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We report a rare case of concurrent pulmonary and cerebral mucormycosis initially misdiagnosed as a metastatic tumor. A 66-year-old man with a complaint of progressive right-sided limb weakness for 3 days. Head MRI showed a left parietal occupying lesion with severe edema, and a chest CT scan showed a parenchymal mass with speculation and pleural invasion in his left lung. The patient was initially diagnosed with brain metastases from lung cancer and underwent a craniotomy. Many fungal hyphae were found in the left parietal lesion, and the final pathological diagnosis of intracranial mucormycosis. After craniotomy and an entire course of treatment with liposomal amphotericin B, the patient was completely cured of both intracranial and pulmonary occupying lesions. We hope that this case experience will help expand neurosurgeons' differential diagnosis and treatment of such diseases.

Abstract Schizophrenia is a complex polygenic disease that is affected by genetic, developmental, and environmental factors. Accumulating evidence indicates that environmental factors such as maternal infection and excessive prenatal neuroinflammation may contribute to the onset of schizophrenia by affecting epigenetic modification. We recently identified a schizophrenia-associated upregulated long noncoding RNA (lncRNA) RP5-998N21.4 by transcriptomic analysis of monozygotic twins discordant for schizophrenia. Importantly, we found that genes coexpressed with RP5-998N21.4 were enriched in immune defense-related biological processes in twin subjects and in RP5-998N21.4-overexpressing (OE) SK-N-SH cell lines. We then identified two genes encoding an interferon-induced protein with tetratricopeptide repeat (IFIT) 2 and 3, which play an important role in immune defense, as potential targets of RP5-998N21.4 by integrative analysis of RP5-998N21.4 OE-induced differentially expressed genes (DEGs) in SK-N-SH cells and RP5-998N21.4-coexpressed schizophrenia-associated DEGs from twin subjects. We further demonstrated that RP5-998N21.4 positively regulates the transcription of IFIT2 and IFIT3 by binding to their promoter regions and affecting their histone modifications. In addition, as a general nuclear coactivator, RMB14 (encoding RNA binding motif protein 14) was identified to facilitate the regulatory role of RP5-998N21.4 in IFIT2 and IFIT3 transcription. Finally, we observed that RP5-998N21.4 OE can enhance IFIT2- and IFIT3-mediated immune defense responses through activation of signal transducer and activator of transcription 1 (STAT1) signaling pathway in U251 astrocytoma cells under treatment with the viral mimetic polyinosinic: polycytidylic acid (poly I:C). Taken together, our findings suggest that lncRNA RP5-998N21.4 is a critical regulator of immune defense, providing etiological and therapeutic implications for schizophrenia.

Mechanical performance evaluation of a new disc spring-cable counter pressure shock absorber is focused on in this study. The proposed shock absorber is always in a compressive working state with energy dissipation capacity under both tension and compression loadings. The design formulas of its axial bearing capacity, vertical stiffness, deformation energy of the shock absorber were derived, and the corresponding specific design process was provided in detail. Experimental and numerical investigations of the mechanical performance were conducted under static and dynamic loadings. The parameters influencing the laws of the mechanical performance of the shock absorber, including loading frequency, pre-compression deformation and loading amplitude, were investigated. The rationality of the proposed shock absorber was firstly verified through comparative analysis using experimental, numerical and theoretical calculations. The shock absorber with a friction coefficient of 0.005 between disc springs, and a friction coefficient of 0.3 between the disc spring and cover plate has the smallest error between experiment and theory for the flattening force. The bearing capacity of the shock absorber exhibits a linear relationship with the loading displacement in static loading. In dynamic loading, however, the bearing capacity shows a trend of slow growth followed by rapid growth. The energy dissipation capacity of the shock absorber shows an increase with the increase of loading displacement. The minimum equivalent damping ratio of all of the dynamic test cases is 7%, with a maximum up to 15.3%. Under the same loading frequency, the equivalent stiffness and equivalent damping ratio have a linear amplification trend with the increase of pre-compression deformation, and the maximum increase of equivalent stiffness is equal to 41.37%. Under the same loading frequency and pre-compression deformation, the energy consumption capacity can be improved by increasing the loading amplitude.

It is very challenging to visualize implantable medical devices made of biodegradable polymers in deep tissues. Herein, we designed a novel macromolecular contrast agent with ultrahigh radiopacity (iodinate content > 50%) via polymerizing an iodinated trimethylene carbonate monomer into the two ends of poly(ethylene glycol) (PEG). A set of thermosensitive and biodegradable polyester-PEG-polyester triblock copolymers with varied polyester compositions synthesized by us, which were soluble in water at room temperature and could spontaneously form hydrogels at body temperature, were selected as the demonstration materials. The addition of macromolecular contrast agent did not obviously compromise the injectability and thermogelation properties of polymeric hydrogels, but conferred them with excellent X-ray opacity, enabling visualization of the hydrogels at clinically relevant depths through X-ray fluoroscopy or Micro-CT. In a mouse model, the 3D morphology of the radiopaque hydrogels after injection into different target sites was visible using Micro-CT imaging, and their injection volume could be accurately obtained. Furthermore, the subcutaneous degradation process of a radiopaque hydrogel could be non-invasively monitored in a real-time and quantitative manner. In particular, the corrected degradation curve based on Micro-CT imaging well matched with the degradation profile of virgin polymer hydrogel determined by the gravimetric method. These findings indicate that the macromolecular contrast agent has good universality for the construction of various radiopaque polymer hydrogels, and can nondestructively trace and quantify their degradation in vivo. Meanwhile, the present methodology developed by us affords a platform technology for deep tissue imaging of polymeric materials.

The crystal structure, Raman vibration, chemical bond characteristics, and microwave dielectric properties of Zn1-xCuxWO4 (x = 0–0.15) ceramics prepared by a solid-state reaction were investigated by XRD refinement, Raman spectroscopy, P-V-L theory and XPS. According to the P-V-L theory, the properties of the W-O bond are stronger than those of the Zn-O bond, which makes a major contribution to the dielectric properties. The relative permittivity is mainly affected by the average bond ionicity, and the variations in the dielectric loss and τf are mainly attributed to the lattice energy and bond energy. XPS shows that the presence of Cu+ could produce oxygen vacancy defects, increasing the dielectric loss. Additionally, Raman spectra show that the increasing molecular polarizability causes the Raman shift to move to a low wavenumber, and the changes in Raman intensity and FWHM lead to a decrease in the degree of short-range ordering. Particularly, Zn0.97Cu0.03WO4 ceramics sintered at 925 °C showed satisfactory properties (εr = 14.20, tanδ = 1.473 × 10−4 at 9.087 GHz, and τf = −40 ppm/°C), which can potentially be applied to LTCC technology and indicate that Cu substitution can not only reduce the sintering temperature, but also optimize the dielectric properties.

Abstract Infrared image enhancement is an effective way to solve contrast reduction or details degradation in infrared imagery. An infrared enhancement approach based on local saliency extraction is proposed here. First, saliency maps are extracted within a local window by combining spatial weight. Second, with the change of the window size, potential targets and details in different sizes can be extracted. Considering window sizes as the scales, the saliency maps are obtained and infrared images are enhanced at different scales, and finally, multi‐scale fusion is used to achieve the enhancement. Eight popular infrared enhancement approaches are introduced for comparison. Subjective qualitative observation experiments show that our strategy based on local saliency analysis and multi‐scale fusion can well extract potential targets and areas of varying size from the source images with different sizes, to obtain a good enhancement effect. Meanwhile, we introduce six objective evaluation methods to measure the results, and the evaluation data to prove the effectiveness of the proposed algorithm. The experiments also indicate the real‐time processing capability of the proposed method. The proposed method is finally well applied in the hardware system and shows its good performance.

