Application of Non-Pharmacologic Therapy in Hair Loss Treatment and Hair Regrowth.

Purpose: Alopecia significantly affects the appearance and psychology of patients, and pharmacological therapies and hair transplantation are the main treatments for alopecia, but both have limitations. This review aimed to summarize the non-pharmacological therapies that promote hair growth and regeneration. Patients and Methods: This is a non-systematic review. Multiple databases was searched with relevant data published between 1997 and 2024. Searching and screening followed the PRISMA guidelines. Results: Novel therapeutic modalities, such as gas molecules, platelet-rich plasma, laser, and microneedling, can change the microenvironment of hair follicles, activate hair follicle stem cells, and promote hair growth and regeneration. Conclusion: This paper reviews research on the application of non-pharmacological therapies in alopecia treatment and hair regeneration, with a view to providing an important basis for future research on alopecia treatment and the postoperative treatment of patients after hair transplantation.

Ursolic Acid Conjugates: A New Frontier in Anticancer Drug Development.

New Ursolic Acid (UA) conjugates were synthesized using optimized synthetic protocols through the molecular hybridization approach at C-3 and C-28. This resulted in the targeted molecules being produced in good yields. Some of the synthesized conjugates showed significantly relevant bioactivity against mammalian cells and in animal models of cancers. Selected UA conjugates were tested against bladder and breast cancer cell lines. The conjugates showed moderate to significantly enhanced antiproliferative activities against Triple Negative Breast Cancer (TNBC; MDA-MB 231), which is an aggressive tumor making up about 10-15% of all breast cancers and bladder (T24 and 5637) cancer cell lines. These properties were superior to the parent UA. Among all the synthesized compounds, 18c and 18d have exhibited promising antiproliferative and cytotoxic properties against all tested cancer cell lines. However, 18d has proved to be exceptionally selective for cancer cell lines, showing more cytotoxicity towards them than normal epithelial cells (MCF-12A). Compound 18d has demonstrated cytotoxicity against tumor cells, including those intrinsically resistant to chemotherapy drugs such as 2-difluoro-deoxy cytidine (Gemcitabine). The activity of the UA conjugates on tumor cells was mediated by multiple cytotoxic mechanisms, including drug-induced cytotoxic autophagy and programmed cell death, indicating a novel possibility of combination therapy.

O-Sialoglycoprotein Endopeptidase Deficiency Impairs Proteostasis and Induces Autophagy in Human Embryonic Stem Cells.

The OSGEP gene encodes O-sialoglycoprotein endopeptidase, a catalytic unit of the highly conserved KEOPS complex (Kinase, Endopeptidase, and Other Proteins of small Size) that regulates the second biosynthetic step in the formation of N-6-threonylcarbamoyladenosine (t6A). Mutations in KEOPS cause Galloway-Mowat syndrome (GAMOS), whose cellular function in mammals and underlying molecular mechanisms are not well understood. In this study, we utilized lentivirus-mediated OSGEP knockdown to generate OSGEP-deficient human embryonic stem cells (hESCs). OSGEP-knockdown hESCs exhibited reduced stemness factor expression and G2/M phase arrest, indicating a potential role of OSGEP in the regulation of hESC fate. Additionally, OSGEP silencing led to enhanced protein synthesis and increased aggregation of proteins, which further induced inappropriate autophagy, as evidenced by the altered expression of P62 and the conversion of LC3-I to LC3-II. The above findings shed light on the potential involvement of OSGEP in regulating pluripotency and differentiation in hESCs while simultaneously highlighting its crucial role in maintaining proteostasis and autophagy, which may have implications for human disease.

Review on Long Non-Coding RNAs as Biomarkers and Potentially Therapeutic Targets for Bacterial Infections.

The confrontation between humans and bacteria is ongoing, with strategies for combating bacterial infections continually evolving. With the advancement of RNA sequencing technology, non-coding RNAs (ncRNAs) associated with bacterial infections have garnered significant attention. Recently, long ncRNAs (lncRNAs) have been identified as regulators of sterile inflammatory responses and cellular defense against live bacterial pathogens. They are involved in regulating host antimicrobial immunity in both the nucleus and cytoplasm. Increasing evidence indicates that lncRNAs are critical for the intricate interactions between host and pathogen during bacterial infections. This paper emphatically elaborates on the potential applications of lncRNAs in clinical hallmarks, cellular damage, immunity, virulence, and drug resistance in bacterial infections in greater detail. Additionally, we discuss the challenges and limitations of studying lncRNAs in the context of bacterial infections and highlight clear directions for this promising field.

Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model.

Sea cucumber viscera contain various naturally occurring active substances, but they are often underutilized during sea cucumber processing. Polydeoxyribonucleotide (PDRN) is an adenosine A2A receptor agonist that activates the A2A receptor to produce various biological effects. Currently, most studies on the activity of PDRN have focused on its anti-inflammatory, anti-apoptotic, and tissue repair properties, yet relatively few studies have investigated its antioxidant activity. In this study, we reported for the first time that PDRN was extracted from the sperm of Apostichopus japonicus (AJS-PDRN), and we evaluated its antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and hydroxyl radical scavenging assays. An in vitro injury model was established using H2O2-induced oxidative damage in RAW264.7 cells, and we investigated the protective effect of AJS-PDRN on these cells. Additionally, we explored the potential mechanism by which AJS-PDRN protects RAW264.7 cells from damage using iTRAQ proteomics analysis. The results showed that AJS-PDRN possessed excellent antioxidant activity and could significantly scavenge DPPH, ABTS, and hydroxyl radicals. In vitro antioxidant assays demonstrated that AJS-PDRN was cytoprotective and significantly enhanced the antioxidant capacity of RAW264.7 cells. The results of GO enrichment and KEGG pathway analysis indicate that the protective effects of AJS-PDRN pretreatment on RAW264.7 cells are primarily achieved through the regulation of immune and inflammatory responses, modulation of the extracellular matrix and signal transduction pathways, promotion of membrane repair, and enhancement of cellular antioxidant capacity. The results of a protein-protein interaction (PPI) network analysis indicate that AJS-PDRN reduces cellular oxidative damage by upregulating the expression of intracellular selenoprotein family members. In summary, our findings reveal that AJS-PDRN mitigates H2O2-induced oxidative damage through multiple pathways, underscoring its significant potential in the prevention and treatment of diseases caused by oxidative stress.

Exploring the Microstructural Effect of FeCo Alloy on Carbon Microsphere Deposition and Enhanced Electromagnetic Wave Absorption.

The rational design of magnetic carbon composites, encompassing both their composition and microstructure, holds significant potential for achieving exceptional electromagnetic wave-absorbing materials (EAMs). In this study, FeCo@CM composites were efficiently fabricated through an advanced microwave plasma-assisted reduction chemical vapor deposition (MPARCVD) technique, offering high efficiency, low cost, and energy-saving benefits. By depositing graphitized carbon microspheres, the dielectric properties were significantly enhanced, resulting in improved electromagnetic wave absorption performances through optimized impedance matching and a synergistic effect with magnetic loss. A systematic investigation revealed that the laminar-stacked structure of FeCo exhibited superior properties compared to its spherical counterpart, supplying a higher number of exposed edges and enhanced catalytic activity, which facilitated the deposition of uniform and low-defect graphitized carbon microspheres. Consequently, the dielectric loss performance of the FeCo@CM composites was dramatically improved due to increased electrical conductivity and the formation of abundant heterogeneous interfaces. At a 40 wt% filling amount and a frequency of 7.84 GHz, the FeCo@CM composites achieved a minimum reflection loss value of -58.2 dB with an effective absorption bandwidth (fE) of 5.13 GHz. This study presents an effective strategy for developing high-performance EAMs.

The Characteristics of Coronary Artery Lesions in COVID-19 Infected Patients With Coronary Artery Disease: An Optical Coherence Tomography Study.

COVID-19 may predispose patients to cardiac injuries but whether COVID-19 infection affects the morphological features of coronary plaques to potentially influence the outcome of patients with coronary artery disease (CAD) remains unknown. By using optical coherence tomography (OCT), this study compared the characteristics of coronary plaque in patients with CAD with/without COVID-19 infection. The 206 patients were divided into 2 groups. The COVID-19 group had 113 patients between December 7, 2022, and March 31, 2023, who received OCT assessment after China decided to lift the restriction on COVID-19 and had a history of COVID-19 infection. The non-COVID-19 group had 93 patients without COVID-19 infection who underwent OCT before December 7, 2022. The COVID-19 group demonstrated a higher incidence of plaque ruptures (53.1% vs 38.7%, p = 0.039), erosions (28.3% vs 11.8%, p = 0.004), fibrous (96.5% vs 89.2%, p = 0.041) and diffuse lesions (73.5% vs 50.5%, p <0.001) compared with the non-COVID-19 group, whereas non-COVID-19 group exhibited a higher frequency of cholesterol crystals (83.9% vs 70.8%, p = 0.027), deep calcifications (65.6% vs 51.3%, p = 0.039) and solitary lesions (57.0% vs 34.5%, p = 0.001). Kaplan-Meier survival analysis revealed a significantly lower major adverse cardiac events-free probability in the COVID-19 group (91.6% vs 95.5%, p = 0.006) than in the non-COVID-19 group. In conclusion, OCT demonstrated that COVID-19 infection is associated with coronary pathological changes such as more plaque ruptures, erosions, fibrosis, and diffuse lesions. Further, COVID-19 infection is associated with a higher propensity for acute coronary events and a higher risk of major adverse cardiac events in patients with CAD.

