Copper Nanosheet-Based Wash-Free Fluorescence Imaging of Cancer Cells.

Near-infrared fluorescence (NIRF) probes greatly facilitate in vivo imaging of various biologically important species. However, there are several significant limitations such as consuming washing steps, photobleaching, and low signal intensity. Herein, we synthesized fluorescent copper nanosheets templated with DNA scaffolds (DNS/CuNSs). We employ them and Cy5.5 of the fluorescence resonance energy transfer (FRET) system, which have a larger Stokes shift (∼12-fold) than the traditional NIRF dye Cy5.5. Based on their excellent fluorescence properties, we employ DNS/CuNSs-Cy5.5 for fluorescence probes in cancer cell imaging. Compared with the free Cy5.5 fluorescence probe, the novel fluorescence imaging probe implements wash-free imaging and exhibits enhanced anti-photobleaching ability (∼5.5-fold). Moreover, the FRET system constructed by DNS/CuNSs has a higher signal amplification ability (∼4.17-fold), which is more similar to that of Cu nanoclusters prepared with DNA nanomonomers as a template. This work provides a new idea for cancer cell MCF-7 imaging and is expected to promote the development of cancer cell fluorescence imaging.

FeNiCo|MnGaOx Heterostructure Nanoparticles as Bifunctional Electrocatalyst for Zn-Air Batteries.

Driven by the pressing demand for stable energy systems, zinc-air batteries (ZABs) have emerged as crucial energy storage solutions. However, the quest for cost-effective catalysts to enhance vital oxygen evolution and reduction reactions remains challenging. FeNiCo|MnGaOx heterostructure nanoparticles on carbon nanotubes (CNTs) are synthesized using liquid-phase reduction and H2 calcination approach. Compared to its component, such FeNiCo|MnGaOx/CNT shows a high synergistic effect, low impedance, and modulated electronic structure, leading to a superior bifunctional catalytic performance with an overpotential of 255 mV at 10 mA cm-2 and half-wave potential of 0.824 V (ω = 1600 rpm and 0.1 m KOH electrolyte). Moreover, ZABs based on FeNiCo|MnGaOx/CNT demonstrate notable features, including a peak power density of 136.1 mW cm-2, a high specific capacity of 808.3 mAh gZn -1, and outstanding stability throughout >158 h of uninterrupted charge-discharge cycling. Theoretical calculations reveal that the non-homogeneous interface can introduce more carriers and altered electronic structures to refine intermediate adsorption reactions, especially promoting O* formation, thereby enhancing electrocatalytic performance. This work demonstrates the importance of heterostructure interfacial modulation of electronic structure and enhancement of adsorption capacity in promoting the implementation of OER/ORR, ZABs, and related applications.

Plasma profiles of inflammatory cytokines in children with moderate to severe traumatic brain injury: a prospective cohort study.

The role of inflammatory cytokines in children with moderate to severe TBI (m-sTBI) is still incompletely understood. We aimed to investigate the associations between early plasma expression profiles of inflammatory cytokines and clinical outcomes in children with m-sTBI. We prospectively recruited children admitted to the intensive care unit (ICU) of a tertiary pediatric hospital due to m-sTBI from November 2022 to May 2023. Plasma interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α concentrations were detected by flow cytometry on admission and on days 5 to 7. The primary outcome was in-hospital mortality. The secondary outcome was the 6-month functional outcome assessed by the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score, dichotomized as favorable (1-4) or unfavorable (5-8). Fifty patients and 20 healthy controls were enrolled. Baseline IL-6, IL-8 and IL-10 levels were significantly higher in TBI patients than in healthy controls. Twelve patients died in the hospital. Compared with survivors, nonsurvivors had significantly increased baseline IL-6 and IL-8 levels. Baseline IL-5, IL-6 and IL-8 levels were also significantly greater in children with unfavorable versus favorable outcomes. The area under the receiver operating characteristic curve (AUC) of the IL-6 and IL-8 levels and motor Glasgow Coma Scale (GCS) score for predicting in-hospital mortality was 0.706, 0.754, and 0.776, respectively. Baseline IL-1ß, IL-2, IL-4, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α and TNF-α levels were not associated with in-hospital mortality or an unfavorable 6-month outcome. On days 5 to 7, the IL-6 and IL-8 levels were significantly decreased in survivors but increased in nonsurvivors compared to their respective baselines. CONCLUSION: After m-sTBI, the plasma profiles of inflammatory cytokines are markedly altered in children. The trends of IL-6 and IL-8 expression vary among m-sTBI children with different outcomes. Elevated plasma IL-6 and IL-8 levels are related to in-hospital mortality and unfavorable 6-month outcomes. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022. WHAT IS KNOWN: • Inflammation is an important secondary physiological response to TBI. WHAT IS NEW: • The plasma profiles of inflammatory cytokines are markedly altered in children with m-sTBI. Elevated IL-6 and IL-8 levels are related to mortality and unfavorable outcomes.

