Actinomycetes are important producers of high-value natural products, and the engineering of actinomycetes to enhance the biosynthesis of target natural products has long been a hot research topic in the scientific community. However, non-rational engineering methods suffer from low beneficial mutation rates, which limit the efficiency of mutant screening. The integration of high-throughput screening (HTS) technologies can effectively enhance the screening efficiency of elite mutants and significantly shorten the cycle of actinomycete strain engineering. This review comprehensively discusses various HTS technologies suitable for the engineering of actinomycete strains and compares them in terms of application scenarios, advantages, and disadvantages. HTS technologies include microplate-based screening, antimicrobial activity screening, antibiotic resistance screening, fluorescence-activated cell sorting (FACS), and fluorescence-activated droplet sorting (FADS). Additionally, this review summarizes the applications of these technologies in assisting actinomycete strain engineering and enhancing the yields of target compounds. The development and application of HTS technologies have not only facilitated the exploration of natural product resources in actinomycetes but also provided strong support for the rapid and efficient construction of high-performance engineered actinomycete strains.
Actinobacteria/metabolism* ; High-Throughput Screening Assays/methods* ; Genetic Engineering/methods* ; Biological Products/metabolism* ; Flow Cytometry ; Metabolic Engineering/methods*

Objective To quantify the mean fat fraction(FF)values of hip abductor muscles using the MR least squares estimation method of iterative water-fat separation(IDEAL-IQ)technique and to analyze the correlation between muscle fat infiltration and cartilage damage in hip osteoarthritis(HOA),age and gender.Methods Ninety-five patients with clinical symptoms of hip joint(HOA group)and volunteers(control group)underwent MRI conventional sequence and IDEAL-IQ sequence scans of the hip joint were selected.Hip cartilage damage was graded based on conventional MRI sequences(mild HOA group and severe HOA group),and the FF values of hip abductor muscles were measured for each group.ANOVA analysis and Pearson correlation tests were used to compare the differences between the groups and correlation analyses were performed.Results The FF values of hip abductor muscles in the mild HOA group and severe HOA group were significantly higher than those in the control group,with statistically significant differences(P＜0.05).There were correlations between the FF values of hip abductor muscles and the degree of HOA cartilage damage,age and gender(r=0.677,0.566,0.311).Conclusion The IDEAL-IQ technique can be used for quantitative research on muscle fat infiltration,and fat infiltration in hip abductor muscles is an important risk factor for HOA cartilage damage.

Objective:A nomogram model for predicting double positivity of microvascular invasion (MVI) and vascular endothelial-to-mesenchymal transition (VETC) in patients with hepatocellular carcinoma (HCC) was constructed and its predictive performance was evaluated.Methods:A retrospective analysis was conducted on 326 HCC patients who were treated at the Third People's Hospital of Nantong and the First Affiliated Hospital of Soochow University from January 2013 to June 2023, including 240 males and 86 females, with an average age of (58.7±9.0) years. The 326 patients were randomly divided into a training set ( n=228) and a test set ( n=98) at a ratio of 7: 3 using the random number table method. The training set was divided into a double-positive group ( n=54) and a control group ( n=174) based on whether the HCC patients were double positive for MVI and VETC. Univariate and multivariate logistic regression analyses were performed to identify the influencing factors of double positivity of microvascular invasion in HCC patients, and a nomogram for predicting double positivity of microvascular invasion patterns was constructed based on the multivariate. The predictive performance and clinical net benefit of the nomogram were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results:There were statistically significant differences in alpha-fetoprotein, gamma-glutamyl transferase, and phosphatidylinositol proteoglycan between the two groups (all P<0.05). Multivariate logistic regression analysis showed that LI-RADS category ( OR=8.58, 95% CI: 1.87-39.38), intratumoral hemorrhage ( OR=2.16, 95% CI: 1.14-4.07), and intratumoral arteries ( OR=2.59, 95% CI: 1.19-5.64) were all influencing factors of double positivity of microvascular invasion patterns in HCC patients (all P<0.05). Based on the multivariate results, a nomogram was constructed. In the training set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.769 (95% CI: 0.720-0.814). In the test set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.756 (95% CI: 0.622-0.850). The calibration curve showed a good fit between the predicted model and the ideal curve. Decision curve analysis showed that the clinical applicability was good when the threshold was 0.01-0.80 in the training set and 0.01-0.65 in the test set. Conclusion:The nomogram model based on LI-RADS category, intratumoral hemorrhage, and intratumoral arteries can effectively predict double positivity of microvascular invasion patterns in HCC patients and has good clinical applicability.

Objective:A nomogram model for predicting double positivity of microvascular invasion (MVI) and vascular endothelial-to-mesenchymal transition (VETC) in patients with hepatocellular carcinoma (HCC) was constructed and its predictive performance was evaluated.Methods:A retrospective analysis was conducted on 326 HCC patients who were treated at the Third People's Hospital of Nantong and the First Affiliated Hospital of Soochow University from January 2013 to June 2023, including 240 males and 86 females, with an average age of (58.7±9.0) years. The 326 patients were randomly divided into a training set ( n=228) and a test set ( n=98) at a ratio of 7: 3 using the random number table method. The training set was divided into a double-positive group ( n=54) and a control group ( n=174) based on whether the HCC patients were double positive for MVI and VETC. Univariate and multivariate logistic regression analyses were performed to identify the influencing factors of double positivity of microvascular invasion in HCC patients, and a nomogram for predicting double positivity of microvascular invasion patterns was constructed based on the multivariate. The predictive performance and clinical net benefit of the nomogram were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Results:There were statistically significant differences in alpha-fetoprotein, gamma-glutamyl transferase, and phosphatidylinositol proteoglycan between the two groups (all P<0.05). Multivariate logistic regression analysis showed that LI-RADS category ( OR=8.58, 95% CI: 1.87-39.38), intratumoral hemorrhage ( OR=2.16, 95% CI: 1.14-4.07), and intratumoral arteries ( OR=2.59, 95% CI: 1.19-5.64) were all influencing factors of double positivity of microvascular invasion patterns in HCC patients (all P<0.05). Based on the multivariate results, a nomogram was constructed. In the training set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.769 (95% CI: 0.720-0.814). In the test set, the area under the ROC curve for predicting double positivity of microvascular invasion patterns in HCC patients was 0.756 (95% CI: 0.622-0.850). The calibration curve showed a good fit between the predicted model and the ideal curve. Decision curve analysis showed that the clinical applicability was good when the threshold was 0.01-0.80 in the training set and 0.01-0.65 in the test set. Conclusion:The nomogram model based on LI-RADS category, intratumoral hemorrhage, and intratumoral arteries can effectively predict double positivity of microvascular invasion patterns in HCC patients and has good clinical applicability.

Objective To quantify the mean fat fraction(FF)values of hip abductor muscles using the MR least squares estimation method of iterative water-fat separation(IDEAL-IQ)technique and to analyze the correlation between muscle fat infiltration and cartilage damage in hip osteoarthritis(HOA),age and gender.Methods Ninety-five patients with clinical symptoms of hip joint(HOA group)and volunteers(control group)underwent MRI conventional sequence and IDEAL-IQ sequence scans of the hip joint were selected.Hip cartilage damage was graded based on conventional MRI sequences(mild HOA group and severe HOA group),and the FF values of hip abductor muscles were measured for each group.ANOVA analysis and Pearson correlation tests were used to compare the differences between the groups and correlation analyses were performed.Results The FF values of hip abductor muscles in the mild HOA group and severe HOA group were significantly higher than those in the control group,with statistically significant differences(P＜0.05).There were correlations between the FF values of hip abductor muscles and the degree of HOA cartilage damage,age and gender(r=0.677,0.566,0.311).Conclusion The IDEAL-IQ technique can be used for quantitative research on muscle fat infiltration,and fat infiltration in hip abductor muscles is an important risk factor for HOA cartilage damage.

Objective:To investigate the cognitive function and its influencing factors among residents in Qingdao city.Methods:The 5 311 research subjects over 65 years old were selected from Qingdao by simple random sampling and stratified sampling. All subjects were investigated by AD8 dementia early screening questionnaire and community screening instrument dementia (CSI-D) to evaluate the prevalence of cognitive decline in this study.The score of AD8 dementia early screening questionnaire ≥2 points or the score of CSI-D ≤7 points was considered to be cognitive decline. Mann-Whitney U test, Chi-square test, Fisher exact probability method, univariate and multivariate Logistic regression analysis and Bootstrap verification were performed using SPSS 26.0 software. Results:Among 5 311 subjects, 1 899 subjects had normal cognitive function (35.76%) and 3 412 subjects had cognitive decline (64.24%). The age of the cognitive decline group was significantly higher than that of the normal group ( P<0.01). There were significant differences in gender, educational level, rural residents, marital status, chronic medical history, hypertension, rheumatoid arthritis, cerebrovascular disease, intervertebral disc disease, ischemic heart disease, monthly household income and alcohol consumption between the two groups (all P<0.05). Univariate Logistic regression analysis showed that female ( β=0.313, OR=1.367, 95% CI=1.221-1.530), age ( β=0.052, OR=1.053, 95% CI=1.043-1.063), rural residents ( β=0.850, OR=2.340, 95% CI=2.042-2.682), widowed ( β=0.557, OR=1.745, 95% CI=1.500-2.029), chronic medical history ( β=0.290, OR=1.336, 95% CI=1.191-1.498), hypertension ( β=0.134, OR=1.143, 95% CI=1.020-1.281), rheumatoid arthritis ( β=0.458, OR=1.581, 95% CI=1.222-2.046), cerebrovascular disease ( β=0.584, OR=1.794, 95% CI=1.352-2.380), intervertebral disc disease ( β=0.578, OR=1.782, 95% CI=1.370-2.319), ischemic heart disease ( β=0.501, OR=1.651, 95% CI=1.272-2.143) were the risk factors for cognitive decline. Higher education level, higher monthly household income and abstinence ( β=-0.244, OR=0.783, 95% CI=0.619-0.992) were protective factors for cognitive decline. Multivariate logistic regression analysis showed that age ( β=0.035, OR=1.036, 95% CI=1.025-1.047), rural residents ( β=0.215, OR=1.239, 95% CI=1.047-1.468), chronic medical history ( β=0.191, OR=1.210, 95% CI=1.067-1.372), cerebrovascular disease ( β=0.480, OR=1.616, 95% CI=1.195-2.187), intervertebral disc disease ( β=0.456, OR=1.578, 95% CI=1.190-2.094) were risk factors for Alzheimer's disease. Higher education level and higher monthly household income were protective factors for Alzheimer's disease. Conclusion:The elderly with chronic diseases, low income and low education level may be at the high risk of cognitive function decline, which should be paid attention to in early screening and intervention.

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
Humans ; Drugs, Chinese Herbal/pharmacology* ; Liver Diseases/drug therapy* ; Antioxidants ; Polysaccharides/therapeutic use* ; Medicine, Chinese Traditional

The biggest challenge of breast cancer treatment is metastasis and drug resistance.Breast cancer metastasis increa-ses mortality and decreases the life quality of patients.At present,the mechanism of breast cancer metastasis is not completely under-stood,and the multi-step process of metastasis,namely metastasis cascade,is determined by the internal characteristics of tumor cells and tumor microenvironment.Among the factors driving breast cancer metastasis,the role of inflammatory reaction has gradually attrac-ted attention.The inflammatory environment composed of immune cells,cytokines,chemokines,and growth factors has an important im-pact on the invasion and metastasis of cancer cells.By studying the interaction between inflammatory reaction,tumor cells and tumor microenvironment,it is expected to discover drug targets for the prevention and treatment of breast cancer metastasis.This article re-views the role of inflammation in the tumor microenvironment of breast cancer metastasis.

Objective:This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN.Methods:A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children′s Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software.Results:(1) The UAN group (77.8%) had a significantly higher rate of ABR wave III L than the SSD group (20.9%) ( P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN ( P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ2=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) ( Fisher′s exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type ( P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups ( P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ2=6.695, P=0.015). Conclusions:Compared to children with SSD, the occurrence of wave III L on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.