Optically Probing Unconventional Superconductivity in Atomically Thin Bi2Sr2Ca0.92Y0.08Cu2O8+δ.

Atomically thin cuprates exhibiting a superconducting phase transition temperature similar to that of the bulk have recently been realized, although the device fabrication remains a challenge and limits the potential for many novel studies and applications. Here, we use an optical pump-probe approach to noninvasively study the unconventional superconductivity in atomically thin Bi2Sr2Ca0.92Y0.08Cu2O8+δ (Y-Bi2212). Apart from finding an optical response due to the superconducting phase transition that is similar to that of bulk Y-Bi2212, we observe that the sign and amplitude of the pump-probe signal in atomically thin flakes vary significantly in different dielectric environments depending on the nature of the optical excitation. By exploiting the spatial resolution of the optical probe, we uncover the exceptional sensitivity of monolayer Y-Bi2212 to the environment. Our results provide the first optical evidence for the intralayer nature of the superconducting condensate in Bi2212 and highlight the role of double-sided encapsulation in preserving superconductivity in atomically thin cuprates.

Response of fine particulate matter and ozone concentrations to meteorology and anthropogenic precursors over the "2+26" cities of northern China.

Analyzing the influencing factors of fine particulate matter and ozone formation and identifying the coupling relationship between the two are the basis for implementing the synergistic pollutants control. However, the current research on the synergistic relationship between the two still needs to be further explored. Using the Geodetector model, we analyzed the effects of meteorology and emissions on fine particulate matter and ozone concentrations over the "2 + 26" cities at multiple timescales, and also explored the coupling relationship between the two pollutants. Fine particulate matter concentrations showed overall decreasing trends on inter-season and inter-annual scale from 2015 to 2021, whereas ozone concentrations showed overall increasing trends. While ozone concentrations displayed an inverted U-shaped distribution from month to month, fine particulate matter concentrations displayed a U-shaped fluctuation. On inter-annual scale, climatic factors, with planet boundary layer height as the main determinant, have higher effects for both pollutants than human precursors. In summer and autumn, sunshine duration had the most influence on fine particulate matter, while planet boundary layer height was the greatest factor in winter. Fine particulate matter is the leading impacting factor on ozone concentrations in summer, and there were positive associations between them on both annual and seasonal scale. The impact of nitrogen oxides and volatile organic compounds for both pollutants concentrations varied significantly between seasons. The two pollutants concentration were enhanced by the interactions between the various components. On inter-annual scale, interactions between the planet boundary layer height and other factors dominated the concentrations of the two pollutants, whereas in summer, interactions between fine particulate matter and other factors dominated the concentrations of ozone. The study has implications for the treatment of atmospheric pollution in China and other nations and can serve as an important reference for the creation of integrated atmospheric pollution regulation policies over the "2 + 26" cities.

Non-volatile electrical polarization switching via domain wall release in 3R-MoS2 bilayer.

Understanding the nature of sliding ferroelectricity is of fundamental importance for the discovery and application of two-dimensional ferroelectric materials. In this work, we investigate the phenomenon of switchable polarization in a bilayer MoS2 with natural rhombohedral stacking, where the spontaneous polarization is coupled with excitonic effects through asymmetric interlayer coupling. Using optical spectroscopy and imaging techniques, we observe how a released domain wall switches the polarization of a large single domain. Our results highlight the importance of domain walls in the polarization switching of non-twisted rhombohedral transition metal dichalcogenides and open new opportunities for the non-volatile control of their optical response.

Single-cell analysis reveals cellular reprogramming in advanced colon cancer following FOLFOX-bevacizumab treatment.

Introduction: The combination of FOLFOX and bevacizumab (FOLFOX-Bev) is a promising treatment for advanced colorectal cancer (CRC). However, the response of the tumor microenvironment to FOLFOX-Bev is still largely unexplored. Methods: We conducted single-cell transcriptomic analysis of CRC samples derived from a patient before and after treatment to gain insights into the cellular changes associated with FOLFOX-Bev treatment. Results: We found that cancer cells with high proliferative, metastatic, and pro-angiogenic properties respond better to FOLFOX-Bev treatment. Moreover, FOLFOX-Bev enhances CD8+ T cell cytotoxicity, thereby boosting the anti-tumor immune response. Conversely, FOLFOX-Bev impairs the functionality of tumor-associated macrophages, plasma cells, and cancer-associated fibroblasts, leading to a decrease in VEGFB-mediated angiogenesis. Furthermore, FOLFOX-Bev treatment reset intercellular communication, which could potentially affect the function of non-cancer cells. Discussion: Our findings provide valuable insights into the molecular mechanisms underlying the response of advanced CRC to FOLFOX-Bev treatment and highlight potential targets for improving the efficacy of this treatment strategy.

