Colorectal cancer cells with stably expressed SIRT3 demonstrate proliferating retardation by Wnt/ß-catenin cascade inactivation.

Colorectal cancer (CRC) is a typical and lethal digestive system malignancy. In this study, we investigated the effect of sirtuin 3 (SIRT3) expression, a fidelity mitochondrial protein, on the proliferation of CRC cells and the mechanisms involved. Using the University of Alabama at Birmingham Cancer Data Analysis Portal database and the Clinical Proteomic Tumour Analysis Consortium database, we discovered that low expression of SIRT3 in CRC was a negative factor for survival prognosis (P < .05). Meanwhile, SIRT3 expression was correlated with distant metastasis and tumour, node, metastasis stage of CRC patients (P < .05). Subsequently, we observed that CRC cells with stable SIRT3 expression exhibited a significant decrease in proliferative capacities both in vitro and in vivo, compared to their counterparts (P < .05). Further investigation using western blot, immunoprecipitation and TOPflash/FOPflash assay showed the mechanism of growth retardation of these cells was highly associated with the degradation of ß-catenin in cytosol, and the localization of ß-catenin/α-catenin complex in the nucleus. In conclusion, our findings suggest that the inhibition of CRC cell proliferation by SIRT3 is closely associated with the inactivation of the Wnt/ß-catenin signalling pathway.

Overexpression of AtMYB2 Promotes Tolerance to Salt Stress and Accumulations of Tanshinones and Phenolic Acid in Salvia miltiorrhiza.

Salvia miltiorrhiza is a prized traditional Chinese medicinal plant species. Its red storage roots are primarily used for the treatment of cardiovascular and cerebrovascular diseases. In this study, a transcription factor gene AtMYB2 was cloned and introduced into Salvia miltiorrhiza for ectopic expression. Overexpression of AtMYB2 enhanced salt stress resistance in S. miltiorrhiza, leading to a more resilient phenotype in transgenic plants exposed to high-salinity conditions. Physiological experiments have revealed that overexpression of AtMYB2 can decrease the accumulation of reactive oxygen species (ROS) during salt stress, boost the activity of antioxidant enzymes, and mitigate oxidative damage to cell membranes. In addition, overexpression of AtMYB2 promotes the synthesis of tanshinones and phenolic acids by upregulating the expression of biosynthetic pathway genes, resulting in increased levels of these secondary metabolites. In summary, our findings demonstrate that AtMYB2 not only enhances plant tolerance to salt stress, but also increases the accumulation of secondary metabolites in S. miltiorrhiza. Our study lays a solid foundation for uncovering the molecular mechanisms governed by AtMYB2 and holds significant implications for the molecular breeding of high-quality S. miltiorrhiza varieties.

Design of Excellent Mechanical Performances and Magnetic Refrigeration via In Situ Forming Dual-Phase Alloys.

Magnetic refrigeration technology can achieve higher energy efficiency based on the magnetocaloric effect. However, the practical application of MCE materials is hindered by their poor mechanical properties, making them challenging to process into devices. Conventional strengthening strategies usually lead to a trade-off with refrigeration capacity reduction. Here, a novel design is presented to overcome this dilemma by forming dual-phase alloys through in-situ precipitation of a tough magnetic refrigeration phase within an intermetallic compound with excellent MCE. In the alloy 87.5Gd-12.5Co, incorporating the interconnected tough phase Gd contributes to enhanced strength (≈ 505 MPa) with good ductility (≈ 9.2%). The strengthening phase Gd simultaneously exhibits excellent MCE, enabling the alloy to achieve a peak refrigeration capacity of 720 J∙kg-1. Moreover, the alloy shows low thermal expansion induced by the synergistic effect of the two phases. It is beneficial for maintaining structural stability during heat exchange in magnetic refrigeration. The coupling interaction between the two magnetic phases can broaden the refrigeration temperature range and reduce hysteresis. This study guides the development of new high-performance materials with an excellent combination of mechanical and magnetic refrigeration properties as needed for gas liquefaction and refrigerators. This article is protected by copyright. All rights reserved.

A polarity-responsive lysosomes-nucleus translocation probe for the dual-emissive visualization of cell apoptosis.

Visualization of cell apoptosis is a critical task playing central roles in the fundamental studies in biology, pathology, and biomedicine. Dual-emissive fluorescent probes are desired molecular tools for study on apoptosis, which however were rarely reported. Herein, utilizing the polarity differences between lysosomes and nucleus, a translocation type of fluorescent probe (NA-S) was developed for the dual-color visualization of cell apoptosis. NA-S was designed to be polarity sensitive, bearing alkalescence group, and with DNA affinity. In living cells, NA-S targeted the lysosomes to give blue fluorescence, which translocated into the nucleus during cell apoptosis to give green emission. Thereby, the cell apoptosis could be visualized with NA-S in dual-emissive manner. With the unique probe, the cell apoptosis induced by oxidative stress, UV irradiation, rotenone, colchicine, and paclitaxel have been successfully visualized.