Background and objectiveAround 33.5 million patients suffered from atrial fibrillation (AF), causing complications and increasing mortality and disability rate. Upstream treatment for AF is getting more popular in clinical practice in recent years. The angiotensin receptor-neprilysin inhibitor (ARNI) is one of the potential treatment options. Our study aimed to investigate the effect of ARNI on atrial electrical instability and structural remodeling in AF.MethodsOur research consisted of two parts – a retrospective real-world clinical study and an animal experiment on calmness to verify the retrospective founding. In the retrospective study, we reviewed all patients (n = 110) who had undergone the first AF ablation from 1 August 2018 to 1 March 2022. Patients with ARNI (n = 36) or angiotensin II receptor antagonist (ARB) (n = 35) treatment were enrolled. Their clinical data, ultrasound cardiogram (UCG) and Holter parameters were collected before radiofrequency catheter ablation (RFCA) as baseline and at 24-week follow-up. Univariate and multivariate logistic regression analysis were performed. In the animal experiment, we established an AF model (n = 18) on canines by rapid atrial pacing. After the successful procedure of pacing, all the 15 alive beagles were equally and randomly assigned to three groups (n = 5 each): Control group, ARB group, and ARNI group. UCG was performed before the pacing as baseline. Physiological biopsy, UCG, and electrophysiological study (EPS) were performed at 8-week.ResultsClinical data showed that the atrial arrhythmia rate at 24-week was significantly lower in ARNI group compared to ARB group (P < 0.01), and ARNI was independently associated with a lower atrial arrhythmia rate (P < 0.05) at 24-week in multivariate regression logistic analysis. In the animal experiment, ARNI group had a higher atrial electrical stability score and a shorter AF duration in the EPS compared to Control and ARB group (P < 0.05). In the left atrium voltage mapping, ARNI group showed less low voltage and disordered zone compared to Control and ARB group. Compared to Control group, right atrium diameter (RAD), left ventricle end-diastolic volume index (LVEDVI), E/A, and E/E′ were lower in ARNI group (P < 0.05) at the 8-weeks follow-up, while left atrium ejection fraction (LAEF) and left ventricle ejection fraction (LVEF) were higher (P < 0.01). Compared to ARB group, LVEF was higher in ARNI group at the 8-week follow-up (P < 0.05). ARB and ARNI group had a lower ratio of fibrotic lesions in the left atrium tissues compared to Control group (P < 0.01), but no difference was found between the ARB and the ARNI group.ConclusionARNI could reduce atrial electrical instability in AF in comparison with ARB in both retrospective study and animal experiment.

Background: Gen1 mutation can cause various phenotypes of congenital anomaly of the kidney and urinary tract (CAKUT). An intrauterine low-protein isocaloric diet can also cause CAKUT phenotypes in offspring. However, single factors such as gene mutation or abnormal environmental factor during pregnancy can only explain part of the pathogenesis of CAKUT. Objectives: A low-protein isocaloric diet was fed to Gen1-mutant mice throughout pregnancy to establish a Gen1-mutant mouse model exposed to a low-protein isocaloric intrauterine environment. The mice were divided into 4 groups: normal (22%) protein diet (ND) + wild-type mice (CON group), ND + Gen1PB/+ mice (Gen1PB/+ group), low (6%)-protein isocaloric diet (LD) + wild-type mice (LD group), and the LD + Gen1PB/+ groups. Methods: The experimental design included observing proportion and distribution of CAKUT phenotypes of neonatal mice; evaluating the number of ureteric buds (UBs) on embryonic day (E) 11.5, the location of UBs on E11.5, and length of the common nephric duct (CND); isolating embryonic kidneys on E11.5 from the Gen1PB/+ group and culturing embryonic kidneys in medium containing 10% serum or serum-free medium to observe the branching of UBs; and detecting the p-PLCγ, p-Akt, and p-ERK1/2 in UBs and CND on E11.5, as well as the apoptosis and proliferation of tissues by immunofluorescence staining. Results: We found that the incidence of CAKUT in offspring of Gen1PB/+ mice under an intrauterine low-protein isocaloric diet environment was significantly increased, and a duplicated collecting system was the dominant phenotype of CAKUT. During the early stage of metanephric development, ectopic protrusion of UBs may appear and lower locations of UBs in Gen1PB/+ mice under an intrauterine low-protein isocaloric diet environment and the number of UB branches in the serum-free culture condition significantly decreased. Further examination revealed that p-PLCγ signaling and tissue apoptosis were abnormal in UBs and the CND at the early stage of kidney development. Conclusions: The aforementioned findings suggest that an intrauterine low-protein isocaloric diet can aggravate the occurrence of CAKUT in Gen1-mutant mice, which might affect key steps in the metanephric development, such as the protrusion of UBs, which might be related to mediate UBs and CND apoptosis through p-PLCγ signaling.

Rhizoma Dioscoreae Bulbiferae (RDB) was effective on relieving cough and expectorant but accompanied by severe toxicity, especially in hepatotoxicity. A previous study found that processing with Angelicae Sinensis Radix (ASR) reduced RDB-induced hepatotoxicity. However, up to now, the optimized processing process of ASR-processed RDB has not been explored or optimized, and the detoxification mechanism is still unknown. This study evaluated the detoxification technology and possible mechanism of processing with ASR on RDB-induced hepatotoxicity. The optimized processing process of ASR-processed RDB was optimized by the content of diosbulbin B (DB), the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and histopathological analysis. The processing detoxification mechanism was evaluated by detecting the antioxidant levels of nuclear factor E2 related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1), glutamylcysteine ligase catalytic subunit (GCLM), and the levels of downstream antioxidant factors of Nrf2. Besides, the antitussive and expectorant efficacy of RDB was also investigated. This work found that processing with ASR attenuated RDB-induced hepatotoxicity, which can be verified by reducing the levels of ALT, AST, and ALP, and reversing the pathological changes of liver histomorphology. And the optimized processing process of ASR-processed RDB is “processing at a mass ratio of 100:20 (RDB:ASR) and a temperature of 140°C for 10 min.” Further results corroborated that the intervention of processed products of ASR-processed RDB remarkably upregulated the Nrf2/HO-1/NQO1/GCLM protein expression levels in liver, and conserved antitussive and expectorant efficacy of RDB. The above findings comprehensively indicated that the optimized processing process of ASR-processed RDB was “processing at a mass ratio of 100:20 (RDB:ASR) and a temperature of 140°C for 10 min,” and the processing detoxification mechanism involved enhancing the level of Nrf2-mediated antioxidant defense in liver as a key target organ.

Pod size is one of the most important agronomic features of peanuts, which directly affects peanut yield. Studies on the regulation mechanism underpinning pod size in cultivated peanuts remain hitherto limited compared to model plant systems. To better understand the molecular elements that underpin peanut pod development, we conducted a comprehensive analysis of chronological transcriptomics during pod development in four peanut accessions with similar genetic backgrounds, but varying pod sizes. Several plant transcription factors, phytohormones, and the mitogen-activated protein kinase (MAPK) signaling pathways were significantly enriched among differentially expressed genes (DEGs) at five consecutive developmental stages, revealing an eclectic range of candidate genes, including PNC, YUC, and IAA that regulate auxin synthesis and metabolism, CYCD and CYCU that regulate cell differentiation and proliferation, and GASA that regulates seed size and pod elongation via gibberellin pathway. It is plausible that MPK3 promotes integument cell division and regulates mitotic activity through phosphorylation, and the interactions between these genes form a network of molecular pathways that affect peanut pod size. Furthermore, two variant sites, GCP4 and RPPL1, were identified which are stable at the QTL interval for seed size attributes and function in plant cell tissue microtubule nucleation. These findings may facilitate the identification of candidate genes that regulate pod size and impart yield improvement in cultivated peanuts.

