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Diagram of the Smart Wound Management Microneedle Patch. Smart microneedle patches combine treatment and monitoring for real-time diagnosis.

Background: Correct tumor subtyping of primary renal tumors is essential for treatment decision in daily routine. Most of the tumors can be classified based on morphology alone. Nevertheless, some diagnoses are difficult, and further investigations are needed for correct tumor subtyping. Besides histochemical investigations, high-mass-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can detect new diagnostic biomarkers and hence improve the diagnostic. Patients and Methods: Formalin-fixed paraffin embedded tissue specimens from clear cell renal cell carcinoma (ccRCC, n = 552), papillary renal cell carcinoma (pRCC, n = 122), chromophobe renal cell carcinoma (chRCC, n = 108), and renal oncocytoma (rO, n = 71) were analyzed by high-mass-resolution MALDI fourier-transform ion cyclotron resonance (FT-ICR) MSI. The SPACiAL pipeline was executed for automated co-registration of histological and molecular features. Pathway enrichment and pathway topology analysis were performed to determine significant differences between RCC subtypes. Results: We discriminated the four histological subtypes (ccRCC, pRCC, chRCC, and rO) and established the subtype-specific pathways and metabolic profiles. rO showed an enrichment of pentose phosphate, taurine and hypotaurine, glycerophospholipid, amino sugar and nucleotide sugar, fructose and mannose, glycine, serine, and threonine pathways. ChRCC is defined by enriched pathways including the amino sugar and nucleotide sugar, fructose and mannose, glycerophospholipid, taurine and hypotaurine, glycine, serine, and threonine pathways. Pyrimidine, amino sugar and nucleotide sugar, glycerophospholipids, and glutathione pathways are enriched in ccRCC. Furthermore, we detected enriched phosphatidylinositol and glycerophospholipid pathways in pRCC. Conclusion: In summary, we performed a classification system with a mean accuracy in tumor discrimination of 85.13%. Furthermore, we detected tumor-specific biomarkers for the four most common primary renal tumors by MALDI-MSI. This method is a useful tool in differential diagnosis and biomarker detection.

Objective. To explore the expression and clinical significance of HER2 and DNMT1 in non-small-cell lung cancer. Methods. The patients with non-small-cell lung cancer treated in the First Affiliated Hospital of Jiamusi University between 2018 and 2020 were enrolled in this study. The serum DNMT1 concentration and the expression of HER2 protein in lung cancer and adjacent tissues of the two groups were analyzed. Results. The DNMT1 protein concentration was significantly correlated with gender, age, and smoking history of patients. HER2-positive expression was significantly related to tumor type, tumor size, tumor differentiation degree, and lymph node metastasis. However, HER2 levels were not related to the gender and smoking history of patients. Conclusion. High expression of DNMT1 protein in serum may increase the risk of non-small-cell lung cancer and may play an important role in the early development of lung cancer. HER2-positive expression may promote the development of advanced and metastatic non-small-cell lung cancer.

Circular RNAs (circRNAs) have been accepted to play key roles in the development and progression of mutiple cancers including colorectal cancer (CRC). Here, we identified circ-METTL9, derived from 2-4 exons of METTL9 gene, may promote CRC progression by accelerating cell cycle progression. However, the role and mechanism of circ-METTL9 in CRC remains unclear. Based on our data, the expression of circ-METTL9 was significantly upregulated in CRC tissues and markedly increased in advanced tumors in CRC patients. Functional experiments demonstrated that circ-METTL9 overexpression promoted CRC cells proliferation and migration in vitro, and simultaneously enhanced CRC tumor growth and metastasis in vivo. Mechanistically, RNA immunoprecipitation (RIP) assays proved that circ-METTL9 might be a miRNA sponge, and RNA pulldown assays showed the interaction between circ-METTL9 and miR-551b-5p. Notably, cyclin-dependent kinase 6 (CDK6), a key regulator in cell cycle, is a conserved downstream target of miR-551b-5p. Taken together, our findings highlight a novel oncogenic function of circ-METTL9 in CRC progression via circ-METTL9/miR-551b-5p/CDK6 axis, which may serve as a prognostic biomarker and therapeutic target for CRC patients.

Photodynamic therapy (PDT) is a noninvasive therapy for cancer and bacterial infection. Metal-free semiconducting conjugated polymers (SCPS) with good stability and optical and electrical properties are promising photosensitizers (PSs) for PDT compared with traditional small-molecule PSs. This review analyzes the latest progress of strategies to improve PDT effect of linear, planar, and three-dimensional SCPS, including improving solubility, adjusting conjugated structure, enhancing PS-doped SCPs, and combining therapies. Moreover, the current issues, such as hypoxia, low penetration, targeting and biosafety of SCPS, and corresponding strategies, are discussed. Furthermore, the challenges and potential opportunities on further improvement of PDT for SCPs are presented.

Two novel hexapeptides with anti-hyperuricemia effect were identified from Apostichopus japonicus hydrolysate, and their effects on modulation of gut microbiota and microRNA profiles were investigated.