A retrospective study on the efficacy of Roxadustat in peritoneal dialysis patients with erythropoietin hyporesponsiveness.

Background/Aims: Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. Methods: Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. Results: The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. Conclusions: For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.

Clinical Manifestation, mNGS Based Diagnosis and Treatment of Pulmonary Mucormycosis with Rhizopus delemar in a Diabetic Patient.

Pulmonary mucormycosis is a severe and often fatal disease that commonly affects patients with underlying conditions, such as diabetes. Early diagnosis and appropriate treatment are crucial for improving survival rates. However, clinical diagnosis remains challenging due to difficulty in obtaining etiological evidence. In this particular case, the patient presented with a cough-producing bloody sputum, and a chest CT revealed lesions in the right upper lobe of the lung. The patient was ultimately diagnosed with pulmonary mucormycosis caused by Rhizopus delemar through clinical bronchoscopy biopsy and metagenomic next-generation sequencing (mNGS) analysis of bronchoalveolar lavage fluid sample. Subsequently, antifungal therapy using the less toxic Amphotericin B cholesterol Organosulfate complex was initiated, improving the patient's condition. In conclusion, our findings underscore the potential of mNGS to provide an accurate and rapid etiological diagnosis of pulmonary mucormycosis, offering a foundation for treatment.

PM2.5-induced iron homeostasis imbalance triggers cardiac hypertrophy through ferroptosis in a selective autophagy crosstalk manner.

Exposure to PM2.5 is correlated with cardiac remodeling, of which cardiac hypertrophy is one of the main clinical manifestations. Ferroptosis plays an important role in cardiac hypertrophy. However, the potential mechanism of PM2.5-induced cardiac hypertrophy through ferroptosis remains unclear. This study aimed to explore the molecular mechanism of cardiac hypertrophy caused by PM2.5 and the intervention role of MitoQ involved in this process. The results showed that PM2.5 could induce cardiac hypertrophy and dysfunction in mice. Meanwhile, the characteristics of ferroptosis were observed, such as iron homeostasis imbalance, lipid peroxidation, mitochondrial damage and abnormal expression of key molecules. MitoQ treatment could effectively mitigate these alternations. After treating human cardiomyocyte AC16 with PM2.5, ferroptosis activator (Erastin) and inhibitor (Fer-1), it was found that PM2.5 could promote ferritinophagy and lead to lipid peroxidation, mitochondrial dysfunction as well as the accumulation of intracellular and mitochondrial labile iron. Subsequently, mitophagy was activated and provided an additional source of labile iron, enhancing the sensitivity of AC16 cells to ferroptosis. Furthermore, Fer-1 alleviated PM2.5-induced cytotoxicity and iron overload in the cytoplasm and mitochondria of AC16 cells. It was worth noting that during the process of PM2.5 caused ferroptosis, abnormal iron metabolism mediated the activation of ferritinophagy and mitophagy in a temporal order. In addition, NCOA4 knockdown reversed the iron homeostasis imbalance and lipid peroxidation caused by PM2.5, thereby alleviating ferroptosis. In summary, our study found that iron homeostasis imbalance-mediated the crosstalk of ferritinophagy and mitophagy played an important role in PM2.5-induced ferroptosis and cardiac hypertrophy.

COVID-19 vaccination affects short-term anti-coagulation levels in warfarin treatment.

Vaccines against SARS-CoV-2 have been recommended across the world, yet no study has investigated whether COVID-19 vaccination influences short-term warfarin anti-coagulation levels. Patients on stable warfarin treatment who received anti-SARS-CoV-2 vaccination were prospectively enrolled and followed up for three months. INR values less than 10 days before vaccination (baseline), 3-5 days (short-term) and 6-14 days (medium-term) after vaccination were recorded as INR0, INR1, and INR2, respectively. The variations of INR values within individuals were compared, and the linear mixed effect model was used to evaluate the variations of INR values at different time points. Logistic regression analysis was performed to determine covariates related to INR variations after COVID-19 vaccination. Vaccination safety was also monitored. There was a significant difference in INR values between INR0 and INR1 (2.15 vs. 2.26, p = 0.003), yet no marked difference was found between INR0 and INR2. The linear mixed effect model also demonstrated that INR variation was significant in short-term but not in medium-term or long-term period after vaccination. Logistic regression analysis showed that no investigated covariates, including age, vaccine dose, genetic polymorphisms of VKORC1 and CYP2C9 etc., were associated with short-term INR variations. Two patients (2.11%) reported gingival hemorrhage in the short-term due to increased INR values. The overall safety of COVID-19 vaccines for patients on warfarin was satisfying. COVID-19 vaccines may significantly influence warfarin anticoagulation levels 3-5 days after vaccination. We recommend patients on warfarin to perform at least one INR monitoring within the first week after COVID-19 vaccination.

