Tuberculosis Vaccines and T Cell Immune Memory.

Tuberculosis (TB) remains a major infectious disease partly due to the lack of an effective vaccine. Therefore, developing new and more effective TB vaccines is crucial for controlling TB. Mycobacterium tuberculosis (M. tuberculosis) usually parasitizes in macrophages; therefore, cell-mediated immunity plays an important role. The maintenance of memory T cells following M. tuberculosis infection or vaccination is a hallmark of immune protection. This review analyzes the development of memory T cells during M. tuberculosis infection and vaccine immunization, especially on immune memory induced by BCG and subunit vaccines. Furthermore, the factors affecting the development of memory T cells are discussed in detail. The understanding of the development of memory T cells should contribute to designing more effective TB vaccines and optimizing vaccination strategies.

MAPK-mediated PHGDH induction is essential for melanoma formation and represents an actionable vulnerability.

Overexpression of PHGDH, the rate-limiting enzyme in the serine synthesis pathway, promotes melanomagenesis, melanoma cell proliferation, and survival of metastases in serine-low environments such as the brain. While PHGDH amplification explains PHGDH overexpression in a subset of melanomas, we find that PHGDH levels are universally increased in melanoma cells due to oncogenic BRAFV600E promoting PHGDH transcription through mTORC1-mediated translation of ATF4. Importantly, PHGDH expression was critical for melanomagenesis as depletion of PHGDH in genetic mouse models blocked melanoma formation. Despite BRAFV600E-mediated upregulation, PHGDH was further induced by exogenous serine restriction. Surprisingly, BRAFV600E inhibition diminished serine restriction-mediated PHGDH expression by preventing ATF4 induction, creating a potential vulnerability whereby melanoma cells could be specifically starved of serine by combining BRAFV600E inhibition with exogenous serine restriction. Indeed, we show that this combination promoted cell death in vitro and attenuated melanoma growth in vivo. This study identified a melanoma cell-specific PHGDH-dependent vulnerability.

Patient- and caregiver-related factors affecting family caregiver burden of urologic cancer patients.

OBJECTIVE: This study aimed to investigate the level of family caregivers' (FC) burden and the extent to which patient- and caregiver-related factors influence the caregiving burden among FCs of urologic cancer (UC) patients. METHOD: A cross-sectional survey was conducted on caregivers of UC patients who sought cancer care. The modified caregiver strain index (MCSI) was used to assess FC burden. RESULTS: Just over half (54.3%) of FCs had moderate/high MCSI scores (score 9-26). By demographics, FCs who were unemployed (OR = 5.55, 95%CI 1.50-20.60) and perceived their current health condition as moderate/poor (OR = 6.05, 95%CI 1.95-18.78) reported higher odds of increased FC burden. Patient performance status played a pivotal role in exacerbating FC burden, whereby the odds of higher FC burden was 13 times higher in caregivers of UC patients having an Eastern Cooperative Oncology Group (ECOG) performance rating score of 3-4 (OR = 13.06, 95%CI 1.44-111.26) than those with a score of 0. Perceived lower levels of confidence in care provision were significantly associated with a higher level of strain (OR = 6.76, 985%CI 1.02-44.90). CONCLUSION: Care recipient performance status was a strong patient-related factor associated with higher FC burden regardless of duration of caregiving and other caregiver-related factors after adjusting for caregiver demographics.

Chinese parents' intention to vaccinate their 0-5-year-old children with the EV-71 vaccine against hand, foot, and mouth disease and willingness-to-pay.

Background: This study aimed to determine the intention and willingness-to-pay (WTP) of Chinese parents/guardians to vaccinate their children with the EV-71 vaccine. Knowledge levels about hand, foot, and mouth disease (HFMD) and the EV-71 vaccine were also investigated. Methods: A cross-sectional, self-administered online survey was conducted between November 2022 and March 2023. A stratified multi-stage random sampling method was used to recruit parents/guardians of children aged 0-5 years in southeastern China. Results: A total of 3,626 complete responses were received. The mean knowledge score of HFMD was 9.99 (±4.23) out of a total of 14 points. The majority of the participants reported a somewhat willing intent (58.8%), followed by an extremely willing intent (28.9%). Participants who did not consider the EV-71 vaccine expensive (OR = 2.94, 95%CI 2.45-3.53) perceived that the EV-71 vaccine is effective (OR = 2.73, 95%CI 1.52-4.90), and a high knowledge level of HFMD (OR = 1.90, 95%CI 1.57-2.29) had the highest significant odds of having an extremely willing intent to vaccinate their children with the EV-71 vaccine. The median (interquartile range [IQR]) of WTP for the EV-71 vaccine was CNY¥200/USD$28 (IQR CNY¥100-400/USD$14-56). The highest marginal WTP for the vaccine was mainly influenced by the perceived high cost of the vaccine. Those participants who did not consider the EV-71 vaccine expensive had more than 10 times higher odds of vaccinating their children (OR = 10.86, 95%CI 8.49-13.88). Perceived susceptibility, perceived benefits, and perceived barriers were also significant influencing factors in the highest marginal WTP. Conclusion: The findings demonstrate the importance of improving health promotion and reducing the barriers to EV-71 vaccination. Therefore, it is important to improve health promotion and reduce the barriers to EV-71 vaccination.

