[Chemical composition analysis of Ganoderma lucidum based on UPLC-Orbitrap-HRMS and virtual screening of FXR activators for treatment of liver fibrosis].

The chemical composition of Ganoderma lucidum ethanol extracts was systematically analyzed and identified by ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Orbitrap-HRMS). The fragmentation pattern of the representative chemical compounds was summarized, and the potential anti-liver fibrosis active compounds of G. lucidum acting on the farnesoid X receptor(FXR) target were studied to elucidate its pharmacodynamic substance basis. Preliminarily, 95 chemical constituents of G. lucidum ethanol extracts were identified, including 24 ganoderic acids, 9 ganoderenic acids, 13 lucidenic acids, 3 ganolucidic acids, 1 ganoderma lactone, 40 other triterpenoids, 4 fatty acids, and 1 other constituent. In addition, the fragmentation patterns of the representative compounds were also analyzed. The structural characteristics of ganoderic acids and ganoderenic acids were the C30 skeleton, containing free-COOH and-OH groups, which could easily lose H_2O and CO_2 to form fragment ions. The D-ring was mostly a five-membered ring, which was prone to breakage. Lucidenic acids were the lanosterolane-type of the C27 skeleton, and the side-chain structure became shorter and contained the same free-COOH and-OH compared with ganoderic acids, which had been reduced from 8 to 5 cartons and prone to lose H_2O and CO_2. Then, six reported FXR receptor agonists were selected to form a training set for establishing a pharmacophore model based on FXR ligands. The 95 identified chemical constituents of G. lucidum were matched with the pharmacophore, and the optimal pharmacophore model 02(sensitivity=0.750 00, specificity=0.555 56, ROC=0.750) was selected for the virtual screening of the G. lucidum compound library through the validation of the test set. Finally, 31 potential G. lucidum active constituents were screened and chosen to activate the FXRs. The ADMET results showed that ganoderic acid H and lucidenic acid J had less than 90% plasma protein binding rate and no hepatotoxicity, which could be used as FXR activators for developing clinical drugs for the treatment of liver fibrosis, either alone or in combination.

Flow-induced fabrication of ZnO nanostructures in pillar-arrayed microchannels.

The emergence of microfluidic devices integrated with nanostructures enables highly efficient, flexible and controllable biosensing, among which zinc oxide (ZnO) nanostructure-based fluorescence detection has been demonstrated to be a promising methodology due to its high electrical point and unique fluorescence enhancement properties. The optimization of microfluidic synthesis of ZnO nanostructures for biosensing on chip has been in demand due to its low cost and high efficiency, but still the flow-induced growth of ZnO nanostructures is not extensively studied. Here, we report a simple and versatile strategy that could manipulate the local flow field by creating periodically arranged micropillars within a straight microchannel. We have explored the effects of perfusion speed and flow direction of seed solution, localized flow variation of growth solution and growth time on the morphology of nanostructures. This provided a comprehensive understanding which governs nanostructure fabrication controlled by flow. The results demonstrated that localized flow in microfluidic devices was essential for the initiation and growth of zinc oxide crystals, enabling precise control over their properties and morphology. Furthermore, a model protein was used to demonstrate the intrinsic fluorescence enhancement of ZnO nanostructures as an example to reveal the morphology-related enhancement properties.

Biodegradable microspheres come into sight: A promising biomaterial for delivering drug to the posterior segment of the eyeball.

