Correlation between Serum 25 (OH) D Levels with Insulin Resistance and Metabolic Associated Fatty Liver Disease - A Retrospective Study based on Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

AIMS: The objective of this study was to investigate the correlation between serum 25 hydroxyvitamin D [25(OH)D] levels and insulin resistance, as well as metabolic associated fatty liver disease (MAFLD) in newly diagnosed with type 2 diabetes mellitus(T2DM) patients. METHOD: A retrospective analysis was conducted on 491 T2DM patients who were newly diagnosed between January 2017 and August 2022 at Peking University International Hospital. These patients were categorized into three groups based on their 25(OH)D levels. RESULTS: The prevalence of MAFLD was significantly elevated in both the Vitamin D(VD) deficiency group and the VD insufficiency group compared to the VD sufficiency group (χ2 = 6.51, p<0.05). The patients in the VD sufficiency group had lower levels of insulin resistance，as assessed by the homeostasis model assessment when compared to the VD deficiency group and the VD insufficiency group (F = 8.61，p < 0.05). Additionally, the VD sufficiency group demonstrated higher levels of ß cell function in comparison to the other two groups(p<0.05， respectively). (2) A significant negative correlation was observed between 25(OH)D levels and insulin resistance, as assessed by the homeostasis model assessment in T2DM patients(r=-0.33，p<0.05 for females; r=-0.32，p<0.05 for males). (3) In male patients, 25(OH)D was identified as a protective factor against MAFLD(OR = 0.42;95%CI:0.19-0.95;p<0.05). Meanwhile，in female patients, 25(OH)D was also associated with a reduced risk of MAFLD(OR = 0.35;95%CI 0.17-0.89;p<0.05). Additionally, the study determined that the threshold values for 25(OH)D were 15.06 ng/ml in female patients and 18.79 ng/ml in male patients for predicting MAFLD. CONCLUSION: In newly diagnosed with T2DM patients, the level of 25(OH)D may be related to insulin resistance and ß cell secretion function independently and VD deficiency is an independent risk factor for MAFLD in patients with newly diagnosed T2DM.

HIV associated lymphoma: latest updates from 2023 ASH annual meeting.

The incidence, clinical characteristics, and prognostic factors of HIV-associated lymphoma remain poorly defined compared to HIV-negative lymphoma. Currently, there are no standard guidelines for treatment of these patients. We summarized several latest reports of HIV associated lymphoma from the 2023 ASH Annual Meeting (ASH2023).

Juvenile dermatomyositis with central nervous system involvement: two case reports from a retrospective single-center cohort, with literature review.

Background: Juvenile dermatomyositis (JDM) is a systemic autoimmune disease primarily involving the muscles and skin; it can also affect the central nervous system (CNS). The relevant literature provides limited information regarding the characteristics of JDM with CNS involvement. Method: We reviewed patients with JDM who were hospitalized at our center between January 2016 and August 2023, with a focus on those with CNS involvement. The aim was to provide detailed case reports on these patients, and to summarize the relevant literature about the characteristics of similar cases. Results: Among 193 hospitalized patients with JDM, two (1.03%) had CNS involvement. Two patients, a 5.5-year-old girl and an 11-year-old boy, were admitted with severe proximal muscle weakness and seizures, and presented with active cutaneous vasculitis. Both were ultimately diagnosed with JDM, with CNS involvement. Both patients had confirmed presence of anti-NXP2 antibody through myositis-specific antibody analysis. Additionally, they all exhibited hyperferritinemia and thrombocytopenia. Salvage therapies like intravenous methylprednisolone (IVMP) pulse therapy and/or plasma exchange were administered successfully. At final follow-up, both patients had achieved complete clinical response and full neurological recovery. Our literature review identified nine similar case studies. CNS involvement usually occurred within the first 10 months of the disease course, and most of these patients had fatal outcomes, with a mortality rate of 66.6% (6/9). Including the two patients described herein, the median age for disease onset is 10.5 years (range 4-17 years), and the male: female ratio is 6:5. Seizures are the most common neurological symptom, accompanied by active cutaneous vasculitis. The brain biopsies showed two distinct pathological presentations: one was central nervous system vasculitis, and the other was cerebral macrophage activation syndrome. Conclusions: CNS involvement is a rare but life-threatening JDM complication. Herein, our cases and the literature indicate that it typically occurs within the first 10 months of the disease course and manifests as seizures, often accompanied by active cutaneous vasculitis, with fatal outcomes. Timely implementation of salvage therapies, like IVMP pulse therapy and plasma exchange, may significantly impact patient outcomes.

