Selectivity of PEG/Salt Aqueous Two-Phase System Enhanced by Surfactant@MWCNT Composites.

Aqueous two-phase systems (ATPS) are considered a new type of green separation system, but their low selectivity to target molecules limits their practical application. In this study, we used surfactant@MWCNT as an adjuvant to improve the selectivity of PEG/(NH4)2SO4 ATPS. The surfactants used include Triton X-100 (TX-100), Tween 80, sodium dodecyl sulfate (SDS), sodium dodecyl benzenesulfonate (SDBS), and bis(2-ethylhexyl)sulfosuccinate sodium salt (AOT). Nine aromatic compounds, including syringic acid, vanillin, tryptophan, phenylalanine, tyrosine, mandelic acid, theophylline, theobromine, and cephalexin, were selected as model extracts. The results showed that the use of the surfactant@MWCNT composite as an adjuvant significantly improved the selectivity of the ATPS toward syringic acid among the nine extracts. Moreover, the selectivity of the ATPS for syringic acid with the TX-100/MWCNT composite as the adjuvant is better than that with the Tween 80/MWCNT composite as the adjuvant, followed by that with the anionic surfactant/MWCNT composite as the adjuvant. The enhanced selectivity of ATPS by the surfactant/MWCNT composite is ascribed to the spatial effect and the electrostatic and hydrophobic interactions between the extract and the surfactant adsorbed on the MWCNT.

Lateral Habenula Neurons Signal Cold Aversion and Participate in Cold Aversion.

The aversion to cold is a fundamental motivated behavior that contributes to the body temperature homeostasis. However, the involvement of the lateral habenula (LHb) as a regulatory hub for negative emotions in this physiological process remains uninvestigated. In this study, we demonstrate an elevation in the population activity of LHb neurons following exposure to cold stimuli. Additionally, we establish the necessity of Vglut2-expressing neurons within the LHb for the encoding of cold aversion behaviors. Furthermore, we have elucidated a neural circuit from excitatory neurons of the dorsomedial hypothalamus (DMH) to LHb that plays a crucial role in this progress. Manipulation of the DMH-LHb circuit has a significant impact on cold aversion behavior in mice. It is worth noting that this circuit does not exhibit any noticeable effects on autonomic thermoregulation or depression-like behavior. The identification of these neural mechanisms involved in behavioral thermoregulation provides a promising avenue for future research.

The Role of Cystathionine-ß-Synthase, H2S, and miRNA-377 in Hypoxic-Ischemic Encephalopathy: Insights from Human and Animal Studies.

We aimed to investigate the mechanism underlying the roles of miRNA-377, Cystathionine-ß-synthase (CBS), and hydrogen sulfide (H2S) in the development of hypoxic-ischemic encephalopathy (HIE). We investigated the relationship between CBS, H2S, and miR-377 in both humans with HIE and animals with hypoxic-ischemic insult. An animal model of fetal rats with hypoxic-ischemic brain injury was established, and the fetal rats were randomly assigned to control and hypoxic-ischemic groups for 15 min (mild) and 30 min (moderate) groups. Human samples were collected from children diagnosed with HIE. Healthy or non-neurological disease children were selected as the control group. Hematoxylin-eosin (HE) staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot were used to conduct this study. Hypoxia-ischemia induced pathological alterations in brain tissue changes were more severe in groups with severe hypoxic insult. miRNA-377 expression levels were upregulated in brain tissue and serum of fetal rats and human samples with HIE compared to controls. Conversely, CBS and H2S expression levels were significantly decreased in both human and animal samples compared to controls. Our findings suggest that CBS is a target gene of miR-377 which may contribute to the development of HIE by regulating CBS/H2S. H2S has a protective effect against hypoxic damage in brain tissue. The study provides new insights into the potential mechanisms underlying the protective role of H2S in hypoxic brain damage and may contribute to the development of novel therapies for HIE.

Identification of disulfidptosis-related subgroups and prognostic signatures in lung adenocarcinoma using machine learning and experimental validation.

