1.Targeting ER lipid raft-associated 1 reveals a coordinated cholesterol-dependent vulnerability in hepatocellular carcinoma
Yiming ZHANG ; Yushan HOU ; Xinxin WANG ; Kaikun XU ; Pei JIANG ; Siqi WANG ; Huimin KANG ; Hu ZHANG ; Jingzhuo JIN ; Xiaofen HUANG ; Zifeng LIU ; Songpeng YANG ; Jiaqi LIU ; Lingqiang ZHANG ; Fuchu HE ; Chunyan TIAN ; Aihua SUN
Clinical and Molecular Hepatology 2026;32(2):866-883
Background/Aims:
Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed.
Methods:
We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models.
Results:
ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis.
Conclusions
ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.
2.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.
3.Research progress of Qifu yin in the treatment of Alzheimer’s disease with marrow-sea insufficiency syndrome
Zilong WEI ; Chenyi ZHAO ; Mingliang QIAO ; Hongwei WANG ; Pei ZHU ; Yi MENG
China Pharmacy 2026;37(10):1376-1380
Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. Marrow-sea insufficiency serves as the fundamental basis for the onset of AD. Early syndrome differentiation-based intervention helps to delay disease progression, and improve patients’ cognitive function. Qifu yin is a representative specialized prescription for AD with marrow-sea insufficiency syndrome. Studies demonstrate that Qifu yin exerts neuroprotective effects through multiple pathways, including inhibiting the abnormal deposition of amyloid β -protein and hyperphosphorylation of tau protein, alleviating neuroinflammation, regulating oxidative stress and mitochondrial dysfunction, modulating the cholinergic system, and improving synaptic plasticity. Qifu yin combined with Western medicine such as donepezil, memantine, and butylphthalide, or combined with external therapies such as acupuncture, can effectively improve cognitive function and activities of daily living in AD patients with favorable safety. Future research should focus on the core pathogenesis and key targets of AD with marrow-sea insufficiency syndrome, provide in-depth elucidation of the scientific connotation of Qifu yin’s “tonifying the kidney to produce marrow”, and further conduct high-quality clinical studies to provide scientific evidence for the prevention and treatment of AD with marrow-sea insufficiency syndrome.
4.Surgical treatment of hepatic alveolar echinococcosis: challenges and innovations
Pei ZHANG ; Lu ZHAO ; Yunfei FANG ; Hui YANG ; Yifan WANG ; Yanqiong MA ; Yu MENG
Organ Transplantation 2026;17(3):512-518
Hepatic alveolar echinococcosis is a highly invasive zoonotic parasitic disease with poor prognosis. Surgical intervention serves as the pivotal approach to achieve radical cure and improve the prognosis of hepatic alveolar echinococcosis patients. In recent years, with the popularization of the concept of precision surgery and the development of the multidisciplinary diagnosis and treatment model, the surgical treatment strategies for hepatic alveolar echinococcosis have been continuously enriched, and the selection of surgical procedures has become increasingly diversified. Although key surgical techniques such as radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation have achieved remarkable progress in clinical application, many insurmountable challenges still remain. Therefore, by sorting out the latest evidence-based advances in the field of surgical treatment for hepatic alveolar echinococcosis, this article focuses on discussing the application status and bottlenecks of radical hepatectomy, autologous liver transplantation and allogeneic liver transplantation in hepatic alveolar echinococcosis, aiming to provide a reference for the clinical treatment of hepatic alveolar echinococcosis.
5.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.
