Abiotic aerobic oxidation pathways of stibnite revealed by oxygen and sulfur isotope systematics of sulfate.

The environmental threat posed by stibnite is an important geoenvironmental issue of current concern. To better understand stibnite oxidation pathways, aerobic abiotic batch experiments were conducted in aqueous solution with varying δ18OH2O value at initial neutral pH for different lengths of time (15-300 days). The sulfate oxygen and sulfur isotope compositions as well as concentrations of sulfur and antimony species were determined. The sulfur isotope fractionation factor (Δ34SSO4-stibnite) values decreased from 0.8‰ to -2.1‰ during the first 90 days, and increased to 2.6‰ at the 180 days, indicating the dominated intermediate sulfur species such as S2O32-, S0, and H2S (g) involved in Sb2S3 oxidation processes. The incorporation of O into sulfate derived from O2 (∼100%) indicated that the dissociated O2 was only directly adsorbed on the stibnite-S sites in the initial stage (0-90 days). The proportion of O incorporation into sulfate from water (27%-52%) increased in the late stage (90-300 days), which suggested the oxidation mechanism changed to hydroxyl attack on stibnite-S sites promoted by nearby adsorbed O2 on stibnite-Sb sites. The exchange of oxygen between sulfite and water may also contributed to the increase of water derived O into SO42-. The new insight of stibnite oxidation pathway contributes to the understanding of sulfide oxidation mechanism and helps to interpret field data.

The correlation between the level of cellular classification in bronchoalveolar lavage fluid of children with severe Mycoplasma pneumoniae and clinical characteristics.

Mycoplasma pneumoniae pneumonia (MPP) is a common respiratory tract infection disease in children. To date, there have been few studies on the relationship between cytological changes in bronchoalveolar lavage fluid (BALF) and clinical features. The objective of this study is to investigate the correlation between changes in the proportion of cell classifications in BALF and the clinical features in children with severe MPP (SMPP). In total, the study included 64 children with SMPP requiring bronchoalveolar lavage who were admitted to our hospital between March and September 2022 (study group) and 11 children with bronchial foreign bodies without co-infection (control group), who were admitted during the same period. The proportion of cell classifications in BALF was determined by microscopic examination after performing Wright-Giemsa staining. Patients were grouped according to different clinical characteristics, and between-group comparisons were made regarding the variations in the proportion of cell classifications in BALF. The levels of blood routine neutrophil percentage (GRA%), C-reactive protein, D-dimer and lactate dehydrogenase in the study group were higher than those in the control group (P < 0.05). There were differences in the GRA% and macrophage percentage in the BALF between the two groups (P < 0.05). The GRA% and blood lymphocyte percentage were associated with pleural effusion. Multiple indicators correlated with extrapulmonary manifestations (P < 0.05). Moreover, the percentage of lymphocytes in the BALF correlated with pleural effusion, extrapulmonary manifestations and refractory MPP (RMPP) (P < 0.05). Logistic regression showed that BALF lymphocytes were protective factors for RMPP, while serum amyloid A and extrapulmonary manifestations were risk factors (P < 0.05). CONCLUSION: The BALF of children with SMPP is predominantly neutrophilic. A lower percentage of lymphocytes is related to a higher incidence of pleural effusion, extrapulmonary manifestations and progression to RMPP, as well as a longer length of hospitalisation. WHAT IS KNOWN: • Mycoplasma pneumonia in children is relatively common in clinical practice. Bronchoalveolar lavage (BAL) is a routine clinical procedure. WHAT IS NEW: However, there are relatively few studies focusing on the cytomorphological analysis of cells in BAL fluid.

Development and internal validation of a model for predicting cefoperazone/sulbactam-associated coagulation disorders in Chinese inpatients.

BACKGROUND AND AIM: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. METHODS: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn't develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. RESULTS: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770). CONCLUSIONS: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation.

Realm of hepatitis E: Challenges and opportunities.

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

Serum anti­KIAA0513 antibody as a common biomarker for mortal atherosclerotic and cancerous diseases.

