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Understanding how environmental factors influence the responsiveness of crop yield to growing season precipitation (GSP) can reduce the risk of yield fluctuations, ensuring stable crop production. This study involved the cultivation of rainfed potatoes at three locations within the climatic transition zone of Northwest China. We employed stepwise linear regression and machine learning techniques to pinpoint the key environmental factors influencing potato tuber yield and the yield-precipitation relationship. The slope of the water-limited yield potential relationship for potatoes was determined to be 172.1 ​kg ​ha−1 ​mm−1, with an intercept at 121.2 ​mm. The potato tuber yield exhibited an upward trend with increasing GSP but declined once the precipitation exceeded 400 ​mm. However, GSP alone explained up to 30% of the variability in potato tuber yield. Factors such as soil moisture at planting, maximum temperatures during the tuber stolon initiation and bulking stages, diurnal temperature fluctuations at maturity, and excessive precipitation events during the growing season significantly influenced potato tuber yield, and consequently, the relationship between yield and GSP. Conversely, climatic factors accounted for more than 63% of the variation in potato tuber yield, with the multiple linear regression model yielding the best results. This was especially evident when the yield-precipitation relationship was categorized into two groups based on the amount and distribution of GSP, maximum temperature, and radiation levels. This analysis suggested that preventing unnecessary water evaporation when precipitation is low, improving drainage when precipitation is high, and planting potato on an optimal date can advance potato production.

Introduction Investigating how circular RNAs (circRNAs) function during tumorigenesis may help uncover novel diagnostic markers for cancer treatment. The oncogenic role of circ_001621 has been verified in osteosarcoma, but its role in lung cancer has yet to be reported. This research is the first to investigate the circ_001621 expression and regulatory mechanism in lung cancer. Material and methods RT-qPCR was performed to assess the circ_001621 expression levels in lung cancer cells and tissues. The influence of circ_001621 on the viability, invasive ability, and apoptosis of lung cancer cells was investigated through CCK-8, transwell, and caspase-3 activity experiments, respectively. A xenograft nude mouse model was designed to evaluate how circ_001621 functions in vivo. The RIP and luciferase reporter experiments confirmed the binding among circRNA, miRNA, and mRNA. Results Circ_001621 was dramatically upregulated in lung cancer tissues and cells. Silencing circ_001621 in lung cancer cells reduced their viability and invasive ability but stimulated apoptosis. The nude mice experiment demonstrated that circ_001621 downregulation considerably stunted tumor growth in vivo. Additionally, circ_001621 could sponge miR-199a-3p. The inhibitor of miR-199a-3p improved the viability and invasion of cells while inhibiting apoptosis. Moreover, it offset the impact of circ_001621 on lung cancer cells. MiR-199a-3p was observed to target GREM1, and the downregulation of GREM1 could counteract miR-199a-3p-induced effects on lung cancer cells. Conclusions The circ_001621/miR-199a-3p/GREM1 axis exhibits an association with the development of lung cancer, suggesting its potential as a future therapeutic target for the disease.

Abstract Inflammation plays a key role in pathogenesis and rupture of aneurysms. Non-invasively and dynamically monitoring aneurysm inflammation is critical. This study evaluated myeloperoxidase (MPO) as an imaging biomarker and therapeutic target for aneurysm inflammation using an elastase-induced rabbit model treated with or without 4-aminobenzoic acid hydrazide (ABAH), an irreversible inhibitor of MPO. Myeloperoxidase-sensitive magnetic resonance imaging (MRI) using Mn-TyrEDTA, a peroxidase activity-dependent contrast agent, revealed weak contrast enhancement in contralateral arteries and decreased contrast enhancement in aneurysm walls with ABAH treatment, indicating MPO activity decreased and inflammation mitigated. This was supported by reduced immune cell infiltration, matrix metalloproteinases (MMP-2 and − 9) activity, ROS production and arterial wall destruction on histology. Finally, the aneurysm expansion rate remained

The study investigated the influence of flexural properties of bamboo spoon raw materials of different ages, parts, and moisture contents on the processing of bamboo spoon. By using the three-point bending test method, the flexural properties and fracture mechanisms of bamboo spoon made from different raw materials under different moisture conditions were analyzed, and the changes in bending performance of raw materials before and after processing into bamboo ladles were compared. The results showed that bamboo spoon had the same bending strength change pattern before and after processing, with better bending after, especially when processed at a moisture content of 10%. In terms of raw materials, bamboo spoon made from bamboo with a age of 7 years in the middle part exhibited the best bending strength. Observation of its fracture mechanism revealed that cracks extended outward when fracture occurred, dissipating energy, thus exhibiting a certain bending toughness during the bending process, while possessing good bending strength and bending toughness at the same time.

Abstract CRISPR/Cas12a‐based combinational screening has shown remarkable potential for identifying genetic interactions. Here, we describe an innovative method for combinational genetic screening with rapid construction of a dual‐CRISPR RNA (crRNA) library using gene splicing through overlap extension PCR (SOE PCR) and the adoption of CeCas12a, which we previously identified with strict PAM recognition and low off‐targeting to guarantee fidelity and efficiency. The custom‐pooled SOE crRNA array (SOCA) library for double‐knockout screening could be conveniently constructed in the laboratory for widespread use, and the CeCas12a‐mediated high‐fidelity screen displayed good performance even under a negative selection screen. By designing a SOCA dual‐crRNA library that covered most of the kinase and metabolism‐associated gene targets of FDA‐approved drugs implicated in hepatocellular carcinoma (HCC) tumourigenesis, novel cross‐talk between the two gene sets was negatively selected to inhibit HCC cell growth in vitro and in vivo and was validated using virtual double‐knockdown screening based on TCGA databases. Thus, this rapid, efficient and high‐fidelity double‐knockout screening system is promising for systemically identifying potential genetic interactions between multiple gene sets or combinations of FDA‐ approved drugs for clinical translational medicine in the future.

Abstract Objective The purpose of the study was to investigate the status of pregnancy stress and to explore factors associated with pregnancy stress among women by China’s two-child policy. Methods A mixed-method study involving both quantitative and qualitative methods was conducted using questionnaires and semi-structured interviews. The questionnaires encompassed socio-demographic and obstetric characteristics, as well as the Pregnancy Stress Rating Scale (PSRS) and the Social Support Rating Scale (SSRS). Initially, the participants were required to complete the questionnaires, enabling us to assess their respective pregnancy stress statuses. Subsequently, we selectively interviewed pregnant women with a second child and exhibited at least mild pregnancy stress. The qualitative study sought to uncover the factors contributing to their stress during pregnancy. Results A total of 463 subjects were enrolled; of the subjects, 22 (4.8%) had no stress, 407 (87.9%) had mild stress, 34 (7.3%) had moderate stress. Generalized linear regression analysis revealed significant factors (P

Abstract Resident memory T (Trm) cells which are specifically located in non-lymphoid tissues showed distinct phenotypes and functions compared to circulating memory T cells and were vital for the initiation of robust immune response within tissues. However, the heterogeneity in the transcriptional features, development pathways, and cancer response of Trm cells in the small intestine was not demonstrated. Here, we integrated scRNA-seq and scTCR-seq data pan-tissue T cells to explore the heterogeneity of Trm cells and their development pathways. Trm were enriched in tissue-specific immune response and those in the DUO specially interacted with B cells via TNF and MHC-I signatures. T cell lineage analyses demonstrated that Trm might be derived from the T_CD4/CD8 subset within the same organ or migrated from spleen and mesenteric lymph nodes. We compared the immune repertoire of Trm among organs and implied that clonotypes in both DUO and ILE were less expanded and hydrophilic TRB CDR3s were enriched in the DUO. We further demonstrated that Trm in the intestine infiltrated the colorectal cancer and several effector molecules were highly expressed. Finally, the TCGA dataset of colorectal cancer implied that the infiltration of Trm from the DUO and the ILE was beneficial for overall survival and the response to immune checkpoint blockade.

