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Yingpeng Li,1 Ting Zhu,2,3 Jingxian Liang,2 Yuanqun Wu,2 Xiantong Guan,2 Tingting Liu,2 Shaowa Lü,2 Yongji Li,2 Yanhong Wang,2 Yang Ping4 1College of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People’s Republic of China; 2Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of China; 3Center of Pharmaceutical Engineering and Technology, College of Pharmacy, Harbin University of Commerce, Harbin, 150076, People’s Republic of China; 4College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, 154007, People’s Republic of ChinaCorrespondence: Yanhong Wang, Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of China, Tel +86 18845587616, Email wang.yanhong@163.com Yang Ping, College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, 154007, People’s Republic of China, Tel +86 18245482328, Email 18245482328@163.comBackground: Black plaster is one of the classic dosage forms of traditional Chinese medicine for external use and has been widely utilized since the Tang and Song Dynasties. In this paper, we take Goupi Gao as the research object and discuss the scientific characteristics of the black plaster dosage form. Goupi Gao ointment is a plaster for external use of traditional Chinese medicine.Methods: Methods for the morphological and quantitative characterization of black plaster’s microstructure, based on FESEM-IPP (Field Emission Scanning Electron Microscope IPP Image Processing) technology, were established. According to the actual operating temperature of Goupi Gao, three temperatures were selected: 28°C, 35°C, and 45°C. A UPLC analysis method was applied to the cinnamaldehyde and eugenol in Goupi Gao, and the release behavior of Goupi Gao from three samples at three temperatures was investigated using the paddle over disk method. Preparation of rabbit model of knee osteoarthritis of cold blood stasis type by cold stimulation combined with drug induction.Results: In terms of morphology, Goupi Gao and the blank black plaster matrix both formed a double continuous phase system with a thicker vegetable oil phase and crossed “branched” soap crystal fibers. Based on the IPP image quantification parameters, the pore area (A) was highly positively correlated with temperature. After the 28 °C treatment, A1 = (216.8± 59.5) μm2; after the 35 °C treatment, A2 = (259.7± 52.8) μm2; after the 45 °C treatment, A3 = (408.0± 57.7) μm2, and there were no significant differences in other pore parameters.Conclusion: The black plaster matrix’s unique structure makes it highly applicable in numerous medications; it exhibits slow-release and performs well in extreme temperatures, with good adhesion and peeling properties.Keywords: black plaster, Goupi Gao, microstructure, quantitative characterization, release behavior, pharmacodynamics

Abstract Although there have been remarkable advances in the treatment of hepatocellular carcinoma (HCC), the prognosis remains poor in those with advanced stage and more effective therapeutic options are urgently needed. Lenvatinib (Len), a multiple receptor tyrosine kinase inhibitor, is an emerging molecular targeted agent for HCC, whose immunomodulatory activities have been investigated. However, Len utilization is limited because of its low metabolic stability, poor bioavailability and dose-dependent toxicity, rendering its direct use insufficient for immune modulation. Stimuli-responsive nanoparticles, which are drug-targeted delivery platforms for on-demand drug release, facilitate deeper and uniform tumour penetration, providing alternative solutions to overcome current limitations. Ultrasound (US) exhibits superior tissue penetration abilities and can produce reactive oxygen species (ROS) at the tumour site to treat deeper tumours. In addition, US serves as an excellent and selective drug delivery mediator for tumour treatment. Herein, we designed US-triggered lenvatinib nanoparticles (Len-RNPs) for selective drug delivery that utilize US-triggered ROS to induce in situ oxidation reactions, resulting in nanoparticle disintegration. Len-RNPs mitigate the toxicity of Len and effectively trigger robust systemic anti-tumour immune responses in a H22 tumour model, resulting in a tumour suppression rate of 95.7%, with 60% of mice being cured. Our study elucidates a novel and precise strategy of combining Len and US therapy for enhanced HCC immunotherapy.

Abstract Plant evolution is driven by key innovations of functional traits that enables their survivals in diverse ecological environments. However, plant adaptive evolution from land to atmospheric niches remains poorly understood. In this study, we use the epiphytic Tillandsioideae subfamily of Bromeliaceae as model plants to explore their origin, evolution and diversification. We provide a comprehensive phylogenetic tree based on nuclear transcriptomic sequences, indicating that core tillandsioids originated approximately 11.3 million years ago in the Andes. The geological uplift of the Andes drives the divergence of tillandsioids into tank-forming and atmospheric types. Our genomic and transcriptomic analyses reveal gene variations and losses associated with adaptive traits such as impounding tanks and absorptive trichomes. Furthermore, we uncover specific nitrogen-fixing bacterial communities in the phyllosphere of tillandsioids as potential source of nitrogen acquisition. Collectively, our study provides integrative multi-omics insights into the adaptive evolution of tillandsioids in response to elevated aerial habitats.

Aquatic ecosystems can harbour more than one non-native fish species and this can represent a threat due to trophic interactions with native fishes. However, research on interactions amongst multiple co-occurring native and non-native fish remains scarce. In this study, 551 organisms from 44 native fish, 11 non-native fish, 35 macroinvertebrates (of which one was non-native), together with 162 samples of basal resources were collected from six rivers of the Lower Pearl River Basin of China. Nitrogen and carbon stable isotope analysis was used to calculate community-wide trophic metrics and the degree of trophic overlap between native and non-native fish at both the community and functional feeding group level, together with diet composition. At the community level, there was a high degree of trophic niche overlap between native and non-native fish as a result of similarities in trophic characteristics. At the functional feeding group level, both native and non-native functional feeding groups demonstrated the capacity to occupy the niche space of each other. A significant trophic niche overlap, exceeding 50%, was found between non-native detritivorous and omnivorous fish, suggesting competition. The difference in diet composition between some native and non-native fish depended on the category of diet source across the rivers, suggesting dietary segregation. Albeit limited, the present findings suggest that trophic interaction between native and non-native fish is likely to reach a dynamic equilibrium status in the community owing to trophic segregation of fish species and the antagonistic effects amongst non-native fish.

