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1.
Indian J Orthop ; 58(5): 575-586, 2024 May.
Article En | MEDLINE | ID: mdl-38694703

Background: To analyze and evaluate the clinical outcomes of using high-viscosity bone cement compared to low-viscosity bone cement in percutaneous vertebroplasty (PVP) for treatment of Kummell's disease. Methods: From July 2017 to July 2019, 68 Kummell's disease patients who underwent PVP were chosen and separated into 2 groups: H group (n = 34), were treated with high-viscosity bone cement and L group (n = 34), treated with low-viscosity bone cement during treatment. The operation time, number of fluoroscopy tests done, and amount of bone cement perfusion were recorded for both groups. Clinical outcomes were compared, by measuring their Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Kyphosis Cobb's angle, vertebral height compression rate, and other complications. Results: High-viscosity group showed less operation time and reduced number of fluoroscopy tests than the low-viscosity group (P < 0.05). When compared to preoperative period, both groups' VAS and ODI scores were significantly reduced at 1 day and 1 year postoperatively (P < 0.05). The vertebral height compression rate and Cobb's angle were significantly lower (P < 0.05) in both groups after surgery compared with those before surgery (P < 0.05). The cement leakage rate in group H was 26.5%, which was significantly lower than that in group L, which was 61.8% (P < 0.05). Conclusions: High-viscosity and low-viscosity bone cement in PVP have similar clinical efficacy in reducing pain in patients during the treatment, but in contrast, high-viscosity bone cement shortens the operative time, reduces number of fluoroscopy views and vertebral cement leakage and improves surgical safety.

2.
Cancer Lett ; 592: 216923, 2024 Jun 28.
Article En | MEDLINE | ID: mdl-38697462

Liver metastasis is common in patients with gallbladder cancer (GBC), imposing a significant challenge in clinical management and serving as a poor prognostic indicator. However, the mechanisms underlying liver metastasis remain largely unknown. Here, we report a crucial role of tyrosine aminotransferase (TAT) in liver metastasis of GBC. TAT is frequently up-regulated in GBC tissues. Increased TAT expression is associated with frequent liver metastasis and poor prognosis of GBC patients. Overexpression of TAT promotes GBC cell migration and invasion in vitro, as well as liver metastasis in vivo. TAT knockdown has the opposite effects. Intriguingly, TAT promotes liver metastasis of GBC by potentiating cardiolipin-dependent mitophagy. Mechanistically, TAT directly binds to cardiolipin and leads to cardiolipin externalization and subsequent mitophagy. Moreover, TRIM21 (Tripartite Motif Containing 21), an E3 ubiquitin ligase, interacts with TAT. The histine residues 336 and 338 at TRIM21 are essential for this binding. TRIM21 preferentially adds the lysine 63 (K63)-linked ubiquitin chains on TAT principally at K136. TRIM21-mediated TAT ubiquitination impairs its dimerization and mitochondrial location, subsequently inhibiting tumor invasion and migration of GBC cells. Therefore, our study identifies TAT as a novel driver of GBC liver metastasis, emphasizing its potential as a therapeutic target.


Cell Movement , Gallbladder Neoplasms , Liver Neoplasms , Ribonucleoproteins , Ubiquitination , Humans , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/metabolism , Liver Neoplasms/secondary , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Animals , Cell Line, Tumor , Male , Ribonucleoproteins/metabolism , Ribonucleoproteins/genetics , Female , Mitophagy , Neoplasm Invasiveness , Mice , Mice, Nude , Middle Aged , Gene Expression Regulation, Neoplastic , Mice, Inbred BALB C
3.
J Org Chem ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38741558

A novel three-component cyclization carbonylation reaction of iodoarene-tethered propargyl ethers with amine and CO is reported. This palladium-catalyzed cascade reaction undergoes a sequence of oxidative addition, unsaturated bond migration, carbonyl insertion, and nucleophilic attack to deliver the benzofuran skeleton. Both aromatic amines and aliphatic amines could proceed smoothly in this transformation under one atm of CO.