Posterior segment disease acts as a major cause of irreversible visual impairments. Successful treatment of posterior segment disease requires the efficient delivery of therapeutic substances to the targeted lesion. However, the complex ocular architecture makes the bioavailability of topically applied drugs extremely low. Invasive delivery approaches like intravitreal injection may cause adverse complications. To enhance the efficiency, several biomedical engineering systems have been developed to increase the penetration efficiency and improve the bioavailability of drugs at the posterior segments. Advantageously, biodegradable microspheres are found to deliver the therapeutic agents in a controlled fashion. The microspheres prepared from novel biomaterials can realize the prolonged release at the posterior segment with minimum side effects. Moreover, it will be degraded automatically into products that are non-toxic to the human body without the necessity of secondary operation to remove the residual polymer matrix. Additionally, biodegradable microspheres have decent thermoplasticity, adjustable hydrophilicity, controlled crystallinity, and high tensile strength, which make them suitable for intraocular delivery. In this review, we introduce the latest advancements in microsphere production technology and elaborate on the biomaterials that are used to prepare microspheres. We discuss systematically the pharmacological characteristics of biodegradable microspheres and compare their potential advantages and limitations in the treatment of posterior segment diseases. These findings would enrich our knowledge of biodegradable microspheres and cast light into the discovery of effective biomaterials for ocular drug delivery.

Harnessing the power of natural alkaloids: the emergent role in epilepsy therapy.

The quest for effective epilepsy treatments has spotlighted natural alkaloids due to their broad neuropharmacological effects. This review provides a comprehensive analysis of the antiseizure properties of various natural compounds, with an emphasis on their mechanisms of action and potential therapeutic benefits. Our findings reveal that bioactive substances such as indole, quinoline, terpenoid, and pyridine alkaloids confer medicinal benefits by modulating synaptic interactions, restoring neuronal balance, and mitigating neuroinflammation-key factors in managing epileptic seizures. Notably, these compounds enhance GABAergic neurotransmission, diminish excitatory glutamatergic activities, particularly at NMDA receptors, and suppress proinflammatory pathways. A significant focus is placed on the strategic use of nanoparticle delivery systems to improve the solubility, stability, and bioavailability of these alkaloids, which helps overcome the challenges associated with crossing the blood-brain barrier (BBB). The review concludes with a prospective outlook on integrating these bioactive substances into epilepsy treatment regimes, advocating for extensive research to confirm their efficacy and safety. Advancing the bioavailability of alkaloids and rigorously assessing their toxicological profiles are essential to fully leverage the therapeutic potential of these compounds in clinical settings.

An investigation into the aging mechanism of disposable face masks and the interaction between different influencing factors.

In the natural environment, a symphony of environmental factors including sunlight exposure, current fluctuations, sodium chloride concentrations, and sediment dynamics intertwine, potentially magnifying the impacts on the aging process of disposable face masks (DFMs), thus escalating environmental risks. Employing Regular Two-Level Factorial Design, the study scrutinized interactive impacts of ultraviolet radiation, sand abrasion, acetic acid exposure, sodium chloride levels, and mechanical agitation on mask aging. Aging mechanisms and environmental risks linked with DFMs were elucidated through two-dimensional correlation analyses and risk index method. Following a simulated aging duration of three months, a single mask exhibited the propensity to release a substantial quantity of microplastics, ranging from 38,800 ± 360 to 938,400 ± 529 particles, and heavy metals, with concentrations from 0.06 ± 0.02 µg/g (Pb) to 29.01 ± 1.83 µg/g (Zn). Besides, specific contaminants such as zinc ions (24.24 µg/g), chromium (VI) (4.20 µg/g), thallium (I) (0.92 µg/g), tetracycline (0.51 µg/g), and acenaphthene (1.73 µg/g) can be adsorbed significantly by aged masks. The study elucidates pivotal role of interactions between ultraviolet radiation and acetic acid exposure in exacerbating the environmental risks associated with masks, while emphasizing the pronounced influence of many other interactions. The research provides a comprehensive understanding of the intricate aging processes and ensuing environmental risks posed by DFMs, offering valuable insights essential for developing sustainable management strategies in aquatic ecosystems.

Cerebroprotein hydrolysate-I ameliorates cognitive dysfunction in APP/PS1 mice by inhibiting ferroptosis via the p53/SAT1/ALOX15 signalling pathway.