Background The development of polycystic ovary syndrome (PCOS) is closely correlated with apoptosis and oxidative stress in ovarian granulosa cells. Kisspeptin plays an important role in reproductive organ function. This study aimed to explore the role of kisspeptin in PCOS and oxidative stress-triggered apoptosis of ovarian granular cells. Methods A PCOS rat model was established by injecting dehydroepiandrosterone (DHEA) and feeding the rats a high-fat diet. The RNA and protein levels of kisspeptin were analysed by quantitative PCR, western blotting, and histological staining. Tissue damage was evaluated using haematoxylin and eosin (H&E) staining. The viability and proliferation of human granulosa cell KGN were measured using the cell counting kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays. Cell cycle and apoptosis were analysed by flow cytometry. Oxidative stress was analysed by measuring reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels. Results Kisspeptin was downregulated in the ovarian granulosa cells of PCOS rats compared to those of control rats. Kisspeptin overexpression enhanced KGN cell proliferation and inhibited apoptosis. ROS generation was suppressed by kisspeptin, along with decreased levels of MDA and increased levels of the antioxidants GSH, SOD, and CAT. Kisspeptin activates PI3K/AKT and ERK signalling, and inactivation of ERK1/2 suppresses the protective role of kisspeptin in ovarian granulosa cells. Conclusion Kisspeptin improves proliferation and alleviates apoptosis and oxidative stress in ovarian granulosa cells by activating PI3K/AKT and ERK signalling.

Wei-Ying Diao,1,&ast; Cheng-Long Ding,1,&ast; Bo-Yang Yuan,2 Zan Li,3 Na Sun,4 Jia-Bin Huang5 1Department of Pathology, The First Affiliated Hospital of Jiamusi University, Jimusi City, Heilongjiang Province, 154002, People’s Republic of China; 2Department of Acupuncture and Moxibustion, The First Affiliated Hospital of Jiamusi University, Jimusi City, Heilongjiang Province, 154002, People’s Republic of China; 3Department of Analytical Chemistry Teaching and Research, Jiamusi University, Jiamusi City, Heilongjiang Province, 154002, People’s Republic of China; 4Graduate Department, Jiamusi University, Jiamusi, Heilongjiang Province, 154002, People’s Republic of China; 5Department of Geratology, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang Province, 154002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia-Bin Huang Email jiadupinglu54972@163.comIntroduction: We aim to investigate the relationship between HER2 gene phenotype and clinical characteristics, distribution and prognosis of non-small cell lung cancer (NSCLC) patients.Methods: A total of 249 NSCLC patients admitted to the oncology department of our hospital from January 2015 to January 2018 were retrospectively analyzed. The clinicopathological information, CT signs, clinical efficacy and long-term prognosis were collected and compared.Results: A total of 249 NSCLC patients underwent HER2 gene testing, 21 of them (8.43%) complied with HER2 alterations [HER2 (+)], and there were significant differences in tumor stages among patients with different HER2 phenotypes (P< 0.05). Among 21 NSCLC patients with HER2 (+), HER2 gene mutation was found in 17 patients (81%), and HER2 gene amplification in 4 patients (19%). Among the HER2 mutations, 12 cases (57%) were 20 exon mutations, and 5 cases (19%) were other mutations. Analysis of CT signs showed that border lobulation/burr, necrosis sign and pleural depression were correlated with HER2 gene mutation (P< 0.05). The incidence of EGRF mutation in HER (+) patients was significantly lower than that in HER (-) patients (P< 0.05), but there was no significant difference in the incidence of ALK gene mutation among different HER phenotypes (P> 0.05). The disease control rate of HER2 (+) patients was significantly lower than that of HER2 (-) patients, and the 12-month progression-free survival rate and survival rate of HER2 (+) patients were significantly higher than those of HER2 (-) patients (P< 0.05). There was no significant difference in the incidence of ADR among HER2 patients with different phenotypes, but the incidence of ADR (adverse drug reaction) in HER2 (+) patients with Grade 3 or 4 was significantly higher than that in the control group (P< 0.05).Discussion: The incidence of HER2 gene mutations in NSCLC patients is relatively low, but it is far commoner in patients with stage IIIB∼IV, among which exon 20 mutations are the most prevalent. In CT signs, the lesion lobulated sign/spiculated sign, necrosis signs, and pleural depression signs are related to HER2 gene mutations. In addition, HER2 gene mutations play a crucial role in the clinical prognosis and treatment safety of patients.Keywords: non-small cell lung cancer, HER2 genotype, CT signs, afatinib

Background Zedoary turmeric oil extracted from the roots of curcuma (Curcuma aeruginosa Roxb.) is used for the treatment of myocarditis in China. EMCV infection causes abortion in pregnant sows and myocarditis in piglets. Our previous studies demonstrated that curcumol significantly increased the expression of IFN-β in EMCV infected HEK-293T cells. The present results showed that curcumol inhibits EMCV replication by interfering the host cell cholesterol homeostasis and reducing ROs production through activation of the JAK/STAT signaling pathway. Method This study was designed to explore whether curcumol can inhibit the replication of encephalomyocarditis viruses (EMCV) in cell culture. The expression level of JAK1, IRF9, STAT2, P-STAT2, CH25H, PI4KA and OSBP in EMCV-infected HEK-293T cells treated with curcumol, ribavirin or hydroxypropyl-β-CD (HPCD) were determined by Western blotting (WB). The cholesterol level in EMCV infected HEK-293T cells treated with curcumol and HPCD were detected using Amplex™ Red Cholesterol Assay Kit. The antiviral effects of curcumol and HPCD on EMCV were also quantitatively detected by real-time fluorescence quantitative PCR (q-PCR). The amount and morphology of ROs were observed by transmission electron microscopy (TEM). Results The results demonstrated that curcumol significantly (P < 0.05) increased the expression of JAK1, IRF9, P-STAT2 and CH25H proteins, while that of STAT2, PI4KA and OSBP were remained unchanged. Compared with virus group (0.134 μg.μg-1 proteins), the total cholesterol level was significantly (P < 0.05) reduced by curcumol (0.108 μg.μg-1 proteins) and HPCD (0.089 μg.μg-1 proteins). Compared with virus group (88237 copies), curcumol (41802 copies) and HPCD (53 copies) significantly (P < 0.05) reduced EMCV load. Curcumol significantly reduced the production of ROs in EMCV-infected HEK-293T cells and activated CH25H through the JAK/STAT signaling pathway. Conclusion Curcumol inhibited EMCV replication by affecting the cholesterol homeostasis and the production of ROs in HEK-293T cell.

