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Abstract Understanding the neuropathogenesis of impaired social cognition in autism spectrum disorders (ASD) is challenging. Altered cortical parvalbumin-positive (PV+) interneurons have been consistently observed in ASD, but their roles and the underlying mechanisms remain poorly understood. In our study, we observed a downward-shifted spectrum of PV expression in the developing medial prefrontal cortex (mPFC) of ASD mouse models due to decreased activity of PV+ neurons. Surprisingly, chemogenetically suppressing PV+ neuron activity during postnatal development failed to induce ASD-like behaviors. In contrast, lowering excitatory activity in the developing mPFC not only dampened the activity state and PV expression of individual PV+ neurons, but also replicated ASD-like social deficits. Furthermore, enhancing excitation, but not PV+ interneuron-mediated inhibition, rescued social deficits in ASD mouse models. Collectively, our findings propose that reduced excitatory activity in the developing mPFC may serve as a shared local circuitry mechanism triggering alterations in PV+ interneurons and mediating impaired social functions in ASD.

Abstract This study employs modified data envelopment analysis (DEA) models and spatial autocorrelation methods to analyze the characteristics of red tourism transformation efficiency and categorize them into efficiency zones. By utilizing geographic detector models, the interactive driving mechanisms behind spatial differentiation are revealed, providing valuable insights for the high-quality transformation and development of China's red tourism economy. The application of modified DEA models facilitates the evaluation of red tourism resource transformation efficiency by decomposing comprehensive efficiency into single-factor efficiency for individual input and output variables. The results indicate that: (1) Expansion of tourism factors is crucial for achieving red tourism resource transformation in China, with low efficiency in resource endowment investment acting as the primary constraint. (2) Local spatial correlation between production efficiency and resource transformation efficiency demonstrates a decreasing trend from east to west, leading to the classification of China’s red tourism resources into five types of efficiency zones. (3) Endogenous ability factors predominantly affect red tourism resource transformation efficiency, with interaction between internal and external factors driving spatial differentiation.

Abstract Background Geographical factors affect the nutritional, therapeutic and commercial values of fruits. Dragon fruit (Hylocereus spp) is a popular fruit in Asia and a potential functional food with diverse pharmacological attributes. Although it is produced in various localities, the information related to the altitudinal variation of dragon fruit nutrients and active compounds is scarce. Hence, this study aimed to investigate the variations in metabolite profiles of H. polyrhizus (variety Jindu1) fruit pulps from three different altitudes of China, including Wangmo (WM, 650 m), Luodian (LD, 420 m), and Zhenning (ZN, 356 m). Jindu1 is the main cultivated pitaya variety in Guizhou province, China. Results The LC-MS (liquid chromatography-mass spectroscopy)-based widely targeted metabolic profiling identified 645 metabolites, of which flavonoids (22.64%), lipids (13.80%), phenolic acids (12.40%), amino acids and derivatives (10.39%), alkaloids (8.84%), and organic acids (8.37%) were dominant. Multivariate analyses unveiled that the metabolite profiles of the fruit differed regarding the altitude. Fruits from WM (highest altitude) were prime in quality, with higher levels of flavonoids, alkaloids, nucleotides and derivatives, amino acids and derivatives, and vitamins. Fruits from LD and ZN had the highest relative content of phenolic acids and terpenoids, respectively. We identified 69 significantly differentially accumulated metabolites across the pulps of the fruits from the three locations. KEGG analysis revealed that flavone and flavonol biosynthesis and isoflavonoid biosynthesis were the most differentially regulated. It was noteworthy that most active flavonoid compounds exhibited an increasing accumulation pattern along with the increase in altitude. Vitexin and isovitexin were the major differentially accumulated flavonoids. Furthermore, we identified two potential metabolic biomarkers (vitexin and kaempferol 3-O-[2-O-β-D-galactose-6-O-a-L-rhamnose]-β-D-glucoside) to discriminate between dragon fruits from different geographical origins. Conclusion Our findings provide insights into metabolic changes in dragon fruits grown at different altitudes. Furthermore, they show that growing pitaya at high altitudes can produce fruit with higher levels of bioactive compounds, particularly flavonoids.

Histopathology image analysis plays a crucial role in cancer diagnosis. However, training a clinically applicable segmentation algorithm requires pathologists to engage in labor‐intensive labeling. In contrast, weakly supervised learning methods, which only require coarse‐grained labels at the image level, can significantly reduce the labeling efforts. Unfortunately, while these methods perform reasonably well in slide‐level prediction, their ability to locate cancerous regions, which is essential for many clinical applications, remains unsatisfactory. Previously, CAMEL is proposed, which achieves comparable results to those of fully supervised baselines in pixel‐level segmentation. However, CAMEL requires 1280 × 1280 image‐level binary annotations for positive WSIs. Here, CAMEL2 is presented, by introducing a threshold of the cancerous ratio for positive bags, it allows one to better utilize the information, consequently enabling us to scale up the image‐level setting from 1280 × 1280 to 5120 × 5120 while maintaining accuracy. The results with various datasets demonstrate that CAMEL2, with the help of 5120 × 5120 image‐level binary annotations, which are easy to annotate, achieves comparable performance to that of a fully supervised baseline in both instance‐ and slide‐level classifications.

Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing the functionality of derived cells within the circuit. Here, we describe a novel method for converting human embryonic stem cells (hESCs) into otic neurons (ONs) and assess their functional connectivity using an optogenetic approach with cells or an organotypic slice of rat cochlear nucleus (CN) in coculture. Embryonic stem cell-derived otic neurons (eONs) exhibited SGN marker expression and generated functional synaptic connection when cocultured with cochlear nucleus neurons (CNNs). Synapsin 1 and VGLUT expression are found in the cochlear nucleus of brain slices, where eONs projected processes during the coculture of eONs and CN brain slices. Action potential spikes and I Na+ /I K+ of CNNs increased in tandem with light stimulations to eONs. These findings provide further evidence that eONs may be a candidate source to treat SGN-deafness.