Image-activated pico-injection for single-cell analysis.

The addition of reagents into preformed droplets is a crucial yet intricate task in droplet-based applications where sequential reactions is required. Pico-injection offers high throughput and robustness in accomplishing this task, but the existing pico-injection techniques work in an indiscriminate manner, making it difficult to target particular groups of droplets. Here we report image-activated pico-injection (imgPico) for label-free, on-demand reagent supplementation into droplets. The imgPico detects the droplets of interest by real-time image analysis and makes decisions for the downstream pico-injection operation. We studied the performance of different algorithms for the image analysis and optimized the experimental settings of the imgPico. In the validation experiment, the imgPico successfully injected fluorescent dyes into droplets encapsulating one, two, and three cells, respectively, as expected. We further demonstrated the utility of imgPico by targeting droplets encapsulating single cells in droplet-based single-cell RNA sequencing (scRNA-seq) using exceedingly high cell density, and the results showed that the imgPico effectively reduced the presence of doublets in the scRNA-seq data. With the merits of being label-free and versatile, the imgPico represents a technical advance with potential applications in single-cell analysis.

The plasma derived exosomal miRNA-483-5p/502-5p serve as potential MCI biomarkers in aging.

Alzheimer's disease (AD) is the leading cause of dementia and is rapidly becoming one of the most costly, fatal diseases, which is typically discovered in the late stage of molecular pathology, at which point medication intervention is irreversible. As a result, there is an urgent need for a low-cost, least-invasive way of screening cognitive impairment, with the goal of identifying persons at risk of AD. Mild cognitive impairment (MCI) has been described as a transitional state between normal cognitive aging and AD. Early detection and timely tracking of MCI can to some extent prevent the progression towards AD. We found a population in Northwestern China has a comparatively high prevalence of MCI. Continued education, consistent exercise, and a secure financial situation can all help older people maintain cognitive function. Due to the critical role of circulating microRNAs in intercellular signaling and the perturbations thereof, their investigation has assumed paramount significance in elucidating various pathological conditions. Numerous investigations have substantiated the significance of circulating miRNAs specifically in MCI. Here, we evaluated miR-483-5p (Area Under the Curve (AUC) is 0.901, sensitivity 79.2 % and specificity 100 %) and miR-502-5p (AUC is 0.872, sensitivity 79.2 % and specificity 83.3 %), which were derived from plasma exosomes and maintained at high levels in elderly people with MCI, could be employed as promising noninvasive biomarkers.

PTEN Lipid Phosphatase Activity Suppresses Melanoma Formation by Opposing an AKT/mTOR/FRA1 Signaling Axis.

Inactivating mutations in PTEN are prevalent in melanoma and are thought to support tumor development by hyperactivating the AKT/mTOR pathway. Conversely, activating mutations in AKT are relatively rare in melanoma, and therapies targeting AKT or mTOR have shown disappointing outcomes in preclinical models and clinical trials of melanoma. This has led to the speculation that PTEN suppresses melanoma by opposing AKT-independent pathways, potentially through noncanonical functions beyond its lipid phosphatase activity. In this study, we examined the mechanisms of PTEN-mediated suppression of melanoma formation through the restoration of various PTEN functions in PTEN-deficient cells or mouse models. PTEN lipid phosphatase activity predominantly inhibited melanoma cell proliferation, invasion, and tumor growth, with minimal contribution from its protein phosphatase and scaffold functions. A drug screen underscored the exquisite dependence of PTEN-deficient melanoma cells on the AKT/mTOR pathway. Furthermore, activation of AKT alone was sufficient to counteract several aspects of PTEN-mediated melanoma suppression, particularly invasion and the growth of allograft tumors. Phosphoproteomics analysis of the lipid phosphatase activity of PTEN validated its potent inhibition of AKT and many of its known targets, while also identifying the AP-1 transcription factor FRA1 as a downstream effector. The restoration of PTEN dampened FRA1 translation by inhibiting AKT/mTOR signaling, and FRA1 overexpression negated aspects of PTEN-mediated melanoma suppression akin to AKT. This study supports AKT as the key mediator of PTEN inactivation in melanoma and identifies an AKT/mTOR/FRA1 axis as a driver of melanomagenesis. SIGNIFICANCE: PTEN suppresses melanoma predominantly through its lipid phosphatase function, which when lost, elevates FRA1 levels through AKT/mTOR signaling to promote several aspects of melanomagenesis.

