Chronic cold stress promotes inflammation and ER stress via inhibiting GLP-1R signaling, and exacerbates the risk of ferroptosis in the liver and pancreas.

The cold climates in autumn and winter threatens human health. The aim of this study was to reveal the effects of prolonged cold exposure on the liver and pancreas based on GLP-1R signaling, oxidative stress, endoplasmic reticulum (ER) stress and ferroptosis by Yorkshire pig models. Yorkshire pigs were divided into the control group and chronic cold stress (CCS) group. The results showed that CCS induced oxidative stress injury, activated Nrf2 pathway and inhibited the expression of GLP-1R in the liver and pancreas (P<0.05). The toll-like receptor 4 (TLR4) pathway was activated in the liver and pancreas, accompanied by the enrichment of IL-1ß and TNF-α during CCS (P<0.05). Moreover, the kinase RNA-like endoplasmic reticulum kinase (PERK), inositol requiring kinase 1 (IRE1), X-box-binding protein 1 (XBP1) and eukaryotic initiation factor 2α (eIF2α) expression in the liver and pancreas was up-regulated during CCS (P<0.05). In addition, CCS promoted the prostaglandin-endoperoxide synthase 2 (PTGS2) expression and inhibited the ferritin H (FtH) expression in the liver. Summarily, CCS promotes inflammation, ER stress and apoptosis by inhibiting the GLP-1R signaling and inducing oxidative stress, and exacerbates the risk of ferroptosis in the liver and pancreas.

Modularized supramolecular assemblies for hypoxia-activatable fluorescent visualization and image-guided theranostics.

Rationale: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution. Methods: We report a modularized theranostics platform to fluorescently visualize hypoxia via light-modulated signal compensation to overcome tumor heterogeneity, thereby serving as a diagnostic tool for image-guided surgical resection and photodynamic therapy. Specifically, the platform integrating dual modules of fluorescence indicator and photodynamic moderator using supramolecular host-guest self-assembly, which operates cooperatively as a cascaded "AND" logic gate. First, tumor enrichment and specific fluorescence turn-on in hypoxic regions were accessible via tumor receptors and cascaded microenvironment signals as simultaneous inputs of the "AND" gate. Second, image guidance by a lighted fluorescence module and light-mediated endogenous oxygen consumption of a photodynamic module as dual inputs of "AND" gate collaboratively enabled light-modulated signal compensation in situ, indicating homogeneity of enhanced hypoxia-related fluorescence signals throughout a tumor. Results: In in vitro and in vivo analyses, the biocompatible platform demonstrated several strengths including a capacity for dual tumor targeting to progressively facilitate specific fluorescence turn-on, selective signal compensation, imaging-time window extension conducive to precise normalized image-guided treatment, and the functionality of tumor glutathione depletion to improve photodynamic efficacy. Conclusion: The hypoxia-activatable, image-guided theranostic platform demonstrated excellent potential for overcoming hypoxia heterogeneity in tumors.

IL-27 disturbs lipid metabolism and restrains mitochondrial activity to inhibit γδ T17 cell-mediated skin inflammation.

IL-17+ γδ T cells (γδ T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on γδ T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from γδ T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient γδ T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining γδ T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, γδ T17 biology and the pathogenesis of psoriasis.

Defective TiOx overlayers catalyze propane dehydrogenation promoted by base metals.

The industrial catalysts utilized for propane dehydrogenation (PDH) to propylene, an important alternative to petroleum-based cracking processes, either use expensive metals or metal oxides that are environmentally unbenign. We report that a typically less-active oxide, titanium oxide (TiO2), can be combined with earth-abundant metallic nickel (Ni) to form an unconventional Ni@TiOx catalyst for efficient PDH. The catalyst demonstrates a 94% propylene selectivity at 40% propane conversion and superior stability under industrially relevant conditions. Complete encapsulation of Ni nanoparticles was allowed at elevated temperatures (>550°C). A mechanistic study suggested that the defective TiOx overlayer consisting of tetracoordinated Ti sites with oxygen vacancies is catalytically active. Subsurface metallic Ni acts as an electronic promoter to accelerate carbon-hydrogen bond activation and hydrogen (H2) desorption on the TiOx overlayer.

