The efficient,precise,and rapid detection of trace copper ions(Cu2+)is of paramount importance in the realms of food safety,environmental monitoring,and medical health.By ingeniously utilizing the chemical properties of benzotriazole compounds in copper protection,and introducing an electrochemical reduction strategy,a silver nanoparticle composite structure supported by a nickel foam substrate was developed as an active platform for surface-enhanced Raman scattering(SERS)detection.This platform employed benzotriazole-5-carboxylic acid(BTAC)as a specific SERS probe molecule to achieve sensitive analysis of metal ion concentrations.The detection mechanism revealed a highly selective coordination between the Cu2+and the nitrogen atom in the triazole ring of BTAC,triggering subtle structural changes in the triazole ring.This was manifested by a significant and quantifiable shift in the characteristic peak of the SERS spectrum(particularly at 1001 cm-1),with a maximum shift of up to 30 cm-1.This phenomenon not only addressed the issue of reproducibility in quantitative analysis caused by the non-uniformity of SERS substrate materials but also significantly broadened the application boundaries of SERS technology for trace metal ion detection.It enabled ultra-sensitive detection of Cu2+concentrations ranging from 1×10-6 to 1×10-11 mol/L,with a detection limit as low as 1×10-11 mol/L,significantly enhancing detection sensitivity and accuracy.This work provided a novel and efficient strategy for rapid detection of trace Cu2+and enriched the application potential of SERS technology in food safety,environmental monitoring and biomedical analysis.

Notum, a negative feedback regulator of the Wnt signaling, has emerged as a promising target for treating glucocorticoid-induced osteoporosis (GIOP). This study showcases an efficient strategy for discovering the anti-Notum constituents from herbal medicines (HMs) as novel anti-GIOP agents. Firstly, a rapid-responding near-infrared fluorogenic substrate for Notum was rationally engineered for high-throughput identifying the anti-Notum HMs. The results showed that Bu-Gu-Zhi (BGZ), a known anti-osteoporosis herb, potently inhibited Notum in a competitive-inhibition manner. To uncover the key anti-Notum constituents in BGZ, an efficient strategy was adapted via integrating biochemical, phytochemical, computational, and pharmacological assays. Among all identified BGZ constituents, three furanocoumarins were validated as strong Notum inhibitors, while 5-methoxypsoralen (5-MP) showed the most potent anti-Notum activity and favorable safety profiles. Mechanistically, 5-MP acted as a competitive inhibitor of Notum via creating strong hydrophobic interactions with Trp128 and Phe268 in the catalytic cavity of Notum. Cellular assays showed that 5-MP remarkably promoted osteoblast differentiation and activated Wnt signaling in dexamethasone (DXMS)-challenged MC3T3-E1 osteoblasts. In dexamethasone-induced osteoporotic mice, 5-MP strongly elevated bone mineral density (BMD) and improved cancellous and cortical bone thickness. Collectively, this study constructs a high-efficient platform for discovering key anti-Notum constituents from HMs, while 5-MP emerges as a promising anti-GIOP agent.

Purpose To investigate the feasibility of a deep learning framework to automatically analyze echocardiographic color Doppler videos in detecting valvular regurgitation.Materials and Methods This study retrospectively collected echocardiographic images of 1 109 patients with valvular regurgitation in the Fourth Medical Center of PLA General Hospital,from June 2015 to September 2019 as the training and validation sets.A prospective continuous collection of 1 562 echocardiography images was used as the test set in the Fourth Medical Center of PLA General Hospital from May 13 to June 13,2023,including 378 cases of mitral regurgitation and 223 cases of aortic regurgitation.This study developed deep learning networks to establish view classification model and valvular regurgitation recognition model,including the efficiency of section classification of deep learning models.Results The deep learning view classification model in this study could automatically identify two views for diagnosing mitral regurgitation and aortic regurgitation.The recognition accuracy for the parasternal long axis color Doppler view and the apical four chamber mitral color Doppler view was 1.00 and 0.93,respectively.The sensitivity,specificity,accuracy and area under the curve of the deep learning model for diagnosing mitral regurgitation were 0.847,0.852,0.849 and 0.930,respectively.The sensitivity,specificity,accuracy and area under the curve of the deep learning model in diagnosing aortic regurgitation were 0.857,0.861,0.859 and 0.940,respectively.Conclusion Deep learning algorithms can automatically identify valvular regurgitation and have the potential to become a screening tool for valvular heart disease.

