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Abstract SPRED3 (Sprouty-related EVH1 domain containing 3) mutants are depicted in various cancers, however, nothing is known about its biofunction in thyroid cancer (THCA). Bioinformatic analyses were conducted to ascertain the level of SPRED3 expression in THCA tissues and its importance in the prognosis of THCA patients. Flag-SPRED3 plasmid and SPRED3-knockout vector were developed to overexpress or deplete the SPRED3 expression in THCA cells. The function of SPRED3 on THCA cell proliferation was examined using the colony formation assay and CCK8 assay. The effect of SPRED3 expression on the transcriptional activity of NF-κB was also examined using luciferase reporter assays. High SPRED3 expression was associated with unfavorable clinical outcomes, advanced tumor characteristics, and traditional molecular markers of papillary thyroid cancer in THCA patients. Genetic analysis revealed differences in mutation rates in key genes between SPRED3-high and SPRED3-low THCA cases. It is also revealed that SPRED3 influenced the immune microenvironment, with increased stromal and immune scores and altered immune cell infiltration. Functionally, SPRED3 overexpression enhanced THCA cell viability and colony formation, while its depletion reduced cell growth and proliferation. In vivo experiments in mice confirmed the inhibitory effect of SPRED3 depletion on tumor growth. Mechanically, we found that SPRED3 activated the NF-κB signaling. For the first time, we found that SPRED3 promotes THCA cell proliferation via the NF-κB signaling pathway. This finding may provide insight into SPRED3’s prognostic potential in thyroid cancer and provide the rationale for SPRED3-targeted druggable interventions.

BackgroundImmune checkpoint inhibitors have demonstrated promising therapeutic outcomes in recurrent/metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC), prompting numerous clinical trials to investigate the safety and efficacy of this approach in neoadjuvant therapy. This systematic review aims to consolidate and analyze the findings from various clinical trials combining neoadjuvant immunotherapy for HNSCC, with the goal of identifying the most effective neoadjuvant immunotherapy regimen.MethodsThe system conducted searches across electronic databases including PubMed, Embase, the Cochrane Library and Web of science from their inception to July 1, 2024. The primary focus was on evaluating efficacy (particularly pathological complete response (pCR), major pathological response (MPR), and overall response rate (ORR)) and safety (primarily assessed by grade 3-4 treatment-related adverse reactions).ResultsA total of 1943 patients from 32 studies were analyzed. Combining neoadjuvant immunotherapy with chemotherapy or radiotherapy demonstrated superiority over neoadjuvant immunotherapy alone in terms of the MPR rate, while showing no statistically significant difference in the pCR rate. Furthermore, the combination of neoadjuvant immunotherapy with chemotherapy or radiotherapy exhibited a lower CR rate compared to neoadjuvant immunotherapy with radiotherapy alone, but a higher PR rate and SD rate. Apart from the neoadjuvant immunotherapy group in isolation, there were no statistically significant differences in grade ≥3 treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) among the other three combination therapy groups.ConclusionThis systematic review and meta-analysis indicate that patients with locally advanced HNSCC might benefit from neoadjuvant immunotherapy, particularly when used in conjunction with chemotherapy or radiotherapy. Nonetheless, additional data is required to definitively confirm its efficacy.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=553753, identifier CRD42024553753.

The potential role of peroxisome proliferator-activated receptor (PPAR) in regulating the biosynthesis of long-chain polyunsaturated fatty acids (LCPUFA) has not been explored in marine gastropod. In this study, we identified and characterized a PPAR gene from the abalone species Haliotis discus hannai Ino. This gene encodes a peptide consisting of 469 amino acids and comprises typical four domains: A/B domain, DNA-binding domain, D domain, and ligand-binding domain. Highest homology with that of the Patella depressa (51.08 %) from multiple alignments and phylogenetic tree analyses revealed it is a direct orthologue of the vertebrate PPAR. Tissue distribution analysis demonstrated that PPAR was highly expressed in muscle and gill, with lower expression observed in the kidney, female gonad, and hepatopancreas. Dual-luciferase reporter assays indicated that abalone PPAR significantly up-regulated the promoter activity of Δ5 fatty acyl desaturase (Δ5fad), a crucial enzyme in LCPUFA biosynthesis. Furthermore, C18PUFA significantly increased the expressions of Δ5fad and PPAR in the hepatopancreas of abalone compared to the control group fed with an LCPUFA-rich diet. These findings suggest that PPAR acts as a positive transcription factor for the fad gene, contributing to the transcriptional regulation of LCPUFA biosynthesis in abalone.

Los agregadores de noticias han aumentado su presencia en el ecosistema mediático de China, especialmente a través de los dispositivos móviles. Estas plataformas se han convertido en el principal canal de adquisición de informaciones para la ciudadanía. Este estudio tiene como objetivo principal conocer los hábitos de uso de los usuarios de estas herramientas en ese país, y contrastarlos cona las características, funcionalidades y servicios presentes en estos agregadores. Tras aplicar una encuesta en línea con 474 respuestas válidas, el resultado muestra los perfiles de usuarios chinos, las tendencias generales de uso y la frecuencia con que se utilizan las diferentes opciones de estas aplicaciones. Estos hallazgos pretenden ser un punto de partida para detectar oportunidades de mejora para la calidad de servicio y la experiencia que brindan los agregadores de noticias.

The goal of this study was to evaluate the trace element pollution in a marine ranching area in China based on molecular responses (expression of metallothionein and antioxidant enzyme genes), and biochemical biomarkers (metallothionein content, antioxidant enzyme activities, and malonaldehyde level) in four indicator species. We collected samples of two fish (Lateolabrax maculatus and Sebastes schlegelii), one crustacean (Charybdis japonica), and one gastropod (Rapana venosa) from the western Furong Island marine ranching area and from an adjacent area in March 2022 and measured the trace element content in these indicator species as well as in the seawater and sediment. We found that the bioaccumulation characteristics of trace elements and the response patterns of biomarkers were species specific. Moreover, not every biomarker was significantly correlated with environmental trace element content. We then established two biomarker combinations indicative of trace element pollution in seawater and sediment, respectively, based on the correlation between biomarkers and trace element contents. The selected biomarkers were integrated using integrated biomarker response version 2 (IBRv2). IBRv2 values in the studied marine ranching area were lower than those in the adjacent area. Additionally, these values were consistent with the bioaccumulation of trace elements in the indicator species, the integrated trace element pollution index for seawater, and the potential risk index for sediment. These results show that this multi-biomarker and multi-species IBRv2 approach provided a comprehensive diagnosis of trace element pollution in the marine ranching area. Therefore, its application may be beneficial for marine environmental monitoring and management in view of the ecotoxicological impact of pollutants on organisms.

Abstract Background Cell senescence is a sign of aging and plays a significant role in the pathogenesis of age-related disorders. For cell therapy, senescence may compromise the quality and efficacy of cells, posing potential safety risks. Mesenchymal stem cells (MSCs) are currently undergoing extensive research for cell therapy, thus necessitating the development of effective methods to evaluate senescence. Senescent MSCs exhibit distinctive morphology that can be used for detection. However, morphological assessment during MSC production is often subjective and uncertain. New tools are required for the reliable evaluation of senescent single cells on a large scale in live imaging of MSCs. Results We have developed a successful morphology-based Cascade region-based convolution neural network (Cascade R-CNN) system for detecting senescent MSCs, which can automatically locate single cells of different sizes and shapes in multicellular images and assess their senescence state. Additionally, we tested the applicability of the Cascade R-CNN system for MSC senescence and examined the correlation between morphological changes with other senescence indicators. Conclusions This deep learning has been applied for the first time to detect senescent MSCs, showing promising performance in both chronic and acute MSC senescence. The system can be a labor-saving and cost-effective option for screening MSC culture conditions and anti-aging drugs, as well as providing a powerful tool for non-invasive and real-time morphological image analysis integrated into cell production.

Spaceborne antennas operated in the very low frequency (VLF: 3-30kHz) ranges play important roles in ionosphere exploration, satellite communication, and submarine communication. In this paper, we idealize the receiving antenna mounted on the satellite as a finite-length conducting cylinder and establish a theoretical approach for scattering characteristics of a cylinder in the ionosphere, behaving as an anisotropic plasma. Analytical expressions of scattered fields and current distributions of cylinders are derived with the integral equation (IE) method and method of moment (MoM). Contributions from the ordinary wave (O-wave) and extra-ordinary wave (E-wave) are combined to represent the total scattering and surface current induced on the cylinder. Numerical results show that the current distribution exhibits sensitivity to the dimension of the structure, including the radius and length of the cylinder and the incident angle. For instance, a symmetrical current distribution is obtained under normal incidence, while an offset current is generally found under oblique incidence. A “cohesion effect” along the direction of the geomagnetic field in the scattered pattern is observed. Moreover, the scattering to the E-wave is greater than that of the O-wave. Interestingly, the radar cross section (RCS) is gradually suppressed as the observation angle increases, in contrast to the conventional scattering in the free space. Potentially, the theoretical formulations and the predicted phenomena would help in understanding the basic properties of the VLF scattering in the ionosphere and planning related ionospheric experiments.

Abstract Reflective displays have the advantages of energy efficiency, high brightness, eye protection, and good readability, making them an attractive display technology. Photonic crystal (PhC) structural color is highly regarded as an ideal choice for reflective displays for its ecofriendliness, colorfastness, and adjustability. In this review, we introduce the fundamental classification and manufacturing methods of PhC reflective displays. We systematically summarize the display principles of PhC‐based displays driven by various stimuli. Furthermore, we present the latest research advancements in PhC displays based on smart actuators. Additionally, we offer a detailed overview of the current research status and application prospects of liquid crystal structural color displays and three‐dimensional PhC displays. Finally, we discuss the challenges faced by PhC displays and provide insights into their prospects.

In response to the incidence of cervical intraepithelial neoplasia and cervical cancer in China and global screening strategies, a collaborative effort was undertaken by seven Chinese medical associations to develop this guideline for cervical cancer screening. The guideline recommends high-risk human papillomavirus (hr-HPV) testing as the preferred method for primary screening, which should have been approved by authoritative institutions and clinically validated for primary screening. In areas without access to HPV testing, cytology can be used as an alternative. However, it is recommended to replace cytology with HPV-based screening as conditions permit. Cotesting (HPV testing in combination with cytology) is recommended for areas with sufficient medical resources, opportunistic screening populations, and partial special populations. The guideline recommends that individuals with a cervix initiate cervical cancer screening at the age 25 years and undergo HPV testing alone or cotesting every five years, or cytology alone every three years. Women over the age of 65 who have had documented adequate negative prior screening in the past may terminate screening. Corresponding screening programs are proposed for different special populations. The development of these guidelines is an important step in the effort to eliminate cervical cancer in China.

Virus-like particles (VLPs) have been studied and used as vaccines to control foot-and-mouth disease (FMD). Mast cells (MCs) express various pattern recognition receptors that recognize pathogens and secrete numerous cytokines to initiate and modulate immune responses. Our previous study showed that bone marrow-derived mast cells (BMMCs) can recognize foot-and-mouth disease virus-like particles (FMDV-VLPs) to differentially express various cytokines and that histone acetylation can regulate the cytokines secreted during BMMC recognition of FMDV-VLPs. To demonstrate the role of DNA methylation in this response process, BMMCs that recognize FMDV-VLPs were treated with azacytidine (5-AZA), an inhibitor of DNA methylation transferase. We prepared FMDV-VLPs as described previously and cultured the BMMCs. The transcription and expression of key cytokines and transcription factors were determined using real-time quantitative PCR (RT-qPCR) and Western blotting. Results showed that pre-treatment with AZA resulted in the increased transcription and expression of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-13, and IL-10, while the changes in IL-13 transcription and IL-6 expression were irrelevant to mannose receptors (MRs). Furthermore, analysis of the transcription factors indicated that both the transcription and expression of nuclear factor-kappa B (NF-κB) increased significantly in the AZA pre-treated group, indicating that DNA methylation may also regulate NF-κB expression to modulate TNF-α, IL-13, and IL-6. However, pre-treatment with AZA did not alter the expression of microphthalmia-associated transcription factor (MITF) or GATA-2. All the data demonstrate that DNA methylation negatively regulates the transcription and expression of TNF-α, IL-13, IL-10, and IL-6 secreted by recognizing FMDV-VLPs. These results provide new ideas for the mast cell-based design of more effective vaccine adjuvants and targeted therapies in the future.

Inter- and intra-specific variations in phenotype are common and can be associated with genomic mutations as well as epigenomic variation. Profiling both genomic and epigenomic variants is at the core of dissecting phenotypic variation. However, an efficient targeted genotyping and epigenotyping system is lacking. We describe a new multiplex targeted genotyping and epigenotyping system called improved bulked-PCR sequencing (iBP-seq). We employed iBP-seq for the detection of genotypes and methylation levels of dozens of target regions in mixed DNA samples. iBP-seq can be adapted for the construction of linkage maps, fine mapping of quantitative-trait loci, and detection of genome editing mutations at a cost as low as $0.016 per site per sample. We developed an automated bioinformatics pipeline, including primer design, a series of bioinformatic analyses for genotyping and epigenotyping, and visualization of results. iBP-seq and its bioinformatics pipeline, available at http://zeasystemsbio.hzau.edu.cn/tools/ibp/, can be adapted to a wide variety of species.

Aims: Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. This study aims to investigate the clinicopathological features and prognosis of NECC. Methods: A retrospective analysis was conducted on twenty-one patients diagnosed with NECC between May 2008 and September 2021 ​at Peking University People's Hospital. The study involved histopathological examination, immunohistochemistry, ThinPrep cytology test (TCT), and high-risk HPV hybrid capture 2 (HC2) assay. Follow-up was conducted through telephone interviews and medical records for a range of 3–160 months, with an average follow-up period of 49.8 months. Results: The average age of the patients was 48.6 years (range: 33–69 years). Seventeen patients were diagnosed with neuroendocrine carcinoma through biopsy. Nine cases underwent TCT and HC2 tests before biopsy, and TCT results of four cases showed high-grade squamous intraepithelial lesion (HSIL). High-risk HPV(HR-HPV) positive was detected in seven cases. The cancer cells exhibited consistent morphological features, including sparse cytoplasm, intensely stained nuclei, and extensive neoplastic necrosis. Thirteen cases were classified as pure NECC (61.9%), while eight cases were mixed types (38.1%). Three cases were associated with squamous cell carcinoma (SCC), and five cases were associated with adenocarcinoma. Prognosis varied significantly among these subtypes (p ​

Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches.

Fhb7 is a major gene that was transferred from Thinopyrum ponticum to chromosome 7D of wheat (Triticum aestivum) and confers resistance to both Fusarium head blight (FHB) and Fusarium crown rot (FCR). However, Fhb7 is tightly linked to the PSY-E2 gene, which causes yellow flour, limiting its application in breeding. To break this linkage, marker K-PSY was developed for tagging PSY-E2 and used with Fhb7 markers to identify recombination between the two genes. Screening 21,000 BC1F2 backcross progeny (Chinese Spring ph1bph1b*2/SDAU 2028) revealed two Fhb7+ wheat-Tp7el2L lines, Shannong 2–16 and Shannong 16–1, that carry a desired truncated Fhb7+ translocation segment without PSY-E2. The two lines show levels of resistance to FHB and FCR similar to those of the original translocation line SDAU 2028, but have white flour. To facilitate Fhb7 use in wheat breeding, STS markers were developed and used to isolate Fhb7 on a truncated Tp7el2 translocation segment. Near-isogenic lines carrying the Fhb7+ segment were generated in the backgrounds of three commercial cultivars, and Fhb7+ lines showed increased FHB and FCR resistance without yield penalty. The breakage of the tight linkage between Fhb7 and PSY-E2 via homoeologous recombination provides genetic resources for improvement of wheat resistance to FHB and FCR and permit the large-scale deployment of Fhb7 in breeding using marker-assisted selection.

Food fraud is widespread in the aquatic food market, hence fast and non-destructive methods of identification of fish flesh are needed. In this study, multispectral imaging (MSI) was used to screen flesh slices from 20 edible fish species commonly found in the sea around Yantai, China, by combining identification based on the mitochondrial COI gene. We found that nCDA images transformed from MSI data showed significant differences in flesh splices of the 20 fish species. We then employed eight models to compare their prediction performances based on the hold-out method with 70% training and 30% test sets. Convolutional neural network (CNN), quadratic discriminant analysis (QDA), support vector machine (SVM), and linear discriminant analysis (LDA) models perform well on cross-validation and test data. CNN and QDA achieved more than 99% accuracy on the test set. By extracting the CNN features for optimization, a very high degree of separation was obtained for all species. Furthermore, based on the Gini index in RF, 11 bands were selected as key classification features for CNN, and an accuracy of 98% was achieved. Our study developed a successful pipeline for employing machine learning models (especially CNN) on MSI identification of fish flesh, and provided a convenient and non-destructive method to determine the marketing of fish flesh in the future.

Ferroptosis is a form of cell death, i.e., programmed cell death characterized by lipid peroxidation and iron dependence, which has unique morphological and biochemical properties. This unique mode of cell death is driven by iron-dependent phospholipid peroxidation and regulated by multiple cell metabolic pathways, including redox homeostasis, iron metabolism, mitochondrial activity, and the metabolism of amino acids, lipids, and sugars. Many organ injuries and degenerative pathologies are caused by ferroptosis. Ferroptosis is closely related to central nervous system injury diseases and is currently an important topic of research globally. This research examined the relationships between ferroptosis and the occurrence and treatment of central nervous system injury diseases. Additionally, ferroptosis was assessed from the aspect of theory proposal, mechanism of action, and related signaling pathways per recent research. This review provides a relevant theoretical basis for further research on this theory, the prospect of its development, and the prevention and treatment of such diseases.

Abstract For a drop on a very hot solid surface, a vapor film will form beneath the drop, which has been discovered by Leidenfrost in 1756. The vapor escaping from the Leidenfrost film causes uncontrollable flows, and actuates the drop to move around. Recently, although numerous strategies have been used to regulate the Leidenfrost vapor, the understanding of surface chemistry for modulating the phase-change vapor dynamics remains incomplete. Here, we report how to rectify vapor by “cutting” the Leidenfrost film using chemically heterogeneous surfaces. We demonstrate that the segmented film cut by a Z-shaped pattern can spin a drop, since the superhydrophilic region directly contacts the drop and vaporizes the water, while a vapor film is formed on the superhydrophobic surrounding to jet vapor and reduce heat transfer. Furthermore, we reveal the general principle between the pattern symmetry design and the drop dynamics. This finding provides new insights into the Leidenfrost dynamics modulation, and opens a promising avenue for vapor-driven miniature devices.

Abstract Gastric cancer is the fourth leading cause of cancer deaths worldwide. Most patients are diagnosed in the advanced stage. Inadequate therapeutic strategies and the high recurrence rate lead to the poor 5-year survival rate. Therefore, effective chemopreventive drugs for gastric cancer are urgently needed. Repurposing clinical drugs is an effective strategy for discovering cancer chemopreventive drugs. In this study, we find that vortioxetine hydrobromide, an FDA-approved drug, is a dual JAK2/SRC inhibitor, and has inhibitory effects on cell proliferation of gastric cancer. Computational docking analysis, pull-down assay, cellular thermal shift assay (CETSA) and in vitro kinase assays are used to illustrate vortioxetine hydrobromide directly binds to JAK2 and SRC kinases and inhibits their kinase activities. The results of non-reducing SDS-PAGE and Western blotting indicate that vortioxetine hydrobromide suppresses STAT3 dimerization and nuclear translocation activity. Furthermore, vortioxetine hydrobromide inhibits the cell proliferation dependent on JAK2 and SRC and suppresses the growth of gastric cancer PDX model in vivo. These data demonstrate that vortioxetine hydrobromide, as a novel dual JAK2/SRC inhibitor, curbs the growth of gastric cancer in vitro and in vivo by JAK2/SRC-STAT3 signaling pathways. Our results highlight that vortioxetine hydrobromide has the potential application in the chemoprevention of gastric cancer.

Abstract Background Maize (Zea mays L.) is one of the most important crops worldwide. Although sophisticated maize gene regulatory networks (GRNs) have been constructed for functional genomics and phenotypic dissection, a multi-omics GRN connecting the translatome and transcriptome is lacking, hampering our understanding and exploration of the maize regulatome. Results We collect spatio-temporal translatome and transcriptome data and systematically explore the landscape of gene transcription and translation across 33 tissues or developmental stages of maize. Using this comprehensive transcriptome and translatome atlas, we construct a multi-omics GRN integrating mRNAs and translated mRNAs, demonstrating that translatome-related GRNs outperform GRNs solely using transcriptomic data and inter-omics GRNs outperform intra-omics GRNs in most cases. With the aid of the multi-omics GRN, we reconcile some known regulatory networks. We identify a novel transcription factor, ZmGRF6, which is associated with growth. Furthermore, we characterize a function related to drought response for the classic transcription factor ZmMYB31. Conclusions Our findings provide insights into spatio-temporal changes across maize development at both the transcriptome and translatome levels. Multi-omics GRNs represent a useful resource for dissection of the regulatory mechanisms underlying phenotypic variation.

WeChat has become the most popular type of social media among youngsters in China. They use it for various reasons including communicating in intimate relationships. This study aims to investigate the impact of the density of individuals’ social networks on WeChat Usage in Intimate Relationships among Chinese youngsters, guided by the Theory of Planned Behaviour (TPB). An online questionnaire was constructed and disseminated to respondents online. In total, 923 undergraduate students from Chinese universities completed the questionnaires. Utilizing Structural Equation Modelling, findings show that the density of individuals’ social networks has a limited impact on WeChat usage. On the other hand, TPB factors such as subjective norms and perceived control bring a substantial impact on WeChat usage, while attitude has a less significant impact. These results indicate that Chinese youngsters exhibit strong attributes of the collective culture. This study also suggests that future social media research should place more emphasis on cultural and social factors.

IntroductionNon-suicidal self-injury (NSSI) is highly prevalent in depression, and is associated with psychosocial factors, emotion dysregulation, and strategies of cognitive emotion regulation. However, the internal combination and interactions of these risk factors in depression remain unclear.MethodsData from 122 patients with depression, including 56 with NSSI and 66 without NSSI, were analyzed. Self-rating scales were used to assess psychosocial factors, emotion dysregulation, and cognitive regulation strategies. Sparse partial least squares discriminant analysis (sPLS-DA) was employed to explore internal combinations in each profile. A moderated mediation model was applied to examine their interactional relationship.ResultsThe results identified an NSSI-related psychosocial profile characterized by high neuroticism, childhood trauma, poor family functioning, and low psychological resilience. Emotion dysregulation, including high levels of alexithymia, anhedonia, and emotion regulation difficulties, mediated the association between this psychosocial profile and NSSI. The mediated effect was further moderated by maladaptive cognitive regulation strategies.LimitationsLack of sufficient information on NSSI frequency and severity. Relatively small sample size for discussing the impact of gender and age of depressive patients with NSSI.ConclusionThese findings hold important implications for the prevention, treatment, and rehabilitation of NSSI.

Abstract Esophageal squamous cell carcinoma (ESCC) is an upper gastrointestinal cancer with high morbidity and mortality. New strategies are urgently needed to prolong patients’ survival. Through screening FDA-approved drugs, we found dasabuvir, a drug approved for hepatitis C virus (HCV) treatment, suppressed ESCC proliferation. Dasabuvir could inhibit the growth of ESCC cells in a time and dose-dependent manner and arrested cell cycle at the G0/G1 phase. The antitumor activity was further validated in vivo using patient-derived xenograft tumor models. In terms of mechanism, we unveil that dasabuvir is a Rho-associated protein kinase 1 (ROCK1) inhibitor. Dasabuvir can bind to ROCK1 and suppress its kinase activity, thus downregulating the phosphorylation of ERK1/2 by ROCK1 and the expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1. These results provide evidence that dasabuvir suppresses ESCC growth in vivo and in vitro through blocking ROCK1/ERK signaling pathway.

Breast cancer occurs in the epithelial tissue of the gland, so the accuracy of gland segmentation is crucial to the physician's diagnosis. An innovative technique for breast mammography image gland segmentation is put forth in this paper. In the first step, the algorithm designed the gland segmentation evaluation function. Then a new mutation strategy is established, and the adaptive controlled variables are used to balance the ability of improved differential evolution (IDE) in terms of investigation and convergence. To evaluate its performance, The proposed method is validated on a number of benchmark breast images, including four types of glands from the Quanzhou First Hospital, Fujian, China. Furthermore, the proposed algorithm is been systematically compared to five state-of-the-art algorithms. From the average MSSIM and boxplot, the evidence suggests that the mutation strategy may be effective in searching the topography of the segmented gland problem. The experiment results demonstrated that the proposed method has the best gland segmentation results compared to other algorithms.

Epidemiological and mechanistic studies suggest that some US Food and Drug Administration (FDA)-approved drugs can reduce the incidence of cancer and inhibit tumor growth. Therefore, investigating FDA-approved drugs for cancer chemoprevention is a promising strategy. In this study, we screened FDA-approved drugs and found that azelnidipine, a Ca channel blocker widely used in the treatment of hypertension, inhibits the growth of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. We identified that MEK1/2 were direct targets of azelnidipine through pull-down assay and cellular thermal shift assay. Azelnidipine could suppress kinase activity of MEK1/2 through in vitro kinase assay. Hypophosphorylation of ERK1/2 decreased the levels of Cyclin D1/CDK6 in ESCC cells after azelnidipine treatment. More importantly, azelnidipine, like trametinib, inhibited the growth of ESCC in vivo. In conclusion, azelnidipine, a novel dual MEK1/2 inhibitor, exerted antitumor effects against ESCC cell lines and patient-derived xenograft in ESCC.

Abstract Luminescence is an essential signal for many plants, insects, and marine organisms to attract the opposite sex, avoid predators, and so on. Most luminescent living organisms have ingenious optical structures which can help them get high luminescent performances. These remarkable and efficient structures have been formed by natural selection from long‐time evolution. Researchers keenly observed the enhanced luminescence phenomena and studied how these phenomena happen in order to learn the characteristics of bio‐photonics. In this review, we summarize the optical structures for enhancing luminescence and their applications. The structures are classified according to their different functions. We focus on how researchers use these biological inspirations to enhance different luminescence processes, such as chemiluminescence (CL), photoluminescence (PL), and electroluminescence (EL). It lays a foundation for further research on the applications of luminescence enhancement. Furthermore, we give examples of luminescence enhancement by bio‐inspired structures in information encryption, biochemical detection, and light sources. These examples show that it is possible to use bio‐inspired optical structures to solve complex problems in optical applications. Our work will provide guidance for research on biomimetic optics, micro‐ and nano‐optical structures, and enhanced luminescence.

Rechargeable Zn metal batteries (RZMBs) have emerged as promising candidates for large-scale energy storage systems due to their high safety, environmental friendliness, and low cost. However, Zn metal anode still faces a series of side reactions, including hydrogen evolution, dendrite, corrosion, and passivation. Moreover, emerging electronic devices such as flexible electronic devices, portable electronic devices and linear energy devices, have different functional requirements for energy storage technologies, which cannot be met by conventional Zn foil anode. In the face of these challenges, designing new configuration of Zn anode is urgently needed. This review summarizes the advances of various new configuration anode materials, including three-dimensional Zn anode, 3D printed Zn anode, printed Zn anode, imprinted Zn anode, linear Zn anode and their energy storage devices. The advantages, challenges and corresponding strategies of these new configuration anode were discussed. Finally, future development directions and perspectives of these anode materials were presented.

Mast cells can recognize foot-and-mouth disease virus-like particles (FMDV-VLPs) via mannose receptors (MRs) to produce differentially expressed cytokines. The regulatory role of chromatin accessibility in this process is unclear. Bone marrow-derived mast cells (BMMCs) were cultured, and an assay of transposase-accessible chromatin sequencing (ATAC-seq) was applied to demonstrate the regulation of chromatin accessibility in response to the BMMCs’ recognition of FMDV-VLPs. A pathway enrichment analysis showed that peaks associated with the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), and other signaling pathways, especially the NF-κB pathway, were involved in the BMMCs’ recognition of VLPs. Moreover, transcription factors including SP1, NRF1, AP1, GATA3, microphthalmia-associated transcription factor (MITF), and NF-κB-p65 may bind to the motifs with altered chromatin accessibility to regulate gene transcription. Furthermore, the expression of NF-κB, interleukin (IL)-9, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the BMMCs of the VLP group increased compared with that of the BMMCs in the control group, whereas the expression of IL-10 did not differ significantly between groups. After inhibiting the MRs, the expression of NF-κB, IL-9, TNF-α, and IFN-γ decreased significantly, whereas the expression of IL-10 increased. The expression of MAPK and IL-6 showed no significant change after MR inhibition. This study demonstrated that MRs expressed on BMMCs can affect the NF-κB pathway by changing chromatin accessibility to regulate the transcription of specific cytokines, ultimately leading to the differential expression of cytokines. These data provide a theoretical basis and new ideas for the development of a novel vaccine for FMD.

Objectives: Deregulation of long non-coding RNAs (lncRNAs) has been frequently reported in breast cancer (BC). This goes to show the importance of understanding its significant contribution towards breast carcinogenesis. In the present study, we clarified a carcinogenic mechanism based on the ARRDC1-AS1 delivered by breast cancer stem cells-derived extracellular vesicles (BCSCs-EVs) in BC. Methods: The isolated and well characterized BCSCs-EVs were co-cultured with BC cells. The expression of ARRDC1-AS1, miR-4731-5p, and AKT1 was determined in BC cell lines. BC cells were assayed for their viability, invasion, migration and apoptosis in vitro by CCK-8, Transwell and flow cytometry, as well as tumor growth in vivo after loss- and gain-of function assays. Dual-luciferase reporter gene, RIP and RNA pull-down assays were performed to determine the interactions among ARRDC1-AS1, miR-4731-5p, and AKT1. Results: Elevation of ARRDC1-AS1 and AKT1 as well as miR-4731-5p downregulation were observed in BC cells. ARRDC1-AS1 was enriched in BCSCs-EVs. Furthermore, EVs containing ARRDC1-AS1 enhanced the BC cell viability, invasion and migration and glutamate concentration. Mechanistically, ARRDC1-AS1 elevated the expression of AKT1 by competitively binding to miR-4731-5p. ARRDC1-AS1-containing EVs were also found to enhance tumor growth in vivo. Conclusion: Collectively, BCSCs-EVs-mediated delivery of ARRDC1-AS1 may promote the malignant phenotypes of BC cells via the miR-4731-5p/AKT1 axis.

Abstract Stimuli‐responsive structural coloration allows the color change of soft substrates in response to environmental stimuli such as heat, humidity, and solvents. Such color‐changing systems enable smart soft devices, such as the camouflageable skin of soft robots or chromatic sensors in wearable devices. However, individually and independently programmable stimuli‐responsive color pixels remain significant challenges among the existing color‐changing soft materials and devices, which are crucial for dynamic display. Inspired by the dual‐color concavities on butterfly wings, a morphable concavity array to pixelate the structural color of two‐dimensional photonic crystal elastomer and achieve individually and independently addressable stimuli‐responsive color pixels is designed. The morphable concavity can convert its surface between concave and flat upon changes in the solvent and temperature, accompanied by angle‐dependent color‐shifting. Through multichannel microfluidics, the color of each concavity can be controllably switched. Based on the system, the dynamic display by forming reversibly editable letters and patterns for anti‐counterfeiting and encryption are demonstrated. It is believed that the strategy of pixelating optical properties through locally altering surface topography can inspire the design of new transformable optical devices, such as artificial compound eyes or crystalline lenses for biomimetic and robotic applications.

The incidence rate and mortality rate of cervical cancer have steadily increased in young women in China. Therefore, it is critical to improve HPV vaccination rates, particularly for the younger population. There are currently five types of prophylactic vaccines in China: bivalent HPV vaccine (AS04-HPV-16/18), quadrivalent HPV vaccine, 9-valent HPV vaccine, homemade Escherichia coli-produced HPV bivalent vaccine, and Pichia pastoris produced HPV bivalent vaccine. All these five HPV vaccines have completed relevant clinical trials in China, and have been proven to be generally well-tolerated and immunogenic, efficacious against persistent HPV-related infections and genital precancerous lesions (data for 9-valent HPV vaccine is absent), and have demonstrated acceptable safety profiles, as previously shown in global studies. Given that the HPV vaccination rate in China is still very low, additional HPV vaccine coverage is needed to reduce the incidence and mortality rates of cervical cancer.

The multi-criteria group decision-making approach, rooted in fuzzy mathematics theory, is employed to address the globally significant issue of green construction in this paper. The construction industry is one of the most prominent contributors to carbon emissions, which is evident throughout the entire supply chain. Meanwhile, the renovation of old residential communities is a large-scale urban construction project in China. In striving to advance the sustainable development of the construction industry and meet decarbonization goals, the attention has shifted towards green construction in the renovation of old residential communities. However, substantial gaps persist in both technical innovation and practical application of green construction. This study aims to identify the factors that influence the popularization and implementation of green construction practices in the renovation of old residential communities. To achieve this, a comprehensive decision-making approach is sought, and these factors are thoroughly investigated. In this paper, we propose a hybrid decision-making framework that incorporates grounded theory, the fuzzy decision-making and trial evaluation laboratory (DEMATEL) method, and the analytic network process (ANP) method. Leveraging triangular fuzzy numbers and other fuzzy mathematical theories, this approach is designed to assess the factors that influence the popularization and implementation of green construction practices, uncovering their interrelationships and mechanisms. The results indicate the comprehensive nature of advancing green construction practices, encompassing the entire supply chain involved in the renovation of old residential communities. Among these factors, social participation and market environment emerge as the most influential. Building upon these conclusions, this paper offers specific recommendations. Ultimately, this study equips the construction industry with both a theoretical foundation and a methodological framework to popularize and implement green construction practices effectively.

In this article, we develop an efficient numerical scheme for dealing with fractional partial integro-differential equations (FPIEs) with a weakly singular kernel. The weight and shift Grünwald difference (WSGD) operator is adopted to approximate a time fractional derivative and the Sinc collocation method is applied for discretizing the spatial derivative.The exponential convergence of our proposed method is demonstrated in detail. Finally, numerical evidence is employed to verify the theoretical results and confirm the expected convergence rate.

To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head, O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol (cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen (FP), isosorbide dinitrate (ISDN) and donepezil (DNP), which were selected based on their physicochemical properties, was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers. The results indicated that (E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate (GER-C14, trans-) achieved the highest enhancement ability for the three drugs; additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum (SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.

BackgroundIdentifying high-risk groups of non-suicidal self-injury (NSSI) with multiple risk factors and different functional subtypes contribute to implementing person-centered interventions.MethodsWe investigated NSSI profiles among a sample of 258 psychiatric inpatients aged 18–25 years. All participants completed well-validated measures of internal personal and external environmental characteristics. One-hundred and ninety patients reported a lifetime history of NSSI and completed an additional NSSI assessment. A k-means cluster analysis was conducted to extract characteristics of risk factors and functional subtypes. Independent sample t-test, analysis of variance and χ2 test were used to test the difference of demographic statistical factors, risk factors and functional scores among groups with different frequency of NSSI.ResultsThe clustering of risk factors analyses supported 4-clusters. The proportion of repeat NSSI patients was the highest (67.1%) in the group with unfavorable personal and unfavorable environmental characteristics. Functional subtype clustering analyses supported 5-clusters. Among patients with repeated NSSI, those with depression were mainly accompanied by the “Sensation Seeking” subtype (39.7%), bipolar disorder mainly supported the “Anti-suicide” subtype (37.9%), and eating disorders were mostly “Social Influence” subtype (33.3%). There was an interaction between functional subtypes and mental disorders.LimitationsAll participants were in treatment in a psychiatric service and the results may not be generalizable to a community sample. The data included retrospective self-report which may be inaccurate due to recall bias.ConclusionIt is necessary to identify high-risk groups of NSSI who with unfavorable personal and environmental characteristics and clinical interventions need to consider the heterogeneity of patients’ functional subtypes of NSSI.

Diet conversion is a key stage of seahorse aquaculture. Herein, we set up five groups to evaluate the probiotic effects of Enterococcus faecium supplementation on the growth, development, intestinal health, and immunity of big-belly seahorses (Hippocampus abdominalis) during this stage, including control (C) (no E. faecium), H2 (1 ×107 CFU mL−1, every 2 d), H4 (1 ×107 CFU mL−1, every 4 d), L2 (1 ×105 CFU mL−1, every 2 d), and L4 (1 × 105 CFU mL−1, every 4 d) groups. After 48 d culture, concentration and frequency of E. faecium supplementation, as well as their interaction, were confirmed to have significant effects on growth performance of seahorses (P < 0.05). Body weight, specific growth rate, body weight increase, standard length and standard length increase of H4 and L4 groups were significantly higher (P < 0.05); Ovary weight but not testis weight and brood pouch length significantly increased in H4 group (P

Selenium (Se) is required for the normal growth and development of aquatic animals. However, excessive Se can have various toxic effects on aquatic animals. In this study, we performed transcriptome analysis to determine the mechanism by which immunity and growth of abalone are affected by toxic dietary concentrations of Se. Four experimental diets were administered to supplement organic Se at concentrations of 0.00 (Control), 0.15 (Se15), 0.30 (Se30), and 0.60 mg/kg (Se60) to provide 0.16 (insufficient), 0.32 (optimal), 0.44 (super nutritional), and 0.60 mg/kg (toxic) Se concentrations in the diet. After feeding for 100 days, the results of the Gene Ontology (GO) analysis showed that the enriched GO terms of differentially expressed genes (DEGs) in the Se15 and Se30 groups were mainly focused on the cellular components, whereas the GO terms enriched in the Se60 group were mainly related to the metabolism of nutrients and the activities of various enzymes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs of the Se30 group were mainly enriched in various disease pathways, whereas the DEGs of the Se60 treatment were associated with the metabolism of various nutrients. Further analysis of DEGs showed that toxic dietary concentrations of Se decreased the immunity of abalone by affecting the biosynthesis and metabolism pathways of various nutrients. Additionally, toxic dietary concentrations of Se retarded the growth of abalone by decreasing the expression of various genes associated with shell formation, including lustrin A, perlucin, perlustrin, dermatopontin, chitin synthase, and chitinase as well as the genes associated with muscle production, including collagen, myosin heavy chain, myosin essential light chain, and paramyosin. In conclusion, the mechanism of the decrease of immunity and growth of abalone by toxic dietary concentrations of Se has been preliminary revealed in this study.

Mycoplankton play a key role in aquatic microbial food webs and nutrient cycling. However, the environmental factors that affect their composition and trophic modes in coastal water remain unclear. In this study, we used fungal metabarcoding to characterize seasonal mycoplanktonic communities in the surface water of the Maowei Sea. Dothideomycetes and Sordariomycetes were the dominant classes in the Maowei Sea. Random forest modeling analyses suggested that Ochroconis, Rhodotorula, Perenniporia and Derxomyces were the best seasonal bioindicators of environmental changes. Spearman’s correlation analysis showed that TOC (total organic carbon) is the main factor affecting mycoplanktonic bioindicators. Through FUNGuild analysis, we classified mycoplankton in the Maowei Sea into eight trophic modes and found that saprotrophs were the most abundant. Random forest analysis and Spearman’s correlation indicated that the mycoplankton trophic modes could reflect environmental changes in the Maowei Sea and were mainly influenced by dissolved inorganic phosphorus (DIP), dissolved oxygen (DO), and total organic carbon (TOC). Mycoplanktonic alpha and beta diversities significantly varied in different seasons (p

To investigate the dietary cholesterol requirements of large red swamp crayfish (Procambarus clarkii), crayfish (initial body weight: 13.49 ± 0.22 g) were hand-fed six diets containing 2.47 (C0), 4.27 (C1), 6.80 (C2), 8.77 (C3), 11.74 (C4), and 14.24 (C5) g/kg cholesterol. After 8 weeks of feeding, the maximum weight gain rate and specific growth rate occurred in group C4. The lowest feed conversion ratio was observed in group C3. Total flesh percentage increased significantly by 15.33% in group C2 compared to group C0. The increase in dietary cholesterol resulted in significant quadratic trends in concentrations of crude protein and lipid in muscle and whole body; cholesterol and free fatty acid in hemolymph, hepatopancreas, and muscle; activities of lipase and amylase in hepatopancreas and intestine; and total antioxidant capacity and catalase activity in hepatopancreas. Group C3 experienced a noteworthy increase in hemolymph glucose and total protein content compared to group C0. Additionally, malondialdehyde content and superoxide dismutase activity in hepatopancreas displayed significant linear and quadratic trends. The optimal dietary cholesterol level for large P. clarkii is between 7.42 and 10.93 g/kg, as revealed by the quadratic regression analysis.

With the increasing attention of the capital market to environmental, social and governance information, sustainability reporting has become an important carrier for stakeholders to gain insight into sustainability of companies. But the emerged "greenwashing" problem has also brought haze to the value creation of capital market. To study the consequences of the pseudo-social responsibility behavior of "greenwashing", this paper takes China's listed companies as the research sample to empirically examine the relationship between sustainability reporting "greenwashing" and "shared value" creation. It is found that the "greenwashing" behavior of corporate sustainability reporting significantly reduces the "shared value" creation, while the degree of sustainability information asymmetry and the quality of information disclosure play a partial mediation role between them. Further analysis shows that the more effective internal control of a company and the greater pressure of external media supervision, the more conducive to weaken the negative impact of "greenwashing" on "shared value" creation. This paper enriches the literature on the economic consequences of "greenwashing" in sustainability disclosure and the influencing factors of "shared value" creation, extends the research on information disclosure and "shared value" from financial information to non-financial information. The results call for the state to promote legislative work, formulate unified standards and compress the "greenwashing" gray space; Governments could implement mandatory disclosure, implement independent authentication and strengthen "greenwashing" social supervision; Companies should strengthen capacity building and improve the "greenwashing" governance mechanism with the help of digital empowerment.

ObjectiveTo explore the ability of PAX1 methylation (PAX1m) to predict the pathological upgrade of cervical intraepithelial neoplasia (CIN) before cold knife conization (CKC).MethodsA total of 218 women that underwent colposcopy-directed biopsy (CDB) pathology for the confirmation of CIN2 and CIN3 between December 2020 to September 2021 were enrolled in this study. The methylation levels of PAX1 (ΔCpPAX1) were determined by quantitative methylation-specific polymerase chain reaction (qMSP). Receiver operating characteristic curve was used to identify the optimal cut-off value of ΔCpPAX1 for predicting the pathological upgrade of disease.ResultsIn the CDB-confirmed CIN2 group, 36% of CIN2 was found to have pathologically upgraded to CIN3 and 30% regressed to low-grade squamous intraepithelial lesion (LSIL) and below, and none of CIN2 upgraded to early-stage cervical cancer (ESCC) after CKC. In the CDB-confirmed CIN3 group, 19.5% (23/118) of CDB-confirmed CIN3 were pathologically upgraded to ESCC after CKC. Regardless of CIN2 or CIN3, the ΔCpPAX1 level of women with upgraded pathology after CKC was significantly lower than that of women with degraded pathology. The optimal △CpPAX1 cut-off value in predicting CIN3 to be upgraded to ESCC after CKC was 6.360 and the area under the curve (AUC) was 0.814, with similar sensitivity (78.3%) and higher specificity (84.2%) than cytology≥LSIL (Se:78.3%;Sp:58.9%) and HPV16/18 positive (Se:73.9%;Sp:46.3%) patients.ConclusionsPAX1m could be a promising auxiliary marker in predicting the pathological upgrade of CIN before CKC. We found that if the △Cp PAX1 cut-off value is lower than 6.360, it is highly suggestive of invasive cervical cancer.

Aspergillus flavus (A. flavus) is one of the most important model environmental fungi which can produce a potent toxin and carcinogen known as aflatoxin. Aflatoxin contamination causes massive agricultural economic loss and a critical human health issue each year. Although a functional vacuole has been highlighted for its fundamental importance in fungal virulence, the molecular mechanisms of the vacuole in regulating the virulence of A. flavus remain largely unknown. Here, we identified a novel vacuole-related protein in A. flavus, the ortholog of phosphatidylinositol-3-phosphate-5-kinase (Fab1) in Saccharomyces cerevisiae. This kinase was located at the vacuolar membrane, and loss of fab1 function was found to affect the growth, conidia and sclerotial development, cellular acidification and metal ion homeostasis, aflatoxin production and pathogenicity of A. flavus. Further functional analysis revealed that Fab1 was required to maintain the vacuole size and cell morphology. Additional quantitative proteomic analysis suggested that Fab1 was likely to play an important role in maintaining vacuolar/cellular homeostasis, with vacuolar dysregulation upon fab1 deletion leading to impaired aflatoxin synthesis in this fungus. Together, these results provide insight into the molecular mechanisms by which this pathogen produces aflatoxin and mediates its pathogenicity, and may facilitate dissection of the vacuole-mediated regulatory network in A. flavus.

Vibrio parahaemolyticus is a foodborne pathogen that can colonize the small intestine of the host and cause diarrhea. The alternative sigma factor RpoN plays a vital role in regulating motility, carbon utilization and affects host colonization in V. parahaemolyticus RIMD2210633. In this study, transcriptome and phenotypic analysis further expanded our understanding of the RpoN regulon in V. parahaemolyticus. A deletion mutant of rpoN (ΔrpoN) was subjected to RNA-seq for systemic identification of the RpoN-controlled genes. Compared with the wild-type (WT), 399 genes were differentially expressed in the ΔrpoN strain. Moreover, 264 genes were down-regulated in the ΔrpoN strain, including those associated with nitrogen utilization (VP0118), glutamine synthetase (VP0121), formate dehydrogenase (VP1511 and VP1513-VP1515), quorum sensing (opaR and luxZ), polar flagellar systems, and type VI secretion system 2 (T6SS2). Quantitative real-time reverse transcription PCR (qRT-PCR) and electrophoretic mobility shift assay (EMSA) further confirmed that RpoN could directly bind to the promoters of these genes associated with polar flagellar systems (flgB and fliE), lateral flagellar systems (flgB2 and lafA), T6SS2 (hcp2 and VPA1044) and glutamine synthetase (VP0121), and then positively regulate the expression of these systems. A RpoN-binding motif was identified in V. parahaemolyticus using the MEME suite and verified by the EMSA. Besides, the deletion of rpoN caused a significant decrease in hemolytic activity, adhesion, and cytotoxicity. Our results provide new cues to better understand the regulatory networks of RpoN protein to motility, T6SS2, and metabolism in V. parahaemolyticus.

The growing threat of antibiotic-resistant bacterial infections to public health necessitates the development of novel antibacterial agents. Inhibiting bacterial cell wall synthesis has remained a key focus for antibiotic development. Our search for inhibitors of undecaprenyl diphosphate synthase (UPPS), an essential enzyme required for bacterial cell wall formation, revealed that two primary components of gamboge, gambogic acid (GA) and neogambogic acid (NGA), significantly inhibited the activity of Enterococcus faecalis UPPS (EfaUPPS) with the half maximal inhibitory concentrations (IC50) of 3.08 μM and 3.07 μM, respectively. In the in vitro antibacterial assay, both GA and NGA also exhibited inhibitory activities against E. faecalis with the minimal inhibitory concentrations (MICs) of 2 μg/mL. Using microscale thermophoresis, molecular docking, and enzymatic assays, we further confirmed that GA and NGA occupy the substrate binding pocket of EfaUPPS with micro-molar binding affinity, preventing the natural substrates farnesyl diphosphate (FPP) from entering. Mutagenesis analysis revealed that L91 and L146 are two key residues in the binding between GA/NGA and UPPS. Furthermore, we also demonstrated that GA and NGA can improve E. faecalis-induced undesirable inflammation in a mouse infection model. Taken together, our findings provide a basis for structural optimization of GA/NGA to develop improved antibiotic leads and enhance treatment success rates in clinical practice.

Satellite drops formed on droplet impact hinder applications from inkjet printing to drop energy harvest. Here, authors reveal that patterned-wettability surfaces can break the symmetry of droplet impacts and suppress the Plateau–Rayleigh instability, preventing satellite drop generation and improving the hydropower harvest.

The quadrivalent human papillomavirus (4vHPV) vaccine has shown confirmative effectiveness in preventing HPV-related diseases among women and men around the globe. The phase III, randomized, double-blind efficacy study (Base study, NCT00834106) conducted in China showed 100% efficacy against HPV 16/18-related cervical intraepithelial neoplasia and efficacy against HPV persistent infection for 78 months. Participants aged 20–45 years who received three doses of 4vHPV vaccine or placebo during the base study were selected and invited for this long-term follow-up (LTFU) study to assess the long-term effectiveness of the 4vHPV vaccine in preventing HPV-related diseases. A total of 368 participants were included in this LTFU study with a median follow-up of 94 months. Among 27 participants (Vaccine vs. Placebo: 8 vs. 19) who underwent colposcopy and biopsy due to cervical cytological abnormalities or HPV infection, no HPV-16/18-related cases of cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), or vaginal intraepithelial neoplasia (VaIN) was observed in the vaccine group while two HPV-16-related cases (CIN1/VaIN) were observed in the placebo group. There were another two HPV-related cases (non-vaccine HPV types) found in the placebo group. Consistent with the findings from global studies that suggested long-term efficacy of 4vHPV vaccine, our study showed continued protective effect of 4vHPV vaccine against HPV-related precancerous diseases through a median follow-up time of 94 months with the longest follow-up time of 125 months after completing three doses of vaccination among Chinese women 20–45 years of age.

A number of studies have confirmed the positive effect of writing reflective journals on L2 learning. However, the relationship between writing reflective journals and the use of self-regulated writing strategies remains unclear. To redress this knowledge gap, we assigned 38 Chinese English as a foreign language (EFL) students three journal-writing tasks in which they reflected on their writing processes and explored (1) the types of self-regulated writing strategies and changes to those strategies that the students’ reflective journals documented; (2) how students with varied writing-proficiency levels differed in their use of self-regulated writing strategies; and (3) the effects of reflective-journal writing on students’ self-perceived use of self-regulated writing strategies in particular, and on their L2 writing in general. Among the 19 kinds of strategies identified in 112 reflective-journal entries, only five (i.e., handling feedback, resource management, text processing, emotion regulation, and idea planning) were demonstrated relatively frequently. The use of seven strategies (i.e., self-monitoring and evaluation, idea planning, perspective change, emotional control, effort regulation, peer learning, and resource management) exhibited significant increases over time, especially during the second-half of the focal semester. In addition, our journal data highlighted individual variation in proficiency levels: with high-proficiency students significantly more likely than others to apply idea planning, feedback handling, and resource management and low-proficiency ones significantly more likely than others to engage in goal-setting. The qualitative results suggest that the practice of journaling raised students’ awareness and may have contributed to an increase in their use of self-regulated writing strategies. In particular, the findings reveal how students internalized and reconstructed the various SRL processes taking place via writing reflective journals. For L2 educators using or considering using reflective journals, these findings contain fresh insights that could help them not only to increase their students’ SRL levels, but also to provide more individualized SRL guidance.

ObjectivesWorldwide, around 18.2% of cervical cancer occurred in China, mainly because of lower screening coverage and screening quality in regional disparities. To assess self-sampling for human papillomavirus (HPV) testing, combined with the internet, as a primary cervical cancer screening (CCS) method in low-resource settings, and to establish an internet-based self-sampling CCS-management model.MethodsThe women who participated registered on a CCS website. We recruited 20,136 women, aged 30–59 years, from 13 provinces in China, to perform vaginal self-sampling for HPV testing as a primary CCS, based on the internet. A questionnaire was subsequently used to investigate the acceptability of self-sampling.ResultsOf the 20,103 women with qualified samples, 35.80% lived in remote areas, 37.69% had never undergone CCS, 59.96% were under-screened, and the overall prevalence of a high-risk of HPV was 13.86%. Of 8,136 respondents, 95.97% of women felt that self-sampling was easy to perform, 84.61% had no discomfort when using a self-sampling brush, 62.37% women were more likely to choose self-sampling for CCS in future, and 92.53% were willing to introduce the concept to others around them. The reliability and ease of self-sampling were independent factors influencing selection of self-sampling (p < 0.05).ConclusionsThe Internet-facilitated self-sampling for HPV testing and management model for cervical cancer prevention is feasible and effective. It can be used as a supplement to the conventional screening, particularly in outlying areas with few medical resources, to improve the coverage of CCS.Clinical trial registrationhttps://www.chictr.org.cn, identifier: ChiCTR2000032331.