Yan Chu,1,* Xiaomin Wang,2,* Min Dou,1 Jin Wang,2 Baoqian Wang,1 Hairong Wang,1 Shasha Lv,1 Shuihua Lu,2,* Tongxia Li1,* 1Qingdao Chest Hospital, Qingdao, Shandong, People’s Republic of China; 2National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tongxia Li; Shuihua Lu, Email qdlitx@163.com; lushuihua66@126.comObjective: To analyze the clinical characteristics, species distribution and drug resistance of patients with non-tuberculous mycobacteria (NTM) lung disease in Qingdao, China.Methods: Clinical data of patients with NTM lung disease and pulmonary tuberculosis (TB) treated at Qingdao Chest Hospital from July 2021 to July 2023 were retrospectively analyzed.Results: The prevalence of NTM lung disease was 8.03%, with a high rate of drug resistance during the study period. Patients with NTM lung disease had higher rates of older age, bronchiectasis, malignancy, HIV infection and bronchial dilatation shadow and lower rates of hollow shadow compared to patients with pulmonary TB.Conclusion: Comprehensive understanding of NTM lung disease, improved laboratory testing techniques and appropriate treatment regimens are essential for the management of NTM lung disease.Keywords: non-tuberculous mycobacteria, pulmonary tuberculosis, clinical characteristics, drug resistance

[Objective] The development of resource-based cities is trapped in a dilemma due to a singular industrial structure and a closed development model. Exploring the mechanism of impact of network externalities on the economic performance of these cities is of great significance for promoting their economic growth and sustainable development. [Methods] This study first elaborated on the mechanism of impact of urban network externalities on the economic performance of resource-based cities, then analyzed the characteristics of change of the Chinese urban network from 2001 to 2019, and finally established an econometric model to test the impact of agglomeration economic externalities and urban network externalities on the economic performance of both resource-based and non-resource-based cities. [Results] The findings are as follows: (1) The network embeddedness of resource-based cities in the national organizational network had increased significantly, but there was still a considerable gap compared to non-resource-based cities. Resource-based cities had relatively fewer connections with core cities in the network and were generally located on the periphery of the urban network. (2) Investment, innovation, and urban network externalities significantly promoted economic growth. Particularly in the early stages of network embeddedness, resource-based cities showed greater heterogeneity and benefit potential in leveraging urban network externalities compared to non-resource-based cities. However, agglomeration economic externalities did not have a significant impact on the economic growth of resource-based cities. (3) Innovation and investment had a significant positive moderating effect on the relationship between urban network externalities and economic growth, and urban network externalities also significantly enhanced the positive impact of innovation and investment on economic growth, aligning with the principle of interaction symmetry. [Conclusion] Actively integrating into broader regional urban networks and enhancing the investment attractiveness and innovation capacity of resource-based cities are key strategies for promoting the transformation and economic growth of these cities.

Abstract A nomogram to estimate the risk of linezolid-induced thrombocytopenia in patients with renal impairment is not available. The aim of the study is to develop a nomogram for predicting linezolid-induced thrombocytopenia in patients with renal impairment and to investigate the incremental value of PNU-142300 concentration beyond clinical factors and linezolid trough concentration (Cmin) for risk prediction. Logistic regression was used to identify independent risk factors for linezolid-induced thrombocytopenia in patients with renal impairment and nomograms were established. The performance of the nomograms was assessed in terms of area under the receiver operating characteristic curve (AUROC), net reclassification improvement (NRI), integrated discrimination improvement (IDI) , decision curve analysis (DCA) and calibration. Internal validation and external validation of the nomograms were also performed. Four nomograms were created: nomogram A including total bilirubin, creatinine clearance and concomitant mannitol use; nomogram B containing linezolid Cmin additionally; nomogram C containing total bilirubin, concomitant mannitol use, linezolid Cmin, and PNU142300 concentration; nomogram D including total bilirubin, concomitant mannitol use, and PNU142300 concentration. Nomogram C improved the prediction performance than nomogram A (AUROC 0.881 vs. 0.749; NRI 0.290; IDI 0.226) and nomogram B (AUROC 0.881 vs. 0.812; NRI 0.152; IDI 0.130) in the training cohort. DCA analysis showed that nomogram C yielded a greater net benefit. Compared with nomogram A and nomogram B, nomogram C also showed superior discriminatory efficacy, good calibration and clinical usefulness in the external validation cohort. The nomogram containing PNU-142300 concentration and linezolid Cmin had better predictive capability than that containing linezolid Cmin for predicting linezolid-induced thrombocytopenia in patients with renal impairment.

Abstract Background Inflammation significantly impacts Parkinson’s disease (PD), yet the intricate relationship between inflammatory markers and PD remains elusive. Objective To identify the peripheral biomarkers of PD and its correlation with the motor and non-motor symptoms of PD. Methods 79 PD patients and 65 controls were included in this study. Clinical information and the serum levels of IL-8, IL-27, IL-33, β-NGF, AgRP, and TRAILR2 in the participants were collected. Appropriate scales were used to assess the symptoms of PD. For the factors with significant differences in the two groups, multivariable logistic regression was used to determine its relationship with PD. Moreover, spearman correlation was conducted to explore the correlation between the factors and PD related symptoms. The IL-27 level was compared between the cognitively healthy PD group and the mild cognitive impairment in PD (PD-MCI). The serum level of TRAILR2 was positively correlated with age and was not associated with other clinical characteristics related to PD. Results Compared to controls, the serum levels of IL-27(P = 0.013) were increased whereas the levels of TRAILR2(P = 0.008) were decreased in PD patients. IL-8, IL-33, β-NGF, and AgRP showed no significant differences between the two groups. After controlling for the other variables, IL-27 was considered as an independent risk factor for PD in the multivariable logistic regression model. The receiver operating characteristic (ROC) curve for diagnosing PD with IL-27 yielded an area under the curve (AUC) of 0.621. Additionally, IL-27 level in PD patients was positively correlated with age, the disease duration, LEDD and negatively correlated with the MoCA scores. However, no significant difference was found in IL-27 levels between cognitively healthy PD and PD-MCI groups. Conclusion Elevated serum IL-27 was a risk factor for PD and positively correlated with the cognitive decline in PD.