In this paper, we study the following fractional Kirchhoff type equation \begin{equation*} \begin{cases} \left(a+b\displaystyle\int_{\mathbb{R}^N}\int_{\mathbb{R}^N}\frac{|u(x)-u(y)|^p}{|x-y|^{N+ps}}dxdy\right)(-\Delta)_p^su=|u|^{q-2}u\ln |u|^2+\frac{\lambda}{u^\gamma}, &\rm \mathrm{in}\ \Omega, \\ u>0, &\rm \mathrm{in}\ \Omega, \\ u=0, &\rm \mathrm{in}\ \mathbb{R}^N\backslash \Omega, \end{cases} \end{equation*} where $\Omega$ $\subset$ $\mathbb{R}^N$ is a bounded domain with Lipschitz boundary, $00, b\geq0$, $N>ps$, $2p0$ is a real parameter. By using the critical point theory for nonsmooth functionals and analytic techniques, the existence and multiplicity of positive solutions are obtained.

The rapid development of generative technologies has made the production of forged products easier, and AI-generated forged images are increasingly difficult to accurately detect, posing serious privacy risks and cognitive obstacles to individuals and society. Therefore, constructing an effective method that can accurately detect and locate forged regions has become an important task. This paper proposes a hierarchical and progressive forged image detection and localization method called HPUNet. This method assigns more reasonable hierarchical multi-level labels to the dataset as supervisory information at different levels, following cognitive laws. Secondly, multiple types of features are extracted from AI-generated images for detection and localization, and the detection and localization results are combined to enhance the task-relevant features. Subsequently, HPUNet expands the obtained image features into four different resolutions and performs detection and localization at different levels in a coarse-to-fine cognitive order. To address the limited feature field of view caused by inconsistent forgery sizes, we employ three sets of densely cross-connected hierarchical networks for sufficient interaction between feature images at different resolutions. Finally, a UNet network with a soft-threshold-constrained feature enhancement module is used to achieve detection and localization at different scales, and the reliance on a progressive mechanism establishes relationships between different branches. We use ACC and F1 as evaluation metrics, and extensive experiments on our method and the baseline methods demonstrate the effectiveness of our approach.

The CRISPR-associated endonuclease Cas12a has become a powerful genome-editing tool in biomedical research due to its ease of use and low off-targeting. However, the size of Cas12a severely limits clinical applications such as adeno-associated virus (AAV)-based gene therapy. Here, we characterized a novel compact Cas12a ortholog, termed EbCas12a, from the metagenome-assembled genome of a currently unclassified Erysipelotrichia. It has the PAM sequence of 5'-TTTV-3' (V = A, G, C) and the smallest size of approximately 3.47 kb among the Cas12a orthologs reported so far. In addition, enhanced EbCas12a (enEbCas12a) was also designed to have comparable editing efficiency with higher specificity to AsCas12a and LbCas12a in mammalian cells at multiple target sites. Based on the compact enEbCas12a, an all-in-one AAV delivery system with crRNA for Cas12a was developed for both in vitro and in vivo applications. Overall, the novel smallest high-fidelity enEbCas12a, this first case of the all-in-one AAV delivery for Cas12a could greatly boost future gene therapy and scientific research.

BackgroundsExtracellular matrix (ECM) is an important component of tumor microenvironment, and its abnormal expression promotes tumor formation, progression and metastasis.MethodsWeighted gene co-expression network analysis (WGCNA) was used to identify ECM-related hub genes based on The Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) data. COAD clinical samples were used to verify the expression of potential biomarkers in tumor tissues, and siRNA was used to explore the role of potential biomarkers in cell proliferation and epithelial−mesenchymal transition (EMT).ResultsThree potential biomarkers (LEP, NGF and PCOLCE2) related to prognosis of COAD patients were identified and used to construct ERGPI. Immunohistochemical analysis of clinical samples showed that the three potential biomarkers were highly expressed in tumor tissues of COAD patients. Knockdown of LEP, NGF or PCOLCE2 inhibited COAD cell proliferation and EMT. Dictamnine inhibited tumor cell growth by binding to these three potential biomarkers based on molecular docking and transplanted tumor model.ConclusionThe three biomarkers can provide new ideas for the diagnosis and targeted therapy of COAD patients.

The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a system is a powerful tool in gene editing; however, crRNA-DNA mismatches might induce unwanted cleavage events, especially at the distal end of the PAM. To minimize this limitation, we engineered a hyper fidelity AsCas12a variant carrying the mutations S186A/R301A/T315A/Q1014A/K414A (termed HyperFi-As) by modifying amino acid residues interacting with the target DNA and crRNA strand. HyperFi-As retains on-target activities comparable to wild-type AsCas12a (AsCas12aWT) in human cells. We demonstrated that HyperFi-As has dramatically reduced off-target effects in human cells, and HyperFi-As possessed notably a lower tolerance to mismatch at the position of the PAM-distal region compared with the wild type. Further, a modified single-molecule DNA unzipping assay at proper constant force was applied to evaluate the stability and transient stages of the CRISPR/Cas ribonucleoprotein (RNP) complex. Multiple states were sensitively detected during the disassembly of the DNA-Cas12a-crRNA complexes. On off-target DNA substrates, the HyperFi-As-crRNA was harder to maintain the R-loop complex state compared to the AsCas12aWT, which could explain exactly why the HyperFi-As has low off-targeting effects in human cells. Our findings provide a novel version of AsCas12a variant with low off-target effects, especially capable of dealing with the high off-targeting in the distal region from the PAM. An insight into how the AsCas12a variant behaves at off-target sites was also revealed at the single-molecule level and the unzipping assay to evaluate multiple states of CRISPR/Cas RNP complexes might be greatly helpful for a deep understanding of how CRISPR/Cas behaves and how to engineer it in future.

Abstract Background Nephrectomy, whether in the era of cytokine therapy or targeted therapy, has an important role in the treatment of metastatic renal cell carcinoma. With the advent of immunotherapy, immunotherapy combined with targeted therapy has become the mainstream of systemic therapy, but the role of nephrectomy in metastatic renal cell carcinoma is unclear. In this study, we retrospectively analyzed the impact of nephrectomy on survival in patients with metastatic renal cell carcinoma who received immune-targeted therapy. Methods Patients with metastatic renal cell carcinoma who received immune-targeted therapy at three centers between May 17, 2019 and August 1, 2022 were collected, who were divided into two groups based on whether nephrectomy was performed or not. Survival, response rate and adverse event were compared between the two groups. The primary end point was progression free survival, Subgroup analysis and univariate and multivariable prognostic analyses were also assessed. Results With a median follow-up time of 29.3 months (95% CI 28.5–30.2), 165 patients were recruited and divided into two groups based on whether they underwent nephrectomy or not. There were 68 patients in the non-nephrectomy group, 97 in the nephrectomy group. Compared to patients treated with immune-targeted therapy, patients treated with immune-targeted therapy plus nephrectomy were able to achieve survival benefits, with a median PFS of 10.8 months (95% CI 8.3–13.3) and 14.4 months (95% CI 12.6–16.2), respectively, as well as an HR of 0.476 (95% CI 0.323–0.701, p = 0.0002). The 12-month and 18-month PFS rates were 30.9% versus 60.8% and 7.4% versus 25.8%, respectively. The objective response rate (ORR) was 52.9% and 60.8%, respectively, in the non-nephrectomy and nephrectomy groups (p = 0.313), and the disease control rate (DCR) was 75% and 83.5%, respectively (p = 0.179). The most common adverse events related to treatment were hypothyroidism, immune-related pneumonitis and rash. Multivariate analysis showed that primary tumor nephrectomy prior to immune-targeted therapy, clear cell renal carcinoma and oligo metastasis were independent prognostic factors. Conclusions Nephrectomy may provide PFS benefit with tolerable safety for patients with metastatic renal cell carcinoma who receive immune-targeted therapy. In multivariate analysis, nephrectomy, clear cell carcinoma, and oligo-organ metastasis were found to be favorable independent prognostic factors.

