OBJECTIVE To design and synthesize mono-carbonyl curcumin analogues（MCACs） and investigate the activities of them against breast cancer. METHODS The analogues F1， F2， and F3 were obtained by aldol condensation reaction， and their antitumor activities（including the activities of human breast cancer cell MCF-7 and human lung cancer cell A549） were detected by MTT assay [evaluated with half inhibitory concentration（IC50）]. The results of MTT assay were compared with those of curcumin. Bioinformatics methods were used to collect the core targets of analogues F1， F2 and F3 acting on breast cancer， and then molecular docking verification was carried out. The cell experiments were conducted to investigate the effects of high， medium and low concentrations （16， 8， 4 μmol/L） of F1， F2 and F3 on the expression of the first core target protein as well as the effects of medium concentration of F1， F2 and F3 on the expression of cleaved-caspase-3. RESULTS Compared with curcumin， IC50 of analogues F1， F2 and F3 to A549 and MCF-7 cells（except for IC50 of analogue F2 to A549 cells） were decreased significantly（P＜ 0.05 or P＜0.01）； among them， IC50 of analogue F2 to MCF-7 cell was the lowest， being（9.67±1.27） μmol/L. Bioinformatics analysis showed that index of affinity of analogues F1， F2 and F3 with the first core target epidermal growth factor receptor （EGFR）， protein kinase B （AKT） and AKT were 5.909 2， 8.402 5 and 6.486 6， respectively； high concentration of F1 could significantly reduce the phosphorylation level of EGFR protein in MCF-7 cells（P＜0.01）， while low， medium， and high concentrations of F2 and high concentration of F3 could significantly reduce the phosphorylation level of AKT protein in MCF-7 cells（P＜0.05 or P＜0.01）. Medium concentration of F1， F2， and F3 could significantly increase the expression level of cleaved- caspase-3 protein in MCF-7 cells（P＜0.01）. CONCLUSIONS Designed and synthesized MCACs F1， F2 and F3 all have good anti- breast cancer activity， and F2 has better anti-breast cancer activity.

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.

Objective To investigate the suitable habitats of Phlebotomus chinensis in Gansu Province, so as provide insights into effective management of mountain-type zoonotic visceral leishmaniasis (MT-ZVL). Methods The geographical coordinates of locations where MT-ZVL cases were reported were retrieved in Gansu Province from 2015 to 2023, and data pertaining to 26 environmental variables were captured, including 19 climatic variables (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest quarter, mean temperature of the coldest quarter, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, precipitation of the warmest quarter, and precipitation of the coldest quarter), five geographical variables (elevation, annual normalized difference vegetation index, vegetation type, landform type and land use type), and two population and economic variables (population distribution and gross domestic product). Twelve species distribution models were built using the biomod2 package in R project, including surface range envelope (SRE) model, generalized linear model (GLM), generalized additive model (GAM), multivariate adaptive regression splines (MARS) model, generalized boosted model (GBM), classification tree analysis (CTA) model, flexible discriminant analysis (FDA) model, maximum entropy (MaxEnt) model, optimized maximum entropy (MAXNET) model, artificial neural network (ANN) model, random forest (RF) model, and extreme gradient boosting (XGBOOST) model. The performance of 12 models was evaluated using the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS), and Kappa coefficient, and single models with high performance was selected to build the optimal ensemble models. Factors affecting the survival of Ph. chinensis were identified based on climatic, geographical, population and economic variables. In addition, the suitable distribution areas of Ph. chinensis were predicted in Gansu Province under shared socioeconomic pathway 126 (SSP126), SSP370 and SSP585 scenarios based on climatic data during the period from 1991 to 2020, from 2041 to 2060 (2050s), and from 2081 to 2100 (2090s) . Results A total of 11 species distribution models were successfully built for prediction of potential distribution areas of Ph. chinensis in Gansu Province, and the RF model had the highest predictive accuracy (AUC = 0.998). The ensemble model built based on the RF model, XGBOOST model, GLM, and MARS model had an increased predictive accuracy (AUC = 0.999) relative to single models. Among the 26 environmental factors, precipitation of the wettest quarter (12.00%), maximum temperature of the warmest month (11.58%), and annual normalized difference vegetation index (11.29%) had the greatest contributions to suitable habitats distribution of Ph. sinensis. Under the climatic conditions from 1991 to 2020, the potential suitable habitat area for Ph. chinensis in Gansu Province was approximately 5.80 × 10⁴ km², of which the highly suitable area was 1.42 × 10⁴ km², and primarily concentrated in the southernmost region of Gansu Province. By the 2050s, the unsuitable and lowly suitable areas for Ph. chinensis in Gansu Province had decreased by varying degrees compared to that of 1991 to 2020 period, while the moderately and highly suitable areas exhibited expansion and migration. By the 2090s, under the SSP126 scenario, the suitable habitat area for Ph. chinensis increased significantly, and under the SSP585 scenario, the highly suitable areas transformed into extremely suitable areas, also showing substantial growth. Future global warming is conducive to the survival and reproduction of Ph. chinensis. From the 2050s to the 2090s, the highly suitable areas for Ph. chinensis in Gansu Province will be projected to expand northward. Under the SSP126 scenario, the suitable habitat area for Ph. chinensis in Gansu Province is expected to increase by 194.75% and 204.79% in the 2050s and 2090s, respectively, compared to that of the 1991 to 2020 period. Under the SSP370 scenario, the moderately and highly suitable areas will be projected to increase by 164.40% and 209.03% in the 2050s and 2090s, respectively, while under the SSP585 scenario, they are expected to increase by 195.98% and 211.66%, respectively. Conclusions The distribution of potential suitable habitats of Ph. sinensis gradually shifts with climatic changes. Intensified surveillance and management of Ph. sinensis is recommended in central and eastern parts of Gansu Province to support early warning of MT-ZVL.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

