1.The Diversity of Filamentous Morphologies and Magnetic Sensitivity Modulated by Diverse MagR Expression in Bacteria
Ya-Fei CHANG ; Jing ZHANG ; Peng ZHANG ; Xiu-Juan ZHOU ; Meng-Ke WEI ; Tian-Tian CAI ; Pei-Qi HE ; Jun-Feng WANG ; Can XIE
Progress in Biochemistry and Biophysics 2026;53(5):1439-1456
Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe2+), whereas clMagR favors ferric iron (Fe3+) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe2+-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe2+/Fe3+ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.
2.Study on the variation patterns of corneal biomechanical parameters and binocular symmetry in children of different genders aged 8 to 16 years
Mei LI ; Biao WANG ; Fen ZHANG ; Yuting ZHANG ; Ze PEI ; Ning LU ; Feng CHANG
International Eye Science 2026;26(3):483-488
AIM: To investigate variation patterns of corneal biomechanical parameters and binocular symmetry among children of different genders aged 8-16 years.METHODS:A retrospective study was conducted, and children who underwent optometric examinations at the ophthalmology department of our hospital were enrolled between January 2022 and December 2024. Measurements included the flat keratometry(K1), steep keratometry(K2), and mean curvature(Km)of the anterior corneal surface, horizontal visible iris diameter(HVID), central corneal thickness(CCT), corneal endothelial cell density(CECD), average cell size(ACS), coefficient of variation(CV), and hexagonality(HEX). Corneal parameters and binocular differences were compared between genders and across age groups.RESULTS:A total of 621 children(1 242 eyes)were enrolled in this study, including 284 males(568 eyes), 337 females(674 eyes), 528 children aged 8-12 years(1 056 eyes), and 93 children aged 13-16 years(186 eyes). In children aged 8-16 years, the K1, K2, Km and CV of both eyes, as well as the interocular CCT differences in boys were significantly lower than those in girls(all P<0.05), while the HVID and HEX of both eyes, as well as the CCT of the left eye in boys were significantly higher than those in girls(all P<0.05). Children aged 8-12 years had significantly higher K1, Km, CECD and HEX in both eyes, and significantly lower ACS in both eyes than those aged 13-16 years(all P<0.05). K1, K2, Km, CECD and HEX in both eyes were negatively correlated with age(P<0.05); ACS in both eyes was positively correlated with age(P<0.001); K1 and Km of the right eye were positively correlated with the CECD of the right eye(P<0.05), and K1 and CCT of the left eye were positively correlated with the CECD of the left eye(P<0.05).CONCLUSION:Significant gender differences exist in corneal parameters among children aged 8 to 16 years, while binocular symmetry remained stable.
3.Investigation and health risk assessment of microbial contamination of indoor air in public places in Xi'an City
Dong LIU ; Fan GAO ; Feng ZHANG ; Ping LIU ; Ling CHANG
Journal of Public Health and Preventive Medicine 2026;37(1):78-82
Objective To investigate the microbial contamination and its influencing factors of indoor air in public places in Xi'an City, to assess the health risk of employees, and to provide a scientific basis for improving the indoor environment of public places. Methods Total bacterial count and total fungal count in indoor air were monitored in hotels/inns, shopping malls/supermarkets, gyms, and waiting rooms in Xi'an from 2023 to 2024. The health risk assessment of employees was evaluated according to the Chinese Population Exposure Parameters Manual (Adult Volume). Results Overall, the standard-exceeding rate of total bacterial count in Xi'an was 3.85%, and the median values of total bacterial count and total fungal count were 350 CFU/m3 and 300 CFU/m3, respectively. The results of the generalized linear model showed that high indoor temperature and PM10 levels were associated with increased indoor bacterial concentrations (β>0, P<0.05), while high daily passenger flow, and high indoor relative humidity and PM10 levels were associated with increased indoor fungal concentrations (β>0, P<0.05). The multivariate logistic regression showed that high levels of indoor bacterial and fungal concentrations were risk factors for respiratory discomfort among employees. The hazard quotient (HQ) values for all types of public places were less than 1, indicating that the health risk of microbial aerosol exposures for employees was relatively low. Conclusion The indoor microbial pollution in public places in Xi'an is relatively mild, but countermeasures still need to be taken to reduce indoor air microbial contamination.
