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Background Sorbus sensu stricto ( Sorbus s.s. ) is a genus with important economical values because of its beautiful leaves, and flowers and especially the colorful fruits. It belongs to the tribe Maleae of the family Rosaceae, and comprises about 90 species mainly distributed in China. There is on-going dispute about its infrageneric classification and species delimitation as the species are morphologically similar. With the aim of shedding light on the circumscription of taxa within the genus, phylogenetic analyses were performed using 29 Sorbus s.s. chloroplast (cp) genomes (16 newly sequenced) representing two subgenera and eight sections. Results The 16 cp genomes newly sequenced range between 159,646 bp and 160,178 bp in length. All the samples examined and 22 taxa re-annotated in Sorbus sensu lato ( Sorbus s.l. ) contain 113 unique genes with 19 of these duplicated in the inverted repeat (IR). Six hypervariable regions including trnR - atpA , petN - psbM , rpl32-trnL , trnH - psbA , trnT - trnL and ndhC-trnV were screened and 44–53 SSRs and 14–31 dispersed repeats were identified as potential molecular markers. Phylogenetic analyses under ML/BI indicated that Sorbus s.l. is polyphyletic, but Sorbus s.s. and the other five segregate genera, Aria , Chamaemespilus , Cormus , Micromeles and Torminalis are monophyletic. Two major clades and four sub-clades resolved with full-support within Sorbus s.s . are not consistent with the existing infrageneric classification. Two subgenera, subg. Sorbus and subg. Albocarmesinae are supported as monophyletic when S. tianschanica is transferred to subg. Albocarmesinae from subg. Sorbus and S. hupehensis var. paucijuga transferred to subg. Sorbus from subg. Albocarmesinae , respectively. The current classification at sectional level is not supported by analysis of cp genome phylogeny. Conclusion Phylogenomic analyses of the cp genomes are useful for inferring phylogenetic relationships in Sorbus s.s . Though genome structure is highly conserved in the genus, hypervariable regions and repeat sequences used are the most promising molecule makers for population genetics, species delimitation and phylogenetic studies.

Sex is determined by multiple factors derived from somatic and germ cells in vertebrates. We have identified amhy , dmrt1 , gsdf as male and foxl2 , foxl3 , cyp19a1a as female sex determination pathway genes in Nile tilapia. However, the relationship among these genes is largely unclear. Here, we found that the gonads of dmrt1 ; cyp19a1a double mutants developed as ovaries or underdeveloped testes with no germ cells irrespective of their genetic sex. In addition, the gonads of dmrt1 ; cyp19a1a ; cyp19a1b triple mutants still developed as ovaries. The gonads of foxl3 ; cyp19a1a double mutants developed as testes, while the gonads of dmrt1 ; cyp19a1a ; foxl3 triple mutants eventually developed as ovaries. In contrast, the gonads of amhy ; cyp19a1a , gsdf ; cyp19a1a , amhy ; foxl2 , gsdf ; foxl2 double and amhy ; cyp19a1a ; cyp19a1b , gsdf ; cyp19a1a ; cyp19a1b triple mutants developed as testes with spermatogenesis via up-regulation of dmrt1 in both somatic and germ cells. The gonads of amhy ; foxl3 and gsdf ; foxl3 double mutants developed as ovaries but with germ cells in spermatogenesis due to up-regulation of dmrt1 . Taking the respective ovary and underdeveloped testis of dmrt1 ; foxl3 and dmrt1 ; foxl2 double mutants reported previously into consideration, we demonstrated that once dmrt1 mutated, the gonad could not be rescued to functional testis by mutating any female pathway gene. The sex reversal caused by mutation of male pathway genes other than dmrt1 , including its upstream amhy and downstream gsdf , could be rescued by mutating female pathway gene. Overall, our data suggested that dmrt1 is the only male pathway gene tested indispensable for sex determination and functional testis development in tilapia.

This paper presents a modelling framework to evaluate travel delay of all vehicles influenced by moving bottlenecks on highways. During the derivation of analytical formulas, the arrival of slow vehicles was approximated by a Poisson process based on the assumption that they occupied a constant low proportion of the traffic stream. The mathematical analysis process was developed from moving bottlenecks with the same velocity to those with multiple different velocities, and the closed-form expression of expected average travel delay was obtained by utilizing kinematic-wave moving bottleneck theory, gap acceptance theory, probability theory and renewal theory. Model validation and parameters sensitive analysis were conducted by simulation relying on the open source database of US highway 10. The maximum passing rate and the macroscopic parameters of initial traffic state with maximum delay could be found by means of approximate formulas. The proposed modeling framework can be applied for evaluating impacts of slow vehicles on highway operation quantifiably, based on which traffic managements like truck prohibited period decision and speed or lane restriction could be made more scientifically.

