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Abstract Microcarrier is a promising drug delivery system demonstrating significant value in treating cancers. One of the main goals is to devise microcarriers with ingenious structures and functions to achieve better therapeutic efficacy in tumors. Here, inspired by the nucleus-cytoplasm structure of cells and the material exchange reaction between them, we develop a type of biorthogonal compartmental microparticles (BCMs) from microfluidics that can separately load and sequentially release cyclooctene-modified doxorubicin prodrug (TCO-DOX) and tetrazine-modified indocyanine green (Tz-ICG) for tumor therapy. The Tz-ICG works not only as an activator for TCO-DOX but also as a photothermal agent, allowing for the combination of bioorthogonal chemotherapy and photothermal therapy (PTT). Besides, the modification of DOX with cyclooctene significantly decreases the systemic toxicity of DOX. As a result, the developed BCMs demonstrate efficient in vitro tumor cell eradication and exhibit notable tumor growth inhibition with favorable safety. These findings illustrate that the formulated BCMs establish a platform for bioorthogonal prodrug activation and localized delivery, holding significant potential for cancer therapy and related applications. Graphical Abstract

The anticancer potential of quassinoids has attracted a great deal of attention for decades, and scientific data revealing their possible applications in cancer management are continuously increasing in the literature. Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes, several quassinoids have exhibited synergistic effects with anticancer drugs. This article provides an overview of the potential anticancer properties of quassinoids, including their cytotoxic and antitumor activities, mechanisms of action, safety evaluation, and potential benefits in combination with anticancer drugs.

Highlights Derived from silica photonic crystals, inverse opal microspheres have a regularly connected porous structure and inherit structural color properties. Combined with the stable scaffold and the photothermal phase-transition of the secondary filling material, the inverse opal composite microspheres are endowed with self-healing properties and the ability for controllable drug release. Inverse opal microspheres were significantly treated for diabetic wound, via promoting tissue regeneration, collagen deposition and angiogenesis. Meanwhile, the release of drugs could be monitored by the structural color characteristic.

Abstract A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L−1 (NCI-H1299), 3.16 ± 0.11 µmol L−1 (A549), and 1.83 ± 0.13 µmol L−1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L−1 (NCI-H1299), 3.86 ± 0.38 µmol L−1 (A549), and 1.69 ± 0.25 µmol L−1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

Abstract Metagenomic binning is an essential technique for genome-resolved characterization of uncultured microorganisms in various ecosystems but hampered by the low efficiency of binning tools in adequately recovering metagenome-assembled genomes (MAGs). Here, we introduce BASALT (Binning Across a Series of Assemblies Toolkit) for binning and refinement of short- and long-read sequencing data. BASALT employs multiple binners with multiple thresholds to produce initial bins, then utilizes neural networks to identify core sequences to remove redundant bins and refine non-redundant bins. Using the same assemblies generated from Critical Assessment of Metagenome Interpretation (CAMI) datasets, BASALT produces up to twice as many MAGs as VAMB, DASTool, or metaWRAP. Processing assemblies from a lake sediment dataset, BASALT produces ~30% more MAGs than metaWRAP, including 21 unique class-level prokaryotic lineages. Functional annotations reveal that BASALT can retrieve 47.6% more non-redundant opening-reading frames than metaWRAP. These results highlight the robust handling of metagenomic sequencing data of BASALT.

Abstract Dipterocarpoideae species form the emergent layer of Asian rainforests. They are the indicator species for Asian rainforest distribution, but they are severely threatened. Here, to understand their adaptation and population decline, we assemble high-quality genomes of seven Dipterocarpoideae species including two autotetraploid species. We estimate the divergence time between Dipterocarpoideae and Malvaceae and within Dipterocarpoideae to be 108.2 (97.8‒118.2) and 88.4 (77.7‒102.9) million years ago, and we identify a whole genome duplication event preceding dipterocarp lineage diversification. We find several genes that showed a signature of selection, likely associated with the adaptation to Asian rainforests. By resequencing of two endangered species, we detect an expansion of effective population size after the last glacial period and a recent sharp decline coinciding with the history of local human activities. Our findings contribute to understanding the diversification and adaptation of dipterocarps and highlight anthropogenic disturbances as a major factor in their endangered status.

Abstract Background The COVID-19 pandemic is a persistent global threat to public health. As for the emerging variants of SARS-CoV-2, it is necessary to develop vaccines that can induce broader immune responses, particularly vaccines with weak cellular immunity. Methods In this study, we generated a double-layered N-S1 protein nanoparticle (N-S1 PNp) that was formed by desolvating N protein into a protein nanoparticle as the core and crosslinking S1 protein onto the core surface against SARS-CoV-2. Results Vaccination with N-S1 PNp elicited robust humoral and vigorous cellular immune responses specific to SARS-CoV-2 in mice. Compared to soluble protein groups, the N-S1 PNp induced a higher level of humoral response, as evidenced by the ability of S1-specific antibodies to block hACE2 receptor binding and neutralize pseudovirus. Critically, N-S1 PNp induced Th1-biased, long-lasting, and cross-neutralizing antibodies, which neutralized the variants of SARS-CoV-2 with minimal loss of activity. N-S1 PNp induced strong responses of CD4+ and CD8+ T cells, mDCs, Tfh cells, and GCs B cells in spleens. Conclusions These results demonstrate that N-S1 PNp vaccination is a practical approach for promoting protection, which has the potential to counteract the waning immune responses against SARS-CoV-2 variants and confer broad efficacy against future new variants. This study provides a new idea for the design of next-generation SARS-CoV-2 vaccines based on the B and T cells response coordination. Graphical Abstract Steps involved in the preparation of double-layered N-S1 protein nanoparticle vaccines and experimental design performed in combating virus infection. After intramuscular immunization of mice, the double-layered N-S1 protein nanovaccine could effectively promote the maturation of antigen-presenting and mature dendritic cells, robust broad-spectrum neutralizing antibody production, cytokines secretion, robust mDC, Tfh cell, and GCs B cell responses induction, T-cell memory formation and durable antibody responses, and unique global transcriptome characteristics, thus achieving a robust cellular immunity and broad antibody responses against SARS-CoV-2 based on the B and T cells response coordination

Abstract The management of infected wounds is always of great significance and urgency in clinical and biomedical fields. Recent efforts in this area are focusing on the development of functional wound patches with effective antibacterial, drug delivery, and sensor properties. Here, we present novel hyaluronic acid (HA) microneedle patches with these features by encapsulating aminobenzeneboronic acid‐modified gold nanoclusters (A‐GNCs) for infected wound management. The A‐GNCs loaded microneedle patches were derived from negative‐mold replication and showed high mechanical strength to penetrate the skin. The release of the A‐GNCs was realized by the degradation of HA, and the self‐monitor of the released actives was based on the dynamic bright orange fluorescence emitted from A‐GNCs under ultraviolet radiation. As the A‐GNCs could destroy bacteria membranes, the microneedle patches were with excellent in vitro antibiosis ability. Based on these features, we have demonstrated the bacteria inhibition, residual drug self‐monitoring, and wound healing promotion abilities of the microneedle patches in Escherichia coli‐ or Staphylococcus aureus‐infected wound management. These results indicated the great potential of such A‐GNCs loaded microneedle patches for clinical applications.

