Cascade Self-Generation of Carbon Monoxide Triggered by Photoinduced Holes for Efficient Hypoxic Tumors Therapy.

It still remains challenging to design multifunctional therapeutic reagents for effective cancer therapy under a unique tumor microenvironment including insufficient endogenous H2O2 and O2, low pH, and a high concentration of glutathione (GSH). In this work, a CO-based phototherapeutic system triggered by photogenerated holes, which consisted of ionic liquid (IL), the CO prodrug Mn2(CO)10, and iridium(III) porphyrin (IrPor) modified carbonized ZIF-8-doped graphitic carbon nitride nanocomposite (IL/ZCN@Ir(CO)), was designed for cascade hypoxic tumors. Upon light irradiation, the photogenerated holes on IL/ZCN@Ir(CO) oxidize water into H2O2, which subsequently induces Mn2(CO)10 to release CO. Meanwhile, IrPor can convert H2O2 to hydroxyl radical (•OH) and subsequent singlet oxygen (1O2), which further triggers CO release. Moreover, the degraded MnO2 shows activity for glutathione (GSH) depletion and mimics peroxidase, leading to GSH reduction and •OH production in tumors. Thus, this strategy can in situ release high concentrations of CO and reactive oxygen species (ROS) and deplete GSH to efficiently induce cell apoptosis under hypoxic conditions, which has a high inhibiting effect on the growth of tumors, offering an attractive strategy to amplify CO and ROS generation to meet therapeutic requirements in cancer treatment.

Clotting Blood into an Adhesive Gel by Hemostatic Powder Based on Cationic/Anionic Polysaccharides and Laponite.

Hemostatic powder is widely employed for emergency bleeding control due to its ability to conform to irregularly shaped wounds, ease of use, and stable storage. However, current powders exhibit limited tissue adhesion and insufficient support for thrombus formation, making them easily washed away by blood. In this study, a hybrid powder (QAL) was produced by mixing quaternized chitosan (QCS) powder, catechol-modified alginate (Cat-SA) powder, and laponite (Lap) powder. Upon addition of QAL, the blood quickly transformed to a robust and adhesive blood gel. The adhesion strength of the blood gel was up to 31.33 ± 1.56 kPa. When compared with Celox, QAL showed superior performance in promoting hemostasis. Additionally, QAL exhibited effectiveness in eliminating bacteria while also demonstrating outstanding biocompatibility with cells and blood. These favorable properties, including strong coagulation, adhesion to wet tissue, antibacterial activity, biosafety, ease of use, and stable storage, make QAL a promising emergency hemostatic agent.

Coagulating blood into adhesive gel by hybrid powder based on oppositely charged polysaccharide/tannic acid-modified mesoporous bioactive glass.

Hemostatic powder is widely utilized in emergency situations to control bleeding due to its ability to work well on wounds with irregular shapes, ease of application, and long-term stability. However, traditional powder often suffers from limited tissue adhesion and insufficient support for blood clot formation, leaving it susceptible to displacement by the flow of blood. This study introduces a hemostatic powder composed of tannic modified mesoporous bioactive glass (TMBG), cationic quaternized chitosan (QCS), and anionic hyaluronic acid modified with catechol group (HADA). The resulting TMBG/QCS/HADA based hemostatic powder (TMQH) rapidly absorbs plasma, concentrating blood coagulation factors. Simultaneously, the water-soluble QCS and HADA interact to form a 3D network structure, which can be strengthened by crosslinking with TMBG. This network effectively captures clustered blood coagulation factors, leading to a strong and adhesive thrombus that resists disruption from blood flow. TMQH exhibits superior efficacy in promoting hemostasis compared to Celox™ both in rat arterial injuries and non-compressible liver puncture wounds. TMQH demonstrates excellent antibacterial activity, cytocompatibility, and blood compatibility. These outstanding superiorities in blood clotting capability, wet tissue adhesion, antibacterial activity, safety for living organisms, ease of application, and long-term stability, make TMQH highly suitable for emergency hemostasis.

Analysis of drug-induced posterior reversible encephalopathy syndrome using the food and drug administration adverse drug events reporting system database.