Relationship between thrombocytopenia and prognosis in children with septic shock: a retrospective cohort study.

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 109/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 109/L had a higher 28-day mortality rate (63.6% vs. 45%, p = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; p = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia (p value from the log-rank test, p = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.

What is the context? Septic shock is a life-threatening disease worldwide, leading to higher mortality.Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation.Although it is known that platelets are associated with prognosis, most studies have focused on adult populations. Limited data are available on the incidence of thrombocytopenia and its correlation with clinical outcomes , specifically, in pediatric patients with sepsis and septic shock. What is new? The present study suggests that thrombocytopenia within 24 hours of septic shock onset reflects a reliable tool for predicting the prognosis of septic shock in pediatric patients.Furthermore, elevated lactate and reduced white-blood-cell count were independent risk factors for the development of thrombocytopenia in pediatric patients with septic shock. What is the impact? This study suggests that thrombocytopenia within 24 hours of septic shock onset is associated with an increased risk of 28-day mortality and decreased ventilation-free, PICU-free days in pediatric patients with septic shock. In septic shock, thrombocytopenia is also associated with increased bleeding events, blood product transfusions, and organ dysfunction.

Closed head injury combined with orbital blowout fracture and displacement of the eyeball into the maxillary sinus in a 14-year-old boy: a case report.

BACKGROUND: Trauma-induced orbital blowout fracture (OBF) with eyeball displacement into the maxillary sinus is rare. CASE PRESENTATION: We present the case of a 14-year-old with a closed head injury, OBF, and displacement of the eyeball into the maxillary sinus following a car accident. A prompt transconjunctival access surgery was performed for eyeball repositioning and orbital reconstruction in a single session, mitigating anaesthesia-related risks associated with multiple surgeries. At the 12-month follow-up, his visual acuity was 20/200. Despite limited eye movement and optic nerve atrophy, overall satisfaction with the ocular appearance was achieved. CONCLUSIONS: This report offers novel insights into the mechanisms of OBF occurrence and the development of postoperative complications.

Modulation of Acute Intestinal Inflammation by Dandelion Polysaccharides: An In-Depth Analysis of Antioxidative, Anti-Inflammatory Effects and Gut Microbiota Regulation.

Acute colitis is a complex disease that can lead to dysregulation of the gut flora, inducing more complex parenteral diseases. Dandelion polysaccharides (DPSs) may have potential preventive and therapeutic effects on enteritis. In this study, LPS was used to induce enteritis and VC was used as a positive drug control to explore the preventive and therapeutic effects of DPS on enteritis. The results showed that DPS could repair the intestinal barrier, down-regulate the expression of TNF-α, IL-6, IL-1ß, and other pro-inflammatory factors, up-regulate the expression of IL-22 anti-inflammatory factor, improve the antioxidant capacity of the body, and improve the structure of intestinal flora. It is proved that DPS can effectively prevent and treat LPS-induced acute enteritis and play a positive role in promoting intestinal health.

Optical Second Harmonic Generation of Low-Dimensional Semiconductor Materials.