According to attitude–behavior theory, the emotions generated by tourists’ travel experiences can influence their subsequent behavioral intentions. This quantitative study analyzed 398 survey questionnaires using a structural equation model to explore the multiple chain mediating effects between tourists’ participation, perceived value, place attachment, and loyalty. The results show that the innovation and interaction dimensions of tourist participation significantly influence the generation of perceived value and place attachment, which is far greater than that of the information exchange dimension. Perceived value significantly affects the formation of place attachment, and the self-enhancement dimension of perceived value significantly influences tourists’ recommendations. Compared to ordinary perceived value, the emotional connection between tourists and the destination is more profound and important, and place attachment plays a crucial role in the formation of tourists’ loyalty. This study confirms the relevance of the attitude–behavior theory in the context of traditional village tourism and extends the theory’s application to encompass the emotional connection between individuals and places. It thoroughly investigates the mechanisms through which tourists’ participation, perceived value, and place attachment impact customer loyalty. The findings of this research hold significant importance in comprehending tourists’ behavioral intention and decision-making processes within destination settings, providing a theoretical basis for exploring and expanding diverse value activities in traditional village tourism.

As the main active component in ginseng, ginsenoside is widely used in food and medicine. Ginsenosides have different properties and functions due to their different chemical structures. The content of rare ginsenosides with high activity is very low in nature, which limits the utilization. It is an important way to obtain rare ginsenosides by transforming high content ginsenosides into rare ginsenosides through different methods. Based on the structure and pharmacology of ginsenosides, this paper reviews the effects of biotransformation on the glycosyl hydrolysis and parent nucleus structure of ginsenosides, and it analyzes the application status and future development trend of rare ginsenosides in food and medicine, providing a theoretical basis for improving the application of ginsenosides resources.

The exchanges between cities and counties in the Northern Slope Economic Belt of Tianshan Mountains (NSEBTM) are increasingly frequent and the economic linkages are increasingly close, but the spatial distribution of economic development and linkages among the cities and counties within NSEBTM is uneven. Therefore, it is of great significance to study the evolution of spatial-temporal pattern of the economic linkage network of cities and counties on NSEBTM to promote the coordinated and integrated development of the regional economy on NSEBTM. In this study, we used the modified gravity model and social network analysis method to analyze the spatio-temporal evolution characteristics of the economic linkage network structure of cities and counties on NSEBTM in 2000, 2010, and 2020. The results showed that the comprehensive development quality level of cities and counties on NSEBTM increased from 2000 to 2020, its growth rate also increased, and its gap between cities and counties continued expanding. Both the spatial distribution patterns of the comprehensive development quality level of cities and counties on NSEBTM in 2000 and 2010 were presented as “high in the middle and low at both ends”, while the spatial distribution pattern of 2020 was exhibited as “high value and low value staggered”. The total amount of external economic linkages of cities and counties on NSEBTM showed an obvious upward trend, and its gap between cities and counties continued expanding, also showing a pattern of “a strong middle section and weak ends”. The direction of economic linkages of NSEBTM existed obvious central orientation and geographical proximity. The density of economic linkage network of NSEBTM increased from 2000 to 2020, and the structure of economic linkage network changed from single-core structure centered with Urumqi City to multicore structure centered with Urumqi City, Karamay City, Shihezi City, and Changji City, shifting from unbalanced development to balanced development. In the future, we should accelerate the construction of urban agglomeration on NSEBTM, cultivate a modern Urumqi metropolitan area, improve the comprehensive development quality of the cities and counties at the eastern and western ends, strengthen the intensity of economic linkages between cities and counties, optimize the economic linkage network, and promote the coordinated and integrated development of regional economy.

ABSTRACT Influenza A virus infection during pregnancy can cause adverse maternal and fetal outcomes but the mechanism responsible remains elusive. Infection of outbred mice with 2009 H1N1 at embryonic day (E) 10 resulted in significant maternal morbidity, placental tissue damage and inflammation, fetal growth restriction, and developmental delays that lasted through weaning. Restriction of pulmonary virus replication was not inhibited during pregnancy, but infected dams had suppressed circulating and placental progesterone (P4) concentrations that were caused by H1N1-induced upregulation of pulmonary cyclooxygenase (COX)-1-, but not COX-2-, dependent synthesis and secretion of prostaglandin (PG) F2α. Treatment with 17-α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin that is safe to use in pregnancy, ameliorated the adverse maternal and fetal outcomes from H1N1 infection and prevented placental cell death and inflammation. These findings highlight the therapeutic potential of progestin treatments for influenza during pregnancy.IMPORTANCEPregnant individuals are at risk of severe outcomes from both seasonal and pandemic influenza A viruses. Influenza infection during pregnancy is associated with adverse fetal outcomes at birth and adverse consequences for offspring into adulthood. When outbred dams, with semi-allogenic fetuses, were infected with 2009 H1N1, in addition to pulmonary virus replication, lung damage, and inflammation, the placenta showed evidence of transient cell death and inflammation that was mediated by increased activity along the arachidonic acid pathway leading to suppression of circulating progesterone. Placental damage and suppressed progesterone were associated with detrimental effects on perinatal growth and developmental delays in offspring. Treatment of H1N1-infected pregnant mice with 17-OHPC, a synthetic progestin treatment that is safe to use in pregnancy, prevented placental damage and inflammation and adverse fetal outcomes. This novel therapeutic option for the treatment of influenza during pregnancy should be explored clinically.

Ecosystem services (ES) are defined as the benefits of the natural environment that sustain human life. The analyses of the balance of ecosystem services (ES balance) and its driving factors are critical for achieving the region’s sustainable development goals. This study explored the ES balance in the Beijing-Tianjin-Hebei-Inner Mongolia (JJJM) region, considering the region’s rapid urbanization, implementation of ecological restoration projects, and intense agricultural and pastoral activities. It quantified the ES balance on different scales and selected nine natural and anthropogenic driving factors to reveal its spatio-temporal heterogeneity and change characteristics in 2000–2020. The main conclusions were as follows: (1) The ES balance in the JJJM region exhibited a significant spatial differentiation: generally higher in its eastern and northern areas and lower in its western and southern parts; (2) The ES balance in the Beijing-Tianjin-Hebei region showed a general trend of initial increase and subsequent decrease, while Inner Mongolia exhibited a continuous upward trend. High-value areas (>46) and low-value areas (

Summary: Background: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC. Methods: In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768. Findings: From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1–15.1). Median OS was 13.7 months (95% CI 9.3–17.7). Median DoR was 8.1 months (95% CI 1.7–10.6). ORR was 20% (95% CI 5.7–43.7). DCR was 95% (95% CI 75.1–99.9). CBR was 60% (95% CI 36.1–80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3–4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of Proteobacteria and Lachnospiraceae family and a low-abundance of Actinobacteriota and Bifidobacterium. The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders. Interpretation: FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population. Funding: This study was supported by the National Natural Science Foundation of China (82102954 to Wensi Zhao) and the Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen).