Shear Strain-Induced Two-Dimensional Slip Avalanches in Rhombohedral MoS2.

Slip avalanches are ubiquitous phenomena occurring in three-dimensional materials under shear strain, and their study contributes immensely to our understanding of plastic deformation, fragmentation, and earthquakes. So far, little is known about the role of shear strain in two-dimensional (2D) materials. Here we show some evidence of 2D slip avalanches in exfoliated rhombohedral MoS2, triggered by shear strain near the threshold level. Utilizing interfacial polarization in 3R-MoS2, we directly probe the stacking order in multilayer flakes and discover a wide variety of polarization domains with sizes following a power-law distribution. These findings suggest that slip avalanches can occur during the exfoliation of 2D materials, and the stacking orders can be changed via shear strain. Our observation has far-reaching implications for the development of new materials and technologies, where precise control over the atomic structure of these materials is essential for optimizing their properties as well as for our understanding of fundamental physical phenomena.

Identifying predictive biomarkers of apatinib in third-line treatment of advanced colorectal cancer through comprehensive genomic profiling.

Apatinib is a selective inhibitor of vascular endothelial growth factor receptor-2. Despite encouraging anticancer activity in different cancer types, some patients may not benefit from apatinib treatment. Herein, we characterized genomic profiles in colorectal cancer (CRC) patients to explore predictive biomarkers of apatinib at molecular level. We retrospectively recruited 19 CRC patients receiving apatinib as third-line treatment. Tissue samples before apatinib treatment were collected and subjected to genomic profiling using a targeted sequencing panel covering 520 cancer-related genes. After apatinib treatment, the patients achieved an objective response rate of 21% (4/19) and disease control rate of 57.9% (11/19). The median progression-free survival (PFS) and overall survival were 5 and 8.7 months, respectively. Genetic alterations were frequently identified in TP53 (95%), APC (53%), KRAS (53%) and PIK3CA (26%). Higher tumor mutation burden levels were significantly observed in patients harboring alterations in ERBB and RAS signaling pathways. Patients harboring FLT1 amplifications ( n = 3) showed significantly worse PFS than wild-type patients. Our study described molecular profiles in CRC patients receiving apatinib treatment and identified FLT1 amplification as a potential predictive biomarker for poor efficacy of apatinib. Further studies are warranted to validate the use of FLT1 amplification during apatinib treatment.

Ultrafast response of spontaneous photovoltaic effect in 3R-MoS2-based heterostructures.

Rhombohedrally stacked MoS2 has been shown to exhibit spontaneous polarization down to the bilayer limit and can sustain a strong depolarization field when sandwiched between graphene. Such a field gives rise to a spontaneous photovoltaic effect without needing any p-n junction. In this work, we show that the photovoltaic effect has an external quantum efficiency of 10% for devices with only two atomic layers of MoS2 at low temperatures, and identify a picosecond-fast photocurrent response, which translates to an intrinsic device bandwidth at ∼100-GHz level. To this end, we have developed a nondegenerate pump-probe photocurrent spectroscopy technique to deconvolute the thermal and charge-transfer processes, thus successfully revealing the multicomponent nature of the photocurrent dynamics. The fast component approaches the limit of the charge-transfer speed at the graphene-MoS2 interface. The remarkable efficiency and ultrafast photoresponse in the graphene-3R-MoS2 devices support the use of ferroelectric van der Waals materials for future high-performance optoelectronic applications.

Development and validation of a survival prediction model for 113,239 patients with colon cancer: a retrospective cohort study.