In recent years, the phenomenon of optical second harmonic generation (SHG) has attracted significant attention as a pivotal nonlinear optical effect in research. Notably, in low-dimensional materials (LDMs), SHG detection has become an instrumental tool for elucidating nonlinear optical properties due to their pronounced second-order susceptibility and distinct electronic structure. This review offers an exhaustive overview of the generation process and experimental configurations for SHG in such materials. It underscores the latest advancements in harnessing SHG as a sensitive probe for investigating the nonlinear optical attributes of these materials, with a particular focus on its pivotal role in unveiling electronic structures, bandgap characteristics, and crystal symmetry. By analyzing SHG signals, researchers can glean invaluable insights into the microscopic properties of these materials. Furthermore, this paper delves into the applications of optical SHG in imaging and time-resolved experiments. Finally, future directions and challenges toward the improvement in the NLO in LDMs are discussed to provide an outlook in this rapidly developing field, offering crucial perspectives for the design and optimization of pertinent devices.

Zhumian Granules improves PCPA-induced insomnia by regulating the expression level of neurotransmitters and reducing neuronal apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep problems, according to Traditional Chinese medicine (TCM) philosophy, are attributed to the imbalance between yin and yang. Zhumian Granules, also known as Sleep-aid Granules or ZG, are a traditional Chinese herbal remedy specifically designed to alleviate insomnia. This formula consists of many components, including Wu Wei Zi (Schisandrae Chinensis Fructus), Suan Zao Ren (Ziziphi Spinosae Semen), and other medicinal plants. According to the pharmacology of Traditional Chinese Medicine (TCM), Wu Wei Zi and Suan Zao Ren have the ability to relax the mind and promote sleep. When taken together, they may balance the opposing forces of yin and yang. Therefore, ZG may potentially be used as a therapeutic treatment for insomnia. AIM OF THE STUDY: This research was specifically developed to establish a strong empirical basis for the subsequent advancement and utilization of ZG in the management of insomnia. This research aimed to gather empirical data to support the effectiveness of ZG, thereby providing useful insights into its potential therapeutic advantages for persons with insomnia. MATERIALS AND METHODS: This study utilized Zhumian Granules (ZG), a traditional Chinese herbal decoction, to examine its sedative and hypnotic effects on mice with PCPA-induced insomnia. The effects were assessed using the pentobarbital-induced sleep test (PIST), Morris water maze test (MWM), and autonomic activity test. The levels of neurotransmitters in each group of mice were evaluated using UPLC-QQQ-MS. The impact of ZG on the quantity and structure of hippocampal neurons was seen in brain tissue slices using immunofluorescence labeling. RESULTS: ZG was shown to possess active sedative properties, effectively lowering the distance of movement and lengthening the duration of sleep. ZG mitigated the sleeplessness effects of PCPA by elevating the levels of 5-hydroxytryptamine (5-HT), 4-aminobutyric acid (GABA), and 5-hydroxyindoleacetic acid (5-HIAA), while reducing the levels of dopamine (DA) and norepinephrine (NE), as well as decreasing neuronal death. CONCLUSIONS: This research confirmed the sedative and hypnotic properties of ZG and elucidated its probable mechanism involving neurotransmitters.

Winter is coming: An investigation of vigilant leadership, antecedents, and outcomes.

