To elucidate the mechanism of "Scrophulariae Radix-Fritillaria" in goiter by integrated metabolomics and serum pharmaco-chemistry.

The pharmacodynamic substances in "Scrophulariae Radix-Fritillaria" and the molecular mechanisms underlying its therapeutic effects against goiter were analyzed through metabolomics and serum pharmaco-chemistry. A rat model of goiter was established using propylthiouracil (PTU), and the animals were treated using "Scrophulariae Radix-Fritillaria." The efficacy of the drug pair was evaluated in terms of thyroid gland histopathology and blood biochemical indices. Serum and urine samples of the rats were analyzed by UPLC-Q-TOF/MS. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to screen potential biomarkers in urine and the corresponding metabolic pathways. The blood components of "Scrophulariae Radix-Fritillaria" were also identified, and their correlation with urine biomarkers was analyzed in order to screen for potential bioactive compounds. "Scrophulariae Radix-Fritillaria" mitigated injury to thyroid tissues and normalized the levels of the thyroid hormones FT3, FT4, and TSH. We also identified 22 urine biomarkers related to goiter, of which 19 were regulated by "Scrophulariae Radix-Fritillaria." Moreover, urine biomarkers are involved in tryptophan metabolism, steroid hormone biosynthesis, and beta-alanine metabolism, and these pathways may be targeted by the drug pair. In addition, 47 compounds of "Scrophulariae Radix-Fritillaria" were detected by serum pharmacochemistry, of which nine components, namely, syringic acid, paeonol, cedrol, and cis-ferulic acid, fetisinine, aucubigenin, linolenic acid, ussuriedine, and 5-(methylsulfanyl)pentanenitrile, were identified as potential effective substances against goiter. To summarize, we characterized the chemical components and mechanisms of "Scrophulariae Radix-Fritillaria" involved in the treatment of goiter, and our findings provide an experimental basis for its clinical application.

Dynamic observation and risk factors analysis of deep vein thrombosis after hip fracture.

OBJECTIVE: To dynamically observe the occurrence of deep vein thrombosis (DVT) after a hip fracture and analyze of the risk factors affecting the dynamic alteration of DVT. METHODS: Data of patients with hip fractures from January 1, 2017 to August 31, 2021 were collected. Patients were divided into DVT and non-DVT groups according to their daily Doppler ultrasonography findings. Survival analysis was used to describe dynamic changes in DVT occurrence with time. Log-rank tests were used to compare the influence of individual factors of patients with DVT occurrence, and a Cox proportional hazards regression model was used to identify the risk factors affecting the dynamic alteration of DVT occurrence. RESULTS: A total of 331 patients were included: 148(44.7%) had preoperative DVT, and 143 (96.6%) had DVT in the first 3days after admission. The probability of DVT was 0.42 on Day 1, 0.11 on Day 2, 0.10 on Day 3, 0.08 on Day 4, 0.20 on Day 5, and 0.00 on Day 6-7, with a median survival time of 3.30 d. Age>70 years, intertrochanteric fracture, admission hemoglobin<130g/L, and admission hematocrit<40% had a significantly higher occurrence rate of DVT. A hematocrit level of <40% (Hazard Ratio 2.079, 95% Confidence Interval:1.148-3.764, P = 0.016) was an independent risk factor for DVT. CONCLUSION: DVT after hip fractures mainly occurred in the first three days after admission, the trend was stabilized within one week, and day 1 had the highest rate of DVT incidence. Age, fracture type, HGB level, and Hct level affected dynamic occurrence of DVT. At constant other factors, Hct<40% was 2.079-fold incidence in the risk of preoperative DVT formation than those with Hct≥40% after hip fracture.

Image reconstruction of electrostatic tomography based on the improved residual network.

