Compared with conventional tumor photothermal therapy (PTT), mild‐temperature PTT brings less damage to normal tissues, but also tumor thermoresistance, introduced by the overexpressed heat shock ...protein (HSP). A high dose of HSP inhibitor during mild‐temperature PTT might lead to toxic side effects. Glucose oxidase (GOx) consumes glucose, leading to adenosine triphosphate supply restriction and consequent HSP inhibition. Therefore, a combinational use of an HSP inhibitor and GOx not only enhances mild‐temperature PTT but also minimizes the toxicity of the inhibitor. However, a GOx and HSP inhibitor‐encapsulating nanostructure, designed for enhancing its mild‐temperature tumor PTT efficiency, has not been reported. Thermosensitive GOx/indocyanine green/gambogic acid (GA) liposomes (GOIGLs) are reported to enhance the efficiency of mild‐temperature PTT of tumors via synergistic inhibition of tumor HSP by the released GA and GOx, together with another enzyme‐enhanced phototherapy effect. In vitro and in vivo results indicate that this strategy of tumor starvation and phototherapy significantly enhances mild‐temperature tumor PTT efficiency. This strategy could inspire people to design more delicate platforms combining mild‐temperature PTT with other therapeutic methods for more efficient cancer treatment.
Thermosensitive liposomes made of DPPC and DSPE‐PEG2000 encapsulating GOx, ICG, and GA are presented. This system is used for synergistic starvation therapy, EEPT, and enhanced mild‐temperature PTT against tumors.
Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, ...industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 μg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1β, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.
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•Perinatal exposure to EHDPHP led to neuroinflammation and oxidative stress in dams and pups.•EHDPHP upregulated the expressions of inflammation and oxidative stress related biomarkers.•Inulin attenuated EHDPHP-associated oxidative stress and neuroinflammation in both dams and pups.
Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut ...microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.
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•Methamphetamine (METH) exposure induced reproductive toxicity in male mice.•METH exposure caused changes in the gut microbiome and compromised the integrity of the intestinal barrier.•METH exposure altered the testicular transcriptome and metabolic expression profiles.•Fecal microbiota transplantation conveyed similar reproductive damage from METH-treated mice to healthy recipient mice.
The degeneration of dopaminergic neurons is a major contributor to the pathogenesis of mid‐brain disorders. Clinically, cell therapeutic solutions, by increasing the neurotransmitter dopamine levels ...in the patients, are hindered by low efficiency and/or side effects. Here, a strategy using electromagnetized nanoparticles to modulate neural plasticity and recover degenerative dopamine neurons in vivo is reported. Remarkably, electromagnetic fields generated by the nanoparticles under ultrasound stimulation modulate intracellular calcium signaling to influence synaptic plasticity and control neural behavior. Dopaminergic neuronal functions are reversed by upregulating the expression tyrosine hydroxylase, thus resulting in ameliorating the neural behavioral disorders in zebrafish. This wireless tool can serve as a viable and safe strategy for the regenerative therapy of the neurodegenerative disorders.
Degeneration of dopaminergic neurons is a most common age‐related disorder in the central nervous system. A break‐through idea using electromagnetized nanoparticles to mediate neural plasticity and recover the functions of degenerative dopaminergic neurons in the midbrain of a Parkinson's disease animal model is conceived. A significant advance in remote and regenerative cell therapy of the neurodegenerative diseases is thus provided.
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•METH induced hepatotoxicity and enterotoxicity.•Propionate, rather than acetate or butyrate, ameliorates METH-induced hepatotoxicity and enterotoxicity.•Propionate supplementation ...ameliorates intestinal permeability and suppressed the LPS-TLR4-NF-κB pathway, ultimately improving the dysfunction of METH-induced liver and colon.
The abuse of methamphetamine (METH) has emerged as a major public health concern, causing liver and intestinal damage upon exposure. Short chain fatty acids (SCFAs) produced by dietary fiber, including acetate, propionate, and butyrate, have been reported to alleviate various liver toxicities and exhibit distinct physiological effects. However, the role of SCFAs in mitigating METH-induced liver and intestinal damage remains unexplored. This study is designed to elucidate this potential therapeutic effect, by administering either METH or saline via injection to BALB/c mice, supplemented with acetate, propionate, or butyrate in their drinking water. We discovered that propionate demonstrated the most significant effect in mitigating pathological changes, glycogen storage, inflammation, and hepatic function impairments in the liver induced by METH. Propionate supplementation attenuated damage to the intestinal epithelial barrier, restored mucus-secreting cells, inhibited intestinal inflammation, suppressed intestinal hyperpermeability, and reduced lipopolysaccharide (LPS) leakage caused by METH. With the alleviation of LPS endotoxemia, the TLR4/MyD88/NF-κB pathway associated with inflammation in the liver and colon was inhibited. In conclusion, propionate supplementation ameliorated hepatic and colon dysfunction and inflammation resulting from METH exposure through suppression of the TLR4/MyD88/NF-κB pathway.