Within the hierarchical taxonomy of effective leadership, change-oriented leadership stands as a distinct and meaningful metacategory, primarily focusing on promoting change by communicating a compelling vision for the future. However, we consider whether there might be room to broaden the scope of change-oriented leadership by examining more negative-focused leadership behaviors. In this article, we explore the concept of vigilant leadership, which we suggest could be a change-oriented and negative-focused leadership style, and investigate its usefulness as a new leadership construct. In Study 1, we take preliminary steps toward developing a measure of vigilant leadership, employing content adequacy assessment and item response theory analysis. Drawing on the integrative trait-behavioral model of leadership effectiveness (DeRue et al., 2011), we further explore how vigilant leadership is associated with an array of antecedents (i.e., leader characteristics) and leadership outcomes. In Studies 2a and 2b, we present initial findings that leaders high on consideration of future consequences, prevention focus, general self-efficacy, and emotional intelligence might be more inclined to exhibit vigilant leadership. In Study 3, our results suggest that, even after controlling for the effect of visionary leadership (a type of positive-focused change-oriented leadership), vigilant leadership is positively related to follower felt responsibility for change, proactivity, specific proactive work behaviors (taking charge, voice, and problem prevention), teamwork proactivity, and teamwork proficiency. However, it does not seem to relate to follower proficiency, follower adaptivity, teamwork adaptivity, organizational citizenship behavior, positive affect toward the leader, leader-member exchange, or relational identification with the leader. With these preliminary findings, we encourage further discussion and investigation into the potential implications of this emerging construct. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Unveiling the hidden potential: Above-ground parts of Paris yunnanensis Franch. Is promise as an anti-acne therapeutic beyond traditional medicinal sites.

The dried rhizomes of Paris yunnanensis Franch. have been extensively utilized in traditional Chinese medicine as hemostatic, antitumor, and antimicrobial agents. An examination of classical texts and renowned Chinese medical formulations showcased its efficacy in acne treatment. Presently, there is a significant scarcity of Paris resources. Consider directing attention towards the non-medicinal parts of Paris to mitigate the strain on medicinal resources within this realm. To address these resource limitations, this study investigated the bioactivity and pharmacodynamics of the above-ground parts of Paris (AGPP). A synergistic approach integrating network pharmacology, molecular docking (in silico validation), and animal experimentation (in vivo validation) was employed to elucidate the potential mechanisms underlying the efficacy of AGPP against acne vulgaris in this study. The active constituents in AGPP extracts were identified via UHPLC-Q-Orbitrap HRMS analysis, with their targets extracted for network pharmacological analysis. KEGG pathway analysis unveiled potential therapeutic mechanisms, validated through molecular docking and rat auricular acne model experiments. Comprehensive chemical characterization revealed fifty constituents, including steroidal saponins, flavonoids, amino acids, organic acids, phytohormones, phenolic acids, and alkaloids. Diosgenin, Quercetin, Kaempferol, Ecdysone, and α-linolenic acid were identified as main constituents with acne-treating potential. Core targets included SRC, MAPK3, and MAPK1, with key signaling pathways implicated. Histologically, AGPP mitigated acne-induced follicular dilatation and inflammation, inhibiting inflammatory cytokine production (IL-6, IL-1ß, TNF-α). This study offers insight into AGPP's mechanism for acne treatment, laying groundwork for Paris development and drug discovery.

Clinical effect of the internal fixation for rib fracture with single utility port complete video-assisted thoracoscopic surgery.

BACKGROUNDS: The internal fixation for rib fracture with single-operation-port (two ports) complete video-assisted thoracoscopic surgery (VATS) is a promising surgical approach for treating multiple rib fractures. The study aimed to investigate the minimally invasive surgical procedure's clinical effect in treating multiple rib fractures. METHODS: Seventy-three patients with multiple rib fractures were divided into two groups according to surgical procedure. In the study group, 42 patients were operated on with the internal fixation of rib fracture with single-operation-port complete VATS. In the control group, this study performed the open operative internal fixation for rib fracture with traditional thoracotomy on 31 patients. The surgical-related indexes were retrospectively analyzed. These included the operative time, the intraoperative blood loss, the drainage amount of the chest tube, the placement time of the chest tube, the postoperative hospital stay, the incidence of postoperative complications, the imaging efficacy of rib fixation of rib fractures, and visual analog scale of pain scoring (VAS scoring). RESULTS: There was no difference in the operative time between the study and control groups (P = 0.806). The intraoperative blood loss, the chest tube drainage amount, the chest tube placement time, the postoperative hospital stay, and the incidence of postoperative complications in the study group were lower than those in the control group (P < 0.05). There was no significant difference in the imaging efficacy of rib fixation of rib fractures between the two groups (P = 0.806). VAS scores in the study group on the seventh postoperative day were significantly reduced compared with the control group (P = 0.026). CONCLUSION: The internal fixation for rib fractures with single-operation-port complete VATS is a feasible, safe, simple, and minimally invasive surgical procedure to treat multiple rib fractures, which is worthy of clinical application.

Comparing the clinical characteristics and outcomes of septic shock children with and without malignancies: a retrospective cohort study.

OBJECTIVE: There is an amelioration in mortality rates of septic shock patients with malignancies over time, but it remains uncertain in children. Therefore, the authors endeavored to compare the clinical characteristics, treatment needs, and outcomes of septic shock children with or without malignancies. METHODS: The authors retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2015 to December 2022 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. RESULTS: A total of 508 patients were enrolled. The proportion of Gram-negative bacteria and fungal infections in children with malignancies was significantly higher than those without malignancies. Septic shock children with malignancies had a longer length of stay (LOS) in the hospital (21 vs. 11 days, p<0.001). However, there were no statistically significant differences in the LOS of PICU (5 vs. 5 days, p = 0.591), in-hospital mortality (43.0 % vs. 49.4 %, p = 0.276), and 28-day mortality (49.2 % vs. 44.7 %, p = 0.452). The 28-day survival analysis (p = 0.314) also showed no significant differences. CONCLUSION: Although there are significant differences in the bacterial spectrum of infections, the septic shock children with or without malignancies showed a similar mortality rate. The septic shock children with malignancies had longer LOS of the hospital.

Development of a novel membrane-based quorum-quenching microbial isolator for biofouling control: Process performance and microbial mechanism.

Quorum quenching (QQ) can mitigate biofouling in membrane bioreactors (MBRs) by inhibiting cell-to-cell communication. However, it is difficult to maintain long-term QQ activity. Here, a novel microbial isolator composed of tubular microfiltration membranes was developed to separate QQ bacteria (Rhodococcus sp. BH4) from sludge. The time to reach a transmembrane pressure of 50 kPa was delayed by 69.55 % (p = 0.002, Student's t test) in MBR with QQ microbial isolator (MBR-Q), compared to that in the control MBR (MBR-C) during stable operation. The concentration of proteins in the extracellular polymeric substances of sludge was reduced by 20.61 % in MBR-Q relative to MBR-C. The results of the bacterial community analyses indicated less enrichment of fouling-associated bacteria (e.g., Acinetobacter) but a higher abundance of QQ enzymes in MBR-Q than in MBR-C. This environmentally friendly technique can decrease the cleaning frequency and increase the membrane lifespan, thus improving the sustainability of MBR technology.

Pan-cancer investigation of RFX family and associated genes identifies RFX8 as a therapeutic target in leukemia.

Background: Several transcription factors and co-factors are encoded by the RFX (Regulatory Factor X) family (RFX1-8) and associated genes (RFXAP and RFXANK). Increasing evidence suggests that the RFX family and associated genes are involved in the development and progression of cancer. However, no prior research has focused on a multi-omic analysis of these genes to evaluate their role in tumor progression. Methods: Using combined TCGA and GTEx pan-cancer data, we investigated the expression patterns and survival profiles of these ten genes. We then focused on RFX8 to analyze its clinicopathological and therapeutic features. Finally, we conducted experimental validation of RFX8 function in acute myeloid leukemia (AML). Results: RFX5 and RFXANK showed higher expression levels, while RFX6 showed lower expression levels in most types of cancer, with RFX8 being the most upregulated in LAML. RFX2 and RFXAP demonstrated prognostic significance in eight types of cancer, and RFX8 showed significance in six types of cancer. The expression of these ten genes exhibited specific characteristics in immune subtypes, tumor microenvironment, and stemness. The expression of RFX8 was correlated with various tumor stages, microsatellite instability (MSI), tumor mutation burden (TMB), immune cell infiltration, and immune-checkpoint expression. Additionally, RFX8 was found to regulate tumorigenesis and sensitivity to chelerythrine in AML. Conclusions: Our work delineated the landscape of the RFX family and associated genes in the pan-cancer context and the specific role of RFX8 in AML. These findings might offer cues for further investigations of these genes in cancer biology.