Background The association between inflammation and major depressive disorder (MDD) remains poorly understood, given the heterogeneity of patients with MDD.Aims We investigated inflammatory markers, such as interleukin (IL)-6, high-sensitivity C reactive protein (hsCRP) and tumour necrosis factor-α (TNF-α) in melancholic, atypical and anxious depression and explored whether baseline inflammatory protein levels could indicate prognosis.Methods The sample consisted of participants (aged 18–55 years) from a previously reported multicentre randomised controlled trial with a parallel-group design registered with ClinicalTrials.gov, including melancholic (n=44), atypical (n=37) and anxious (n=44) patients with depression and healthy controls (HCs) (n=33). Subtypes of MDD were classified according to the 30-item Inventory of Depressive Symptomatology, Self-Rated Version and the 17-item Hamilton Depression Rating Scale. Blood levels of TNF-α, IL-6 and hsCRP were assessed using antibody array analysis.Results Patients with MDD, classified according to melancholic, atypical and anxious depression subtypes, and HCs did not differ significantly in baseline TNF-α, IL-6 and hsCRP levels after adjustment. In patients with anxious depression, hsCRP levels increased significantly if they experienced no pain (adjusted (adj.) p=0.010) or mild to moderate pain (adj. p=0.038) compared with those with severe pain. However, the patients with anxious depression and severe pain showed a lower trend in hsCRP levels than patients with atypical depression who experienced severe pain (p=0.022; adj. p=0.155). Baseline TNF-α (adj. p=0.038) and IL-6 (adj. p=0.006) levels in patients in remission were significantly lower than those in patients with no remission among the participants with the atypical depression subtype at the eighth-week follow-up.Conclusions This study provides evidence of differences in inflammatory proteins in patients with varied symptoms among melancholic, atypical and anxious depression subtypes. Further studies on the immunoinflammatory mechanism underlying different subtypes of depression are expected for improved individualised therapy.Trial registration number NCT03219008.

American ginseng extract (AGE) is an efficient and low-toxic adjuvant for type 2 diabetes mellitus (T2DM). However, the metabolic mechanisms of AGE against T2DM remain unknown. In this study, a rat model of T2DM was created and administered for 28 days. Their biological (body weight and serum biochemical indicators) and pathological (pancreatic sections stained with HE) information were collected for further pharmacodynamic evaluation. Moreover, an ultra-performance liquid chromatography–mass spectrometry–based (UHPLC–MS/MS–based) untargeted metabolomics method was used to identify potential biomarkers of serum samples from all rats and related metabolic pathways. The results indicated that body weight, fasting blood glucose (FBG), fasting blood insulin (FINS), blood triglyceride concentration (TG), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI), and impaired islet cells were significantly improved after the high dose of AGE (H_AGE) and metformin treatment. Metabolomics analysis identified 101 potential biomarkers among which 94 metabolites had an obvious callback. These potential biomarkers were mainly enriched in nine metabolic pathways linked to amino acid metabolism and lipid metabolism. Tryptophan metabolism and glutathione metabolism, as differential metabolic pathways between AGE and metformin for treating T2DM, were further explored. Further analysis of the aforementioned results suggested that the anti-T2DM effect of AGE was closely associated with inflammation, oxidative stress, endothelial dysfunction, dyslipidemia, immune response, insulin resistance, insulin secretion, and T2DM-related complications. This study can provide powerful support for the systematic exploration of the mechanism of AGE against T2DM and a basis for the clinical diagnosis of T2DM.

Salt stress decreases plant growth and is a major threat to crop yields worldwide. The present study aimed to alleviate salt stress in plants by inoculation with halophilic plant growth-promoting rhizobacteria (PGPR) isolated from an extreme environment in the Qinghai–Tibetan Plateau. Wheat plants inoculated with Bacillus halotolerans KKD1 showed increased seedling morphological parameters and physiological indexes. The expression of wheat genes directly involved in plant growth was upregulated in the presence of KKD1, as shown by real-time quantitative PCR (RT-qPCR) analysis. The metabolism of phytohormones, such as 6-benzylaminopurine and gibberellic acid were also enhanced. Mining of the KKD1 genome corroborated its potential plant growth promotion (PGP) and biocontrol properties. Moreover, KKD1 was able to support plant growth under salt stress by inducing a stress response in wheat by modulating phytohormone levels, regulating lipid peroxidation, accumulating betaine, and excluding Na+. In addition, KKD1 positively affected the soil nitrogen content, soil phosphorus content and soil pH. Our findings indicated that KKD1 is a promising candidate for encouraging wheat plant growth under saline conditions.

Dandelions (Taraxacum spp.) play an important role in the treatment of inflammatory diseases. In this study, we investigated the anti-inflammatory effects of Dandelion Extract (DE) in LPS-induced RAW264.7 macrophages and copper sulfate (CuSO4)-induced zebrafish larvae. DE was not toxic to RAW264.7 cells at 75 μg/ml as measured by cell viability, and DE inhibited LPS-induced cell morphological changes as measured by inverted microscopy. In survival experiments, DE at 25 μg/ml had no toxicity to zebrafish larvae. By using an enzymatic standard assay, DE reduced the production of nitric oxide (NO) in LPS-induced RAW264.7 cells. Fluorescence microscopy results show that DE reduced LPS-induced ROS production and apoptosis in RAW264.7 cells. DE also inhibited CuSO4-induced ROS production and neutrophil aggregation in zebrafish larvae. The results of flow cytometry show that DE alleviated the LPS-induced cell cycle arrest. In LPS-induced RAW264.7 cells, RT-PCR revealed that DE decreased the expression of M1 phenotypic genes iNOS, IL-6, and IL-1β while increasing the expression of M2 phenotypic genes IL-10 and CD206. Furthermore, in CuSO4-induced zebrafish larvae, DE reduced the expression of iNOS, TNF-α, IL-6, and IL-10. The findings suggest that DE reduces the LPS-induced inflammatory response in RAW264.7 cells by regulating polarization and apoptosis. DE also reduces the CuSO4-induced inflammatory response in zebrafish larvae.

BackgroundTwo-thirds of major depressive disorder (MDD) patients initially present with somatic symptoms, yet no study has used approaches based on somatic symptoms to subtype MDD. This study aimed to classify MDD via somatic symptoms and tracked the prognosis of each subtype.MethodsData were obtained from the study of Algorithm Guided Treatment Strategies for Major Depressive Disorder (AGTs-MDD). We recruited 395 subjects who received monotherapy of mirtazapine or escitalopram and conducted 2-, 4-, 6-, 8-, and 12-week follow-up assessments (n = 311, 278, 251, 199, and 178, respectively). Latent profile analysis (LPA) was performed on somatic symptom items of the depression and somatic symptoms scale (DSSS). Generalized linear mixed models (GLMM) were used to study the longitudinal prognosis of the subtypes classed by LPA. Primary outcome measures were the Hamilton Depression Rating Scale (HAMD), HAMD score reduction rate, as well as somatic and depressive items of DSSS.ResultsThree subtypes of MDD were found, namely, depression with mild somatic symptoms (68.9%), depression with moderate somatic symptoms (19.2%), and depression with severe somatic symptoms (11.9%). Scores of HAMD (F = 3.175, p = 0.001), somatic (F = 23.594, p < 0.001), and depressive (F = 4.163, p < 0.001) DSSS items throughout the 12-week follow-up showed statistical difference among the three subtypes. The moderate group displayed a higher HAMD-17 score and a lower reduction rate at the 6th week, and more severe depressive symptoms both at the 4th and 6th weeks.ConclusionThe results indicate that somatic symptoms should be emphasized in patients with MDD, and more attention is needed for those with moderate somatic symptoms, which may be relevant to a worse prognosis.

