Destabilization mechanisms of Semi-aerobic aged refuse biofilters under harsh treatment conditions: Evidence from fluorescence and microbial characteristics.

Semi-aerobic aged refuse biofilters (SAARB) are commonly-used biotechnologies for treating landfill leachate. In actual operation, SAARB often faces harsh conditions characterized by high concentrations of chemical oxygen demand (COD) and Cl-, as well as a low carbon-to-nitrogen ratio (C/N), which can disrupt the microbial community within SAARB, leading to operational instability. Maintaining the stable operation of SAARB is crucial for the efficient treatment of landfill leachate. However, the destabilization mechanism of SAARB under harsh conditions remains unclear. To address this, the study simulated the operation of SAARB under three harsh conditions, namely, high COD loading (H-COD), high chloride ion (Cl-) concentration environment (H-Cl-), and low C/N ratio environment (L-C/N). The aim is to reveal the destabilization mechanism of SAARB under harsh conditions by analyzing the fluorescence characteristics of effluent DOM and the microbial community in aged refuse. The results indicate that three harsh conditions have different effects on SAARB. H-COD leads to the accumulation of proteins; H-Cl- impedes the reduction of nitrite nitrogen; L-C/N inhibits the degradation of humic substances. These outcomes are attributed to the specific effects of different factors on the microbial communities in different zones of SAARB. H-COD and L-C/N mainly affect the degradation of organic matter in aerobic zone, while H-Cl- primarily impedes the denitrification process in the anaerobic zone. The abnormal enrichment of Corynebacterium, Castellaniella, and Sporosarcina can indicate the instability of SAARB under three harsh conditions, respectively. To maintain the steady operation of SAARB, targeted acclimation of the microbial community in SAARB should be carried out to cope with potentially harsh operating conditions. Besides, timely mitigation of loads should be implemented when instability characteristics emerge, and carbon sources and electron donors should be provided to restore treatment performance effectively.

Investigation into the genotoxic impurity, 1-methyl-4-nitrosopiperazine, in rifampicin.

This study assessed the presence of the genotoxic impurity 1-methyl-4-nitrosopiperazine (MNP) in 27 batches of rifampicin capsules obtained from 11 manufacturers in China. While they were below the temporary limit of 5 ppm set by the US Food and Drug Administration, the observed levels (0.33-2.36 ppm) exceeded the acceptable threshold of 0.16 ppm. Building upon preliminary findings and degradation experiments, we concluded that MNP is a by-product of the oxidative degradation of rifampicin or is introduced via oxidation or nitrosation during the synthesis process involving 1-methyl-4-aminopiperazine. The pathways of MNP formation were confirmed in this study. Furthermore, we observed that the addition of antioxidants, sealed storage, and selection of dominant crystal forms can aid in controlling MNP levels.

PRM1201 effectively inhibits colorectal cancer metastasis via shaping gut microbiota and short- chain fatty acids.

