Zinc ions activate AKT and promote prostate cancer cell proliferation via disrupting AKT intramolecular interaction.

Prostate is a zinc rich organ and the physiological function of the abundant zinc ions is relatively less understood. AKT kinase is a pivotal regulator downstream of cytokines, growth factors and other extracellular stimuli, and the attachment of its PH domain to PtdIns-3,4,5-P3 (PIP3) and the subsequent phosphorylation of its kinase domain by PDPK1 are considered important for its activation. Herein, we report a regulatory mechanism of AKT kinase by zinc ions. Mechanistically, zinc ions directly bind to AKT and facilitate AKT activation through disrupting the interaction between PH and kinase domains within AKT molecule. Consistently, AKT1-H89A/E91A mutant (zinc-binding-deficient) fails to respond to zinc ions and exhibits strong interaction between PH and kinase domains, and it is less oncogenic in orthotopic xenograft model of prostate cancer. On the other hand, the AKT1-W80L mutant with minimum intra-molecular interaction between PH and kinase domains shows strong tumor promoting capacity although it could not be further stimulated by zinc ions. Overall, this study reveals a distinctive regulatory mechanism of AKT activation and implies a tumor promoting role of the zinc ions in prostate cancer.

CRISPR/Cas12 System-Based Assay for Rapid, Sensitive Detection of Rotavirus in Food Samples.

Foodborne viruses have become an important threat to food safety and human health. Among the foodborne viruses, group A rotavirus is the most important pathogen of diarrhea in autumn and winter. The field detection of rotavirus is crucial for the early control of infection and patient management. Quantitative real-time reverse transcription-polymerase chain reaction is the most widely used in virus detection. However, the technique relies on high-cost instruments and trained personnel, which limit its use in field detection. In this study, we developed accurate, realizable, and simple detection methods by combining optimized CRISPR (clustered regularly interspaced short palindromic repeats) Cas12 and reverse transcription loop-mediated isothermal amplification (RT-LAMP) (reverse transcription loop-mediated isothermal amplification) to reduce the requirements for temperature control and costly real-time fluorescence polymerase chain reaction instruments. We investigated two nucleic acid detection systems combining RT-LAMP with CRISPR Cas12a and RT-LAMP with CRISPR Cas12b and compared them with reverse transcription-quantitative polymerase chain reaction. The resulting detection system only needs a reaction temperature and in single tube to react for 60 min with the detection sensitivity of 38 copies/µL. Overall, this study developed an innovative method for the rapid detection of rotavirus in food samples, which will help to effectively identify food contaminated by pathogens and prevent human infections and economic losses caused by disease outbreaks.

Genetically Encoded Fluorescence Resonance Energy Transfer Biosensor for Live-Cell Visualization of Lamin A Phosphorylation at Serine 22.

Extensive phosphorylation at serine 22 (pSer22) on lamin A is the hallmark of cell mitosis, which contributes to the breakdown of nuclear envelope. In the interphase, pSer22 lamin A exists in low abundance and is involved in mechanotransduction, virus infection, and gene expression. Numerous evidences emerge to support lamin A regulation on cell function and fate by phosphorylation. However, live-cell imaging tools for visualizing the dynamics of pSer22 lamin A are yet to be established. Herein, we developed a novel lamin A phosphorylation sensor (LAPS) based on fluorescence resonance energy transfer (FRET) with high sensitivity and specificity. We observed the dynamic lamin A phosphorylation during the cell cycle progression in single living cells: the increase of pSer22 modification when cells entered the mitosis and recovered upon the mitosis exit. Our biosensor also showed the gradual reduction of pSer22 modification during cell adhesion and in response to hypotonic environment. By applying LAPS, we captured the propagation of pSer22 modification from inside to outside of the inner nuclear membrane, which further led to the breakdown of nuclear envelope. Meanwhile, we found the synchronous phosphorylation of pSer22 lamin A and H3S10ph at mitosis entry. Inhibition of Aurora B, the responsible kinase for H3S10ph, could shorten the mitotic period without obvious effect on the pSer22 modification level of lamin A. Thus, LAPS allows the spatiotemporal visualization of the lamin A pSer22, which will be useful for elucidating the molecular mechanisms underlying cell mitosis and mechanoresponsive processes.

The roles of different gene expression regulators in acoustic variation in the intermediate horseshoe bat revealed by long-read and short-read RNA sequencing data.