Objective:To evaluate the short-term safety and efficacy of total laparoscopic, laparoscopy-assisted, and open total gastrectomy in patients with gastric cancer who have undergone neoadjuvant therapy.Methods:In this retrospective cohort study, relevant clinical data on 243 patients who had undergone radical total gastrectomy after receiving neoadjuvant therapy were collected. These patients had been admitted to the First Affiliated Hospital of Air Force Medical University, Yuncheng Central Hospital of Shanxi Province, and Heji Hospital Affiliated to Changzhi Medical College between January 2020 and April 2024. Among them, 202 were male (83.1%) and 41 were female (16.9%), and their average age was 61.3±8.1 years. The patients were allocated to three groups according to surgical procedure: total laparoscopic (68 cases), laparoscopic- assisted (79 cases), and open surgery (96 cases). We compared relevant baseline characteristics, neoadjuvant treatment, intraoperative and postoperative conditions, postoperative histopathological findings, and related complications between these three groups.Results:There were no statistically significant differences in baseline characteristics or neoadjuvant treatment between the three groups (all P>0.05). The operative time was longer in the total laparoscopic group than in the laparoscopic-assisted and open surgery groups (267.7±37.9 minutes vs. 243.9±38.3 minutes vs. 219.7±41.2 minutes, respectively; F=7,112.278; P<0.001). However, more lymph nodes were harvested in the total laparoscopic group than in the laparoscopic-assisted and open surgery groups (27.8±4.8 vs. 27.4±6.3 vs. 27.2±5.1, respectively; F=6.042; P=0.002). Additionally, the total laparoscopic group had shorter times to first postoperative flatus (2.3±0.7 days vs. 2.4±0.7 days vs. 2.6±0.6 days, respectively; F=5.094; P=0.006] and first postoperative bowel movement (2.9±0.5 days vs. 3.0±0.6 days vs. 3.0±0.6 days, respectively; F=3.929; P=0.020). There were no statistically significant differences in intraoperative blood loss, intraoperative transfusion rates, postoperative intensive care unit admission rates, maximum tumor diameter, number of positive lymph nodes dissected, TNM stage, time to first postoperative oral intake, time to drain removal, or length of hospital stay between the three groups (all P>0.05). Among the 243 patients, 22 developed postoperative complications, making the overall complication rate 9.1%. Six patients (8.8%) in the total laparoscopic group developed complications, comprising two (2.9%) Grade IIIa Clavien-Dindo complications. One of these patients (1.5%) was readmitted within 30 days due to complications. Seven patients (8.9%) in the laparoscopic-assisted group developed complications, comprising two (2.5%) Grade IIIa Clavien-Dindo complications. One of these patients was readmitted within 30 days and another was within 90 days due to complications. Nine patients (9.4%) in the open surgery group developed complications, comprising four (4.2%) Grade IIIa Clavien-Dindo complications. Two patients (2.1%) were readmitted within 30 days and another (1.0%) within 90 days due to complications. There were no statistically significant differences among the three surgical approaches in overall postoperative complication rates, Clavien-Dindo grades, or readmission rates 30 and 90 days postoperatively (all P>0.05). Conclusions:In patients with gastric cancer who have undergone neoadjuvant therapy, there are no significant differences in the overall safety and short-term effectiveness of the three surgical procedures. Although the operative time is longer for total laparoscopic total gastrectomy, this procedure offers the advantages of faster postoperative recovery and earlier resumption of feeding.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective:To analyze the correlation between sex hormone levels and micropenis after mild hypospadias surgery in children.Methods:A case control study was carried out.The clinical data of 71 children aged 1 to 13 years who underwent mild hypospadias surgery at the First Affiliated Hospital of Xinxiang Medical University from April 2022 to April 2024 were analyzed.Preoperatively, the children were divided into a mild hypospadias group (Group A) and a mild hypospadias with micropenis group (Group B) based on the stretched penile length (SPL).Prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone, and testosterone (TES) levels of the 2 groups were measured.Multivariate Logistic regression analysis was used to construct a risk prediction model.The discrimination capability of the model was evaluated using the receiver operating characteristic (ROC) curve.SPL and sex hormone levels were measured again 6 months after surgery.The children were divided into a normal penile group (Group AA) and a micropenis group (Group BB) after mild hypospadias according to SPL.Multivariate Logistic regression analysis was used to construct a risk prediction model, which was evaluated using the ROC curve.Results:The levels of FSH, LH and TES in group A before the operation were 3.28(2.02, 4.46) IU/L, 0.53(0.25, 0.79) IU/L and 25.24(17.94, 36.67) ng/dL, respectively, and those in group B were 1.42(1.10, 1.84) IU/L, 0.14(0.09, 0.23) IU/L and 15.73 (12.92, 17.00) ng/dL, respectively.The difference was all statistically significant (all P<0.05).Multivariate Logistic regression analysis showed statistical significance ( OR=0.515, 95% CI: 0.271-0.977; OR=0.035, 95% CI: 0.002-0.542; OR=0.883, 95% CI: 0.796-0.980).The area under the ROC curve (AUC) of the prediction model was 0.906, with a sensitivity of 75.00% and a specificity of 95.74%.The levels of FSH, LH and TES in the postoperative AA group were 2.97 (1.88, 4.28) IU/L, 0.46 (0.23, 0.78) IU/L and 20.92 (17.34, 33.27) ng/dL, respectively.The median levels of FSH, LH and TES in the BB group were 1.52 (1.27, 1.82) IU/L, 0.17 (0.12, 0.26) IU/L and 15.08(11.68, 16.68) ng/dL, respectively.The difference was all statistically significant (all P<0.05).Multivariate Logistic regression analysis showed statistical significance ( OR=0.484, 95% CI: 0.236-0.992; OR=0.061, 95% CI: 0.004-0.939; OR=0.891, 95% CI: 0.795-0.999).The AUC of the prediction model constructed was 0.877, with a sensitivity of 94.12% and a specificity of 68.52%. Conclusions:Lower FSH, LH and TES levels are risk factors for the micropenis after mild hypospadias surgery, and preoperative hormone levels have higher predictive value.

