Search

Abstract Brain injury is the leading cause of mortality among patients who survive cardiac arrest (CA). Clinical studies have shown that the presence of post-CA hypoxic hepatitis or pre-CA liver disease is associated with increased mortality and inferior neurological recovery. In our in vivo global cerebral ischemia model, we observed a larger infarct area, elevated tissue injury scores, and increased intravascular CD45+ cell adhesion in reperfused brains with simultaneous hepatic ischemia than in those without it. In the ex vivo brain normothermic machine perfusion (NMP) model, we demonstrated that addition of a functioning liver to the brain NMP circuit significantly reduced post-CA brain injury, increased neuronal viability, and improved electrocortical activity. Furthermore, significant alterations were observed in both the transcriptome and metabolome in the presence or absence of hepatic ischemia. Our study highlights the crucial role of the liver in the pathogenesis of post-CA brain injury.

BackgroundA definite diagnosis goes undiscovered for a percentage of children with undiagnosed disorders, with significant medical, psychological, and social effects. Other than specialized clinical centers, exceptional molecular studies, common procedures, and devoted activities at the national and international levels, children with complex undiagnosed disorders require innovative approaches.MethodsIn March 2016, Children’s hospital of Fudan university represented the Children’s Undiagnosed Diseases Program (UDP). The purpose of this study is to describe the project findings and underline the critical significance of multidisciplinary teamwork in China’s undiagnosed rare illnesses program. We investigated the 758 cases in our UDP system retrospectively. Demographic information, laboratory test results, and genetic information were gathered.ResultsBetween January 2017 and December 2021, 758 cases were examined. Males made up 436 (57.5%) of the total. Over half of the patients were children under the age of five. The average patient course time preceding admission to UDP was 6.0 months (95% CI 10.512.6). These patients visited an average of 1.8 clinics during their diagnostic journey. Except for 69 individuals (90.9%), all had more than one presenting symptom in various organs: 460 (60.7%) had neurology difficulties, 151 (19.9%) had endocrine problems, and 141 (18.6%) had immunology problems. UDP has a diagnosis rate of 61.3%. Genetic testing was performed on 469 of the 758 patients, for a genetic diagnosis rate of 15.8%. The UDP method has a sensitivity of 94.5%, a specificity of 86.4%, a positive predictive value of 92.8%, and an negative predictive value of 89.5%.ConclusionOur UDP targets an unmet need, namely the diagnosis of patients with complicated, multisystem illnesses. Using a multidisciplinary team model approach, this UDP pilot study achieved a reasonable diagnosis success rate, increasing the possibility of more diagnoses and new scientific discoveries of difficult and rare diseases.

BackgroundConditional survival (CS) considers the duration since the initial diagnosis and can provide supplementary informative insights. Our objective was to evaluate CS among gliosarcoma (GSM) patients and develop a CS-incorporated nomogram to predict the conditional probability of survival.MethodsThis retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database included patients with GSM between 2000 and 2017. The CS was defined as the probability of surviving additional y years after already surviving for x years. The formula utilized for CS was: CS(y|x) = S(y + x)/S(x), where S(x) denotes the overall survival at x years. Univariate Cox regression, best subset regression (BSR) and the least absolute shrinkage and selection operator (LASSO) were used for significant prognostic factors screening. Following this, backward stepwise multivariable Cox regression was utilized to refine predictor selection. Finally, a novel CS-integrated nomogram model was developed and we also employed diverse evaluation methods to assess its performance.ResultsThis study included a total of 1,015 GSM patients, comprising 710 patients in training cohort and 305 patients in validation cohort. CS analysis indicated a gradual increase in the probability of achieving a 5-year survival, ascending from 5% at diagnosis to 13, 31, 56, and 74% with each subsequent year survived after 1, 2, 3, and 4 years post-diagnosis, respectively. Following variable screening through univariate Cox regression, BSR, and LASSO analysis, five factors-age, tumor stage, tumor size, radiotherapy, and chemotherapy-were ultimately identified for constructing the CS-nomogram model. The performance of the nomogram model was validated through discrimination and calibration assessments in both the training and validation cohorts. Furthermore, we confirmed that the effectiveness of the CS-nomogram in stratifying GSM patient risk status.ConclusionThis nationwide study delineated the CS of patients diagnosed with GSM. Utilizing national data, a CS-nomogram could provide valuable guidance for patient counseling during follow-up and risk stratification.

In the context of hepatocellular carcinoma (HCC) treatment, this study introduces a biomimetic “bomb” approach to target HCC by utilizing macrophages (MAs) as ultrasound-responsive carriers. This advanced biomimetic drug delivery system (MAs-DOX/PFP/Ms, MAs-DPM) encapsulates doxorubicin (DOX) and perfluoropentane (PFP) and is designed to precisely target HCC. MAs-DPM exhibits excellent drug loading capacity and biocompatibility, can effectively release DOX and enhance ultrasound imaging capabilities under ultrasound irradiation (UI). Experiments confirmed that MA maintained its biological activity and vitality during co-incubation and phagocytosis with DOX-loaded DPM, and microscopy confirmed that MA effectively engulfed DPM without changing cell morphology or function. Transwell experiments demonstrated that this bionic “bomb” (MAs-DPMs) not only retained the tumor targeting ability of macrophages, but also successfully delivered therapeutic drugs to tumor cells. Compared with samples without UI treatment, UI significantly increased the release of DOX from MAs-DPM, enhanced the drug release rate and inhibited the growth of HCC cells. Live/Dead staining experiments further intuitively revealed the precise “biobomb” effect of MAs-DPM under UI, effectively proving its ability to inhibit HCC cell proliferation. In vivo studies demonstrated that MAs-DPM was able to proficiently localize tumor sites within 24 h. Furthermore, the ultrasound-mediated phase transition of PFP enhanced the imaging efficacy, confirming the feasibility of macrophage-mimicking biological bombs for real-time in vivo ultrasound tracking. In the tumor-bearing nude mouse model, UI-treated MAs-DPMs remarkably delayed tumor growth and prolonged survival time compared with other groups. Subsequent histological and serum index evaluation further confirmed the in vivo safety of MAs-DPMs, and UI-treatment did not induce significant histological or pathological changes or statistical differences in vital organ or serum markers. These experiment results highlight the great potential of MAs-DPM as a strategic approach for the diagnosis and treatment of HCC.

Summary: Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.