Hippo kinases Mst1 and Mst2 maintain NK cell homeostasis by orchestrating metabolic state and transcriptional activity.

Natural killer (NK) cells play a crucial role in immune response against viral infections and tumors. However, further investigation is needed to better understand the key molecules responsible for determining the fate and function of NK cells. In this study, we made an important discovery regarding the involvement of the Hippo kinases Mst1 and Mst2 as novel regulators in maintaining mouse NK cell homeostasis. The presence of high Mst1 and Mst2 (Mst1/2) activity in NK cells is essential for their proper development, survival and function in a canonical Hippo signaling independent mode. Mechanistically, Mst1/2 induce cellular quiescence by regulating the processes of proliferation and mitochondrial metabolism, thereby ensuring the development and survival of NK cells. Furthermore, Mst1/2 effectively sense IL-15 signaling and facilitate the activation of pSTAT3-TCF1, which contributes to NK cell homeostasis. Overall, our investigation highlights the crucial role of Mst1/2 as key regulators in metabolic reprogramming and transcriptional regulation for mouse NK cell survival and function, emphasizing the significance of cellular quiescence during NK cell development and functional maturation.

Exosome-loaded hyaluronic acid hydrogel composite with oxygen-producing 3D printed polylactic acid scaffolds for bone tissue repair and regeneration.

Bone defects can interfere with bone healing by disrupting the local environment, resulting in vascular damage and hypoxia. Under these conditions, insufficient oxygen availability is a significant factor that exacerbates disease by blocking angiogenesis or osteogenesis. Exosomes play a crucial role in intercellular communication and modulation of inflammation to aid bone regeneration. However, the distance between exosomes and areas of damage can hinder efficient bone generation and cell survival. To overcome this limitation, we fabricated a continuous oxygen-supplying composite scaffold, with the encapsulation of calcium peroxide in a polylactic acid three-dimensional (3D) printing construct (CPS), as both an oxygen source and hydroxyapatite (HAP) precursor. Furthermore, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were incorporated into hyaluronic acid (HA) hydrogels to stimulate cell growth and modulate inflammation. The release of exosomes into cells leads to an increase in alkaline phosphatase production. In vivo results demonstrated that the composite scaffold regulated the inflammatory microenvironment, relieved tissue hypoxia, and promoted new bone formation. These results indicate that the synergistic effect of exosomes and oxygen promoted the proliferation of BMSCs, alleviated inflammation and exhibited excellent osteogenic properties. In conclusion, this osteogenic functional composite scaffold material offers a highly effective approach for bone repair.

Aridity affects soil organic carbon concentration and chemical stability by different forest types and soil processes across Chinese natural forests.

Forest soils play a critical role in carbon (C) reservoirs and climate change mitigation globally. Exploring the driving factors of soil organic carbon (SOC) concentration and stability in forests on a large spatial scale can help us evaluate the role of forest soils in regulating C sequestration. Based on SOC quantification and solid-state 13C nuclear magnetic resonance spectroscopy, we investigated the SOC concentration and SOC chemical stability (indicated by alkyl-to-O-alkyl ratio and hydrophobic-to-hydrophilic ratio) in top 0-5 and 5-10 cm soils from 65 Chinese natural forest sites and explored their driving factors. Results showed that SOC concentration in 0-5 cm soils were highest in mixed forests but SOC chemical stability in 0-5 cm soils were highest in coniferous forests, while SOC concentration and chemical stability in 5-10 cm soil layers did not differ across forest types. SOC concentration in 0-5 cm was directly related to soil pH and soil bacterial diversity. Structural equation models showed that aridity indirectly affected SOC concentration in 0-5 cm by directly affecting soil pH. While SOC chemical stability in 0-5 cm soils was higher with increased aridity. According to the correlations, the potential mechanisms could be attributed to higher proportion of coniferous forests in more arid forest sites, lower relative abundance of O-alkyl C, higher MgO and CaO contents, and higher bacterial diversity in soils from more arid forest sites. Our study reveals the important role of aridity in mediating SOC concentration and chemical stability in top 0-5 cm soils in Chinese natural forests on a large-scale field investigation. These results will help us better understand the different mechanisms underlying SOC concentration and stability in forests and assess the feedback of forest SOC to future climate change.

