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Abstract Background In small cell lung cancer (SCLC), the pathological N category is identical to it in non-small cell lung cancer (NSCLC) and remains unchanged over a decade. Here we verified the discriminability of number of involved nodal stations (nS) in SCLC and compared its efficacy in predicting survival with currently used pathological nodal (pN) staging. Methods We retrospectively analyzed the patients who received operations and were pathologically diagnosed as SCLC at Shanghai Pulmonary Hospital between 2009 and 2019. X-tile software was adopted to determine optimal cut-off values for nS groups. Kaplan–Meier method and Cox regression analysis were used to compare survival between different groups. Decision curve analysis (DCA) was employed to evaluate the standardized net benefit. Results A total of 369 patients were included. The median number of sampled stations was 6 (range 3–11), and the median number of positive stations was 1 (range 0–7). The optimal cutoff for nS groups was: nS0 (no station involved), nS1-2 (one or two stations involved), and nS ≥ 3 (three or more stations involved). Overall survival (OS) and relapse-free survival (RFS) were statistically different among all adjacent categories within the nS classification (p

Abstract Electrochemical urea oxidation offers a sustainable avenue for H2 production and wastewater denitrification within the water-energy nexus; however, its wide application is limited by detrimental cyanate or nitrite production instead of innocuous N2. Herein we demonstrate that atomically isolated asymmetric Ni–O–Ti sites on Ti foam anode achieve a N2 selectivity of 99%, surpassing the connected symmetric Ni–O–Ni counterparts in documented Ni-based electrocatalysts with N2 selectivity below 55%, and also deliver a H2 evolution rate of 22.0 mL h–1 when coupled to a Pt counter cathode under 213 mA cm–2 at 1.40 VRHE. These asymmetric sites, featuring oxygenophilic Ti adjacent to Ni, favor interaction with the carbonyl over amino groups in urea, thus preventing premature resonant C⎓N bond breakage before intramolecular N–N coupling towards N2 evolution. A prototype device powered by a commercial Si photovoltaic cell is further developed for solar-powered on-site urine processing and decentralized H2 production.

Abstract The Early Cenozoic sedimentary archives of Tibet are crucial for elucidating the geodynamic processes related to continental collision, particularly crustal deformation and shortening. However, the lack of a reliable chronostratigraphic framework for the Cenozoic sedimentary basins in central Tibet has hindered a comprehensive understanding of the influence of the continuous India‐Asia convergence process on the tectonic evolution of the Tibetan hinterland. Here, we report new magnetostratigraphic ages and paleomagnetic results for the Niubao Formation exposed in the northern bank of the Siling Co. Positive field tests and microscopic observations suggest that the remanence is primary. We determine that the depositional age of the measured section was between 59.2 and 48.6 Ma. Our results reveal that the paleogeographic location of the Bangong‐Nujiang Suture Zone during the Late Paleocene–Early Eocene was 25.4 ± 2.1°N, thus supporting the model of two‐stage collision between India and Asia.

In recent years, advancements in medical treatment and imaging technologies have revolutionized the assessment of tumor response. However, the Response Evaluation Criteria in Solid Tumors (RECIST) has long been established as the gold standard for evaluating tumor treatment. As treatment modalities evolve, the need for continuous refinement and adaptation of RECIST becomes increasingly apparent. This review explores the historical evolution, current applications, limitations, and future directions of RECIST. It discusses the challenges of distinguishing true progression from pseudo-progression in ICIs (immune checkpoint inhibitors), the integration of advanced imaging tools, and the necessity for RECIST criteria tailored to specific therapies like neoadjuvant treatments. The review highlights the ongoing efforts to enhance RECIST’s accuracy and reliability in clinical decision-making and the potential for developing new standards to better evaluate treatment efficacy in the rapidly evolving landscape of oncology.

Abstract Background Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. Patients and methods Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy’s effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. Results A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295–4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV–H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). Conclusions The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. Trial registration Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228).

Freight has become one of the major contributors to air pollution. This research proposes a method to systematically estimate truck vehicle emissions at the road segment level through localizing MOVES, a widely-used vehicle emission estimation model. We first design a protocol of converting percentage values of rotating speed and torque of engine to second-by-second vehicle speed to accommodate the differences between driving cycles adopted in local emission standards and those used in MOVES. In order to identify the best model year for estimating emissions under different local emission standards, we propose an approach of comparing emission outcomes rather than emission factors, considering the differences in unit used between MOVES and emission standards. To calculate road segment level emission factors, we weight original factors by integrating vehicle fleet information which contains the shares of vehicles under different emission standards and at different ages. We apply the approach to a major freight corridor area in Shanghai and calculate emission factors by air pollutant, average speed of road sections, and road type. Dynamic emissions of each road section per hour are calculated to reflect the spatial distribution of truck emissions. The research outcomes may help local departments, especially in developing countries, better estimate freight vehicle emissions and make policies correspondingly to control their impacts on public health.

Submerged vegetation commonly grows and plays a vital role in aquatic ecosystems, but it is also regarded as a barrier to the passing flow. Numerical simulations of flow through and over submerged vegetation were carried out to investigate the effect of vegetation density on flow field. Numerical simulations were computationally set up to replicate flume experiments, in which vegetation was mimicked with flexible plastic strips. The fluid–structure interaction between flow and flexible vegetation was solved by coupling the two modules of the COMSOL packages. Two cases with different vegetation densities were simulated, and the results were successfully validated against the experimental data. The contours of the simulated time-averaged streamwise velocity and Reynolds stress were extracted to highlight the differences in mean and turbulent flow statistics. The turbulence intensity was found to be more sensitive to vegetation density than the time-averaged velocity. The developing length increased with the spacing between plants. The snapshots of the bending vegetation under instantaneous velocity and vorticity revealed that flexible vegetation responded to the effects of eddies in the shear layer by swaying periodically. The first two rows of vegetation suffered stronger approaching flow and were prone to more streamlined postures. In addition, the origin of tip vortices was investigated via the distribution of vorticity. The results reveal the variation of flow properties with bending submerged vegetation and provide useful reference for optimization of restoration projects.

Background and aimGastroesophageal reflux disease (GERD) patients often report sleep disturbance (SD); however, the relationship between GERD and SD is unknown. This study investigated whether SD affects symptoms, acid reflux, and autonomic function in GERD patients.MethodsA total of 257 subjects (126 patients with SD and 99 patients without SD) participated in this survey from January 2020 to August 2022. Participants were required to complete questionnaires including the GERD impact scale (GIS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Esophageal mucosal injury, acid exposure, peristaltic function, and autonomic function were assessed by upper endoscopy, high-resolution esophageal manometry (HRAM), 24-h multichannel intraluminal impedance with pH (24 h-MII-pH), and electrocardiography (ECG).ResultsGastroesophageal reflux disease patients with SD experienced a higher frequency of prolonged reflux (p

This research delves into the cutting-edge realm of solar-powered dual-temperature refrigeration, adhering to the 3E model emphasizing Energy, Economic, and Environmental considerations with a key focus on financial optimization. The study investigates the implementation of advanced refrigeration technologies, notably the integration of supercritical CO2 and ammonia cycles, tailored for dual-temperature applications. A distinctive aspect of this research is the strategic use of excess thermal energy, enhancing the efficiency of the refrigeration systems under varied climatic conditions. Central to the study is a thorough economic analysis aimed at reducing the Levelized Cost of Cooling (LCOC), while simultaneously enhancing the overall efficiency of the system. With the aid of the Engineering Equation Solver (EES) software, the system is modeled and the preliminary results indicate a promising decrease in cooling expenses (reaching to 90.25 $/GJ) alongside an increase in system efficiency (an improved efficiency of 33.17 %), with the total Coefficient of Performance (COP) demonstrating a significant advancement over traditional refrigeration models. This research underscores the effectiveness of harnessing solar energy in refrigeration technologies, contributing to financially viable and environmentally responsible cooling solutions. It provides valuable insights for the future development of refrigeration systems, which are both economically and environmentally sustainable.