4.
Sci Total Environ ; 927: 172143, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38569967

Atmospheric organic peroxides (POs) play a key role in the formation of O3 and secondary organic aerosol (SOA), impacting both air quality and human health. However, there still remain technical challenges in investigating the reactivity of POs in ambient aerosols due to the instability and lack of standards for POs, impeding accurate evaluation of their environmental impacts. In the present study, we conducted the first attempt to categorize and quantify POs in ambient PM2.5 through hydrolysis, which is an important transformation pathway for POs, thus revealing the reactivities of various POs. POs were generally categorized into hydrolyzable POs (HPO) and unhydrolyzable POs (UPO). HPO were further categorized into three groups: short-lifetime HPO (S-HPO), intermediate-lifetime HPO (I-HPO), and long-lifetime HPO (L-HPO). S-HPO and L-HPO are typically formed from Criegee intermediate (CI) and RO2 radical reactions, respectively. Results show that L-HPO are the most abundant HPO, indicating the dominant role of RO2 pathway in HPO formation. Despite their lower concentration compared to L-HPO, S-HPO make a major contribution to the HPO hydrolysis rate due to their faster rate constants. The hydrolysis of PM2.5 POs accounts for 19 % of the nighttime gas-phase H2O2 growth during the summer observation, constituting a noteworthy source of gas-phase H2O2 and contributing to the atmospheric oxidation capacity. Seasonal and weather conditions significantly impact the composition of POs, with HPO concentrations in summer being significantly higher than those in winter and elevated under rainy and nighttime conditions. POs are mainly composed of HPO in summer, while in winter, POs are dominated by UPO.

5.
Article En | MEDLINE | ID: mdl-38574309

Purpose: Uniportal video-assisted thoracoscopic surgery (VATS) is recognized for its minimally invasive nature, widely adopted globally. However, the evident scarring it leaves often triggers psychological apprehension and resistance to surgery. Transareolar incision, known for its superior cosmetic outcome with no visible scars, poses challenges in women due to the risk of mammary gland damage. In this report, we present successful pulmonary ground glass nodule (GGN) resection using transareolar VATS in female patients, aiming to address these concerns. Materials and Methods: We retrospectively analyzed the clinical data of 35 female patients who underwent GGN resection through transareolar VATS between August 2020 and March 2022. Results: There were no serious complications or perioperative deaths in this cohort of 35 female patients undergoing GGN resection through transareolar VATS. The operations, including local resection or segmentectomy, had an average duration of 70.1 ± 26.4 minutes, with a tube duration of 4.7 ± 2.1 days and a hospitalization time of 7.2 ± 2.3 days. The surgical approach varied, with 21 cases using transareolar uniport, 8 cases assisted by a 3-mm tiny port, and 6 cases converted to two-port VATS. Scar outcomes varied, with 21 cases showing no scar, 8 cases displaying a microscar, and 6 cases presenting a dominant scar of 1.7 ± 0.5 cm. Postoperative pain scores at 1 week and 1 month were 1.9 ± 0.9 and 1.0 ± 0.9, respectively, and the wound numbness occurred in 2.86% (1/35) of cases. Regarding breast complications, 2 patients suffered delayed healing of the incision. No damage and inflammation of glands were detected by breast B-mode ultrasonography. Conclusions: The transareolar incision emerges as a novel approach for VATS in female patients, offering advantages in terms of pain management and cosmetic outcomes.

6.
Molecules ; 29(7)2024 Mar 29.
Article En | MEDLINE | ID: mdl-38611821

This study aimed to investigate the volatile flavor compounds and tastes of six kinds of sauced pork from the southwest and eastern coastal areas of China using gas chromatography-ion mobility spectroscopy (GC-IMS) combined with an electronic nose (E-nose) and electronic tongue (E-tongue). The results showed that the combined use of the E-nose and E-tongue could effectively identify different kinds of sauced pork. A total of 52 volatile flavor compounds were identified, with aldehydes being the main flavor compounds in sauced pork. The relative odor activity value (ROAV) showed that seven key volatile compounds, including 2-methylbutanal, 2-ethyl-3, 5-dimethylpyrazine, 3-octanone, ethyl 3-methylbutanoate, dimethyl disulfide, 2,3-butanedione, and heptane, contributed the most to the flavor of sauced pork (ROAV ≥1). Multivariate data analysis showed that 13 volatile compounds with the variable importance in projection (VIP) values > 1 could be used as flavor markers to distinguish six kinds of sauced pork. Pearson correlation analysis revealed a significant link between the E-nose sensor and alcohols, aldehydes, terpenes, esters, and hetero-cycle compounds. The results of the current study provide insights into the volatile flavor compounds and tastes of sauced pork. Additionally, intelligent sensory technologies can be a promising tool for discriminating different types of sauced pork.