Background: Disulfidptosis is a newly identified variant of cell death characterized by disulfide accumulation, which is independent of ATP depletion. Accordingly, the latent influence of disulfidptosis on the prognosis of lung adenocarcinoma (LUAD) patients and the progression of tumors remains poorly understood. Methods: We conducted a multifaceted analysis of the transcriptional and genetic modifications in disulfidptosis regulators (DRs) specific to LUAD, followed by an evaluation of their expression configurations to define DR clusters. Harnessing the differentially expressed genes (DEGs) identified from these clusters, we formulated an optimal predictive model by amalgamating 10 distinct machine learning algorithms across 101 unique combinations to compute the disulfidptosis score (DS). Patients were subsequently stratified into high and low DS cohorts based on median DS values. We then performed an exhaustive comparison between these cohorts, focusing on somatic mutations, clinical attributes, tumor microenvironment, and treatment responsiveness. Finally, we empirically validated the biological implications of a critical gene, KYNU, through assays in LUAD cell lines. Results: We identified two DR clusters and there were great differences in overall survival (OS) and tumor microenvironment. We selected the "Least Absolute Shrinkage and Selection Operator (LASSO) + Random Survival Forest (RFS)" algorithm to develop a DS based on the average C-index across different cohorts. Our model effectively stratified LUAD patients into high- and low-DS subgroups, with this latter demonstrating superior OS, a reduced mutational landscape, enhanced immune status, and increased sensitivity to immunotherapy. Notably, the predictive accuracy of DS outperformed the published LUAD signature and clinical features. Finally, we validated the DS expression using clinical samples and found that inhibiting KYNU suppressed LUAD cells proliferation, invasiveness, and migration in vitro. Conclusions: The DR-based scoring system that we developed enabled accurate prognostic stratification of LUAD patients and provides important insights into the molecular mechanisms and treatment strategies for LUAD.

Photocatalytic synthesis of azaheterocycle-fused piperidines and pyrrolidines via tandem difunctionalization of unactivated alkenes.

A variety of azaheterocycle-fused piperidines and pyrrolidines bearing CF3 and CHF2 functionalities were obtained using CF3SO2Na and CHF2SO2Na by visible light photocatalysis. This protocol involves a radical cascade cyclization via tandem tri- and difluoromethylation-arylation of pendent unactivated alkenes. Benzimidazole, imidazole, theophylline, purine, and indole serve as applicable anchors, thereby enriching the structural diversity of piperidine and pyrrolidine derivatives. This method features mild, additive-free and transition metal-free conditions.

PRM-D* Method for Mobile Robot Path Planning.

Various navigation tasks involving dynamic scenarios require mobile robots to meet the requirements of a high planning success rate, fast planning, dynamic obstacle avoidance, and shortest path. PRM (probabilistic roadmap method), as one of the classical path planning methods, is characterized by simple principles, probabilistic completeness, fast planning speed, and the formation of asymptotically optimal paths, but has poor performance in dynamic obstacle avoidance. In this study, we use the idea of hierarchical planning to improve the dynamic obstacle avoidance performance of PRM by introducing D* into the network construction and planning process of PRM. To demonstrate the feasibility of the proposed method, we conducted simulation experiments using the proposed PRM-D* (probabilistic roadmap method and D*) method for maps of different complexity and compared the results with those obtained by classical methods such as SPARS2 (improving sparse roadmap spanners). The experiments demonstrate that our method is non-optimal in terms of path length but second only to graph search methods; it outperforms other methods in static planning, with an average planning time of less than 1 s, and in terms of the dynamic planning speed, our method is two orders of magnitude faster than the SPARS2 method, with a single dynamic planning time of less than 0.02 s. Finally, we deployed the proposed PRM-D* algorithm on a real vehicle for experimental validation. The experimental results show that the proposed method was able to perform the navigation task in a real-world scenario.

Improved BDS-2/3 Satellite Ultra-Fast Clock Bias Prediction Based with the SSA-ELM Model.