The core of electrostatic tomography (EST) is to solve the inverse problem, but the EST independent measurement data are much smaller than the value that needs to be reconstructed, resulting in a more serious inverse problem. This paper presents an improved ResNet-34 network (P-ResNet), which consists of an input layer, a residual feature extraction layer, and an output layer. The number of residual blocks is 3, 4, 4, and 3. After the second convolution in the main path of each residual block, a ReLU activation function is added to enhance the nonlinear expression ability of the network, and the generalization ability of the model is improved by introducing the L2 regularization loss function. A total of 15 930 sets of samples were simulated for the simulation test. After 200 rounds of iteration, the reconstruction results show that the network achieves high accuracy in EST image reconstruction tasks. In addition, the model is tested under different degrees of Gaussian white noise to verify its anti-noise ability. Compared with the traditional algorithms, the image correlation coefficients of this proposed model network are higher. In addition, this paper designs a small sensor to obtain the induced charge values through the principle of electrostatic induction. The reconstructed results obtained from the experimental data are consistent with the simulation results, which verifies the effectiveness and generalization ability of the proposed model.

Predicting Osteoporosis and Osteopenia by Fusing Deep Transfer Learning Features and Classical Radiomics Features Based on Single-Source Dual-energy CT Imaging.

RATIONALE AND OBJECTIVES: To develop and validate a predictive model for osteoporosis and osteopenia prediction by fusing deep transfer learning (DTL) features and classical radiomics features based on single-source dual-energy computed tomography (CT) virtual monochromatic imaging. METHODS: A total of 606 lumbar vertebrae with dual-energy CT imaging and quantitative CT (QCT) evaluation were included in the retrospective study and randomly divided into the training (n = 424) and validation (n = 182) cohorts. Radiomics features and DTL features were extracted from 70-keV monochromatic CT images, followed by feature selection and model construction, radiomics and DTL features models were established. Then, we integrated the selected two types of features into a features fusion model. We developed a two-level classifier for the hierarchical pairwise classification of each vertebra. All the vertebrae were first classified into osteoporosis and non-osteoporosis groups, then non-osteoporosis group was classified into osteopenia and normal groups. QCT was used as reference. The predictive performance and clinical usefulness of three models were evaluated and compared. RESULTS: The area under the curve (AUC) of the features fusion, radiomics and DTL models for the classification between osteoporosis and non-osteoporosis were 0.981, 0.999, 0.997 in the training cohort and 0.979, 0.943, 0.848 in the validation cohort. Furthermore, the AUCs of the previously mentioned models for the differentiation between osteopenia and normal were 0.994, 0.971, 0.996 in the training cohort and 0.990, 0.968, 0.908 in the validation cohort. The overall accuracy of the previously mentioned models for two-level classifications was 0.979, 0.955, 0.908 in the training cohort and 0.918, 0.885, 0.841 in the validation cohort. Decision curve analysis showed that all models had high clinical value. CONCLUSION: The feature fusion model can be used for osteoporosis and osteopenia prediction with improved predictive ability over a radiomics model or a DTL model alone.

Two-sample Mendelian randomization analysis reveals causal relationships between blood lipids and venous thromboembolism.

Venous Thromboembolism (VTE) is a complex disease that can be classified into two subtypes: Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE). Previous observational studies have shown associations between lipids and VTE, but causality remains unclear. Hence, by utilizing 241 lipid-related traits as exposures and data from the FinnGen consortium on VTE, DVT, and PE as outcomes, we conducted two-sample Mendelian randomization (MR) analysis to investigate causal relationships between lipids and VTE, DVT and PE. The MR results identified that fatty acid (FA) unsaturation traits (Ratio of bis-allylic bonds to double bonds in lipids, and Ratio of bis-allylic bonds to total fatty acids in lipids) were associated with VTE (OR [95% CI]: 1.21 [1.15-1.27]; 1.21 [1.13-1.30]), DVT (OR [95%CI]: 1.24 [1.16-1.33]; 1.26 [1.16-1.36]) and PE (OR [95%CI]: 1.18 [1.08-1.29]; 1.18 [1.09-1.27]). Phosphatidylcholines exhibit potential causal effects on VTE and PE. Phosphatidylcholine acyl-alkyl C40:4 (PC ae C40:4) was negatively associated with VTE (OR [95% CI]: 0.79 [0.73-0.86]), while phosphatidylcholine diacyl C42:6 (PC aa C42:6) and phosphatidylcholine acyl-alkyl C36:4 (PC ae C36:4) were positively associated with PE (OR [95%CI]: 1.44 [1.20-1.72]; 1.22 [1.10-1.35]). Additionally, we found that medium LDL had a protective effect on VTE. Our study indicates that higher FA unsaturation may increase the risk of VTE, DVT, and PE. Different types of phosphatidylcholine have either promotive or inhibitory effects on VTE and PE, contributing to a better understanding of the risk factors for VTE.