Sensitive sensing platform based on Co, Mo doped electrospun nanofibers for simultaneous electrochemical detection of dopamine and uric acid.

Abnormal levels of dopamine (DA) and uric acid (UA) in the human body are valuable indicators for monitoring human health, as they are associated with certain diseases. Therefore, it is crucial to develop sensitive and simultaneous analytical techniques for DA and UA in diagnosing the related diseases. Herein, the Co- and Mo- doped carbon nanofibers (Co, Mo@CNFs) electrochemical biosensor was developed successfully for the sensitive and accurate simultaneous detection of DA and UA. A straightforward electrospinning technique followed by a carbonization process was employed for the synthesis of Co, Mo@CNFs, and the encapsulation of Co and Mo within CNFs served to not only prevent nanoparticle agglomeration, thus providing more active sites, but also to facilitate rapid electron transfer. By incorporating Co and Mo into CNFs, the electrocatalytic activity of the modified electrode was greatly improved due to the beneficial conductivity and synergistic effects of transition metals. This enhancement effectively addressed issues such as the overlapping anodic peaks that occur when DA and UA are oxidized concurrently. Due to the mentioned synergistic contributions, the modified Co, Mo@CNFs electrode (Co, Mo@CNFs/GCE) achieved remarkable sensitivity for the simultaneous detection of DA and UA, while also exhibiting strong anti-interference ability. The detection limits for DA and UA were 2.35 nmol L-1 and 0.16 µmol L-1, respectively. We applied the developed Co, Mo@CNFs/GCE electrochemical biosensor to detect DA and UA in 50-fold diluted serum and urine samples. The results affirm the biosensor's reliability and precision. Moreover, the developed Co, Mo@CNFs/GCE biosensor demonstrated excellent performance in simultaneously detecting DA and UA, providing an efficient and dependable detection approach for clinical diagnosis and bioanalysis.

Two chromosome-level genomes of Smittia aterrima and Smittia pratorum (Diptera, Chironomidae).

Chironomids are one of the most abundant aquatic insects and are widely distributed in various biological communities. However, the lack of high-quality genomes has hindered our ability to study the evolution and ecology of this group. Here, we used Nanopore long reads and Hi-C data to produce two chromosome-level genomes from mixed genomic data. The genomes of Smittia aterrima (SateA) and Smittia pratorum (SateB) were assembled into three chromosomes, with sizes of 78.45 Mb and 71.56 Mb, scaffold N50 lengths of 25.73 and 23.53 Mb, and BUSCO completeness of 98.5% and 97.8% (n = 1,367), 5.68 Mb (7.24%) and 1.94 Mb (2.72%) of repetitive elements, and predicted 12,330 (97.70% BUSCO completeness) and 11,250 (97.40%) protein-coding genes, respectively. These high-quality genomes will serve as valuable resources for comprehending the evolution and environmental adaptation of chironomids.

The regulatory mechanism of m6A modification in gastric cancer.

To the best of our knowledge, N6-Methyladenosine (m6A) exerts a significant role in the occurrence and development of various tumors. Gastric cancer (GC), originating from the mucosal epithelium in the digestive tract, is the fifth most common cancer and the third most common cause of cancer death around the world. Therefore, it is urgent to explore the specific mechanism of tumorigenesis of GC. As we all know, m6A modification as the most common RNA modification, is involved in the modification of mRNA and ncRNA at the post-transcriptional level, which played a regulatory role in various biological processes. As identified by numerous studies, the m6A modification are able to influence the proliferation, apoptosis, migration, and invasion of GC. What's more, m6A modification are associated with EMT, drug resistance, and aerobic glycolysis in GC. m6A related-ncRNAs may be a valuable biomarker used by the prediction of GC diagnosis in the future. This review summarizes the role of m6A modification in the mechanism of gastric cancer, with the aim of identifying biological progress.

Comprehensive chromatographic assessment of forced degraded in vitro transcribed mRNA.

Heightened interest in messenger RNA (mRNA) therapeutics has accelerated the need for analytical methodologies that facilitate the production of supplies for clinical trials. Forced degradation studies are routinely conducted to provide an understanding of potential weak spots in the molecule that are exploited by stresses encountered during bulk purification, production, shipment, and storage. Consequently, temperature fluctuations and excursions are often experienced during these unit operations and may accelerate mRNA degradation. Here, we present a concise panel of chromatography-based stability-indicating assays for evaluating thermally stressed in vitro transcribed (IVT) mRNA as part of a forced degradation study. We found that addition of EDTA to the mRNAs prior to heat exposure reduced the extent of degradation, suggesting that transcripts may be fragmenting via a divalent metal-ion mediated pathway. Trace divalent metal contamination that can accelerate RNA instability is likely carried over from upstream steps. We demonstrate the application of these methods to evaluate the critical quality attributes (CQAs) of mRNAs as well as to detect intrinsic process- and product-related impurities.

Exosomal miR-151-3p in saliva: A potential non-invasive marker for gastric cancer diagnosis and prognosis modulated by Sijunzi decoction (SJZD) in mice.

Gastric cancer (GC) is one of the most prominent malignancies that originate in the epithelial cells of the gastric mucosa and is one of the main causes of cancer-related mortality worldwide. New circulating biomarkers of exosomal RNA might have great potential for non-invasive early prognosis of GC. Sijunzi Decoction (SJZD) is a typical representative formula of the method of benefiting Qi and strengthening the spleen in Traditional Chinese Medicine (TCM). However, the effects and mechanism of SJZD in treating GC remain unclear. This study looked for biomarkers of exosomal RNA for early prognosis of GC, and explored the mechanism of SJZD in treating GC. A gastric cancer model with spleen deficiency syndrome was established in nude mice, and the curative effects of SJZD were investigated. Differentially expressed miRNAs in plasma and saliva exosomes were sequenced and analyzed. Potential target genes of these miRNAs were predicted and applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment annotation. Overlapping miRNAs in saliva and plasma samples were analyzed, and qRT-PCR was performed for verification. miR-151a-3p was selected, and qRT-PCR further determined that miR-151a-3p was downregulated in saliva and plasma exosomes from the SJZD group. The intersected miR-151a-3p target genes were predicted and enriched in the extrinsic apoptotic signaling pathways. SJZD significantly ameliorates gastric cancer with spleen deficiency syndrome in mouse models, and exosomal miRNAs, particularly miR-151-3p, might be modulated by SJZD in plasma and saliva. The exosomal miR-151-3p in saliva may serve as a non-invasive potential marker for gastric cancer diagnosis and prognosis.

S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens.

Oxidative (or respiratory) burst confers host defense against pathogens by generating reactive species, including reactive nitrogen species (RNS). The microbial infection-induced excessive RNS damages many biological molecules via S-nitrosothiol (SNO) accumulation. However, the mechanism by which the host enables innate immunity activation during oxidative burst remains largely unknown. Here, we demonstrate that S-nitrosoglutathione (GSNO), the main endogenous SNO, attenuates innate immune responses against herpes simplex virus-1 (HSV-1) and Listeria monocytogenes infections. Mechanistically, GSNO induces the S-nitrosylation of stimulator of interferon genes (STING) at Cys257, inhibiting its binding to the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Alcohol dehydrogenase 5 (ADH5), the key enzyme that metabolizes GSNO to decrease cellular SNOs, facilitates STING activation by inhibiting S-nitrosylation. Concordantly, Adh5 deficiency show defective STING-dependent immune responses upon microbial challenge and facilitates viral replication. Thus, cellular oxidative burst-induced RNS attenuates the STING-mediated innate immune responses to microbial infection, while ADH5 licenses STING activation by maintaining cellular SNO homeostasis.