Inflammation Can Be a High-Risk Factor for Mucosal Nonunion of MRONJ by Regulating SIRT1 Signaling When Treated with an Oncologic Dose of Zoledronate.

Purpose: Zoledronate (ZA) stands as a highly effective antiresorptive agent known to trigger medication-related osteonecrosis of the jaw (MRONJ). Its clinical dosages primarily encompass those used for oncologic and osteoporosis treatments. While inflammation is recognized as a potential disruptor of mucosal healing processes associated with ZA, prior research has overlooked the influence of varying ZA dosages on tissue adaptability. Therefore, a deeper understanding of the specific mechanisms by which inflammation exacerbates ZA-induced MRONJ, particularly when inflammation acts as a risk factor, remains crucial. Methods: Cell proliferation and migration of human oral keratinocytes (HOK) was analyzed after treatment with different doses of ZA and/or lipopolysaccharide (LPS) to assess their possible effect on mucosal healing of extraction wounds. Mouse periodontitis models were established using LPS, and histological changes in extraction wounds were observed after the administration of oncologic dose ZA. Hematoxylin and eosin (HE) staining and immunofluorescence were used to evaluate mucosal healing. Results: In vitro, LPS did not exacerbate the effects of osteoporosis therapeutic dose of ZA on the proliferation and migration of HOK cells, while aggravated these with the oncologic dose of ZA treatment by inducing mitochondrial dysfunction and oxidative stress via regulating SIRT1 expression. Furthermore, SIRT1 overexpression can alleviate this process. In vivo, local injection of LPS increased the nonunion of mucous membranes in MRONJ and decreased the expression of SIRT1, PGC-1α, and MnSOD. Conclusion: Inflammation aggravates oncologic dose of ZA-induced mitochondrial dysfunction and oxidative stress via a SIRT1-dependent pathway, enhancing the risk of impaired mucosal healing in MRONJ. Our study implies that inflammation becomes a critical risk factor for MRONJ development at higher ZA concentrations. Elucidating the mechanisms of inflammation as a risk factor for mucosal non-healing in MRONJ could inform the development of SIRT1-targeted therapies.

Abnormal static and dynamic brain network connectivity associated with chronic tinnitus.

In order to comprehensively understand the changes of brain networks in patients with chronic tinnitus, this study combined static and dynamic analysis methods to explore the abnormalities of brain networks. Thirty-two patients with chronic tinnitus and 30 age-, sex- and education-matched healthy controls (HC) were recruited. Independent component analysis was used to identify resting-state networks (RSNs). Static and dynamic functional network connectivity (FNC) were performed. The temporal properties of brain network including mean dwell time (MDT), fraction time (FT) and numbers of transitions (NT) were calculated. Two-sample t test and Spearman's correlation were used for group compares and correlation analysis. Four RSNs showed abnormal FNC including auditory network (AUN), default mode network (DMN), attention network (AN) and sensorimotor network (SMN). For static analysis, tinnitus patients showed significantly decreased FNC in AUN-DMN, AUN-AN, DMN-AN, and DMN-SMN than HC [p < 0.05, false discovery rate (FDR) corrected]. For dynamic analysis, tinnitus patients showed significantly decreased FNC in DMN-AN in state 3 (p < 0.05, FDR corrected). MDT in state 3 was significantly decreased in tinnitus patients (t = 2.039, P = 0.046). In the tinnitus group, the score of tinnitus functional index (TFI) was negatively correlated with MDT and FT in state 4, and the duration of tinnitus was positively correlated with FT in state 1 and NT. Chronic tinnitus causes abnormal brain network connectivity. These abnormal brain networks help to clarify the mechanism of tinnitus generation and chronicity, and provide a potential basis for the treatment of tinnitus.

Soil enzyme profile analysis for indicating decomposer micro-food web.

