A case of treatment for pulmonary infection caused by multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a major pathogen in hospital-acquired infections notorious for its strong acquired resistance and complex drug resistance mechanisms. Owing to the lack of effective drugs, the mortality rate of extensively drug-resistant A. baumannii pneumonia can reach as high as 65%. This article analyzes a case where a combination of cefoperazone-sulbactam, polymyxin B, and minocycline with rifampicin successfully treated XDR-AB pulmonary infection. Combination therapy is effective and has a particular clinical value.

Hepatitis B virus X protein and TGF-ß: partners in the carcinogenic journey of hepatocellular carcinoma.

Hepatitis B infection is substantially associated with the development of liver cancer globally, with the prevalence of hepatocellular carcinoma (HCC) cases exceeding 50%. Hepatitis B virus (HBV) encodes the Hepatitis B virus X (HBx) protein, a pleiotropic regulatory protein necessary for the transcription of the HBV covalently closed circular DNA (cccDNA) microchromosome. In previous studies, HBV-associated HCC was revealed to be affected by HBx in multiple signaling pathways, resulting in genetic mutations and epigenetic modifications in proto-oncogenes and tumor suppressor genes. In addition, transforming growth factor-ß (TGF-ß) has dichotomous potentials at various phases of malignancy as it is a crucial signaling pathway that regulates multiple cellular and physiological processes. In early HCC, TGF-ß has a significant antitumor effect, whereas in advanced HCC, it promotes malignant progression. TGF-ß interacts with the HBx protein in HCC, regulating the pathogenesis of HCC. This review summarizes the respective and combined functions of HBx and TGB-ß in HCC occurrence and development.

Aggravating effect of abnormal low-density protein cholesterol level on coronary atherosclerotic plaque in type 2 diabetes mellitus patients assessed by coronary computed tomography angiography.

BACKGROUND: The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM. MATERIALS AND METHODS: This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression. RESULTS: A total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: ß = 0.116; positive remodelling: ß = 0.138; spotty calcification: ß = 0.091; NOS: ß = 0.427; OS: ß = 0.659: SIS: ß = 1.114; SSS: ß = 2.987; PID: ß = 2.716, all P value < 0.001). CONCLUSIONS: Abnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.

Impact of DEHP on mitochondria-associated endoplasmic reticulum membranes and reproductive toxicity in ovary.

Di(2-ethylhexyl) phthalate (DEHP) is a widely recognized environmental endocrine disruptor that potentially impacts female reproductive function, although the specific mechanisms leading to such impairment remain unclear. A growing body of research has revealed that the endoplasmic reticulum and mitochondrial function significantly influence oocyte quality. The structure of mitochondria-associated endoplasmic reticulum membranes (MAMs) is crucial for facilitating the exchange of Ca2+, lipids, and metabolites. This study aimed to investigate the alterations in the composition and function of MAMs after DEHP exposure and to elucidate the underlying mechanisms of ovarian toxicity. The female mice were exposed to DEHP at doses of 5 and 500 mg/kg/day for one month. The results revealed that DEHP exposure led to reduced serum anti-Müllerian hormone levels and increased atretic follicles in mice. DEHP induced endoplasmic reticulum stress and disrupted calcium homeostasis in oocytes. Furthermore, DEHP impaired the mitochondrial function of oocytes and reduced their membrane potential, and promoting apoptosis. Similar results were observed in human granulosa cells after exposure to mono-(2-ethylhexyl) phthalate (MEHP, metabolites of DEHP) in vitro. Proteomic analysis and transmission electron microscopy revealed modifications in the functional proteins and structure of the MAMs, and the suppression of oxidative phosphorylation pathways. The findings of this investigation provide a new perspective on the mechanism underlying the reproductive toxicity of DEHP in females.

Impact and migration behavior of triclosan on waste-activated sludge anaerobic digestion.

Triclosan (TCS), a hydrophobic antibacterial agent, is extensive application in daily life. Despite a low biodegradability rate, its hydrophobicity results in its accumulation in waste-activated sludge (WAS) during domestic and industrial wastewater treatment. While anaerobic digestion is the foremost strategy for WAS treatment, limited research has explored the interphase migration behavior and impacts of TCS on WAS degradation during anaerobic digestion. This study revealed TCS migration between solid- and liquid-phase in WAS digestion. The solid-liquid distribution coefficients of TCS were negative for proteins and polysaccharides and positive for ammonium. High TCS levels promoted volatile-fatty-acid accumulation and reduced methane production. Enzyme activity tests and functional prediction indicated that TCS increased enzyme activity associated with acid production, in contrast to the inhibition of key methanogenic enzymes. The findings of the TCS migration behavior and its impacts on WAS anaerobic digestion provide an in-depth understanding of the evolution of enhanced TCS-removing technology.