6.Traditional Chinese Medicine Alleviates Dry Eye Disease by Regulating Tear Film Homeostasis: A Review
Sainan TIAN ; Bin'an WANG ; Yao CHEN ; Guicheng LIU ; Li TANG ; Pei LIU ; Genyan QIN ; Jun PENG ; Qinghua PENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):172-181
Dry eye (DE) is a prevalent multifactorial disease of the ocular surface, clinically characterized by tear film homeostasis imbalance accompanied by related ocular surface symptoms. Specifically, the tear film is a thin liquid layer of tears covering the cornea and conjunctiva through blinking, while tear film homeostasis serves as the foundation for maintaining normal ocular surface structure and function. Insufficient tear secretion and excessive tear film evaporation lead to tear hyperosmolarity and the production of inflammatory mediators, disrupting tear film homeostasis and subsequently forming DE. Additionally, cascade reactions are triggered, resulting in a "vicious cycle of DE" that exacerbates the disease severity and prolongs its duration. Therefore, for DE treatment, it is crucial to restore tear film homeostasis and terminate this vicious cycle. Traditional Chinese medicine (TCM), which differentiates and treats DE based on systemic conditions, often achieves favorable therapeutic outcomes, offering additional treatment options for DE. Studies have demonstrated that TCM can alleviate DE by regulating tear film homeostasis and terminating the vicious cycle. This review systematically summarizes recent basic experimental research in China and abroad on TCM in alleviating DE by regulating tear film homeostasis, aiming to provide a theoretical basis for clinical treatment and an insight for research design.
7.Interventional effect and mechanism of Bifidobacterium in chronic liver disease
Liyi PAN ; Yueqiao CHEN ; Yu CHEN ; Yuyun HUANG ; Hao PEI ; Fenglan WU ; Lyuping YE ; Na WANG
Journal of Clinical Hepatology 2026;42(2):464-471
Compared with traditional therapies for chronic liver disease (CLD), Bifidobacterium has the characteristics of multi-target intervention, high biosafety, and good host compatibility and provides new strategies for intervention of CLD progression in terms of microecological regulation. Various studies have shown that Bifidobacterium regulates liver homeostasis and exerts a therapeutic effect on CLD by regulating intestinal flora, maintaining antioxidation, promoting energy consumption, alleviating inflammation, improving glycolipid metabolism, and exerting an antitumor effect. This article systematically reviews the studies on Bifidobacterium in the treatment of CLD in China and globally, explores their different mechanisms, and elaborates on the interaction between related signaling pathways (such as the nuclear factor erythroid 2-related factor 2 signaling pathway and the adenosine monophosphate-activated protein kinase signaling pathway) and the liver, in order to provide a basis for probiotic intervention in liver pathology, as well as new ideas for the comprehensive treatment of CLD.
8.Research progress on the regulation of JNK signaling pathway by traditional Chinese medicine for intervention in central nervous system diseases
Hongwei WANG ; Mingliang QIAO ; Chenyi ZHAO ; Pei ZHU ; Zilong WEI ; Yi MENG
China Pharmacy 2026;37(2):257-262
The c-Jun N-terminal kinase (JNK) signaling pathway, a key member of the mitogen-activated protein kinase (MAPK) family, plays a central role in the pathogenesis and progression of central nervous system (CNS) diseases by regulating core biological processes such as apoptosis, inflammatory responses, synaptic plasticity, and autophagy. This article sorts out and analyzes relevant literature published domestically and internationally in recent years, summarizing the mechanisms of action of the JNK signaling pathway in common CNS diseases and the research progress in traditional Chinese medicine (TCM) interventions in CNS diseases through the regulation of the JNK signaling pathway. Studies have shown that active components of TCM, such as berberine, paeoniflorin, and astragaloside Ⅳ, as well as compound formulations like Heixiaoyao san, Ditan tang, and Buyang huanwu tang, can exert neuroprotective effects in various CNS disorders, including Alzheimer’s disease, Parkinson’s disease, cerebral ischemia-reperfusion injury, and epilepsy, by inhibiting the aberrant activation of the JNK signaling pathway, thereby alleviating neuroinflammation, oxidative stress, and neuronal apoptosis, while improving synaptic function and cognitive behavioral deficits, regulating autophagy, and maintaining blood-brain barrier integrity.
