A new isocoumarin derivative from endophytic fungus Pezicula neosporulosa VDB39 from Vaccinium dunalianum.

Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.

Magnetic chitosan/ZrO2 composites for vanadium(V) adsorption while concurrently being transformed to a dual functional catalyst.

Spent adsorbents for recycling as catalysts have drawn considerable attention due to their environmentally benign chemistry properties. However, traditional thermocatalytic strategies limit their applications. Here, we developed an enhanced photocatalytic strategy to expand the range of their applications. A magnetic chitosan/ZrO2 composites (MZT) for V(V) adsorption, which were prepared using chitosan, ZrO2 and Fe3O4 by one-pot synthesis. The spent MZT as a catalyst was used to synthesize 2-phenylbenzimidazole, yielding up to 89.7%. It also was implemented to photocatalysis reactions for recycle. The discolored rates of rhodamine B (RhB) were 72.3% and 97.4% by new and spent MZT, respectively. The new and spent MZT showed the forbidden bands were 251 nm and 561 nm, respectively. The result displayed spent MZT red shifted to the cyan light region. The mechanism of catalysis also has been studied in detail.

IVF laboratory management through workflow-based RFID tag witnessing and real-time information entry.

BACKGROUND: Dual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records. METHODS: This study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups. RESULTS: The study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn't affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups. CONCLUSIONS: RFID tag witnessing doesn't negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist's confidence.

The efficacy and safety of cervical polypectomy with vaginoscopy in pregnant women.

PURPOSES: This study aims to assess the effectiveness and safety of cervical polypectomy performed via vaginoscopy in pregnant women. METHODS: Pregnant patients diagnosed with cervical polyps were retrospectively included in Beijing Tiantan Hospital between April 2017 and April 2023. Group A underwent cervical polypectomy using a vaginoscopy technique without speculum, cervical forceps and anesthesia, while Group B received conservative management. The incidence of spontaneous abortion, preterm birth, preterm rupture of membranes (PROM), visual analog scale (VAS) scores, timing and method of delivery, and neonatal outcomes were analyzed. RESULTS: Of 90 pregnant patients included in the study, 48 patients receiving polypectomy under vaginoscopy were included into group A while 42 patients receiving conservative treatment were assigned into group B. At baseline, group A exhibited higher rates of vaginal bleeding pre-operation, as well as larger cervical polyp dimensions compared to group B. The median interval between vaginal bleeding and polypectomy was 3.5 weeks, with the median procedure typically performed at gestational week 19 in group A. There was no significant difference in the incidence of spontaneous abortion between the two groups (4.2% vs. 4.8%, p = 1.000). However, group A showed a significantly lower frequency of preterm birth (4.2% vs. 21.4%, p = 0.030) and premature rupture of membranes (PROM) (18.8% vs. 45.2%, p = 0.025) compared to group B. No disparities were observed in the timing, mode of delivery, and neonatal outcomes between the two groups. CONCLUSIONS: The utilization of vaginoscopy for cervical polypectomy has been shown to decrease the likelihood of preterm delivery and premature rupture of membranes in pregnant women with symptomatic cervical polyps. Therefore, performing cervical polypectomy via vaginoscopy without anesthesia provide a feasible and optimal ways in the management of this population.

Enhanced Stability and Detection Range of Microbial Electrochemical Biotoxicity Sensor by Polydopamine Encapsulation.

With the rapid development of modern industry, it is urgently needed to measure the biotoxicity of complex chemicals. Microbial electrochemical biotoxicity sensors are an attractive technology; however, their application is usually limited by their stability and reusability after measurements. Here, we improve their performance by encapsulating the electroactive biofilm with polydopamine (PDA), and we evaluate the improvement by different concentrations of heavy metal ions (Cu2+, Ag+, and Fe3+) in terms of inhibition ratio (IR) and durability. Results indicate that the PDA-encapsulated sensor exhibits a more significant detection concentration than the control group, with a 3-fold increase for Cu2+ and a 1.5-fold increase for Ag+. Moreover, it achieves 15 more continuous toxicity tests than the control group, maintaining high electrochemical activity even after continuous toxicity impacts. Images from a confocal laser scanning microscope reveal that the PDA encapsulation protects the activity of the electroactive biofilm. The study, thus, demonstrates that PDA encapsulation is efficacious in improving the performance of microbial electrochemical biotoxicity sensors, which can extend its application to more complex media.