Background: Colon cancer (CC) is the third most commonly diagnosed malignant tumor and remains the second leading cause of cancer-related deaths worldwide. However, the risk assessment of poor prognosis of CC is limited in previous studies. This study aimed to develop a predictive nomogram for the survival of CC patients. Methods: In this retrospective cohort study, 113,239 CC patients from the Surveillance, Epidemiology, and End Results (SEER) database were randomly divided into training (n=56,619) and testing (n=56,620) sets with a ratio of 1:1. Demographic, clinical data and survival status of patients were extracted. The outcomes were 3- and 5-year survival of CC. Univariate and multivariate Cox regression analyses were used to screen the predictors to develop the predictive nomogram. Internal validation and stratified analyses were further assessed the nomogram. The C-index and area under the curve (AUC) were calculated to estimate the model's predictive capacity, and calibration curves were adopted to estimate the model fit. Results: Totally 38,522 (34.02%) patients died during the 5-year follow-up. The nomogram incorporated variables associated with the prognosis of CC patients, including age, gender, marital status, insurance status, tumor grade, stage (T/N/M), surgery, and number of nodes examined, with a C-index of 0.775 in the training set and 0.774 in the testing set. The AUCs of the nomogram for the 3- and 5-year survival prediction in the training set were 0.817 and 0.808, with the sensitivity of 0.688 and 0.716, and the specificity of 0.785 and 0.740, respectively. Similar results were found in the testing set. The C-index of the predictive nomogram for male, female, White, Black, and other races was 0.769, 0.779, 0.773, 0.770, and 0.770, respectively. The calibration curves for the nomogram in the above five cohorts showed a good agreement between actual and predicted values. Conclusions: The nomogram may exhibit a certain predictive performance based on the SEER database, which may provide individual survival predictions for CC patients.

Predictive value of the presence of Prevotella and the ratio of Porphyromonas gingivalis to Prevotella in saliva for esophageal squamous cell carcinoma.

Background: Imbalance of oral salivary microbiota has been linked to the pathogenesis of a variety of systemic diseases, and oral bacterial species have been shown to be useful biomarkers for systemic diseases.This study aimed to characterize the alterations of oral microbiota in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the diagnostic performance of oral microbial biomarkers for ESCC. Methods: The relative abundance of flora in saliva samples was analyzed by 16S rDNA sequencing, and differences in the species present in samples from ESCC patients and healthy controls (HCs) were identified by analyzing species diversity and performing LEfSe analysis. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of the characteristic bacteria individually and in combination. Results: Differences in bacterial diversity indexes were observed for the saliva of ESCC patients versus HCs (P<0.05), but principal coordinate analysis did not detect a significant difference in the composition of oral microbiota between ESCC patients and HCs (P>0.05). LEfSe analysis showed that Leptotrichia, Porphyromonas (Pg), Streptococcus, Rothia, Lactobacillus and Peptostreptococcus were more abundant in ESCC patient saliva than in HC saliva, whereas Haemophilus, Alloprevotella (All), Prevotella_7, Prevotella (Pre), Prevotella_6, Pasteurellaceae and Pasteurellales were significantly less abundant in ESCC patient saliva (P<0.05). From ROC curve analysis, Pg could detect ESCC with an area under the ROC curve (AUC) of 0.599, sensitivity of 62.2%, and specificity of 70%, whereas the ratio of Pg/Pre had an AUC of 0.791, sensitivity of 93.3%, and specificity of 62.3%. Moreover, the combination of the Pg/Pre and Pg/All ratios showed further improved diagnostic performance for ESCC (AUC=0.826) and even good sensitivity and specificity for the diagnosis of early ESCC (68.2% and 86%, respectively; AUC=0.786). Conclusion: This study shows that Pg in saliva can be used as a characteristic marker of ESCC, and the ratios of Pg/Pre and Pg/All offered significantly improved diagnostic performance, especially for early ESCC.

Effects of anthropogenic precursor emissions and meteorological conditions on PM2.5 concentrations over the "2+26" cities of northern China.

