Explore the vast range of titles available.

• Many flowering plant taxa contain allopolyploids that share one or more genomes in common. In the Brassica genus, crop species Brassica juncea and Brassica carinata share the B genome, with 2n = AABB and 2n = BBCC genome complements, respectively. Hybridization results in 2n = BBAC hybrids, but the fate of these hybrids over generations of self-pollination has never been reported. • We produced and characterized B. juncea × B. carinata (2n = BBAC) interspecific hybrids over six generations of self-pollination under selection for high fertility using a combination of genotyping, fertility phenotyping, and cytogenetics techniques. • Meiotic pairing behaviour improved from 68% bivalents in the F₁ to 98% in the S₅/S₆ generations, and initially low hybrid fertility also increased to parent species levels. The S₅/S₆ hybrids contained an intact B genome (16 chromosomes) plus a new, stable A/C genome (18–20 chromosomes) resulting from recombination and restructuring of A and C-genome chromosomes. • Our results provide the first experimental evidence that two genomes can come together to form a new, restructured genome in hybridization events between two allotetraploid species that share a common genome. This mechanism should be considered in interpreting phylogenies in taxa with multiple allopolyploid species.

Dysregulation of pericellular proteolysis is strongly implicated in cancer metastasis through alteration of cell invasion and the microenvironment. Matriptase-2 (MT-2) is a membrane-anchored serine protease which can suppress prostate cancer (PCa) cell invasion. In this study, we showed that MT-2 was down-regulated in PCa and could suppress PCa cell motility, tumor growth, and metastasis. Using microarray and biochemical analysis, we found that MT-2 shifted TGF-β action towards its tumor suppressor function by repressing epithelial-to-mesenchymal transition (EMT) and promoting Smad2 phosphorylation and nuclear accumulation to upregulate two TGF-β1 downstream effectors (p21 and PAI-1), culminating in hindrance of PCa cell motility and malignant growth. Mechanistically, MT-2 could dramatically up-regulate the expression of nuclear receptor NR4A3 via iron metabolism in PCa cells. MT-2-induced NR4A3 further coactivated Smad2 to activate p21 and PAI-1 expression. In addition, NR4A3 functioned as a suppressor of PCa and mediated MT-2 signaling to inhibit PCa tumorigenesis and metastasis. These results together indicate that NR4A3 sustains MT-2 signaling to suppress PCa cell invasion, tumor growth, and metastasis, and serves as a contextual factor for the TGF-β/Smad2 signaling pathway in favor of tumor suppression via promoting p21 and PAI-1 expression.

Interspecific hybridization is widespread in nature and can result in the formation of new hybrid species as well as the transfer of traits between species. However, the fate of newly formed hybrid lineages is relatively understudied. We undertook pairwise crossing between multiple genotypes of three Brassica allotetraploid species Brassica juncea (2n = AABB), Brassica carinata (2n = BBCC), and Brassica napus (2n = AACC) to generate AABC, BBAC, and CCAB interspecific hybrids and investigated chromosome inheritance and fertility in these hybrids and their self-pollinated progeny. Surprisingly, despite the presence of a complete diploid genome in all hybrids, hybrid fertility was very low. AABC and BBAC first generation (F1) hybrids both averaged ~16% pollen viability compared to 3.5% in CCAB hybrids: most CCAB hybrid flowers were male-sterile. AABC and CCAB F1 hybrid plants averaged 5.5 and 0.5 seeds per plant, respectively, and BBAC F1 hybrids ~56 seeds/plant. In the second generation (S1), all confirmed self-pollinated progeny resulting from CCAB hybrids were sterile, producing no self-pollinated seeds. Three AABC S1 hybrids putatively resulting from unreduced gametes produced 3, 14, and 182 seeds each, while other AABC S1 hybrids averaged 1.5 seeds/plant (0–8). BBAC S1 hybrids averaged 44 seeds/plant (range 0–403). We also observed strong bias towards retention rather than loss of the haploid genomes, suggesting that the subgenomes in the Brassica allotetraploids are already highly interdependent, such that loss of one subgenome is detrimental to fertility and viability. Our results suggest that relationships between subgenomes determine hybridization outcomes in these species.