Abstract Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron‐dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron‐induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

Abstract Electrochemical nitrate reduction to ammonia offers an attractive solution to environmental sustainability and clean energy production but suffers from the sluggish *NO hydrogenation with the spin–state transitions. Herein, we report that the manipulation of oxygen vacancies can contrive spin−polarized Fe1−Ti pairs on monolithic titanium electrode that exhibits an attractive NH3 yield rate of 272,000 μg h−1 mgFe −1 and a high NH3 Faradic efficiency of 95.2% at −0.4 V vs. RHE, far superior to the counterpart with spin−depressed Fe1−Ti pairs (51000 μg h–1 mgFe –1) and the mostly reported electrocatalysts. The unpaired spin electrons of Fe and Ti atoms can effectively interact with the key intermediates, facilitating the *NO hydrogenation. Coupling a flow−through electrolyzer with a membrane-based NH3 recovery unit, the simultaneous nitrate reduction and NH3 recovery was realized. This work offers a pioneering strategy for manipulating spin polarization of electrocatalysts within pair sites for nitrate wastewater treatment.

This work presents a novel laser continuous powder bed fusion (L-CPBF) process technique, tailored for the additive manufacturing of intricate components with annular hollow structures, emphasizing both precision and efficiency. Utilizing this advanced L-CPBF method, Ti-6.5Al-2Zr-Mo-V (TA15) titanium alloy samples were successfully fabricated, and their microstructures and properties were investigated. The optimized process parameter window for L-CPBF processing of TA15 was determined through Taguchi experiments, ranging from 100 to 125 J/mm3, with the relative density of the samples achieved an outstanding 99.95%. Microstructural evolution under varying volumetric energy densities (VED) was revealed through characterization methods such as SEM and EBSD. The formation of acicular α′-martensites was observed during initial the cooling phase, with thermal cycling temperature playing a pivotal role in the development of martensites of varying sizes. Furthermore, through process optimization, remarkable mechanical properties, with a tensile strength of 1200.5 ± 98.5 MPa, a yield strength of 1109 ± 102 MPa, and an elongation of 7.05 ± 1.35% were achieved. These mechanical properties are comparable to those of TA15 alloys prepared by traditional reciprocating scraper powder spreading L-PBF. However, our approach boasts a substantial increase in manufacturing efficiency, surpassing the traditional method by over 45%. Collectively, this study offers invaluable theoretical and experimental insights, paving the way for accelerated additive manufacturing of hollow annular components in demanding sectors such as aerospace and beyond.

Abstract Background Patients with non‐small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal‐associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD‐associated NSCLC and their involvement in the immune response. Methods Flow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti‐programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5‐OP‐RU using a mouse subcutaneous tumor model. Results Tumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5‐OP‐RU enhanced the antitumor effects of anti‐PD1. Conclusions In patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells.

Abstract Background Hypoxia is a frequent characteristic observed in solid tumors and is strongly associated with tumor metastasis, angiogenesis, and drug resistance. While the vasculature of hypoxic tumor tissues poses obstacles to the efficient administration of conventional drugs, it may prove advantageous in sustaining hyperthermia. Photothermal therapy (PTT) offers a promising treatment strategy that utilizes the activation of photosensitizers to produce heat, thus facilitating the selective ablation of tumor tissues. Method To enhance the accumulation of photothermal agents in tumor tissue and improve the effectiveness of PTT, we developed a self-propelled hybrid called Bif@PAu-NPs. This hybrid consists of polydopamine (PDA)-coated gold nanoparticles (Au-NPs) loaded onto the anaerobic Bifidobacterium infantis (Bif). Results The Bif@PAu-NPs actively aggregated at the tumor site because the ability of Bif can target hypoxic regions, and PAu-NPs achieved precise PTT due to their high photothermal conversion efficiency (η = 67.8%). The tumor tissues were ablated by PTT, resulting in the release of antigens through immunogenic cell death (ICD), which stimulates an immune response. The inclusion of GM-CSF enhanced the immune response by recruiting dendritic cells and initiating long-term anti-tumor immunity. Conclusion The Bif@PAu-NPs hybrid effectively suppressed the growth of both primary tumors and re-challenged tumors. The utilization Bif@PAu-NPs in conjunction with GM-SCF exhibits great potential as a photothermal-immunotherapeutic strategy for precisely treating solid tumors. Graphical Abstract In this study, the bacterial Bif@PAu-NPs biohybrid is exploited the self-driving ability of anaerobic Bifidobacterium infantis to deliver polydopamine-modified gold nanoparticles to hypoxic region of tumor. Under irradiation with 808 nm NIR laser, the hybrid exerts precise photothermal therapy to stimulate the immune response, which is further enhanced by GM-CSF, leading to recruitment of dendritic cells and initiation of a long-term anti-tumor immunity remember to prevent tumor recurrence.

Abstract Edible bird’s nest (EBN) mainly made of saliva that secreted by a variety of swiftlets is a kind of precious traditional Chinese medicine. EBNs from different biological and geographical origins exhibit varieties in morphology, material composition, nutritive value and commercial value. Here, we collected four different EBN samples from Huaiji, China (Grass EBN), Nha Trang, Vietnam (Imperial EBN) and East Kalimantan, Indonesia (White EBN and Feather EBN) respectively, and applied label-free quantitative MS-based proteomics technique to identify its protein composition. First, phylogenetic analysis was performed based on cytb gene to identify its biological origin. Second, a total of 37 proteins of EBNs were identified, among which there were six common proteins that detected in all samples and exhibited relatively higher content. Gene ontology analysis revealed the possible function of EBN proteins, and principal component analysis and hierarchical clustering analysis based on 37 proteins were performed to compare the difference of various EBNs. In summary, our study deciphered the common and characteristic protein components of EBNs of different origins and described their possible functions by GO enrichment analysis, which helps to establish an objective and reliable quality evaluation system.

Breeding for nitrogen use efficiency (NUE) is becoming more important as global uncertainty makes the production and application of nitrogen (N) fertilizers more expensive and environmentally unfriendly. Despite this, most cereal breeding programs still use yield-related components as proxies for NUE, likely due to the prohibitive cost and time of collecting and analyzing samples through traditional lab-based methods. Drone-based NUE phenotyping provides a viable and scalable alternative as it is quicker, non-destructive, and consistent. Here, we present a study that utilized financially accessible cost-effective drones mounted with red-green-blue (RGB) image sensors coupled with the open-source AirMeasurer platform and advanced statistical analysis to exclude low-NUE lines in multi-seasonal field experiments. The method helped us to identify high N agronomic use efficiency lines but was less effective with a high N recovery efficiency line. We found that the drone-powered approach was very effective at 180 kg N per hectare (N180, an optimized N-rate) as it completely removed low-NUE wheat lines in the trial, which would facilitate breeders to quickly reduce the number of lines taken through multi-year breeding programs. Hence, this encouraging and scalable approach demonstrates its ability to conduct NUE phenotyping in wheat. With continuous refinements in field experiments, this method would be employable as an openly accessible platform to identify NUE lines at different N-rates for breeding and resource use efficiency studies in wheat.

Oil well cement is easily damaged by carbon dioxide (CO2) corrosion, and the corrosion of oil well cement is affected by many factors in complex environments. The anti-corrosion performance of oil well cement can be improved by polymer materials. In order to explore the influence of different corrosion factors on the corrosion depth of polymer-modified oil well cement, the influence of different corrosion factors on corrosion depth was studied based on the Box–Behnken experimental design. The interaction of different influencing factors and the influence of multiple corrosion depths were analyzed based on the response surface method, and a response surface model was obtained for each factor and corrosion depth. The results indicate that within the scope of the study, the corrosion depth of polymer-modified oil well cement was most affected by time. The effects of temperature and the pressure of CO2 decreased sequentially. The response surface model had good significance, with a determination coefficient of 0.9907. The corrosion depth was most affected by the interaction between corrosion time and the pressure of CO2, while the corrosion depth was less affected by the interaction between corrosion temperature and corrosion time. Improving the CO2 intrusion resistance of cement slurry in an environment with a high concentration of CO2 gas can effectively ensure the long-term structural integrity of cement.

