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Therapeutic cancer vaccines fail to produce satisfactory outcomes against solid tumors since vaccine‐induced anti‐tumor immunity is significantly hampered by immunosuppression. Generating an in situ cancer vaccine targeting immunological cold tumor microenvironment (TME) appears attractive. Here, a type of free‐field based whole‐body ultrasound (US)‐driven nanovaccines are constructed, named G5‐CHC‐R, by conjugating the sonosensitizer, Chenghai chlorin (CHC) and the immunomodulator, resiquimod (R848) on top of a super small‐sized dendrimeric nanoscaffold. Once entering tumors, R848 can be cleaved from a hypoxia‐sensitive linker, thus modifying the TME via converting macrophage phenotypes. The animals bearing orthotopic pancreatic cancer with intestinal metastasis and breast cancer with lung metastasis are treated with G5‐CHC‐R under a free‐field based whole‐body US system. Benefit from the deep penetration capacity and highly spatiotemporal selectiveness, G5‐CHC‐R triggered by US represented a superior alternative for noninvasive irradiation of deep‐seated tumors and magnification of local immune responses via driving mass release of tumor antigens and "cold‐warm‐hot" three‐state transformation of TME. In addition to irradiating primary tumors, a robust adaptive anti‐tumor immunity is potentiated, leading to successful induction of systemic tumor suppression. The sono‐nanovaccines with good biocompatibility posed wide applicability to a broad spectrum of tumors, revealing immeasurable potential for translational research in oncology. [ABSTRACT FROM AUTHOR]

Aims: To analyse spatial and temporal changes in the global burden of diabetes mellitus (DM) attributable to dietary factors from 1990 to 2019. Materials and Methods: The burden of DM was analysed in terms of age‐standardized disability‐adjusted life‐year (DALY) rates and age‐standardized death rates (ASDRs), which were obtained from the Global Burden of Disease Study 2019, and their corresponding estimated annual percentage changes (EAPCs). Results: The ASDR exhibited a decreasing trend (EAPC = −0.02), while the age‐standardized DALY rate exhibited an increasing trend (EAPC = 0.65). Forty‐four percent of the burden of DM was attributable to dietary factors, with the three largest contributors being high intake of red meat, high intake of processed meat, and low intake of fruit. Residence in a region with a high sociodemographic index (SDI) was associated with a diet low in whole grains and high in red meat and processed meat, while residence in a low‐SDI region was associated with a diet low in whole grains and fruits, and high in red meat. Conclusions: The age‐standardized DALYs of DM attributable to dietary factors increased between 1990 and 2019 but differed among areas. The three largest dietary contributors to the burden of DM were high intake of red meat, high intake of processed meat, and low intake of fruit. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cell (MSC) implantation is a promising option for liver repair, but their poor retention in the injured liver milieu critically blunts therapeutic effects. The aim is to clarify the mechanisms underlying massive MSC loss post‐implantation and establish corresponding improvement strategies. MSC loss primarily occurs within the initial hours after implantation into the injured liver milieu or under reactive oxygen species (ROS) stress. Surprisingly, ferroptosis is identified as the culprit for rapid depletion. In ferroptosis‐ or ROS‐provoking MSCs, branched‐chain amino acid transaminase‐1 (BCAT1) is dramatically decreased, and its downregulation renders MSC susceptible to ferroptosis via suppressing the transcription of glutathione peroxidase‐4 (GPX4), a vital ferroptosis defensing enzyme. BCAT1 downregulation impedes GPX4 transcription via a rapid‐responsive metabolism‐epigenetics coordinating mechanism, involving α‐ketoglutarate accumulation, histone 3 lysine 9 trimethylation loss, and early growth response protein‐1 upregulation. Approaches to suppress ferroptosis (e.g., incorporating ferroptosis inhibitors in injection solvent and overexpressing BCAT1) significantly improve MSC retention and liver‐protective effects post‐implantation. This study provides the first evidence indicating that excessive MSC ferroptosis is the nonnegligible culprit for their rapid depletion and insufficient therapeutic efficacy after implantation into the injured liver milieu. Strategies suppressing MSC ferroptosis are conducive to optimizing MSC‐based therapy. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to depict the clinical features, including myositis specific or associated antibody (MSA/MAA) profile of systemic lupus erythematosus (SLE) patients with muscle involvement in a Chinese cohort. Methods: We retrospectively studied a cohort of 1696 SLE inpatients and screened for concurrent myositis features from January 2013 to June 2021. Propensity score matching was applied to enroll controls without myositis features from our cohort. Demographic, clinical and laboratory variables were collected. MSA/MAA panels containing 16 autoantibodies (TIF1‐γ, MDA5, NXP2, Mi‐2α/β, SAE1, Jo‐1, PL‐7, PL‐12, EJ, OJ, SRP, HMGCR, cN‐1A, PM‐Scl75/100, Ku and Ro52) were tested by line‐blotting assay. Binary logistic regression and K‐means clustering were applied. Results: Forty‐one of 1696 (2.42%) SLE patients in our SLE inpatient cohort showed features of myositis. Binary logistic regression revealed that new‐onset SLE (odds ratio [OR] = 4.77, 95% CI = 1.10–20.57), interstitial lung disease (ILD) (OR = 10.07, 95% CI = 1.65–61.51), positive anti‐U1RNP antibody (OR = 4.38, 95% CI = 1.08–17.75), and Raynaud's phenomenon (OR = 7.94, 95% CI = 1.41–44.69) were associated with muscle involvement. Except for anti‐Ro52 (50%), anti‐Ku antibody (38.2%) was the next frequently detected MSA/MAA in the panel, followed by anti‐NXP2 antibody (11.8%). It was noteworthy that multiple MSA/MAAs (≥2, excluding anti‐Ro52) coexisted in 9 patients. Patients with myositis features were clustered into 2 subgroups. Cluster 1 was characterized by anti‐Ku or anti‐Ro52 with high SLE Disease Activity Index, whereas cluster 2 presented with anti‐U1RNP, Raynaud's phenomenon and pulmonary arterial hypertension resembling mixed connective tissue disease. Conclusion: In our Chinese SLE inpatient cohort, muscle involvement was infrequent. Nevertheless, distinct features in these SLE patients deserve further study. [ABSTRACT FROM AUTHOR]