4.Time-series analysis of daily temperature, atmospheric pressure, and pre-hospital cardiovascular and cerebrovascular disease emergencies in Yantai, Shandong Province, 2016–2022
Mingshun WU ; Qing ZHANG ; Liang CHANG ; Lan LI ; Suqiu YANG ; Jiarong LI ; Xinhui YU ; Linlin LI ; Jiawei FENG ; Tieying NI
Journal of Environmental and Occupational Medicine 2026;43(4):458-466
Background Meteorological factors are among the key extrinsic triggers for the onset and exacerbation of cardiovascular and cerebrovascular diseases (CVD). Against the backdrop of sustained global warming, elucidating the impact of ambient temperature and atmospheric pressure on CVD, especially on pre-hospital CVD emergent events, has become imperative for evidence-based prevention and emergency preparedness. Objective To quantify the temporal trends of daily mean temperature and atmospheric pressure and their associations with pre-hospital CVD emergent events in Yantai, and to explore effect modification by demographic subgroups and geographic areas, thereby providing an empirical basis for the rational allocation of emergency medical resources. Methods Pre-hospital CVD emergency data from January 1, 2016 to December 31, 2022 were selected from the Yantai 120 Emergency Medical Command System. Synchronous meteorological factors and environmental pollutant data were obtained from the websites of the National Oceanic and Atmospheric Administration and the National Centers for Environmental Information of the United States. Time-series analysis combined with distributed lag non-linear model was used to analyze the association between daily temperature, atmospheric pressure, and pre-hospital CVD emergencies. Average annual percentage changes (AAPC) were calculated using Joinpoint (version 5.2.0.0) to reflect temporal trends. Spearman correlation analysis was employed to screen variables with low collinearity for inclusion in the multi-pollutant adjusted models. Results From 2016 to 2022, a total of
5.Quercetin Ameliorates Gouty Arthritis in Rats via ROS/NLRP3/IL-1β Signaling Pathway
Baowei FENG ; Yan WANG ; Chang LI ; Yujing ZHANG ; Dingxing FAN ; Xin LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):145-153
ObjectiveTo investigate the effect of quercetin on acute gouty arthritis (GA) in rats by inhibiting the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway. MethodsSixty SPF-grade male SD rats were randomized into normal, model, colchicine (0.3 mg·kg-1), and low-, medium-, and high-dose (25, 50, 100 mg·kg-1, respectively) quercetin groups (n=10). The rats in the dosing groups were administrated with the corresponding drugs (10 mL·kg-1) by gavage once a day for one week. An equal volume of normal saline was given by gavage to rats in normal and model groups. One hour after drug administration on day 5, an acute GA model was established in other groups except the control group via intra-articular injection of monosodium urate (MSU) suspension into the right posterior ankle joint cavity. The joint swelling and gait were scored at the time points of 6, 12, 24, 48 h after modeling. Histopathological alterations in the ankle joint tissue from each group were assessed by hematoxylin-eosin (HE) staining. Malondialdehyde (MDA), xanthine oxidase (XOD), and total superoxide dismutase (T-SOD) assay kits were used to assess the levels of MDA, XOD, and T-SOD in the serum. The levels of tumor interleukin-6 (IL-6), necrosis factor-α (TNF-α), and IL-1β in the rat serum, as well as ROS in the ankle joint tissue, were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to determine the protein levels of NLRP3, thioredoxin-interacting protein (TXNIP), apoptosis-associated speck-like protein containing a CARD domain (ASC), precursor cysteinyl aspartate-specific proteinase-1 (pro-Caspase-1), cleaved Caspase-1 (Caspase-1 p20), and IL-1β in the ankle joint tissue. Real-time PCR was employed to assess the mRNA levels of TXNIP, NLRP3, ASC, IL-1β, and TNF-α in the