Objective: To investigate the prognostic factors in and role of postoperative radiotherapy (PORT) for surgically resected thymomas. Methods: A total of 1540 patients with pathologically confirmed thymomas undergoing resection between 2000 and 2018 were identified retrospectively from the SEER (Surveillance, Epidemiology, and End Results) database. Tumors were restaged as local (limited to thymus), regional (invasion to mediastinal fat and other neighboring structures), or distant stage. Disease-specific survival (DSS) and overall survival (OS) were estimated by the Kaplan–Meier method and the log-rank test. Adjusted hazard ratios (HRs) with 95% CIs were calculated by Cox proportional hazards modeling. Results: Tumor stage and histology were independent predictors of both DSS (regional: HR, 3.711; 95% CI, 2.006-6.864; distant: HR, 7.920; 95% CI, 4.061-15.446; type B2/B3: HR, 1.435; 95% CI, 1.008-2.044) and OS (regional: HR, 1.461; 95% CI, 1.139-1.875; distant: HR, 2.551; 95% CI, 1.855-3.509; type B2/B3: HR, 1.409; 95% CI, 1.153-1.723). For patients with regional stage and type B2/B3 thymomas, PORT was associated with better DSS after thymectomy/thymomectomy (HR, 0.268; 95% CI, 0.099-0.727), but the association was not significant after extended thymectomy (HR, 1.514; 95% CI, 0.516-4.44). Among patients with lymph node metastases, those who received PORT (HR, 0.372; 95% CI, 0.146-0.949), chemotherapy (HR, 0.843; 95% CI, 0.303-2.346), or both (HR, 0.296, 95% CI, 0.071-1.236) had a better OS. Conclusions: The extent of invasion and tumor histology were independent predictors of worse survival following surgical resection of thymoma. Patients with regional invasion and type B2/B3 thymoma who undergo thymectomy/thymomectomy may benefit from PORT, while patients with nodal metastases may benefit from multimodal therapy, including PORT and chemotherapy.

Glioblastoma is the most aggressive brain tumor with extremely poor prognosis in adults. Routine treatments include surgery, chemotherapy, and radiotherapy; however, these may lead to rapid relapse and development of therapy-resistant tumor. Glioblastoma cells are known to communicate with macrophages, microglia, endothelial cells, astrocytes, and immune cells in the tumor microenvironment (TME) to promote tumor preservation. It was recently demonstrated that Glioblastoma-derived extracellular vesicles (EVs) participate in bidirectional intercellular communication in the TME. Apart from promoting glioblastoma cell proliferation, migration, and angiogenesis, EVs and their cargos (primarily proteins and miRNAs) can act as biomarkers for tumor diagnosis and prognosis. Furthermore, they can be used as therapeutic tools. In this review, the mechanisms of Glioblastoma-EVs biogenesis and intercellular communication with TME have been summarized. Moreover, there is discussion surrounding EVs as novel diagnostic structures and therapeutic tools for glioblastoma. Finally, unclear questions that require future investigation have been reviewed.

Wheat (Triticum aestivum) is one of the most important staple crops worldwide. To ensure its global supply, the timing and duration of its growth cycle needs to be closely monitored in the field so that necessary crop management activities can be arranged in a timely manner. Also, breeders and plant researchers need to evaluate growth stages (GSs) for tens of thousands of genotypes at the plot level, at different sites and across multiple seasons. These indicate the importance of providing a reliable and scalable toolkit to address the challenge so that the plot-level assessment of GS can be successfully conducted for different objectives in plant research. Here, we present a multimodal deep learning model called GSP-AI, capable of identifying key GSs and predicting the vegetative-to-reproductive transition (i.e., flowering days) in wheat based on drone-collected canopy images and multiseasonal climatic datasets. In the study, we first established an open Wheat Growth Stage Prediction (WGSP) dataset, consisting of 70,410 annotated images collected from 54 varieties cultivated in China, 109 in the United Kingdom, and 100 in the United States together with key climatic factors. Then, we built an effective learning architecture based on Res2Net and long short-term memory (LSTM) to learn canopy-level vision features and patterns of climatic changes between 2018 and 2021 growing seasons. Utilizing the model, we achieved an overall accuracy of 91.2% in identifying key GS and an average root mean square error (RMSE) of 5.6 d for forecasting the flowering days compared with manual scoring. We further tested and improved the GSP-AI model with high-resolution smartphone images collected in the 2021/2022 season in China, through which the accuracy of the model was enhanced to 93.4% for GS and RMSE reduced to 4.7 d for the flowering prediction. As a result, we believe that our work demonstrates a valuable advance to inform breeders and growers regarding the timing and duration of key plant growth and development phases at the plot level, facilitating them to conduct more effective crop selection and make agronomic decisions under complicated field conditions for wheat improvement.

Extreme climate events can have severe impacts on both vegetation and the carbon cycle. However, whether land management exacerbates or mitigates the effects of extreme climate events on vegetation remains unknown. We investigated the case of an extreme precipitation event that occurred in a region dominated by double–cropping (DC) systems located in the Yangtze–Huai plain in China. Waterlogging disasters were triggered by an extreme precipitation event in October 2016, which severely affected the sowing and seedling emergence of winter crops (mainly winter wheat). The lack of sowing and low seedling emergence rate subsequently led to months of low growth, as evidenced by negative enhanced vegetation index (EVI) anomalies, especially from March to May 2017. Local agricultural meteorological monthly reports, government announcements, and winter wheat data based on statistics and remote sensing confirmed the reduced yields. The influence on vegetation ended in June 2017, when summer crops were planted. Our results demonstrate that, in such a DC system, when extreme events occur during the key sowing period, the impacts will continue through the entire crop growth period, until the next sowing. More generally, agricultural land management could extend the duration and magnitude of the impacts of extreme climate events on vegetation.

Introduction: Pembrolizumab is well-tolerated in pediatric patients with advanced tumors, consistent with results in adults. However, information on the safety and efficacy of adjuvant pembrolizumab in children and adolescents with melanoma is lacking. Objectives: To compare pembrolizumab versus high-dose interferon-α2b (HDI) as adjuvant therapy in pediatric patients with melanoma. Methods: We performed a retrospective study of pediatric patients diagnosed with melanoma between January 2008 and April 2022. Relapse-free survival (RFS) and the 1-year RFS rate were compared between patients receiving adjuvant pembrolizumab or HDI. Results: Seventy-five pediatric patients with melanoma were screened from a database of 6,013 patients. Twenty-four patients were finally enrolled, of whom 9 received pembrolizumab and 15 received HDI as adjuvant therapy. By August 31, 2022, the median follow-up times were 23.6 months and 98.7 months in the pembrolizumab and HDI groups, respectively. There was no significant difference in median RFS between two groups (not reached versus 38.7 months, P = 0.11). The median overall survival was not reached in either group. The 1-year RFS rates were 88.9% and 66.7% in the pembrolizumab and HDI groups, respectively. All adverse events in the pembrolizumab group were grade 1 or 2, but grade 3–5 adverse events occurred in two (13%) patients receiving HDI. Conclusions: RFS was similar in pediatric patients with melanoma receiving adjuvant pembrolizumab or HDI, but pembrolizumab was associated with a reduced risk of recurrence and a more favorable safety profile. However, due to the small sample size and differences in follow-up time, larger and prospective studies are still warranted to explore better adjuvant therapies for pediatric melanoma.