Validation of the PowerPlex®35GY System: a novel eight-dye STR multiplex kit on the Spectrum Compact CE System.

The PowerPlex® 35GY System (Promega, USA) is an advanced eight-dye multiplex STR kit, incorporating twenty-three autosomal STR loci, eleven Y chromosome STR loci, one sex determining marker Amelogenin, and two quality indicators. This multiplex system includes 20 CODIS loci and up to 15 mini-STR loci with sizing values less than 250 bases. In this study, validation for PowerPlex® 35GY System was conducted following the guidelines of SWGDAM, encompassing sensitivity, precision, accuracy, concordance, species specificity, stutter, mixture, stability, and degraded DNA. The results from experiments demonstrated that the PowerPlex® 35GY System could effectively amplify DNA samples, with complete allele detection achieved at 125 pg. Moreover, over 90% of alleles from minor contributors were detected at a mixed ratio of 1:4. Additionally, the system was found to yield full profiles even in the presence of hematin, humic acid, and indigo. The PowerPlex® 35GY System demonstrated superior performance in the sensitivity and degraded DNA studies compared to a six-dye STR kit. Hence, it is evident that the PowerPlex® 35GY System is well-suited for forensic practice, whether in casework or for database samples. These findings provide strong support for the efficacy and reliability of the PowerPlex® 35GY System in forensic applications.

Intermolecular Regioselective Alkylarylation of Vinylarenes via Photoredox/Nickel Dual Catalysis.

A novel photoredox/nickel dual catalytic intermolecular alkylarylation of vinylarenes with tertiary and secondary alkyltrifluoroborates and aryl bromides is described, which affords 1,1-diarylalkane frameworks that are found in various natural products as well as functionalized molecules in good to excellent yield and regioselectivity through a radical relay process. Notably, this redox-neutral reaction could proceed efficiently with good tolerance of various substrates, including a great diversity of commercially available (hetero)aryl bromides, alkyltrifluoroborates, and vinylarenes.

Nogo-A exacerbates sepsis-associated encephalopathy by modulating microglial SHP-2/NLRP3 balance and inducing ROS and M1 polarization.

Sepsis, a systemic inflammatory response caused by infection, can lead to sepsis-associated encephalopathy (SAE), characterized by brain dysfunction without direct central nervous system infection. The pathogenesis of SAE involves blood-brain barrier disruption, neuroinflammation and neuronal death, with neuroinflammation being the core process. Nogo-A, a neurite growth-inhibitory protein in the central nervous system, is not well understood in sepsis. This study explores Nogo-A's mechanisms in sepsis, focusing on SAE. Using in vivo and in vitro methods, healthy SPF C57BL/6J male mice were divided into Sham, Nogo-A-NC-Model, and Nogo-A-KD-Model groups, with sepsis induced by abdominal ligation and puncture. Morris water maze tests assessed learning and memory, and brain tissues underwent hematoxylin-eosin (HE) staining, Nissl staining, and Western blot analysis. In vitro, Nogo-A gene knockdown models were constructed using BV-2 microglia cells to study inflammation and oxidative stress. Results showed Nogo-A expression affected learning and memory in septic mice, with knockdown reducing neuronal damage. Bioinformatics analysis suggested Nogo-A may activate reactive oxygen species (ROS) to inhibit p-SHP2, activating mitochondrial autophagy and promoting neuronal apoptosis. Western blot results confirmed that Nogo-A affects mitochondrial autophagy and neuronal survival by inhibiting SHP2 and activating ROS. Nogo-A's role in neuroinflammation and neuroprotection was emphasized, revealing its impact on endoplasmic reticulum (ER) stress, mitochondrial autophagy, and NLRP3 inflammasome activation. This study provides a theoretical basis for SAE treatment, suggesting further multi-gene and multi-pathway analyses and validation in clinical samples. Developing gene therapy and drug interventions targeting Nogo-A pathways will offer more effective treatment strategies.

Tibial post loading increases the risk of aseptic loosening of posterior-stabilized tibial prosthesis.