OBJECTIVE: To observe the clinical efficacy of Fu's subcutaneous needling based on "multi-joint muscle spiral balance chain" theory for cervical vertigo (CV) and its effect on blood flow velocity of vertebral artery. METHODS: A total of 60 patients with CV were randomized into a Fu's subcutaneous needling group and a medication group, 30 cases in each one. In the Fu's subcutaneous needling group, Fu's subcutaneous needling was delivered at Dazhui (GV14), the flexible tube was retained for 5 min after sweeping manipulation, and the treatment was given once every other day, 3 times a week for 3 weeks. In the medication group, betahistine mesylate tablet and diclofenac sodium dual-release enteric capsule were taken orally for continuous 3 weeks. Before treatment, after treatment, and in follow-up of one month after treatment completion, the scores of dizziness handicap inventory (DHI) and visual analogue scale (VAS) were observed; before and after treatment, the blood flow velocity of vertebral artery was measured by transcranial Doppler, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment and in follow-up, each item scores and total scores of DHI were decreased compared with those before treatment in the two groups (P<0.05); the VAS scores after treatment in the two groups, as well as the VAS score in follow-up of the Fu's subcutaneous needling group, were decreased compared with those before treatment (P<0.05). In the Fu's subcutaneous needling group, after treatment and in follow-up, the physical scores and the total scores of DHI, and the VAS scores were lower than those in the medication group (P<0.05); in follow-up, the emotional and functional scores of DHI were lower than those in the medication group (P<0.05). After treatment, the mean blood flow velocity (Vm) of the left vertebral artery (LVA) and the right vertebral artery (RVA) was increased compared with that before treatment in the two groups (P<0.05), and the Vm of LVA and RVA in the Fu's subcutaneous needling group was higher than that in the medication group (P<0.05). The total effective rate was 100.0% (30/30) in the Fu's subcutaneous needling group, which was superior to 73.3% (22/30) in the medication group (P<0.05). CONCLUSION Fu's subcutaneous needling based on the "multi-joint muscle spiral balance chain" theory can effectively alleviate the vertigo and neck pain, and improve the blood flow velocity of vertebral artery in CV patients, and has a long-term therapeutic effect.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/instrumentation* ; Vertebral Artery/physiopathology* ; Adult ; Vertigo/physiopathology* ; Aged ; Blood Flow Velocity ; Treatment Outcome ; Acupuncture Points ; Young Adult

The plant F-box protein more axillary growth 2 (MAX2) is a key factor in the signal transduction of strigolactones (SLs) and karrinkins (KARs). As the main component of the SKP1-CUL1-FBX (SCF) complex ubiquitin ligase E3, MAX2 is responsible for specifically recognizing the target proteins, suppressor of MAX2 1/SMAX1-like proteins (SMAX1/SMXLs), which would be degraded after ubiquitination. It can thereby regulate plant morphogenesis and stress responses. There exist homologous genes of MAX2 in the important grain and oil crop soybean (Glycine max). However, its role in plant defense responses has not been investigated yet. Here, GmMAX2b, a homologous gene of MAX2, was successfully cloned from stressed soybean. Bioinformatics analysis revealed that there were two MAX2 homologous genes, GmMAX2a and GmMAX2b, with a similarity of 96.2% in soybean. Their F-box regions were highly conserved. The sequence alignment and cluster analysis of plant MAX2 homologous proteins basically reflected the evolutionary relationship of plants and also suggested that soybean MAX2 might be a multifunctional protein. Expression analysis showed that plant pathogen infection and salicylic acid treatment induced the expression of GmMAX2b in soybean, which is consistent with that of MAX2 in Arabidopsis. Ectopic expression of GmMAX2b compensated for the susceptibility of Arabidopsis max2-2 mutant to pathogen, indicating that GmMAX2b positively regulated plant disease resistance. In addition, yeast two hybrid technology was used to explore the potential target proteins of GmMAX2b. The results showed that GmMAX2b interacted with SMXL6 and weakly interacted with SMXL2. In summary, GmMAX2b is a positive regulator in plant defense responses, and its expression is induced by pathogen infection and salicylic acid treatment. GmMAX2b might exert its effect through interaction with SMXL6 and SMXL2. This study expands the theoretical exploration of soybean disease resistant F-box and provides a scientific basis for future soybean disease resistant breeding.
Glycine max/metabolism* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plant Proteins/genetics* ; Cloning, Molecular ; Gene Expression Regulation, Plant ; F-Box Proteins/genetics* ; Arabidopsis/genetics* ; Phylogeny

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes