Exploring the impact of computer game playing on cognitive function, Alzheimer's disease risk, and brain-derived neurotrophic factor levels: Basic evidence from Mendelian randomization.

Introduction: The potential positive impact of computer game playing on cognitive function and its potential role in reducing the risk of Alzheimer's disease (AD) has been suggested. However, current observational studies have certain limitations. We utilized Mendelian randomization (MR) alongside extensive genome-wide association study (GWAS) data to examine the relationship between computer game playing, cognitive function, risk of AD, and levels of brain-derived neurotrophic factor (BDNF). Methods: We collected datasets on computer game playing, cognition function, risk of AD, and BDNF level from the IEU Open GWAS project. Causal effects were assessed using various MR methods, including inverse variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure the accuracy of the results, sensitivity analyses were conducted. Results: Our analysis revealed a significant association between computer game playing and cognitive function (ß = 0.801, 95% CI: 0.351, 1.328, P = 0.001). There was no statistically significant association between computer game playing and either BDNF level or risk of AD (ß = -0.112, 95%CI: -1.315, 1.091, P = 0.855; OR = 1.000, 95% CI: 1.004, 0.997, P = 0.891, respectively). We further confirmed the reliability of our evidence through the MR-Egger intercept test, MR-PRESSO global test, Cochran's Q test, and funnel plots. Conclusion: The results of our study indicate that engaging in computer game playing may confer a safeguarding influence on cognitive function. This underscores the potential advantages associated with computer gaming. Nevertheless, given the constraints inherent in our research, further investigation is warranted to substantiate our findings and delve into the underlying mechanisms.

Efficacy and Safety in Early application of Ruxolinitib for high-risk: Acute lymphoblastic leukemia to prevent GVHD and recurrence after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been identified as the potentially curative treatment for high-risk acute lymphoblastic leukemia (ALL) in adult patients. However, relapse of the disease and/or development of graft-versus-host disease (GVHD) remain to be the most common barriers for successful allo-HSCT. Preclinical studies showed that ruxolitinib, a Janus tyrosine kinase (Jak)1 and Jak2 inhibitor, has a selective anti-GVHD effects while preserving a potent graft-versus-leukemia (GVL) effect. Our study aimed to investigate the efficacy and safety in early application of ruxolitinib for the high-risk ALL patients to prevent GVHD. METHODS: There were eight patients undergoing allo-HSCT at the Bone Marrow Transplantation Center of the Third Xiangya Hospital of Central South University between April 2020 and April 2021. Ruxolitinib (5-10 mg twice daily) was administered early (median time: 45 days) after stem cell infusion. RESULTS: After a median follow-up of 14 months (range from 8 to 18 months), the ALL disease relapse occurred in two cases. Among all eight patients, two of them developed grade I/II acute (a) GVHD, while no patient developed grade III/IV aGVHD, and one patient developed chronic (c) GVHD. As for the virus activation, no patient developed EBV activation or EBV related lymphoproliferative disease, and three patients developed CMV activation. Our results suggest that the early application of ruxolitinib could safely and effectively prevent the occurrence of GVHD after allo-HSCT for the high-risk ALL patients. However, it may have a limited effect on preventing the recurrence of high-risk ALL and thus may require additional therapy with other anti-relapse drugs. CONCLUSIONS: Our preliminary observations suggest that an early application of ruxolitinib can safely and effectively prevent the occurrence of GVHD after allo-HSCT for the high-risk ALL patients. However, ruxolitinib may have a limited effect on preventing the ALL recurrence of high-risk patients.

The Relationship Between Physical Exercise and Aggressive Behavior Among College Students: The Mediating Roles of Life Satisfaction, Meaning in Life, and Depression.

