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Abstract Background This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells. Results Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1. Conclusions The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.

AIM: To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy (IVCM). METHODS: This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals. Among the glaucoma patients, 54 were treated with medication, while 25 remained untreated. Central corneal images were evaluated by IVCM, and then ACCMetrics was used to calculate the following parameters: corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman's rank correlation coefficient. RESULTS: The CNFD was reduced in glaucoma groups compared to healthy subjects (P

Abstract In recent years, museums have become valuable venues for students to develop career awareness outside of school. However, optimizing the educational potential of museums and improving learners’ outcomes presents a significant challenge in museum learning design. This study integrates three main game elements—goals, stories, and role-playing—into museum visits to design a Gamified Learning Activity (GLA). To verify the effectiveness of the GLA, we conducted a quasi-experiment with 66 elementary school students at the Handicraft Museum. Using a mixed-methods approach with convergent parallel design, we collected quantitative data from knowledge tests and qualitative data from DAST (Draw-a-Scientist-Test) and interviews for a comprehensive analysis. The results showed that learners who participated in the GLA paid more attention to the details of the handicrafts, appreciated the craftsmen more, and eliminated stereotypes about the age of craftsmen. This indicates that the GLA not only enhances learners’ acquisition of museum knowledge but also has a profound impact on their non-cognitive aspects, such as career awareness.

Accurate prediction of pollutants in grain processing is of great significance to ensure food safety. However, due to the complexity of grain processing and the difficulty of pollutant detection, the data volume is too small to meet the needs of modeling and forecasting, so it is necessary to develop a method for expanding pollutant data from small samples. At the same time, pollutant data of small samples in grain processing often lacks sufficient prior knowledge. Traditional supervised learning method has low prediction accuracy, and the existing continuous deep learning model is not suitable for grain processing, being intermittent. Hence, there is a need to develop a prediction method based on unsupervised learning and deep learning for pollutants in grain processing. This study proposed a prediction method for pollutants in grain processing based on data expansion with time generative adversarial networks (TimeGAN) or based on generative adversarial networks (GAN) combined with deep forest (DF). First, a TimeGAN model was constructed to learn from small sample data and generate multiple sets of sample data, achieving data augmentation. Then, combining the GAN model with unsupervised learning with the DF model suitable for a discrete process, a GAN-DF model was constructed for pollutant prediction. Next, the DF and long short-term memory (LSTM)-DF models were embedded into GAN as generators, separately, and the resulting DFGAN and LSTM-DFGAN models had improved accuracy in pollutant prediction. The results of simulation and verification using the data of the heavy metal pollutant lead (Pb) in rice processing showed that the TimeGAN method was feasible to expand data, and the LSTM-DFGAN model had the best comprehensive prediction performance. After data expansion, the average absolute error and root mean square error were as low as 7.50 × 10-5 and 1.60 × 10-8 mg/kg, respectively.

Abstract The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC.

Abstract Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial–mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity. Graphical Abstract

Abstract Phasing down fossil fuels is crucial for climate mitigation. Even though 80–90% of fossil fuels are used to provide energy, their use as feedstock to produce plastics, fertilizers, and chemicals, is associated with substantial CO2 emissions. However, our understanding of hard-to-abate chemical production remains limited. Here we developed a chemical process-based material flow model to investigate the non-energy use of fossil fuels and CO2 emissions in China. Results show in 2017, the chemical industry used 0.18 Gt of coal, 88.8 Mt of crude oil, and 12.9 Mt of natural gas as feedstock, constituting 5%, 15%, and 7% of China’s respective total use. Coal-fed production of methanol, ammonia, and PVCs contributes to 0.27 Gt CO2 emissions ( ~ 3% of China’s emissions). As China seeks to balance high CO2 emissions of coal-fed production with import dependence on oil and gas, improving energy efficiency and coupling green hydrogen emerges as attractive alternatives for decarbonization.