    Purpose Psychological and social support are crucial in treating cancer. Cancer resource centers provide patients with cancer and their families with services that can help them through cancer treatment, ensure that patients receive adequate treatment, and reduce cancer-related stress. These centers offer various services, including medical guidance, health education, emotional assistance (e.g., consultations for cancer care), and access to resources such as financial aid and post recovery programs. In this study, we comprehensively analyzed how cancer resource centers assist patients with cancer and improve their clinical outcomes. Methods The study participants comprised patients initially diagnosed with head and neck cancer or esophageal cancer. A total of 2442 patients from a medical center in Taiwan were included in the study. Data were analyzed through logistic regression and Cox proportional hazards regression. Results The results indicate that unemployment, blue-collar work, and a lower education level were associated with higher utilization of cancer resource center services. The patients who were unemployed or engaged in blue-collar work had higher risks of mortality than did their white-collar counterparts. Patient education programs can significantly improve the survival probability of patients with cancer. On the basis of our evaluation of the utilization and benefits of services provided by cancer resource centers, we offer recommendations for improving the functioning of support systems for patients with cancer and provide suggestions for relevant future research. Conclusions We conclude that cancer resource centers provide substantial support for patients of low socioeconomic status and improve patients’ survival.

Highly sensitive, simple and reliable colorimetric probe for Cu2+-ion detection was visualized with the L-cysteine functionalized gold nanoparticle (LS-AuNP) probes. The pronounced sensing of Cu2+ with high selectivity was rapidly featured with obvious colour change that enabled to visually sense Cu2+ ions by naked eyes. By employing systemic investigations on crystallinities, elemental compositions, microstructures, surface features, light absorbance, zeta potentials and chemical states of LS-AuNP probes, the oxidation-triggered aggregation effect of LS-AuNP probes was envisioned. The results indicated that the mediation of Cu2+ oxidation coordinately caused the formation of disulfide cystine, rendering the removal of thiol group at AuNPs surfaces. These features reflected the visual colour change for the employment of tracing Cu2+ ions in a quantitative way.

A small fenbufen library comprising 18 compounds was prepared via Suzuki Miyara coupling. The five-step preparations deliver 9–17% biphenyl compounds in total yield. These fenbufen analogs exert insignificant activity against the IL-1 release as well as inhibiting cyclooxygenase 2 considerably. Both the para-amino and para-hydroxy mono substituents display the most substantial COX-2 inhibition, particularly the latter one showing a comparable activity as celecoxib. The most COX-2 selective and bioactive disubstituted compound encompasses one electron-withdrawing methyl and one electron-donating fluoro groups in one arene. COX-2 is selective but not COX-2 to bioactive compounds that contain both two electron-withdrawing groups; disubstituted analogs with both resonance-formable electron-donating dihydroxy groups display high COX-2 activity but inferior COX-2 selectivity. In silico simulation and modeling for three COX-2 active—p-fluoro, p-hydroxy and p-amino—fenbufens show a preferable docking to COX-2 than COX-1. The most stabilization by the p-hydroxy fenbufen with COX-2 predicted by theoretical simulation is consistent with its prominent COX-2 inhibition resulting from experiments.

Wearable cuffless photoplethysmographic blood pressure monitors have garnered widespread attention in recent years; however, the long-term performance values of these devices are questionable. Most cuffless blood pressure monitors require initial baseline calibration and regular recalibrations with a cuffed blood pressure monitor to ensure accurate blood pressure estimation, and their estimation accuracy may vary over time if left uncalibrated. Therefore, this study assessed the accuracy and long-term performance of an upper-arm, cuffless photoplethysmographic blood pressure monitor according to the ISO 81060-2 standard. This device was based on a nonlinear machine-learning model architecture with a fine-tuning optimized method. The blood pressure measurement protocol followed a validation procedure according to the standard, with an additional four weekly blood pressure measurements over a 1-month period, to assess the long-term performance values of the upper-arm, cuffless photoplethysmographic blood pressure monitor. The results showed that the photoplethysmographic signals obtained from the upper arm had better qualities when compared with those measured from the wrist. When compared with the cuffed blood pressure monitor, the means ± standard deviations of the difference in BP at week 1 (baseline) were −1.36 ± 7.24 and −2.11 ± 5.71 mmHg for systolic and diastolic blood pressure, respectively, which met the first criterion of ≤5 ± ≤8.0 mmHg and met the second criterion of a systolic blood pressure ≤ 6.89 mmHg and a diastolic blood pressure ≤ 6.84 mmHg. The differences in the uncalibrated blood pressure values between the test and reference blood pressure monitors measured from week 2 to week 5 remained stable and met both criteria 1 and 2 of the ISO 81060-2 standard. The upper-arm, cuffless photoplethysmographic blood pressure monitor in this study generated high-quality photoplethysmographic signals with satisfactory accuracy at both initial calibration and 1-month follow-ups. This device could be a convenient and practical tool to continuously measure blood pressure over long periods of time.

