Evaluating the impact of extended dosing intervals on mRNA COVID-19 vaccine effectiveness in adolescents.

BACKGROUND: Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. METHODS: We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. RESULTS: We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. CONCLUSIONS: Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Clinical characteristics, treatment, and outcomes of nivolumab induced immune thrombocytopenia.

Immune thrombocytopenia (ITP) represents an uncommon hematological side effect associated with nivolumab, and its distinct clinical attributes remain poorly defined. This research aimed to explore the clinical manifestations and outcomes of ITP induced by nivolumab. Reports on nivolumab induced ITP up to April 30, 2024, were collected for retrospective analysis. The study involved 34 patients with a median age of 67 years (range 32, 82). The onset of ITP varied from 10 to 100 days post initial dosage, with a median onset at 70 days. The majority of patients exhibited no symptoms, with only 23.5% experiencing clinically significant bleeding and 11.8% facing non-clinically significant bleeding. The median platelet count was 12 × 109/L (range 0, 115), with 67.6% of patients having platelet levels below 25 × 109/L. Bone marrow biopsy revealed mainly elevated megakaryocytes. Platelet-associated IgG levels were elevated with a median of 210 ng/107 cells (range 73, 1130). Subsequent interventions, which included cessation of nivolumab, administration of systemic corticosteroids, intravenous immunoglobulin therapy, a thrombopoietin receptor agonist, platelet transfusion, and rituximab treatment, resulted in 82.4% of subjects achieving normalized platelet counts, whereas 5.9% passed away due to ITP. ITP is a rare life-threatening immune-related adverse event and necessitates close monitoring. Systemic steroids are the primary treatment for ITP, while intravenous immunoglobulin, thrombopoietin receptor agonist and rituximab are other options.

Carbon dots for efficient detection of water content in organic solvents.

The trace amount of water in organic solvents can affect the progress of chemical reactions, which will adversely affect chemical production in many industries, resulting in a doubling of costs. In this work, carbon dots (CDs) with abundant polar groups were synthesized by a simple one-step hydrothermal method. The prepared CDs showed superior dispersibility and fluorescence performance compared to the CDs that have been reported for the detection of water content in organic solvents. It can realize the fluorescence detection of trace water in several water-soluble organic solvents such as N,N-dimethylformamide, ethanol and methanol with wide linear range (0 %-100 %) and high sensitivity. This will provide a powerful tool for the rapid detection of water content in organic solvents in chemical production.

Dual response signal CdTe QDs@ZIF-8 with butterfly spectrum for dual-mode fluorescence/colorimetric detection of tetracycline in animal feeds.

In this study, a ratiometric fluorescent sensor CdTe QDs@ZIF-8 with butterfly spectra is successfully constructed by in situ encapsulating mercaptopropionic acid-modified CdTe quantum dots in zeolitic imidazolate framework-8 (ZIF-8) with a simple strategy, and used for the detection of tetracycline in fluorescence/smartphone colorimetry dual-mode. ZIF-8 not only reduces the agglomeration of the quantum dots but also surprisingly generates a new green fluorescence signal at 524 nm while the red fluorescence of the CdTe quantum dots at 650 nm quenches when tetracycline is added. The two opposing fluorescence signals create a butterfly-shaped fluorescence spectrum, allowing the sensor to detect tetracycline over a linear range of 0-70 µM with the detection limit (LOD) of 0.0155 µM by using a ratiometric fluorescence technique. What is more, based on the obvious color change of the fluorescent sensor gradually from red to green under UV light, a highly stable point-of-care testing sensor has been developed for on-site detection of tetracycline through color recognition by smartphones, which can be used for real-time detection of this antibiotic in the range of 0-1000 µM with the LOD of 0.0249 µM. This work provides a simple and efficient method for the on-site detection of tetracycline.

Characterization of Cl-doped two-dimensional (PEA)2PbBr4 perovskite single crystals for fast neutron and gamma ray detection.