Elucidating the characteristics and influencing mechanisms of PM2.5 concentrations is the premise and key to the precise prevention and control of air pollution. However, the temporal and spatial heterogeneity of PM2.5 concentrations and its driving mechanism are complex and need to be further analyzed. We analyzed the temporal and spatial variations of PM2.5 concentrations in the "2 + 26" cities from 2015 to 2021, and quantified the influence of meteorological factors and anthropogenic emissions and their interactions on PM2.5 concentrations based on geographic detector model. We find the inter-annual and inter-season PM2.5 concentrations show downward trend from 2015 to 2021, and the inter-month PM2.5 concentrations present a U-shaped distribution. The PM2.5 concentrations in the "2 + 26" cities manifest a spatial distribution pattern of high in the south and low in the north, and high in the middle and low in the surroundings. Meteorological conditions have stronger effects on PM2.5 concentrations than anthropogenic emissions, and planetary boundary layer height and temperature are the two main driving factors at the annual scale. On the seasonal scale, sunshine duration is the dominant factor of PM2.5 concentrations in summer and autumn, and planetary boundary layer height is the dominant factor of PM2.5 concentrations in winter. The effect of anthropogenic emissions on PM2.5 concentration is higher in winter and spring than in summer and autumn, and ammonia and ozone have stronger effects on PM2.5 concentrations than other anthropogenic emissions. Interactions between the factors significantly enhance the PM2.5 concentrations. The interactions between planetary boundary layer height and other impacting factors play dominant roles on PM2.5 concentrations at annual scale and in winter. Our results not only provide crucial information for further developing air quality policies of the "2 + 26" cities, but also bear out several important implications for clean air policies in China and other regions of the world.

PM2.5 Concentrations Variability in North China Explored with a Multi-Scale Spatial Random Effect Model.

Compiling fine-resolution geospatial PM2.5 concentrations data is essential for precisely assessing the health risks of PM2.5 pollution exposure as well as for evaluating environmental policy effectiveness. In most previous studies, global and local spatial heterogeneity of PM2.5 is captured by the inclusion of multi-scale covariate effects, while the modelling of genuine scale-dependent variabilities pertaining to the spatial random process of PM2.5 has not yet been much studied. Consequently, this work proposed a multi-scale spatial random effect model (MSSREM), based a recently developed fixed-rank Kriging method, to capture both the scale-dependent variabilities and the spatial dependence effect simultaneously. Furthermore, a small-scale Monte Carlo simulation experiment was conducted to assess the performance of MSSREM against classic geospatial Kriging models. The key results indicated that when the multiple-scale property of local spatial variabilities were exhibited, the MSSREM had greater ability to recover local- or fine-scale variations hidden in a real spatial process. The methodology was applied to the PM2.5 concentrations modelling in North China, a region with the worst air quality in the country. The MSSREM provided high prediction accuracy, 0.917 R-squared, and 3.777 root mean square error (RMSE). In addition, the spatial correlations in PM2.5 concentrations were properly captured by the model as indicated by a statistically insignificant Moran's I statistic (a value of 0.136 with p-value > 0.2). Overall, this study offers another spatial statistical model for investigating and predicting PM2.5 concentration, which would be beneficial for precise health risk assessment of PM2.5 pollution exposure.

Assessment of durable chemoimmunotherapy response via circulating tumor DNA in advanced esophageal squamous cell carcinoma.

Immune checkpoint inhibitor (ICI)-based therapies have shown promising advances for the first-line treatment of advanced or metastatic esophageal cancer (EC). However, few studies concerning the identification of patients who achieve durable response from ICIs have been previously reported. In the present study, pre- and on-treatment plasma circulating tumor DNA (ctDNA) were analyzed in 10 patients with advanced esophageal squamous cell cancer (ESCC) receiving first-line chemoimmunotherapy. Patients with decreased molecular tumor burden index (mTBI) >7% experienced longer progression-free survival (PFS) and durable clinical benefit (DCB, PFS ≥ 6 months). In addition, five patients showed stable disease at first scan, all three patients with decreased mTBI > 7% achieved DCB, while two cases with decreased mTBI ≤ 7% experienced non-DCB. Our results demonstrate that ctDNA monitor might help identify which ESCC patients respond to chemoimmunotherapy.

Salivary microbiota may predict the presence of esophageal squamous cell carcinoma.