【Objective】 To analyze the correlation between the distribution interval of minipool nucleic acid testing(NAT) positive CT value and the resolution rate, so as to improve the retest model and reduce residual risk of blood transfusion. 【Methods】 The resolution testing results by Cobas S201 system of our blood center from January 2017 to December 2021 were retrospective analyzed, and the retest model was developed based on the distribution interval of CT values. For minipool NAT HBV positive samples from March 2022 to March 2023, synchronous detection was conducted by Cobas S201 and Panther detection system, and the detection results were statistically analyzed. 【Results】 From 2017 to 2021, 474 were minipool NAT positive, among which 324 were HBV positive, accounting for 68.35%. From 2017 to 2020, the proportion of HBV positive per year was significantly higher than that of HCV and HIV(P<0.05). In resolution testing, 167 were HBV repeatable positive and 157 were HBV non-repeatable positive, accounting for 51.54% and 48.46% of HBV minipool NAT positive. HBV repeatable positive samples were with three intervals: CT value≤36, 3640, with the resolution rate at 95.8%, 56.5% and 14.8% respectively(P<0.05). The proportion of 3640, 36

Nanozymes, a groundbreaking discovery by Chinese scientists, represent a novel and remarkable property of nanomaterials. They not only exhibit catalytic activity comparable to natural enzymes, but also boast exceptional stability, tunable reactivity, and the ability to catalyze reactions under mild conditions. The identification of nanozymes has unveiled the biocatalytic potential of inorganic nanomaterials. In parallel, inorganic minerals have long been regarded as pivotal catalysts in the origin of life, driving the synthesis of early biomolecules. These minerals not only facilitate redox reactions that convert simple inorganic compounds into organic molecules but also enable chiral selection, the synthesis of biomacromolecules, and radioprotective functions via their surface structures. Recent advances suggest that inorganic nanomaterials can delicately catalyze the formation of biomolecules, aid in macromolecular assembly, and provide radiation shielding. Furthermore, nanominerals are found in abundance across Earth and extraterrestrial environments. This paper seeks to explore the potential of nanozymes as catalytic agents in the processes that gave rise to life, integrating the catalytic roles of inorganic minerals with the unique attributes of nanozymes, which will provide a new perspective for research of origin of life.

Objective: To understand towards core competence of integrated medicine-education health teachers of graduates with undergraduate major of health education in China, so as to provide evidence for improving the quality of teaching workforce. Methods: From January to May 2023, a questionnaire survey was conducted on 92 primary and secondary school health teachers who graduated from Sanda University. All the participants reported the achievement of core competence after graduation, the performance of core competence at present and the importance of competencies. Group comparisons were conducted by using t-test or analysis of variance, while open ended questions were analyzed by using word cloud analysis. Results: In the nine dimensions of core competency, the top three dimensions among scores of achievement and performance were general quality as a teacher, emergency response to accidents(4.52±0.59, 4.38±0.61, 4.32±0.70), and prevention and control of public health events in schools ( 4.58 ±0.55, 4.49±0.62, 4.50±0.61). Compared with the achievement after graduation, the mean score of the current performance of core competence has increased in all dimensions except for basic health education literacy ( t=2.28-4.69, P <0.05). Among them, the rank of Basic Literacy of Health Education decreased significantly compared to graduation time (ranking down from 5th to 8th), and School Health Management and Improvement increased significantly (ranking up from 8th to 5th). There were no statistically significant differences in the achievement and the current performance scores of the core competence among graduates with different graduation years ( F=0.56-1.45, 0.73-1.23, P >0.05). According to the respondents, the most important competencies were associated with emergency response to accidents, prevention and control of infectious diseases, identification and management of common disease symptoms, and teachers moral cultivation. Conclusions The development of core competencies for healthcare teachers in integrated medical and educational schools is not yet balanced, the core competency performance of graduates with major of health education varied significantly by graduation time. Medical related abilities and professional ethics are considered the most important core competencies for graduates.