Background The sagittal imbalance (SI) of spine triggers compensatory mechanisms (CMs) of lower extremity (LE) to restore trunk balance. These CMs can cause long‐period stress on the femur and may possibly alter the femoral morphology. This cross‐sectional observational study aimed to answer the following questions: (a) Do SI subjects exhibit greater femoral bowing compared to subjects with sagittal balance? (b) Are there associations between femoral bowing and CMs of LE in SI subjects? Methods Subjects who underwent biplanar full body radiographs with the EOS imaging system between January 2016 and September 2021 were recruited. Sagittal parameters included T1‐pelvic angle (TPA), pelvic incidence (PI), pelvic tilt (PT), sacral slope, lumbar lordosis (LL), PI‐LL, and PT/PI ratio. LE parameters were femoral obliquity angle (FOA), knee flexion angle (KA), and ankle dorsiflexion angle. Femoral bowing was quantified as 3D radius of femoral curvature (RFC). Associations between 3D RFC and the radiographic parameters were analyzed. Results A total of 105 subjects were included, classified into balance group (TPA < 14°, n = 40), SI group (TPA ≥ 14° and KA <5°, n = 30), and SI with knee flexion group (TPA ≥ 14° and KA ≥ 5°, n = 35). 3D RFC was significantly lower in SI with knee flexion group compared to the other two groups (both p < 0.001). Stepwise linear regression showed that age, SI and knee flexion, femoral length (FL), FOA, and KA were independent predictors for 3D RFC. Conclusion Greater femoral bowing is observed in subjects with SI and knee flexion compared to the balanced population. CM parameters, including KA and FOA, are associated with 3D RFC. Further longitudinal study is needed to investigate the cause‐and‐effect relationship between SI, CMs of LE, and femoral bowing. This retrospective cohort study reviewed EOS images of 105 patients and revealed the correlation between spinal sagittal imbalance and femoral bowing. Greater femoral bowing is observed in subjects with sagittal imbalance and knee flexion compared to the balanced population. In addition, parameters of compensatory mechanisms for sagittal imbalance, including knee flexion angle and femoral oblique angle, are associated with 3D femoral curvature.

This study integrates cone-beam computed tomography (CBCT)/laser scan image superposition, computer-aided design (CAD), and 3D printing (3DP) to develop a technology for producing customized dental (orthodontic) miniscrew surgical templates using polymer material. Maxillary bone solid models with the bone and teeth reconstructed using CBCT images and teeth and mucosa outer profile acquired using laser scanning were superimposed to allow miniscrew visual insertion planning and permit surgical template fabrication. The customized surgical template CAD model was fabricated offset based on the teeth/mucosa/bracket contour profiles in the superimposition model and exported to duplicate the plastic template using the 3DP technique and polymer material. An anterior retraction and intrusion clinical test for the maxillary canines/incisors showed that two miniscrews were placed safely and did not produce inflammation or other discomfort symptoms one week after surgery. The fitness between the mucosa and template indicated that the average gap sizes were found smaller than 0.5 mm and confirmed that the surgical template presented good holding power and well-fitting adaption. This study addressed integrating CBCT and laser scan image superposition; CAD and 3DP techniques can be applied to fabricate an accurate customized surgical template for dental orthodontic miniscrews.

Ligand-targeting drug conjugates are a class of clinically validated biopharmaceutical drugs constructed by conjugating cytotoxic drugs with specific disease antigen targeting ligands through appropriate linkers. The integrated linker-drug motif embedded within such a system can prevent the premature release during systemic circulation, thereby allowing the targeting ligand to engage with the disease antigen and selective accumulation. We have designed and synthesized new thioester-linked maytansinoid conjugates. By performing in vitro cytotoxicity, targeting ligand binding assay, and in vivo pharmacokinetic studies, we investigated the utility of this new linker-drug moiety in the small molecule drug conjugate (SMDC) system. In particular, we conjugated the thioester-linked maytansinoids to the phosphatidylserine-targeting small molecule zinc dipicolylamine and showed that Zn8_DM1 induced tumor regression in the HCC1806 triple-negative breast cancer xenograft model. Moreover, in a spontaneous sorafenib-resistant liver cancer model, Zn8_DM1 exhibited potent antitumor growth efficacy. From quantitative mRNA analysis of Zn8_DM1 treated-tumor tissues, we observed the elevation of gene expressions associated with a “hot inflamed tumor” state. With the identification and validation of a plethora of cancer-associated antigens in the “omics” era, this work provided the insight that antibody- or small molecule-based targeting ligands can be conjugated similarly to generate new ligand-targeting drug conjugates.