Yanyu Zhong,1,&ast; Nan Wang,1,&ast; Sihui Lu,2 Yaqian Lu,2 Xin Pan,3 Ying Zhou1 1Reproductive Medicine Centre, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhou, Reproductive Medicine Centre, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, Jiangsu Province, 215008, People’s Republic of China, Tel +86-0512-67973182, Email zhouyingzzzyyy@163.com Xin Pan, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Gusu District, Suzhou, Jiangsu Province, 215008, People’s Republic of China, Tel +86-0512-67973182, Email panxinxin9@outlook.comObjective: This study aimed to analyze uterine artery and spiral artery hemodynamics in patients with unexplained recurrent pregnancy loss (URPL) with varying pregnancy outcomes.Methods: 174 pregnant women with URPL and 144 pregnant women without adverse pregnancy histories were enrolled in this retrospective study. Based on pregnancy outcomes, these patients were divided into two groups: normal pregnancy outcomes (URPL-N, n=138) and adverse pregnancy outcomes (URPL-A, n=36). Control group participants were categorized into normal pregnancy outcomes (CON-N, n=129) and adverse pregnancy outcomes (CON-A, n=15). We compared uterine artery and spiral artery hemodynamics during different stages of gestation and the predictive value of these parameters for pregnancy outcomes.Results: URPL-N group had fewer pregnancy losses and lower BMI compared to URPL-A group (P< 0.05). Spiral artery hemodynamics in URPL-N and CON-N groups were lower than those in URPL-A and CON-A groups during the mid-luteal phase, 11– 13 weeks, 15– 17 weeks, and 19– 21 weeks of gestation, respectively. Uterine artery hemodynamics ((Pulsatility index (mPI), resistive index (mRI), and systolic-to-diastolic ratio (mS/D)) in the mid-luteal period were lower in URPL-N group than URPL-A group. Similarly, in CON-N group were lower than CON-A group. The URPL-A and CON-A groups had higher uterine artery and spiral artery hemodynamics when compared to the URPL-N and CON-N groups. Spiral artery hemodynamics exhibited larger areas under the ROC curve compared to uterine artery parameters.Conclusion: Abnormal hemodynamics in these arteries may contribute to URPL and adverse pregnancy outcomes. Spiral artery hemodynamics are more reliable predictors of pregnancy outcomes than uterine artery parameters.Keywords: unexplained recurrent pregnancy loss, spiral artery, uterine artery, blood flow, pregnancy outcome

Yijia Guo,1– 3,&ast; Ruyun Zhang,4,&ast; Xinling Gan,5 Erli Wang,6 Shuihua Lu,7 Hui Jiang,3 Hongfei Duan,8 Zhengzhou Yuan,9 Weimin Li,2,3,10 Yong Liu1 1Department of Neurology, Chengdu Medical College, The First Affiliated Hospital, Chengdu, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Radiology, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 7National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 8Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 9Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 10National Tuberculosis Clinical Laboratory of China, Beijing Key Laboratory in Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this work as first authorsCorrespondence: Yong Liu, Chengdu Medical College, The First Affiliated Hospital, No. 278, Middle Section, Baoguang Avenue, Xindu District, Chengdu, 610500, People’s Republic of China, Email 410578100@qq.comBackground: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment.Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels.Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14– 1.33; P< 0.001), and poor outcome (OR=1.34; 95% CI, 1.26– 1.45; P< 0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42– 1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49– 2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification.Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.Keywords: tuberculous meningitis, systemic inflammation, neurological outcome

Yongjiao Zhang,1,2 Xiaolei Xuan,2 Diwen Ye,1,2 Dong Liu,2 Yufan Song,2 Fei Gao,2 Sumei Lu2 1School of Medical Laboratory, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Sumei Lu; Fei Gao, Email lsmqianyi@126.com; 448617003@qq.comAbstract: Absent in melanoma 2 (AIM2) is a protein encoded by the AIM2 gene located on human chromosomes, AIM2 can recognize and bind to double stranded DNA (dsDNA), leading to the assembly of the AIM2 inflammasome. The AIM2 inflammasome plays important proinflammation role in many diseases, and can induce pyroptotic cell death. It has also been closely linked to the development and progression of metabolic diseases and can be activated in obesity, diabetes, nonalcoholic fatty liver disease, and atherosclerosis. In this article, we mainly review the role of AIM2 in glucose metabolism, especially in obesity-related disorders of glucose and lipid metabolism, and provide insights to better understand the role of AIM2 in the pathogenesis, and clinical treatment of metabolic disease.Keywords: AIM2, obesity, metabolic diseases, diabetes, glucose metabolism disorders

Shang-Yu Lu,1,&ast; Han-Yao Sun,1,&ast; Yan Zhou,2 Xi Luo,3 Sheng Liu,1 Wei-Zhong Zhou,1 Hai-Bin Shi,1 Wei Yang,1 Wei Tian1 1Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Yang; Wei Tian, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-18705164897 ; +86-13770615508, Email youngwei1988@163.com; tianwei@jsph.org.cnPurpose: Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE).Patients and Methods: This was a retrospective study that included 295 HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification.Results: The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set.Conclusion: For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE.Keywords: hepatocellular carcinoma, transarterial chemoembolization, prognostic model, risk assessment, AD score

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by massive neuronal loss in the brain. Both cortical glutamatergic neurons and basal forebrain cholinergic neurons (BFCNs) in the AD brain are selectively vulnerable. The degeneration and dysfunction of these two subtypes of neurons are closely associated with the cognitive decline of AD patients. The determination of cellular and molecular mechanisms involved in AD pathogenesis, especially in the early stage, will largely facilitate the understanding of this disease and the development of proper intervention strategies. However, due to the inaccessibility of living neurons in the brains of patients, it remains unclear how cortical glutamatergic neurons and BFCNs respond to pathological stress in the early stage of AD. In this study, we established in vitro differentiation systems that can efficiently differentiate patient-derived iPSCs into BFCNs. We found that AD-BFCNs secreted less Aβ peptide than cortical glutamatergic neurons did, even though the Aβ42/Aβ40 ratio was comparable to that of cortical glutamatergic neurons. To further mimic the neurotoxic niche in AD brain, we treated iPSC-derived neurons with Aβ42 oligomer (AβO). BFCNs are less sensitive to AβO induced tau phosphorylation and expression than cortical glutamatergic neurons. However, AβO could trigger apoptosis in both AD-cortical glutamatergic neurons and AD-BFCNs. In addition, AD iPSC-derived BFCNs and cortical glutamatergic neurons exhibited distinct electrophysiological firing patterns and elicited different responses to AβO treatment. These observations revealed that subtype-specific neurons display distinct neuropathological changes during the progression of AD, which might help to understand AD pathogenesis at the cellular level.

