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Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer. Despite advances in tissue culture techniques, a robust model for ATC spheroid culture is yet to be developed. In this study, we created an efficient and cost-effective 3D tumor spheroids culture system from human ATC cells and existing cell lines that better mimic patient tumors and that can enhance our understanding of in vivo treatment response. We found that patient-derived ATC cells and cell lines can readily form spheroids in culture with a unique morphology, size, and cytoskeletal organization. We observed both cohesive (dense and solid structures) and discohesive (irregularly shaped structures) spheroids within the same culture condition across different cell lines. BRAF WT ATC spheroids grew in a cohesive pattern, while BRAF V600E -mutant ATC spheroids had a discohesive organization. In the patient-derived BRAF V600E -mutant ATC spheroids, we observed both growth patterns, but mostly the discohesive type. Histologically, ATC spheroids had a similar morphology to the patient's tumor through H&E staining and proliferation marker staining. Moreover, RNA sequencing analysis revealed that the gene expression profile of tumor cells derived from the spheroids closely matched parental patient tumor-derived cells in comparison to monolayer cultures. In addition, treatment response to combined BRAF and MEK inhibition in BRAF V600E -mutant ATC spheroids exhibited a similar sensitivity to the patient clinical response. Our study provides a robust and novel ex vivo spheroid model system that can be used in both established ATC cell lines and patient-derived tumor samples to better understand the biology of ATC and to test therapeutics., (© 2024. The Author(s).)

Background: Arterial transit artifact (ATA) observed on arterial spin labeling (ASL) was recently suggested to be associated with improved functional outcomes following acute ischemic stroke (AIS). AIS is a heterogeneous disease with diverse pathogenic mechanisms depending on the stroke subtype. This study aimed to investigate the association between ATA and 3-month functional outcomes in AIS patients according to etiology subtypes., Methods: Consecutive patients with AIS were included. All patients underwent ASL MRI with postlabeling delay (PLD) of 1.5 and 2.5 s. ATA was assessed from the ASL images of both PLDs. Stroke etiologic subtypes were determined according to the modified TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Short-term functional outcomes were evaluated using the 3-month modified Rankin scale (mRS). Log-binomial regression was applied to analyze the association between ATA and functional outcomes at 3 months after stroke., Results: Ninety-eight AIS patients (62.73 ± 13.05 years; 68 men) were finally included. ATA was detected in forty-six patients and most frequently seen in the large-artery atherosclerosis (LAA) subtype (35/46). The ATA group exhibited a lower percentage of patients with mRS > 2 compared to the group without ATA (36.5% vs. 19.6%; P < 0.001). ATA was independently associated with better 3-month clinical outcomes (adjusted risk ratio, 0.35[95% CI, 0.16-0.74]) in the multivariate log-binomial regression model. After stratification by TOAST subtypes, a significant association was found between ATA and better outcomes in the LAA subtype (adjusted risk ratio, 0.20[ 95% CI, 0.05-0.72]) but not in cardioembolism and small artery occlusion (SVO) subtype., Conclusion: ATA is associated with better outcomes at 3 months in patients with AIS, especially in the LAA subtype, but this association attenuated in the cardioembolism and SVO subtypes., (© 2024. The Author(s).)

Aims: Extracellular vesicles from Lacticaseibacillus paracasei PC-H1 have antiproliferative activity of colon cells, but the effect on glycolytic metabolism of cancer cell remains enigmatic. The authors investigated how Lacticaseibacillus paracasei extracellular vesicles (LpEVs) inhibit the growth of colon cancer cells by affecting tumor metabolism. Materials & methods: HCT116 cells were treated with LpEVs and then differentially expressed genes were analyzed by transcriptome sequencing, the sequencing results were confirmed in vivo and in vitro . Results: LpEVs entered colon cancer cells and inhibited their growth. Transcriptome sequencing revealed differentially expressed genes were related to glycolysis. Lactate production, glucose uptake and lactate dehydrogenase activity were significantly reduced after treatment. LpEVs also reduced HIF-1α, GLUT1 and LDHA expression. Conclusion: LpEVs exert their antiproliferative activity of colon cancer cells by decreasing HIF-1α-mediated glycolysis.

Mucosal vaccinations for respiratory pathogens provide effective protection as they stimulate localized cellular and humoral immunities at the site of infection. Currently, the major limitation of intranasal vaccination is using effective adjuvants capable of withstanding the harsh environment imposed by the mucosa. Herein, we describe the efficacy of using a unique biopolymer, N-dihydrogalactochitosan (GC), as a nasal mucosal vaccine adjuvant against respiratory infections. Specifically, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV), an MF-59 equivalent. In contrast to AV, intranasal application of GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. Moreover, GC+S+NC-vaccinated animals were largely resistant to the lethal SARS-CoV-2 challenge and experienced drastically reduced morbidity and mortality, with animal weights and behavior returning to normal 22 days post-infection. In contrast, animals intranasally vaccinated with AV+S+NC experienced severe weight loss, mortality, and respiratory distress, with none surviving beyond 6 days post-infection. Our findings demonstrate that GC can serve as a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses. STATEMENT OF SIGNIFICANCE: We demonstrated that a unique biopolymer, N-dihydrogalactochitosan (GC), was an effective nasal mucosal vaccine adjuvant against respiratory infections. Specifically, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV). In contrast to AV, GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. About 90 % of the GC+S+NC-vaccinated animals survived the lethal SARS-CoV-2 challenge and remained healthy 22 days post-infection, while the AV+S+NC-vaccinated animals experienced severe weight loss and respiratory distress, and all died within 6 days post-infection. Our findings demonstrate that GC is a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses., Competing Interests: Declaration of competing interest The authors have no conflict of interest. WRC is a co-founder and a member of the Board of Directors of Immunophotonics, Inc. LA, SSKL, and TH declare a conflict of interest as employees with minority ownership stakes of Immunophotonics, Inc., the manufacturer of the proprietary adjuvant GC., (Copyright © 2023. Published by Elsevier Ltd.)