Wide QRS complex tachycardia with a mysterious mask-Tricuspid isthmus-dependent atrial flutter with preexcitation syndrome and dual atrioventricular nodal pathway conduction.

Key Clinical Message: Atrial flutter (AFL) and supraventricular tachycardia (SVT) are common arrhythmias in clinic. However, some AFL cases may present additional complexities, such as both accessory pathways (AP) and dual atrioventricular node pathways, putting on a mysterious mask and making it challenging to distinguish on electrocardiograms (ECGs). Abstract: A 60-year-old male patient had a sudden syncope, and an ECG showed wide QRS complex tachycardia. This diagnostic ambiguity is further compounded by the fact that SVT via AP conduction can exhibit wide QRS complex tachycardia characteristics resembling ventricular tachycardia (VT). Consequently, a definitive diagnosis through electrophysiological (EP) examination becomes imperative, as it dictates subsequent ablation strategies. In this article, we present a rare case involving three distinct arrhythmias including AFL, AP, and dual atrioventricular node pathways, and successfully treated through ablation.

Genetically engineered mouse models of head and neck cancers.

The head and neck region is one of the anatomic sites commonly afflicted by cancer, with ~1.5 million new diagnoses reported worldwide in 2020 alone. Remarkable progress has been made in understanding the underlying disease mechanisms, personalizing care based on each tumor's individual molecular characteristics, and even therapeutically exploiting the inherent vulnerabilities of these neoplasms. In this regard, genetically engineered mouse models (GEMMs) have played an instrumental role. While progress in the development of GEMMs has been slower than in other major cancer types, several GEMMs are now available that recapitulate most of the heterogeneous characteristics of head and neck cancers such as the tumor microenvironment. Different approaches have been employed in GEMM development and implementation, though each can generally recapitulate only certain disease aspects. As a result, appropriate model selection is essential for addressing specific research questions. In this review, we present an overview of all currently available head and neck cancer GEMMs, encompassing models for head and neck squamous cell carcinoma, nasopharyngeal carcinoma, and salivary and thyroid gland carcinomas.

Novel pneumonia score based on a machine learning model for predicting mortality in pneumonia patients on admission to the intensive care unit.

BACKGROUND: Scores for predicting the long-term mortality of severe pneumonia are lacking. The purpose of this study is to use machine learning methods to develop new pneumonia scores to predict the 1-year mortality and hospital mortality of pneumonia patients on admission to the intensive care unit (ICU). METHODS: The study population was screened from the MIMIC-IV and eICU databases. The main outcomes evaluated were 1-year mortality and hospital mortality in the MIMIC-IV database and hospital mortality in the eICU database. From the full data set, we separated patients diagnosed with community-acquired pneumonia (CAP) and ventilator-associated pneumonia (VAP) for subgroup analysis. We used common shallow machine learning algorithms, including logistic regression, decision tree, random forest, multilayer perceptron and XGBoost. RESULTS: The full data set of the MIMIC-IV database contained 4697 patients, while that of the eICU database contained 13760 patients. We defined a new pneumonia score, the "Integrated CCI-APS", using a multivariate logistic regression model including six variables: metastatic solid tumor, Charlson Comorbidity Index, readmission, congestive heart failure, age, and Acute Physiology Score III. The area under the curve (AUC) and accuracy of the integrated CCI-APS were assessed in three data sets (full, CAP, and VAP) using both the test set derived from the MIMIC-IV database and the external validation set derived from the eICU database. The AUC value ranges in predicting 1-year and hospital mortality were 0.784-0.797 and 0.691-0.780, respectively, and the corresponding accuracy ranges were 0.723-0.725 and 0.641-0.718, respectively. CONCLUSIONS: The main contribution of this study was a benchmark for using machine learning models to build pneumonia scores. Based on the idea of integrated learning, we propose a new integrated CCI-APS score for severe pneumonia. In the prediction of 1-year mortality and hospital mortality, our new pneumonia score outperformed the existing score.

