Four novel β-galactoside prodrugs were designed and synthesized from anthraquinones HAQ-OH and AQ-OH in an attempt to use the prodrugs to selectively release superoxide anion (O2−) in cancer cells and to achieve selected anticancer activity by utilizing the Warburg effect and the elevated level of β-galactosidase in certain cancer cells. Cellular assays showed that the prodrugs Gal-HAQ and Gal-AQ selectively inhibited the proliferation and induced apoptosis of ovarian cancer OVCAR-3 cells overexpressing β-galactosidase. Using O2− fluorescent probe, it was found that in OVCAR-3 cells Gal-HAQ and Gal-AQ could time-dependently release O2−, which was essential for their anticancer activity. Furthermore, it was found that Gal-HAQ and Gal-AQ were effective senolytics toward senescent cells overexpressing β-galactosidase without affecting the viability of corresponding non-senescent cells, further confirming the β-galactosidase-dependent cytotoxicity of the prodrugs. In conclusion, Gal-HAQ and Gal-AQ, which release O2− in response to β-galactosidase, are expected to serve as candidate prodrugs targeting cancer cells.

ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

Fragility fractures represent the final clinical manifestation of osteoporosis and are influenced by a range of risk factors. This article discusses the findings from two large-scale studies utilizing biobank and genomic data to investigate the relationships among obesity, type 2 diabetes and fracture risk, and to explore their implications for health management. The studies suggest that general obesity(defined by body mass index, BMI), central obesity(defined by waist circumference), and peripheral obesity exert different effects on fracture risk in older adults. Specifically, individuals who are overweight based on BMI have a lower fracture risk compared to those with normal weight, whereas an increased waist circumference is associated with a higher fracture risk. Moreover, genetic research indicates that genetically determined type 2 diabetes is not causally associated with increased fracture risk. In contrast, observational studies have reported a higher fracture risk in patients with type 2 diabetes; however, this association becomes non-significant after adjusting for diabetes-related risk factors. These findings highlight that maintaining a moderately elevated BMI may benefit bone formation in the elderly by providing mechanical loading to stimulate bone formation. Additionally, effective management of type 2 diabetes complications is essential for reducing fracture risk, and a certain degree of obesity may confer a protective effect against fractures in individuals with type 2 diabetes.

Objective·To investigate an optimal severe periodontitis mouse model by comparing two induction methods:simple ligature and ligature combined with injection of Porphyromonas gingivalis lipopolysaccharide(P.g.LPS).Methods·Fifteen C57BL/6 mice were divided into three groups:a healthy control group,a simple ligature-induced periodontitis group,and a ligature combined with P.g.LPS injection-induced periodontitis group.After 14 d,the following evaluations were conducted:tooth mobility and probing depth under a stereomicroscope;alveolar bone resorption[bone volume fraction,bone mineral density,the distance from the cemento-enamel junction(CEJ)to the alveolar bone crest(ABC),and the area between CEJ and ABC]analyzed via micro computed tomography(Micro-CT)and stereomicroscopic examination.The serum levels of inflammatory cytokines interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were assessed by enzyme-linked immunosorbent assay(ELISA).Results·Compared with the simple ligature group,mice in the ligature with P.g.LPS injection group exhibited significantly increased tooth mobility[(2.20±0.45)vs(1.40±0.55)]and probing depth[(1.05±0.21)mm vs(0.58±0.39)mm],with statistically significant differences(P＜0.05).The ligature with P.g.LPS injection group also demonstrated significantly reduced bone volume fraction[(16.44%±3.35%)vs(28.97%±7.90%)]and bone mineral density[(0.42±0.04)g/cm3 vs(0.55±0.08)g/cm3],as well as increased distance from CEJ to ABC[(0.88±0.03)mm vs(0.74±0.12)mm]and area between CEJ and ABC[(0.34±0.01)mm2 vs(0.30±0.02)mm2],all with statistically significant differences(all P＜0.05).Additionally,serum levels of TNF-α and IL-1β were significantly elevated in the ligature with P.g.LPS injection group compared to the simple ligature group(both P＜0.05).Conclusion·The method of ligature combined with continuous P.g.LPS injection is more effective for constructing a severe periodontitis mouse model,making it suitable for studying the progression and treatment of severe periodontitis.