Coccidiosis is an intestinal protozoan disease of sheep, that causes substantial economic losses in the industry due to its intestinal protozoan origins. Many anti-protozoan drugs including ionophores, triazines, and sulfonamides have been widely used to treat sheep coccidiosis. Still, anticoccidial resistance and drug residues in edible tissues have prompted an urgent search for alternatives. In this study, the anti-coccidial effectiveness of the Radix dichroae extract was compared to that of the conventional anti-coccidial drug diclazuril. Here, eighteen 45-day-old lambs naturally-infected with Eimeria spp. were randomly allocated in three groups: control group, Radix dichroae extract group and diclazuril group. The results showed that the body weight gain (BWG) during the treatment and withdrawal periods was considerably improved in the coccidiosis-infected sheep treated with Radix dichroae extract and diclazuril compared to the control group, respectively. Additionally, the Radix dichroae extract and diclazuril had fewer oocysts per gram (OPG) than the control group, showing similar anti-coccidial effects on days 14, 21, 28, 35 and 78, respectively. Furthermore, Radix dichroae extract and diclazuril treatment altered the structure and composition of gut microbiota, promoting the relative abundance of Actinobacteriota, Firmicutes, Alistipes, and Bifidobacterium, while decreasing the abundance of Bacteroidota, Marinilaceae, Helicobacteraceae, and Prevotella. Moreover, Spearman's correlation analysis further revealed a correlation between the OPG and BWG and gut microorganisms. Collectively, the results indicated that Radix dichroae extract had similar anti-coccidial effects as diclazuril, and could regulate gut microbiota balance in growing lambs., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

As a new type of pollutant in the marine environment and terrestrial ecosystems, microplastics have attracted widespread attention. Assessing the ecological risk of microplastics relies on accurately detecting small-sized particles in the environment. Microplastics exhibit unique "fingerprint" characteristics in Raman spectroscopy, making them suitable for rapid identification. In this study, we achieved visualization of microplastics through pseudo-color images generated by Raman spectroscopy imaging. Pseudo-color imaging maps were generated by selecting characteristic peaks and the classical least-squares fitting method was used to visually represent the distribution of different microplastics. The study explored the potential of Raman spectroscopy and its mapping mode in distinguishing various types of mixed microplastics and demonstrated that this approach can identify microplastics in complex environmental samples. Specifically, a cloud-point extraction followed by membrane filtration method was successfully applied to identifying mixed-component microplastics. In summary, the category, quantity, location, and differentiation of microplastics can be accurately analyzed by Raman spectroscopy, which provides a basis for assessing their ecological risk.

Nitrogen (N), phosphorus (P), and potassium (K) exert various effects on strawberry (Fragaria ananassa Duchesne) yields. In this study, we employed an orthogonal experimental design (T1-T9) with three fertilization treatments (N, P, and K) at three levels to identify an optimal fertilization scheme for strawberry cultivation. The effects of fertilizer combinations the rhizosphere soil microbial community were also explored by using bacterial full-length 16S rRNA and fungal ITS (internal transcribed spacer) sequencing (30 samples for each analysis). The results showed that the average plant height and leaf area of the fertilized groups were 24.6% and 41.6% higher than those of the non-fertilized group (T0). After 60 d of planting, the sucrase activity in the T6 group increased by 76.67% compared to the T0 group, with phosphate fertilizer exerting a more significant impact on sucrase activity. The T6 treatment group had the highest alpha diversity index among bacterial and fungal microorganisms, and had a different microbial community structure compared with the control group. The most abundant bacterial taxa in the strawberry rhizosphere soil were Proteobacteria, Bacteroidota, and Acidobacteriota, and the most abundant fungal phyla were Monoblepharomycota, Glomeromycota, and Mucoromycota. Application of the optimal combined fertilizer treatment (T6) significantly increased the abundance of Proteobacteria and altered the abundance of Gemmatimonas compared to other treatment groups. Notably, Gemmatimonas abundance positively correlated with strawberry plant height and soil N, P, and K levels. These findings indicated that the relative abundance of beneficial bacteria could be enhanced by the application of an optimal fertilizer ratio, ultimately improving strawberry agronomic traits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Defect sites present on the surface of catalysts serve a crucial role in different catalytic processes. Herein, we have investigated defect engineering within a hybrid system composed of "soft" polymer catalysts and "hard" metal nanoparticles, employing the disparity in their thermal expansions. Electron paramagnetic resonance, X-ray photoelectron spectroscopy, and mechanistic studies together reveal the formation of new abundant defects and their synergistic integrability with plasmonic enhancement within the hybrid catalyst. These active defects, co-localized with plasmonic Ag nanoparticles, promote the utilization efficiency of hot electrons generated by local plasmons, thereby enhancing the CO 2 photoreduction activity while maintaining the high catalytic selectivity.