Reducing methane emissions in the oil and gas industry is a top priority for the current international community in addressing climate change. Methane emissions from the energy sector exhibit strong temporal variability and ground monitoring networks can provide time-continuous measurements of methane concentrations, enabling the rapid detection of sudden methane leaks in the oil and gas industry. Therefore, identifying specific locations within oil fields to establish a cost-effective and reliable methane monitoring ground network is an urgent and significant task. In response to this challenge, this study proposes a technical workflow that, utilizing emission inventories, atmospheric transport models, and intelligent computing techniques, automatically determines the optimal locations for monitoring stations based on the input quantity of monitoring sites. This methodology can automatically and quantitatively assess the observational effectiveness of the monitoring network. The effectiveness of the proposed technical workflow is demonstrated using the Shengli Oilfield, the second-largest oil and gas extraction base in China, as a case study. We found that the Genetic Algorithm can help find the optimum locations effectively. Besides, the overall observation effectiveness grew from 1.7 to 5.6 when the number of site increased from 1 to 9. However, the growth decreased with the increasing site number. Such a technology can assist the oil and gas industry in better monitoring methane emissions resulting from oil and gas extraction.

IntroductionNitrososphaeria, formerly known as Thaumarchaeota, constitute a diverse and widespread group of ammonia-oxidizing archaea (AOA) inhabiting ubiquitously in marine and terrestrial environments, playing a pivotal role in global nitrogen cycling. Despite their importance in Earth’s ecosystems, the cellular organization of AOA remains largely unexplored, leading to a significant unanswered question of how the machinery of these organisms underpins metabolic functions.MethodsIn this study, we combined spherical-chromatic-aberration-corrected cryo-electron tomography (cryo-ET), scanning transmission electron microscopy (STEM), and energy dispersive X-ray spectroscopy (EDS) to unveil the cellular organization and elemental composition of Nitrosopumilus maritimus SCM1, a representative member of marine Nitrososphaeria.Results and DiscussionOur tomograms show the native ultrastructural morphology of SCM1 and one to several dense storage granules in the cytoplasm. STEM-EDS analysis identifies two types of storage granules: one type is possibly composed of polyphosphate and the other polyhydroxyalkanoate. With precise measurements using cryo-ET, we observed low quantity and density of ribosomes in SCM1 cells, which are in alignment with the documented slow growth of AOA in laboratory cultures. Collectively, these findings provide visual evidence supporting the resilience of AOA in the vast oligotrophic marine environment.

Current research has increasingly focused on the preventive role of individual legal socialization in crime. The socialization of legal emotions is an important part of legal socialization. Building upon existing literature, this study, conducted through two sub-studies, investigated the influencing factors of legal emotions in N mainland Chinese university students and the mechanisms through which legal emotions impact aggressive behavior. In study 1, the results indicated that mother-child attachment, innovation spirit, and positive emotional expression positively predicted positive legal emotion, while mother-child attachment, dependency dimension in adult attachment, and positive emotional expression negatively predicted negative legal emotions. The anxiety dimension in adult attachment and negative emotional expression positively predicted negative legal emotions. In study 2, Positive legal emotion among university students could directly negatively predict aggressive behavior or exert influence through social alienation. Negative legal emotions could not only directly positively predict aggressive behavior but also partly affect it through social alienation. In summary, our study not only identified factors that influence legal emotions, but also found that legal emotions have an impact on aggressive behavior directly or indirectly through social alienation. Our research findings have significant implications for cultivating positive legal emotion in university students and curbing aggressive behavior. This can be achieved by promoting the legal socialization of university students and ultimately contributing to crime prevention.

Coronavirus disease 2019 (COVID-19), a severely spreading pandemic, has dramatically brought physiological and economical burdens to people. Although the injectable vaccines have some achievements for coronavirus defense, they still generate accompanied pain, untoward reaction and cannot take part in mucosal immunity. Inhalable vaccines, as a safe, facile and efficient strategy, have been presented to protect body from virus by inducing robust mucosal immunity. Here, we give a perspective of an inhalable COVID-19 vaccine composed of lung-derived exosomes (a type of virus-like particle) conjugated with viral receptor-binding domain. The lung-derived exosomes act as carriers, such inhalable particles successfully reach at lung and reveal wider distribution and longer retention on respiratory mucosa. In addition, such vaccines induce the high production of specific antibodies and T cells in lung, significantly protecting host against coronavirus invasion. It is conceived that inhalable virus-like particles with long-term stability wound open a new avenue for vaccines delivery and further achieve vaccine popularization to against with COVID-19 pandemic.

Abstract As a “third code”, translational language attracts considerable attention in linguistics research due to its distinctive features. Adopting the quantitative linguistic approach, the current study examines its features by investigating the mean dependency distance (MDD), as well as the probability distribution of the individual dependency distances (DDs) and distribution of a high-frequency dependency type in translational language. The MDD and the distributions were tested in a self-built corpus which contains parallel and comparable language materials in both Chinese-English and English-Chinese translations. The results show that: (1) compared with source texts and native texts, translated texts in both translation directions yield an MDD in between; (2) both the distribution of DDs and that of the dependency type nsubj follow the Zipf-Alekseev distribution in translated texts, as in source texts and native texts; (3) the in-between feature is further confirmed by parameters a and b in Chinese-English translation materials when fitting the distribution of DDs to Zipf-Alekseev distribution; (4) translational texts in both directions show higher a and lower b than their source and native texts when fitting the DD Distribution of dependency type nsubj to Zipf-Alekseev distribution. These findings suggest that, on the one hand, dependency distance minimization (DDM) occurs in translational language, which is consistent with native language and reflects a general tendency of natural languages to reduce cognitive load; on the other hand, translational language presents distinctive feature in nsubj type, but in most cases, it is subject to the gravitational pull of both source and target language systems, exhibiting a “compromise” feature in between. The current study highlights the contribution of syntactic quantitative methods to deeper understanding of the complexity of translational language and its cognitive underpinnings.

Objective: To systematically evaluate the efficacy and safety of Gong Liu Ning as a complimentary therapy in treatment for uterine fibroids. Methods: Randomized controlled trials on Gong Liu Ning for uterine fibroids from China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, PubMed, Cochrane Library, Embase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were retrieved from inception to March 20, 2023. The risk of bias tool was used to evaluate the quality of the selected studies after they met inclusion and exclusion criteria. The GRADE tool was used to evaluate the quality of evidence, and the RevMan5.3 software was used for data analysis. Results: Twenty studies with 1907 patients were analyzed. The meta-analysis results of 15 studies showed that Gong Liu Ning combined with mifepristone was more efficacious than those observed in controls taking only Western medicine (risk ratio [RR] = 1.22, 95% confidence interval [CI] = [1.11, 1.33], P

Range-resolved CH4 concentration measurement is important prior data for atmospheric physical and chemical models. Ground-based differential absorption lidar (DIAL) can measure the vertical distribution of CH4 concentration in the atmosphere. The traditional method uses lidar observational data and the lidar equation to calculate profiles, but the inversion accuracy is greatly affected by noise. Although some denoising methods can improve accuracy at low altitudes, the low signal-to-noise ratio caused by the effect of aerosol Mie scattering and lower aerosol concentrations at high altitudes cannot be solved. Here, an improved cubic smoothing spline fitting CH4 concentration profile inversion method is proposed to address this challenge. By adding a penalty term of the second derivative of the conventional cubic spline function to the objective function, this penalty term acts to smooth the fitting, allowing the fitting function to avoid necessarily passing through those noisy sampling points. This avoids the large fluctuations caused by noisy sampling points, effectively suppresses noise, captures signals with lower noise levels, and thereby enhances the inversion accuracy of the profiles. Simulations and case studies demonstrated the superiority of the proposed method. Compared with the traditional method, cubic smoothing spline fitting can reduce the mean error of the whole CH4 profile by 85.54%. The standard deviation of CH4 concentration retrieved is 3.59 ppb–90.29 ppb and 0.01 ppb–6.75 ppb smaller than the traditional method and Chebyshev fitting, respectively. Three real cases also indicate that the CH4 concentration retrieved by cubic smoothing spline fitting is more consistent with in-situ measurements. In addition, long-term DIAL observations have also revealed notable diurnal and seasonal trends in CH4 concentration at observation sites.

