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Abstract Phosphorescence is ubiquitous in heavy atom-containing organic phosphors, which attracts considerable attention in optoelectronics and bioelectronics. However, heavy atom-free organic materials with efficient phosphorescence are rare under ambient conditions. Herein, we report a series of adaptive host-guest materials derived from dibenzo-heterocyclic analogues, showing host-dependent color-tunable phosphorescence with phosphorescence efficiency of up to 98.9%. The adaptive structural deformation of the guests arises from the hyperconjugation, namely the n→π* interaction, enabling them to inhabit the cavity of host crystals in synergy with steric effects. Consequently, a perfect conformation match between host and guest molecules facilitates the suppression of triplet exciton dissipation, thereby boosting the phosphorescence of these adaptive materials. Moreover, we extend this strategy to a ternary host-guest system, yielding both excitation- and time-dependent phosphorescence with a phosphorescence efficiency of 92.0%. This principle provides a concise way for obtaining efficient and color-tunable phosphorescence, making a major step toward potential applications in optoelectronics.

The groundwater environment in low-lying coastal regions is significantly impacted by global sea-level fluctuation. In Laizhou Bay, three large-scale transgressions have occurred since the late Pleistocene, resulting in the transformation of ancient seawater into brine. This brine has become a major contributor to groundwater salinity in the area. This study establishes a correlation between groundwater occurrence and paleoclimate changes in Laizhou Bay using borehole sediment data. The source and mechanism of groundwater salinity are analyzed based on sediment pore water characteristics and hydrogen and oxygen isotopes. The study reveals that the stratigraphic structures in the area consist of four layers: a Holocene transgressive layer, a continental confining bed from the late Pleistocene, a Cangzhou transgressive layer from the late Pleistocene, and a fluvial aquifer from the middle Pleistocene. All aquifers in the study area have been infiltrated by modern seawater, with the uppermost Holocene aquifer influenced by evaporation and leaching processes, the central late Pleistocene aquifer remaining relatively stable, and the lower middle Pleistocene aquifer affected by subsurface low salinity runoff and exhibiting an increasing trend with depth. Given the presence of numerous hydrogeological environments globally that are similar to the study area, the obtained mechanisms of groundwater salinization in this study will provide theoretical support for groundwater management in similar regions worldwide.

Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease with phenotypic changes closely associated with both genetic variants and imaging pathology. Brain imaging biomarker genomics has been developed in recent years to reveal potential AD pathological mechanisms and provide early diagnoses. This technique integrates multimodal imaging phenotypes with genetic data in a noninvasive and high-throughput manner. In this review, we summarize the basic analytical framework of brain imaging biomarker genomics and elucidate two main implementation scenarios of this technique in AD studies: (1) exploring novel biomarkers and seeking mutual interpretability and (2) providing a diagnosis and prognosis for AD with combined use of machine learning methods and brain imaging biomarker genomics. Importantly, we highlight the necessity of brain imaging biomarker genomics, discuss the strengths and limitations of current methods, and propose directions for development of this research field.

BackgroundStomach adenocarcinoma (STAD) is one of the primary contributors to deaths that are due to cancer globally. At the moment, STAD does not have any universally acknowledged biological markers, and its predictive, preventive, and personalized medicine (PPPM) remains sufficient. Oxidative stress can promote cancer by increasing mutagenicity, genomic instability, cell survival, proliferation, and stress resistance pathways. As a direct and indirect result of oncogenic mutations, cancer depends on cellular metabolic reprogramming. However, their roles in STAD remain unclear.Method743 STAD samples from GEO and TCGA platforms were selected. Oxidative stress and metabolism-related genes (OMRGs) were acquired from the GeneCard Database. A pan-cancer analysis of 22 OMRGs was first performed. We categorized STAD samples by OMRG mRNA levels. Additionally, we explored the link between oxidative metabolism scores and prognosis, immune checkpoints, immune cell infiltration, and sensitivity to targeted drugs. A series of bioinformatics technologies were employed to further construct the OMRG-based prognostic model and clinical-associated nomogram.ResultsWe identified 22 OMRGs that could evaluate the prognoses of patients with STAD. Pan-cancer analysis concluded and highlighted the crucial part of OMRGs in the appearance and development of STAD. Subsequently, 743 STAD samples were categorized into three clusters with the enrichment scores being C2 (upregulated) > C3 (normal) > C1 (downregulated). Patients in C2 had the lowest OS rate, while C1 had the opposite. Oxidative metabolic score significantly correlates with immune cells and immune checkpoints. Drug sensitivity results reveal that a more tailored treatment can be designed based on OMRG. The OMRG-based molecular signature and clinical nomogram have good accuracy for predicting the adverse events of patients with STAD. Both transcriptional and translational levels of ANXA5, APOD, and SLC25A15 exhibited significantly higher in STAD samples.ConclusionThe OMRG clusters and risk model accurately predicted prognosis and personalized medicine. Based on this model, high-risk patients might be identified in the early stage so that they can receive specialized care and preventative measures, and choose targeted drug beneficiaries to deliver individualized medical services. Our results showed oxidative metabolism in STAD and led to a new route for improving PPPM for STAD.