Purpose: The deleterious impact of aggressive behavior on college students necessitates urgent mitigation. To explore the influencing factors and underlying mechanisms of aggressive behaviors among college students, this study aims to validate the mediating roles of life satisfaction, meaning in life, and depression by examining the relationship between physical exercise and aggressive behaviors among college students. Methods: The Physical Activity Rating Scale-3 (PARS-3), Satisfaction with Life Scale, Meaning in Life Questionnaire, Chinese Version DASS-21 and 12-item Perception of Aggression Scale (POAS) were tested on 1596 college students from three universities in western China, and SPSS 26.0 and Mplus 8.3 were used for analysis. Results: Physical exercise exhibited a significant negative correlation with both aggressive behaviors and depression among college students (r = -0.57, P < 0.001; r = -0.36, P < 0.001), as well as a significant positive correlation with life satisfaction and meaning in life (r = 0.45, P < 0.001; r = 0.27, P < 0.001). Regarding the impact of physical exercise on aggressive behaviors among college students, the mediating effects of life satisfaction, meaning in life, and depression were significant. The respective effect sizes were -0.11, -0.08, and -0.03. The chain mediation effect of life satisfaction through depression was also found to be significant, with an effect size of -0.02. Conclusion: This study elucidates the mechanistic pathways through which physical exercise influences aggressive behavior among college students. The relationship between physical exercise and aggressive behavior is influenced by the individual mediating effects of life satisfaction, meaning in life, and depression, as well as the chain mediation effect of life satisfaction through depression. These findings provide a novel perspective on the prevention and intervention of aggressive behaviors among college students in China and potentially worldwide. This suggests that more attention should be paid to the organic combination of students' physical activity and mental health education.

Nanostructure Effect on Magnetization Processes in FePt Polytwin Crystals.

In FePt polytwin crystals with large magnetocrystalline anisotropy, the boundaries may play a crucial role in the magnetization processes occurring under an external magnetic field. In this study, we employed phase-field modeling and computer simulations to systematically investigate the effect of three types of polytwin boundaries-namely, symmetric (Type I), asymmetric (Type II), and mixed (Type III) boundaries-on magnetization processes as well as coercive fields under an external magnetic field along various directions. Because of the large anisotropy of FePt, the domain wall motion mechanism is usually dominant in the domain switching processes, while the magnetization rotation mechanism only becomes important at the late magnetization stage under a high external magnetic field. Among these three types of polytwin boundaries, the low coercivity is mainly due to the domain wall motion process, which starts from the intersection point at the polytwin boundary. The coercive field for the mixed polytwin boundary (Type III) is always in between the values of Type I and II.

Discovery of dihydropyridinone derivative as a covalent EZH2 degrader.

EZH2 is overexpressed in multiple types of cancer and high expression level of EZH2 correlates with poor prognosis. Besides the regulation of H3K27 trimethylation, EZH2 itself regulates its downstream proteins in a PRC2- and methylation-independent way. Starting from an approved EZH2 inhibitor EPZ-6438, we used covalent drug design and medicinal chemistry approaches to discover a novel covalent EZH2 degrader 38, which forms a covalent bond with EZH2 Cys663 and showed strong biochemical activities against EZH2 WT and mutants. Compound 38 exhibited potent antiproliferation effects against both B-cell lymphoma and TNBC cell lines by reducing the levels of H3K27me3 and EZH2. The mass spectrometry, washout and competition experiments confirmed the covalent binding of 38 to EZH2. This study demonstrates that covalent EZH2 degraders could provide an opportunity for the development of promising new drug candidates.

BALF metagenomic next-generation sequencing analysis in hematological malignancy patients with suspected pulmonary infection: clinical significance of negative results.

Purpose: Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) is gradually being used in hematological malignancy (HM) patients with suspected pulmonary infections. However, negative results are common and the clinical value and interpretation of such results in this patient population require further analysis. Methods: Retrospective analysis of 112 HM patients with suspected pulmonary infection who underwent BALF mNGS and conventional microbiological tests. The final diagnosis, imaging findings, laboratory results and treatment regimen of 29 mNGS-negative patients were mainly analyzed. Results: A total of 83 mNGS positive and 29 negative patients (15 true-negatives and 14 false-negatives) were included in the study. Compared to false-negative patients, true-negative patients showed more thickening of interlobular septa on imaging (p < 0.05); fewer true-negative patients had acute respiratory symptoms such as coughing or sputum production (p < 0.05) clinically; On the aspect of etiology, drug-related interstitial pneumonia (6/15, 40%) was the most common type of lung lesion in true-negative patients; on the aspect of pathogenesis, false-negative patients mainly missed atypical pathogens such as fungi and tuberculosis (8/14, 57.1%). Regarding treatment, delayed anti-infection treatment occurred after pathogen missing in mNGS false-negative patients, with the longest median time delay observed for anti-tuberculosis therapy (13 days), followed by antifungal therapy (7 days), and antibacterial therapy (1.5 days); the delay in anti-tuberculosis therapy was significantly longer than that in antibacterial therapy (p < 0.05). Conclusion: For HMs patients with imaging showing thickening of interlobular septa and no obvious acute respiratory symptoms, lung lesions are more likely caused by drug treatment or the underlying disease, so caution should be exercised when performing BALF mNGS. If BALF mNGS is negative but infection is still suspected, atypical pathogenic infections should be considered.

