Endovascular treatment of a large bone cement pulmonary embolism: Case report.

We report a case of endovascular treatment of bone cement embolism after percutaneous vertebroplasty. The patient underwent percutaneous vertebroplasty for acute L1 compression fracture. Two weeks later, the patient developed symptoms of pulmonary embolism. Computed tomography pulmonary angiogram confirmed the presence of a bone cement foreign body in the pulmonary artery. Endovascular treatment was performed, and the cement embolism was caught, pulled to the level of the iliac vein, and fixed with stents. At the 1-year follow-up, the patient did not have any complaints, postoperative computed tomography pulmonary angiogram showed no obvious manifestations of pulmonary embolism, and angiography showed that the bone cement was fixed in place and that the iliac veins were normal.

Tracheobronchomegaly associated with tracheobronchopathia osteochondroplastica: a case report.

Tracheobronchomegaly (TBM) is a rare condition characterized by the dilatation of the trachea and bronchi due to severe atrophy of elastic fibers, accompanied by the thinning of the muscularis mucosae and the development of diverticula between cartilaginous rings. The etiology of this condition remains unclear. Tracheobronchopathia osteochondroplastica (TO) is another uncommon airway disease with an unknown etiology. The co-occurrence of these two diseases has not been reported. In this study, we report and discuss a case involving an elderly man with TBM and TO with a history of recurrent pneumonia over the past 6 years.

Single-cell RNA sequencing revealed the roles of macromolecule epidermal growth factor receptor (EGFR) in the hybrid sterility of hermaphroditic Argopecten scallops.

The macromolecule epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that belongs to the protein kinase superfamily, which plays versatile functions in cell proliferation, development and fertility regulation. Almost all F1 hybrids obtained from the hermaphroditic bay scallops and Peruvian scallops exhibit infertility, and the genetic mechanism remains unclear. In this study, the comprehensive scRNA-seq was first conducted in the gonads of hybrid scallops, deducing the developmental sequence of germ cells and identifying the critical regulators in hybrid sterility: epidermal growth factor receptor. During the development from oogenesis phase germ cells to oocytes, the expression of the EGFR gene gradually decreased in sterile hybrids but increased in fertile hybrids. The significantly lower EGFR expression and ATP content, but higher ROS production rate was detected in the gonad of sterile hybrids than that in fertile hybrids, which might cause slow development of oocytes, stagnation of cell cycle, insufficient energy supply, high level of apoptosis and final sterility. Specific knock-down of EGFR gene led to decreased ATP content, increased ROS production rate, and inhibited oocyte maturation and gonadal development. These findings provide new insights into the roles of EGFR in hybrid infertility of bivalves and the healthy development of scallop breeding.

Potential roles of lipases and antioxidases on longevity under nutrient restriction in two Argopecten scallops with distinct lifespans.

Nutrient restriction (NR) extends lifespan in many species. High latitudes are characterized by cold-water temperature and food limitations, where bivalves may mimic NR like vertebrates, which could result in a prolonged life expectancy. The long-lived Peruvian scallop (7-10 years) distributes naturally at relatively higher latitudes than the annual bay scallop. However, the relationship and the mechanism underlying the food availability and lifespan are unclear in bivalves. In this study, the genetic response to NR was first investigated in bivalves with distinct lifespans. Peruvian scallops persistently responded to NR mainly via metabolic pathways, but that began to play roles in bay scallops after 56 days. Significant down-regulated expression of long-chain saturated fatty acid synthetase in both two scallops and increased expression of SCD5 and LIPN2 in Peruvian scallops might contribute to MUFA accumulation under NR. SOD1 was more highly expressed in Peruvian scallops than in bay scallops under NR, and strong autophagy was detected only in Peruvian scallops. Peruvian scallops presented much lower MDA levels and higher SOD1 activities than bay scallops. These findings help us understanding the role of lipases and antioxidases in longevity of bivalves, and provide potential biomarkers for breeding long-lived larger scallops.

TRIM35 triggers cardiac remodeling by regulating SLC7A5-mediated amino acid transport and mTORC1 activation in fibroblasts.

BACKGROUND: Cardiac maladaptive remodeling is one of the leading causes of heart failure with highly complicated pathogeneses. The E3 ligase tripartite motif containing 35 (TRIM35) has been identified as a crucial regulator governing cellular growth, immune responses, and metabolism. Nonetheless, the role of TRIM35 in fibroblasts in cardiac remodeling remains elusive. METHODS: Heart tissues from human donors were used to verify tissue-specific expression of TRIM35. Fibroblast-specific Trim35 gene knockout mice (Trim35cKO) were used to investigate the function of TRIM35 in fibroblasts. Cardiac function, morphology, and molecular changes in the heart tissues were analyzed after transverse aortic constriction (TAC) surgery. The mechanisms by which TRIM35 regulates fibroblast phenotypes were elucidated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA sequencing (RNA-Seq). These findings were further validated through the use of adenoviral and adeno-associated viral transfection systems, as well as the mTORC1 inhibitor Rapamycin. RESULTS: TRIM35 expression is primarily up-regulated in cardiac fibroblasts in both murine and human fibrotic hearts, and responds to TGF-ß1 stimulation. Specific deletion of TRIM35 in cardiac fibroblasts significantly improves cardiac fibrosis and hypertrophy. Consistently, the overexpression of TRIM35 promotes fibroblast proliferation, migration, and differentiation. Through paracrine signaling, it induces hypertrophic growth of cardiomyocytes. Mechanistically, we found that TRIM35 interacts with, ubiquitinates, and up-regulates the amino acid transporter SLC7A5, which enhances amino acid transport and activates the mTORC1 signaling pathway. Furthermore, overexpression of SLC7A5 significantly reverses the reduced cardiac fibrosis and hypertrophy caused by conditional knockout of TRIM35. CONCLUSION: Our findings demonstrate a novel role of fibroblast-TRIM35 in cardiac remodeling and uncover the mechanism underlying SLC7A5-mediated amino acid transport and mTORC1 activation. These results provide a potential novel therapeutic target for treating cardiac remodeling.

Li2ZnCu3 modified Cu current collector to regulate Li deposition.

Rationally designing a current collector that can maintain low lithium (Li) porosity and smooth morphology while enduring high-loading Li deposition is crucial for realizing the high energy density of Li metal batteries, but it is still challengeable. Herein, a Li2ZnCu3 alloy-modified Cu foil is reported as a stable current collector to fulfill the stable high-loading Li deposition. Benefiting from the in-situ alloying, the generated numerous Li2ZnCu3@Cu heterojunctions induce a homogeneous Li nucleation and dense growth even at an ultrahigh capacity of 12 mAh cm-2. Such a spatial structure endows the overall Li2ZnCu3@Cu electrode with the manipulated steric hindrance and outmost surface electric potential to suppress the side reactions during Li stripping and plating. The resultant Li||Li2ZnCu3@Cu asymmetric cell preserves an ultrahigh average Coulombic efficiency of 99.2% at 3 mA cm-2/6 mAh cm-2 over 200 cycles. Moreover, the Li-Li2ZnCu3@Cu||LiFePO4 cell maintains a cycling stability of 87.5% after 300 cycles. After coupling with the LiCoO2 cathode (4 mAh cm-2), the cell exhibits a high energy density of 407.4 Wh kg-1 with remarkable cycling reversibility at an N/P ratio of 3. All these findings present a doable way to realize the high-capacity, dendrite-free, and dense Li deposition for high-performance Li metal batteries.

Ventricular system-unrelated cerebellar ependymoma: A case report.