Perception of UV radiation has important applications in medical health, industrial production, electronic communication, etc. In numerous application scenarios, there is an increasing demand for the ...intuitive and low‐cost detection of UV radiation through colorimetric visual behavior, as well as the efficient and multi‐functional utilization of UV radiation. However, photodetectors based on photoconductive modes or photosensitive colorimetric materials are not conducive to portable or multi‐scene applications owing to their complex and expensive photosensitive components, potential photobleaching, and single‐stimulus response behavior. Here, a multifunctional visual sensor based on the “host–guest photo‐controlled permutation” strategy and the “lock and key” model is developed. The host–guest specific molecular recognition and electrochromic sensing platform is integrated at the micro‐molecular scale, enabling multi‐functional and multi‐scene applications in the convenient and fast perception of UV radiation, military camouflage, and information erasure at the macro level of human–computer interaction through light–electrical co‐controlled visual switching characteristics. This light–electrical co‐controlled visual sensor based on an optoelectronic multi‐mode sensing system is expected to provide new ideas and paradigms for healthcare, microelectronics manufacturing, and wearable electronic devices owing to its advantages of signal visualization, low energy consumption, low cost, and versatility.
This work reports a portable visual sensor by integrating a multi‐mode sensing platform of photo‐controlled host–guest specific molecular recognition and electrochromism, which can perceive optical and electrical dual‐mode stimuli, and efficiently realize light‐controlled stealth in military camouflage and information erasure through the visual anti‐counterfeiting signal of human–computer interaction.
Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to ...increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
Polystyrene microplastics (PS-MPs) have emerged as a concerning pollutant in modern society due to their widespread production and usage. Despite ongoing research efforts, the impact of PS-MPs on ...mammalian behavior and the mechanisms driving these effects remain incompletely elucidated. Consequently, effective strategies for prevention have yet to be developed. To fill these gaps, C57BL/6 mice were orally administered with 5 μm PS-MPs for 28 consecutive days in this study. The open-field test and the elevated plus-maze test were performed to evaluate the anxiety-like behavior, 16S rRNA sequencing and untargeted metabolomics analysis were used to detect the changes of gut microbiota and serum metabolites. Our results indicated that PS-MPs exposure activated hippocampal inflammation and induced anxiety-like behavior in mice. Meanwhile, PS-MPs disturbed the gut microbiota, impaired the intestinal barrier, and aroused peripheral inflammation. Specifically, PS-MPs increased the abundance of pathogenic microbiota Tuzzerella, while lowered the abundance of probiotics Faecalibaculum and Akkermansia. Interestingly, eliminating the gut microbiota protected against the deleterious effects of PS-MPs on intestinal barrier integrity, reduced the levels of peripheral inflammatory cytokines, and ameliorated anxiety-like behavior. Additionally, green tea's primary bioactive constituent, epigallocatechin-3-gallate (EGCG), optimized gut microbial composition, improved intestinal barrier function, reduced peripheral inflammation, and exerted anti-anxiety effects by inhibiting the hippocampal TLR4/MyD88/NF-κB signaling cascade. EGCG also remodeled serum metabolism, especially modulated purine metabolism. These findings suggested that gut microbiota participates in PS-MPs-induced anxiety-like behavior by modulating the gut-brain axis, and that EGCG could serve as a potential preventive strategy.
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•PS-MPs stimulated hippocampal inflammation and induced anxiety-like behavior in mice.•PS-MPs disturbed gut microbiota and impaired intestinal barrier function.•PS-MPs exposure increased serum LPS level and peripheral inflammation.•Eliminating gut microbiota protected against impairment of the gut barrier by PS-MPs.•EGCG optimized gut microbiota and serum metabolism, improved anxiety-like behavior.
Herein, we report a method for C3-selective C–H tri- and difluoromethylthiolation of pyridines. The method relies on borane-catalyzed pyridine hydroboration for generation of nucleophilic ...dihydropyridines; these intermediates react with trifluoromethylthio and difluoromethylthio electrophiles to form functionalized dihydropyridines, which then undergo oxidative aromatization. The method can be used for late-stage functionalization of pyridine drugs for the generation of new drug candidates.
Inherent chirality is used to describe chiral cyclic molecules devoid of central, axial, planar, or helical chirality and has tremendous applications in chiral recognition and enantioselective ...synthesis. Catalytic and divergent syntheses of inherently chiral molecules have attracted increasing interest from chemists. Herein, we report the enantioselective synthesis of inherently chiral tribenzocycloheptene derivatives via chiral phosphoric acid (CPA)‐catalyzed condensation of cyclic ketones and hydroxylamines. This chemistry paves the way to accessing the less stable derivatives of 7‐membered rings with inherent chirality. A series of chiral tribenzocycloheptene oxime ethers was synthesized in good yields (up to 97 %) with excellent enantioselectivities (up to 99 % ee).
Developing efficient protocols to construct inherent chirality is highly desirable owing to its tremendous application in chiral recognition and enantioselective synthesis. Herein, we report the first enantioselective synthesis of 7‐membered inherently chiral derivatives via chiral phosphoric acid‐catalyzed condensation. This chemistry highlights the broad substrate scope and excellent stereocontrol (up to 99 % ee).
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