Revealing the Charge Storage Mechanism in Porous Carbon to Achieve Efficient K Ion Storage.

Constructing a porous structure is considered an appealing strategy to improve the electrochemical properties of carbon anodes for potassium-ion batteries (PIBs). Nevertheless, the correlation between electrochemical K-storage performance and pore structure has not been well elucidated, which hinders the development of high-performance carbon anodes. Herein, various porous carbons are synthesized with porosity structures ranging from micropores to micro/mesopores and mesopores, and systematic investigations are conducted to establish a relationship between pore characteristics and K-storage performance. It is found that micropores fail to afford accessible active sites for K ion storage, whereas mesopores can provide abundant surface adsorption sites, and the enlarged interlayer spacing facilitates the intercalation process, thus resulting in significantly improved K-storage performances. Consequently, PCa electrode with a prominent mesoporous structure achieves the highest reversible capacity of 421.7 mAh g-1 and an excellent rate capability of 191.8 mAh g-1 at 5 C. Furthermore, the assembled potassium-ion hybrid capacitor realizes an impressive energy density of 151.7 Wh kg-1 at a power density of 398 W kg-1. The proposed work not only deepens the understanding of potassium storage in carbon materials with distinctive porosities but also paves a path toward developing high-performance anodes for PIBs with customized energy storage capabilities.

Differentiation of testicular seminomas from nonseminomas based on multiphase CT radiomics combined with machine learning: A multicenter study.

BACKGROUND: Differentiating seminomas from nonseminomas is crucial for formulating optimal treatment strategies for testicular germ cell tumors (TGCTs). Therefore, our study aimed to develop and validate a clinical-radiomics model for this purpose. METHODS: In this study, 221 patients with TGCTs confirmed by pathology from four hospitals were enrolled and classified into training (n = 126), internal validation (n = 55) and external test (n = 40) cohorts. Radiomics features were extracted from the CT images. After feature selection, we constructed a clinical model, radiomics models and clinical-radiomics model with different machine learning algorithms. The top-performing model was chosen utilizing receiver operating characteristic (ROC) curve analysis. Decision curve analysis (DCA) was also conducted to assess its practical utility. RESULTS: Compared with those of the clinical and radiomics models, the clinical-radiomics model demonstrated the highest discriminatory ability, with AUCs of 0.918 (95 % CI: 0.870 - 0.966), 0.909 (95 % CI: 0.829 - 0.988) and 0.839 (95 % CI: 0.709 - 0.968) in the training, validation and test cohorts, respectively. Moreover, DCA confirmed that the combined model had a greater net benefit in predicting seminomas and nonseminomas. CONCLUSION: The clinical-radiomics model serves as a potential tool for noninvasive differentiation between testicular seminomas and nonseminomas, offering valuable guidance for clinical treatment.

Unconventional Superconducting Diode Effects via Antisymmetry and Antisymmetry Breaking.

Symmetry breaking plays a pivotal role in unlocking intriguing properties and functionalities in material systems. For example, the breaking of spatial and temporal symmetries leads to a fascinating phenomenon: the superconducting diode effect. However, generating and precisely controlling the superconducting diode effect pose significant challenges. Here, we take a novel route with the deliberate manipulation of magnetic charge potentials to realize unconventional superconducting flux-quantum diode effects. We achieve this through suitably tailored nanoengineered arrays of nanobar magnets on top of a superconducting thin film. We demonstrate the vital roles of inversion antisymmetry and its breaking in evoking unconventional superconducting effects, namely a magnetically symmetric diode effect and an odd-parity magnetotransport effect. These effects are nonvolatilely controllable through in situ magnetization switching of the nanobar magnets. Our findings promote the use of antisymmetry (breaking) for initiating unconventional superconducting properties, paving the way for exciting prospects and innovative functionalities in superconducting electronics.

Genetic variation for sexual dimorphism in developmental traits in Drosophila melanogaster.

