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Adjuvant chemotherapy (ACT) is usually used to reduce the risk of disease relapse and improve survival for stage II/III colorectal cancer (CRC). However, only a subset of patients could benefit from ACT. Thus, there is an urgent need to identify improved biomarkers to predict survival and stratify patients to refine the selection of ACT. We used high-throughput proteomics to analyze tumor and adjacent normal tissues of stage II/III CRC patients with /without relapse to identify potential markers for predicting prognosis and benefit from ACT. The machine learning approach was applied to identify relapse-specific markers. Then the artificial intelligence (AI)-assisted multiplex IHC was performed to validate the prognostic value of the relapse-specific markers and construct a proteomic-derived classifier for stage II/III CRC using 3 markers, including FHL3, GGA1, TGFBI. The proteomics profiling-derived signature for stage II/III CRC (PS) not only shows good accuracy to classify patients into high and low risk of relapse and mortality in all three cohorts, but also works independently of clinicopathologic features. ACT was associated with improved disease-free survival (DFS) and overall survival (OS) in stage II (pN0) patients with high PS and pN2 patients with high PS. This study demonstrated the clinical significance of proteomic features, which serve as a valuable source for potential biomarkers. The PS classifier provides prognostic value for identifying patients at high risk of relapse and mortality and optimizes individualized treatment strategy by detecting patients who may benefit from ACT for survival.

Background Neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision are standard treatment regimen for patients with locally advanced rectal cancer (LARC). This sphincter-saving treatment strategy may be accompanied by a series of anorectal functional disorders. Yet, prospective studies that dynamically evaluating the respective roles of radiotherapy, chemotherapy and surgery on anorectal function are lacking. Patients/design The study is a prospective, observational, controlled, multicentre study. After screening for eligibility and obtaining informed consent, a total of 402 LARC patients undergoing NCRT followed by surgery, or neoadjuvant chemotherapy followed by surgery, or surgery only would be included in the trial. The primary outcome measure is the average resting pressure of anal sphincter. The secondary outcome measures are maximum anal sphincter contraction pressure, Wexner continence score and low anterior resection syndrome (LARS) score. Evaluations will be carried out at the following stages: baseline (T1), after radiotherapy or chemotherapy (before surgery, T2), after surgery (before closing the temporary stoma, T3), and at follow-up visits (every 3 to 6 months, T4, T5……). Follow-up for each patient will be at least 2 years. Discussion We expect the program to provide more information of neoadjuvant radiotherapy and/or chemotherapy on anorectal function, and to optimize the treatment strategy to reduce anorectal dysfunction for LARC patients. Trial registration ClinicalTrials.gov (NCT05671809). Registered on 26 December 2022.

Rice panicle architecture determines the grain number per panicle and therefore impacts grain yield. The OsER1–OsMKKK10–OsMKK4–OsMPK6 pathway shapes panicle architecture by regulating cytokinin metabolism. However, the specific upstream ligands perceived by the OsER1 receptor are unknown. Here, we report that the EPIDERMAL PATTERNING FACTOR (EPF)/EPF-LIKE (EPFL) small secreted peptide family members OsEPFL6, OsEPFL7, OsEPFL8, and OsEPFL9 synergistically contribute to rice panicle morphogenesis by recognizing the OsER1 receptor and activating the mitogen-activated protein kinase cascade. Notably, OsEPFL6, OsEPFL7, OsEPFL8, and OsEPFL9 negatively regulate spikelet number per panicle, but OsEPFL8 also controls rice spikelet fertility. A osepfl6 osepfl7 osepfl9 triple mutant had significantly enhanced grain yield without affecting spikelet fertility, suggesting that specifically suppressing the OsEPFL6–OsER1, OsEPFL7–OsER1, and OsEPFL9–OsER1 ligand–receptor pairs can optimize rice panicle architecture. These findings provide a framework for fundamental understanding of the role of ligand–receptor signaling in rice panicle development and demonstrate a potential method to overcome the trade-off between spikelet number and fertility.