Abstract The improvement of enterprise ESG performance is one of the key driving forces to achieve the goal of economic and social green development. There is a gap between knowledge and practice in the ESG performance of Chinese enterprises, and digital transformation (DT) provides new ideas for ESG development. The research purpose of this paper is to explore the impact mechanism of DT on ESG and the specific path of DT to drive ESG. It provides a reference for listed enterprises to rely on DT to empower their sustainable development capability. This paper takes the panel data of A-share listed enterprises from 2011 to 2021 as the sample and measures the core indicators using the text mining method, modified Jones model, and Roy-Chowdhury model. On this basis, using a combination of econometric models and qualitative comparative analysis, we empirically analyze the impact mechanisms of DT on ESG as well as the specific grouping paths that drive ESG performance. The main conclusions are shown as follows. First, DT can significantly reduce ESG, with an impact coefficient of − 0.013, which is significant at the 5% level. It reflects that the DT of enterprises at this stage has certain deficiencies. There is a matching lag in the enterprise's internal organizational resources. The entry of digital technology will have a certain impact on traditional operations, and the high uncertainty of DT adds some hidden costs to the enterprise. Secondly, there is an indirect suppression effect of accrued earnings management (AEM) in the transmission mechanism of DT affecting ESG. It is verified that DT can reduce information asymmetry and inhibit EM activities, thus reducing the impact on ESG. Finally, a total of six configurations achieved high ESG valuations. High technology practice-low performance manipulation; digital intelligence-low performance manipulation; digital intelligence-digital resources; digital resources-inadequate digital infrastructure.; high technology practice-bottom technology deficiency; digital intelligence-high performance manipulation. Through configuration analysis, the suppression effect of EM is further verified. The lack of AEM is usually the core condition of the high-valuation group. Meanwhile, digital intelligence, digital resources, and digital technology practice can drive the improvement of enterprise ESG. The instrumental variables approach and robustness tests support these findings.

Abstract Recent technological breakthroughs in single-particle cryo-electron microscopy (cryo-EM) enable rapid atomic structure determination of biological macromolecules. A major bottleneck in the current single particle cryo-EM pipeline is the preparation of good quality frozen cryo-EM grids, which is mostly a trial-and-error process. Among many issues, preferred particle orientation and sample damage by air–water interface (AWI) are common practical problems. Here we report a method of applying metallo-supramolecular branched polymer (MSBP) in the cryo-sample preparation for high-resolution single-particle cryo-EM. Our data shows that MSBP keeps a majority of particles away from air–water interface and mitigates preferred orientation as verified by the analyses of apoferritin, hemagglutinin) trimer and various sample proteins. The use of MSBP is a simple method to improve particle distribution for high-resolution structure determination in single-particle cryo-EM.

Abstract ‘Urban Dry (Wet) Islands’ (UDI/UWI) represents microclimate change that impacts ecosystems and human well-being. However, causes of the UDI (UWI) phenomena are not fully understood due to the lack of empirical data. Here, we quantify UDI (UWI) using global observations of atmospheric humidity, evapotranspiration (ET), and land surface characteristics across 25 large urban agglomerations. We show that UDI (17) and UWI (8) are closely tied to local ET, global warming, and ‘Urban Heat Islands’ through intertwined linkages with water and energy balances. UDI is most pronounced in humid vegetated regions where mean urban-rural annual ET differences are as high as 215 mm, whereas UWI is found in arid regions or in climates with dry summers. We conclude that ET can be used as a single variable to explain emerging urban environmental changes. Our study supports a concerted strategy of restoring nature’s ET power as effective ‘Nature-based Solutions’ to mitigate the negative environmental effects of urbanization.

Abstract Background Sevoflurane (Sev) is a commonly used volatile anesthetic that might suppress the process of breast cancer. Also, circular RNAs (circRNAs) have been reported to partake in the pathogenesis of breast cancer. Accordingly, this research was designed to investigate the mechanism of hsa_circ_0005962 on Sev‐mediated breast cancer development. Methods Sev was applied to treat breast cancer cells. Cell proliferation ability, migration, invasion, and apoptosis were detected using Cell Counting Kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), Transwell, and flow cytometry assay. Proliferating cell nuclear antigen (PCNA), Matrix metallopeptidase 9 (MMP9), B‐cell lymphoma‐2 (Bcl‐2)‐associated X protein (Bax), and Epithelial stromal interaction 1 (EPSTI1) were assessed using western blot assay. circ_0000129, microRNA‐578 (miR‐578), and EPSTI1 levels were determined using real‐time quantitative polymerase chain reaction (RT‐qPCR). Using bioinformatics software (Circinteractome and Targetscan), the binding between miR‐578 and circ_0000129 or EPSTI1 were predicted, and proved using dual‐luciferase reporter and RNA pull‐down assay. The biological roles of circ_0000129 and Sevoflurane on tumor growth were analyzed using a xenograft tumor model in vivo. Results Sevoflurane blocked tumor cell proliferation, migration, invasion, and promoted apoptosis. Circ_0000129 and EPSTI1 expression were increased, and miR‐578 was decreased in breast cancer cells. Also, they presented an opposite trend in Sev‐treated tumor cells. Circ_0000129 upregulation might abolish Sev‐mediated tumor progression in vitro. Mechanically, circ_0000129 can affect EPSTI1 expression by sponging miR‐578. Sev might inhibit tumor growth by regulating circ_0000129 in vivo. Conclusion Circ_0000129 relieved Sev‐triggered suppression impacts on breast cancer development partly via the miR‐578/EPSTI1 axis, which provides a new mechanism for studying mediated therapy of breast cancer treatment.