Sexual dimorphism in traits of insects during the developmental stages could potentially be the direct or indirect result of sex-specific selection provided that genetic variation for sexual dimorphism is present. We investigated genetic variation in sexual dimorphism in a set of Drosophila melanogaster inbred lines for 2 traits: egg to adult development time and pupation site preference. We observed considerable genetic variation in sexual dimorphism among lines in both traits. The sexual dimorphic patterns remained relatively consistent across multiple trials, despite both traits being sensitive to environmental conditions. Additionally, we measured 2 sexually dimorphic adult morphological traits in 6 sampled lines and investigated correlations in the sexual dimorphism patterns with the 2 developmental traits. The abundance of genetic variation in sexual dimorphism for D. melanogaster developmental traits demonstrated in this study provides evidence for a high degree of evolvability of sex differences in preadult traits in natural populations.

Exemestane plus everolimus and palbociclib in metastatic breast cancer: clinical response and genomic/transcriptomic determinants of resistance in a phase I/II trial.

The landscape of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) resistance is still being elucidated and the optimal subsequent therapy to overcome resistance remains uncertain. Here we present the final results of a phase Ib/IIa, open-label trial (NCT02871791) of exemestane plus everolimus and palbociclib for CDK4/6i-resistant metastatic breast cancer. The primary objective of phase Ib was to evaluate safety and tolerability and determine the maximum tolerated dose/recommended phase II dose (100 mg palbociclib, 5 mg everolimus, 25 mg exemestane). The primary objective of phase IIa was to determine the clinical benefit rate (18.8%, n = 6/32), which did not meet the predefined endpoint (65%). Secondary objectives included pharmacokinetic profiling (phase Ib), objective response rate, disease control rate, duration of response, and progression free survival (phase IIa), and correlative multi-omics analysis to investigate biomarkers of resistance to CDK4/6i. All participants were female. Multi-omics data from the phase IIa patients (n = 24 tumor/17 blood biopsy exomes; n = 27 tumor transcriptomes) showed potential mechanisms of resistance (convergent evolution of HER2 activation, BRAFV600E), identified joint genomic/transcriptomic resistance features (ESR1 mutations, high estrogen receptor pathway activity, and a Luminal A/B subtype; ERBB2/BRAF mutations, high RTK/MAPK pathway activity, and a HER2-E subtype), and provided hypothesis-generating results suggesting that mTOR pathway activation correlates with response to the trial's therapy. Our results illustrate how genome and transcriptome sequencing may help better identify patients likely to respond to CDK4/6i therapies.

Biphase Pd Nanosheets with Atomic-Hybrid RhOx/Pd Amorphous Skins Disentangle the Activity-Stability Trade-Off in Oxygen Reduction Reaction.

The activity-stability trade-off relationship of oxygen reduction reaction (ORR) is a tricky issue that strikes the electrocatalyst population and hinders the widespread application of fuel cells. Here neoteric biphase Pd nanosheets that are structured with ultrathin two-dimensional crystalline Pd inner cores and ≈1 nm thin atomic-hybrid RhOx/Pd amorphous skins, named c/a-Pd@PdRh NSs, for disentangling this trade-off dilemma for alkaline ORR are developed. The superthin amorphous skins significantly amplify the quantity of flexibly low-coordinated atoms for electrocatalysis. An in situ selected oxidation of the top-surface Rh dopants creates atomically hybrid RhOx/Pd disorder surfaces. Detailed energy spectra and theoretical simulation confirm that these RhOx/Pd interfaces can arouse a surface charge redistribution, causing significant electron deficiency and lowered d-band center for surface Pd. Meanwhile, anticorrosive Rh/RhOx species can thermodynamically passivate the neighboring Pd atoms from oxidative dissolution. Thanks to these amplified interfacial effects, the biphase c/a-Pd@PdRh NSs simultaneously exhibit a superhigh ORR activity (5.92 A mg-1, 22.8 times that of Pt/C) and an outstanding long-lasting stability after 100k cycles of accelerated durability test, showcasing unprecedented electrocatalysts for breaking the activity-stability trade-off relationship of ORR. This work paves a bran-new strategy for designing high-performance electrocatalysts through creating modulated amorphous skins on low-dimensional nanomaterials.

Renal function alters the association of lipoprotein(a) with cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a prospective cohort study.

Background and hypothesis: Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60-90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)]. Results: Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without. Conclusion: The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.

Single Fluorescent Probe for Multiple Tasks: Illuminating Lipid Droplets and Lysosomes in Dual Channels and Distinguishing Autophagy and Apoptosis.