Highly diverse exoenzymes mediate the energy flow from substrates to the multitrophic microbiota within the soil decomposer micro-food web. Here, we used a "soil enzyme profile analysis" approach to establish a series of enzyme profile indices; those indices were hypothesized to reflect micro-food web features. We systematically evaluated the shifts in enzyme profile indices in relation to the micro-food web features in the restoration of an abandoned cropland to a natural area. We found that enzymatic C:N stoichiometry and decomposability index were significantly associated with substrate availability. Furthermore, the higher Shannon diversity index in the exoenzyme profile, especially for the C-degrading hydrolase, corresponded to a greater microbiota community diversity. The increased complexity and stability of the exoenzyme network reflected similar changes with the micro-food web networks. In addition, the gross activity of the enzyme profile as a parameter for soil multifunctionality, effectively predicted the substrate content, microbiota community size, diversity, and network complexity. Ultimately, the proposed enzymic channel index was closely associated with the traditional decomposition channel indices derived from microorganisms and nematodes. Our results showed that soil enzyme profile analysis reflected very well the decomposer food web features. Our study has important implications for projecting future climate change or anthropogenic disturbance impacts on soil decomposer micro-food web features by using soil enzyme profile analysis.

Target Identification and Mechanistic Characterization of Indole Terpenoid Mimics: Proper Spindle Microtubule Assembly Is Essential for Cdh1-Mediated Proteolysis of CENP-A.

Centromere protein A (CENP-A), a histone H3 variant specific to centromeres, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure-activity relationship (SAR) study of the cell-cycle-arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)-6-Br-JP18 and (+)-6-Cl-JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X-ray crystallography analysis reveals that both molecules bind to the colchicine-binding site of ß-tubulin. Treatment of human cells with microtubule-targeting agents (MTAs), including these two compounds, results in CENP-A accumulation by destabilizing Cdh1, a co-activator of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP-A accumulation using small-molecule tools and highlights the role of Cdh1 in CENP-A proteolysis.

5,7,4'-Trimethoxyflavone triggers cancer cell PD-L1 ubiquitin-proteasome degradation and facilitates antitumor immunity by targeting HRD1.

Targeting the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway has been identified as a successful approach for tumor immunotherapy. Here, we identified that the small molecule 5,7,4'-trimethoxyflavone (TF) from Kaempferia parviflora Wall reduces PD-L1 expression in colorectal cancer cells and enhances the killing of tumor cells by T cells. Mechanistically, TF targets and stabilizes the ubiquitin ligase HMG-CoA reductase degradation protein 1 (HRD1), thereby increasing the ubiquitination of PD-L1 and promoting its degradation through the proteasome pathway. In mouse MC38 xenograft tumors, TF can activate tumor-infiltrating T-cell immunity and reduce the immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells, thus exerting antitumor effects. Moreover, TF synergistically exerts antitumor immunity with CTLA-4 antibody. This study provides new insights into the antitumor mechanism of TF and suggests that it may be a promising small molecule immune checkpoint modulator for cancer therapy.

Integrated immunogenomic analysis of single-cell and bulk profiling reveals novel tumor antigens and subtype-specific therapeutic agents in lung adenocarcinoma.

Background: In recent years, mRNA-based vaccines with promising safety and functional characteristics have gained significant momentum in cancer immunotherapy. However, stable immunological molecular subtypes of lung adenocarcinoma (LUAD) and novel tumor antigens for LUAD mRNA vaccine development remain elusive. Therefore, a novel approach is urgently needed to identify suitable LUAD subtypes and potential tumor antigens. Methods: The Cancer Genome Atlas (TCGA), the Genotype Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases were utilized to retrieve gene expression data. The LUAD Immunological Multi-Omics Classification (LIMOC) system was developed using seven machine learning (ML) algorithms by performing integrative immunogenomic analysis of single-cell and bulk tissue transcriptome profiling. Subsequently, a panel of approaches was applied to identify novel tumor antigens. Results: First, the LIMOC system was construct to identify three subtypes: LIMOC1, LIMOC2, and LIMOC3. Second, we identified CHIT1, LILRA4, and MEP1A as novel tumor antigens in LUAD; these genes were up-regulated, amplified, and mutated, and showed a positive association with APC infiltration, making them promising candidates for designing mRNA vaccines. Notably, the LIMOC2 subtype had the worst prognosis and could benefit most from mRNA immunization. Furthermore, we performed a comprehensive in silico screening of approximately 2000 compounds and identified Sorafenib and Azacitidine as potential subtype-specific therapeutic agents. Conclusions: Overall, our study established a robust LIMOC system and identified CHIT1, LILRA4, and MEP1A as promising tumor antigen candidates for development of anti-LUAD mRNA vaccines, particularly for the LIMOC2 subtype.

