Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia.

INTRODUCTION: The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML). METHODS: The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection. RESULTS: A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress. CONCLUSION: Ferroptosis-related gene HSPB1 is highly expressed in patients with AML. In addition, HSPB1 may be involved in the occurrence and development of AML by regulating oxidative stress and ferroptosis-related pathways. This study provides new clues for further understanding of AML molecular mechanisms. Also, HSPB1 is expected to be a potential therapeutic target for AML in the future.

Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma.

Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. The mechanism underlying the TPF chemoresistance remains unclear. Here, by analyzing gene-expression microarray data and survival of patients who received TPF chemotherapy, we identify transcription factor ATMIN as a chemoresistance gene in response to TPF chemotherapy in NPC. Mass spectrometry and Co-IP assays reveal that USP10 deubiquitinates and stabilizes ATMIN protein, resulting the high-ATMIN expression in NPC. Knockdown of ATMIN suppresses the cell proliferation and facilitates the docetaxel-sensitivity of NPC cells both in vitro and in vivo, while overexpression of ATMIN exerts the opposite effect. Mechanistically, ChIP-seq combined with RNA-seq analysis suggests that ATMIN is associated with the cell death signaling and identifies ten candidate target genes of ATMIN. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.

Broadening oncological boundaries: the intratumoral microbiota.

The microbiota of solid tumors was identified >100 years ago; however, heterogeneous composition and diversity have been revealed only recently. Growing evidence has suggested that several functional mechanisms of the intratumoral microbiota affect tumorigenesis and progression, suggesting that the intratumoral microbiota is a promising biomarker for multiple cancers. The low biomass of the intratumoral microbiota poses a major challenge to related research, thus necessitating the use of a multiple-modality integrated framework to resolve this dilemma. Advanced techniques such as single-cell sequencing provide significant clues, and the gradual optimization of functional experiments and culture-based methods enables deeper investigation of the underlying mechanisms involved. In this review, we outline the current state of research on the intratumoral microbiota and describe the challenges and comprehensive strategies for future research.

UV-induced photodegradation of emerging para-phenylenediamine quinones in aqueous environment: Kinetics, products identification and toxicity assessments.

Substituted para-phenylenediamine quinones (PPD-quinones) are a class of emerging contaminants frequently detected in the aqueous environment. One of them, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q), was found to cause acute toxicities to aquatic species at extremely low environmental levels. The ubiquitousness and ecotoxicity of such pollutants underscore the importance of their transformation and elimination. In this work, we demonstrated effective removals of five PPD-quinones in aqueous environments under UV irradiation, with up to 94% of 6PPD-Q eliminated after a 40-min treatment. By applying high-resolution mass spectrometry (HRMS) non-targeted screening in combination with isotope labeling strategies, a total of 22 transformation products (TPs) were identified. Coupling with the time-based dynamic patterns, potential transformation mechanisms were identified as an •OH-induced photocatalysis reaction involving bond cleavage, hydroxylation, and oxidation. Computational toxicity assessment predicted lower aquatic toxicity of the TPs than their parent PPD-quinones. Our results in parallel evidenced an obvious reduction of PPD-quinones accompanied by the presence of their TPs in the effluent after UV disinfection in real municipal wastewater. This work builds a comprehensive understanding of the fate, transformation products, and related toxicological characteristics of emerging PPD-quinone contaminants in the aqueous environment.

Emerging clinical relevance of microbiome in cancer: promising biomarkers and therapeutic targets.

The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years, leading to numerous researches on cancer microbiome entering clinical evaluation. As promising biomarkers and therapeutic targets, the critical involvement of microbiota in cancer clinical practice has been increasingly appreciated. Here, recent progress in this field is reviewed. We describe the potential of tumor-associated microbiota as effective diagnostic and prognostic biomarkers, respectively. In addition, we highlight the relationship between microbiota and the therapeutic efficacy, toxicity, or side effects of commonly utilized treatments for cancer, including chemotherapy, radiotherapy, and immunotherapy. Given that microbial factors influence the cancer treatment outcome, we further summarize some dominating microbial interventions and discuss the hidden risks of these strategies. This review aims to provide an overview of the applications and advancements of microbes in cancer clinical relevance.