Gene expression changes contribute greatly to phenotypic variations in nature. Studying patterns of regulators of gene expression is important to fully understand the molecular mechanism underlying phenotypic variations. In horseshoe bats, the cochleae are finely tuned to echoes of call frequency. Here, using 2 recently diverged subspecies of the intermediate horseshoe bat (Rhinolophus affinis hainanus and R. a. himalayanus) with great acoustic variations as the system, we aim to explore relative roles of different regulators of gene expression (differential gene expression, alternative splicing (AS) and long non-coding RNAs (lncRNAs)) in phenotypic variation with a combination of Illumina short-read and Nanopore long-read RNA-seq data from the cochlea. Compared to R. a. hainanus, R. a. himalayanus exhibited much more upregulated differentially expressed genes (DEGs) and multiple of them may play important roles in the maintenance and damage repair of auditory hair cells. We identified 411 differentially expressed lncRNAs and their target DEGs upregulated in R. a. himalayanus were also mainly involved in a protective mechanism for auditory hair cells. Using 3 different methods of AS analysis, we identified several candidate alternatively spliced genes (ASGs) that expressed different isoforms which may be associated with acoustic divergence of the 2 subspecies. We observed significantly less overlap than expected between DEGs and ASGs, supporting complementary roles of differential gene expression and AS in generating phenotypic variations. Overall, our study highlights the importance of a combination of short-read and long-read RNA-seq data in examining the regulation of gene expression changes responsible for phenotypic variations.

Evaluation of proximod, a selective agonist of sphingosine-1-phosphate receptor-1, in healthy volunteers and patients with rheumatoid arthritis: a phase 1, double-blind, randomised, placebo-controlled, ascending dose trial.

BACKGROUND: Proximod is a selective agonist of sphingosine-1-phosphate receptor-1 (S1PR1). It acts by redirecting lymphocytes from the circulation to secondary lymph nodes, and is under development as an immunomodulator for rheumatoid arthritis. We aimed to evaluate the safety, pharmacokinetics, and preliminary efficacy of proximod in healthy volunteers and patients with rheumatoid arthritis. METHODS: We did a two part, phase 1, double-blind, randomised, placebo-controlled, ascending dose trial at a single centre in China. Eligible participants were adults aged 18-50 years with a BMI of 18-28 kg/m2 for healthy volunteers and aged 18-70 years with a BMI of 18-30 kg/m2 for patients with rheumatoid arthritis. In part 1, healthy volunteers were randomly assigned within ten cohorts to receive a single oral dose of proximod (0·125 mg, 0·25 mg, 0·5 mg, 1 mg, 1·5 mg, 2 mg, 3 mg, 5 mg, 10 mg, or 15 mg in cohorts 1-10) or placebo. In part 2, healthy volunteers were randomly assigned to receive once-daily doses of proximod 5 mg or placebo, and patients with rheumatoid arthritis were randomly assigned to receive once-daily doses of proximod 5 mg, proximod 10 mg, or placebo, for 28 days. Patients and investigators were masked to treatment assignment. The primary outcomes were safety, tolerability, and pharmacokinetic profile of proximod for 72 days in healthy volunteers and for 48 days in patients with rhematoid arthritis, assessed in all treated participants. This trial is registered with ClinicalTrials.gov (NCT06361199, NCT06361186), and is complete. FINDINGS: Between Nov 1, 2017, and June 22, 2021, 124 healthy volunteers were randomly assigned in part 1 of the study and 124 were included in the analyses (mean age 34·3 years [SD 6·9], 62 [50%] of 124 participants were women and 62 [50%] were men, and 116 [94%] were Han Chinese ethnicity). Between Feb 16, 2022, and Oct 8, 2023, 113 participants were screened for inclusion in part 2 (80 healthy volunteers and 33 patients with rheumatoid arthritis). 79 participants were excluded and 34 were randomly assigned (10 healthy participants and 24 patients with rheumatoid arthritis), 34 of whom were included in the analyses. Ten (100%) of ten healthy participants were Han Chinese ethnicity, with a mean age of 39·9 years (SD 7·3). Five (50%) of ten healthy volunteers were women and five (50%) were men). 22 (92%) of 24 participants with rheumatoid arthritis were Han Chinese ethnicity, with a mean age of 52·7 years (SD 6·8). 22 (92%) of 24 patients with rheumatoid arthritis were women and two (8%) were men. In part 1, all doses of proximod were well tolerated, with no dose-related adverse reactions or serious adverse events observed. In part 2, 74 adverse reactions were reported in eight (80%) of ten healthy volunteers and 22 (92%) of 24 patients with rheumatoid arthritis. Adverse events associated with proximod were predominantly mild or moderate. In part 2, the concentration of proximod and its active metabolite, proximod-phosphate, gradually increased in all three groups receiving proximod and the EC50 of the S1PR1 agonist for proximod-phosphate (6·1 ng/mL) was reached on day 14 for both 5 mg groups, and on day 7 for the 10 mg group. The mean Ctrough values for proximod-phosphate on day 28 were 7·7 ng/mL and 10·2 ng/mL for 5 mg in healthy volunteers and patients with rheumatoid arthritis, respectively, and 15·3 ng/mL for 10 mg in patients with rheumatoid arthritis. In patients with rheumatoid arthritis, lymphocyte count decreased after treatment in all proximod groups reaching nadir at approximately day 28, with a corresponding percentage decline from baseline of 65·25% in the 5 mg group, 71·64% in the 10 mg group, and 20·57% in the placebo group. INTERPRETATION: Proximod exhibited good tolerability over the 28-day treatment period, demonstrating its potential in reducing blood lymphocyte count. These results highlight the promise of the S1PR1 agonist proximod as a potential candidate for rheumatoid arthritis treatment, warranting further investigation in subsequent clinical studies. FUNDING: Beijing Union Pharmaceutical Factory and Jian Kuan (Suzhou) Biotechnology.