Abstract Aim To find a rapid, scientific, rational and accurate method of allocating nursing human resources during the COVID‐19 pandemic. Design A longitudinal prospective study. Methods Lean management tool is used to implement four‐level scheduling of nursing human resources, which is departmental level, district level, hospital level and city level, according to the daily reporting data of the whole hospital, such as Lianfan scheduling data, Dingding sensitive data and Hospital Information System daily report data. Results Fifty batches of nursing manpower, 294 nurses and 3813 working days were deployed during the pandemic, and the nursing human resources allocation mathematical models of the hospital and all departments were constructed. Since COVID‐19 occurred, the infection rate of nurses with novel coronavirus and the mortality rate of critical patients have been keeping 0%, and the cure rate of common patients has been 100%. Conclusion The use of lean management tool to allocate nursing human resources plays a positive role in ensuring zero infection of nurses, improving the cure rate of common patients and reducing the mortality rate of critically ill patients with COVID‐19.

Tumor-infiltrating immune cells (TICs) affect tumorigenesis and tumor development in head and neck squamous cell carcinoma (HNSCC). We constructed a novel predictive model for HNSCC based on immune-related genes (IRGs) from The Cancer Genome Atlas and the Immunology Database and Analysis Portal. After identifying the IRGs, a predictive model involving 13 IRGs with high stratification value of overall survival (OS) was constructed by multiple support vector machine recursive feature elimination and least absolute shrinkage and selection operator regression. We explored the relationship between the risk score (RS) and clinical characteristics. The nomogram showed high concordance and good agreement in OS. Four TICs affected the OS and were in agreement with the abundance analysis of the RS levels. Furthermore, the low-risk HNSCC group showed higher expression of PD-1, CTLA4, and TIGIT, while the high-risk group showed higher expression of EGFR. The high-risk HNSCC showed high sensitivity to eight drugs.

In recent years, human beings have paid more and more attention to the exploration of the underwater world. As an important part of underwater resources, fish can be detected by using the fish image data collected by underwater imaging systems, which can help us better understand fish species richness and assess fish populations. In this paper, we proposed a fish target detection algorithm YOLOv5-fish for underwater blurred scenes. For underwater blurred scenes, the algorithm first uses the auto-MSRCR algorithm to enhance the acquired low-quality underwater blurred image data and obtains the enhanced fish images as the dataset for model training. Then the YOLOv5s algorithm is improved through the following methods. First, replacing the original activation function with Meta-ACON to realize the model autonomously control the nonlinearity degree of the activation function; Second, adding the Shuffle Attention mechanism to enhance the model’s attention to the detection object; Third, introducing RepVGG structure to the backbone network to accelerate the model’s inference speed. The experimental results show that the improved YOLOv5-fish algorithm achieves an mAP of 97.6% and a detection speed of 84 FPS, which can achieve accurate and fast detection for fish targets in underwater blurred scenes.

Barium and iridium supported on Zeolite Socony Mobil-5 (ZSM-5) are efficient catalysts for the selective catalytic reduction of nitric oxide by carbon monoxide (CO-SCR), with enhanced cyclic stability. The introduction of Ba hindered the oxidation of metallic Ir active species and enabled Ir to maintain an active metallic state, thereby preventing a decrease in catalytic activity in the CO-SCR reaction. Moreover, the Ba modification increased the NO adsorption of the catalyst, further improving the catalytic activity. Owing to the better anti-oxidation ability of Ir0 in IrBa0.2/ZSM-5(27) than in Ir/ZSM-5(27), IrBa0.2/ZSM-5(27) showed better stability than Ir/ZSM-5(27). Considering that all samples in the present study were tested to simulate actual flue gases (such as sintering flue gas and coke oven flue gas), NH3 was introduced into the reaction system to serve as an extra reductant for NOx. The NOx conversion to N2 (77.1%) was substantially improved using the NH3-CO-SCR system. The proposed catalysts and reaction systems are promising alternatives for treating flue gas, which contains considerable amounts of NOx and CO in oxygen-enriched environments.

Objectives The application of artificial intelligence (AI) to the field of pathology has facilitated the development of digital pathology, hence, making AI-assisted diagnosis possible. Due to the variety of lung cancers and the subjectivity of manual evaluation, invasive non-mucinous lung adenocarcinoma (ADC) is difficult to diagnose. We aim to offer a deep learning solution that automatically classifies invasive non-mucinous lung ADC histological subtypes.Design For this investigation, 523 whole-slide images (WSIs) were obtained. We divided 376 of the WSIs at random for model training. According to WHO diagnostic criteria, six histological components of invasive non-mucinous lung ADC, comprising lepidic, papillary, acinar, solid, micropapillary and cribriform arrangements, were annotated at the pixel level and employed as the predicting target. We constructed the deep learning model using DeepLab v3, and used 27 WSIs for model validation and the remaining 120 WSIs for testing. The predictions were analysed by senior pathologists.Results The model could accurately predict the predominant subtype and the majority of minor subtypes and has achieved good performance. Except for acinar, the area under the curve of the model was larger than 0.8 for all the subtypes. Meanwhile, the model was able to generate pathological reports. The NDCG scores were greater than 75%. Through the analysis of feature maps and incidents of model misdiagnosis, we discovered that the deep learning model was consistent with the thought process of pathologists and revealed better performance in recognising minor lesions.Conclusions The findings of the deep learning model for predicting the major and minor subtypes of invasive non-mucinous lung ADC are favourable. Its appearance and sensitivity to tiny lesions can be of great assistance to pathologists.