Background Examine how Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) can be used to manage patient safety and improve the standard of care for patients.Methods In order to improve key medical training in areas like surgical safety management, blood transfusion closed-loop management, drug safety management and identity recognition, we apply the TeamSTEPPS teaching methodology. We then examine the effects of this implementation on changes in pertinent indicators.Results Our hospital’s perioperative death rate dropped to 0.019%, unscheduled reoperations dropped to 0.11%, and defined daily doses fell to 24.85. Antibiotic usage among hospitalised patients declined to 40.59%, while the percentage of antibacterial medicine prescriptions for outpatient patients decreased to 13.26%. Identity recognition requirements were implemented at a rate of 94.5%, and the low-risk group’s death rate dropped to 0.01%. Critical transfusion episodes were less common, with an incidence of 0.01%. The physician’s TeamSTEPPS Teamwork Perceptions Questionnaire and Teamwork Attitudes Questionnaire scores dramatically improved following the TeamSTEPPS team instruction course.Conclusion An evidence-based team collaboration training programme called TeamSTEPPS combines clinical practice with team collaboration skills to enhance team performance in the healthcare industry and raise standards for medical quality, safety, and effectiveness.

Increasing production and inadequate management of plastic waste have resulted in the accumulation of plastic debris in the global biogeochemical cycles. In natural environments, these plastics become micronized by various physicochemical reactions, leading to the formation of microplastics. This review provides a concise literature account of the current state of MP contamination in sea sediments worldwide. We report on the capacity of the adopted sampling, pretreatment, and identification methods and provide recommendations for sustainable long-term deep-sea sediment monitoring programs. Our systematic review showed that for MP contamination in marine sediments, the number density of MPs with a minimum particle size of 0.1 Em ranges from 10 to 1,000 items/kg-dry weight. On the other hand, the number density of MPs with a minimum particle size of 0.01 Em ranges from 100 to 10,000 items/kg-dry weight. In all 31 papers analyzed, the percentage of fragments and fibers was over 50%. Polyethylene, used in containers and packaging, and polyester, a fiber used in clothing, were the most common polymer components. Analysis of sediment cores can reveal the history of MPs contamination. In addition, the deep-sea sediments have been identified as the endpoints of MPs that occur in the environment.

In this study, we investigated the antioxidant properties of dry-cured beef crude peptide (BPH) at different storage periods. The combination characteristics of different concentrations of Phe-Asp-Gly-Asp-Phe (FDGDF) and superoxide dismutase (SOD) at different temperatures were analyzed by ultraviolet–visible spectroscopy, fluorescence spectroscopy, and FT-IR spectroscopy, combined with the detection of a SOD activity detection box. It was found that FDGDF could improve the activity of SOD by changing its secondary structure. Bonds were formed at O32/O40/O52 using quantum chemical simulation calculations, and the Fukui index was higher than that of most atoms, indicating that these atoms were more likely to participate in the reaction. SPR biological force analysis showed that FDGDF and SOD were in a fast binding and dissociation mode. This study revealed the theoretical basis for studying the antioxidant mechanism of dry-cured beef and provided ideas for developing new dry-cured beef products.

Here, by performing multi-omics microbiome analyses in a cohort of children with new-onset T1D, the authors characterize altered microbial functional and metabolic traits involved in T1D, which they validate in animal experiments, together providing potential avenues for microbiome-based interventions.

Hepatectomy is an effective surgical method for the treatment of liver diseases, but intraoperative bleeding and postoperative liver function recovery are still key issues. This study aims to develop a composite hydrogel dressing with excellent hemostatic properties, biocompatibility, and ability to promote liver cell regeneration. The modified gelatin matrix (GelMA, 10%) was mixed with equal volumes of sodium alginate-dopamine (Alg-DA) at concentrations of 0.5%, 1%, and 2%. Then a cross-linking agent (0.1%) was added to prepare different composite hydrogels under UV light, named GelMA/Alg-DA-0.5, GelMA/Alg-DA-1 and GelMA/Alg-DA-2, respectively. All the prepared hydrogel has a porous structure with a porosity greater than 65%, and could be stabilized in a gel state after being cross-linked by ultraviolet light. Physicochemical characterization showed that the elastic modulus, water absorption, adhesion, and compressibility of the composite hydrogels were improved with increasing Alg-DA content. Furthermore, the prepared hydrogel exhibits in vitro degradability, excellent biocompatibility, and good hemostatic function. Among all tested groups, the group of GelMA/Alg-DA-1 hydrogel performed the best. To further enhance its application potential in the field of liver regeneration, adipose-derived mesenchymal stem cell exosomes (AD-MSC-Exo) were loaded into GelMA/Alg-DA-1 hydrogel. Under the same conditions, GelMA/Alg-DA-1/Exo promoted cell proliferation and migration more effectively than hydrogels without extracellular vesicles. In conclusion, the prepared GelMA/Alg-DA-1 composite hydrogel loaded with AD-MSC-Exo has great application potential in liver wound hemostasis and liver regeneration.

Antioxidant biomaterials have attracted much attention in various biomedical fields because of their effective inhibition and elimination of reactive oxygen species (ROS) in pathological tissues. However, the difficulty in ensuring biocompatibility, biodegradability and bioavailability of antioxidant materials has limited their further development. Novel bioavailable antioxidant materials that are derived from natural resources are urgently needed. Here, an integrated multi-omics method was applied to fabricate antioxidant biomaterials. A key cysteine-rich thrombospondin-1 type I repeat-like (TSRL) protein was efficiently discovered from among 1262 adhesive components and then used to create a recombinant protein with a yield of 500 mg L−1. The biocompatible TSRL protein was able to self-assemble into either a water-resistant coating through Ca2+-mediated coordination or redox-responsive hydrogels with tunable physical properties. The TSRL-based hydrogels showed stronger 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging rates than glutathione (GSH) and ascorbic acid (Aa) and protected cells against external oxidative stress significantly more effectively. When topically applied to mice skin, TSRL alleviated epidermal hyperplasia and suppressed the degradation of collagen and elastic fibers caused by ultraviolet radiation B (UVB) irradiation, confirming that it enhanced antioxidant activity in vivo. This is the first study to successfully characterize natural antioxidant biomaterials created from marine invertebrate adhesives, and the findings indicate the excellent prospects of these biomaterials for great applications in tissue regeneration and cosmeceuticals.