Gut microbiota and inflammatory factor characteristics in major depressive disorder patients with anorexia.

BACKGROUND: This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. METHODS: 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. RESULTS: 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P < 0.05). 3). The ß-diversity analysis shows differences in the composition of microbial communities between the MDA0, MDA1, and HC group. 4). A correlation analysis showed that Blautia positively correlated with anorexia, HAMD scores, and CRP level, whereas Faecalibacterium, Bacteroides, Roseburia, and Parabacteroides negatively correlated with anorexia, HAMD scores, and CRP level. 5). The receiver operating characteristic (ROC) curve was drawn using the differential bacterial genera between MDD patients with or without anorexia as biomarkers to identify whether MDD patients were accompanied with anorexia, and its area under curve (AUC) was 0.85. The ROC curve was drawn using the differential bacterial genera between MDD patients with anorexia and healthy controls as biomarkers to diagnose MDD patients with anorexia, with its AUC was 0.97. CONCLUSION: This study suggested that MDD patients with anorexia had a distinct gut microbiota compared to healthy individuals, with higher level of CRP. Blautia was more abundant in MDD patients with anorexia and positively correlated with CRP, HAMD scores, and anorexia. The gut microbiota might have influenced MDD and anorexia through the inflammatory factor CRP.

Full life cycle changes of low impacted mandibular third molar associated cystic lesions and adjacent tooth root resorption: a retrospective study.

OBJECTIVE: Low impacted third molars are usually asymptomatic and are often found by X-ray examination. The removal of asymptomatic low impacted third molars is one of the most controversial clinical issues in oral and maxillofacial surgery. METHODS: In this study, 806 patients with low impacted mandibular third molars (LIMTMs) (full bony impaction) were analyzed to determine the prevalence and risk factors for cystic lesions and adjacent tooth root resorption throughout the patients' entire life cycle. RESULTS: The results showed that the prevalence of adjacent tooth root resorption and cystic lesions was age-related, exhibiting a trend of first increasing and then decreasing; prevalence peaked at the age of 41 to 45 years old, the prevalence rates were 12.50% and 11.11% respectively. And the lowest prevalence rate was 2.86% and 2.44% in ≥ 61 group and 56- to 60-year age group respectively. Age was an independent risk factor for adjacent tooth root resorption of LIMTMs, whereas age and impaction type (especially inverted impaction) were independent risk factors for cystic lesions. CONCLUSIONS: The full life cycle management strategy for LIMTMs may need to be individualized. Surgical removal is recommended for LIMTMs in patients younger than 41 to 45 years, especially for inverted, mesioangular, and horizontally impacted LIMTMs. LIMTMs in patients older than 41 to 45 years may be treated conservatively with regular follow-up, but surgical removal of inverted impacted LIMTMs is still recommended to avoid cyst formation.

Impact of Probiotic Lactiplantibacillus plantarum ATCC 14917 on atherosclerotic plaque and its mechanism.