Confounding amplifies the effect of environmental factors on COVID-19.

The global COVID-19 pandemic has severely impacted human health and socioeconomic development, posing an enormous public health challenge. Extensive research has been conducted into the relationship between environmental factors and the transmission of COVID-19. However, numerous factors influence the development of pandemic outbreaks, and the presence of confounding effects on the mechanism of action complicates the assessment of the role of environmental factors in the spread of COVID-19. Direct estimation of the role of environmental factors without removing the confounding effects will be biased. To overcome this critical problem, we developed a Double Machine Learning (DML) causal model to estimate the debiased causal effects of the influencing factors in the COVID-19 outbreaks in Chinese cities. Comparative experiments revealed that the traditional multiple linear regression model overestimated the impact of environmental factors. Environmental factors are not the dominant cause of widespread outbreaks in China in 2022. In addition, by further analyzing the causal effects of environmental factors, it was verified that there is significant heterogeneity in the role of environmental factors. The causal effect of environmental factors on COVID-19 changes with the regional environment. It is therefore recommended that when exploring the mechanisms by which environmental factors influence the spread of epidemics, confounding factors must be handled carefully in order to obtain clean quantitative results. This study offers a more precise representation of the impact of environmental factors on the spread of the COVID-19 pandemic, as well as a framework for more accurately quantifying the factors influencing the outbreak.

A co-assembly process for high strength and injectable dual network gels with sustained doxorubicin release performance.

Adopting a non-covalent co-assembly strategy shows great potential in loading drugs efficiently and safely in drug delivery systems. However, finding an efficient method for developing high strength gels with thixotropic characteristics is still challenging. In this work, by hybridizing the low molecular weight gelator fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-F) (first single network, 1st SN) and alginate (second single network, 2nd SN) into a dual network (DN) gel, gels with high strength as well as thixotropy were prepared efficiently. The DN gels showed high strength (103 Pa in SN gels and 105 Pa in DN gels) and thixotropic characteristics (yield strain <25%; recovery ratio >85% within 100 seconds). The application performance was verified by loading doxorubicin (DOX), showing better encapsulation capacity (77.06% in 1st SN, 59.11% in 2nd SN and 96.71% in DN) and sustained release performance (lasting one week under physiological conditions) than single network gels. Experimental and DFT results allowed the elaboration of the specific non-covalent co-assembly mechanism for DN gel formation and DOX loading. The DN gels were formed by co-assembly driven by H-bond and π-π stacking interactions and then strengthened by Ca2+-coupling. Most DOX molecules co-assembled with Fmoc-F and alginate through π-π stacking and H-bond interactions (DOX-I), with a few free DOX molecules (DOX-II) left. Proven by the release dynamics test, DOX was released through a diffusion-erosion process, in an order of DOX-I first and then DOX-II. This work suggests that non-covalent co-assembly is a useful technique for effective material strengthening and drug delivery.

Characteristics analysis of hepatitis B core-related antigen in children with hepatitis B e antigen-positive chronic viral hepatitis B infection.

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups (P = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB (R2 = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

Scalable Fabrication of Black Phosphorous Films for Infrared Photodetector Arrays.

Bulk black phosphorous (bP) exhibits excellent infrared (IR) optoelectronic properties, but most reported bP IR photodetectors are fabricated from single exfoliated flakes with lateral sizes of < 100 µm. Here, scalable thin films of bP suitable for IR photodetector arrays are realized through a tailored solution-deposition method. The properties of the bP film and their protective capping layers are optimized to fabricate bP IR photoconductors exhibiting specific detectivities up to 4.0 × 108 cm Hz1/2 W-1 with fast 30/60 µs rise/fall times under λ = 2.2 µm illumination. The scalability of the bP thin film fabrication is demonstrated by fabricating a linear array of 25 bP photodetectors and obtaining 25 × 25 pixel IR images at ≈203 ppi with good spatial fidelity. This research demonstrates a commercially viable method of fabricating scalable bP thin films for optoelectronic devices including room temperature-operable IR photodetector arrays.

Entropy drives the ligand recognition in G-protein-coupled receptor subtypes.

