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Energy metabolism disorder, mainly exhibiting the inhibition of fatty acid degradation and lipid accumulation, is highly related with aging acceleration. However, the intervention measures are deficient. Here, we reported Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), especially EPA, exerted beneficial effects on maintaining energy metabolism and lipid homeostasis to slow organ aging. As the endogenous agonist of peroxisome proliferator–activated receptor α (PPARα), Omega-3 PUFAs significantly boosted fatty acid β-oxidation and ATP production in multiple aged organs. Consequently, Omega-3 PUFAs effectively inhibited age-related pathological changes, preserved organ function, and retarded aging process. The beneficial effects of Omega-3 PUFAs were also testified in mfat-1 transgenic mice, which spontaneously generate abundant endogenous Omega-3 PUFAs. In conclusion, our study innovatively demonstrated Omega-3 PUFAs administration in diet slow aging through promoting energy metabolism. The supplement of Omega-3 PUFAs or fat-1 transgene provides a promising therapeutic approach to promote healthy aging in the elderly.

Abstract The nuclear receptor Nur77 plays paradoxical roles in numerous cancers. However, whether Nur77 inhibits esophageal squamous cell carcinoma (ESCC) growth and affects immunological responses against ESCC has not been determined. The functional role of Nur77 in ESCC was investigated in this study using human ESCC cell lines, quantitative real-time polymerase chain reaction (PCR), cell proliferation and colony formation assays, flow cytometry analysis, western blotting and animal models. The target gene controlled by Nur77 was verified using dual-luciferase reporter assays, chromatin immunoprecipitation analysis and functional rescue experiments. To examine the clinical importance of Nur77, 72 human primary ESCC tissues were subjected to immunohistochemistry. Taken together, these findings showed that, both in vitro and in vivo, Nur77 dramatically reduced ESCC cell growth and triggered apoptosis. Nur77 directly interacts with the interferon regulatory factor 1 (IRF1) promoter to inhibit its activity in ESCC. Pharmacological induction of Nur77 using cytosporone B (CsnB) inhibited ESCC cell proliferation and promoted apoptosis both in vitro and in vivo. Furthermore, CsnB increased CD8+ T-cell infiltration and cytotoxicity to inhibit the formation of ESCC tumors in an immunocompetent mouse model. In ESCC tissues, Nur77 expression was downregulated, and IRF1 expression was increased; moreover, their expression levels were negatively related. IRF1 and Nur77 were strongly correlated with overall survival. These findings suggested that Nur77 targets and regulates the IRF1/PD-L1 axis to serve as a tumor suppressor in ESCC. Graphical abstract of the regulatory mechanism of Nur77 overexpression downregulates IRF1 in the inhibition of ESCC progression and enhance anti-PD-1 therapy efficacy.

Abstract Background The efficacy of anti-PD-1 therapy is primarily hindered by the limited T-cell immune response rate and immune evasion capacity of tumor cells. Autophagy-related protein 7 (ATG7) plays an important role in autophagy and it has been linked to cancer. However, the role of ATG7 in the effect of immune checkpoint blockade (ICB) treatment on high microsatellite instability (MSI-H)/mismatch repair deficiency (dMMR) CRC is still poorly understood. Methods In this study, patients from the cancer genome altas (TCGA) COAD/READ cohorts were used to investigate the biological mechanism driving ATG7 development. Several assays were conducted including the colony formation, cell viability, qRT-PCR, western blot, immunofluorescence, flow cytometry, ELISA, immunohistochemistry staining and in vivo tumorigenicity tests. Results We found that ATG7 plays a crucial role in MSI-H CRC. Its knockdown decreased tumor growth and caused an infiltration of CD8+ T effector cells in vivo. ATG7 inhibition restored surface major histocompatibility complex I (MHC-I) levels, causing improved antigen presentation and anti-tumor T cell response by activating reactive oxygen species (ROS)/NF-κB pathway. Meanwhile, ATG7 inhibition also suppressed cholesterol accumulation and augmentation of anti-tumor immune responses. Combining ATG7 inhibition and statins improved the therapeutic benefit of anti-PD-1 in MSI-H CRC. Importantly, CRC patients with high expression of both ATG7 and recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) experienced worse prognosis compared to those with low ATG7 and HMGCR expression. Conclusions Inhibition of ATG7 leads to upregulation of MHC-I expression, augments immune response and suppresses cholesterol accumulation. These findings demonstrate that ATG7 inhibition has therapeutic potential and application of statins can increase the sensitivity to immune checkpoint inhibitors.

