Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that severely affects the health of the elderly, marked by its incurability, high prevalence, and extended latency period. The current approach to AD prevention and treatment emphasizes early detection and intervention, particularly during the pre-AD stage of mild cognitive impairment (MCI), which provides an optimal “window of opportunity” for intervention. Clinical detection methods for MCI, such as cerebrospinal fluid monitoring, genetic testing, and imaging diagnostics, are invasive and costly, limiting their broad clinical application. Speech, as a vital cognitive output, offers a new perspective and tool for computer-assisted analysis and screening of cognitive decline. This is because elderly individuals with cognitive decline exhibit distinct characteristics in semantic and audio information, such as reduced lexical richness, decreased speech coherence and conciseness, and declines in speech rate, voice rhythm, and hesitation rates. The objective presence of these semantic and audio characteristics lays the groundwork for computer-based screening of cognitive decline. Speech information is primarily sourced from databases or collected through tasks involving spontaneous speech, semantic fluency, and reading, followed by analysis using computer models. Spontaneous language tasks include dialogues/interviews, event descriptions, narrative recall, and picture descriptions. Semantic fluency tasks assess controlled retrieval of vocabulary items, requiring participants to extract information at the word level during lexical search. Reading tasks involve participants reading a passage aloud. Summarizing past research, the speech characteristics of the elderly can be divided into two major categories: semantic information and audio information. Semantic information focuses on the meaning of speech across different tasks, highlighting differences in vocabulary and text content in cognitive impairment. Overall, discourse pragmatic disorders in AD can be studied along three dimensions: cohesion, coherence, and conciseness. Cohesion mainly examines the use of vocabulary by participants, with a reduction in the use of nouns, pronouns, verbs, and adjectives in AD patients. Coherence assesses the ability of participants to maintain topics, with a decrease in the number of subordinate clauses in AD patients. Conciseness evaluates the information density of participants, with AD patients producing shorter texts with less information compared to normal elderly individuals. Audio information focuses on acoustic features that are difficult for the human ear to detect. There is a significant degradation in temporal parameters in the later stages of cognitive impairment; AD patients require more time to read the same paragraph, have longer vocalization times, and produce more pauses or silent parts in their spontaneous speech signals compared to normal individuals. Researchers have extracted audio and speech features, developing independent systems for each set of features, achieving an accuracy rate of 82% for both, which increases to 86% when both types of features are combined, demonstrating the advantage of integrating audio and speech information. Currently, deep learning and machine learning are the main methods used for information analysis. The overall diagnostic accuracy rate for AD exceeds 80%, and the diagnostic accuracy rate for MCI also exceeds 80%, indicating significant potential. Deep learning techniques require substantial data support, necessitating future expansion of database scale and continuous algorithm upgrades to transition from laboratory research to practical product implementation.

Perfluorobutyric acid (PFBA) is a representative short-chain compound of per- and polyfluoroalkyl substances (PFAS), which is widely used in fluorochemical manufacturing, food packaging, and outdoor textile processing industries. PFBA primarily enters into the human body via oral intake, inhalation, and dermal exposure and can be efficiently metabolized. PFBA exhibits cytotoxicity by disrupting cell proliferation, inducing oxidative stress, and disturbing lipid metabolism, thereby impairing cellular homeostasis. In addition, PFBA can induce abnormal activation of peroxisome proliferator-activated receptor α-dependent and/or independent pathways, leading to lipid metabolism disorders and subsequent liver injury. Animal studies have demonstrated that PFBA exposure alters renal biochemical parameters and induces epidermal inflammation, abnormal keratinization, and even necrosis, suggesting potential nephrotoxicity and dermal toxicity. PFBA is capable of crossing the placental barrier, and PFBA levels in umbilical cord blood have been negatively correlated with insulin and insulin-like growth factor 1. Moreover, plasma PFBA levels in patients infected with coronavirus disease 2019 have been associated with infection severity, indicating potential reproductive, developmental, and immunotoxic effects. At present, systematic occupational and environmental exposure monitoring data for PFBA remain limited, the toxic mechanisms in certain target organs have not been fully elucidated, and the molecular regulatory networks underlying reproductive and immune toxicity remain unclear. Future research should focus on improving PFBA monitoring strategies, strengthening studies on PFBA occupational exposure detection methods, toxic effects and mechanisms, and refining occupational risk assessment systems, to provide a scientific basis for establishing occupational exposure limits, optimizing risk management strategies, and safeguarding public health.