BACKGROUND: PRM1201 is a traditional medicine with beneficial effects against colorectal cancer (CRC) metastasis. However, the underlying mechanism of this action remains to be determined. HYPOTHESIS: Remodeling microbiota and short-chain fatty acids (SCFAs) metabolism might be a potential mechanism to explain the anti-metastatic action of PRM1201, as this gut-microbiota dependent effect involves downregulation of histone deacetylation and EMT. METHODS: To investigate this possibility, clinical specimens were sequenced and the correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFA-producing bacteria was studied. To obtain solid causal evidence, a mouse metastasis model was established to detect the influence of PRM1201 on cancer metastasis. Specifically, 16S amplicon sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, and bacterial manipulation were used to examine the gut microbiota-driven anti-metastatic action of PRM1201. RESULTS: Clinical data showed that PRM1201 increased both the number of SCFA-producing bacteria and generation of SCFAs in the feces of CRC patients. A positive correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFAs observed. The animal experiments demonstrated that PRM1201 effectively blocked CRC metastasis in a dose-dependent manner. PRM1201 treatment modulated the composition of gut microbiota, and promoted the proliferation of beneficial SCFAs producers such as Akkermansia, Lachnospiraceae_NK4A136_group and Blautia, while simultaneously reducing the abundance of pathogenic bacteria like Escherichia-Shigella. In addition, PRM1201 led to augmentation of SCFAs content. Further results indicated that the anti-cancer metastatic mechanism of PRM1201 was linked to inhibition of histone deacetylation and suppression of epithelial-to-mesenchymal transition (EMT) in metastatic lesions. Microbiota depletion treatment and fecal microbiota transplantation (FMT) underscored the microbiota-dependent nature of this phenomenon. Moreover, this anti-colorectal cancer metastatic effect and mechanism of total SCFAs and single SCFA were also confirmed. CONCLUSION: In summary, PRM1201 exerts its anti-metastatic effects by modulating SCFA-producing bacteria and enhancing the production of SCFAs. Furthermore, the prebiotic-like actions of PRM1201, along with the PRM1201-treated bacteria, function as inhibitors of histone deacetylases (DHACs) thereby effectively suppressing EMT events.

nCas9 Engineering for Improved Target Interaction Presents an Effective Strategy to Enhance Base Editing.

Base editors (BEs) are a recent generation of genome editing tools that couple a cytidine or adenosine deaminase activity to a catalytically impaired Cas9 moiety (nCas9) to enable specific base conversions at the targeted genomic loci. Given their strong application potential, BEs are under active developments toward greater levels of efficiency and safety. Here, a previously overlooked nCas9-centric strategy is explored for enhancement of BE. Based on a cytosine BE (CBE), 20 point mutations associated with nCas9-target interaction are tested. Subsequently, from the initial positive X-to-arginine hits, combinatorial modifications are applied to establish further enhanced CBE variants (1.1-1.3). Parallel nCas9 modifications in other versions of CBEs including A3A-Y130F-BE4max, YEE-BE4max, CGBE, and split-AncBE4max, as well as in the context of two adenine BEs (ABE), likewise enhance their respective activities. The same strategy also substantially improves the efficiencies of high-fidelity nCas9/BEs. Further evidence confirms that the stabilization of nCas9-substrate interactions underlies the enhanced BE activities. In support of their translational potential, the engineered CBE and ABE variants respectively enable 82% and 25% higher rates of editing than the controls in primary human T-cells. This study thus demonstrates a highly adaptable strategy for enhancing BE, and for optimizing other forms of Cas9-derived tools.

Explore the mechanism of Astragalus membranaceus and Poria cocos drug pair in improving immunity based on network pharmacology.

The aim of this study was to investigate the key targets and molecular mechanisms of the drug pair Astragalus membranaceus and Poria cocos (HFDP) in the treatment of immunity. We utilized network pharmacology, molecular docking, and immune infiltration techniques in conjunction with data from the GEO database. Previous clinical studies have shown that HFDP has a positive impact on immune function. We first identified the active ingredients and targets of HFDP from the Traditional Chinese Medicine Systems Pharmacology database and the Swiss Target Prediction database, respectively. Next, we retrieved the differentially expressed genes (DEGs) related to immunity from the GEO databases. The intersection targets of the drugs and diseases were then analyzed using the STRING database for protein-protein interaction (PPI) network analysis, and the core targets were determined through topological analysis. Finally, the intersection genes were further analyzed using the DAVID database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, by analyzing the expression and prognostic survival of 12 core targets, 5 core target genes were identified, and molecular docking between the hub genes and immunity was performed. Finally, we used the CIBERSORT algorithm to analyze the immune infiltration of immunity genes In this study, 34 effective ingredients of HFDP, 530 target genes, and 568 differential genes were identified. GO and KEGG analysis showed that the intersection genes of HFDP targets and immunity-related genes were mainly related to complement and coagulation cascades, cytokine receptors, and retinol metabolism pathways. The molecular docking results showed that the 5 core genes had obvious affinity for the active ingredients of HFDP, which could be used as potential targets to improve the immunity of HFDP. Our findings suggest that HFDP is characterized by "multiple components, multiple targets, and multiple pathways" in regulating immunity. It may play an essential role in regulating immunity by regulating the expression and polymorphism of the central target genes ESR1, JUN, CYP3A4, CYP2C9, and SERPINE1.