Breast cancer is characterized by insidious onset, rapid progression, easy recurrence, and metastasis. Conventional monotherapies are usually ineffective due to insufficient drug delivery. Therefore, the combination of multimodal therapy with tumor microenvironment (TME)-responsive nanoplatforms is increasingly being considered for the targeted treatment of breast cancer. We synthesized bioactive hybrid nanoparticles for synergistic chemotherapy and photothermal therapy. Briefly, doxorubicin (DOX) and indocyanine green (ICG)-loaded nanoparticles (DI) of average particle size 113.58 ± 2.14 nm were synthesized, and their surface were modified with polydopamine (PDA) and attached to the anaerobic probiotic Bifidobacterium infantis (Bif). The bioactive Bif@DIP hybrid showed good photothermal conversion efficiency of about 38.04%. In addition, the self-driving ability of Bif allowed targeted delivery of the PDA-coated DI nanoparticles (DIP) to the hypoxic regions of the tumor. The low pH and high GSH levels in the TME stimulated the controlled release of DOX and ICG from the Bif@DIP hybrid, which then triggered apoptosis of tumor cells and induced immunogenic cell death (ICD), resulting in effective and sustained anti-tumor effect with minimum systemic toxicity. Thus, the self-driven Bif@DIP hybrid is a promising nanodrug for the targeted chemotherapy and photothermal therapy against solid cancers.

Coral reefs are threatened globally by compounding stressors of accelerating climate change and deteriorating water quality. Water quality plays a central role in coral reef health. Yet, accurately quantifying water quality at large scales meaningful for monitoring impacts on coral health remains a challenge due to the complex optical conditions typical of shallow water coastal systems. Here, we report the performance of 32 remote sensing water quality models for suspended particulate matter and chlorophyll concentrations as well as colored dissolved organic matter absorption, over concentration ranges relevant for reef ecology using airborne imaging spectroscopy and field measurements across 62 stations in nearshore Hawaiian waters. Models were applied to reflectance spectra processed with a suite of approaches to compensate for glint and other above-water impacts on reflectance spectra. Results showed reliable estimation of particulate matter concentrations (RMSE = 2.74 mg L−1) and accurate but imprecise estimation of chlorophyll (RMSE = 0.46 μg L−1) and colored dissolved organic matter (RMSE = 0.03 m−1). Accurately correcting reflectance spectra to minimize sun and sky glint effects significantly improved model performance. Results here suggest a role for both hyperspectral and multispectral platforms and rapid application of simple algorithms can be useful for nearshore water quality monitoring over coral reefs.

Accurate retrieval of canopy nutrient content has been made possible using visible-to-shortwave infrared (VSWIR) imaging spectroscopy. While this strategy has often been tested on closed green plant canopies, little is known about how nutrient content estimates perform when applied to pixels not dominated by photosynthetic vegetation (PV). In such cases, contributions of bare soil (BS) and non-photosynthetic vegetation (NPV), may significantly and nonlinearly reduce the spectral features relied upon for nutrient content retrieval. We attempted to define the loss of prediction accuracy under reduced PV fractional cover levels. To do so, we utilized VSWIR imaging spectroscopy data from the Global Airborne Observatory (GAO) and a large collection of lab-calibrated field samples of nitrogen (N) content collected across numerous crop species grown in several farming regions of the United States. Fractional cover values of PV, NPV, and BS were estimated from the GAO data using the Automated Monte Carlo Unmixing algorithm (AutoMCU). Errors in prediction from a partial least squares N model applied to the spectral data were examined in relation to the fractional cover of the unmixed components. We found that the most important factor in the accuracy of the partial least squares regression (PLSR) model is the fraction of photosynthetic vegetation (PV) cover, with pixels greater than 60% cover performing at the optimal level, where the coefficient of determination (R2) peaks to 0.66 for PV fractions of more than 60% and bare soil (BS) fractions of less than 20%. Our findings guide future spaceborne imaging spectroscopy missions as applied to agricultural cropland N monitoring.

With the increasing availability and volume of remote sensing data, imaging spectroscopy is an expanding tool for agricultural studies. One of the fundamental applications in agricultural research is crop mapping and classification. Previous studies have mostly focused at local to regional scales, and classifications were usually performed for a limited number of crop types. Leveraging fine spatial resolution (60 cm) imaging spectroscopy data collected by the Global Airborne Observatory (GAO), we investigated canopy-level spectral variations in 16 crop species from different agricultural regions in the U.S. Inter-specific differences were quantified through principal component analysis (PCA) of crop spectra and their Euclidean distances in the PC space. We also classified the crop species using support vector machines (SVM), demonstrating high classification accuracy with a test kappa of 0.97. A separate test with an independent dataset also returned high accuracy (kappa = 0.95). Classification using full reflectance spectral data (320 bands) and selected optimal wavebands from the literature resulted in similar classification accuracies. We demonstrated that classification involving diverse crop species is achievable, and we encourage further testing based on moderate spatial resolution imaging spectrometer data.

In response to the problem of germanium adsorption loss caused by lead sulfate adsorption during the leaching process of zinc oxide dust containing germanium, this article simulates and identifies the mechanism of lead sulfate adsorbing germanium, and innovatively introduces ultrasonic to suppress the adsorption of germanium by lead sulfate. Research has shown that the adsorption process of lead sulfate on germanium conforms to the pseudo-second-order kinetic adsorption model. The diffusion process of germanium adsorbed on lead sulfate particles can be divided into three stages: fast, slow, and equilibrium. The adsorption of germanium by lead sulfate conforms to the Langmuir isotherm adsorption model, and is mainly monolayer adsorption and chemical adsorption. In addition, the adsorption at 298–328 K is a spontaneous, endothermic, and entropy increasing process, while at 328–358 K it is a spontaneous, exothermic, and entropy decreasing process. At the same time, it was also found that low temperature, high temperature, and high-power ultrasonic can inhibit the adsorption process. Under ultrasound conditions of 358 K and 60.0 W, the equilibrium adsorption capacity of lead sulfate on germanium was 7.48 mg/g, and the germanium adsorption efficiency was 18.09%, which was 48.01% and 6.73% lower than conventional methods, respectively. Moreover, the leaching efficiency of germanium in actual dust leaching is increased by 6.17%, reaching 89.64%, verifying the simulation results. The new process of ultrasonic suppression of germanium adsorption by lead sulfate in the leaching process of zinc oxide dust containing germanium established in this article can effectively achieve efficient recovery of germanium from zinc oxide dust, providing a process and theoretical basis for the sustainable development of the world's germanium industry, and is of great significance for ensuring the safety of the world's important strategic resource supply chain.

Abstract Background This trial aimed to analyse the safety, effectiveness and transcriptomic characteristics of neoadjuvant toripalimab plus chemotherapy in II–III non-small-cell lung cancer (NSCLC). Methods Patient eligibility mainly involved treatment-naive, clinical stage II–III and wild-type EGFR/ALK NSCLC. The patients received 2–4 cycles of toripalimab (240 mg q3w) plus carboplatin-based chemotherapy. After the second treatment cycle, all patients were re-evaluated by a multidisciplinary team. Candidates eligible for surgery underwent surgery; otherwise, patients received the remaining treatment cycles. The primary endpoints were safety and major pathological response (MPR). Secondary endpoints were R0 resection rate, progression-free survival (PFS) and overall survival (OS). RNA sequencing of baseline and post-treatment samples was conducted to explore the transcriptomic characteristics of the therapeutic response. Results In total, 50 eligible patients were enrolled, including 12 (24.0%) with resectable disease (RD) and 38 (76.0%) with potentially resectable disease (PRD). Treatment-related adverse events (TRAEs) were recorded in 48 cases (96.0%). Severe TRAEs occurred in 3 (6.0%) cases, including myelosuppression, drug-induced liver injury and death related to haemoptysis. The objective response rate (ORR) was 76.0%, with 8 (16.0%) patients having a complete response (CR), 30 (60.0%) partial response (PR), 10 (20.0%) stable disease (SD) and 2 (4.0%) progressive disease (PD). Surgery could be achieved in 12 (100%) patients with RD and 25 (65.8%) with PRD; 1 (2.0%) with PRD refused surgery. Therefore, R0 resection was performed for all 36 (100%) patients who underwent surgery; 20 (55.6%) achieved MPR, including 10 (27.8%) with a complete pathological response (pCR). The CHI3L1 (chitinase-3-like protein 1) immunohistochemistry (IHC) expression of baseline tumour samples could predict the therapeutic response (AUC=0.732), OS (P=0.017) and PFS (P=0.001). Increased PD-1 expression, T cell abundance and immune-related pathway enrichment were observed in post-treatment samples compared to baseline in the response group (CR+PR) but not in the non-response group (SD+PD). Conclusions Neoadjuvant toripalimab plus chemotherapy was safe and effective, with a high MPR and manageable TRAEs for II–III NSCLC, even converting initially PRD to RD. Disparate transcriptomic characteristics of therapeutic efficiency were observed, and CHI3L1 expression predicted therapeutic response and survival. Trial registration ChiCTR1900024014, June 22, 2019.

