Among gynecologic malignancies, ovarian cancer is the most lethal, primarily due to its insidious early symptoms, lack of effective screening methods, and high risk of recurrence. It poses substantial challenges to clinical diagnosis and treatment. In recent years, the clinical application of poly ADP-ribose polymerase inhibitors has promoted a comprehensive management model that integrates targeted therapy with conventional treatments. This review, aiming to provide new perspectives and approaches for future research, summarizes the high-risk factors and first-line treatment strategies for ovarian cancer. Further studies should focus on optimizing personalized treatment strategies and exploring novel targeted therapies to improve patient survival outcomes.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Hydroxyectoine, a vital compatible solute, is widely utilized in cosmetics, food, pharmaceutical industries, and biologics. However, the current microbial fermentation methods for hydroxyectoine production face challenges including insufficient precursor supply and low yields. Therefore, developing engineering microbial strains capable of efficiently synthesizing hydroxyectoine is of great significance. In this study, we first constructed a high-yield ectoine-producing strain ECT04 by multi-copy integration of the ectoine synthesis genes ectABC into the pseudogene loci of Escherichia coli MG1655(DE3), achieving an ectoine titer of 6.03 g/L. Subsequently, we employed plasmids with varying copy numbers to express ectD from Chromohalobacter salexigens to enable the conversion for hydroxyectoine production. We further investigated the effects of promoter, co-substrate ɑ-ketoglutarate, Fe²⁺ concentration, and dissolved oxygen on hydroxyectoine synthesis. Through fed-batch fermentation in a 7-L bioreactor, we significantly enhanced the hydroxyectoine production efficiency, attaining a final titer of 8.58 g/L and a productivity of 0.24 g/(L·h). This work successfully achieved the de novo synthesis of hydroxyectoine in E. coli, laying a foundation for the efficient bioproduction of this compound.
Escherichia coli/genetics* ; Fermentation ; Amino Acids, Diamino/biosynthesis* ; Bioreactors/microbiology* ; Metabolic Engineering/methods* ; Chromohalobacter/genetics* ; Plasmids/genetics*

Colorectal cancer is the most common malignant tumor of digestive tract, and BRAF V600E mutations occur in approximately 10% of patients with metastatic colorectal cancer (mCRC). Cancer patients harboring this mutation have a unique molecular profile and clinical phenotype; they show poor response to systemic chemotherapy, insensitivity to single BRAF inhibitor, and short survival rate. It is important to develop new therapeutic agents and clinical strategies to improve the prognosis of these patients. This review mainly introduces treatment methods for BRAF V600E-mutated mCRC and rationally derived combinations of targeted agents and immunotherapy.

School-age children are in a specific development stage corresponding to juvenility, when the white matter of the brain experiences ongoing maturation. Diffusion-weighted magnetic resonance imaging (DWI), especially diffusion tensor imaging (DTI), is extensively used to characterize the maturation by assessing white matter properties in vivo. In the analysis of DWI data, spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space. Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization. However, there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development. Here, we established the school-age children diffusion tensor (SACT) template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years. With an age-balanced design, the SACT template represented the entire age range well by showing high similarity to the age-specific templates. Compared with the tensor template of adults, the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of school-age children. A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template. Although similar spatial patterns were found, the SACT template showed significant effects on the distributions of the statistical results, which may be related to the performance of spatial normalization. Looking forward, the SACT template could contribute to future studies of white matter development in both healthy and clinical populations. The SACT template is publicly available now ( https://figshare.com/articles/dataset/SACT_template/14071283 ).

The diagnosis of food allergy in children is one hotspot attracting people′s attention in recent years.The incidence of it shows an increasing trend which exposes problems in the understanding of children′s food allergy in China, especially in the misdiagnosis and missed diagnosis.To further standardize the diagnosis and treatment of food allergy in children, based on the current domestic, foreign guidelines and relevant research evidence, the guideline recommends 16 clinical hot-button issues in the 4 aspects of diagnosis, treatment, prognosis, and prevention.Finally, a diagnosis flowchart has been formulated.The guideline aims to improve the standard diagnosis and treatment of food allergies in children in China.