Pork Meat , Red Meat , Swine , Animals , Electronic Nose , China , Spectrum Analysis , Aldehydes , Chromatography, Gas
7.
Rehabil Psychol ; 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38602819

PURPOSE/OBJECTIVE: This study aims to understand the reciprocal relationships among acceptance of disability, attitudes toward disability, and coping among Chinese adolescents with visual impairments. RESEARCH DESIGN: Adolescents with visual impairments (NT1 = 311, NT2 = 170) from four Chinese special education schools completed three questionnaires twice over 1 year. Cross-lagged panel modeling was carried out to analyze the questionnaire data. RESULTS: The findings revealed that attitudes toward disability and self-directed coping at Time 1 (T1) positively predicted acceptance of disability at Time 2 (T2). Self-directed coping at T1 positively predicted attitudes toward disability at T2, and attitudes toward disability at T1 negatively predicted relinquished-control coping at T2. CONCLUSION/IMPLICATIONS: Visually impaired adolescents' attitudes toward disability and coping serve as antecedents of their acceptance of disability. There is a positive reciprocal relationship between coping and attitudes toward disability. Psychological interventions aimed at optimizing psychosocial adjustment among students with visual impairments may benefit from targeting coping strategies and attitudes toward disability. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

8.
PeerJ Comput Sci ; 10: e1948, 2024.
Article En | MEDLINE | ID: mdl-38660210

Fusarium head blight (FHB) is a destructive disease that affects wheat production. Detecting FHB accurately and rapidly is crucial for improving wheat yield. Traditional models are difficult to apply to mobile devices due to large parameters, high computation, and resource requirements. Therefore, this article proposes a lightweight detection method based on an improved YOLOv8s to facilitate the rapid deployment of the model on mobile terminals and improve the detection efficiency of wheat FHB. The proposed method introduced a C-FasterNet module, which replaced the C2f module in the backbone network. It helps reduce the number of parameters and the computational volume of the model. Additionally, the Conv in the backbone network is replaced with GhostConv, further reducing parameters and computation without significantly affecting detection accuracy. Thirdly, the introduction of the Focal CIoU loss function reduces the impact of sample imbalance on the detection results and accelerates the model convergence. Lastly, the large target detection head was removed from the model for lightweight. The experimental results show that the size of the improved model (YOLOv8s-CGF) is only 11.7 M, which accounts for 52.0% of the original model (YOLOv8s). The number of parameters is only 5.7 × 106 M, equivalent to 51.4% of the original model. The computational volume is only 21.1 GFLOPs, representing 74.3% of the original model. Moreover, the mean average precision (mAP@0.5) of the model is 99.492%, which is 0.003% higher than the original model, and the mAP@0.5:0.95 is 0.269% higher than the original model. Compared to other YOLO models, the improved lightweight model not only achieved the highest detection precision but also significantly reduced the number of parameters and model size. This provides a valuable reference for FHB detection in wheat ears and deployment on mobile terminals in field environments.

9.
Org Lett ; 26(18): 3691-3696, 2024 May 10.
Article En | MEDLINE | ID: mdl-38662519

O-Acylhydroxylamine has been widely employed as an electrophilic amination reagent in transition-metal-catalyzed C-N coupling reactions, but its use as an electrophilic oxygen source has not been disclosed. Here, we report a Pd-catalyzed 1,2-oxyarylation of alkenes with O-acylhydroxylamines as an oxidant and an oxygen source for the first time. With simple amide as the monodentate directing group, this method features a broad substrate scope, good functional group tolerance, and mild conditions.

10.
Org Lett ; 26(17): 3575-3580, 2024 May 03.
Article En | MEDLINE | ID: mdl-38636450

We introduce switchable chemoselectivity strategies based on the hydrazone phosphaketene intermediate to synthesize three classes of 1,2,4-diazaphosphol derivatives. First, the five-membered heterocyclic P and O anion intermediates acted as nucleophilic agents in the selective construction of C-P and C-O bonds. Second, the phosphinidene served as a phosphorus synthon, allowing for the formation of C-P and C-N bonds. Finally, a stepwise mechanism, supported by DFT calculations, was invoked to explain the reaction selectivity.