Nanomedicine has been widely studied for the diagnosis and treatment of hepatocellular carcinoma (HCC). How to synthesize a nanoplatform possessing a high synergistic therapeutic efficacy remains a challenge in this emerging research field. In this study, a convenient all-in-one therapeutic nanoplatform (FTY720@AM/T7-TL) is designed for HCC. This advanced nanoplatform consists of multiple functional elements, including gold-manganese dioxide nanoparticles (AM), tetraphenylethylene (T), fingolimod (FTY720), hybrid-liposome (L), and T7 peptides (T7). The nanoplatform is negatively charged at physiological pH and can transit to a positively charged state once moving to acidic pH environments. The specially designed pH-responsive charge-reversal nanocarrier prolongs the half-life of nanodrugs in blood and improves cellular uptake efficiency. The platform achieves a sustained and controllable drug release through dual stimulus-response, with pH as the endogenous stimulus and near-infrared as the exogenous stimulus. Furthermore, the nanoplatform realizes in situ O2 generation by catalyzing tumor over-expressed H2O2, which alleviates tumor microenvironment hypoxia and improves photodynamic therapy. Both in vitro and in vivo studies show the prepared nanoplatform has good photothermal conversion, cellular uptake efficiency, fluorescence/magnetic resonance imaging capabilities, and synergistic anti-tumor effects. These results suggest that the prepared all-in-one nanoplatform has great potential for dual-modal imaging-guided synergistic therapy of HCC.

Background and Aim The relationship between the oral microbiota and type 1 diabetes (T1D) remains unclear. We aimed to evaluate the variations in the oral microbiome in T1D and identify potentially associated bacterial factors.Methods We performed high-throughput sequencing of the V3-V4 area of the 16S rRNA gene to profile the oral bacterial composition of 47 healthy children (CON group), 46 children with new-onset T1D in the acute phase (NT1D group), and 10 children with T1D in the chronic phase receiving insulin treatment (CT1D group). Multivariate statistical analysis of sequencing data was performed.Results Compared to the CON group, the NT1D group was characterized by decreased diversity and increased abundance of genera harboring opportunistic pathogens, while this trend was partially reversed in the CT1D group. Differential genera between groups could distinguish the NT1D group from the CON group (AUC = 0.933) and CT1D group (AUC = 0.846), respectively. Moreover, T1D-enriched genera were closely correlated with HbA1c, FBG and WBCs levels.Conclusion Our results showed that the acute phase of T1D was characterized by oral microbiota dysbiosis, which could be partially ameliorated via glycemic control. The possible role of oral microbiota dysbiosis on oral health and systemic metabolic status in T1D warrants further mechanistic investigation.

Background: The incidence and mortality of influenza in children had risen, but data are limited on children with severe influenza virus infection in China. Methods: We conducted a retrospective case–control study and collected the patients' clinical data. Clinical data including demography, clinical presentation, laboratory findings, radiologic findings, treatment and outcomes were collected. Children were clinically confirmed to have virus infection in Shanghai in three hospitals from June 2014 to June 2019. Results: During the study, 36,047 children were enrolled. Among them, 118 met the criteria for severe flu. Clinical symptoms such as fever, cough, gastrointestinal symptoms, coma and epilepsy were higher in the severe group. Complications such as pneumorrhagia, heart failure, septic shock, acute renal failure and influenza-associated encephalitis were higher in the severe influenza group than the death group. The laboratory findings including decreased hemoglobin, high alanine aminotransferase, high urea nitrogen and high lactate levels were risk factors for death in children with influenza. Conclusion: Influenza-associated encephalopathy (IAE), acute respiratory distress syndrome (ARDS) were the common clinical manifestations and complications for the severe influenza, and delayed use of oseltamivir was found to be associated with fatality.

Abstract Background Primary adrenal insufficiency (PAI) is life-threatening, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features. Methods Seventy children were enrolled in this cross-sectional study. Clinical information was collected, and combined genetic tests were performed according to the children’s manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants. Results Among the 70 children, 84.3% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and 21-hydroxylase deficiency (21-OHD) was genetically confirmed in 91.5% of these cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.1% (39/59), 30.5% (18/59), and 3.4% (2/59) of the cases, respectively. The 17-hydroxyprogesterone (17-OHP) and testosterone (TES) levels were significantly higher in children with SW than with SV. The 17-OHP and cortisol levels in female SW patients were significantly higher than those in males. The 17-OHP, cortisol, dehydroepiandrosterone (DHEAS) and TES levels in female SW patients were significantly higher than those in female SV patients. Additionally, 72.7% (8/11) of uncharacterized PAI patients had positive genetic findings. Among all the patients, two novel variants in the CYP21A2 gene (c.833dupT and c.651 + 2T > G) were found. A microdeletion (Xp21.2–21.3) and five novel variants, including 2 in the NR0B1 gene (c.323–324CG > GA and c.1231_1234delCTCA), 2 in the AAAS gene (c.399 + 1G > A and c.250delT) and 1 in the NNT gene (c.2274delT), were detected. The novel variant c.399 + 1G > A in the AAAS gene was further confirmed to lead to exon 4 skipping during mRNA transcription and produce a truncated ALADIN protein. Conclusions We found ethnicity-based differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and TES levels, which warrants caution in relation to the effects of virilization. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of PAI, however, further improvement of genetic testing tools beyond our protocol are still needed to uncover the complete aetiology of PAI in children.

IntroductionLifestyle changes including COVID-19 lockdown cause weight gain and may change obesity trends; however, timely changes are largely unknown and monitoring measures are usually lack. This first large-scale study aimed to analyze the real-world national trends of obesity prevalence of Chinese children in the past five years, and the impact of COVID-19 pandemic on pediatric obesity development through both mobile- and hospital-based data.MethodsThis study included children aged 3 to 19 years old all over China from January 2017 to April 2021. Hospital-measured and parent-reported cases from XIGAO database were analyzed. Body mass index (BMI) z-score calculation and obesity status evaluation were made according to Chinese standards. We evaluated obesity/overweight prevalence over the past five years and the changes of BMI z-score during COVID-19 lockdown.ResultsA total of 656396 children from 31 provinces were involved, including 447481 hospital-measured cases and 208915 parent-reported cases. The obesity and overweight prevalence were 8.05% (95%CI 7.76%–8.39%) and 10.06% (95%CI 10.79%–11.55%), comparable to those of China National Nutrition Surveys during 2015–2019. Northern China had the highest obesity prevalence. Parent-reported data had higher obesity/overweight prevalence than hospital-measured data (18.3% [95%CI 17.7%–18.9%] vs. 21.7% [95%CI 20.7%–23.0%]). The trend of obesity prevalence remained stable with slight decrease, but COVID-19 lockdown caused a significant increase of 1.86% in 2020. Both mobile- and hospital-based data showed weight gain in the first half of 2020. High BMI z-score increase were found among primary and junior middle school children, and children in northeast area during lockdown.ConclusionWeight gain during COVID-19 among Chinese children had regional differences and mainly affect primary and junior middle school children, thus warrants targeted interventions. The mobile growth assessment based on parent-reported data was a feasible, efficient and timely way for obesity monitoring among Chinese children, especially during epidemic.