Facile low-temperature supercritical carbonization method to prepare high-loading nickel single atom catalysts for efficient photodegradation of tetracycline.

Environmental photocatalysis is a promising technology for treating antibiotics in wastewater. In this study, a supercritical carbonization method was developed to synthesize a single-atom photocatalyst with a high loading of Ni (above 5 wt.%) anchored on a carbon-nitrogen-silicate substrate for the efficient photodegradation of a ubiquitous environmental contaminant of tetracycline (TC). The photocatalyst was prepared from an easily obtained metal-biopolymer-inorganic supramolecular hydrogel, followed by supercritical drying and carbonization treatment. The low-temperature (300°C) supercritical ethanol treatment prevents the excessive structural degradation of hydrogel and greatly reduces the metal clustering and aggregation, which contributed to the high Ni loading. Atomic characterizations confirmed that Ni was present at isolated sites and stabilized by Ni-N and Ni-O bonds in a Ni-(N/O)6C/SiC configuration. A 5% Ni-C-Si catalyst, which performed the best among the studied catalysts, exhibited a wide visible light response with a narrow bandgap of 1.45 eV that could efficiently and repeatedly catalyze the oxidation of TC with a conversion rate of almost 100% within 40 min. The reactive species trapping experiments and electron spin resonance (ESR) tests demonstrated that the h+, and ·O2- were mainly responsible for TC degradation. The TC degradation mechanism and possible reaction pathways were provided also. Overall, this study proposed a novel strategy to synthesize a high metal loading single-atom photocatalyst that can efficiently remove TC with high concentrations, and this strategy might be extended for synthesis of other carbon-based single-atom catalysts with valuable properties.

Stable isotope-assisted mass spectrometry reveals in vivo distribution, metabolism, and excretion of tire rubber-derived 6PPD-quinone in mice.

6PPD-quinone (6PPD-Q) has been identified as a ubiquitous contaminant in the surrounding locality, including air particles, roadside soils, dust, and water. Recently, the prevalence of 6PPD-Q in human urine has accentuated the urgency for investigating its biological fate. To address this, we conducted a stable isotope-assisted high-resolution mass spectrometry (HRMS) assay to unveil the distribution, metabolism, excretion, and toxicokinetic properties of this contaminant in a mouse model. Mice were fed with a single dose of deuterated 6PPD-Q-d5 at human-relevant exposure levels. Results indicated that 6PPD-Q was quickly assimilated and distributed into bloodstream and main organs of mice, with the concentrations reaching peaks under 1 h following administration. Notably, 6PPD-Q was primarily distributed in the adipose tissue, marked by a significant Cmax (p < 0.05), followed by the kidney, lung, testis, liver, spleen, heart, and muscle. In addition, our measurement demonstrated that 6PPD-Q can penetrate the blood-brain barrier of mice within 0.5 h after exposure. The half-lives (t1/2) of 6PPD-Q in serum, lung, kidney, and spleen of mice were measured at 12.7 ± 0.3 h, 20.7 ± 1.4 h, 21.6 ± 5.3 h, and 20.6 ± 2.8 h, respectively. Using HRMS combined with isotope tracing techniques, two novel hydroxylated metabolites of 6PPD-Q in the mice liver were identified for the first time, which provides new insights into its rapid elimination in-vivo. Meanwhile, fecal excretion was identified as the main excretory pathway for 6PPD-Q and its hydroxylated metabolites. Collectively, our findings extend the current knowledge on the biological fate and exposure status of 6PPD-Q in a mouse model, which has the potential to be extrapolated to humans.

The Characteristics of Transcription Factors Regulating T Cell Exhaustion Were Analyzed to Predict the Prognosis and Therapeutic Effect in Patients with HCC.