Decoding wheat contamination through self-assembled whole-cell biosensor combined with linear and non-linear machine learning algorithms.

The contamination of mycotoxins is a serious problem around the world. It has detrimental effects on human beings and leads to tremendous economic loss. It is essential to develop a rapid and non-destructive method for contamination recognition particularly for early alarm. In this study, the whole-cell biosensor array was constructed and employed for rapid recognition of wheat contamination by combining with machine learning algorithms. Seven key VOCs were explored through univariate coupling to multivariate analysis of orthogonal partial least squares-discrimination analysis (OPLS-DA) models. The promoters of dnaK, katG, oxyR, soxS obtained from the stress-responsive of key VOCs were fused to the bacterial operon and fabricated on the whole-cell biosensor. The constructed whole-cell biosensor array was consisted with four kinds of sensors and 18 sensor unit. The bioluminescent intensity combined with linear machine learning algorithm of partial least squares discriminant analysis (PLS-DA) and non-linear algorithms of back propagating artificial neural network (BP-ANN) and least square support vector machine (LS-SVM) were employed to establish discrimination models for mold contamination especially for early warning. The Monte-Carlo strategy was performed to generate thirty subsets for modeling to give more reliable results. As a result, the whole-cell biosensor combined with non-linear algorithm of LS-SVM was practicable for detecting mold identification for wheat early-warning with the accuracy of 97.24%. Additionally, this study provides practical and effective methods not only for wheat quality guarantee and supervision but also for other foodstuffs.

Multifunctional nanoplatform with near-infrared triggered nitric-oxide release for enhanced tumor ferroptosis.

Ferroptosis has emerged as a promising strategy for cancer treatment. Nevertheless, the efficiency of ferroptosis-mediated therapy remains a challenge due to high glutathione (GSH) levels and insufficient endogenous hydrogen peroxide in the tumor microenvironment. Herein, we presented a nitric-oxide (NO) boost-GSH depletion strategy for enhanced ferroptosis therapy through a multifunctional nanoplatform with near-infrared (NIR) triggered NO release. The nanoplatform, IS@ATF, was designed that self-assembled by loading the NO donor L-arginine (L-Arg), ferroptosis inducer sorafenib (SRF), and indocyanine green (ICG) onto tannic acid (TA)-Fe3+‒metal-phenolic networks (MPNs) modified with hydroxyethyl starch. Inside the tumor, SRF could inhibit GSH biosynthesis, impair the activation of glutathione peroxidase 4, and disrupt the ferroptosis defensive system. In conjunction with TA-Fe3+‒MPNs, which has cascaded Fenton catalytic activity, it could navigate the lethal ferroptosis to cancer cells. Upon NIR laser irradiation, the ICG-generated ROS oxidated L-Arg to a substantial quantity of NO, which further depleted the intracellular GSH and caused LPO accumulation, enhancing cell ferroptosis. Moreover, ICG also serves as a photothermal agent that can produce hyperthermia when exposed to irradiation, further potentiating ferroptosis therapy. In addition, the nanoplatform showed significantly improved tumor therapeutic efficacy and anti-metastasis efficiency. This work thus demonstrated that utilizing NO boost-GSH depletion to enhance ferroptosis induction is a feasible and promising strategy for cancer treatment.