11.
J Mol Graph Model ; 130: 108782, 2024 Jul.
Article En | MEDLINE | ID: mdl-38685182

The interactions of the micro-mechanism of hydroxymethanesulfonic acid (HMSA) with the typical small organic molecule in atmospheric (X = methanol, formaldehyde, formic acid, methyl formate, dimethyl ether, acetone) has been investigated by density functional theory (DFT), quantum theory of atoms in molecules (QTAIM), Generalized Kohn-Sham Enery Decomposition Analysis (GKS-EDA) and the atmospheric clusters dynamic code (ACDC). The results of DFT show that the stable six- to eight-membered ring structures are easily formed in HMSA-X clusters. According to the topological analysis results of the AIM theory and the IRI method, a strong hydrogen bonding interaction is present in the complex. GKS-EDA results show that electrostatic energy is the main contributor to the interaction energy as it accounts for 51 %-55 % of the total attraction energy. The evaporation rates of HMSA-HMSA and HMSA-HCOOH clusters were much lower than those of the other HMSA complexes. In addition, the Gibbs energy of formation (ΔG) of HMSA-X dimers is investigated under atmosphere temperature T = 217-298 K and p = 0.19-1.0 atm, the ΔG decreased with decreasing of the atmosphere temperature and increased with the decrease of atmospheric pressure, indicating that the low temperature and high pressure may significantly facilitate to the formation of dimers.


Atmosphere , Hydrogen Bonding , Atmosphere/chemistry , Thermodynamics , Organic Chemicals/chemistry , Models, Molecular , Quantum Theory , Mesylates/chemistry , Static Electricity , Temperature
12.
BMC Ophthalmol ; 24(1): 148, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38566041

BACKGROUND: Bilateral retinal detachment and choroidal detachment in a patient are rare occurrences. The presence of bilateral diabetic retinopathy (DR) in such a case is even rarer and complicates the condition. CASE PRESENTATION: In this study, we document a case of unconventional VKH. Manifestations in this patient included intense peripheral retinal detachment and choroidal detachment, along with vitreous opacities akin to cotton wool spots, concurrent with DR. The diagnosis was considered as probable VKH with DR. Treatment according to VKH protocols, including high-dose corticosteroids, yielded positive results. CONCLUSIONS: VKH can co-occurrence with DR. VKH manifestations vary, and early, aggressive, and long-term treatment is essential. The complexity of treatment increases with concurrent DR, necessitating the use of immunosuppressants.


Choroidal Effusions , Diabetes Mellitus , Diabetic Retinopathy , Papilledema , Retinal Detachment , Uveomeningoencephalitic Syndrome , Humans , Uveomeningoencephalitic Syndrome/complications , Uveomeningoencephalitic Syndrome/diagnosis , Uveomeningoencephalitic Syndrome/drug therapy , Retinal Detachment/etiology , Retinal Detachment/complications , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Papilledema/etiology
13.
Inorg Chem ; 63(11): 5235-5245, 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38452249

Cancer treatment has faced severe obstacles due to the smart biological system of cancer cells. Herein, we report a three-in-one agent Ir-CA via attenuation of cancer cell stemness with the down-regulated biomarker CD133 expression from the mitochondria-directed chemotherapy. Over 80% of Ir-CA could accumulate in mitochondria, result in severe mitochondrial dysfunctions, and subsequently initiate mitophagy and cell cycle arrest to kill cisplatin-resistant A549R cells. In vitro and in vivo antimetastatic experiments demonstrated that Ir-CA can effectively inhibit metastasis with down-regulated MMP-2/MMP-9. RNA seq analysis and Western blotting indicated that Ir-CA also suppresses the GSTP1 expression to decrease the intracellular Pt-GS adducts, resulting in the detoxification and resensitization to cisplatin of A549R cells. In vivo evaluation indicated that Ir-CA restrains the tumor growth and has minimal side effects and superior biocompatibility. This work not only provides the first three-in-one agent to attenuate cancer cell stemness and simultaneously realize anticancer, antimetastasis, and conquer metallodrug resistance but also demonstrates the effectiveness of the mitochondria-directed strategy in cancer treatment.