Chemotherapy is the primary treatment for advanced non-small-cell lung cancer (NSCLC). However, related dose-dependent toxicity limits its clinical use. Therefore, it is necessary to explore new strategies for improving the clinical outcomes while reducing the side effects of chemotherapy in the treatment of NSCLC. In this study, we designed and synthesized epidermal growth factor (EGF)-modified doxorubicin nanoparticles (EGF@DOX-NPs) that selectively targets the epidermal growth factor receptor (EGFR) overexpressed in lung tumor cells. When administered in combination with low-dose X-ray radiotherapy (RT), the NPs preferentially accumulated at the tumor site due to radiation-induced outburst of the local intra-tumoral blood vessels. Compared with DOX alone, EGF@DOX-NPs significantly decreased the viability and migration and enhanced the apoptosis rates of tumor cells in vitro. Also, the EGF@DOX-NPs significantly inhibited tumor growth in vivo, increasing the survival of the tumor-bearing mice without apparent systemic toxic effects through RT-induced aggregation. The tumor cell proliferation was greatly inhibited in the RT + EGF@DOX-NPs group. Contrarily, the apoptosis of tumor cells was significantly higher in this group. These results confirm the promising clinical application of radiotherapy in combination with EGF@DOX-NPs for lung cancer treatment.

Abstract Background HIV drug resistance increased with the widespread use of antiretroviral drugs, and posed great threat to antiretroviral therapy (ART). Pu’er Prefecture, lying in the southwest of Yunnan Province, China, borders Myanmar, Laos and Vietnam, is also the area where AIDS was discovered earlier, however, in which there has been no information on HIV drug resistance. Methods A cross-sectional survey of pretreatment drug resistance (PDR) was conducted in Pu’er Prefecture in 2021. Partial pol gene sequences were obtained to analyze drug resistance and construct genetic transmission network. HIV drug resistance was analyzed using the Stanford University HIVdb algorithm. Results A total of 295 sequences were obtained, among which 11 HIV-1 strain types were detected and CRF08_BC (62.0%, 183/295) was the predominant one. Drug resistance mutations (DRMs) were detected in 42.4% (125/295) of the sequences. The prevalence of PDR to any antiretroviral drugs, nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 10.8% (32/295), 9.5% (28/295), 1.0% (3/295) and 0.3% (1/295), respectively. The risk of PDR occurrence was higher among individuals with CRF01_AE strain types. HIV-1 molecular network was constructed, in which 56.0% (42/75) of links were transregional, and 54.7% (41/75) of links were associated with Lancang County. Among the sequences in the network, 36.8% (35/95) harbored DRMs, and 9.5% (9/95) were drug resistance strains. Furthermore, 8 clusters had shared DRM. Conclusion The overall prevalence of PDR in this study was in a moderate level, but NNRTIs resistance was very approaching to the threshold of public response initiation. PDR was identified in the transmission network, and DRMs transmission was observed. These findings suggested that the consecutive PDR surveillance should be conducted in this region.

Low leaching efficiency of germanium has always been a difficult point hindering the efficient utilization of zinc oxide dust containing germanium. Based on the previous research results that the formation of insoluble Fe4Ge3O12 leads to germanium loss in the leaching process, a new process of reduction leaching of zinc oxide dust containing germanium enhanced by ultrasonic and iron powder is proposed. Under optimized conditions, the germanium leaching efficiency can be increased by 9.17%, reaching 93.43%. When leaching, the addition of iron powder can reduce the Fe3+ formed in the leaching process and hinder the formation of insoluble Fe4Ge3O12, which can increase the leaching efficiency of germanium by 5.30%. At the same time, strong mechanical action of ultrasonic can fully disperse the iron powder in the leaching system, avoiding the phenomenon of insufficient local reduction. More importantly, the addition of ultrasonic can reduce the dissolved oxygen in the solution system and produce strong reducing hydrogen free radicals (·H), strengthening the reduction leaching effect, thus the germanium leaching efficiency is further increased by 3.87%. The research results provide a new method and theoretical guidance for the efficient utilization of zinc oxide dust containing germanium, which is of great significance.

Chemotherapy is one of the main therapeutic strategies for the treatment of malignant melanoma. Conventional chemotherapeutic agents often lack targeting abilities, and efficacy is hampered by their high toxic effects to normal tissues and rapid clearance from the circulation. In this study, porous paclitaxel (PTX)-loaded polylactide (PLA) microspheres (PPMSs) were prepared by a modified double-emulsion-solvent evaporation method. In addition, PPMSs and cisplatin (DDP) were co-embedded in a thermosensitive hydrogel to construct a dual-drug co-delivery hydrogel system (PPMSs/DDP@Gel) for in-situ chemotherapy to treat melanoma by means of an intra-tumoral injection. The system allows for the sustained release of two drugs and exhibits good temperature-sensitive properties. In vitro antitumor activity showed that this hydrogel composite can induce B16 cell apoptosis and inhibit its migration. In vivo, anti-tumor studies have shown that the PPMSs/DDP@Gel significantly inhibited tumor growth, prolonged the survival of tumor-bearing mice, and had no obvious toxic side effects on major organs. Furthermore, immunohistochemical analysis revealed that PPMSs/DDP@Gel significantly inhibited tumor cell proliferation and promoted apoptosis of tumor cells. Taken together, the injectable temperature-sensitive PPMSs/DDP@Gel is a promising candidate for the local treatment of melanoma.

BackgroundThe purpose of this study was to evaluate the role of differentiation-related genes (DRGs) in tumor-associated macrophages (TAMs) in non-small cell lung cancer (NSCLC).MethodsSingle cell RNA-seq (scRNA-seq) data from GEO and bulk RNA-seq data from TCGA were analyzed to identify DRGs using trajectory method. Functional gene analysis was carried out by GO/KEGG enrichment analysis. The mRNA and protein expression in human tissue were analyzed by HPA and GEPIA databases. To investigate the prognostic value of these genes, three risk score (RS) models in different pathological types of NSCLC were generated and predicted NSCLC prognosis in datasets from TCGA, UCSC and GEO databases.Results1,738 DRGs were identified through trajectory analysis. GO/KEGG analysis showed that these genes were predominantly related to myeloid leukocyte activation and leukocyte migration. 13 DRGs (C1QB, CCL4, CD14, CD84, FGL2, MS4A6A, NLRP3, PLEK, RNASE6, SAMSN1, SPN, TMEM176B, ZEB2) related to prognosis were obtained through univariate Cox analysis and Lasso regression. C1QB, CD84, FGL2, MS4A6A, NLRP3, PLEK, SAMSN1, SPN, and ZEB2 were downregulated in NSCLC compared to non-cancer tissue. The mRNA of 13 genes were significantly expressed in pulmonary macrophages with strong cell specificity. Meanwhile, immunohistochemical staining showed that C1QB, CCL4, SPN, CD14, NLRP3, SAMSN1, MS4A6A, TMEM176B were expressed in different degrees in lung cancer tissues. ZEB2 (HR=1.4, P