Grain size is a key component trait of grain weight and yield. Numbers of quantitative trait loci (QTLs) have been identified in various bioprocesses, but there is still little known about how metabolism-related QTLs influence grain size and yield. The current study report GS3.1, a QTL that regulates rice grain size via metabolic flux allocation between two branches of phenylpropanoid metabolism. GS3.1 encodes a MATE (multidrug and toxic compounds extrusion) transporter that regulates grain size by directing the transport of p-coumaric acid from the p-coumaric acid biosynthetic metabolon to the flavonoid biosynthetic metabolon. A natural allele of GS3.1 was identified from an African rice with enlarged grains, reduced flavonoid content and increased lignin content in the panicles. Notably, the natural allele of GS3.1 caused no alterations in other tissues and did not affect stress tolerance, revealing an ideal candidate for breeding efforts. This study uncovers insights into the regulation of grain size though metabolic-flux distribution. In this way, it supports a strategy of enhancing crop yield without introducing deleterious side effects on stress tolerance mechanisms., Zhang et al. report QTL GS3.1 as regulating rice grain size via metabolic flux allocation between two branches of phenylpropanoid metabolism. Their results identify the biosynthetic pathway for grain size regulation via a multidrug and toxic compounds extrusion transporter, and demonstrate enlarged grains, reduced flavonoid content, and increased lignin content in the panicles with GS3.1.

Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. Here, we characterize GSA1, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops., Increasing grain yield needs to be put in the context of environmental stress. Here, the authors reveal that a UDP-glucosyltransferase is associated with regulation of rice grain size, abiotic stress tolerance, flavonoid-mediated auxin signaling, and redirection of carbon flux to flavonoid glycosides synthesis.

We studied the whole-genome point mutation and structural variation patterns of 133 tumors (59 high-grade serous (HGSC), 35 clear cell (CCOC), 29 endometrioid (ENOC), and 10 adult granulosa cell (GCT)) as a substrate for class discovery in ovarian cancer. Ab initio clustering of integrated point mutation and structural variation signatures identified seven subgroups both between and within histotypes. Prevalence of foldback inversions identified a prognostically significant HGSC group associated with inferior survival. This finding was recapitulated in two independent cohorts (n = 576 cases), transcending BRCA1 and BRCA2 mutation and gene expression features of HGSC. CCOC cancers grouped according to APOBEC deamination (26%) and age-related mutational signatures (40%). ENOCs were divided by cases with microsatellite instability (28%), with a distinct mismatch-repair mutation signature. Taken together, our work establishes the potency of the somatic genome, reflective of diverse DNA repair deficiencies, to stratify ovarian cancers into distinct biological strata within the major histotypes.

The jacking pinions and rack chocks of the fixation system of a jack-up sustain tremendous load in the elevated condition, especially when there exists a remarkable non-uniformity of the load distribution. Failures of these structural components may lead to disastrous consequence of the jack-up. Despite the importance of these components, it is difficult to give an accurate prediction of the load distribution on these components in engineering application due to the complex nonlinear interaction mechanism, which is influenced by the relative stiffness of the components, leg-guide clearance and backlash. Previous studies mainly focus on the global performance of the jack-up and pay little attention to the load distribution on the pinions and chocks. The strength of the jacking system is often guaranteed by the manufacturer for an estimate load level, which brings in uncertainty to the safety of the jack-up. The characteristics of the hull-leg interaction are discussed in this paper, and a simplified method using gap elements is proposed. The nonlinear structural analyses are carried out for a specific jack-up using the proposed method and the three-dimensional finite element method (FEM) with contact algorithm. The proposed method is proved accurate and effective for the engineering application. The characteristics of the load distribution of the specific jack-up are discussed, and the conclusions are presented.

This study aimed to investigate the association between Epstein-Barr virus (EBV)-related biomarkers and TNM classification according to the seventh edition of AJCC/UICC staging system for nasopharyngeal carcinoma. Serum VCA-IgA and EA-IgA titers and plasma EBV-DNA load were quantified at baseline in 779 patients; the rates of positivity and titers/load were compared by TNM classification. The VCA-IgA-positive rate was significantly associated with advanced N classification and stage; the EA-IgA-positive rate with advanced T and N classifications and stage; the EBV-DNA-positive rate with advanced T, N and M classifications and stage. The percentage of triple-positive patients was higher in patients with advanced TNM classification. The VCA-IgA titer and EA-IgA titer correlated positively with T classification, N classification and disease stage (1:117 in Stage I, 1:188.4 in Stage II, 1:231.12 in Stage III, 1:265.91 in Stage IV, and 1:18.34 in Stage I, 1:32.11 in Stage II, 1:34.77 in Stage III, 1:37.65 in Stage IV, respectively). EBV DNA load correlated positively with T, N and M classification and stage [median lg (EBV DNA): 0 (IQ range 0-1.85) in Stage I, 1.32 (0-3.51) in Stage II, 3.33 (0-4.30) in Stage III, 3.83 (2.85-4.71) in Stage IV]. Serum VCA-IgA/EA-IgA titers and plasma EBV DNA correlated strongly with TNM classification according to the seventh edition of the AJCC/UICC; however, plasma EBV DNA load could accurately predict metastatic disease. EBV serological biomarkers may enhance the accuracy of TNM staging and help to avoid excessive imaging examinations in routine evaluation.