Modifications of noncoding RNAs in cancer and their therapeutic implications.

In the last 50 years, over 150 various chemical modifications on RNA molecules, including mRNAs, rRNAs, tRNAs, and other noncoding RNAs (ncRNAs), have been identified and characterized. These RNA modifications regulate RNA biogenesis and biological functions and are widely involved in various physiological processes and diseases, including cancer. In recent decades, broad interest has arisen in the epigenetic modification of ncRNAs due to the increased knowledge of the critical roles of ncRNAs in cancer. In this review, we summarize the various modifications of ncRNAs and highlight their roles in cancer initiation and progression. In particular, we discuss the potential of RNA modifications as novel biomarkers and therapeutic targets in cancer.

Worldwide Trends in Registering Real-World Studies at ClinicalTrials.gov: A Cross-Sectional Analysis.

Objective: The purpose of this study was to characterize real-world studies (RWSs) registered at ClinicalTrials.gov to help investigators better conduct relevant research in clinical practice. Methods: A retrospective analysis of 944 studies was performed on February 28, 2023. Results: A total of 944 studies were included. The included studies involved a total of 48 countries. China was the leading country in terms of the total number of registered studies (37.9%, 358), followed by the United States (19.7%, 186). Regarding intervention type, 42.4% (400) of the studies involved drugs, and only 9.1% (86) of the studies involved devices. Only 8.5% (80) of the studies mentioned both the detailed study design type and data source in the "Brief Summary". A total of 49.4% (466) of studies had a sample size of 500 participants and above. Overall, 63% (595) of the studies were single-center studies. A total of 213 conditions were covered in the included studies. One-third of the studies (32.7%, 309) involved neoplasms (or tumors). China and the United States were very different regarding the study of different conditions. Conclusion: Although the pandemic has provided new opportunities for RWSs, the rigor of scientific research still needs to be emphasized. Special attention needs to be given to the correct and comprehensive description of the study design in the Brief Summary of registered studies, thereby promoting communication and understanding. In addition, deficiencies in ClinicalTrials.gov registration data remain prominent.

Oxygen Vacancy-Rich Ni-CeO2 Heterojunction Catalyst for Hydrogenating Halogenated Nitroarenes with High Activity and Selectivity.

Halogenated arylamines are important intermediates for the synthesis of dyes, pesticides, herbicides, and other chemicals. One important way to prepare halogenated arylamines is catalytic hydrogenation of halogenated nitroarenes. Ni-based catalysts have been used in the hydrogenation of halogenated nitroarenes but suffer from low activity and dehalogenation side reaction. In this paper, Ni-CeO2/SiO2 heterojunction catalyst with a "raisin-bun" structure was prepared by reverse microemulsion. A built-in electric field and more oxygen vacancies were formed due to electron transfer from Ni to CeO2 as a result of their work function difference. The built-in electric field leads to the heterolytic cleavage of H2, thereby improving the hydrogenation activity. Oxygen vacancies preferentially adsorb and activate nitro groups, inhibiting the dehalogenation side reaction. Through the cooperation of built-in electric field and oxygen vacancy, synchronous enhancement of the activity and selectivity is obtained successfully. This finding provides a new view for the design of non-noble metal-based catalysts with high activity and selectivity.

ATOH8 binds SMAD3 to induce cellular senescence and prevent Ras-driven malignant transformation.

The process of oncogene-induced senescence (OIS) and the conversion between OIS and malignant transformation during carcinogenesis is poorly understood. Here, we show that following overactivation of oncogene Ras in lung epithelial cells, high-level transforming growth factor ß1 (TGF-ß1)-activated SMAD3, but not SMAD2 or SMAD4, plays a determinant role in inducing cellular senescence independent of the p53/p16/p15 senescence pathways. Importantly, SMAD3 binds a potential tumor suppressor ATOH8 to form a transcriptional complex that directly represses a series of cell cycle-promoting genes and consequently causes senescence in lung epithelial cells. Interestingly, the prosenescent SMAD3 converts to being oncogenic and essentially facilitates oncogenic Ras-driven malignant transformation. Furthermore, depleting Atoh8 rapidly accelerates oncogenic Ras-driven lung tumorigenesis, and lung cancers driven by mutant Ras and Atoh8 loss, but not by mutant Ras only, are sensitive to treatment of a specific SMAD3 inhibitor. Moreover, hypermethylation of the ATOH8 gene can be found in approximately 12% of clinical lung cancer cases. Together, our findings demonstrate not only epithelial cellular senescence directed by a potential tumor suppressor-controlled transcriptional program but also an important interplay between the prosenescent and transforming effects of TGF-ß/SMAD3, potentially laying a foundation for developing early detection and anticancer strategies.