Phellodendron chinense is an extraordinary medicinal plant, and its stem bark is a famous traditional Chinese medicine in China, containing a number of phytochemicals with biological and pharmacological functions. Studies have shown that the medicinal ingredients in P. chinense from various regions are different, as soil types might be important factors affecting the growth and quality of P. chinense. In this study, the effects of acidic purple soil, alkaline purple soil, yellow soil and red soil on the growth, nutrient element accumulation and partitioning in P. chinense seedlings were studied. Our results showed that the biomass of leaves and stems in acidic purple soil was significantly higher than in other soils, and the root biomass was significantly lower than that in yellow soil. C, N, P and Ca contents cultured in acidic purple soil were the highest compared to other soils, and K and Mg content were the highest in yellow soil and red soil, respectively. The distribution of carbon between different organs can reflect environmental stress. N has become a limiting factor for the growth and development of P. chinense seedlings. C:N and C:P ratios in the leaves were significantly lower than those in the stem and roots. Among four soil types, the highest N:P ratio was 1.65 in P. chinense seedlings. These results suggest that four soil types may significantly affect the accumulation and distribution of biomass and nutrient elements in P. chinense seedlings. The characteristic patterns in different organs have different responses. Acidic purple soil is more suitable for the growth of P. chinense. These findings will help to understand the distribution characteristics and requirements of nutrient elements in P. chinense seedlings, and further provide a theoretical basis and reference for site selection and cultivation strategy.

Summary: Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, with the highest single-cause mortality. Monocarboxylate transporter 4 (Mct4) transports intracellular lactate outside, but its role in regulating host immune response against Mtb infection remains unknown. Mct4 expression was upregulated in Mtb-infected macrophages and in patients with TB. Mct4 silencing/deficiency significantly decreased Mtb survival in macrophages and in lungs and spleens of mice, while Mct4 overexpression facilitated Mtb survival in macrophages. Furthermore, Mct4 promoted intracellular lactate transport, nuclear factor κB (NF-κB) p65 activation, and interleukin-10 (IL-10) production upon Mtb infection. Mechanistically, IL-10 silencing and IL-10-neutralizing antibody blocked Mct4 overexpressing increased Mtb survival. Replenishing lactate and NF-κB p65 inhibitor JSH23 treatment could inhibit Mct4 overexpressing increased NF-κB p65 activation, IL-10 production, and Mtb survival in macrophages. This study demonstrates that Mct4 promotes Mtb survival through restricting intracellular lactate accumulation to promote NF-κB p65-mediated IL-10 production and suggests Mct4-NF-κB p65-IL-10 axis a potential target for TB treatment.

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Connexin is a transmembrane protein involved in gap junctions (GJs) formation. Our previous study found that connexin 37 (Cx37), encoded by gap junction protein alpha 4 (GJA4), expressed on fibroblasts acts as a promoter of CRC and is closely related to epithelial-mesenchymal transition (EMT) and tumor immune microenvironment. However, to date, the mechanism concerning the malignancy of GJA4 in tumor stroma has not been studied. Methods: Hematoxylin-eosin (HE) and immunohistochemical (IHC) staining were used to validate the expression and localization of GJA4. Using single-cell analysis, enrichment analysis, spatial transcriptomics, immunofluorescence staining (IF), Sirius red staining, wound healing and transwell assays, western blotting (WB), Cell Counting Kit-8 (CCK8) assay and in vivo experiments, we investigated the possible mechanisms of GJA4 in promoting CRC. Results: We discovered that in CRC, GJA4 on fibroblasts is involved in promoting fibroblast activation and promoting EMT through a fibroblast-dependent pathway. Furthermore, GJA4 may act synergistically with M2 macrophages to limit T cell infiltration by stimulating the formation of an immune-excluded desmoplasic barrier. Finally, we found a significantly correlation between GJA4 and pathological staging (P < 0.0001) or D2 dimer (R = 0.03, P < 0.05). Conclusion: We have identified GJA4 expressed on fibroblasts is actually a promoter of the tumor mesenchymal phenotype. Our findings suggest that the interaction between GJA4+ fibroblasts and M2 macrophages may be an effective target for enhancing tumor immunotherapy.