In this paper, a high-quality Cl-doped two-dimensional halide perovskite (PEA)2Pb(Br0.95Cl0.05)4 crystal was prepared using a seed-induced volatile solvent method. On optimizing the Cl- doping concentration, we found that 5% Cl-doping results in (PEA)2PbBr4 with the highest optical and photon yield. Based on the Cl-doped (PEA)2PbBr4 single crystal, the response characterization of the (PEA)2Pb(Br0.95Cl0.05)4 crystal in the mixed field of neutrons and gamma rays (n/γ) has been verified. Using the time-of-flight method and the linear relationship between integral charge and neutron yield, it was proved that (PEA)2Pb(Br0.95Cl0.05)4 crystal can be used for n/γ screening. The time difference between the fast neutron released by a single nuclear reaction and the γ photon arriving at the detector was 130 ns, and the arrival time of the γ photon is earlier than that of the fast neutron. This work has a broad application prospect in the study of nuclear reaction kinetics, the monitoring of the neutron yield of fusion devices and the total energy released by nuclear reactions.

Evaluating the impact of extended dosing intervals on mRNA COVID-19 vaccine effectiveness in adolescents.

Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. Here, we quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022. We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21-27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR: 1.66; 95% CI: 1.07, 2.59; p = 0.02) after the first dose. Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Covalent post-synthetic modification of MOFs as a fluorescent sensor for the efficient detection of the biomarker of cystinuria.

Cystinuria is a genetic disorder, and in severe cases, it might lead to kidney failure. As an important biomarker for cystinuria, the level of arginine (Arg) in urine is a vital indicator for cystinuria screening. Therefore, it is urgently needed to detect Arg with high selectivity and sensitivity. In this work, a boric acid functionalized Zr-based metal-organic framework UiO-PhbA is prepared by grafting phenylboronic acid on UiO-66-NH2 through a Schiff base reaction using a covalent post-synthesis modification (CPSM) strategy. The prepared UiO-PhbA exhibits a sensitive and specific fluorescence "turn-on" response to Arg and can be exploited to detect Arg in human serum and urine samples with a broad linear range of 0.6-350 µM and low limit of detection (LOD) of 18.45 nM. This study provides a new and reliable rapid screening protocol for sulfite oxidase deficiency-related diseases.

Enhanced properties of the mid-infrared superluminescent emitter with a composite waveguide.

This study reports on a composite structure composing tilted taper, and tilted and curved waveguides with the aim of enhancing the spectral width and output power of mid-infrared quantum cascade superluminescent emitters (QC-SLEs). The computational results indicate that a tilt angle of 10° and a curved angle of 20° can avoid the selectivity of a certain wavelength due to interference effects at tilt angles of 6° and 8°, resulting in the minimum reflectivity of 1.3×10-4 and 4.4×10-4 for each wide and narrow cavity surface. Simultaneously, the modes propagating perpendicular to the cavity surface exist the least. The corresponding experimental results show a significant enhancement in the spectral width to 168.5c m -1 and a high power output of 5.1 mW for the device. This study presents what we believe to be a novel concept for the designing of superluminescent emitters with both a broadband and high power output.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

Olaparib and niraparib as maintenance therapy in patients with newly diagnosed and platinum-sensitive recurrent ovarian cancer: A single-center study in China.

BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes (BRCA) mutations (BRCAm) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs. 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs. 91.4% (32/35), P <0.001]. The 24-month PFS rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCAm, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS: Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCAm, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.

Integrated analysis of metabolome, transcriptome, and bioclimatic factors of Acer truncatum seeds reveals key candidate genes related to unsaturated fatty acid biosynthesis, and potentially optimal production area.

