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Abstract Background The neonatal outcomes across different percentiles of birth weight for gestational age are still unclear. Methods This retrospective cohort study was conducted within 57 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 25 provinces throughout China. Infants with gestational age (GA) 24+0-31+6 weeks who were admitted within 7 days after birth were included. The composite outcome was defined as mortality or any one of neonatal major morbidities, including necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (cPVL), severe retinopathy of prematurity (ROP), and sepsis. Multivariable logistic regressions using generalized estimating equation approach were conducted. Results A total of 8380 infants were included with a mean GA of 30 (28–31) weeks. Of these, 1373 (16.5%) were born at less than 28 weeks, while 6997 (83.5%) had a GA between 28 and 32 weeks. Our analysis indicated that the risk of composite outcomes was negatively associated with birth weight for gestational age, and compared to the reference group, the multiple-adjusted ORs (95%CI) of composite outcomes were 4.89 (3.51–6.81) and 2.16 (1.77–2.63) for infants with birth weight for gestational less than 10th percentile and 10th -30th percentile, respectively. The ORs (95%CI) of mortality, NEC, BPD, severe ROP, and sepsis in infants with birth weight for gestational age at 10th-30th percentile were 1.94 (1.56–2.41), 1.08 (0.79–1.47), 2.48 (2.03–3.04), 2.35 (1.63–3.39), and 1.39 (1.10–1.77), respectively. Conclusion Our study suggested that the risk of adverse neonatal outcomes increased significantly when the birth weight for gestational age was below the 30th percentile. Regular monitoring and early intervention are crucial for these high-risk infants.

Abstract Controllable photofluorochromic systems with high contrast and multicolor in both solutions and solid states are ideal candidates for the development of dynamic artificial intelligence. However, it is still challenging to realize multiple photochromism within one single molecule, not to mention good controllability. Herein, we report an aggregation-induced emission luminogen TPE-2MO2NT that undergoes oxidation cleavage upon light irradiation and is accompanied by tunable multicolor emission from orange to blue with time-dependence. The photocleavage mechanism revealed that the self-generation of reactive oxidants driving the catalyst-free oxidative cleavage process. A comprehensive analysis of TPE-2MO2NT and other comparative molecules demonstrates that the TPE-2MO2NT molecular scaffold can be easily modified and extended. Further, the multicolor microenvironmental controllability of TPE-2MO2NT photoreaction within polymer matrices enables the fabrication of dynamic fluorescence images and 4D information codes, providing strategies for advanced controllable information encryption.

BackgroundKawasaki disease (KD) is a self-limiting and acute systemic vasculitis of unknown etiology, mainly affecting children. Ferulic acid (FA), a natural phenolic substance, has multiple pharmacological properties, including anti-inflammatory, anti-apoptosis, and anti-fibrosis, and so on. So far, the protective effects of FA on KD have not been explored.MethodsIn this study, we established Candida albicans water soluble fraction (CAWS)-induced mouse coronary artery vasculitis of KD model and the tumor necrosis factor α (TNF-α)-induced human umbilical vein endothelial cells (HUVECs) injury model to investigate the anti-inflammatory and anti-apoptosis effects of FA on KD, and try to elucidate the underlying mechanism.ResultsOur in vivo results demonstrated that FA exerted anti-inflammatory effects on KD by inhibiting the infiltration of CD45-positive leukocytes and fibrosis around the coronary artery. Additionally, FA downregulated the levels of inflammatory and chemotactic cytokines, alleviated splenomegaly, and exhibited anti-apoptotic effects on KD by reducing TUNEL-positive cells, downregulating BAX expression, and upregulating BCL-2 expression. In addition, Our in vitro findings showed that FA could effectively inhibit TNF-α-induced HUVEC inflammation like NF-κB inhibitor QNZ by downregulating the expression of pro-inflammatory cytokines as well as attenuated TNF-α-induced HUVEC apoptosis by reducing apoptotic cell numbers and the BAX/BCL-2 ratio, which could be reversed by the AMPK inhibitor compound c (CC). The further mechanistic study demonstrated that FA could restrain vascular endothelial cell inflammation and apoptosis in KD through activating the AMPK/mTOR/NF-κB pathway. However, FA alone is hard to completely restore KD into normal condition.ConclusionIn conclusion, FA has potential protective effects on KD, suggesting its promising role as an adjuvant for KD therapy in the future.

Abstract Background Sepsis-associated encephalopathy (SAE) refers to the widespread impairment of brain function caused by noncentral nervous system infection mediated by sepsis. Lipid peroxidation-induced ferroptosis contributes to the occurrence and course of SAE. This study aimed to investigate the relationship between neuronal injury and lipid peroxidation-induced ferroptosis in SAE. Methods Baseline data were collected from pediatric patients upon admission, and the expression levels of various markers related to lipid peroxidation and ferroptosis were monitored in the serum and peripheral blood mononuclear cells (PBMCs) of patients with SAE as well as SAE model mice. The hippocampal phosphatidylethanolamine-binding protein (PEBP)-1/15-lysine oxidase (LOX)/ glutathione peroxidase 4 (GPX4) pathway was assessed for its role on the inhibitory effect of ferroptosis in SAE treatment. Results The results showed elevated levels of S100 calcium-binding protein beta (S-100β), glial fibrillary acidic protein, and malondialdehyde in the serum of SAE patients, while superoxide dismutase levels were reduced. Furthermore, analysis of PBMCs revealed increased transcription levels of PEBP1, LOX, and long-chain fatty acyl-CoA synthetase family member 4 (ACSL4) in SAE patients, while the transcription levels of GPX4 and cystine/glutamate transporter xCT (SLC7A11) were decreased. In comparison to the control group, the SAE mice exhibited increased expression of S-100β and neuron-specific enolase (NSE) in the hippocampus, whereas the expression of S-100β and NSE were reduced in deferoxamine (DFO) mice. Additionally, iron accumulation was observed in the hippocampus of SAE mice, while the iron ion levels were reduced in the DFO mice. Inhibition of ferroptosis alleviated the mitochondrial damage (as assessed by transmission electron microscopy, hippocampal mitochondrial ATP detection, and the JC-1 polymer-to-monomer ratio in the hippocampus) and the oxidative stress response induced by SAE as well as attenuated neuroinflammatory reactions. Further investigations revealed that the mechanism underlying the inhibitory effect of ferroptosis in SAE treatment is associated with the hippocampal PEBP-1/15-LOX/GPX4 pathway. Conclusion These results offer potential therapeutic targets for the management of neuronal injury in SAE and valuable insights into the potential mechanisms of ferroptosis in neurological disorders.

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) has been harming the pig industry worldwide for nearly 40 years. Although scientific researchers have made substantial efforts to explore PRRSV pathogenesis, the immune factors influencing PRRSV infection still need to be better understood. Infectious virus-antibody immune complexes (ICs) formed by PRRSV and sub-or non-neutralizing antibodies specific for PRRSV may significantly promote the development of PRRS by enhancing PRRSV replication through antibody-dependent enhancement. However, nothing is known about whether PRRSV infection is affected by non-infectious ICs (NICs) formed by non-pathogenic/infectious antigens and corresponding specific antibodies. Here, we found that PRRSV significantly induced the transcripts and proteins of interferon-α (IFN-α), IFN-β, IFN-γ, IFN-λ1, and tumor necrosis factor-α (TNF-α) in vitro primary porcine alveolar macrophages (PAMs) in the early stage of infection. Our results showed that NICs formed by rabbit-negative IgG (RNI) and pig anti-RNI specific IgG significantly reduced the transcripts and proteins of IFN-α, IFN-β, IFN-γ, IFN-λ1, and TNF-α in vitro PAMs and significantly elevated the transcripts and proteins of interleukine-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in vitro PAMs. NICs-mediated PRRSV infection showed that NICs not only significantly decreased the induction of IFN-α, IFN-β, IFN-γ, IFN-λ1, and TNF-α by PRRSV but also significantly increased the induction of IL-10 and TGF-β1 by PRRSV and considerably enhanced PRRSV replication in vitro PAMs. Our data suggested that NICs could downregulate the production of antiviral cytokines (IFN-α/β/γ/λ1 and TNF-α) during PRRSV infection in vitro and facilitated PRRSV proliferation in its host cells by inhibiting innate antiviral immune response. This study elucidated one novel immune response to PRRSV infection, which would enhance our understanding of the pathogenesis of PRRSV.