Ferulic acid (FA), the most abundant phenolic acid in cereals, widely exists in both free and bound forms in grains, legumes and other plant-based foods. FA has various functional activities, such as antioxidant, anti-inflammatory and antibacterial properties, thus exhibiting high application values in the fields of food and medicine. To date, although a large number of in vivo and in vitro experiments have shown the importance of cereal FA in maintaining intestinal health, it is still unclear how FA is metabolized by the gut microbiota. In order to offer new insights into the molecular mechanism of the regulatory effect of FA the gut microbiota and offer a theoretical reference for better development and utilization of cereal FA and its metabolites, this paper provides a systematic review of the recent literature concerning intestinal microbial metabolism of cereal FA from three aspects of the existing forms, intestinal release and metabolism, and physiological health effects.

Abstract Climate assessments have largely overlooked the radiative effect of anthropogenic coarse particulate matter (PMcoarse, with an aerodynamic diameter between 2.5 and 10 µm) in China. Despite its similar mass concentration to fine particulate matter (PM2.5), anthropogenic sources of PMcoarse in China have been much less studied and typically underrepresented in models. Here, we present a new model simulation for PMcoarse in China that incorporates various anthropogenic sources. The model successfully captures the magnitude and distribution of observed PMcoarse and recently available aerosol optical depth measurements at near-infrared wavelengths, which are substantially underestimated if anthropogenic PMcoarse is not included. We find that anthropogenic PMcoarse exerts a cooling effect of -0.11 Wm−2 (-0.03 to -0.42 Wm−2) in China by aerosol–radiation interaction, capable of completely offsetting the warming effect from black carbon by 2060 under Dynamic Projection model for Emissions in China (DPEC) 1.1 scenario. We conclude that the radiative effect due to anthropogenic PMcoarse will likely dampen the warming penalty caused by the emission reduction of other aerosols in China and should be incorporated into climate models.

Abstract Background Modified Si-Miao granule (mSMG), a traditional Chinese medicine, is beneficial for T2DM and insulin resistance (IR), but the underlying mechanism remains unknown. Methods Using network pharmacology, we screened the compounds of mSMG and identified its targets and pathway on hepatic IR in T2DM. Using molecular docking, we identified the affinity between the compounds and hub target TNF-α. Then these were verified in KK-Ay mice and HepG2 cells. Results 50 compounds and 170 targets of mSMG against IR in T2DM were screened, and 9 hub targets such as TNF and MAPK8 were identified. 170 targets were mainly enriched in insulin resistance and TNF pathway, so we speculated that mSMG might act on TNF-α, JNK1 and then regulate insulin signaling to mitigate IR. Experimental validation proved that mSMG ameliorated hyperglycemia, IR, and TNF-α, enhanced glucose consumption and glycogen synthesis, relieved the phosphorylation of JNK1 and IRS-2 (Ser388), and elevated the phosphorylation of Akt (Ser473) and GSK-3β (Ser9) and GLUT2 expression in KK-Ay mice. Molecular docking further showed berberine from mSMG had excellent binding capacity with TNF-α. Then, in vitro validation experiments, we found that 20% mSMG-MS or 50 μM berberine had little effect in IR-HepG2 cell viability, but significantly increased glucose consumption and glycogen synthesis and regulated TNF-α/JNK1/IRS-2 pathway. Conclusion Network pharmacology and molecular docking help us predict potential mechanism of mSMG and further guide experimental validation. mSMG and its representative compound berberine improve hepatic IR and glycogen synthesis, and its mechanism may be related to the inhibition of TNF-α/JNK1/IRS-2 pathway.

Shengli Oilfield has entered the middle and later development stages， and higher requirements for development seismic technologies have been set to develop reservoirs and further enhance oil recovery finely. The distribution and connectivity of conventional reservoirs in Jiyang Depression are complex due to different buried depths， multi-stage tectonic movements， various sedimentary types， and other factors. At the same time， constrained by seismic recognition， the well-seismic correspondences of some reservoirs are unclear， limiting the accuracy of fine reservoir characterization. In response to the development needs of different types of conventional reservoirs in Shengli Oilfield， a series of development seismic technologies have been formed through practice. These technologies include multi-method integrated reservoir prediction technology for middle and shallow fluvial facies reservoirs， integrated fine description technology for fracture systems in complex fault block reservoirs combing fine fault edge depiction and multiple attributes， prediction technology for middle-deep reservoirs with low permeability， and description technology of buried hill reservoirs fusing multiple parameters of “fault-fracture-dissolution composite storage space.” These technologies provide strong support for reservoir development. However， as the target reservoirs for development get deeper， thinner， and smaller and expand into unconventional reservoirs， the development seismic technologies faces higher requirements and challenges. It is necessary to accelerate the integration process of processing and interpretation， strengthen the theoretical research of rock physics， promote the application of OVT domain pre-stack inversion in the description of multi-type oil reservoirs， tackle the fine description technologies of complex fault block-lithofacies reservoirs， break through the technical bottleneck of well-ground joint acquisition and gravity-magnetic-electric-seismic technology， and realize the application of artificial intelligence technology in the development seismic field， so as to further promote reservoir development.

This study investigated the effect of forkhead box M1 (FOXM1) and Aurora kinase B (AURKB) on the epidermal function of keratinocytes.

Abstract Objective The purpose of this study is to construct an organ system-centered undergraduate nursing professional training model and explore its application effect. Methods This study is divided into two steps. In the early stage, literature review and expert consultation were used to establish the training mode (curriculum and assessment standard) of nursing undergraduate specialty based on organ system reform. Secondly, a cross-sectional survey method was used to investigate the training quality of nursing students who graduated from Jinzhou Medical University from 2007 to 2017 under this model. Results A five-module curriculum system was established, including general courses, public basic courses, professional education courses, expanding elective courses and concentrated practical teaching. Under the teaching reform of organ system, the nursing graduates of Jinzhou Medical University, who are mainly employed in public hospitals, are generally not satisfied with their jobs, salaries, contents and prospects. Their overall satisfaction with their alma mater is very high; Graduates have certain independent core competence; Employers are basically satisfied with graduates. Conclusion The training mode of undergraduate nursing specialty based on organ system reform basically meets the training requirements and objectives.