BACKGROUND: Lipids found in plant seeds are essential for controlling seed dormancy, dispersal, and defenses against biotic and abiotic stress. Additionally, these lipids provide nutrition and energy and are therefore important to the human diet as edible oils. Acer truncatum, which belongs to the Aceaceae family, is widely cultivated around the world for its ornamental value. Further because its seed oil is rich in unsaturated fatty acids (UFAs)- i.e. α-linolenic acid (ALA) and nervonic acid (NA)- and because it has been validated as a new food resource in China, the importance of A. truncatum has greatly risen. However, it remains unknown how UFAs are biosynthesized during the growth season, to what extent environmental factors impact their content, and what areas are potentially optimal for their production. RESULTS: In this study, transcriptome and metabolome of A. truncatum seeds at three representative developmental stages was used to find the accumulation patterns of all major FAs. Cumulatively, 966 metabolites and 87,343 unigenes were detected; the differential expressed unigenes and metabolites were compared between stages as follows: stage 1 vs. 2, stage 1 vs. 3, and stage 2 vs. 3 seeds, respectively. Moreover, 13 fatty acid desaturases (FADs) and 20 ß-ketoacyl-CoA synthases (KCSs) were identified, among which the expression level of FAD3 (Cluster-7222.41455) and KCS20 (Cluster-7222.40643) were consistent with the metabolic results of ALA and NA, respectively. Upon analysis of the geographical origin-affected diversity from 17 various locations, we found significant variation in phenotypes and UFA content. Notably, in this study we found that 7 bioclimatic variables showed considerable influence on FAs contents in A. truncatum seeds oil, suggesting their significance as critical environmental parameters. Ultimately, we developed a model for potentially ecological suitable regions in China. CONCLUSION: This study provides a comprehensive understanding of the relationship between metabolome and transcriptome in A. truncatum at various developmental stages of seeds and a new strategy to enhance seed FA content, especially ALA and NA. This is particularly significant in meeting the increasing demands for high-quality edible oil for human consumption. The study offers a scientific basis for A. truncatum's novel utilization as a woody vegetable oil rather than an ornamental plant, potentially expanding its cultivation worldwide.

Comparative epidemiology of outbreaks caused by SARS-CoV-2 Delta and Omicron variants in China.

From 2020 to December 2022, China implemented strict measures to contain the spread of severe acute respiratory syndrome coronavirus 2. However, despite these efforts, sustained outbreaks of the Omicron variants occurred in 2022. We extracted COVID-19 case numbers from May 2021 to October 2022 to identify outbreaks of the Delta and Omicron variants in all provinces of mainland China. We found that omicron outbreaks were more frequent (4.3 vs. 1.6 outbreaks per month) and longer-lasting (mean duration: 13 vs. 4 weeks per outbreak) than Delta outbreaks, resulting in a total of 865,100 cases, of which 85% were asymptomatic. Despite the average Government Response Index being 12% higher (95% confidence interval (CI): 9%, 15%) in Omicron outbreaks, the average daily effective reproduction number (Rt) was 0.45 higher (95% CI: 0.38, 0.52, p < 0.001) than in Delta outbreaks. Omicron outbreaks were suppressed in 32 days on average (95% CI: 26, 39), which was substantially longer than Delta outbreaks (14 days; 95% CI: 11, 19; p = 0.004). We concluded that control measures effective against Delta could not contain Omicron outbreaks in China. This highlights the need for continuous evaluation of new variants' epidemiology to inform COVID-19 response decisions.

Preoperative evaluation and a nomogram prediction model for pelvic lymph node metastasis in endometrial cancer.