Global trends and performances of infrared imaging technology studies on acupuncture: a bibliometric analysis.

Objectives: To summarize development processes and research hotspots of infrared imaging technology research on acupuncture and to provide new insights for researchers in future studies. Methods: Publications regarding infrared imaging technology in acupuncture from 2008 to 2023 were downloaded from the Web of Science Core Collection (WoSCC). VOSviewer 1.6.19, CiteSpace 6.2.R4, Scimago Graphica, and Microsoft Excel software were used for bibliometric analyses. The main analyses include collaboration analyses between countries, institutions, authors, and journals, as well as analyses on keywords and references. Results: A total of 346 publications were retrieved from 2008 to 2023. The quantity of yearly publications increased steadily, with some fluctuations over the past 15 years. "Evidence-Based Complementary and Alternative Medicine" and "American Journal of Chinese Medicine" were the top-cited journals in frequency and centrality. China has the largest number of publications, with the Shanghai University of Traditional Chinese Medicine being the most prolific institution. Among authors, Litscher Gerhard from Austria (currently Swiss University of Traditional Chinese Medicine, Switzerland) in Europe, was the most published and most cited author. The article published by Rojas RF was the most discussed among the cited references. Common keywords included "Acupuncture," "Near infrared spectroscopy," and "Temperature," among others. Explore the relationship between acupoints and temperature through infrared thermography technology (IRT), evaluate pain objectively by functional near-infrared spectroscopy (fNIRS), and explore acupuncture for functional connectivity between brain regions were the hotspots and frontier trends in this field. Conclusion: This study is the first to use bibliometric methods to explore the hotspots and cutting-edge issues in the application of infrared imaging technology in the field of acupuncture. It offers a fresh perspective on infrared imaging technology research on acupuncture and gives scholars useful data to determine the field's hotspots, present state of affairs, and frontier trends.

The Simpler the Better: Ultrafast Air-Plasma Synthesis of 3D Crosslinked Graphene Nanoscroll-Nanosheet Aerogels at Room Temperature for Capacitive Deionization.

Graphene nanoscroll (GNS) is an important 1D tubular form of graphene-derivative materials, which has garnered widely attention. However, conventional fabrication methods commonly suffer from complex processing and time-consuming. Herein, with graphene oxide (GO) as a precursor, the study puts forward a facile air-plasma synthesis strategy to fabricate 3D graphene nanoscroll-nanosheet aerogels (GSSA). It is demonstrated that without using any chemical additives, a highly efficient reduction-exfoliation-scrolling process can be achieved all-in-one at room temperature within 1 s. The GNSs "grew" from 2D graphene sheets and firmly cross-linked them together, and they not only provide a shortcut path for electron transport but also act as intrinsic spacers to prevent restacking of graphene sheets. When using as an electrode material for capacitive deionization (CDI), GSSA exhibits excellent merits of salt-removal performance. These findings open a new pathway to large-scale synthesis of high-quality and high-purity GNS-based materials with promising applications in CDI and beyond.

Phagocytosis in Marine Coccolithophore Gephyrocapsa huxleyi: Comparison between Calcified and Non-Calcified Strains.