Aseptic loosening is the primary cause of failure following posterior-stabilized total knee arthroplasty. It is unclear whether tibial post loading of posterior-stabilized prosthesis increases the risk of aseptic loosening of the tibial prosthesis. The purpose of this study is to investigate the biomechanical effects of tibial post loading on the tibial prosthesis fixation interface during level walking, squatting, stair descent, and standing up-sitting down activities. In this paper, finite element models with and without post were established to compare the effects of tibial post loading on the von Mises stress of the proximal tibia, shear stress of the cement, and the bone-prosthesis interface micromotion during four physiological activities. The tibial post loading had an insignificant influence on tibial biomechanics and bone-prosthesis interface micromotion during leveling walking activity. However, compared to the insert without post condition, tibial post loading significantly increased the maximum tibial von Mises stress, the maximum shear stress in the medial of cement, and the bone-prosthesis interface peak micromotion by 912.84%, 612.77%, and 921.09%, respectively, at the moment of the maximum flexion angle for the stair descent activity, and 637.92%, 351.43%, and 519.13%, respectively, at the moment of the maximum flexion angle for the standing up-sitting down activity. Tibial post loading increased the risk of postoperative aseptic loosening of tibial prosthesis in patients with posterior-stabilized total knee arthroplasty, and it was recommended that the post-cam contact mechanism of posterior-stabilized prosthesis should be optimized to reduce the biomechanical impact of tibial post loading on tibial prosthesis fixation.

Photochromic Spiropyran-Based Dual-Emitting Luminescent Hybrid Films for Dynamic Information Anticounterfeiting.

Photoluminescent materials are widely used for information storage and anticounterfeiting, while most of them have the disadvantages of static information performance and weak processability, which is still a challenging task in developing dynamic anticounterfeiting materials with high security levels. Herein, we fabricated a novel photostimuli-responsive dual-emitting luminescent material UPTES-SPn-Tb-hfa, which was obtained by introducing the photochromic molecule spiropyran (SP) and lanthanide complex (Tb-hfa) into a siloxane-polyether matrix using the sol-gel process. Due to the conformation-dependent photochromic fluorescence resonance energy transfer between the Tb-hfa donor and SP acceptor, the ring-closing (SP)/ring-opening (MC) isomerization of the SP unit leads to a reversible luminescence switching in UPTES-SPn-Tb-hfa. This composite material has great potential for advanced anticounterfeiting because of the advantage of rapidly repeatable encryption/decryption for at least 8 times and dynamic luminescent colors within 15 s. In addition, due to its two luminescent centers (Tb3+ and MC), the luminescent color of this material can be regulated by 254 and 365 nm UV-light irradiation, which facilitates the design of multicolored anticounterfeiting labels. Our work presents a novel design methodology to fabricate dynamic anticounterfeiting materials, significantly enhancing the security of anticounterfeiting applications.

Tremendous and infrequently adenoid cystic carcinoma of the breast without any metastasis for more than 20 years: A case report.

RATIONALE: Breast adenoid cystic carcinoma is an extremely rare tumor that is incompletely understood, accounting for less than <0.1% of all breast cancers, with an average diameter of 3 cm, and it is extremely rare to see a large, non-metastatic breast adenoid cystic carcinoma with a diameter of about 30 cm. Since this disease is extremely rare, there are few reports in the literature and limited data on clinical diagnosis and treatment. We present a case of a 71-year-old woman with a large, non-metastatic adenoid cystic carcinoma of the left breast and share our opinion on the diagnosis and treatment of this case. PATIENT CONCERNS: A 71-year-old woman with a 20-year-old left breast mass with local bleeding and rupture for 1 hour presented to our hospital for further diagnosis and treatment. A computed tomography scan showed a large soft tissue mass shadow in the left breast and malignancy was considered. Subsequently, tissue aspiration pathology was performed and the results confirmed adenoid cystic carcinoma of the breast. DIAGNOSIS: Intraoperative pathology results of radical mastectomy for left breast cancer diagnosed adenoid cystic carcinoma of the breast and immunohistochemistry results of triple-negative breast cancer. INTERVENTIONS AND OUTCOMES: Treatment of adenoid cystic carcinoma of the breast included neoadjuvant chemotherapy for breast cancer, radical mastectomy of the left breast, and postoperative chemotherapy. Initially, neoadjuvant chemotherapy for breast cancer was performed, and the TAC regimen was used to successfully reduce the size of the tumor and gain access to surgical treatment for breast cancer. The patient has recovered well after the surgery, with no wound infection or ulceration, and is now waiting for the patient's physical function to recover for postoperative chemotherapy, with no obvious discomfort. LESSONS: Adenoid cystic carcinoma tumors are usually around 3 cm; such a huge 30 cm adenoid cystic carcinoma of the breast is extremely rare, and it is extremely rare to find a breast malignancy that has not developed regional lymph node and distant metastases for more than 20 years. Clinicians must remain vigilant for early breast malignancies at a high age of incidence and conduct further research for diagnosis to avoid delays.