Targeting ferroptosis has attracted exponential attention to eradicate cancer cells with high iron‐dependent growth. Increasing the level of intracellular labile iron pool via small molecules and iron‐containing nanomaterials is an effective approach to induce ferroptosis but often faces insufficient efficacy due to the fast drug metabolism and toxicity issues on normal tissues. Therefore, developing a long‐acting and selective approach to regulate ferroptosis is highly demanded in cancer treatment. Herein, a lysosome‐targeted magnetic nanotorquer (T7‐MNT) is proposed as the mechanical tool to dynamically induce the endogenous Fe2+ pool outbreak for ferroptosis of breast cancer. T7‐MNTs target lysosomes via the transferrin receptor‐mediated endocytosis in breast cancer cells. Under the programmed rotating magnetic field, T7‐MNTs generate torques to trigger endogenous Fe2+ release by disrupting the lysosomal membrane. This magneto‐mechanical manipulation can induce oxidative damage and antioxidant defense imbalance to boost frequency‐ and time‐dependent lipid peroxidization. Importantly, in vivo studies show that T7‐MNTs can efficiently trigger ferroptosis under the magnetic field and play as a long‐acting physical inducer to boost ferrotherapy efficacy in combination with RSL3. It is anticipated that this dynamic targeted strategy can be coupled with current ferroptosis inducers to achieve enhanced efficacy and inspire the design of mechanical‐based ferroptosis inducers for cancer treatment. Under the programmed magnetic field stimulation, the lysosome‐targeted magnetic nanotorquer (T7‐MNTs) generated torques to disrupt the lysosomal membrane and dynamically induce the endogenous Fe2+ pool outbreak. T7‐MNTs induced oxidative damage and antioxidant defense imbalance to trigger frequency‐ and time‐dependent ferroptosis, and played as an effective physical inducer for anticancer treatment.

Immunological-related genes (IRGs) play a critical role in the immune microenvironment of tumors. Our study aimed to develop an IRG-based survival prediction model for hepatocellular carcinoma (HCC) patients and to investigate the impact of IRGs on the immune microenvironment. Differentially expressed IRGs were obtained from The Genomic Data Commons Data Portal (TCGA) and the immunology database and analysis portal (ImmPort). The univariate Cox regression was used to identify the IRGs linked to overall survival (OS), and a Lasso-regularized Cox proportional hazard model was constructed. The International Cancer Genome Consortium (ICGC) database was used to verify the prediction model. ESTIMATE and CIBERSORT were used to estimate immune cell infiltration in the tumor immune microenvironment (TIME). RNA sequencing was performed on HCC tissue specimens to confirm mRNA expression. A total of 401 differentially expressed IRGs were identified, and 63 IRGs were found related to OS on the 237 up-regulated IRGs by univariate Cox regression analyses. Finally, five IRGs were selected by the LASSO Cox model, including , , , , and . This prognostic model demonstrated satisfactory predictive value in the ICGC dataset. The risk score was an independent predictive predictor for OS in HCC patients. Immune-related analysis showed that the immune infiltration level in the high-risk group was higher, suggesting that the 5-IRG signature may play an important role in mediating immune escape and immune resistance in the TIME of HCC. Finally, we confirmed the 5-IRG signature is highly expressed in 65 HCC patients with good predictive power. We established and verified a new prognosis model for HCC patients based on survival-related IRGs, and the signature could provide new insights into the prognosis of HCC.

Purpose: With the widespread prevalence of Corona Virus Disease 2019 (COVID-19), cancer patients are suggested to wear a surgical mask during radiation treatment. In this study, cone beam CT (CBCT) was used to investigate the effect of surgical mask on setup errors in head and neck radiotherapy. Methods: A total of 91 patients with head and neck tumors were selected. CBCT was performed to localize target volume after patient set up. The images obtained by CBCT before treatment were automatically registered with CT images and manually fine-tuned. The setup errors of patients in 6 directions of Vrt, Lng, Lat, Pitch, Roll and Rotation were recorded. The patients were divided into groups according to whether they wore the surgical mask, the type of immobilization mask used and the location of the isocenter. The setup errors of patients were calculated. A t-test was performed to detect whether it was statistically significant. Results: In the 4 groups, the standard deviation in the directions of Lng and Pitch of the with surgical mask group were all higher than that in the without surgical mask group. In the head-neck-shoulder mask group, the mean in the Lng direction of the with surgical mask group was larger than that of the without surgical mask group. In the lateral isocenter group, the mean in the Lng and Pitch directions of the with surgical mask group were larger than that of the without surgical mask group. The t-test results showed that there was significant difference in the setup error between the 2 groups (p = 0.043 and p = 0.013, respectively) only in the Lng and Pitch directions of the head-neck-shoulder mask group. In addition, the setup error of 6 patients with immobilization open masks exhibited no distinguished difference from that of the patients with regular immobilization masks. Conclusion: In the head and neck radiotherapy patients, the setup error was affected by wearing surgical mask. It is recommended that the immobilization open mask should be used when the patient cannot finish the whole treatment with a surgical mask.