OBJECTIVE: In this retrospective pharmacovigilance study, we gathered data on drug-induced posterior reversible encephalopathy syndrome (PRES). Our goal was to identify the primary suspect drugs in PRES by analyzing the Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHODS: We identified and analyzed reports of PRES listed in the FAERS database between 2004 and 2021. Using the reporting odds ratio and 95% confidence interval, we evaluated the safety signals for each of the drugs associated with PRES. RESULTS: We reviewed 11,077 reports of adverse events corresponding to PRES. The primary suspect drug categories were antineoplastics, immunosuppressants, and glucocorticoids. PRES was 24.77% more likely to occur in females than in males. Drug-induced PRES usually occurs in individuals with cancer, those who have undergone an organ/stem cell transplant, and those with autoimmune conditions. CONCLUSION: Our results show that the drugs most commonly suspected to cause PRES were antineoplastics, immunosuppressants, and glucocorticoids. Future studies are needed to illuminate the pathophysiological alterations that underlie PRES. In the meantime, prescribers and patients should be made aware of the potential risks of PRES associated with pharmaceutical therapy, and the summaries of product characteristics for individual drugs should be updated to include this information.

ALK upregulates POSTN and WNT signaling to drive neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor of childhood. While MYCN and mutant anaplastic lymphoma kinase (ALKF1174L) cooperate in tumorigenesis, how ALK contributes to tumor formation remains unclear. Here, we used a human stem cell-based model of neuroblastoma. Mis-expression of ALKF1174L and MYCN resulted in shorter latency compared to MYCN alone. MYCN tumors resembled adrenergic, while ALK/MYCN tumors resembled mesenchymal, neuroblastoma. Transcriptomic analysis revealed enrichment in focal adhesion signaling, particularly the extracellular matrix genes POSTN and FN1 in ALK/MYCN tumors. Patients with ALK-mutant tumors similarly demonstrated elevated levels of POSTN and FN1. Knockdown of POSTN, but not FN1, delayed adhesion and suppressed proliferation of ALK/MYCN tumors. Furthermore, loss of POSTN reduced ALK-dependent activation of WNT signaling. Reciprocally, inhibition of the WNT pathway reduced expression of POSTN and growth of ALK/MYCN tumor cells. Thus, ALK drives neuroblastoma in part through a feedforward loop between POSTN and WNT signaling.

Gluing blood into adhesive gel by oppositely charged polysaccharide dry powder inspired by fibrin fibers coagulation mediator.

Hemostatic powders that adapt to irregularly shaped wounds, allowing for easy application and stable storage, have gained popularity for first-aid hemorrhage control. However, traditional powders often provide weak thrombus support and exhibit limited tissue adhesion, making them susceptible to dislodgment by the bloodstream. Inspired by fibrin fibers coagulation mediator, we have developed a bi-component hemostatic powder composed of positively charged quaternized chitosan (QCS) and negatively charged catechol-modified alginate (Cat-SA). Upon application to the wound, the bi-component powders (QCS/Cat-SA) rapidly absorb plasma and dissolve into chains. These chains interact with each other to form a network, which can effectively bind and entraps clustered red blood cells and platelets, ultimately leading to the creation of a durable and robust thrombus. Significantly, these interconnected polymers adhere to the injury site, offering protection against thrombus disruption caused by the bloodstream. Benefiting from these synthetic properties, QCS/Cat-SA demonstrates superior hemostatic performance compared to commercial hemostatic powders like Celox™ in both arterial injuries and non-compressible liver puncture wounds. Importantly, QCS/Cat-SA exhibits excellent antibacterial activity, cytocompatibility, and hemocompatibility. These advantages of QCS/Cat-SA, including strong blood clotting, wet tissue adherence, antibacterial activity, biosafety, ease of use, and stable storage, make it a promising hemostatic agent for emergency situations.

Cohering Plasma into Adhesive Gel by Natural Biopolymer-Nanoparticle Hybrid Powder for Efficient Hemostasis and Wound Healing.