A Leucine-Rich Repeat Receptor-like Kinase TaBIR1 Contributes to Wheat Resistance against Puccinia striiformis f. sp. tritici.

Plant cell surface-localized receptor-like kinases (RLKs) recognize invading pathogens and transduce the immune signals inside host cells, subsequently triggering immune responses to fight off pathogen invasion. Nonetheless, our understanding of the role of RLKs in wheat resistance to the biotrophic fungus Puccinia striiformis f. sp. tritici (Pst) remains limited. During the differentially expressed genes in Pst infected wheat leaves, a Leucine-repeat receptor-like kinase (LRR-RLK) gene TaBIR1 was significantly upregulated in the incompatible wheat-Pst interaction. qRT-PCR verified that TaBIR1 is induced at the early infection stage of Pst. The transient expression of TaBIR1-GFP protein in N. bentamiana cells and wheat mesophyll protoplasts revealed its plasma membrane location. The knockdown of TaBIR1 expression by VIGS (virus induced gene silencing) declined wheat resistance to stripe rust, resulting in reduced reactive oxygen species (ROS) production, callose deposition, and transcripts of pathogenesis-related genes TaPR1 and TaPR2, along with increased Pst infection area. Ectopic overexpression of TaBIR1 in N. benthamiana triggered constitutive immune responses with significant cell death, callose accumulation, and ROS production. Moreover, TaBIR1 triggered immunity is dependent on NbBAK1, the silencing of which significantly attenuated the defense response triggered by TaBIR1. TaBIR1 interacted with the NbBAK1 homologues in wheat, co-receptor TaSERK2 and TaSERK5, the transient expression of which could restore the impaired defense due to NbBAK1 silencing. Taken together, TaBIR1 is a cell surface RLK that contributes to wheat stripe rust resistance, probably as a positive regulator of plant immunity in a BAK1-dependent manner.

Efficient non-fullerene organic solar cells employing aqueous solution-processed MoO3as a hole-transporting layer.

Organic solar cell (OSC) has drawn considerable interest in recent decades owing to their advantages of light weight, flexible, large area and potentially low-cost. Employing an appropriate hole-transporting layer (HTL) into an OSC device has been proved as an efficient method to obtain high efficiency OSC due to the enhancement of the hole transporting and extraction of the device. In this work, aqueous solution-processed MoO3(s-MoO3) thin films were employed as HTLs to construct non-fullerene PM6:Y6 OSCs. The s-MoO3thin film was prepared by using an aqueous solution process from an isopolymolybdate [NH4]6Mo7O24.4H2O precursor followed by thermal annealing treatment to convert the precursor to MoO3. The s-MoO3HTL based PM6:Y6 device demonstrates a power conversion efficiency of 15.75%, which is 38% improved than that of the device with thermally evaporated-MoO3as HTL and 8% improved than that of the device with PEDOT:PSS as HTL. The enhancement of the device performance could be attributed to the enhanced hole mobility and better band matching of the s-MoO3HTL. Moreover, the s-MoO3HTL based PM6:Y6 device exhibited higher device stability than those of the reference devices. Our finding indicates that this s-MoO3film has great potential as efficient HTL for high performance non fullerene OSCs.

Organocatalytic (Z/E)-Selective Synthesis of 3-Vinylnaphthofurans via a Formal (3 + 2) Cycloaddition.

A formal (3 + 2) cycloaddition of 1,4-enediones with 2-naphthols was established under the catalysis of trifluoromethanesulfonic acid as an organocatalyst, leading to the efficient synthesis of structurally diverse 3-vinylnaphthofurans with high yields and excellent (Z/E)-selectivities (up to 96% yield, all >20:1 Z/E). This formal (3 + 2) cycloaddition involved a cascade reaction process, and the intramolecular hydrogen bond in the structure of 3-vinylnaphthofurans should play an important role in controlling the (Z/E)-selectivity of the newly formed vinyl group. Moreover, this class of 3-vinylnaphthofurans was discovered to have an axial chirality. This work provides an organocatalytic approach for constructing multi-substituted vinylnaphthofurans via a cascade reaction with excellent control of the (Z/E)-selectivity, which will serve as a useful strategy for synthesizing vinylnaphthofurans via in situ construction of the furan core and formation of the vinyl group.