Achieving ligand subtype selectivity within highly homologous subtypes of G-protein-coupled receptor (GPCR) is critical yet challenging for GPCR drug discovery, primarily due to the unclear mechanism underlying ligand subtype selectivity, which hampers the rational design of subtype-selective ligands. Herein, we disclose an unusual molecular mechanism of entropy-driven ligand recognition in cannabinoid (CB) receptor subtypes, revealed through atomic-level molecular dynamics simulations, cryoelectron microscopy structure, and mutagenesis experiments. This mechanism is attributed to the distinct conformational dynamics of the receptor's orthosteric pocket, leading to variations in ligand binding entropy and consequently, differential binding affinities, which culminate in specific ligand recognition. We experimentally validated this mechanism and leveraged it to design ligands with enhanced or ablated subtype selectivity. One such ligand demonstrated favorable pharmacokinetic properties and significant efficacy in rodent inflammatory analgesic models. More importantly, it is precisely due to the high subtype selectivity obtained based on this mechanism that this ligand does not show addictive properties in animal models. Our findings elucidate the unconventional role of entropy in CB receptor subtype selectivity and suggest a strategy for rational design of ligands to achieve entropy-driven subtype selectivity for many pharmaceutically important GPCRs.

Discovery of first-in-class PROTACs targeting maternal embryonic leucine zipper kinase (MELK) for the treatment of Burkitt lymphoma.

Maternal embryonic leucine zipper kinase (MELK) is a novel target for the treatment of various kinds of B-cell malignancies. However, the toxicity of inhibitors of MELK has led to clinical failures in cancer treatments. Moreover, inactivation of MELK catalytic domain is insufficient for achieving cancer cell apoptosis. To further confirm the role of MELK in Burkitt lymphoma treatment, we describe herein a structure-guided design of PROTACs targeting MELK. Through design, computer-assisted optimization and SAR studies, we developed the first-in-class MELK-targeting PROTAC MGP-39, which promoted a rapid and potent degradation of MELK in RAMOS cells. Additionally, the newly designed MELK degrader induced significant cell cycle arrest and apoptosis in cancer cells. Notably, compared to MELK inhibitors, MGP-39 has better anti-cancer activity and lower toxicity, indicating the practical role of PROTACs in avoiding the side effects of traditional inhibitors. More importantly, our results show that the use of a PROTAC can be adopted as a general and effective strategy for targeted cancer therapy.

Entropy-Dominated Triplet Exciton Emission in Carbon Dots.

Phosphorescence in carbon dots (CDs) from triplet exciton radiative recombination at room temperature has achieved significant advancement. Confinement and nanoconfinement, serving as valuable techniques, are commonly utilized to brighten triplet exciton in CDs, thereby enhancing their phosphorescence. However, a comprehensive and universally applicable physical description of confinement-enhanced phosphorescence is still lacking, despite efforts to understand its underlying nature. In this study, the dominance of entropy is revealed in triplet exciton emission from CDs through the establishment of a microscopic vibration state model. CDs with varying entropy levels are studied, indicating that in a low entropy system, the multi-energy triplet exciton emission in CDs exhibits enhanced brightness, accompanied by a corresponding increase in their lifetimes. The product of lifetime and intensity in CDs serves as a descriptor for their phosphorescence properties. Moreover, an entropy-dependent information variation system based on the CDs is demonstrated. Specifically, in a low-entropy system, information is retained, whereas the corresponding information is erased in a high-entropy system. This work elucidates the underlying physical nature of confinement-enhanced triplet exciton emission, offering a deeper understanding of achieving ultralong phosphorescence in the future.

Substrate calibration method of a computer-generated hologram based on ray propagation in a three-dimensional model.

In interferometry with a computer-generated hologram (CGH), the substrate error of the CGH limits its high-precision aspheric measurement application. The propagation form of the substrate error is still ambiguous although 0th-order calibration can partly correct it. We established the ray propagation in a three-dimensional model in order to solve the ambiguity of substrate error propagation. This method shows the modulation process of the CGH substrate error on the transmitted wavefront for the first time, until now, to the best of our knowledge. The experiments show that the propagation of the substrate error can be accurately analyzed, and the CGH design efficiency also is significantly improved after applying this method.

Efficient Anti-Icing of a Stable PFA Coating for Wind Power Turbine Blades.