Coccolithophores play a significant role in marine calcium carbonate production and carbon cycles, attributing to their unique feature of producing calcareous plates, coccoliths. Coccolithophores also possess a haplo-diplontic life cycle, presenting distinct morphology types and calcification states. However, differences in nutrient acquisition strategies and mixotrophic behaviors of the two life phases remain unclear. In this study, we conducted a series of phagocytosis experiments of calcified diploid and non-calcified haploid strains of coccolithophore Gephyrocapsa huxleyi under light and dark conditions. The phagocytosis capability of each strain was examined based on characteristic fluorescent signals from ingested beads using flow cytometry and fluorescence microscopy. The results show a significantly higher phagocytosis percentage on fluorescent beads in the bacterial prey surrogates of the non-calcified haploid Gephyrocapsa huxleyi strain, than the calcified diploid strain with or without light. In addition, the non-calcified diploid cells seemingly to presented a much higher phagocytosis percentage in darkness than under light. The differential phagocytosis capacities between the calcified diploid and non-calcified haploid Gephyrocapsa huxleyi strains indicate potential distinct nutritional strategies at different coccolithophore life and calcifying stages, which may further shed light on the potential strategies that coccolithophore possesses in unfavorable environments such as twilight zones and the expanding coccolithophore niches in the natural marine environment under the climate change scenario.

A high-performance, sensitive, low-cost LIG/PDMS strain sensor for impact damage monitoring and localization in composite structures.

Health monitoring of composite structures in aircraft is critical, as these structures are commonly utilized in weight-sensitive areas and innovative designs that directly impact flight safety and reliability. Traditional monitoring methods have limitations in monitoring area, strain limit, and signal processing. In this paper, a multifunctional sensor has been developed using acid-treated laser-induced graphene (A-LIG) with a multi-layer three-dimensional conductive network. Compared to untreated laser-induced graphene, the sensitivity of A-LIG sensor is increased by 100%. Furthermore, PDMS is used to fill the pores, which improves the fatigue performance of the A-LIG sensor. To obtain clear monitoring results, a data conversion algorithm is provided to convert the electrical signal obtained by the sensor into a strain field contour cloud map. The impact test of the A-LIG/PDMS sensor on the carbon fiber panel of the aircraft wing box segment verifies the effectiveness of its strain sensing. This work introduces a novel approach to fabricating flexible sensors with improved sensitivity, extended strain range, and cost-effectiveness. The sensor exhibits high sensitivity (gauge factor,GF≈ 387), is low hysteresis (∼53 ms), and has a wide working range (up to 47%), and a highly stable and reproducible response over multiple test cycles (>18 000) with good switching response. It presents a promising and innovative direction for utilizing flexible sensors in the field of aircraft structural health monitoring.

Dauresorcinols A and B, two pairs of merosesquiterpenoid enantiomers with new carbon skeletons from Rhododendron dauricum.

Five pairs of new merosesquiterpenoid enantiomers, named dauresorcinols A-E (1-5), were isolated from the leaves of Rhododendron dauricum. Their structures were elucidated by comprehensive spectroscopic data analysis, quantum chemical calculations, Rh2(OCOCF3)4-induced ECD, and single-crystal X-ray diffraction analysis. Dauresorcinols A (1) and B (2) possess two new merosesquiterpene skeletons bearing an unprecedented 2,6,7,10,14-pentamethyl-11-oxatetracyclo[8.8.0.02,7.012,17]octadecane and a caged 15-isohexyl-1,5,15-trimethyl-2,10-dioxatetracyclo[7.4.1.111,14.03,8]pentadecane motif, respectively. Plausible biosynthetic pathways of 1-5 are proposed involving key oxa-electrocyclization and Wagner-Meerwein rearrangement reactions. (+)/(-)-1 and 3-5 showed potent α-glucosidase inhibitory activity, 3 to 22 times stronger than acarbose, an antidiabetic drug targeting α-glucosidase. Docking results provide a basis to design and develop merosesquiterpenoids as potent α-glycosidase inhibitors.

A chronic stress-induced microbiome perturbation, highly enriched in Ruminococcaceae_UCG-014, promotes colorectal cancer growth and metastasis.