OBJECTIVE: The primary objective of this study is to explore the preoperative risk factors of pelvic lymph node metastasis (PLNM) in endometrial cancer patients, and construct a nomogram prediction model. MATERIALS AND METHODS: We retrospectively collected various preoperative clinical characteristics of patients and analyzed their relationship with PLNM. Logistic regression analysis was used to screen for independent risk factors for PLNM of endometrial cancer. A nomogram prediction model was constructed, the receiver operating characteristic (ROC), calibration curve and decision curve analysis (DCA) were constructed and used to assess discrimination, calibration, and net benefit. RESULTS: Out of the 276 patients, 74 (26.81%) with postoperative pathological confirmation of PLNM. Multivariate logistic regressive analysis demonstrated that preoperative depth of myometrial invasion (DIM) ≥50% determined by Magnetic Resonance Imaging (MRI) (p = 0.003), carbohydrate antigen 125 (CA125) (p = 0.030), carbohydrate antigen 19-9 (CA 19-9) (p = 0.044), and platelet/lymphocyte ratio (PLR) (p = 0.025) could serve as independent risk factors for PLNM. A risk factors-based nomogram prediction model was constructed, which showed good discrimination (AUC = 0.841, p < 0.001) and good efficacy (C-index = 0.842) and good calibration (mean absolute error = 0.046). DCA showed that the model can provide clinical benefits. CONCLUSIONS: Preoperative DIM ≥50% determined by MRI, serum CA 19-9, CA125 and PLR could be utilized to predict PLNM in endometrial cancer patients. This nomogram prediction model can provide preoperative help for evaluation and identification of patients with endometrial cancer, and provide a theoretical basis for clinical intervention.

The functional significance of circRNA/miRNA/mRNA interactions as a regulatory network in lung cancer biology.

Lung cancer, the leading cause of cancer-related deaths, presents significant challenges to patients due to its poor prognosis. Recent research has increasingly implicated circular RNAs in the development and progression of lung cancer. These circular RNAs have been found to impact various aspects of tumor behavior, including proliferation, metastasis, cell cycle regulation, apoptosis, cancer stem cells, therapy response, and the tumor microenvironment. One of the key mechanisms by which circular RNAs exert their influence is through their ability to act as miRNA sponges, sequestering microRNAs and preventing them from targeting other RNA molecules. Accumulating evidence suggests that circular RNAs can function as competing endogenous RNAs, affecting the expression of target mRNAs by sequestering microRNAs. Dysregulation of competing endogenous RNAs networks involving circular RNAs, microRNAs, and mRNAs leads to the aberrant expression of oncogenes and tumor suppressors involved in lung cancer pathogenesis. Understanding the dynamic interplay and molecular mechanisms among circular RNAs, microRNAs, and mRNAs holds great promise for advancing early diagnosis, personalized therapeutic interventions, and improved patient outcomes in lung cancer. Therefore, this study aims to provide an in-depth exploration of the executive roles of circular RNAs/microRNAs/ mRNAs interactions in lung cancer pathogenesis and their potential utility for diagnosing lung cancer, predicting patient prognosis, and guiding targeted therapies. By offering a comprehensive overview of the dysregulation of the axes as driving factors in lung cancer, we aim to pave the way for their translation into clinical practice in the future.

Fluorescent sensor based on bismuth metal-organic frameworks (Bi-MOFs) mimic enzyme for H2O2 detection in real samples and distinction of phenylenediamine isomers.

Although peroxidase-like nano-enzymes have been widely utilized in biosensors, nano-enzyme based biosensors are seldom used for both quantitative analysis of H2O2 and differentiation of isomers of organic compounds simultaneously. In this study, a dual-functional mimetic enzyme-based fluorescent sensor was constructed using metal-organic frameworks (Bi-MOFs) with exceptional oxidase activity and fluorescence properties. This mimetic enzyme sensor facilitated quantitative analysis of H2O2 and accurate discrimination of phenylenediamine isomers. The sensor exhibited a wide linear range (0.5-400 µM) and low detection limit (0.16 µM) for the detection of H2O2. Moreover, the sensor can also be used for the discrimination of phenylenediamine isomers, in which the presence of o-phenylenediamine (OPD) leads to the appearance of a new fluorescence emission peak at 555 nm, while the presence of p-phenylenediamine (PPD) significantly quenched its fluorescence due to the internal filtration effect. The proposed strategy exhibited a commendable capability in distinguishing phenylenediamine isomers, thereby paving the way for novel applications of MOFs in the field of environmental science.

