The Epidemiological Characteristics of Mpox Cases - China, 2023.

What is already known about this topic?: Since May 2022, a global outbreak of mpox has emerged in more than 100 non-endemic countries. As of December 2023, over 90,000 cases had been reported. The outbreak has predominantly affected men who have sex with men (MSM), with sexual contact identified as the principal mode of transmission. What is added by this report?: Since June 2023, China has faced an occurrence of mpox, predominantly affecting the MSM population. Approximately 90% of those affected reported engaging in homosexual behavior within 21 days prior to symptom onset, a trend that aligns with the global outbreak pattern. The prompt identification of cases, diligent tracing of close contacts, and the implementation of appropriate management strategies have successfully mitigated the spread of mpox virus in China. What are the implications for public health practice?: We propose that mpox is transmitted locally within China. Drawing from our experiences in controlling the virus spread, it is crucial to investigate and formulate effective surveillance and educational strategies. Importantly, we must encourage high-risk populations to promptly seek medical care upon the onset of symptoms.

Structural analysis of type 3 resistant starch from Canna edulis during in vitro simulated digestion and its post-digested residue impact on human gut microbiota.

Introduction: Resistant starch (RS) has garnered attention for its health benefits, including modulating the gut microbiota and promoting the production of short-chain fatty acids (SCFAs). Methods: This study investigates structural changes of type 3 resistant starch from Canna edulis (CE) during in vitro simulated digestion and explores its health-relevant properties using healthy individuals' fecal microbiota. Results: CE, prepared with a RS content of 59.38%, underwent a comprehensive analysis employing X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). During simulated digestion, XRD analysis demonstrated a significant rise in CE's relative crystallinity from 38.92 to 49.34%. SEM illustrated the transition of CE from a smooth to a rough surface, a notable morphological shift. Post-digestion, CE was introduced into microbial fermentation. Notably, propionic acid and valeric acid levels significantly increased compared to the control group. Furthere more, beneficial Bifidobacterium proliferated while pathogenic Escherichia-Shigella was suppressed. When comparing CE to the well-known functional food fructo-oligosaccharide (FOS), CE showed a specific ability to support the growth of Bifidobacterium and stimulate the production of short-chain fatty acids (SCFAs) without causing lactic acid accumulation. Discussion: CE demonstrates potential as a functional health food, with implications for gut health enhancement and SCFAs production.

Structural brain changes associated with cocaine use and digital cognitive behavioral therapy in cocaine use disorder treatment.

Background: Few studies have investigated changes in brain structure and function associated with recovery from cocaine use disorder (CUD), and fewer still have identified brain changes associated with specific CUD treatments, which could inform treatment development and optimization. Methods: In this longitudinal study, T1-weighted magnetic resonance imaging scans were acquired from 41 methadone-maintained individuals with CUD (15 women) at the beginning of and after 12 weeks of outpatient treatment. As part of a larger randomized controlled trial, these participants were randomly assigned to receive (or not) computer-based training for cognitive behavioral therapy (CBT4CBT), and galantamine (or placebo). Results: Irrespective of treatment condition, whole-brain voxel-based morphometry analyses revealed a significant decrease in right caudate body, bilateral cerebellum, and right middle temporal gyrus gray matter volume (GMV) at post-treatment relative to the start of treatment. Subsequent region of interest analyses found that greater reductions in right caudate and bilateral cerebellar GMV were associated with higher relative and absolute levels of cocaine use during treatment, respectively. Participants who completed more CBT4CBT modules had a greater reduction in right middle temporal gyrus GMV. Conclusions: These results extend previous findings regarding changes in caudate and cerebellar GMV as a function of cocaine use and provide the first evidence of a change in brain structure as a function of engagement in digital CBT for addiction. These data suggest a novel potential mechanism underlying how CBT4CBT and CBT more broadly may exert therapeutic effects on substance-use-related behaviors through brain regions implicated in semantic knowledge.

The interplay of psychological resilience and adolescent mobile phone addiction in Henan province, China: insights from latent class analysis.