Arsenic-induced downregulation of BRWD3 suppresses proliferation and induces apoptosis in lung adenocarcinoma cells through the p53 and p65 pathways.

Bromodomain and WD-repeat domain-containing protein 3 (BRWD3) exhibits high expression in lung adenocarcinoma (LUAD) tissues and cells; however, its function in arsenic-induced toxicological responses remains unclear. This study aimed to investigate BRWD3 expression in response to arsenic-induced conditions and its impact on the proliferation and apoptosis of LUAD cell line SPC-A1 upon BRWD3 knockdown. The results revealed a decrease in BRWD3 expression in SPC-A1 cells treated with sodium arsenite (NaAsO2), but not sodium arsenite's metabolites. BRWD3 knockdown suppressed cell proliferation and induced apoptosis in SPC-A1 cells. Western blot analysis revealed that BRWD3 knockdown resulted in the upregulation of p53, phospho-p53-Ser392, and its downstream factors including MDM2, Bak, and Bax. Additionally, we observed the downregulation of p65, phospho-p65-Ser276, phospho-p65-Ser536, and its downstream factors, including IκBα, BIRC3, XIAP and CIAP1. Moreover, polymerase chain reaction analysis showed that BRWD3 knockdown also resulted in the downregulation of proliferation-related genes and upregulation of apoptosis-related genes. In conclusion, BRWD3 mediated proliferation and apoptosis via the p53 and p65 pathways in response to arsenic exposure, suggesting potential implications for LUAD treatment through BRWD3 downregulation by arsenic.

Follicular unit extraction combined with fractional carbon dioxide laser therapy for post-traumatic eyebrow scar with defects: A prospective and comparative study.

BACKGROUND: Eyebrows play a crucial role in the human body. While Follicular Unit Extraction (FUE) is a widely utilized and highly effective treatment for typical eyebrow deficiencies, it may not yield satisfactory outcomes for patients with post-traumatic eyebrow scars and defects. OBJECTIVE: A prospective comparative clinical study was conducted to explore the treatment outcomes of post-traumatic eyebrow scars accompanied by defects using a combination of ablative fractional CO2 laser therapy with FUE. METHOD: Between January 2019 and January 2023, we enrolled 30 patients with post-traumatic eyebrow scars and accompanying eyebrow defects, randomly assigning them to experimental and control groups. Patients in the control group received FUE treatment exclusively, whereas patients in the experimental group underwent CO2 fractional laser therapy on the eyebrow scars prior to FUE treatment. Alongside the patients' baseline data and the quantity of transplanted follicular units during surgery, we will compare the follicular survival rates between the two groups at 6 and 12 months post-treatment. RESULTS: Prior to FUE, there were no notable variances in baseline data between the two-patient groups. At 6 and 12 months postoperatively, the follicular survival rate in the experimental group was significantly higher compared to the control group. Additionally, patients in the control group were more prone to experiencing postoperative asymmetry between their eyebrows and developing curly hair. CONCLUSION: For patients with post-traumatic eyebrow scars accompanied by eyebrow defects, we applied ablative fractional CO2 laser therapy in combination with FUE treatment. This approach not only resulted in a higher follicular survival rate postoperatively but also led to the achievement of a well-defined eyebrow shape.

Investigation of cannabidiol-induced cytotoxicity in human hepatic cells.