Hypoxia is a major stressor and a prominent feature of pathological conditions, such as bacterial infections, inflammation, wounds, and cardiovascular defects. In this study, we investigated whether reoxygenation has a protective effect against hypoxia-induced acute injury and burn using the C57BL/6 mouse model. C57BL/6 mice were exposed to hypoxia and treated with both acute and burn injuries and were in hypoxia until wound healing. Next, C57BL/6 mice were exposed to hypoxia for three days and then transferred to normoxic conditions for reoxygenation until wound healing. Finally, skin wound tissue was collected to analyze healing-related markers, such as inflammation, vascularization, and collagen. Hypoxia significantly increased inflammatory cell infiltration and decreased vascular and collagen production, and reoxygenation notably attenuated hypoxia-induced infiltration of inflammatory cells, upregulation of pro-inflammatory cytokine levels (IL-6 and TNF-α) in the wound, and remission of inflammation in the wound. Immunofluorescence analysis showed that reoxygenation increased the expression of the angiogenic factor α-SMA and decreased ROS expression in burn tissues compared to hypoxia-treated animals. Moreover, further analysis by qPCR showed that reoxygenation could alleviate the expression of hypoxic-induced inflammatory markers (IL-6 and TNF), increase angiogenesis (SMA) and collagen synthesis (Col I), and thus promote wound healing. It is suggested that oxygen can be further evaluated in combination with oxygen-releasing materials as a supplementary therapy for patients with chronic hypoxic wounds.

Enteropathogenic Escherichia coli (EPEC), which belongs to the attaching and effacing diarrheagenic E. coli strains, is a major causative agent of life-threatening diarrhea in infants in developing countries. Most EPEC isolates correspond to certain O serotypes; however, many strains are nontypeable. Two EPEC strains, EPEC001 and EPEC080, which could not be serotyped during routine detection, were isolated. In this study, we conducted an in-depth characterization of their putative O-antigen gene clusters (O-AGCs) and also performed constructed mutagenesis of the O-AGCs for functional analysis of O-antigen (OAg) synthesis. Sequence analysis revealed that the occurrence of O-AGCs in EPEC001 and E. coli O132 may be mediated by recombination between them, and EPEC080 and E. coli O2/O50 might acquire each O-AGC from uncommon ancestors. We also indicated that OAgknockout bacteria were highly adhesive in vitro, except for the EPEC001 wzy derivative, whose adherent capability was less than that of its wild-type strain, providing direct evidence that OAg plays a key role in EPEC pathogenesis. Together, we identified two EPEC O serotypes in silico and experimentally, and we also studied the adherent capabilities of their OAgs, which highlighted the fundamental and pathogenic role of OAg in EPEC.

Background:. Macrophages are involved in the pathogenesis of idiopathic pulmonary fibrosis, partially by activating lung fibroblasts. However, how macrophages communicate with lung fibroblasts is largely unexplored. Exosomes can mediate intercellular communication, whereas its role in lung fibrogenesis is unclear. Here we aim to investigate whether exosomes can mediate the crosstalk between macrophages and lung fibroblasts and subsequently induce fibrosis. Methods:. In vivo, bleomycin (BLM)-induced lung fibrosis model was established and macrophages infiltration was examined. The effects of GW4869, an exosomes inhibitor, on lung fibrosis were assessed. Moreover, macrophage exosomes were injected into mice to observe its pro-fibrotic effects. In vitro, exosomes derived from angiotensin II (Ang II)-stimulated macrophages were collected. Then, lung fibroblasts were treated with the exosomes. Twenty-four hours later, protein levels of α-collagen I, angiotensin II type 1 receptor (AT1R), transforming growth factor-β (TGF-β), and phospho-Smad2/3 (p-Smad2/3) in lung fibroblasts were examined. The Student's t test or analysis of variance were used for statistical analysis. Results:. In vivo, BLM-treated mice showed enhanced infiltration of macrophages, increased fibrotic alterations, and higher levels of Ang II and AT1R. GW4869 attenuated BLM-induced pulmonary fibrosis. Mice with exosomes injection showed fibrotic features with higher levels of Ang II and AT1R, which was reversed by irbesartan. In vitro, we found that macrophages secreted a great number of exosomes. The exosomes were taken by fibroblasts and resulted in higher levels of AT1R (0.22 ± 0.02 vs. 0.07 ± 0.02, t = 8.66, P = 0.001), TGF-β (0.54 ± 0.05 vs. 0.09 ± 0.06, t = 10.00, P

Ming Zhong,1,&ast; Tingting Pan,1,&ast; Na-Na Sun,1 Ruo-Ming Tan,1 Wen Xu,1 Yu-Zhen Qiu,1 Jia-Lin Liu,1 Er-Zhen Chen,2 Hong-Ping Qu1 1Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Emergency Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-Ping QuDepartment of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaEmail hongpingqu0412@hotmail.comEr-Zhen ChenDepartment of Emergency Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaEmail chenerzhen@hotmail.comObjective: To find the predictors for persistent inflammation-immunosuppression catabolism syndrome in ICU surgical septic patients.Design: Single center observation study.Participants: Inclusion: 1) patients ≥ 18, 2) admitted to the ICU after major surgery or transferred to the ICU within 48 hours after the diagnosis of sepsis following the definition of sepsis-3.0. Exclusion: 1) pregnant or lactating patients, 2) patients with severe immune deficiency, 3) patients that expired within 14 days after the diagnosis of sepsis.Results: A total of 169 participants were included. After propensity score matching, PICS patients were found to have higher intensive care unit (ICU) mortality (32.4% vs 12.4%, p=0.046), 90-day mortality (32.4% vs 9.1%, p=0.006), and ICU-acquired infection rate (44.1% vs 12.7%, p< 0.001), and longer ICU stays (29 vs 11 days, p< 0.001) comparing to non-PICS patients. In multivariate logistic regression, it demonstrated that the SOFA score, Charlson co-morbidity index (CCI), albumin level on the ICU day 1, and lymphocyte count on the ICU day 3 were statistically significant. Sensitivity analysis was conducted with the receiver operating characteristic curve for a combination of the four parameters and the area under the curve was 0.838 (95% confidence interval 0.774– 0.901).Conclusion: The chronic disease condition and decreased immunity in the early course of sepsis were crucial for PICS. The combination of CCI, SOFA score, albumin level on ICU Day 1 and lymphocyte count on ICU Day 3 can be early predictor for PICS.Keywords: sepsis, persistent inflammation-immunosuppression catabolism syndrome