Discovery of IHMT-337 as a potent irreversible EZH2 inhibitor targeting CDK4 transcription for malignancies.

Enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of PRC2 complex, plays an important role in tumor development and progression through its catalytic and noncatalytic activities. Overexpression or gain-of-function mutations of EZH2 have been significantly associated with tumor cell proliferation of triple-negative breast cancer (TNBC) and diffuse large B-cell lymphoma (DLBCL). As a result, it has gained interest as a potential therapeutic target. The currently available EZH2 inhibitors, such as EPZ6438 and GSK126, are of benefit for clinical using or reached clinical trials. However, certain cancers are resistant to these enzymatic inhibitors due to its noncatalytic or transcriptional activity through modulating nonhistone proteins. Thus, it may be more effective to synergistically degrade EZH2 in addition to enzymatic inhibition. Here, through a rational design and chemical screening, we discovered a new irreversible EZH2 inhibitor, IHMT-337, which covalently bounds to and degrades EZH2 via the E3 ligase CHIP-mediated ubiquitination pathway. Moreover, we revealed that IHMT-337 affects cell cycle progression in TNBC cells through targeting transcriptional regulating of CDK4, a novel PRC2 complex- and enzymatic activity-independent function of EZH2. More significantly, our compound inhibits both DLBCL and TNBC cell proliferation in different preclinical models in vitro and in vivo. Taken together, our findings demonstrate that in addition to enzymatic inhibition, destroying of EZH2 by IHMT-337 could be a promising therapeutic strategy for TNBC and other malignancies that are independent of EZH2 enzymatic activity.

An excipient-free "sugar-coated bullet" for the targeted treatment of orthotopic hepatocellular carcinoma.

Several components of traditional nanoformulations that result in structural heterogeneity, poor reproducibility, excipient-trigged biotoxicity, and low retention of antitumor drugs in neoplastic foci are important barriers limiting clinical translation. We report an excipient-free nanoformulation prepared by a reactive oxygen species (ROS)-responsive amphiphilic prodrug (Gal-MB-DOX) for the targeted treatment of orthotopic hepatocellular carcinoma (HCC). Gal-MB-DOX can form monocomponent nanoparticles with a galactose-rich surface similar to a "sugar-coated bullet" through self-assembly in aqueous solution. This nanoformulation can be decomposed quickly by ROS and release free hydrophobic drugs that further precipitate into larger particles, potentially promoting the retention of drugs in tumor cells. These sugar-coated bullets selectively target tumor cells through passive and active targeting, resulting in high in vivo therapeutic efficacy in an orthotopic HCC mouse model. This monocomponent nanomedicine system provides a simple but effective strategy for the treatment of tumors.

How physical exercise impacts academic burnout in college students: The mediating effects of self-efficacy and resilience.

Background and aims: Academic burnout is harmful to college students, their institutions of learning, and society at large. While research has shown that physical exercise may be associated with reduced academic burnout, the underlying mechanisms require further exploration. This study explored the relationship between physical exercise and academic burnout in a sample of college students, with a focus on the serial mediating roles of self-efficacy and resilience. Methods: This study adopted a cross-sectional survey approach among a sample of undergraduate college students in China. We recruited 1,270 participants in the second half of the 2021-2022 academic year (476 men and 794 women), all of whom completed questionnaires containing the Physical Activity Rating Scale, Academic Burnout Scale for College Students, 10-item General Self-Efficacy Scale, and 25-item Connor-Davidson Resilience Scale. We then subjected the collected data to a series of statistical analyses. Results and conclusion: Physical exercise was significantly and negatively associated with academic burnout and its three subfactors (i.e., emotional exhaustion, improper behavior, and low personal achievement). Participants in the high physical exercise group showed lower levels of academic burnout than those in the moderate and low physical exercise groups. Finally, our serial mediation model showed that physical exercise had a significant direct effect on academic burnout (ß = -0.1104, 95% CI = [-0.1421, -0.0791]) in addition to significant indirect effects on academic burnout via self-efficacy and resilience (ß = -0.0802, 95% CI = [-0.1088, -0.0527]); the more exercise participation, the lower the academic burnout among college students. These findings suggest that physical exercise is an important interventional target when aiming to reduce academic burnout.

Sparrow Search Algorithm-Optimized Long Short-Term Memory Model for Stock Trend Prediction.