Background: Traditional Chinese medicine in China is an important adjuvant therapy for the treatment of hepatocellular carcinoma (HCC) and traditional Chinese medicines injections have a wide range of clinical applications. The purpose of this study was to identify the active ingredients and related genes of traditional Chinese medicine injections that can treat hepatocellular carcinoma.Methods: Effective small molecule components were extracted from 14 types of traditional Chinese medicines from 8 injections and the main gene targets were identified. The 968 patients with HCC were classified based on the target gene set, and the characteristics of patients with different subtypes were analyzed. Patients with two subtypes of HCC were compared with normal tissues and cirrhosis to identify important gene targets related to traditional Chinese medicines in HCC progression.Results: In this study, 138 important genes associated with traditional Chinese medicines were identified and two HCC subtypes were identified. By analyzing the differences between the two subtypes, 25 related genes were associated with HCC subtypes. Through clinical and pharmacological analysis, this study identified quercetin as an important traditional Chinese medicines small molecule and secreted phosphoprotein 1 (SPP1) as an important oncogene in HCC.Conclusion: Traditional Chinese medicines injection is an important adjuvant treatment modality for HCC. SPP1 is an important oncogene in HCC.

High individual variation in the subjective cognitive decline (SCD) population makes functional connectivity (FC) biomarkers unstable. This study proposed a novel individual FC index, named individual proportion loss of functional connectivity strength (IPLFCS), and explored potential biomarkers for SCD using this new index. We proposed an IPLFCS analysis framework and compared it with traditional FC in Chinese and Western cohorts. Post hoc tests were used to determine biomarkers. Pearson’s correlation analysis was used to investigate the correlation between neuropsychological scores or cortical amyloid deposits and IPLFCS biomarkers. Receiver operating characteristic curves were utilized to evaluate the ability of potential biomarkers to distinguish between groups. IPLFCS of the left middle temporal gyrus (LMTG) was identified as a potential biomarker. The IPLFC was correlated with the traditional FC (r = 0.956, p < 0.001; r = 0.946, p < 0.001) and cortical amyloid deposition (r = −0.245, p = 0.029; r = −0.185, p = 0.048) in both cohorts. Furthermore, the IPLFCS decreased across the Alzheimer’s disease (AD) continuum. Its diagnostic efficiency was superior to that of existing fMRI biomarkers. These findings suggest that IPLFCS of the LMTG could be a potential biomarker of SCD.

Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types. Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs). CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity. Here we show lineage reprogramming to iCPCs through a dead Cas9 (dCas9)-based transcription activation system. Targeted and robust activation of endogenous cardiac factors, including GATA4, HAND2, MEF2C and TBX5 (G, H, M and T; GHMT), can reprogram human fibroblasts toward iCPCs. The iCPCs show potentials to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. Addition of MEIS1 to GHMT induces cell cycle arrest in G2/M and facilitates cardiac reprogramming. Lineage reprogramming of human fibroblasts into iCPCs provides a promising cellular resource for disease modeling, drug discovery and individualized cardiac cell therapy. Key words: Lineage reprogramming, Human foreskin fibroblasts, Induced cardiac progenitor cells, CRISPR/Cas9, SAM, Cardiac transcription factors