The continuous development of antitumor therapy has significantly reduced the mortality of patients with malignancies. However, the antitumor-related cardiotoxicity has become the leading cause of long-term mortality in patients with malignancies. Besides, the pathogenesis of antitumor-related cardiotoxicity is still unclear, and practical means of prevention and treatment are lacking in clinical practice. Therefore, the major challenge is how to combat the cardiotoxicity of antitumor therapy effectively. More and more studies have shown that antitumor therapy kills tumor cells while causing damage to sensitive tissues such as the intestinal mucosa, leading to the increased permeability of the intestine and the dysbiosis of intestinal microecology. In addition, the dysbiosis of intestinal microecology contributes to the development and progression of cardiovascular diseases through multiple pathways. Thus, the dysbiosis of intestinal microecology may be a potential mechanism and target for antitumor-related cardiotoxicity. We summarized the characteristics of intestinal microecology disorders induced by antitumor therapy and the association between intestinal microecological dysbiosis and CVD. And on this basis, we hypothesized the potential mechanisms of intestinal microecology mediating the occurrence of antitumor-related cardiotoxicity. Then we reviewed the previous studies targeting intestinal microecology against antitumor-associated cardiotoxicity, aiming to provide a reference for future studies on the occurrence and prevention of antitumor-related cardiotoxicity by intestinal microecology.

The aim of this systematic review was to describe the efficacy and acceptability of natural products in the management of oral mucositis caused by radiation. From the day it started to August 7, 2023, a thorough search for randomized controlled trials (RCTs) was carried out among seven databases: the Web of Science, PubMed, Embase, OVID, Scopus, the Cochrane Library and the CINAHL database. Only English-language articles were identified during the search. Using the revised Cochrane risk-of-bias tool, version 2, two researchers screened the articles, collected information on study characteristics, and appraised risks of bias. The data were analyzed and descriptively presented with a narrative synthesis methodology involving the Synthesis Without Meta-Analysis (SWiM) reporting element applied in detail. The PROSPERO registration number of this study is CRD42023476932. Thirty-six clinical trials were included in the study; the included studies included a variety of 20 types of natural products. Honey and Curcuma longa were the most commonly assessed natural products. A total of 2,400 participants reported taking part in therapy with natural products for oral mucositis. Natural products demonstrated substantial efficacy in terms of influencing intensity, incidence, pain score, quality of life, and symptoms such as xerostomia and dysphagia. Except for manuka honey, most natural products were well accepted. Regarding the clinical trials' risk of bias, 2 clinical trials (5.56%) had a high risk of bias, 17 studies (47.2%) had a low risk of bias, and 17 studies (47.2%) were rated with "some concern." Natural remedies work well as alternate treatments for managing oral mucositis caused by radiation therapy. However, additional clinical trials are still needed. The safety of these conventional medications as well as their effectiveness and safety when used in combination with other conventional or naturopathic therapies should be fully examined.

Abstract Background The interaction among microorganisms in the anaerobic digestion of food waste (ADFW) reactors lead to the degradation of organics and the recycling of energy. Viruses are an important component of the microorganisms involved in ADFW, but are rarely investigated. Furthermore, little is known about how viruses affect methanogenesis. Results Thousands of viral sequences were recovered from five full-scale ADFW reactors. Gene-sharing networks indicated that the ADFW samples contained substantial numbers of unexplored anaerobic-specific viruses. Moreover, the viral communities in five full-scale reactors exhibited both commonalities and heterogeneities. The lab-scale dynamic analysis of typical ADFW scenarios suggested that the viruses had similar kinetic characteristics to their prokaryotic hosts. By associating with putative hosts, a majority of the bacteria and archaea phyla were found to be infected by viruses. Viruses may influence prokaryotic ecological niches, and thus methanogenesis, by infecting key functional microorganisms, such as sulfate-reducing bacteria (SRB), syntrophic acetate-oxidizing bacteria (SAOB), and methanogens. Metabolic predictions for the viruses suggested that they may collaborate with hosts at key steps of sulfur and long-chain fatty acid (LCFA) metabolism and could be involved in typical methanogenesis pathways to participate in methane production. Conclusions Our results expanded the diversity of viruses in ADFW systems and suggested two ways that viral manipulated ADFW biochemical processes. Video Abstract

Climate change has a significant impact on agriculture. However, the impact investigation is currently limited to the analysis of meteorological data, and there is a dearth of long-term monitoring of crop phenology and soil moisture associated with climate change. In this study, temperature and precipitation (1957–2020) were recorded, crop growth (1981–2019) data were collected, and field experiments were conducted at central and eastern Gansu and southern Ningxia, China. The mean temperature increased by 0.36°C, and precipitation decreased by 11.17 mm per decade. The average evapotranspiration (ET) of winter wheat in 39 years from 1981 to 2019 was 362.1 mm, demonstrating a 22.1-mm decrease every 10 years. However, the ET of spring maize was 405.5 mm over 35 years (1985–2019), which did not show a downward trend. Every 10 years, growth periods were shortened by 5.19 and 6.47 d, sowing dates were delayed by 3.56 and 1.68 d, and maturity dates advanced by 1.76 and 5.51 d, respectively, for wheat and maize. A film fully-mulched ridge–furrow (FMRF) system with a rain-harvesting efficiency of 65.7-92.7% promotes deep rainwater infiltration into the soil. This leads to double the soil moisture in-furrow, increasing the water satisfaction rate by 110-160%. A 15-year grain yield of maize increased by 19.87% with the FMRF compared with that of half-mulched flat planting. Grain yield and water use efficiency of maize increased by 20.6 and 17.4% when the density grew from 4.5×104 to 6.75×104 plants ha–1 and improved by 12.0 and 12.7% when the density increased from 6.75×104 to 9.0×104 plants ha–1, respectively. Moreover, responses of maize yield to density and the corresponding density of the maximum yield varied highly in different rainfall areas. The density parameter suitable for water planting was 174 maize plants ha–1 with 10 mm rainfall. Therefore, management strategies should focus on adjusting crop planting structure, FMRF water harvesting system, and water-suitable planting to mitigate the adverse effects of climate change and enhance sustainable production of maize in the drylands.