Shexiang Baoxin Pill enriches Lactobacillus to regulate purine metabolism in patients with stable coronary artery disease.

BACKGROUND: It has been clinically confirmed that the Shexiang Baoxin Pill (SBP) dramatically reduces the frequency of angina in patients with stable coronary artery disease (SCAD). However, potential therapeutic mechanism of SBP has not been fully explored. PURPOSE: The study explored the therapeutic mechanism of SBP in the treatment of SCAD patients. METHODS: We examined the serum metabolic profiles of patients with SCAD following SBP treatment. A rat model of acute myocardial infarction (AMI) was established, and the potential therapeutic mechanism of SBP was explored using metabolomics, transcriptomics, and 16S rRNA sequencing. RESULTS: SBP decreased inosine production and improved purine metabolic disorders in patients with SCAD and in animal models of AMI. Inosine was implicated as a potential biomarker for SBP efficacy. Furthermore, SBP inhibited the expression of genes involved in purine metabolism, which are closely associated with thrombosis, inflammation, and platelet function. The regulation of purine metabolism by SBP was associated with the enrichment of Lactobacillus. Finally, the effects of SBP on inosine production and vascular function could be transmitted through the transplantation of fecal microbiota. CONCLUSION: Our study reveals a novel mechanism by which SBP regulates purine metabolism by enriching Lactobacillus to exert cardioprotective effects in patients with SCAD. The data also provide previously undocumented evidence indicating that inosine is a potential biomarker for evaluating the efficacy of SBP in the treatment of SCAD.

Photo-Deactivation Strategy for Switchable ATRP with the Assistance of Molecular Switches.

Light irradiation is an external stimulus, rapidly developed in switchable atom transfer radical polymerization (ATRP) via photo-activation methods in recent years. Herein, a photo-deactivation strategy is introduced to regulate ATRP with the assistance of photoswitchable hexaarylbiimidozole (HABI). Under visible light irradiation and in the presence of HABI, ATRP is greatly decelerated or quenched depending on the concentration of HABI. Interestingly, with visible light off, ATRP can proceed smoothly and follow a first-order kinetics. Moreover, photo-switchable ATRP alternatively with light off and on is demonstrated. Besides, the mechanism of photo-deactivation ATRP involving radical quenching is proposed in the presence of HABI.

A systematic approach to adaptive sequential design for clinical trials: using simulations to select a design with desired operating characteristics.

The failure rates of phase 3 trials are high. Incorrect sample size due to uncertainty of effect size could be a critical contributing factor. Adaptive sequential design (ASD), which may include one or more sample size re-estimations (SSR), has been a popular approach for dealing with such uncertainties. The operating characteristics (OCs) of ASD, including the unconditional power and mean sample size, can be substantially affected by many factors, including the planned sample size, the interim analysis schedule and choice of critical boundaries and rules for interim analysis. We propose a systematic, comprehensive strategy which uses iterative simulations to investigate the operating characteristics of adaptive designs and help achieve adequate unconditional power and cost-effective mean sample size if the effect size is in a pre-identified range.

Multiple pulmonary sclerosing pneumocytoma, based on a study of 36 cases worldwide.

To analyze the clinical characteristics and to improve clinicians' understanding of multiple pulmonary sclerosing pneumocytoma (PSP) patients. A total of 36 PSP patients with multiple tumor characteristics were identified from the literature search. They were compared with 43 solitary PSP patients diagnosed and treated in our hospital in the past 5 years. Thus, the pathogenesis, clinical symptoms, diagnosis methods, treatment strategies, and prognosis of pulmonary sclerosing pneumocytoma (PSP) patients with multiple tumors were explored. Patients with multiple PSP are mostly distributed in Asia (88.89%) and are females (83.33%). PSP can be located in any one lobe (19.44%), or grow across ipsilateral lobes (44.44%), or even, bilateral lobes (36.11%). It can be accompanied by metastasis (9.09%) and is prone to misdiagnosis (27.78%). Compared with solitary PSP, the occurrence age of multiple PSP was younger (mean ± standard deviation [SD]: 40.36 ± 18.12: 51.28 ± 12.74 years), but there was no significant difference in sex, tumor size (mean ± SD: 43.54 ± 46.18: 30.56 ± 17.62 mm), or symptoms. Individualized surgical resection is required for treatment, including pneumonectomy (17.65%), lobectomy (23.53%), subpulmonary lobectomy (38.24%), or combined lobectomy (5.88%). Multiple PSP is relatively rare. Surgical resection within a limited time should be the main treatment for such patients. The prognosis of patients with multiple PSP is generally good, but inappropriate diagnosis and treatment plans may lead to poor prognosis.