Purpose: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths, posing a significant threat to people in diverse regions. T-cell exhaustion (Tex) can hinder the efficacy of immunotherapy in patients with HCC, and the transcription factors that regulate Tex in HCC have not yet been fully elucidated. Patients and Methods: We used the single sample gene set enrichment analysis (ssGSEA) method to define the transcription factor pathway that regulates Tex and employed LASSO regression analysis to establish Tex related genes (TEXRS). To predict differences in immunotherapy efficacy between the two groups, we used the immunophenotype score and submap algorithm. RT-qPCR was used to detect the expression levels of the model genes in 21 pairs of HCC tissues. Finally, we assessed the cell communication strength and identified ligand receptors using the "CellChat" R package. Results: Nine Tex transcription factors were identified as regulators of the HCC immune microenvironment, with Tex scores affecting patient survival. Patients with a high Tex Risk Score (TEXRS) had significantly worse overall survival compared to patients with low TEXRS. After adjusting for confounding factors, TEXRS remained an independent prognostic factor. Importantly, TEXRS performed well in multiple independent external validation cohorts. Various algorithms have shown that patients in the low-TEXRS group might benefit more from immunotherapy. Finally, RT-qPCR analysis of 21 HCC samples showed that C7, CD5L, and SDS were significantly downregulated in HCC tissues, consistent with the bioinformatics analysis results. Conclusion: TEXRS proved to be a valuable predictor of immunotherapy and transcatheter arterial chemoembolization efficacy in patients with HCC. This holds promise for enhancing the prognosis and treatment outcomes of patients with HCC.

An adolescent with primary cutaneous follicle center lymphoma: a case report and literature review.

Primary cutaneous follicle center lymphoma (PCFCL) differs from follicular lymphoma in biological behavior and molecular profile and is treated as a distinct entity, according to the 5th edition of the World Health Organization classification of hematolymphoid tumors. It is an uncommon cutaneous B-cell lymphoma that is considerably rare in children and adolescents. To date, only 13 cases of individuals younger than 20 years of age have been reported in the literature. The lack of relevant clinical epidemiological data in this population has hampered the investigation of its clinical and diagnostic aspects. Here we report the case of a 17-year-old male with PCFCL, who may be the first PCFCL patient under 20 years of age reported in China. He was admitted to the hospital with a solitary nodule on his face. After complete surgical excision, the patient's facial mass was histologically identified as PCFCL. The patient's prognosis was favorable, with no recurrence at 17 months of follow-up after the surgical resection. We present a case of an adolescent PCFCL patient and systematically review the literature with a view to increase the awareness of the disease and inform the diagnosis and treatment of this age group.

Exploration of the mechanism of aloin ameliorates of combined allergic rhinitis and asthma syndrome based on network pharmacology and experimental validation.

Background: Aloin, as a bioactive compound, has a variety of pharmacological functions, but its effects on combined allergic rhinitis and asthma syndrome (CARAS) have not been studied. To clarify the protective effect and mechanism of aloin in the treatment of CARAS by network pharmacology, molecular dynamics simulation and experiment. Methods: The targets of aloin, allergic rhinitis and asthma were obtained from various databases. The protein interaction network was constructed for the common targets, and molecular docking and molecular dynamics simulations were performed for the core targets. Functional and pathway enrichment analysis of common targets was also performed using R software. Varieties of biological experiments were conducted to verify the effect of aloin on the inflammatory changes of CARAS and its regulatory mechanism. Results: A total of 42 anti-allergic rhinitis and 58 anti-asthma targets were obtained, and 5 core anti-allergic rhinitis and 6 core anti-asthma targets were identified using topological analysis. GO and KEGG analyses showed that endopeptidase activity and MAPK signaling pathway played important roles in allergic rhinitis and asthma. Molecular docking and molecular dynamics simulations showed that aloin could stably bind to the core target proteins. Experimental verification showed that aloin significantly inhibited the expression of inflammatory factors, and may regulate CARAS by down-regulating MAPK signaling related proteins. Conclusion: This study identified the protective effect, potential target and mechanism of aloin on CARAS. It provides reference for understanding the molecular mechanism and clinical application of aloin in the ameliorates of CARAS.