Purpose: Mounting evidence indicates that psychological stress adversely affects cancer progression including tumor growth and metastasis. The aim of this study was to investigate the role of chronic stress-induced microbiome perturbation in colorectal cancer (CRC) progression. Methods: Chronic restraint stress (CRS) was used to establish the chronic stress mouse model, behavioral tests were used for the CRS model evaluation. Subcutaneous xenograft model and lung metastasis model were established to investigate the growth and metastasis of CRC promoted by CRS exposure. 16S rRNA gene sequencing and liquid chromatograph-mass spectrometer (LC-MS) were applied to observe the effects of CRS exposure on the alteration of the gut microbiome and microbial metabolites. Bioinformatics analysis and correlation analyses were applied to analyse the changes in the frequency of body mass, tumor volume, inflammatory factors, neuroendocrine hormones and metabolites of the gut microbiota. Results: In this study, we identifed that CRS exposure model was appropriately constructed by achieving expected increases in disease activity index and enhanced depressive-like behaviors. CRS exposure can promote growth and metastasis of CRC. Besides, the data indicated that CRS exposure not only increased the neuro- and immune-inflammation, but also weakened the gut mucosal immunological function. The 16s rRNA gene sequencing data showed that CRS exposure increased the abundance of g_Ruminococcaceae_UCG_014. Furthermore, the LC-MS data indicated that with only 2 exceptions of carpaine and DG (15:0/20:4(5Z,8Z,11Z,14Z)/0:0), the majority of these 24 metabolites were less abundant in CRS-exposed mice. Bioinformatics analysis and correlation analyses indicated that only Ruminoscoccaceae-UCG-014 was significantly associated with inflammation (IL-6), neurotransmission (5-HT), and microbial metabolism (PS). Conclusion: CRS exposure altered diversity, composition and metabolites of the gut microbiome, with Ruminococcaceae_UCG-014 perturbation consistently correlated to inflammatory responses, suggesting a particular role of this bacterial genus in CRC growth and metastasis.

Research progress on chitosan and its derivatives in the fields of corrosion inhibition and antimicrobial activity.

Chitosan stands out as the only known polysaccharide of its kind, second only to cellulose. As the second-largest biopolymer globally, chitosan and its derivatives are extensively used in diverse areas such as metal anti-corrosion prevention, food production, and medical fields. Its benefits include environmental friendliness, non-toxicity, cost-effectiveness, and biodegradability. Notably, the use of chitosan and its derivatives has gained substantial attention and has been extensively researched in the fields of metal anti-corrosion prevention and antibacterial applications. By means of chemical modification or synergistic action, the inherent limitations of chitosan can be substantially improved, thereby enhancing its biological and physicochemical properties to meet a wider range of applications and more demanding application requirements. This article offers a comprehensive review of chitosan and its modified composite materials, focusing on the enhancement of their anticorrosion and antibacterial properties, as well as the mechanisms by which they serve as anticorrosion and antibacterial agents. Additionally, it summarizes the synthesis routes of various modification methods of chitosan and their applications in different fields, aiming to contribute to the interdisciplinary development and potential applications of chitosan in various areas.

Development of a prognostic model based on different disulfidptosis related genes typing for kidney renal clear cell carcinoma.