Ultra-fast satellite clock bias (SCB) products play an important role in real-time precise point positioning. Considering the low accuracy of ultra-fast SCB, which is unable to meet the requirements of precise point position, in this paper, we propose a sparrow search algorithm to optimize the extreme learning machine (SSA-ELM) algorithm in order to improve the performance of SCB prediction in the Beidou satellite navigation system (BDS). By using the sparrow search algorithm's strong global search and fast convergence ability, we further improve the prediction accuracy of SCB of the extreme learning machine. This study uses ultra-fast SCB data from the international GNSS monitoring assessment system (iGMAS) to perform experiments. First, the second difference method is used to evaluate the accuracy and stability of the used data, demonstrating that the accuracy between observed data (ISUO) and predicted data (ISUP) of the ultra-fast clock (ISU) products is optimal. Moreover, the accuracy and stability of the new rubidium (Rb-II) clock and hydrogen (PHM) clock onboard BDS-3 are superior to those of BDS-2, and the choice of different reference clocks affects the accuracy of SCB. Then, SSA-ELM, quadratic polynomial (QP), and a grey model (GM) are used for SCB prediction, and the results are compared with ISUP data. The results show that when predicting 3 and 6 h based on 12 h of SCB data, the SSA-ELM model improves the prediction model by ~60.42%, 5.46%, and 57.59% and 72.27%, 44.65%, and 62.96% as compared with the ISUP, QP, and GM models, respectively. When predicting 6 h based on 12 h of SCB data, the SSA-ELM model improves the prediction model by ~53.16% and 52.09% and by 40.66% and 46.38% compared to the QP and GM models, respectively. Finally, multiday data are used for 6 h SCB prediction. The results show that the SSA-ELM model improves the prediction model by more than 25% compared to the ISUP, QP, and GM models. In addition, the prediction accuracy of the BDS-3 satellite is better than that of the BDS-2 satellite.

Daidzein ameliorates doxorubicin-induced cardiac injury by inhibiting autophagy and apoptosis in rats.

Backgrounds: Doxorubicin (Dox) is a classical antitumor antibiotic widely restricted for use due to its cardiotoxicity. Daidzein (Daid) is a soy isoflavone that enhances antioxidant enzyme systems and inhibits apoptosis to prevent cardiovascular diseases. In this study, we intended to assess whether Daid protects against Dox-induced cardiotoxicity and explored its underlying mechanisms. Methods: Male Sprague-Dawley (SD) rats were divided into five groups: control (Ctrl), 40 mg per kg per day Daidzein (Daid), 3 mg per kg per week doxorubicin (Dox), 20 mg per kg per day Daidzein + 3 mg per kg per week doxorubicin (Daid20 + Dox) and 40 mg per kg per day Daidzein + 3 mg per kg per week doxorubicin (Daid40 + Dox) groups. Cardiac function assessments, immunohistochemistry (IHC) and immunofluorescence (IF) analyses were initially performed in each group of rats. Secondly, the cell proliferative capacity analysis, AO staining, and LC3 puncta analysis were employed to evaluate the cellular response to Dox in H9c2 cells. Ultimately, the protein expressions of cleaved caspase3, LC3 II, Bcl-2, Bax, Akt, p-Akt, and cyclin D1 were examined by western blotting. Results: Pretreatment with a low dose of Daid rather than a high dose significantly enhanced cardiac function and alleviated histopathological deterioration of cardiomyocytes induced by Dox. Daid downregulated the protein levels of Bax, LC3 II, cleaved caspase3 and p-Akt, while up-regulating Bcl-2 and cyclin D1. The Akt agonist SC79 could invalidate all the protective effects of Daid both in vivo and in vitro. Conclusions: Daid reduced autophagy and apoptosis by inhibiting the PI3K/Akt pathway, thereby protecting the hearts from Dox-induced cardiac damage.

The relationship between miRNA-210 and SCN1B in fetal rats with hypoxic-ischemic brain injury.

