ObjectiveTo investigate the role of 4-week high-intensity interval training (HIIT) in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress (CUMS) to improve their depressive-like behavior. MethodsForty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups: the normal quiet group (C), the CUMS quiet group (M), the normal exercise group (HC), and the CUMS exercise group (HM). The M and HM groups received 8 weeks of CUMS modeling, while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week (3 min (85%-90%) S_max+1 min (50%-55%) S_max, 3-5 cycles, S_max is the maximum movement speed). A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0, 2, 4, 8, 12, and 24 h after exercise, as well as in the quiet state of rats in each group at week 8. Behavioral indexes such as sucrose preference rate, number of times of uprightness and number of traversing frames in the absenteeism experiment, and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8. The rats were anesthetized on the next day after the behavioral test in week 8, and hippocampal tissues were taken for assay. LC-MS non-targeted metabolomics, target quantification, ELISA and Western blot were used to detect the changes in metabolite content, lactate and pyruvate concentration, the content of key metabolic enzymes in the pyruvate-lactate axis, and the protein expression levels of monocarboxylate transporters (MCTs). Results4-week HIIT intervention significantly increased the sucrose preference rate, the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats; non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C, and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups, respectively, after the 4-week HIIT intervention; the quantitative results of the targeting showed that, compared to group C, lactate concentration in the hippocampal tissues of M group, compared with group C, lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased, and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group; the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue; compared with group C, the LDHB content of group M was significantly increased, the content of PKM2 and PDH, as well as the protein expression level of MCT2 and MCT4 were significantly reduced. The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group. ConclusionThe 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats, and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization, which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

BACKGROUND:Mesenchymal stem cells are pluripotent stromal cells isolated from a variety of tissues,which can differentiate into osteoblasts under certain conditions.Photobiomodulation,as an external stimulus,can promote osteogenic differentiation combined with other inducers or alone,providing new ideas for solving a series of bone diseases. OBJECTIVE:To review the relevant literature and mechanisms of photobiomodulation-induced osteogenic differentiation of mesenchymal stem cells,which will lay a theoretical foundation for bone tissue engineering using mesenchymal stem cells as seed cells and may offer some suggestions for future studies. METHODS:Relevant articles were searched on CNKI,PubMed and Wed of Science databases with Chinese search terms of"photobiomodulation,low power laser,low level laser,light-emitting diode,mesenchymal stem cells,osteogenic differentiation,biomaterials"and English search terms of"photobiomodulation,low level laser(light),light-emitting diode(LED),mesenchymal stem cell,osteogenic differentiation,biomaterials".Finally,88 articles were included for analysis. RESULTS AND CONCLUSION:(1)Photobiomodulation represented by low level laser and diode laser has a positive effect on promoting the proliferation and differentiation of mesenchymal stem cells.(2)Photobiomodulation can induce osteogenic differentiation of mesenchymal stem cells,whose feasibility has been verified in cell and animal experiments.On one hand,photobiomodulation can promote the expansion and differentiation of stem cells in vitro by activating related signaling pathways and up-regulating the expression of osteogenic molecules.On the other hand,photobiomodulation can improve the survival rate of stem cells in vivo,promote homing effect and shorten the healing time of bone defects after stem cells are injected into the body.However,photobiomodulation has a biphasic dose effect,whose laser parameters,experimental environment,cell type and other factors in various studies are different,making the research results lack consistency and difficult to apply in the clinic.(3)Combined with biological materials,other physical factors and drugs,photobiomodulation can also accelerate osteogenic differentiation.(4)In conclusion,photobiomodulation has been used increasingly widely in the medical field with its advantages of non-invasive,efficient and less-side reactions,and its role in bone tissue engineering has gradually become prominent,which provides a new method for the treatment of bone defects and related diseases.Further exploration should be focused on the standardized treatment parameters of photobiomodulation.

Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.