Background and Aims: In vitro fertilization‐embryo transfer (IVF‐ET) may increase the risk of mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV). The purpose of this study was to investigate the impact and safety of IVF‐ET on MTCT in women with chronic HBV infection (CHB). Methods: The data of 298 women who got pregnant by IVF‐ET and their 375 children were collected retrospectively. Mothers were divided into the CHB group (n = 224) and the control group (HBsAg negative, n = 74). After birth, newborns were routinely vaccinated with the hepatitis B vaccine, and infants in the CHB group were injected with hepatitis B immunoglobulin within 2 h after birth. Demographic information, clinical data and laboratory test results were collected. The primary outcome measures were the MTCT rate of HBV, and the secondary outcome measures were the safety of the mother and infant. Results: There was no case of HBV MTCT in all 282 newborns born in the CHB group and 93 neonates born in the control group. Of the two groups, the birth weight (3056.74 ± 601.65 vs. 2926.24 ± 704.86, P =.083), length (49.22 ± 1.97 vs. 48.74 ± 3.09, P =.167), 5‐min Apgar score (9.97 ± 0.21 vs. 9.90 ± 0.51, P =.212), days of pregnancy (265.70 ± 12.73 vs. 262.02 ± 17.50, P =.064) and neonatal malformation rate (0.71% vs. 0, P = 1.000) were similar. Two cases of neonatal malformation occurred in the CHB group. The incidences of pregnancy and childbirth complications were similar between the two groups. Conclusion: IVF‐ET does not increase the risk of MTCT in women with chronic HBV infection, and it is safe for mothers and infants. [ABSTRACT FROM AUTHOR]

SUMMARY: Occupation of living space is one of the main driving forces of adaptive evolution, especially for aquatic plants whose leaves float on the water surface and thus have limited living space. Euryale ferox, from the angiosperm basal family Nymphaeaceae, develops large, rapidly expanding leaves to compete for space on the water surface. Microscopic observation found that the cell proliferation of leaves is almost completed underwater, while the cell expansion occurs rapidly after they grow above water. To explore the mechanism underlying the specific development of leaves, we performed sequences assembly and analyzed the genome and transcriptome dynamics of E. ferox. Through reconstruction of the three sub‐genomes generated from the paleo‐hexaploidization event in E. ferox, we revealed that one sub‐genome was phylogenetically closer to Victoria cruziana, which also exhibits gigantic floating leaves. Further analysis revealed that while all three sub‐genomes promoted the evolution of the specific leaf development in E. ferox, the genes from the sub‐genome closer to V. cruziana contributed more to this adaptive evolution. Moreover, we found that genes involved in cell proliferation and expansion, photosynthesis, and energy transportation were over‐retained and showed strong expression association with the leaf development stages, such as the expression divergence of SWEET orthologs as energy uploaders and unloaders in the sink and source leaf organs of E. ferox. These findings provide novel insights into the genome evolution through polyploidization, as well as the adaptive evolution regarding the leaf development accomplished through biased gene retention and expression sub‐functionalization of multi‐copy genes in E. ferox. Significance Statement: Through the separation, reconstruction and evolutionary dissection of the three sub‐genomes of Euryale ferox, we reveal that the three sub‐genomes have different origins, with one sub‐genome showing a closer phylogenetic relationship to Victoria cruziana, which shows a similar adult leaf development process as that in E. ferox. Further analysis revealed that while all three sub‐genomes promoted the evolution of the specific leaf development process in E. ferox, the genes from the sub‐genome closer to V. cruziana contributed more to this adaptive evolution. Moreover, we found that genes involved in cell proliferation and expansion, photosynthesis, and energy transportation were over‐retained in multi‐copies and showed strong expression association with the different leaf development stages in E. ferox. [ABSTRACT FROM AUTHOR]