Hemostatic powder is commonly used in emergency bleeding control due to its suitability for irregularly shaped wounds, ease of use, and stable storage. However, traditional powder often has limited tissue adhesion and weak thrombus support, which makes it vulnerable to displacement by blood flow. Herein, we have developed a tricomponent hemostatic powder (MQS) composed of mesoporous bioactive glass nanoparticle (MBG), positively charged quaternized chitosan (QCS), and negatively charged catechol-modified alginate (SADA). Upon application to the wound, MBG with its high specific surface area quickly absorbs plasma, concentrating the blood coagulation factor. Simultaneously, the water-soluble QCS and SADA interact with each other and form a net, which can be further cross-linked by MBG. This network efficiently binds and entraps clustered blood coagulation factors, ultimately resulting in the formation of a durable and robust thrombus. Furthermore, the formed net adheres to the injury site, offering protection against thrombus disruption caused by the bloodstream. Benefiting from the synergistic effect of these three components, MQS demonstrates superior hemostatic performance compared to commercial hemostatic powders like Celox in both arterial injuries and noncompressible liver puncture wounds. Furthermore, MQS can effectively accelerate wound healing. In addition, MQS exhibits excellent antibacterial activity, cytocompatibility, and hemocompatibility. These advantages of MQS, including strong blood clotting, wet tissue adherence, antibacterial activity, wound healing ability, biosafety, ease of use, and stable storage, make it a promising hemostatic agent for emergency situations.

Development of a Competitive Chemiluminescent Assay for Quantitative Determination of TP53 Fusion Protein Using Reagent Strips.

Recent studies have shown that almost half of all cancers occur due to DNA damage. For the early diagnosis of cancer, a highly sensitized and swift identification for TP53 is needed since the corresponding TP53 protein is effectively recognized as "the guardian of the genome." To improve the detection sensitivity, numerous analytical methods were previously used for the determination of the TP53 protein, including denaturing high-performance liquid chromatography and enzyme-linked immunosorbent assay (ELISA). Currently, immunochromatographic tests (ICTs) that are simple to use, stable over time, and show low interference are regarded as valuable tools for the quick screening of food and environmental monitoring along with clinical diagnosis. ICTs often have limited sensitivity even if a variety of novel reporters possessing optimum photostability and improved brightness are used as signal-intensity reporters. Compared with N-(4-aminobutyl)-N-(ethylisoluminol) or luminol, a novel luminescent probe, 2',6'-diMethyl-4'-(N-succiniMidyloxycarbonyl) phenyl-10-sulfopropylacridiniuM-9-carboxylate (NSP-DMAE-NHS) has achieved a much higher efficiency, improvement in the biosensor's performance, and amplification of the signal without causing any damage to the biomolecule in terms of its biochemical activity. In this study, the reagent strip method was initially used to detect TP53 fusion protein by combining the advantages of NSP-DMAE-NHS and immunochromatography. In our experiment, the control and study lines on the strips were immobilized through HRP-conjugated goat anti-rabbit IgG and TP53 antigen, respectively. The optimized concentration of the anti-TP53 antibody-NSP-DMAE-NHS immunoconjugates was then added to the TP53 antigen samples. After, the test strips were inserted and left in the aforementioned buffer solution for an additional 20 min. Finally, a lab-made luminous measurement device was used to analyze the corresponding control and study lines on the strips. Under optimized conditions, this method was found to be ultrasensitive, with a wide range of linear responses from 0.0008 ng mL-1 to 1 µg mL-1 and a limit of detection of 0.0008 ng mL-1 (0.013 pM). Thus, a novel competitive chemiluminescent assay based on reagent strips was established for the determination of the TP53 fusion proteins. The strategy has potential applications for ultrasensitive detection in the early diagnosis of cancer.

Antibacterial and hemostatic chitin sponge directly constructed from Pleurotus Eryngii via top-down approach.

Chitin, the second most abundant polysaccharide on earth, possesses unique characteristics, including biosafety, biodegradability, and procoagulant activity, making it an attractive material for hemostasis. However, the conventional bottom-up construction of chitin-based materials is intricate and time-consuming. In this study, we have developed a top-down strategy to prepare a 3D porous chitin-based hemostatic sponge with exceptional hemostatic properties and antibacterial activity, directly from the spongy Pleurotus eryngii. The top-down method involves deproteinization, in situ quaternization, and tannin acid crosslinking. The obtained sponge has an interconnected microporous structure with high porosity (89.7 ± 3.2 %), endowing it with high water absorption (2047 ± 105 %) and rapid water-triggered shape-memory behavior (< 2 s). The sponge exhibits superior blood coagulant activity and outperforms standard medical gauze, gelatin sponge, and chitosan sponge in both topical artery and non-compressive liver puncture wound. In addition, the sponge exhibited significant antibacterial activity against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. In summary, this study provides a straightforward and practical approach for constructing an antibacterial and hemostatic chitin sponge that could be a valuable option for treating bleeding wounds.

A polyglutamic acid/tannic acid-based nano drug delivery system: Antibacterial, immunoregulation and sustained therapeutic strategies for oral ulcers.

Oral ulcers are a common inflammatory mucosal ulcer, and the moist and dynamic environment in the oral cavity makes topical pharmacological treatment of oral ulcers challenging. Herein, oral ulcer tissue adhesion nanoparticles were prepared by using esterification reaction between polyglutamic acid and tannic acid, and at the same time doxycycline hydrochloride was loaded into the nanoparticles. The obtained slow drug release effect of the drug-loaded nanoparticles reduced the toxicity of the drug, and by penetrating into the fine crevice region of the wound tissue and adhering to it, they could in-situ release the carried drug more effectively and thus have shown significant antibacterial effects. In addition, tannic acid in the system conferred adhesion, antioxidant and immune regulation activities to the nanocarriers. A rat oral ulcer model based on fluorescent labeling was established to investigate the retention of nanoparticles at the ulcer, and the results showed that the retention rate of drug-loaded nanoparticles at the ulcer was 17 times higher than that of pure drug. Due to the antibacterial and immune regulation effects of the drug-loaded nanoparticles, the healing of oral ulcer wounds was greatly accelerated. Such application of doxycycline hydrochloride loaded polyglutamic acid/tannic acid nanoparticles is a novel and effective treatment strategy for oral ulcer.

A Molecularly Imprinted Electrochemical Sensor Based on TiO2@Ti3C2Tx for Highly Sensitive and Selective Detection of Chlortetracycline.

In view of the serious side effects of chlortetracycline (CTC) on the human body, it is particularly important to develop rapid, sensitive, and selective technologies for the detection of CTC in food. In this work, a molecularly imprinted electrochemical sensor with [Fe(CN)6]3-/4- as signal probe was proposed for the highly sensitive and selective detection of CTC. For this purpose, TiO2, which acts as an interlayer scaffold, was uniformly grown on the surface of Ti3C2Tx sheets through a simple two-step calcination process using Ti3C2Tx as the precursor to effectively avoid the stacking of Ti3C2Tx layers due to hydrogen bonding and van der Waals forces. This endowed TiO2@Ti3C2Tx with large specific surface, abundant functional sites, and rapid mass transfer. Then, polypyrrole molecularly imprinted polymers (MIPs) with outstanding electrical conductivity were modified on the surface of TiO2@Ti3C2Tx via simple electro-polymerization, where the pyrrole was employed as a polymeric monomer and the CTC provided a source of template molecules. This will not only provide specific recognition sites for CTC, but also facilitate electron transport on the electrode surface. The synergistic effects between TiO2@Ti3C2Tx and polypyrrole MIPs afforded the TiO2@Ti3C2Tx/MIP-based electrochemical sensor excellent detection properties toward CTC, including ultra-low limits of detection (LOD) (0.027 nM), a wide linear range (0.06-1000 nM), and outstanding stability, reproducibility, selectivity, and feasibility in real samples. The results indicate that this strategy is feasible and will broaden the horizon for highly sensitive and selective detection of CTC.

pH-Responsive Multifunctional Nanoplatforms with Reactive Oxygen Species-Controlled Release of CO for Enhanced Oncotherapy.

Recently, various nanomaterials have drawn increasing attention for enhanced tumor therapy. However, a lack of tumor uptake and insufficient generation of cytotoxic agents have largely limited the antitumor efficacy in vivo. Herein, a multifunctional nanoplatform (IL@CPPor(CO)) was constructed with pH-responsive copper peroxide nanoparticles (CPNP) that are capable of self-supplying H2O2, a radical-sensitive carbonic oxide (CO) donor (Fe3(CO)12), photosensitizer Iridium(III) meso-tetra (N-methyl-4-pyridyl)porphyrin pentachloride (IrPor), and ionic liquid (IL) for enhanced oncotherapy. Under acidic conditions, the CPNP could decompose to release H2O2 and Cu2+. The concomitant generation of H2O2 could efficiently trigger Fe3(CO)12 to release the CO in situ. On the other hand, Cu2+ possesses both glutathione depletion and Fenton-like properties. In addition, IrPor has both peroxidase-like activity and photosensitizer properties to produce reactive oxygen species (ROS) in tumors. The released ROS could trigger the rapid intracellular release of CO. More importantly, released CO and ROS could promote cell apoptosis and improve the therapeutic efficacy. Moreover, due to the pH-dependent ROS generation property, the IL@CPPor(CO) exhibited high tumor accumulation, low toxicity, and good biocompatibility, which enabled effective tumor growth inhibition with minimal side effects in vivo. This work provides a novel multifunctional nanoplatform that combined photodynamic therapy with CDT and CO to improve therapeutic efficacy.

Efficient Adsorption and Electrochemical Detection of Cd2+ with a Ternary MgZnFe-Layered Double Hydroxides Engineered Porous Biochar Composite.

Their unique layered structure, large specific surface area, good stability, high negative charge density between layers, and customizable composition give layered double hydroxides (LDHs) excellent adsorption and detection performance for heavy metal ions (HMIs). However, their easy aggregation and low electrical conductivity limit the practical application of untreated LDHs. In this work, a ternary MgZnFe-LDHs engineered porous biochar (MgZnFe-LDHs/PBC) heterojunction was proposed as a sensing and adsorption material for the effective detection and removal of Cd2+ from wastewater. The growth of MgZnFe-LDHs in the PBC pores not only reduces the accumulation of MgZnFe-LDHs, but also improves the electrical conductivity of the composite. The synergistic effect between MgZnFe-LDHs and PBC enables the composite to achieve a maximum adsorption capacity of up to 293.4 mg/g for Cd2+ in wastewater. Meanwhile, the MgZnFe-LDHs/PBC-based electrochemical sensor shows excellent detection performance for Cd2+, presenting a wide linear range (0.01 ng/L-1 mg/L), low detection limit (3.0 pg/L), good selectivity, and stability. The results indicate that MgZnFe-LDHs/PBC would be a potential material for detecting and removing Cd2+ from wastewater.

PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression.

SNCAIP duplication may promote Group 4 medulloblastoma via induction of PRDM6, a poorly characterized member of the PRDF1 and RIZ1 homology domain-containing (PRDM) family of transcription factors. Here, we investigated the function of PRDM6 in human hindbrain neuroepithelial stem cells and tested PRDM6 as a driver of Group 4 medulloblastoma. We report that human PRDM6 localizes predominantly to the nucleus, where it causes widespread repression of chromatin accessibility and complex alterations of gene expression patterns. Genome-wide mapping of PRDM6 binding reveals that PRDM6 binds to chromatin regions marked by histone H3 lysine 27 trimethylation that are located within, or proximal to, genes. Moreover, we show that PRDM6 expression in neuroepithelial stem cells promotes medulloblastoma. Surprisingly, medulloblastomas derived from PRDM6-expressing neuroepithelial stem cells match human Group 3, but not Group 4, medulloblastoma. We conclude that PRDM6 expression has oncogenic potential but is insufficient to drive Group 4 medulloblastoma from neuroepithelial stem cells. We propose that both PRDM6 and additional factors, such as specific cell-of-origin features, are required for Group 4 medulloblastoma. Given the lack of PRDM6 expression in normal tissues and its oncogenic potential shown here, we suggest that PRDM6 inhibition may have therapeutic value in PRDM6-expressing medulloblastomas.

Electroactive poly(thionine) as imprinted polymer and reference probe simultaneously for ratiometric ion imprinted electrochemical Pb2+sensor.

In this work, an electrochemical sensor based on ion-imprinted polymer/Au nanoparticles/porous biochar (IIP/AuNPs/PBC) composite was proposed for the highly selective and sensitive detection of Pb2+. In this work, poly (thionine) (pTHI) served simultaneously as imprinted polymer and reference probe. It could not only realize the specific detection of Pb2+, but also provide an internal reference signal to eliminate the influence of human and environmental factors on the detection signal and further improve the stability of the sensor. In addition, the AuNPs/PBC composite with large specific surface area, excellent electron transport and electrocatalytic performance could effectively enhance the detection signal as a carrier material. At the same time, the AuNPs on the PBC surface would promote the formation of uniform and stable IIP through Au-S bonds. The synergistic effect between IIP, AuNPs/PBC and ratiometric signal mode gave the Pb2+sensor excellent performance, including a wide linear range (0.1-1000µg l-1), low detection limit (0.03µg l-1, S/N = 3), excellent selectivity and stability. All these results indicate that the proposed sensor could provide a meaningful reference for highly selective detection of heavy metal ions (HMIs).

Hedgehog target genes regulate lipid metabolism to drive basal cell carcinoma and medulloblastoma.

Hedgehog (Hh) signaling is essential for development, homeostasis, and regeneration1. Misactivation of the Hh pathway underlies medulloblastoma, the most common malignant brain tumor in children, and basal cell carcinoma (BCC), the most common cancer in the United States2. Primary cilia regulate Hh signal transduction3, but target genes that drive cell fate decisions in response to ciliary ligands or oncogenic Hh signaling are incompletely understood. Here we define the Hh gene expression program using RNA sequencing of cultured cells treated with ciliary ligands, BCCs from humans, and Hh-associated medulloblastomas from humans and mice (Fig. 1a). To validate our results, we integrate lipidomic mass spectrometry and bacterial metabolite labeling of free sterols with genetic and pharmacologic approaches in cells and mice. Our results reveal novel Hh target genes such as the oxysterol synthase Hsd11ß1 and the adipokine Retnla that regulate lipid metabolism to drive cell fate decisions in response to Hh pathway activation. These data provide insights into cellular mechanisms underlying ciliary and oncogenic Hh signaling and elucidate targets to treat Hh-associated cancers.

An Electrochemical Sensor Based on a Porous Biochar/Cuprous Oxide (BC/Cu2O) Composite for the Determination of Hg(II).

Mercuric ion (Hg2+) in aqueous media is extremely toxic to the environment and organisms. Therefore, the ultra-trace electrochemical determination of Hg2+ in the environment is of critical importance. In this work, a new electrochemical Hg2+ sensing platform based on porous activated carbon (BC/Cu2O) modified with cuprous oxide was developed using a simple impregnation pyrolysis method. Differential pulse anodic stripping voltammetry (DPASV) was used to investigate the sensing capability of the BC/Cu2O electrode towards Hg2+. Due to the excellent conductivity and large specific surface area of BC, and the excellent catalytic activity of Cu2O nanoparticles, the prepared BC/Cu2O electrode exhibited excellent electrochemical activity. The high sensitivity of the proposed system resulted in a low detection limit of 0.3 ng·L-1 and a wide linear response in the ranges from 1.0 ng·L-1 to 1.0 mg·L-1. In addition, this sensor was found to have good accuracy, acceptable precision, and reproducibility. All of these results show that the BC/Cu2O composite is a promising material for Hg2+ electrochemical detection.

A cell-surface-anchored DNA probe coupled with hybridization chain reaction enzyme-free dual signal amplification for sensitive electrochemical detection of the cellular microenvironment.