Integrating single-cell and spatial analysis reveals MUC1-mediated cellular crosstalk in mucinous colorectal adenocarcinoma.

BACKGROUND: Mucinous colorectal adenocarcinoma (MCA) is a distinct subtype of colorectal cancer (CRC) with the most aggressive pattern, but effective treatment of MCA remains a challenge due to its vague pathological characteristics. An in-depth understanding of transcriptional dynamics at the cellular level is critical for developing specialised MCA treatment strategies. METHODS: We integrated single-cell RNA sequencing and spatial transcriptomics data to systematically profile the MCA tumor microenvironment (TME), particularly the interactome of stromal and immune cells. In addition, a three-dimensional bioprinting technique, canonical ex vivo co-culture system, and immunofluorescence staining were further applied to validate the cellular communication networks within the TME. RESULTS: This study identified the crucial intercellular interactions that engaged in MCA pathogenesis. We found the increased infiltration of FGF7+/THBS1+ myofibroblasts in MCA tissues with decreased expression of genes associated with leukocyte-mediated immunity and T cell activation, suggesting a crucial role of these cells in regulating the immunosuppressive TME. In addition, MS4A4A+ macrophages that exhibit M2-phenotype were enriched in the tumoral niche and high expression of MS4A4A+ was associated with poor prognosis in the cohort data. The ligand-receptor-based intercellular communication analysis revealed the tight interaction of MUC1+ malignant cells and ZEB1+ endothelial cells, providing mechanistic information for MCA angiogenesis and molecular targets for subsequent translational applications. CONCLUSIONS: Our study provides novel insights into communications among tumour cells with stromal and immune cells that are significantly enriched in the TME during MCA progression, presenting potential prognostic biomarkers and therapeutic strategies for MCA. KEY POINTS: Tumour microenvironment profiling of MCA is developed. MUC1+ tumour cells interplay with FGF7+/THBS1+ myofibroblasts to promote MCA development. MS4A4A+ macrophages exhibit M2 phenotype in MCA. ZEB1+ endotheliocytes engage in EndMT process in MCA.

Achieving deep intratumoral penetration and multimodal combined therapy for tumor through algal photosynthesis.

BACKGROUND: Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and therapeutic outcomes. RESULTS: In this study, based on the photosynthetic characteristics of algae, an active drug carrier (CP@ICG) derived from Chlorella pyrenoidosa (CP) was designed and constructed. Leveraging the hypoxia tropism and phototropism exhibited by CP, we achieved targeted transport of the carrier to tumor sites. Additionally, dual near-infrared (NIR) irradiation at the tumor site facilitated photosynthesis in CP, enabling the breakdown of excessive intratumoral interstitial fluid by generating oxygen from water decomposition. This process effectively reduced the interstitial pressure, thereby promoting enhanced perfusion of blood into the tumor, significantly improving deep-seated penetration of chemotherapeutic agents, and alleviating tumor hypoxia. CONCLUSIONS: CP@ICG demonstrated a combined effect of photothermal/photodynamic/starvation therapy, exhibiting excellent in vitro/in vivo anti-tumor efficacy and favorable biocompatibility. This work provides a scientific foundation for the application of microbial-enhanced intratumoral drug delivery and tumor therapy.