Wenyu Li,1 Yanqiu Hou,1 Jiayu An,1 Linxuan Chen,1 Shan Lu1,2 1School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Research Centre for Rural Health Service, Key Research Institute of Humanities & Social Sciences of Hubei Provincial Department of Education, Wuhan, People’s Republic of ChinaCorrespondence: Shan Lu, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Hang Kong Road 13, Wuhan, 430030, People’s Republic of China, Tel +86 15827079650, Email shanlu@hust.edu.cnPurpose: The objective of this study was to explore the connection between family doctor contract services and preventable hospitalizations. Additionally, we sought to examine the role of primary health care quality as a mediating factor in the link between family doctor contract services and preventable hospitalizations among patients with hypertension.Patients and Methods: This cross-sectional study was performed in Dangyang (Hubei Province, Central China) and Xishui (Guizhou Province, Western China) counties in July–August 2023. Participants comprised 625 patients selected via a multi-stage sampling method. Causal mediation analysis was conducted to explore the effect of family doctor contract services on preventable hospitalizations and the mediating effect of primary healthcare quality on this relationship.Results: Utilization rate of family doctor contract services of hypertensive patients was 58.6%, score of primary health service quality was 70.75 and incidence of preventable hospitalizations was 28.2%. Amongst hypertensive patients, utilization of family doctor contract services decreased the occurrence of preventable hospitalizations, with a total effect of − 0.22 (p < 0.001). Primary healthcare quality mediates the association, with a mediate effect of − 0.05 (p < 0.001), explaining 22.73% of the total effect.Conclusion: Improving the utilization of family doctor contract services and primary healthcare quality may result in lower rates of preventable hospitalizations amongst hypertensive patients.Keywords: family doctor contract services, preventable hospitalizations, primary healthcare quality, hypertension, mediation analysis

C48H35Fe2NO4P2Se2, monoclinic, P21/c, a = 20.3289(18) Å, b = 12.6909(11) Å, c = 17.6743(16) Å, β = 109.767(4)∘, V = 4291.1(7) Å3, Z = 4, Rgt(F) = 0.0638, wRref(F2) = 0.1439, T = 298(2) K.

C33H22O6Sn, triclinic, P1̄ (no. 2), a = 9.5394(11) Å, b = 10.2394(12) Å, c = 15.3202(18) Å, α = 105.195(3)°, β = 91.321(2)°, γ = 105.703(3)°, V = 1383.1(3) Å3, Z = 2, Rgt(F) = 0.0452, wRref(F2) = 0.1115, T = 298(2) K.

The accessibility and quality of ambulatory care (including outpatient and emergency services in primary care facilities, hospitals and other healthcare facilities) determine the efficiency of overall health care system and population health. Ambulatory care is also the core component of continuing care in an aging society. The concept of ambulatory care sensitive conditions (ACSCs) was firstly introduced by American researchers in 1990s. Since then, hospitalization for ambulatory care sensitive conditions (ACSHs) was widely used to evaluate the accessibility and quality of ambulatory care. In recent years, research on ACSH has gradually attracted the attention of scholars from all over the world, and preliminary research evidence from China indicated that the issue should not be ignored. This paper firstly introduces the origin of the concept of ACSH, then identifies the mixing concepts such as ACSH, avoidable hospitalization and inappropriate hospital admission, systematically summarizes the cutting-edge international identification criteria of ACSH, and finally discusses the policy value of ACSH as an indicator in the context of domestic and international research advances, clarifies the problems that should be noted in the identification of ACSCs in China, proposes strategies to reduce ACSH.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Abstract Objective Existing evidence suggests telomerase activation is a crucial step in tumorigenesis. The telomerase reverse transcriptase (TERT), encoded by the human TERT gene, is critical for telomerase expression. The TERT rs10069690 (C > T) variant was identified to be associated with the risk of cancer, however, there have been inconsistent results. Therefore, we performed a comprehensive meta-analysis aiming to clarify the association between this variant and cancer susceptibility. Methods We conducted literature search in PubMed, EMbase, MEDLINE and Cochrane Library up to April 30, 2024. Overall, there are 55 studies involving 334,196 patients with cancer and 741,187 controls included in the present study. All statistical analyses were performed by STATA software (version 11.0). Results The pooled results showed a significant association between rs10069690 and an increased risk of cancer under allele model (OR = 1.10, 95% CI: 1.07–1.13, P

Abstract Severe PM2.5 pollution threatens public health in India. Atmospheric stagnation traps emitted pollutants, worsening their health impacts. Global warming is anticipated to alter future stagnation patterns, impacting the effectiveness of air quality policies. Here, we develop a region-specific index that characterizes meteorological conditions driving stagnation and associated PM2.5 increases. Applying this index to an ensemble of climate models and global warming scenarios, we find that future stagnation changes result from both global CO2-driven circulation changes and local aerosol-driven meteorological responses. By 2100, we project an increase in winter stagnation in the Indo-Gangetic Plain (IGP) of 7 ± 3 days that leads to an increase in PM2.5 of ~7 ug/m3 in a high-warming and high-aerosol scenario. However, annual stagnation occurrences decrease across most of India. Thus, stringent air quality regulations in the IGP during winters will be critical to reduce surface PM2.5 concentrations as climate warms. Such regulations will directly improve air quality while reducing future stagnation occurrences, providing additional air quality benefits.

Abstract Background Calcium silicate-based bioceramics have been applied in endodontics as advantageous materials for years, many chemical components and new synthesizing methods were used to improve the base formulation of the materials for positively affecting the sealers properties. Recently, a novel biomaterial formulation, grounded in strontium silicate, has been introduced to the market, offering potential advancements in the field. Objective To comparatively analyze the cytotoxicity and cell migration effects of a novel strontium silicate-based bioceramic material (CRoot SP) and those of calcium silicate-based (iRoot SP) and epoxide amine resin (AH Plus) sealers on stem cells derived from rat apical papilla(rSCAPs). Methods rSCAPs were isolated and characterized in vitro and subsequently cultured in the presence of various concentrations of CRoot SP, iRoot SP and AH Plus extracts. Cytotoxicity was assessed by CCK-8 assay, and cell-migration capacity was assessed by using wound healing assays . Results No significant differences in cell viability were observed in the 0.02 mg/mL and 0.2 mg/mL sealer groups. The cell viability of CRoot SP was consistently greater than that of iRoot SP at concentrations of 5 mg/mL and 10 mg/mL across all time points. Maximum cytotoxic effect was noted on day 5 with 10 mg/mL AH Plus.The scratch was partly healed by cell migration in all groups at 24 h, and the 0.02 mg/mL, and 0.2 mg/mL CRoot SP exerted beneficial effects on rSCAPs migration. Conclusions CRoot SP exhibited less cytotoxic than the iRoot SP and AH Plus extracts after setting. A lower concentration of CRoot SP thus promotes the cell migration capacity of rSCAPs, and it may achieve better tissue repair during root canal treatment.