Cannabidiol (CBD) is one of the primary cannabinoids present in extracts of the plant Cannabis sativa L. A CBD-based drug, Epidiolex, has been approved by the U.S. FDA for the treatment of seizures in childhood-onset epileptic disorders. Although CBD-associated liver toxicity has been reported in clinical studies, the underlying mechanisms remain unclear. In this study, we demonstrated that CBD causes cytotoxicity in primary human hepatocytes and hepatic HepG2 cells. A 24-h CBD treatment induced cell cycle disturbances, cellular apoptosis, and endoplasmic reticulum (ER) stress in HepG2 cells. A potent ER stress inhibitor, 4-phenylbutyrate, markedly attenuated CBD-induced apoptosis and cell death. Additionally, we investigated the role of cytochrome P450 (CYP)-mediated metabolism in CBD-induced cytotoxicity using HepG2 cell lines engineered to express 14 individual CYPs. We identified CYP2C9, 2C19, 2D6, 2C18, and 3A5 as participants in CBD metabolism. Notably, cells overexpressing CYP2C9, 2C19, and 2C18 produced 7-hydroxy-CBD, while cells overexpressing CYP2C9, 2C19, 2D6, and 2C18 generated 7-carboxy-CBD. Furthermore, CBD-induced cytotoxicity was significantly attenuated in the cells expressing CYP2D6. Taken together, these data suggest that cell cycle disturbances, apoptosis, and ER stress are associated with CBD-induced cytotoxicity, and CYP2D6-mediated metabolism plays a critical role in decreasing the cytotoxicity of CBD.

Multi-Functional Lanthanide Metallopolymer: Self-Healing and Photo-Stimuli-Responsive Dual-Emitting Luminescence for Diverse Applications.

Photoluminescent metallopolymers displaying photo-stimuli-responsive properties are emerging as promising materials with versatile applications in photo-rewritable patterns, wearable UV sensors, and optical encryption anti-counterfeiting. However, integrating these materials into practical applications that require fast response times, lightweight qualities, fatigue resistance, and multiple encryption capabilities poses challenges. In this study, luminescent photochromic lanthanide (Ln) metallopolymers with rapid self-healing properties are developed by cross-linking terpyridine (Tpy)- and spiropyran (SP)- functionalized polyurethane chains through Ln-Tpy coordination bonds and H-bonds among polymer chains. The resulting products exhibit a range of intriguing features: i) photo-stimuli responsiveness using spiropyran monomers without additional dopants; ii) dual-emitting performance under UV-light due to Ln-Tpy and open-ring spiropyran moieties; iii) satisfactory mechanical properties and self-healing abilities from polymer chains; iv) multiple control switches for luminescence colors through photostimulation or feed ratio adjustments. Leveraging these attributes, the developed material introduces novel opportunities for light-writing applications, advanced information encryption, UV-sensing wearable devices, and insights into designing multifunctional intelligent materials for the future.

Identification of characteristic flavor compounds of boletus edulis from different regions based on by E-nose, HS-GC-IMS and HS-SPME-GC-MS.

In this study, E-nose, HS-GC-IMS, and HS-SPME-GC-MS technologies were used to evaluate the flavor characteristics of the pileus and stipe of Boletus edulis from eight origins. 23 key Volatile organic compounds (VOCs) with odor activity values (OAVs) > 1 were identified, and 19 aroma types have been identified in Boletus edulis at the same time. Vegetable and earthy were defined as the dominant aroma types for all pileus and stipe samples. Balsamic and musty were the main and characteristic aroma types for the pileus. The highest concentrations of VOCs in the pileus and stipe were originated from Chuxiong Prefecture and Aba Prefecture, respectively. 19 and 16 key VOCs were detected Chuxiong pileus and Aba stipe, respectively, and Methional was the decisive compound that influenced the vegetable aroma type. The results of this study could be helpful for flavor identification and application of pileus and stipe from Boletus edulis.

Multi-angle property analysis and stress-strain curve prediction of cementitious sand gravel based on triaxial test.