Background and objective: Spirometry is commonly used to assess small airway dysfunction (SAD). Impulse oscillometry (IOS) can complement spirometry. However, discordant spirometry and IOS in the diagnosis of SAD were not uncommon. We examined the association between spirometry and IOS within a large cohort of subjects to identify variables that may explain discordant spirometry and IOS findings.Methods: 1,836 subjects from the ECOPD cohort underwent questionnaires, symptom scores, spirometry, and IOS, and 1,318 subjects were examined by CT. We assessed SAD with R5-R20 > the upper limit of normal (ULN) by IOS and two of the three spirometry indexes (maximal mid-expiratory flow (MMEF), forced expiratory flow (FEF)50%, and FEF75%) < 65% predicted. Multivariate regression analysis was used to analyze factors associated with SAD diagnosed by only spirometry but not IOS (spirometry-only SAD) and only IOS but not spirometry (IOS-only SAD), and line regression was used to assess CT imaging differences.Results: There was a slight agreement between spirometry and IOS in the diagnosis of SAD (kappa 0.322, p < 0.001). Smoking status, phlegm, drug treatment, and family history of respiratory disease were factors leading to spirometry-only SAD. Spirometry-only SAD had more severe emphysema and gas-trapping than IOS-only SAD in abnormal lung function. However, in normal lung function subjects, there was no statistical difference in emphysema and gas-trapping between discordant groups. The number of IOS-only SAD was nearly twice than that of spirometry.Conclusion: IOS may be more sensitive than spirometry in the diagnosis of SAD in normal lung function subjects. But in patients with abnormal lung function, spirometry may be more sensitive than IOS to detect SAD patients with clinical symptoms and CT lesions.

ObjectivesConventional biochemical indexes may have predictive values in clinical identification between bipolar disorder (BD) and major depressive disorder (MDD).MethodsThis study included 2,470 (BD/MDD = 1,333/1,137) hospitalized patients in Shanghai as training sets and 2,143 (BD/MDD = 955/1,188) in Hangzhou as test sets. A total of 35 clinical biochemical indexes were tested, including blood cells, immuno-inflammatory factors, liver enzymes, glycemic and lipid parameters, and thyroid and gonadal hormones. A stepwise analysis of a multivariable logistic regression was performed to build a predictive model to identify BD and MDD.ResultsMost of these biochemical indexes showed significant differences between BD and MDD groups, such as white blood cell (WBC) in the hematopoietic system, uric acid (UA) in immuno-inflammatory factors, direct bilirubin (DBIL) in liver function, lactic dehydrogenase (LDH) in enzymes, and fasting blood glucose (FBG) and low-density lipoprotein (LDL) in glucolipid metabolism (p-values < 0.05). With these predictors for discrimination, we observed the area under the curve (AUC) of the predictive model to distinguish between BD and MDD to be 0.772 among men and 0.793 among women, with the largest AUC of 0.848 in the luteal phase of women. The χ2 values of internal and external validation for male and female datasets were 2.651/10.264 and 10.873/6.822 (p-values < 0.05), respectively. The AUCs of the test sets were 0.696 for males and 0.707 for females.ConclusionDiscrimination and calibration were satisfactory, with fair-to-good diagnostic accuracy and external calibration capability in the final prediction models. Female patients may have a higher differentiability with a conventional biochemical index than male patients.Trial RegistrationICTRP NCT03949218. Registered on 20 November 2018. Retrospectively registered. https://www.clinicaltrials.gov/ct2/show/NCT03949218?id=NCT03949218&rank=1.

In this study, we introduced two small molecule compounds, hexadecyltrimethylammonium chloride (CTAC) and triethylene glycol bis(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate (AO245) to control the mechanical performance of acrylonitrile-butadiene rubber/clay (NBR/clay) nanocomposites. The NBR/clay nanocompound was prepared by gel compounding method, and the CTAC and AO245 were incorporated by mechanical blending. The phenolic hydroxyl group on AO245 enhanced the NBR/clay nanocomposite cross-linking network through hydrogen bond interaction with the cyanide group on the NBR macromolecular chain, which was evidenced by FTIR. In contrast, CTAC could plasticize NBR matrix by weakening the dipole-dipole interaction between clay and NBR. As compared to the NBR/clay nanocomposites, the nanocomposite with AO245 exhibited higher tensile strength, while the nanocomposite with CTAC showed higher elongation at break.

Summary: Extracellular vesicles (EVs) participate in intercellular communication and contribute to the angiogenesis. However, the understanding of the mechanisms underlying EVs secretion by neurons and their action on the vascular system of the central nervous system (CNS) remain rudimentary. Here, we show that vacuolar protein sorting 28 (Vps28) is essential for the sprouting of brain central arteries (CtAs) and for the integrity of blood-brain barrier (BBB) in zebrafish. Disruption of neuron-enriched Vps28 significantly decreased EVs secretion by regulating the formation of intracellular multivesicular bodies (MVBs). EVs derived from zebrafish embryos or mouse cortical neurons partially rescued the brain vasculature defect and brain leakage. Further investigations revealed that neuronal EVs containing vascular endothelial growth factor A (VEGF-A) are key regulators in neurovascular communication. Our results indicate that Vps28 acts as an intercellular endosomal regulator mediating the secretion of neuronal EVs, which in turn communicate with endothelial cells to mediate angiogenesis through VEGF-A trafficking.

This study was to investigate the characteristics of seasonal symptoms and non-enzymatic oxidative stress in the first hospitalized patients with bipolar and unipolar depression, aiming to differentiate bipolar depression from unipolar depression and reduce their misdiagnosis. A total of 450 patients with bipolar depression and 855 patients with depression were included in the present study. According to the season when the patients were admitted to the hospital due to the acute onset of depression, they were further divided into spring, summer, autumn and winter groups. According to the characteristics of symptoms of bipolar disorder in the DSM-5, the characteristic symptoms of bipolar disorder were collected from the medical record information, and clinical biochemical indicators that can reflect the oxidative stress were also recorded. The seasonal risk factors in patients with bipolar or unipolar depression were analyzed. The relationship of age and gender with the bipolar or unipolar depression which attacked in winter was explored. There were significant differences between groups in the melancholic features, atypical features and conjugated bilirubin in spring. In summer, there were significant differences between groups in the melancholic features, uric acid and conjugated bilirubin. In autumn, there were marked differences between groups in melancholic features, anxiety and pain, atypical features, uric acid, total bilirubin, conjugated bilirubin and albumin. In winter, the conjugated bilirubin and prealbumin were significantly different between two groups. The melancholic features and uric acid that in summer as well as melancholic features, uric acid and total bilirubin in autumn were the seasonal independent risk factors for the unipolar depression as compared to bipolar depression. In winter, significant difference was noted in the age between two groups. In conclusion, compared with patients with unipolar depression, patients with bipolar depression have seasonal characteristics. Clinical symptoms and indicators of oxidative stress may become factors for the differentiation of seasonal unipolar depression from bipolar depression. Young subjects aged 15–35 years are more likely to develop bipolar depression in winter.

Abstract Aims Many studies have explored the clinical characteristics of patients with coronavirus disease (COVID‐19), especially patients with cardiovascular disease. However, associated mechanisms and markers remain to be further investigated. This study aimed to investigate the effect of α‐hydroxybutyrate dehydrogenase (α‐HBDH) levels on disease progression and prognosis of patients with COVID‐19. Methods and results One thousand seven hundred and fifty‐one patients from the Leishenshan hospital in Wuhan were divided into elevated and normal groups by α‐HBDH level, and the clinical information between the two groups was compared retrospectively. The main outcome evaluation criteria included in‐hospital death and disease severity. Univariate and multivariate regression analyses, survival curves, logistic regression, and receiver operating characteristic curve models were performed to explore the relationship between elevated α‐HBDH and the two outcomes. Besides, curve fitting analyses were conducted to analyse the relationship between computed tomography score and survival. Among 1751 patients with confirmed COVID‐19, 15 patients (0.87%) died. The mean (SD) age of patients was 58 years in normal α‐HBDH group and 66 years in elevated α‐HBDH group (P

In this paper, an adaptive variable neighborhood search ant colony algorithm (AVNSACA) is proposed to solve the vehicle routing problem with soft time windows (VRPSTW). The ant colony algorithm's pheromone update strategy is improved to make up for the lack of pheromone in the algorithm's early stage. In order to avoid the algorithm falling into local optimum, two variable neighborhood search operators are designed, and the conditions for the algorithm to enter the variable neighborhood search are set. The effectiveness of AVNSACA in solving vehicle routing problem with soft time windows is verified by Solomon benchmark problem. Through the comparative analysis of the experimental results of the two algorithms, the advantages of the improved ant colony algorithm are illustrated. The experimental results show that the proposed algorithm can effectively obtain better solutions.