The long short-term memory (LSTM) network is especially suitable for dealing with time series-related problems, which has led to a wide range of applications in analyzing stock market quotations and predicting future price trends. However, the selection of hyperparameters in LSTM networks was often based on subjective experience and existing research. The inability to determine the optimal values of the parameters results in a reduced generalization capability of the model. Therefore, we proposed a sparrow search algorithm-optimized LSTM (SSA-LSTM) model for stock trend prediction. The SSA was used to find the optimal hyperparameters of the LSTM model to adapt the features of the data to the structure of the model, so as to construct a highly accurate stock trend prediction model. With the Shanghai Composite Index stock data in the last decade, the mean absolute percentage error, root mean square error, mean absolute error, and coefficient of determination between stock prices predicted by the SSA-LSTM method and actual prices are 0.0093, 41.9505, 30.5300, and 0.9754. The result indicates that the proposed model possesses higher forecasting precision than other traditional stock forecasting methods and enhances the interpretability of the network model structure and parameters.

Diagnosis and treatment of multiple myeloma in Hunan Province. / 湖南省多发性骨髓瘤诊治现状.

OBJECTIVES: There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM. METHODS: The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0. RESULTS: Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%). CONCLUSIONS: In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.

Design, synthesis and biological evaluation of novel dual-targeting fluorescent probes for detection of Fe3+ in the lysosomes of hepatocytes mediated by galactose-morpholine moieties.

In this work, novel dual-targeting probes composed of galactose and morpholine were designed and synthesized for monitoring Fe3+ levels in the lysosome of hepatocyte. MP-Gal-1, MP-Gal-2 and MP-Gal-3 showed good selectivity and sensitivities toward Fe3+ with the detection limits of 9.40 × 10-8 M, 7.68 × 10-8 M and 7.10 × 10-8 M, respectively. 1:2 stoichiometry is the most likely recognition mode between probe and Fe3+. Low toxic MP-Gal-1, MP-Gal-2 and MP-Gal-3 exhibited favorable hepatic targeting effect in both cell and tissue levels, which was because the galactose group of probe could be recognized by ASGPR overexpressed on the hepatocytes. The hepatocyte-targeting capacity followed MP-Gal-1 < MP-Gal-2 < MP-Gal-3 trend, which was attributed to the galactose cluster effect. MP-Gal-1, MP-Gal-2 and MP-Gal-3 also displayed good lysosomes-targeting capacities, because the basic morpholine moiety of probes could be easily attracted by the acidic lysosome. Therefore, MP-Gal-1, MP-Gal-2 and MP-Gal-3 have good dual targeting capacities (liver and lysosome) and could be used to detect lysosomal Fe3+ in the liver, which is great significant for precise diagnosis and treatment of liver lysosomal iron-related diseases.

Nintedanib overcomes drug resistance from upregulation of FGFR signalling and imatinib-induced KIT mutations in gastrointestinal stromal tumours.

Drug resistance remains a major challenge in the clinical treatment of gastrointestinal stromal tumours (GISTs). While acquired on-target mutations of mast/stem cell growth factor receptor (KIT) kinase is the major resistance mechanism, activation of alternative signalling pathways may also play a role. Although several second- and third-generation KIT kinase inhibitors have been developed that could overcome some of the KIT mutations conferring resistance, the low clinical responses and narrow safety window have limited their broad application. The present study revealed that nintedanib not only overcame resistance induced by a panel of KIT primary and secondary mutations, but also overcame ERK-reactivation-mediated resistance caused by the upregulation of fibroblast growth factor (FGF) activity. In preclinical models of GISTs, nintedanib significantly inhibited the proliferation of imatinib-resistant cells, including GIST-5R, GIST-T1/T670I and GIST patient-derived primary cells. In addition, it also exhibited dose-dependent inhibition of ERK phosphorylation upon FGF ligand stimulation. In vivo antitumour activity was also observed in several xenograft GIST models. Considering the well-documented safety and pharmacokinetic profiles of nintedanib, this finding provides evidence for the repurposing of nintedanib as a new therapy for the treatment of GIST patients with de novo or acquired resistance to imatinib.

Galactose-imidazole mediated dual-targeting fluorescent probe for detecting Fe3+ in the lysosomes of hepatocytes: Design, synthesis and evaluation.