Multiferroic BiFeO3/Bi3.25La0.75Ti3O12 films annealed in different atmospheres (N2 or O2) were prepared on Pt/Ti/SiO2/Si substrates via a metal organic decomposition method. Based on our experimental results, it is considered that, in the films annealed in N2, fewer Fe2+ ions while more oxygen vacancies are involved. As a result, at room temperature, predominated by the reduced Fe2+ fraction, lower leakage current and dielectric loss, better ferroelectric property while reduced magnetization are observed. However, the oxygen vacancies might be thermally activated at elevated temperature; thus, more strongly temperature-dependent leakage current and a higher dielectric relaxation peak are observed for the films annealed in N2.

For the sake of fabricating the ultrahigh density ultralarge scale integration (ULSI) memory chips, the ferroelectric nanostructures fabricated through self-assembly are studied. In this paper, we synthesized the neodymium substituted Bi4Ti3O12 nanostructures on Pt/Ti/SiO2/Si substrates. The method we used here was spin coating precursors with a series of different concentrations on the substrates and then annealing at 750 °C in the oxygen atmosphere to get the self-patterning nanoparticles. In order to avoid the influence of the Pt/Ti/SiO2/Si substrates to the largest extent, the substrates were annealed first for different time in oxygen atmosphere to select appropriate conditions. Scanning probe microscope, and X-ray diffraction were used to detect the morphology and the crystalline structure of the nanoparticles respectively. The well-separated Bi3.15Nd0.85Ti3O12 particles have a typical lateral size about 100–150 nm and height about 20–25 nm. XRD reveals pyrochlore phase in the low concentration samples. The lower the precursor’s concentration, the higher the excess of Bi element is needed to form the pure perovskite nanoparticles.

The online version of the original article can be found underdoi:10.1007/s10787-011-0097-1.Z. Sternberg (&) A. Cesario Y.-K. Leung T. Whitcomb D. S. Sternberg F. E. MunschauerDepartment of Neurology, Baird MS Center,Jacobs Neurological Institute, 100 High Street,Buffalo, NY 14203, USAe-mail: zs2@buffalo.eduK. Rittenhouse-OlsonDepartment of Biotechnical and NeurologicalLaboratory Sciences, University of Buffalo,3435 Main Street, Buffalo, NY, USAR. A. SobelDepartment of Pathology, VA Health Care System,3801 Miranda Avenue, Palo Alto, CA, USAO. PankewyczDepartment of Surgery, Buffalo General Hospital,State University of New York, University at Buffalo,100 High Street, Buffalo, NY, USAB. ZhuCenter for Neurologic Diseases, Brigham and Women’sHospital, 75 Francis Street, Boston, MA, USAInflammopharmacol (2012) 20:49DOI 10.1007/s10787-012-0120-1

Black carbon (BC) aerosols constitute unique and important anthropogenic climate forcers that potentially accelerate the retreat of glaciers over the Himalayas and Tibetan Plateau (HTP). Here we show that a large amount of BC emissions produced in India and China-a region of BC emissions to which the HTP is more vulnerable compared with other regions-are related to the consumption of goods and services in the USA and Europe through international trade. These processes lead to a virtual transport pathway of BC from distant regions to the HTP glaciers. From a consumption perspective, the contribution from India to the HTP glaciers shows a rapid increasing trend while the contributions from the USA, Europe, and China decreased over the last decade. International trade aggravates the BC pollution over the HTP glaciers and may cause significant climate change there. Global efforts toward reducing the cascading of BC emissions to Asia, especially the Indian subcontinent, are urgently needed.