Biofilms formed on metal surfaces strongly affect metallic instruments serving in marine environments. However, due to sampling difficulty, less has been known about the bacterial communities of the biofilm on metallic surfaces in hadal environments, so the failure process of these deep-sea metallic instruments influenced by microbial communities could be hardly predicted. In this research, seven alloys, including titanium, aluminum, and copper alloys, were exposed in Yap Trench hadal environment for 1 year. Thus, the communities of the biofilms formed on metallic surfaces at 5,772 m undersea in Yap Trench were initially reported in previous studies. Then, 16S rRNA gene sequencing was performed to visualize the in situ bacterial communities of the biofilms formed on titanium, aluminum, and copper alloys at 5,772 m undersea in Yap Trench. It was found that Proteobacteria was the dominant phylum in all samples, but distinct genera were discovered on various alloys. The titanium alloy provided a suitable substrate for a mutualistic symbiotic biofilm with abundant bacterial richness. Aluminum alloys without copper components showed the least bacterial richness and formed a cold-adapted and oligotrophic-adapted biofilm containing the genera Sulfurimonas and PS1 Clade, while copper-present alloys showed relatively high bacterial richness with copper-resistant or even copper-utilizing biofilms constituting the genera Stenotrophomonas, Burkholderia-Caballeronia-Paraburkholderia, and Achromobacter on the surfaces. Furthermore, among all the element components contained in alloys investigated in this research, copper element showed the strongest influences on the composition and function of microbial communities in the biofilms formed on various metallic surfaces.

Abstract Background Hepatitis B virus (HBV) infection is a global health problem and interferon-alpha (IFN-α) is one of the effective therapies. However, little is known about the genetic background of the HBV infection or the genetic determinants of the IFN-α treatment response. Thus, we aim to explore the possible molecular mechanisms of HBV infection and its response to the IFN-α therapy with a comprehensive bioinformatics analysis. Methods The Gene Expression Omnibus datasets (GSE83148, GSE84044 and GSE66698) were collected and the differentially expressed genes (DEGs), key biological processes and intersecting pathways were analyzed. The expression of the co-expressed DEGs in the clinical samples was verified by quantitative real time polymerase chain reaction (qRT-PCR). Results Analysis of all the 3 datasets revealed that there were eight up-regulated and one down-regulated co-expressed DEGs following the HBV infection and after IFN-α treatment. In clinical samples, the mRNA level of HKDC1, EPCAM, GSN, ZWINT and PLD3 were significantly increased, while, the mRNA level of PLEKHA2 was significantly decreased in HBV infected liver tissues compared to normal liver tissues. PI3K-Akt signaling pathway, focal adhesion, HTLV-I infection, cytokine-cytokine receptor interaction, metabolic pathways, NF-κB signaling pathway were important pathways associated with the HBV infection and the response of IFN-α treatment. Conclusions The co-expressed genes, common biological processes and intersecting pathways identified in the study might play an important role in HBV infection and response of IFN-α treatment. The dysregulated genes may act as novel biomarkers and therapeutic targets for HBV.

Abstract Background Mandibulofacial dysostosis with microcephaly (MFDM) is characteristic of multiple skeletal anomalies comprising craniofacial anomalies/dysplasia, microcephaly, dysplastic ears, choanal atresia, and short stature. Heterozygous loss of function variants of EFTUD2 was previously reported in MFDM; however, the mechanism underlying EFTUD2-associated skeletal dysplasia remains unclear. Results We identified a novel frameshift variant of EFTUD2 (c.1030_1031delTG, p.Trp344fs*2) in an MFDM Chinese patient with craniofacial dysmorphism including ear canal structures and microcephaly, mild intellectual disability, and developmental delay. We generated a zebrafish model of eftud2 deficiency, and a consistent phenotype consisting of mandibular bone dysplasia and otolith loss was observed. We also showed that EFTUD2 deficiency significantly inhibited proliferation, differentiation, and maturation in human calvarial osteoblast (HCO) and human articular chondrocyte (HC-a) cells. RNA-Seq analysis uncovered activated TP53 signaling with increased phosphorylation of the TP53 protein and upregulation of five TP53 downstream target genes (FAS, STEAP3, CASP3, P21, and SESN1) both in HCO and in eftud2−/− zebrafish. Additionally, inhibition of p53 by morpholino significantly reduced the mortality of eftud2−/− larvae. Conclusions Our results confirm a novel de novo variant of the EFTUD2 gene and suggest that EFTUD2 may participate in the maturation and differentiation of osteoblasts and chondrocytes, possibly via activation of the TP53 signaling pathway. Thus, mutations in this gene may lead to skeletal anomalies in vertebrates.

Summary: Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences.Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT).Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p

ContextLong-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending.ObjectiveWe studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children.Design, Setting, and PatientsThis multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children.InterventionSubjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks.Main Outcome MeasureThe primary outcome was height SD scores for chronological age (HtSDSCA) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes.ResultsAt week 26, the median HtSDSCA changed from −2.75, −2.82, and −2.78 to −2.31, −2.43, and −2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDSCA was 0.17 ± 0.28 between weekly and biweekly PEG-rhGH, and 0.17 ± 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%–90.34% and 76.08%–90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups.ConclusionsAlthough notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions.Clinical Trial Registrationclinicaltrials.gov, identifier NCT02976675.

This study reports the clinical manifestations, genetics, and efficacy of treatment with the efficacy of recombinant human granulocyte macrophage colony-stimulating factor (rhGM-GSF) of a 2-year-old female patient with severe congenital neutropenia (SCN) type 7 (SCN7) caused by novel biallelic mutations in the colony-stimulating factor 3 receptor (CSF3R) gene. Genetic diagnosis of the patient was performed by whole-exome and Sanger sequencing. Expression of the CSF3R gene in the peripheral neutrophils of the patient was detected by real-time PCR and Western blotting. The patient presented with recurrent suppurative tonsillitis and decreased absolute neutrophil count A). The patient's neutrophils had lower CSF3R mRNA and protein levels than those of the parents. Low-dose rhGM-CSF (3 μg/kg/day once a week) prevented recurrent infection in the patient. These results demonstrate that the clinical manifestations of SCN7 with biallelic CSF3R mutations and downregulated CSF3R can be effectively treated with rhGM-CSF.

Abstract Background MicroRNAs (miRNAs) play a pivotal role in hepatocellular carcinoma (HCC) progression and have been confirmed to participate in the carcinogenesis and development of HCC. However, the relationship between miR-497-5p and HCC remains unclear. Methods Kaplan–Meier curve analysis and the log-rank test were used to investigate the efficacy of miR-497-5p on overall survival (OS) and disease-free survival (DFS) in patients with HCC. According to in vitro experiments, programmed cell death 4 (PDCD4) was a target of miR-497-5p by the dual-luciferase activity assay. The efficacy of PDCD4 on cell proliferation and metastasis in HCC was examined by transwell assays, CCK-8 assays and reverse transcription quantitative PCR (RT-qPCR). Additionally, we conducted a luciferase activity reporter assay to confirm the interaction between lncRNA XIST and miR-49-5p. Then, to evaluate the relationship between lncRNA XIST and miR-497-5p, several mechanistic experiments, including qRT-PCR, Western blotting, transwell assays and tumor xenograft assays, were performed. Results miR-497-5p was upregulated in HCC tissues, and high expression of miR-497-5p resulted in increases in tumor size and tumor number and a higher tumor-node-metastasis (TNM) stage and Edmondson grade in patients with HCC. Silencing miR-497-5p inhibited the proliferation and migration of HCC cells. PDCD4, which was downregulated in HCC tissues, was shown to be a target of miR-497-5p and was negatively correlated with the expression of miR-497-5p. lncRNA XIST was found to act as a miR-497-5p sponge and to regulate the level of PDCD4, which is targeted by miR-497-5p. lncRNA XIST was observed to be downregulated in the HCC tissues and positively correlated with the expression of PDCD4. Conclusions Our findings reveal that the XIST/miR-497-5p/PDCD4 axis participates in HCC development and that XIST could be used as a biomarker of HCC.

Performance effective task scheduling algorithms are essential for taking advantage of the heterogeneous multi-processor in heterogeneous computing environments. In this paper, we present a task scheduling algorithm named as Dependency-ratio Bundling Earliest Finish Time (DBEFT). DBEFT is a list based scheduling algorithm combined with task duplication, which can achieve high performance and low time complexity simultaneously. DBEFT selects the task from the perspective of extending parallelism between tasks instead of giving priorities to tasks on the critical path. Also, DBEFT reduces communication cost by adopting a bundling scheduling strategy. The experiments were conducted on both random graph set and real-world applications, and the results show that DBEFT obtained significant performance improvement, outperforming CEFT by 15%, PEFT by 30% and HEFT 33% in terms of SLR respectively.

ObjectivesTo explore the glycemic control [represented by glycated hemoglobin (HbA1c) concentrations] in children with diabetes mellitus (DM) in east China and middle- and low-income countries, from 2010 to 2019.MethodsRetrospective data of children with DM from two hospital-based health records were reviewed. Data on HbA1c concentrations, hospitalization due to diabetic ketoacidosis, and patient demographics were collected and analyzed. A systematic review was subsequently performed to analyze publications that report HbA1c concentrations in patients aged

Objective. Our recent study demonstrated that growth differentiation factor 5 (GDF5) could promote white adipose tissue thermogenesis and alleviate high-fat diet- (HFD-) induced obesity in fatty acid-binding protein 4- (Fabp4-) GDF5 transgenic mice (TG). Here, we further investigated the effects of systemic overexpression of the GDF5 gene in adipocytes HFD-induced nonalcoholic fatty liver disease (NAFLD). Methods. Fabp4-GDF5 TG mice were administered an HFD feeding. NAFLD-related indicators associated with lipid metabolism and inflammation were measured. A GDF5 lentiviral vector was constructed, and the LO2 NAFLD cell model was induced by FFA solution (oleic acid and palmitic acid). The alterations in liver function, liver lipid metabolism, and related inflammatory indicators were analyzed. Results. The liver weight was significantly reduced in the TG group, which was in accordance with the significantly downregulated expression of TNFα, MCP1, Aim2, and SREBP-1c and significantly upregulated expression of CPT-1α and ACOX2 in TG mouse livers. Compared to that of cells in the FAA-free control group, LO2 cells with in situ overexpression of GDF5 developed lipid droplets after FFA treatment; the levels of triglycerides, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly increased in both the GDF5 lentivirus and control lentivirus groups compared with those of the FAA-free group. Additionally, the levels of FAS, SREBP-1, CPT-1α, and inflammation-associated genes, such as ASC and NLRC4, were unaltered despite GDF5 treatment. Conclusion. Systemic overexpression of GDF5 in adipose tissue in vivo significantly reduced HFD-induced NAFLD liver damage in mice. The overexpression of GDF5 in hepatocytes failed to improve lipid accumulation and inflammation-related reactions induced by mixed fatty acids, suggesting that the protective effect of GDF5 in NAFLD was mainly due to the reduction in adipose tissue and improvements in metabolism. Hence, our study suggests that the management of NAFLD should be targeted to reduce the overall amount of body fat and improve metabolic status before the progression to nonalcoholic steatohepatitis occurs.

Natriuretic peptide receptor 2 (NPR2) plays a key role in cartilage and bone morphogenesis. The NPR2 gene mutations result in acromesomelic dysplasia, Maroteaux type (AMDM), short stature with nonspecific skeletal abnormalities (SNSK), and epiphyseal chondrodysplasia, Miura type (ECDM). However, the pathogenic mechanism remains unclear. In our study, we identified one de novo (R557C) and six novel variants (G602W, V970F, R767*, R363*, F857S, and Y306S) in five independent Chinese families with familial short stature. Three patients with heterozygous mutations (G602W, V970F, and R767*) were diagnosed with SNSK (height SD score ranged from −2.25 to −5.60), while another two with compound heterozygous mutations (R363* and F857S, R557C and Y306S) were diagnosed with AMDM (height SD score ranged from −3.10 to −5.35). Among three patients with heterozygous status, two patients before puberty initiation with rhGH treatment significantly improved their growth (height velocity 7.2 cm/year, 6.0 cm/year), and one patient in puberty had a poor response to the rhGH treatment (height velocity 2.5 cm/year). Seven NPR2 gene variants were constructed and overexpressed in HEK293T and ATDC5 cells, and we found that ATDC5 cells with mutant NPR2 gene showed decreased differentiation, as evidenced by lower expression of ColII, ColX, and BMP4 and higher expression of Sox9. Moreover, the apoptosis rate was elevated in ATDC5 cells expressing the mutant NPR2 gene. N-glycosylation modification, plasma membrane localization, and ER stress resulted from the accumulation of mutant protein in ER, as shown by the higher expression of GRP78 and p-IRE1α. Overall, our results provide a novel insight into NPR2 loss of function, which could promote chondrocyte apoptosis and repress cell differentiation through ER stress and the unfolded protein response.

Plastic contamination in the environment is common but the characterisation of plastic ingested by fish in different environments is lacking. Hence, a meta-analysis was conducted to identify the prevalence of plastic ingested by fish globally. Based on a qualitative analysis of plastic size, it was determined that small microplastics (

As a new type of pollutant, microplastics have attracted widespread attention in recent years. Studies have shown that microplastics can affect the growth of microalgae, but little study has been done on macroalgae. In this paper, the enrichment and the characteristics of microplastics on Ulva prolifera, a green tide species, from the Yellow Sea of China were studied. Our results showed that U. prolifera enriched microplastic with an average abundance of 4603.3 ​± ​1167.2 items kg−1 d. w., which was more than 10,000 times of the microplastics in the ambient water (448.9 ​± ​145.68 items m−3). U. prolifera showed different enrichment capacity for microplastics with different shapes, with foam and film being the dominant shapes. The microplastic trapped by U. prolifera were usually in the size range of 2–5 ​mm and the main polymer types were polystyrenepe (PS) and polyethylene terephthalate (PET). The adsorption mechanism of microplastics on U. prolifera showed that its binding to microplastics was mainly through physical interaction. By salvaging U. prolifera at an amount of roughly 239,000 tons/year, a large amount of microplastics (approximately 35.6 ​tons/year.) can be removed from the Yellow Sea, which obviously plays a role in reducing the pollution of microplastics in the marine environment.

Circular RNAs (circRNAs) constitute a class of covalently circular non-coding RNA molecules formed by 5′ and 3′ end back-splicing. The rapid development of bioinformatics and large-scale sequencing has led to the identification of functional circRNAs. Despite an overall upward trend, studies focusing on the roles of circRNAs in immune diseases remain relatively scarce. In the present study, we obtained a differential circRNA expression profile based on microarray analysis of peripheral blood mononuclear cells (PBMCs) in children with type 1 diabetes mellitus (T1DM). We characterized one differentially expressed circRNA back-spliced from the MYB Proto-Oncogene Like 2 (MYBL2) gene in patients with T1DM, termed as hsa_circ_0060450. Subsequent assays revealed that hsa_circ_0060450 can serve as the sponge of miR-199a-5p, release its target gene, Src homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), encoded by the tyrosine-protein phosphatase non-receptor type 11 gene (PTPN11), and further suppress the JAK-STAT signaling pathway triggered by type I interferon (IFN-I) to inhibit macrophage-mediated inflammation, which indicates the important roles of circRNAs in T1DM and represents a promising therapeutic molecule in the treatment of T1DM.

Biodiversity of hydrothermal vents in the Indian Ocean, particularly those on the Southwest Indian Ridge (SWIR), are still relatively poorly understood. The Tiancheng field on the SWIR was initially reported with only a low-temperature diffuse flow venting area, but here we report two new active areas, including a chimney emitting high-temperature vent fluids. Biological sampling in these new sites doubled the known megafauna and macrofauna richness reported from Tiancheng. Significantly, we found several iconic species, such as the scaly-foot snail and the first Alviniconcha population on the SWIR. Tiancheng shares a high proportion of taxa with vents on the Central Indian Ridge (CIR) and lacks a number of key taxa that characterize other vents investigated so far on the SWIR. Population genetics of the scaly-foot snail confirmed this, as the Tiancheng population was clustered with populations from the CIR, showing low connectivity with the Longqi field. Unlike the previously examined populations, scales of the Tiancheng scaly-foot snail were coated in zinc sulfide, although this results only from precipitation. The close connection between Tiancheng and CIR vents indicates that the dispersal barrier for vent endemic species is not the Rodriguez Triple Junction as previously suggested but the transformation faults between Tiancheng and Longqi, warranting further studies on deep currents in this area to resolve the key barrier, which has important implications for biological conservation.

Wastewater treatment plants (WWTPs) are considered as one of the important sources of microplastics (MPs) in the marine environment. In this paper, the characteristics of MPs in the effluent discharged from five WWTPs in Qingdao, China, in winter and summer were analyzed. The results showed that only fibers and fragments were observed, with fibers as a dominant part. Rayon was the most domain polymer type, followed by Polyethylene terephthalate (PET) and chlorinated polyethylene (CPE). The average sizes of fiber MPs were 1010 ± 924 µm and 610 ± 691 µm in winter and summer, respectively. The contents of rayon were higher in summer than in winter. More small and transparent MPs were observed in summer. Rayon abundances ranged from 4.1 to 19.9 items/L and 33.3 to 116.7 items/L, with 12.3 ± 5.6 items/L and 67.6 ± 30.6 items/L as the average value in winter and in summer, respectively. The abundances of other polymer type MPs were 7.23~19.65 items/L with average value of 12.7 ± 4.7 items/L in winter and 12.0~20.0 items/L with 16.8 ± 4.7 items/L in summer. The daily emissions were estimated as 8.38 × 109~4.25 × 1010 items (9.2~27.8 kg) for rayon and 8.0 × 109~1.2 × 1010 items (7.6~5.3 kg) discharged for the other polymer type MPs from the five WWTPs. The results indicated that the seasonal variation of characteristics and emission of MPs in the effluent from WWTPs was mainly caused by increasing discharge of rayon, which may relate to people’s living habits and tourism activities.

The global outbreak of Corona Virus Disease 2019 (COVID-19) has led to an extreme increase in the use of disposable masks. If the used disposable masks are not appropriately disposed of, they will enter the natural environment and lead to environmental pollution. In order to understand the impacts of disposable masks after being disposed of into the natural environment, aging experiments with simulated natural conditions were performed on the outer, inner, and middle layers of the masks to verify the aging characteristics of disposable masks. We analyzed the mechanical behavior, surface morphology, and Fourier Transform Infrared Spectroscopy (FT-IR) spectra of disposable masks treated with different levels of UV irradiation to understand the possible changes in the masks under UV. Results showed that the elongation at break, tensile strength, and maximum force of all three polypropylene (PP) mask layers decreased after UV irradiation, indicating chemical bond breakage. In the process of photoaging, each layer of the disposable masks showed a different degree of microscopic surface changes after UV irradiation, and these changes gradually intensified with the extension of UV exposure time. FT-IR results showed that functional groups, such as hydroxyl and carbonyl groups increased in each layer after UV irradiation. The results of this study support that, although the different layers of the disposable masks are all made of PP, they age differently in the environment. With the ever-increasing number of disposable masks in the environment, we need to further study the aging and degradation of disposable masks to better understand their potential impacts on the environment in the future.

Abstract Background Teeth treated endodontically are more susceptible to vertical root fracture (VRF). Some studies have suggested that obturating the root canals with Gutta-percha or Resilon can reinforce endodontically treated teeth, but a few others have presented conflicting results. These inconsistent results cannot guide clinicians in determining clinical approaches. The objective of this meta-analysis is to evaluate and compare the vertical fracture resistance of endodontically treated root canals obturated with Gutta-percha/AH plus and the Resilon system. Methods Comprehensive literature searches were performed in the PubMed, Cochrane Library, ScienceDirect, Web of Science and Embase databases. The titles and abstracts of all of the retrieved articles were independently assessed by two authors according to predefined selection criteria. Data in the included articles were independently extracted. Statistical analyses were conducted using Review Manager 5.3 and Stata 12.0 software. The pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for the outcome indicators. The level of statistical significance was set at p

Abstract Background Mutations in the aggrecan (ACAN) gene can cause short stature (with heterogeneous clinical phenotypes), impaired bone maturation, and large variations in response to growth hormone (GH) treatment. For such cases, long-term longitudinal therapy data from China are still scarce. We report that a previously unknown ACAN gene variant reduces adult height and we analyze the GH response in children from an affected large Chinese family. Methods Two children initially diagnosed with idiopathic short stature (ISS) and a third mildly short child from a large Chinese family presented with poor GH response. Genetic etiology was identified by whole exome sequencing and confirmed via Sanger sequencing. Adult heights were analyzed, and the responses to GH treatment of the proband and two affected relatives are summarized and compared to other cases reported in the literature. Results A novel ACAN gene variant c.7465 T > C (p. Gln2364Pro), predicted to be disease causing, was discovered in the children, without evident syndromic short stature; mild bone abnormity was present in these children, including cervical-vertebral clefts and apophyses in the upper and lower thoracic vertebrae. Among the variant carriers, the average adult male and female heights were reduced by − 5.2 and − 3.9 standard deviation scores (SDS), respectively. After GH treatment of the three children, first-year heights increased from 0.23 to 0.33 SDS (cases in the literature: − 0.5 to 0.8 SDS), and the average yearly height improvement was 0.0 to 0.26 SDS (cases in the literature: − 0.5 to 0.9 SDS). Conclusions We report a novel pathogenic ACAN variant in a large Chinese family which can cause severe adult nonsyndromic short stature without evident family history of bone disease. The evaluated cases and the reports from the literature reveal a general trend of gradually diminishing yearly height growth (measured in SDS) over the course of GH treatment in variant-carrying children, highlighting the need to develop novel management regimens.

A new method has been developed to simultaneously determine 7 pyrethroid residues in tea brew using gas chromatography-mass spectrometry (GC-MS) combined with solid phase microextraction (SPME) with multiwalled carbon nanotubes (MWCNTs) coated fiber. The MWCNTs coated fiber of SPME was homemade by using stainless steel wire as coating carrier and polyacrylonitrile (PAN) solution as adhesive glue. Under the optimized conditions, a good linearity was shown for bifenthrin, fenpropathrin, permethrin, and cyfluthrin in 1–50 ng mL−1 and for cypermethrin, fenvalerate, and deltamethrin in 5–50 ng mL−1. The correlation coefficients were in the range of 0.9948–0.9999. The average recoveries of 7 pyrethroids were 94.2%–107.3% and the relative standard deviations (RSDs) were less than 15%. The detection limit of the method ranged from 0.12 to 1.65 ng mL−1. The tea brew samples made from some commercial tea samples were analyzed. Among them, bifenthrin, fenpropathrin, and permethrin were found. The results show that the method is rapid and sensitive and requires low organic reagent consumption, which can be well used for the detection of the pyrethroids in tea brew.

In this study, immobilized COX-2 was successfully constructed through glutaraldehyde-mediated covalent coupling on functional silica gel microspheres. The optimum conditions, properties, and morphological characteristics of the immobilized COX-2 were investigated. The optimal immobilization process was as follows: about 0.02 g of aminated silica gel microspheres was activated by 0.25% GA solution for 6 h and mixed with 5 U of free recombinant COX-2 solution. Then, the mixture was shaken for 8 h at 20 °C. Results showed that the immobilized COX-2 produced by this method exhibited excellent biocatalytic activity, equivalent to that of free COX-2 under the test conditions employed. The best biocatalytic activity of immobilized COX-2 appeared at pH 8.0 and still maintained at about 84% (RSD < 7.39%, n = 3) at pH 10.0. For temperature tolerance, immobilized COX-2 exhibited its maximum biocatalytic activity at 40 °C and about 68% (RSD < 6.99%, n = 3) of the activity was maintained at 60 °C. The immobilized COX-2 retained over 85% (RSD < 7.26%, n = 3) of its initial biocatalytic activity after five cycles, and after 10 days storage, the catalytic activity of immobilized COX-2 still maintained at about 95% (RSD < 3.08%, n = 3). These characteristics ensured the convenient use of the immobilized COX-2 and reduced its production cost.

Many marine organisms harness diverse protein molecules as underwater adhesives to achieve strong and robust interfacial adhesion under dynamic and turbulent environments. Natural underwater adhesion phenomena thus provide inspiration for engineering adhesive materials that can perform in water or high-moisture settings for biomedical and industrial applications. Here we review examples of biological adhesives to show the molecular features of natural adhesives and discuss how such knowledge serves as a heuristic guideline for the rational design of biologically inspired underwater adhesives. In view of future bio-inspired research, we propose several potential opportunities, either in improving upon current L-3, 4-dihydroxyphenylalanine-based and coacervates-enabled adhesives with new features or engineering conceptually new types of adhesives that recapitulate important characteristics of biological adhesives. We underline the importance of viewing natural adhesives as dynamic materials, which owe their outstanding performance to the cellular coordination of protein expression, delivery, deposition, assembly, and curing of corresponding components with spatiotemporal control. We envision that the emerging synthetic biology techniques will provide great opportunities for advancing both fundamental and application aspects of underwater adhesives.

A cross-linked biomass-polymer composite with a lignin content of up to 60% was prepared by blending lignin with an epoxy resin and polyamine using a hot press molding process. The characteristics of the curing reaction of lignin with epoxy resin were studied using DSC and FTIR analysis. The effect of molding temperature and molding pressure on the mechanical properties and microstructure of the lignin/epoxy resin composite was also studied by SEM, DMA, and TG analyses. The results showed that the epoxy resin can be cured by lignin, and the curing temperature for the blends can be reduced by the introduction of a polyamine cure agent. The properties of the composite, such as bending strength, impact strength, glass-transition temperature, and thermal stability, were evidently influenced by the molding process. A good interfacial combination was formed between lignin and epoxy resin. Increasing the molding temperature and pressure proved beneficial to achieve a better interfacial combination for the composite, and the degree of ductile fracture was increased in the fracture surface of the composite.

A novel series of 3-(2-furyl)acrylate monosaccharide esters Ia–f and menthyloxycarbonyl monosaccharide esters IIa–f were designed and synthesized. The chemical structures of the target compounds were confirmed by IR, 1H- and 13C-NMR and ESI-MS, and the target compounds were investigated for their in vitro antibacterial and antifungal activities. The antibacterial screening results showed that the 3-(2-furyl)acrylate monosaccharide ester derivatives Ia–f were either inactive or only weakly active against the three Gram-positive bacterial strains tested, whereas the menthyloxycarbonyl monosaccharide ester derivatives IIa–f exhibited higher levels of activity, with compound IIe being especially potent. The results of the antifungal screening revealed that compounds Ib, Ie, IIb and IIc displayed potent in vitro activities, whereas If and IIf showed promising activities against all of the microorganisms tested, with If exhibiting levels of activity deserving of further investigation.

MoS2 quantum dots (QDs) functionalized g-C3N4 nanosheets (MoS2@CNNS) were prepared through a protonation-assisted ion exchange method, which were developed as a highly efficient biomimetic catalyst. Structural analysis revealed that uniformly-dispersed MoS2 QDs with controllable size and different loading amount grew in-situ on the surface of CNNS, forming close-contact MoS2@CNNS nanostructures and exhibiting distinct surface properties. Compared to MoS2 QDs and CNNS, the MoS2@CNNS nanocomposites exhibited a more than four times stronger peroxidase-like catalytic activity, which could catalyze the oxidation of 3,3’,5,5’-tetramethylbenzidine (TMB) in the presence of H2O2 to generate a blue oxide. Among the MoS2@CNNS nanocomposites, MoS2@CNNS(30) was verified to present the best intrinsic peroxidase-like performance, which could be attributed to the more negative potential and larger specific surface area. A simple, rapid and ultrasensitive system for colorimetric detection of H2O2 was thus successfully established based on MoS2@CNNS, displaying nice selectivity, reusability, and stability. The detection limit of H2O2 could reach as low as 0.02 μM. Furthermore, the kinetic and active species trapping experiments indicated the peroxidase-like catalytic mechanism of MoS2@CNNS. This work develops a novel, rapid, and ultrasensitive approach for visual assay of H2O2, which has a potential application prospect on clinical diagnosis and biomedical analysis.

Extracellular toxins released by marine toxigenic algae into the marine environment have attracted increasing attention in recent years. In this study, profiling, characterization and quantification of extracellular toxin compounds associated with diarrhetic shellfish poison (DSP) in the culture medium of toxin-producing dinoflagellates were performed using high-performance liquid chromatography–high-resolution mass spectrometry/tandem mass spectrometry for the first time. Results showed that solid-phase extraction can effectively enrich and clean the DSP compounds in the culture medium of Prorocentrum lima (P. lima), and the proposed method achieved satisfactory recoveries (94.80%–100.58%) and repeatability (relative standard deviation ≤9.27%). Commercial software associated with the accurate mass information of known DSP toxins and their derivatives was used to screen and identify DSP compounds. Nine extracellular DSP compounds were identified, of which seven toxins (including OA-D7b, OA-D9b, OA-D10a/b, and so on) were found in the culture medium of P. lima for the first time. The results of quantitative analysis showed that the contents of extracellular DSP compounds in P. lima culture medium were relatively high, and the types and contents of intracellular and extracellular toxins apparently varied in the different growth stages of P. lima. The concentrations of extracellular okadaic acid and dinophysistoxin-1 were within 19.9–34.0 and 15.2–27.9 μg/L, respectively. The total concentration of the DSP compounds was within the range of 57.70–79.63 μg/L. The results showed that the proposed method is an effective tool for profiling the extracellular DSP compounds in the culture medium of marine toxigenic algae.

Introduction During conventional liver transplantation (CLT), ischaemia-reperfusion injury (IRI) is inevitable and is associated with complications such as early allograft dysfunction (EAD), primary non-function and ischaemictype biliary lesions. We have established a novel procedure called ischaemia-free liver transplantation (IFLT). The results from a pilot study suggest that IFLT might prevent IRI and yield better transplant outcomes than CLT. The purpose of this study was to further assess the efficacy and safety of IFLT versus CLT in patients with end-stage liver disease. Methods and analysis This is an investigator-initiated, open-label, phase III, prospective, single-centre randomised controlled trial on the effects of IFLT in patients with endstage liver disease. Adult patients (aged 18–75 years) eligible for liver transplantation will be screened for participation in this trial and will be randomised between the IFLT group (n=34) and the CLT group (n=34). In the IFLT group, the donor liver will be procured, preserved and implanted with continuous normothermic machine perfusion (NMP). In the CLT group, the donor liver will be procured after a fast cold flush, preserved in 0°C–4°Csolution and implanted under hypothermic and hypoxic conditions. Patients in both groups will be managed according to the standard protocol of our centre. The primary end point is the incidence of EAD after liver transplantation. Intraoperative and postoperative parameters of donor livers and recipients will be observed and recorded, and postoperative liver graft function, complications and recipient and graft survival will be evaluated. After a 12-month follow-up of the last enrolled recipient, the outcomes will be analysed to evaluate the safety and efficacy of IFLT versus CLT in patients with end stage liver disease. Ethics and dissemination The protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals. [ABSTRACT FROM AUTHOR]

Objective: Type 1 diabetes (T1D) is a highly heritable disease with much lower incidence but more adult-onset cases in the Chinese population. Although genome-wide association studies (GWAS) have identified >60 T1D loci in Caucasians, less is known in Asians.Research Design and Methods: We performed the first two-stage GWAS of T1D using 2,596 autoantibody-positive T1D case subjects and 5,082 control subjects in a Chinese Han population and evaluated the associations between the identified T1D risk loci and age and fasting C-peptide levels at T1D diagnosis.Results: We observed a high genetic correlation between children/adolescents and adult T1D case subjects (rg = 0.87), as well as subgroups of autoantibody status (rg ≥ 0.90). We identified four T1D risk loci reaching genome-wide significance in the Chinese Han population, including two novel loci, rs4320356 near BTN3A1 (odds ratio [OR] 1.26, P = 2.70 × 10-8) and rs3802604 in GATA3 (OR 1.24, P = 2.06 × 10-8), and two previously reported loci, rs1770 in MHC (OR 4.28, P = 2.25 × 10-232) and rs705699 in SUOX (OR 1.46, P = 7.48 × 10-20). Further fine mapping in the MHC region revealed five independent variants, including another novel locus, HLA-C position 275 (omnibus P = 9.78 × 10-12), specific to the Chinese population. Based on the identified eight variants, we achieved an area under the curve value of 0.86 (95% CI 0.85-0.88). By building a genetic risk score (GRS) with these variants, we observed that the higher GRS were associated with an earlier age of T1D diagnosis (P = 9.08 × 10-11) and lower fasting C-peptide levels (P = 7.19 × 10-3) in individuals newly diagnosed with T1D.Conclusions: Our results extend current knowledge on genetic contributions to T1D risk. Further investigations in different populations are needed for genetic heterogeneity and subsequent precision medicine. [ABSTRACT FROM AUTHOR]