9.Seasonal variation of adult mosquitoes in Yantai, Shandong Province, China: a study based on the circular distribution method
Chun-hui LI ; Cheng-juan LIU ; Ting WANG ; Xiao-ge ZHOU ; Pei-Jun GUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):108-113
Objective This study aimed to investigate the seasonal variation of mosquitoes in Yantai, Shandong Province, and provide a scientific basis for mosquito and mosquito-borne disease control. Methods From March to November for each of the years between 2020 and 2023, adult mosquitoes were collected from different habitats, including parks, hospitals, urban residential areas, rural households and livestock sheds, in 13 counties of Yantai City using a mosquito trap lamp method, among which, female mosquitoes were separated and identified, and the numbers were counted. We used the circular distribution method to analyze the temporal distribution characteristics of mosquito density. Results The γ values obtained for mosquitoes in Yantai from 2020 to 2023, the distribution of mosquitoes in different habitats, and dominant mosquito species in different months showed strong seasonality, with values ranging from 0.7461 to 0.8531(P < 0.05). The peak period of seasonal variation in mosquitoes occurred from June 28thto September 13th, with August 5thbeing identified as the peak day. The peak periods of seasonal variation in mosquitoes in residential areas, parks, hospitals, peasant households, and animals sheds were observed from June 24thto September 14th, June 25thto September 10th, June 22ndto September 12th, July 1stto September 9th, and July 2ndto September 17th, respectively, with corresponding peak days on August 4th,3rd, 2nd, 5th, and 9th, respectively. The peak periods of Culex pipiens pallens, Aedes albopictus, and Anopheles sinensis were from June 26thto September 11th, June 28thto September 17th, and July 12thto September 17th, respectively, with corresponding peak days on August 3rd,7th, and 14th, respectively. Conclusions Our findings in this study revealed that the peak of mosquito activity in Yantai was concentrated in early August, with a peak period extending from June 28thto September 13th, and there were differences between different habitats(with peak periods for rural households and livestock sheds occurring later than those in residential areas, parks, and hospitals). Moreover, with respect to the mosquito species, populations of Cx. pipiens pallens and Ae. albopictus peaked earlier than those of An. sinensis. Based on these findings, we recommend that city-wide mosquito control work should commence in late June, and include appropriate early prevention and control measures for key habitats, such as livestock sheds, and dominant mosquito species, such as Cx. pipiens pallens, to minimize the density of mosquito vectors and the risk of disease transmission.
10.Research advances in robot-assisted partial nephrectomy for anterior and posterior lip tumors of the kidney:focusing on postoperative complications
Yuanhao PEI ; Lulin MA ; Shuilong ZHAI ; Yimin WANG ; Zhang LIANG
Journal of Modern Urology 2026;31(4):376-381
Renal hilar tumors pose significant surgical challenges due to their proximity to major renal vessels and the collecting system. In robot-assisted partial nephrectomy, although both anterior and posterior lip tumors are considered renal hilar tumors, their operative difficulty and complication profiles differ markedly owing to distinct anatomical relationships and vascular adjacency. Anterior lip tumors, often involving tributaries of the renal vein, carry a relatively higher risk of intraoperative and postoperative bleeding. In contrast, posterior lip tumors, closer to the renal artery, are more likely to prolong warm ischemia time, thereby increasing the risk of postoperative renal impairment. Regarding urine leakage, although anterior lip tumors are theoretically closer to the collecting system and may pose a slightly elevated risk, precision reconstruction strategies—such as lip reconstruction based on sinus space anatomy—can effectively mitigate this risk. However, the specific difference in urine leakage risk between anterior and posterior lip tumors warrants further investigation. Both anterior and posterior lip tumors of the kidney can achieve low positive surgical margin rates in experienced centers. Complication risks are affected by multiple factors, including tumor anatomical complexity, warm ischemia time, and surgeon experience. Notably, R.E.N.A.L. score>8 is associated with significantly increased complication risks. Preoperative meticulous imaging evaluation, selection of an appropriate surgical approach based on tumor location, controlled warm ischemia time, and application of delicate suturing and reconstruction techniques are essential strategies to reduce complications.


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