Complete remission in a pretreated, microsatellite-stable, KRAS-mutated colon cancer patient after treatment with sintilimab and bevacizumab and platinum-based chemotherapy: a case report and literature review.

Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (MSS) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for MSS colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had KRAS mutation and MSS-type colon cancer, and his PD-1+CD8+ and CD3-CD19-CD14+CD16-HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated, MSS-type and KRAS-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.

Molecular characterization, expression and antibacterial function of a macin, HdMac, from Haliotis discus hannai.

Macins are a family of antimicrobial peptides, which play multiple roles in the elimination of invading pathogens. In the present study, a macin was cloned and characterized from Pacific abalone Haliotis discus hannai (Designated as HdMac). Analysis of the conserved domain suggested that HdMac was a new member of the macin family. In non-stimulated abalones, HdMac transcripts were constitutively expressed in all five tested tissues, especially in hemocytes. After Vibrio harveyi stimulation, the expression of HdMac mRNA in hemocytes was significantly up-regulated at 12 hr (P < 0.01). RNAi-mediated knockdown of HdMac transcripts affected the survival rates of abalone against V. harveyi. Moreover, recombinant protein of HdMac (rHdMac) exhibited high antibacterial activities against invading bacteria, especially for Vibrio anguillarum. In addition, rHdMac possessed binding activities towards glucan, lipopolysaccharides (LPS), and peptidoglycan (PGN), but not chitin in vitro. Membrane integrity analysis revealed that rHdMac could increase the membrane permeability of bacteria. Meanwhile, both the phagocytosis and chemotaxis ability of hemocytes could be significantly enhanced by rHdMac. Overall, the results showed that HdMac could function as a versatile molecule involved in immune responses of H. discus hannai.

New strategy for intraoperative phonosurgical management of recurrent laryngeal nerve infiltrated by thyroid carcinoma.

PURPOSE: Treating an infiltration of the recurrent laryngeal nerve (RLN) by thyroid carcinoma remains a subject of ongoing debate. Therefore, this study aims to provide a novel strategy for intraoperative phenosurgical management of RLN infiltrated by thyroid carcinoma. METHODS: Forty-two patients with thyroid carcinoma infiltrating the RLN were recruited for this study and divided into three groups. Group A comprised six individuals with medullary thyroid cancer who underwent RLN resection and arytenoid adduction. Group B consisted of 29 differentiated thyroid cancer (DTC)patients who underwent RLN resection and ansa cervicalis (ACN)-to-RLN anastomosis. Group C included seven patients whose RLN was preserved. RESULTS: The videostroboscopic analysis and voice assessment collectively indicated substantial improvements in voice quality for patients in Groups A and B one year post-surgery. Additionally, the shaving technique maintained a normal or near-normal voice in Group C one year post-surgery. CONCLUSION: The new intraoperative phonosurgical strategy is as follows: Resection of the affected RLN and arytenoid adduction is required in cases of medullary or anaplastic carcinoma, regardless of preoperative RLN function. Suppose RLN is found infiltrated by well-differentiated thyroid cancer (WDTC) during surgery, and the RLN is preoperatively paralyzed, we recommend performing resection the involved RLN and ACN-to-RLN anastomosis immediately during surgery. If vocal folds exhibit normal mobility preoperatively, the MACIS scoring system is used to assess patient risk stratification. When the MACIS score > 6.99, resection of the involved RLN and immediate ACN-to-RLN anastomosis were performed. RLN preservation was limited to patients with MACIS scores ≤ 6.99.