Abstract Background Studies have reported that polyphyllin I (PPI) had effective anti-tumor activity against hepatocellular carcinoma (HCC). However, the precise molecular mechanism of this action and the direct target remain unclear. The aim of this study was to discover the molecular targets and the exact mechanism of PPI in the treatment of HCC. Methods Various HCC cells and Zebrafish xenotransplantation models were used to examine the efficacy of PPI against HCC. A proteome microarray, surface plasmon resonance (SPR) analysis, small molecule transfection, and molecular docking were conducted to confirm the direct binding targets of PPI. Transcriptome and Western blotting were then used to determine the exact responding mechanism. Finally, the anticancer effect and its precise mechanism, as well as the safety of PPI, were verified using a mouse tumor xenograft study. Results The results demonstrated that PPI had significant anticancer activity against HCC in both in vitro studies of two cells and the zebrafish model. Notably, PPI selectively enhanced the action of the Zinc finger and BTB domain-containing 16 (ZBTB16) protein by directly binding to it. Furthermore, specific knockdown of ZBTB16 markedly attenuated PPI-dependent inhibition of HCC cell proliferation and migration caused by overexpression of the gene. The transcriptome and Western blotting also confirmed that the interaction between ZBTB16 and PPI also activated the PPARγ/RXRα pathway. Finally, the mouse experiments confirmed the efficacy and safety of PPI to treat HCC. Conclusions Our results indicate that ZBTB16 is a promising drug target for HCC and that PPI as a potent ZBTB16 agonist has potential as a therapeutic agent against HCC by regulating the ZBTB16/PPARγ/RXRα signaling axis.

Gang Deng, Yuanyuan Yang, Song Lu, Lin Ma, Guohua Wu College of Biotechnology and Sericultural Research Institute, Jiangsu University of Science and Technology, Zhenjiang, 212100, People’s Republic of ChinaCorrespondence: Guohua Wu, Email ghwu@just.edu.cnIntroduction: With the development of technology, personal heat management has become a focus of attention. Phase change fabrics, as intelligent materials, are expected to be widely used in multiple fields, bringing comfortable, intelligent and convenient living experience.Methods: In this study, miniature phase change microcapsules (MPCM) with n-octadecane as core and poly(methyl methacrylate) as shell were successfully prepared. Using the in-situ reduction property of polydopamine, gold nanoparticles were deposited on the surface of the microcapsules, which retained the heat storage function and imparted photothermal and antibacterial properties. The MPCM with photothermal conversion function was modified on the surface of silk fabric using aqueous polyurethane after verified by comprehensive material characterisation techniques.Results: Under the near infrared light of 808 nm wavelength and 0.134 W/cm² irradiation intensity, the MPCM@PDA@Au modified silk fabrics showed excellent photothermal conversion performance, which could be increased from 25°C to 60°C in 50s. After the light source was cut off, the fabrics showed good heat release ability, with melting enthalpy and crystallisation enthalpy reaching 41.58 J/g and 43.3 J/g, respectively, which were not changed after repeated cycles. After the light source is cut off, the fabric has good heat release ability, and the enthalpy of melting and crystallisation reaches 41.58 J/g and 43.3 J/g, respectively, and the photothermal efficiency remains unchanged after many cycles of use, which proves that it has excellent durability and stability. The antimicrobial test shows that the fabric has significant antibacterial effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus).Discussion: MPCM@PDA@Au silk fabrics bring new possibilities for the future of personal thermal management and antimicrobial protection in the field of medical health, outdoor sports and other areas of broad application prospects, heralding the birth of a series of innovative applications and solutions.Keywords: photothermal conversion, phase change material, thermal energy storage, functional textile

Yibin Lin,1,2 Lehua Liu,1 Siyang Lu,1 Linqi Fan,1 Huaqi Hu,1 Xuanyin Wang,1 Jichao Zhu,3 Xinhua Qiang,4 Jie He,5 Hongchang Zhou,1,2,6 Shengwen Shao,1,6 Gaoming Zheng7 1School of Medicine, Huzhou University, Huzhou, 313000, People’s Republic of China; 2Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, 31300, People’s Republic of China; 3Clinical Laboratory, Huzhou Central Hospital, Huzhou, 313000, People’s Republic of China; 4Clinical Laboratory, First People’s Hospital Affiliated to Huzhou University, Huzhou, 313000, People’s Republic of China; 5Infectious Diseases Department, First People’s Hospital Affiliated to Huzhou University, Huzhou, 313000, People’s Republic of China; 6Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou, 313000, People’s Republic of China; 7Clinical Laboratory, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, People’s Republic of ChinaCorrespondence: Gaoming Zheng; Shengwen Shao, Email zheng151031@sina.com; shaoshw@zjhu.edu.cnBackground: Bacillus cereus is a common bacterium found in the environment. Some strains can cause food poisoning, and very few can cause clinically severe infections, leading to death. Here, we characterized the genome sequence of B. cereus LIN78 isolated from teeth with deep caries and compared it with those of 25 other related species.Methods: Third-generation sequencing technology, bacteriological analyses, biochemistry, and mass spectrometry were applied to characterize the drug-resistance genes and virulence factors of B. cereus LIN78.Results: The complete genome sequence of B. cereus Lin78 consists of 5647 genes distributed on a circular chromosome, a 393 kbp plasmid, and 928 pseudogenes (37.4% of whole-genome DNA). The LIN78 genome contains 14 sets of 16s, 23s, and 5s ribosomal RNA operons; 106 tRNA genes, one tmRNA, 12 genomic islands, six prophases, 64 repeats; 37 antibiotic-resistant genes; and 1119 putative virulence genes, including enterotoxins and cytolysins. The B. cereus LIN78 genome carries multiple copies of non-ribosomal polypeptide synthetase (NRPS) and post-translationally modified peptides (RiPPs). Phylogenetic analysis of the 26 B. cereus strains showed that B. cereus LIN78 is evolutionarily closely related to B. thuringiensis ATCC 10792 and B. cereus ATCC 14579.Conclusion: The newly isolated B. cereus carries many virulence genes, including enterotoxins and hemolysins, similar to B. anthracis, and multiple antibiotic resistance genes. These findings suggest that the strain has a potential risk of causing disease. Our studies are vital for further exploration of the evolution of B. cereus, its pathogenic mechanisms, and the control and treatment of bacterial infections.Keywords: bacillus cereus, whole-genome DNA sequencing, virulence factor, drug resistance gene, human teeth