An intensive breast array sensor was designed based on three-dimensional electrical impedance tomography in this work.Firstly,an electrical impedance sensor for detection of breast cancer was developed.The sensor adopted the integrated design of excitation electrode array and ground electrode to achieve structural simplification.It realized electric field densification through conical matrix and double-layer circumferentially arranged electrode array and improved the detection accuracy of target object through taper optimization.Secondly,the imaging system was designed,and the sensor was optimized by numerical simulation.The simulation results showed that halving the number of electrodes did not affect imaging accuracy of the sensor,but could improve the imaging speed.Finally,the performance of the sensor was verified by experiment.The signal-to-noise ratio and channel consistency of the system were at a good level.The sensor was used to reconstruct three-dimensional image of the experimental model with relative volume of the detection field of 0.4%.The image correlation coefficient of the single target imaging was above 0.6 and the position of the double target object could be clearly identified,and thus the visual detection of breast cancer was realized.

Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.

Objective:To investigate the current situation and influence factors of prehospital thrombolysis treatment for ST segment elevation myocardial infarction (STEMI) in China, to analyze the main factors affecting prehospital thrombolysis implementation, and optimize the pre-hospital thrombolysis strategy for STEMI to reduce mortality.Methods:A multicenter cross-sectional survey was conducted. 21 cities from six major geographical regions in China were selected by using convenient sampling method. An anonymous online electronic questionnaire was used to investigate the current situation and influence factors of prehospital emergency physicians and grassroots physicians implementing prehospital thrombolysis treatment for STEMI patients. Chi-square test was used to analyze the differences in count data between groups, and multivariate logistic regression was used to analyze the factors affecting prehospital thrombolysis in STEMI.Results:A total of 5 163 prehospital emergency physicians and physicians from grassroots township health centers/community health service centers or village clinics participated in this survey. Among them, 3208 (62.13%) have never implemtent thrombolysis, and 1 955 (37.87%) have did it before. The results of the multivariate logistic regression analysis indicated that physicians with 5-10 years of experience ( OR=1.41, 95% CI: 1.18-1.69, P<0.01), 11-20 years of experience ( OR=1.25, 95% CI: 1.03-1.52, P=0.02), those working in village clinics ( OR=1.30, 95% CI: 1.05-1.61, P=0.02), those in pre-hospital emergency medical institutions/departments ( OR=3.19, 95% CI: 2.80-3.64, P<0.01), those whose units are equipped with remote ECG transmission capabilities ( OR=1.72, 95% CI: 1.50-1.96, P<0.01), or ECG AI-assisted diagnostic tools ( OR=1.31, 95% CI: 1.15-1.49, P<0.01), and those who believe that thrombolysis is highly effective and should be widely adopted ( OR=2.55, 95% CI: 2.09-3.12, P<0.01) or consider it somewhat effective but warranting caution ( OR=2.11, 95% CI: 1.73-2.59, P<0.001), were more likely to make pre-hospital thrombolysis decisions for STEMI patients. To improve the current situation of pre-hospital thrombolysis for STEMI, the top four measures prioritized by pre-hospital emergency and grassroots physicians were enhancing the rescue capabilities of primary care doctors (92.22%), strengthening guidance from higherlevel hospitals (84.99%), increasing support for information technology (83.37%), and improving public health education (74.75%). Conclusions:The implementation rate of prehospital thrombolysis for STEMI in China still needs to be improved. Optimizing the prehospital thrombolysis strategy for STEMI, strengthening the allocation of basic medical resources and information technology support, and improving the referral mechanism are conducive to the implementation of prehospital thrombolysis for STEMI.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Heme oxygenase-1(HO-1)is an inducible heme oxygenase and a catalytic enzyme for heme decomposition reactions,which can catalyze the heme decomposition into CO,biliverdin and Fe2+.HO-1 and its metabolites have anti-inflammatory,antioxidant and anti-apoptotic effects in human body,and play an important role in neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,and Huntington's disease.This article will review the production,distribution,and gene structure of HO-1,the biological characteristics of its metabolites,and the role and mechanism of HO-1 in neurodegenerative diseases,in order to provide a theoretical basis for the clinical application of HO-1.