Superhydrophobic coatings are increasingly recognized as a promising approach to enhancing power generation efficiency and prolonging the operational lifespan of wind turbines. In this research, a durable superhydrophobic perfluoroalkoxy alkane (PFA) coating was developed and specifically designed for spray application onto the surface of wind turbine blades. The PFA coating features a micronano hierarchical structure, exhibiting a high water contact angle of 167.0° and a low sliding angle of 1.7°. The optimal PFA coating exhibits stability and maintains a superhydrophobic performance during mechanical and chemical tests. The findings of this study establish a positive association between the surface energy of the coating and its effectiveness in anti-icing. The delayed icing time for the PFA-coated surface is 46.83 times longer than that of an uncoated surface, and the ice adhesion strength is only 1.875 kPa. Additionally, the PFA coating demonstrates remarkably high ice suppression efficiencies of 94.7 and 99.5% in anti-icing experiments at ambient temperatures of -6 and -10 °C, respectively. It is anticipated that this stable superhydrophobic PFA coating will be a candidate for anti-icing applications in wind turbine blades.

Zinc finger translocation­associated protein promotes ferroptosis through the upregulation of ACSL4 expression in vascular endothelial cells.

Numerous studies have reported the potential involvement of ferroptosis in the development of atherosclerosis (AS). Acyl-CoA synthetase long chain family member 4 (ACSL4) is an essential component in the promotion of ferroptosis. The present study aimed to investigate the role of ACSL4 and zinc finger translocation-associated protein (ZFTA) in the regulation of endothelial cell ferroptosis in AS. Human umbilical vein endothelial cells (HUVECs) with ACSL4 knockout were generated using CRISPR/Cas9 technology. To assess ferroptosis, malondialdehyde concentration, iron content and reactive oxygen species levels were quantified in the present study. In addition, western blot analysis was conducted to explore the potential mechanisms underlying ACSL4 and ZFTA in the modulation of ferroptosis in HUVECs. The results of the present study demonstrated that the expression levels of ACSL4 and ZFTA were significantly increased in human atherosclerotic plaques. In addition, ACSL4 knockout led to a reduced susceptibility to ferroptosis, while ZFTA contributed to ferroptosis in HUVECs. Results of the present study also demonstrated that ZFTA overexpression upregulated ACSL4 expression in HUVECs, whereas ZFTA knockdown led to decreased ACSL4 expression. Co-transfection experiments demonstrated that the ZTFA overexpression-mediated increase in ferroptosis was reversed following ACSL4 knockdown. Collectively, results of the present study highlighted that ACSL4 mediated the effects of ZFTA on the ferroptosis of HUVECs. Thus, the present study demonstrated the potential role of ACSL4 and ZFTA in the regulation of ferroptosis, and highlighted that ferroptosis-related pathways may act as potential targets in the treatment of AS.

Research of Pulmonary Fibrosis Lesions Based on FLIM and SHG Imaging Microscopy.

Two-photon fluorescence lifetime microscopy (TP-FLIM) is a powerful quantitative imaging technique that characterizes and analyzes the structure and function of biological samples through a combination of intensity and lifetime imaging. Because TP-FLIM is independent of the fluorescence signal intensity and the fluorophore concentration, it is widely used in high-throughput, high-content drug screening and clinical diagnostics. Second harmonic generation (SHG) imaging technology has the advantages of high spatial resolution and imaging depth inherent to nonlinear optical imaging. Second harmonics often appear in noncentrosymmetric structures. Collagen tissue in biological organisms is a good example of these structures, showing strong harmonic effects. Therefore, SHG has been widely used for imaging of specific tissue structure imaging. TP-FLIM technology is highly sensitive for quantitatively detecting changes in microenvironments. The objective of this study is to examine pathological pulmonary fibrosis slices using a combined approach of TP-FLIM and SHG technology. The fluorescence lifetime data of pulmonary collagen fibers are analyzed by using phasor plot analysis methods, and normal collagen fibers and fibrotic collagen fibers are distinguished by calculating the aspect ratio from the SHG images formed by the collagen fibers. Our study provides a new method for a deeper understanding of the pathological mechanisms and clinical diagnosis of pulmonary fibrosis and other collagen fiber-related disorders.

Dichorionic diamniotic twin pregnancy after preimplantation genetic testing and single blastocyst transfer.