The aim is to explore the predictive value of salivary bacteria for the presence of esophageal squamous cell carcinoma (ESCC). Saliva samples were obtained from 178 patients with ESCC and 101 healthy controls, and allocated to screening and verification cohorts, respectively. In the screening phase, after saliva DNA was extracted, 16S rRNA V4 regions of salivary bacteria were amplified by polymerase chain reaction (PCR) with high-throughput sequencing. Highly expressed target bacteria were screened by Operational Taxonomic Units clustering, species annotation and microbial diversity assessment. In the verification phase, the expression levels of target bacteria identified in the screening phase were verified by absolute quantitative PCR (Q-PCR). Receiver operating characteristic (ROC) curves were plotted to investigate the predictive value of target salivary bacteria. LEfSe analysis revealed higher proportions of Fusobacterium, Streptococcus and Porphyromonas, and Q-PCR assay showed significantly higher numbers of Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in patients with ESCC, when compared with healthy controls (all P < 0.05). The areas under the ROC curves for Streptococcus salivarius, Fusobacterium nucleatum, Porphyromonas gingivalis and the combination of the three bacteria for predicting patients with ESCC were 69%, 56.5%, 61.8% and 76.4%, respectively. The sensitivities corresponding to cutoff value were 69.3%, 22.7%, 35.2% and 86.4%, respectively, and the matched specificity were 78.4%, 96.1%, 90.2% and 58.8%, respectively. These highly expressed Streptococcus salivarius, Fusobacterium nucleatum and Porphyromonas gingivalis in the saliva, alone or in combination, indicate their predictive value for ESCC.

Interplay of Environmental Regulation and Local Protectionism in China.

Environmental regulation (ER) and local protectionism (LP) are important policy tools for Chinese local governments to improve the environment and promote growth, respectively, but we know little about their interplay in dealing with pollution-intensive industries and enterprises. Using spatial correlation analysis and spatial panel simultaneous equations models, we investigated the spatial characteristics and interactions of the ER and LP in China's 285 prefectural cities. We found that the high-ER-intensity areas were spreading from the eastern to the central and western regions, and the patterns of LP transited from high in the north and low in the south to high in the west and low in the east. There was a negative correlation spatially between ER and LP. LP could inhibit the increase in ER intensity, while the continuously increasing ER intensity could restrict LP through the competitive behavior from the "race to the bottom" to the "race to the top" among local governments. The effect of ER restricting LP was significant from 2008 to 2013 and prominent in the east, which was dominated by "race to the top" competition, while LP had a greater inhibitory effect on ER in the central and western regions, which preferred to obtain tax revenues from pollution-intensive industries. The results imply that removing the roots of local protectionism, improving the environmental governance system, and formulating differentiated regional environmental regulatory measures will help local governments balance economic growth and environmental protection.

Correlation of c-MET expression with clinical characteristics and the prognosis of colorectal cancer.

BACKGROUND: The proto-oncogene c-MET (mesenchymal-epithelial transition factor gene) plays a critical role in cellular proliferation, survival, migration, and invasion in cancers. The aim of this study is to explore the relationship between c-MET expression and the clinicopathological characteristics of colorectal cancer (CRC) patients. METHODS: A total of 337 enrolled patients were collected in present study. Here, the c-MET and EGFR expression were detected by immunohistochemistry (IHC). The mutational statuses of KRAS in exons 2, 3, and 4, NRAS in exons 2, 3, and 4, and BRAF in exon 15 from formalin-fixed sections were detected by direct DNA sequencing. RESULTS: Our results showed that high c-MET expression was significantly associated with tumor perineural invasion (P=0.007) and gender (P=0.016). High level c-MET expression (c-MET-high) in the primary tumors was observed in 68.2% of patients. In the 337 enrolled patients, 43.2% of patients had KRAS mutations, 3.3% of patients had NRAS mutations, and 4.7% of patients had BRAF mutations. However, KRAS, NRAS, and BRAF gene mutations had no association with c-MET protein levels in primary tumors. Additionally, c-MET protein expression had a strong correlation with EGFR expression (P=0.002). The survival time was not significantly longer for patients with c-MET-high primary tumors than for those with c-MET-low primary tumors. CONCLUSIONS: c-MET immunohistochemistry was significantly higher in primary tumors with perineural invasion, female gender, and EGFR high expression. However, c-MET-high in the primary tumors was not significantly associated with longer survival compared with c-MET-low tumors. Further studies are required to investigate c-MET as potential molecular marker of progression and to test the possibility of its incorporation as a new therapeutic target.