Atherosclerosis is viewed as not just as a problem of lipid build-up in blood vessels, but also as a chronic inflammatory disease involving both innate and acquired immunity. In atherosclerosis, the inflammation of the arterial walls is the key characteristic that significantly contributes to both the instability of plaque and the occlusion of arteries by blood clots. These events ultimately lead to stroke and acute coronary syndrome. Probiotics are living microorganisms that, when consumed in the right quantities, offer advantages for one's health. The primary objective of this study was to investigate the influence of Lactiplantibacillus plantarum ATCC 14917 (ATCC 14917) on the development of atherosclerotic plaques and its underlying mechanism in Apo lipoprotein E-knockout (Apoe-/- mice). In this study, Apoe-/- mice at approximately 8 weeks of age were randomly assigned to three groups: a Normal group that received a normal chow diet, a high fat diet group that received a gavage of PBS, and a Lactiplantibacillus plantarum ATCC 14917 group that received a high fat diet and a gavage of 0.2 ml ATCC 14917 (2 × 109 CFU/mL) per day for a duration of 12 weeks. Our strain effectively reduced the size of plaques in Apoe-/- mice by regulating the expression of inflammatory markers, immune cell markers, chemokines/chemokine receptors, and tight junction proteins (TJPs). Specifically, it decreased the levels of inflammatory markers (ICAM-1, CD-60 MCP-1, F4/80, ICAM-1, and VCAM-1) in the thoracic aorta, (Ccr7, cd11c, cd4, cd80, IL-1ß, TNF-α) in the colon, and increased the activity of ROS-scavenging enzymes (SOD-1 and SOD-2). It also influenced the expression of TJPs (occludin, ZO-1, claudin-3, and MUC-3). In addition, the treatment of ATCC 14917 significantly reduced the level of lipopolysaccharide in the mesenteric adipose tissue. The findings of our study demonstrated that our strain effectively decreased the size of atherosclerotic plaques by modulating inflammation, oxidative stress, intestinal integrity, and intestinal immunity.

The Relationship Between Perceived Stress, Impulsivity, Executive Dysfunction and Non-Suicidal Self-Injury Thoughts Among Chinese College Students: A Gender Difference Study.

Background: The present study aimed to investigate the potential role of perceived stress, impulsivity trait, executive dysfunction in non-suicidal self-injury (NSSI) thoughts among college students, as well as the gender differences. Methods: A sample of 890 university students completed self-report measures of NSSI thoughts in the past month, the level of perceived stress, impulsivity traits, and executive dysfunction. Results: Compared to those with low level of perceived stress, participants with high level of perceived stress reported significant higher levels of impulsivity trait and executive dysfunction, and higher frequency of NSSI thoughts, and there were no gender differences. Male participants with NSSI thoughts, compared to males without NSSI thoughts, reported significant higher levels of perceived stress and executive dysfunction. Female participants with NSSI thoughts, compared to females without NSSI thoughts, reported significant higher levels of perceived stress, impulsivity trait, and executive dysfunction. Hierarchical regression analysis revealed only executive dysfunction was associated with NSSI thoughts in males, while only perceived stress was associated with NSSI thoughts in females. Conclusion: This study revealed different influence factors for NSSI thoughts in male and female college students. NSSI thoughts in males were more likely associated with executive dysfunction while in females were due to recently perceived stress.

Estimated Number of Children Who Lost a Parent to Drug Overdose in the US From 2011 to 2021.