Antineoplastic Agents , Neoplasms , Cisplatin/pharmacology , Cell Line, Tumor , Cell Cycle , Mitochondria , Apoptosis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/metabolism , Neoplasms/metabolism
14.
Breastfeed Med ; 2024 Mar 19.
Article En | MEDLINE | ID: mdl-38501370

Objectives: This study aimed to explore the associations of growth and body composition with gut microbiome and metabolome in preterm infants. Materials and Methods: A prospective cohort study including 73 human milk-fed very preterm infants was conducted. During hospitalization, fecal samples were collected to detect microbes and metabolites using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry. Growth and body composition indices were measured at term equivalent age (TEA) and 6 months of corrected age (CA). Associations of the fecal microbiome and metabolome profiles with growth and body composition indices, as well as their changes, were analyzed. Results: A higher abundance of Streptococcus was associated with a lower fat-free mass (FFM) z-score at 6 months of CA (p = 0.002) and a smaller increase in FFM z-score from TEA to 6 months of CA (p = 0.018). Higher levels of 3'-sialyllactose and 6'-sialyllactose (6'-SL) in feces were correlated with a lower z-score of percentage body fat (PBF) (p = 0.018 and 0.020, respectively) and a lower z-score of fat mass (p = 0.044 and 0.043, respectively) at 6 months of CA. A higher level of 6'-SL in feces was correlated with a greater increase in FFM z-score from TEA to 6 months of CA (p = 0.021). Conclusions: This study sheds light on the role of specific microbial-host interactions in metabolic changes in preterm infants, indicating the potential role of sialylated human milk oligosaccharides in optimizing body composition.

15.
Mol Psychiatry ; 2024 Mar 13.
Article En | MEDLINE | ID: mdl-38480874

BACKGROUND: Painful physical symptoms (PPS) are highly prevalent in patients with major depressive disorder (MDD). Presence of PPS in depressed patients are potentially associated with poorer antidepressant treatment outcome. We aimed to evaluate the association of baseline pain levels and antidepressant treatment outcomes. METHODS: We searched PubMed, Embase and Cochrane Library databases from inception through February 2023 based on a pre-registered protocol (PROSPERO: CRD42022381349). We included original studies that reported pretreatment pain measures in antidepressant treatment responder/remitter and non-responder/non-remitter among patients with MDD. Data extraction and quality assessment were performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses by two reviewers independently. The primary outcome was the difference of the pretreatment pain levels between antidepressant treatment responder/remitter and non-responder/non-remitter. Random-effects meta-analysis was used to calculate effect sizes (Hedge's g) and subgroup and meta-regression analyses were used to explore sources of heterogeneity. RESULTS: A total of 20 studies were included. Six studies reported significantly higher baseline pain severity levels in MDD treatment non-responders (Hedge's g = 0.32; 95% CI, 0.13-0.51; P = 0.0008). Six studies reported the presence of PPS (measured using a pain severity scale) was significantly associated with poor treatment response (OR = 1.46; 95% CI, 1.04-2.04; P = 0.028). Five studies reported significant higher baseline pain interference levels in non-responders (Hedge's g = 0.46; 95% CI, 0.32-0.61; P < 0.0001). Four studies found significantly higher baseline pain severity levels in non-remitters (Hedge's g = 0.27; 95% CI, 0.14-0.40; P < 0.0001). Eight studies reported the presence of PPS significantly associated with treatment non-remission (OR = 1.70; 95% CI, 1.24-2.32; P = 0.0009). CONCLUSIONS: This study suggests that PPS are negatively associated with the antidepressant treatment outcome in patients with MDD. It is possible that better management in pain conditions when treating depression can benefit the therapeutic effects of antidepressant medication in depressed patients.

17.
Small Methods ; : e2301705, 2024 Mar 26.
Article En | MEDLINE | ID: mdl-38530062

Polymer materials formed by conventional metal-ligand bonds have very low branch functionality, the crosslinker of such polymer usually consists of 2-4 polymer chains and a single metal ion. Thus, these materials are weak, soft, humidity-sensitive, and unable to withstand their shape under long-term service. In this work, a new hyperbranched metal-organic cluster (MOC) crosslinker containing up to 16 vinyl groups is prepared by a straightforward coordination reaction. Compared with the current typical synthesis of metal-organic cages (MOCs) or metal-organic-polyhedra (MOP) crosslinkers with complex operations and low yield, the preparation of the MOC is simple and gram-scale. Thus, MOC can serve as a high-connectivity crosslinker to construct hyper-crosslinked polymer networks. The as-prepared elastomer exhibits mechanical robustness, creep-resistance, and humidity-stability. Besides, the elastomer possesses self-healing and recyclability at mild condition as well as fluorescence stability. These impressive comprehensive properties are proven to originate from the hyper-crosslinked topological structure and microphase-separated morphology. The MOC-driven hyper-crosslinked elastomers provide a new solution for the construction of mechanically robust, durable, and multifunctional polymers.