Successful Treatment of Severe Steroid-Resistant Engraftment Syndrome Following Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia with Emapalumab: A Case Report.

Engraftment syndrome (ES) is an early complication of hematopoietic stem cell transplantation (HSCT) characterized by fever and additional clinical manifestations including rash, diarrhea, lung infiltrates, weight gain, and neurological symptoms. Steroid-resistant ES following HSCT significantly affects the efficacy of transplantation and may even result in patient mortality. As ES essentially represents a cytokine storm induced by engrafted donor cells with interferon-gamma (IFN-γ) playing a central role, we hypothesized that emapalumab (an anti-IFN-γ monoclonal antibody) may be an effective approach to treat steroid-resistant ES. Here, we present a case report of a 14-year-old female patient who received a second haploidentical HSCT due to a relapse of acute myeloid leukemia. Nine days after the transplantation, the patient developed a fever and exhibited a poor response to antimicrobials (ceftazidime/avibactam). A few days later, the patient presented with a new-onset rash, weight gain, and impaired liver function, leading to a diagnosis of ES. Initial immunosuppressive (tacrolimus and mycophenolate mofetil) treatment failed to control the disease. On day 16 post-transplantation, the patient received two infusions of 50 mg of emapalumab. Following the initiation of emapalumab treatment, the patient's fever returned to normal and ES was effectively controlled. This case report demonstrated that emapalumab had a possible efficacy for steroid-resistant ES and provided a novel therapeutic strategy to treat this clinical complication.

Hg2+-enhanced oxidase-like activity of platinum nanoparticles immobilized on porphyrin-based porous organic polymer for the colorimetric detection and removal of Hg2.

Porphyrin-based porous organic polymer (POP) with uniformly immobilized platinum nanoparticles (Pt NPs) were designed and synthesized, and it was demonstrated that such nanocomposites (Pt/POP) have oxidase-like activity. Surprisingly, Hg2+ significantly enhanced the oxidase-like activity of Pt/POP. The enhancement was attributed to the capture of Hg2+ by the thioether group in Pt/POP and the subsequent redox reaction of Hg2+ with Pt NPs, accelerating the electron transfer. In the presence of Hg2+, Pt/POP catalyzed the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to turn blue rapidly and changed its absorbance at 652 nm. Based on this, a fast-response colorimetric sensor was constructed for the sensitive detection of Hg2+ with a linear range of 0.2-50 µM and a detection limit of 36.5 nM. Importantly, Pt/POP can be used as an adsorbent for the efficient removal of Hg2+ with a removal efficiency as high as 99.4%. This work provides a valuable strategy for colorimetric detection and efficient removal of Hg2+.

Transition experiences of patients with post stroke dysphagia and family caregivers: A longitudinal, qualitative study.

BACKGROUND: Stroke patients with dysphagia and family caregivers will experience multiple transitions during the whole process of the disease and various nursing needs will be generated. There is a lack of knowledge about their experiences at different transition stages. Thus, we aimed to explore the transition experiences of patients with post stroke dysphagia and family caregivers from admission to discharge home. METHODS: A semi-structured interview based on Meleis's transition theory was used during hospitalization and telephone follow-up interviews were conducted in the first, third, and sixth month after the diagnosis of dysphagia. Interview transcripts were analyzed using the conventional content analysis method. RESULTS: A total of 17 participants enrolled in the first face-to-face interview, 16 participants took part in the first month's telephone follow-up interview, 14 participants in the third month, and 12 participants in the sixth month. The transition experiences of patients with post stroke dysphagia and family caregivers could be summarized into three themes: (1)transition from onset to admission; (2)transition from discharge to other rehabilitation institutions; and (3)transition from discharge to home. Each theme had identified interrelated subthemes. CONCLUSIONS: The experiences of patients with post stroke dysphagia and family caregivers during transition are a dynamic process with enormous challenges in each phase. Collaboration with health care professionals, follow-up support after discharge, and available community and social support should be integrated into transitional nursing to help patients facilitate their transition.