This research investigated the effect of different storage temperatures on the compositional changes, physicochemical characteristics, and functional properties of hawthorn berries. Storage at 25 °C resulted in the gradual decrease of the moisture, hardness, sugar, titratable acid, and colour of hawthorn berries. These changes decreased with decreasing storage temperature, and the minimal changes happened at frozen storage (–18 °C). Similarly, the decreasing rate of ascorbic acid, extractable polyphenol (EPP), and flavonoids during storage also decreased with reducing storage temperature (25 °C > 4 °C > –18 °C). Hydrolysable polyphenol (HPP) was relatively stable during the hawthorn storage, and non-extractable proanthocyanidins (NEPA) increased with decreasing temperature. Ferric reducing antioxidant power (FRAP) of EPP and HPP decreased at 25 °C, while polyphenolic oxidase (PPO) and peroxidase (POD) activities decreased. Decreasing the storage temperature can improve the stability of the nutritional properties, antioxidant capacity, and enzyme activity of hawthorn. The specific storage temperature depends on the final processing conditions and the purposes of the hawthorn berries.

Background Prostate cancer (PCa) is the most common tumor in the male urogenital system. Radical prostatectomy, radiation, chemotherapy and endocrine therapy are common clinical treatment methods. Oncogene-induced senescence (OIS) is a special type of cellular senescence believed to have anti-tumor effects, may serve as an initial barrier for preventing tumor growth and development. As of yet, the effects of OIS on the occurrence, development, prognosis of prostate cancer and its related mechanisms are poorly understood, so further study is urgently needed. Materials and methods Gene transcriptomic data and clinical information data for PCa were downloaded from TCGA and GEO databases, OISGs were obtained from the Reactome database. We identified OIS-related subtypes based on consistent cluster analysis. Univariate Cox regression analysis was performed to identify PR-OISGs. LASSO regression analysis finally screened prognosis-related key genes and constructed a risk score model. Patients were classified into high-/ low-risk groups based on the median risk score. We assessed the TMB, immune cell infiltration level, immune checkpoint expression and drug sensitivity between high-/ low-risk groups. A nomogram was constructed and validated using calibration curves and clinical decision curves. RT-qPCR and IHC staining analysis were performed to verify the mRNA and protein expression levels of target genes. Results The study identified two OIS-associated subtypes of PCa. We screened seven PRGs and established a risk model for PCa patients. It was found that BFS (biochemical recurrence-free survival) was significantly lower in high-risk group. Patients in the high-risk group showed greater immune infiltration and high expression of immune checkpoint, as well as higher TMB. Furthermore, stratifying the risk score appropriately allowed the predictive nomogram model to accurately predict the outcome of prostate cancer patients. Also, docetaxel and Olaparib sensitivity was higher in the high-risk group, whereas bicalutamide was more sensitive in the low-risk group. IHC and PCR confirmed CDK6 was highly upregulated in PCa. Conclusion Our study screened seven genes with potential value for predicting long-term survival of patients with PCa and developed a prognostic model. These findings are expected to guide future development of effective therapies.

Background Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis‐related genes on survival in hepatitis B virus (HBV)‐related hepatocellular carcinoma (HBV‐HCC) patients remains unknown. Methods We used two‐stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosis‐related genes and overall survival (OS) of 866 HBV‐HCC patients. Results We identified that two potentially functional SNPs (CREB3 rs10814274 C > T and GALNT14 rs17010547 T > C) were significantly independently associated with the OS of HBV‐HCC patients (CT + TT verse CC, hazards ratio (HR) = 0.77, 95% confidence interval (CI) = 0.67–0.89, p < 0.001 for rs10814274 and TC + CC verse TT, HR = 0.66, 95% CI = 0.53–0.82, p < 0.001 for rs17010547, respectively). Additional joint assessment of protective genotypes of these two SNPs showed that patients with 1–2 protective genotypes had a significantly better OS compared with those carrying 0 protective genotypes (HR = 0.56, 95% CI = 0.45–0.70, p < 0.001). Moreover, the expression quantitative trait loci (eQTL) analysis revealed that the survival‐associated SNP rs10814274 T allele was significantly correlated with reduced CREB3 transcript levels in both normal liver tissues and whole blood cells, while the GALNT14 rs17010547 C allele had a significant correlation with increased GALNT14 transcript levels in whole blood cells. Conclusion These results suggest that genetic variants of CREB3 and GALNT14 may affect the survival of HBV‐HCC patients, likely via transcriptional regulation of respective genes. However, further studies are required to confirm these findings.

Background Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)‐related HCC. Methods In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway‐related genes and overall survival (OS) of 866 patients with HBV‐related HCC. Results It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV‐related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose‐response manner (ptrend <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3‐year and 5‐year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10‐3), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10−5 and 0.033, respectively). Conclusions Three potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV‐related HCC. In this study, we adopted a two‐stage study design to explore the associations between single nucleotide polymorphisms (SNPs) in the Notch pathway genes and the survival of HBV‐related hepatocellular carcinoma (HCC) patients. We found three independent SNPs (NEURL1B rs4868192 T>C, CNTN1 rs444927 G>A, and FCER2 rs1990975 C>T) were significantly associated with the OS of HBV‐related HCC, which may serve as potential prognostic biomarkers. Our study could provide reference for improving the survival of HCC.