Lipid droplets (LDs) and lysosomes play key roles in autophagy and cell apoptosis, and the discriminative visualization of the two organelles and simultaneously of autophagy and apoptosis is very helpful to understand their internal relationships. However, fluorescent probes that can concurrently achieve these tasks are not available currently. Herein, we delicately fabricate a robust probe CAQ2 for multiple tasks: illumination of LDs and lysosomes in dual emission colors as well as discriminative visualization of cell apoptosis and autophagy. The probe exhibited both lipophilic and basic properties and displayed different emission colors in neutral and protonated forms; thus, LDs and lysosomes emitted blue and red fluorescence colors, respectively. Because of the lysosomal acidification during autophagy, CAQ2 detected autophagy with evidently enhanced red emission. Because of the lysosomal alkalization during apoptosis, CAQ2 imaged apoptosis with a drastically decreased red fluorescence intensity. With the robust probe, the autophagy under starvation and lipidless conditions was visualized, and the apoptosis induced by H2O2, ultraviolet (UV) irradiation, and rotenone treatment was successfully observed. The efficient detoxification of Na2S against rotenone treatment was successfully revealed.

The Joint Operations of Teacher-Student and Peer Relationships on Classroom Engagement among Low-Achieving Elementary Students: A Longitudinal Multilevel Study.

Although both teacher-student relationship (TSR) and peer relationship (PR) have been found important for the development of students' classroom engagement, little research has been done regarding the joint operations of these two factors. Guided by a developmental systems framework, this study examined longitudinal between-person and within-person associations between TSR/ PR and classroom engagement in a sample of 784 low-achieving students in the first three years of elementary school. A multidimensional approach was used to distinguish positive and negative dimensions of TSR, as well as peer liking and disliking. At the between-person level, results showed that students' classroom engagement was positively predicted by positive TSR and PR liking and was negatively predicted by negative TSR and PR disliking. Both positive and negative TSR interacted with PR disliking at the between-person level, such that the associations between positive/negative TSR and classroom engagement were stronger for students with lower levels of PR disliking. At the within-person level, changes in classroom engagement were associated with contemporaneous year-to-year changes in positive/negative TSR and PR disliking. No within-person level interaction effects were found. Cross-level interaction showed that the effects of within-person negative TSR on classroom engagement were stronger for students with lower overall levels of PR disliking. Findings highlighted the importance of using a multilevel multidimensional approach to understand the joint operations of TSR and PR in the development of classroom engagement in low-achieving students in early elementary school.

High voltage electrolytes for lithium-ion batteries with micro-sized silicon anodes.

Micro-sized silicon anodes can significantly increase the energy density of lithium-ion batteries with low cost. However, the large silicon volume changes during cycling cause cracks for both organic-inorganic interphases and silicon particles. The liquid electrolytes further penetrate the cracked silicon particles and reform the interphases, resulting in huge electrode swelling and quick capacity decay. Here we resolve these challenges by designing a high-voltage electrolyte that forms silicon-phobic interphases with weak bonding to lithium-silicon alloys. The designed electrolyte enables micro-sized silicon anodes (5 µm, 4.1 mAh cm-2) to achieve a Coulombic efficiency of 99.8% and capacity of 2175 mAh g-1 for >250 cycles and enable 100 mAh LiNi0.8Co0.15Al0.05O2 pouch full cells to deliver a high capacity of 172 mAh g-1 for 120 cycles with Coulombic efficiency of >99.9%. The high-voltage electrolytes that are capable of forming silicon-phobic interphases pave new ways for the commercialization of lithium-ion batteries using micro-sized silicon anodes.

Oxygen Vacancy and Bandgap Simultaneous Modulation to Achieve High Lithiophilicity and Mechanical Strength of Lithium Metal Anodes.

Metal oxides with conversion and alloying mechanisms are more competitive in suppressing lithium dendrites. However, it is difficult to simultaneously regulate the conversion and alloying reactions. Herein, conversion and alloying reactions are regulated by modulation of the zinc oxide bandgap and oxygen vacancies. State-of-the-art advanced characterization techniques from a microcosmic to a macrocosmic viewpoint, including neutron diffraction, synchrotron X-ray absorption spectroscopy, synchrotron X-ray microtomography, nanoindentation, and ultrasonic C-scan demonstrated the electrochemical gain benefit from plentiful oxygen vacancies and low bandgaps due to doping strategies. In addition, high mechanical strength 3D morphology and abundant mesopores assist in the uniform distribution of lithium ions. Consequently, the best-performed ZnO-2 offers impressive electrochemical properties, including symmetric Li cells with 2000 h and full cells with 81% capacity retention after 600 cycles. In addition to providing a promising strategy for improving the lithiophilicity and mechanical strength of metal oxide anodes, this work also sheds light on lithium metal batteries for practical applications.