BACKGROUND: In addition to the potential for multiple pregnancies, natural conception occurring in preimplantation genetic testing (PGT) increases undesired genetic risk. Some studies showed that a dichorionic diamniotic twin pregnancy after a single blastocyst transfer could be caused by embryo splitting or concurrent spontaneous conception. CASE: We describe a patient undergoing PGT who had a dichorionic diamniotic twin pregnancy after single blastocyst transfer in a natural cycle. In this case, we recommended to determine genetic status of the twins by prenatal diagnosis. The results showed that karyotype, chromosome copy number variation, and parental ACAT1 variation of the twins were all normal and similar. To investigate the origin of pregnancy, we used the genotype data of single-nucleotide polymorphisms typical of genome-wide association studies. Dizygotic twins were inferred by robust estimation of kinship coefficients, which confirmed the occurrence of a spontaneous conception. CONCLUSIONS: This case strengthens the importance of genetic counseling to inform couples with reproductive genetic risk, such as those who undergo PGT, that intercourse should be avoided, especially in natural transfer cycles. Moreover, prenatal diagnosis remains essential and is strongly recommended to avoid genetic risks.

Association between the serum uric acid levels and prostate cancer: evidence from National Health and Nutrition Examination Survey (NHANES) 1999-2010.

Background: Uric acid may play a critical role in protection against cancer by the suppression of inflammation. The association between serum uric acid (SUA) levels and prostate cancer risk is debatable yet has received little attention in the American population. Therefore, we used data from the National Health and Nutrition Examination Survey (NHANES) to determine their correlation. Methods: Using information from NHANES 1999-2010, a total of 62,160 individuals from the general population were included in this cross-sectional study. Additionally, a number of covariates were acquired. Prostate cancer was used to divide the participants into two groups: prostate cancer group (n=315) and non-prostate cancer group (n=7,545). A weighted adjusted logistic regression analysis was conducted to examine the potential correlation between SUA and prostate cancer. Results: Our study comprised a total of 7,860 participants. After full adjustment for confounders, SUA was not significantly associated with prostate cancer [odds ratio (OR) 0.91, 95% confidence interval (CI): 0.82-1.00, P=0.058]. In participants aged 60 years and above (≥60 years), a higher SUA was significantly associated with a lower risk of prostate cancer (OR 0.88, 95% CI: 0.80-0.96, P=0.003). However, among those younger than 60 years (<60 years), there was no association between SUA and prostate cancer risk (OR 1.29, 95% CI: 0.69-2.42, P=0.42). In addition, in the subgroup analysis stratified by body mass index, hypertension and diabetes, there was no significant correlation between SUA and prostate cancer. Conclusions: SUA is negatively associated with the risk of prostate cancer in older men, especially for those 60 years of age and beyond.

Structural basis of neuropeptide Y signaling through Y1 and Y2 receptors.

Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro34]-NPY and [Leu31, Pro34]-NPY, mainly acting on Y1R, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N-terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through Y2R. However, the recognition mechanisms of Y1R and Y2R with specific agonists remain elusive, thereby hindering subtype receptor-selective drug development. In this study, we report three cryo-electron microscopy (cryo-EM) structures of Gi2-coupled Y1R and Y2R in complexes with NPY, as well as Y1R bound to a selective agonist [Leu31, Pro34]-NPY. Combined with cell-based assays, our study not only reveals the conserved peptide-binding mode of NPY receptors but also identifies an additional sub-pocket that confers ligand selectivity. Moreover, our analysis of Y1R evolutionary dynamics suggests that this sub-pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family.

Integrated analysis of single-cell and bulk RNA sequencing data reveals a cellular senescence-related signature in hepatocellular carcinoma.

The mortality of hepatocellular carcinoma (HCC) is on the rise globally, particularly in the Western world, with etiology gradually shifting from virus-related liver diseases to metabolic disorders such as non-alcoholic fatty liver disease. Early detection of HCC is challenging, and effective prognostic indicators are currently lacking, urgently necessitating reliable markers to assist in treatment planning and clinical management. Here, we introduce hepatocellular carcinoma senescence genes (HSG) to assess cellular senescence in HCC and devise a hepatocellular carcinoma senescence score (HSS) for prognostic prediction. Higher HSS levels signify poorer prognosis and increased tumor proliferation activity. Additionally, we observe alterations in the tumor immune microenvironment with higher HSS levels, such as increased infiltration of Treg, potentially providing a basis for immunotherapy. Furthermore, we identify key genes, such as PTTG1, within the senescence gene set and demonstrate their regulatory roles in HCC cells and Treg through experimentation. In summary, we establish a scoring system based on hepatocellular carcinoma senescence genes for prognostic prediction in HCC, potentially offering guidance for clinical treatment planning.