This paper studies the mechanism and influencing factors of resonance overvoltage of EHV transmission lines caused by lightning. By analyzing the time domain steady state of the simplified resonance circuit, the physical mechanism of resonance is revealed. The characteristics of resonance transient process and overvoltage waveform are analyzed by using electromagnetic transient simulation. The main influencing factors of overvoltage amplitude are also studied. The results show that: 1) During uneven open-phase conditions, resonant circuit involving shunt inductors and line equivalent capacitor obtains energy from lightning strikes, which may lead to resonance. 2) the transient process of resonance can be divided into three stages, including lightning stage, lightning-resonance conversion stage and steady-state resonance stage, among which the voltage of the first two stages are higher; 3) the lightning strike time, lightning current parameters and subsequent lightning strike affect on the overvoltage amplitude, which leads to the random amplitude in overvoltage.

AbstractBackground In ureterorenoscopy, anaesthesiologists are preferring regional anaesthesia to avoid postoperative complications, while surgeons are preferring general anaesthesia to avoid ureteral trauma. China has not published its guidelines and not referring to the European Association of Urology guidelines. The objectives of study were to evaluate the effects of general, spinal, and epidural anaesthesia on ureter access and surgical outcomes of ureterorenoscopy.Methods Charts of a total of 392 patients with the American Society of Anaesthesiologists grade I or II, and underwent flexible ureterorenoscopy for removal of the proximal, middle, or distal ureteral single stone under general anaesthesia (GA group; n = 145) or spinal anaesthesia (SA group; n = 131) or epidural anaesthesia (EA group; n = 116) were reviewed retrospectively.Results The dilatation time for patients of GA group was fewer than those of SA (104.01 ± 12.77 sec/patient vs. 130.55 ± 22.53 sec/patient, p

Metal chalcogenides are attractive anode materials for lithium-ion batteries (LIBs) due to their high theoretical capacities. With the advantages of low cost and abundance reserves, ZnS is regarded as the prime candidate anode material for future generations, but its practical application is hindered by the large volume expansion during repeated cycling processes and inherent poor conductivity. Rational design of the microstructure with large pore volume and high specific surface area is of great significance to solve these problems. Here, a carbon-coated ZnS yolk-shell structure (YS-ZnS@C) has been prepared by selective partial oxidation of a core-shell structured ZnS@C precursor in air and subsequent acid etching. Studies show that the carbon wrapping and proper etching to bring cavities can not only improve the material’s electrical conductivity, but can also effectively alleviate the volume expansion problem of ZnS during its cycles. As a LIB anode material, the YS-ZnS@C exhibits an obvious superiority in capacity and cycle life compared to ZnS@C. The YS-ZnS@C composite shows a discharge capacity of 910 mA h g−1 at the current density of 100 mA g−1 after 65 cycles, compared to only 604 mA h g−1 for ZnS@C after 65 cycles. Notably, at a large current density of 3000 mA g−1, a capacity of 206 mA h g−1 can still be maintained after 1000 cycles (over three times of the capacity for ZnS@C). It is expected that the synthetic strategy developed here is applicable to designing various high-performance metal chalcogenide-based anode materials for LIBs.

Abstract Background Electronic cigarette use is on the rise despite a number of reports linking electronic cigarettes with adverse health outcomes. Recent studies have suggested that alterations in lipid signaling may be one mechanism by which electronic cigarettes contribute to lung pulmonary function. Vitamin E acetate, for example, is synthetic form of Vitamin E transported via lipids, found to be associated with electronic cigarette associated lung injury. Lipids are absolutely critical for normal lung physiology and perturbations in a number of lipid pathways have been associated with respiratory illness. Is it conceivable that electronic cigarette use even in seemingly healthy cohorts are associated with alterations in lipid pathways? Methods To investigate quantitative alterations in the plasma lipidome associated with electronic cigarette use in healthy we obtained plasma samples from 119 male and female participants with who were either: (1) chronic tobacco cigarette (TC) smokers (> 12 months of self-reported TC use), (2) chronic Electronic cigarette (EC) users (> 12 months of self-reported EC use), or (3) non-users. We measured quantitative lipid species across different lipid sub-classes from plasma samples using the Sciex Lipidyzer. Results We found that male and female tobacco and electronic cigarette users had distinct lipidome signatures across a number of lipid species although the vast majority of lipids were unchanged when compared to non-users. Intriguingly, we found that female but not male electronic cigarette users had lower levels of plasmalogens, critical glycerophospholipids secreted by alveoli and required for normal surfactant function. Conclusions In summary, our study does not reveal striking changes associated with electronic cigarette use but we observed sex-specific changes in lipids known to be critical for lung function.

Based on predictable, complementary base pairing, DNA can be artificially pre-designed into versatile DNA nanostructures of well-defined shapes and sizes. With excellent addressability and biocompatibility, DNA nanostructures have been widely employed in biomedical research, such as bio-sensing, bio-imaging, and drug delivery. With the development of the chemical biology of nucleic acid, chemically modified nucleic acids are also gradually developed to construct multifunctional DNA nanostructures. In this review, we summarize the recent progress in the construction and functionalization of chemically modified DNA nanostructures. Their applications in the delivery of chemotherapeutic drugs and nucleic acid drugs are highlighted. Furthermore, the remaining challenges and future prospects in drug delivery by chemically modified DNA nanostructures are discussed.

Red ginseng is a traditional Chinese herbal medicine that has long been used to treat diabetes, and its blood sugar-lowering activity has been confirmed. However, the mechanism of action of red ginseng on type 2 diabetes mellitus (T2DM) at the metabolic level is still unclear. The purpose of this study is to investigate the effect of red ginseng extract in the treatment of T2DM rats based on untargeted metabolomics. The rat model of T2DM was induced by a high-fat diet (HFD) combined with streptozotocin (STZ), and serum samples were collected after four weeks of treatment. The ultra-high-performance liquid chromatography coupled with Q Exactive HF-X Mass Spectrometer was used to analyze the level of metabolites in serum to evaluate the differences in metabolic levels between different groups. The results of biochemical analysis showed that red ginseng extract intervention significantly improved the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), serum glucose (GLU), and fasting insulin (FINS) after four weeks. Orthogonal partial least squares discriminant analysis was used to study the overall changes of rat metabolomics. After the intervention of red ginseng extract, 50 biomarkers showed a callback trend. Metabolic pathway enrichment analysis showed that the regulated pathways were D-arginine and D-ornithine metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Generally, the results demonstrated that red ginseng extract had beneficial effects on T2DM, which could be mediated via ameliorating the metabolic disorders.

BackgroundInsulin resistance (IR) plays a key role in the development of type 2 diabetes mellitus (T2DM) and is one of its most important characteristics. Previous studies have shown that IR and T2DM were independent risk factors for a variety of cardiovascular and cerebrovascular diseases. However, there are few studies on the relationship between IR and aortic dissection (AD). The goal of this research was to find evidence that IR promotes the occurrence of AD.MethodsThrough the statistical analysis, we determined the proportion of glycosylated hemoglobin (HbA1c) abnormalities (HbA1c > 5.7) in people with acute thoracic aortic dissection (ATAD) and compared the difference of messenger RNA (mRNA) and protein expression of GluT1 in the thoracic aorta of normal people and those with ATAD to find evidence that IR is a causative factor in AD. The mouse model of IR and AD and the IR model of human aortic vascular smooth muscle cells (HA-VSMC) were established. Real time-PCR (RT-PCR) and Western blotting were used to study the mRNA and protein expression. Hematoxylin and eosin (H&E), Masson, and elastic fiber staining, and immunofluorescence were used to study the morphological structure.ResultsThe proportion of HbA1c abnormalities in patients with ATAD was 59.37%, and the mRNA and protein expression of GluT1 were significantly lower than that in normal people. Fasting glucose concentration (FGC), serum insulin concentration (SIC), and the homeostasis model assessment of insulin resistance (HOMA-IR) of mice was obviously increased in the high-fat diet group and the protein expressions of Glut1 and GluT4 were reduced, indicating that the mouse IR model was successfully established. The incidence of AD was different between the two groups (IR: 13/14, Ctrl: 6/14), and the protein expression of MMP2, MMP9, and OPN were upregulated and SM22 and α-SMA were downregulated in mice. The expressions of mRNA and protein of GluT1 and SM22 in HA-VSMCs with IR were reduced and OPN was increased.ConclusionCombined results of clinical findings, mouse models, and cell experiments show that IR induced the phenotypic switching of vascular smooth muscle cells (VSMCs) from contractile to synthetic, which contributes to the occurrence of AD. It provides a basis for further research on the specific mechanism of how IR results in AD and a new approach for the prevention and treatment of AD.