Abstract Landscape evolution has profound effects on ecosystems. Recently, some studies suggest that China has implemented plans leading in the greening of the world by mainly describing the changes based on satellite data. However, few studies have analyzed the policy effect on ecosystem improvement from the perspective of landscape pattern evolution. Among the numerous ecological policy plans, China’s key ecological function zones plan is an important one. In this study, we focus on depicting the long-term and large-scale landscape evolution in China’s key ecological function zones, which are accounting for 40.2% of China’s land area, and include four-type ecoregions where ecosystems are fragile or important, to comprehensively explore the environmental influences of policy planning. For this purpose, we first described the landscape composition changes and conversion mechanisms in China’s key ecological function zones from 1990 to 2015. Then we captured the detailed pattern evolution characteristics by landscape indices. The results show that these ecoregions were mostly evolving in an unfavorable direction in these 25 years, i.e. destruction of habitats and increment of fragmentation. Although greening areas increased based on other recent researches, the landscape pattern became worse, indicating it is necessary for the detailed analysis of landscape ecology and more accurate ecological planning. We also found the deterioration of the ecological environment had been uncharacteristically stopped or even improved in wind prevention and sand fixation ecoregions and biodiversity maintenance ecoregions after the implementation of this plan. Furthermore, we assumed that the policy is more prominent in these prohibiting sabotages and protecting areas with fragile ecological bases, which may be caused by the differentiated transfer payments in different ecoregions. Finally, some planning suggestions, such as stricter land use control, the regional balance of ecological transfer payments and deepening of ecological migration policies, etc., were proposed for promoting better future environmental changes.

Abstract Proper differentiation of corneal epithelial cells (CECs) from limbal stem/progenitor cells (LSCs) is required for maintenance of ocular homeostasis and clear vision. Here, using a single-cell transcriptomic atlas, we delineate the comprehensive and refined molecular regulatory dynamics during human CEC development and differentiation. We find that RORA is a CEC-specific molecular switch that initiates and drives LSCs to differentiate into mature CECs by activating PITX1. RORA dictates CEC differentiation by establishing CEC-specific enhancers and chromatin interactions between CEC gene promoters and distal regulatory elements. Conversely, RORA silences LSC-specific promoters and disrupts promoter-anchored chromatin loops to turn off LSC genes. Collectively, our work provides detailed and comprehensive insights into the transcriptional dynamics and RORA-mediated epigenetic remodeling underlying human corneal epithelial differentiation.

Limbal epithelial stem/progenitor cells (LESCs) proliferate, migrate and differentiate into mature corneal epithelium cells (CECs) that cover the ocular surface. LESCs play a crucial role in the maintenance and regeneration of the corneal epithelium, and their dysfunction can lead to various corneal diseases. Neuregulin 1 (NRG1) is a member of the epidermal growth factor family that regulates the growth and differentiation of epithelial tissues. Here, we depicted the dynamic transcriptomic profiles during human CEC differentiation, identifying six gene co-expression modules that were specific to different differentiation stages. We found that the expression of NRG1 was high in human LESCs and decreased dramatically upon differentiation. Knockdown of NRG1 significantly inhibited LESC proliferation and upregulated the expression of the terminal differentiation marker genes KRT3, KRT12 and CLU. In addition, the scratch wound closure assay showed that knockdown of NRG1 attenuated wound closure of LESCs over 24 h. Together, we dissected the transcriptional regulatory dynamics during CEC differentiation and identified NRG1 as a key regulator that promoted LESC proliferation and migration and maintained the undifferentiated state.

The growing concern over pollution from vehicle exhausts has underscored the need for effective detection of black smoke emissions from motor vehicles. We believe that the optimal approach for the detection of black smoke is to leverage existing roadway CCTV cameras. To facilitate this, we have collected and publicly released a black smoke detection dataset sourced from roadway CCTV cameras in China. After analyzing the existing detection methods on this dataset, we found that they have subpar performance. As a result, we decided to develop a novel detection model that focuses on temporal information. This model utilizes the continuous nature of CCTV video feeds rather than treating footage as isolated images. Specifically, our model incorporates a 3D convolution module to capture short-term dynamic and semantic features in consecutive black smoke video frames. Additionally, a cross-scale feature fusion module is employed to integrate features across different scales, and a self-attention mechanism is used to enhance the detection of black smoke while minimizing the impact of noise, such as occlusions and shadows. The validation of our dataset demonstrated that our model achieves a detection accuracy of 89.42%,showing around 3% improvement over existing methods. This offers a novel and effective solution for black smoke detection in real-world applications.

This paper summarizes the music demixing (MDX) track of the Sound Demixing Challenge (SDX’23). We provide a summary of the challenge setup and introduce the task of robust music source separation (MSS), i.e., training MSS models in the presence of errors in the training data. We propose a formalization of the errors that can occur in the design of a training dataset for MSS systems and introduce two new datasets that simulate such errors: SDXDB23_LabelNoise and SDXDB23_Bleeding.1 We describe the methods that achieved the highest scores in the competition. Moreover, we present a direct comparison with the previous edition of the challenge (the Music Demixing Challenge 2021): the best performing system achieved an improvement of over 1.6dB in signal-to-distortion ratio over the winner of the previous competition, when evaluated on MDXDB21. Besides relying on the signal-to-distortion ratio as objective metric, we also performed a listening test with renowned producers and musicians to study the perceptual quality of the systems and report here the results. Finally, we provide our insights into the organization of the competition and our prospects for future editions.

AbstractBackgrounds The Naples prognosis score (NPS) is a novel prognostic biomarker-based immune and nutritional status and that can be used to evaluate prognosis. Our study aimed to investigate the prognostic role of NPS in SCLC patients.Methods Patients treated with chemoradiotherapy were retrospectively analyzed between June 2012 and August 2017. We divided patients into three groups depending on the NPS: group 0, n = 31; group 1, n = 100; and group 2, n = 48, and associations between clinical characteristics and NPS group were analyzed. The univariable and multivariable Cox analyses were used to evaluate the prognostic value of clinicopathological characteristics and laboratory indicators for overall survival (OS) and progression-free survival (PFS).Results Data from 179 patients were analyzed. Treatment modality (p < 0.001) and serum CEA (p = 0.03) were significantly different among the NPS groups. The age, sex, smoking status, KPS, Karnofsky performance score (KPS), disease extent, and number of metastatic sites were not correlated with NPS (all p > 0.05). KPS, disease extent, prophylactic cranial irradiation, treatment response and NPS Group were associated with OS. In addition, KPS, disease extent, prophylactic cranial irradiation, treatment response and NPS Group were associated with PFS. Multivariate analysis results showed that NPS was identified as an independent prognostic factor for OS (Group 1: hazard ratio [HR] = 2.704, 95% confidence interval [CI] = 1.403-5.210; p = 0.003; Group 2: HR = 5.154, 95% CI = 2.614-10.166; p

Abstract Objective According to the different characteristics of patients and cervical lymph node metastasis of oral and oropharyngeal cancer, the marginal mandibular branches of facial nerves were treated by different surgical procedures, and the safety and protective effects of different surgical procedures were investigated. Methods One hundred ninety-seven patients with oral and oropharyngeal cancer satisfying the inclusion criteria were selected. According to the different characteristics of patients and cervical metastatic lymph nodes, three different surgical procedures were used to treat the marginal mandibular branches of the facial nerve: finding and exposing the marginal mandibular branches of the facial nerves at the mandibular angles of the platysma flaps, finding and exposing the marginal mandibular branches of facial nerves at the intersections of the distal ends of facial arteries and veins with the mandible, and not exposing the marginal mandibular branches of the facial nerves. The anatomical position, injury, and complications of the marginal mandibular branches of the facial nerves were observed. Results The marginal mandibular branches of the facial nerves were found and exposed at the mandibular angles of the platysma flaps in 102 patients; the marginal mandibular branches of facial nerves were found and exposed at the intersections of the distal ends of the facial arteries and veins with the mandibles in 64 patients; the marginal mandibular branches of facial nerves were not exposed in 31 patients; among them, four patients had permanent injury of the marginal mandibular branches of the facial nerves, and temporary injury occurred in seven patients. There were statistically significant differences in the protection of the mandibular marginal branch of the facial nerve among the three different surgical methods (P = 0.0184). The best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap, and the injury rate was only 2.94%. Conclusion The three different surgical procedures were all safe and effective in treating the marginal mandibular branches of the facial nerves, the best protective effect was to find and expose the mandibular marginal branch of the facial nerve at the mandibular angle of the platysma muscle flap.

ObjectiveThymoid carcinoma of the thyroid gland is a rare thyroid tumor, which is often presented in case reports.MethodsThe clinical data of two patients with thymic carcinoma of the thyroid gland were retrospectively reviewed.ResultsCase 1: a middle-aged woman who was admitted to the hospital because of “progressive enlargement of the anterior cervical mass for 8 months.” Color Doppler ultrasound and CT showed malignant tumor with high possibility of bilateral cervical lymph node metastasis. Total thyroidectomy and bilateral central cervical lymph node dissection were performed. Lymph node biopsy showed the metastasis of small cell undifferentiated thyroid carcinoma. Because the biopsy pathological result was not consistent with the pathology of the primary lesion, immunohistochemistry was performed again, and the final diagnosis was thymic carcinoma in the thyroid gland. Case 2: the patient was an elderly man who was admitted to the hospital due to hoarseness for half a month. During the operation, the tumor invaded the trachea, esophagus, internal jugular vein, common carotid artery, and surrounding tissues. Palliative resection of the tumor was performed. The tumor postoperative pathology suggested thymoid carcinoma of the thyroid gland. It recurred and compressed the trachea 4 months after the operation, resulting in dyspnea of the patient, and finally tracheotomy was performed to alleviate the symptoms.ConclusionCase 1 showed multiple differences in pathological diagnosis, suggesting that the lack of specific imaging and clinical manifestations of thymoid-differentiated thyroid carcinoma made the diagnosis so difficult. Case 2 progressed rapidly, suggesting that thymoid-differentiated thyroid carcinoma was not always inert, and the treatment and follow-up should follow the principle of individualization.

Genome topology provides a structural basis for epigenome-mediated transcriptional regulation in eukaryotes. Here the authors characterized the 3D genome of stratified squamous epithelia. They generated a Hi-C map of human limbal stem/progenitor cells (LSCs) and integrated these data with epigenomics, transcription factor binding maps, and transcriptome data.

Quantifying the aggregation patterns of urban population, economic activities, and land use are essential for understanding compact development, but little is known about the difference among the distribution characteristics and how the built environment influences urban aggregation. In this study, five elements are collected in Wuhan, China, namely population density, floor area ratio, business POIs, road network and built-up area as the representative of urban population, economic activities and land use. An inverse S-shape function is employed to fit the elements’ macro distribution. An aggregation degree index is proposed to measure the aggregation level of urban elements. The kernel density estimation is used to identify the aggregation patterns. The spatial regression model is used to identify the built environment factors influencing the spatial distribution of urban elements. Results indicates that all urban elements decay outward from the city center in an inverse S-shape manner. The business Point-of-Interest (POI) density and population density are highly aggregated; floor area ratio and road density are moderately aggregated, whereas the built-up density is poorly aggregated. Three types of spatial aggregation patterns are identified: a point-shaped pattern, an axial pattern and a planar pattern. The spatial regression modeling shows that the built environment is associated with the distribution of the urban population, economic activities and land use. Destination accessibility factors, transit accessibility factors and land use diversity factors shape the distribution of the business POI density, floor area ratio and road density. Design factors are positively associated with population density, floor area ratio and built-up density. Future planning should consider the varying spatial concentration of urban population, economic activities and land use as well as their relationships with built environment attributes. Results of this study will provide a systematic understanding of aggregation of urban land use, population, and economic activities in megacities as well as some suggestions for planning and compact development.

A series of highly fluorinated polyimide/allomelanin nanoparticles (FPI/AMNPs) films were prepared with FPI as the matrix and AMNPs as the filler. Due to the formation of hydrogen bonds, significantly reinforced mechanical and UV-shielding properties are acquired. Stress–strain curves demonstrated a maximum tensile strength of 150.59 MPa and a fracture elongation of 1.40% (0.7 wt.% AMNPs), respectively, 1.78 and 1.56× that of pure FPI. The measurements of the UV-vis spectrum, photodegradation of curcumin and repeated running tests confirmed the splendid UV-shielding capabilities of FPI/AMNPs films. The enhancement mechanisms, such as synergistic UV absorption of the charge transfer complexes in FPI and AMNPs and photothermal conversion, were the reasons for its exceptional UV shielding. The excellent comprehensive properties above enable FPI/AMNPs nanocomposites to be potential candidates in the field of UV shielding.

ObjectiveThe aim of this study was to evaluate the prognostic significance of the combination of the magnetic resonance spectroscopy (MRS) parameters and systemic immune-inflammation index (SII) in patients with brain metastases (BMs) from non-small cell lung cancer (NSCLC) treated with stereotactic radiotherapy.MethodsA total of 118 NSCLC patients with BM who were treated with stereotactic radiotherapy were retrospectively enrolled in this study. All patients underwent MRS and blood samples test for SII analysis before the initiation of stereotactic radiotherapy. The correlation between the parameters of MRS and SII level was assessed using Spearman’s correlation coefficient. The cutoff values for the parameters of MRS, SII, and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis to quantify these predictive values. The prognostic factors of overall survival (OS) and progression-free survival (PFS) curves were assessed using the Kaplan–Meier and Cox proportional hazards models.ResultsThe median follow-up time was 25 months (range, 12–49 months). The optimal cutoff point for the choline/creatine (Cho/Cr) ratio and SII were 1.50 and 480, respectively. The Cho/Cr ratio was negatively correlated with SII (rs = 0.164, p = 0.075), but there was a trend. The C-SII score was established by combining the Cho/Cr ratio and SII. Patients with both an elevated Cho/Cr ratio (>1.50) and an elevated SII (>480) were given a C-SII score of 2, and patients with one or neither were given a C-SII score of 1 or 0, respectively. The Kaplan–Meier analysis showed that a C-SII score of 2 was significantly linked with poor OS and PFS (p < 0.001 and p < 0.001, respectively). In the Cox proportional hazards model, the C-SII score independently predicted OS [hazard ratio (HR), 1.749; 95% CI, 1.176–2.601; p = 0.006] and PFS (HR, 2.472; 95% CI, 1.624–3.763; p < 0.001).ConclusionThe C-SII score was more accurate for predicting the clinical outcomes of NSCLC patients with BM who underwent stereotactic radiotherapy. The C-SII score, which was superior to either score alone, could be used to identify BM in NSCLC patients with poor outcomes.

Abstract Forkhead box C1 (FOXC1) is required for neural crest and ocular development, and mutations in FOXC1 lead to inherited Axenfeld–Rieger syndrome. Here, we find that FOXC1 and paired box 6 (PAX6) are co-expressed in the human limbus and central corneal epithelium. Deficiency of FOXC1 and alternation in epithelial features occur in patients with corneal ulcers. FOXC1 governs the fate of the corneal epithelium by directly binding to lineage-specific open promoters or enhancers marked by H3K4me2. FOXC1 depletion not only activates the keratinization pathway and reprograms corneal epithelial cells into skin-like epithelial cells, but also disrupts the collagen metabolic process and interferon signaling pathways. Loss of interferon regulatory factor 1 and PAX6 induced by FOXC1 dysfunction is linked to the corneal ulcer. Collectively, our results reveal a FOXC1-mediated regulatory network responsible for corneal epithelial homeostasis and provide a potential therapeutic target for corneal ulcer.

High-performance InAs/GaSb type-II superlattice infrared detectors and focal plane arrays (FPAs) are normally grown by molecular beam epitaxy (MBE). In this work, we demonstrate the first long-wavelength infrared InAs/GaSb superlattice FPA grown by metalorganic chemical vapor deposition (MOCVD) with clear image. High-quality superlattice material was obtained evidenced by sharp X-ray diffraction peaks and atomic flat surface. Electrical and optical measurements performed on single element detectors showed a 50% cut-off wavelength of $\sim 10.1~\mu \text{m}$ , a dark current density of $2.5\times 10^{-5}$ A/cm2, a peak responsivity of 0.88 A/W and a peak detectivity of $1.7\times 10^{11}$ cm $\cdot $ Hz1/2/W at 80 K. A $320\times256$ FPA with $30~\mu \text{m}$ pixel pitch was then fabricated. With an integration time of 1.9 ms and an applied bias of -0.1 V, the FPA shows an average operability of 96.96%, a non-uniformity of 4.97%, a noise equivalent temperature difference of 51.1 mK and a peak detectivity of $2.3\times 10^{10}$ cm $\cdot $ Hz1/2/W at 80 K without thinning down the substrate.