Occurrence and Fate of Substituted p-Phenylenediamine-Derived Quinones in Hong Kong Wastewater Treatment Plants.

para-Phenylenediamine quinones (PPD-Qs) are a newly discovered class of transformation products derived from para-phenylenediamine (PPD) antioxidants. These compounds are prevalent in runoff, roadside soil, and particulate matter. One compound among these, N-1,3-dimethylbutyl-n'-phenyl-p-phenylenediamine quinone (6PPD-Q), was found to induce acute mortality of coho salmon, rainbow trout, and brook trout, with the median lethal concentrations even lower than its appearance in the surface and receiving water system. However, there was limited knowledge about the occurrence and fate of these emerging environmental contaminants in wastewater treatment plants (WWTPs), which is crucial for effective pollutant removal via municipal wastewater networks. In the current study, we performed a comprehensive investigation of a suite of PPD-Qs along with their parent compounds across the influent, effluent, and biosolids during each processing unit in four typical WWTPs in Hong Kong. The total concentrations of PPDs and PPD-Qs in the influent were determined to be 2.7-90 and 14-830 ng/L. In the effluent, their concentrations decreased to 0.59-40 and 2.8-140 ng/L, respectively. The median removal efficiency for PPD-Qs varied between 53.0 and 91.0% across the WWTPs, indicating that a considerable proportion of these contaminants may not be fully eliminated through the current processing technology. Mass flow analyses revealed that relatively higher levels of PPD-Qs were retained in the sewage sludge (20.0%) rather than in the wastewater (16.9%). In comparison to PPDs, PPD-Qs with higher half-lives exhibited higher release levels via effluent wastewater, which raises particular concerns about their environmental consequences to aquatic ecosystems.

Polymyxin resistance caused by large-scale genomic inversion due to IS26 intramolecular translocation in Klebsiella pneumoniae.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S2 (S2) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S2 for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S2, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S2 resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

A pan-cancer analysis of ABI3BP: a potential biomarker for prognosis and immunoinfiltration.

Objective: ABI Family Member 3 Binding Protein (ABI3BP) is an extracellular matrix protein that affects the carcinogenesis of lung and esophageal cancer. However, the relevance of ABI3BP in different forms of cancer is uncertain. Methods: ABI3BP expression was interpreted using the Cancer Genome Atlas (TCGA) database, the Genotype Tissue Expression Atlas (GTEx) database, the Human Protein Atlas (HPA) database, the Cancer Cell Line Encyclopedia (CCLE) database, and immunohistochemistry. The R programming language was used to analyze the association between ABI3BP expression and patient prognosis and evaluate the relationship between ABI3BP and the immune characteristics of tumors. Using the GDSC and CTRP databases, a drug sensitivity analysis of ABI3BP was conducted. Results: ABI3BP mRNA expression was shown by differential analysis to be down-regulated in 16 tumor types relative to normal tissues, corresponding with its protein expression level as determined by immunohistochemistry. Abnormal expression of ABI3BP accurately predicts the prognosis of patients with renal chromophobe carcinoma (KICH), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD). Meanwhile, aberrant expression of ABI3BP was associated with immune checkpoints, TMB, MSI, tumor purity, HRD, LOH, and drug sensitivity. A correlation between ABI3BP expression and the amount of infiltration of several immune-related cells in pan-cancer was determined by Immune Score, Stromal Score, and Estimated Score. Conclusion: Our results show that ABI3BP might be employed as a molecular biomarker to predict prognosis, treatment susceptibility, and immunological response in patients with pan-cancer.

Enhancing global thinking can reduce the misconception of accumulation: A potential way to mitigate climate change.

Climate change and global warming have long been attention and concern all over the world. However, there is always a debate about when and to what degree to take action like reducing carbon dioxide emissions. Recently, researchers found that the public has misconceptions about climate dynamics, which might be a reason for people do not support prompt mitigation of greenhouse gas emissions. The core problem of misconceptions is the stock-flow (SF) problem, which refers to the difficulty of inferring the behavior of a stock variable given information regarding its inflows and outflows. We elaborated on the idea that global thinking is beneficial for comprehending SF problems and proposed that global thinking enhancing display based on highlighting the areas of difference could be a possible way to shift one's thinking process to the right one, which was proved by two studies. Theoretical and practical implications are discussed.