Phase fluctuations-induced bit error ratio of deep-space optical communication systems during superior solar conjunction.

Deep-space optical communication has garnered increasing attention for its high data transfer rate, wide bandwidth, and high transmission speed. However, coronal plasma turbulence severely degrades optical signals during superior solar conjunction. In this study, we introduce the models for plasma density and generalized non-Kolmogorov turbulence power spectrum. Based on these models, we derive the variance of the phase fluctuations with the assistance of the Rytov theory in the weak turbulence regime involving various variables, such as turbulence outer scale, spectral index, relative fluctuation factor, and wavelength. Subsequently, we evaluate the bit error ratio (BER) performance of the deep-space optical communication system, considering phase fluctuations and intensity scintillations, under binary phase shift keying modulation. Numerical calculations reveal that small heliocentric distance, large relative fluctuation factor and spectral index, could induce severe phase fluctuations and high BER. Fortunately, the effects of the plasma irregularities on the BER performance can be mitigated by short optical wavelength under large outer scale.

Evidence for non-Arrhenius behavior of EPDM rubber by combining Arrhenius and time-temperature superposition (TTS) extrapolations.

Studying the non-Arrhenius behavior of rubber is crucial to ensure appropriate lifetime prediction and reduce ineffective acceleration experiments. In this paper, accelerated thermal aging from 70 °C to 130 °C is conducted on an ethylene propylene diene monomer (EPDM) rubber and the tensile characteristics of the rubber are tested. Further, the popular Mooney-Rivlin equation is employed to analyze the influence of aging temperature and time on the effective crosslink densities. The enormous increase in the physical crosslinking density when the aging temperature reaches 115 °C demonstrates that the activation energy varied during the degradation process. By combining the Arrhenius extrapolation with the time-temperature superposition (TTS) extrapolation, a novel method to prove the non-Arrhenius behavior of EPDM rubber is provided. Based on the method proposed in this study, the activation energies for the high- and low-temperature processing of rubber can be determined.

Identifying chemical markers in wine-processed Salvia miltiorrhiza using ultrahigh-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry.

To find the chemical markers of wine-processed Salvia miltiorrhiza (WSM), 76 constituents, including diterpenoid quinones and phenolic acids in Salvia miltiorrhiza (SM) and WSM, were profiled using ultrahigh-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry (UPLC-Q-TOF-MS/MS) in positive- and the negative-ion modes. Thirty compounds were screened out as candidate differential components using chemometrics analysis, and the concentration of most compounds increased after processing with wine. Seven compounds, namely tanshinone IIA, magnesium lithospermate B, salvianolic acid G, cryptotanshinone, isocryptotanshinone, salvianolic acid B, and rosmarinic acid, were selected as chemical markers of WSM using variable importance of the project. This study revealed the chemical markers of WSM and confirmed that WSM can improve the extraction and solubility effect of chemical constituents.

Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis.

Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.

Oxophilic Ce single atoms-triggered active sites reverse for superior alkaline hydrogen evolution.

The state-of-the-art alkaline hydrogen evolution catalyst of united ruthenium single atoms and small ruthenium nanoparticles has sparked considerable research interest. However, it remains a serious problem that hydrogen evolution primarily proceeds on the less active ruthenium single atoms instead of the more efficient small ruthenium nanoparticles in the catalyst, hence largely falling short of its full activity potential. Here, we report that by combining highly oxophilic cerium single atoms and fully-exposed ruthenium nanoclusters on a nitrogen functionalized carbon support, the alkaline hydrogen evolution centers are facilely reversed to the more active ruthenium nanoclusters driven by the strong oxophilicity of cerium, which significantly improves the hydrogen evolution activity of the catalyst with its mass activity up to -10.1 A mg-1 at -0.05 V. This finding is expected to shed new light on developing more efficient alkaline hydrogen evolution catalyst by rational regulation of the active centers for hydrogen evolution.