Plant AT-rich sequence and zinc-binding (PLATZ) proteins are a class of plant-specific zinc finger transcription factors that perform critical functions in plant development and resistance. However, the function of PLATZs in heavy metal tolerance has not yet been investigated. Moreover, only a few PLATZ proteins have been functionally characterized in tree species. In this study, we identified 18 PtPLATZ genes in Populus trichocarpa, an important woody model plant, and classified them into five groups. PtPLATZ genes attributed to the same clade usually possess similar exon-intron structures containing two or three introns, as well as a similar motif composition. Furthermore, chromosomal location analysis indicated an uneven distribution of PtPLATZ genes on 13 of the 19 Populus chromosomes. Promoter cis-acting element prediction and gene expression analysis showed that PtPLATZ genes were highly responsive to heavy metal stress. Heterologous yeast expression revealed that PtPLATZ1, PtPLATZ2, PtPLATZ3, PtPLATZ4, PtPLATZ8 and PtPLATZ9 are significantly involved in Cd tolerance. In addition, transgenic expression of PtPLATZ3 significantly enhanced Cd tolerance and accumulation, slowed the decline in chlorophyll content, maintained membrane integrity in Populus, and increased the expression of genes related to Cd tolerance and accumulation. In conclusion, our results suggest the potential of PtPLATZ3 to improve Cd tolerance and accumulation in Populus, which is of great significance for phytoremediation.

As a kind of natural protein derived material, gelatin has been widely used in the preparation of medical hydrogels due to its good biocompatibility, non-immunogenicity and the ability of promoting cell adhesion. Functionalization of gelatin-based hydrogels is a hot topic in research and its clinic application. Herein, a novel gelatin-based adhesive hydrogel was prepared via mussel-inspired chemistry. Gelatin was firstly functionalized by dopamine to form dopamine grafted gelatin (GelDA). After the mixture with 1,4-phenylenebisboronic acid and graphene oxide (GO), the GelDA/GO hydrogels were obtained by H2O2/HRP (horseradish peroxidase) catalytic system. Based on the self-healing and tissue adhesion of the hydrogels, the hemostatic property has been exhibited in the rat hepatic hemorrhage model. Additionally, the incorporation of GO endowed conductivity and enhanced the mechanical property of GelDA/GO hydrogels. The electromyography (EMG) signals of finger movement were successfully monitored by using hydrogel as the adhesive electrodes of EMG monitor. L929 cell experiments showed that the hydrogels had good cytocompatibility. The results indicated the potential application of GelDA/GO hydrogels in tissue adhesives, wound dressings, and wearable devices.

In this study, the effect of pulsed electric field (PEF) on apparent morphology and molecular structure of shell-like ferritin obtained from horse spleen was determined by circular dichroic (CD), fluorescence spectroscopy, Raman spectroscopy, cold field emission scanning electron microscopy (CF-SEM) and transmission electron microscopy (TEM), and verified by molecule dynamics (MD) simulation. After PEF treatment, the α-helix content of the samples reached a minimum value at 10 kV/cm, which indicated that the ferritin structure has been partially unfolded. However, the α-helix content peaked again after resting for 2 h at 25 ± 1 °C. This indicated that the PEF-treated ferritin tended to restore its original spherical morphology probably owing to the reversible assembly characteristic of ferritin. In addition, microstructure analysis revealed that ferritin particles aggregated after PEF treatment. Therefore, PEF treatment could induce the "exposure" of hydrophobic amino acids and conversion of disulfide bond configuration, and consequently, regulate the internal cavity stability of ferritin. The research will be beneficial to expand the application of PEF treatment in the modification of protein structure, and provide a theoretical basis for the application of ferritin as a carrier of bioactive molecules in food.

Long-term potentiation (LTP) is a neurobiological mechanism of cognitive function, and the N-methyl-D-aspartate (NMDA) receptors is fundamental for LTP. Previous studies showed that over activation of NMDA receptors may be a crucial cause of LTP and cognitive impairment induced by stress or corticosterone. However, other studies showed that the function of NMDA receptors is insufficient since the NMDA receptors co-agonist D-serine could improve stress-induced cognitive impairment. The purpose of this study is to clarify whether over activation of NMDA receptors or hypofunction of NMDA receptors is involved in hippocampal impairment of LTP by corticosterone and the underlying mechanisms. Results showed that hippocampal LTP and object location recognition memory were impaired in corticosterone-treated mice. Corticosterone increased the glutamate level in hippocampal tissues, neither NMDA receptors antagonist nor its subtype antagonists alleviated impairment of LTP, while enhancing the function of NMDA receptors by D-serine did alleviate impairment of LTP by corticosterone, suggesting that hypofunction of NMDA receptors might be one of the main reasons for impairment of LTP by corticosterone. Further results showed that the level of D-serine and its precursor L-serine did not change. D-serine release-related protein Na+-independent alanine-serine-cysteine transporter-1 (ASC-1) in the cell membrane was decreased and increasing D-serine release by the selective activator of ASC-1 antiporter activity alleviated impairment of LTP by corticosterone. Taken together, this study demonstrates that hypofunction of NMDA receptors may be involved in impairment of LTP by corticosterone and reduced D-serine release may be an important reason for its hypofunction, which is an important complement to existing mechanisms of corticosterone-induced LTP and cognitive impairment.