Abstract [Objective] To enhance the resistance of non-heading Chinese cabbage to turnip mosaic virus (TuMV), this study preliminarily explored the interaction mechanism between BcCHC1 protein of nonheading Chinese cabbage and TuMV. [Methods] The study firstly identified members of the heavy chain clathrin (CHC) gene family, BcCHCs, from non-heading Chinese cabbage, and then cloned CHC1 gene. BcCHC1 subcellular localization was analyzed, and bimolecular fluorescence complementation (BiFC) assay was used to verify the interaction between TuMV and BcCHC1. Finally, virus-induced gene silencing (VIGS) was employed to silence BcCHC1 expression and its function was assessed. [Results] BcCHC1 gene from non-heading Chinese cabbage was cloned, with a coding sequence length of 5 124 bp, encoding 1 708 amino acids. qRT-PCR results showed a significant decrease in the relative expression level of Bc- CHC1 gene in non-heading Chinese cabbage infected with TuMV after 30 days. Subcellular localization revealed that BcCHC1 protein was located in the cell membrane and nucleus of tobacco epidermal cells. BiFC assay analysis confirmed that BcCHC1 interacted with CI and 6K2: Interaction with CI was mainly occurring in the nucleus, while interaction with 6K2 mainly on the cell membrane. Observations of BcCHC1-silenced lines showed that silencing BcCHC1 gene led to plant death. [Conclusion] BcCHC1 regulates the infection of non-heading Chinese cabbage by TuMV through interaction with CI and 6K2, thereby affecting the clathrin-dependent endocytosis pathway and virus replication. However, the mechanism by which Bc- CHC1 regulates TuMV infection in non-heading Chinese cabbage requires further study.

Abstract Purpose Liver was one of the most common distant metastatic sites in breast cancer. Patients with distant metastasis were identified as American Joint Committee on Cancer (AJCC) stage IV indicating poor prognosis. However, few studies have predicted the survival in females with T1-2N0-1 breast cancer who developed liver metastasis. This study aimed to explore the clinical features of these patients and establish a nomogram to predict their overall survival. Results 1923 patients were randomly divided into training (n = 1154) and validation (n = 769) cohorts. Univariate and multivariate analysis showed that age, marital status, race, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), chemotherapy, surgery and bone metastasis, brain metastasis were considered the independent prognostic indicators. We developed a nomogram according to these ten parameters. The consistency index (c-index) was 0.72 (95% confidence interval CI 0.70–0.74) in the training cohort, 0.72 (95% CI 0.69–0.74) in the validation cohort. Calibration plots indicated that the nomogram-predicted survival was consistent with the recorded 1-, 3- and 5-year prognoses. Decision curve analysis curves in both the training and validation cohorts demonstrated that the nomogram showed better prediction than the AJCC TNM (8th) staging system. Kaplan Meier curve based on the risk stratification system showed that the low-risk group had a better prognosis than the high-risk group (P

Abstract Background To investigate the cross-sectional and longitudinal associations between depressive symptoms and the prevalence of frailty and its components in a nationally representative sample of middle-aged and older Chinese adults. Method The China Health and Retirement Longitudinal Study (CHARLS) provided data on 2581 (after inclusion and exclusion criteria) adults aged ≥ 45 years. Every two years, face-to-face, computer-aided personal interviews (CAPI), and structured questionnaires were used to follow up with the respondents. The Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D) was used to evaluate depressive symptoms, and the Fried criteria were used to measure frailty. The odds ratio (OR) and 95% confidence interval (CI) for the association of exposure (depressive symptoms at baseline) with the onset of the outcome (frailty and its components) in the individuals at baseline were analyzed by binary logistic regression. Results At baseline, 11.62% of participants had frailty, and 57.92% had depressive symptoms. In the cross-sectional analysis, depressive symptoms (OR = 5.222, 95%CI 3.665–7.442) were associated with frailty. In the longitudinal analysis, after adjusting for the full set of covariates among participants free of baseline frailty, depressive symptoms were significantly associated with incident frailty during the short term (OR = 2.193, 95%CI 1.324–3.631) and the long term (OR = 1.926, 95%CI 1.021–3.632). Meanwhile, depressive symptoms were associated with an increased risk of weakness (OR = 1.990, 95%CI 1.250–3.166), slowness (OR = 1.395, 95%CI 1.044–1.865), and exhaustion (OR = 2.827, 95%CI 2.150–3.719) onset during the short-term. Depressive symptoms were associated with an increased risk of exhaustion (OR = 2.869, 95%CI 2.004–4.109) onset during the long-term. Conclusion Among middle-aged and older adults, depressive symptoms could predict frailty during 2 years of follow-up and 4 years of follow-up. When considering potential confounding factors, depressive symptoms were considered a predictor of weakness, slowness, and exhaustion. Interventions aimed at preventing depressive symptoms may be beneficial in reducing frailty and its components.

Abstract Background Preeclampsia is a severe obstetric disorder that significantly affects the maternal and neonatal peri-partum safety and long-term quality of life. However, there is limited research exploring the common mechanisms and potential clinical significance between early-onset preeclampsia and full-term preeclampsia from an immunological perspective. Methods In this study, data analysis was conducted. Initially, immune-related co-expressed genes involving both subtypes of preeclampsia were identified through Weighted Gene Co-expression Network Analysis (WGCNA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were further employed to investigate the shared pathways regulated by immune-related genes. Binary logistic regression identified co-expressed genes with diagnostic value for preeclampsia, and a diagnostic model was constructed. Gene Set Enrichment Analysis (GSEA) predicted the potential biological functions of the selected genes. Lasso and Cox regression analyses identified genes closely associated with gestational duration, and a risk score model was established. A 4-gene feature, immune-related gene model for predicting the risk of preterm birth in preeclamptic pregnant women, was developed and validated through qPCR experiments. Immune cell infiltration analysis determined differences in immune cell infiltration between the two subtypes of preeclampsia. Results This study identified 4 immune-related co-expressed genes (CXCR6, PIK3CB, IL1RAP, and OSMR). Additionally, diagnostic and preterm birth risk prediction models for preeclampsia were constructed based on these genes. GSEA analysis suggested the involvement of these genes in the regulation of galactose metabolism, notch signaling pathway, and RIG-I like receptor signaling pathway. Immune pathway analysis indicated that the activation of T cell co-inhibition could be a potential intervention target for immunotherapy in early-onset preeclampsia. Conclusion Our study provides promising insights into immunotherapy and mechanistic research for preeclampsia, discovering novel diagnostic and intervention biomarkers, and offering personalized diagnostic tools for preeclampsia.

