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Background For locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (nCRT), there are no reliable indicators to accurately predict pathological complete response (pCR) before surgery. For patients with clinical complete response (cCR), a 'Watch and Wait' (W&W) approach can be adopted to improve quality of life. However, W&W approach may increase the recurrence risk in patients who are judged to be cCR but have minimal residual disease (MRD). Magnetic resonance imaging (MRI) is a major tool to evaluate response to nCRT; however, its ability to predict pCR needs to be improved. In this prospective cohort study, we explored the value of circulating tumor DNA (ctDNA) in combination with MRI in the prediction of pCR before surgery and investigated the utility of ctDNA in risk stratification and prognostic prediction for patients undergoing nCRT and total mesorectal excision (TME). Methods and findings We recruited 119 Chinese LARC patients (cT3-4/N0-2/M0; median age of 57; 85 males) who were treated with nCRT plus TME at Fudan University Shanghai Cancer Center (China) from February 7, 2016 to October 31, 2017. Plasma samples at baseline, during nCRT, and after surgery were collected. A total of 531 plasma samples were collected and subjected to deep targeted panel sequencing of 422 cancer-related genes. The association among ctDNA status, treatment response, and prognosis was analyzed. The performance of ctDNA alone, MRI alone, and combining ctDNA with MRI was evaluated for their ability to predict pCR/non-pCR. Ranging from complete tumor regression (pathological tumor regression grade 0; pTRG0) to poor regression (pTRG3), the ctDNA clearance rate during nCRT showed a significant decreasing trend (95.7%, 77.8%, 71.1%, and 66.7% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.008), while the detection rate of acquired mutations in ctDNA showed an increasing trend (3.8%, 8.3%, 19.2%, and 23.1% in pTRG 0, 1, 2, and 3 groups, respectively, P = 0.02). Univariable logistic regression showed that ctDNA clearance was associated with a low probability of non-pCR (odds ratio = 0.11, 95% confidence interval [95% CI] = 0.01 to 0.6, P = 0.04). A risk score predictive model, which incorporated both ctDNA (i.e., features of baseline ctDNA, ctDNA clearance, and acquired mutation status) and MRI tumor regression grade (mrTRG), was developed and demonstrated improved performance in predicting pCR/non-pCR (area under the curve [AUC] = 0.886, 95% CI = 0.810 to 0.962) compared with models derived from only ctDNA (AUC = 0.818, 95% CI = 0.725 to 0.912) or only mrTRG (AUC = 0.729, 95% CI = 0.641 to 0.816). The detection of potential colorectal cancer (CRC) driver genes in ctDNA after nCRT indicated a significantly worse recurrence-free survival (RFS) (hazard ratio [HR] = 9.29, 95% CI = 3.74 to 23.10, P < 0.001). Patients with detectable driver mutations and positive high-risk feature (HR_feature) after surgery had the highest recurrence risk (HR = 90.29, 95% CI = 17.01 to 479.26, P < 0.001). Limitations include relatively small sample size, lack of independent external validation, no serial ctDNA testing after surgery, and a relatively short follow-up period. Conclusions The model combining ctDNA and MRI improved the predictive performance compared with the models derived from individual information, and combining ctDNA with HR_feature can stratify patients with a high risk of recurrence. Therefore, ctDNA can supplement MRI to better predict nCRT response, and it could potentially help patient selection for nonoperative management and guide the treatment strategy for those with different recurrence risks., Author(s): Yaqi Wang 1,2,3, Lifeng Yang 1,2,3, Hua Bao 4, Xiaojun Fan 4, Fan Xia 1,2,3, Juefeng Wan 1,2,3, Lijun Shen 1,2,3, Yun Guan 2,5, Hairong Bao 6, Xue Wu [...]

To examine the adaptability of connecting gallery using pipe jacking method under large deflection angle, a case study is conducted on a connecting gallery using pipe jacking method with a deflection angle of 5°. Analysis is conducted on the force of the special lining ring and the direction of local optimization and transformation of equipment. Conclusions are drawn as follows: (1) The assembly error of the special lining ring at the connecting gallery causes the deflection angle between the main axis of the boring machine and the propulsion axis rangeing from 3 ° to 7 °, affecting normal construction. (2) The static analysis using the established finite element model of the main tunnel show that the force applied on the special lining ring under maximum jacking force and vertical component force meets requirements. (3) Through local optimization and transformation of the equipment jacking system, the hoisting and transportation system in the tunnel, and the trailer platform, the normal construction is guaranteed, the influence of the assembly error of the special lining ring is minimized, greatly expanding the application area of the connecting gallery using pipe jacking method. [ABSTRACT FROM AUTHOR]

Singleton distractors may inadvertently capture attention, interfering with the task at hand. The underlying neural mechanisms of how we prevent or handle distractor interference remain elusive. Here, we varied the type of salient distractor introduced in a visual search task: the distractor could be defined in the same (shape) dimension as the target, a different (color) dimension, or a different (tactile) modality (intra‐dimensional, cross‐dimensional, and, respectively, cross‐modal distractor, all matched for physical salience); and besides behavioral interference, we measured lateralized electrophysiological indicators of attentional selectivity (the N2pc, Ppc, PD, CCN/CCP, CDA, and cCDA). The results revealed the intra‐dimensional distractor to produce the strongest reaction‐time interference, associated with the smallest target‐elicited N2pc. In contrast, the cross‐dimensional and cross‐modal distractors did not engender any significant interference, and the target‐elicited N2pc was comparable to the condition in which the search display contained only the target singleton, thus ruling out early attentional capture. Moreover, the cross‐modal distractor elicited a significant early CCN/CCP, but did not influence the target‐elicited N2pc, suggesting that the tactile distractor is registered by the somatosensory system (rather than being proactively suppressed), without, however, engaging attention. Together, our findings indicate that, in contrast to distractors defined in the same dimension as the target, distractors singled out in a different dimension or modality can be effectively prevented to engage attention, consistent with dimension‐ or modality‐weighting accounts of attentional priority computation. This study contributes to resolving hot debates of attentional capture. Participants ignored task‐irrelevant distractors without attentional engagement rather than actively suppressing them. Especially, the cross‐modal distractor elicited sensorimotor ERPs, but participants did not deploy attentional resources to it. The results supported distractor handling via down‐weighted or no‐engagement to task‐irrelevant features. [ABSTRACT FROM AUTHOR]

Photocatalytic processes are efficient methods to solve water contamination problems, especially considering dyeing wastewater disposal. However, high-efficiency photocatalysts are usually very expensive and have the risk of heavy metal pollution. Recently, an iron oxides@hydrothermal carbonation carbon (HTCC) heterogeneous catalyst was prepared by our group through co-hydrothermal treatment of carbohydrates and zinc extraction tailings of converter dust. Herein, the catalytic performance of the iron oxides@HTCC was verified by a nonbiodegradable dye, methylene blue (MB), and the catalytic mechanism was deduced from theoretical simulations and spectroscopic measurements. The iron oxides@HTCC showed an excellent synergy between photocatalysis and Fenton-like reactions. Under visible-light illumination, the iron oxides@HTCC could be excited to generate electrons and holes, reacting with H2O2 to produce ·OH radicals to oxidize and decompose organic pollutants. The removal efficiency of methylene blue over iron oxides@HTCC at 140 min was 2.86 times that of HTCC. The enhanced catalytic performance was attributed to the advantages of iron oxides modification: (1) promoting the excitation induced by photons; (2) improving the charge transfer. Furthermore, the iron oxides@HTCC showed high catalytic activity in a wide pH value range of 2.3–10.4, and the MB removal efficiency remained higher than 95% after the iron oxides@HTCC was recycled 4 times. The magnetically recyclable iron oxides@HTCC may provide a solution for the treatment of wastewater from the textile industry. [ABSTRACT FROM AUTHOR]