Importance: Parents' overdose death can have a profound short- and long-term impact on their children, yet little is known about the number of children who have lost a parent to drug overdose in the US. Objective: To estimate the number and rate of children who have lost a parent to drug overdose from 2011 to 2021 overall and by parental age, sex, and race and ethnicity. Design, Setting, and Participants: This was a cross-sectional study of US community-dwelling persons using data from the National Survey on Drug Use and Health (2010-2014 and 2015-2019) and the National Vital Statistics System (2011-2021). Data were analyzed from January to June 2023. Exposure: Parental drug overdose death, stratified by age group, sex, and race and ethnicity. Main Outcomes and Measures: Numbers, rates, and average annual percentage change (AAPC) in rates of children losing a parent aged 18 to 64 years to drug overdose, overall and by age, sex, and race and ethnicity. Results: From 2011 to 2021, 649 599 adults aged 18 to 64 years died from a drug overdose (mean [SD] age, 41.7 [12.0] years; 430 050 [66.2%] male and 219 549 [33.8%] female; 62 606 [9.6%] Hispanic, 6899 [1.1%] non-Hispanic American Indian or Alaska Native, 6133 [0.9%] non-Hispanic Asian or Pacific Islander, 82 313 [12.7%] non-Hispanic Black, 485 623 [74.8%] non-Hispanic White, and 6025 [0.9%] non-Hispanic with more than 1 race). Among these decedents, from 2011 to 2021, an estimated 321 566 (95% CI, 276 592-366 662) community-dwelling children lost a parent aged 18 to 64 years to drug overdose. The rate of community-dwelling children who lost a parent to drug overdose per 100 000 children increased from 27.0 per 100 000 in 2011 to 63.1 per 100 000 in 2021. The highest rates were found among children of non-Hispanic American Indian or Alaska Native individuals, who had a rate of 187.1 per 100 000 in 2021, more than double the rate among children of non-Hispanic White individuals (76.5 per 100 000) and non-Hispanic Black individuals (73.2 per 100 000). While rates increased consistently each year for all parental age, sex, and race and ethnicity groups, non-Hispanic Black parents aged 18 to 25 years had the largest AAPC (23.8%; 95% CI, 16.5-31.6). Rates increased for both fathers and mothers; however, more children overall lost fathers (estimated 192 459; 95% CI, 164 081-220 838) than mothers (estimated 129 107; 95% CI, 112 510-145 824). Conclusions and Relevance: An estimated 321 566 children lost a parent to drug overdose in the US from 2011 to 2021, with significant disparities evident across racial and ethnic groups. Given the potential short- and long-term negative impact of parental loss, program and policy planning should ensure that responses to the overdose crisis account for the full burden of drug overdose on families and children, including addressing the economic, social, educational, and health care needs of children who have lost parents to overdose.

Ozone as an environmental driver of influenza.

Under long-standing threat of seasonal influenza outbreaks, it remains imperative to understand the drivers of influenza dynamics which can guide mitigation measures. While the role of absolute humidity and temperature is extensively studied, the possibility of ambient ozone (O3) as an environmental driver of influenza has received scant attention. Here, using state-level data in the USA during 2010-2015, we examined such research hypothesis. For rigorous causal inference by evidence triangulation, we applied 3 distinct methods for data analysis: Convergent Cross Mapping from state-space reconstruction theory, Peter-Clark-momentary-conditional-independence plus as graphical modeling algorithms, and regression-based Generalised Linear Model. The negative impact of ambient O3 on influenza activity at 1-week lag is consistently demonstrated by those 3 methods. With O3 commonly known as air pollutant, the novel findings here on the inhibition effect of O3 on influenza activity warrant further investigations to inform environmental management and public health protection.

The Relationship Between Fracture and Mortality in a Chinese Maintenance Hemodialysis Patients Cohort.

Background: Patients on maintenance hemodialysis have an increased risk of fracture. However, the relationship between fracture and poor prognosis is not clear. Methods: A total of 182 maintenance hemodialysis patients were enrolled in the study. The relationship between fracture and poor prognosis (cardiovascular events, stroke, malignancy and 5-year all-cause mortality) were analyzed. Results: 21 of 182 patients had a history of fracture at the time of enrollment. 26 patients had a new fracture after enrollment. A total of 57 fractures occurred in 47 patients, the most common fracture site was the rib. Patients with fracture group had a higher proportion of elderly and female, higher serum phosphorus and B-type natriuretic peptide and lower hemoglobin, albumin, and potassium compared with those without fracture. Age (OR=3.809, 95% CI: 1.064-8.966, p=0.038), hemoglobin (OR=0.961, 95% CI: 0.925-0.997, p=0.035), and serum phosphorus (OR=3.325, 95% CI:1.104-10.019, p=0.033) were the independent risk factors of new fractures in MHD patients. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture (p<0.05). But there was no significant difference in the incidence of acute myocardial infarction or stroke. Conclusion: 25.8% of maintenance hemodialysis patients had at least one fracture, with rib fractures accounting for the highest proportion. Age, hemoglobin and serum phosphorus were the independent risk factors of new fractures. The incidence of malignancy and 5-year all-cause mortality in patients with fracture was higher than those without fracture, but there was no significant difference in the incidence of acute myocardial infarction and stroke.