Hypoxic-ischemic brain injury contributes to major neurodevelopmental disorders and is one of the leading causes of seizures, which substantially results in neurodevelopmental impairments with long-lasting outcomes and is one of the main causes of death in neonates. We aimed to investigate the correlation between miRNA-210 and SCN1B, a voltage-gated sodium channel gene, in brain tissue of fetal rats with hypoxic-ischemic brain injury. We found that after 10 min of hypoxia-ischemia, all reperfusion groups showed different degrees of damage. The degree of the injury increased in all the groups after 30 min of hypoxia-ischemia. Those changes include changes in the pericellular lumen, capillaries in the cortex, erythrocytes, enlarged pericellular lumen, the enlarged pericapillary lumen in the cortex, edema around glial cells, enlarged gap to form multiple necrotic foci, deformation of neurons, and loss of cell structure. The expression levels of HIF-1α, miRNA-210, and HIF-1α mRNA were higher in the hypoxic-ischemic groups than that in the control groups, among which the expression levels in the severe group were higher than that in mild group. SCN1B is down-regulated in both the mild and severe groups, and the lowest level was found at 30 min after hypoxia in both groups. MiRNA-210 plays a role in the development of hypoxic-ischemic encephalopathy (HIE) by regulating the expression changes of SCN1B. The brain tissue of fetal rats in the hypoxic-ischemic animal model showed pathological changes of brain injury.

A copper-catalyzed four-component reaction of arylcyclopropanes, nitriles, carboxylic acids and N-fluorobenzenesulfonimide: facile synthesis of imide derivatives.

An unprecedented copper-catalyzed four-component reaction of arylcyclopropanes, nitriles, carboxylic acids and N-fluorobenzenesulfonimide (NFSI) has been successfully developed, which represents the first example of a four-component reaction of non-donor-acceptor cyclopropanes. A wide range of imide derivatives were efficiently synthesized in excellent yields under mild conditions.

Transient Heat Transfer Characteristics in a Flat Plate Heat Sink with Mini-Channels for Cooling High Heat Flux IGBT.

Effective cooling of a high heat flux IGBT electronic system is highly related to system efficiency and safety. A flat plate heat sink was designed to experimentally investigate the transient heat transfer characteristics of IGBT cooling. It is made of aluminum with 20 mini-channels of 249 mm × 3 mm × 4 mm dimensions, which were manufactured by milling machines and melt inert gas (MIG) welding technology to ensure no deformation. Experiments were conducted using deionized water at atmospheric pressure with flow rates of 3.2-9.5 L/min and heat fluxes of 104-347 W/cm2. It was found that instantaneous start-stop and transient heating power variation might cause IGBT failure, especially under low Reynolds and Nusselt number conditions. The temperature rise rate and cooling rate vary with different system parameters. Heating rate can be reduced by high flow rate due to local subcooled boiling. The concept of respond time (RT) based on the piecewise function is suggested to evaluate the influence of transient condition on heating rate. Analysis of flow fluctuation indicated that it would not be a threat to the system except for in extreme cases. These findings provide a reference for the considerations of the design and manufacture of IGBT cooling flat plate heat sinks with mini-channels.

Efficient Synthesis of 2-OH Thioglycosides from Glycals Based on the Reduction of Aryl Disulfides by NaBH4.

An improved method to efficiently synthesize 2-OH thioaryl glycosides starting from corresponding per-protected glycals was developed, where 1,2-anhydro sugars were prepared by the oxidation of glycals with oxone, followed by reaction of crude crystalline 1,2-anhydro sugars with NaBH4 and aryl disulfides. This method has been further used in a one-pot reaction to synthesize glycosyl donors having both "armed" and "NGP (neighboring group participation)" effects.

Endoscopic or Follow-up Treatment for Gastric Indeterminate Tumors Is the Preferred Method of Management.

Background: Endoscopic forceps biopsy (EFB) lacks precision in diagnosing indeterminate tumors. When the presence of early gastric cancer (EGC) is macroscopically suspected, but biopsy pathology fails to give a diagnosis of neoplasia, it causes problems in clinical management. The purpose of this study was to discuss the outcome of gastric indeterminate tumors and the clinical factors associated with predicting EGC. Methods: The medical records of 209 patients diagnosed with gastric indeterminate neoplasia by biopsy forceps were retrospectively studied. Initial endoscopic findings were analyzed and predictors of EGC were evaluated. Results: The final pathological diagnosis in 209 patients included adenocarcinoma (n = 7), high-grade intraepithelial neoplasia (n = 11), low-grade intraepithelial neoplasia (n = 21), and non-neoplastic lesion (n = 170). Multivariate analysis showed that older age (OR = 1.78; 95% CI = 1.17-2.71; p = 0.008), patients undergoing narrow band imaging (NBI) (OR = 3.40; 95% CI = 1.37-8.43; p = 0.008), and surface erosion (OR = 3.53; 95% CI = 1.41-8.84; p = 0.007) were associated with the upgraded group, and were significantly associated with risk. Univariate logistic regression analysis showed that among patients with NBI, the presence of demarcation line (DL) (OR = 24.00; 95% CI = 4.99-115.36; p < 0.0001), microvascular (MV) pattern irregularity (OR = 9.129; 95% CI = 2.36-35.34; p = 0.001), and the presence of white opaque substance (WOS) (OR = 10.77; 95% CI = 1.14-101.72; p = 0.038) were significant risk factors. Conclusions: For gastric indeterminate tumors, older patient age, lesion surface with erosion, clear DL visible under NBI observation, presence of WOS, and irregular MV pattern are suggestive of the high possibility of neoplasia and need to be focused on and may benefit more from endoscopic resection treatment as opposed to simple endoscopic follow-up.

Novel Bimetallic Activated Center Alloying Mechanism Positive Electrodes for Aluminum Storage.

Aluminum is the most abundant metal element in the Earth's crust, thus developing the rechargeable aluminum-ion batteries (AIBs) provides an ideal opportunity to realize cells with pleasing energy-to-price ratios. However, the further development of AIBs is plagued by the scarcity of suitable positive electrode materials. Here, for the first time, a tin-based alloy positive electrode material for AIBs, Co3 Sn2 wrapped with graphene oxide (Co3 Sn2 @GO composite) is well-designed and investigated to understand the aluminum storage behavior. A series of experimental measurements and theoretical calculations results reveal that a novel "bimetallic activated center alloying reaction" aluminum storage mechanism is occurred on the prepared Co3 Sn2 positive electrode. The reversible alloying/de-alloying process in AlCl3 /[EMIm]Cl ionic liquid, where both Co and Sn in Co3 Sn2 alloys react electrochemically with Al3+ to form Alx Sn and Aly Co is first put forward. This study delineates new insights on the aluminum storage mechanism, which may guide to ultimately exploit the energy benefits of "bimetallic activated center alloying redox".

Copper-catalyzed radical cascade reaction of simple cyclobutanes: synthesis of highly functionalized cyclobutene derivatives.

Cyclobutenes as versatile and highly valuable synthons have been widely applied in synthesis. Although various methods for their synthesis have been well established, new strategies for the construction of the cyclobutene skeleton from simple substrates are still highly desirable. Starting from simple cyclobutanes, the construction of the cyclobutene skeleton especially introducing multiple functional groups simultaneously had never been achieved. Here, we developed a novel radical cascade strategy for the synthesis of highly functionalized cyclobutenes directly from cyclobutanes involving rare cleavage of four or five C-H bonds and formation of two C-N/C-S or three C-Br bonds. With copper as catalyst and N-fluorobenzenesulfonimide (NFSI) as oxidant, a wide range of diaminated, disulfonylated and tribrominated cyclobutene derivatives were efficiently synthesized.

A Visualized Dynamic Prediction Model for Overall Survival in Elderly Patients With Pancreatic Cancer for Smart Medical Services.