The role of KLRG1: a novel biomarker and new therapeutic target.

Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy.

Dual-Mechanism Peptide SR25 has Broad Antimicrobial Activity and Potential Application for Healing Bacteria-infected Diabetic Wounds.

The rise of antibiotic resistance poses a significant public health crisis, particularly due to limited antimicrobial options for the treatment of infections with Gram-negative pathogens. Here, an antimicrobial peptide (AMP) SR25 is characterized, which effectively kills both Gram-negative and Gram-positive bacteria through a unique dual-targeting mechanism without detectable resistance. Meanwhile, an SR25-functionalized hydrogel is developed for the efficient treatment of infected diabetic wounds. SR25 is obtained through genome mining from an uncultured bovine enteric actinomycete named Nonomuraea Jilinensis sp. nov. Investigations reveal that SR25 has two independent cellular targets, disrupting bacterial membrane integrity and restraining the activity of succinate:quinone oxidoreductase (SQR). In a diabetic mice wound infection model, the SR25-incorporated hydrogel exhibits high efficacy against mixed infections of Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), accelerating wound healing. Overall, these findings demonstrate the therapeutic potential of SR25 and highlight the value of mining drugs with multiple mechanisms from uncultured animal commensals for combating challenging bacterial pathogens.

Proton energy enhancement by optimizing a laser pulse profile.

Based on current laboratory laser parameters and the low density target that is induced by the inevitable prepulse, we propose what we believe to be a new scheme to enhance the proton energy by employing a laser pulse with two different peak intensities. Initially, the lower-intensity peak of the laser pulse P1, irradiates the low-density plasma target induced by the prepulse to form a significantly denser plasma target. Such a compressed high-density target is critical for supporting the subsequent main pulse P2 with higher peak intensity to drive proton acceleration. As an example, particle-in-cell (PIC) simulations reveal that when using a circularly polarized (CP) flat-top P1 with a peak intensity of approximately 1.71 × 10 19 W/cm2, full-width at half-maximum(FWHM) duration of 325 fs and a CP P2 with a peak intensity of 1.54 × 10 22 W/cm2, FWHM duration of 26.5 fs, and focal spot radius of 4 µm successively acting on a target with an initial density of 8nc, protons with cut-off energy of 940 MeV can be obtained from the cascaded acceleration scheme. Compared with the case without P1, the cutoff energy increased by 340 MeV. Owing to the intervention of P1, this scheme overcomes the limitation of laser contrast and is more feasible to be implemented experimentally.

Targeting neddylation and sumoylation in chemoresistant triple negative breast cancer.

Triple negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases in the United States. Systemic neoadjuvant chemotherapy (NACT), with or without immunotherapy, is the current standard of care for patients with early-stage TNBC. However, up to 70% of TNBC patients have significant residual disease once NACT is completed, which is associated with a high risk of developing recurrence within two to three years of surgical resection. To identify targetable vulnerabilities in chemoresistant TNBC, we generated longitudinal patient-derived xenograft (PDX) models from TNBC tumors before and after patients received NACT. We then compiled transcriptomes and drug response profiles for all models. Transcriptomic analysis identified the enrichment of aberrant protein homeostasis pathways in models from post-NACT tumors relative to pre-NACT tumors. This observation correlated with increased sensitivity in vitro to inhibitors targeting the proteasome, heat shock proteins, and neddylation pathways. Pevonedistat, a drug annotated as a NEDD8-activating enzyme (NAE) inhibitor, was prioritized for validation in vivo and demonstrated efficacy as a single agent in multiple PDX models of TNBC. Pharmacotranscriptomic analysis identified a pathway-level correlation between pevonedistat activity and post-translational modification (PTM) machinery, particularly involving neddylation and sumoylation targets. Elevated levels of both NEDD8 and SUMO1 were observed in models exhibiting a favorable response to pevonedistat compared to those with a less favorable response in vivo. Moreover, a correlation emerged between the expression of neddylation-regulated pathways and tumor response to pevonedistat, indicating that targeting these PTM pathways may prove effective in combating chemoresistant TNBC.