Background Post‐traumatic stress disorder (PTSD) is a serious mental health condition that is triggered by a terrifying event. We aimed to investigate the occurrence and risk factors of PTSD among discharged COVID‐19 patients. Methods This study included 144 discharged COVID‐19 patients. PTSD was assessed by using validated cut‐offs of the impact of event scale‐revised (IES‐R, score ≥25). All patients completed a detailed questionnaire survey, and clinical parameters were routinely measured in the hospital. Binary logistic regression models were applied to identify factors associated with PTSD. Results Of the 144 participants with laboratory‐confirmed COVID‐19, the occurrence of PTSD was 16.0%. In multivariable analyses, age above 40 years (adjusted OR [95% CI], 5.19 [2.17–12.32]), female sex (adjusted OR [95% CI], 7.82 [3.18–18.21]), current smoker (adjusted OR [95% CI], 6.72 [3.23–15.26]), and ≥3 involved pulmonary lobes (adjusted OR [95% CI], 5.76 [1.19–15.71]) were significantly associated with a higher risk of PTSD. Conversely, history of hypertension and serum hemoglobin levels were significantly associated with a lower risk of PTSD with adjusted ORs (95% CI) of 0.37 (0.12–0.87) and 0.91 (0.82–0.96), respectively. Conclusion Old age, gender (being female), current smoking, bacterial pneumonia, and ≥3 involved pulmonary lobes were associated with an increased occurrence of PTSD among discharged COVID‐19 patients.

Single-cell RNA sequencing (scRNA-seq) methods are typically unable to quantify the expression levels of all genes in a cell, creating a need for the computational prediction of missing values ('dropout imputation'). Most existing dropout imputation methods are limited in the sense that they exclusively use the scRNA-seq dataset at hand and do not exploit external gene-gene relationship information. Further, it is unknown if all genes equally benefit from imputation or which imputation method works best for a given gene. Here, we show that a transcriptional regulatory network learned from external, independent gene expression data improves dropout imputation. Using a variety of human scRNA-seq datasets we demonstrate that our network-based approach outperforms published state-of-the-art methods. The network-based approach performs particularly well for lowly expressed genes, including cell-type-specific transcriptional regulators. Further, the cell-to-cell variation of 11.3% to 48.8% of the genes could not be adequately imputed by any of the methods that we tested. In those cases gene expression levels were best predicted by the mean expression across all cells, i.e. assuming no measurable expression variation between cells. These findings suggest that different imputation methods are optimal for different genes. We thus implemented an R-package called ADImpute (available via Bioconductor https://bioconductor.org/packages/release/bioc/html/ADImpute.html) that automatically determines the best imputation method for each gene in a dataset. Our work represents a paradigm shift by demonstrating that there is no single best imputation method. Instead, we propose that imputation should maximally exploit external information and be adapted to gene-specific features, such as expression level and expression variation across cells.

The differences in reproductive processes at the molecular level between viviparous and oviparous animals are evident, and the site in the ovary that synthesizes sex hormones (androgens and oestrogens) and the trends for enriching sex hormones during follicle development in chickens are different from those in mammals, suggesting that the effect of sex hormones on follicle development in chickens is probably different from that in viviparous animals. To explore the specific role of androgen receptors (ARs) on chicken follicular development, we matched the correspondence of follicular development stages among chickens, humans, cows and identified chicken-specific genes related to follicle development (GAL-SPGs) by comparing follicle development-related genes and their biological functions among species (chickens, humans, and cows). A comparison of the core transcription factor regulatory network of granulosa cells (or ovaries) based on super-enhancers among species (chicken, human, and mouse) revealed that AR is a core transcriptional regulator specific to chickens. In vivo experiments showed that inhibition of AR significantly reduced the number of syf (selected stage follicles) in chickens and decreased the expression of GAL-SPGs in F5 follicles, while in vitro experiments showed that inhibition of AR expression in chicken granulosa cells (GCs) significantly down-regulated the expression levels of GAL-SPGs, indicating that AR could regulate follicle selection through chicken-specific genes related to follicle development. A comparison among species (77 vertebrates) of the conserved genomic regions, where chicken super-enhancers are located, revealed that the chicken AR super-enhancer region is conserved in birds, suggesting that the role of AR in follicle selection maybe widespread in birds. In summary, we found that AR can regulate follicle selection through chicken-specific genes related to follicle development, which also emphasizes the important role of AR in follicle selection in chickens and provides a new perspective for understanding the unique process of follicle development in chickens. Our study will contribute to the application of androgens to the control of egg production in chickens and suggests that researchers can delve into the mechanisms of follicle development in birds based on androgen/androgen receptors.

Background: In this study, we investigated the relationship between serum lactate dehydrogenase (LDH) level and disease progression and prognosis of patients with COVID-19.Methods: We retrospectively reviewed the information of 1,751 patients with COVID-19 from Leishenshan Hospital in Wuhan, China. Univariate and multivariate Cox regression analyses as well as Logistics regression analyses, and Kaplan-Meier curves were used to determine the association between LDH levels and the prognosis of COVID-19 patients.Results: LDH was an independent risk factor for in-hospital death no matter it was taken as classified variable and continuous variable (all P = 0.001) but not for severe or critical illness status. The Kaplan-Meier curves for LDH level showed that an elevated level of LDH was associated with in-hospital death.Conclusions: In patients with COVID-19, the increased LDH level is associated with a higher risk of negative clinical prognosis and higher mortality. This will provide a reference for clinicians and researchers to understand, diagnose, and treat patients with COVID-19. Further prospective studies with larger sample sizes are needed to verify these findings.

Congenital anomalies of the kidney and urinary tract (CAKUT) are some of the most common developmental defects and have a complicated etiology, indicating an interaction of (epi-) genetic and environmental factors. Single gene mutations and copy number variations (CNVs) do not explain most cases of CAKUT, and simultaneous contributions of more than one gene (di-, oligo-, or polygenic effects; i.e., complex genetics) may lead to the pathogenesis of CAKUT. Robo2 plays a key role in regulating ureteric bud (UB) formation in the embryo, with mutations leading to supernumerary kidneys. Gen1 is a candidate gene associated with CAKUT because of its important role in early metanephric development in mice. We established a mouse model with double disruption of Robo2 and Gen1 using a piggyBac transposon and found that double gene mutation led to significantly increased CAKUT phenotypes in Robo2PB/+Gen1PB/+ mouse offspring, especially a duplicated collecting system. Increased ectopic UB formation was observed in the Robo2PB/+Gen1PB/+ mice during the embryonic period. Robo2 and Gen1 exert synergistic effects on mouse kidney development, promoting cell proliferation by activating the GDNF/RET pathway and downstream MAPK/ERK signaling. Our findings provide a disease model for CAKUT as an oligogenic disorder.