The cellular microenvironment plays key roles in regulating physiological processes. However, it is still a challenge to detect it with quantification. Here, a simple, biocompatible, and universal strategy based on cell surface-anchored specific DNAzymes and hybridization chain reaction enzyme-free signal amplification for cellular microenvironment electrochemical detection is presented. In this strategy, the cell could be captured on the surface of the electrode via aptamer-target recognition. On the other hand, the DNAzyme hybridized with the substrate strand as a metal ion probe was anchored on the surface of the cell. In the presence of metal ions, the substrate strand could be cleaved into two fragments by the DNAzyme and released from the cell surface. Then, the DNA modified gold nanoparticles (AuNPs) could be captured on the electrode. Subsequently, an alternative hybridization reaction of two hairpin probes was triggered by the carried initiators forming nicked double helices. For signal readout, hemin could be inserted into the double-helix DNA long chain via electrostatic interaction, which could electro-reduce hydrogen peroxide to generate an electrochemical signal. Based on the intrinsic advantages of DNAzymes, including rapid kinetics, high sensitivity, and high selectivity, and the signal amplification strategy, this method should be able to monitor and semi-quantify target metal ions in the cellular microenvironment. Furthermore, this method shows potential for various targets by employing different DNA probes in the cellular microenvironment, providing a platform for bioanalysis.

Data mining for signal detection of adverse events for taxanes based on the food and drug administration adverse drug events reporting system database.

BACKGROUND: This study aimed to mine and compare the positive signals of adverse drug events (ADE) in paclitaxel, docetaxel, and nab-paclitaxel to evaluate the accuracy of current drug package information inserts and enable clinicians to select the appropriate treatment. RESEARCH DESIGN AND METHODS: ADE data reported from January 2006 to December 2020 were extracted from the Food and Drug Adverse Drug Events Reporting System (FAERS) database, and the reporting odds ratio (ROR) was used to detect the risk signals of the 3 taxanes. The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA). RESULTS: A total of 39,163 case reports on paclitaxel, docetaxel and nab-paclitaxel involving 25 different system organ classes (SOCs) were retrieved from the database. The ADE paclitaxel and nab-paclitaxel reports mainly focused on 'general disorders and administration site conditions' and the docetaxel ADE reports focused on 'skin and subcutaneous tissue diseases.' Among the three taxanes, nab-paclitaxel had the highest positive signal for serious adverse events. CONCLUSIONS: Overall, the most common ADE signals and ADE mapping systems obtained in this study were consistent with the package inserts. However, some inconsistencies were noted. Further research is recommended to confirm some of the strong risk signals for ADEs for taxanes before updating the drug package information inserts.

Myocardial structure and functional alterations in a preclinical model of exertional heat stroke.

AIM: Relatively little information is available about the effect of an acute exertional heat stroke (EHS) on myocardium structure and function. Herein, we used a survival male rat model of EHS to answer the question. MAIN METHODS: Adult male Wistar rats underwent forced treadmill running at a 36 °C room temperature and 50 % relative humidity until EHS onset, characterized by hyperthermia and collapse. All rats that were followed for 14 days survived. Injury severity scores of both gastrocnemius and myocardium were determined histologically. Following an EHS event, pathological echocardiography, skeletal muscle and myocardial damage scores and indicators, myocardial fibrosis, hypertrophy, and autophagy were elucidated. KEY FINDINGS: Rats with EHS onset displayed skeletal muscle damage, elevated serum levels of skeletal muscle damage indicators (e.g., creatinine kinase, myoglobin, and potassium), and myocardial injury indicators (e.g., cardiac troponin I, creatinine kinase, and lactate dehydrogenase) returning to homeostasis within 3 days post-EHS. However, EHS-induced myocardial damage, pathological echocardiography, myocardial fibrosis, hypertrophy, and deposited misfolded proteins lasted up to 14 days post-EHS at least. SIGNIFICANCE: First, we provide evidence to confirm that despite the apparent return to homeostasis, underlying processes may still be ongoing after EHS onset. Second, we provide several key findings emphasizing the pathophysiology and risk factors of EHS, highlighting gaps in knowledge with the aim of stimulating future studies.