thermal and in vitro simulated degradation for poly(p-dioxanone)/poly(lactide-co-glycolide)/poly(ethylene succinate-co-glycolide).

Bio-absorbable polymers are widely desired to be applied and used as biomaterials for surgery hemostatic and medical tissue engineering devices. Ring-opening copolymerization reaction was applied to synthesize poly(ethylene succinate-co-glycolide) (PES-b-PGA). Stannous octoate was used as a catalyst whereas poly(ethylene succinate) was used as a macro-initiator to react with glycolide. PES-b-PGA was then used as a compatibilizer to prepare the blend biomaterial of PPDO/PLGA/PES-b-PGA by melt blending poly(p-dioxanone) (PPDO) with poly(lactide-co-glycolide) (PLGA). This would enhance the interactions of the inter-molecular chains and intra-molecular segments thus improving the compatibility. To obtain the biomaterial of PPDO/PLGA/PES-b-PGA with a regulated and controlled degradation and/or hydrolysis period, various ratios of PPDO, PLGA, and PES-b-PGA was blended. Behaviors of the thermal and in vitro simulated degradation, biological compatibility, cytotoxicity and subcutaneous implantation of PPDO/PLGA/PES-b-PGA were investigated. The results show that the in vitro hydrolytic degradation cycle is consistent with the wound healing time and that the biomaterial has slight cytotoxicity and it will do good to the cell proliferation, with 1 grade of cytotoxicity and the relative growth rate being the range from 92.5% to 96.2%. The implantation of the biomaterial into the rabbits' ears will not adversely affect the wound healing and the tissues surrounding the implanted sites. Therefore, the biomaterial has good biocompatibility and potential applications in medical tissue engineering devices.

Alternative splicing and duplication of PI-like genes in maize.

Alternative splicing and duplication provide the possibility of functional divergence of MADS-box genes. Compared with its Arabidopsis counterpart PI gene, Zmm16 in maize recruits a new role in carpel abortion and floral asymmetry, whereas the other two duplicated genes, Zmm18/29, have not yet been attributed to any function in flower development as a typical B class gene does. Here, alternatively spliced transcripts of three PIL genes were analyzed, among which we described the candidate functional isoforms and analyzed the potential effects of alternative splicing (AS) on protein-protein interactions as well, then their phylogenetic relationships with orthologs in typical grasses were further analyzed. Furthermore, we compared the cis-acting elements specific for three maize PIL genes, especially the elements related to methyl jasmonate (MeJA) and gibberellic acid (GA), both hormones involved in the sex-determination process in maize. Together with the results from the co-expression networks during reproductive organ development, we speculated that, due to duplication and alternative splicing, Zmm18/29 may play a role in GA- and MeJA-related developmental process. These results provide novel clues for experimental validation of the evolutional meaning of maize PIL genes.