Abstract Sustainable development of agriculture is the basis for achieving social sustainable development. As the basic industry of national economy, green development of agriculture has become an important support for building an environment-friendly society. Agricultural fiscal expenditure is a direct channel for the government to support agriculture and promote agricultural transformation. It is important to analyze the impact of agricultural fiscal expenditure (AFE) on agricultural green total factor productivity (AGTFP) for sustainable agricultural development. Therefore, this paper employs the random effect model and spatial Durbin model to empirically analyze the direct effect and spatial spillover effect of AFE on AGTFP by using the agricultural panel data of 30 provinces in China from 2008 to 2020. Then, by taking the policy proposal as the time node, this paper also conducts a time heterogeneity analysis to measure the impact of policy enactment on AFE and AGTFP. The main conclusions are as follows: (1) AGTFP exists significant positive spatial spillover effect. The "radiation effect" of agricultural green development is significant. (2) AFE can significantly reduce the AGTFP in the local area, that is, 1% increase of AFE in the local area will reduce AGTFP by 0.037%. At present, agriculture is still yield-oriented. The improvement of AFE in the local area will lead to the expansion of local agricultural production and increase pollution emission. (3) AFE has a significant negative spatial spillover effect on AGTFP, that is, for every 1% increase in AFE, the AGTFP will decrease 0.123% in geographically similar areas, while the AGTFP will decrease by 0.116% in economically and geographically similar areas. It is obvious that AFE will promote the optimization of agricultural production conditions in the province, with the "demonstration effect" on the surrounding areas, the enthusiasm of production in the surrounding areas will increase, thus expanding the pollution emission. (4) According to the analysis of different periods, AFE has a negative impact on AGTFP mainly before the reform innovation is proposed in 2015. It indicates that reform policies have a significant impact on agricultural sustainability.

PURPOSEThis systematic review and meta-analysis of conventional enhanced magnetic resonance imaging (MRI) were conducted to evaluate the diagnostic performance of imaging features of microvascular invasion (MVI) prediction in hepatocellular carcinoma (HCC).METHODSRelevant studies on diagnosing MVI in HCC by MRI were searched in the MEDLINE, PUBMED, EMBASE, Cochrane library, and Web of Science databases. The pooled mean sensitivity and specificity were calculated using a random effects model. The corresponding positive likelihood ratio (PLR), negative likelihood ratio (NLR), and pooled diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curve was used to summarize the overall diagnostic accuracy. Diagnostic performance was evaluated by determining the area under the curve (AUC). Regression analysis by subgroup and sensitivity analysis were used to explore potential sources of heterogeneity.RESULTSA total of 19 studies comprising 1920 HCC patients with 2033 tumors were ultimately enrolled. For the signs of the presence of peritumoral enhancement in the arterial phase, peritumoral hypointensity in the hepatobiliary phase, irregular non-smooth margin, and rim-like enhancement in the arterial phase, the pooled sensitivity values, the pooled specificity values, the pooled PLR values, the pooled NLR values, the pooled DOR values, and the values of the AUC of SROC curves were determined.CONCLUSIONThe conventional MRI features for predicting MVI showed poor diagnostic performance in HCC. Only signs of the presence of peritumoral enhancement in the arterial phase showed a moderate diagnostic accuracy.

Although the literature demonstrates that rural industrial integration can enhance farmers' income, foster rural development, its impact on agricultural total factor productivity (ATFP), a critical aspect of sustainable food systems remains unclear. Using provincial-level data from 2008 to 2018, this paper constructs a composite index of rural industrial integration and examines its effect, heterogeneity, and spatial spillover on ATFP growth in China. The findings indicate that the levels of rural industry integration and ATFP experienced a gradual increase from 2008 to 2018. Rural industry integration promotes ATFP growth through technical progress and improved technical efficiency. An analysis of regional heterogeneity reveals that rural industry integration has the most significant impact on ATFP promotion in the western region, followed by the central region, with the least impact in the eastern region of China. Unconditional quantile regression suggests that rural industrial integration has a more considerable impact on ATFP in regions with higher ATFP. Furthermore, the spatial Durbin model results demonstrate that rural industry integration directly supports rural industry integration development in a region while simultaneously inhibiting ATFP growth in surrounding areas. Finally, the findings also reveal that enhancing rural industrial integration can have positive impacts on sustainable agricultural production in China. These findings offer valuable insights for other developing countries aiming to promote sustainable consumption and production.

The species and population size of marine fish are important for maintaining the ecological environment and reflecting climate change. Traditional fish detection methods mainly rely on manual or traditional computer vision, which has disadvantages such as complex design, low detection accuracy, and poor generalization. The widespread use of ocean observation systems has accumulated a large number of images and videos, which makes the application of deep learning on marine fish detection possible. In this paper, a real-time high-precision fish detection algorithm based on YOLOv5s is constructed. Considering the enhancement of the channel representation and spatial interaction ability of the model, the attention mechanism and gated convolution are introduced, respectively, and GhostNet is introduced to lighten the model. Through a series of model comparisons, two improved models, S-Head-Ghost-Fish9 and S-SE-HorBlock-Head-Ghost-Fish9, are finally obtained. Compared with the original model, in terms of model size, the former reduces by 19% and the latter increases by 9.5%; in terms of computation, the former reduces by 15.7% and the latter reduces by 3.1%; in terms of detection speed, both take about 17 ms to detect a single image, and both can meet the real-time detection requirements; in terms of detection accuracy, the former improves by 3% and the latter by 3.6%. Compared with the latest detection algorithms of YOLOv6 and YOLOv8, the detection accuracy is slightly lower than 1%, but the model size and computation amount are only 1/3 to 1/2 of them. The improved models can help assess the population size and growth of the fish, which is of great significance in maintaining the stability of the fish population.

Abstract Bound states in the continuum (BICs) have a superior ability to confine electromagnetic waves and enhance light–matter interactions. However, the quality‐factor of quasi‐BIC is extremely sensitive to structural perturbations, thus the BIC metasurfaces usually require a very‐high precision nanofabrication technique that greatly restricts their practical applications. Here, distinctive 2.5D out‐of‐plane architectures based plasmonic symmetry protected (SP)‐BIC metasurfaces are proposed, which could deliver robust quality factors even with large structural perturbations. The high‐throughput fabrication of such SP‐BIC metasurfaces is realized by using the binary‐pore anodic aluminum oxide template technique. Moreover, the deep neural network (DNN) is adapted to conduct multiparameter fittings, where the 2.5D hetero‐out‐of‐plane architectures with robust high quality‐factors and figures of merit are rapidly predicted and fabricated. Finally, owning to its large second‐order surface sensitivity, the desired 2.5D hetero‐out‐of‐plane architecture demonstrates a detection limit of endotoxin as low as 0.01 EU mL‐1, showing a good perspective of biosensors and others.