Quasi-Zero Stiffness Vibration Sensing and Energy Harvesting Integration Based on Buckled Piezoelectric Euler Beam.

This paper presents a novel quasi-zero stiffness vibration sensing and energy harvesting integration system for absolute displacement measurements based on a buckled piezoelectric Euler beam (BPEB) with quasi-zero stiffness (QZS) characteristics. On one hand, BPEB provides negative stiffness to the system, thus creating a vibration-free point within the system and transforming the absolute displacement measurement problem into a relative motion sensing problem. On the other hand, during the measurement process, the BPEB collects the vibration energy from the system, which can provide electrical energy for low-power relative motion sensing devices and remarkably suppress the frequency range of the jump phenomenon, thereby further expanding the frequency domain measurement range of the sensing system. The research results have shown that this system can measure the absolute motion signal of the tested object in low-frequency vibration with small excitation. By adjusting parameters such as the force-electric coupling coefficient and damping ratio, the measurement accuracy of the sensing system can be improved. Furthermore, the system can convert the mechanical energy of vibrations into electrical energy to power the surrounding low-power sensors or provide partial power. This could potentially achieve self-powering integrated quasi-zero stiffness vibration sensing, offering another approach and possibility for the automation development in wireless sensing systems and the Internet of Things field.

Generation of a human induced pluripotent stem cell line (LZUSHi002-A) from a MADD patient with ETFDH mutation.

Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is an inborn metabolic disorder that affects fatty acid oxidation and the catabolism of branched-chain amino acids, vitamins B and energy metabolism. In this study, the induced pluripotent stem cell (iPSC) line LZUSHi002-A from PBMCs of a 10-year-old male patient with ETFDH mutations using the episomal plasmids was established, which is an ideal in vitro model to understand the exact pathogenesis of MADD.

Multi-dimensional psychosocial factors influencing the willingness to receive a COVID-19 vaccine booster: A survey among the public in Mainland China.

This study aimed to investigate multi-dimensional psychological and social factors that influence the willingness to receive a COVID-19 vaccine booster in China. A nationwide cross-sectional online survey was conducted between March and April 2022. A total of 6375 complete responses were received. The majority were of age 18 to 40 years old (80.0%) and college-educated (49.2%). In total, 79% responded extremely willing to receive a COVID-19 vaccine booster. By demographics, younger age, females, higher education, and participants with the lowest income reported higher willingness. Having a very good health status (odds ratio [OR] 3.56, 95% confidence interval [CI] 2.92-4.34) and a higher score of vaccine confidence (OR 3.50, 95% CI 2.98-4.11) were associated with an increased willingness to receive a booster shot. Experiencing no side effects with primary COVID-19 vaccination (OR 2.46, 95% CI 1.89-3.20) and higher perceived susceptibility of COVID-19 infection (OR 2.38, 95% CI 1.92-2.95) were also associated with an increased willingness to receive a booster shot. A variety of psychosocial factors, namely having no chronic diseases, lower perceived concern over the safety of a booster shot, higher perceived severity of COVID-19 infection, and a higher level of institutional trust, were also significantly associated with greater willingness to get a booster shot. In conclusion, the present study adds evidence to the significant role of psychosocial factors in predicting COVID-19 vaccine booster acceptance and provides insights to design interventions to increase booster uptake in certain targeted demographic groups.

Gain of Chromosome 1q Perturbs a Competitive Endogenous RNA Network to Promote Melanoma Metastasis.