Summary: Background: Since the initial identification of the Severe Fever with Thrombocytopenia Syndrome (SFTS) in ticks in rural areas of China in 2009, the virus has been increasingly isolated from a diverse array of hosts globally, exhibiting a rising trend in incidence. This study aims to conduct a systematic analysis of the temporal and spatial distribution of SFTS cases, alongside an examination of the infection rates across various hosts, with the objective of addressing public concerns regarding the spread and impact of the disease. Methods: In this systematic review and meta-analysis, an exhaustive search was conducted across multiple databases, including PubMed, Web of Science, Embase, and Medline, CNKI, WanFang, and CQVIP. The literature search was confined to publications released between January 1, 2009, and May 29, 2023. The study focused on collating data pertaining to animal infections under natural conditions and human infection cases reported. Additionally, species names were unified using the National Center for Biotechnology Information (NCBI) database. The notification rate, notification death rate, case fatality rate, and infection rates (or MIR) were assessed for each study with available data. The proportions were pooled using a generalized linear mixed-effects model (GLMM). Meta-regressions were conducted for subgroup analysis. This research has been duly registered with PROSPERO, bearing the registration number CRD42023431010. Findings: We identified 5492 studies from database searches and assessed 238 full-text studies for eligibility, of which 234 studies were included in the meta-analysis. For human infection data, the overall pooled notification rate was 18.93 (95% CI 17.02–21.05) per ten million people, the overall pooled notification deaths rate was 3.49 (95% CI 2.97–4.10) per ten million people, and the overall pooled case fatality rate was 7.80% (95% CI 7.01%–8.69%). There was an increasing trend in notification rate and deaths rate, while the case fatality rate showed a significant decrease globally. Regarding animal infection data, among 94 species tested, 48 species were found to carry positive nucleic acid or antibodies. Out of these, 14 species were classified under Arthropoda, while 34 species fell under Chordata, comprising 27 Mammalia and 7 Aves. Interpretation: This systematic review and meta-analysis present the latest global report on SFTS. In terms of human infections, notification rates and notification deaths rates are on the rise, while the case fatality rate has significantly decreased. More SFTSV animal hosts have been discovered than before, particularly among birds, indicating a potentially broader transmission range for SFTSV. These findings provide crucial insights for the prevention and control of SFTS on a global scale. Funding: None.

AIM: To identify disease-causative mutations in families with congenital cataract. METHODS: Two Chinese families with autosomal-dominant congenital cataract (ADCC) were recruited and underwent comprehensive eye examinations. Gene panel next-generation sequencing of common pathogenic genes of congenital cataract was performed in the proband of each family. Sanger sequencing was used to valid the candidate gene mutations and sequence the other family members for co-segregation analysis. The effect of sequence changes on protein structure and function was predicted through bioinformatics analysis. Major intrinsic protein (MIP)-wildtype and MIP-G29R plasmids were constructed and microinjected into zebrafish single-cell stage embryos. Zebrafish embryonic lens phenotypes were screened using confocal microscopy. RESULTS: A novel heterozygous mutation (c.85G>A; p.G29R) in the MIP gene was identified in the proband of one family. A known heterozygous mutation (c.97C>T; p.R33C; rs864309693) in MIP was found in the proband of another family. In-silico prediction indicated that the novel mutation might affect the MIP protein function. Zebrafish embryonic lens was uniformly transparent in both wild-type PCS2+MIP and mutant PCS2+MIP. CONCLUSION: Two missense mutations in the MIP gene in Chinese cataract families are identified, and one of which is novel. These findings expand the genetic spectrum of MIP mutations associated with cataracts. The functional studies suggest that the novel MIP mutation might not be a gain-of-function but a loss-of-function mutation.

Abstract Background The primary purpose of this study was to investigate the predictive value of alterations in cervical artery hemodynamic parameters induced by a simulated end-inspiratory occlusion test (sEIOT) measured by ultrasound for predicting postinduction hypotension (PIH) during general anesthesia. Methods Patients undergoing gastrointestinal tumor resection under general anesthesia were selected for this study. Ultrasound has been utilized to assess hemodynamic parameters in carotid artery blood flow before induction, specifically focusing on variations in corrected flow time (ΔFTc) and peak blood flow velocity (ΔCDPV), both before and after sEIOT. Anesthesia was induced by midazolam, sufentanil, propofol, and rocuronium, and blood pressure (BP) and heart rate (HR) were recorded within the first 10 min following endotracheal intubation. PIH was defined as fall in systolic blood pressure (SBP) or mean arterial pressure (MAP) by > 30% of baseline or MAP to