Background: Pancreatic cancer (PC) is a highly malignant tumor of the digestive system. The number of elderly patients with PC is increasing, and older age is related to a worse prognosis. Accurate prognostication is crucial in treatment decisions made for people diagnosed with PC. However, an accurate predictive model for the prognosis of these patients is still lacking. We aimed to construct nomograms for predicting the overall survival (OS) of elderly patients with PC. Methods: Patients with PC, older than 65 years old from 2010 to 2015 in the Surveillance, Epidemiology, and End Results database, were selected and randomly divided into training cohort (n = 4,586) and validation cohort (n = 1,966). Data of patients in 2016-2018 (n = 1,761) were used for external validation. Univariable and forward stepwise multivariable Cox analysis was used to determine the independent prognostic factors. We used significant variables in the training set to construct nomograms predicting prognosis. The performance of the models was evaluated for their discrimination and calibration power based on the concordance index (C-index), calibration curve, and the decision curve analysis (DCA). Results: Age, insurance, grade, surgery, radiation, chemotherapy, T, N, and American Joint Commission on Cancer were independent predictors for OS and thus were included in our nomogram. In the training cohort and validation cohort, the C-indices of our nomogram were 0.725 (95%CI: 0.715-0.735) and 0.711 (95%CI: 0.695-0.727), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves showed similar results. The calibration curves showed a high consensus between observations and predictions. In the external validation cohort, C-index (0.797, 95%CI: 0.778-0.816) and calibration curves also revealed high consistency between observations and predictions. The nomogram-related DCA curves showed better clinical utility compared to tumor-node-metastasis staging. In addition, we have developed an online prediction tool for OS. Conclusions: A web-based prediction model for OS in elderly patients with PC was constructed and validated, which may be useful for prognostic assessment, treatment strategy selection, and follow-up management of these patients.

The key sulfometuron-methyl degrading bacteria isolation based on soil bacterial phylogenetic molecular ecological networks and application for bioremediation of contaminated soil by immobilization.

The analysis of soil bacterial community has guiding significance for fully utilization of soil microbial resources. The results of high-throughput sequencing (HTS) showed that the bacteria in the three sulfometuron-methyl contaminated soil samples were mainly composed of 677 genera, including Phenylobacterium, Bacillus, belonging to 28 phyla, including Proteobacteria, Firmicutes. The diversity and richness of bacterial community decreased with the increase in sulfometuron-methyl concentration. In addition, sulfometuron-methyl could also affect the soil bacterial function based on PICRUSt functional predictive analysis. Combined with the results of HTS and phylogenetic molecular ecological networks (pMENs), 12 genera, including Ralstonia (Pi=0.64), were identified as the key soil microflora (intra-module connectivity Zi ≥ 2.5 or inter-module connectivity Pi ≥ 0.62), and the abundance of Ralstonia significantly increased with the concentration of sulfometuron-methyl, indicating that the strains of this genus might be the potential degrading bacteria and could form a stable relationship with indigenous microorganisms. Among the isolated bacteria of genus Ralstonia, one strain, named Ralstonia sp. JM-1, was verified to possess higher sulfometuron-methyl degradation efficiency, which completely degraded 20 mg L-1 of sulfometuron-methyl within 96 h. Furthermore, the immobilized strains generated by the mixture of 2.0 g bamboo charcoal and 3.0 mL bacterial suspension for 24 h had the highest sulfometuron-methyl degradation rate than that under other conditions, and the dynamic process degrading 10-30 mg L-1 of sulfometuron-methyl conforms to the zero-order kinetic equation. The bioremediation of contaminated soil showed the immobilized strains could completely degrade sulfometuron-methyl (1.39 mg kg-1) in contaminated soil within 9 d, which is higher than that application of strains in the free state (74.8%). This study could provide ideas for the isolation of functional strains and a theoretical basis for the bioremediation of STM and other contaminated soils.

Irregular shape as an independent predictor of prognosis in patients with primary intracerebral hemorrhage.