Environmental context: Soil carbon sequestration plays an important role in achieving the goal of carbon neutrality. We studied the characteristics of organic carbon distribution and sequestration by stable carbon isotopes in nine types of soils in China and found that macro-aggregates possessed more organic carbon with a low degree of decomposition, while the overall direction of organic carbon transfer between aggregates was from macro-aggregates through micro-aggregates to the grain-size fractions of chalky clay. These results provide a foundation for understanding soil carbon sequestration in China's cultivated lands. Rationale: Soil is the largest carbon reservoir of terrestrial ecosystems. Studying carbon turnover in cultivated soils is vital for China to achieve its carbon neutrality goal. Methodology: In this research, we investigated the distribution characteristics of soil organic carbon and its turnover among aggregates in nine major soil types in China by 13C stable isotopes. Results: Since the second national soil survey in China 1979, the surface soil organic carbon (SOC) content of cultivated lands in boggy soils, black soils and dark brown forest soils in northeastern China has decreased (129.06, 2.70 and 7.78 g kg−1, respectively) while increased in cinnamon soils, brown soils, red soils, latosols, paddy soils and chestnut soils (0.85-7.79 g kg−1). Overall, the SOC content was highest in 1-0.25 mm aggregates, lowest in 0.053-0.02 mm aggregates and higher in <0.02 mm aggregates. The Δ13C value showed that the silt-clay size class fraction > micro-aggregates > macro-aggregates. Discussion: The overall turnover direction of SOC among aggregates starts from macro-aggregates to micro-aggregates and ends with the silt-clay size class fraction. The result directly confirms both the 'hierarchical development model' and 'embryonic development model' of soil aggregate formation. The SOC flow direction and mobility potential between aggregates, as indicated by Δ13C values, suggest that cultivated soils are more susceptible to soil type than wasteland soils. [ABSTRACT FROM AUTHOR]

Streptomyces are one of the most prolific sources of bioactive and structurally diverse secondary metabolites for natural product drug discovery. Genome sequencing and bioinformatics analysis revealed that the genomes of Streptomyces harbor a wealth of cryptic secondary metabolite biosynthetic gene clusters that could encode novel compounds. In this work, a genome mining approach was employed to investigate the biosynthetic potential of Streptomyces sp. HP-A2021, isolated from rhizosphere soil of Ginkgobiloba L. The complete genome of HP-A2021 was sequenced and contained the 9,607,552 base pair linear chromosome with a GC content of 71.07%. The annotation results revealed the presence of 8534 CDSs, 76 tRNA genes, and 18 rRNA genes in HP-A2021. The highest dDDH and ANI values based on genome sequences between HP-A2021 and the most closely related type strain, Streptomycescoeruleorubidus JCM 4359, were 64.2% and 92.41%, respectively. In total, 33 secondary metabolite biosynthetic gene clusters with an average length of 105,594 bp were identified, including the putative thiotetroamide, alkylresorcinol, coelichelin, and geosmin. The antibacterial activity assay confirmed that the crude extracts of HP-A2021 showed potent antimicrobial activity against human pathogenic bacteria. Our study demonstrated that Streptomyces sp. HP-A2021 will propose a potential use in biotechnological and novel bioactive secondary metabolite biosynthetic applications. [ABSTRACT FROM AUTHOR]

The molecular landscapes of diffuse large B-cell lymphoma (DLBCL) remained to be comprehensively investigated with an urgent need to identify novel prognostic biomarkers guiding prognostic stratification and disease monitoring. Baseline tumor samples of 148 DLBCL patients were analyzed using targeted next-generation sequencing (NGS) for mutational profiling, whose clinical reports were retrospectively reviewed. In this cohort, the subgroup of old DLBCL patients (age at diagnosis > 60, N = 80) exhibited significantly higher Eastern Cooperative Oncology Group scores and International Prognostic Index than their young counterparts (age at diagnosis ≤ 60, N = 68). As revealed by the NGS results, PIM1 (43.9%), KMT2D (31.8%), MYD88 (29.7%), and CD79B (27.0%) were identified as the most frequently mutated genes. Aberrations of genes of the immune escape pathway were significantly enriched in the young subgroup, while the altered epigenetic regulators were more abundant in the old patients. FAT4 mutation was identified as a positive prognostic biomarker, associated with longer progression-free survival and overall survival in the entire cohort and the old subgroup, using the Cox regression analyses. However, the prognostic function of FAT4 was not reproduced in the young subgroup. We comprehensively analyzed the pathological and molecular characteristics of old and young DLBCL patients and demonstrated the prognostic value of FAT4 mutation, which requires further validation with sizable cohorts in future research. [ABSTRACT FROM AUTHOR]