Objective : To investigate the effects of glycated low density lipoprotein (Gly⁃LDL) on the growth of human umbilical vein endothelial cells (HUVECs) and the expression of toll like receptor 4 (TLR4) and hypoxia inducible factor⁃1α (HIF⁃1α), and to explore its possible mechanism . Methods : HUVECs were cultured in vitro and divided into control group, positive control group[50 mg/L normal low density lipoprotein(n⁃LDL)], low concentration, medium concentration and high concentration Gly⁃LDL(50, 75, 100 mg/L) groups . Respectively, the effects of different concentrations of Gly⁃LDL on survival rate of HUVECs were detected by CCK⁃8; The motility of HUVECs under different treatments were detected by wound healing assays; The level of inflammatory cytokine, such as tumor inducing factor⁃α(TNF⁃α), interleukin⁃6(IL⁃6), intercellular adhesion molecule⁃1(ICAM⁃1) and vascular cell adhesion molecule⁃1(VCAM⁃1) were detected by ELISA; The mRNA levels of TLR4, HIF⁃1α, TNF⁃α and IL⁃6 were detected by qRT⁃PCR; Protein expressions of TLR4, HIF⁃1α, TNF⁃α and IL⁃6 were detected by Western blot; Respectively, si⁃RNA of TLR4 and HIF⁃1α was used to intervene the effects of Gly⁃LDL on HUVECs . The experiment was divided into control group, model group (Gly⁃LDL 100 mg/L), si⁃TLR4 group (Gly⁃LDL 100 mg/L + si⁃TLR4), TLR4 unloading group( Gly⁃LDL 100 mg/L + si⁃NC1), si⁃HIF⁃1α group ( Gly⁃LDL 100 mg/L + si⁃HIF⁃1α) and HIF⁃1α unloading group ( Gly⁃LDL 100 mg/L + si⁃NC2) . Protein expressions of TLR4 and HIF⁃1α were detected by Western blot to verify the interaction between TLR4 and HIF⁃1α . Results: The survival rate and migration rate of HUVECs were inhibited in Gly⁃LDL(50 mg/L, 75 mg/L, 100 mg/L) group (P < 0. 01), the inflammatory cytokines, such as TNF⁃α, IL⁃6, ICAM⁃1,VCAM⁃1 increased by Gly⁃LDL function on HUVECs(P < 0. 001), and the mRNA and protein levels of TLR4, HIF⁃1α, TNF⁃α and IL⁃6 increased by Gly⁃LDL in a dose dependent manner. After TLR4 was knocked out, the proteins expression of TLR4 and HIF⁃1α were down⁃regulated compared with model group(P < 0. 05),but after HIF⁃1α was knockout, only the protein expression of HIF⁃1α was down⁃regulated compared with model group( P < 0. 01),while the protein expression of TLR4 was up⁃regulated under the influence of Gly⁃LDL. Conclusion Gly⁃LDL may inhibit the proliferation and migration of HUVECs by up⁃regulating TLR4/HIF⁃1α inflammatory signaling pathway, and promote the expression of inflamma⁃tory cytokines, leading to vascular endothelial injury .

Primary bone lymphoma (PBL) is a rare extranodal lymphoma that lacks specific clinical symptoms and imaging manifestations. Patients with PBL have been commonly treated with chemotherapy, radiotherapy or the combination of both. The prognosis of PBL is generally better than that of other extranodal lymphomas. This paper reviews the clinical symptoms, pathological diagnosis and treatment methods of PBL to deepen the understanding of the disease.