Fe/Cu bimetallic catalysts have a synergistic effect that can effectively enhance catalytic activity, so Fe/Cu bimetallic catalysts have been extensively studied. However, the efficacy and mechanisms of Fe/Cu bimetallic catalysts’ peroxidation activation have rarely been explored. In this study, Fe/Cu bimetallic materials were fabricated to catalyze different oxidizing agents, including peroxymonosulfate (PMS), peroxydisulfate (PDS), peroxyacetic acid (PAA), and hydrogen peroxide (H2O2), for the degradation of sulfamethoxazole (SMX). The Fe/Cu/oxidant systems exhibited an excellent degradation efficiency of sulfamethoxazole (SMX). In the Fe/Cu/PMS, Fe/Cu/PDS, and Fe/Cu/PAA systems, the main reactive oxygen species (ROS) responsible for SMX degradation were hydroxyl radical (•OH) and singlet oxygen (1O2), while the main ROS was only •OH in the H2O2 system. The differences in the surface structure of the materials before and after oxidation were examined, revealing the presence of a large amount of flocculent material on the surface of the oxidized PMS material. Anion experiments and actual body experiments also revealed that the PMS system had a strong anti-interference ability. Finally, a comprehensive comparison concluded that the PMS system was the optimal system among the four oxidation systems. Overall, this work revealed that the PMS oxidant has a better catalytic degradation of SMX compared to other oxidizers for Fe/Cu, that PMS generates more ROS, and that the PMS system has a stronger resistance to interference.

Oral antibiotics have served as a primary strategy for bacterial infection. However, the increasingly prominent issues including antibiotics resistance and intestinal dysbiosis sounded the alarm to this traditional administration strategy. Herein, we summarize the state-of-the-art advances in the delivery of oral antibiotics. In this review, the emergency of bacterial infection and the effect of excessive antibiotics are discussed at first. Then, current attempts to prevent microflorae from resistance and dysbiosis are briefly enumerated, including oral co-administration systems (like protectors, adsorbents, activity enhancers, etc.) and nanoparticle-based delivery systems. Moreover, we also briefly introduce the development of mimetic antibiotics based on metal particles and highlight a novel micelle nanoparticle system, which possesses a positive charge and glucosylated surface to achieve targeted treatment. We strongly believe such an ingenious design could be applied in more scenarios for oral antibiotics delivery. Ultimately, we also put forward a concise summary and perspective of this field.

Abstract Background Pancreatic adenocarcinoma (PAAD) is a leading cause of malignancy-related deaths worldwide, and the efficacy of immunotherapy on PAAD is limited. Studies report that long non-coding RNAs (lncRNAs) play an important role in modulating genomic instability and immunotherapy. However, the identification of genome instability-related lncRNAs and their clinical significance has not been investigated in PAAD. Methods The current study developed a computational framework for mutation hypothesis based on lncRNA expression profile and somatic mutation spectrum in pancreatic adenocarcinoma genome. We explored the potential of GInLncRNAs(genome instability-related lncRNAs) through co-expression analysis and function enrichment analysis. We further analyzed GInLncRNAs by Cox regression and used the results to construct a prognostic lncRNA signature. Finally, we analyzed the relationship between GILncSig (genomic instability derived 3-lncRNA signature) and immunotherapy. Results A GILncSig was developed using bioinformatics analyses. It could divide patients into high-risk and low-risk groups, and there was a significant difference in OS between the two groups. In addition, GILncSig was associated with genome mutation rate in pancreatic adenocarcinoma, indicating its potential value as a marker for genomic instability. The GILncSig accurately grouped wild type patients of KRAS into two risk groups. The prognosis of the low-risk group was significantly improved. GILncSig was significantly correlated with the level of immune cell infiltration and immune checkpoint. Conclusions In summary, the current study provides a basis for further studies on the role of lncRNA in genomic instability and immunotherapy. The study provides a novel method for identification of cancer biomarkers related to genomic instability and immunotherapy.

Abstract Objectives To investigate the relationship between prior coronavirus disease 2019 (COVID‐19) infection in females and subsequent treatment outcomes of assisted reproductive technology (ART). Methods A systematic literature review was carried out up to 16 December 2022, in PubMed, Web of Science, EMBASE, and Cochrane Library. Random‐effect models were adopted to estimate the pooled effects as mean differences (MDs) or odds ratios (ORs). I2 statistic and Egger's test were applied to assess heterogeneity and publication bias, respectively. Results After screening 1480 records, 15 cohort studies totalling 1905 cycles were included in this meta‐analysis. In a comparison of previously COVID‐19‐infected versus uninfected women, no significant differences were observed in the primary outcomes of the retrieved oocytes number (MD = 0.06; 95% confidence interval [CI]: ‐0.75–0.88; I2 = 0) and clinical pregnancy rate (OR = 0.96; 95% CI: 0.74–1.24; I2 = 0). Pooled analyses of other predefined outcomes, which encompassed four cycle characteristics, six laboratory indicators and four pregnancy results, also showed no adverse effects of prior COVID‐19 infection. Most outcomes remained consistent after further sensitivity and subgroup analyses, and no significant publication bias was observed. Conclusions Our work provides the first systematic evidence that COVID‐19 infection history in females may have no measurable detrimental impact on the subsequent ART cycle. More data are needed to assess the live birth outcome and the optimal time interval from infection to assisted reproduction.

ABSTRACT Transcription factors (TFs) play a crucial role in regulating gene expression in living organisms, and any malfunction in their functions can lead to severe physiological consequences. The regulation of TFs occurs at multiple levels, with autogenous regulation being a common mode of regulation where the expression of a TF gene is dependent on its own function. Although bioinformatics analysis of promoter sequences is frequently used to predict autogenous regulation events, it is not entirely reliable. In this study, we present a simple yet effective strategy to identify the autogenous regulation of a TF. We have demonstrated the effectiveness of this method on three fungal TFs (the Carbon Catabolite Repressor CreA and two uncharacterized TFs of secondary metabolism) and have generated a set of plasmids to facilitate the construction of experimental strains in fungi. Our method can be applied to both positive and negative-acting TFs and generalized for other organisms. Hence, this work provides a reliable and straightforward method for identifying autogenous regulation events, which is useful for understanding TFs’ functions. IMPORTANCE Transcription factors (TFs) play a crucial role in deciphering biological information from the DNA of living organisms. Improper regulation of their functions can disrupt cellular physiology and lead to diseases in humans. As one of the key regulatory mechanisms, some TFs control their own expression levels through autogenous regulation. However, identifying autogenous regulation events of TFs has been a tedious task. In this study, we present a straightforward approach that provides a reliable means to identify TF autogenous regulation events. Our method provides a valuable means for understanding the function of this important class of proteins in cells.

Abstract The development of bioactive scaffolds by mimicking bone tissue extracellular matrix is promising for bone regeneration. Herein, inspired by the bone tissue composition, a novel pearl powder (PP) hybrid fish gelatin methacrylate (GelMa) hydrogel scaffold loaded with vascular endothelial growth factor (VEGF) for bone regeneration is presented. With the help of microfluidic‐assisted 3D printing technology, the composition and structure of the hybrid scaffold can be accurately controlled to meet clinical requirements. The combination of fish skin GelMa and PP also endowed the hybrid scaffold with good biocompatibility, cell adhesion, and osteogenic differentiation ability. Moreover, the controlled release of VEGF enables the scaffold to promote angiogenesis. Thus, the bone regeneration in the proposed scaffolds could be accelerated under the synergic effect of osteogenesis and angiogenesis, which has been proved in the rat skull defect model. These features indicate that the PP hybrid scaffolds will be an ideal candidate for bone regeneration in clinical applications.

IntroductionPlants that display heteroblasty possess conspicuous variations in leaf morphology between their juvenile and adult phases, with certain species retaining juvenile-like leaves even in adulthood. Nevertheless, the ecological advantages of maintaining two or more distinct leaf types in heteroblastic plants at the adult stage remain unclear.MethodThe aim of this study is to examine the adaptive significance of heteroblastic leaves sampled from branches with divergent functions (sterile and fertile branches) of mature Ficus pumila individuals by comparing their morphological, anatomical, and physiological characteristics.ResultLeaves on sterile branches (LSs) exhibited a significantly larger specific leaf area, thinner palisade and spongy tissues, lower chlorophyll contents, and lower light saturation points than leaves on fertile branches (LFs). These results demonstrate that LSs are better adapted to low light environments, while LFs are well equipped to take advantages of high light conditions. However, both LFs and LSs have a low light compensation point with no significant difference between them, indicating that they start to accumulate photosynthetic products under similar light conditions. Interestingly, significant higher net photosynthetic rate was detected in LFs, showing they have higher photosynthetic capacity. Furthermore, LFs produced significant more nutrients compared to LSs, which may associate to their ability of accumulating more photosynthetic products under full light conditions and higher photosynthetic capacity.DiscussionOverall, we observed a pattern of divergence in morphological features of leaves on two functional branches. Anatomical and physiological features indicate that LFs have an advantage in varied light conditions, providing amounts of photosynthetic products to support the sexual reproduction, while LSs adapt to low light environments. Our findings provide evidence that heteroblasty facilitates F. pumila to utilize varying light environments, likely associated with its growth form as a climbing plant. This strategy allows the plant to allocate resources more effectively and optimize its overall fitness.

Abstract The proper organization of cells and tissues is essential for their functionalization in living organisms. To create materials that mimic natural structures, researchers have developed techniques such as patterning, templating, and printing. Although these techniques own several advantages, these processes still involve complexity, are time‐consuming, and have high cost. To better simulate natural materials with micro/nanostructures that have evolved for millions of years, the use of ice templates has emerged as a promising method for producing biomimetic materials more efficiently. This article explores the historical approaches taken to produce traditional biomimetic structural biomaterials and delves into the principles underlying the ice‐template method and their various applications in the creation of biomimetic materials. It also discusses the most recent biomedical uses of biomimetic materials created via ice templates, including porous microcarriers, tissue engineering scaffolds, and smart materials. Finally, the challenges and potential of current ice‐template technology are analyzed.

In recent years, an increasing number of studies have examined the mechanisms underlying nonverbal emotional information processing in people with high social anxiety (HSA). However, most of these studies have focused on the processing of facial expressions, and there has been scarce research on gesture or even face-gesture combined processing in HSA individuals. The present study explored the processing characteristics and mechanism of the interaction between gestures and facial expressions in people with HSA and low social anxiety (LSA). The present study recruited university students as participants and used the Liebowitz Social Anxiety Scale scores to distinguish the HSA and LSA groups. We used a 2 (group: HSA and LSA) × 2 (emotion valence: positive, negative) × 2 (task: face, gesture) multifactor mixed design, and videos of a single face or gesture and combined face-gesture cues were used as stimuli. We found that (1) there is a distinction in the processing of faces and gestures, with individuals recognizing gestures faster than faces; (2) there is an attentional enhancement in the processing of gestures, particularly for negative gestures; and (3) when the emotional valence of faces and gestures align, it facilitates the recognition of both. However, incongruent gestures have a stronger impact on the processing of facial expressions compared to facial expressions themselves, suggesting that the processing of facial emotions is more influenced by environmental cues provided by gestures. These findings indicated that gestures played an important role in emotional processing, and facial emotional processing was more dependent on the environmental cues derived from gestures, which helps to clarify the reasons for biases in the interpretation of emotional information in people with HSA.

Abstract Background The early diagnosis of sepsis is beneficial to put forward a reasonable clinical treatment plan as soon as possible. This study was to explore the expression of Tripartite Motif 7 (TRIM7) in peripheral blood mononuclear cells (PBMCs) of patients with sepsis and its diagnostic value. Methods This is a cross-sectional study. A total of 69 patients with infectious diseases were enrolled in the emergency room. They were divided into the sepsis group (34 cases) and the non-sepsis infection group (35 cases). There were 25 healthy subjects who were selected as the control group. The expression of TRIM7 in PBMCs was observed by immunofluorescence staining. The correlation between the expression of TRIM7 mRNA and acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor (TNF)-α and interleukin (IL)-6 was discussed. The receiver operating characteristic (ROC) curve was utilized for evaluating the value of TRIM7 expression for the early diagnosis of sepsis. Results The fluorescence intensity representing the expression level of TRIM7 in PBMCs of patients in the sepsis group was the lowest among three groups. The TRIM7 mRNA expression in PBMCs of the sepsis group was greatly decreased in comparison with that of the non-sepsis infection group and control group (P

Abstract Background Occupational exposure to blood and body fluids poses a threat to medical providers and to nurses especially. This harm is not only physical, but psychology as well and can ultimately impact patient safety. This study aims to understand the prevalence of occupational exposure to blood and body fluids among Chinese registered nurses and explores the factors that influence this exposure. Methods A cross-sectional online survey was conducted for 31 province-level divisions in China, using a self-created questionnaire entitled Status Survey on Occupational Exposure in Nurses. Descriptive statistics were used to describe both the demographic characteristics of the respondents and the characteristics of occupational exposure. Categorical variables were presented as frequencies and percentage, and the relationship between possible influential factors and the occurrence of occupational exposure was determined using binary logistic regression. Results Out of a total of 20,791 nurses analyzed, over half (52.1%) of them had experienced occupational exposure to blood or body fluids, but over 1/3 (34.6%) of them did not ever report their exposures to a supervisor/official. The top three causes of under-reporting were: the source patient failed to test positive for infectious pathogens (43.6%), perception of a burdensome reporting process (24.6%), and indifferent attitude towards being infected (16.9%). Nurses who worked over 8 hours per day had higher risks of exposure (OR 1.199, 95% CI 1.130 to 1.272, P

Abstract Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued “Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline”. Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette–Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

Objective: To explore the structural and functional characteristics of microbiota in oropharynx of sub-healthy children with gastrointestinal heat retention syndrome (GHRS) differentiated by traditional Chinese medicine, and screen the biometric operational taxonomic units (OTUs) to assist the clinical diagnosis. Methods: We recruited children according to the “GHRS diagnostic scale”, collected their oropharyngeal swabs, and sequenced the 16S rDNA V4 region. We described the bacterial structure with alpha-indexes, beta-distances, and relative abundances; moreover, we screened the differential genera/OTUs with Wilcoxon rank-sum test, MetagenomeSeq analysis, and linear discriminant analysis effect size (LEfSe) analysis, in which biometric OTUs were selected to construct the receiver operating characteristic curve to verify the diagnostic value. The bacterial function was predicted with Kyoto Encyclopedia of Genes and Genomes pathways according to 16S rDNA gene by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. Results: The study population was composed of 10 children with GHRS and 10 healthy control children. GHRS children were more likely to overeat (gluttony, P = .033). Alpha-indexes, such as Sobs, abundance-based coverage estimator, Bootstrap, and Qstat, were significantly higher in the GHRS group, while beta-distances did not exhibit any significant intergroup differences. There were 9 differently distributed non-predominant genera between the groups in Wilcoxon rank-sum test, as well as 13 non-predominant genera in MetagenomeSeq analysis and 3 non-predominant OTUs in LEfSe analysis. OTU44 and OTU196 were used to construct the receiver operating characteristic curve, and the area under curve was 0.92. Predicted functions showed that pathways related to oxidative phosphorylation and carbon metabolism were enriched in healthy control samples, while the pathway related to renin secretion was remarkably enriched in GHRS samples. Conclusion: Unique oropharyngeal microbial structure and function were identified in GHRS children. OTU44 and OTU196 were specific OTUs, which could be used as biomarkers of GHRS to assist clinical diagnosis.

Abstract Hard‐healing diabetic wound brings burgeoning physical and mental burdens to patients. Current treatment strategies tend to achieve multistage promotion and real‐time reporting to facilitate wound management. Herein, a biomimetic enzyme cascade inverse opal microparticles system for wound healing, which is intergated with glucose oxidase (GOD) and copper peroxide (CP). Such microparticles are composed of biofriendly hyaluronic acid methacryloyl (HAMA) and pH‐responsive acrylic acid (AA), which provided abundant binding sites and spaces for chemical immobilizing and physical doping of enzymes and metal bioinorganics. When the cascade catalytic system is applied on wound sites, hyperglycemia environment would serve as a hydrogen peroxide (H2O2) generator through GOD catalysis, while acidic environment triggers the decomposition of CP, further catalyzing H2O2 to generate reactive oxygen species (ROS). Additionally, the distinctive structural color of the microparticles can visually reflect the wound pH and intelligently estimate the healing state. It is demonstrated that such microparticle systems exhibit excellent broad‐spectrum antibacterial and angiogenesis‐promoting properties, as well as significant real‐time reporting ability for wound healing. These features indicate that enzyme cascade structural color microparticles possess valuable potential in wound healing and related field.

Marine group II (MGII) archaea (Ca. Poseidoniales) are among the most abundant microbes in global oceanic surface waters and play an important role in driving marine biogeochemical cycles. Magroviruses – the viruses of MGII archaea have been recently found to occur ubiquitously in surface ocean. However, their diversity, distribution, and potential ecological functions in coastal zones especially brackish waters are unknown. Here we obtained 234 non-redundant magroviral genomes from brackish surface waters by using homology searches for viral signature proteins highlighting the uncovered vast diversity of this novel viral group. Phylogenetic analysis based on these brackish magroviruses along with previously reported marine ones identified six taxonomic groups with close evolutionary connection to both haloviruses and the viruses of Marine Group I archaea. Magroviruses were present abundantly both in brackish and open ocean samples with some showing habitat specification and others having broad spectrums of distribution between different habitats. Genome annotation suggests they may be involved in regulating multiple metabolic pathways of MGII archaea. Our results uncover the previously overlooked diversity and ecological potentials of a major archaeal virial group in global ocean and brackish waters and shed light on the cryptic evolutionary history of archaeal viruses.

Abstract Background Prokaryote-virus interactions play key roles in driving biogeochemical cycles. However, little is known about the drivers shaping their interaction network structures, especially from the host features. Here, we compiled 7656 species-level genomes in 39 prokaryotic phyla across environments globally and explored how their interaction specialization is constrained by host life history traits, such as growth rate. Results We first reported that host growth rate indicated by the reverse of minimal doubling time was negatively related to interaction specialization for host in host-provirus network across various ecosystems and taxonomy groups. Such a negative linear growth rate-specialization relationship (GrSR) was dependent on host optimal growth temperature (OGT), and stronger toward the two gradient ends of OGT. For instance, prokaryotic species with an OGT ≥ 40 °C showed a stronger GrSR (Pearson’s r = −0.525, P < 0.001). Significant GrSRs were observed with the presences of host genes in promoting the infection cycle at stages of adsorption, establishment, and viral release, but nonsignificant with the presence of immune systems, such as restriction-modification systems and CRISPR-Cas systems. Moreover, GrSR strength was increased with the presence of temperature-dependent lytic switches, which was also confirmed by mathematical modeling. Conclusions Together, our results advance our understanding of the interactions between prokaryotes and proviruses and highlight the importance of host growth rate in interaction specialization during lysogenization. Video Abstract

BackgroundNeck-shoulder pain is one of the most common discomfort symptoms among nursing staff, mostly caused by a heavy workload, restricted workstation, and prolonged poor posture.ObjectiveTo investigate the prevalence of neck-shoulder pain among nursing staff in tertiary general hospitals in Hunan Province, and to analyze workload-related risk factors.MethodsFrom October to December 2018, a multi-stage stratified randomized cluster sampling method was adopted to select a total of 1 200 nursing staff who met the inclusion andexclusion criteria in six tertiary general hospitals from five geographic subdivisions of Hunan Province were selected. A self-designed questionnaire was used to collect demographic characteristics, and past 1-month prevalence of neck-shoulder pain, a neck disability index (NDI) was used to assess the impact of neck pain on daily life, and functional disability was graded by the index of impaired neck function; a self-designed questionnaire was adopted to evaluate potential workload-related risk factors (working time, postural load, and force load) of neck-shoulder pain after a Delphi expert consultation. A total of 1 161 valid questionnaires were returned, and χ２test and logistic regression model were used to screen the potential risk factors for neck-shoulder pain.ResultsThe prevalence rate of neck-shoulder pain in the past 1 month was 87.5% (1 016/1 161) and varied by different characteristics of the nursing staff, ranging from 76.9% to 91.2%. The scores of the 10 items of the NDI ranged from 0 to 5, but most of them were 0, 1, and 2; of the 10 items, neck pain had the greatest impact on sleep (1.30±1.21) and the least impact on self-care behaviors (0.35±0.65). The index of impaired neck function showed that the majority (65.4%) of nurses had mild cervical spine dysfunction and 30.1% had moderate cervical spine dysfunction. The univariate analysis results revealed that 24 out of the 31 workload-related risk factors had significant differences, and further multiple analysis results showed that three variables entered the logistic regression model. Under the same conditions, nurses with ≥5 h of cumulative head-down tasks per shift had 3.03 times higher neck-shoulder pain risks compared with those with ＜1 h. Compared with “occasionally or never”, nurses who “sometimes” and “often” tilted their necks back and maintained this posture for a long time showed 2.36 and 2.94 times higher risks for neck-shoulder pain respectively. The nurses who reported “sometimes” and “often” having difficulty using their force at work due to unnatural posture had 2.78 times and 7.08 times higher neck-shoulder pain risks than those who “occasionally or never” respectively.ConclusionThe reported rate of neck-shoulder pain among nurses in tertiary general hospitals in Hunan Province is high, but most of them are mild dysfunction. Working hours and posture load may affect the risk of neck-shoulder pain.

As one of the typical emerging contaminants, microplastics exist widely in the environment because of their small size and recalcitrance, which has caused various ecological problems. This paper summarizes current adsorption and removal technologies of microplastics in typical aquatic environments, including natural freshwater, marine, drinking water treatment plants (DWTPs), and wastewater treatment plants (WWTPs), and includes abiotic and biotic degradation technologies as one of the removal technologies. Recently, numerous studies have shown that enrichment technologies have been widely used to remove microplastics in natural freshwater environments, DWTPs, and WWTPs. Efficient removal of microplastics via WWTPs is critical to reduce the release to the natural environment as a key connection point to prevent the transfer of microplastics from society to natural water systems. Photocatalytic technology has outstanding pre-degradation effects on microplastics, and the isolated microbial strains or enriched communities can degrade up to 50% or more of pre-processed microplastics. Thus, more research focusing on microplastic degradation could be carried out by combining physical and chemical pretreatment with subsequent microbial biodegradation. In addition, the current recovery technologies of microplastics are introduced in this review. This is incredibly challenging because of the small size and dispersibility of microplastics, and the related technologies still need further development. This paper will provide theoretical support and advice for preventing and controlling the ecological risks mediated by microplastics in the aquatic environment and share recommendations for future research on the removal and recovery of microplastics in various aquatic environments, including natural aquatic environments, DWTPs, and WWTPs.