Background: Kidney renal clear cell carcinoma (KIRC) is a common and clinically significant subtype of kidney cancer. A potential therapeutic target in KIRC is disulfidptosis, a novel mode of cell death induced by disulfide stress. The aim of this study was to develop a prognostic model to explore the clinical significance of different disulfidptosis gene typings from KIRC. Methods: A comprehensive analysis of the chromosomal localization, expression patterns, mutational landscape, copy number variations, and prognostic significance of 10 disulfide death genes was conducted. Patients were categorized into distinct subtypes using the Non-negative Matrix Factorization (NMF) typing method based on disulfidptosis gene expression patterns. Weighted Gene Co-expression Network Analysis (WGCNA) was used on the KIRC dataset to identify differentially expressed genes between subtype clusters. A risk signature was created using LASSO-Cox regression and validated by survival analysis. An interaction between risk score and immune cell infiltration, tumor microenvironment characteristics and pathway enrichment analysis were investigated. Results: Initial findings highlight the differential expression of specific DRGs in KIRC, with genomic instability and somatic mutation analysis revealing key insights into their role in cancer progression. NMF clustering differentiates KIRC patients into subgroups with distinct survival outcomes and immune profiles, and hierarchical clustering identifies gene modules associated with key biological and clinical parameters, leading to the development of a risk stratification model (LRP8, RNASE2, CLIP4, HAS2, SLC22A11, and KCTD12) validated by survival analysis and predictive of immune infiltration and drug sensitivity. Pathway enrichment analysis further delineates the differential molecular pathways between high-risk and low-risk patients, offering potential targets for personalized treatment. Lastly, differential expression analysis of model genes between normal and KIRC cells provides insights into the molecular mechanisms underlying KIRC, highlighting potential biomarkers and therapeutic targets. Conclusion: This study contributes to the understanding of KIRC and provides a potential prognostic model using disulfidptosis gene for personalized management in KIRC patients. The risk signature shows clinical applicability and sheds light on the biological mechanisms associated with disulfide-induced cell death.

Constructing CoNi-LDH/Fe MOF/NF Heterostructure Catalyst for Energy-Efficient OER and UOR at High Current Density.

The sluggish kinetics of the oxygen evolution reaction (OER) always results in a high overpotential at the anode of water electrolysis and an excessive electric energy consumption, which has been a major obstacle for hydrogen production through water electrolysis. In this study, we present a CoNi-LDH/Fe MOF/NF heterostructure catalyst with nanoneedle array morphology for the OER. In 1.0 M KOH solution, the heterostructure catalyst only required overpotentials of 275 and 305 mV to achieve high current densities of 500 and 1000 mA/cm2 for OER, respectively. The catalytic activities are much higher than those of the reference single-component CoNi-LDH/NF and Fe MOF/NF catalysts. The improved catalytic performance of the heterostructure catalyst can be ascribed to the synergistic effect of CoNi-LDH and Fe MOF. In particular, when the anodic OER is replaced with the urea oxidation reaction (UOR), which has a relatively lower thermodynamic equilibrium potential and is expected to reduce the cell voltage, the overpotentials required to achieve the same current densities can be reduced by 80 and 40 mV, respectively. The cell voltage required to drive overall urea splitting (OUS) is only 1.55 V at 100 mA/cm2 in the Pt/C/NF||CoNi-LDH/Fe MOF/NF two-electrode electrolytic cell. This value is 60 mV lower compared with that required for overall water splitting (OWS). Our results indicate that a reasonable construction of a heterostructure catalyst can significantly give rise to higher electrocatalytic performance, and using UOR to replace the anodic OER of the OWS can greatly reduce the electrolytic energy consumption.

Biochar and hydrochar application influence soil ammonia volatilization and the dissolved organic matter in salt-affected soils.

Biochar, which including pyrochar (PBC) and hydrochar (HBC), has been tested as a soil enhancer to improve saline soils. However, the effects of PBC and HBC application on ammonia (NH3) volatilization and dissolved organic matter (DOM) in saline paddy soils are poorly understood. In this research, marsh moss-derived PBC and HBC biochar types were applied to paddy saline soils at 0.5 % (w/w) and 1.5 % (w/w) rates to assess their impact on soil NH3 volatilization and DOM using a soil column experiment. The results revealed that soil NH3 volatilization significantly increased by 56.1 % in the treatment with 1.5 % (w/w) HBC compared to the control without PBC or HBC. Conversely, PBC and the lower application rate of HBC led to decrease in NH3 volatilization ranging from 2.4 % to 12.1 %. Floodwater EC is a dominant factor in NH3 emission. Furthermore, the fluorescence intensities of the four fractions (all humic substances) were found to be significantly higher in the 1.5 % (w/w) HBC treatment applied compared to the other treatments, as indicated by parallel factor analysis modeling. This study highlights the potential for soil NH3 losses and DOM leaching in saline paddy soils due to the high application rate of HBC. These findings offer valuable insights into the effects of PBC and HBC on rice paddy saline soil ecosystems.