To determine the incidence of fractures in hemodialysis patients, we conducted this single center, prospective observational study. 182 patients were enrolled. We also recorded the 5-year incidence of acute myocardial infarction(AMI), stroke, malignancy, and mortality. Our results showed that the incidence of fracture in hemodialysis patients was 25.8%. The most common fracture site was the rib. There were significant statistical differences in age, gender, hemoglobin, serum albumin, B-type natriuretic peptide, potassium and phosphorus between patients with and without fractures. Logistic regression analysis suggested that advanced age, anaemia and hyperphosphatemia were independent risk factors for new fractures in hemodialysis patients. We followed 182 patients for 5 years and recorded the incidence of stroke, AMI and malignancy. The rates of AMI and stroke did not differ significantly between the two groups. However, the incidence of malignancy in patients with fractures is significantly higher than that in patients without fractures. In our study, a total of 74 patients died, including 24 deaths in the fracture group and 50 deaths in the non-fracture group. The main causes of death in 74 cases were cardiovascular events. Our study provides some insight into the association between fractures and poor outcomes in hemodialysis patients.

Mud Cake Improver Mul-GX with Lubrication and Interface Enhancement Effect and Its Action Mechanism.

In view of the problems in which the solid content of drilling fluid increases in the middle and late stages of horizontal well drilling, the lubricity of mud cakes on the borehole wall decreases, and the friction of pipe string increases due to the gradual thickening of mud cakes, which leads to the sticking and the obvious decrease of cementing strength at the second interface, a mud cake improver Mul-GX with lubrication and interface enhancement effect was studied in this paper. Based on the hydration and filling mechanism, the lubricity of the mud cake was improved, its thickness was reduced, and its strength was improved through synergistic effects of solvated water film lubrication and buffering, hardening and crystallization of gelled substances, and filling and dispersion of elastic particles. The mud cake improver Mul-GX is composed of the metasilicate GX-ZQ, polymer copolymer GX-JB, and polymer GX-TX, and the mass ratio of each component was GX-ZQ: GX-JB: GX-TX = 15:1:0.5. The effect of Mul-GX was evaluated through the performance determination of the mud cake and interface cementing simulation experiments. In addition, the microscopic characterization by SEM and XRD were carried out to analyze the mechanism of Mul-GX. The experimental results showed that when Mul-GX was added to the water-based drilling fluid with the 1.0%-1.5% adding quantity, the mud cake lubricity improved by more than 60%, its thickness reduced by 53.9% on average, and its strength increased by 54.3% on average. At the same adding quantity, the interfacial bonding strength was 4.4 times more than the data before adding Mul-GX. All of the results showed that Mul-GX has obvious mud cake lubrication effect and interface enhancement effect.

Encapsulation engineering of porous crystalline frameworks for delayed luminescence and circularly polarized luminescence.

Delayed luminescence (DF), including phosphorescence and thermally activated delayed fluorescence (TADF), and circularly polarized luminescence (CPL) exhibit common and broad application prospects in optoelectronic displays, biological imaging, and encryption. Thus, the combination of delayed luminescence and circularly polarized luminescence is attracting increasing attention. The encapsulation of guest emitters in various host matrices to form host-guest systems has been demonstrated to be an appealing strategy to further enhance and/or modulate their delayed luminescence and circularly polarized luminescence. Compared with conventional liquid crystals, polymers, and supramolecular matrices, porous crystalline frameworks (PCFs) including metal-organic frameworks (MOFs), covalent-organic frameworks (COFs), zeolites and hydrogen-bonded organic frameworks (HOFs) can not only overcome shortcomings such as flexibility and disorder but also achieve the ordered encapsulation of guests and long-term stability of chiral structures, providing new promising host platforms for the development of DF and CPL. In this review, we provide a comprehensive and critical summary of the recent progress in host-guest photochemistry via the encapsulation engineering of guest emitters in PCFs, particularly focusing on delayed luminescence and circularly polarized luminescence. Initially, the general principle of phosphorescence, TADF and CPL, the combination of DF and CPL, and energy transfer processes between host and guests are introduced. Subsequently, we comprehensively discuss the critical factors affecting the encapsulation engineering of guest emitters in PCFs, such as pore structures, the confinement effect, charge and energy transfer between the host and guest, conformational dynamics, and aggregation model of guest emitters. Thereafter, we summarize the effective methods for the preparation of host-guest systems, especially single-crystal-to-single-crystal (SC-SC) transformation and epitaxial growth, which are distinct from conventional methods based on amorphous materials. Then, the recent advancements in host-guest systems based on PCFs for delayed luminescence and circularly polarized luminescence are highlighted. Finally, we present our personal insights into the challenges and future opportunities in this promising field.