Abstract Background Photoresponsive drug delivery can achieve spatiotemporal control of drug accumulation at desired sites. Long-wavelength light is preferable owing to its deep tissue penetration and low toxicity. One-photon upconversion-like photolysis via triplet–triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups. However, such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states. Results Herein, we report a strategy that uses red light to trigger disassembly of small-molecule nanoparticles by one-photon upconversion-like photolysis for cancer therapy. A photocleavable trigonal molecule, BTAEA, self-assembled into nanoparticles and enclosed photosensitizer, PtTPBP. Such nanoparticles protected TTET-based photolysis from oxygen quenching in normoxia aqueous solutions, resulting in efficient red light-triggered BTAEA cleavage, dissociation of nanoparticles and subsequent cargo release. With paclitaxel as the model drug, the red light-triggered drug release system demonstrated promising anti-tumor efficacy both in vitro and in vivo. Conclusions This study provides a practical reference for constructing photoresponsive nanocarriers based on the one-photon upconversion-like photolysis. Graphical Abstract

The accurate pathological diagnosis of endometrial cancer (EC) improves the curative effect and reduces the mortality rate. Deep learning has demonstrated expert-level performance in pathological diagnosis of a variety of organ systems using whole-slide images (WSIs). It is urgent to build the deep learning system for endometrial cancer detection using WSIs. The deep learning model was trained and validated using a dataset of 601 WSIs from PUPH. The model performance was tested on three independent datasets containing a total of 1,190 WSIs. For the retrospective test, we evaluated the model performance on 581 WSIs from PUPH. In the prospective study, 317 consecutive WSIs from PUPH were collected from April 2022 to May 2022. To further evaluate the generalizability of the model, 292 WSIs were gathered from PLAHG as part of the external test set. The predictions were thoroughly analyzed by expert pathologists. The model achieved an area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of 0.928, 0.924, and 0.801, respectively, on 1,190 WSIs in classifying EC and non-EC. On the retrospective dataset from PUPH/PLAGH, the model achieved an AUC, sensitivity, and specificity of 0.948/0.971, 0.928/0.947, and 0.80/0.938, respectively. On the prospective dataset, the AUC, sensitivity, and specificity were, in order, 0.933, 0.934, and 0.837. Falsely predicted results were analyzed to further improve the pathologists’ confidence in the model. The deep learning model achieved a high degree of accuracy in identifying EC using WSIs. By pre-screening the suspicious EC regions, it would serve as an assisted diagnostic tool to improve working efficiency for pathologists.

Abstract Hirschsprung's disease (HSCR) is a common congenital defect. It occurs when bowel colonization by neural crest‐derived enteric nervous system (ENS) precursors is incomplete during the first trimester of pregnancy. Several sources of candidate cells have been previously studied for their capacity to regenerate the ENS, including enteric neural crest stem cells (En‐NCSCs) derived from native intestine or those simulated from human pluripotent stem cells (hPSCs). However, it is not yet known whether the native NCSCs other than En‐NCSCs would have the potential of regenerating functional enteric neurons and producing neuron dependent motility under the intestinal environment. The present study was designed to determine whether premigratory NCSCs (pNCSCs), as a type of the nonenteric NCSCs, could form enteric neurons and mediate the motility. pNCSCs were firstly transplanted into the colon of adult mice, and were found to survive, migrate, differentiate into enteric neurons, and successfully integrate into the adult mouse colon. When the mixture of pNCSCs and human intestinal organoids was implanted into the subrenal capsule of nude mice and grown into the mature tissue‐engineered intestine (TEI), the pNCSCs‐derived neurons mediated neuron‐dependent peristalsis of TEI. These results show that the pNCSCs that were previously assumed to not be induced by intestinal environment or cues can innervate the intestine and establish neuron‐dependent motility. Future cell candidates for ENS regeneration may include nonenteric NCSCs.

Abstract Background Diabetic osteoporosis (DOP) is a systemic metabolic bone disease caused by diabetes mellitus (DM). Adipose-derived stem cells (ASCs) play an important role in bone regeneration. Our previous study confirmed that ASCs from DOP mice (DOP-ASCs) have a lower osteogenesis potential compared with control ASCs (CON-ASCs). However, the cause of this poor osteogenesis has not been elucidated. Therefore, this study investigated the underlying mechanism of the decline in the osteogenic potential of DOP-ASCs from the perspective of epigenetics and explored methods to enhance their osteogenic capacity. Methods The expression level of JNK1-associated membrane protein (JKAMP) and degree of DNA methylation in CON-ASCs and DOP-ASCs were measured by mRNA expression profiling and MeDIP sequencing, respectively. JKAMP small interfering RNA (siRNA) and a Jkamp overexpression plasmid were used to assess the role of JKAMP in osteogenic differentiation of CON-ASCs and DOP-ASCs. Immunofluorescence, qPCR, and western blotting were used to measure changes in expression of Wnt signaling pathway-related genes and osteogenesis-related molecules after osteogenesis induction. Alizarin red and ALP staining was used to confirm the osteogenic potential of stem cells. Bisulfite-specific PCR (BSP) was used to detect JKAMP methylation degree. Results Expression of JKAMP and osteogenesis-related molecules (RUNX2 and OPN) in DOP-ASCs was decreased significantly in comparison with CON-ASCs. JKAMP silencing inhibited the Wnt signaling pathway and reduced the osteogenic ability of CON-ASCs. Overexpression of JKAMP in DOP-ASCs rescued the impaired osteogenic capacity caused by DOP. Moreover, JKAMP in DOP-ASCs contained intragenic DNA hypermethylated regions related to the downregulation of JKAMP expression. Conclusions Intragenic DNA methylation inhibits the osteogenic ability of DOP-ASCs by suppressing expression of JKAMP and the Wnt signaling pathway. This study shows an epigenetic explanation for the reduced osteogenic ability of DOP-ASCs and provides a potential therapeutic target to prevent and treat osteoporosis.