Application of Carbon Nanoparticles in Transoral Endoscopic Thyroidectomy Vestibular Approach for Unilateral Papillary Thyroid Cancer.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is newly applied technology. Carbon nanoparticles (CNs) are novel lymph node tracers that have been widely used in China to help remove central lymph nodes (CLNs) and protect the parathyroid glands (PGs) in open thyroid cancer surgery. This study is to evaluate the effectiveness and safety of CNs in TOETVA. MATERIALS AND METHODS: A total of 158 patients who underwent TOETVA with unilateral papillary thyroid carcinoma were enrolled in this study from March 2019 to February 2022. The participants were divided into a CNs group (n=88) and a control group (n=70), based on whether they received a intraoperative injection of CNs or not. Meanwhile, the CNs group were additionally divided into 2 subgroups, leakage subgroup (n=26) and standard subgroup (n=62). The 2 groups and subgroups were compared in terms of patient characteristics, perioperative clinical results, and postoperative outcomes. RESULTS: All common metrics had no significant differences were found between the CNs group and the control group ( P >0.05). The standard subgroup of CNs group had advantage over the control group on PGs identification (59/62 vs. 59/70 for superior PG, 56/62 vs. 52/70 for inferior PG, P <0.05). Moreover, the standard subgroup harvested more CLNs than the control group (8.97±2.96 vs. 7.47±2.93, P <0.05). More operation time was spent on the leakage subgroup of CNs group than the control group (160.00±17.61 vs. 140.00±13.32, P <0.05). Meanwhile, the leakage subgroup had disadvantage on intraoperative hemorrhage (26.15±10.80 vs. 21.21±7.09, P <0.05) and hospital durations (4.96±0.72 vs. 4.57±0.69, P <0.05). Furthermore, the leakage group identified fewer inferior PG than the control group (7/26 vs. 52/70, P <0.05). Contrary to the standard subgroup, the CLNs of the leakage subgroup was also unsatisfactory compared with the control group (4.96±1.84 vs. 7.47±2.93, P <0.05). CONCLUSIONS: The application of CNs suspension tracing technology has a definite effect in TOETVA. It can improve the thoroughness of lymph node dissection in the central region and enhance recognition of the PG. However, refined extracapsular anatomy is indispensable to prevent CN leakage. Leaked CNs will also be counterproductive to the operation.

Seleno-amino Acid Metabolism Reshapes the Tumor Microenvironment: from Cytotoxicity to Immunotherapy.

Selenium (Se) is an essential trace element for biological processes. Seleno-amino acids (Se-AAs), known as the organic forms of Se, and their metabolic reprogramming have been increasingly recognized to regulate antioxidant defense, enzyme activity, and tumorigenesis. Therefore, there is emerging interest in exploring the potential application of Se-AAs in antitumor therapy. In addition to playing a vital role in inhibiting tumor growth, accumulating evidence has revealed that Se-AA metabolism could reshape the tumor microenvironment (TME) and enhance immunotherapy responses. This review presents a comprehensive overview of the current progress in multifunctional Se-AAs for antitumor treatment, with a particular emphasis on elucidating the crosstalk between Se-AA metabolism and various cell types in the TME, including tumor cells, T cells, macrophages, and natural killer cells. Furthermore, novel applications integrating Se-AAs are also discussed alongside prospects to provide new insights into this emerging field.

Efficient residual network using hyperspectral images for corn variety identification.

Corn seeds are an essential element in agricultural production, and accurate identification of their varieties and quality is crucial for planting management, variety improvement, and agricultural product quality control. However, more than traditional manual classification methods are needed to meet the needs of intelligent agriculture. With the rapid development of deep learning methods in the computer field, we propose an efficient residual network named ERNet to identify hyperspectral corn seeds. First, we use linear discriminant analysis to perform dimensionality reduction processing on hyperspectral corn seed images so that the images can be smoothly input into the network. Second, we use effective residual blocks to extract fine-grained features from images. Lastly, we detect and categorize the hyperspectral corn seed images using the classifier softmax. ERNet performs exceptionally well compared to other deep learning techniques and conventional methods. With 98.36% accuracy rate, the result is a valuable reference for classification studies, including hyperspectral corn seed pictures.

A non-antibiotic erythromycin derivative improves muscle endurance by regulating endogenous anti-fatigue protein orosomucoid in mice.

At present, there are no official approved drugs for improving muscle endurance. Our previous research found acute phase protein orosomucoid (ORM) is an endogenous anti-fatigue protein, and macrolides antibiotics erythromycin can elevate ORM level to increase muscle bioenergetics and endurance parameters. Here, we further designed, synthesized and screened a new erythromycin derivative named HMS-01, which lost its antibacterial activity in vitro and in vivo. Data showed that HMS-01 could time- and dose-dependently prolong mice forced-swimming time and running time, and improve fatigue index in isolated soleus muscle. Moreover, HMS-01 treatment could increase the glycogen content, mitochondria number and function in liver and skeletal muscle, as well as ORM level in these tissues and sera. In Orm-deficient mice, the anti-fatigue and glycogen-elevation activity of HMS-01 disappeared. Therefore, HMS-01 might act as a promising small molecule drug targeting ORM to enhance muscle endurance.