Priming of hippocampal microglia by IFN-γ/STAT1 pathway impairs social memory in mice.

Social behavior is inextricably linked to the immune system. Although IFN-γ is known to be involved in social behavior, yet whether and how it encodes social memory remains unclear. In the current study, we injected with IFN-γ into the lateral ventricle of male C57BL/6J mice, and three-chamber social test was used to examine the effects of IFN-γ on their social preference and social memory. The morphology of microglia in the hippocampus, prelimbic cortex and amygdala was examined using immunohistochemistry, and the phenotype of microglia were examined using immunohistochemistry and enzyme-linked immunosorbent assays. The IFN-γ-injected mice were treated with lipopolysaccharide, and effects of IFN-γ on behavior and microglial responses were evaluated. STAT1 pathway and microglia-neuron interactions were examined in vivo or in vitro using western blotting and immunohistochemistry. Finally, we use STAT1 inhibitor or minocycline to evaluated the role of STAT1 in mediating the microglial priming and effects of primed microglia in IFN-γ-induced social dysfunction. We demonstrated that 500 ng of IFN-γ injection results in significant decrease in social index and social novelty recognition index, and induces microglial priming in hippocampus, characterized by enlarged cell bodies, shortened branches, increased expression of CD68, CD86, CD74, CD11b, CD11c, CD47, IL-33, IL-1ß, IL-6 and iNOS, and decreased expression of MCR1, Arg-1, IGF-1 and BDNF. This microglia subpopulation is more sensitive to LPS challenge, which characterized by more significant morphological changes and inflammatory responses, as well as induced increased sickness behaviors in mice. IFN-γ upregulated pSTAT1 and STAT1 and promoted the nuclear translocation of STAT1 in the hippocampal microglia and in the primary microglia. Giving minocycline or STAT1 inhibitor fludarabin blocked the priming of hippocampal microglia induced by IFN-γ, ameliorated the dysfunction in hippocampal microglia-neuron interactions and synapse pruning by microglia, thereby improving social memory deficits in IFN-γ injected mice. IFN-γ initiates STAT1 pathway to induce priming of hippocampal microglia, thereby disrupts hippocampal microglia-neuron interactions and neural circuit link to social memory. Blocking STAT1 pathway or inhibiting microglial priming may be strategies to reduce the effects of IFN-γ on social behavior.

Type VII secretion system extracellular protein B targets STING to evade host anti-Staphylococcus aureus immunity.

Staphylococcus aureus (S. aureus) can evade antibiotics and host immune defenses by persisting within infected cells. Here, we demonstrate that in infected host cells, S. aureus type VII secretion system (T7SS) extracellular protein B (EsxB) interacts with the stimulator of interferon genes (STING) protein and suppresses the inflammatory defense mechanism of macrophages during early infection. The binding of EsxB with STING disrupts the K48-linked ubiquitination of EsxB at lysine 33, thereby preventing EsxB degradation. Furthermore, EsxB-STING binding appears to interrupt the interaction of 2 vital regulatory proteins with STING: aspartate-histidine-histidine-cysteine domain-containing protein 3 (DHHC3) and TNF receptor-associated factor 6. This persistent dual suppression of STING interactions deregulates intracellular proinflammatory pathways in macrophages, inhibiting STING's palmitoylation at cysteine 91 and its K63-linked ubiquitination at lysine 83. These findings uncover an immune-evasion mechanism by S. aureus T7SS during intracellular macrophage infection, which has implications for developing effective immunomodulators to combat S. aureus infections.

Discrimination of three commercial tuna species through species-specific peptides: From high-resolution mass spectrometry discovery to MRM validation.