Dendritic cells (DCs) are recognized as a key orchestrator of immune response and homeostasis, deregulation of which may lead to autoimmunity such as experimental autoimmune encephalomyelitis (EAE). Herein we show that the phosphatase PP2Cδ played a pivotal role in regulating DC activation and function, as PP2Cδ ablation caused aberrant maturation, activation, and Th1/Th17-priming of DCs, and hence induced onset of exacerbated EAE. Mechanistically, PP2Cδ restrained the expression of the essential subunit of mTORC2, Rictor, primarily through de-phosphorylating and proteasomal degradation of the methyltransferase NSD2 via CRL4DCAF2 E3 ligase. Loss of PP2Cδ in DCs accordingly sustained activation of the Rictor/mTORC2 pathway and boosted glycolytic and mitochondrial metabolism. Consequently, ATP-citrate lyse (ACLY) was increasingly activated and catalyzed acetyl-CoA for expression of the genes compatible with hyperactivated DCs under PP2Cδ deletion. Collectively, our findings demonstrate that PP2Cδ has an essential role in controlling DCs activation and function, which is critical for prevention of autoimmunity.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) play critical roles in the biogenesis, localization and transport of RNA. Here authors investigate a role for hnRNPs in sterol metabolism in mice and provide insights into their role in selective promoter activation.

Abstract Background High-risk human papillomavirus (HR-HPV) testing is more sensitive than cytology for the detection of cervical cancer and its precursors. However, limited and inconsistent data are available about the efficacy of the combination of these two methods for screening cervical adenocarcinoma. This multicenter retrospective study investigated the screening results of a cohort of Chinese patients who were subsequently diagnosed with invasive cervical adenocarcinoma, with the goal of identifying the optimal cervical adenocarcinoma screening method. Methods We retrospectively retrieved and analyzed the data from patients with histologically confirmed primary invasive cervical adenocarcinoma from eight local pathology laboratories operated by KingMed Diagnostics, the largest independent operator of pathology laboratories in China, over a 2-year period. Only patients who underwent cytology and/or HR-HPV testing within 6 months before the adenocarcinoma diagnosis were included. HR-HPV DNA was detected using one of two HPV test kits: the Hybrid Capture 2 (HC2) assay (Qiagen, Hilden, Germany) and an HPV genotyping panel (Yaneng Bio, Shenzhen, China). Results Of the 311 patients, 136 underwent cytology alone, 106 underwent HR-HPV testing alone, and 69 underwent cytology and HR-HPV co-testing. The sensitivities of cytology alone (64.0, 95% confidence interval [CI]: 55.9–72.0) and HR-HPV testing alone (66.0, 95% CI: 57.0–75.1) were similar (P = 0.738). The sensitivity of cytology and HR-HPV co-testing (87.0, 95% CI: 79.0–94.9) was significantly higher than that of either cytology (P = 0.001) or HR-HPV testing alone (P = 0.002). Conclusions Both cytology alone and HR-HPV testing alone showed poor screening efficiency, whereas the combination of the two clearly increased the efficiency of primary cervical adenocarcinoma screening. Thus, cytology and HR-HPV co-testing might be the most efficient cervical adenocarcinoma screening method.

Increasing evidence indicates that DNA polymerase epsilon (POLE), which mediates DNA damage repair, is significantly associated with tumor prognosis. This study aimed to analyze POLE expression in tumor samples and its prognostic value for patients with clear cell renal cell carcinoma (ccRCC). We found significantly elevated POLE expression in ccRCC tissues compared with normal tissues of multiple independent cohorts. The POLE expression levels of 523 patients with ccRCC (The Cancer Genome Atlas RNA-seq data) and 179 patients with ccRCC with immunohistochemical data (Fudan University Shanghai Cancer Center) were analyzed to investigate the prognostic implications of POLE expression. Cox regression analyses were implemented to explore the effect of POLE expression on the prognosis of pan-cancer. These findings revealed that elevated POLE expression levels significantly correlated with shorter overall survival (p < 0.001, n = 701) of patients with ccRCC. These data indicate that POLE expression may serve as a prognostic biomarker for cancers. Although POLE mutations were not significantly associated with survival benefits conferred upon patients with ccRCC, a CD4+ T cell-regulated immune microenvironment was significantly activated. Moreover, we found that POLE expression in cancers significantly correlated with an immunosuppressive tumor microenvironment, higher intratumoral heterogeneity, and expression of immune checkpoint genes PDCD1, CTLA4, and CD86, possibly mediated via the JAK/STAT and Notch signaling pathways. In conclusion, the present study is the first to our knowledge to indicate that elevated POLE expression is significantly associated with poor survival and an immune-suppressive tumor microenvironment in ccRCC. These findings suggest that POLE can serve as a biomarker for guiding molecular diagnosis and facilitating the development of novel individual therapeutic strategies for patients with advanced ccRCC.

BackgroundCoronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients.MethodsPatient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality.ResultsLogistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19.ConclusionElevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.

Background: Comorbid somatic diseases increase the death risk and affect the condition, treatment, and prognosis of older psychiatric patients. We investigated the comorbidity and drug treatment in older patients with psychosis.Methods: This retrospective study used data from 3,115 older psychiatric in-patients hospitalized at the Shanghai Mental Health Center Affiliated to Shanghai Jiaotong University School of Medicine, China discharged from 2005 to 2015. Descriptive analyses of patients' age, sex, treatment drugs, diagnoses (based on ICD-10), and time trend were performed.Results: Patients' median age was 56 (range, 50-98) years; 1,824 (58.6%) were female. The top five first-level diagnoses were schizophrenia (F20) (n = 1,818, 58.3%), depressive episode (F32) (n = 457, 14.6%), bipolar affective disorder (F31) (n = 151, 4.8%), manic episode (F30), (n = 143, 4.6%), and vascular dementia (F01) (n = 136, 4.4%). Mental (99.9%), central nervous system (85.2%), digestive system (83.5%), cardiovascular system (72.5%), and anti-infective (59.6%) drugs had the highest prescription rates. The combined use of antidepressants, anti-anxiety, anti-arrhythmic, hormones and endocrine system drugs were significantly higher in female than in male patients, while mood stabilizers and genitourinary system drugs significantly more frequent in men. With increasing age, the F20-F29 patients decreased, while F00-F09 patients increased, with the corresponding changes to prescription in those patients. In comparison to that in 2005-2010, the combined prescriptions for genitourinary and cardiovascular drugs increased between 2011 and 2015, and F00-F09 and F40-F48 older patients doubled, accordingly anti-Alzheimer's disease drugs and antidepressants more than doubled. F30-F39 patients increased by 49.1%, and anti-anxiety drugs, mood stabilizers, etc. increased by ≥50%; F20-F29 older patients decreased by 26.7%, while antipsychotics only increased by 4.4%.Conclusions: This study found the combined drug treatment of somatic diseases, particularly for central nervous, digestive, cardiovascular, respiratory and genitourinary drugs were extremely common among older psychiatric in-patients in China. With increasing age, the F20-F29 patients decreased, while F00-F09 patients increased; the antipsychotics prescriptions decreased, and almost all comorbidity drugs increased. Compared with that in 2005-2010, the older patients with all diagnosis except F20-F29 increased in 2011-2015, and the prescriptions for psychotropic, genitourinary, and cardiovascular drugs increased.

The purpose of this study is to explore the correlation between ferroptosis-related genes and schizophrenia in order to explore the new direction of diagnosis and treatment of schizophrenia. We screened the datasets related to schizophrenia from the Gene Expression Comprehensive Database (GEO) and obtained ferroptosis-related genes from the FerrDB database. Bioinformatics methods were used to analyze differentially expressed genes (DEGs) and genes associated with ferroptosis-related between schizophrenia patients and healthy controls. On this basis, the hub genes were finally screened by enrichment analysis and PPI interaction analysis. Hub genes associated with ferroptosis were validated using other schizophrenia datasets in the GEO database. Finally, the hub gene-microRNA (miRNA), gene-transcription factor interaction network was constructed, and three ferroptosis-related hub genes (TP53, VEGFA and PTGS2) were screened. The validation results of these three genes in other datasets also support this conclusion. A miRNA: hsa-mir-16-5p was found to be related to the three hub genes, and pPHF8, SAP30 and lKDM5B were identified as common regulators of the three hub genes. Our results indicate that TP53, VEGFA and PTGS2 are significantly associated with schizophrenia, and may be ferroptosis-related markers of the disease.