Transcriptome analysis of the genes and regulators involving in vitamin E biosynthesis in Elaeagnus mollis diels.

Elaeagnus mollis is an important newly developing woody oil plant species and the vitamin E (VitE) content in its kernel oil is relatively high. In the present study, the VitE component content and functional genes involving in VitE biosynthesis in E. mollis kernel at different developmental stage were investigated. The VitE content increased with kernel development, reaching up to ~ 7.96 mg/g oil in kernel mature stage. The content of tocopherol was much higher than that of tocotrienol and γ-tocopherol became the dominant component. E. mollis kernel extracts had relatively strong antioxidant capacity. We identified 17 genes (16 VTEs and 1 homogentisic acid geranylgeranyl transferase (HGGT)) directly involving in VitE biosynthesis in RNA-Seq data. Phylogenetic and qRT-PCR results indicated that the annotation and reliability of the RNA-Seq were accurate. Transient overexpression of EmVTE3 and EmWRKY13 in tobacoo leaves increased and decreased the VitE content to 192.18 and 118.29 µg/g, respectively. Weighted gene co-expression analysis elucidated that the blue module showed significant correlation with tocopherol content. Co-expression network analysis revealed that 2-methyl-6-phytobenzoquinone methyltransferase (MPBQ-MT/VTE3) played a vital role and EmWRKY13 may be a key negative regulator in E. mollis VitE biosynthesis. This study not only revealed the traditional VitE biosynthesis pathway in E. mollis, but also set a solid foundation for future genetic breeding of this species.

The mediating role of intentional self-regulation in the constructive and pathological compensation processes of problematic social networking use.

Perceived social isolation is a key predictor of college students' problematic social networking site use (PSNSU). According to the Fear-Driven/Compensation-Seeking Hypothesis, reducing the fear of social isolation and compensating for social deficits serve as negative reinforcement motivations for SNS use, which may potentially result in PSNSU. This study investigated the association between perceived social isolation and PSNSU through the mediating roles of intentional self-regulation and parasocial relationships from a compensatory perspective. Additionally, gender differences in the mediating model were examined. Findings from an online survey of 893 college students in China revealed a positive relationship between perceived social isolation and PSNSU. The serial mediation model showed that intentional self-regulation and parasocial relationships both had positive individual mediating effects, as well as a negative serial mediating effect. Moreover, these mediating effects were only significant among women. The findings suggest that in the association between perceived social isolation and PSNSU, the mediating role of intentional self-regulation forms a constructive compensatory process, while its serial mediating role through parasocial relationships forms a pathological compensatory process. Interventions for PSNSU should take the mediating role of intentional self-regulation in constructive compensation process and the gender difference into consideration.

Targeted V-type peptide-decorated nanoparticles prevent colitis by inhibiting endosomal TLR signaling and modulating intestinal macrophage polarization.

Inflammatory bowel disease (IBD) has become a serious and challenging health problem globally without curative medical treatments. Mounting evidence suggests that intestinal macrophages and their phenotypes are key players in the pathogenesis of IBD. Modulating the phenotypes and functions of intestinal macrophages through targeted interventions could be a promising approach to manage detrimental gut inflammation in IBD. In this study, we rationally design and fabricate a novel class of V-type peptide-decorated nanoparticles, VP-NP, with potent anti-inflammatory activity. Such a design allows two functional motifs FFD in a single peptide molecule to enhance the bioactivity of the nanoparticles. As expected, VP-NP exhibits a strong inhibitory activity on endosomal Toll-like receptor (TLR) signaling. Surprisingly, VP-NP can inhibit M1 polarization while facilitating M2 polarization in mouse bone marrow-derived macrophages through regulating the key transcription factors NF-κB, STAT1 and PPAR-γ. Mechanistically, VP-NP is internalized by macrophages in the endosomes, where it blocks endosomal acidification to inhibit endosomal TLR signaling; the transcriptomic analysis reveals that VP-NP potently down-regulates many genes in TLR, NF-κB, JAK-STAT, and cytokine/chemokine signaling pathways associated with inflammatory responses. In a colitis mouse model, the intraperitoneally administered VP-NP effectively alleviates the disease activities by decreasing colon inflammation and injuries, pro-inflammatory cytokine production, and myeloid cell infiltration in the gut. Furthermore, VP-NP primarily targets intestinal macrophages and alters their phenotypes from inflammatory M1-type toward the anti-inflammatory M2-type. This study provides a new nanotherapeutic strategy to specifically regulate macrophage activation and phenotypes through a dual mechanism to control gut inflammation, which may augment current clinical treatments for IBD.