ankle joint tissue. ResultsCompared with the normal group, the model group exhibited decreased spontaneous activity, mental fatigue, increased ankle joint swelling and gait scores (P<0.01), aggravated synovial tissue edema and inflammatory cell infiltration (P<0.01), elevated levels of XOD, MDA, TNF-α, IL-1β, and IL-6 in the serum and ROS in the joint tissue (P<0.01), a declined level of T-SOD (P<0.01), up-regulated protein levels of NLRP3, TXNIP, ASC, pro-Caspase-1, Caspase-1 p20, and IL-1β in the ankle joint tissue (P<0.01), and up-regulated mRNA levels of NLRP3, TXNIP, ASC, IL-1β, and TNF-α in the ankle joint tissue (P<0.01). Compared with the model group, the medium- and high-dose quercetin groups showed improved general conditions, decreased gait scores (P<0.05, P<0.01), reduced joint swelling (P<0.01), alleviated synovial tissue edema and inflammatory cell infiltration (P<0.05, P<0.01), lowered levels of XOD, MDA, TNF-α, IL-1β, and IL-6 in the serum and ROS in the joint tissue (P<0.01), increased levels of T-SOD (P<0.01), down-regulated protein levels of TXNIP, NLRP3, ASC, pro-Caspase-1, Caspase-1 p20, and IL-1β in the ankle joint tissue (P<0.05, P<0.01), and down-regulated mRNA levels of TXNIP, NLRP3, ASC, IL-1β, and TNF-α in the ankle joint tissue (P<0.01). Low-dose quercetin also ameliorated some of the above parameters (P<0.05, P<0.01). ConclusionQuercetin exerts anti-GA effects by blocking the ROS/NLRP3/IL-1β signaling pathway, downregulating NLRP3 inflammasome activation, and inhibiting the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6.
6.The first record of Anopheles messeae (Diptera: Culicidae) parasitized by water mites in China
Xue-ru CHEN ; Wen-zhen YAO ; Yu-hao LI ; Gui-chang LI ; Tao MENG ; Qun-ling FENG ; Xin-hui LIU ; Li-hong QIAO ; Xiang-ting WU ; Xue-feng ZHANG ; Cheng-lin LI ; Xue-cheng DONG ; Da-wei WANG ; Xiao-yan SI ; Yu-hong GUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):53-57
Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.
7.The Diversity of Filamentous Morphologies and Magnetic Sensitivity Modulated by Diverse MagR Expression in Bacteria
Ya-Fei CHANG ; Jing ZHANG ; Peng ZHANG ; Xiu-Juan ZHOU ; Meng-Ke WEI ; Tian-Tian CAI ; Pei-Qi HE ; Jun-Feng WANG ; Can XIE
Progress in Biochemistry and Biophysics 2026;53(5):1439-1456
Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe2+), whereas clMagR favors ferric iron (Fe3+) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe2+-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe2+/Fe3+ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.
8.The Mechanisms of Quercetin in Improving Alzheimer’s Disease
Yu-Meng ZHANG ; Yu-Shan TIAN ; Jie LI ; Wen-Jun MU ; Chang-Feng YIN ; Huan CHEN ; Hong-Wei HOU
Progress in Biochemistry and Biophysics 2025;52(2):334-347
Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.
9.A randomized,double-blind,placebo-controlled,multicenter clinical study of Shengxuebao Mixture in treating cancer-related anemia
Zhu LIU ; Xiangrong LI ; Xiaojun DAI ; Yanjun WANG ; Xiao LI ; Keqiong WANG ; Tao WU ; Miaowen ZHONG ; Hongjiang YU ; Ji FENG ; Zuowei HU ; Kainan LI ; Shaowei CHEN ; Chunhua LI ; Zhengchuan FU ; Rui ZHANG ; Yongfa CHEN ; Hongyu XU ; Tao REN ; Yibo YAO ; Jianxu JIN ; Pengyin WANG ; Zhijiang HE ; Jian SHEN ; Lei WANG ; Min LI ; Wenming CHANG ; Xinyi CHEN ; Li HOU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(10):1447-1459
Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.
10.Construction of CD8+T cell-associated Risk Model in Hepatocellular Carcinoma Based on Bulk and Single-cell RNA-seq Data
Xin-Tong ZHANG ; Jian-Jun ZHU ; Jin WU ; Hao WU ; Fan LU ; Wen-Tao ZHANG ; Jing-Jia CHANG ; Ting TANG ; Zhi-Gao OU ; Feng-Feng JIA ; Li LI ; Peng-Fei YU ; Ming LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1511-1528
Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8+T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.


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