BackgroundBlood pressure variability (BPV) has been reported to be a predictor of cardiovascular and some cognitive diseases. However, the association between napping and BPV remains unknown. This study aimed to explore the association between napping and BPV.Materials and methodsA cross-sectional study including 105 university students was conducted. Participants’ 24 h ambulatory blood pressure monitoring (24 h ABPM) were measured, and napping behaviors were investigated. BPV were measured by the 24 h ABPM, included standard deviation (SD), coefficient of variation (CV), and average real variability (ARV).ResultsAmong the participants, 61.9% reported daytime napping. We found that nap duration was significantly associated with daytime CV of diastolic blood pressure (DBP) (r = 0.250, P = 0.010), nighttime CV of systolic blood pressure (SBP) (r = 0.217, P = 0.026), 24 h WCV of DBP (r = 0.238, P = 0.014), 24 h ARV of SBP (r = 0.246, P = 0.011) and 24 h ARV of DBP (r = 0.291, P = 0.003). Compared with the no napping group, 24 h WCV of DBP, daytime CV of DBP, and daytime SD of DBP were significantly higher in participants with napping duration >60 min. With multiple regression analysis we found that nap duration was an independent predictor for 24 h ARV of SBP (β = 0.859, 95% CI, 0.101–1.616, P = 0.027) and 24 h ARV of DBP (β = 0.674, 95% CI, 0.173–1.175, P = 0.009).ConclusionsNapping durations are associated with BPV among university students. Especially those with napping durations >60 min had a significantly higher BPV than those non-nappers.

Abstract Adenoid cystic carcinoma (AdCC) of the breast is a rare indolent carcinoma of salivary gland-type tumors, frequently associated with MYB genetic alteration. Solid and basaloid adenoid cystic carcinoma (SB-AdCC) is considered a sparse variant of AdCC. This study sought to search for clinicopathological and genomic features in SB-AdCC. Registered clinicopathological data on a cohort of 13 AdCC of the breast cases, including six conventional adenoid cystic carcinoma (C-AdCC) cases and seven SB-AdCC cases, were collected. MYB gene rearrangement via fluorescent in situ hybridization was investigated and MYB protein expression was evaluated by immunohistochemistry. Compared with C-AdCC, we found that the distribution of SB-AdCC cases were shifted to older age and were more frequently distant metastasis. Moreover, metastasis cases also showed a high (exceed 30%) Ki-67 index. Both groups showed MYB rearrangements and MYB protein expression, but they were less frequent in SB-AdCC than C-AdCC. To conclude, our results suggest that SB-AdCC is an aggressive variant of mammary AdCC with a higher incidence of distant metastases compared with C-AdCC, though they share common molecular features. A high Ki-67 index may be an adverse prognostic factor for metastasis.

While renewable H2 production offers a promising route for clean energy production, there is an urgent need to improve catalyst performances. Here, authors design a Pt-containing complex oxide that utilizes atomic-scale hydrogen spillover to promote H2 evolution electrocatalysis in acidic media.

In this paper, the effects of different combinations of permeable spur dikes installed in the bend section of spillway on flow characteristics and energy dissipation rate were experimentally and numerically investigated. The results indicate that the permeable spur dikes installed in the spillway bend appreciably contributes to the improvement on the water surface uniformity, and the water surface uniformity can reach 90.13% with three permeable spur dikes installed in the bend. The permeable spur dike can lead to different degrees of decrease in the time-averaged longitudinal velocity in each zone of spillway bend. Different from previous study, no circulation zone is formed upstream and downstream of permeable spur dike due to the presence of permeable holes, and the flow upstream of permeable spur dikes could be divided into three distinctly different flow modes according to dye tracing. The presence of permeable spur dikes causes the concentration of TKE zone at concave bank of the spillway bend, except for TKE zone immediately next to the bottom plate. The TKE first increases and then decreases with the increase in the vertical distance from the bottom plate of the spillway bend, exhibiting a typical parabolic distribution. The energy dissipation rate in the spillway bend with permeable spur dike was calculated using a modified integral method, and the dissipation rate can reach as high as 21.08% with three spur dikes installed in the bend. HIGHLIGHTS Permeable spur dike was proven to be able to improve the flow characteristics in spillway.; Up to 20% energy dissipation rate can be achieved by using permeable spur dike in spillway.; The distribution of velocity in spillway with permeable spur dike was obviously decreased.; The arrangement of three permeable spur dikes has the best effect on improving the flow characteristics of spillway.;

Inefficient nitrogen (N) utilization in agricultural production has led to many negative impacts such as excessive use of N fertilizers, redundant plant growth, greenhouse gases, long-lasting toxicity in ecosystem, and even effect on human health, indicating the importance to optimize N applications in cropping systems. Here, we present a multiseasonal study that focused on measuring phenotypic changes in wheat plants when they were responding to different N treatments under field conditions. Powered by drone-based aerial phenotyping and the AirMeasurer platform, we first quantified 6 N response-related traits as targets using plot-based morphological, spectral, and textural signals collected from 54 winter wheat varieties. Then, we developed dynamic phenotypic analysis using curve fitting to establish profile curves of the traits during the season, which enabled us to compute static phenotypes at key growth stages and dynamic phenotypes (i.e., phenotypic changes) during N response. After that, we combine 12 yield production and N-utilization indices manually measured to produce N efficiency comprehensive scores (NECS), based on which we classified the varieties into 4 N responsiveness (i.e., N-dependent yield increase) groups. The NECS ranking facilitated us to establish a tailored machine learning model for N responsiveness-related varietal classification just using N-response phenotypes with high accuracies. Finally, we employed the Wheat55K SNP Array to map single-nucleotide polymorphisms using N response-related static and dynamic phenotypes, helping us explore genetic components underlying N responsiveness in wheat. In summary, we believe that our work demonstrates valuable advances in N response-related plant research, which could have major implications for improving N sustainability in wheat breeding and production.

Background Accumulating data suggest that mucosal melanoma, well known for its poor response to immune checkpoint blockade (ICB) and abysmal prognosis, is a heterogeneous subtype of melanoma with distinct genomic and clinical characteristics between different anatomic locations of the primary lesions. Primary malignant melanoma of the esophagus (PMME) is a rare, highly aggressive disease with a poorer prognosis compared with that of non-esophageal mucosal melanoma (NEMM). In this study, we retrospectively analyzed the efficacy of anti-programmed death (PD)-1 in patients with PMME and explored its molecular basis.Methods The response and survival of patients with PMME and NEMM under anti-PD-1 monotherapy were retrospectively analyzed. To explore the molecular mechanisms of the difference in therapeutic efficacy between PMME and NEMM, we performed genomic analysis, bulk RNA sequencing, and multiplex immunohistochemistry staining.Results We found that PMME (n=28) responded better to anti-PD-1 treatment than NEMM (n=64), with a significantly higher objective response rate (33.3% (95% CI 14.3% to 52.3%) vs 6.6% (95% CI 0.2% to 12.9%)) and disease control rate (74.1% (95% CI 56.4% to 91.7%) vs 37.7% (95% CI 25.2% to 50.2%)). Genomic sequencing analysis revealed that the genomic aberration landscape of PMME predominated in classical cancer driver genes, with approximately half of PMME cases harboring mutations in BRAF, N/KRAS, and NF1. In contrast, most NEMM cases were triple wild-type. Transcriptome analysis revealed that, compared with NEMM, PMME displayed more significant proliferation and inflammatory features with higher expression of genes related to antigen presentation and differentiation, and a less immunosuppressive signature with lower expression of inhibitory immune checkpoints and dedifferentiation-related genes. The multiplex immunohistochemical analysis also demonstrated higher CD8+ T-cell infiltration in PMME than in NEMM.Conclusions PMME is an outlier of mucosal melanoma showing a malicious phenotype but a particularly high response rate to ICB because of its distinct molecular characteristics. Patient stratification based on anatomic origin can facilitate clinical decision-making in patients with mucosal melanoma following the verification of our results in future prospective studies.