Objective:To explore the value of susceptibility weighted imaging (SWI) in evaluating renal excess iron deposition.Methods:Thirty New Zealand white rabbits were randomly divided into iron group (injected iron dextran) with 15 rabbits and control group with 15 rabbits. All rabbits underwent SWI examination at 0th week before and 8th week after the injection of iron. MRI images of the control and iron group at the 0th and 8th week were analyzed. The phase value of renal cortex was measured on the phase images and the angle radian value was calculated. The distribution of renal iron deposition was observed by Prussian blue stain. The renal iron content was measured by atomic absorption spectrophotometer. The Mann-Whitney U or Wilcoxon test was used to compare the difference in angular radian value between the two groups. The independent sample t test was used to compare the difference in renal iron content between the two groups. Results:Only in iron group at 8th week, the SWI signal intensity of renal cortex was significantly lower than that of medulla. The renal cortical SWI signal intensity of iron group at 8th week was significantly lower than that of iron group at 0th week and control group at 8th week, respectively. The angle radian value of iron group at 8th week [0.202 3(0.161 8, 0.272 5)] was significantly higher than that of iron group at 0th week [-0.045 4 (-0.013 9, 0.008 0)] and control group at 8th week [-0.011 2 (-0.052 9, -0.001 4)], respectively ( Z=-3.408, -4.666, all P<0.05). Only in the iron group at 8th week, the obvious blue iron deposition were observed in renal cortex and few were observed in medulla. The renal iron content [(135.3±14.1) mg/kg] of iron group at 8th week was significantly higher than that [(75.5±9.8) mg/kg] of control group at 8th week ( t=13.938, P<0.001). Conclusions:SWI can evaluate the excess iron deposition in kidney. Excess iron is mainly deposited in the renal cortex and reduces its SWI signal intensity. The angle radian value calculated from the phase value can quantify the iron deposition.

Objective:To explore the value of susceptibility-weighted imaging (SWI) in quantitative evaluation of iron load in diabetic kidneys.Methods:Thirty two healthy New Zealand white rabbits were randomly divided into diabetic group (DM, n = 20) and control group (NC, n = 12). DM model was established by injecting 5% alloxan solution (100 ml/kg) through ear vein. 12 rats were finally enrolled into the group. NC group was injected with the same dose of normal saline. DM group and NC group were intramuscularly injected with 60 mg/kg iron dextran. The left kidney was scanned by MRI immediately after iron injection (0 weeks) and 12 weeks after feeding. The left kidney was killed after 12 weeks of scanning. The left kidney was examined by Prussian blue staining and atomic absorption spectrophotometer. The value of SWI in quantitative evaluation of renal iron content was evaluated by using the iron content measured by atomic absorption spectrophotometer as the gold standard. On SWI phase diagram, the region of interest (ROI) was manually drawn along the renal cortical vagal area, and the measured phase values were converted into angular radians. Mann Whitney U test was used to compare the blood glucose value and the angle radian value at 0 week and 12 week between the two groups; independent sample t test was used to compare the difference of iron content between the two groups; nonparametric Wilcoxon signed rank test was used to compare the difference of angle radian between DM group and NC group at 0 and 12 weeks; Spearman correlation analysis was used to study the correlation between angle radian value and atomic absorption spectrophotometer results. Results:The blood glucose level in DM group [28.0 (10.6) mmol/L] was significantly higher than that in NC Group [6.5 (1.9) mmol/L], and the difference was statistically significant (U = 0, P<0.001). At week 0, there was no significant difference between DM group [-0.04 (-0.02)] and NC Group [-0.02 (0.06)] in angle radian value (U=105.50, P>0.05); at 12 weeks, the angle radian value of DM group [0.22 (0.17)] was higher than that of NC Group [0.17 (0.05)], the difference was statistically significant (U=35.50, P<0.05). The angle radian of DM group and NC group at 12 weeks were higher than that of 0 weeks, and the differences were statistically significant ( P<0.05). Prussian blue staining showed that iron was mainly deposited in renal cortex, and the blue staining in DM group was more obvious than that in NC group. The signal intensity of renal cortex on SWI images in DM group was significantly lower than that in 0 week group at 12 weeks, and slightly decreased in NC group. The iron content of DM group and NC group were (171.39±20.13) mg/kg and (116.21±28.90) mg/kg, respectively, and the difference was statistically significant ( t=5.428, P<0.001). Spearman correlation analysis showed that the angle radian was positively correlated with iron content ( r=0.67, P<0.001). Conclusions:Diabetic kidneys have more iron deposits than normal kidneys. As a non-invasive, simple and convenient examination technique, SWI has the potential to quantitatively evaluate the iron load of diabetic kidneys.