Background: The aim of this study was to classify distinct subgroups of adolescents based on the severity levels of their mobile phone addiction and to investigate how these groups differed in terms of their psychosocial characteristics. We surveyed a total of 2,230 adolescents using three different questionnaires to assess the severity of their mobile phone addiction, stress, anxiety, depression, psychological resilience, and personality. Latent class analysis was employed to identify the subgroups, and we utilized Receiver Operating Characteristic (ROC) curves and multinomial logistic regression for statistical analysis. All data analyses were conducted using SPSS 26.0 and Mplus 8.5. Methods: We classified the subjects into subgroups based on their mobile phone addiction severity, and the results revealed a clear pattern with a three-class model based on the likelihood level of mobile phone addiction (p < 0.05). We examined common trends in psychosocial traits such as age, grade at school, parental education level, anxiety levels, and resilience. ROC analysis of sensitivity versus 1-specificity for various mobile phone addiction index (MPAI) scores yielded an area under the curve (AUC) of 0.893 (95% CI, 0.879 to 0.905, p < 0.001). We also determined diagnostic value indices for potential cutoff points ranging from 8 to 40. The optimal cutoff value for MPAI was found to be >14, which corresponded to the maximum Youden index (Youden index = 0.751). Results: The latent classification process in this research confirmed the existence of three distinct mobile phone user groups. We also examined the psychosocial characteristics that varied in relation to the severity levels of addiction. Conclusion: This study provides valuable insights into the categorization of adolescents based on the severity of mobile phone addiction and sheds light on the psychosocial characteristics associated with different addiction levels. These findings are expected to enhance our understanding of mobile phone addiction traits and stimulate further research in this area.

O-GlcNAc signaling: implications for stress-induced adaptive response pathway in the tumor microenvironment.

The tumor microenvironment (TME) consists of tumor cells, non-tumor cells, extracellular matrix, and signaling molecules, which can contribute to tumor initiation, progression, and therapy resistance. In response to starvation, hypoxia, and drug treatments, tumor cells undergo a variety of deleterious endogenous stresses, such as hypoxia, DNA damage, and oxidative stress. In this context, to survive the difficult situation, tumor cells evolve multiple conserved adaptive responses, including metabolic reprogramming, DNA damage checkpoints, homologous recombination, up-regulated antioxidant pathways, and activated unfolded protein responses. In the last decades, the protein O-GlcNAcylation has emerged as a crucial causative link between glucose metabolism and tumor progression. Here, we discuss the relevant pathways that regulate the above responses. These pathways are adaptive adjustments induced by endogenous stresses in cells. In addition, we systematically discuss the role of O-GlcNAcylation-regulated stress-induced adaptive response pathways (SARPs) in TME remodeling, tumor progression, and treatment resistance. We also emphasize targeting O-GlcNAcylation through compounds that modulate OGT or OGA activity to inhibit tumor progression. It seems that targeting O-GlcNAcylated proteins to intervene in TME may be a novel approach to improve tumor prognosis.

Cancer cell extravasation requires iplectin-mediated delivery of MT1-MMP at invadopodia.

BACKGROUND: Invadopodia facilitate cancer cell extravasation, but the molecular mechanism whereby invadopodia-specific proteases such as MT1-MMP are called to invadopodia is unclear. METHODS: Mass spectrometry and immunoprecipitation were used to identify interactors of MT1-MMP in metastatic breast cancer cells. After identification, siRNA and small molecule inhibitors were used to assess the effect these interactors had on cellular invasiveness. The chicken embryo chorioallantoic membrane (CAM) model was used to assess extravasation and invadopodia formation in vivo. RESULTS: In metastatic breast cancer cells, MT1-MMP was found to associate with plectin, a cytolinker and scaffolding protein. Complex formation between plectin and MT1-MMP launches invadopodia formation, a subtype we termed iplectin (i = invadopodial). iPlectin delivers MT1-MMP to invadopodia and is indispensable for regulating cell surface levels of the enzyme. Genetic depletion of plectin with siRNA reduced invadopodia formation and cell invasion in vitro. In vivo extravasation efficiency assays and intravital imaging revealed iplectin to be a key contributor to invadopodia ultrastructure and essential for extravasation. Pharmacologic inhibition of plectin using the small molecule Plecstatin-1 (PST-1) abrogated MT1-MMP delivery to invadopodia and extravasation efficiency. CONCLUSIONS: Anti-metastasis therapeutic approaches that target invadopodia are possible by disrupting interactions between MT1-MMP and iplectin. CLINICAL TRIAL REGISTRATION NUMBER: NCT04608357.

Endometriosis is a disease of immune dysfunction, which could be linked to microbiota.

Background: Endometriosis, characterized by extrauterine endometrial tissue, leads to irregular bleeding and pelvic pain. Menstrual retrograde theory suggests fragments traverse fallopian tubes, causing inflammation and scar tissue. Prevalent among infertile women, risk factors include fewer pregnancies, delayed childbirth, irregular cycles, and familial predisposition. Treatments, medication, and surgery entail side effects. Studies link gut microbiota alterations to endometriosis, necessitating research to establish causation. We used Mendelian randomization to investigate the potential link between endometriosis and gut microbiota through genetic variants. Methods: Two-sample Mendelian randomization analyzed gut microbiota's potential causal effects on endometriosis. Instrumental variables, robustly associated with exposures, leveraged GWAS data from MiBioGen for gut microbiota and FinnGen R8 release for endometriosis. SNPs strongly associated with exposures were instrumental variables. Rigorous assessments ensured SNP impact scrutiny on endometriosis. Results: At the genus level, Anaerotruncus, Desulfovibrio, Haemophilus, and Holdemania showed causal association with endometriosis. Specific gut microbiota exhibited causal effects on different endometriosis stages. Holdemania and Ruminococcaceae UCG002 exerted reversible, stage-specific impacts. Conclusion: Mendelian randomization provides evidence for the causal link between specific gut microbiotas and endometriosis, emphasizing the pivotal role of gut microbiota dysbiosis. Modulating gut microbiota emerges as a promising strategy for preventing and treating endometriosis.

Pezizomycotina species associated with rotten plant materials in Guizhou Province, China.

Nine Pezizomycotina strains were isolated from rotten dead branches and leaves collected from Guizhou Province. To obtain their accurate taxonomic placement, we provided the morphological characteristics of conidiophore cells and conidia. Phylogenetic relationships, based on ITS, rpb2, SSU, LSU and tub2 gene sequences, confirmed our strains represented three novel species, Peglioniafalcata, Neoascochytapseudofusiformis and Neomicrosphaeropsiscylindrica. Peglioniafalcata produced falcate conidia and Neoa.pseudofusiformis generated fusiform conidia, while Neom.cylindrica possessed cylindrical conidia. The phylogenetic results also supported them as novel taxa. All the new species in the present study were found as saprophytic on forest litter with high rainfall, which suggest they may have a certain effect on nutrient decomposition and redistribution in forest ecosystems. Thus, it opened a way for further research on related ecological roles and their application production.

Expanding the targeting scope of CRISPR/Cas9-mediated genome editing by Cas9 variants in Brassica.

CRISPR/Cas9, presently the most widely used genome editing technology, has provided great potential for functional studies and plant breeding. However, the strict requirement for a protospacer adjacent motif (PAM) has hindered the application of the CRISPR/Cas9 system because the number of targetable genomic sites is limited. Recently, the engineered variants Cas9-NG, SpG, and SpRY, which recognize non-canonical PAMs, have been successfully tested in plants (mainly in rice, a monocot). In this study, we evaluated the targeted mutagenesis capabilities of these Cas9 variants in two important Brassica vegetables, Chinese cabbage (Brassica rapa spp. pekinensis) and cabbage (Brassica oleracea var. capitata). Both Cas9-NG and SpG induced efficient mutagenesis at NGN PAMs, while SpG outperformed Cas9-NG at NGC and NGT PAMs. SpRY achieved efficient editing at almost all PAMs (NRN > NYN), albeit with some self-targeting activity at transfer (T)-DNA sequences. And SpRY-induced mutants were detected in cabbage plants in a PAM-less fashion. Moreover, an adenine base editor was developed using SpRY and TadA8e deaminase that induced A-to-G conversions within target sites using non-canonical PAMs. Together, the toolboxes developed here induced successful genome editing in Chinese cabbage and cabbage. Our work further expands the targeting scope of genome editing and paves the way for future basic research and genetic improvement in Brassica. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00155-7.

Brain-machine interactive neuromodulation research tool with edge AI computing.

Closed-loop neuromodulation with intelligence methods has shown great potentials in providing novel neuro-technology for treating neurological and psychiatric diseases. Development of brain-machine interactive neuromodulation strategies could lead to breakthroughs in precision and personalized electronic medicine. The neuromodulation research tool integrating artificial intelligent computing and performing neural sensing and stimulation in real-time could accelerate the development of closed-loop neuromodulation strategies and translational research into clinical application. In this study, we developed a brain-machine interactive neuromodulation research tool (BMINT), which has capabilities of neurophysiological signals sensing, computing with mainstream machine learning algorithms and delivering electrical stimulation pulse by pulse in real-time. The BMINT research tool achieved system time delay under 3 ms, and computing capabilities in feasible computation cost, efficient deployment of machine learning algorithms and acceleration process. Intelligent computing framework embedded in the BMINT enable real-time closed-loop neuromodulation developed with mainstream AI ecosystem resources. The BMINT could provide timely contribution to accelerate the translational research of intelligent neuromodulation by integrating neural sensing, edge AI computing and stimulation with AI ecosystems.

Multimodal Machine Learning-Based Marker Enables Early Detection and Prognosis Prediction for Hyperuricemia.

Hyperuricemia (HUA) has emerged as the second most prevalent metabolic disorder characterized by prolonged and asymptomatic period, triggering gout and metabolism-related outcomes. Early detection and prognosis prediction for HUA and gout are crucial for pre-emptive interventions. Integrating genetic and clinical data from 421287 UK Biobank and 8900 Nanfang Hospital participants, a stacked multimodal machine learning model is developed and validated to synthesize its probabilities as an in-silico quantitative marker for hyperuricemia (ISHUA). The model demonstrates satisfactory performance in detecting HUA, exhibiting area under the curves (AUCs) of 0.859, 0.836, and 0.779 within the train, internal, and external test sets, respectively. ISHUA is significantly associated with gout and metabolism-related outcomes, effectively classifying individuals into low- and high-risk groups for gout in the train (AUC, 0.815) and internal test (AUC, 0.814) sets. The high-risk group shows increased susceptibility to metabolism-related outcomes, and participants with intermediate or favorable lifestyle profiles have hazard ratios of 0.75 and 0.53 for gout compared with those with unfavorable lifestyles. Similar trends are observed for other metabolism-related outcomes. The multimodal machine learning-based ISHUA marker enables personalized risk stratification for gout and metabolism-related outcomes, and it is unveiled that lifestyle changes can ameliorate these outcomes within high-risk group, providing guidance for preventive interventions.

Quantitative phosphoproteomic profiling of mouse sperm maturation in epididymis revealed kinases important for sperm motility.

Transcriptionally and translationally silent sperm undergo functional maturation during epididymis traverse, which provides sperm ability to move and is crucial for successful fertilization. However, the molecular mechanisms governing sperm maturation remain poorly understood, especially at protein post-translational modification level. In this study, we conducted a comprehensive quantitative phosphoproteomic analysis of mouse epididymal sperm from different regions (caput, corpus, and cauda) to unveil the dynamics of protein phosphorylation during sperm maturation. We identified 6,447 phosphorylation sites in 1,407 phosphoproteins, and 345 phosphoproteins were differentially phosphorylated between caput and cauda sperm. Gene ontology and KEGG pathway analyses showed enrichment of differentially phosphorylated proteins in energy metabolism, sperm motility and fertilization. Kinase substrate network analysis followed by inhibition assay and quantitative phosphoproteomics analysis showed that TSSK2 kinase is important for sperm motility and progressive motility. This study systemically characterized the intricate phosphorylation regulation during sperm maturation in the mouse epididymis, which can be a basis to elucidate sperm motility acquisition, and to offer potential targets for male contraception and the treatment of male infertility.

Impact of post-thrombectomy isolated subarachnoid hemorrhage on neurological outcomes in patients with anterior ischemic stroke - a retrospective single-center observational study.

PURPOSE: We aimed to investigate the impact of post-thrombectomy isolated subarachnoid hemorrhage (i-SAH) and other types of intracranial hemorrhage (o-ICH) on patient's neurological outcomes. METHODS: Stroke data from 2018 to 2022 in a tertiary care center were retrospectively analyzed. Patients with large vessel occlusion from ICA to M2 branch were included. Post-thrombectomy intracranial hemorrhages at 24 h were categorized with Heidelberg Bleeding Classification. Neurological impairment of patients was continuously assessed at admission, at 24 h, 48 h and 72 h, and at discharge. Predictors of i-SAH and o-ICH were assessed. RESULTS: 297 patients were included. i-SAH and o-ICH were found in 12.1% (36/297) and 11.4% (34/297) of patients. Overall, NIHSS of i-SAH patients at discharge were comparable to o-ICH patients (median 22 vs. 21, p = 0.889) and were significantly higher than in non-ICH patients (22 vs. 7, p < 0.001). i-SAH often resulted in abrupt deterioration of patient's neurological symptoms at 24 h after thrombectomy. Compared to non-ICH patients, the occurrence of i-SAH was frequently associated with worse neurological outcome at discharge (median NIHSS increase of 4 vs. decrease of 4, p < 0.001) and higher in-hospital mortality (41.7% vs. 23.8%, p = 0.022). Regardless of successful reperfusion (TICI 2b/3), the beneficial impact of thrombectomy appeared to be outweighed by the adverse effect of i-SAH. Incomplete reperfusion and shorter time from symptom onset to admission were associated with higher probability of i-SAH, whereas longer procedure time and lower baseline ASPECTS were predictive for o-ICH occurrence. CONCLUSION: Post-thrombectomy isolated subarachnoid hemorrhage is a common complication with significant negative impact on neurological outcome.

Comparison of non-volatile compounds of Penaeus vannemei with different drying treatments via multidimensional infrared spectroscopy.

To analyze the effect of various drying treatments (microwave drying (MD), hot air drying (HAD), vacuum drying (VD), and vacuum freeze drying (VFD)) on taste compounds in Penaeus vannamei, relevant indicators such as free amino acids, 5'-nucleotides, and organic acids were performed. Multidimensional infrared spectroscopy (MM-IR) results found that there were notable variations in taste properties of P. vannamei. There were 18 autocorrelation peaks in 3400-900 cm-1 were screened using second-derivative infrared spectroscopy (SD-IR) and two-dimensional correlation infrared spectroscopy (2DCOS-IR). Variations in functional groups were the major contributors to taste profiles. The TAV of glutamic acid (Glu), guanine (GMP), and inosinemonphosphate (IMP) were greater than one and had notable impacts on taste profiles. VD had the highest equivalent umami value, followed by VFD, HAD, and MD. This study may provide a theoretical guide for the production of dried P. vannamei products on an industrial scale.

Polymer colloidal motors with photodynamic-regulated propulsion.

Artificial colloidal motors capable of converting various external energy into mechanical motion, have emerged as attractive photosensitizer (PS) nanocarriers with good deliverability for photodynamic therapy. However, photoactivated 3O2-to-1O2 transformation as the most crucial energy transfer of the photodynamic process itself is still challenging to convert into autonomous transport. Herein, we report on PS-loaded thiophane-containing semiconducting conjugated polymer (SCP)-based polymer colloidal motors with asymmetric geometry for photodynamic-regulated propulsion in the liquid. The asymmetrical presence of the SCP phases within the colloidal motors would lead to significant differences in the 3O2-to-1O2 transformation and 1O2 release manners between asymmetrical polymer phases, spontaneously creating asymmetrical osmotic pressure gradients across the nanoparticles for powering the self-propelled motion under photodynamic regulation. This photoactivated energy-converting behavior can be also combined with the photothermal conversion of the SCP phases to create two energy gradients exerting diffusiophoretic/thermophoretic force on the colloidal motors for achieving multimode synergistic propulsion. This unique motile feature endows the light-driven PS nanocarriers with good permeability against various physiological barriers in the tumor microenvironment for enhancing antitumor efficacy, showing great potential in phototherapy.

Efficient pyramid channel attention network for pathological myopia recognition with pretraining-and-finetuning.

Pathological myopia (PM) is the leading ocular disease for impaired vision worldwide. Clinically, the characteristics of pathology distribution in PM are global-local on the fundus image, which plays a significant role in assisting clinicians in diagnosing PM. However, most existing deep neural networks focused on designing complex architectures but rarely explored the pathology distribution prior of PM. To tackle this issue, we propose an efficient pyramid channel attention (EPCA) module, which fully leverages the potential of the clinical pathology prior of PM with pyramid pooling and multi-scale context fusion. Then, we construct EPCA-Net for automatic PM recognition based on fundus images by stacking a sequence of EPCA modules. Moreover, motivated by the recent pretraining-and-finetuning paradigm, we attempt to adapt pre-trained natural image models for PM recognition by freezing them and treating the EPCA and other attention modules as adapters. In addition, we construct a PM recognition benchmark termed PM-fundus by collecting fundus images of PM from publicly available datasets. The comprehensive experiments demonstrate the superiority of EPCA-Net over state-of-the-art methods in the PM recognition task. For example, EPCA-Net achieves 97.56% accuracy and outperforms ViT by 2.85% accuracy on the PM-fundus dataset. The results also show that our method based on the pretraining-and-finetuning paradigm achieves competitive performance through comparisons to part of previous methods based on traditional fine-tuning paradigm with fewer tunable parameters, which has the potential to leverage more natural image foundation models to address the PM recognition task in limited medical data regime.

Construction of H-Doped PdB Nanocrystals as Electrocatalysts to Modulate Formic Acid Oxidation.

The strong ligand effect in B-doped Pd-based (PdB) catalysts renders them a promising anode for constructing formic acid fuel cells (FAFCs) exhibiting high power density and outstanding stability. However, the enhancement of the oxidation barrier is unavoidable in this alloy system owing to the electron transfer (ET) from B to Pd. In this study, a hydrogen doping strategy is employed to open charge freedom in PdB compounds and boost their formic acid oxidation reaction (FAOR) activity by suppressing the ET process. The resulting hydrogen-doped PdB (PdBH) exhibits an ultrahigh mass activity of up to 1.2A mg-1 Pd, which is 3.23 times that of the PdB catalyst and 9.55 times that of Pd black. Detailed experimental and theoretical studies show that the interstitial hydrogen leads to enhanced orbital hybridization and reduced electron density around Pd. This optimized ligand effect weakens the carbon monoxide adsorption and increases the direct pathway preference of PdBH, resulting in its outstanding catalytic activity for the FAOR. The development of this high-performance hydrogen-doped PdB catalyst is an important step toward the construction of advanced light element co-doped metal catalysts.

M6A-mediated upregulation of lncRNA TUG1 in liver cancer cells regulates the antitumor response of CD8+ T cells and phagocytosis of macrophages.