Chinese government has set the Environmental Complaint Reporting System (ECRS) to monitor and manage industrial water pollution in a timely manner for years. Citizens can give feedback on water pollution incidents both online and offline, and report the human health risk. By combining methods of Pooled Least Squares, Instrumental Variable Estimation and Poisson Distribution to examine, the empirical results show that when control for the effects of instrumental variables such as the spread of information through mobile phones and internet, a higher pressure of improving the quality of environment would force and prompt the government to prevent industrial water pollution.

ObjectiveMirror movements (MMs) are common abnormal motor performance in patients with poststroke hemiparesis. The study aimed to utilize the Electromyography (EMG) characterization of MMs in stroke patients and explore the relationship between MMs and the motor function of affected limbs.MethodsSixty patients with stroke who had used to undergo clinical assessment and surface Electromyography (sEMG) were selected in this study. We investigated the standardized net excitation (SNE) and overflow percentage (OF) as a measure of mirror activities on bilateral muscles of stroke patients.ResultsIn stroke patients, mirror activities occurred in both affected and unaffected muscles during maximal contractions. We found that OF at unilateral contraction on the affected side (UCA) was significantly greater than that at unilateral contraction on the unaffected side (UCU). Additionally, a negative correlation between OF at UCA and Brunnstrom stages on admission and discharge. However, there were no significant correlations between OF and disease duration, Barthel Index, or the degree of improvement in all clinical evaluations. We still found a positive correlation between SNE at UCA and the improvement of the Brunnstrom stage of the hand. But we could not find any significant correlation between SNE and other clinical evaluation scores.ConclusionIn conclusion, the study found mirror activities in both affected and unaffected muscles, confirming an asymmetry between them. Although the mechanisms are still unclear, we confirmed a significant correlation between MMs at UCA and the motor function of the affected upper extremity, which might provide further evidences for understanding MMs in stroke patients and a new research direction on evaluation for motor function and outcomes of stroke patients.

Abstract Background Schizophrenia is a polygenic disease; however, the specific risk genetic variants of schizophrenia are still largely unknown. Single nucleotide polymorphism (SNP) is important genetic factor for the susceptibility of schizophrenia. Investigating individual candidate gene contributing to disease risk remains important. Methods In a case-control study, five SNPs located in 6p21.3-p23.1 including rs2021722 in human leukocyte antigen (HLA) locus and rs107822, rs383711, rs439205 and rs421446 within the upstream of microRNA-219a-1 were genotyped in 454 schizophrenia patients and 445 healthy controls to investigate the possible association between the loci and schizophrenia in a Han Chinese population. Results Our results showed significant associations between the rs2021722 and schizophrenia in allele (A vs. G: adjusted OR = 1.661, 95%CI = 1.196–2.308), co-dominant (AG vs. GG: OR = 1.760, 95%CI = 1.234–2.510) and dominant genetic model (AG + AA vs. GG: OR = 1.756, 95%CI = 1.237–2.492), respectively. Haplotype analysis showed that TGGT and CAAC were protective factor for schizophrenia compared with TAAC haplotype (OR = 0.324, 95% CI = 0.157–0.672; OR = 0.423, 95% CI = 0.199–0.900). Conclusions These findings indicate that rs2021722 in HLA locus might be involved in pathogenesis of schizophrenia and that genotypes AG and allele A of the locus are risk factors for schizophrenia in the Han Chinese population, confirming the association between immune system and schizophrenia.

BackgroundSurvival outcomes of early-stage T1-2N0M0 small cell lung cancer (SCLC) patients differ widely, and the existing Veterans Administration Lung Study Group (VALSG) or TNM staging system is inefficient at predicting individual prognoses. In our study, we developed and validated nomograms for individually predicting overall survival (OS) and lung cancer-specific survival (LCSS) in this special subset of patients.MethodsData on patients diagnosed with T1-2N0M0 SCLC between 2000 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. All enrolled patients were split into a training cohort and a validation cohort according to the year of diagnosis. Using multivariable Cox regression, significant prognostic factors were identified and integrated to develop nomograms for 1-, 3-, and 5-year OS and LCSS prediction. The prognostic performance of our new model was measured by the concordance index (C-index) and calibration curve. We compared our latest model and the 8th AJCC staging system using decision curve analyses (DCA). Kaplan–Meier survival analyses were applied to test the application of the risk stratification system.ResultsA total of 1,147 patients diagnosed from 2000 to 2011 were assigned to the training cohort, and 498 cases that were diagnosed from 2012 to 2015 comprised the validation cohort. Age, surgery, lymph node removal (LNR), and chemotherapy were independent predictors of LCSS. The variables of sex, age, surgery, LNR, and chemotherapy were identified as independent predictors of OS. The above-mentioned prognostic factors were entered into the nomogram construction of OS and LCSS. The C-index of this model in the training cohort was 0.663, 0.702, 0.733, and 0.658, 0.702, 0.733 for predicting 1-, 3-, and 5-year OS and LCSS, respectively. Additionally, in the validation cohort, there were 0.706, 0.707, 0.718 and 0.712, 0.691, 0.692. The calibration curve showed accepted prediction accuracy between nomogram-predicted survival and actual observed survival, regardless of OS or LCSS. In addition, there were significant distinctions in the survival curves of OS and LCSS between different risk groups stratified by prognostic scores. Compared with the 8th AJCC staging system, our new model also improved net benefits.ConclusionsWe developed and validated novel nomograms for individual prediction of OS and LCSS, integrating the characteristics of patients and tumors. The model showed superior reliability and may help clinicians make treatment strategies and survival predictions for early-stage T1-2N0M0 SCLC patients.

Background: Although the clinical application of osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been a new step forward in the first-line treatment of non-small cell lung cancer (NSCLC), an increasing number of patients with progression on osimertinib represents a great challenge clinically. The patterns of resistance mechanisms and subsequent treatment strategies after first-line osimertinib resistance are not well established. Methods: Between January 1, 2016 and October 31, 2020, a consecutive of 56 EGFR-mutant lung cancer patients treated with osimertinib as first-line therapy at Daping Hospital (Chongqing, China) were retrospective screened. The samples of pre-osimertinib and osimertinib-resistance were all detected by next-generation sequencing (NGS) panels. Statistical analyses were carried out using SPSS 23.0 software. Survival analyses were performed using the Kaplan–Meier method and compared using a log-rank test between groups. Results: Among 47 patients with osimertinib effectiveness analysis, the median progression free survival (mPFS) was 15.4 months (95% confidence interval [CI]: 12.2-24.9 months), and median overall survival (mOS) was 35.5 months (95% CI: 23.9 months -NA). A total of 21 patients underwent repeated NGS tests upon osimertinib resistance. MET amplification was the most common resistance mechanism (6/21, 28.6%), followed by C797S mutation (5/21, 23.8%). A total of 15 patients received subsequent treatments, with mPFS of 7.3 months (95% CI 5.0 months -NA). Among them, 7 patients with EGFR C797 S or/and MET amplification received subsequent second-line targeted therapy, achieving mPFS of 7.3 months (95% CI 4.5 months -NA). Of note, 3 patients received immunotherapy as second- or third-line treatment after osimertinib resistance, achieving median clinical benefit of 37.3 months. Conclusions: MET amplification and C797S mutation are main resistance mechanisms, which could be targeted by crizotinib and gefitinib, respectively. More than 50% patients could receive subsequent anticancer targetable therapies after first-line osimertinib resistance. Immunotherapy may also be an acceptable choice after osimertinib resistance.