Alkaline-earth ion stabilized sub-nano-platinum tin clusters for propane dehydrogenation.

The strong promotion effects of alkali/alkaline earth metals are frequently reported for heterogeneous catalytic processes such as propane dehydrogenation (PDH), but their functioning principles remain elusive. This paper describes the effect of the addition of calcium (Ca) on reducing the deactivation rate of platinum-tin (Pt-Sn) catalyzed PDH from 0.04 h-1 to 0.0098 h-1 at 873 K under a WHSV of 16.5 h-1 of propane. The Pt-Sn-Ca catalyst shows a high propylene selectivity of >96% with a propylene production rate of 41 molC3H6 (gPt h)-1 and ∼1% activity loss after regeneration. The combination of characterization and DFT simulations reveals that Ca acts as a structural promoter favoring the transition of Snn+ in the parent catalyst to Sn0 during reduction, and the latter is an electron donor that increases the electron density of Pt. This greatly suppresses coke formation from deep dehydrogenation. Moreover, it was found that Ca promotes the formation of a highly reactive and sintering-resistant sub-nano Pt-Sn alloy with a diameter of approximately 0.8 nm. These lead to high activity and selectivity for the Pt-Sn-Ca catalyst for PDH.

Palladium-Catalyzed Deuteration of Arylketone Oxime Ethers.

We report herein the development of palladium-catalyzed deacylative deuteration of arylketone oxime ethers. This protocol features excellent functional group tolerance, heterocyclic compatibility, and high deuterium incorporation levels. Regioselective deuteration of some biologically important drugs and natural products are showcased via Friedel-Crafts acylation and subsequent deacylative deuteration. Vicinal meta-C-H bond functionalization (including fluorination, arylation, and alkylation) and para-C-H bond deuteration of electro-rich arenes are realized by using the ketone as both directing group and leaving group, which is distinct from aryl halide in conventional dehalogenative deuteration.

Metastable gallium hydride mediates propane dehydrogenation on H2 co-feeding.

In heterogeneous catalysis, the catalytic dehydrogenation reactions of hydrocarbons often exhibit a negative pressure dependence on hydrogen due to the competitive chemisorption of hydrocarbons and hydrogen. However, some catalysts show a positive pressure dependence for propane dehydrogenation, an important reaction for propylene production. Here we show that the positive activity dependence on H2 partial pressure of gallium oxide-based catalysts arises from metastable hydride mediation. Through in situ spectroscopic, kinetic and computational analyses, we demonstrate that under reaction conditions with H2 co-feeding, the dissociative adsorption of H2 on a partially reduced gallium oxide surface produces H atoms chemically bonded to coordinatively unsaturated Ga atoms. These metastable gallium hydride species promote C-H bond activation while inhibiting deep dehydrogenation. We found that the surface coverage of gallium hydride determines the catalytic performance. Accordingly, benefiting from proper H2 co-feeding, the alumina-supported, trace additive-modified gallium oxide catalyst GaOx-Ir-K/Al2O3 exhibited high activity and selectivity at high propane concentrations.

Biocompatibility and osteogenic potential of choline phosphate chitosan-coated biodegradable Zn1Mg.