The aim of the study was to investigate the factors influencing contrast-induced acute kidney injury (CI-AKI) after percutaneous intervention (PCI) in patients with acute coronary syndrome (ACS) with diabetes mellitus (DM). A total of 1073 patients with ACS combined with DM who underwent PCI at the Affiliated Hospital of Xuzhou Medical University were included in this study. We divided the patients into the CI-AKI and non-CI-AKI groups according to whether CI-AKI occurred or not. The patients were then randomly assigned to the training and validation sets at a proportion of 7 : 3. Based on the results of the LASSO regression and multivariate analyses, we determined that the subtypes of ACS, age, multivessel coronary artery disease, hyperuricemia, low-density lipoprotein cholesterol, triglyceride-glucose index, and estimated glomerular filtration rate were independent predictors on CI-AKI after PCI in patients with ACS combined with DM. Using the above indicators to develop the nomogram, the AUC-ROC of the training and validation sets were calculated to be 0.811 (95% confidence interval (CI): 0.766-0.844) and 0.773 (95% CI: 0.712-0.829), respectively, indicating high prediction efficiency. After verification by the Bootstrap internal verification, we found that the calibration curves showed good agreement between the nomogram predicted and observed values. And the DCA results showed that the nomogram had a high clinical application. In conclusion, we constructed and validated the nomogram to predict CI-AKI risk after PCI in patients with ACS and DM. The model can provide a scientific reference for predicting the occurrence of CI-AKI and improving the prognosis of patients.

The two-dimensional nanosheets are conducive to not only endow opened surfaces for loading active metal atoms but also boost the mass transfer for the heterogeneous reactions. The challenge is how to load and stabilize single-atoms on nanosheets in high-areal densities. This work reports an efficient micro-gas blasting (MGB) strategy to access versatile noble metal single-atoms/metal oxide nanosheets, including Ir

Harmful algal blooms caused by Heterocapsa bohaiensis have broken out in aquaculture areas near Liaodong Bay, China, since 2012, resulting in mass mortality of Eriocheir sinensis larvae and substantial economic loss. Chlorella pyrenoidosa is a local phytoplankton species that is found in aquaculture ponds. However, the reason why H. bohaiensis dominated and proliferated in the phytoplankton community remains unknown. Previous studies have revealed the toxicity and hemolytic activity of H. bohaiensis. It is suspected that the out-competition of H. bohaiensis to C. pyrenoidosa was associated with toxicity. Filtrate and bi-algal cultures were investigated to determine the interspecific competition between H. bohaiensis and C. pyrenoidosa in this study. Filtrate experiments revealed that H. bohaiensis showed no toxin allelopathy in C. pyrenoidosa. However, the C. pyrenoidosa filtrates had significant allelopathic effects on the growth of H. bohaiensis. The bi-algal culture experiments and the simulation showed that the dominant species were dependent on the initial cell density ratios of the species and nutrient ratios. Therefore, H. bohaiensis achieved competitive advantage through exploitation competition but not allelopathy. The results contribute to the reasons for the occurrence of H. bohaiensis blooms in a further study.

To investigate and analyse the prevalence of depression among patients with lung cancer, identify risk factors of depression, and develop a visual, non-invasive, and straightforward clinical prediction model that can be used to predict the risk probability of depression in patients with lung cancer quantitatively.Depression is one of the common concomitant symptoms of patients with lung cancer, which can increase the risk of suicide. However, the current assessment tools cannot combine multiple risk factors to predict the risk probability of depression in patients.A cross-sectional study.The clinical data from 297 patients with lung cancer in China were collected and analysed in this cross-sectional study. The clinical prediction model was constructed according to the results of the Chi-square test and the logistic regression analysis, evaluated by discrimination, calibration, and decision curve analysis, and visualised by a nomogram. This study was reported using the TRIPOD checklist.130 patients with lung cancer had depressive symptoms with a prevalence of 43.77%. A visual prediction model was constructed based on age, disease duration, exercise, stigma, and resilience. This model showed good discrimination at an AUC of 0.842. Calibration curve analysis indicated a good agreement between experimental and predicted values, and the decision curve analysis showed a high clinical utility.The visual prediction model developed in this study has excellent performance, which can accurately predict the occurrence of depression in patients with lung cancer at an early stage and assist the medical staff in taking targeted preventative measures.The visual, non-invasive, and simple nomogram can help clinical medical staff to calculate the risk probability of depression among patients with lung cancer, formulate personalised preventive care measures for high-risk groups as soon as possible, and improve the quality of life of patients.

Thrips pests cause increasing damage to crops around the world. Widespread usage of some insecticides against thrips has now led to the evolution of resistance to several active ingredients, and new insecticides are required. This study examined the toxicity of the novel insecticide broflanilide to multiple populations of several thrips pests.Bioassays showed that thrips populations had LCBroflanilide is potentially a useful insecticide for controlling Thrips hawaiiensis, Frankliniella intonsa, Megalurothrips usitatus. E. americanus, and some populations of T. palmi. However, the variation in toxicity of this insecticide to different species, populations, and developmental stages indicates that target species and life stages may need to be carefully considered. © 2022 Society of Chemical Industry.

