The rising concerns of the recurrence and bone deficiency in surgical treatment of malignant bone tumors have raised an urgent need of the advance of multifunctional therapeutic platforms for efficient tumor therapy and bone regeneration. Herein, the construction of a multifunctional biomaterial system is reported by the integration of 2D Nb2C MXene wrapped with S‐nitrosothiol (RSNO)‐grafted mesoporous silica with 3D‐printing bioactive glass (BG) scaffolds (MBS). The near infrared (NIR)‐triggered photonic hyperthermia of MXene in the NIR‐II biowindow and precisely controlled nitric oxide (NO) release are coordinated for multitarget ablation of bone tumors to enhance localized osteosarcoma treatment. The in situ formed phosphorus and calcium components degraded from BG scaffold promote bone‐regeneration bioactivity, augmented by sufficient blood supply triggered by on‐demand NO release. The tunable NO generation plays a crucial role in sequential adjuvant tumor ablation, combinatory promotion of coupled vascularization, and bone regeneration. This study demonstrates a combinatory osteosarcoma ablation and a full osseous regeneration as enabled by the implantation of MBS. The design of multifunctional scaffolds with the specific features of controllable NO release, highly efficient photothermal conversion, and stimulatory bone regeneration provides an intriguing biomaterial platform for the diversified treatment of bone tumors.

Malignant bone tumors are one of the major serious diseases in clinic. Inferior reconstruction of new bone and rapid propagation of residual tumor cells are the main challenges to surgical intervention. Herein, a bifunctional DTC@BG scaffold for near‐infrared (NIR)‐activated photonic thermal ablation of osteosarcoma and accelerated bone defect regeneration is engineered by in situ growth of NIR‐absorbing cocrystal (DTC) on the surface of a 3D‐printing bioactive glass (BG) scaffold. The prominent photothermal conversion performance and outstanding bone regeneration capability of DTC@BG scaffolds originate from the precise tailoring of the bandgap between the electron donors and acceptors of DTC and promote new bone growth performance of BG scaffolds. DTC@BG scaffolds not only significantly promote tumor cell ablation in vitro, but also effectively facilitate bone tumor suppression in vivo. In particular, DTC@BG scaffolds exhibit excellent capability in stimulating osteogenic differentiation and angiogenesis, and finally promote newborn bone formation in the bone defects. This research represents the first paradigm for ablating osteosarcoma and facilitating new bone formation through precise modulation of electron donors and acceptors in the cocrystal, which offers a new avenue to construct high‐efficiency therapeutic platforms based on cocrystal strategy for ablation of malignant bone tumor.

Transition metal‐based nanoparticles have shown their broad applications in versatile biomedical applications. Although traditional iron‐based nanoparticles have been extensively explored in biomedicine, transition metal manganese (Mn)‐based nanoparticulate systems have emerged as a multifunctional nanoplatform with their intrinsic physiochemical property and biological effect for satisfying the strict biomedical requirements. This comprehensive review focuses on recent progress of Mn‐based functional nanoplatforms in biomedicine with the particular discussion on their elaborate construction, physiochemical property, and theranostic applicability. Several Mn‐based nanosystems are discussed in detail, including solid/hollow MnOx nanoparticles, 2D MnOx nanosheets, MnOx‐silica/mesoporous silica nanoparticles, MnOx‐Fe3O4 nanoparticles, MnOx‐Au, MnOx‐fluorescent nanoparticles, Mn‐based organic composite nanosystem, and some specific/unique Mn‐based nanocomposites. Their versatile biomedical applications include pH/reducing‐responsive T1‐weighted positive magnetic resonance imaging, controlled drug loading/delivery/release, protection of neurological disorder, photothermal hyperthermia, photodynamic therapy, chemodynamic therapy, alleviation of tumor hypoxia, immunotherapy, and some specific synergistic therapies, which are based on their disintegration behavior under the mildly acidic/reducing condition, multiple enzyme‐mimicking activity, catalytic‐triggering Fenton reaction, etc. The biological effects and biocompatibility of these Mn‐based nanosystems are also discussed, accompanied with a discussion on challenges/critical issues and an outlook on the future developments and clinical‐translation potentials of these intriguing Mn‐based functional nanoplatforms.

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BACKGROUND: Altered mental status (AMS) is a very common emergency case, but the exact etiology of many AMS patients is unknown. Patients often manifest vague symptoms, thus, AMS diagnosis and treatment are highly challenging for emergency physicians. The aim of this study is to provide a framework for the assessment of AMS patients. This assessment should allow providers to better understand the etiology of mental status changes and therefore improve diagnostic skills and management. METHODS: This is a prospective cohort observational study. We recruited all adult patients with undifferentiated AMS at a single center tertiary care academic emergency department over 24 months (June 2009 to June 2011). Demographic characteristics, clinical manifestations, assessment approaches, causative factors, emergency treatments and outcomes were collected prospectively. RESULTS: In 1934 patients with AMS recruited, accounting for 0.93% of all emergency department (ED) patients, 1 026 (53.1%) were male, and 908 (46.9%) female. Their average age was 51.95±15.71 years. Etiologic factors were neurological (n=641; 35.0%), pharmacological and toxicological (n=421; 23.0%), systemic and organic (n=266; 14.5%), infectious (n=167; 9.1%), endocrine/metabolic (n=145; 7.9%), psychiatric (n=71; 3.9%), traumatic (n=38; 2.1%), and gynecologic and obstetric (n=35; 1.9%). Total mortality rate was 8.1% (n=156). The death rate was higher in elderly patients (≥60) than in younger patients (10.8% vs. 6.9%, P=0.003). CONCLUSIONS: Patients with AMS pose a challenge for ED physicians. The most frequently encountered diagnostic categories causing AMS were primary CNS disorders, intoxication, organ system dysfunction, and endocrine/metabolic diseases. AMS has a high fatality rate in the ED. AMS is an important warning signal for ED patients because of its potentially fatal and reversible effects. Prompt evaluation and treatment are essential to decreasing morbidity and mortality associated with AMS.