Abstract Background Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia. Methods Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8–15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0–1 mm (central fovea), 1–3 mm (parafovea), 3–6 mm (perifovea), and 6–9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants. Results The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0–6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P

Abstract Background The prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients. Methods We analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes. Results Patients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration. Conclusions The immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings.

Abstract Background Enterococcus gallinarum is an infrequently intestinal symbiotic pathogen associated with nosocomial infection in immunocompromised individuals. To date, rare cases of pulmonary infection attributable to Enterococcus gallinarum were reported. Herein, we presented the first case of empyema resulting from Enterococcus gallinarum infection. Case presentation An 81-year-old male presented with fever and dyspnea upon admission. Chest CT scan and thoracic ultrasonography confirmed the presence of right pleural effusion. Thoracoscopy revealed extensive adhesion, purulent fluid, and necrotic materials within the thoracic cavity. Enterococcus gallinarum was identified through pleural effusion culture. The patient underwent an intrathoracic injection of urokinase along with thoracic drainage. Following surgery, He took oral linezolid for over one month. Undergoing comprehensive treatment, the patient exhibited favorable recovery. Conclusions We reported the first case of empyema due to Enterococcus gallinarum infection. It should be suspected in patients with impaired immune function and invasive therapies, without responding to conventional anti-infectious treatment.

The aim of this research is to conduct a comparative analysis of the regulation and implementation of e-commerce taxation rules in each country, as measured through their impact on the economies of these nations. This study employs a normative juridical approach. The findings indicate that Indonesia could benefit from learning from Singapore, one of the leading Asian countries in terms of economic growth derived from the e-commerce sector. This serves as evidence of the success of implementing taxation regulations and legal frameworks related to e-commerce in Singapore. Minister of Finance Regulation Number 60 of 2022 (PMK Number 60/2022) represents a strategic step in regulating e-commerce taxation in Indonesia, granting the government the authority to establish order, fairness, and sustainable economic growth in the digital era. In response to the challenges presented by e-commerce, Singapore has made adjustments to its taxation regulations, even though there are no specific provisions in place for the digital economy. The guidelines issued by the Inland Revenue Authority of Singapore (IRAS) serve as crucial reference points for determining tax obligations in e-commerce transactions, taking into account factors such as production location and website hosting

Indonesian Migrant Workers refer to any citizen who is currently or has engaged in employment beyond the borders of Indonesia, receiving wages or compensation. The prevalent issue at hand is the rising number of Indonesian Migrant Workers operating illegally, driven by individuals offering unofficial services with enticing proposals to the public. This study employs a normative legal research approach, utilizing secondary data that encompasses primary legal materials such as Law Number 18 of 2017 concerning the Protection of Indonesian Migrant Workers, secondary legal materials including articles, news, and other literature, as well as tertiary legal materials. Indonesia actively takes part in addressing the concerns of Indonesian Migrant Workers by enacting Law Number 18 of 2017 to ensure the fulfillment of their rights and legal protection, including criminal provisions against wrongdoers. Efforts to address this issue involve public awareness campaigns and legal measures against those engaging in criminal activities.

Technological developments and digital transformation have had a significant impact on the banking industry sector, triggering the rapid growth of digital banking. This research aims to examine the regulation of digital banking in the era of digital banking transformation by focusing on the comparison between Indonesia and Singapore. This research uses normative juridical research with a statute approach and comparative approach. The results of this research provide in-depth insight into the differences and similarities in regulatory approaches to the level of security, innovation and digital banking penetration between Indonesia and Singapore. The results of this research bring a comprehensive understanding of how the two countries respond to the challenges and opportunities in the era of digital banking transformation which is expected to contribute to the development of digital banking in Indonesia today.

In recent years, driven by policy incentives and regulatory reforms, the research and development of rare disease drugs in China has begun to show a promising future. As of March 2024, more than 30 gene therapy products for rare diseases in China have been approved for clinical trials. In order to guide the clinical trial design of gene therapy products for rare diseases, Center for Drug Evaluation, National Medical Products Administration has issued Guideline for Clinical Trials Design of Gene Therapy Products for Rare Diseases (Trial Version). Now we try to interpret this guideline to provide recommendations for the industry.

Abstract Epithelial ovarian cancer (EOC) is a deadly disease with limited diagnostic biomarkers and therapeutic targets. Here we conduct a comprehensive proteomic profiling of ovarian tissue and plasma samples from 813 patients with different histotypes and therapeutic regimens, covering the expression of 10,715 proteins. We identify eight proteins associated with tumor malignancy in the tissue specimens, which are further validated as potential circulating biomarkers in plasma. Targeted proteomics assays are developed for 12 tissue proteins and 7 blood proteins, and machine learning models are constructed to predict one-year recurrence, which are validated in an independent cohort. These findings contribute to the understanding of EOC pathogenesis and provide potential biomarkers for early detection and monitoring of the disease. Additionally, by integrating mutation analysis with proteomic data, we identify multiple proteins related to DNA damage in recurrent resistant tumors, shedding light on the molecular mechanisms underlying treatment resistance. This study provides a multi-histotype proteomic landscape of EOC, advancing our knowledge for improved diagnosis and treatment strategies.

Abstract Background Addressing presbyopia in the aging population, particularly in non-cataractous patients, remains a challenge. This study evaluates the outcomes of refractive lens exchange (RLE) with AT LISA tri 839MP trifocal intraocular lens (IOL) implantation in a Chinese presbyopic population without cataracts. Methods The study included 164 eyes from 82 patients undergoing bilateral RLE at Peking Union Medical College Hospital. Comprehensive evaluations encompassed visual acuities, refraction, ocular aberrometry, and subjective outcomes via the VF-14 questionnaire. The focus was on postoperative visual performance, refractive outcomes, safety, objective optical quality, and patient satisfaction. Results 100%, 90.2%, and 89.0% of patients achieved binocular UDVA, UNVA, and UIVA of logMAR 0.1 or better at 6 months postoperatively. 97.6% of eyes were within ± 1.00 D of emmetropia postoperatively. Optical quality assessments showed increases in modulation transfer function and Strehl ratios (p