Organic Materials with Ultrabright Phosphorescence at Room Temperature under Physiological Conditions for Bioimaging.

In contrast to the high efficiency of room temperature phosphorescence in crystal states, the generally utilized nanoparticles of organic materials in bioimaging demonstrated sharply decreased performance by orders of magnitude under physiological conditions, badly limiting the realization of their unique advantages. This case, especially for organic red/near-infrared (NIR) phosphorescence materials, is not only the challenge present in reality but more importantly, for the theoretical problem of deeply understanding and avoiding the quenching effect by oxygen and water toward excited triplet states. Herein, thanks to the intelligent molecular design by the introduction of abundant hydrophobic chains and highly-branched structures, bright and persistent red/NIR phosphorescence under physiological conditions has been realized, which demonstrated the shielding effect towards oxygen, and strengthened the intermolecular interactions to suppress the non-radiative transitions. Accordingly, the record phosphorescence intensity of nanoparticles in bioimage, up to 8.21 ± 0.36 × 108 p s-1 cm-2 sr-1, was achieved, to realize the clear phosphorescence imaging of liver and tumors in living mice, even lymph nodes in rabbit models with high SBRs. This work afforded an efficient way to achieve the bright red/NIR phosphorescence nanoparticles, guiding their further applications in biology and medicine.

Study on Preclinical Safety and Toxic Mechanism of Human Umbilical Cord Mesenchymal Stem Cells in F344RG Rats.

Mesenchymal stem cells have made remarkable progress in recent years. Many studies have reported that human umbilical cord mesenchymal stem cells (hUC-MSCs) have no toxicity, but thromboembolism appeared in patients treated with hUC-MSCs. Therefore, people are still worried about the safety of clinical application. The study aims to determine the safety, potential toxic mechanism and biodistribution of hUC-MSCs. F344RG rats were given 5 or 50 million cells/kg of hUC-MSCs by single administration in compliance with Good Laboratory Practice standards. Standard toxicity was performed. RNA sequencing was then performed to explore the potential toxic mechanisms. In parallel, the biodistribution of hUC-MSCs was examined. The dose of 5 million cells/kg hUC-MSCs had no obvious toxicity on symptom, weight, food intake, hematology, serum biochemistry, urine biochemistry, cytokines, and histopathology. However, blood-tinged secretions in the urethral orifice and 20% mortality occurred at 50 million cells/kg. Disseminated intravascular coagulopathy (DIC) is the leading cause of death. hUC-MSCs significantly upregulated complement and coagulation cascade pathways gene expression, resulting in DIC. Besides, hUC-MSCs upregulated fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2. hUC-MSCs survived in rats for less than 28 days, no hUC-MSC was detected in tissues outside the lungs. There was no toxicity in F344RG rats at 5 million cells/kg, but some toxicities were detected at 50 million cells/kg. hUC-MSCs significantly upregulated complement and coagulation cascade pathways, upregulated the expression of fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2, to inhibit fibrinolytic system, caused DIC, which provided a new insight into the toxic mechanism of hUC-MSCs.

Manufacturing of Bionic Adhesion Microstructure with Expanded Ends Based on Electroplating in the Restricted Area.

The organisms of animals with full spatial motion ability present fine and complex 3D structures, showing reliable adhesion ability to the substrate. As core issues, the design and manufacture of complex morphology are essential in bionic adhesion technology. Specifically, the end-expanded microstructure array of high adhesion under low preload has widespread potential in the nondestructive fixation and handling of fragile objects. In the fabrication of end-expanded microstructures, the design and manufacture of metal molds with good mechanical strength are the key. In this paper, a microfabrication technology for manufacturing nickel molds based on three-dimensional printing and electroplating was proposed. The effect of the electric field inhomogeneity on the electrodeposition morphology was systematically studied. Typical bionic adhesives with expanded ends were obtained by a roll-to-roll hot embossing (R2R-HE) process. The normal adhesion force of the bionic adhesives is 9.5 N/cm2, which is comparable to that of the gecko. The electroplating process assisted by 3D printing provides a new approach for the fabrication of complex bionic morphologies and large-area bionic adhesion structures.