Ionic Liquid Gating Induces Anomalous Permeation through Membrane Channel Proteins.

Membrane channel proteins (MCPs) play key roles in matter transport through cell membranes and act as major targets for vaccines and drugs. For emerging ionic liquid (IL) drugs, a rational understanding of how ILs affect the structure and transport function of MCP is crucial to their design. In this work, GPU-accelerated microsecond-long molecular dynamics simulations were employed to investigate the modulating mechanism of ILs on MCP. Interestingly, ILs prefer to insert into the lipid bilayer and channel of aquaporin-2 (AQP2) but adsorb on the entrance of voltage-gated sodium channels (Nav). Molecular trajectory and free energy analysis reflect that ILs have a minimal impact on the structure of MCPs but significantly influence MCP functions. It demonstrates that ILs can decrease the overall energy barrier for water through AQP2 by 1.88 kcal/mol, whereas that for Na+ through Nav is increased by 1.70 kcal/mol. Consequently, the permeation rates of water and Na+ can be enhanced and reduced by at least 1 order of magnitude, respectively. Furthermore, an abnormal IL gating mechanism was proposed by combining the hydrophobic nature of MCP and confined water/ion coordination effects. More importantly, we performed experiments to confirm the influence of ILs on AQP2 in human cells and found that treatment with ILs significantly accelerated the changes in cell volume in response to altered external osmotic pressure. Overall, these quantitative results will not only deepen the understanding of IL-cell interactions but may also shed light on the rational design of drugs and disease diagnosis.

Artificial intelligence-based classification of breast lesion from contrast enhanced mammography: a multicenter study.

PURPOSE: The authors aimed to establish an artificial intelligence (AI)-based method for preoperative diagnosis of breast lesions from contrast enhanced mammography (CEM) and to explore its biological mechanism. MATERIALS AND METHODS: This retrospective study includes 1430 eligible patients who underwent CEM examination from June 2017 to July 2022 and were divided into a construction set (n=1101), an internal test set (n=196), and a pooled external test set (n=133). The AI model adopted RefineNet as a backbone network, and an attention sub-network, named convolutional block attention module (CBAM), was built upon the backbone for adaptive feature refinement. An XGBoost classifier was used to integrate the refined deep learning features with clinical characteristics to differentiate benign and malignant breast lesions. The authors further retrained the AI model to distinguish in situ and invasive carcinoma among breast cancer candidates. RNA-sequencing data from 12 patients were used to explore the underlying biological basis of the AI prediction. RESULTS: The AI model achieved an area under the curve of 0.932 in diagnosing benign and malignant breast lesions in the pooled external test set, better than the best-performing deep learning model, radiomics model, and radiologists. Moreover, the AI model has also achieved satisfactory results (an area under the curve from 0.788 to 0.824) for the diagnosis of in situ and invasive carcinoma in the test sets. Further, the biological basis exploration revealed that the high-risk group was associated with the pathways such as extracellular matrix organization. CONCLUSIONS: The AI model based on CEM and clinical characteristics had good predictive performance in the diagnosis of breast lesions.

Assessing the Diagnostic Efficacy of Handgrip Dynamometry and Diaphragmatic Ultrasound in Intensive Care Unit-Acquired Weakness.