Adaptive sequential design for phase II single-arm oncology trials: an expansion of Simon's design.

Single-arm phase II trials are very common in oncology. A fixed sample trial may lack sufficient power if the true efficacy is less than the assumed one. Adaptive designs have been proposed in the literature. We propose a Simon's design based, adaptive sequential design. Simon's design is the most used fixed sample design for single-arm phase II oncology trials. A prominent feature of Simon's design is that it minimizes the sample size when there is no clinically meaningful efficacy. We identify Simon's trial as a special group sequential design. Established methods for sample size re-estimation (SSR) can be readily applied to Simon's design. Simulations show that simply adding SSR to Simon's design may still not provide desirable power. We propose some expansions to Simon's design. The expanded design with SSR can provide even more power.

Visible-Light-Mediated Three-Component Strategy for the Synthesis of Isoxazolines and Isoxazoles.

Isoxazolines and isoxazoles commonly serve as core structures of many therapeutic agents and natural products. However, the metal-free and catalysis-free strategy for the synthesis of these privileged motifs at room temperature remains a challenging task. Herein, we report a three-component strategy to afford diverse isoxazolines and isoxazoles via [3 + 2] cycloadditions of in situ-formed nitronates and olefins/alkynes under visible-light irradiation.

In Silico Discovery of Stapled Peptide Inhibitor Targeting the Nur77-PPARγ Interaction and Its Anti-Breast-Cancer Efficacy.

The binding of peroxisome proliferator-activated receptor γ (PPARγ) to the orphan nuclear receptor Nur77 facilitates the ubiquitination and degradation of Nur77, and leads to aberrant fatty acid uptake for breast cancer progression. Because of its crucial role in clinical prognosis, the interaction between Nur77 and PPARγ is an attractive target for anti-breast-cancer therapy. However, developing an inhibitor of the Nur77-PPARγ interaction poses a technical challenge due to the absence of the crystal structure of PPARγ and its corresponding interactive model with Nur77. Here, ST-CY14, a stapled peptide, is identified as a potent modulator of Nur77 with a KD value of 3.247 × 10-8 M by in silico analysis, rational design, and structural modification. ST-CY14 effectively increases Nur77 protein levels by blocking the Nur77-PPARγ interaction, thereby inhibiting lipid metabolism in breast tumor cells. Notably, ST-CY14 significantly suppresses breast cancer growth and bone metastasis in mice. The findings demonstrate the feasibility of exploiting directly Nur77-PPARγ interaction in breast cancer, and generate what to the best knowledge is the first direct inhibitor of the Nur77-PPARγ interaction available for impeding fatty acid uptake and therapeutic development.

Safety-Preserving Lyapunov-Based Model Predictive Rendezvous Control for Heterogeneous Marine Vehicles Subject to External Disturbances.

This article investigates the cooperative rendezvous control problem for perturbed heterogeneous marine systems composed of an autonomous underwater vehicle (AUV) and an autonomous surface vehicle (ASV). A novel Lyapunov-based model predictive control (LMPC) framework is presented to accomplish safe and precise rendezvous under input limitations and external disturbances. First, by incorporating the prescribed performance control (PPC) technique into the LMPC framework, we transform the original ascending state of the AUV into a self-constrained state, which serves as the decision variable of the model predictive control (MPC) optimization problem. Then, PPC-aided auxiliary control laws based on disturbance observers (DOBs) are designed to establish a robust contractive constraint to provide stability margins. Combining the LMPC with the PPC technique makes the original state-constrained problem an equivalent state-constraint-free problem. By addressing the MPC problem for the equivalent unconstrained system, the proposed method preserves the rendezvous safety. With the robust contractive constraint, the proposed safety-preserving LMPC (SP-LMPC) controller can inherit robustness and stability from the robust auxiliary control laws. Furthermore, theoretical analyses are conducted to assess recursive feasibility and closed-loop stability. With comprehensive theoretical support, the proposed method provides a new framework to simultaneously address state constraints and disturbances for highly nonlinear marine systems. Finally, simulations and comparisons are conducted to demonstrate the effectiveness and advantages of the proposed algorithm.