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ABSTRACT Background Despite significant advances in lung cancer treatment, cisplatin (DDP)‐based chemotherapy remains a cornerstone for managing the disease. However, the prevalence of chemoresistance presents a major challenge, limiting its effectiveness and contributing to poor outcomes. This underscores the urgent need for novel therapeutic strategies to overcome chemoresistance and improve chemotherapy efficacy in lung cancer patients. Exploring approaches to sensitize tumors to cisplatin could enhance treatment responses and overall survival rates. Methods and Results Our study utilized a variety of lung cancer models, including cell lines, mouse models, and patient‐derived organoids, to validate the synergistic cytotoxic effects of dihydroartemisinin (DHA) and cisplatin (DDP). When combined with DDP, we demonstrate that DHA is a promising therapeutic agent that effectively triggers ferroptosis in lung cancer cells, offering a potential strategy for overcoming chemoresistance. Mechanistically, the combination of DHA and DDP synergistically enhances ZIP14 expression, modulating iron homeostasis and upregulating oxidative stress, leading to both in vitro and in vivo ferroptosis. Notably, our findings revealed that the sequential administration of DDP followed by DHA significantly increases ZIP14 expression and induces superior therapeutic outcomes compared to the simultaneous administration or DHA followed by DDP. This observation underscores the importance of the drug administration order in optimizing treatment efficacy, providing new insights into enhancing chemotherapy response in lung cancer. Conclusion Our findings suggest that combining dihydroartemisinin (DHA) with cisplatin (DDP) presents a promising strategy to overcome chemoresistance in lung cancer patients. Importantly, administering DHA during chemotherapy intervals could further optimize treatment outcomes, enhancing the overall efficacy of lung cancer chemotherapy.

Abstract Skeletal muscle and thermogenic adipose tissue are both critical for the maintenance of body temperature in mammals. However, whether these two tissues are interconnected to modulate thermogenesis and metabolic homeostasis in response to thermal stress remains inconclusive. Here, we report that human and mouse obesity is associated with elevated Musclin levels in both muscle and circulation. Intriguingly, muscle expression of Musclin is markedly increased or decreased when the male mice are housed in thermoneutral or chronic cool conditions, respectively. Beige fat is then identified as the primary site of Musclin action. Muscle-transgenic or AAV-mediated overexpression of Musclin attenuates beige fat thermogenesis, thereby exacerbating diet-induced obesity and metabolic disorders in male mice. Conversely, Musclin inactivation by muscle-specific ablation or neutralizing antibody treatment promotes beige fat thermogenesis and improves metabolic homeostasis in male mice. Mechanistically, Musclin binds to transferrin receptor 1 (Tfr1) and antagonizes Tfr1-mediated cAMP/PKA-dependent thermogenic induction in beige adipocytes. This work defines the temperature-sensitive myokine Musclin as a negative regulator of adipose thermogenesis that exacerbates the deterioration of metabolic health in obese male mice and thus provides a framework for the therapeutic targeting of this endocrine pathway.

In order to identify volatile oil synthesis related genes in Illicium verum, transcriptome sequencing and assembly annotation were carried out on the leaves of the superior clone Guijiao 69 and common variety Zhen 01, two varieties with significant difference in volatile oil content. Then GO and KEGG pathways analyses of differentially expressed genes (DEGs) were performed. The results were as follows: (1) A total of 84 182 Unigenes were obtained after transcripts assembly, and 59 161 Unigenes were annotated in NR, NT, Swissprot, KEGG, KOG, GO, and Pfam databases. A total of 30 572 DEGs were obtained after filtering the low abundance genes, and 15 025 up-regulated and 15 547 down-regulated genes were identified in Guijiao 69 compared to the common variety Zhen 01. (2) GO classification results showed that 20 287 DEGs were annotated. In addition, 21 600 DEGs were involved in 133 KEGG pathways. Among them, genes encoding the key enzymes related to volatile oil synthesis such as linalool synthase, myrcene synthase, geranyl geranyl pyrophosphate synthase, cinnamoyl CoA reductase, caffeic acid 3-O-methyltransferase and cinnamyl alcohol dehydrogenase were differentially expressed and enriched in monoterpene biosynthesis pathway, terpene skeleton biosynthesis pathway and phenylpropanoid biosynthesis pathway. (3) Transcription factor analysis showed that the DEGs were distributed in 31 transcription factor families, of which MYB family had the most Unigenes. In this study, transcriptome sequencing was performed to analyze the DEGs superior clones and common varieties of I. verum as well as their related functions and pathways. The candidate genes obtained provide the references for further exploring the synthesis mechanism of characteristic components of volatile oil and molecular breeding of I. verum.

IntroductionThe leaf-chewing pest Heortia vitessoides severely threatens the growth and development of Aquilaria sinensis. In our previous study, we found that mechanical damage (MD) to stem enhanced A. sinensis sapling resistance to H. vitessoides larvae.MethodsTo reveal the defense mechanisms underlying this observation, we analyzed the types and contents of volatile organic compounds (VOCs), phytohormone contents, and expression of phytohormone-related genes in response to MD and herbivory wounding(HW).ResultsHere, we identified several VOCs, such as the pesticides fenobucarb and 2,4-di-tert-butylphenol, in mature leaf (ML) of MD-treated plants. Compared with salicylic acid (SA) or the ethylene (ET) pathway, jasmonic acid (JA) content and JA-related genes were more strongly upregulated. Interestingly, we found a dramatic difference between JA-related upstream and downstream genes expression in YL and ML, which confirmed that JA-Ile accumulation in MD-ML and HW-ML could be derived from local damaged site.DiscussionTaken together, we provide evidence that the JA pathway plays a dominant role in the A. sinensis response to MD and HW.

As the byproduct in the smelting process of vanadium titano-magnetite, titanium-bearing blast furnace slag (TBFS) can be converted to a titanyl sulfate (TiOSO4) solution containing MgSO4 and Al2(SO4)3 impurities via dissociation by concentrated H2SO4 (80–95%) at 80–200 °C, followed by leaching with H2O at 60–85 °C. In this study, hydrated TiO2 was prepared by hydrothermal hydrolysis of a Mg/Al-bearing TiOSO4 solution at 120 °C and the hydrolysis law was investigated. The experimental results indicate that MgSO4 and Al2(SO4)3 accelerated the hydrolysis and significantly affected the particle size (increasing the primary agglomerate size from 40 to 140 nm) and dispersion (reducing the aggregate size from 12.4 to 1.5 μm) of hydrated TiO2. A thermodynamic equilibrium calculation showed TiOSO4 existed as TiO2+ and SO42− in the solution, and MgSO4 and Al2(SO4)3 led to little change of [TiO2+], but an obvious decrease of [H+], which favored the hydrolysis process. At the same time, the coordination–dissociation mechanism of SO42− and Al(SO4)2− facilitated the lap bonding of Ti-O-Ti, promoting the growth of hydrated TiO2 synergistically.

With population growth and aging, more and more patients with cerebral infarction have varying degrees of disability. ATP-sensitive potassium (KATP) channels regulate many cellular functions by coupling metabolic status with cell membrane electrical activity. Nicorandil (N-(2-hydroxyethyl)-nicotinamide nitrate) is the first KATP channel opener approved for clinical use. It has been reported that it might exert protective effects on the cerebral infarction by increasing cerebral blood flow and reducing inflammation. However, only a few studies explored its role in synaptogenesis. We made the rat model of middle cerebral artery occlusion (MCAO). Nicorandil was administered to rats via oral administration immediately after the surgery at a dose of 7.5 mg/kg and then daily for the next days. Infarct volume, cerebral edema, neurological deficits, cognitive impairment, and the level of Synaptophysin (SYP)、Growth associated protein-43 (GAP43) and neuronal nuclear antigen (NeuN) levels were measured to evaluate the effect of nicorandil. Our data showed that nicorandil treatment could decrease brain damage, improve learning and memory, and increase SYP、GAP43 and NeuN level. Taken together, we propose that nicorandil, as an opener of the KATP channel, provides a neuroprotective role in MCAO by promoting synaptic connections.

Painful neuropathy is present in 13% to 35% of diabetic patients, and the reasons for the differential clinical manifestations of painful and painless diabetic neuropathy (DNP) in diabetic patients are unclear. This review focuses on the latest clinical advances. It is observed that gender, diabetes type, glycosylated hemoglobin, and blood lipid levels have certain predictive effects on painful DNP. Clinical attention should be paid to pain and paresthesia caused by small fiber neuropathy. Existing diagnostic Methods have limited differential effect, and active drug treatment is required after the diagnosis of painful DNP is confirmed. Further research on the pathogenesis of painful DNP is required in order to find new therapeutic target.