Research on the optimal ratio of improved electrolytic manganese residue substrate about Pennisetum sinese Roxb growth effects.

Electrolytic manganese slag (EMR) is a solid waste generated in the manganese hydrometallurgy process. It not only takes up significant land space but also contains Mn2+, which can lead to environmental contamination. There is a need for research on the treatment and utilization of EMR. Improved EMR substrate for Pennisetum sinese Roxb growth was determined in pot planting experiments. The study tested the effects of leaching solution, microorganisms, leaf cell structures, and growth data. Results indicated a substrate of 45% EMR, 40% phosphogypsum, 5% Hericium erinaceus fungi residue, 5% quicklime, and 5% dolomite sand significantly increased the available phosphorus content (135.54 ± 2.88 µg·g-1) by 17.95 times, compared to pure soil, and enhanced the relative abundance of dominant bacteria. After 240 days, the plant height (147.00 ± 0.52 cm), number of tillers (6), and aerial dry weight (144.00 ± 15.99g) of Pennisetum sinese Roxb increased by 5.81%, 200%, and 32.58%, respectively. Analyses of leaves and leaching solution revealed that the highest leaf Mn content (46.84 ± 2.91 µg·g-1) being 3.38 times higher than in pure soil, and the leaching solution Mn content (0.66 ± 0.13 µg·g-1) was lowest. Our study suggested P. sinese Roxb grown in an improved EMR substrate could be a feasible option for solidification treatment and resource utilization of EMR.

The waste solid resource utilization was achieved.The growth and ecological restoration value of Pennisetum sinese Roxb in an improved EMR substrate was found.An optimal ratio of improved EMR substrate was proposed.

A Spatial-Spectral Relation-Guided Fusion Network for Multisource Optical RS Image Classification.

Multisource optical remote sensing (RS) image classification has obtained extensive research interest with demonstrated superiority. Existing approaches mainly improve classification performance by exploiting complementary information from multisource data. However, these approaches are insufficient in effectively extracting data features and utilizing correlations of multisource optical RS images. For this purpose, this article proposes a generalized spatial-spectral relation-guided fusion network ( S2 RGF-Net) for multisource optical RS image classification. First, we elaborate on spatial-and spectral-domain-specific feature encoders based on data characteristics to explore the rich feature information of optical RS data deeply. Subsequently, two relation-guided fusion strategies are proposed at the dual-level (intradomain and interdomain) to integrate multisource image information effectively. In the intradomain feature fusion, an adaptive de-redundancy fusion module (ADRF) is introduced to eliminate redundancy so that the spatial and spectral features are complete and compact, respectively. In interdomain feature fusion, we construct a spatial-spectral joint attention module (SSJA) based on interdomain relationships to sufficiently enhance the complementary features, so as to facilitate later fusion. Experiments on various multisource optical RS datasets demonstrate that S2 RGF-Net outperforms other state-of-the-art (SOTA) methods.

Factors linked to prognosis in children with provisional tic disorder: a prospective cohort study.

The purpose of the present study was to estimate the factors linked to the prognosis of children with provisional tic disorder (PTD). We conducted a prospective cohort study enrolled children with PTD who were subsequently followed-up at three-month intervals for 1 year post-enrolment. A total of 259 PTD patients were included in the final analysis. At the end of the follow-up period, 77 (30%) of the patients had achieved clinical remission. Result of the LASSO logistic regression analysis revealed that a disease duration >3 months (OR=4.20, 95% CI 1.20-14.73), moderate/severe tic severity (OR=5.57, 95% CI 2.26-13.76), and comorbid behavioral problems (OR=2.78, 95% CI 1.15-6.69) were significant factors linked to remission in the PTD patients. The path analysis model showed that comorbid behavioral problems and recurrence partially mediated the association between tic severity and remission, with a mediating effect of 37%. Conclusions: We have identified several significant factors linked to prognosis in children with PTD, including comorbid behavioral problems and recurrence, which were found to be important mediators. These findings provide new insights for the clinical management of patients with PTD.