The risk of tuna adulteration is high driven by economic benefits. The authenticity of tuna is required to protect both consumers and tuna stocks. Given this, the study is designed to identify species-specific peptides for distinguishing three commercial tropical tuna species. The peptides derived from trypsin digestion were separated and detected using ultrahigh-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) in data-dependent acquisition (DDA) mode. Venn analysis showed that there were differences in peptide composition among the three tested tuna species. The biological specificity screening through the National Center for Biotechnology Information's Basic Local Alignment Search Tool (NCBI BLAST) revealed that 93 peptides could serve as potential species-specific peptides. Finally, the detection specificity of species-specific peptides of raw meats and processed products was carried out by multiple reaction monitoring (MRM) mode based on a Q-Trap mass spectrometer. The results showed that three, one and two peptides of Katsuwonus pelamis, Thunnus obesus and Thunnus albacores, respectively could serve as species-specific peptides.

Development and validation of a nomogram for preoperative prediction of ipsilateral cervical central lymph node metastasis in papillary thyroid cancer: a population-based study.

Background: The incidence of papillary thyroid cancer (PTC) has increased dramatically, and it is susceptible to cervical lymph node metastasis (LNM), predominantly in the ipsilateral cervical central lymph node metastasis (CLNM). Ipsilateral cervical CLNM affects patients' surgical options and survival rates. In this study, we integrated multiple factors to establish a nomogram-based preoperative prediction model of ipsilateral cervical CLNM in PTC. Methods: Data were retrospectively collected from 609 patients with PTC admitted to Peking University International Hospital, all of whom underwent ipsilateral cervical lymph node dissection. They were randomly divided into a modeling set and validation set in the ratio of 7:3. Binary logistic regression was used to analyze independent risk factors for ipsilateral cervical CLNM in PTC and to construct a nomogram model. The performance of nomogram CLNM prediction was evaluated by the receiver operating characteristic (ROC) curve and calibration curve. Results: Binary Logistic Regression showed that age, history of osteoporosis, complicated by Hashimoto's thyroiditis, enlarged lymph nodes in the central neck, and extrathyroidal extension were risk factors for ipsilateral cervical CLNM. Combining these five independent risk factors, a nomogram prediction model was developed. In the modeling set, the area under the curve (AUC) of the nomogram ROC was 0.782 [95% confidence interval (CI): 0.730-0.833], and the sensitivity and specificity of the model were 0.761 and 0.763, respectively, with a well-calibrated curve fit. Moreover, the model presented better discrimination than any of the independent risk factors. The nomogram performed well in the validation set (AUC 0.753; 95% CI: 0.648-0.858). Conclusions: A non-invasive, and accurate nomogram prediction model for ipsilateral cervical CLNM of PTC was established. It can help physicians identify patients with a high risk of ipsilateral cervical CLNM of PTC preoperative for individualized treatment.

Differentiation of three commercial tuna species through GC-Q-TOF and UPLC-Q/Orbitrap mass spectrometry-based metabolomics and chemometrics.

Food fraud is common in the tuna industry because of the economic benefits involved. Ensuring the authenticity of tuna species is crucial for protecting both consumers and tuna stocks. In this study, GC-Q-TOF and UPLC-Q/Orbitrap mass spectrometry-based metabolomics were used to investigate the metabolite profiles of three commercial tuna species (skipjack tuna, bigeye tuna and yellowfin tuna). A total of 22 and 77 metabolites were identified with high confidence using GC-Q-TOF and UPLC-Q/Orbitrap mass spectrometry, respectively. Further screening via chemometrics revealed that 38 metabolites could potentially serve as potential biomarkers. Hierarchical cluster analysis showed that the screened metabolite biomarkers successfully distinguished the three tested tuna species. Furthermore, a total of 27 metabolic pathways were identified through enrichment analysis based on the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways.

Elevations in presepsin, PCT, hs-CRP, and IL-6 levels predict mortality among septic patients in ICU.