Objective: The aim of this study is to examine the diagnostic significance of using handgrip dynamometry and diaphragmatic ultrasound in intensive care unit-acquired weakness (ICU-AW). Methods: This study included patients who received mechanical ventilation in the ICU at the Fourth Hospital of Hebei Medical University from July to December 2020. We collected comprehensive demographic data and selected conscious patients for muscle strength and ICU-AW assessments. The evaluation comprised grip strength measurement and bedside ultrasound for diaphragmatic excursion (DE) and thickening fraction (DTF). Results were documented for comparative analysis between patient groups, focusing on the diagnostic efficacy of grip strength, DE, DTF, and their combined application in diagnosing ICU-AW. Results: A total of 95 patients were initially considered for inclusion in this study. Following the exclusion of 20 patients, a final cohort of 75 patients were enrolled, comprising of 32 patients (42.6%) diagnosed with ICU-AW and 43 patients (57.4%) classified as non-ICU-AW. Comparative analysis revealed that grip strength, DE, and DTF were significantly lower in the ICU-AW group (P < 0.05). Subgroup analysis specific to male patients demonstrated a noteworthy decrease in grip strength, DE, and DTF within the ICU-AW group (P < 0.05). Receiver operating characteristic curve analysis indicated statistically significant diagnostic value for ICU-AW with grip strength, DE, DTF, and grip strength and diaphragmatic ultrasound (P < 0.01). Furthermore, it was observed that the amalgamation of grip strength and diaphragmatic ultrasound significantly enhanced the diagnostic accuracy of ICU-AW in patients who are critically ill. Conclusion: Grip strength, DE, DTF, and the combined use of grip strength with diaphragm ultrasound demonstrated diagnostic efficacy in ICU-AW. Notably, the integration of grip strength with diaphragm ultrasound exhibited a heightened capacity to enhance the diagnostic value specifically in patients diagnosed who are critically ill with ICU-AW.

Increased water content in multifidus muscles of young adults with chronic nonspecific low back pain detected by dual-energy CT and MRI.

OBJECTIVES: To demonstrate the feasibility of better diagnosing young adults with chronic nonspecific low back pain (CNLBP) by measuring water content in paraspinal muscles using water-muscle decomposition technique in dual-energy CT (DECT) and T2-mapping in MRI. METHODS: This prospective cross-sectional study included 110 young individuals (56 with CNLBP at age of 25.7 ± 2.0 years and 54 of asymptomatic at age of 25.1 ± 1.9 years) who underwent both MRI and DECT on the spine. T2 values on T2 mapping in MRI and water density (WD) value on water(muscle) images in DECT were generated at the L1-L4 levels for erector spinae muscle and L2-L5 for multifidus muscle. Pain duration time, Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) were recorded for CNLBP patients. Difference of T2 value and WD between the two patient groups, and correlations between T2 value and WD, and T2 value and WD with clinical indicators were analyzed. RESULTS: Compared with asymptomatic participants, the mean WD of multifidus muscle at L4-L5 and mean T2 values of multifidus muscle at L5 were significantly higher in CNLBP patients (all P < 0.05). T2 values had moderate to strong positive correlations (r = 0.34-0.60, all P < 0.05) with DECT WD in CNLBP patients and healthy volunteers. There was a weak correlation between VAS and WD in L5-level multifidus muscle (r = 0.29, P < 0.05). CONCLUSIONS: The T2 values in MRI and WD in DECT are higher in multifidus muscles of lower vertebra levels for young CNLBP patients, and there exists positive correlation between WD and T2 values, providing useful information for diagnosing CNLBP.

Efficient expansion and CRISPR-Cas9-mediated gene correction of patient-derived hepatocytes for treatment of inherited liver diseases.

Cell-based ex vivo gene therapy in solid organs, especially the liver, has proven technically challenging. Here, we report a feasible strategy for the clinical application of hepatocyte therapy. We first generated high-quality autologous hepatocytes through the large-scale expansion of patient-derived hepatocytes. Moreover, the proliferating patient-derived hepatocytes, together with the AAV2.7m8 variant identified through screening, enabled CRISPR-Cas9-mediated targeted integration efficiently, achieving functional correction of pathogenic mutations in FAH or OTC. Importantly, these edited hepatocytes repopulated the injured mouse liver at high repopulation levels and underwent maturation, successfully treating mice with tyrosinemia following transplantation. Our study combines ex vivo large-scale cell expansion and gene editing in patient-derived transplantable hepatocytes, which holds potential for treating human liver diseases.