Corneal epithelium shares similar molecular signatures to other stratified epithelia. Here, the authors map super-enhancers and accessible chromatin in corneal epithelium, identifying a transcription regulatory circuit, including RUNX1, PAX6, and SMAD3, required for corneal epithelial identity and homeostasis.

Podocyte injury and proteinuria are the most common features of glomerular disease, which is the leading cause of end-stage renal failure. Hyperactivated Wnt/β-catenin signaling is closely associated with podocyte injury, but the underlying mechanisms are incompletely understood. Here we show that miRNA-671-5p (miR-671-5p) plays a crucial role in mediating β-catenin-triggered podocyte injury by targeting Wilms tumor 1 (WT1). Microarray-based expression profiling revealed that miR-671-5p was the most upregulated miRNA in podocytes after β-catenin activation. MiR-671-5p was colocalized with β-catenin in the glomeruli of proteinuric CKD in vivo. Bioinformatics analyses and luciferase reporter assays confirmed that miR-671-5p targeted WT1 mRNA. Overexpression of miR-671-5p mimics inhibited WT1 and impaired podocyte integrity, whereas miR-671-5p antagomir preserved the expression of WT1 and other podocyte-specific proteins under basal conditions or after β-catenin activation. In mouse remnant kidney model, overexpression of miR-671-5p aggravated podocyte injury, worsened kidney dysfunction and exacerbated renal fibrosis after 5/6 nephrectomy. In contrast, miR-671-5p antagomir alleviated podocyte injury and attenuated proteinuria and renal fibrotic lesions after glomerular injury in vivo. These studies underscore a pivotal role of miR-671-5p in mediating WT1 depletion and podocyte injury induced by β-catenin. Targeting miR-671-5p may serve as a new approach to prevent podocyte injury and proteinuria in proteinuric CKD.

Background. Papillary thyroid carcinoma (PTC) is the most common thyroid neoplasm, whereas transcription factor E2F1 has been previously implicated in PTC progression. The current study sought to elucidate the underlying mechanism of E2F1 in PTC cell biological activities via regulation of long intergenic noncoding RNA 152 (LINC00152). Methods. Firstly, the expression patterns of LINC00152 and E2F1 in PTC were determined. Besides, TPC-1 and IHH-4 cells were adopted to carry out a series of experiments. Cell proliferation was detected by means of a cell counting kit-8 assay and colony formation assay, while cell migration and invasion abilities were assessed using a Transwell assay. Next, the interaction between E2F1 and LINC00152 was certified. Lastly, xenograft transplantation was carried out to validate the effects of E2F1 depletion on PTC. Results. Both LINC00152 and E2F1 were highly expressed in PTC cells. Knockdown of LINC00152 led to reduced cell activity, while LINC00152 overexpression brought about the opposing trends. Likewise, E2F1 knockdown quenched cell proliferation, migration, and invasion. However, the combination of E2F1 knockdown and LINC00152 overexpression resulted in augmented cell growth. In addition, E2F1 induced LINC00152 overexpression, which accelerated cell proliferation, migration, and invasion by activating the PI3K/AKT axis, whereas the administration of LY294002, the inhibitor of PI3K, led to reversal of the same. Finally, xenograft transplantation validated that E2F1 inhibition could suppress LY294002, thereby discouraging tumor growth. Conclusion. Our findings highlighted that E2F1 augmented PTC cell proliferation and invasion by upregulating LINC00152 and the PI3K/AKT axis. Our discovery provides therapeutic implications for PTC alleviation.