The long duration of landfill stabilization is one of the challenges faced by municipalities. In this paper, a combination of micro-aeration and leachate recirculation is used to achieve rapid degradation of organic matter in landfill waste. The results showed that the content of volatile fatty acids (VFAs) in the hydrolysis phase increased significantly and could enter the methanogenic phase quickly. Until the end of the landfill, the removal rates of chemical oxygen demand (COD), total phosphorus (TP) and ammonia nitrogen (NH 4 + -N) by micro-aeration and leachate recirculation reached 80.17 %, 48.30 % and 48.56 %, respectively, and the organic matter degradation rate reached 50 %. Micro-aeration and leachate recirculation enhanced the abundance of facultative hydrolytic bacteria such as Rummeliibacillus and Bacillus and the oxygen tolerance of Methanobrevibacter and Methanoculleus. Micro-aeration and leachate recirculation improved the organic matter degradation efficiency of landfill waste by promoting the growth of functional microorganisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Engineering human tissue with diverse cell types and architectures remains challenging. The cerebral cortex, which has a layered cellular architecture composed of layer-specific neurons organised into vertical columns, delivers higher cognition through intricately wired neural circuits. However, current tissue engineering approaches cannot produce such structures. Here, we use a droplet printing technique to fabricate tissues comprising simplified cerebral cortical columns. Human induced pluripotent stem cells are differentiated into upper- and deep-layer neural progenitors, which are then printed to form cerebral cortical tissues with a two-layer organization. The tissues show layer-specific biomarker expression and develop a structurally integrated network of processes. Implantation of the printed cortical tissues into ex vivo mouse brain explants results in substantial structural implant-host integration across the tissue boundaries as demonstrated by the projection of processes and the migration of neurons, and leads to the appearance of correlated Ca 2+ oscillations across the interface. The presented approach might be used for the evaluation of drugs and nutrients that promote tissue integration. Importantly, our methodology offers a technical reservoir for future personalized implantation treatments that use 3D tissues derived from a patient's own induced pluripotent stem cells., (© 2023. Springer Nature Limited.)

Introduction: Natural menopause is an inevitable biological process with significant implications for women's health. However, the molecular mechanisms underlying menopause are not well understood. This study aimed to investigate the molecular and cellular changes occurring in the ovary before and after perimenopause., Methods: Single-cell sequencing data from the GTEx V8 cohort (30-39: 14 individuals; 40-49: 37 individuals; 50-59: 61 individuals) and transcriptome sequencing data from ovarian tissue were analyzed. Seurat was used for single-cell sequencing data analysis, while harmony was employed for data integration. Cell differentiation trajectories were inferred using CytoTrace. CIBERSORTX assessed cell infiltration scores in ovarian tissue. WGCNA evaluated co-expression network characteristics in pre- and post-perimenopausal ovarian tissue. Functional enrichment analysis of co-expression modules was conducted using ClusterprofileR and Metascape. DESeq2 performed differential expression analysis. Master regulator analysis and signaling pathway activity analysis were carried out using MsViper and Progeny, respectively. Machine learning models were constructed using Orange3., Results: We identified the differentiation trajectory of follicular cells in the ovary as ARID5B+ Granulosa -> JUN+ Granulosa -> KRT18+ Granulosa -> MT-CO2+ Granulosa -> GSTA1+ Granulosa -> HMGB1+ Granulosa. Genes driving Granulosa differentiation, including RBP1, TMSB10, SERPINE2, and TMSB4X, were enriched in ATP-dependent activity regulation pathways. Genes involved in maintaining the Granulosa state, such as DCN, ARID5B, EIF1, and HSP90AB1, were enriched in the response to unfolded protein and chaperone-mediated protein complex assembly pathways. Increased contents of terminally differentiated HMGB1+ Granulosa and GSTA1+ Granulosa were observed in the ovaries of individuals aged 50-69. Signaling pathway activity analysis indicated a gradual decrease in TGFb and MAPK pathway activity with menopause progression, while p53 pathway activity increased. Master regulator analysis revealed significant activation of transcription factors FOXR1, OTX2, MYBL2, HNF1A, and FOXN4 in the 30-39 age group, and GLI1, SMAD1, SMAD7, APP, and EGR1 in the 40-49 age group. Additionally, a diagnostic model based on 16 transcription factors (Logistic Regression L2) achieved reliable performance in determining ovarian status before and after perimenopause., Conclusion: This study provides insights into the molecular and cellular mechanisms underlying natural menopause in the ovary. The findings contribute to our understanding of perimenopausal changes and offer a foundation for health management strategies for women during this transition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Wei, Wang, Liu, Zhang, Liu, Liu and Ye.)

Food waste (FW) anaerobic digestion systems are prone to imbalance during long-term operation, and the imbalance mechanism is complex. Anaerobic co-digestion (AcoD) of FW and other substrates can overcome the performance limitations of single digestion, allowing for the mutual use of multiple wastes and resource recovery. Research on the AcoD of FW has been widely conducted and successfully applied to a practical engineering scale. Therefore, this review describes the research progress of AcoD of FW with other substrates. By analyzing the problems and challenges faced by AcoD of FW, the synergistic effects and influencing factors of different biomass wastes are discussed, and improvement strategies to improve the performance of AcoD of FW are summarized from different reaction stages of anaerobic digestion. By combing the research progress of AcoD of FW, it provides a reference for the optimization and improvement of the performance of the co-digestion system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Although cellular and animal studies have reported that resolvin D1 (RvD1) and resolvin D2 (RvD2) are mechanisms involved in the development of type 2 diabetes mellitus (T2DM), the impact of RvD1 and RvD2 on the risk of T2DM at a population level remains unclear., Methods: We included 2755 non-diabetic adults from a community-based cohort in China and followed them for seven years. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of RvD1 and RvD2 with T2DM probability. Time-dependent receiver operator characteristics (ROC) curve was used to evaluate the predictive performance of RvD1 and RvD2 for the risk of T2DM based on the Chinese CDC T2DM prediction model (CDRS)., Results: A total of 172 incident T2DM cases were identified. Multivariate-adjusted HRs (95% CI) for T2DM across quartiles of RvD1 levels (Q1, Q2, Q3 and Q4) were 1.00, 1.64 (1.03-2.63), 1.80 (1.13-2.86) and 1.61 (1.01-2.57), respectively. Additionally, body mass index (BMI) showed a significant effect modification in the association of RvD1 with incident T2DM ( P interaction = 0.026). After multivariate adjustment, the HR (95% CI) for T2DM in the fourth compared with the first quartile of RvD2 was 1.94 (95% CI: 1.24-3.03). Time-dependent ROC analysis showed that the area under time-dependent ROC curves of the "CDRS+RvD1+RvD2" model for the 3-, 5- and 7-year risk of T2DM were 0.842, 0.835 and 0.828, respectively., Conclusions: Higher RvD1 and RvD2 levels are associated with a higher risk of T2DM at the population level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Wang, Jing, Liu, Jin, Wang, Zhang, Liu, Chen, Zhou and Dong.)

The landfill is still the primary waste treatment method in developing countries. Due to the long stability time and long-term occupation of a large amount of land, the landfill poses a significant threat to the ecological environment and affects the process of urbanization. This study conducted a landfill simulation reactor (LSR) experiment to achieve rapid landfill stabilization through micro-aeration and leachate recirculation. More than 60 % of the degradable organic carbon in the enhanced process (LSR-IV contains 24 % of the retained carbon) can be relatively quickly converted to a gaseous state, which is nearly half higher than the degradation efficiency of the traditional process (LSR-I contains 59.3 % of the retained carbon). A comprehensive environmental assessment is developed for the enhanced process, and better environmental benefits are obtained from the whole landfill process. Compared with conventional treatment process, the enhanced process is applied to the actual landfill to analyze the economic cost. In terms of the total cost, the enhanced process cost (60.1 CNY) is about 44 % lower than the conventional landfill process cost (107.6 CNY). The enhanced process saves nearly half of the time cost and reduces the cost of land acquisition. This study can provide a reference for governmental and municipal administrations to carry out the technological transformation of traditional landfills from the aspects of technology, economy and environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Metabolic syndrome (MS) is a group of complex medical conditions that can lead to serious cardiovascular and cerebrovascular diseases. According to the theory of traditional Chinese medicine (TCM), MS can be divided into two main subtypes termed 'phlegm-dampness syndrome' (TSZE) and 'qi-yin deficiency syndrome' (QYLX). At present, the research into intestinal microbiota of different TCM syndromes of MS and its association with clinical manifestation is lacking., Materials and Methods: Using 16S rRNA sequencing, we performed a cross-sectional analysis of human gut microbiota between two different TCM syndromes (QYLX and TSZE, n=60) of MS, and their differences with healthy participants (n=30)., Results: We found that the QYLX and TSZE groups differ from the healthy control group in the overall gut microbiota composition, and some specific microbial taxa and functional pathways. Moreover, significantly differentially abundant taxa and distinct BMI-correlated taxa were observed between QYLX and TSZE groups, suggesting the potential contribution of gut microbiota to the distinction between the two TCM syndromes. The predicted functional profiles also showed considerable differences, especially pathways related to amino acid metabolism and lipopolysaccharide synthesis., Conclusion: Our study highlights the gut microbiota's contribution to the differentiation between two TCM syndromes of MS and may provide the rationale for adopting different microbiota-directed treatment strategies for different TCM syndromes of MS in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shang, Zhang, Xiao, Zhang, Ruan, Zhang, Liu, Yu, Ni and Wang.)

Broiler leg diseases are a common abnormal bone metabolism issue that leads to poor leg health in growing poultry. Bone metabolism is a complicated regulatory process controlled by genetic, nutritional, feeding management, environmental, or other influencing factors. The gut microbiota constitutes the largest micro-ecosystem in animals and is closely related to many metabolic disorders, including bone disease, by affecting the absorption of nutrients and the barrier function of the gastrointestinal tract and regulating the immune system and even the brain-gut-bone axis. Recently, probiotic-based dietary supplementation has emerged as an emerging strategy to improve bone health in chickens by regulating bone metabolism based on the gut-bone axis. This review aims to summarize the regulatory mechanisms of probiotics in the gut microbiota on bone metabolism and to provide new insights for the prevention and treatment of bone diseases in broiler chickens.

Background: Metastatic breast cancer poses great challenge in cancer treatment. N-dihydrogalactochitosan (GC) is a novel immunoadjuvant that stimulates systemic immune responses when administered intratumourally following local tumour ablation. A combination of photothermal therapy (PTT) and GC, referred to as localized ablative immunotherapy (LAIT), extended animal survival and generates an activated B cell phenotype in MMTV-PyMT mouse mammary tumour microenvironment (TME). However, how T cell populations respond to LAIT remains to be elucidated., Methods: Using depletion antibodies, we studied the contributions of CD8 + and CD4 + T cells to the therapeutic effect of LAIT. Using single-cell RNA-sequencing (scRNAseq), we analysed tumour-infiltrating T cell heterogeneity and dissected their transcriptomes upon treatments of PTT, GC, and LAIT (PTT+GC)., Results: Loss of CD8 + T cells after LAIT abrogated the therapeutic benefits of LAIT. Ten days after treatment, proportions of CD8 + and CD4 + T cells in untreated TME were 19.2% and 23.0%, respectively. Upon LAIT, both proportions were increased to 25.5% and 36.2%, respectively. In particular, LAIT increased the proportions of naïve and memory cells from a resting state to an activated state. LAIT consistently induced the expression of co-stimulatory molecules, type I IFN responsive genes, and a series of antitumor cytokines, Ifng, Tnf, Il1, and Il17 in CD8 + and CD4 + T cells. LAIT also induced immune checkpoints Pdcd1, Ctla4, and Lag3 expression, consistent with T cell activation. Relevant to clinical translation, LAIT also upregulated genes in CD8 + and CD4 + T cells that positively correlated with extended survival of breast cancer patients., Conclusions: Overall, our results reveal that LAIT prompts immunological remodelling of T cells by inducing broad proinflammatory responses and inhibiting suppressive signalling to drive antitumour immunity., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: This study aimed to explore the value of native T1-mapping and diffusion-weighted imaging (DWI) in differentiating the pathological types and degree of tumor differentiation of lung cancer and their correlation with Ki-67 protein expression., Methods: A total of 78 consecutive lung cancer patients who received chest magnetic resonance imaging (MRI) scans between May 2020 and June 2021 were enrolled in this study. Two radiologists independently analyzed the apparent diffusion coefficient (ADC) and T1 values for each lesion. The intraclass correlation coefficient (ICC) and Bland-Altman plots were generated to assess interobserver agreement of the T1 and ADC mean values in lesions. The difference in ADC and T1 values among different pathological types, as well as between high- and low-differentiated lung cancers were analyzed, and diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve analysis. The correlation between ADC value, T1 value, and Ki-67 protein expression index was determined., Results: The ADC and T1 values showed excellent interobserver agreement (ICC 0.820, 0.942, respectively). There was a significant difference in ADC values between small cell carcinoma and squamous carcinoma (P<0.05), and between small cell carcinoma and adenocarcinoma (P<0.05), but not between squamous carcinoma and adenocarcinoma (P>0.05). A significant difference in T1 values was observed between small cell carcinoma (P<0.05) and adenocarcinoma, and between squamous carcinoma (P<0.05) and adenocarcinoma, but not between squamous carcinoma and small cell carcinoma (P>0.05). There were statistically significant differences in ADC and T1 values between the moderately and highly differentiated group and the poorly differentiated group (P<0.05). ROC curve analysis showed that the T1 combined with ADC value had high diagnostic value for the degree of differentiation of the tumor [area under the curve (AUC) =0.912]. Pearson correlation analysis showed a significant positive correlation between T1 value and Ki-67 index (r=0.66, P<0.001) and a significant negative correlation between ADC value and Ki-67 index (r=-0.45, P<0.01)., Conclusions: T1 and ADC values can be used to distinguish the pathological type and differentiation degree of lung cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-77/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Pancreatic cancer (PC) is the most lethal malignancy due to its high metastatic ability and poor drug permeability. Here, a synergized interventional photothermal-immunotherapy strategy was developed with imaging guidance and temperature monitoring by magnetic resonance imaging (MRI) technique, for the local treatment of metastatic PC. A tumor microenvironment (TME)-responsive nanoplatform was fabricated via coating of DSPE-PEG and indocyanine green (ICG) onto imiquimod (IMQ) loaded amorphous iron oxide nanoparticles (IONs). This unique nanoplatform, IMQ@IONs/ICG, served as a contrast agent for MRI, a drug delivery vehicle for IMQ and ICG, and a catalyst for TME modulation. The biodegradable IMQ@IONs/ICG was also non-toxic, and improved the penetration of the loaded drugs in PC to maximize thermal ablation of the tumor and minimize damage to the surrounding healthy tissue. For the treatment of aggressive, metastatic Panc02-H7 pancreatic tumors in mice, ION-assisted MRI was employed to guide the administration of interventional photothermal therapy (IPTT) and monitor the temperature distribution in target tumor and surrounding tissue during treatment. The local IPTT treatment induced in situ immunogenic cell death (ICD), and, in combination with released IMQ, triggered a strong antitumor immunity, leading to decreased metastases and increased CD8 + in spleen and tumors. With precise local treatment and monitoring, treated primary tumors were completely eradicated, mesentery metastases were dramatically reduced, and the survival time was significantly prolonged, without damage to normal tissue and systemic autoimmunity. Overall, this synergistic strategy represents a promising approach to treat PC with significant potential for clinical applications. STATEMENT OF SIGNIFICANCE: Pancreatic cancer (PC) is one of the most lethal malignancies because it is non-permeable to drugs and highly metastatic. In this study, we designed a tumor microenvironment-responsive amorphous iron oxide nanoplatform (ION) to co-deliver photothermal agent (ICG) and toll-like-receptor-7 agonist (IMQ). This biodegradable nanoplatform IMQ@IONs/ICG improved the penetration of the loaded drugs in pancreatic tumor. With MR imaging guidance and temperature monitoring, the precise interventional photothermal therapy on mouse Panc02-H7 orthotopic tumors releases tumor antigens to initiate tumor-special immune responses, amplified by the released IMQ. Our results demonstrate that IMQ@IONs/ICG overcomes the obstacle of drug delivery to pancreatic tumors, and when combined with photothermal therapy, induces a systemic antitumor immunity to control metastatic tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The thymus has a high capacity to support the differentiation of ILCs, especially when E protein transcription factors are ablated. Whether it contributes to the homeostasis of ILC pools in tissues is not clear. Single-cell RNA sequencing analysis shows a substantial amount of ILC precursors in wild type but not athymic nude blood. The precursors express CD3 intracellularly (ic) but not on the surface. The abundance of Lin - CD127 + CD62L + icCD3ε + precursors varies with age, peaking at 2-3 months. These cells can differentiate into various ILC subsets on OP9-DL1 stroma in vitro . In the lung, small intestine, and epidermis, icCD3ε + cells differentiate into diverse ILC subsets in different tissue environments in steady state. Helminth infection promotes their differentiation toward functional ILC2s. Thus, the thymus appears to play a role in replenishing ILC pools in different peripheral tissues. Because thymic activity is age-dependent, this finding may help explain age-related differences in immune responses., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Rationale: B cells have emerged as key regulators in protective cancer immunity. However, the activation pathways induced in B cells during effective immunotherapy are not well understood. Methods: We used a novel localized ablative immunotherapy (LAIT), combining photothermal therapy (PTT) with intra-tumor delivery of the immunostimulant N-dihydrogalactochitosan (GC), to treat mice bearing mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT). We used single-cell RNA sequencing to compare the transcriptional changes induced by PTT, GC and PTT+GC in B cells within the tumor microenvironment (TME). Results: LAIT significantly increased survival in the tumor-bearing mice, compared to the treatment by PTT and GC alone. We found that PTT, GC and PTT+GC increased the proportion of tumor-infiltrating B cells and induced gene expression signatures associated with B cell activation. Both GC and PTT+GC elevated gene expression associated with antigen presentation, whereas GC elevated transcripts that regulate B cell activation and GTPase function and PTT+GC induced interferon response genes. Trajectory analysis, where B cells were organized according to pseudotime progression, revealed that both GC and PTT+GC induced the differentiation of B cells from a resting state towards an effector phenotype. The analyses confirmed upregulated interferon signatures in the differentiated tumor-infiltrating B cells following treatment by PTT+GC but not by GC. We also observed that breast cancer patients had significantly longer survival time if they had elevated expression of genes in B cells that were induced by PTT+GC therapy in the mouse tumors. Conclusion: Our findings show that the combination of local ablation and local application of immunostimulant initiates the activation of interferon signatures and antigen-presentation in B cells which is associated with positive clinical outcomes for breast cancer. These findings broaden our understanding of LAIT's regulatory roles in remodeling TME and shed light on the potentials of B cell activation in clinical applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models., Methods: The expression of tumour necrosis factor (TNF)-α was evaluated in normal and preeclampsia pregnant women. PYR (20 mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-α (150 ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-α-stimulated primary human umbilical endothelial cells (HUVEC) was assessed., Results: Preeclampsia women had higher placental TNF-α expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-α-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-α decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment., Conclusion: Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-α but also by acting against TNF-α-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

An atomically dispersed structure is attractive for electrochemically converting carbon dioxide (CO 2 ) to fuels and feedstock due to its unique properties and activity. Most single-atom electrocatalysts are reported to reduce CO 2 to carbon monoxide (CO). Herein, we develop atomically dispersed indium (In) on a nitrogen-doped carbon skeleton (In-N-C) as an efficient catalyst to produce formic acid/formate in aqueous media, reaching a turnover frequency as high as 26771 h -1 at -0.99 V relative to a reversible hydrogen electrode (RHE). Electrochemical measurements show that trace amounts of In loaded on the carbon matrix significantly improve the electrocatalytic behavior for the CO 2 reduction reaction, outperforming conventional metallic In catalysts. Further experiments and density functional theory (DFT) calculations reveal that the formation of intermediate *OCHO on isolated In sites plays a pivotal role in the efficiency of the CO 2 -to-formate process, which has a lower energy barrier than that on metallic In.

The sorption removal of radionuclides Sr 2+ using a freestanding functional membrane is an interesting and significant research area in the remediation of radioactive wastes. Herein, a novel self-assembled membrane consisting of metal-organic framework (MOF) nanobelts and graphene oxides (GOs) are synthesized through a simple and facile filtration method. The membrane possesses a unique interwove morphology as evidenced from SEM images. Batch experiments suggest that the GO/Ni-MOF composite membrane could remove Sr 2+ ions from aqueous solutions and the Sr 2+ adsorption capacity and efficiency of the GO/Ni-MOF composite membrane is relevant to the MOF content in the composite. Thus, the dominant interaction mechanism was interface or surface complexation, electrostatic interaction as well as ion substitution. The maximum effective sorption of Sr 2+ over GO/Ni-MOF membrane is 32.99% with 2 mg composite membrane containing a high content of Ni-MOF at 299 K in 100 mg/L Sr 2+ aqueous solution. The FT-IR and XPS results suggest that the synergistic effect between GO and Ni-MOF is determinant in the sorption Sr 2+ process. The GO/Ni-MOF composite membrane is demonstrated to have the advantages of efficient removal of Sr 2+ , low cost and simple synthesis route, which is promising in the elimination of radionuclide contamination., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Analysis of gene expression has the potential to assist in the understanding of multiple cellular processes including proliferation, cell-fate specification, senesence, and activity in both healthy and disease states. Zebrafish model has been increasingly used to understand the process of hearing and the development of the vertebrate auditory system. Within the zebrafish inner ear, there are three otolith organs, each containing a sensory macula of hair cells. The saccular macula is primarily involved in hearing, the utricular macula is primarily involved in balance and the function of the lagenar macula is not completely understood. The goal of this study is to understand the transcriptional differences in the sensory macula associated with different otolith organs with the intention of understanding the genetic mechanisms responsible for the distinct role each organ plays in sensory perception. The sensory maculae of the saccule, utricle, and lagena were dissected out of adult Et(krt4:GFP) sqet4 zebrafish expressing green fluorescent protein in hair cells for transcriptional analysis. The total RNAs of the maculae were isolated and analyzed by RNA GeneChip microarray. Several of the differentially expressed genes are known to be involved in deafness, otolith development and balance. Gene expression among these otolith organs was very well conserved with less than 10% of genes showing differential expression. Data from this study will help to elucidate which genes are involved in hearing and balance. Furthermore, the findings of this study will assist in the development of the zebrafish model for human hearing and balance disorders. Anat Rec, 303:527-543, 2020. © 2019 American Association for Anatomy., (© 2019 American Association for Anatomy.)

Phototherapies offer promising alternatives to traditional cancer therapies. Phototherapies mainly rely on manipulation of target tissue through photothermal, photochemical, or photomechanical interactions. Combining phototherapy with immunotherapy has the benefit of eliciting a systemic immune response. Specifically, photothermal therapy (PTT) has been shown to induce apoptosis and necrosis in cancer cells, releasing tumor associated antigenic peptides while sparing healthy host cells, through temperature increase in targeted tissue. However, the tissue temperature must be monitored and controlled to minimize adverse thermal effects on normal tissue and to avoid the destruction of tumor-specific antigens, in order to achieve the desired therapeutic effects of PTT. Techniques for monitoring PTT have evolved from post-treatment quantification methods like enzyme linked immunosorbent assay, western blot analysis, and flow cytometry to modern methods capable of real-time monitoring, such as magnetic resonance thermometry, computed tomography, and photoacoustic imaging. Monitoring methods are largely chosen based on the type of light delivery to the target tissue. Interstitial methods of thermometry, such as thermocouples and fiber-optic sensors, are able to monitor temperature of the local tumor environment. However, these methods can be challenging if the phototherapy itself is interstitially administered. Increasingly, non-invasive therapies call for non-invasive monitoring, which can be achieved through magnetic resonance thermometry, computed tomography, and photoacoustic imaging techniques. The purpose of this review is to introduce the feasible methods used to monitor tissue temperature during PTT. The descriptions of different techniques and the measurement examples can help the researchers and practitioners when using therapeutic PTT., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest.

Microglial activation occurs in divergent neuropathological conditions. Such microglial event has the key involvement in the progression of CNS diseases. However, the transcriptional mechanism governing microglial activation remains poorly understood. Here, we investigate the microglial response to traumatic injury-induced neurodegeneration by the 3D fluorescence imaging technique. We show that transcription factors IRF8 and PU.1 are both indispensible for microglial activation, as their specific post-developmental deletion in microglia abolishes the process. Mechanistically, we reveal that IRF8 and PU.1 directly target the gene transcription of each other in a positive feedback to sustain their highly enhanced expression during microglial activation. Moreover, IRF8 and PU.1 dictate the microglial response by cooperatively acting through the composite IRF-ETS motifs that are specifically enriched on microglial activation-related genes. This action of cooperative transcription can be further verified biochemically by the synergetic binding of IRF8 and PU.1 proteins to the composite-motif DNA. Our study has therefore elucidated the central transcriptional mechanism of microglial activation in response to neurodegenerative condition.

A novel poly(glycine) (p-GLY)/graphene oxide (GO) composite based sensor (p-GLY/GO) was successfully prepared on glassy carbon electrode by simple electropolymerization. Electrochemical responses of analytes on p-GLY/GO modified electrode were studied by cyclic voltammetry and differential pulse voltammetry. The results demonstrated that p-GLY/GO modified electrode showed a favorable application for the simultaneous determination of dopamine (DA), uric acid (UA), guanine (GU) and adenine (AD). Owing to the synergistic effect of p-GLY and GO, the oxidation peaks of four analytes separated well from each other, and the potential separations of oxidation peaks of DA-UA, UA-GU and GU-AD were large up to 170, 350 and 300 mV, respectively. As-prepared p-GLY/GO modified electrode offered wide linear responses for DA, UA, GU and AD over the ranges of 0.20-62, 0.10-105, 0.15-48 and 0.090-103 μM with detection limits of 0.011, 0.061, 0.026 and 0.030 μM (S/N = 3), respectively. Moreover, p-GLY/GO modified electrode presented favorable selectivity, stability and reproducibility, which was a promising candidate as an electrochemical sensor for the simultaneous determination of DA, UA, GU and AD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Two-dimensional transition-metal dichalcogenides (TMDs) have attracted much research interest in the hydrogen evolution reaction (HER) due to their superior electrocatalytic properties. Beyond binary TMDs, ternary TMD alloys, as electrocatalysts, were also gradually acknowledged for their remarkable efficiency in HER. Herein, we successfully synthesized monolayer dendritic ternary WS 2(1-x) Se 2x flakes possessing abundant active edge sites on a single crystalline SrTiO 3 (STO(100)). And the obtained dendritic WS 2(1-x) Se 2x flakes could be transferred intact to arbitrary substrates, for example, SiO 2 /Si and Au foils. Intriguingly, the transferred dendritic WS 2(1-x) Se 2x flakes on Au foil demonstrate a significant HER performance, reflected by a rather lower Tafel slope of ∼69 mV dec -1 and a much higher exchange current density of ∼50.1 μA cm -2 outshining other CVD-grown two-dimensional TMD flakes. Furthermore, our new material shows excellent stability in electro-catalyzing the HER, suggestive of its robustness for being an excellent electrocatalyst. We believe that this work broadens the outlook for the synthesis of two-dimensional TMDs toward satisfying the applications in electrocatalysis.