Somatic copy-number alterations (CNA) promote cancer, but the underlying driver genes may not be comprehensively identified if only the functions of the encoded proteins are considered. mRNAs can act as competitive endogenous RNAs (ceRNA), which sponge miRNAs to posttranscriptionally regulate gene expression in a protein coding-independent manner. We investigated the contribution of ceRNAs to the oncogenic effects of CNAs. Chromosome 1q gains promoted melanoma progression and metastasis at least in part through overexpression of three mRNAs with ceRNA activity: CEP170, NUCKS1, and ZC3H11A. These ceRNAs enhanced melanoma metastasis by sequestering tumor suppressor miRNAs. Orthogonal genetic assays with miRNA inhibitors and target site blockers, along with rescue experiments, demonstrated that miRNA sequestration is critical for the oncogenic effects of CEP170, NUCKS1, and ZC3H11A mRNAs. Furthermore, chromosome 1q ceRNA-mediated miRNA sequestration alleviated the repression of several prometastatic target genes. This regulatory RNA network was evident in other cancer types, suggesting chromosome 1q ceRNA deregulation as a common driver of cancer progression. Taken together, this work demonstrates that ceRNAs mediate the oncogenicity of somatic CNAs. SIGNIFICANCE: The function of CEP170, NUCKS1, and ZC3H11A mRNAs as competitive endogenous RNAs that sequester tumor suppressor microRNAs underlies the oncogenic activity of chromosome 1q gains.

Vancomycin, Daptomycin, Antistaphylococcal ß-Lactam, and Trimethoprim-Sulfamethoxazole Monotherapy and Combination Therapy in the Management of Methicillin-Resistant Staphylococcus aureus: A Network Meta-Analysis.

Objective: The aim was to evaluate the efficacy and safety of vancomycin or daptomycin (VAN/DAP), antistaphylococcal ß-lactam (ASBL), trimethoprim-sulfamethoxazole (TMP-SMX), and combination therapy of VAN/DAP + ASBL in the management of methicillin-resistant Staphylococcus aureus (MRSA). Methods: Databases including PubMed, Cochrane Library, Embase database, and google scholar were searched on 1 September 2021. The randomized control trials (RCTs) and comparable clinical studies of VAN/DAP, VAN/DAP + ASBL, ASBL, and TMP-SMX in the management of MRSA were identified. A network meta-analysis was conducted with STATA 14.0. Results: Seven RCTs and two matched cohorts with 1,048 patients were included in the analysis. The pooled results showed that VAN/DAP + ASBL had a significantly lower rate of persistent bacteremia >3 days than VAN/DAP alone [OR:0.46, 95%CI (0.26, 0.81), p < 0.001]. No obvious differences were observed in the outcomes of all-cause mortality, relapsed bacteremia, microbiological treatment failure, embolic or metastatic infection, and total adverse events. However, the ranking results showed that VAN/DAP + ASBL had slightly better efficacy (all-cause mortality, persistent bacteremia >3 days, duration of bacteremia, microbiological treatment failure, and relapsed bacteremia) but slightly higher adverse events than VAN/DAP alone. No obvious differences in the comparisons of VAN/DAP vs. ASBL, and VAN/DAP vs TMP-SMX in the analyzed outcomes. The ranking results revealed that ASBL and TMP-SMX did not have better efficacy or lower adverse events compared with the treatment of VAN/DAP. Conclusion: The efficacy of VAN/DAP + ASBL was slightly but not significantly better than VAN/DAP alone in the management of MRSA.

Insulin-incubated palladium clusters promote recovery after brain injury.

Traumatic brain injury (TBI) is a cause of disability and death worldwide, but there are currently no specific treatments for this condition. Release of excess reactive oxygen species (ROS) in the injured brain leads to a series of pathological changes; thus, eliminating ROS could be a potential therapeutic strategy. Herein, we synthesized insulin-incubated ultrasmall palladium (Pd@insulin) clusters via green biomimetic chemistry. The Pd@insulin clusters, which were 3.2 nm in diameter, exhibited marked multiple ROS-scavenging ability testified by the theoretical calculation. Pd@insulin could be rapidly excreted via kidney-urine metabolism and induce negligible adverse effects after a long-time treatment in vivo. In a TBI mouse model, intravenously injected Pd@insulin clusters aggregated in the injured cortex, effectively suppressed excessive ROS production, and significantly rescued motor function, cognition and spatial memory. We found that the positive therapeutic effects of the Pd@insulin clusters were mainly attributed to their ROS-scavenging ability, as they inhibited excessive neuroinflammation, reduced cell apoptosis, and prevented neuronal loss. Therefore, the ability of Pd@insulin clusters to effectively eliminate ROS, as well as their simple structure, easy synthesis, low toxicity, and rapid metabolism may facilitate their clinical translation for TBI treatment.