Axial superior facet slope may determine anterior or posterior atlantoaxial displacement secondary to os odontoideum and compensatory mechanisms of the atlantooccipital joint and subaxial cervical spine.

OBJECTIVE: To introduce novel parameters in determining directions of os odontoideum (OO) with atlantoaxial displacement (AAD) and compensations of cervical sagittal alignment after displacement. METHODS: Analysis was performed on 96 cases receiving surgeries for upper cervical myelopathy caused by OO with AAD from 2011 to 2021. Twenty-four patients were included in the OO group and divided into the OO-anterior displacement (AD) group and the OO-posterior displacement (PD) group by displacement. Seventy-two patients were included as the control (Ctrl) group and divided into Ctrl-positive (Ctrl-P) group and Ctrl-negative (Ctrl-N) group by axial superior facet slope (ASFS) in a neutral position. ASFS, the sum of C2 slope (C2S) and axial superior facet endplate angle (ASFEA), was measured and calculated by combining cervical supine CT with standing X-ray. Cervical sagittal parameters were measured to analyse the atlantoaxial facet and compensations after AAD. RESULTS: Atlas inferior facet angle (AIFA), ASFS, and ASFEA in Ctrl-P significantly differed from OO-AD.C0-C1, C1-C2, C0-C2, C2-C7, C2-C7 SVA, and C2S in Ctrl-P significant differed from the OO-AD group. C2-C7 SVA and C2S in Ctrl-N significantly were smaller than the OO-PD group. C1-C2 correlated with C0-C1 and C2-C7 negatively in the OO group. Slight kyphosis of C1-C2 in OO-AD was compared with lordosis of C1-C2 in Ctrl-P, inducing increased extension of C0-C1 and C2-C7. Mildly increased lordosis of C1-C2 in OO-PD was compared with C1-C2 in Ctrl-N, triggering augmented flexion of C0-C1 and C2-C7. CONCLUSION: ASFS was vital in determining directions of OO with AAD and explaining compensations. ASFS and ASFEA could provide pre- and intraoperative guidelines. KEY POINTS: • ASFS may determine the directions and compensatory mechanisms of AAD secondary to OO. • ASFS could be achieved by the sum of ASFEA and C2S.

TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models.

Although radiotherapy can promote antitumour immunity, the mechanisms underlying this phenomenon remain unclear. Here, we demonstrate that the expression of the E3 ubiquitin ligase, tumour cell-intrinsic tripartite motif-containing 21 (TRIM21) in tumours, is inversely associated with the response to radiation and CD8+ T cell-mediated antitumour immunity in nasopharyngeal carcinoma (NPC). Knockout of TRIM21 modulates the cGAS/STING cytosolic DNA sensing pathway, potentiates the antigen-presenting capacity of NPC cells, and activates cytotoxic T cell-mediated antitumour immunity in response to radiation. Mechanistically, TRIM21 promotes the degradation of the mitochondrial voltage-dependent anion-selective channel protein 2 (VDAC2) via K48-linked ubiquitination, which inhibits pore formation by VDAC2 oligomers for mitochondrial DNA (mtDNA) release, thereby inhibiting type-I interferon responses following radiation exposure. In patients with NPC, high TRIM21 expression was associated with poor prognosis and early tumour relapse after radiotherapy. Our findings reveal a critical role of TRIM21 in radiation-induced antitumour immunity, providing potential targets for improving the efficacy of radiotherapy in patients with NPC.

Chemotherapy-Induced Senescence Reprogramming Promotes Nasopharyngeal Carcinoma Metastasis by circRNA-Mediated PKR Activation.