BACKGROUND: Aim to investigate the predictive value of changes in presepsin (PSEP), procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) levels to for mortality in septic patients in intensive care unit (ICU). METHOD: This study enrolled septic patients between November 2020 and December 2021. Levels of PSEP, PCT, hsCRP, and IL-6 were measured on 1st (PSEP_0, PCT_0, hsCRP_0, IL-6_0) and 3rd day (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. RESULTS: The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional-hazards regression (Cox) analysis, △PSEP (= PSEP_3- PSEP_0) > 211.49 pg/ml (hazard ratio (HR) 2.70, 95% confidence interval (CI) 1.17-6.22), △PCT (= PCT_3- PCT_0) > -0.13 ng/ml (HR 7.31, 95% CI 2.68-19.80), △hsCRP (= hsCRP_3- hsCRP_0) > -19.29 mg/L (HR 6.89, 95% CI 1.61-29.40), and △IL-6 (= IL-6_3- IL-6_0) > 1.00 pg/ml (HR 3.13, 95% CI 1.35-7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all four distinct biomarkers was highest (concordance index 0.83, 95% CI 0.76-0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the APACHE Ⅱ and SOFA scores, the combination of the four biomarkers had a larger net benefit. Interestingly, IL-6 was predominantly produced by monocytes upon LPS stimulation in PBMCs. CONCLUSIONS: △PSEP, △PCT, △hsCRP, and △IL-6 are reliable biomarkers for predicting mortality in septic patients in ICU, and their combination has the best performance.

Quantification of Allergic Crustacean Tropomyosin Using Shared Signature Peptides in Processed Foods with a Mass Spectrometry-Based Proteomic Strategy.

Crustacean shellfish are major allergens in East Asia. In the present study, a major allergic protein in crustaceans, tropomyosin, was detected accurately using multiple reaction monitoring mode-based mass spectrometry, with shared signature peptides identified through proteomic analysis. The peptides were deliberately screened through thermal stability and enzymatic digestion efficiency to improve the suitability and accuracy of the developed method. Finally, the proposed method demonstrated a linear range of 0.15 to 30 mgTM/kgfood (R2 > 0.99), with a limit of detection of 0.15 mgTM/kg food and a limit of quantification of 0.5mgTM/kgfood and successfully applied to commercially processed foods, such as potato chips, biscuits, surimi, and hot pot seasonings, which evidenced the applicability of proteomics-based methodology for food allergen analysis.

Unraveling novel umami peptides from yeast extract (Saccharomyces cerevisiae) using peptidomics and molecular interaction modeling.

Yeast extract is increasingly becoming an attractive source for unraveling novel umami peptides that are healthier and more nutritious than traditional seasonings. In the present study, a strategy for screening novel umami peptides was established using mass spectrometry-based peptidomics combined with molecular interaction modeling, emphasizing on smaller peptides than previously reported. Four representative novel umami peptides of FE, YDQ, FQEY, and SPFSQ from yeast extract (Saccharomyces cerevisiae) were identified and validated by sensory evaluation, with thresholds determined as 0.234 ± 0.045, 0.576 ± 0.175, 0.327 ± 0.057 and 0.456 ± 0.070 mmol/L, respectively. Hydrogen and ionic bonds were the main characteristic interactions between the umami peptides and the well-recognized receptor T1R1/T1R3, in which Asp 110, Thr 112, Arg 114, Arg 240, Lys 342, and Glu 264 were the key sites in ligand-receptor recognition. Our study provides accurate sequences of umami peptides and molecular interaction mechanism for the umami effect.

Cell-membrane engineering strategies for clinic-guided design of nanomedicine.

Cells are the fundamental units of life. The cell membrane primarily composed of two layers of phospholipids (a bilayer) structurally defines the boundary of a cell, which can protect its interior from external disturbances and also selectively exchange substances and conduct signals from the extracellular environment. The complexity and particularity of transmembrane proteins provide the foundation for versatile cellular functions. Nanomedicine as an emerging therapeutic strategy holds tremendous potential in the healthcare field. However, it is susceptible to recognition and clearance by the immune system. To overcome this bottleneck, the technology of cell membrane coating has been extensively used in nanomedicines for their enhanced therapeutic efficacy, attributed to the favorable fluidity and biocompatibility of cell membranes with various membrane-anchored proteins. Meanwhile, some engineering strategies of cell membranes through various chemical, physical and biological ways have been progressively developed to enable their versatile therapeutic functions against complex diseases. In this review, we summarized the potential clinical applications of four typical cell membranes, elucidated their underlying therapeutic mechanisms, and outlined their current engineering approaches. In addition, we further discussed the limitation of this technology of cell membrane coating in clinical applications, and possible solutions to address these challenges.