Abstract Background Parent‒child communication in migrant families is essential to family bonds and the mental health of left-behind children (LBC). Little is known about the different patterns of communication between migrant parents and LBC and associated communication quality and mental health outcomes. Methods A sample of 2,183 Chinese children (mean age = 12.95 ± 1.29 years) from Anhui province, including LBC whose parents had both migrated (n = 1,025) and children whose parents had never migrated (never-LBC, n = 1,158), was analyzed. With the LBC sample, latent class analysis was applied to identify the patterns of parent‒child communication. Multinomial logistic regression analysis was conducted to assess the associations between the sociodemographic variables and class membership of LBC. Analysis of covariance and chi-square tests were used to compare communication quality and mental health outcome differences among the classes of LBC and between each of the classes and never-LBC. Results Five latent classes of communication formed through different media or channels between migrant parents and their LBC were identified. Higher household economic status (OR = 2.81, p

According to the speech learning model [Flege, J. E. (1995). Second language speech learning: Theory, findings, and problems. In W. Strange (Ed.), "Speech perception and linguistic experience: Issues in cross-language research" (pp. 233-277). York Press], learners whose first language (L1) is a tonal language (e.g. Cantonese) can be confused by similar yet different tones in their L1 and another tonal language (e.g. Mandarin). Encouraged by the biliteracy and trilingualism language policy in Hong Kong, L1 Cantonese learners of Mandarin have been committed to learning the third language (L3) Mandarin tones but are struggling with that task. The main purpose of this study is to examine Cantonese learners' perceptions and production of Mandarin tones, and to investigate learners' performance in production tasks before and after implementing metaphonological awareness protocols. Twenty-five Cantonese learners studying at a local university were recruited to complete the production, perception and verbal protocol tasks. Based on Wrembel's [2015. Metaphonologcial awareness in multilinguals: A case of L3 Polish. "Language Awareness," 24(1), 60-83. https://doi.org/10.1080/09658416.2014.890209] framework, this study categorised the participants' statements of metaphonological awareness shown in their self-correction and self-reflection performances in the introspective and retrospective protocols. The error rates and patterns in the production and perception tasks were analysed. Metaphonological awareness training has a significant positive effect on improving learners' Mandarin tone pronunciation.

In regular dance teaching, teachers find it difficult to pay attention to and meet the specific needs of each student. Extended-reality (XR) has the potential to help students get more information to dance learning. This study developed an XR interactive learning system to assist teachers in dance teaching, and explored the impact of XR on the process and results of dance skills. To assess the effectiveness of XR in dance education, a quasi-experiment was designed. Students majoring in preschool education in vocational high school in Hangzhou, China were recruited as research participants. 54 female students were divided into two groups with the same teaching pace, each with 27 students. The experimental group was taught dance lessons using a developed XR interactive learning system, while the control group was taught dance lessons using traditional methods. The experiment lasted for eight weeks and consisted of 16 lessons. Finally, the results indicate that XR has the potential to improve students' learning performance and facilitate learning interactions in dance learning; to provide real-time personalized feedback to students and improve autonomous learning. Moreover, XR has the potential to enhance learning experience by reducing the cognitive load of students in dance learning. The results of this study is expected to help those considering the use of XR to supplement dance instruction.

BackgroundOsteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors.Methods135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function.ResultsBMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r2 = −0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r2 = −0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (β = 0.712, p < 0.001), knee flexor muscle strength (β = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: β = −0.428, p < 0.001) and flexor muscle strength (6MGS: β = 0.367, p < 0.001), were the main predictors with performance-based physical function.ConclusionPain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.

Background: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. Objectives: Diagnostic yield evaluation of biopsy using ENB for PPNs

Abstract Lactobacillus rhamnosus GG (LGG), the well‐characterized human‐derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase‐3−GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)‐producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2−GSDMEb pyroptosis pathway. Further analysis reveals the Caspase‐3−GSDMEa pyroptosis is initiated by the species‐specific recognition of SpaC by TLR4ba, which accounts for the species‐specificity of the SpaC‐inducing intestinal pyroptosis in zebrafish. The observed pyroptosis‐driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host‐specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.