The rational design of Earth abundant electrocatalysts for efficiently catalyzing hydrogen evolution reaction (HER) is believed to lead to the generation of carbon neutral energy carrier. Owing to their fascinating chemical and physical properties, transition metal dichalcogenides (TMDs) are widely studied for this purpose. Of particular note is that doping by foreign atom can bring the advent of electronic perturbation, which affects the intrinsic catalytic property. Hence, through doping, the catalytic activity of such materials could be boosted. A rational synthesis approach that enables phosphorous atom to be doped into WS 2 without inducing phase impurity to form WS 2(1- x ) P 2 x nanoribbon (NRs) is herein reported. It is found that the WS 2(1- x ) P 2 x NRs exhibit considerably enhanced HER performance, requiring only -98 mV versus reversible hydrogen electrode to achieve a current density of -10 mA cm -2 . Such a high performance can be attributed to the ease of H-atom adsorption and desorption due to intrinsically tuned WS 2 , and partial formation of NRs, a morphology wherein the exposure of active edges is more pronounced. This finding can provide a fertile ground for subsequent works aiming at tuning intrinsic catalytic activity of TMDs., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Developing earth-abundant and efficient bifunctional electrocatalysts for realizing the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) under alkaline conditions is an intriguing challenge. Here, ternary necklace-like CoP 2x Se 2(1-x) nanowire arrays are synthesized via simultaneously phosphorizing and selenizing Co(OH) 2 nanowires. Owing to the substitution of the P atom in the ternary system, the optimal electronic structure of CoP 2x Se 2(1-x) can be obtained and the stability can also be enhanced for hydrogen evolution. Thus, the ternary CoP 2x Se 2(1-x) NWs are highly active for electrochemical hydrogen evolution in both acidic and alkaline media, achieving a current density of 10 mA cm -2 at overpotentials of 70 mV and 98 mV, respectively. To realize the overall water splitting, we further performed the experiment using the CoP 2x Se 2(1-x) NWs as a cathode and Co(OH) 2 NWs as an anode, which requires a cell voltage of 1.65 V to afford a water splitting current density of 10 mA cm -2 in strong alkaline media (1.0 M KOH).

Thermal decomposition method was employed to prepare a Ti/SnO 2 -RuO 2 electrode, on which electrocatalytic degradation of bromocresol green (BCG) was investigated in detail. Scanning electron microscopy, an X-ray diffraction analyzer and an X-ray fluorescence spectrometer were adopted to characterize the morphology, crystal structure and element analysis of the as-prepared Ti/SnO 2 -RuO 2 electrode. It was indicated that the Ti/SnO 2 -RuO 2 electrode had a 'cracked-mud' structure and exhibited a superior specific surface area. The removal efficiency of BCG on the Ti/SnO 2 -RuO 2 electrode was determined in terms of chemical oxygen demand and ultraviolet-visible absorption spectrometry. The results of the batch experiment indicated that the removal efficiency of BCG was influenced by the following factors in descending order: initial pH 0 , reaction temperature, current density and electrolysis time. The removal efficiency of BCG reached up to 91% at the optimal experiment conditions (initial concentration of 100 mg L -1 , initial pH 0 7, reaction temperature of 30 °C, current density of 12 mA cm -2 and electrolysis time of 150 min). As a result, it was concluded that BCG wastewater was efficiently removed by electrochemical oxidation on the Ti/SnO 2 -RuO 2 electrode.

Transition metal dichalcogenides (TMDs), as one of potential electrocatalysts for hydrogen evolution reaction (HER), have been extensively studied. Such TMD-based ternary materials are believed to engender optimization of hydrogen adsorption free energy to thermoneutral value. Theoretically, cobalt is predicted to actively promote the catalytic activity of WS2 . However, experimentally it requires systematic approach to form Cox W(1- x ) S2 without any concomitant side phases that are detrimental for the intended purpose. This study reports a rational method to synthesize pure ternary Cox W(1- x ) S2 nanosheets for efficiently catalyzing HER. Benefiting from the modification in the electronic structure, the resultant material requires overpotential of 121 mV versus reversible hydrogen electrode (RHE) to achieve current density of 10 mA cm(-2) and shows Tafel slope of 67 mV dec(-1) . Furthermore, negligible loss of activity is observed over continues electrolysis of up to 2 h demonstrating its fair stability. The finding provides noticeable experimental support for other computational reports and paves the way for further works in the area of HER catalysis based on ternary materials., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Binary transition metal dichalcogenides (TMDs) have emerged as efficient catalysts for the hydrogen evolution reaction (HER). Co-based TMDs, such as CoS2 and CoSe2, demonstrate promising HER performance due to their intrinsic metallic nature. Recently, the ternary electrocatalysts were widely acknowledged for their prominent efficiency as compared to their binary counterparts due to increased active sites caused by the incorporation of different atoms. Herein, we successfully grew the ternary CoS2xSe2(1-x) (x = 0.67) nanowires (NWs) on a flexible carbon fiber. As a superior electrocatalyst, ternary CoS2xSe2(1-x) NWs arrays demonstrated excellent catalytic activity for electrochemical hydrogen evolution in acidic media, achieving current densities of 10 mA cm(-2) and 100 mA cm(-2) at overpotentials of 129.5 mV and 174 mV, respectively. Notably, the high stability of CoS2xSe2(1-x) NWs suggested that the ternary CoS2xSe2(1-x) NWs are a scalable catalyst for electrochemical hydrogen evolution.

Electrocatalytic hydrogen production at low overpotential is a promising route towards a clean and sustainable energy. Layered transition metal dichalcogenides (LTMDs) have attracted copious attention for their outstanding activities in hydrogen evolution reaction (HER). However, the horizontally laid nanosheets suffer from a paucity of active edge sites. Herein, we report the successful synthesis of vertical-oriented WS2 nanosheets through a hydrothermal method followed by a facile sulfurization process. Furthermore, the surface of synthesized WS2 nanosheets was decorated by ultrathin reduced graphene oxide (rGO) nanoplates. This is achieved for the first time by bringing the rGO on the surface of vertical-oriented WS2 nanosheets, which is conducive to rapid electron transport during the HER process. Significantly, the as-synthesized rGO/WS2 nanosheets exhibit improved HER activity as compared to the undecorated ones. It needs a low overpotential of only 229 mV vs. RHE to afford a current density of 10 mA cm(-2). We believe that this hybrid structure demonstrated remarkable HER activity brought about by a compatible synergism between rGO and WS2.