BACKGROUND:In recent years,it has been found that physical interventions play a significant role in influencing proliferation,differentiation,and migration of bone marrow mesenchymal stem cells.However,the current physical intervention still exists such as basic research data to be strengthened,unified parameter standards need to be further improved and other shortcomings.OBJECTIVE:To review the effects of physical interventions on the differentiation of bone marrow mesenchymal stem cells.METHODS:PubMed and CNKI databases were searched for relevant articles using"bone marrow mesenchymal stem cells(BMSC),bone marrow stromal cells,osteogenesis differentiation,chondrocytes differentiation,electrical stimulation,mechanical stimulation,hypoxia,electromagnetic fields,low intensity pulsed ultrasound"as English and Chinese search terms.A total of 58 articles were selected for review.RESULTS AND CONCLUSION:(1)Physical interventions have been applied to regulate the proliferation and differentiation of bone marrow mesenchymal stem cells by altering specific microenvironments,but the parameters have not yet been unified.The future investigation should further optimize and explore the best parameters and conditions of action of the relevant physical factors on the role of bone marrow mesenchymal stem cell proliferation and differentiation.(2)It is difficult to carry out the application of certain special physical environmental conditions through low-cost conventional means,pending subsequent research and development to further reduce the difficulty of constructing special physical conditions.(3)The use of physical factors to rationally intervene in differentiation and proliferation of bone marrow mesenchymal stem cells has not yet been widely applied in the clinic,and further research is needed to promote clinical translation in the future.

Objective: To investigate the scientific research capacity building of administrative offices of Centers for Disease Control and Prevention (CDCs) across 31 provinces (autonomous regions, municipalities), the Xinjiang Production and Construction Corps, and 5 separately listed cities in China, so as to provide the reference for improving the positioning of office functions and promoting the enhancement of scientific research capabilities. Methods: A self-administered questionnaire survey was conducted among heads and staff members of administrative offices in 37 CDCs. Data on office setup, general information, staffing, scientific research incentive measures and outputs were collected and analyzed. Results: The 37 administrative offices of the CDCs had an average authorized staffing size of 12 personnel. There were 17 of them setting independently allocated budgets. A total of 511 staff members were surveyed, comprising 238 males and 273 females, resulting in a male-to-female ratio of 0.87∶1. In terms of educational attainment, the majority held bachelor's degrees (225 individuals, 44.03%) or master's degrees and above (157 individuals, 30.72%). Professional technical personnel constituted the main occupational category, 302 individuals accounting for 59.10%. Intermediate professional titles were most common, 138 individuals accounting for 27.00%. From 2021 to 2023, a total of 68 research incentive measures have been implemented, and 579 personnel have received further training. These offices cumulatively led or participated in 80 scientific research projects and published 253 papers. Sixteen offices reported 10 and above scientific research outputs. These offices generally exhibited higher proportions of independently allocated budgets, greater numbers of senior professional titles, more staff with master's degrees or above, more implemented research incentive measures, and higher frequencies of staff further trainings. Conclusions The staff in the administrative offices of CDCs generally have a high level of educational attainment and include a significant number of professional technical personnel. However, their scientific research capacity remains relatively underdeveloped. It is recommended to conduct targeted professional training and research-focused lectures to enhance research literacy, leverage the strengths of multidisciplinary backgrounds, and promote cross-departmental and cross-institutional scientific research activities.