Abstract Purpose To study the relationship between blastomere number and pregnancy outcomes of day 3 embryo transfers. Methods This retrospective cohort study included 2237 fresh single day 3 embryo transfer cycles from October 2013 to November 2020. Patients were divided into six groups according to the blastomere number on day 3: ≤ 6-cell (n = 100), 7-cell (n = 207), 8-cell (n = 1522), 9-cell (n = 187), 10-cell (n = 91) and ≥ 11-cell (n = 130). Generalized estimating equation analysis based on multivariate logistic regression model was performed to adjust for potential confounders. Results The live birth rate (LBR) was 19.0%, 27.1%, 38.9%, 32.1%, 44.0% and 53.8% for the ≤ 6-cell, 7-cell, 8-cell, 9-cell, 10-cell and ≥ 11-cell groups, respectively (P

Abstract Background Mucus production is a process involved in the pathogenesis of Community-acquired pneumonia (CAP). The study is to determine Mucin 5B (MUC5B) protein concentration and its proportion in the bronchoalveolar lavage fluid (BALF) of CAP patients and evaluate its value to help assess disease severity. Methods A total of 118 patients were enrolled in this cross-sectional study, including 45 with severe CAP (SCAP) and 73 with non-severe CAP (NSCAP). MUC5B concentration in BALF were determined by immunoblotting analysis. Total protein concentration of BALF was detected by Pierce BCA kit. Cytokines IL6, IL10, IFNγ, IL13, and IL17 in BALF were measured using commercial enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was applied to evaluate the relationships between MUC5B concentration or MUC5B/total protein ratio and the CURB-65 score, as well as cytokines. Logistic regression analysis was used to identify the independent factors associated with severe CAP. Receiver operating characteristic (ROC) curve was used to evaluate the assessment value of MUC5B/total protein ratio and other indexes for CAP severity. Results MUC5B concentration in the BALF of NSCAP group was higher than that in SCAP group [NSCAP 13.56 µg/ml (IQR 5.92–25.79) vs. SCAP 8.20 µg/ml (IQR 4.97–14.03), p = 0.011]. The total protein concentration in the BALF of NSCAP group was lower than that in SCAP group [NSCAP 0.38 mg/ml (IQR 0.15–1.10) vs. SCAP 0.68 mg/ml (IQR 0.46–1.69), p = 0.002]. The MUC5B/total protein ratio was remarkably higher in NSCAP group than that in SCAP groups [NSCAP 3.66% (IQR 1.50–5.56%) vs. SCAP 1.38% (IQR 0.73–1.76%), p

Abstract Background Several surveys have reported that patients treated with gonadotropin-releasing hormone antagonist (GnRH-ant) protocol showed a significantly lower rate of implantation and clinical pregnancy compared to GnRH agonist (GnRH-a) protocol during in vitro fertilization-fresh embryo transfer. Subsequent studies imputed this poor outcome to the negative effects of GnRH-ant on endometrial receptive. However, the mechanisms were not fully understood. Methods The clinical data of 2815 patients undergoing fresh embryo transfer in our center were analyzed. Human endometrial stromal cells (ESCs) from healthy women undergoing elective pregnancy termination of a normal pregnancy at 8–10 weeks gestation were treated with GnRH-analogs or imatinib (c-kit receptor inhibitor). CCK8 and Flow cytometry were used to investigated the growth ability of ESCs. Immunofluorescence staining and western blot was used to detected the target proteins. Results The clinical data showed that the endometrial thickness on HCG Day were significantly lower in GnRH-ant group. Although no difference of embryo quality in these two groups, GnRH-ant group showed remarkably decreased rate of HCG positive, embryo implantation and pregnancy. Moreover, GnRH-ant significantly reduced the proliferation and induced the apoptosis of ESCs. Furthermore, the expression and activation of c-kit receptor, which played pivotal roles during embryo implantation, were observably decreased by GnRH-ant. Inhibiting the activation of c-kit by imatinib remarkably suppressed the proliferation and promoted the apoptosis of ESCs. Additionally, the phosphorylation of AKT and expression of Cyclin D1, which were closely related with cellular growth, were distinctly lessened after treating with imatinib. Conclusions In summary, our study showed that GnRH-ant weakened the activization of c-kit receptor by decreasing its expression, causing the impaired growth ability of ESCs. Our findings provided a new insight into the effects of GnRH-ant on endometrium.

Abstract Background Increased evidence supports the relationship between chromobox protein homolog 3 (CBX3) and tumorigenesis of some cancers. However, the role of CBX3 in pan-cancers remains poorly defined. In the research, we aimed to investigate the prognostic value and the immunological functions of CBX3. Results We explored the potential oncogenic roles of CBX3 in mRNA and protein levels based on the diverse databases, including the expression, the correlation with prognosis, tumor microenvironment (TME), DNA methylation, protein phosphorylation and enrichment analysis across all TCGA tumors. The results show that CBX3 is overexpressed in multiple cancers, and significant correlations exist between high expression and adverse prognosis in most tumor patients. We observed an enhanced phosphorylation level in uterine corpus endometrial carcinoma, colon cancer and lung adenocarcinoma. A distinct relationship was also found between CBX3 expression and TME, including immune infiltration of tumor-infiltrating lymphocytes and cancer-associated fibroblasts, immune score or matrix score, immune checkpoints. The correlative transcription factors and miRNAs of CBX3-binding hub genes were analyzed to investigate the molecular mechanism. Moreover, alcoholism and alteration of DNA cellular biology may be involved in the functional mechanisms of CBX3. Conclusion The first pan-cancer study offers a relatively comprehensive cognition on the oncogenic roles of CBX3 as a prognostic and immunological marker in various malignant tumors.

Measurement(s) bacteria • Archaea • viruses Technology Type(s) Shotgun Sequencing Sample Characteristic - Organism estuary metagenome Sample Characteristic - Environment subtropical estuarine Sample Characteristic - Location Pearl river estuary Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.17139998

Traditional Chinese medicine and Chinese herbs have a demonstrated value for disease therapy and sub-health improvement. Attempts in this area tend to develop new forms to make their applications more convenient and wider. Here, we propose a novel Chinese herb microneedle (CHMN) patch by integrating the herbal extracts, Premna microphylla and Centella asiatica, with microstructure of microneedle for wound healing. Such path is composed of sap extracted from the herbal leaves via traditional kneading method and solidified by plant ash derived from the brine induced process of tofu in a well-designed mold. Because the leaves of the Premna microphylla are rich in pectin and various amino acids, the CHMN could be imparted with medicinal efficacy of heat clearing, detoxicating, detumescence and hemostatic. Besides, with the excellent pharmaceutical activity of Asiatic acid extracted from Centella asiatica, the CHMN is potential in promoting relevant growth factor genes expression in fibroblasts and showing excellent performance in anti-oxidant, anti-inflammatory and anti-bacterial activity. Taking advantages of these pure herbal compositions, we have demonstrated that the derived CHMN was with dramatical achievement in anti-bacteria, inhibiting inflammatory, collagen deposition, angiogenesis and tissue reconstruction during the wound closure. These results indicate that the integration of traditional Chinese herbs with progressive technologies will facilitate the development and promotion of traditional Chinese medicine in modern society.