Numerous antibody biomarkers have been reported for cancer and atherosclerosis-related diseases. The major complications of atherosclerosis and diabetes mellitus (DM) are acute ischemic stroke (AIS), cardiovascular disease (CVD) and chronic kidney disease (CKD). Cancer development is accompanied by arterial disorders, such as angiogenesis and atherosclerosis, and DM is a risk factor for the development of certain types of cancer. Atherosclerosis-related diseases and cancers are therefore interrelated and could be detected using a common biomarker. In the present study, the initial screening using the protein array method identified KIAA0513 as an antigen recognized by serum IgG antibodies in patients with atherosclerosis. The amplified luminescent proximity homogeneous assay-linked immunosorbent assay revealed significantly higher serum antibody levels against recombinant KIAA0513 protein in patients with AIS, transient ischemic attack (TIA), DM, CVD, obstructive sleep apnea syndrome (OSAS), CKD and solid cancers, such as esophageal, gastric, colon, lung and breast cancers, compared with healthy donors. A receiver operating characteristic (ROC) analysis revealed that the highest areas under the ROC curves of anti-KIAA0513 antibodies were obtained for esophageal cancer, nephrosclerosis-type CKD and DM. Spearman's correlation analysis revealed that serum anti-KIAA0513 antibody levels were associated with maximum intima-media thickness and plaque score, which are indices of atherosclerosis and stenosis. Serum anti-KIAA0513 antibody markers appear to be useful for diagnosing AIS, TIA, DM, CVD, OSAS, CKD and solid cancers, and may reflect common arterial alterations leading to atherosclerotic and cancerous diseases.

Dysregulated Wnt/ß-catenin signaling confers resistance to cuproptosis in cancer cells.

Cuproptosis is characterized by the aggregation of lipoylated enzymes of the tricarboxylic acid cycle and subsequent loss of iron-sulfur cluster proteins as a unique copper-dependent form of regulated cell death. As dysregulation of copper homeostasis can induce cuproptosis, there is emerging interest in exploiting cuproptosis for cancer therapy. However, the molecular drivers of cancer cell evasion of cuproptosis were previously undefined. Here, we found that cuproptosis activates the Wnt/ß-catenin pathway. Mechanistically, copper binds PDK1 and promotes its interaction with AKT, resulting in activation of the Wnt/ß-catenin pathway and cancer stem cell (CSC) properties. Notably, aberrant activation of Wnt/ß-catenin signaling conferred resistance of CSCs to cuproptosis. Further studies showed the ß-catenin/TCF4 transcriptional complex directly binds the ATP7B promoter, inducing its expression. ATP7B effluxes copper ions, reducing intracellular copper and inhibiting cuproptosis. Knockdown of TCF4 or pharmacological Wnt/ß-catenin blockade increased the sensitivity of CSCs to elesclomol-Cu-induced cuproptosis. These findings reveal a link between copper homeostasis regulated by the Wnt/ß-catenin pathway and cuproptosis sensitivity, and suggest a precision medicine strategy for cancer treatment through selective cuproptosis induction.

Myeloid sarcoma with maxillary gingival swelling as the initial symptom: A case report and review of literature.

BACKGROUND: Myeloid sarcoma (MS), also referred to as granulocytic sarcoma or chloroma, is a rare type of extramedullary malignant tumor. MS comprises primitive granulocytic precursor cells that play a key role in the early stages of white blood cell development. Notably, the occurrence of this tumor in the gingiva is rare. CASE SUMMARY: The present study reported the case of MS with gingival swelling in the maxillary region, with aleukemic presentation in a 32-year-old male patient. Following two courses of chemotherapy, computed tomography of the region demonstrated complete clearance of the tumor. At the 12-month follow-up appointment, the patient was in a stable condition with the absence of progression. The etiology, clinical features, diagnosis, and relevant treatment of MS are discussed in the present study. CONCLUSION: Diagnosis of MS may be confirmed following histological and immunohistochemical examinations.

Processing and validation of inpatient Medicare Advantage data for use in hospital outcome measures.