The effect of nurse assisted colonoscopy on adenoma detection rates: A meta-analysis of randomized controlled trials.

BACKGROUND: Adenoma's detection rates have been reported to vary with the participation status of endoscopic nurses during colonoscopy. This meta-analysis was conducted to determine whether the participation of endoscopy nurses during colonoscopy contributed to the improved detection rate of polyps and adenomas. METHODS: We retrieved English original research from PubMed, Embase, Web of Science, and Cochrane library databases and Chinese original research from the CNKI Data database. We searched for randomized controlled trials (RCTs) comparing the effect of participation of endoscopy nurses during colonoscopy of colorectal polyps and adenomas on polyp detection rates to that of nonparticipation. RevMan5.4 software was used to perform the meta-analysis. RESULTS: This meta-analysis included 11 randomized controlled trials involving 8278 patients. The results showed no significant difference between colonoscopies performed by nurses and endoscopists, but colonoscopies performed by two nurses significantly improved the detection rate of polyps and adenomas. In the random effects model, there was a significant difference in PDR between the single-observation and dual-observation groups (RR, 1.27; 95%CI, 1.05, 1.54; Z = 2.51; P = 0.01). The ADR difference between the single observation group and the double observation group was statistically significant (RR, 1.15; 95%CI, 1.05, 1.26; Z = 2.91; P = 0.004). CONCLUSION: Endoscopy nurses' participation in colonoscopy can improve the detection rate of polyps and adenomas, However, more research is needed to confirm the results.

A dual-functional fluorescence probe CDs@ZIF-90 for highly specific detection of Al3+ and Hg2+ in environmental water samples.

In recent years, the escalating water pollution has resulted in serious harm to human health and ecological environment due to the excessive discharge of toxic metal ions such as Al3+ and Hg2+. Therefore, it is crucial to develop a simple, efficient, and rapid detection method for monitoring the levels of the metal ions in water environment to ensure public health and ecological safety. In this study, carbon dots (CDs) containing heteroatom Si were successfully synthesized by the solvothermal method. Subsequently, a novel dual-functional fluorescent sensor (CDs@ZIF-90) was constructed by integrating CDs with zeolitic imidazolate framework-90 (ZIF-90). The fluorescent composite CDs@ZIF-90 showed outstanding optical properties and excellent structural and luminescence stability in aqueous medium. Particularly, its fluorescence at 453 nm can be remarkably enhanced by Al3+ and quenched upon exposure to Hg2+. As a result, the CDs@ZIF-90 was applied in sensitive and selective determination of Al3+ and Hg2+ ions with wide linear ranges (1-200 µM and 0.05-240 µM) and low detection limits (0.81 µM and 19.6 nM). Moreover, a convenient and rapid fluorescence test strip was also successfully prepared for visual detection of Al3+ and Hg2+ ions. This work is the first try to use the CDs@ZIF-90 fluorescence sensing material for highly sensitive and selective determination of Al3+ and Hg2+ based on "turn-on" and "turn-off" dual modes, respectively and it provides a new idea for monitoring quality of drinking water and environmental water. It is of great significance for human health and environmental protection.

WTAP Mediates NUPR1 Regulation of LCN2 Through m6A Modification to Influence Ferroptosis, Thereby Promoting Breast Cancer Proliferation, Migration and Invasion.