Exploring the oral processing mechanisms for saltiness enhancement with NaCl nanocrystals in oleogel systems based on black pepper oleoresin and sunflower seed oil.

Reducing salt content in processed foods while maintaining flavor is crucial for human health. This study investigates the sensory interaction between the pungency of black pepper oleoresin and saltiness within an oleogel matrix by incorporating NaCl nanocrystals into a black pepper oleoresin formulated with glyceryl monostearate and soy lecithin (G-L-P). Psychophysical results revealed that the salt content in the G-L-P and G-L systems (G-L-P without black pepper oleoresin) was reduced by up to 66.77 % and 37.08 % compared to the G system (G-L without soy lecithin), respectively. During oral processing, the G-L and G-L-P systems formed oil-in-water emulsions with smaller and more numerous oil droplets. Within 5 s, the Na+ concentration was lowest in the G system (2.2 g/L), while the G-L and G-L-P systems showed higher concentrations (3.1 g/L and 3.0 g/L, respectively). This research provides a theoretical basis for the food industry to develop low-salt products without compromising flavor.

Super-exchange interaction enables Fe2-xMnxO3 perovskite with excellent catalytic oxidation activity toward hexabromocyclododecane under humidity.

Although enhancing the catalytic oxidation activity is a hotspot in thermal-driven catalytic disposal of persistent organic pollutants, few studies have managed to improve catalysts' water-resistance properties. Herein, we developed Fe2-xMnxO3 perovskite to boost the catalytic oxidation of hexabromocyclododecane under humidity by modulating its super-exchange interaction (SEI, Fe3+ + Mn3+ → Fe2+ + Mn4+). Fe0.4Mn1.6O3, with the strongest SEI, exhibits the biggest oxidation rate-constant, which is 3 times higher than that of commonly used Fe2O3 without SEI. Notably, unlike Fe2O3 which deactivates at a relative humidity of 5 %. Fe0.4Mn1.6O3 maintains its activity and is even boosted by 22 % compared to dry conditions. Mechanistic insights reveal that SEI between Fe and Mn enhances the reactivity of Mn4+- linked Olatt by lowering the reductive temperature from Mn4+ to Mn3+. Meanwhile, SEI promotes the adsorption of the associatively adsorbed H2O (HOH-type water) by reducing adsorption energy, thereby facilitating the formation of hydroxyl species, which are crucial for the oxidation process under humidity.

Efficacy of photodynamic therapy using hematoporphyrin derivative nanomedicine on hepatocellular carcinoma cells.

Objective: To demonstrate the efficacy of photodynamic therapy (PDT) using hematoporphyrin derivative (HPD) nanomedicine in combination with conventional chemotherapy based on gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) magnetic resonance imaging (MRI) for hepatocellular carcinoma (HCC) therapy. Methods: HPD nanomedicine was prepared, and the cytotoxicity of HPD nanomedicine at different concentrations on HCC cells and the half-maximal inhibitory concentration (IC50) were analyzed. Sixty HCC patients who visited our hospital from 2021 to 2023 were retrospectively analyzed. Patient data were analyzed, with 30 cases in control group (CG) receiving conventional chemotherapy for HCC, and 30 cases in observation group (OG) receiving conventional chemotherapy combined with HPD nanomedicine PDT. Gd-DTPA MRI was utilized to monitor the morphological and biological characteristics of the lesions in patients. After treatment completion, the long-term efficacy of patients and the levels of bcl-2 and bax proteins in primary HCC cells were evaluated. Results: The IC50 values of HPD on HepG2 cell proliferation and the cell inhibition rates gradually increased with increasing doses of HPD (50 µM, 25 µM, 12.5 µM, 6.25 µM, 3.13 µM, 1.56 µM, 0.78 µM). HPD exhibited great anti-proliferative effects on HepG2 cells at relatively low concentrations. The differences in expression rates of bcl-2 protein and bax protein between groups were considerable (P<0.05). There were neglectable changes in AST and ALT levels between the two groups before treatment, but they were markedly reduced after treatment versus before treatment (P<0.05), with OG showing considerably lower levels than CG after treatment (P<0.05). Additionally, patients in OG exhibited better survival rates after the course of treatment versus those in CG. Conclusion: This study demonstrates that the combination of conventional chemotherapy based on Gd-DTPA MRI with HPD nanomedicine PDT greatly improves the efficacy of treatment for HCC patients. This combined treatment strategy not only enhances therapeutic outcomes but also alleviates adverse reactions associated with conventional treatment, providing a novel approach for future research in the treatment of HCC.