The complete chloroplast genome of the Syzygium buxifolium Hook. Et Arn.1833 and its phylogenetic analysis.

Syzygium buxifolium. Hook. Et Arn.1833 is a member of the Myrtaceae family. This species is used in traditional Chinese medicines. It possesses numerous synonyms, reflecting the ambiguity in its taxonomy. The chloroplast genome has been widely used for species identification and phylogenetic analysis. Regrettably, there is a lack of information regarding the chloroplast genome of S. buxifolium. Here, we intend to obtain the chloroplast genome of S. buxifolium to resolve its classification problems. In particular, we utilized Illumina sequencing technology to sequence, GetOrganelle to assemble, and CPGAVAS2 to characterize the chloroplast genome of S. buxifolium. The chloroplast genome of S. buxifolium had a length of 158,581 bp and consisted of 111 unique genes, comprising 78 protein-coding genes, 29 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. In addition, we identified 86 Simple Sequence Repeats, 345 tandem repetitive sequences, and 34 dispersed repetitive sequences using modules implemented in CPGAVAS2. Lastly, we carried out phylogenetic analysis using Phylosuite. The results indicated a close relationship between S. buxifolium and S. grijsii. This study offers novel genetic data for the molecular identification and subsequent phylogenetic analysis of the Syzygium genus.

A proposed novel digital condylar position adjustment technique to help restore a normal disc-condyle relationship.

Objectives: To demonstrate a novel digital technique that enables real-time visualisation of occlusal transfer and adjustment of condyle position, to (1) improve the repeatability of occlusal transfer and the accuracy of condyle position adjustment and (2) be clinically effective in helping to restore the disc-condyle relationship. Materials and methods: Three participants were included in the study and underwent facebow transfers using two different methods. The digital method used patient-related three-dimensional imaging data matched with digital dental casts for occlusal transfer. The conventional method used anatomical facebows. The condylar position was adjusted based on occlusal transfer results. The results were evaluated and compared in three dimensions. In addition, clinical application data from 36 patients were analysed before and after condylar position adjustment. Statistical significance was set at p < 0.05. Results: Differences in the spatial positions of the three anatomical structures reproduced by both methods were statistically significant (p = 0.000). After adjusting the rotation of the condylar position, the positional deviation of the condylar point along the X- and Z-axes was significantly lower in the digital group (p < 0.05). After adjustment for translation (X and Z), the positional deviation showed no difference along the X- and Z-axes (p > 0.05) but a significant difference along the Y-axis (p < 0.001). Conclusion: A novel digital technique for occlusal transfer and condylar position adjustment was presented. This technique simplifies clinical practice, improves the accuracy of results, and can help restore a normal disc-condyle relationship.

Interfacial epitaxy of multilayer rhombohedral transition-metal dichalcogenide single crystals.

Rhombohedral-stacked transition-metal dichalcogenides (3R-TMDs), which are distinct from their hexagonal counterparts, exhibit higher carrier mobility, sliding ferroelectricity, and coherently enhanced nonlinear optical responses. However, surface epitaxial growth of large multilayer 3R-TMD single crystals is difficult. We report an interfacial epitaxy methodology for their growth of several compositions, including molybdenum disulfide (MoS2), molybdenum diselenide, tungsten disulfide, tungsten diselenide, niobium disulfide, niobium diselenide, and molybdenum sulfoselenide. Feeding of metals and chalcogens continuously to the interface between a single-crystal Ni substrate and grown layers ensured consistent 3R stacking sequence and controlled thickness from a few to 15,000 layers. Comprehensive characterizations confirmed the large-scale uniformity, high crystallinity, and phase purity of these films. The as-grown 3R-MoS2 exhibited room-temperature mobilities up to 155 and 190 square centimeters per volt second for bi- and trilayers, respectively. Optical difference frequency generation with thick 3R-MoS2 showed markedly enhanced nonlinear response under a quasi-phase matching condition (five orders of magnitude greater than monolayers).

Effects of Simvastatin on inflammatory response and biological behavior of adamantinomatous craniopharyngioma.