Ferroptosis is involved in various pathophysiological diseases, including triple-negative breast cancer (TNBC). Targeting ferroptosis is considered as a novel anti-TNBC strategy. Nevertheless, the regulatory mechanism of ferroptosis during TNBC progression is unclear. Here, the role of WTAP in ferroptosis during TNBC progression  was investigated. The clinicopathological significance of WTAP, NUPR1 and LCN2 was analyzed by Kaplan-Meier method. Cell viability was assessed using MTT assay. Transwell assay was employed to analyze cell migration and invasion. GSH/GSSG and Fe2+ levels in TNBC cells were analyzed using kits. m6A level was examined using m6A dot blot assay. NUPR1 mRNA stability was analyzed using RNA degradation assay. RIP was performed to analyze the interaction between eIF3a and NURP1. Herein, our results revealed that WTAP, NUPR1 and LCN2 expressions were significantly elevated in TNBC. NUPR1 silencing inhibited TNBC cell proliferation, migration and invasion by inducing ferroptosis. NUPR1 positively regulated LCN2 expression in TNBC cells, and LCN2 knockdown induced ferroptosis to suppress TNBC cell malignant behaviors. Our molecular study further revealed that WTAP promoted NUPR1 expression in an m6A-EIF3A mediated manner. And, as expected, WTAP knockdown promoted ferroptosis to suppress TNBC cell malignant behaviors, which were abrogated by NUPR1 overexpression. WTAP upregulated LCN2 by regulation of NUPR1 m6A modification, thereby suppressing ferroptosis to contribute to accelerate TNBC progression. Our study revealed the cancer-promoting effect of WTAP, NUPR1 and LCN2 in TNBC and clarified the relevant mechanism, providing a theoretical basis for developing novel diagnostic and therapeutic strategies for TNBC.

Oxidative stress is the pivot for PM2.5-induced lung injury.

Fine particulate matter (PM2.5) is a primary air pollutant recognized worldwide as a serious threat to public health. PM2.5, which has a diameter of less than 2.5 µm, is known to cause various diseases, including cardiovascular, respiratory, metabolic, and neurological diseases. Studies have shown that the respiratory system is particularly susceptible to PM2.5 as it is the first line of defense against external pollutants. PM2.5 can cause oxidative stress, which is triggered by the catalyzation of biochemical reactions, the activation of oxidases and metabolic enzymes, and mitochondrial dysfunction, all of which can lead to lung injury and aggravate various respiratory diseases including chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, and cancer. Oxidative stress plays a crucial role in the harmful effects and mechanisms of PM2.5 on the respiratory system by activating several detrimental pathways related to inflammation and cellular damage. However, experimental studies have shown that antioxidative therapy methods can effectively cure PM2.5-induced lung injury. This review aims to clarify how PM2.5 induces oxidative stress and the mechanisms by which it is involved in the aggravation of various lung diseases. Additionally, we have listed antioxidant treatments to protect against PM2.5-induced lung injury.

Molecular characteristics of circulating B cells and kidney cells at the single-cell level in special types of primary membranous nephropathy.

Background: Although primary membranous nephropathy (pMN) associated with podocyte autoantibodies (POS) is becoming well-known, the molecular characteristics of the specific type of pMN that is negative for podocyte autoantibodies (NEG) is still unclear. Methods: We performed single-cell transcriptome sequencing and single-cell B cell receptor sequencing on circulating CD19+ cells and kidney cells of a NEG paediatric patient with pMN. The single-cell datasets of POS patients and healthy control individuals were included for integrative analysis. Results: The gene expression characteristics and clonal expansion of naïve and memory B cells in the NEG patient changed significantly. We found that a group of CD38+ naïve B cells expanded in the NEG patient, which had the functional characteristics of cell activation. In addition, the conversion between immunoglobulin M (IgM)/IgD and IgG1 in the NEG patient was increased. Parietal epithelial cells (PECs) and podocytes shared similar signature genes (WT1, CLIC5), and new candidate marker genes for PECs, such as NID2, CAV1 and THY1, might contribute to the definition of cell subsets. PECs might have undergone significant changes in the disease, mainly manifested by changes in the expression of CCN2, PLAAT4 and SEPTIN2. The scores of gene sets related to extracellular matrix, cell adhesion and calcium channel in podocytes of the NEG patient was significantly increased. The gene expression of sodium transporter in a group of proximal tubule cells in the disease was significantly increased, especially SLC5A12, which might be related to the oedema of patients. Conclusions: Our research demonstrated the cell type-specific molecular features in the circulation and kidney of the NEG pMN patient.