18.
Plants (Basel) ; 13(4)2024 Feb 17.
Article En | MEDLINE | ID: mdl-38498537

Aboveground biomass (AGB) is a key indicator of the physiological status and productivity of grasslands, and its accurate estimation is essential for understanding regional carbon cycles. In this study, we developed a suitable AGB model for grasslands in Xinjiang based on the random forest algorithm, using AGB observation data, remote sensing vegetation indices, and meteorological data. We estimated the grassland AGB from 2000 to 2022, analyzed its spatiotemporal changes, and explored its response to climatic factors. The results showed that (1) the model was reliable (R2 = 0.55, RMSE = 64.33 g·m-2) and accurately estimated the AGB of grassland in Xinjiang; (2) the spatial distribution of grassland AGB in Xinjiang showed high levels in the northwest and low values in the southeast. AGB showed a growing trend in most areas, with a share of 61.19%. Among these areas, lowland meadows showed the fastest growth, with an average annual increment of 0.65 g·m-2·a-1; and (3) Xinjiang's climate exhibited characteristics of warm humidification, and grassland AGB showed a higher correlation with precipitation than temperature. Developing remote sensing models based on random forest algorithms proves an effective approach for estimating AGB, providing fundamental data for maintaining the balance between grass and livestock and for the sustainable use and conservation of grassland resources in Xinjiang, China.

19.
Mater Horiz ; 2024 Mar 25.
Article En | MEDLINE | ID: mdl-38525789

The research found that after doping with rare earth elements, a large number of electrons and holes will be produced on the surface of AlN, which makes the material have the characteristics of spontaneous polarization. A new type of ferroelectric material has made a new breakthrough in the application of nitride-materials in the field of integrated devices. In this paper, the application prospects and development trends of ferroelectric material ScAlN in memristors are reviewed. Firstly, various fabrication processes and structures of the current ScAlN thin films are described in detail to explore the implementation of their applications in synaptic devices. Secondly, a series of electrical properties of ScAlN films, such as the current switching ratio and long-term cycle durability, were tested to explore whether their electrical properties could meet the basic needs of memristor device materials. Finally, a series of summaries on the current research studies of ScAlN thin films in the synaptic simulation are made, and the working state of ScAlN thin films as a synaptic device is observed. The results show that the ScAlN ferroelectric material has high residual polarization, no wake-up function, excellent stability and obvious STDP behavior, which indicates that the modified material has wide application prospects in the research and development of memristors.

20.
Hepatology ; 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38537134

BACKGROUND AND AIMS: HBV infection is a major etiology of acute-on-chronic liver failure (ACLF). At present, the pattern and regulation of hepatocyte death during HBV-ACLF progression are still undefined. Evaluating the mode of cell death and its inducers will provide new insights for developing therapeutic strategies targeting cell death. In this study, we aimed to elucidate whether and how immune landscapes trigger hepatocyte death and lead to the progression of HBV-related ACLF. APPROACH AND RESULTS: We identified that pyroptosis represented the main cell death pattern in the liver of patients with HBV-related ACLF. Deficiency of MHC-I in HBV-reactivated hepatocytes activated cytotoxic NK cells, which in turn operated in a perforin/granzyme-dependent manner to trigger GSDMD/caspase-8-dependent pyroptosis of hepatocytes. Neutrophils selectively accumulated in the pyroptotic liver, and HMGB1 derived from the pyroptotic liver constituted an important factor triggering the generation of pathogenic extracellular traps in neutrophils (NETs). Clinically, elevated plasma levels of myeloperoxidase-DNA complexes were a promising prognostic biomarker for HBV-related ACLF. More importantly, targeting GSDMD pyroptosis-HMGB1 release in the liver abrogates NETs that intercept the development of HBV-related ACLF. CONCLUSIONS: Studying the mechanisms that selectively modulate GSDMD-dependent pyroptosis, as well as its immune landscapes, will provide a novel strategy for restoring the liver function of patients with HBV-related ACLF.

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