Purpose: This study aims to investigate the experiences, emotional coping strategies, and help-seeking needs of women with PCOS from their perspective, considering common psychological issues such as stress, anxiety, and depression that are prevalent among individuals with PCOS. Materials and Methods: The study recruited 14 women with PCOS for semi-structured interviews between October and November 2022, using a descriptive phenomenology method design. The interviews were analyzed using NVivo 12 software. Results: Four themes and eleven subthemes were derived from the semi-structured interviews: (1) Negative Mental Health Status; (2) Four Patterns of Emotion Regulation; (3) The Psychological Double-Edged Sword: Family Social Network; (4) Strong Demands for Psychological Counseling and Lifestyle Guidance. Conclusion: The study suggests that interventions should focus on fostering internalized self-efficacy and emotional expression, promoting constructive familial support, and providing psychological counseling and lifestyle recommendations to alleviate psychological distress experienced by women with PCOS.

SARS-CoV-2 infection during pregnancy is associated with severe COVID-19 and adverse fetal outcomes, but the underlying mechanisms remain poorly understood. Moreover, clinical studies assessing therapeutics against SARS-CoV-2 in pregnancy are limited. To address these gaps, we developed a mouse model of SARS-CoV-2 infection during pregnancy. Outbred CD1 mice were infected at E6, E10, or E16 with a mouse-adapted SARS-CoV-2 (maSCV2) virus. Outcomes were gestational age–dependent, with greater morbidity, reduced antiviral immunity, greater viral titers, and impaired fetal growth and neurodevelopment occurring with infection at E16 (third trimester equivalent) than with infection at either E6 (first trimester equivalent) or E10 (second trimester equivalent). To assess the efficacy of ritonavir-boosted nirmatrelvir, which is recommended for individuals who are pregnant with COVID-19, we treated E16-infected dams with mouse-equivalent doses of nirmatrelvir and ritonavir. Treatment reduced pulmonary viral titers, decreased maternal morbidity, and prevented offspring growth restriction and neurodevelopmental impairments. Our results highlight that severe COVID-19 during pregnancy and fetal growth restriction is associated with heightened virus replication in maternal lungs. Ritonavir-boosted nirmatrelvir mitigated maternal morbidity along with fetal growth and neurodevelopment restriction after SARS-CoV-2 infection. These findings prompt the need for further consideration of pregnancy in preclinical and clinical studies of therapeutics against viral infections.

BackgroundSevere community-acquired pneumonia (sCAP) is life-threatening and characterized by intensive care unit (ICU) admission and high mortality. And they are vulnerable to hospital-acquired infection. In such a severe condition, metagenomic next-generation sequencing (mNGS) outperforms for short turnaround time and broad detection spectrum.Case presentationA 15-year-old male with severe influenza and methicillin-resistant Staphylococcus aureus (MRSA) pneumonia progressed rapidly, initially misdiagnosed as influenza co-infected with Aspergillus for misleading bronchoscopy manifestations. The turnaround time of mNGS is 13 h, which has the potential to expedite the clinical medication process. With the powerful support of mNGS and extracorporeal membrane oxygenation (ECMO), anti-infective therapy was adjusted accordingly, and vital signs gradually stabilized. After tortuous treatment and unremitting efforts, the patient recovered well.ConclusionsRapid mNGS applications, timely medication adjustments, strong ECMO support and active family compliance contribute to this miracle of life. False-negative or false-positive results are alarming, anti-infective medications should be adjusted after a comprehensive review of physical status and other indicators.

Abstract Face forgery represented by DeepFake technique has raised severe societal concerns. Due to the different scales of tampering traces and the different resolutions of face images, adopting common processing pipelines and standard form of convolutional neural networks (CNNs) will lead to problems such as omission, redundancy, and bias when extracting key discriminative features. To solve the above issues, unlike most existing methods that treat face forensics as a vanilla binary classification task, the authors instead reformulate it as a multi‐scale object detection problem and propose a novel framework called MSFRNet based on multi‐scale feature extraction. Concretely, to alleviate the issues of features omission and redundancy, the authors construct a two‐stream prediction network, where the shallow branch discovers small‐scale objects such as tiny noise by capturing low‐level features with higher resolution and more details, while the deep stream exploits larger receptive fields to detect large‐scale blocky artefacts. Moreover, a multi‐scale feature extraction module is designed to enrich feature representations in each stream. To solve the problem of features bias and ensure that unbiased feature representations are learned, more appropriate data augmentation approaches are proposed by introducing counterfactual causal reasoning. Extensive experiments demonstrate that our framework outperforms most ordinary binary classifiers and achieves positive performance.

Abstract Background Ginseng, Panax ginseng Meyer, is a traditional herb that is immensely valuable both for human health and medicine and for medicinal plant research. The homeodomain leucine zipper (HD-Zip) gene family is a plant-specific transcription factor gene family indispensable in the regulation of plant growth and development and plant response to environmental stresses. Results We identified 117 HD-Zip transcripts from the transcriptome of ginseng cv. Damaya that is widely grown in Jilin, China where approximately 60% of the world’s ginseng is produced. These transcripts were positioned to 64 loci in the ginseng genome and the ginseng HD-Zip genes were designated as PgHDZ genes. Identification of 82 and 83 PgHDZ genes from the ginseng acc. IR826 and cv. ChP genomes, respectively, indicated that the PgHDZ gene family consists of approximately 80 PgHDZ genes. Phylogenetic analysis showed that the gene family originated after Angiosperm split from Gymnosperm and before Dicots split from Monocots. The gene family was classified into four subfamilies and has dramatically diverged not only in gene structure and functionality but also in expression characteristics. Nevertheless, co-expression network analysis showed that the activities of the genes in the family remain significantly correlated, suggesting their functional correlation. Five hub PgHDZ genes were identified that might have central functions in ginseng biological processes and four of them were shown to be actively involved in plant response to environmental pH stress in ginseng. Conclusions The PgHDZ gene family was identified from ginseng and analyzed systematically. Five potential hub genes were identified and four of them were shown to be involved in ginseng response to environmental pH stress. The results provide new insights into the characteristics, diversity, evolution, and functionality of the PgHDZ gene family in ginseng and lay a foundation for comprehensive research of the gene family in plants.

Exosome DNA (exoDNA) can be used for liquid biopsy. This study was the first to use droplet digital PCR (ddPCR) to detect tumor-specific mutations in exoDNA and to evaluate the prognosis of hepatocellular carcinoma (HCC) patients. 60 HCC patients were enrolled in the study. We used ddPCR to detect c.747 G > T mutation in TP53 gene. We analyzed the correlation between detectable mutation in exoDNA and clinicopathologic characteristics using Multivariate logistics regression analysis. We performed Cox regression to assess the correlation between mutation frequency (mutant droplets/total droplets, MD/TD) and prognostic. We found that 48 of 60 patients had c.747 G > T mutation in TP53 gene in exoDNA (80.0%). We found that detectable mutation in exoDNA and age were associated with microvascular invasion (MVI) (P 67%) had shorted median recurrence-free survival (RFS) with 63 days (range, 53–202 days), compared with 368 days (range, 51–576 days) for patients with low-frequency mutation (

This paper deals with the following Kirchhoff–Schrödinger–Newton system with critical growth \begin{equation*} \begin{cases} \displaystyle-M\left(\int_{\Omega}|\nabla u|^2dx\right)\Delta u=\phi |u|^{2^*-3}u+\lambda|u|^{p-2}u, &\rm \mathrm{in}\ \ \Omega, \\ \displaystyle-\Delta \phi=|u|^{2^*-1}, &\rm \mathrm{in}\ \ \Omega, \\ \displaystyle u=\phi=0, &\rm \mathrm{on}\ \ \partial\Omega, \end{cases} \end{equation*} where $\Omega$ $\subset$ $\mathbb{R}^N(N\geq3)$ is a smooth bounded domain, $M(t)=1+bt^{\theta-1}$ with $t>0$, $10$, $10$ is a parameter, $2^*=\frac{2N}{N-2}$ is the critical Sobolev exponent. By using the variational method and the Brézis–Lieb lemma, the existence and multiplicity of positive solutions are established.