In this work, three novel dual-targeting fluorescent probes were designed with modification by imidazole and one galactose (IM-Gal-1), by imidazole and two galactoses (IM-Gal-2), and by imidazole and three galactoses (IM-Gal-3), separately. These probes showed good selectivity and sensitivity toward Fe3+ with 1:2 stoichiometry recognition mode. The detection limits toward Fe3+ were (1.293 ± 0.005) × 10-7 M for IM-Gal-1, (7.735 ± 0.005) × 10-8 M for IM-Gal-2, and (1.325 ± 0.023) × 10-7 M for IM-Gal-3. These low-toxic probes exhibited excellent hepatic targeting capacity, which is attributed to the specific recognition of asialoglycoprotein receptor (ASGPR) overexpressed on hepatocytes by the galactose group of probes. The hepatic targeting capacity followed IM-Gal-1 < IM-Gal-2< IM-Gal-3 trend due to the galactose cluster effect. Under the attraction between acidic lysosome and basic imidazole group, these imidazole-modified probes were confirmed to possess good lysosome-targeting capacities, earlier demonstrating imidazole as a lysosome-targeting group. Overall, these dual-targeting probes co-modified by galactose and imidazole exhibited unique advantages in precise diagnosis and treatment of liver lysosomal iron-related diseases.

A Smart Theranostic Prodrug System Activated by Reactive Oxygen Species for Regional Chemotherapy of Metastatic Cancer.

Metastatic cancer is difficult to cure because of its uncontrollable nature and side effects during treatment. We constructed a reactive oxygen species (ROS)-activated smart theranostic prodrug system based on an ROS active site linked with both a targeting group and an anticancer drug for efficient regional chemotherapy of metastatic cancers. The optimized prodrug (Bio-(8)-MB-CPT) with biotin as the targeting group displayed high sensitivity towards ROS and selectively targeting ability towards cervical cancer cells, showing highly efficient drug release (up to 92 %) in vitro. Bio-(8)-MB-CPT thus exerted strong toxicity towards cervical cancer cells, but unlike the parent drug (camptothecin), showed no toxicity towards normal cells. Moreover, the prodrug displayed significantly enhanced antitumor efficacy in vivo and eradicated the tumor with no obvious side effects (inhibition of the tumor reached up to 99.9 %).

Machine learning-based infection prediction model for newly diagnosed multiple myeloma patients.

Objective: To understand the infection characteristics and risk factors for infection by analyzing multicenter clinical data of newly diagnosed multiple myeloma (NDMM) patients. Methods: This study reviewed 564 NDMM patients from 2 large tertiary hospitals from January 2018 to December 2021, of whom 395 comprised the training set and 169 comprised the validation set. Thirty-eight variables from first admission records were collected, including patient demographic characteristics, clinical scores and characteristics, laboratory indicators, complications, and medication history, and key variables were screened using the Lasso method. Multiple machine learning algorithms were compared, and the best performing algorithm was used to build a machine learning prediction model. The model performance was evaluated using the AUC, accuracy, and Youden's index. Finally, the SHAP package was used to assess two cases and demonstrate the application of the model. Results: In this study, 15 important key variables were selected, namely, age, ECOG, osteolytic disruption, VCD, neutrophils, lymphocytes, monocytes, hemoglobin, platelets, albumin, creatinine, lactate dehydrogenase, affected globulin, ß2 microglobulin, and preventive medicine. The predictive performance of the XGBoost model was significantly better than that of the other models (AUROC: 0.8664), and it also performed well for the expected dataset (accuracy: 68.64%). Conclusion: A machine learning algorithm was used to establish an infection prediction model for NDMM patients that was simple, convenient, validated, and performed well in reducing the incidence of infection and improving the prognosis of patients.

The Influence of Chinese College Students' Physical Exercise on Life Satisfaction: The Chain Mediation Effect of Core Self-evaluation and Positive Emotion.

Physical exercise is an important way for college students to maintain their physical health, and life satisfaction is one of the important indicators of college students' mental health. Therefore, this study aims to explore the relationship between physical exercise and life satisfaction of college students. Additionally, we also seek to demonstrate the chain mediating effects of core self-evaluation and positive emotion on this relationship. A total of 794 Chinese college students, 324 men and 470 women, participated in the study. The participants were 17-25years old (M=19.96±1.54). They completed the Exercise Adherence Questionnaire, Core Self-evaluation Scale, Positive Affect and Negative Affect Scale, and Satisfaction with Life Scale. Results showed a strong positive relationship between physical exercise and life satisfaction and verified the mediating effect of core self-evaluation and positive emotion on this relationship. The results also confirmed the chain mediating model between physical exercise, core self-evaluation, positive emotion, and life satisfaction. It enlightens us that we should pay more attention to the organic combination of students' physical activities and mental health education.