Tumor immune evasion relies on the crosstalk between tumor cells and adaptive/innate immune cells. Immune checkpoints play critical roles in the crosstalk, and immune checkpoint inhibitors have achieved promising clinical effects. The long non-coding RNA taurine-upregulated gene 1 (TUG1) is upregulated in hepatocellular carcinoma (HCC). However, how TUG1 is upregulated and the effects on tumor immune evasion are incompletely understood. Here, METTL3-mediated m6A modification led to TUG1 upregulation is demonstrated. Knockdown of TUG1 inhibited tumor growth and metastasis, increased the infiltration of CD8+ T cells and M1-like macrophages in tumors, promoted the activation of CD8+ T cells through PD-L1, and improved the phagocytosis of macrophages through CD47. Mechanistically, TUG1 regulated PD-L1 and CD47 expressions by acting as a sponge of miR-141 and miR-340, respectively. Meanwhile, TUG1 interacted with YBX1 to facilitate the upregulation of PD-L1 and CD47 transcriptionally, which ultimately regulated tumor immune evasion. Clinically, TUG1 positively correlated with PD-L1 and CD47 in HCC tissues. Moreover, the combination of Tug1-siRNA therapy with a Pdl1 antibody effectively suppressed tumor growth. Therefore, the mechanism of TUG1 in regulating tumor immune evasion is revealed and can inform existing strategies targeting TUG1 for enhancing HCC immune therapy and drug development.

A strategy of "adding fuel to the flames" enables a self-accelerating cycle of ferroptosis-cuproptosis for potent antitumor therapy.

Cuproptosis in antitumor therapy faces challenges from copper homeostasis efflux mechanisms and high glutathione (GSH) levels in tumor cells, hindering copper accumulation and treatment efficacy. Herein, we propose a strategy of "adding fuel to the flames" for potent antitumor therapy through a self-accelerating cycle of ferroptosis-cuproptosis. Disulfiram (DSF) loaded hollow mesoporous copper-iron sulfide (HMCIS) nanoparticle with conjugation of polyethylene glycol (PEG) and folic acid (FA) (i.e., DSF@HMCIS-PEG-FA) was developed to swiftly release DSF, H2S, Cu2+, and Fe2+ in the acidic tumor microenvironment (TME). The hydrogen peroxide (H2O2) levels and acidity within tumor cells enhanced by the released H2S induce acceleration of Fenton (Fe2+) and Fenton-like (Cu2+) reactions, enabling the powerful tumor ferroptosis efficacy. The released DSF acts as a role of "fuel", intensifying catalytic effect ("flame") in tumor cells through the sustainable Fenton chemistry (i.e., "add fuel to the flames"). Robust ferroptosis in tumor cells is characterized by serious mitochondrial damage and GSH depletion, leading to excess intracellular copper that triggers cuproptosis. Cuproptosis disrupts mitochondria, compromises iron-sulfur (Fe-S) proteins, and elevates intracellular oxidative stress by releasing free Fe3+. These interconnected processes form a self-accelerating cycle of ferroptosis-cuproptosis with potent antitumor capabilities, as validated in both cancer cells and tumor-bearing mice.

Nicotinamide riboside restores nicotinamide adenine dinucleotide levels and alleviates brain injury by inhibiting oxidative stress and neuroinflammation in a mouse model of intracerebral hemorrhage.

Hemorrhagic stroke is a global health problem owing to its high morbidity and mortality rates. Nicotinamide riboside is an important precursor of nicotinamide adenine dinucleotide characterized by a high bioavailability, safety profile, and robust effects on many cellular signaling processes. This study aimed to investigate the protective effects of nicotinamide riboside against collagenase-induced hemorrhagic stroke and its underlying mechanisms of action. An intracerebral hemorrhage model was constructed by stereotactically injecting collagenase into the right striatum of adult male Institute for Cancer Research mice. After 30 minutes, nicotinamide riboside was administered via the tail vein. The mice were sacrificed at different time points for assessments. Nicotinamide riboside reduced collagenase-induced hemorrhagic area, significantly reduced cerebral water content and histopathological damage, promoted neurological function recovery, and suppressed reactive oxygen species production and neuroinflammation. Nicotinamide riboside exerts neuroprotective effects against collagenase-induced intracerebral hemorrhage by inhibiting neuroinflammation and oxidative stress.