PurposeThe Liyang cohort study on chronic diseases and risk factors monitoring in China (Liyang Study) is a prospective population-based study which aims to investigate and identify the determinants of the most prevalent chronic non-communicable diseases (NCDs) and to evaluate the impact of demographic characteristics, lifestyle, dietary habits, cognition, disability and NCDs on the health-related quality of life.ParticipantsBetween March 2019 and June 2020, 10 056 individuals aged ≥18 years were administered a baseline survey through a multistage cluster random sampling in Liyang City, southern Jiangsu Province, China.Findings to dateThe Liyang Study included detailed sociodemographic, anthropometric and health-related behaviour, common NCDs and blood sample information. Moreover, the study gathered a series of data on specific scales including the activities of daily living, instrumental activities of daily living, abbreviated mental test, Food Frequency Questionnaire and EuroQol 5-Dimensions 5-Levels Scale. Of the 10 056 participants, 52.92% (n=5322) were female and 92.26% (n=9278) came from rural areas. The mean age was 49.9±16.2 years. Men were more likely to have a higher level of education, annual income and a paid job than women (pFuture plansThe current study will give valuable insights into the association between sociodemographic factors, health-related behaviour, diet, cognition, disability and genetic factors and the most prevalent NCDs among local community residents. Starting from 2022, a follow-up survey will be conducted every 3 years to further explore the causal relationship between the above factors and NCDs.

Hypoxic nonhealing wounds are a common complication in chronic patients, and chronic hypoxia is the main reason for delayed wound healing, so local wound oxygenation may be an effective way to address this problem. Here, we proposed a system consisting of oxygen-releasing microsphere (GC) and self-healing hydrogel (QGO). QGO/GC hydrogel could promote survival, migration and tube formation of human umbilical vein endothelial cells under hypoxic conditions. Moreover, QGO/GC hydrogels exhibited biocompatibility in vitro and in vivo. The hypoxic mouse burn model further confirmed that QGO/GC hydrogel could promote tissue repair by reducing inflammation (TNF-α and IL-1β), increasing angiogenesis (CD31, VEGF and α-SMA) and collagen deposition. This study provided an effective oxygen-releasing hydrogel that could offer a simple and effective method for the clinical treatment of chronic hypoxic wounds. STATEMENT OF SIGNIFICANCE: Burn injury is caused by various exogenous factors such as friction, cold, radiations, electricity, chemicals, hot surfaces or liquids. Severe burn can damage the entire skin layer, and the healing process is delayed due to an unbalanced inflammatory response, excessive reactive oxygen species, lack of angiogenesis (insufficient nutrient and oxygen availability), and susceptibility to infection. In the present study, we proposed an oxygen-releasing hydrogel (QGO/GC). QGO/GC hydrogel could promote survival, migration, and tube formation of human umbilical vein endothelial cells under hypoxic conditions. And QGO/GC hydrogels could promote tissue repair by reducing inflammation, increasing angiogenesis and collagen deposition. This work provided an effective oxygen-releasing hydrogel for the clinical management of chronic hypoxic wounds.

Hederasaponin C (HSC), one of the main components of Pulsatilla chinensis, is considered as a potential drug for the treatment of inflammatory bowel disease. In the present research, we developed a pharmacokinetics-pharmacodynamics model to describe the concentration-effect course of drug action following the intraperitoneal injection of HSC in colitis rats. A sensitive UPLC-MS/MS method was established for the the determination of HSC in rat plasma to explore the pharmacokinetics properties. The separation was performed on an Accucore C

Cancer seriously endangers human life and health. Recently, the development of AIEgens with aggregation-induced emission (AIE) effect as a new generation of photosensitizers (PSs) to circumvent aggregation-induced fluorescence quenching and reduction of ROS generation has received extensive attention in photodynamic therapy (PDT), a non-invasive anticancer therapy. Rational molecular design can enhance the photosensitization of AIE PSs to achieve effective PDT and can realize the construction of functionalized AIE PSs and synergistic therapy based on AIE PSs. To improve the efficacy of AIE PSs for cancer treatment, many groups have conducted molecular design studies and produced exciting results. This review summarizes the molecular design strategies of three types of AIE PSs for effective photodynamic therapy, focusing on the design strategies of pure organic small molecule type AIE PSs, and reviews the existing design strategies of metal complexes and conjugated polymers. Subsequently, the design strategy to achieve synergistic treatment of AIE PSs from molecular modifications is summarized. The challenges and prospects of the AIE PSs research field are further discussed.

Mammalian orthoreoviruses (MRVs) can infect many mammals including human, and numerous higher virulent MRVs have been reported in recent years. The first mink orthoreovirus was reported in China in 2011. In the present study, three new strains of mammalian orthoreoviruses were isolated from mink, and found to be most closely related to human strain MRV2Tou05 and other human strains. Mink experiments demonstrated that the isolated mink reoviruses did not lead to severe pathogenicity. Viruses were eliminated within 2 weeks after infection, but they may cause viral enteritis disease in puppies.