OBJECTIVE: To determine the feasibility of integrating Medicare Advantage (MA) admissions into the Centers for Medicare & Medicaid Services (CMS) hospital outcome measures through combining Medicare Advantage Organization (MAO) encounter- and hospital-submitted inpatient claims. DATA SOURCES AND STUDY SETTING: Beneficiary enrollment data and inpatient claims from the Integrated Data Repository for 2018 Medicare discharges. STUDY DESIGN: We examined timeliness of MA claims, compared diagnosis and procedure codes for admissions with claims submitted both by the hospital and the MAO (overlapping claims), and compared demographic characteristics and principal diagnosis codes for admissions with overlapping claims versus admissions with a single claim. DATA COLLECTION/EXTRACTION METHODS: We combined hospital- and MAO-submitted claims to capture MA admissions from all hospitals and identified overlapping claims. For admissions with only an MAO-submitted claim, we used provider history data to match the National Provider Identifier on the claim to the CMS Certification Number used for reporting purposes in CMS outcome measures. PRINCIPAL FINDINGS: After removing void and duplicate claims, identifying overlapped claims between the hospital- and MAO-submitted datasets, restricting claims to acute care and critical access hospitals, and bundling same admission claims, we identified 5,078,611 MA admissions. Of these, 76.1% were submitted by both the hospital and MAO, 14.2% were submitted only by MAOs, and 9.7% were submitted only by hospitals. Nearly all (96.6%) hospital-submitted claims were submitted within 3 months after a one-year performance period, versus 85.2% of MAO-submitted claims. Among the 3,864,524 admissions with overlapping claims, 98.9% shared the same principal diagnosis code between the two datasets, and 97.5% shared the same first procedure code. CONCLUSIONS: Inpatient MA data are feasible for use in CMS claims-based hospital outcome measures. We recommend prioritizing hospital-submitted over MAO-submitted claims for analyses. Monitoring, data audits, and ongoing policies to improve the quality of MA data are important approaches to address potential missing data and errors.

Generation of an induced pluripotent stem cell line (CSBZZUi001-A) from a female Alzheimer's patient carrying the PSEN1 709 T > C heterozygous mutation.

Pluripotent stem cells were generated through the electroporation of episomal plasmids, containing crucial reprogramming factors, into skin fibroblasts extracted from a female Alzheimer's patient harboring the PSEN1 709 T > C (p.Phe237Leu) heterozygous mutation. The pluripotent stem cells exhibit a normal karyotype and express pivotal stem cell markers including TRA-1-60, Nanog, SOX2, and OCT4. Furthermore, their capacity to differentiate into the three germ layers in in vivo teratoma experiments has been substantiated. The pluripotent stem cell line can serve as a cellular model for Alzheimer's disease, offering significant value in elucidating the pathogenesis and therapeutic strategies of the disease.

Real-world treatment patterns and outcomes for patients with CLL using the Australian pharmaceutical benefits scheme (PBS) dataset.

This real-world retrospective cohort study using Australian Pharmaceutical Benefits Scheme (PBS) 10% investigated changes in chronic lymphocytic leukemia (CLL) treatment by line of therapy, time-to-next-treatment, treatment duration, and overall survival (OS). Overall, 803 patients received their first PBS-reimbursed CLL medication between 1 January 2011 to 31 July 2021 (median age: 70 years; 64.6% male), 289 post-1 August 2020. In 2011, most first-line (1 L) prescribing was fludarabine, cyclophosphamide, and rituximab (FCR). By 2021, common 1L were chlorambucil ± CD20 (26.1%), Bruton Tyrosine Kinase inhibitor (BTKi) (26.1%), and CD20 monotherapy (23.9%). In 2011, relapsed/refractory (R/R) CLL treatment was CD20 monotherapy or FCR. By 2021, BTKi (57.7%) and venetoclax ± CD20 (26.1%) were most common. Compared to FCR, 1 L treatment duration (Hazard Ratio) was shorter for CD20 monotherapy (1.7) or chlorambucil ± CD20 (2.5). In R/R CLL, median duration was 24 (ibrutinib) and 19 months (venetoclax). Median OS was 127 months. CLLtreatment pattern shave greatly changed in Australia since the introduction of novel therapies.