Growth of infants delivered by mothers with HIV in Guangxi, China: An 18-month longitudinal follow-up study, 2015-2021.

OBJECTIVES: The prevention of mother-to-child transmission of HIV has been a global success. But little is known about the growth parameters of infants delivered by mothers with HIV or the drug resistance of infants with HIV in China. The study aimed to assess growth parameters and drug resistance in Chinese infants exposed to HIV. METHODS: We conducted an 18-month longitudinal follow-up study of 3283 infants (3222 without HIV; 61 with HIV) born to mothers with HIV in the Guangxi Zhuang Autonomous Region between January 2015 and December 2021. The weight and length of all participants was recorded. In addition, genetic subtypes and drug resistance analysis were performed for infants with HIV. RESULTS: Compared with infants without HIV, those with HIV had significantly lower weight/length Z-scores, except at 18 months of age. The length/age Z-scores of infants with HIV was significantly reduced, except at 1 month of age. The weight/age Z-scores of infants with HIV were significantly lower at all follow-up time points. The weight/length Z-scores of male infants without HIV were significantly lower than for female infants without HIV at all follow-up time points. Male infants without HIV had lower length/age and weight/age Z-scores than female infants at the remaining follow-up points, except at 1 month of age. Of a total of 61 infants with HIV, subtype and drug-resistance data were obtained from 37 (60.66%) samples. Infants with HIV were dominated by the CRF01_AE genotype and showed a diversity of mutation sites dominated by non-nucleoside reverse transcriptase inhibitor resistance. CONCLUSION: Our study demonstrates the growth of infants exposed to HIV in southwest China and provides detailed information on subtype distribution and drug resistance of those with HIV. Nutritional support and drug-resistance surveillance for infants exposed to HIV need to be strengthened.

IGF-1R mediates crosstalk between nasopharyngeal carcinoma cells and osteoclasts and promotes tumor bone metastasis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) poses a significant health burden in specific regions of Asia, and some of NPC patients have bone metastases at the time of initial diagnosis. Bone metastasis can cause pathologic fractures and pain, reducing patients' quality of life, and is associated with worse survival. This study aims to unravel the complex role of insulin-like growth factor 1 receptor (IGF-1R) in NPC bone metastasis, offering insights into potential therapeutic targets. METHODS: We assessed IGF-1R expression in NPC cells and explored its correlation with bone metastasis. Experiments investigated the impact of osteoclast-secreted IGF-1 on the IGF-1R/AKT/S6 pathway in promoting NPC cell proliferation within the bone marrow. Additionally, the reciprocal influence of tumor-secreted Granulocyte-macrophage colony-stimulating factor (GM-CSF) on osteoclast differentiation and bone resorption was examined. The effects of IGF-1 neutralizing antibody, IGF-1R specific inhibitor (NVP-AEW541) and mTORC inhibitor (rapamycin) on nasopharyngeal carcinoma bone metastasis were also explored in animal experiments. RESULTS: Elevated IGF-1R expression in NPC cells correlated with an increased tendency for bone metastasis. IGF-1, secreted by osteoclasts, activated the IGF-1R/AKT/S6 pathway, promoting NPC cell proliferation in the bone marrow. Tumor-secreted GM-CSF further stimulated osteoclast differentiation, exacerbating bone resorption. The IGF-1 neutralizing antibody, NVP-AEW541 and rapamycin were respectively effective in slowing down the rate of bone metastasis and reducing bone destruction. CONCLUSION: The intricate interplay among IGF-1R, IGF-1, and GM-CSF highlights potential therapeutic targets for precise control of NPC bone metastasis, providing valuable insights for developing targeted interventions.