The slender structure is prone to be affected by horizontal force; therefore, the seismic performance needs to be considered carefully. Meanwhile, due to the low cost and good performance on the seismic resistance of the Tuned liquid dampers (TLDs) system, it has been widely used for vibration control. Regarding the abovementioned background, in this study, we conduct the experiment to investigate the seismic performance of the slender structure with the integral water tank, and two designed parameters (the placement location and the water level of the water tank) are studied. The experimental phenomenon and the structural accelerations are recorded to be analyzed further and discussed, then a useful design guide for an integral water tank is summarized. Finally, some practical and helpful advice and conclusions are put forward for the design of the water tank that is used for the purpose of seismic resistance in the slender structure. Our research can fill the blank in the research on the integral water tank of TLDs system, which also has good potential to achieve the enhancement of slender structure seismic performance.

The Himalaya Plateau including Nepal is ‘greening up’ that has important implications to ecosystem services such as water supply, carbon sequestration, and local livelihoods. Understanding the combined causes behind greening is critical for effective policy makings in forest management and climate change adaptation towards achieving sustainable development goals. This national scale study comprehensively examined the natural and anthropogenic drivers of the long-term trend of vegetation dynamics across Nepal by correlation analysis and multiple linear regression analysis. We integrated multiple sources of data including global satellite-based leaf area index (LAI), climate data, landcover data, and forest land management information. Our study reveals a remarkable annual mean LAI increase of 22% (0.009 m ^2 m ^−2 yr ^−1 ) ( p < 0.05) from 1982 to 2020, with an acceleration in the rate of increase to 0.016 m ^2 m ^−2 yr ^−1 ( p < 0.05) after 2004. The community forestry (CF) program, forest area changes, and soil moisture availability accounted for 40%, 12%, and 10% of LAI temporal variability, respectively. Our analysis found soil moisture and forest area changes to be the primary drivers of the greening trend before 2004, while CF and forest expansion were the dominant factors thereafter. Additionally, interannual vegetation dynamics were significantly influenced by winter precipitation, incoming solar radiation, and pre-monsoon soil moisture. The projections based on four Earth System Models from Coupled Model Intercomparison Project Phase 6 suggest that Nepal’s greening trend is expected to continue at a rate of 0.009 m ^2 m ^−2 yr ^−1 ( p < 0.05) throughout the 21st century. We conclude that forest management program (CF) amid climate change that alters water and energy conditions have enhanced land greening, posing both opportunities and risks to ecosystem services in Nepal. This study provides much needed national-level information for developing forest management policies and designing Nature-based Solutions to respond to climate change and increasing demands for ecosystem services in Nepal.

High-standard farmland construction is an important initiative in China that promotes sustainable agricultural development and ensures food security through land consolidation. This study measures the growth of agricultural total factor productivity (ATFP) in China, which is used to characterize the sustainable development of agriculture. Using provincial panel data from China and a continuous difference-in-difference (DID) model, the study examines the impact of high-standard farmland construction policy on ATFP growth. Results show that ATFP in China has an increasing trend with an average annual growth rate of 3.6%. The average enhancement effect of high-standard farmland construction policy on ATFP is 1.0%, which remains significant after various robustness tests. The positive effect of the policy on ATFP becomes apparent in the third year of implementation and shows a gradually increasing trend. The study also finds that the impact of high-standard farmland construction on ATFP is more pronounced in the central regions of China, the main grain-producing regions, and the regions with higher ATFP. High-standard farmland construction policy enhances ATFP by promoting agricultural technology change and technical efficiency. To promote the growth of ATFP and achieve sustainable agricultural development, China should continue to promote the construction of high-standard farmland and explore suitable construction models for different regions.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, of which the occurrence and development involve a variety of pathophysiological processes, such as liver fibrosis, hepatocellular malignant proliferation, metastasis, and tumor angiogenesis. Some important cytokines, such as TGF-β, PI3K, protein kinase B (Akt), VEGF and NF-κB, can regulate the growth, proliferation, diffusion, metastasis, and apoptosis of HCC cells by acting on the corresponding signaling pathways. Besides, many studies have shown that the formation of HCC is closely related to the main components of renin-angiotensin system (RAS), such as Ang II, ACE, ACE2, MasR, AT1R, and AT2R. Therefore, this review focused on liver fibrosis, HCC cell proliferation, metastasis, tumor angiogenesis, and corresponding protective measures. ACE-Ang II-AT1 axis and ACE2-Ang-(1−7)-MasR axis were taken as the main lines to introduce the mechanism of RAS in the occurrence and development of HCC, so as to provide references for future clinical work and scientific research.

Bovine Viral Diarrhea Virus (BVDV) is the main pathogen of bovine viral diarrhea disease (BVD), which leads to enormous economic losses in the cattle industry. A sensitive and specific detection for BVDV is advantageous to the control of BVDV. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have been used for detecting virus RNA. In this study, the expression and purification of LwCas13a protein was optimized and the RNase activity of LwCas13a in vitro was verified. CRISPR-LwCas13a system could detect BVDV virus and BVDV RNA with high specificity and simplicity. The detection limit of the LwCas13a system was 103 pM, and there were no cross-reactions with HEK293T and MDBK. In summary, a sensitive, specific, and simple nucleic acid detection method based on CRISPR-Cas13a was developed for BVDV. This method provides a new detection strategy for early diagnosis of BVDV.