The “warm-humid” climate change across the Tibetan Plateau (TP) has promoted grassland growth and an overall greening trend has been observed by remote sensing products. Many of the current generations of Earth System Models (ESMs) incorporate advanced process-based vegetation growth in the land surface module that can simulate vegetation growth, but the evaluation of their performance has not received much attention, especially over hot spots where projections of the future climate and vegetation growth are greatly needed. In this study, we compare the leaf area index (LAI) simulations of 35 ESMs that participated in CMIP6 to a remote-sensing-derived LAI product (GLASS LAI). The results show that about 40% of the models overestimated the Tibetan Plateau’s greening, 48% of the models underestimated the greening, and 11% of the models showed a declining LAI trend. The CMIP6 models generally produced poor simulations of the spatial distribution of LAI trend, and overestimated the LAI trend of alpine vegetation, grassland, and forest, but underestimated meadow and shrub. Compared with other vegetation types, simulations of the forest LAI trend were the worst, the declining trend in forest pixels on the TP was generally underestimated, and the greening of the meadow was underestimated as well. However, the greening of the grassland, was greatly overestimated. For the Tibetan Plateau’s averaged LAI, more than 70% of the models overestimated this during the growing seasons of 1981–2014. Similar to the forest LAI trend, the performance of the forest LAI simulation was the worst among the different vegetation types, and the forest LAI was underestimated as well.

A high required number of interactions with the environment is one of the most important problems in reinforcement learning (RL). To deal with this problem, several data-efficient RL algorithms have been proposed and successfully applied in practice. Unlike previous research, that focuses on optimal policy evaluation and policy improvement stages, we actively select informative samples by leveraging entropy-based optimal sampling strategy, which takes the initial samples set into consideration. During the initial sampling process, information entropy is used to describe the potential samples. The agent selects the most informative samples using an optimization method. This way, the initial sample is more informative than in random and fixed strategy. Therefore, a more accurate initial dynamic model and policy can be learned. Thus, the proposed optimal sampling method guides the agent to search in a more informative region. The experimental results on standard benchmark problems involving a pendulum, cart pole, and cart double pendulum show that our optimal sampling strategy has a better performance in terms of data efficiency.

A quantitative description is the basis for correctly understanding the urban expansion process. Previous approaches were dedicated to identifying expansion types based on the boundary sharing rate, thereby depicting the evolution of urban expansion. These methods, however, focused on describing neighborhood relations and ignored urban global expansion structure and form information. In this study, we first propose a new index, the location centrality index (LCI), to capture the expansion structure characteristics by incorporating an “area-inverse distance” weighting algorithm and geometric features. Then, we propose another index, the location centrality aggregation index (LCAI), to depict the heterogeneous evolution of urban form by considering the attribute of the new patch. The location centrality and location aggregation types are identified to reflect the effect of new patches on the urban expansion structure and form based on LCI and LCAI, respectively. Two variants of LCI and LCAI are also proposed to reflect the global bottom-up characteristics of urban expansion. The LCI and LCAI were verified using four periods of Landsat images (1995, 2000, 2005, and 2010) of the Wuhan metropolitan area, China. The results show that the overall development trend of the expansion structure in the Wuhan metropolitan area was toward decentralization. The urban form had become generally separated, but tended toward aggregation from 2005 to 2010. Our findings also reveal that the LCI fills the gap in the dynamic assessment of urban expansion with previous indices by explicitly uncovering global structure characteristics. The LCAI achieves better performance than previous indices in identifying heterogeneous aggregation.