Objective: This study sought to determine the mean prognostic usefulness of seleniumphosphate synthase ( SEPHS1) by investigating its expression in 33 human malignancies and its relationship to tumor immunity. Methods: The expression of selenophosphate synthase 1 ( SEPHS1) in 33 human malignant tumors was examined using the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), and TIMER databases. Furthermore, the TCGA cohort was used to investigate relationships between SEPHS1 and immunological checkpoint genes (ICGs), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs). To establish independent risk factors and calculate survival probabilities for liver hepatocellular carcinoma (LIHC) and brain lower-grade glioma (LGG), Cox regression models and Kaplan-Meier curves were utilized. Eventually, the Genomics of Cancer Drug Sensitivity (GDSC) database was used to evaluate the drug sensitivity in LGG and LIHC patients with high SEPHS1 expression. Results: Overall, in numerous tumor tissues, SEPHS1 was highly expressed, and it significantly linked with the prognosis of LGG, ACC, and LIHC ( P < .05). Furthermore, in numerous cancers, SEPHS1 expression was linked to tumor-infiltrating immune cells (TIICs), TMB, MSI, and MMRs. According to univariate and multivariate Cox analyses, SEPHS1 expression was significant for patients with LGG and LIHC. Conclusion: High SEPHS1 expression has a better prognosis for LGG, while low SEPHS1 expression has a better prognosis for LIHC. Chemotherapy was advised for LGG patients, particularly for those with high SEPHS1 expression because it can predict how responsive patients will be to 5-Fluorouracil and Temozolomide. This interaction between SEPHS1 and chemoradiotherapy has a positive clinical impact and may be used as evidence for chemotherapy for LGG and LIHC patients.

We aimed to evaluate the prognostic value of 18F-FDG PET/CT in patients with relapsed or refractory T-Lymphoblastic lymphoma (T-LBL) undergoing hematopoietic stem cell transplantation (HSCT). PET/CT was performed in 21 consecutive relapsed or refractory T-LBL patients scheduled for HSCT. All PET/CT images were assessed using the Deauville criteria, and patients were divided into negative (Deauville ≤ 3) and positive (Deauville > 3) groups for comparison. The predictive value of sex, age, Ann Arbor stage, presence of B symptoms, lactate dehydrogenase level, presence of extranodal disease, and PET/CT results before and after HSCT were evaluated. Kaplan–Meier analysis showed that only PET/CT after HSCT (post-PET) was correlated with progression-free survival (PFS) (P = 0.030). The Cox regression model also showed that the post-PET-positive group had a higher hazard ratio (HR) than the negative group (HR = 3.884 and P = 0.049). However, none of the evaluated factors were predictive of overall survival (OS). Pre-PET cannot predict the PFS and OS of patients with T-LBL undergoing HSCT, which means that 18F-FDG PET/CT cannot be used for identifying patients who can benefit from HSCT. Post-PET is not predictive for OS in patients with T-LBL undergoing HSCT. However, post-PET showed strong correlations with PFS, which means that it may be useful for guiding subsequent clinical treatment decisions.

Enzymatic hydrolysis could be one of the crucial means to limit the allergenicity of allergens. The allergenicity of pea peptides was evaluated using indirect ELISA and RBL-2H3 cell assay, thereby obtaining hypoallergenic pea peptide sequences. Results indicated that pea protein-sensitized mice produced higher levels of total IgG1 and IgE antibodies than the mice in the control group (P < 0.05). Moreover, the allergenicity of hydrolysates decreased significantly after enzymolysis, and the allergenicity of ultrafiltration component F1 and purified component F1–2 was significantly lower than that of other isolated and purified components (P < 0.05). Furthermore, ADLYNPR identified from F1–2 had lower binding capacity to specific IgE and IgG1 and lower degree of cell degranulation with a higher EC50 value of 6.63 ng mL−1, which was about 36.83 times that of pea protein (P < 0.05). Based on the above results, ADLYNPR might be a potential source of hypoallergenic peptides.

For reliable downstream molecular analysis, it is crucially important to recover circulating tumor cells (CTCs) from clinical blood samples with high purity and viability. Herein, magnetic nanoparticles coated with an antifouling hydrogel layer based on the polymerization method were developed to realize cell-friendly and efficient CTC capture and recovery. Particularly, the hydrogel layer was fabricated by zwitterionic sulfobetaine methacrylate (SBMA) and methacrylic acid (MAA) cross-linked with N,N-bis(acryloyl)cystamine (BACy), which could not only resist nonspecific adhesion but also gently recover the captured cells by glutathione (GSH) responsiveness. Moreover, the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody was modified onto the surface of the hydrogel to provide high specificity for CTC capture. As a result, 96% of target cells were captured in the mimic clinical blood samples with 5-100 CTCs per mL in 25 min of incubation time. After the GSH treatment, about 96% of the obtained cells were recovered with good viability. Notably, the hydrogel-coated magnetic nanoparticles were also usefully applied to isolate CTCs from the blood samples of cancer patients. The favorable results indicate that the hydrogel-modified magnetic nanoparticles may have a promising opportunity to capture and recover CTCs for subsequent research.

Aurora-A has attracted a great deal of interest as a potential therapeutic target for patients with CRC. However, the outcomes of inhibitors targeting Aurora-A are not as favorable as expected, and the basis behind the ineffectiveness remains unknown. Here, we found that signal transducer and activator of transcription 1 (STAT1) was highly expressed in colorectal cancer (CRC) xenograft mouse models that were resistant to alisertib, an Aurora-A inhibitor. Unexpectedly, we found that alisertib disrupted Aurora-A binding with ubiquitin-like with plant homeodomain and ring finger domain 1 (UHRF1), leading to UHRF1 mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1), which in turn resulted in demethylation of CpG islands of STAT1 promoter and STAT1 overexpression. Simultaneous silencing Aurora-A and UHRF1 prevented STAT1 overexpression and effectively inhibited CRC growth. Hence, concomitant targeting Aurora-A and UHRF1 can be a promising therapeutic strategy for CRC.