Senescence is associated with tumor metastasis and chemotherapy resistance, yet the mechanisms remain elusive. Here, it is identified that nasopharyngeal carcinoma (NPC) patients who developed distant metastasis are characterized by senescence phenotypes, in which circWDR37 is a key regulator. CircWDR37 deficiency limits cisplatin or gemcitabine-induced senescent NPC cells from proliferation, migration, and invasion. Mechanistically, circWDR37 binds to and dimerizes double-stranded RNA-activated protein kinase R (PKR) to initiate PKR autophosphorylation and activation. Independent of its kinase activity, phosphorylated PKR induces I-kappaB kinase beta (IKKß) phosphorylation, binds to and releases RELA from NF-κB inhibitor alpha (IκBα) to trigger nuclear factor kappa B (NF-κB) activation, thereby stimulating cyclin D1 (CCND1) and senescence-associated secretory phenotype component gene transcription in a circWDR37-dependent manner. Low circWDR37 levels correlate with chemotherapy response and favorable survival in NPC patients treated with gemcitabine or cisplatin induction chemotherapy. This study uncovers a new mechanism of circWDR37 activated PKR in senescence-driven metastasis and provides appealing therapeutic targets in NPC.

Temperature effects on microbial dissolved organic matter metabolisms: Linking size fractions, fluorescent compositions, and functional groups.

This study elucidated the compositional and structural variations of size fractions of microbially-induced dissolved organic matter (DOM) caused by short-term temperature changes (5 to 35 °C), taking riverine DOM as an example. A simple and efficient method combining fractionation-[parallel factor analysis and two-dimensional Fourier-transform infrared correlation spectroscopy (PARAFAC-2D FTIR COS)]-correlation was introduced to link fluorescent DOM components and their structures in terms of surface functional groups. Results indicated that the higher temperature stimulated the decomposition of aromatics (sizes decreased from 10 kDa-0.22 µm to <10 kDa) and the transformation of proteins to humics (with sizes <0.22 µm); while both the higher and lower temperatures inhibited the utilization of larger-sized DOM (>0.22 µm, especially the non-fluorescence part) and synthesis of larger-sized microbial-derived proteins and humics (>0.22 µm), which may result in more smaller-sized (<10 kDa) and refractory aromatics transported from rivers to oceans in the warming future. However, the structure-determined DOM behaviors could be less affected by temperature since the fluorescent proteins and humics revealed similar functional group compositions, such as carboxyl, hydroxyl, carbonyl/aldehyde, carboxylic anhydride, and carboxamide groups. These findings have strong implications for DOM biogeochemistry in future temperature-shock scenarios. The proposed method will support in-depth analyses of structure-regulated processes from a mechanistic perspective.

Recent applications of mass spectrometry in the analysis of transformation products of emerging contaminants in PM2.5.

Ambient pollution correlated to fine particulate matter (PM2.5) is a worldwide environmental issue as it is highly associated with human health and eco-environmental safety. A significant part regarding the toxicity of PM2.5 is attributed to its bonded contaminants. Appreciable efforts have been performed to study the occurrence, exposure, and toxicological properties of chemicals of emerging concerns in PM2.5. Recent works indicated a broad environmental transformation of emerging contaminants in the atmospheric environment and highlighted the significance of PM2.5 bonded transformation products, which may exhibit higher environmental concentrations and toxicities compared to their parent compounds. Among these studies, mass spectrometry has been widely applied for the analysis of transformation products of emerging contaminants in PM2.5 on the aspects of suspect/non-target screening, structure elucidation, concentration profiling, and toxicity determination. This review describes key mass spectrometry-based analytical strategies and applications for determining transformation products in PM2.5 and presents outlooks for their analysis.

Emerging platinum(0) nanotherapeutics for efficient cancer therapy.

Platinum (Pt)-based chemotherapy has been necessary for clinical cancer treatment. However, traditional bivalent drugs are hindered by poor physicochemical properties, severe toxic side effects, and drug resistance. Currently, elemental Pt(0) nanotherapeutics (NTs) have emerged to tackle the dilemma. The inherent acid-responsiveness of Pt(0) NTs could help to improve tumor selectivity and alleviate toxic effects. Moreover, the metal nature of Pt facilitates the great combination of Pt(0) NTs with photothermal and photodynamic therapy and imaging-guided diagnosis. Based on recent important researches, this review provides an updated introduction to Pt(0) NTs. First, the challenges of traditional Pt-based chemotherapy have been outlined. Then, Pt(0) NTs with multiple applications of tumor theranostics have been overviewed. Furthermore, the combinations of Pt(0) NTs with other therapeutical modalities are introduced. Last but not least, we envision the possible challenges and prospects associated with Pt(0) NTs.