Lung cancer: Targeting a vicious circle Therapies targeting a molecular feedback loop involved in tumor growth may prove valuable for treating non-small-cell lung cancer. Fangbao Ding, Jianbing Huang, and co-workers at Shanghai Jiao Tong University in Shanghai, China, have shown how an enzyme called USP21 promotes cancer cell proliferation and tumor growth in non-small-cell lung cancer. The team took cancerous and non-cancerous lung tissue samples from 42 patients, and analyzed the expression and behavior of USP21. The enzyme was highly expressed in cancerous tissues, where it stabilized a known gene with the potential to cause cancer called YY1. This gene also regulated the expression of a particular RNA molecule, which in turn worked to increase levels of USP21. This cyclical process encouraged the proliferation, migration and invasion of non-small-cell lung cancer cells, and may provide a future therapeutic target.

PurposeTo evaluate the feasibility of apparent diffusion coefficient (ADC) value combined with texture analysis (TA) in preoperatively predicting the expression levels of Ki-67 and p53 in endometrial carcinoma (EC) patients.MethodsClinical, pathological and MRI findings of 110 EC patients were analyzed retrospectively. The expression levels of Ki-67 and p53 in EC tissues were detected by immunohistochemistry. ADC value was calculated, and three-dimensional (3D) texture features were measured on T2-weighted images (T2WI), diffusion-weighted images (DWI), and contrast-enhanced T1-weighted images (CE-T1WI). The univariate and multivariate logistic regression and cross-validations were used for the selection of texture features. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic efficiency of prediction model by the area under the curve (AUC) in the training and validation cohorts.ResultsSignificant differences of the ADC values were found in predicting Ki-67 and p53 (P=0.039, P=0.007). The AUC of the ADC value in predicting the expression levels of Ki-67 and p53 were 0.698, 0.853 and 0.626, 0.702 in the training and validation cohorts. The AUC of the TA model based on T2WI, DWI, CE-T1WI, and ADC value combined with T2WI + DWI + CE-T1WI in the training and validation cohorts for predicting the expression of Ki-67 were 0.741, 0.765, 0.733, 0.922 and 0.688, 0.691, 0.651, 0.938, respectively, and for predicting the expression of p53 were 0.763, 0.805, 0.781, 0.901 and 0.796, 0.713, 0.657, 0.922, respectively.ConclusionADC values combined with TA are beneficial for predicting the expression levels of Ki-67 and p53 in EC patients before surgery, and they provide higher auxiliary diagnostic values for clinical application.

Abstract Background Intimate partner violence (IPV) among pregnant women constitutes a global public health problem and a potential risk factor for adverse maternal and fetal outcomes. The present study aimed to examine the associations among IPV during pregnancy, prenatal depression, and adverse birth outcomes in Wuhan, China. Methods A cross-sectional study was performed from April 2013 to March 2014 in Wuhan, China. Sociodemographic characteristics, IPV during pregnancy, and depressive symptoms during pregnancy were assessed in the third trimester of pregnancy. Birth outcomes were collected after delivery using medical records. Chi-square tests and logistic regression analysis were used to examine the association between IPV and prenatal depression, as well as the association between IPV combined with prenatal depression and adverse birth outcomes. Results After adjustment for covariates, there was a statistically significant association between IPV during pregnancy and prenatal depression (adjusted odds ratio [aOR] = 2.50, 95% confidence interval [CI]: 1.60–3.90). IPV during pregnancy (aOR = 1.67, 95% CI: 1.08–2.56) and prenatal depression (aOR = 1.72, 95% CI: 1.11–2.68) were significantly associated with adverse birth outcomes. Women experiencing psychological abuse had a significantly higher odds of prenatal depression (aOR = 2.04, 95% CI: 1.19–3.49) and of adverse birth outcomes (aOR = 2.13, 95% CI: 1.08–2.58), compared with women who did not experience IPV and prenatal depression. Conclusions IPV during pregnancy and prenatal depression were significantly associated with adverse birth outcomes, after adjustment for socio-demographic and behavior factors. The findings suggest that early recognition of IPV and prenatal depression during antenatal care may protect pregnant women and improve birth outcomes.