BACKGROUND: An ependymoma is a glial tumor that usually occurs in or near the ventricle, close to the ependyma. It rarely occurs exclusively in the brain parenchyma without being associated with the ventricle. CASE SUMMARY: Here, we report a rare case of a cerebellar ependymoma completely located in the brain parenchyma. A previously healthy 32-year-old female with a 1-month history of dizziness was admitted to our hospital. During hospitalization, magnetic resonance imaging of the brain revealed a space-occupying lesion measuring 57 mm × 41 mm × 51 mm in the right cerebellar hemisphere and inferior cerebellar vermis. The patient underwent surgical resection for the right cerebellar mass. Postoperative pathological examination revealed an ependymoma. At 1 year follow-up, the patient was doing well and showed no recurrence. CONCLUSION: We conducted a literature review and summarized three theories regarding ependymomas located exclusively in the brain parenchyma, which are key to the diagnosis of intraparenchymal cerebellar ependymomas. Surgery and postoperative radiotherapy are the primary treatment options for ependymomas.

Enhancing diagnostic precision in EBV-related HLH: a multifaceted approach using 18F-FDG PET/CT and nomogram integration.

BACKGROUND: The hyperinflammatory condition and lymphoproliferation due to Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) affect the detection of lymphomas by 18F-FDG PET/CT. We aimed to improve the diagnostic capabilities of 18F-FDG PET/CT by combining laboratory parameters. METHODS: This retrospective study involved 46 patients diagnosed with EBV-positive HLH, who underwent 18F-FDG PET/CT before beginning chemotherapy within a 4-year timeframe. These patients were categorized into two groups: EBV-associated HLH (EBV-HLH) (n = 31) and EBV-positive lymphoma-associated HLH (EBV + LA-HLH) (n = 15). We employed multivariable logistic regression and regression tree analysis to develop diagnostic models and assessed their efficacy in diagnosis and prognosis. RESULTS: A nomogram combining the SUVmax ratio, copies of plasma EBV-DNA, and IFN-γ reached 100% sensitivity and 81.8% specificity, with an AUC of 0.926 (95%CI, 0.779-0.988). Importantly, this nomogram also demonstrated predictive power for mortality in EBV-HLH patients, with a hazard ratio of 4.2 (95%CI, 1.1-16.5). The high-risk EBV-HLH patients identified by the nomogram had a similarly unfavorable prognosis as patients with lymphoma. CONCLUSIONS: The study found that while 18F-FDG PET/CT alone has limitations in differentiating between lymphoma and EBV-HLH in patients with active EBV infection, the integration of a nomogram significantly improves the diagnostic accuracy and also exhibits a strong association with prognostic outcomes.

Van der Waals phase transition investigation toward high-voltage layered cathodes.

High-voltage phase transition constitutes the major barrier to accessing high energy density in layered cathodes. However, questions remain regarding the origin of phase transition, because the interlayer weak bonding features cannot get an accurate description by experiments. Here, we determined van der Waals (vdW) interaction (vdWi) in LixCoO2 via visualizing its electron density, elucidating the origin of O3─O1 phase transition. The charge around oxygen is distorted by the increasing Co─O covalency. The charge distortion causes the difference of vdW gap between O3 and O1 phases, verified by a gap corrected vdW equation. In a high charging state, excessive covalency breaks the vdW gap balance, driving the O3 phase toward a stable O1 one. This interpretation of vdWi-dominated phase transition can be applied to other layered materials, as shown by a map regarding degree of covalence. Last, we introduce the cationic potential to provide a solution for designing high-voltage layered cathodes.

A Low-Temperature Na-MoS2 Rechargeable Battery.

It is generally accepted that the low-temperature environment typically augments electrolyte viscosity and impedes electrochemical kinetics, thereby diminishing battery performance. However, this prevailing notion, while valid in certain contexts, lacks universality, particularly regarding cycling stability. In this context, the Na-MoS2 batteries serve as a model to elucidate the impacts of low temperatures. By significantly suppressing the pulverization and amorphization of MoS2, the low-temperature milieu effectively mitigates the risk of micro-short circuits induced by the mass shuttling to the Na metal anode, thereby averting performance degradation by self-discharge. Upon cycling, the generated NaxMo3S4 intermediates only at low temperatures benefit the structural and electrochemical stabilizations to counteract the intrinsic performance degradation. The attenuation of kinetics at low temperatures facilitates the accumulation of Na2S, akin to a sustained-release agent within the electrode, steadily furnishing the capacity in long cycling. Moreover, the suppression of polysulfide dissolution and shuttling emerges as a pivotal factor contributing to the cycling stability at low-temperature. These findings provide a rewarding avenue toward understanding of the influence of low temperature on battery performance, as well as the design of practical electrodes and batteries for low-temperature applications.

A False-Negative 123I-MIBG SPECT/CT With True-Positive 68Ga-DOTATATE PET/CT in a Patient With Neuroblastoma Following 177Lu-DOTATATE Therapy.

ABSTRACT: A 10-year-old girl with high-risk neuroblastoma underwent 123I-MIBG SPECT/CT and 68Ga-DOTATE PET/CT, which both showed multiple bone metastases. However, following 177Lu-DOTATATE therapy, only 68Ga-DOTATATE PET/CT identified residual lesions with negative 123I-MIBG SPECT/CT results. The case emphasized the complementary role of 68Ga-DOTATATE PET/CT and 123I-MIBG SPECT/CT after 177Lu-DOTATATE therapy.

CLK2 Condensates Reorganize Nuclear Speckles and Induce Intron Retention.

Intron retention (IR) constitutes a less explored form of alternative splicing, wherein introns are retained within mature mRNA transcripts. This investigation demonstrates that the cell division cycle (CDC)-like kinase 2 (CLK2) undergoes liquid-liquid phase separation (LLPS) within nuclear speckles in response to heat shock (HS). The formation of CLK2 condensates depends on the intrinsically disordered region (IDR) located within the N-terminal amino acids 1-148. Phosphorylation at residue T343 sustains CLK2 kinase activity and promotes overall autophosphorylation, which inhibits the LLPS activity of the IDR. These CLK2 condensates initiate the reorganization of nuclear speckles, transforming them into larger, rounded structures. Moreover, these condensates facilitate the recruitment of splicing factors into these compartments, restricting their access to mRNA for intron splicing and promoting the IR. The retained introns lead to the sequestration of transcripts within the nucleus. These findings extend to the realm of glioma stem cells (GSCs), where a physiological state mirroring HS stress inhibits T343 autophosphorylation, thereby inducing the formation of CLK2 condensates and subsequent IR. Notably, expressing the CLK2 condensates hampers the maintenance of GSCs. In conclusion, this research unveils a mechanism by which IR is propelled by CLK2 condensates, shedding light on its role in coping with cellular stress.

Jejunal Undifferentiated Spindle Cell Sarcoma with Intussusception Revealed by 18F-FDG PET/CT.

Spindle cell sarcoma is a malignant tumor with low incidence. They can occur in the soft tissue, bone, or viscera. The characteristics of morphology, density, and metabolism of spindle cell sarcoma are related to the location of the lesion. A 61-year-old woman presented with vomiting after eating for 2 weeks. Signs of peritoneal irritation were involved, but no response for symptomatic treatment included antiemetic and antispasmodic therapy. Abdominal computed tomography (CT) indicated a mass in the intestinal tract in the pelvic cavity. Then, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/CT was performed, which interestingly detected a jejunal malignancy mass in the left upper abdomen with annular high uptake of 18F-FDG, which was complicated by intussusception and intestinal obstruction. Finally, the jejunal mass was pathologically clarified as an undifferentiated spindle cell sarcoma.

Novel hypoxia-induced HIF-1αactivation in asthma pathogenesis.

BACKGROUND: Asthma's complexity, marked by airway inflammation and remodeling, is influenced by hypoxic conditions. This study focuses on the role of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) and P53 ubiquitination in asthma exacerbation. METHODS: High-throughput sequencing and bioinformatics were used to identify genes associated with asthma progression, with an emphasis on GO and KEGG pathway analyses. An asthma mouse model was developed, and airway smooth muscle cells (ASMCs) were isolated to create an in vitro hypoxia model. Cell viability, proliferation, migration, and apoptosis were assessed, along with ELISA and Hematoxylin and Eosin (H&E) staining. RESULTS: A notable increase in HIF-1α was observed in both in vivo and in vitro asthma models. HIF-1α upregulation enhanced ASMCs' viability, proliferation, and migration, while reducing apoptosis, primarily via the promotion of P53 ubiquitination through MDM2. In vivo studies showed increased inflammatory cell infiltration and airway structural changes, which were mitigated by the inhibitor IDF-11,774. CONCLUSION: The study highlights the critical role of the HIF-1α-MDM2-P53 axis in asthma, suggesting its potential as a target for therapeutic interventions. The findings indicate that modulating this pathway could offer new avenues for treating the complex respiratory disorder of asthma.

Near-infrared photoactivatable three-in-one nanoagents to aggravate hypoxia and enable amplified photo-chemotherapy.

Solid tumors create a hypoxic microenvironment and this character can be utilized for cancer therapy, but the hypoxia levels are insufficient to achieve satisfactory therapeutic benefits. Some tactics have been used to improve hypoxia, which however will cause side effects due to the uncontrolled drug release. We herein report near-infrared (NIR) photoactivatable three-in-one nanoagents (PCT) to aggravate tumor hypoxia and enable amplified photo-combinational chemotherapy. PCT are formed based on a thermal-responsive liposome nanoparticle containing three therapeutic agents: a hypoxia responsive prodrug tirapazamine (TPZ) for chemotherapy, a vascular targeting agent combretastatin A-4 (CA4) for vascular disturbance and a semiconducting polymer for both photodynamic therapy (PDT) and photothermal therapy (PTT). With NIR laser irradiation, PCT generate heat for PTT and destructing thermal-responsive liposomes to achieve activatable releases of TPZ and CA4. Moreover, PCT produce singlet oxygen (1O2) for PDT via consuming tumor oxygen. CA4 can disturb the blood vessels in tumor microenvironment to aggravate the hypoxic microenvironment, which results in the activation of TPZ for amplified chemotherapy. PCT thus enable PTT, PDT and hypoxia-amplified chemotherapy to afford a high therapeutic efficacy to almost absolutely eradicate subcutaneous 4 T1 tumors and effectively inhibit tumor metastases in lung and liver. This work presents an activatable three-in-one therapeutic nanoplatform with remotely controllable and efficient therapeutic actions to treat cancer.

BATF promotes tumor progression and association with FDG PET-derived parameters in colorectal cancer.

PURPOSE: The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters. METHODS: The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcription­quantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative 18F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated. RESULTS: In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUVmax was an independent predictor of BATF expression. With 15.96 g/cm3 as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854. CONCLUSION: BATF may be an oncogene associated with 18F-FDG PET/CT parameters in CRC. SUVmax may be an independent predictor of BATF expression.

Interfacial Layers with Desolvation Function Induced Stable Deposition of Lithium Metal for Long-Cycling Lithium Metal Batteries.

The unstable solid electrolyte interface (SEI) formed by uncontrollable electrolyte degradation, which leads to dendrite growth and Coulombic efficiency decay, hinders the development of Li metal anodes. A controllable desolvation process is essential for the formation of stable SEI and improved lithium metal deposition behavior. Here, we show a functional artificial interface protective layer comprised of chondroitin sulfate-reduced graphene oxide (CrG), on which polar functional groups are distributed to effectively reduce the energy barrier for desolvation of Li+ and effectively alienate solvent molecules to avoid solvent involvement in SEI formation, thus promoting the formation of a LiF-rich SEI. Consequently, stable Coulombic efficiencies of 98.4% were achieved after 500 cycles in a Li//Cu cell. Moreover, the LiFePO4 full cells achieve steady circulation (470 cycles at 80%, 1 C) with a negative/positive electrode capacity ratio of 2.87. Our multifunctional artificial interface protective layer provides a new way to advance Li metal batteries.

Radioactive hybrid semiconducting polymer nanoparticles for imaging-guided tri-modal therapy of breast cancer.

Due to the rapid progression and aggressive metastasis of breast cancer, its diagnosis and treatment remain a great challenge. The simultaneous inhibition of tumor growth and metastasis is necessary for breast cancer to obtain ideal therapeutic outcomes. We herein report the development of radioactive hybrid semiconducting polymer nanoparticles (SPNH) for imaging-guided tri-modal therapy of breast cancer. Two semiconducting polymers are used to form SPNH with a diameter of around 60 nm via nano-coprecipitation and they are also labeled with iodine-131 (131I) to enhance the imaging functions. The formed SPNH show good radiolabeling stability and excellent photodynamic and photothermal effects under 808 nm laser irradiation to produce singlet oxygen (1O2) and heat. Moreover, SPNH can generate 1O2 with ultrasound irradiation via their sonodynamic properties. After intravenous tail vein injection, SPNH can effectively accumulate in the subcutaneous 4T1 tumors of living mice as verified via fluorescence and single photon emission computed tomography (SPECT) imaging. With the irradiation of tumors using an 808 nm laser and US, SPNH mediate photodynamic therapy (PDT), photothermal therapy (PTT) and sonodynamic therapy (SDT) to kill tumor cells. Such a tri-modal therapy leads to an improved efficacy in inhibiting tumor growth and suppressing tumor metastasis compared to the sole SDT and combinational PDT-PTT. This study thus demonstrates the applications of SPNH to diagnose tumors and combine different therapies for effective breast cancer treatment.

Transcriptomic profiling of the thermal tolerance in two subspecies of the bay scallop Argopecten irradians.

The bay scallop is a eurythermal species with high economic value and now represents the most cultured bivalve species in China. Two subspecies of the bay scallop, the northern subspecies Argopecten irradians irradians Korean population (KK) and the southern subspecies Argopecten irradians concentricus (MM), exhibited distinct adaptations to heat stress. However, the molecular mechanism of heat resistance of the two subspecies remains unclear. In this study, we compared the transcriptomic responses of the two subspecies to heat stress and identified the involved differentially expressed genes (DEGs) and pathways. More DEGs were found in the KK than in the MM when exposed to high temperatures, indicating elevated sensitivity to thermal stress in the KK. Enrichment analysis suggests that KK scallops may respond to heat stress more swiftly by regulating GTPase activity. Meanwhile, MM scallops exhibited higher resistance to heat stress mainly by effective activation of their antioxidant system. Chaperone proteins may play different roles in responses to heat stress in the two subspecies. In both subspecies, the expression levels of antioxidants such as GST were significantly increased; the glycolysis process regulated by PC and PCK1 was greatly intensified; and both apoptotic and anti-apoptotic systems were significantly activated. The pathways related to protein translation and hydrolysis, oxidoreductase activity, organic acid metabolism, and cell apoptosis may also play pivotal roles in the responses to heat stress. The results of this study may provide a theoretical basis for marker-assisted breeding of heat-resistant strains.

Dual-Site Doping in Transition Metal Oxide Cathode Enables High-Voltage Stability of Na-Ion Batteries.

Designing cathode materials that effectively enhancing structural stability under high voltage is paramount for rationally enhancing energy density and safety of Na-ion batteries. This study introduces a novel P2-Na0.73K0.03Ni0.23Li0.1Mn0.67O2 (KLi-NaNMO) cathode through dual-site synergistic doping of K and Li in Na and transition metal (TM) layers. Combining theoretical and experimental studies, this study discovers that Li doping significantly strengthens the orbital overlap of Ni (3d) and O (2p) near the Fermi level, thereby regulates the phase transition and charge compensation processes with synchronized Ni and O redox. The introduction of K further adjusts the ratio of Nae and Naf sites at Na layer with enhanced structural stability and extended lattice space distance, enabling the suppression of TM dissolution, achieving a single-phase transition reaction even at a high voltage of 4.4 V, and improving reaction kinetics. Consequently, KLi-NaNMO exhibits a high capacity (105 and 120 mAh g-1 in the voltage of 2-4.2 V and 2-4.4 V at 0.1 C, respectively) and outstanding cycling performance over 300 cycles under 4.2 and 4.4 V. This work provides a dual-site doping strategy to employ synchronized TM and O redox with improved capacity and high structural stability via electronic and crystal structure modulation.