Investigating the neural mechanisms of transcranial direct current stimulation effects on human cognition: current issues and potential solutions.

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.

Dynamical Symmetry-Reduction-Induced Giant Anharmonicity in IV-VI Compounds: Role of Cation Lone-Pair s Electrons.

The low thermal conductivity of group IV-VI semiconductors is often attributed to the soft phonons and giant anharmonicity observed in these materials. However, there is still no broad consensus on the fundamental origin of this giant anharmonic effect. Utilizing first-principles calculations and group symmetry analysis, we find that the cation lone-pairs s electrons in IV-VI materials cause a significant coupling between occupied cation s orbitals and unoccupied cation p orbitals due to the symmetry reduction when atoms vibrate away from their equilibrium positions under heating. This leads to an electronic energy gain, consequently flattening the potential energy surface and causing soft phonons and strong anharmonic effects. Our findings provide an intrinsic understanding of the low thermal conductivity in IV-VI compounds by connecting the anharmonicity with the dynamical electronic structures, and can also be extended to a large family of hybrid systems with lone-pair electrons, for promising thermoelectric applications and predictive designs.

The N545S and K717N substitution at the N-glycosylation sites of the S2 subunit of avian infectious bronchitis virus can significantly enhance viral pathogenicity.

The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.

Crystal-Rigidifying Strategy in Hybrid Manganese Halide to Achieve Narrow Green Emission and High Structural Stability.

Although organic-inorganic hybrid Mn2+ halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C-H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4 [BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4 display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor ß-SiAlON:Eu2+ and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2- units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron-phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4 realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+ halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.

Construction of an expression platform for fungal secondary metabolite biosynthesis in Penicillium crustosum.

Filamentous fungi are prolific producers of bioactive natural products and play a vital role in drug discovery. Yet, their potential cannot be fully exploited since many biosynthetic genes are silent or cryptic under laboratory culture conditions. Several strategies have been applied to activate these genes, with heterologous expression as one of the most promising approaches. However, successful expression and identification of new products are often hindered by host-dependent factors, such as low gene targeting efficiencies, a high metabolite background, or a lack of selection markers. To overcome these challenges, we have constructed a Penicillium crustosum expression host in a pyrG deficient strain by combining the split-marker strategy and CRISPR-Cas9 technology. Deletion of ligD and pcribo improved gene targeting efficiencies and enabled the use of an additional selection marker in P. crustosum. Furthermore, we reduced the secondary metabolite background by inactivation of two highly expressed gene clusters and abolished the formation of the reactive ortho-quinone methide. Finally, we replaced the P. crustosum pigment gene pcr4401 with the commonly used Aspergillus nidulans wA expression site for convenient use of constructs originally designed for A. nidulans in our P. crustosum host strain. As proof of concept, we successfully expressed a single polyketide synthase gene and an entire gene cluster at the P. crustosum wA locus. Resulting transformants were easily detected by their albino phenotype. With this study, we provide a highly efficient platform for heterologous expression of fungal genes. KEY POINTS: Construction of a highly efficient Penicillium crustosum heterologous expression host Reduction of secondary metabolite background by genetic dereplication strategy Integration of wA site to provide an alternative host besides Aspergillus nidulans.

Pyruvate dehydrogenase complex E1 subunit α crotonylation modulates cocaine-associated memory through hippocampal neuron activation.

Neuronal activation is required for the formation of drug-associated memory, which is critical for the development, persistence, and relapse of drug addiction. Nevertheless, the metabolic mechanisms underlying energy production for neuronal activation remain poorly understood. In the study, a large-scale proteomics analysis of lysine crotonylation (Kcr), a type of protein posttranslational modification (PTM), reveals that cocaine promoted protein Kcr in the hippocampal dorsal dentate gyrus (dDG). We find that Kcr is predominantly discovered in a few enzymes critical for mitochondrial energy metabolism; in particular, pyruvate dehydrogenase (PDH) complex E1 subunit α (PDHA1) is crotonylated at the lysine 39 (K39) residue through P300 catalysis. Crotonylated PDHA1 promotes pyruvate metabolism by activating PDH to increase ATP production, thus providing energy for hippocampal neuronal activation and promoting cocaine-associated memory recall. Our findings identify Kcr of PDHA1 as a PTM that promotes pyruvate metabolism to enhance neuronal activity for cocaine-associated memory.