Using data from 30-province/autonomous in China, this study systematically examines the impact and transmission mechanism of increased income and climate change on energy consumption. This study innovatively uses urbanization and industrial structure upgrade indicators to examine the indirect mechanism of income impact on energy consumption. The findings indicate that income has direct and indirect impacts on energy consumption. Income can directly affect energy consumption and the impact has an inverted U shape. In addition, income can indirectly reduce energy consumption by promoting urbanization and industrial structure upgrading. Climate change also has a significant negative effect on energy consumption; however, the climate effect of energy consumption is smaller than the income effect. Additionally, the impact of income on energy consumption has significant temporal and regional differences. Temporally, income shows a significant upward trend in reducing energy consumption. Regionally, in the developed eastern region, income has a negative impact on energy consumption. In the underdeveloped western region, income has a significant positive impact on energy consumption. Considering the characteristics of China's energy consumption, we should resist the “one size fits all” energy policy and focus on improving energy consumption on income growth, urbanization, and industrial structure, enhancing the efficiency and targeting.

BackgroundPeriodontitis, a complex inflammatory condition, has been associated with dietary habits and antioxidants. While the association between certain dietary patterns and periodontitis has been documented, the bidirectional relationship remains unclear. This study utilizes Mendelian randomization (MR) analysis to investigate the bidirectional associations between dietary factors comprising dietary antioxidants, and periodontitis.MethodsEmploying a two-sample MR approach, this study analyzed genome-wide association study (GWAS) data on diets and periodontitis from large databases and published literature. Instrumental variables (IVs) were selected and filtered based on genetic variants associated with dietary factors and periodontitis, respectively. Various MR methods, including Inverse Variance Weighted, MR-Egger, Weighted Median, Weighted Mode, and Simple Mode were applied to assess the bidirectional associations. Sensitivity analyses were conducted to validate the robustness of the findings.ResultsOur analysis revealed significant associations between certain dietary factors and the risk of periodontitis. Specifically, higher intake of filtered coffee, low-calorie drinks, and other cereals, as well as increased metabolic circulating levels of gamma-tocopherol, were associated with an elevated risk of periodontitis. Conversely, consumption of cheese, white rice, chocolate bars, unsalted peanuts, and higher absolute circulating levels of vitamin C were linked to a reduced risk. Additionally, the study suggests that periodontitis may influence dietary habits, indicating a bidirectional relationship.ConclusionThis study provides additional evidence of a bidirectional association between dietary factors and periodontitis. It highlights the importance of dietary interventions in the prevention and management of periodontitis. The findings underscore the need for incorporating dietary counseling into periodontal disease management protocols and suggest the potential of personalized dietary strategies for periodontitis patients. Further research is warranted to explore the mechanisms underlying these associations and to confirm these findings in diverse populations.

Neural Radiation Field (NeRF) technology can learn a 3D implicit model of a scene from 2D images and synthesize realistic novel view images. This technology has received widespread attention from the industry and has good application prospects. In response to the problem that the rendering quality of NeRF images needs to be improved, many researchers have proposed various methods to improve the rendering quality in the past three years. The latest relevant papers are classified and reviewed, the technical principles behind quality improvement are analyzed, and the future evolution direction of quality improvement methods is discussed. This study can help researchers quickly understand the current state and evolutionary context of technology in this field, which is helpful in inspiring the development of more efficient algorithms and promoting the application of NeRF technology in related fields.

Abstract The present study investigated the composition, abundance, and diversity of gut microbes in full-term and late-preterm infants from a medical center in eastern China. A total of 144 genomes of stool samples were captured for 16S rRNA metagenomic analyses. A high abundance of commensal intestinal bacteria was detected in these samples such as Phocaeicola vulgatus, Escherichia coli, and Faecalibacterium prausnitzii, indicating a relatively consistent diversity of gut microbes in the present full-term infants aged 38–40 weeks. However, late preterm infants (n = 50) with mandatory antimicrobials feeding exhibited lower diversity but a higher composition of opportunistic pathogens such as Enterococcus species. Centralized on the situation, we explored the regulatory effect of Clostridium butyricum as probiotics on these late preterm infants. The consumption of C. butyricum did not restore the composition of gut microbes altered by antimicrobials to normal levels, although several opportunistic pathogens decreased significantly after probiotic therapy including Staphylococcus aureus, Sphingomonas echinoides, and Pseudomonas putida. We also compared the effects of day-fed versus night-fed probiotics. Intriguingly, the nighttime feeding showed a higher proportion of C. butyricum compared with probiotic day-feeding. Finally, fecal metabolome and metabolites were analyzed in late preterm infants with (n = 20) or without probiotic therapy (n = 20). The KEGG enrichment analysis demonstrated that vitamin digestion and absorption, synaptic vesicle cycle, and biotin metabolism were significantly increased in the probiotic-treated group, while MSEA indicated that a series of metabolism were significantly enriched in probiotic-treated infants including glycerolipid, biotin, and lysine, indicating the complex effects of probiotic therapy on glutathione metabolism and nutrients digestion and absorption in late preterm infants. Overall, this study provided metagenomic and metabolomic profile of the gut microbes in full-term newborns and late preterm infants in eastern China. Further studies are needed to support and elucidate the role of probiotic feeding in late preterm infants with mandatory antimicrobial treatment.

Lung adenocarcinoma remains one of the most frequent and deadly tumour entities. Early-stage lung adenocarcinoma is extremely difficult to detect and is also easy to recur or metastasize after treatment. Since the new adenocarcinoma classification was presented in 2011, several studies have shown that patients with solid and/or micropapillary (S/MP) predominant patterns showed a worse prognosis. Here we report the case of a 54-year-old woman who was diagnosed with stage Ib lung adenocarcinoma with S/MP components and developed an isolated brain oligometastasis after resection and adjuvant therapy. A craniocerebral operation was performed, combined with radiotherapy and targeted therapy, and the patient eventually achieved a good quality of life. Our work reviews the clinical features of lung cancer complicated with S/MP components, the relationship between MP and epidermal growth factor receptor (EGFR) mutation, as well as treatment strategies for such a patient with postoperative brain oligometastasis of lung adenocarcinoma complicated with EGFR Exon19del mutation.

BackgroundExposure to perfluoroalkyl and polyfluoroalkyl substances (PFAS) during pregnancy might affect thyroid-related hormone levels in pregnant women. However, most previous studies focused on the effects of PFAS containing 8-10 carbon atoms, and few studies have estimated the associations between PFAS with longer carbon chain and thyroid-related hormone levels. ObjectiveTo examine the associations between PFAS exposure and thyroid-related hormones in pregnant women. MethodsThe present study was based on the Jiashan Birth Cohort from September 2016 to April 2018. We analyzed 13 PFAS in maternal blood samples (n=781) by high-performance liquid chromatography-tandem mass spectrometry, as well as total triiodothyronine (T3), total thyroxine (T4), free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), and thyroid peroxidase antibody (TPOAb) by electrochemiluminescence immunoassay. PFAS were divided into three groups:low concentration, medium concentration and high concentration according to the tertile of their concentrations. We estimated the associations between PFAS concentrations and thyroid-related hormones in pregnant women by multiple linear regression. ResultsIn the multiple linear regression models, a change in perfluorododecanoic acid (PFDoA) concentrations from the low concentration group to the high concentration group was associated with a −0.10 (95%CI: −0.20, 0) nmol·L−1 change in T3, −0.15 (95%CI: −0.28, −0.02) pmol·L−1 change in FT3, and −3.02 (95%CI: −5.66, −0.39) pmol·L−1 change in FT4, respectively. A change in perfluorotridecanoic acid (PFTrDA) concentrations from the low concentration group to the high concentration group was associated with a −0.10 (95%CI: −0.20, 0) nmol·L−1 change in T3. Compared with the low concentration group, the concentration of T4 in the medium concentration group of perfluorohexane sulfonate (PFHxS) increased by 6.10 (95%CI: 0.44, 11.75) nmol·L−1. No statistically significant associations were found between PFAS and TSH concentration. The negative associations of PFAS with thyroid-related hormones were more pronounced in pregnant women with positive TG-Ab and/or TPOAb. ConclusionExposure to PFAS during pregnancy may affect thyroid-related hormone homeostasis in pregnant women, and the effect is stronger in TG-Ab and/or TPOAb-positive pregnant women.

Traditional non-steroidal anti-inflammatory drugs (NSAIDs) show serious adverse effects during clinical use, which limits their usage. Oxicams (e.g., piroxicam, meloxicam) are widely used as NSAIDs. However, selectivity to cyclooxygenase (COX) 2 may cause cardiovascular problems considering the long-term use of the drugs. Therefore, it is important to develop new non-steroidal compounds as anti-inflammatory drugs. In the present study, we evaluated the anti-inflammatory activity of a newly developed nonsteroidal drug XK01. Our data showed that XK01 reduced the contents of nitric oxide (NO) and reactive oxygen species (ROS)and inhibited the transcription levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages. XK01 showed no significant inhibitory effect on COX-1, but inhibited the expression of COX-2. At molecular level, XK01 prevented the translocation of p65 protein from the cytoplasm to the nucleus and inhibited the phosphorylation of p65, IκB, and MAPKs proteins. And high concentration of XK01 also inhibited the phosphorylation of JNK, p38 and ERK, showing stronger effect than that of meloxicam. In addition, the anti-inflammatory activity of XK01 was further validated in Xylene-induced mouse ear swelling model. Thus, this study verified that XK01 inhibits the expression of inflammatory mediators and COX-2, and exhibits potential anti-inflammatory effects via suppressing the NF-κB and MAPK pathway.

BackgroundHemodynamic instability is the main factor responsible for the development of intraventricular hemorrhage (IVH) in premature newborns. Herein, we evaluated the predictive ability of blood pressure variability (BPV) and anterior cerebral artery (ACA) blood flow parameters in IVH in premature infants with gestational age (GA) ≤32 weeks and birth weight (BW) ≤ 1,500 g.MethodsPreterm infants with GA ≤32 weeks and BW ≤ 1,500 g admitted to the neonatal intensive care unit (NICU) of the hospital affiliated to Yangzhou University from January 2020 to January 2023 were selected as the research subjects. All preterm infants were admitted within 1 h after birth, and systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) were monitored at 1-h intervals. The difference between maximum and minimum values (max-min), standard deviation (SD), coefficient of variation (CV), and successive variation (SV) were used as BPV indicators. On the 1st, 3rd, and 7th day after birth, transcranial ultrasound examination was performed to screen for the occurrence of IVH. On the 24 ± 1 h after birth, systolic velocity (Vs), diastolic velocity (Vd), and resistance index (RI) of the ACA were measured simultaneously. Preterm infants were divided into the IVH group and non-IVH group based on the results of transcranial ultrasound examination, and the correlation between BPV indicators, ACA blood flow parameters, and development of IVH was analyzed.ResultsA total of 92 premature infants were enrolled, including 49 in the IVH group and 43 in the non-IVH group. There was no statistically significant difference in baseline characteristics such as BW, GA, sex, and perinatal medical history between the two groups of preterm infants (P > 0.05). The SBP SD (OR: 1.480, 95%CI: 1.020–2.147) and ACA-RI (OR: 3.027, 95%CI: 2.769–3.591) were independent risk factors for IVH in premature newborns. The sensitivity and specificity of combined detection of SBP SD and ACA-RI in predicting IVH were 61.2% and 79.1%, respectively.ConclusionHigh BPV and ACA-RI are related to IVH in premature infants with GA ≤32 w and BW ≤1,500 g. Combined detection of SBP SD and ACA-RI has a certain predictive effect on early identification of IVH.

Abstract Background Left-to-right shunt congenital heart disease is more likely to induce recurrent respiratory infections in the patients which exacerbate pulmonary hypertension and thereby impairs cardiac function. It is urgent to explore a non-invasive and accurate diagnostic method that can show the cardiac anatomy and associated malformations in clinical research. Objective To determine the diagnostic value of peripheral mucin domain protein-3 (Tim-3), N-terminal pro-brain natriuretic peptide (NT proBNP), sestrin2 testing in patients with the left-to-right shunt congenital heart disease and heart failure. Methods Fifty-two neonates with with left to right shunt congenital heart disease and 30 healthy neonates were enrolled. Blood samples were collected within 24 h of admission from newborns for determining the content of TiM-3, NT proBNP, and Sestrin2. Analyzing the ROC curve provided insight into the diagnostic accuracy. Both a Spearman’s rank correlation test and a logistic regression analysis were carried out. Results TiM-3, NT proBNP, and Sestrin2 levels in peripheral blood were statistically different in the three groups (P

Abstract Large-scale trapped-ion quantum computers hold great promise to outperform classical computers and are crucially desirable for finance, pharmaceutical industry, fundamental chemistry and other fields. Currently, a big challenge for trapped-ion quantum computers is the poor scalability mainly brought by the optical elements that are used for optical addressing. Metasurfaces provide a promising solution due to their excellent flexibility and integration ability. Here, we propose and numerically demonstrate a scalable off-axis metalens array for optical addressing working at the wavelength of 350 nm. Metalens arrays designed for x linearly polarized and left circularly polarized light respectively can focus the collimated addressing beam array into a compact focused spot array with spot spacing of 5 μm, featuring crosstalk below 0.82%. Graphical Abstract

Hematopoietic stem cells (HSCs) rely on a combination of paracrine signals produced by their niche, including SCF. Here the authors show that HSCs and hematopoietic progenitors compete for limited amounts of membrane-bound SCF.

Abstract The WD‐repeat (WDR) family affects carcinogenesis, but its role in the immune microenvironment is poorly characterized. Although functional loss or gain of WDR6 does not markedly change in vitro proliferative and invasive capacity of HCC cells, its deficiency in hepa1‐6 cells drastically inhibits the growth and lung metastasis of orthotopically implanted tumors in immune‐competent C57BL/6J mice. Mechanistically, WDR6 targets tumor suppressor UVRAG to the CUL4A‐DDB1‐ROC1 E3 ubiquitin ligase complex through a unique WDxR motif and promotes its degradation. This upregulates chromatin accessibility at the TNFα locus by blocking autophagic degradation of p65, elevates intratumoral myeloid‐derived suppressor cell (MDSC) number, and reduces CD8+ T cell infiltration, thereby promoting HCC progression. These immunosuppressive effects are reversed by TNFα blockade. TNFα recruits NF‐κB to activate the transcription of WDR6, establishing a WDR6‐TNFα loop. Clinically, the WDR6/UVRAG/NF‐κB pathway is hyperactivated in HCC, predicting a poor prognosis. Importantly, a WDxR‐like peptide disrupts the WDR6/UVRAG complex and enhances the efficiency of anti‐PD‐L1 against HCC with WDR6 dysregulation.

Background: Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart. Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocytes. However, it remains unclear whether and how lymphangiogenesis contributes to exercise-induced physiological cardiac growth. We aimed to investigate the role and mechanism of lymphangiogenesis in exercise-induced physiological cardiac growth. Methods: Adult C57BL6/J mice were subjected to 3 weeks of swimming exercise to induce physiological cardiac growth. Oral treatment with vascular endothelial growth factor receptor 3 (VEGFR3) inhibitor SAR131675 was used to investigate whether cardiac lymphangiogenesis was required for exercise-induced physiological cardiac growth by VEGFR3 activation. Furthermore, human dermal lymphatic endothelial cell (LEC)-conditioned medium was collected to culture isolated neonatal rat cardiomyocytes to determine whether and how LECs could influence cardiomyocyte proliferation and hypertrophy. Results: Swimming exercise induced physiological cardiac growth accompanied by a remarkable increase of cardiac lymphangiogenesis as evidenced by increased density of lymphatic vessel endothelial hyaluronic acid receptor 1–positive lymphatic vessels in the heart and upregulated LYVE-1 and Podoplanin expressions levels. VEGFR3 was upregulated in the exercised heart, while VEGFR3 inhibitor SAR131675 attenuated exercise-induced physiological cardiac growth as evidenced by blunted myocardial hypertrophy and reduced proliferation marker Ki67 in cardiomyocytes, which was correlated with reduced lymphatic vessel density and downregulated LYVE-1 and Podoplanin in the heart upon exercise. Furthermore, LEC-conditioned medium promoted both hypertrophy and proliferation of cardiomyocytes and contained higher levels of insulin-like growth factor-1 and the extracellular protein Reelin, while LEC-conditioned medium from LECs treated with SAR131675 blocked these effects. Functional rescue assays further demonstrated that protein kinase B (AKT) activation, as well as reduced CCAAT enhancer-binding protein beta (C/EBPβ) and increased CBP/p300-interacting transactivators with E (glutamic acid)/D (aspartic acid)–rich-carboxylterminal domain 4 (CITED4), contributed to the promotive effect of LEC-conditioned medium on cardiomyocyte hypertrophy and proliferation. Conclusion: Our findings reveal that cardiac lymphangiogenesis is required for exercise-induced physiological cardiac growth by VEGFR3 activation, and they indicate that LEC-conditioned medium promotes both physiological hypertrophy and proliferation of cardiomyocytes through AKT activation and the C/EBPβ-CITED4 axis. These results highlight the essential roles of cardiac lymphangiogenesis in exercise-induced physiological cardiac growth.

Due to its good p-type semiconductor characteristics, MnSe has a great application prospect in high-performance electronic and optoelectronic devices. However, heterojunctions of MnSe still need to be deeply studied to improve its electrical and photoelectric properties. Here, it is reported that the two-dimensional (2D) MnSe/WSe2 heterojunction is structured by the non-layered MnSe nanosheets synthesized by chemical vapor deposition (CVD) method and the mechanically exfoliated layered WSe2. The heterojunction device exhibits a rectification effect and a current on/off ratio of 6,557. Meanwhile, it has a broad spectral range response from ultraviolet (UV) to short-wave infrared radiation (SWIR) (300–2,200 nm), and achieves an ultra-high responsivity of 156 A/W, along with an excellent detectivity of 2.21 × 1012 jones, and an outstanding external quantum efficiency (EQE) of 36,400%. Moreover, the type II band alignment and the built-in potential in the MnSe/WSe2 heterojunction can facilitate the separation of the photoexcited electron-hole pairs, which enables the significant photovoltaic characteristics and self-powered photoswitching response. This work reveals the novel performance of the 2D MnSe/WSe2 heterojunction and a great potential in photoswitching, photodetector, and photovoltaic applications.

Acute lymphoblastic and myeloblastic leukemias (ALL and AML) have been known to modify the bone marrow microenvironment and disrupt non-malignant hematopoiesis. However, the molecular mechanisms driving these alterations remain poorly defined. Using mouse models of ALL and AML, here we show that leukemic cells turn off lymphopoiesis and erythropoiesis shortly after colonizing the bone marrow. ALL and AML cells express lymphotoxin α1β2 and activate lymphotoxin beta receptor (LTβR) signaling in mesenchymal stem cells (MSCs), which turns off IL7 production and prevents non-malignant lymphopoiesis. We show that the DNA damage response pathway and CXCR4 signaling promote lymphotoxin α1β2 expression in leukemic cells. Genetic or pharmacological disruption of LTβR signaling in MSCs restores lymphopoiesis but not erythropoiesis, reduces leukemic cell growth, and significantly extends the survival of transplant recipients. Similarly, CXCR4 blocking also prevents leukemia-induced IL7 downregulation and inhibits leukemia growth. These studies demonstrate that acute leukemias exploit physiological mechanisms governing hematopoietic output as a strategy for gaining competitive advantage.

Fc gamma receptor-mediated antibody-dependent enhancement (ADE) can promote virus invasion of target cells, sometimes exacerbating the severity of the disease. ADE may be an enormous hurdle to developing efficacious vaccines for certain human and animal viruses. ADE of porcine reproductive and respiratory syndrome virus (PRRSV) infection has been demonstrated in vivo and in vitro. However, the effect of PRRSV-ADE infection on the natural antiviral immunity of the host cells is yet to be well investigated. Specifically, whether the ADE of PRRSV infection affects the levels of type II (interferon-gamma, IFN-γ) and III (interferon-lambdas, IFN-λs) interferons (IFNs) remains unclear. In this study, our results showed that PRRSV significantly induced the secretion of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in porcine alveolar macrophages (PAMs) in early infection, and weakly inhibited the production of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 in PAMs in late infection. Simultaneously, PRRSV infection significantly increased the transcription of interferon-stimulated gene 15 (ISG15), ISG56, and 2′, 5′-oligoadenylate synthetase 2 (OAS2) in PAMs. In addition, our results showed that PRRSV infection in PAMs via the ADE pathway not only significantly decreased the synthesis of IFN-γ, IFN-λ1, IFN-λ3, and IFN-λ4 but also significantly enhanced the generation of transforming growth factor-beta1 (TGF-β1). Our results also showed that the ADE of PRRSV infection significantly reduced the mRNAs of ISG15, ISG56, and OAS2 in PAMs. In conclusion, our studies indicated that PRRSV-ADE infection suppressed innate antiviral response by downregulating the levels of type II and III IFNs, hence facilitating viral replication in PAMs in vitro. The ADE mechanism demonstrated in the present study furthered our understanding of persistent pathogenesis following PRRSV infection mediated by antibodies.

BackgroundHepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Long non-coding RNAs (lncRNAs) play important roles in the occurrence and development of HCC through multiple pathways. Our previous study reported the specific molecular mechanism for sulfatide regulation of integrin αV expression and cell adhesion in HCC cells through lncRNA AY927503. Next, it is necessary to identify more sulfatide-related lncRNAs, explore their clinical signifcance, and determine new targeted treatment strategies.MethodsMicroarrays were used to screen a complete set of lncRNAs with different expression profiles in sulfatide-treated cells. Sulfatide-related lncRNAs expression data and corresponding HCC patient survival information were obtained from the The Cancer Genome Atlas (TCGA) database, and the prognosis prediction model was constructed based on Cox regression analysis. Methylated RNA immunoprecipitation with next generation sequencing (MeRIP-seq) was used to detemine the effect of sulfatide on lncRNAs m6A modification. Tumor Immune Estimation Resource (TIMER) and Gene set nnrichment analysis (GSEA) were utilized to enrich the immune and functional pathways of sulfatide-related lncRNAs.ResultsA total of 85 differentially expressed lncRNAs (|Fold Change (FC)|>2, P

Strength, as an important indicator of structural materials, has always been an important research topic in materials science. Theoretically, building a strength model is a rewarding method to understand the relationship between the mechanical properties and microstructure of materials. Although many strength models can reduplicate experimental values very well, they are empirical models, and their applicability is limited to materials for which empirical parameters have been obtained. Here, a non-empirical strength model is proposed based on the two-dimensional (2D) displacement potential of dislocation slipping, which can be applied to different chemically bonded crystals. Owing to the large electron localization function (ELF), covalent and ionic crystals have a high 2D displacement potential of dislocation slipping, and their dislocation slip mode prefers the kink-pair mode, further exhibiting a high critical resolved shear stress (CRSS). In contrast, metallic crystals with a small ELF have a low 2D displacement potential of dislocation slipping, and their dislocation slip mode is more inclined to the string mode, showing a low CRSS. This work provides new insights into dislocation-slipping configurations that will be useful for the development of new high-performance structural materials.

Visceral leishmaniasis (VL) is a chronic infectious disease transmitted by sandflies. The primary clinical manifestations are remittent fever, pancytopenia, and splenomegaly. As VL is rare with atypical symptoms, its diagnosis is often incorrect, missed, or delayed. Without appropriate treatment, the case fatality rate of symptomatic disease is more than 95%, but the prognosis is good if diagnosed and treated timeously. We report a case of VL that was diagnosed using metagenomic next-generation sequencing (mNGS) of a peripheral blood sample. By using mNGS and a bone marrow smear, we were able to make a timely diagnosis. The patient was treated with antimony, rapidly recovered, and was discharged from the hospital. This case illustrates the value of mNGS for making a timely diagnosis of VL.

Objective To investigate the correlation of olfactory function and cognitive function and motor symptoms in patients with primary Parkinson's disease (PD). Methods Total 152 patients with PD diagnosed and treated were recruited from August 2018 to October 2019 in The First Affiliated Hospital of Anhui Medical University. The Chinese Smell Indentification Test (CSIT) was used to evaluate the olfactory recognition function. According to the test results, patients were divided into the normal olfactory group (n=62) and the olfactory disorder group (n=90). The Unified Parkinson's Disease Assessment Scale Ⅲ (UPDRS Ⅲ) was used to evaluate the motor function, the Montreal Cognitive Assessment Scale (MoCA) Beijing edition was used to evaluate the degree of cognitive function, the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) were used to assess the patients' depression and anxiety levels. Patients' visual spatial working memory function were tested by the n⁃back test. Pearson correlation analysis and Spearman rank correlation analysis were used to investigate the correlation between olfactory function with cognitive function and motor symptoms in patients with PD. Results CSIT⁃self score (Z=⁃2.081, P=0.037) and CSIT⁃OI score (t=13.966, P=0.000) were lower in patients with anosmia than in those with normal smell. Overall MoCA score (t=3.008, P=0.003), as well as the scores of visuospatial executive function (Z=⁃2.277, P=0.023), naming (Z=⁃2.397, P=0.017), attention (Z=⁃3.203, P=0.001), language (Z=⁃2.229, P=0.026), delayed memory (Z=⁃2.426, P=0.015) were all decreased. The accuracy of 1⁃back test (t=2.341, P=0.027) and 2⁃back test (t=2.406, P=0.024) decreased, and the response time of 0⁃back test (t=⁃2.309, P=0.029) and 2⁃back test (t=⁃2.314, P=0.029) increased. Correlation analysis showed that olfactory function score was positively correlated with total MoCA score (rs=0.298, P=0.000). Conclusions The olfactory function of PD patients is closely related to cognitive function, PD patients with olfactory disorder have poor visual spatial working memory function. Therefore such patients should be paid more attention to cognitive function and visual spatial working memory function.

Abstract Most Alzheimer’s disease drugs do not work efficiently because of the blood–brain barrier. Therefore, we designed a new nanopreparation (PS-DZP-CHP): cholesterol-modified pullulan (CHP) nanoparticle with polysorbate 80(PS) surface coverage, as donepezil (DZP) carrier to realize brain tissue delivery. By size analysis and isothermal titration calorimetry, we chose the optimal dosing ratio of the drug with nanomaterials (1:5) and designed a series of experiments to verify the efficacy of the nanoparticles. The results of in vitro release experiments showed that the nanoparticles can achieve continuous drug release within 72 h. The results of fluorescence observation in mice showed a good brain targeting of PS-DZP-CHP nanoparticles. Furthermore, the nanoparticle can enhance the drug in the brain tissue concentration in mice. DZP-CHP nanoparticles were used to pretreat nerve cells with Aβ protein damage. The concentration of lactate dehydrogenase was determined by MTT, rhodamine 123 and AO-EB staining, which proved that DZP-CHP nanoparticles had a protective effect on the neurotoxicity induced by Aβ25–35 and were superior to free donepezil. Microthermal perpetual motion meter test showed that PS-DZP-CHP nanoparticles have an affinity with apolipoprotein E, which may be vital for this nanoparticle targeting to brain tissue.

Delayed exchange transfusion therapy (ETT) after phototherapy failure for newborns with severe hyperbilirubinemia could lead to serious complications such as bilirubin encephalopathy (BE). In this current manuscript we developed and validated a model using admission data for early prediction of phototherapy failure. We retrospectively examined the medical records of 292 newborns with severe hyperbilirubinemia as the training cohort and another 52 neonates as the validation cohort. Logistic regression modeling was employed to create a predictive model with seven significant admission indicators, i.e., age, past medical history, presence of hemolysis, hemoglobin, neutrophil proportion, albumin (ALB), and total serum bilirubin (TSB). To validate the model, two other models with conventional indicators were created, one incorporating the admission indicators and phototherapy failure outcome and the other using TSB decrease after phototherapy failure as a variable and phototherapy outcome as an outcome indicator. The area under the curve (AUC) of the predictive model was 0.958 [95% confidence interval (CI): 0.924–0.993] and 0.961 (95% CI: 0.914–1.000) in the training and validation cohorts, respectively. Compared with the conventional models, the new model had better predictive power and greater value for clinical decision-making by providing a possibly earlier and more accurate prediction of phototherapy failure. More rapid clinical decision-making and interventions may potentially minimize occurrence of serious complications of severe neonatal hyperbilirubinemia.

Introduction The objective of the Chinese Neonatal Network (CHNN) is to provide a platform for collaborative research, outcomes evaluation and quality improvement for preterm infants with gestational age less than 32 weeks in China. The CHNN is the first national neonatal network and has the largest geographically representative cohort from neonatal intensive care units (NICUs) in China.Methods and analysis Individual-level data from participating NICUs will be collected using a unique database developed by the CHNN on an ongoing basis from January 2019. Data will be prospectively collected from all infants

Our previous studies have demonstrated that TP53-induced glycolysis and apoptosis regulator (TIGAR) can protect neurons after cerebral ischemia/reperfusion. However, the role of TIGAR in neonatal hypoxic-ischemic brain damage (HIBD) remains unknown. In the present study, 7-day-old Sprague-Dawley rat models of HIBD were established by permanent occlusion of the left common carotid artery followed by 2-hour hypoxia. At 6 days before induction of HIBD, a lentiviral vector containing short hairpin RNA of either TIGAR or gasdermin D (LV-sh_TIGAR or LV-sh_GSDMD) was injected into the left lateral ventricle and striatum. Highly aggressively proliferating immortalized (HAPI) microglial cell models of in vitro HIBD were established by 2-hour oxygen/glucose deprivation followed by 24-hour reoxygenation. Three days before in vitro HIBD induction, HAPI microglial cells were transfected with LV-sh_TIGAR or LV-sh_GSDMD. Our results showed that TIGAR expression was increased in the neonatal rat cortex after HIBD and in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation. Lentivirus-mediated TIGAR knockdown in rats markedly worsened pyroptosis and brain damage after hypoxia/ischemia in vivo and in vitro. Application of exogenous nicotinamide adenine dinucleotide phosphate (NADPH) increased the NADPH level and the glutathione/oxidized glutathione ratio and decreased reactive oxygen species levels in HAPI microglial cells after oxygen/glucose deprivation/reoxygenation. Additionally, exogenous NADPH blocked the effects of TIGAR knockdown in neonatal HIBD in vivo and in vitro. These findings show that TIGAR can inhibit microglial pyroptosis and play a protective role in neonatal HIBD. The study was approved by the Animal Ethics Committee of Soochow University of China (approval No. 2017LW003) in 2017.

Circadian rhythm disorder is a common, but often neglected, consequence of neonatal hypoxic-ischemic brain damage (HIBD). However, the underlying molecular mechanisms remain largely unknown. We previously showed that, in a rat model of HIBD, up-regulation of microRNA-325 (miR-325) in the pineal gland is responsible for the suppression of Aanat, a key enzyme involved in melatonin synthesis and circadian rhythm regulation. To better understand the mechanism by which miR-325 affects circadian rhythms in neonates with HIBD, we compared clinical samples from neonates with HIBD and samples from healthy neonates recruited from the First Affiliated Hospital of Soochow University (Dushuhu Branch) in 2019. We found that circulating miR-325 levels correlated positively with the severity of sleep and circadian rhythm disorders in neonates with HIBD. Furthermore, a luciferase reporter gene assay revealed that LIM homeobox 3 (LHX3) is a novel downstream target of miR-325. In addition, in miR-325 knock-down mice, the transcription factor LHX3 exhibited an miR-325-dependent circadian pattern of expression in the pineal gland. We established a neonatal mouse model of HIBD by performing double-layer ligation of the left common carotid artery and exposing the pups to a low-oxygen environment for 2 hours. Lhx3 mRNA expression was significantly down-regulated in these mice and partially rescued in miR-325 knockout mice subjected to the same conditions. Finally, we showed that improvement in circadian rhythm-related behaviors in animals with HIBD was dependent on both miR-325 and LHX3. Taken together, our findings suggest that the miR-325-LHX3 axis is responsible for regulating circadian rhythms and provide novel insights into the identification of potential therapeutic targets for circadian rhythm disorders in patients with neonatal HIBD. The clinical trial was approved by Institutional Review Board of Children’s Hospital of Soochow University (approval No. 2015028) on July 20, 2015. Animal experiments were approved by Animal Care and Use Committee, School of Medicine, Soochow University, China (approval No. XD-2016-1) on January 15, 2016.

Due to the rapid development of wireless electrommunication and electronic techniques in current age, electromagnetic radiation and electromagnetic interference (EMI) have brought serious threat to the normal operation of precision electronic instruments and human health. Herein, the reclaimed straw of sorghum derived biochar/(Fe,Ni) hybrid has been prepared via a facile calcination process. The as-prepared hybrid possesses an outstanding low-frequency electromagnetic absorbing performance i.e. the maximum RL of T-600 can achieve −44.18 dB with effective absorption bandwidth (EAB) of 0.17~0.99 GHz for 2 mm and a board EAB of 0.53~2.49 GHz for only 1 mm. Meanwhile, the maximum RL of T-700 can attain −46.36 dB with EAB of 0.49~1.43 GHz and the board EAB of 0.89~2.81 GHz for the same thickness, which are owing to the cooperative effect of interface polarization, dipole polarization, natural resonance, eddy current and conduction loss, multi-reflection and scatter, better impedance matching and so on. This environmentally-friendly biochar/(Fe,Ni) hybrid can be employed as a novel low-frequency microwave absorbent for its good performance and reclamation of waste straw in sorghum.

Neonatal hypoxic-ischemic brain damage (HIBD) often results in various neurological deficits. Among them, a common, yet often neglected, symptom is circadian rhythm disorders. Previous studies revealed that the occurrence of cysts in the pineal gland, an organ known to regulate circadian rhythm, is associated with circadian problems in children with HIBD. However, the underlying mechanisms of pineal dependent dysfunctions post HIBD remain largely elusive. Here, by performing 10x single cell RNA sequencing, we firstly molecularly identified distinct pineal cell types and explored their transcriptome changes at single cell level at 24 and 72 h post neonatal HIBD. Bioinformatic analysis of cell prioritization showed that both subtypes of pinealocytes, the predominant component of the pineal gland, were mostly affected. We then went further to investigate how distinct pineal cell types responded to neonatal HIBD. Within pinealocytes, we revealed a molecularly defined β to α subtype conversion induced by neonatal HIBD. Within astrocytes, we discovered that all three subtypes responded to neonatal HIBD, with differential expression of reactive astrocytes markers. Two subtypes of microglia cells were both activated by HIBD, marked by up-regulation of Ccl3. Notably, microglia cells showed substantial reduction at 72 h post HIBD. Further investigation revealed that pyroptosis preferentially occurred in pineal microglia through NLRP3-Caspase-1-GSDMD signaling pathway. Taken together, our results delineated temporal changes of molecular and cellular events occurring in the pineal gland following neonatal HIBD. By revealing pyroptosis in the pineal gland, our study also provided potential therapeutic targets for preventing extravasation of pineal pathology and thus improving circadian rhythm dysfunction in neonates with HIBD.

Nowadays, non-small cell lung cancer (NSCLC) is threatening the health of all mankind. Although many progresses on treatment of lung cancer have been achieved in the past few decades, the current treatment methods are still traditional surgery, radiotherapy, and chemotherapy, which had poor selectivity and side effects. Lower-toxicity and more efficient treatments are in sore need. In this paper, a smart nanodelivery platform based on photothermal therapy, chemotherapy, and immunotherapy was constructed. The nanoparticles are composed of novel photothermal agents, Mn-modified phthalocyanine derivative (MnIIIPC), docetaxel (DTX), and an effective targeting molecule, hyaluronic acid. The nanoplatform could release Mn2+ from MnIIIPC@DTX@PLGA@Mn2+@HA(MDPMH) and probably activate tumor immunity through cGAS-STING and chemotherapy, respectively. Furthermore, DTX could be released in the process for removal of tumor cells. The “one-for-all” nanomaterial may shed some light on treating NSCLC in multiple methods.

Summary: Human pluripotent stem cell (hPSC) technology has offered nearly infinite opportunities to model all kinds of human diseases in vitro. Cardiomyocytes derived from hPSCs have proved to be efficient tools for cardiac disease modeling, drug screening and pathological mechanism studies. In this review, we discuss the advantages and limitations of 2D hPSC-cardiomyocyte (hPSC-CM) system, and introduce the recent development of three-dimensional (3D) culture platforms derived from hPSCs. Although the development of bioengineering technologies has greatly improved 3D platform construction, there are certainly challenges and room for development for further in-depth research.

Abstract Background Transcobalamin (TC) transports vitamin B12 from blood into cells. TC II deficiency is a rare autosomal recessive disorder. It is characterized by failure to thrive, diarrhoea, pallor, anaemia, pancytopenia or agammaglobulinemia. It is usually confirmed by molecular analysis of the TCN2 gene. We report a 2-month-old girl with two novel mutations, which were first reported in humans. Case presentation We present a 2-month-old Chinese girl with pancytopenia, severe combined immunodeficiency disease, and megaloblastic anaemia. Targeted next-generation sequencing (NGS) was performed, which detected compound heterozygous variants in exon 7 of the TCN2 gene (Mutation 1: c.1033 C > T; Mutation 2: c.1017-1031delinsGTAACAGAGATGGTT). These mutations result in stop codons in TCN2. The c.1033C > T mutation causes a stop at codon 345 (p.Gln345Ter), and the c.1017-1031delinsGTAACAGAGATGGTT mutation causes a stop at codon 340 (p.Leu340Ter). After being diagnosed, she was treated with intramuscular 1 mg hydroxycobalamin (OH-Cbl) every day for 2 months. The CBC value returned to normal after half a month. The peripheral blood lymphocyte subsets and immunoglobulin recovered after 2 months. Then, the dosage of OH-Cbl was gradually reduced. Conclusions TC II deficiency is a serious complication that requires lifelong treatment. Its diagnosis is difficult due to the lack of clearly identifiable symptoms. Genetic testing should be performed as early as possible if this disease is suspected. The specific observations of this case report make a considerable contribution to the literature and provide a reference for the diagnosis and treatment of future cases.

The use of multi-walled carbon nanotubes (MWC-NTs), as excellent mechanical and conductive fibers, for making self-sensing cementitious composites has attracted great interest. However, few researches have focused on the durability of mortar with MWCNTs. This paper attempts to explore the corrosion of embedded steel rebar in cement mortar with different contents of MWC-NTs. Tests for compressive strength, chloride migration coefficient, conductivity, and corrosion behaviors of MWCNT-cement mortar were carried out. The results show that the addition of MWCNTs to the cement mortar accelerated the development of the steel corrosion under chloride environment. The migration behavior of chlorine ions and steel corrosion rate were related to the carbon nanotube content. The increase in carbon nanotube content resulted in higher steel corrosion intensities. Moreover, the rates of chloride transport into the mortar increased with the nanotube content under both accelerated and natural chloride conditions.

Abstract Background To evaluate whether soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) can be used as an early predictor of ventilator-associated pneumonia (VAP). Methods Ventilated neonatal patients admitted into the neonatology department between January 2017 and January 2018 were divided into VAP (n = 30) and non-VAP (n = 30) groups. Serum sTREM, procalcitonin (PCT), C-reactive protein and interleukin-6 levels were measured at 0, 24, 72, and 120 h after initiation of mechanical ventilation (MV). Correlations between blood biomarker concentrations and VAP occurrence were analyzed. Predictive factors for VAP were identified by logistic regression analysis and Hosmer-Lemeshow test, and the predictive value of sTREM-1 and biomarker combinations for VAP was determined by receiver operating characteristic curve analysis. Results The serum sTREM-1 concentration was significantly higher in the VAP group than in the non-VAP group after 72 and 120 h of MV (72 h: 289.5 (179.6–427.0) vs 202.9 (154.8–279.6) pg/ml, P

Abstract Background This study aimed to describe the causative organisms of neonatal late-onset sepsis (LOS) and their antimicrobial resistance in Suzhou, Southeast China over a 7-year period. Methods We performed a retrospective study on neonates with LOS from Jan1, 2011 to Dec 31, 2017. The demographic, clinical, and laboratory data of neonates with LOS were analyzed. Logistic regression was used to investigate the risk factors with mortality. Results During the study period, 202 neonates with LOS were finally identified. The most common pathogens were Escherichia coli (29.2%), followed by Klebsiella pneumoniae (19.3%), and Coagulase-negative Staphylococcus (CoNS) (16.8%). Nearly 90% of the K. pneumoniae were resistant to cefazolin and 71.8% to ceftazidime. Thirty-four patients (16.8%) died. Multivariable logistic regression showed that significant predictors of mortality were birth weight

Abstract Background A prompt diagnosis of HIE remains a challenge clinically. This study aimed to identify potential biomarkers of neonatal hypoxic-ischemic encephalopathy (HIE) via a novel proteomic approach, the isobaric tags for absolute and relative quantification (iTRAQ) method. Methods Blood samples were collected from neonates with mild (n = 4), moderate (n = 4), or severe (n = 4) HIE who were admitted to the neonatal intensive care unit of Children’s Hospital of Soochow University between Oct 2015 and Oct 2017. iTRAQ was performed in HIE patients and healthy controls (n = 4). Bioinformatics analyses including Gene Ontology and KEGG pathway enrichment analysis were performed to evaluate the potential features and capabilities of the identified differentially expressed proteins. Results A total of 51 commonly differentially expressed proteins were identified among the comparisons between mild, moderate, and severe HIE as well as healthy controls. Haptoglobin (HP) and S100A8 were most significantly up-regulated in patients with HIE and further validated via real-time PCR and western blotting. The differentially expressed proteins represented multiple biological processes, cellular components and molecular functions and were markedly enriched in complement and coagulation cascades. Conclusions HP and S100A8 may serve as a potential biomarker for neonatal HIE and reflects the severity of HIE. The complement and coagulation cascades play crucial roles in the development of neonatal HIE.

The novel coronavirus disease 2019 (COVID-19) infection broke out in December 2019 in Wuhan, and rapidly overspread 31 provinces in mainland China on 31 January 2020. In the face of the increasing number of daily confirmed infected cases, it has become a common concern and worthy of pondering when the infection will appear the turning points, what is the final size and when the infection would be ultimately controlled. Based on the current control measures, we proposed a dynamical transmission model with contact trace and quarantine and predicted the peak time and final size for daily confirmed infected cases by employing Markov Chain Monte Carlo algorithm. We estimate the basic reproductive number of COVID-19 is 5.78 (95%CI: 5.71–5.89). Under the current intervention before 31 January, the number of daily confirmed infected cases is expected to peak on around 11 February 2020 with the size of 4066 (95%CI: 3898–4472). The infection of COVID-19 might be controlled approximately after 18 May 2020. Reducing contact and increasing trace about the risk population are likely to be the present effective measures.

As a noninvasive and quantitative method, fluorescence molecular tomography (FMT) has many potential applications in biomedical field. It has the power to resolve in three-dimension (3D), the molecular processes in small animal in-vivo in both theory and practice. This paper proposes to solve the problem of reconstruction error and speed by using stacked auto-encoders (SAE). A finite element method (FEM) solution to the Laplace transformed time-domain coupled diffusion equations is employed as the forward model. The reconstruction model is formulated under the framework of SAE. Numerical simulation experiments were conducted to compare the reconstruction results of SAE and algebraic reconstruction technique (ART). We demonstrated that the proposed reconstruction algorithm can retrieve the positions and shapes of the targets more accurately than ART. This advantage of SAE is especially reflected in the reconstruction for small targets with a radius of 2 mm and 3 mm.

Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage (HIBD). Although previous studies have implicated Toll-like receptor 4 (TLR4) and nuclear factor kappa-B (NF-κB) in the neuroinflammatory response elicited by brain injury, the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear. We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD. Hence, we established a neonatal HIBD rat model using the Rice-Vannucci method, and injected 0.75, 1.5, or 3 mg/kg of the TLR4 inhibitor resatorvid (TAK-242) 30 minutes after hypoxic ischemia. Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema, alleviate neuronal damage and neurobehavioral impairment, and decrease the expression levels of TLR4, phospho-NF-κB p65, Beclin-1, microtubule-associated protein l light chain 3, tumor necrosis factor-α, and interleukin-1β in the hippocampus. Thus, TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway. This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University, China (approval No. 20180114-15) on January 14, 2018.

Transient receptor potential melastatin 2 (TRPM2) is an important ion channel that represents a potential target for treating injury caused by cerebral ischemia. However, it is unclear whether reducing TRPM2 expression can help repair cerebral injury, and if so what the mechanism underlying this process involves. This study investigated the protective effect of reducing TRPM2 expression on pheochromocytoma (PC12) cells injured by oxygen-glucose deprivation (OGD). PC12 cells were transfected with plasmid encoding TRPM2 shRNAS, then subjected to OGD by incubation in glucose-free medium under hypoxic conditions for 8 hours, after which the cells were allowed to reoxygenate for 24 hours. Apoptotic cells, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels were detected using flow cytometry. The relative expression of C-X-C motif chemokine ligand 2 (CXCL2), NACHT, LRR, and PYD domain–containing protein 3 (NALP3), and caspase-1 were detected using fluorescence-based quantitative reverse transcription-polymerase chain reaction and western blotting. The rates of apoptosis, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels in the TRPM2-shRNA + OGD group were lower than those observed in the OGD group. Taken together, these results suggest that TRPM2 knockdown reduces OGD-induced neuronal injury, potentially by inhibiting apoptosis and reducing oxidative stress levels, mitochondrial membrane potentials, intracellular calcium concentrations, and NLRP3 inflammasome activation.

Objective: To forecast the visceral leishmaniasis cases using autoregress integrated moving average (ARIMA) and hybrid ARIMA-EGARCH model, which offers a scientific basis to control visceral leishmaniasis spread in Kashgar Prefecture of Xinjiang, China. Methods: The data used in this paper are monthly visceral leishmaniasis cases in the Kashgar Prefecture of Xinjiang from 2004 to 2016. The sample data between 2004 and 2015 were used for the estimation to choose the best model and the sample data in 2016 were used for the forecast. Time series of visceral leishmaniasis started on 1 January 2004 and ended on 31 December 2016, consisting of 1 790 observations reported in Kashgar Prefecture. Results: For Xinjiang, the total number of reported cases were 2 187, the male-to-female ratio of cases was 1:1.42. Patients aged between 0 and 10 years accounted for 82.72% of all reported cases and the largest percentage of visceral leishmaniasis cases was detected among scattered children who accounted for 68.82%. The monthly incidences fitted by ARIMA (2, 1, 2) (1, 1, 1)12 model were consistent with the real data collected from 2004 to 2015. However, the predicted cases failed to comply with the observed case number; we then attempted to establish a hybrid ARIMA-EGARCH model to fit visceral leishmaniasis. Finally, the ARIMA (2, 1, 2) (1, 1, 1)12- EGARCH (1, 1) model showed a good estimation when dealing with volatility clustering in the data series. Conclusions: The combined model has been determined as the best prediction model with the root-mean-square error (RMSE) of 7.23% in the validation phase, which means that this model has high validity and rationality and can be used for short-term prediction of visceral leishmaniasis and could be applied to the prevention and control of the disease.

The nanoscratch test has been identified as one of the important tools for evaluating the mechanical and tribological properties of materials. This paper reviews the current researches on the nanoscratch test using to characterise the mechanical properties of three typical materials, including thin film, polymer composite and concrete, from the perspectives of the Berkovich indenter, parameter selection, mode selection, and analysis of resulting data. In addition, to provide a deep understanding on the test from different magnitude, a comparison between the microscratch test and nanoscratch test on the evaluation of tribological performance is also provided in this paper. The characterisation by nanoscratch test of two structural samples, in terms of layered film structures (thin film and coating sample) and single layer block structure (polymer composite sample and concrete samples) are also described in this paper, which aims to provides a deep understand on the evaluation the adhesion, tribological and interfacial properties of the typical materials samples by nanoscratch test. Finally, the coefficient of friction and critical load are discussed, which are two important parameters in tribological properties and adhesion properties.

Mitochondria play a central role in the survival or death of neuronal cells, and they are regulators of energy metabolism and cell death pathways. Many studies support the role of mitochondrial dysfunction and oxidative damage in the pathogenesis of Alzheimer’s disease. Biatractylolide (BD) is a kind of internal symmetry double sesquiterpene novel ester compound isolated from the Chinese medicinal plant Baizhu, has neuroprotective effects in Alzheimer’s disease. We developed a systematic pharmacological model based on chemical pharmacokinetic and pharmacological data to identify potential compounds and targets of Baizhu. The neuroprotective effects of BD in PC12 (rat adrenal pheochromocytoma cells) and SH-SY5Y (human bone marrow neuroblastoma cells) were evaluated by in vitro experiments. Based on the predicted results, we selected 18 active compounds, which were associated with 20 potential targets and 22 signaling pathways. Compound-target, target-disease and target-pathway networks were constructed using Cytoscape 3.2.1. And verified by in vitro experiments that BD could inhibit Aβ by reducing oxidative stress and decreasing CytC release induced mPTP opening. This study provides a theoretical basis for the development of BD as an anti-Alzheimer’s disease drug.

Background: The Chinese Neonatal Network (CHNN) is a nationwide neonatal network that aims to improve clinical neonatal care quality and short- and long-term health outcomes of infants. This study aims to assess the quality of the Chinese Neonatal Network database by conducting an internal audit of data extraction.Methods: A data audit was performed by independently replicating the data collection and entry process in all 58 tertiary neonatal intensive care units (NICU) participating in the CHNN. Eighty-eight data elements selected for re-abstraction were classified into three categories (critical, important, less important), and agreement rates for original and re-abstracted data were predefined. Three to five records were randomly selected at each site for re-abstraction, including one short- (0–7 days), two medium- (8–28 days), and two long-stay (more than 28 days) cases. Agreement rates for each data item were calculated for individual NICUs and across the network, respectively.Results: A total of 283 cases and 24,904 data fields were re-abstracted. The agreement rates for original and re-abstracted data elements were 96.1% overall, and 97.2, 94.3, and 96.6% for critical, important, and less important data elements, respectively. Individual site variation for discrepancies ranged between 0.0 and 18.4% for all collected data elements.Conclusion: The completeness, precision, and quality of data in the CHNN database are high, providing assurance for multipurpose use, including health service evaluation, quality improvement, clinical trials, and other research.

Antibody-dependent enhancement (ADE) is an event in preexisting sub-, or non-neutralizing antibodies increasing the viral replication in its target cells. ADE is one crucial factor that intensifies porcine reproductive and respiratory syndrome virus (PRRSV) infection and results in PRRSV-persistent infection. Nevertheless, the exact mechanisms of PRRSV-ADE infection are poorly understood. In the current research, the results of the ADE assay showed that porcine immunoglobulin G (IgG) specific for the PRRSV significantly enhanced PRRSV proliferation in porcine alveolar macrophages (PAMs), suggesting that the ADE activity of PRRSV infection existed in pig anti-PRRSV IgG. The results of the RNA interference assay showed that knockdown of the Fc gamma receptor I (FcγRI) or FcγRIII gene significantly suppressed the ADE activity of PRRSV infection in PAMs, suggesting that FcγRI and FcγRIII were responsible for mediating PRRSV-ADE infection. In addition, the results of the antibody blocking assay showed that specific blocking of the Sn1, 2, 3, 4, 5, or 6 extracellular domain of the sialoadhesin (Sn) protein or selective blockade of the scavenger receptor cysteine-rich (SRCR) 5 domain of the CD163 molecule significantly repressed the ADE activity of PRRSV infection in PAMs, suggesting that Sn and CD163 were involved in FcγR-mediated PRRSV-ADE infection. The Sn1–6 domains of porcine Sn protein and the SRCR 5 domain of porcine CD163 molecule might play central roles in the ADE of PRRSV infection. In summary, our studies indicated that activating FcγRs (FcγRI and FcγRIII) and viral receptors (Sn and CD163) were required for ADE of PRRSV infection. Our findings provided a new insight into PRRSV infection that could be enhanced by FcγRs and PRRSV receptors-mediated PRRSV-antibody immune complexes (ICs), which would deepen our understanding of the mechanisms of PRRSV-persistent infection via the ADE pathway.