In order to further promote the application of cementitious sand gravel (CSG), the mechanical properties and variation rules of CSG material under triaxial test were studied. Considering the influence of fly ash content, water-binder ratio, sand rate and lateral confining pressure, 81 cylinder specimens were designed and made for conventional triaxial test, and the influence laws of stress-strain curve, failure pattern, elastic modulus, energy dissipation and damage evolution of specimens were analyzed. The results showed that the peak of stress-strain curve increased with the increase of confining pressure, and the peak stress, peak strain and energy dissipation all increased significantly, but the damage variable D decreased with the increase of confining pressure. Under triaxial compression, the specimen was basically sheared failure from the bonding surface, and the aggregate generally did not break. Sand rate had a significant effect on the peak stress of CSG, and decreased with the increase of sand rate. Under the conditions of the same cement content, fly ash content and confining pressure, the optimal water-binder ratio 1.2 existed when the sand rate was 0.2 and 0.3. After analyzing and processing the stress-strain curve of triaxial test, a Cuckoo Search-eXtreme Gradient Boosting (CS-XGBoost) curve prediction model was established, and the model was evaluated by evaluation indexes R2, RMSE and MAE. The average R2 of the XGBoost model based on initial parameters under 18 different output features was 0.8573, and the average R2 of the CS-XGBoost model was 0.9516, an increase of 10.10%. Moreover, the prediction curve was highly consistent with the test curve, indicating that the CS algorithm had significant advantages. The CS-XGBoost model could accurately predict the triaxial stress-strain curve of CSG.

Current Status and Development Trend of Research on Polymer-Based Kinetic Inhibitors for Natural Gas Hydrates.

As the understanding of natural gas hydrates as a vast potential resource deepens, their importance as a future clean energy source becomes increasingly evident. However, natural gas hydrates trend towards secondary generation during extraction and transportation, leading to safety issues such as pipeline blockages. Consequently, developing new and efficient natural gas hydrate inhibitors has become a focal point in hydrate research. Kinetic hydrate inhibitors (KHIs) offer an effective solution by disrupting the nucleation and growth processes of hydrates without altering their thermodynamic equilibrium conditions. This paper systematically reviews the latest research progress and development trends in KHIs for natural gas hydrates, covering their development history, classification, and inhibition mechanisms. It particularly focuses on the chemical properties, inhibition effects, and mechanisms of polymer inhibitors such as polyvinylpyrrolidone (PVP) and polyvinylcaprolactam (PVCap). Studies indicate that these polymer inhibitors provide an economical and efficient solution due to their low dosage and environmental friendliness. Additionally, this paper explores the environmental impact and biodegradability of these inhibitors, offering guidance for future research, including the development, optimization, and environmental assessment of new inhibitors. Through a comprehensive analysis of existing research, this work aims to provide a theoretical foundation and technical reference for the commercial development of natural gas hydrates, promoting their safe and efficient use as a clean energy resource.

Communication between alveolar macrophages and fibroblasts via the TNFSF12-TNFRSF12A pathway promotes pulmonary fibrosis in severe COVID-19 patients.

BACKGROUND: Severe COVID-19 infection has been associated with the development of pulmonary fibrosis, a condition that significantly affects patient prognosis. Understanding the underlying cellular communication mechanisms contributing to this fibrotic process is crucial. OBJECTIVE: In this study, we aimed to investigate the role of the TNFSF12-TNFRSF12A pathway in mediating communication between alveolar macrophages and fibroblasts, and its implications for the development of pulmonary fibrosis in severe COVID-19 patients. METHODS: We conducted single-cell RNA sequencing (scRNA-seq) analysis using lung tissue samples from severe COVID-19 patients and healthy controls. The data was processed, analyzed, and cell types were annotated. We focused on the communication between alveolar macrophages and fibroblasts and identified key signaling pathways. In vitro experiments were performed to validate our findings, including the impact of TNFRSF12A silencing on fibrosis reversal. RESULTS: Our analysis revealed that in severe COVID-19 patients, alveolar macrophages communicate with fibroblasts primarily through the TNFSF12-TNFRSF12A pathway. This communication pathway promotes fibroblast proliferation and expression of fibrotic factors. Importantly, silencing TNFRSF12A effectively reversed the pro-proliferative and pro-fibrotic effects of alveolar macrophages. CONCLUSION: The TNFSF12-TNFRSF12A pathway plays a central role in alveolar macrophage-fibroblast communication and contributes to pulmonary fibrosis in severe COVID-19 patients. Silencing TNFRSF12A represents a potential therapeutic strategy for mitigating fibrosis in severe COVID-19 lung disease.