Objective To investigate the relationship between the development of terminal rectal ganglion and spinal cord/sacral abnormalities in boys with complex anorectal malformations(ARMs)in order to improve the understanding of rectal ganglion development abnormalities in ARMs patients.Methods A retrospective trial was conducted on the male patients with complex ARMs admitted to our hospital from 2015 to 2021.The terminal rectal specimens were taken from them during anoplasty.According to the findings on development of terminal rectal ganglion after HE staining,the patients were classified into G1 group(ganglion cells observed)and G2 group(no ganglion cells observed).Imaging techniques were used to evaluate whether there were abnormalities in the spinal cord and sacrum,and their correlation with the terminal rectal ganglion development was analyzed.Results A total of 139 patients were enrolled,and their median age at anoplasty was 5.77(4.57,6.97)months.There were no significant differences between the G1(n=80,57.6％)and G2(n=59,42.4％)groups in ARMs pathological type(P=0.706)and age at surgery(P=0.140).Radiological findings showed there were 48 cases(34.5％)of spinal cord anomalies(SCA),25 cases(18.0％)of sacral abnormalities and 18 cases(12.9％)of coccyx abnormalities.No significant differences were observed in the incidences of SCA and sacral abnormalities between the G1 and G2 groups(P＜0.05).Moreover,the differences of fatty filum terminale and syrinx were statistically significant(P＜0.05).In addition,the ratio of sacrum to coccyx between the G1 and G2 groups were 0.72±0.10 vs 0.67±0.12(P＜0.05)of the anteroposterior position and 0.77±0.09 vs 0.72±0.09(P＜0.05)of the lateral position.Multivariate logistic regression analysis showed that sacral abnormalities,fatty filum terminale and syrinx were independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.Conclusion The development of terminal rectal ganglia in male patients with ARMs is closely associated with the abnormalities of spinal cord and sacrum.Sacral abnormalities,fatty filum terminale and syrinx are independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.

Amantadine(AMD)residue can accumulate in organisms through the food chain and cause serious harm to human body.AMD can specifically bind to AMD specific aptamer and cause its conformation to change from a random single strand to a stem-loop structure.To avoid the influence of excess nucleotides on binding of aptamer to AMD,the truncation of the AMD original aptamer J was optimized by retaining an appropriate stem-loop structure,and a new type of truncation aptamers was developed in this work.By comparing the truncated aptamer with the original aptamer,it was found that the truncated aptamer J-7 had better affinity and specificity with AMD.The detection limit of AMD was 0.11 ng/mL by using J-7 as specific recognition element and molybdenum disulfide nanosheet(MoS2Ns)as signal amplification element.The developed method base on truncated aptamer J-7 was used for detection of AMD in milk,yogurt and SD rat serum samples for the first time with recoveries of 86.6%-108.2%.This study provided a reference for truncating other long sequence aptamers and provided a more sensitive detection method for monitoring AMD residues in food.

Objective:To observe the effects of modified Xuanfuhua Decoction on pain behaviour and spinal cord neuroinflammation mediated by phosphorylated mitogen-activated protein kinase p38 (p38MAPK) signaling pathway in rats with sciatic nerve injury; To analyse the mechanism of its effects.Methods:Totally 108 SD rats were randomly divided into sham-operation group, model group, pregabalin group, decoction low-, medium- and high-dosage groups, with 18 rats in each group. The CCI model was established by ligation of sciatic nerve in other groups except sham-operation group. On the postoperative day, the decoction low-, medium-, high-dosage groups were gavaged with 2.5, 5.0 and 10.0 g/kg of modified Xuanfuhua Decoction concentrate, respectively. The pregabalin group was gavaged with 15 mg/kg of pregabalin. The sham-operation group and the model group were gavaged with equal amounts of saline once/d for 15 days. Pain behavioural assays were performed before, on the 3rd, 7th, 11th and 15th day of administration respectively. The levels of interleukin (IL)-1β, tumour necrosis factor-α (TNF-α), IL-10 were detected by ELISA method. The expressions of Toll-like receptor 4 (TLR4), nuclear factor-κB p65 (NF-κB p65) were detected by immunohistochemistry staining. The phosphorylated p38MAPK (p-p38MAPK) were measured in the spinal cord by Western blot.Results:Compared with the model group, the scores of spontaneous pain in decoction high-dosage group decreased ( P<0.05), the thermal foot shrinkage latency (TWL) was prolonged ( P<0.05), and the mechanical foot shrinkage reflex threshold (MWT) increased ( P<0.05); the levels of IL-1β and TNF-α in spinal cord tissue of decoction low-, medium- and high-dosage groups decreased ( P<0.05), the level of IL-10 increased ( P<0.05), the average gray values of TLR4 and NF-κB p65 in spinal cord decreased ( P<0.05), and the expression of P-P38MAPK protein decreased ( P<0.05). Conclusion:Modified Xuanfuhua Decoction can effectively improve neurogenic pain in CCI rats, and the mechanism may be related to inhibition of p38MAPK-TLR4 signaling pathway activation-mediated spinal cord neuroinflammation.