Regional Recurrences and Hyams Grade in Esthesioneuroblastoma.

Objective The aim of this study is to determine if Hyams grade may help predict which patients with esthesioneuroblastoma (ENB) tumors are likely to develop regional recurrences, and to determine the impact of tumor extent on regional failure in ENB patients without evidence of nodal disease at presentation. Design The study was designed as a retrospective review for ENB patients. Settings The study was prepared at tertiary care academic center for ENB patients. Participants Patients with ENB were included in the study. Main Outcome Measures Oncologic outcomes (5-year regional and locoregional control (LRC) and overall survival) in patients with Hyams low grade versus high grade. Oncologic outcomes based on radiographic disease extent. Results A total of 43 patients were included. Total 25 patients (58%) had Hyams low-grade tumor, and 18 (42%) had high-grade tumor. Of the 34 patients without regional disease at presentation, 8 (24%) were treated with elective nodal radiation. There were no statistically significant differences in 5-year regional control in the Hyams low-grade versus high-grade groups (78 vs. 89%; p = 0.4). The 5-year LRC rates in patients with low grade versus high grade were 73 versus 89% ( p = 0.6). The 5-year overall survival rates in patients with low-grade versus high-grade tumors were 86 versus 63% ( p = 0.1). Radiographic extension of disease into the olfactory groove, olfactory nerve, dura, and periorbita were statistically associated with decreased 5-year overall survival (5-year OS 49 vs. 91% [ p = 0.04], 49 vs. 91% [ p = 0.04], 44 vs. 92% [ p = 0.02], and 44 vs. 80% [ p = 0.04], respectively). Conclusion ENBs are associated with a risk of regional failure. The current analysis suggests that Hyams low-grade and high-grade malignancies have comparable rates of early and delayed regional recurrences, although small sample size may limit our conclusions.

Association of frailty with clinical outcomes in myelofibrosis: a retrospective cohort study.

There is limited understanding of the impact of frailty on clinical outcomes in patients with myelofibrosis (MF). In this retrospective cohort study on 439 chronic phase MF patients [mean age: 68·7 ± 12 years; median follow-up: 3·4 years (IQR 0·4-8·6)] from 2004 till 2018, we used a 35-variable frailty index (FI) to categorise patient's frailty status as fit (FI < 0·2, reference), prefrail (FI 0·2-0·29) or frail (FI ≥ 0·3). The association of frailty with overall survival (OS) and cumulative JAK inhibitor (JAKi) therapy failure was measured using hazard ratio (HR, 95% CI). In multivariable analysis, prefrail (HR 1·7, 1·1-2·5) and frail patients (HR 2·9, 1·6-5·5), those with higher DIPSS score (HR 2·5, 1·6-3·9) and transfusion dependency (HR 1·9, 1·3-2·9) had shorter OS. In a subset analysis of patients on JAKi treatment (n = 222), frail patients (HR 2·5, 1·1-5·7), patients with higher DIPSS score (HR 1·7, 1·0-3·1) and transfusion dependence (HR 1·7, 1·1-2·7) had higher cumulative incidence of JAKi failure. Age, comorbidities, ECOG performance status, and MPN driver mutations did not impact outcomes. Thus, higher frailty scores are associated with worse OS and increased JAKi failure in MF, and is a superior indicator of fitness in comparison to age, comorbidities, and performance status.

Optimizing locations of waste transfer stations in rural areas.

Many studies have considered the location of rural waste transfer stations, but most have omitted the impact of transportation network conditions. Traffic accessibility must be considered in optimizing the location of rural waste transfer stations, which is an important difference from the location of rural waste transfer stations. On the basis of previous studies, this study will consider the impact of traffic network on the optimization locations of waste transfer station in the rural areas. The objective of this study was to ensure the minimum Euclidean distance between the waste transfer station and the population center is the maximum, minimize the garbage transportation cost of each population center, construction costs for waste transfer stations, construction and upgrade costs for roads on a traffic network. A multi-objective facility location-network design model and an improved multi-objective simulated annealing algorithm was used to solve the problem. A detailed practical case study was used to illustrate the application of the proposed mathematical model. The results show that transportation network plays an important role in facility location optimization, and the improvement of traffic network conditions can greatly reduce waste transportation costs.