OBJECTIVE To explore the mechanism of gallic acid targeting β-arrestin2 to inhibit astrocyte inflammation.METHODS Potential targets of gallic acid were found by PharmMapper and verified by thermal shift and molecular docking experi-ments.Western blot was used to detect the expression of β-arrestin2,NF-κB signaling pathway and NLRP3 inflammasome-related proteins;qPCR was used to detect the mRNA levels of proinflammatory cytokines such as IL-1β,IL-6 and TNF-α.A subacute PD mouse model induced by MPTP was established,and the behavioral ability of mice was evaluated by open field test,rotating rod test and climbing pole test;the number of TH+and GFAP+cells in the SNc area of mice was detected by immunohistochemistry;Western blot was used to detect the expression of NF-κB signaling pathway and NLRP3 inflammasome-related proteins in the homogenate pro-tein of mouse midbrain tissue.RESULTS Molecular docking experiments and thermal shift experiments showed that gallic acid could directly bind to β-arrestin2.Gallic acid could reduce the expression of p-IKK and p-P65 proteins in astrocytes(P<0.001,P<0.000 1),reduce the mRNA levels of IL-1β,IL-6 and TNF-α(P<0.05,P<0.01),and reduce the expression of caspase-1 and IL-1β proteins(P<0.000 1),but had no effect on the expression of β-arrestin2 protein(P>0.05).Gallic acid could improve the be-havioral ability of PD model mice,increase the number of TH+neurons and GFAP+cells in PD model mice(P<0.05,P<0.001),and reduce the expression of caspase-1,IL-1β,NLRP3 and p-IKK proteins in the brain of PD model mice(P<0.05).CONCLU-SION Gallic acid inhibits the activation of NF-κB signaling pathway and NLRP3 inflammasome by binding to β-arrestin2 to reduce astrocyte inflammation,and has a neuroprotective effect on MPTP-induced PD model mice.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective: To analyze the relationship between vitamin D and ferritin nutritional status with physical indicators in primary and secondary school students in the key nutrition monitoring counties of Xinjiang, so as to provide reference for early prevention and intervention of students nutrition issues. Methods: From November to December 2023, 1 071 students aged 6-18 from key nutrition monitoring counties in the Xinjiang Nutrition Improvement Plan area were selected via stratified random sampling for physical and biochemical tests. The U test and Kruskal-Wallis H-test were used to compare the differences in physical indicators and the distribution of vitamin D and ferritin levels. Chi-square test was used to compare the prevalence of vitamin D and ferritin deficiencies among different groups of primary and secondary school students. Pearson correlation was used to analyze the relationship between the nutritional levels of vitamin D and ferritin and physical indicators. Results: The median vitamin D level was 14.7 (10.7, 19.0)ng/mL, with deficiency and insufficiency rates of 30.8% and 37.4% among primary and secondary school students in the key nutrition monitoring counties of Xinjiang Nutrition Improvement Plan area. Ferritin levels were 57.4 (37.7, 83.9)μg/L, with a deficiency rate of 5.7%. Males, primary school students, and rural residents had higher vitamin D and ferritin levels than females, secondary school students, and urban residents ( U =-11.35, -6.88, -4.52; -3.94, -9.17, -5.23, P <0.05). Vitamin D deficiency was more prevalent in females, secondary school students, and urban students ( χ 2=97.52, 49.01, 21.89, P <0.05), while ferritin deficiency was higher in primary school students and urban areas ( χ 2=34.11, 5.63, P <0.05). Significant differences in body mass index (BMI) and waist circumstance (WC) were observed across vitamin D/ferritin statuses ( U/H =35.47, 22.82; -4.19 , -5.36, P <0.05). Vitamin D and ferritin levels negatively correlated with age, BMI, and WC but positively with waist-to-height ratio (WHtR) ( r = -0.31, -0.19, -0.19, 0.20; -0.32, -0.13, -0.21, 0.08, P <0.05). Conclusions Vitamin D and ferritin levels in primary and secondary school students in key nutritional monitoring counties in Xinjiang are correlated with age, BMI, WC and WHtR, and there are nutrient deficiencies. Targeted measures are recommended to improve nutritional status and physical health.

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To explore the nephrotoxic effects of exposure to perfluorobutanoic acid (PFBA) and its mechanism in mice, with a particular focus on analyzing the changes in kidney metabolism and their potential implications. Methods The specific pathogen free C57BL/6 mice were randomly divided into control group, low-dose group, and high-dose group, with 10 mice in each group. Mice in the three groups received intragastric administration of PFBA solution at doses of 0, 35 and 350 mg/kg body weight, once per day for seven consecutive days. The histopathological changes of kidneys of mice in these three groups were evaluated. Metabolomic profiling of mouse kidneys was performed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Differentially accumulated metabolites (DAMs) were identified based on the Human Metabolome Database, and related metabolic pathways were analyzed through MetaboAnalyst 6.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Histopathological analysis of kidneys showed that the renal pelvis mucosa of mice in the low-dose group presented focal mild inflammatory changes without marked structural damage, whereas mice in the high-dose group showed severe inflammation and partial destruction of renal structure. The kidney coefficient of mice in both low-dose group and the high-dose group decreased (both P<0.05), and the Paller scores of renal tissues increased (both P<0.05) compared with that in the control group. The Paller score of mouse renal tissue in the high-dose group was higher than that in the low-dose group (P<0.05). Metabolomic profiling identified 46 DAMs (26 upregulated, 20 downregulated) in the low-dose group and 104 DAMs (54 upregulated, 50 downregulated) in the high-dose group, with 26 shared DAMs between the two dose groups. KEGG pathway analysis revealed that DAMs were mainly involved in metabolic pathways such as glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid and steroid hormone synthesis. Conclusion Acute exposure to PFBA can cause kidney injury in mice. Lipid metabolism pathways such as glycerophospholipid and sphingolipid metabolism is involved in the development of acute renal toxicity of PFBA.

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*