The utility of noncontrast computed tomography markers in the prognosis of spontaneous intracerebral hemorrhage has been studied. This study aimed to investigate the predictive value of the computed tomography (CT) irregularity shape for poor functional outcomes in patients with spontaneous intracerebral hemorrhage. We retrospectively reviewed all 782 patients with intracranial hemorrhage in our stroke emergency center from January 2018 to September 2019. Laboratory examination and CT examination were performed within 24 h of admission. After three months, the patient's functional outcome was assessed using the modified Rankin Scale. Multinomial logistic regression analyses were applied to identify independent predictors of functional outcome in patients with intracerebral hemorrhage. Out of the 627 patients included in this study, those with irregular shapes on CT imaging had a higher proportion of poor outcomes and mortality 90 days after discharge (P < 0.001). Irregular shapes were found to be significant independent predictors of poor outcome and mortality on multiple logistic regression analysis. In addition, the increase in plasma D-dimer was associated with the occurrence of irregular shapes (P = 0.0387). Patients with irregular shapes showed worse functional outcomes after intracerebral hemorrhage. The elevated expression level of plasma D-dimers may be directly related to the formation of irregular shapes.

Study of Sex Differences in Unmedicated Patients With Major Depressive Disorder by Using Resting State Brain Functional Magnetic Resonance Imaging.

Some important clinical characteristics of major depressive disorder (MDD) differ between sexes. We explored abnormal spontaneous neuronal activity in MDD patients using the amplitude of low-frequency fluctuation (ALFF) and its relationship to clinical manifestations in male and female patients, to seek the neural mechanisms underlying sex-related differences in depression. Twenty-five male MDD patients, 36 female MDD patients, and 25 male and 36 female matched healthy controls (HC) were included. The ALFF difference was investigated among four groups, and partial correlation analysis was used to explore a possible clinical relevance. The main effect results of sex difference were located in the bilateral caudate nucleus and posterior cingulate gyrus. Post hoc comparisons found that the male MDD patients showed decreased ALFF in the bilateral caudate nucleus and posterior cingulate gyrus when compared with female MDD patients/female HCs, and female MDD patients showed increased ALFF in the bilateral caudate nucleus and posterior cingulate gyrus when compared with male HCs. The average ALFF of the right caudate nucleus was positively correlated with illness duration in female MDD patients. Our results suggest that the sex-specific abnormal brain activity might be a potential pathomechanism of different symptoms in male and female MDD patients.

Study on endocrine disruption effect of paclobutrazol and uniconazole on the thyroid of male and female rats based on lipidomics.

The present study investigated the effects of paclobutrazol and uniconazole on thyroid endocrine system in rats. Lipidomic analysis was performed to obtain the biomarkers of thyroid endocrine disruption induced by paclobutrazol and uniconazole. Network pharmacology was further used to discover potential targets of biomarkers related to drugs and diseases. After paclobutrazol and uniconazole administration, seven and four common biomarkers related to thyroid endocrine disruption for female and male rats were obtained, respectively. Paclobutrazol and uniconazole significantly increased the biomarker levels of PG (12:0/15:0), PS (14:0/16:0), PA (20:1/15:0) and PG (13:0/17:0) in both sexes of rats. Exposure to paclobutrazol additionally caused a significant decrease of PG (22:6/20:2), PE (24:1/18:1) and PE (24:0/18:0) in female rats, while an increase in male rats. Changes of the common biomarkers for paclobutrazol and uniconazole revealed similar endocrine disruption effect, which was higher in the females. Network pharmacology and KEGG pathway analysis indicated that the thyroid endocrine disrupting effects of paclobutrazol and uniconazole may be related to V-akt murine thymoma viral oncogene homolog (Akts), mitogen-activated protein kinase (MAPKs), epidermal growth factor receptor (EGFR), Insulin-like growth factor (IGF-1), IGF-IR and V-Raf murine sarcoma viral oncogene homolog B1 (BRAF). The results demonstrated that paclobutrazol and uniconazole could cause thyroid endocrine disorders in male and female rats, which were sex-specific, thus highlighting the importance of safe and effective application of these plant growth regulators.