INTRODUCTION: To investigate the autoinflammatory effect and biological behaviour of simvastatin (SIM) on adamantinomatous craniopharyngioma (ACP) cells. METHODS: Craniopharyngiomas imaging, intraoperative observations, and tumour histopathology were employed to investigate the correlation between esters and craniopharyngiomas. Filipin III fluorescent probe verified the validity of SIM on the alternations of synthesized cholesterol in craniopharyngioma cells. The cell counting kit-8 (CCK8) assay detected the impacts of SIM on cell proliferation and determined the IC50 value of tumour cells. Reverse transcription polymerase chain reaction (RT-PCR) measured the expression of inflammatory factors. Flow cytometry technique detected the cell cycle and apoptosis, and cell scratch assay judged the cell migration. Meanwhile, Western blot was adopted to determine the expression of proteins related to inflammation, proliferation, and apoptosis signalling pathways. RESULTS: In the ACP tumour parenchyma, many cholesterol crystalline clefts were observed, and the deposition of esters was closely associated with craniopharyngioma inflammation. After simvastatin intervention, a reduction in cholesterol synthesis within ACP was noted. RT-PCR analysis revealed SIM inhibited the transcription of inflammatory factors in ACP cells. Western blot analysis demonstrated SIM inhibited nuclear factor-kappa B (NF-κB) p65 activation expression while promoted the expressions of Cl-caspase-3 and P38 MAPK. CCK8 assay indicated a decrease in ACP cell activity upon SIM treatment. Scratch assay signified that SIM hindered ACP cell migration. Flow cytometry results suggested that the drug promoted ACP cell apoptosis. CONCLUSION: SIM suppressed the inflammatory response to craniopharyngiomas by inhibiting craniopharyngioma cholesterol synthesis, inhibited proliferation of ACP cells, and promoted their apoptosis.

Regulation of H9C2 cell hypertrophy by 14-3-3η via inhibiting glycolysis.

It has been reported that Ywhah (14-3-3η) reduces glycolysis. However, it remains unclear about the downstream mechanism by which glycolysis is regulated by 14-3-3η in cardiac hypertrophy. As an important regulator, Yes-associated protein (YAP) interacts with 14-3-3η to participate in the initiation and progression of various diseases in vivo. In this study, the model of H9C2 cardiomyocyte hypertrophy was established by triiodothyronine (T3) or rotenone stimulation to probe into the action mechanism of 14-3-3η. Interestingly, the overexpression of 14-3-3η attenuated T3 or rotenone induced cardiomyocyte hypertrophy and decreased glycolysis in H9C2 cardiomyocytes, whereas the knockdown of 14-3-3η had an opposite effect. Mechanistically, 14-3-3η can reduce the expression level of YAP and bind to it to reduce its nuclear translocation. In addition, changing YAP may affect the expression of lactate dehydrogenase A (LDHA), a glycolysis-related protein. Meanwhile, LDHA is also a possible target for 14-3-3η to mediate glycolysis based on changes in pyruvate, a substrate of LDHA. Collectively, 14-3-3η can suppress cardiomyocyte hypertrophy via decreasing the nucleus translocation of YAP and glycolysis, which indicates that 14-3-3η could be a promising target for inhibiting cardiac hypertrophy.

Screening tools to evaluate the neurotoxic potential of botanicals: building a strategy to assess safety.

AREAS COVERED: This paper outlines the selection of NAMs, including in vitro assays using primary rat cortical neurons, zebrafish embryos, and Caenorhabditis elegans. These assays aim to assess neurotoxic endpoints such as neuronal activity and behavioral responses. Microelectrode array recordings of rat cortical neurons provide insights into the impact of botanical extracts on neuronal function, while the zebrafish embryos and C. elegans assays evaluate neurobehavioral responses. The paper also provides an account of the selection of botanical case studies based on expert judgment and existing neuroactivity/toxicity information. The proposed battery of assays will be tested with these case studies to evaluate their utility for neurotoxicity screening. EXPERT OPINION: The complexity of botanicals necessitates the use of multiple NAMs for effective neurotoxicity screening. This paper discusses the evaluation of methodologies to develop a robust framework for evaluating botanical safety, including complex neuronal models and key neurodevelopmental process assays. It aims to establish a comprehensive screening framework.

SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, but the underlying molecular mechanisms remain largely unclear. The transcription factor (TF) specificity protein 1 (SP1) plays a crucial role in the development of various cancers, including LUAD. Recent studies have indicated that master TFs may form phase-separated macromolecular condensates to promote super-enhancer (SE) assembly and oncogene expression. In this study, we demonstrated that SP1 undergoes phase separation and that its zinc finger 3 in the DNA-binding domain is essential for this process. Through Cleavage Under Targets & Release Using Nuclease (CUT&RUN) using antibodies against SP1 and H3K27ac, we found a significant correlation between SP1 enrichment and SE elements, identified the regulator of the G protein signaling 20 (RGS20) gene as the most likely target regulated by SP1 through SE mechanisms, and verified this finding using different approaches. The oncogenic activity of SP1 relies on its phase separation ability and RGS20 gene activation, which can be abolished by glycogen synthase kinase J4 (GSK-J4), a demethylase inhibitor. Together, our findings provide evidence that SP1 regulates its target oncogene expression through phase separation and SE mechanisms, thereby promoting LUAD cell progression. This study also revealed an innovative target for LUAD therapies through intervening in SP1-mediated SE formation.

USP13 ameliorates nonalcoholic fatty liver disease through inhibiting the activation of TAK1.

BACKGROUND: The molecular mechanisms underlying nonalcoholic fatty liver disease (NAFLD) remain to be fully elucidated. Ubiquitin specific protease 13 (USP13) is a critical participant in inflammation-related signaling pathways, which are linked to NAFLD. Herein, the roles of USP13 in NAFLD and the underlying mechanisms were investigated. METHODS: L02 cells and mouse primary hepatocytes were subjected to free fatty acid (FFA) to establish an in vitro model reflective of NAFLD. To prepare in vivo model of NAFLD, mice fed a high-fat diet (HFD) for 16 weeks and leptin-deficient (ob/ob) mice were used. USP13 overexpression and knockout (KO) strategies were employed to study the function of USP13 in NAFLD in mice. RESULTS: The expression of USP13 was markedly decreased in both in vitro and in vivo models of NAFLD. USP13 overexpression evidently inhibited lipid accumulation and inflammation in FFA-treated L02 cells in vitro. Consistently, the in vivo experiments showed that USP13 overexpression ameliorated hepatic steatosis and metabolic disorders in HFD-fed mice, while its deficiency led to contrary outcomes. Additionally, inflammation was similarly attenuated by USP13 overexpression and aggravated by its deficiency in HFD-fed mice. Notably, overexpressing of USP13 also markedly alleviated hepatic steatosis and inflammation in ob/ob mice. Mechanistically, USP13 bound to transforming growth factor ß-activated kinase 1 (TAK1) and inhibited K63 ubiquitination and phosphorylation of TAK1, thereby dampening downstream inflammatory pathways and promoting insulin signaling pathways. Inhibition of TAK1 activation reversed the exacerbation of NAFLD caused by USP13 deficiency in mice. CONCLUSIONS: Our findings indicate the protective role of USP13 in NAFLD progression through its interaction with TAK1 and inhibition the ubiquitination and phosphorylation of TAK1. Targeting the USP13-TAK1 axis emerges as a promising therapeutic strategy for NAFLD treatment.

Predicting the 28-day prognosis of acute-on-chronic liver failure patients based on machine learning.

BACKGROUND: We aimed to establish a prognostic predictive model based on machine learning (ML) methods to predict the 28-day mortality of acute-on-chronic liver failure (ACLF) patients, and to evaluate treatment effectiveness. METHODS: ACLF patients from six tertiary hospitals were included for analysis. Features for ML models' development were selected by LASSO regression. Models' performance was evaluated by area under the curve (AUC) and accuracy. Shapley additive explanation was used to explain the ML model. RESULTS: Of the 736 included patients, 587 were assigned to a training set and 149 to an external validation set. Features selected included age, hepatic encephalopathy, total bilirubin, PTA, and creatinine. The eXtreme Gradient Boosting (XGB) model outperformed other ML models in the prognostic prediction of ACLF patients, with the highest AUC and accuracy. Delong's test demonstrated that the XGB model outperformed Child-Pugh score, MELD score, CLIF-SOFA, CLIF-C OF, and CLIF-C ACLF. Sequential assessments at baseline, day 3, day 7, and day 14 improved the predictive performance of the XGB-ML model and can help clinicians evaluate the effectiveness of medical treatment. CONCLUSIONS: We established an XGB-ML model to predict the 28-day mortality of ACLF patients as well as to evaluate the treatment effectiveness.