Background Walnuts are among the most important dry fruit crops worldwide, typically exhibiting green leaves and yellow–brown or gray–yellow seed coats. A specific walnut accession with red leaves and seed coats, ‘RW-1’, was selected for study because of its high anthocyanin and proanthocyanidin (PA) contents. Anthocyanins and PAs are important secondary metabolites and play key roles in plant responses to biotic and abiotic stresses. However, few studies have focused on the molecular mechanism of anthocyanin biosynthesis in walnuts. Methods In this study, we determined the anthocyanin and PA components and their contents in different color leaves of ‘RW-1’ natural hybrid progenies at various developmental stages. Integrated transcriptome and metabolome analyses were used to identify the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs). We also performed conjoint analyses on DEGs and DAMs to ascertain the degree pathways, and explore the regulation of anthocyanin and PA biosynthesis. Results The results of widely targeted metabolome profiling and anthocyanin detection revealed 395 substances, including four PAs and 26 anthocyanins, in red (SR) and green leaves (SG) of ‘RW-1’ natural hybrid progenies. From the research, the contents of all anthocyanin components in SR were higher than that in SG. Among them, the contents of delphinidin 3-O-galactoside, cyanidin 3-O-galactoside, delphinidin 3-O-arabinoside and cyanidin 3-O-glucoside were significantly higher than others, and they were considered as the main types of anthocyanins. However, nine anthocyanins were detected only in SR. For PAs, the content of procyanidin C1 was higher in SR compared with SG, while procyanidin B1 and procyanidin B3 were higher in SR-1 and SR-3 but downregulated in SR-2 compared with the controls. Furthermore, transcriptome analysis revealed that the expressions of structural genes (C4H, F3H, F3′5′H, UFGT, LAR and ANR), three MYBs predicted as the activators of anthocyanin and PA biosynthesis, two MYBs predicted as the repressors of anthocyanin biosynthesis, and five WD40s in the anthocyanin and PA biosynthetic pathways were significantly higher in the SR walnuts. Gene-metabolite correlation analyses revealed a core set of 31 genes that were strongly correlated with four anthocyanins and one PA metabolites. The alteration of gene coding sequence altered the binding or regulation of regulatory factors to structural genes in different color leaves, resulting in the effective increase of anthocyanins and PAs accumulation in red walnut. Conclusions This study provides valuable information on anthocyanin and PA metabolites and candidate genes for anthocyanin and PA biosynthesis, yielding new insights into anthocyanin and PA biosynthesis in walnuts.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by persistent abnormally elevated blood sugar levels. T2DM affects millions of people and exerts a significant global public health burden. Danggui Buxue decoction (DBD), a classical Chinese herbal formula composed of Astragalus membranaceus (Huangqi) and Angelica sinensis (Danggui), has been widely used in the clinical treatment of diabetes and its complications. However, the effect of DBD on the gut microbiota of individuals with diabetes and its metabolism are still poorly understood. In this study, a T2DM model was established in Goto-Kakizaki (GK) rats, which were then treated with a clinical dose of DBD (4 g/kg) through tube feeding for 6 weeks. Next, we used 16S rRNA sequencing and untargeted metabolomics by liquid chromatography with mass spectrometry (LC–MS) to detect changes in the composition of the microbiota and cecal metabolic products. Our data show that DBD mediates the continuous increase in blood glucose in GK rats, improves insulin sensitivity, reduces expression of inflammatory mediators, and improves systemic oxidative stress. Moreover, DBD also improves microbial diversity (e.g., Romboutsia, Firmicutes, and Bacilli) in the intestines of rats with T2DM. Further, DBD intervention also regulates various metabolic pathways in the gut microbiota, including alanine, aspartate, and glutamate metabolism. In addition, arginine biosynthesis and the isoflavone biosynthesis may be a unique mechanism by which DBD exerts its effects. Taken together, we show that DBD is a promising therapeutic agent that can restore the imbalance found in the gut microbiota of T2DM rats. DBD may modify metabolites in the microbiota to realize its antidiabetic and anti-inflammatory effects.

Bioactive cations, including calcium, copper and magnesium, have shown the potential to become the alternative to protein growth factor-based therapeutics for bone healing. Ion substitutions are less costly, more stable, and more effective at low concentrations. Although they have been shown to be effective in providing bone grafts with more biological functions, the precise control of ion release kinetics is still a challenge. Moreover, the synergistic effect of three or more metal ions on bone regeneration has rarely been studied. In this study, vaterite-calcite CaCO3 particles were loaded with copper (Cu2+) and magnesium (Mg2+). The polyelectrolyte multilayer (PEM) was deposited on CaCuMg-CO3 particles via layer-by-layer technique to further improve the stability and biocompatibility of the particles and to enable controlled release of multiple metal ions. The PEM coated microcapsules were successfully combined with collagen at the outmost layer, providing a further stimulating microenvironment for bone regeneration. The in vitro release studies showed remarkably stable release of Cu2+ in 2 months without initial burst release. Mg2+ was released in relatively low concentration in the first 7 days. Cell culture studies showed that CaCuMg-PEM-Col microcapsules stimulated cell proliferation, extracellular maturation and mineralization more effectively than blank control and other microcapsules without collagen adsorption (Ca-PEM, CaCu-PEM, CaMg-PEM, CaCuMg-PEM). In addition, the CaCuMg-PEM-Col microcapsules showed positive effects on osteogenesis and angiogenesis in gene expression studies. The results indicate that such a functional and controllable delivery system of multiple bioactive ions might be a safer, simpler and more efficient alternative of protein growth factor-based therapeutics for bone regeneration. It also provides an effective method for functionalizing bone grafts for bone tissue engineering.

Legal consciousness is the individual consciousness which reflects legal phenomena. Well-developed legal consciousness plays a crucial role in informing citizens of his legal right and ability to exercise these rights, therefore forms certain connections of individuals and society, and its development is a key part of individual’s socialization process. Here, we investigated the emotion aspect of legal consciousness (henceforth legal emotion) and tried to identify several factors affecting the development of legal emotion and several factors affected by legal emotion. A large sample of Chinese junior middle school students (N = 967) completed a battery of self-reported questionnaires regarding legal emotion, peer attachment, self-esteem, prosocial tendencies, and interpersonal trust. The results indicated that for early adolescents, peer attachment predicts both positive and negative legal emotion. Importantly, peer attachment affects legal emotion partially through self-esteem. We also showed that negative legal emotion acted as a mediator on the relationship between interpersonal trust and prosocial tendencies. The results provided important insights into the role of legal emotion, the emotion aspect of legal consciousness, in the social interactions and its potential psychological mechanism.

The process of storing oil depots and combined station tanks is affected by factors such as process technology, equipment, and management methods. Inevitably, some heavy hydrocarbon components will condense. According to the available literature, the existing detection methods are not enough to accurately measure the component composition so that the proportion of heavy hydrocarbon substances in the lost gas is reduced. In this paper, by inventing a homogeneous reduction device, the lost gas in the entire laboratory process was kept in a homogeneous state so that the gas components were well-retained. Using the homogeneous reduction method and a traditional inspection method, gas chromatography was performed on a standard gas and the on-site lost gas, respectively. The standard gas measurement results show that the mean deviations of the homogeneous reduction method and the traditional test method were −3.45% and −11.62%, respectively, and the reduction degree reached 96.55% with the homogeneous reduction method. The results of the on-site gas loss measurements show that the proportions of most hydrocarbon substances in each lost gas increase to varying degrees after using the homogeneous reduction technology. Therefore, it is proved that these components can be better preserved using the homogeneous reduction method. It can effectively avoid the condensation of components, which is of great significance to the study of oil and gas loss.