GSTM3 enhances radiosensitivity of nasopharyngeal carcinoma by promoting radiation-induced ferroptosis through USP14/FASN axis and GPX4.

BACKGROUND: Radiotherapy is a critical treatment modality for nasopharyngeal carcinoma (NPC). However, the mechanisms underlying radiation resistance and tumour recurrence in NPC remain incompletely understood. METHODS: Oxidised lipids were assessed through targeted metabolomics. Ferroptosis levels were evaluated using cell viability, clonogenic survival, lipid peroxidation, and transmission electron microscopy. We investigated the biological functions of glutathione S-transferase mu 3 (GSTM3) in cell lines and xenograft tumours. Co-immunoprecipitation, mass spectrometry, and immunofluorescence were conducted to explore the molecular mechanisms involving GSTM3. Immunohistochemistry was performed to investigate the clinical characteristics of GSTM3. RESULTS: Ionising radiation (IR) promoted lipid peroxidation and induced ferroptosis in NPC cells. GSTM3 was upregulated following IR exposure and correlated with IR-induced ferroptosis, enhancing NPC radiosensitivity in vitro and in vivo. Mechanistically, GSTM3 stabilised ubiquitin-specific peptidase 14 (USP14), thereby inhibiting the ubiquitination and subsequent degradation of fatty acid synthase (FASN). Additionally, GSTM3 interacted with glutathione peroxidase 4 (GPX4) and suppressed GPX4 expression. Combining IR treatment with ferroptosis inducers synergistically improved NPC radiosensitivity and suppressed tumour growth. Notably, a decrease in GSTM3 abundance predicted tumour relapse and poor prognosis. CONCLUSIONS: Our findings elucidate the pivotal role of GSTM3 in IR-induced ferroptosis, offering strategies for the treatment of radiation-resistant or recurrent NPC.

Reciprocal expression of MADS-box genes and DNA methylation reconfiguration initiate bisexual cones in spruce.

The naturally occurring bisexual cone of gymnosperms has long been considered a possible intermediate stage in the origin of flowers, but the mechanisms governing bisexual cone formation remain largely elusive. Here, we employed transcriptomic and DNA methylomic analyses, together with hormone measurement, to investigate the molecular mechanisms underlying bisexual cone development in the conifer Picea crassifolia. Our study reveals a "bisexual" expression profile in bisexual cones, especially in expression patterns of B-class, C-class and LEAFY genes, supporting the out of male model. GGM7 could be essential for initiating bisexual cones. DNA methylation reconfiguration in bisexual cones affects the expression of key genes in cone development, including PcDAL12, PcDAL10, PcNEEDLY, and PcHDG5. Auxin likely plays an important role in the development of female structures of bisexual cones. This study unveils the potential mechanisms responsible for bisexual cone formation in conifers and may shed light on the evolution of bisexuality.

Single-cell RNA sequencing reveals that the immunosuppression landscape induced by chronic stress promotes colorectal cancer metastasis.

The high prevalence of depressive disorders in individuals with cancer and their contribution to tumour progression is a topic that is gradually gaining attention. Recent evidence has shown that there are prominent connections between immune gene variants and mood disorders. The homeostasis of the tumour immune microenvironment (TIME) and the infiltration and activation of immune cells play a very important role in the antitumour effect. In this study, we established a compound mouse model with chronic unpredictable mild stress (CUMS) and orthotopic colorectal cancer to simulate colorectal cancer (CRC) patients with depression. Using 10✕Genomics single-cell transcriptome sequencing technology, we profiled nearly 30,000 cells from tumour samples of 8 mice from the control and CUMS groups, revealed that immune cells in tumours under a chronic stress state trend toward a more immunosuppressive and exhaustive status, and described the crosstalk between the overall inflammatory environment and immunosuppressive landscape to provide mechanistic information or efficacious strategies for immune-oncology treatments in CRC with depressive disorders.