DNA methylation patterns in plants are dynamically shaped by the antagonistic actions of DNA methylation and demethylation pathways. Although the DNA methylation pathway has been well studied, the DNA demethylation pathway, however, are not fully understood so far. To gain deeper insights into the mechanisms of DNA demethylation pathway, we conducted a genetic screening for proteins that were involved in preventing epigenetic gene silencing, and then the ones, which were also implicated in DNA demethylation pathway, were used for further studies. Eventually, a mutant with low luciferase luminescence (low LUC luminescence) was recovered, and named reduced LUC luminescence 6–1 (rll6-1). Map-based cloning revealed that rll6-1 mutation was located on chromosome 4, and there were a total of 10 candidate genes residing within such a region. Analyses of genome-wide methylation patterns of rll6-1 mutant showed that mutation of RLL6 locus led to 3,863 hyper-DMRs (DMRs for differentially methylated regions) throughout five Arabidopsis chromosomes, and elevated DNA methylation level of 2 × 35S promoter, which was similar to that found in the ros1 (repressor of silencing 1) mutant. Further analysis demonstrated that there were 1,456 common hyper-DMRs shared by rll6-1 and ros1-7 mutants, suggesting that both proteins acted together in a synergistic manner to remove DNA methylation. Further investigations demonstrated that mutation of RLL6 locus did not affect the expression of the four genes of the DNA glycosylase/lyase family. Thus, our results demonstrate that RLL6 locus-encoded protein not only participates in transcriptional anti-silencing of a transgene, but is also involved in DNA demethylation pathway.

The extragynoecial compitum formed by the incomplete fusion of carpel margins, while allowing intercarpellary growth of pollen tubes in apocarpous angiosperms, may also increase the risk of reproductive interference caused by heterospecific pollen (HP) deposition. In Sagittaria, congeneric HP tubes grow via different paths and enter the ovules later than conspecific pollen (CP) tubes. However, it is unclear how the growth advantage of the CP tube helps ensure reproductive success when HP is deposited on the stigmas. We performed molecular characterization of interspecies-pollinated seeds to examine the consequences of interspecific pollen deposition between Sagittaria pygmaea and S. trifolia. We also conducted CP–HP (1:1) mixed pollination and delayed CP pollination treatments to explore the seed-siring abilities of CP and HP. Our results showed that although HP could trigger the development of fruits, the interspecies-pollinated seeds contained partially developed embryos and could not germinate. More than 70% of the embryos in these seeds were molecularly identified as hybrids of both species, suggesting that HP tubes could enter the ovules and fertilize the egg cells. Moreover, CP could sire more offspring (≥70%) after the CP–HP (1:1) mixed pollination treatment, even when HP reached the stigma 0.5–1 h earlier than CP (≥50%). Following adequate CP vs. HP (1:1) pollination on carpels on two sides of the apocarpous gynoecium, both species produced > 70% conspecific seeds, indicating that the CP tubes could occupy ovules that should be occupied by HP via the extragynoecial compitum. Our results reveal that in Sagittaria, pollen deposition from co-existing congeneric heterospecies leads to interspecific seed discounting. However, the CP advantage mediated by the extragynoecial compitum is an effective strategy to mitigate the effects of interspecific pollen deposition. This study improves our understanding of how apocarpous angiosperms with an extragynoecial compitum can maintain species stability and mitigate the negative reproductive interference effect from sympatrically distributed related species.

BackgroundAdjuvant chemotherapy has been shown to produce a favorable prognosis for patients with resectable mucosal melanoma (MM), resulting in the need for stratification to optimally select patients to benefit from adjuvant therapy. This study analyzed Ki67 as a potential stratification index for adjuvant chemotherapy in resectable MM.MethodsPatients with resected MM who received subsequent adjuvant therapy in Beijing Cancer Hospital between 2010 and 2018 were retrospectively enrolled and analyzed. Relapse-free survival (RFS) and melanoma-specific survival (MSS) curves were used to perform the survival comparisons across different subgroups.ResultsFrom Jan 2010 to Dec 2018, 1106 MM patients were screened from a database of 4706 patients and 175 of these patients were finally enrolled. A total of 100 patients received temozolomide (TMZ)-based adjuvant chemotherapy and 75 patients received high-dose interferon-α2b (HDI) adjuvant therapy. Compared with HDI, patients who received TMZ-based adjuvant chemotherapy had significantly superior RFS (21.0 vs. 9.6 months, P = 0.002). For patients with low Ki67 expression (

The Middle-Upper Cambrian Xixiangchi carbonates in the Sichuan Basin have been pervasively dolomitized. In the presented work, petrographic investigation revealed three generations of the Xixiangchi dolomites, consisting of dolomicrite (D1, 5–20 μm) with a planar-s to non-planar texture, fabric destructive dolomite (D2, 50–150 μM) with a planar-s to planar-e texture, and saddle dolomite (D3, 300 μm to 4 mm) with a planar-s to planar-e texture. D1 and D2 dolomites are presented as matrix dolomites, whereas D3 dolomites are observed as fracture-filling dolomites. Compared with the matrix D1 and D2 dolomites, which are interpreted as products of dolomitization under near-surface or at shallow burial conditions, the depleted δ13C and δ18O values of D3 than D1 and D2 dolomites are probably caused by the temperature-controlled isotopic fractionation within an increasing fluid–rock interaction at burial. The enriched Mn, Sr, and Ba concentrations of D3 than D1 and D2 dolomites suggest a newly introduced type of diagenetic fluids, which is probably related to the upwelling of magmatic activities (Emeishan large igneous province). By contrast, the abnormally depleted Fe concentration in D3 dolomites is attributed to its preferential incorporation into other solid phases rather than its true concentration. The similar rare earth element (REE) partition patterns of D1 and D2 dolomites demonstrate similar dolomitization fluids related to seawater or marine-origin fluids. The hydrothermal-derived D3 dolomites exhibit a different REE partition pattern by contrast. The negative Eu anomalies of D3 dolomites may represent hydrothermal fluid cooling or an association with intermediate-felsic igneous rocks. The findings of the presented work would enhance our understanding on the hydrothermal dolomitization of the Middle-Upper Cambrian Xixiangchi Formation.

Abstract Desertification land in Gonghe Basin of Tibetan Plateau, China accounts for 91.9% of the total land area. Vegetation restoration and reconstruction with desert shrubs in degraded ecosystem are effective ways to prevent and control desertification. However, the evaluation studies of fine root dynamic characteristics of desert shrubs and their contribution to carbon sequestration of plantation are limited. To gain a better understanding of vegetation restoration, the vertical distribution of fine root biomass, fine root decomposition, fine root turnover was investigated, as well as their coupling effect on carbon sequestration of plantation in three desert vegetation. The results estimated that the total decomposition time of fine roots of Salix cheilophila (S. cheilophila), Salix psammophila (S. psammophila), and Salix microstachya (S. microstachya) are 39.00, 27.99 and 35.95 years. Biomass carbon density for three Salix plantations ranged from 1.42 to 2.39 t/hm2, which showed that three Salix plantations in alpine sandy land are an important carbon pool. In addition, fine root biomass carbon density for the three shrub plantations varied significantly. Fine root biomass carbon density for S. psammophila reached the largest among the three plantations, which was 1.48 t/hm2, accounting for the ratio of 62% of the plantation total biomass carbon density. The results indicated that the root system of S. psammophila, especially the fine roots, was very developed, which was conducive to soil water transportation and carbon sequestration. Therefore, S. psammophila might be a better species for carbon sequestration of plantation in alpine sandy areas. The carbon input from the fine roots of the three shrub plantations through decomposition and turnover into the plantations accounts for 11.5% to 15.5% of total carbon sequestration of plantations. Therefore, the fine roots dynamics must be considered for long‐term carbon pool estimations in three Salix plantations, otherwise the total carbon sequestration of plantations would be underestimated.