ABSTRACT Bacterial persisters exhibit noninherited antibiotic tolerance and are linked to the recalcitrance of bacterial infections. It is very urgent but also challenging to develop antipersister strategies. Here, we report that 10-s freezing with liquid nitrogen dramatically enhances the bactericidal action of aminoglycoside antibiotics by 2 to 6 orders of magnitude against many Gram-negative pathogens, with weaker potentiation effects on Gram-positive bacteria. In particular, antibiotic-tolerant Escherichia coli and Pseudomonas aeruginosa persisters—which were prepared by treating exponential-phase cells with ampicillin, ofloxacin, the protonophore cyanide m-chlorophenyl hydrazone (CCCP), or bacteriostatic antibiotics—can be effectively killed. We demonstrated, as a proof of concept, that freezing potentiated the aminoglycosides' killing of P. aeruginosa persisters in a mouse acute skin wound model. Mechanistically, freezing dramatically increased the bacterial uptake of aminoglycosides regardless of the presence of CCCP, indicating that the effects are independent of the proton motive force (PMF). In line with these results, we found that the effects were linked to freezing-induced cell membrane damage and were attributable, at least partly, to the mechanosensitive ion channel MscL, which was able to directly mediate such freezing-enhanced aminoglycoside uptake. In view of these results, we propose that the freezing-induced aminoglycoside potentiation is achieved by freezing-induced cell membrane destabilization, which, in turn, activates the MscL channel, which is able to effectively take up aminoglycosides in a PMF-independent manner. Our work may pave the way for the development of antipersister strategies that utilize the same mechanism as freezing but do so without causing any injury to animal cells. IMPORTANCE Antibiotics have long been used to successfully kill bacterial pathogens, but antibiotic resistance/tolerance usually has led to the failure of antibiotic therapy, and it has become a severe threat to human health. How to improve the efficacy of existing antibiotics is of importance for combating antibiotic-resistant/tolerant pathogens. Here, we report that 10-s rapid freezing with liquid nitrogen dramatically enhanced the bactericidal action of aminoglycoside antibiotics by 2 to 6 orders of magnitude against many bacterial pathogens in vitro and also in a mouse skin wound model. In particular, such combined treatment was able to effectively kill persister cells of Escherichia coli and Pseudomonas aeruginosa, which are per se tolerant of conventional treatment with bactericidal antibiotics for several hours. We also demonstrated that freezing-induced aminoglycoside potentiation was apparently linked to freezing-induced cell membrane damage that may have activated the mechanosensitive ion channel MscL, which, in turn, was able to effectively uptake aminoglycoside antibiotics in a proton motive force-independent manner. Our report sheds light on the development of a new strategy against bacterial pathogens by combining existing antibiotics with a conventional physical treatment or with MscL agonists.

High operating temperature mid-wavelength InAs/GaSb superlattice infrared photodetectors with a single heterojunction structure grown by metal–organic chemical vapor deposition are reported. By inserting a fully-depleted wider-gap barrier layer between the absorber and the p-contact, “diffusion-limited” behavior has been achieved for the heterojunction “PNn” device, in contrast to the conventional pin homojunction device. The PNn device with a 50% cutoff wavelength of 4.5 μm exhibited a dark current of 2.05 × 10−4 A/cm2 and a peak specific detectivity of 1.28 × 1011 cm·Hz·W−1 at 150 K and a reverse bias of −0.1 V.

Existing crowd evacuation guidance systems require the manual design of models and input parameters, incurring a significant workload and a potential for errors. This paper proposed an end-to-end intelligent evacuation guidance method based on deep reinforcement learning, and designed an interactive simulation environment based on the social force model. The agent could automatically learn a scene model and path planning strategy with only scene images as input, and directly output dynamic signage information. Aiming to solve the “dimension disaster” phenomenon of the deep Q network (DQN) algorithm in crowd evacuation, this paper proposed a combined action-space DQN (CA-DQN) algorithm that grouped Q network output layer nodes according to action dimensions, which significantly reduced the network complexity and improved system practicality in complex scenes. In this paper, the evacuation guidance system is defined as a reinforcement learning agent and implemented by the CA-DQN method, which provides a novel approach for the evacuation guidance problem. The experiments demonstrate that the proposed method is superior to the static guidance method, and on par with the manually designed model method.

Dynamic weather conditions, which mainly include rain and snow, make prevailing algorithms for many applications of outdoor video analysis and computer vision lapse. To remove dynamic weather conditions, the authors propose a pixel‐wise framework combining a detection method with a removal approach. Dynamic weather conditions are detected by a strategy‐driven state transition, which integrates static initialisation using K‐means clustering with dynamic maintenance of Gaussian mixture model. Moreover, a variable time window is presented for removal of rain and snow. Each component of the framework is addressed using detailed descriptions of corresponding algorithms. Experiments demonstrate the effectiveness of the method on detection and removal of dynamic weather conditions.

A new method of banknote image retrieval is proposed by using new set of rotated quaternion wavelet filters (RQWF) and standard quaternion wavelet transform (QWT) jointly. The robust and rotationally invariant features are extracted from QWT and RQWF decomposed sub-bands of banknote image. Three different sets of databases are used to demonstrate the effectiveness of the proposed method. The experimental results show that the proposed method improves the recognition rate from 78.79% to 91.22% on (16000 images) database D1, form 74.08% to 94.62% on (20000 images) database D2 and from 76.44% to 88.78% on (10000 images) database D3. The proposed method can also obtain a reasonable level of computational complexity.