Abstract Introduction Sex differences modulate catechol‐O‐methyltransferase (COMT) genotype effect at a synaptic dopamine level, which influences brain function as well as cognitive performance. In this study, we investigated how COMT Val158Met polymorphism and sex affect intrinsic functional connectivity and memory. Methods Intrinsic functional networks were extracted using independent component analysis of resting‐state functional magnetic resonance imaging data from 186 healthy young COMT‐genotyped participants. The association of these functional networks and memory function was tested to investigate whether the effect of COMT × sex interaction influences the association of intrinsic functional connectivity and memory performance. Quadratic curve fit estimation was used to examine the relationship between functional connectivity and speculative dopamine level among groups. Results COMT MM/MV carriers, relative to VV carriers, showed increased functional connectivity in left superior parietal lobule and right inferior frontal gyrus. Further, male MM/MV carriers showed significant higher mean functional connectivity in left inferior parietal lobule relative to male VV carriers and female MM/MV carriers, which was associated with worse immediate verbal recall performance. Additionally, the relationship between inferior parietal lobule functional connectivity and speculative dopamine level among groups fits the quadratic curve. Conclusions These findings suggest that the interaction of COMT genotype and sex might regulate synaptic dopaminergic concentrations and influence the association of intrinsic functional connectivity and immediate verbal memory in left inferior parietal lobule.

BACKGROUND:Adverse childhood experiences (ACEs) have been associated with poor health status later in life. The objective of the present study was to examine the relationship between ACEs and health-related behaviors, chronic diseases, and mental health in adults. METHODS:A cross-sectional study was performed with 1501 residents of Macheng, China. The ACE International Questionnaire (ACE-IQ) was used to assess ACEs, including psychological, physical, and sexual forms of abuse, as well as household dysfunction. The main outcome variables were lifetime drinking status, lifetime smoking status, chronic diseases, depression, and posttraumatic stress disorder. Multiple logistic regression models were used to examine the associations between overall ACE score and individual ACE component scores and risk behaviors/comorbidities in adulthood after controlling for potential confounders. RESULTS:A total of 66.2% of participants reported at least one ACE, and 5.93% reported four or more ACEs. Increased ACE scores were associated with increased risks of drinking (adjusted odds ratio [AOR] = 1.09, 95% confidence intervals [CI]: 1.00-1.09), chronic disease (AOR = 1.17, 95% CI: 1.06-1.28), depression (AOR = 1.37, 95% CI: 1.27-1.48), and posttraumatic stress disorder (AOR = 1.32, 95% CI: 1.23-1.42) in adulthood. After adjusting for confounding factors, the individual ACE components had different impacts on risk behavior and health, particularly on poor mental health outcomes in adulthood. CONCLUSIONS:ACEs during childhood were significantly associated with risk behaviors and poor health outcomes in adulthood, and different ACE components had different long-term effects on health outcomes in adulthood.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disease featuring executive control deficits as a prominent neuropsychological trait. Executive functions are implicated in multiple sub-networks of the brain; however, few studies examine these sub-networks as a whole in ADHD. By combining resting-state functional MRI and graph-based approaches, we systematically investigated functional connectivity patterns among four control-related networks, including the frontoparietal network (FPN), cingulo-opercular network, cerebellar network, and default mode network (DMN), in 46 drug-naive children with ADHD and 31 age-, gender-, and intelligence quotient-matched healthy controls (HCs). Compared to the HCs, the ADHD children showed significantly decreased functional connectivity that primarily involved the DMN and FPN regions and cross-network long-range connections. Further graph-based network analysis revealed that the ADHD children had fewer connections, lower network efficiency, and more functional modules compared with the HCs. The ADHD-related alterations in functional connectivity but not topological organization were correlated with clinical symptoms of the ADHD children and differentiated the patients from the HCs with a good performance. Taken together, our findings suggest a less-integrated functional brain network in children with ADHD due to selective disruption of key long-range connections, with important implications for understanding the neural substrates of ADHD, particularly executive dysfunction.