Fragility fractures represent the final clinical manifestation of osteoporosis and are influenced by a range of risk factors. This article discusses the findings from two large-scale studies utilizing biobank and genomic data to investigate the relationships among obesity, type 2 diabetes and fracture risk, and to explore their implications for health management. The studies suggest that general obesity(defined by body mass index, BMI), central obesity(defined by waist circumference), and peripheral obesity exert different effects on fracture risk in older adults. Specifically, individuals who are overweight based on BMI have a lower fracture risk compared to those with normal weight, whereas an increased waist circumference is associated with a higher fracture risk. Moreover, genetic research indicates that genetically determined type 2 diabetes is not causally associated with increased fracture risk. In contrast, observational studies have reported a higher fracture risk in patients with type 2 diabetes; however, this association becomes non-significant after adjusting for diabetes-related risk factors. These findings highlight that maintaining a moderately elevated BMI may benefit bone formation in the elderly by providing mechanical loading to stimulate bone formation. Additionally, effective management of type 2 diabetes complications is essential for reducing fracture risk, and a certain degree of obesity may confer a protective effect against fractures in individuals with type 2 diabetes.

ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury， as well as the protective role of Huoxue Huayu Jiedu prescription （HXHYJDF） against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups： sham group， model group， deferoxamine （DFO） group （100 mg·kg^-1）， low-dose HXHYJDF group （4.52 g·kg^-1）， medium-dose HXHYJDF group （9.04 g·kg^-1）， and high-dose HXHYJDF group （18.07 g·kg^-1）， with ten rats in each group. Except for the sham group， the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1^st， 3^rd， 5^th， and 7^th days post-reperfusion using the modified neurological severity scores （m-NSS）. Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin （HE） staining and transmission electron microscopy. The contents of malondialdehyde （MDA）， glutathione （GSH）， divalent iron ions （Fe²⁺）， and reactive oxygen species （ROS） in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot （WB） were used to detect the expression of iron death marker proteins glutathione peroxidase 4 （GPX4）， ferroportin-1 （FPN1）， transferrin receptor protein 1 （TfR1）， and ferritin mitochondrial （FtMt） in brain tissue. ResultsCompared with the sham group， the mNSS score of the model group was significantly increased （P<0.01）. HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced， and the intercellular space was widened. The nucleus was fragmented， and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded， and the mitochondrial cristae decreased. The matrix was lost and vacuolated， and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS increased significantly （P<0.01）. The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased （P<0.01）， and the expression of FtMt and TfR1 proteins was significantly increased （P<0.01）. Compared with those of the model group， the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3^rd and 5^th days， respectively （P<0.05， P<0.01）. The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS decreased significantly （P<0.05， P<0.01）. The content of GSH in the low-dose HXHYJDF group increased significantly （P<0.01）， and the contents of MDA and ROS decreased significantly （P<0.01）. The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly （P<0.01）， and the expression of FtMt and TfR1 decreased significantly （P<0.01）. The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly （P<0.05）， and the expression of TfR1 decreased significantly （P<0.01）. WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose， medium-dose， and low-dose HXHYJDF groups were significantly up-regulated （P<0.01）， and the expression levels of FtMt and TfR1 proteins were significantly down-regulated （P<0.01）. ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury， improve the pathological morphology of the infarcted brain tissue， and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury， with increased levels of MDA， Fe²⁺， ROS， and TfR1 and decreased levels of FtMt， FPN1， GPX4， and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins， promoting the discharge of free iron， reducing brain iron deposition， alleviating oxidative stress， and inhibiting ferroptosis.

Growth and development-related diseases result from the interplay of biological, psychological, and social factors. The collaboration between healthcare, sports, and education sectors integrates multidisciplinary resources and strengths to promote standardized diagnostic and therapeutic processes. This approach establishes a comprehensive closed-loop system encompassing early screening and referral, diagnosis and comprehensive evaluation, intervention and support plan formulation, as well as long-term management andoutcome assessment. It provides systematic scientific support for the healthy growth of children and adolescents, shifting disease intervention to the subclinical stage. Against the backdrop of societal informatization and intelligent development, this diagnostic and therapeutic model not only safeguards the holistic health of children and adolescents but also offers novel perspectives and feasible pathways for managing growth and development-related diseases. The implementation of this systematic diagnostic and therapeutic paradigm presents an innovative solution with Chinese characteristics for addressing such conditions, while injecting new vitality into the advancement of national health initiatives.