Zearalenone (ZEA), present in animal grain feed is produced by Fusarium fungi and this toxin targets ovarian granulosa cells (GCs) to cause reproductive disorders in female animals. Current research on drugs that can rescue ZEA-induced ovarian GC damage is limited. The purpose of this study was to explore the effect of scutellarin (Scu) on ZEA-induced apoptosis of mouse ovarian GCs and its mechanism. In one set of experiments, the primary cultured mouse ovarian GCs were co-treated with ZEA and Scu for 24 h. The results showed that Scu significantly alleviated ZEA-induced cell damage, restored cell cycle arrest, and inhibited apoptosis by reducing the ratio of cleaved-caspase-3, cleaved-PARP, and Bax/Bcl-2. In another set of experiments, six-week-old mice were intragastrically administered with 40 mg kg-1 ZEA for 2 h, followed by 100 mg kg-1 Scu for 3 days. It was observed that Scu inhibited ZEA-induced apoptosis and positive signal expression of cleaved-caspase-3 in the ovarian granulosa layer, with the involvement of the mitochondrial apoptotic pathway. These data provide strong evidence that Scu can be further developed as a potential new therapeutic drug for preventing or treating reproductive toxicity caused by the exposure of animals to ZEA found in the grains of animal feeds.

Three peptides containing three glutamic acid (Glu) residues at different positions derived from Antarctic krill were obtained to investigate their iron-binding properties, digestive stability, and effectiveness on enhancing iron solubility and absorption. Results indicated that Fe2+ bound to the carbonyl, carboxyl, or hydroxyl groups of DELEDSLER, EEEFDATR, and DTDSEEEIR at stoichiometric ratios of 0.453, 0.466, and 0.490, respectively. DTDSEEEIR with three consecutive Glu in the middle of the sequence possessed higher iron-binding ability and iron release potential than EEEFDATR with three consecutive Glu in the N-terminal, and DELEDSLER with three discontinuous Glu showed the lowest values. Although EEEFDATR showed remarkably lower digestion stability than DTDSEEEIR, the effect of EEEFDATR–iron on iron solubility and absorption was comparable to that of DTDSEEEIR–iron, but better than that of DELEDSLER–iron and FeSO4. Thus, peptides with consecutive Glu have the potential as an effective iron carrier to improve iron absorption.

BACKGROUND 45,X/46,XY mosaicism is a rare chromosomal abnormality with a wide range of phenotypes in both males and females, from normal individuals with different degrees of genital ambiguity to those who show signs of Turner’s syndrome. More rarely, cases of 45,X/46,XY mosaicism with a normal-appearing male phenotype are not found until a chromosome test is performed to investigate the cause of male infertility. CASE SUMMARY In this study, a 29-year-old male patient with complete azoospermia is reported. Chromosomal analyses of his lymphocytes revealed the karyotype 45,X[93%]/46,X,+mar(Y)[7%]. In addition, Y chromosome-specific markers, such as SRY, ZFY, AZFa, AZFb and AZFc, were not observed in his blood DNA according to multiplex polymerase chain reaction test. A literature review identified several 45,X/46,XY cases with a normal-appearing male phenotype, most of whom were diagnosed during infertility investigation. However, the present case is the first SRY-negative 45,X/46,XY male case diagnosed during a premarital medical examination. CONCLUSION This finding further suggests that sex determination is a complex process regulated by multiple genetic and environmental factors.

Iron deficiency is a global nutritional problem, and adding iron salts directly to food will have certain side effects on the human body. Therefore, there is growing interest in food-grade iron delivery systems. This review provides an overview of iron delivery systems, with emphasis on the controlled release of iron during gastrointestinal digestion, as well as the enhancement of iron absorption and bioavailability. Iron-bearing proteins are easily degraded by digestive enzymes and absorbed through receptor-mediated endocytosis. Instead, protein aggregates are slowly degraded in the stomach, which delays iron release and serves as a potential iron supplement. Amino acids, peptides and polysaccharides can bind iron through iron binding sites, but the formed compounds are prone to dissociation in the stomach. Moreover, peptides and polysaccharides can deliver iron by mediating the formation of ferric oxyhydroxide which is absorbed through endocytosis or bivalent transporter 1. In addition, liposomes are unstable during gastric digestion and iron is released in large quantities. Complexes formed by polysaccharides and proteins, and microcapsules formed by polysaccharides can delay the release of iron in the gastric environment and prolong iron release in the intestinal environment. This review is conducive to the development of iron functional ingredients and dietary supplements.

Objective. To systematically evaluate the effects of peritoneal dialysis and hemodialysis on renal function and quality of life in patients with end-stage renal disease. An evidence-based medical rationale would be provided for peritoneal dialysis or hemodialysis treatment in patients with end-stage renal disease. Methods. The PubMed, EMBASE, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure (CNKI), China VIP Database, Wanfang, and China Biomedical Literature Database (CBM) online databases were searched. Comparisons on the effects of peritoneal dialysis on renal function and quality of life were taken between patients with end-stage renal disease (RD). The data were extracted independently by two researchers. The bias-risk-included literatures were assessed according to the Cochrane manual 5.1.0 standard. RevMan 5.4 statistical software was used to analyze the collected data via meta-analysis. Results. Seven RCT articles were finally included. A total of 745 samples were analyzed via meta-analysis. The obvious heterogeneities of serum creatinine (Scr) and blood urea nitrogen (BUN) were discovered ( P < 0.00001 ) in the selective investigations. According to the results of this analysis, it was indicated that the renal function of patients with end-stage renal disease treated by peritoneal dialysis was significantly better than that of hemodialysis. According to the meta-analysis, there was obvious heterogeneity of life quality among the included research data. It was indicated that the score of quality of life of patients with end-stage renal disease treated by peritoneal dialysis was significantly better than that of hemodialysis. Conclusion. Compared with hemodialysis in the treatment of end-stage renal disease, the renal function and quality of life of patients with peritoneal dialysis are better than those of hemodialysis. More further studies and follow-up with higher methodological quality and longer intervention time are still needed for further verification.