Volatilomics of Cabernet Sauvignon grapes and sensory perception of wines are affected by canopy side in vineyards with different row orientations.

This study aimed to clarify how microclimate diversity altered volatilomics in Cabernet Sauvignon grapes and wines. Four row-oriented vineyards were selected, and metabolites of grapes and wines were determined from separate canopy sides. Results showed that shaded sides received 59% of the solar radiation and experienced 55% of the high-temperature days compared to the exposed sides on average. Grape primary metabolites were slightly affected by the canopy side. Herbaceous aromas were consistently more abundant in grapes and wines from shaded clusters. Heat-stressed canopy sides accelerated terpenoid loss and increased norisoprenoid levels in grapes, while ß-damascenone in north-side wines was 13%-32% higher than that in south-side wines of the east-west vineyard. The northeast-southwest vineyard showed the most notable variation in taste and aroma sensory scores, with four parameters significantly different. There were 32 aroma series identified in wines, and banana, pineapple, and strawberry odors were highly correlated with aroma sensory score.

Integration analysis of miRNA-mRNA uncovers the molecular immune mechanism of macrophage response to Aeromonas veronii infection.

Macrophages are innate immunity cells which play pivotal roles in infectious immunity. Aeromonas veronii is a zoonotic agent capable of causing sepsis and poses a serious threat to public health. However, few studies have focused on miRNA-mRNA integration analysis to address the immune mechanisms of macrophage response to A. veronii infection. Herein, we characterized the immunophysiological, biochemical, and transcriptome changes of macrophage under A. veronii infection. We found that macrophages infected with A. veronii released large amounts of cytokines and triggered NLRP3-dependent pyroptosis. Subsequently, 603 differentially expressed miRNAs (DEMIs) and 3693 differentially expressed mRNAs (DEMs) were identified by RNA-seq analysis under A. veronii infection. Moreover, integrated analysis of miRNA-mRNA yielded 66 miRNA-target gene pairs composed of 41 DEMIs and 27 DEMs. We next identified the Toll-like receptor, NOD-like receptor, TNF and NF-κB pathways as necessary for macrophage to respond to A. veronii infection. miR-847 and miR-627 were involved in macrophage response to A. veronii infection by negatively regulating Pannexin-1 and thioredoxin interacting protein (TXNIP). Our findings elucidate the molecular mechanism of macrophage response to A. veronii infection at the miRNA level, providing many candidate miRNAs and mRNAs therapeutic targets for the prevention and treatment of A. veornii infectious diseases.

Efferocytosis: Unveiling its potential in autoimmune disease and treatment strategies.

Efferocytosis is a crucial process whereby phagocytes engulf and eliminate apoptotic cells (ACs). This intricate process can be categorized into four steps: (1) ACs release "find me" signals to attract phagocytes, (2) phagocytosis is directed by "eat me" signals emitted by ACs, (3) phagocytes engulf and internalize ACs, and (4) degradation of ACs occurs. Maintaining immune homeostasis heavily relies on the efficient clearance of ACs, which eliminates self-antigens and facilitates the generation of anti-inflammatory and immunosuppressive signals that maintain immune tolerance. However, any disruptions occurring at any of the efferocytosis steps during apoptosis can lead to a diminished efficacy in removing apoptotic cells. Factors contributing to this inefficiency encompass dysregulation in the release and recognition of "find me" or "eat me" signals, defects in phagocyte surface receptors, bridging molecules, and other signaling pathways. The inadequate clearance of ACs can result in their rupture and subsequent release of self-antigens, thereby promoting immune responses and precipitating the onset of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. A comprehensive understanding of the efferocytosis process and its implications can provide valuable insights for developing novel therapeutic strategies that target this process to prevent or treat autoimmune diseases.