Ferroptosis, an iron-dependent lipid peroxidation-driven cell death pathway, has been linked to the development of Alzheimer's disease (AD). However, the role of ferroptosis in the pathogenesis of AD remains unclear. Cerebroprotein hydrolysate-I (CH-I) is a mixture of peptides with neurotrophic effects that improves cognitive deficits and reduces amyloid burden. The present study investigated the ferroptosis-induced signalling pathways and the neuroprotective effects of CH-I in the brains of AD transgenic mice. Seven-month-old male APPswe/PS1dE9 (APP/PS1) transgenic mice were treated with intraperitoneal injections of CH-I and saline for 28 days. The Morris water maze test was used to assess cognitive function. CH-I significantly improved cognitive deficits and attenuated beta-amyloid (Aß) aggregation and tau phosphorylation in the hippocampus of APP/PS1 mice. RNA sequencing revealed that multiple genes and pathways, including ferroptosis-related pathways, were involved in the neuroprotective effects of CH-I. The increased levels of lipid peroxidation, ferrous ions, reactive oxygen species (ROS), and altered expression of ferroptosis-related genes (recombinant solute carrier family 7, member 11 (SLC7A11), spermidine/spermine N1-acetyltransferase 1 (SAT1) and glutathione peroxidase 4 (GPX4)) were significantly alleviated after CH-I treatment. Quantitative real-time PCR and western blotting were performed to investigate the expression of key ferroptosis-related genes and the p53/SAT1/arachidonic acid 15-lipoxygenase (ALOX15) signalling pathway. The p53/SAT1/ALOX15 signalling pathway was found to be involved in mediating ferroptosis, and the activation of this pathway was significantly suppressed in AD by CH-I. CH-I demonstrated neuroprotective effects against AD by attenuating ferroptosis and the p53/SAT1/ALOX15 signalling pathway, thus providing new targets for AD treatment.

Resveratrol Alleviates Liver Fibrosis Induced by Long-Term Inorganic Mercury Exposure through Activating the Sirt1/PGC-1α Signaling Pathway.

Liver disease has become an important risk factor for global health. Resveratrol (Res) is a natural polyphenol which is widely found in foods and has a variety of biological activities. This study investigated the role of the microbiota-gut-liver axis in the Res relieving the liver fibrosis induced by inorganic mercury exposure. Twenty-eight mice were divided into four groups (n = 7) and treated with mercuric chloride and/or Res for 24 weeks, respectively. The results showed that Res mitigated the ileum injury induced by inorganic mercury and restrained LPS and alcohol entering the body circulation. Network pharmacological and molecular analyses showed that Res alleviated oxidative stress, metabolism disorders, inflammation, and hepatic stellate cell activation in the liver. In conclusion, Res alleviates liver fibrosis induced by inorganic mercury via activating the Sirt1/PGC-1α signaling pathway and regulating the microbial-gut-liver axis, particularly, increasing the relative enrichment of Bifidobacterium in the intestinal tract.

Enhancing the SWAT model for creating efficient rainwater harvesting and reuse strategies to improve water resources management.

Rain barrels/cisterns are a type of green infrastructure (GI) practice that can help restore urban hydrology. Roof runoff captured and stored by rain barrels/cisterns can serve as a valuable resource for landscape irrigation, which would reduce municipal water usage and decrease runoff that other stormwater infrastructures need to treat. The expected benefits of rainwater harvesting and reuse with rain barrels/cisterns are comprehensive but neither systematically investigated nor well documented. A comprehensive tool is needed to help stakeholders develop efficient strategies to harvest rainwater for landscape irrigation with rain barrels/cisterns. This study further improved the Soil and Water Assessment Tool (SWAT) in simulating urban drainage networks by coupling the Storm Water Management Model (SWMM)'s closed pipe drainage network (CPDN) simulation methods with the SWAT model that was previously improved for simulating the impacts of rainwater harvesting for landscape irrigation with rain barrels/cisterns. The newly improved SWAT or SWAT-CPDN was applied to simulate the urban hydrology of the Brentwood watershed (Austin, TX) and evaluate the long-term effects of rainwater harvesting for landscape irrigation with rain barrels/cisterns at the field and watershed scales. The results indicated that the SWAT-CPDN could improve the prediction accuracy of urban hydrology with good performance in simulating discharges (15 min, daily, and monthly), evapotranspiration (monthly), and leaf area index (monthly). The impacts of different scenarios of rainwater harvesting and reuse strategies (rain barrel/cistern sizes, percentages of suitable areas with rain barrels/cisterns implemented, auto landscape irrigation rates, and landscape irrigation starting times) on each indicator (runoff depth, discharge volume, peak runoff, peak discharge, combined sewer overflow-CSO, freshwater demand, and plant growth) at the field or watershed scale varied, providing insights for the long-term multi-functional impacts (stormwater management and rainwater harvesting/reuse) of rainwater harvesting for landscape irrigation with rain barrels/cisterns. The varied rankings of scenarios found for achieving each goal at the field or watershed scale indicated that tradeoffs in rainwater harvesting and reuse strategies exist for various goals, and the strategies should be evaluated individually for different goals to optimize the strategies. Efficient rainwater harvesting and reuse strategies at the field or watershed scale can be created by stakeholders with the assist of the SWAT-CPDN to reduce runoff depth, discharge volume, peak runoff, peak discharge, CSO, and freshwater demand, as well as improve plant growth.

Hydroxylamine-induced activation of permanganate for enhanced oxidation of sulfamethoxazole: Mechanism and products.

Recently, many reagents have been introduced to accelerate the formation of highly reactive intermediate Mn species from permanganate (KMnO4), thereby improving the oxidation activity of KMnO4 towards pollutants. However, most studies have mainly focused on sulfur-containing reducing agents (e.g., bisulfite and sodium sulfite), with little attention paid to nitrogen-containing reducing agents. This study found that hydroxylamine (HA) and hydroxylamine derivatives (HAs) can facilitate KMnO4 in pollutant removal. Taking sulfamethoxazole (SMX) as a target contaminant, the effect of pH, SMX concentration, KMnO4 and HA dosages, and the molar ratio of HA and KMnO4 on the degradation of SMX in the KMnO4/HA process was systematically investigated. Quenching experiments and probe analysis revealed MnO2-catalyzed KMnO4 oxidation, Mn(III) and reactive nitrogen species as the primary active species responsible for SMX oxidation in the KMnO4/HA system. Proposed transformation pathways of SMX in the KMnO4/HA system mainly involve hydroxylation and cleavage reactions. The KMnO4/HA system was more conducive to selective oxidation of SMX, 2,4-dichlorophenol, and several other pollutants, but reluctant to bisphenol S (BPS). Overall, this study proposed an effective system for eliminating pollutants, while providing mechanistic insight into HA-driven KMnO4 activation for environmental remediation.

Aromatic compound 2-acetyl-1-pyrroline coordinates nitrogen assimilation and methane mitigation in fragrant rice.

Rice paddy has been the main source of anthropogenic methane (CH4) emissions, with significant variations among rice varieties. 2-Acetyl-1-pyrroline (2-AP) is the key component of the pleasant aroma in fragrant rice. Here, we show that fragrant rice is metabolically active in nitrogen assimilation and exhibits high levels of 2-AP and that CH4 fluxes at the booting stage and cumulative emissions are 25.5% and 14.8% lower, respectively, in fragrant rice paddies compared with nonfragrant rice paddies. Three precursors involved in 2-AP synthesis-proline, glutamic acid, and ornithine-are identified as crucial nitrogen compounds that significantly promote CH4 oxidation in the rhizosphere. Augmenting 2-AP synthesis, either through foliar spraying or by utilizing CRISPR-Cas9 technology to generate knockout lines of BETAINE ALDEHYDE DEHYDROGENASE 2 gene, effectively enhances CH4 oxidation and reduces CH4 fluxes. Our findings reveal that the 2-AP metabolic pathway coordinates the carbon/nitrogen cycle to improve nitrogen assimilation along with high 2-AP levels and mitigate CH4 emissions in paddy ecosystems.

A strategy to distinguish similar traditional Chinese medicines by liquid chromatography-mass spectrometry, electronic senses, and gas chromatography-ion mobility spectrometry: Marsdeniae tenacissimae Caulis and Paederiae scandens Caulis as examples.

INTRODUCTION: Marsdeniae tenacissimae Caulis (MTC), a popular traditional Chinese medicine, has been widely used in the treatment of tumor diseases. Paederiae scandens Caulis (PSC), which is similar in appearance to MTC, is a common counterfeit product. It is difficult for traditional methods to effectively distinguish between MTC and PSC. Therefore, there is an urgent need for a rapid and accurate method to identify MTC and PSC. OBJECTIVES: The aim is to distinguish between MTC and PSC by analyzing the differences in nonvolatile organic compounds (NVOCs), taste, odor, and volatile organic compounds (VOCs). METHODS: Liquid chromatography-mass spectrometry (LC-MS) was utilized to analyze the NVOCs of MTC and PSC. Electronic tongue (E-tongue) and electronic nose (E-nose) were used to analyze their taste and odor respectively. Gas chromatography-ion mobility spectrometry (GC-IMS) was applied to analyze VOCs. Finally, multivariate statistical analyses were conducted to further investigate the differences between MTC and PSC, including principal component analysis, orthogonal partial least squares discriminant analysis, discriminant factor analysis, and soft independent modeling of class analysis. RESULTS: The results of this study indicate that the integrated strategy of LC-MS, E-tongue, E-nose, GC-IMS, and multivariate statistical analysis can be effectively applied to distinguish between MTC and PSC. Using LC-MS, 25 NVOCs were identified in MTC, while 18 NVOCs were identified in PSC. The major compounds in MTC are steroids, while the major compounds in PSC are iridoid glycosides. Similarly, the distinct taste difference between MTC and PSC was precisely revealed by the E-tongue. Specifically, the pronounced bitterness in PSC was proven to stem from iridoid glycosides, whereas the bitterness evident in MTC was intimately tied to steroids. The E-nose detected eight odor components in MTC and six in PSC, respectively. The subsequent statistical analysis uncovered notable differences in their odor profiles. GC-IMS provided a visual representation of the differences in VOCs between MTC and PSC. The results indicated a relatively high relative content of 82 VOCs in MTC, contrasted with 32 VOCs exhibiting a similarly high relative content in PSC. CONCLUSION: In this study, for the first time, the combined use of LC-MS, E-tongue, E-nose, GC-IMS, and multivariate statistical analysis has proven to be an effective method for distinguishing between MTC and PSC from multiple perspectives. This approach provides a valuable reference for the identification of other visually similar traditional Chinese medicines.

Hepatoprotective effects of Radix Bupleuri extract on aflatoxin B1-induced liver injury in ducks.

Aflatoxin B1 (AFB1) is recognized as the most toxic mycotoxin, widely present in nature and known to specifically target the liver, leading to severe consequences to animal and human health. The mechanisms underlying AFB1-induced hepatotoxicity involve oxidative stress and apoptosis. Radix Bupleuri (RB) and its extracts (RBE), traditional Chinese herbs with a rich history spanning over 2000 years, have been reported to possess hepatoprotective properties. Nevertheless, the impact of RBE on AFB1-induced liver injury remains to be fully elucidated. The current study utilized Pekin ducks as experimental models to explore the effects of RBE on AFB1-induced liver injury both in vitro and in vivo. In vitro findings indicated that RBE mitigated AFB1-induced cytotoxicity, improved primary duck hepatocytes (PDHs) morphology, and reduced intracellular reactive oxygen species (ROS) levels. In vivo experiments demonstrated that: I) RBE alleviated the growth inhibitory caused by AFB1, as evidenced by improved final body weight and weight gain. II) AFB1 led to significant alterations in serum biochemical parameters (AST, ALT, TP, and ALB) and liver lesions attenuated by RBE supplementation at 2.5 g/kg. III) RBE significantly mitigated oxidative stress induced by AFB1. IV) AFB1-induced changes in mRNA and protein levels associated with oxidative stress and apoptosis were counteracted by RBE. In conclusion, our results suggest that RBE offers protection against AFB1-induced liver injury in ducks, primarily through its antioxidative and anti-apoptotic properties. These findings indicate the potential of RBE in preventing and treating AFB1 poisoning.

Biomarker Identification for Gender Specificity of Alzheimer's Disease Based on the Glial Transcriptome Profiles.

Many sex-specific biomarkers have been recently revealed in Alzheimer's disease (AD); however, cerebral glial cells were rarely reported. This study analyzed 220,095 single-nuclei transcriptomes from the frontal cortex of thirty-three AD individuals in the GEO database. Sex-specific Differentially Expressed Genes (DEGs) were identified in glial cells, including 243 in astrocytes, 1,154 in microglia, and 572 in oligodendrocytes. Gene Ontology (GO) functional annotation analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed functional concentration in synaptic, neural, and hormone-related pathways. Protein-protein interaction network (PPI) identified MT3, CALM2, DLG2, KCND2, PAKACB, CAMK2D, and NLGN4Y in astrocytes, TREM2, FOS, APOE, APP, and NLGN4Y in microglia, and GRIN2A, ITPR2, GNAS, and NLGN4Y in oligodendrocytes as key genes. NLGN4Y was the only gene shared by the three glia and was identified as the biomarker for the gender specificity of AD. Gene-transcription factor (TF)-miRNA coregulatory network identified key regulators for NLGN4Y and its target TCMs. Ecklonia kurome Okam (Kunbu) and Herba Ephedrae (Mahuang) were identified, and the effects of the active ingredients on AD were displayed. Finally, enrichment analysis of Kunbu and Mahuang suggested that they might act as therapeutic candidates for gender specificity of AD.

van der Waals Integration of Large-Area Monocrystalline 3D Perovskite Thin Films on Arbitrary Semiconductor Substrates for Heterojunctions.

Perovskite monocrystalline films are regarded as desirable candidates for the integration of high-performance optoelectronics due to their unique photophysical properties. However, the heterogeneous integration of a perovskite monocrystalline film with other semiconductors is fundamentally limited by the lattice mismatch, which hinders direct epitaxy. Herein, the van der Waals (vdW) integration strategy for 3D perovskites is developed, where perovskite monocrystalline films are epitaxially grown on the mother substrate, followed by its peeling off and transferring to arbitrary semiconductors, forming monocrystalline heterojunctions. The as-achieved CsPbBr3-Nb-doped SrTiO3 (Nb:STO) vdW p-n heterojunction exhibited comparable performance to their directly epitaxial counterpart, demonstrating the feasibility of vdW integration for 3D perovskites. Furthermore, the vdW integration could be extended to silicon substrates, rendering the CsPbBr3-n-Si and CsPbCl3-p-Si p-n heterojunction with apparent rectification behaviors and photoresponse. The vdW integration significantly enriches the selections of semiconductors hybridizing with perovskites and provides opportunities for monocrystalline perovskite optoelectronics with complex configurations and multiple functionalities.

Enhancing Rab7 Activity by Inhibiting TBC1D5 Expression Improves Mitophagy in Alzheimer's Disease Models.

Background: Mitochondrial dysfunction exists in Alzheimer's disease (AD) brain, and damaged mitochondria need to be removed by mitophagy. Small GTPase Rab7 regulates the fusion of mitochondria and lysosome, while TBC1D5 inhibits Rab7 activation. However, it is not clear whether the regulation of Rab7 activity by TBC1D5 can improve mitophagy and inhibit AD progression. Objective: To investigate the role of TBC1D5 in mitophagy and its regulatory mechanism for Rab7, and whether activation of mitophagy can inhibit the progression of AD. Methods: Mitophagy was determined by western blot and immunofluorescence. The morphology and quantity of mitochondria were tracked by TEM. pCMV-Mito-AT1.03 was employed to detect the cellular ATP. Amyloid-ß secreted by AD cells was detected by ELISA. Co-immunoprecipitation was used to investigate the binding partner of the target protein. Golgi-cox staining was applied to observe neuronal morphology of mice. The Morris water maze test and Y-maze were performed to assess spatial learning and memory, and the open field test was measured to evaluate motor function and anxiety-like phenotype of experimental animals. Results: Mitochondrial morphology was impaired in AD models, and TBC1D5 was highly expressed. Knocking down TBC1D5 increased the expression of active Rab7, promoted the fusion of lysosome and autophagosome, thus improving mitophagy, and improved the morphology of hippocampal neurons and the impaired behavior in AD mice. Conclusions: Knocking down TBC1D5 increased Rab7 activity and promoted the fusion of autophagosome and lysosome. Our study provided insights into the mechanisms that bring new possibilities for AD therapy targeting mitophagy.

Photothermal and ferroptosis synergistic therapy for liver cancer using iron-doped polydopamine nanozymes.

An innovative nanozyme, iron-doped polydopamine (Fe-PDA), which integrates iron ions into a PDA matrix, conferred peroxidase-mimetic activity and achieved a substantial photothermal conversion efficiency of 43.5 %. Fe-PDA mediated the catalysis of H2O2 to produce toxic hydroxyl radicals (•OH), thereby facilitating lipid peroxidation in tumour cells and inducing ferroptosis. Downregulation of solute carrier family 7 no. 11 (SLC7A11) and solute carrier family 3 no. 2 (SLC3A2) in System Xc- resulted in decreased intracellular glutathione (GSH) production and inactivation of the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) pathway, contributing to ferroptosis. Moreover, the application of photothermal therapy (PTT) enhanced the effectiveness of chemodynamic therapy (CDT), accelerating the Fenton reaction for targeted tumour eradication while sparing adjacent non-cancerous tissues. In vivo experiments revealed that Fe-PDA significantly hampered tumour progression in mice, emphasizing the potential of the dual-modality treatment combining CDT and PTT for future clinical oncology applications.

Role of MIC levels and 23S rRNA mutation sites to clarithromycin in 14-day clarithromycin bismuth quadruple therapy for Helicobacter pylori eradication: A prospective trial in Beijing.

Background: Rising clarithromycin resistance undermines Helicobacter pylori (H. pylori) treatment efficacy. We aimed to determine clarithromycin's minimum inhibitory concentration (MIC) levels and identify specific mutation sites in the 23S ribosomal subunit (23S rRNA) that predict treatment outcomes in a 14-day regimen of clarithromycin bismuth quadruple therapy (amoxicillin 1g, clarithromycin 500 mg, rabeprazole 10 mg, and colloidal bismuth pectin 200 mg). Materials and methods: We included adult H. pylori patients who hadn't previously undergone clarithromycin-based treatment, either as initial or rescue therapy. Exclusions were made for penicillin allergy, recent use of related medications, severe illnesses, or inability to cooperate. Patients underwent a 14-day clarithromycin bismuth quadruple therapy. Gastric mucosa specimens were obtained during endoscopy before eradication. MIC against amoxicillin and clarithromycin was determined using the E-test method. The receiver operating characteristic (ROC) curve helped to find the optimal clarithromycin resistance MIC breakpoint. Genetic sequences of H. pylori 23S rRNA were identified through Sanger Sequencing. (ChiCTR2200061476). Results: Out of 196 patients recruited, 92 met the inclusion criteria for the per-protocol (PP) population. The overall intention-to-treat (ITT) eradication rate was 80.00 % (84/105), while the modified intention-to-treat (MITT) and PP eradication rates were 90.32 % (84/93) and 91.30 % (84/92) respectively. No amoxicillin resistance was observed, but clarithromycin resistance rates were 36.19 % (38/105), 35.48 % (33/93), and 34.78 % (33/92) in the ITT, MITT, and PP populations respectively. Compared with the traditional clarithromycin resistance breakpoint of 0.25 µg/mL, a MIC threshold of 12 µg/mL predicted better eradication. Among 173 mutations on 152 sites in the 23S rRNA gene, only the 2143A > G mutation could predict eradication outcomes (p < 0.000). Conclusions: Interpretation of elevated MIC values is crucial in susceptibility testing, rather than a binary "susceptible" or "resistant" classification. The 2143A > G mutation has limited specificity in predicting eradication outcomes, necessitating further investigation into additional mutation sites associated with clarithromycin resistance.