Continual aeration, a fouling control strategy that causes high energy consumption, is the major obstacle in the deployment of membrane bioreactors (MBRs) for wastewater treatment. In recent years, a technology has been developed which adopts mechanical reciprocity for membrane vibration, and it has been proven efficient for membrane scouring, as well as for saving energy: the low-energy POREFLON non-aerated membrane bioreactor (LEP-N-MBR). In this study, a pilot-scale LEP-N-MBR system was designed, established, and operated at various frequencies and amplitudes, and with various membrane models, so as to evaluate energy usage and membrane fouling. The results showed that a slower TMP rise occurred when the frequency and amplitude were set to 0.5 Hz and 10 cm, respectively. Under a suitable frequency and amplitude, the TMP increasing rate of model B (sealed only with epoxy resin) was slower than that of model A (sealed with a combination of polyurethane and epoxy resin). The average specific energy demand (SED) of the LEP-N-MBR was 0.18 kWh·m−3, much lower than the aerated MBR with 0.43 kWh·m−3 (obtained from a previous study), indicating a significant decrease of 59.54% in the SED. However, the uneven distribution of sludge within the membrane tank indicated that the poor hydraulic mixing in the reactor may result in sludge accumulation, which requires further operational optimization. The findings of this pilot-scale study suggest that the LEP-N-MBR system is promising and effective for municipal wastewater treatment with a much lower level of energy usage. More research is needed to further optimize the operation of the LEP-N-MBR for wide application.

Production scheduling is the key to manufacturing process decision support, which directly affects the efficiency and competitiveness of enterprises. The production process of discrete workshops is complex and changeable, and it is usually difficult to make adjustments quickly and accurately in response to disturbance events. In this paper, a workshop production scheduling method based on digital twin is proposed and applied to the manufacturing workshop of an aerospace factory. Combined with the advantages of real-time virtual real interaction fusion of digital twin technology, the dynamic scheduling problem under fault disturbance factors is studied. A high-fidelity digital twin workshop is established to realize the mapping and interaction between the real production and the virtual factory. Based on the vibration data of machine tool spindle, a fault prediction method of learning vector quantization neural network is proposed. The dynamic scheduling strategy of workshop production based on digital twin is constructed and compared with the scheduling results without digital twin under fault disturbance. The results show that the scheduling method based on digital twin can effectively deal with disturbances and improve workshop productivity. This study can be used for the application of digital twin and production scheduling in practical factories.

Polymerized, functionalized solution styrene–butadiene rubber (F-SSBR) is a new type of polymerized styrene–butadiene rubber solution containing specific terminal groups, which can be used in treads for high performances. However, the wet skid resistance related to safety, the rolling resistance to energy consumption, and the wear resistance to service life are often contradictory and form the performance “magic triangle”. In this work, oligomeric resins, including Coumarone resin, C9 resin, C5/C9 resin and a styrene-α-methyl styrene copolymer (SSC), were used as tire functional additives and selected to replace treated distillate aromatic extract (TDAE) to improve the performances of silica-filled F-SSBR composites. The C9 resin, C5/C9 resin and SSC could enhance the modulus at 300% and tensile strength of the F-SSBR composite. The four resins could improve the wet skid resistance and wear resistance of the composites. However, Coumarone resin caused poor silica dispersion in the F-SSBR matrix and eventually, the lower modulus, higher loss factor at 60 °C and the higher heat buildup in the composite were comparative to the composite with TDAE. Furthermore, the synergistic effect of the C5/C9 resin and SSC was found to improve the mechanical performance of the composites and it resulted in higher tensile strength and modulus, and a lower heat buildup, compared to the case when only TDAE was used. It is noted that the properties “magic triangle” was broken by the C5/C9 resin and SSC, and the C5/C910T15 increased the wet skid resistance by 21.7%, fuel-saving rate by 2.3%, and wear resistance by 8.3%, while S20T5 increased the wet skid resistance by 30.4%, fuel-saving rate by 7%, and wear resistance by 25% compared with CG.

Purpose: The coronavirus disease (COVID-19) pandemic poses a global threat, and identification of its prognostic biomarkers could prove invaluable. Fibrinogen (FIB) could be one such indicator as coagulation and fibrinolysis abnormalities are common among COVID-19 patients. We examined the role of FIB levels in the prognosis of COVID-19.Methods: This retrospective cohort study enrolled 1,643 COVID-19 patients from the Leishenshan Hospital in Wuhan, China. The follow-up was conducted from February 8, 2020 to April 15, 2020. The cohort was divided into three groups according to the FIB level on admission, and associations with mortality and disease severity were determined using Cox and logistic regression analyses, respectively. Further, Kaplan–Meier (K–M) analyses by log-rank tests were used to assess the survival of patients with varying FIB levels.Results: Patients with FIB < 2.2 g/L [hazard ratio (HR): 9.02, 95% confidence interval (CI): 1.91–42.59, P = 0.006] and >4.2 g/L (HR: 4.79, 95% CI: 1.14–20.20, P = 0.033) showed higher mortality risks compared to those with FIB between 2.2 and 4.2 g/L. The survival curves showed similar results in K–M analyses (P < 0.001). Additionally, an elevated FIB level was associated with a greater risk of developing critical disease (odds ratio: 2.16, 95% CI: 1.04–4.46, P = 0.038) than a FIB level within the normal range.Conclusion: Abnormal FIB levels may be associated with mortality risk among COVID-19 patients and could predict critical disease development. Thus, assessment of FIB levels may assist in determining the prognosis of COVID-19 patients.

Codonopsis Radix is a traditional Chinese medicine best known for its effects in treating digestive, cardiovascular, immunological and hematopoitic diseases. It also appears in the traditional Chinese medical prescriptions against ascites. However, the physiological effect and molecular mechanism of Codonopsis Radix in water and electrolytes homeostasis have not been well studied. We found that Codonopsis Radix decoction increased water intake and the urine volume, but decreased food intake in mice. The treatment significantly reduced angiotensin II receptor (AT1R) transcription and serum aldosterone level in animals, suggested perturbed function of renin-angiotensin system. RNAseq analysis of Codonopsis Radix treated NCI–H295R cells detected suppressed AT1R, SP1, and TEF transcription as well. Thus, Codonopsis Radix may regulate water and electrolytes homeostasis by affecting AT1R expression and aldosterone biosynthesis, possibly through downregulating SP1 and TEF transcription.

Abstract Background Single-cell RNA-sequencing (scRNA-seq) is fast becoming a powerful tool for profiling genome-scale transcriptomes of individual cells and capturing transcriptome-wide cell-to-cell variability. However, scRNA-seq technologies suffer from high levels of technical noise and variability, hindering reliable quantification of lowly and moderately expressed genes. Since most downstream analyses on scRNA-seq, such as cell type clustering and differential expression analysis, rely on the gene-cell expression matrix, preprocessing of scRNA-seq data is a critical preliminary step in the analysis of scRNA-seq data. Results We presented scNPF, an integrative scRNA-seq preprocessing framework assisted by network propagation and network fusion, for recovering gene expression loss, correcting gene expression measurements, and learning similarities between cells. scNPF leverages the context-specific topology inherent in the given data and the priori knowledge derived from publicly available molecular gene-gene interaction networks to augment gene-gene relationships in a data driven manner. We have demonstrated the great potential of scNPF in scRNA-seq preprocessing for accurately recovering gene expression values and learning cell similarity networks. Comprehensive evaluation of scNPF across a wide spectrum of scRNA-seq data sets showed that scNPF achieved comparable or higher performance than the competing approaches according to various metrics of internal validation and clustering accuracy. We have made scNPF an easy-to-use R package, which can be used as a versatile preprocessing plug-in for most existing scRNA-seq analysis pipelines or tools. Conclusions scNPF is a universal tool for preprocessing of scRNA-seq data, which jointly incorporates the global topology of priori interaction networks and the context-specific information encapsulated in the scRNA-seq data to capture both shared and complementary knowledge from diverse data sources. scNPF could be used to recover gene signatures and learn cell-to-cell similarities from emerging scRNA-seq data to facilitate downstream analyses such as dimension reduction, cell type clustering, and visualization.