Zinc alloys have demonstrated considerable potentials as implant materials for biodegradable vascular and orthopedic applications. However, the high initial release of Zn2+ can trigger intense immune responses that impede tissue healing. To address this challenge and enhance the osteogenic capacity of zinc alloys, the surface of Zn1Mg was subjected to CO2 plasma modification (Zn1Mg-PP) followed by grafting with choline phosphate chitosan (Zn1Mg-PP-PCCs). This study aims to investigate the in vitro and in vivo biocompatibility of the surface-modified Zn1Mg. The effect of the surface modification on the inflammatory response and osteogenic repair process was investigated. Compared with unmodified Zn1Mg, the degradation rate of Zn1Mg-PP-PCCs was significantly decreased, avoiding the cytotoxicity triggered by the release of large amounts of Zn2+. Moreover, PCCs significantly enhanced the cell-material adhesion, promoted the proliferation of osteoblasts (MC3T3-E1) and upregulated the expression of key osteogenic factors in vitro. Notably, the in vivo experiments revealed that the surface modification of Zn1Mg suppressed inhibited the expression of inflammatory cytokines, promoting the secretion of anti-inflammatory factors, thereby reducing inflammation and promoting bone tissue repair. Furthermore, histological analysis of tissue sections exhibited strong integration between the material and the bone, along with well-defined new bone formation and reduced osteoclast aggregation on the surface. This was attributed to the improved immune microenvironment by PCCs, which promoted osteogenic differentiation of osteoblasts. These findings highlight that the preparation of PCCs coatings on zinc alloy surfaces effectively inhibited ion release and modulated the immune environment to promote bone tissue repair. STATEMENT OF SIGNIFICANCE: Surface modification of biodegradable Zn alloys facilitates the suppression of intense immune responses caused by excessive ion release concentrations from implants. We modified the surface of Zn1Mg with choline phosphate chitosan (PCCs) and investigated the effects of surface modification on the inflammatory response and osteogenic repair process. In vitro results showed that the PCCs coating effectively reduced the degradation rate of Zn1Mg to avoid cytotoxicity caused by high Zn2+ concentration, favoring the proliferation of osteoblasts. In addition, in vivo results indicated that Zn1Mg-PP-PCCs attenuated inflammation to promote bone repair by modulating the release of inflammation-related factors. The surface-modified Zn1Mg implants demonstrated strong osseointegration, indicating that the PCCs coating effectively modulated the immune microenvironment and promoted bone healing.

Effects of Zr Addition on the Microstructural Evolution, Mechanical Properties, and Corrosion Behavior of Novel Biomedical Ti-Zr-Mo-Mn Alloys.

ß-Type Ti alloys have been widely investigated as implant materials owing to their excellent mechanical properties, corrosion resistance, and biocompatibility. In the present work, the effects of Zr on the microstructure, mechanical properties, and corrosion behaviors of Ti-Zr-Mo-Mn alloys were systematically studied. With the increase of Zr content, the phase composition gradually changed from intragranular-α + ß of (TZ)5:1MM alloy to grain-boundary-α + ß of (TZ)2:1MM alloy and finally transferred to a single ß phase structure of (TZ)1:1MM alloy. The (TZ)1:1MM alloy exhibited a good mechanical combination with a yield strength of 750.8 MPa, an elastic modulus of 61.3 GPa, and a tensile ductility of 14.6%. Moreover, the addition of Zr can effectively stabilize the passivation film and reduce the sensitivity of microgalvanic corrosion in simulated body fluid, leading to enhanced corrosion resistance in the TZMM alloys. X-ray photoelectron spectroscopy analysis together with the ion-sputtering technique revealed that the passivation films formed on TZMM alloys possessed a bilayered structure (outer Ti+Zr mixed-oxide layer and inner Zr-oxide-rich layer), in which the inner Zr oxide layer plays an important role in the corrosion resistance of the TZMM alloys. In vitro biocompatibility evaluations demonstrated that the TZMM alloys can support cell adhesion and proliferation with high biocompatibility comparable to that of CP-Ti, while in vivo biocompatibility evaluations validated the bone osteointegration ability of TZMM alloys after long-term implantation. The above results indicate that novel TZMM alloys are promising candidates for implant material.