Purpose: Photodynamic therapy (PDT) is an emerging focal treatment modality for prostate cancer. However, the efficacy, safety, and functional outcomes of PDT are not clear. We performed a meta-analysis of available single-arm studies and control trials which used PDT for prostate cancer. Materials and methods: We searched Pubmed, Embase, Ovid and the Cochrane library (until March,2018) for studies about PDT in patients with prostate cancer. The negative biopsy rate after PDT, PSA decreasing rate, pooled rate of functional outcome (IPSS or IIEF-5), and adverse events were analyzed. Results: 14 studies containing 654 patients were included. Nine of the 14 included studies had evaluated a negative biopsy rate after PDT. The pooled rate was 55.0% (95.0% CI: 0.44–0.66, I2 = 85.7%). Twelve of the 14 included studies which evaluated PSA decreasing rate with the pooled rate of 35.0% (95.0% CI: 0.24–0.47, I2 = 88.7%). Six of the included studies evaluated IPSS with decreasing rate of 29.1% (95.0 % CI: 2.7%–55.5%, I2 = 96.9%). Five of the included studies evaluated IIEF-5 with decreasing rate of 14.9% (95.0% CI: 6.8%–23.0%, I2 = 44.2%). The most common adverse events were haematuria (28.1%, 95.0% CI: 17.1%–39.2%, I2 = 79.8%), erectile dysfunction (23.1%, 95.0% CI: 9.7%–36.5%, I2 = 87.7%), and dysuria (18.6%, 95.0% CI: 12.1%–25.0 %, I2 = 53.4 %). Conclusions: The meta-analysis results shows that PDT for patients with prostate cancer can be considered as effective based on single-arm clinical trials. Meanwhile, this study reveals that there are not only low levels of side effect rates but also insignificant effect on both urinary and erectile function. However, more high-quality RCTs are needed to evaluate the comparative efficacy, safety, and functional outcomes of PDT for patients with prostate cancer. Keywords: Meta-analysis, Photochemotherapy, Prostatic neoplasms

In this paper, under the condition of bidirectional stress, the buckling deformation of the side plate in a rectangular concrete-filled steel tube (CFST) column has been studied in detail. We have conducted a theocratical analysis, an experimental validation and a finite element simulation to investigate the influences of the height-width ratios and Nominal Poisson’s ratios on the buckling form of the side plate, and we also try to explain the change of buckling form between unidirectional and bidirectional stress, both of them can provide a good reference and basis for design and application of the CFST column. The specific work can be summarized as follows: Firstly, a theoretical analysis has been conducted to study the buckling coefficient solution method of the thin plate under the conditions of axial compress and transverse tension. Then, under the conditions of the unidirectional and the bidirectional stress, a comparative study is carried out to investigate the changing relationship of the buckling coefficient (k) of the side plate; the results indicate that the buckling characteristic is changed due to the bidirectional stress, meanwhile, the buckling coefficient and the number of buckling half-wave will increase. Furthermore, the existing outcomes and the numerical simulations are adopted to study the relevance between the number of the elastic buckling half-wave in the side plate and the corresponding height-width ratio of the component; the results indicate that the former is larger than the latter. Finally, based on the obtained, the buckling relationship curve, the conclusion can be drawn as follows: when the bidirectional stress has been applied to the side plate, there is an equal interval between the different buckling half-waves; meanwhile, the interval shows a quadratic function reduce trend with the increase of nominal Poisson’s ratio.

The possible existence of stable up-down quark matter (udQM) was recently proposed, and it was shown that the properties of udQM stars are consistent with various pulsar observations. In this work we investigate the stability of udQM nuggets and found at certain size those objects are more stable than others if a large symmetry energy and a small surface tension were adopted. In such cases, a crust made of udQM nuggets exists in quark stars. A new family of white dwarfs comprised entirely of udQM nuggets and electrons were also obtained, where the maximum mass approaches to the Chandrasekhar limit.

The developmental process of inflorescence and gametophytes is vital for sexual reproduction in rice. Multiple genes and conserved miRNAs have been characterized to regulate the process. The changes of miRNAs expression during the early development of rice inflorescence remain unknown. In this study, the analysis of miRNAs profiles in the early stage of rice inflorescence development identified 671 miRNAs, including 67 known and 44 novel differentially expressed miRNAs (DEMs). Six distinct clusters of miRNAs expression patterns were detected, and Cluster 5 comprised 110 DEMs, including unconserved, rice-specific osa-miR5506. Overexpression of osa-miR5506 caused pleiotropic abnormalities, including over- or under-developed palea, various numbers of floral organs and spikelet indeterminacy. In addition, the defects of ovaries development were frequently characterized by multiple megasporocytes, ovule-free ovary, megasporocyte degenerated and embryo sac degenerated in the transgenic lines. osa-miR5506 targeted REM transcription factor LOC_Os03g11370. Summarily, these results demonstrated that rice-specific osa-miR5506 plays an essential role in the regulation of floral organ number, spikelet determinacy and female gametophyte development in rice.

Lightweight alkali-activated concrete (LAAC) is a type of highly environmentally friendly concrete, which can provide the benefits of both alkali-activated material and lightweight concrete. The study aimed to investigate the influence of different water/solid (W/S) ratios on the properties of normal-weight/lightweight fly ash–slag alkali-activated concrete manufactured at ambient temperature. The relative performance of the alkali-activated concrete (AAC) mixes with limestone and sintered fly ash lightweight aggregates as the coarse aggregates was also compared to the conventional ordinary Portland cement (OPC) concrete mix in terms of their compressive stress–strain relationship, splitting tensile strength and fracture parameters. The morphologies and microstructure of the four types of interfacial transition zones (ITZs) were characterized by scanning electron microscopy (SEM). Results indicated that the AAC had a higher tensile strength, stress intensity factor, brittleness and lower elastic modulus than its cement counterpart. With the decrease in the W/S ratio, the density, compressive and tensile strength, ultrasonic pulse velocity, fracture energy, brittleness and elastic modulus of the AAC increase. However, the influence of the W/S ratio on the mechanical properties of the LAAC with lightweight porous aggregates was less than that of the normal-weight AAC. Predictive models of the splitting tensile strength, fracture energy and elastic modulus of the AAC were also suggested, which were similar to those of the OPC concrete. Furthermore, the microstructure investigation showed that no wall effect occurred in the ITZ of the AAC. The ITZ structure of the hardened AAC was also more compact and uniform than that of the OPC concrete.