Genetic and molecular knowledge of a species is crucial to its gene discovery and enhanced breeding. Here, we report the genetic and molecular dissection of ginseng, an important herb for healthy food and medicine. A mini-core collection consisting of 344 cultivars and landraces was developed for ginseng that represents the genetic variation of ginseng existing in its origin and diversity center. We sequenced the transcriptomes of all 344 cultivars and landraces; identified over 1.5 million genic SNPs, thereby revealing the genic diversity of ginseng; and analyzed them with 26,600 high-quality genic SNPs or a selection of them. Ginseng had a wide molecular diversity and was clustered into three subpopulations. Analysis of 16 ginsenosides, the major bioactive components for healthy food and medicine, showed that ginseng had a wide variation in the contents of all 16 ginsenosides and an extensive correlation of their contents, suggesting that they are synthesized through a single or multiple correlated pathways. Furthermore, we pair-wisely examined the relationships between the cultivars and landraces, revealing their relationships in gene expression, gene variation, and ginsenoside biosynthesis. These results provide new knowledge and new genetic and genic resources for advanced research and breeding of ginseng and related species.

ObjectiveRobotic surgery has more advantages than traditional surgical approaches to complex liver resection; however, the robotic approach is invariably associated with increased cost. Enhanced recovery after surgery (ERAS) protocols are beneficial in conventional surgeries.MethodsThe present study investigated the effects of robotic surgery combined with an ERAS protocol on perioperative outcomes and hospitalization costs of patients undergoing complex hepatectomy. Clinical data from consecutive robotic and open liver resections (RLR and OLR, respectively) performed in our unit in the pre-ERAS (January 2019–June 2020) and ERAS (July 2020–December 2021) periods were collected. Multivariate logistic regression analysis was performed to determine the impact of ERAS and surgical approaches—alone or in combination—on LOS and costs.ResultsA total of 171 consecutive complex liver resections were analyzed. ERAS patients had a shorter median LOS and decreased total hospitalization cost, without a significant difference in the complication rate compared with the pre-ERAS cohort. RLR patients had a shorter median LOS and decreased major complications, but with increased total hospitalization cost, compared with OLR patients. Comparing the four combinations of perioperative management and surgical approaches, ERAS + RLR had the shortest LOS and the fewest major complications, whereas pre-ERAS + RLR had the highest hospitalization costs. Multivariate analysis found that the robotic approach was protective against prolonged LOS, whereas the ERAS pathway was protective against high costs.ConclusionsThe ERAS + RLR approach optimized postoperative complex liver resection outcomes and hospitalization costs compared with other combinations. The robotic approach combined with ERAS synergistically optimized outcome and overall cost compared with other strategies, and may be the best combination for optimizing perioperative outcomes for complex RLR.

Panax ginseng as a traditional medicinal plant with a long history of medicinal use. Ginsenoside Ro is the only oleanane-type ginsenoside in ginseng, and has various pharmacological activities, including anti-inflammatory, detoxification, and antithrombotic activities. UDP-dependent glycosyltransferase (UGT) plays a key role in the synthesis of ginsenoside, and the excavation of UGT genes involved in the biosynthesis of ginsenoside Ro has great significance in enriching ginsenoside genetic resources and further revealing the synthesis mechanism of ginsenoside. In this work, ginsenoside-Ro-synthesis-related genes were mined using the P. ginseng reference-free transcriptome database. Fourteen hub transcripts were identified by differential expression analysis and weighted gene co-expression network analysis. Phylogenetic and synteny block analyses of PgUGAT252645, a UGT transcript among the hub transcripts, showed that PgUGAT252645 belonged to the UGT73 subfamily and was relatively conserved in ginseng plants. Functional analysis showed that PgUGAT252645 encodes a glucuronosyltransferase that catalyzes the glucuronide modification of the C3 position of oleanolic acid using uridine diphosphate glucuronide as the substrate. Furthermore, the mutation at 622 bp of its open reading frame resulted in amino acid substitutions that may significantly affect the catalytic activity of the enzyme, and, as a consequence, affect the biosynthesis of ginsenoside Ro. Results of the in vitro enzyme activity assay of the heterologous expression product in E. coli of PgUGAT252645 verified the above analyses. The function of PgUGAT252645 was further verified by the result that its overexpression in ginseng adventitious roots significantly increased the content of ginsenoside Ro. The present work identified a new UGT gene involved in the biosynthesis of ginsenoside Ro, which not only enriches the functional genes in the ginsenoside synthesis pathway, but also provides the technical basis and theoretical basis for the in-depth excavation of ginsenoside-synthesis-related genes.

Currently, biomineralization is widely used as a surface modification approach to obtain ideal material surfaces with complex hierarchical nanostructures, morphologies, unique biological functions, and categorized organizations. The fabrication of biomineralized coating for the surfaces of scaffolds, especially synthetic polymer scaffolds, can alter surface characteristics, provide a favorable microenvironment, release various bioactive substances, regulate the cellular behaviors of osteoblasts, and promote bone regeneration after implantation. However, the biomineralized coating fabricated by immersion in a simulated body fluid has the disadvantages of non-uniformity, instability, and limited capacity to act as an effective reservoir of bioactive ions for bone regeneration. In this study, in order to promote the osteoinductivity of 3D-printed PCL scaffolds, we optimized the surface biomineralization procedure by nano-topographical guidance. Compared with biomineralized coating constructed by the conventional method, the nano-topographically guided biomineralized coating possessed more mineral substances and firmly existed on the surface of scaffolds. Additionally, nano-topographically guided biomineralized coating possessed better protein adsorption and ion release capacities. To this end, the present work also demonstrated that nano-topographically guided biomineralized coating on the surface of 3D-printed PCL scaffolds can regulate the cellular behaviors of USCs, guide the osteogenic differentiation of USCs, and provide a biomimetic microenvironment for bone regeneration.

In the context of the global decline in the capacity of ecosystem services (ESs) to meet increasing human demands, assessing and quantifying ESs is crucial for ecological policy formulation. To address this, our study employs an adjusted land-use matrix method and the patch-generating land-use simulation (PLUS) model for a quantitative analysis of the ES balance in the Beijing–Tianjin–Hebei–Inner Mongolia (JJJM) region from 2000 to 2020, projecting to 2040. Focusing on the JJJM region, a focal area for ecological policy exhibits significant socioeconomic disparities, revealing a synergistic interplay in the ESs balance. Areas with high vegetation cover, like forests and grasslands, demonstrate an elevated ESs balance, with Inner Mongolia having the highest total ESs balance at 71.40. Conversely, highly urbanized areas, such as Beijing and Tianjin, face deficits in the ESs balance, with Tianjin recording the lowest at 17.83. Our results show an upward trend in total ESs balance in the JJJM region (slope: 0.08 year−1). In particular, regulating services are declining (slope: −0.04 year−1), cultural services are increasing (slope: 0.08 year−1), and provisioning services remain relatively stable. Projecting to 2040, our analysis indicates a slight decline in ESs balance, attributed to Inner Mongolia’s urban expansion. This emphasizes the need for industrial transfers and proactive urbanization promotion to enhance ESs balance and support sustainable management and ecological civilization development in the JJJM region.

Abstract Background NCAPG, non-SMC subunit in the concentrate I complex, might promote the proliferation of hepatocellular carcinoma (HCC), but the mechanism is unclear. The aim of this study was to explore how NCAPG affects PTEN to influence the proliferation of HCC. Methods Western blotting, qRT-PCR and immunohistochemistry were used to detect NCAPG expression in HCC tissues. The effect of NCAPG on the proliferation of HCC cell lines was evaluated using an EdU incorporation assay, a Cell Counting Kit-8 assay and Fluorescence in situ hybridization (FISH). BALB/c-nu/nu mice were used for the in vivo proliferation experiment. Transcriptome sequencing was used to determine the relationship between NCAPG and PTEN. Immunocoprecipitation-mass spectrometry (IP-MS), proteomic sequencing and Co-immunoprecipitation (CO-IP) were used to identify and examine the interaction between the NCAPG and CKII proteins. Results We confirmed that NCAPG was abnormally overexpressed in HCC and promoted the proliferation of HCC cells. Transcriptome sequencing revealed that NCAPG inhibited the transcription of PTEN and promoted the activation of the PI3K-AKT pathway. We found a close association between NCAPG and CKII through proteomic sequencing; their interaction was confirmed by Co-IP. There was a positive correlation between NCAPG and CKII that promoted the phosphorylation of PTEN and thus inhibited its transcription and functions. We also proved that CKII was the key factor in the induction of proliferation by NCAPG. Conclusion We revealed the mechanism by which NCAPG regulates the proliferation of HCC: NCAPG inhibits PTEN through its interaction with CKII, and then activates the PI3K-AKT pathway to promote the proliferation of HCC.

The topographic evolution of tidal flats is critical for local ecological conservation, coastal zone management, and physical oceanographic studies. However, obtaining this knowledge is often challenging due to the lack of frequently updated topographic data over large areas. With the explosion of remotely sensed data, the waterline method has become the most operational method for tidal flat topography acquisition. In this study, digital elevation models (DEMs) of the tidal flats around Tongzhou Bay on the Jiangsu coast were constructed using the waterline method for three periods (2013, 2015, and 2017) before and after the construction of phase I of the reclamation project. Furthermore, the topographic evolution characteristics were analyzed from four aspects: contours, area changes, erosion–deposition distribution, and typical cross-sections. The results showed that: 1) During the 5 years from 2013 to 2017, the overall tidal flat area (500 km2) of Tongzhou Bay on the Jiangsu coast had been in a state of deposition, with a total siltation thickness of 0.19 m. 2) The reclamation activities affected the topography of the tidal flats quickly, but the recovery was also rapid. During the implementation of the project (in 2015), the area of the tidal flats above the −2-m contour was rapidly reduced by 20 km2 but rapidly recovered to the pre-project level after the completion of the project (in 2017). 3) The reclamation project directly affected the distribution of erosion and siltation. Outside the seawall on the east side of the Yaosha sand ridge, the 0-m contour expanded rapidly to the outer sea, reaching more than 250 m/year. 4) The sandbars in Tongzhou Bay on the Jiangsu coast generally had a southward-moving trend. Over the past 40 years, the Yaosha sand ridge had shifted southward by 2,500 m and the Lengjiasha sand ridge by more than 5,000 m. This study provides a remote sensing solution for the topographic evolution of large tidal flats under the influence of human reclamation activities.

PurposeThe purpose of this study was to examine trends in the incidence and incidence-based (IB) mortality of functional pancreatic neuroendocrine tumors(F-PNETs), and to identify factors associated with survival times.MethodsData were obtained from the Surveillance, Epidemiology, and End Results database from 2000 to 2017. Trends in the age-adjusted incidence of F-PNETs and IB mortality were examined using the Joinpoint Regression Program. Statistical analyses were run using chi-square tests, Kaplan–Meier curves, and the Cox proportional hazards model. Multiple imputation was used to deal with missing data.ResultsA total of 142 patients with F-PNETs met the study inclusion criteria. It was found that the incidence of F-PNETs decreased over the study period, with an annual percent change (APC) of -2. 5% (95% CI [-4. 3, -0. 5], P

Although there have been many discussions on negative group velocity (NGV), disagreements over its counter-intuitive explanations are still on the way. In this paper, it is proposed that the negative group velocity is just a component of the actual wave group, which has to be accompanied by a positive group velocity (PGV) component. A composite wave with the NGV component propagates forward in the form of a tumbling vortex as an attenuated or evanescent wave. Negative group velocity exists only in the anomalous dispersion band with resonance absorption. This wave group model is confirmed by the NGV characteristics of spoof surface plasmon polaritons (SSPPs) of spiral-shaped periodic units. In this case, the PGV and NGV waves are formed by the resonance coupling of periodic cells, and the composite SSPP modes have both resonance absorption attenuation and vortex cancellation attenuation.

ObjectiveTo evaluate the outcomes of patient-centered enhanced recovery after surgery (ERAS) in ­percutaneous nephrolithotomy (PCNL) for staghorn stones.Patients and methodsA retrospective analysis of 106 patients with staghorn calculi who underwent PCNL treatment at the Third Xiangya Hospital from October 01, 2018 to September 30, 2021 was performed. The patients were divided into the ERAS group (n = 56) and traditional group (n = 50). The ERAS program focused on a patient-centered concept, with elaboration on aspects, such as patient education, nutritional support, analgesia, body warming, early mobilization, nephrostomy tube removal, and strict follow-up.ResultsThe total stone free rate and total complication rate were similar in both groups. The visual analogue scale (VAS) 6 h after surgery, ambulation off bed time, indwelling fistula time, indwelling catheter time, and postoperative hospital stays were lower in the ERAS group than in the traditional group (P

In this article, we deal with the following fractional $ p $-Kirchhoff type equation $ \begin{equation*} \begin{cases} M\left( \int_{\mathbb{R}^{N}}\int_{\mathbb{R}^{N}}\frac{|u(x)-u(y)|^p}{|x-y|^{N+ps}}dxdy\right)(-\Delta)_p^su=\frac{|u|^{p_\alpha^*-2}u}{|x|^\alpha}+\frac{\lambda}{|x|^\beta} , &\rm \mathrm{in}\ \ \Omega, \\ u>0, &\rm \mathrm{in}\ \ \Omega, \\ u=0, &\rm \mathrm{in}\ \ \mathbb{R}^N\backslash \Omega, \end{cases} \end{equation*} $ where $ \Omega\subset \mathbb{R}^N $ is a smooth bounded domain containing $ 0 $, $ (-\Delta)_p^s $ denotes the fractional $ p $-Laplacian, $ M(t)=a+bt^{k-1} $ for $ t\geq0 $ and $ k>1 $, $ a, b>0 $, $ \lambda>0 $ is a parameter, $ 0

Evidence shows that some class I human leucocyte antigen (HLA) alleles are related to durable HIV controls. The T18A TCR, which has the alloreactivity between HLA-B∗42:01 and HLA-B∗81:01 and the cross-reactivity with different antigen mutants, can sustain long-term HIV controls. Here the structural basis of the T18A TCR binding to the immunodominant HIV epitope TL9 (TPQDLNTML180-188) presented by HLA-B∗42:01 was determined and compared to T18A TCR binding to the TL9 presented by the allo-HLA-B∗81:01. For differences between HLA-B∗42:01 and HLA-B∗81:01, the CDR1α and CDR3α loops adopt a small rearrangement to accommodate them. For different conformations of the TL9 presented by different HLA alleles, not like the conventional recognition of CDR3s to interact with peptide antigens, CDR3β of the T18A TCR shifts to avoid the peptide antigen but intensively recognizes the HLA only, which is different with other conventional TCR structures. Featured sequence pairs of CDR3β and HLA might account for this and were additionally found in multiple other diseases indicating the popularity of the unconventional recognition pattern which would give insights into the control of diseases with epitope mutating such as HIV.

Abstract Background Liver tumours between the root angle of the middle and right hepatic veins are a special type of liver segment VIII tumour. In this study, we designed a modified median hepatic fissure approach to remove these tumours. The safety and effectiveness of the approach were evaluated. Materials and methods From April 2015 to November 2019, 11 patients with liver tumours between the angle of the middle and right hepatic veins underwent this modified median hepatic fissure approach. We retrospectively analysed data from the perioperative periods of these 11 patients, including general condition, operation time, intraoperative bleeding, and postoperative complications. Disease-free survival and overall survival were assessed. Results Of the 11 patients, 9 patients had primary hepatocellular carcinoma and 2 had colorectal liver metastases. The average intraoperative blood loss was 285 mL (150–450 mL). Two patients developed postoperative bile leakage, but there were no significant serious complications, such as intraabdominal bleeding and liver failure, in any of the patients. The liver function returned to the normal range on the 5th day after surgery. Of the 11 patients, 5 have survived for more than 3 years (45.5%), and 4 have been disease-free for more than 3 years (36.3%). Conclusions For liver tumours between the root angle of the middle and right hepatic veins, the modified median hepatic fissure approach is a safe and feasible method.

Abstract Generative adversarial network‐based deep generative model is widely applied in creating hyper‐realistic face‐swapping images and videos. However, its malicious use has posed a great threat to online contents, thus making detecting the authenticity of images and videos a tricky task. Most of the existing detection methods are only suitable for one type of forgery and only work for low‐quality tampered images, restricting their applications. This paper concerns the construction of a novel discriminator with better comprehensive capabilities. Through analysis of the visual characteristics of manipulated images from the perspective of image quality, it is revealed that the synthesized face does have different degrees of quality degradation compared to the source content. Therefore, several kinds of image quality‐related handicraft features are extracted, including texture, sharpness, frequency domain features, and deep features, to unveil the inconsistent information and modification traces in the fake faces. In this way, a 1065‐dimensional vector of each image is obtained through multi‐feature fusion, and it is then fed into RF to train a targeted binary classification detector. Extensive experiments have shown that the proposed scheme is superior to the previous methods in recognition accuracy on multiple manipulation databases including the Celeb‐DF database with better visual quality.

BackgroundExosome is an important component of the tumor immune microenvironment and plays critical role in cancer pathogenesis. The exosome transcriptome of gastric cancer (GC) response to paclitaxel chemotherapy has not been investigated in the past.MethodsceRNA microarrays were performed in exosomes from six advanced GC patients before and after paclitaxel treatment. Bioinformatics tools were used to identify differential expressing genes and construct competing endogenous RNA (ceRNA) networks. The importance of hub genes in the ceRNA network was confirmed by survival analysis and functional analysis.ResultsA total of 213 differential mRNAs, 370 lncRNAs, and 376 circRNAs were identified, and hub genes in ceRNA networks were screened. The differential genes were associated with GO terms SNAP complex, gap junction, protein transporter activity, cytokine receptor, and KEGG pathways synaptic vesicle cycle, propanoate metabolism, Epstein–Barr virus infection, heparin, and steroid biosynthesis, and beta-alanine metabolism. ULK2, CYP2R1, BTLA, and miR-105-5p are prognostic genes for overall survival. Paclitaxel may target ULK2 which is involved in mitosis and cell cycle. miR-105-5p may target ULK2 3’UTR.ConclusionThe work for the first time identified exosomal RNA biomarkers and constructed a ceRNA network in GC response to paclitaxel, revealed novel molecular mechanisms of GC, and provided new candidates for GC diagnosis and treatment.

The placental inflammatory processes induced maternally result in preterm birth (PTB). Serum amyloid A (SAA) is a well-known biomarker of inflammation. The objective of this study was to investigate whether murine placental SAA isoforms (SAA1–4) participate in the mechanism of spontaneous PTB and whether maternal regulation of SAA production may serve as a therapeutic approach. During the gestation, all isoforms of SAA were detectable except SAA2. The mouse model of intrauterine inflammation was established using LPS infusion to the uterus. Following intrauterine inflammation, placental SAA2 increased significantly. Inhibition of Saa2, using siSaa2, markedly decreased PTB. The increased placental expression of pro-inflammatory cytokines Il1β, Il6, and Tnfα were downregulated by siSaa2 treatment. Maternal inhibition of Saa2 did not change the expression of Saa1–4 in the fetal brain. Explant inflammatory culture of placentas with siSaa2 showed similar results to our in vivo experiments. This study demonstrates the highly expressed placental SAA2 as a novel therapeutic target, and maternal administration of siRNA as a promising approach to alleviate PTB.

This study investigated the effects of interactional, motivational, self-regulatory, and situational factors on university students’ online learning outcomes and continuation intentions during the COVID-19 pandemic. Data were collected from 255 students taking a business course at a university in southern China. Hierarchical multiple regression analyses revealed that while family financial hardship caused by COVID-19 was a marginally significant negative predictor of students’ learning outcomes, learner–content interaction; instructors’ provision of e-resources, course planning, and organisation; and students’ intrinsic goal orientation and meta-cognitive self-regulation were significant positive predictors with the latter two sets of predictors mediating the effects of learner–instructor and learner–learner interactions, respectively. Multinominal logistic regression analyses showed that learner–instructor interaction, learner–content interaction, and private learning space were significant positive predictors of students’ intentions to continue with online learning, but learner–learner interaction was a significant negative predictor. These findings point to the differential effects of various types of interactional and situational factors on learning outcomes and continuation intentions, and the instructor- and learner-level factors that mediate the effects of learner–instructor and learner–learner interactions on learning outcomes. They contribute to our understandings of emergency online learning and provide implications for facilitating it.

In recent years, with the rapid development of technology, artificial intelligence (AI) security issues represented by adversarial sample attack have aroused widespread concern in society. Adversarial samples are often generated by surrogate models and then transfer to attack the target model, and most AI models in real-world scenarios belong to black boxes; thus, transferability becomes a key factor to measure the quality of adversarial samples. The traditional method relies on the decision boundary of the classifier and takes the boundary crossing as the only judgment metric without considering the probability distribution of the sample itself, which results in an irregular way of adding perturbations to the adversarial sample, an unclear path of generation, and a lack of transferability and interpretability. In the probabilistic generative model, after learning the probability distribution of the samples, a random term can be added to the sampling to gradually transform the noise into a new independent and identically distributed sample. Inspired by this idea, we believe that by removing the random term, the adversarial sample generation process can be regarded as the static sampling of the probabilistic generative model, which guides the adversarial samples out of the original probability distribution and into the target probability distribution and helps to boost transferability and interpretability. Therefore, we proposed a score-matching-based attack (SMBA) method to perform adversarial sample attacks by manipulating the probability distribution of the samples, which showed good transferability in the face of different datasets and models and provided reasonable explanations from the perspective of mathematical theory and feature space. Compared with the current best methods based on the decision boundary of the classifier, our method increased the attack success rate by 51.36% and 30.54% to the maximum extent in non-targeted and targeted attack scenarios, respectively. In conclusion, our research established a bridge between probabilistic generative models and adversarial samples, provided a new entry angle for the study of adversarial samples, and brought new thinking to AI security.

With the shortage of land resources, there has been a trend toward increasingly deep foundation pit engineering in urban areas. It is extremely important to reflect on the behavior and safety of deep foundation pits and conduct risk assessments in time. A nonhomologous and multi-indicator deep foundation pit risk assessment model was studied for nine types of nonhomologous on-site data monitored in the deep foundation pit. Based on the BIM (Building Information Modeling) technology, a family of monitored points was created that reflects the information on site from a deep foundation pit. The data visualization module was redeveloped by using Visual Studio 2019 to map the on-site data monitored to the components in the BIM model, which can visualize the data monitored in the BIM model of deep foundation pits. On this basis, the assessment of the safety level of deep foundation pits was realized in combination with a risk assessment model. Through the instance of the deep foundation pit of Zibo light rail, the analysis shows that the new visualization and risk assessment method can help construction workers locate dangerous units and formulate corresponding prevention and control measures better and faster.

Abstract Background Ginseng is an important medicinal herb in Asia and Northern America. The basic leucine zipper (bZIP) transcription factor genes play important roles in many biological processes and plant responses to abiotic and biotic stresses, such as drought stress. Nevertheless, the genes remain unknown in ginseng. Results Here, we report 91 bZIP genes identified from ginseng, designated PgbZIP genes. These PgbZIP genes were alternatively spliced into 273 transcripts. Phylogenetic analysis grouped the PgbZIP genes into ten groups, including A, B, C, D, E, F, G, H, I and S. Gene Ontology (GO) categorized the PgbZIP genes into five functional subcategories, suggesting that they have diversified in functionality, even though their putative proteins share a number of conserved motifs. These 273 PgbZIP transcripts expressed differentially across 14 tissues, the roots of different ages and the roots of different genotypes. However, the transcripts of the genes expressed coordinately and were more likely to form a co-expression network. Furthermore, we studied the responses of the PgbZIP genes to drought stress in ginseng using a random selection of five PgbZIP genes, including PgbZIP25, PgbZIP38, PgbZIP39, PgbZIP53 and PgbZIP54. The results showed that all five PgbZIP genes responded to drought stress in ginseng, indicating that the PgbZIP genes play important roles in ginseng responses to drought stress. Conclusions These results provide knowledge and gene resources for deeper functional analysis of the PgbZIP genes and molecular tools for enhanced drought tolerance breeding in ginseng.

On an industrial plant, we observed and examined the ammonia-poisoning catalyst for the synthesis of dimethyl oxalate (DMO). We investigated the catalytic activity in response to the amount of ammonia and revealed the mechanism of such poisoning by X-ray photoelectron spectroscopy (XPS) characterization. Our results show that only 0.002% ammonia in the feed gas can significantly deactivate the Pd-based catalyst. Two main reasons were proposed: one is that the competitive adsorption of ammonia on the active component Pd hinders the carbon monoxide (CO) coupling reaction and the redox cycle between Pd0 and Pd2+; and the other is that the high-boiling nitrogen-containing amine compounds formed by reacting with ammonia have adsorbed on the catalyst, which hinders the progress of the catalytic reaction. The deactivation caused by the latter is irreversible. The catalytic activity can be completely restored by a low-temperature liquid-phase in-situ regeneration treatment. Copyright © 2021 by Authors, Published by BCREC Group. This is an open access article under the CC BY-SA License (https://creativecommons.org/licenses/by-sa/4.0).

In this paper, we consider a Neumann problem of Kirchhoff type equation \begin{equation*} \begin{cases} \displaystyle-\left(a+b\int_{\Omega}|\nabla u|^2dx\right)\Delta u+u= Q(x)|u|^4u+\lambda P(x)|u|^{q-2}u, &\rm \mathrm{in}\ \ \Omega, \\ \displaystyle\frac{\partial u}{\partial v}=0, &\rm \mathrm{on}\ \ \partial\Omega, \end{cases} \end{equation*} where $\Omega$ $\subset$ $\mathbb{R}^3$ is a bounded domain with a smooth boundary, $a,b>0$, $10$ is a real parameter, $Q(x)$ and $P(x)$ satisfy some suitable assumptions. By using the variational method and the concentration compactness principle, we obtain the existence and multiplicity of nontrivial solutions.

Abstract Background Intussusception is the most common abdominal emergency in children. The first line treatment of uncomplicated pediatric intussusception is enema reduction. Until now, there have been no multi-center studies comparing the effectiveness and safety of UGHR and FGAR in the treatment of pediatric intussusception. The aim of this study was to compare the effectiveness and safety of the two most commonly used enema methods of pediatric intussusception: ultrasound-guided hydrostatic reduction (UGHR) and fluoroscopy-guided air reduction (FGAR). Methods From November 1, 2017 to October 31, 2018, we conducted a multi-center, prospective, cohort study. Children diagnosed with intussusception in four large Children’s Medical Centers in China were divided into UGHR and FGAR groups. Stratified analysis and subgroup analysis were used for further comparison. The success and recurrence rates were used to evaluate the effectiveness of enema reduction. The perforation rate was used to evaluate the safety of enema reduction. Results A total of 2124 cases met the inclusion criteria (UGHR group: 1119 cases; FGAR group: 1005 cases). The success and recurrence rates in the UGHR group were higher than in the FGAR group (95.80%, 9.28% vs. 93.13%, 10.65%) (P < 0.05, P > 0.05), respectively. The perforation rate in the UGHR group was 0.36% compared with 0.30% in the FGAR group (P > 0.05). Subgroup analysis showed the success rates in the UGHR group were higher than in the FGAR group of patients with onset time between 12 and 24 h (95.56% vs. 90.57%) (P < 0.05). Of patients aged 4 to 24 months, the success rates in the UGHR group were also higher than in the FGAR group (95.77% vs. 91.60%) (P < 0.05). Stratified analysis showed the success rates in the UGHR group were higher than in the FGAR group in patients with the symptom of bloody stool (91.91% vs 85.38%) (P < 0.05). Conclusions UGHR and FGAR are safe, nonsurgical treatment methods for acute pediatric intussusception. UGHR is superior to FGAR, no radiation risk, its success rate is higher, without a difference in perforation rate, especially for patients aged 4–24 months. Level of evidence Level II.

Batch mode active learning, where a batch of samples is simultaneously selected and labeled, is a challenging task. The challenge lies in how to maintain the informativeness and keep the diversity of selected samples concurrently. We propose a novel batch mode active learning that balances the informativeness and representativeness using multi-set clustering. Our method utilizes a sequential active learner to retain the informativeness by providing a ranking of unlabeled samples and constructing multiple informative sets for the subsequent clusterings. K-means clustering is used to minimize the redundancy among these samples and to improve the representativeness. Finally, the optimal batch chosen is the one minimizing the expected predictive variance on all the data. Our experimental results on a large number of benchmark datasets demonstrate excellent performance of the proposed method in comparison with current state-of-the-art batch mode active learning approaches.