The excess sludge in the petrochemical industry is large in quantity, complex in composition, and highly harmful, and its rational disposal is of great significance for environmental protection and sustainable development. In the present study, a classification and disposal strategy for the excess sludge in the petrochemical industry is proposed. The strategy first analyzes the dioxin, flammability, corrosivity, reactivity, and leaching properties of the sludge, from which the waste type of the sludge (general waste or hazardous waste) can be determined. Then, methods of disposal can be selected depending on the type of waste and the corresponding risk analysis, enabling rationalized disposal of the sludge. To verify the effectiveness and practicability of the proposed sludge classification and disposal strategy, research on petrochemical excess sludge samples (i.e., Ah, Bl, and Cq) originated from three different regions in China is carried out as a case study. The component analysis of the above three sludge samples revealed that they are all general wastes. In addition, the possibility of employing Cq sludge for landfill, soil modification, and greening mud, as well as the risk of landfill and incineration disposal in solid waste landfills are investigated. Furthermore, natural radioactive elements uranium and thorium in Cq sludge sample are studied. The results show that Cq sludge cannot be used for landfill, soil modification, and greening mud due to excessive arsenic content. The proposed strategy provides a basis for the selection of reasonable petrochemical excess sludge disposal methods.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disease featuring executive control deficits as a prominent neuropsychological trait. Executive functions are implicated in multiple sub-networks of the brain; however, few studies examine these sub-networks as a whole in ADHD. By combining resting-state functional MRI and graph-based approaches, we systematically investigated functional connectivity patterns among four control-related networks, including the frontoparietal network (FPN), cingulo-opercular network, cerebellar network, and default mode network (DMN), in 46 drug-naive children with ADHD and 31 age-, gender-, and intelligence quotient-matched healthy controls (HCs). Compared to the HCs, the ADHD children showed significantly decreased functional connectivity that primarily involved the DMN and FPN regions and cross-network long-range connections. Further graph-based network analysis revealed that the ADHD children had fewer connections, lower network efficiency, and more functional modules compared with the HCs. The ADHD-related alterations in functional connectivity but not topological organization were correlated with clinical symptoms of the ADHD children and differentiated the patients from the HCs with a good performance. Taken together, our findings suggest a less-integrated functional brain network in children with ADHD due to selective disruption of key long-range connections, with important implications for understanding the neural substrates of ADHD, particularly executive dysfunction. [ABSTRACT FROM AUTHOR]

The Yellow River (Huanghe) is the second largest river in China and is known for its high turbidity. It also has remarkably high levels of dissolved uranium (U) concentrations (up to 38 nmol 1-1). To examine the mixing behavior of dissolved U between river water and seawater, surface water samples were collected along a salinity gradient from the Yellow River plume during September 2004 and were measured for dissolved U concentration, 254U:238U activity ratio, phosphate (PO43-), and suspended particulate matter. Laboratory experiments were also conducted to simulate the mixing process in the Yellow River plume using unfiltered Yellow River water and filtered seawater. The results showed a nonconservative behavior for dissolved U at salinities < 20 with an addition of U to the plume waters estimated at about 1.4 × 105 mol yr-1. A similarity between variations in dissolved U and PO43- with salinity was also found. There are two major mechanisms, desorption from suspended sediments and diffusion from interstitial waters of bottom sediments, that may cause the elevated concentrations of dissolved U and PO43- in mid-salinity waters. Mixing experiments indicate that desorption seems more responsible for the elevated dissolved U concentrations, whereas diffusion influences more the enrichment of PO43-. [ABSTRACT FROM AUTHOR]

An analytical method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established for the detection of 59 illegally added drugs in health foods with hypoglycemic, hypolipidemic and antihypertensive activity. Samples were extracted with methanol, and the extract was purified by the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method and blown to dryness under nitrogen gas. The residue was dissolved in 1 mL of 40% (V/V) methanol aqueous solution. The chromatographic separation was performed using reverse-phase chromatography on an ACQUITY UPLC HSS T3 column through gradient elution using a mobile phase consisting of acetonitrile and 0.1% aqueous formic acid (containing 5 mmol/L ammonium acetate). The mass spectrometer was operated in both the positive and negative ion modes using multi-reaction monitoring (MRM), and quantitative analysis was performed using a matrix-matched external standard method. The results showed that the calibration curves for the 59 illegally added drugs were linear with coefficient of determination (R2) greater than 0.980. Recoveries ranged from 60.2% to 119.5%, and relative standard deviations (RSDs) ranged from 1.2% to 15.0%. This method is characterized by simple pre-treatment, short analysis time, good sensitivity, high accuracy, and low impurity interference, and can be used to the detection of multiple illegal drugs in health foods with hypoglycemic, hypolipidemic and antihypertensive activity.