Aegilops tauschii Ais a wild relative of common wheat (Triticum aestivum) and acts as an important resource of elite genes including genes for resistance to biotic and abiotic stresses. To improve the cadmium (Cd) tolerance of wheat varieties using A. tauschii resources, we investigated the genetic variation of biomass-based Cd tolerance in 235 A. tauschii accessions treated with 0 (control) and 100 μmol L− 1 CdCl2 (as Cd stress). Simultaneously, we performed a genomewide association study (GWAS) using a single-nucleotide polymorphism chip containing 7185 markers. Six markers were found to be significantly associated with Cd tolerance by a general linear model and a mixed linear model. These markers were close to several candidate/flanking genes associated with Cd tolerance according to results in public databases, including pdil5-1, Acc-1, DME-5A, TaAP2-D, TaAP2-B, Vrn-B1, and FtsH-like protein gene. The A. tauschii accessions were classified as high, moderate, and low Cd-tolerant according to a secondary index, the synthetic index (SI), in proportions of 9%, 57%, and 34%, respectively. By the average SI, accessions from Afghanistan, Turkey, Azerbaijan, and Iran showed relatively high Cd tolerance.

This paper investigated the performance of actively confined geopolymer concrete (GPC) through experiments. The mechanical properties of GPC under triaxial stress states were analyzed and discussed from the prospects of failure modes, axial peak stress and strain, monotonic and cyclic constitutive relationships. The experimental results demonstrated that the loading modes (monotonic loading and cyclic loading) had little effect on the failure mode and axial peak stress and strain. The improvement of the strength and ductility of GPC with the increase in confinement level was consistent with that of the conventional cement concrete while the strain enhancement of confined GPC was lower than that of confined conventional cement concrete at the same confinement level. The curves of the monotonic stress–strain and the envelop of cyclic compression were predicted through Mander’s model with good accuracy. The unloading/reloading models proposed by Lokuge were modified and the predicted cyclic hysteresis curves for actively confined GPC were in good agreement with the cyclic compression results. Findings from this study provide references for the application of geopolymer concrete.

This study aimed to research the whole stress–strain curves of coral Fly Ash-Slag Alkali-Activated Concrete (CAAC) in different strength grades. Fly ash-slag alkali-activated concrete was used as cementing materials to produce coral aggregate concrete. A monotonic loading test was conducted on the prismatic specimens to obtain elastic modulus (Ec), Poisson’s ratio (μ) and the constitutive relationship of CAAC under uniaxial compression. When the strain of CAAC reached the maximum value, the specimen was split and damaged rapidly. As the strength grade increased, the ratio of residual stress (σri) to peak stress (σ0i) decreased in the range of 0.17–0.28. The Ec of CAAC increased gradually, and μ increased to the peak value and then decreased. According to the test results, the constitutive equation of CAAC can be expressed by piecewise expression, which can better reflect all the experimental characteristics. It was also found that CAAC has many similar characteristics with coral concrete and lightweight aggregate concrete. To improve the strength and toughness of CAAC, some fibers, such as organic fiber, can be added to expand the application of CAAC in engineering projects.

Objective. This study was designed to compare the effects of catheter drainage alone and combined with ozone in the management of multiloculated pyogenic liver abscess (PLA). Methods. The prospective study included 60 patients diagnosed with multiloculated PLA. All patients were randomly divided into two groups: catheter drainage alone (group I) and catheter drainage combined with ozone (group II). Drainage was considered successful when (1) the abscess cavity was drained and (2) clinical symptoms were resolved. Kruskal-Wallis nonparametric test was used to compare the success rates, length of stay (LOS), and need for further surgery of the two groups. P

3,3'Diindolylmethane (DIM), a natural phytochemical, has shown inhibitory effects on the growth and migration of a variety of cancer cells; however, whether DIM has similar effects on vascular smooth muscle cells (VSMCs) remains unknown. The purpose of this study was to assess the effects of DIM on the proliferation and migration of cultured VSMCs and neointima formation in a carotid injury model, as well as the related cell signaling mechanisms.DIM dose-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs without cell cytotoxicity. This inhibition was caused by a G0/G1 phase cell cycle arrest demonstrated by fluorescence-activated cell-sorting analysis. We also showed that DIM-induced growth inhibition was associated with the inhibition of the expression of cyclin D1 and cyclin-dependent kinase (CDK) 4/6 as well as an increase in p27(Kip1) levels in PDGF-stimulated VSMCs. Moreover, DIM was also found to modulate migration of VSMCs and smooth muscle-specific contractile marker expression. Mechanistically, DIM negatively modulated PDGF-BB-induced phosphorylation of PDGF-recptorβ (PDGF-Rβ) and the activities of downstream signaling molecules including Akt/glycogen synthase kinase(GSK)3β, extracellular signal-regulated kinase1/2 (ERK1/2), and signal transducers and activators of transcription 3 (STAT3). Our in vivo studies using a mouse carotid arterial injury model revealed that treatment with 150 mg/kg DIM resulted in significant reduction of the neointima/media ratio and proliferating cell nuclear antigen (PCNA)-positive cells, without affecting apoptosis of vascular cells and reendothelialization. Infiltration of inflammatory cells was also inhibited by DIM administration.These results demonstrate that DIM can suppress the phenotypic modulation of VSMCs and neointima hyperplasia after vascular injury. These beneficial effects on VSMCs were at least partly mediated by the inhibition of PDGF-Rβ and the activities of downstream signaling pathways. The results suggest that DIM has the potential to be a candidate for the prevention of restenosis.