Unveiling the role of CaMKII in retinal degeneration: from biological mechanism to therapeutic strategies.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca2+-dependent signaling pathways. Its significance as an intracellular Ca2+ sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy. CaMKII can induce the aberrant proliferation of retinal blood vessels, influence the synaptic signaling, and exert dual effects on the survival of retinal ganglion cells and pigment epithelial cells. Researchers have put forth multiple therapeutic agents, encompassing small molecules, peptides, and nucleotides that possess the capability to modulate CaMKII activity. Due to its broad range isoforms and splice variants therapeutic strategies seek to inhibit specifically the CaMKII are confronted with considerable challenges. Therefore, it becomes crucial to discern the detrimental and advantageous aspects of CaMKII, thereby facilitating the development of efficacious treatment. In this review, we summarize recent research findings on the cellular and molecular biology of CaMKII, with special emphasis on its metabolic and regulatory mechanisms. We delve into the involvement of CaMKII in the retinal signal transduction pathways and discuss the correlation between CaMKII and calcium overload. Furthermore, we elaborate the therapeutic trials targeting CaMKII, and introduce recent developments in the zone of CaMKII inhibitors. These findings would enrich our knowledge of CaMKII, and shed light on the development of a therapeutic target for degenerative retinopathy.

Identification and validation of stable reference genes for RT-qPCR analyses of Kobresia littledalei seedlings.

BACKGROUND: Kobreisa littledalei, belonging to the Cyperaceae family is the first Kobresia species with a reference genome and the most dominant species in Qinghai-Tibet Plateau alpine meadows. It has several resistance genes which could be used to breed improved crop varieties. Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) is a popular and accurate gene expression analysis method. Its reliability depends on the expression levels of reference genes, which vary by species, tissues and environments. However, K.littledalei lacks a stable and normalized reference gene for RT-qPCR analysis. RESULTS: The stability of 13 potential reference genes was tested and the stable reference genes were selected for RT-qPCR normalization for the expression analysis in the different tissues of K. littledalei under two abiotic stresses (salt and drought) and two hormonal treatments (abscisic acid (ABA) and gibberellin (GA)). Five algorithms were used to assess the stability of putative reference genes. The results showed a variation amongst the methods, and the same reference genes showed tissue expression differences under the same conditions. The stability of combining two reference genes was better than a single one. The expression levels of ACTIN were stable in leaves and stems under normal conditions, in leaves under drought stress and in roots under ABA treatment. The expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression was stable in the roots under the control conditions and salt stress and in stems exposed to drought stress. Expression levels of superoxide dismutase (SOD) were stable in stems of ABA-treated plants and in the roots under drought stress. Moreover, RPL6 expression was stable in the leaves and stems under salt stress and in the stems of the GA-treated plants. EF1-alpha expression was stable in leaves under ABA and GA treatments. The expression levels of 28 S were stable in the roots under GA treatment. In general, ACTIN and GAPDH could be employed as housekeeping genes for K. littledalei under different treatments. CONCLUSION: This study identified the best RT-qPCR reference genes for different K. littledalei tissues under five experimental conditions. ACTIN and GAPDH genes can be employed as the ideal housekeeping genes for expression analysis under different conditions. This is the first study to investigate the stable reference genes for normalized gene expression analysis of K. littledalei under different conditions. The results could aid molecular biology and gene function research on Kobresia and other related species.