Abstract: In this work, a coarse‐grained Dense Discrete Phase Model (DDPM) coupled with the Energy‐Minimization Multi‐Scale (EMMS) drag, was used to simulate the hydrodynamics of a 3D semi‐industrial scale Circulating Fluidized Bed (CFB) with Geldart A particles. The effect of particle numbers in a parcel, an important parameter in a coarse‐grained approach, was investigated. It was found that when parcel diameter falls into the size range of clusters, simulation results are insensitive to particle number in a parcel and generally agree with the experimental data. Further, a comparison between DDPM and Eulerian Two‐Fluid Modelling (TFM) approaches was investigated, both coupled with EMMS and conventional homogenous drag. The simulation results suggested that the effect of meso‐scale structures on drag force needs to be considered in both modelling approaches. [ABSTRACT FROM AUTHOR]

Abstract: A decrease in the specific activity of an enzyme is commonly observed when the enzyme is inappropriately handled or is stored over an extended period. Here, we reported a functional transition of an FMN‐bound diaphorase (FMN–DI) that happened during the long‐term storage process. It was found that FMN–DI did not simply lose its β‐nicotinamide adenine diphosphate (NADH) dehydrogenase activity after a long‐time storage, but obtained a new enzyme activity of NADH oxidase. Further mechanistic studies suggested that the alteration of the binding strength of an FMN cofactor with a DI protein could be responsible for this functional switch of the enzyme. [ABSTRACT FROM AUTHOR]

Chitosan, produced from chitin, is one of the polymers with promising applications in various fields. However, despite diverse research studies conducted on its biocompatibility, its uses are still limited. The main reason is the degree of deacetylation (DOD), which represents the proportion of deacetylated units in the polymer and is directly correlated with its biocompatibility property. In this article, the in vivo biocompatibility of three chitosan-hydroxyapatite composite films composed of chitosan with different DOD values was investigated by traditional biological protocols and novel optical spectroscopic analyses. The DOD of the chitosan obtained from three different manufacturers was estimated and calculated by Raman spectroscopy, Fourier transform infrared spectroscopy, and proton nuclear magnetic resonance spectroscopy. The chitosan with the higher DOD induced a higher incidence of inflammation in skin cells. The amino group density, biodegradability, and crystallinity of chitosan are the three possible factors that need to be considered when determining the biocompatibility of the films for in vivo application, as they led to complicated biological results, resulting in either better or worse inflammation even when using chitosan products with the same DOD. This basic study on the relationship between the DOD and inflammation is valuable for the development of further chitosan-based researches. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1637-1645, 2017. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) are promising candidates as novel scaffolds for peripheral nerve regeneration. Schwann cells (SCs) are attractive therapeutic targets due to their pivotal role in peripheral nerve regeneration, but primary SCs have limitations for clinical application. However, adipose-derived stem cells (ASCs) may differentiate into Schwann-like cells. The present study assesses the potential applicability of multiwall CNTs (MWNTs) composited with polydimethylsiloxane (PDMS), which were then seeded with differentiated adipose-derived stem cells (dASCs) to promote neuronal differentiation and growth. Aqueous MWNT dispersion was filtered, and the PDMS/MWNT sheets were prepared using a simple printing-transfer method. Characterization of PDMS/MWNT sheets indicated their unique physical properties, such as superior mechanical strength and electroconductivity, compared with bare PDMS sheets. ASCs were differentiated into Schwann-like cells using a mixture of glial growth factors. Dorsal root ganglion (DRG) neurons were co-cultured with SCs and dASCs on PDMS/MWNTs sheets or noncoated dishes. An alamar blue proliferation assay of dASC and SCs showed significantly more dASC and SCs cultured on PDMS/MWNT sheets at 48 h and 72 h than when cultured on noncoated dishes ( p < 0.05). Additionally, when DRG were cultured on PDMS/MWNT sheets seeded with dASCs, the proliferation of DRG neurons and the longest neurite outgrowth length per neuron were significantly greater than when DRG were cultured on PDMS/MWNT sheets alone or on noncoated dishes seeded with SCs or dASCs ( p < 0.05). Overall, PDMS/MWNT sheets exhibited excellent biocompatibility for culturing Schwann-like cells differentiated from ASCs. Seeding the dASCs on PDMS/MWNT sheets may produce synergistic effects in peripheral nerve regeneration, similarly to SCs. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3642-3648, 2015. [ABSTRACT FROM AUTHOR]

Artificial nerve guidance conduits (aNGCs) prepared from polymer scaffolds and carbon nanotubes (CNTs) possess unique chemical and physical properties, and have been widely used in preclinical trials to promote neuronal differentiation and growth. However, there have been only a few reports on the clinical applicability of CNT sheets for proliferation of primary neuronal cells due to safety concerns. The present study assesses the ability and potential applicability of multiwalled CNTs (MWNTs) composited with polydimethylsiloxane (PDMS) sheets to promote and enhance the proliferation of primary neuronal cells. In this study, the aqueous MWNT dispersion was filtered, and the PDMS/MWNT sheets were prepared using a simple printing transfer method. Characterization of PDMS/MWNT sheets demonstrated their unique physical properties such as superior mechanical strength and electroconductivity when compared with PDMS sheets. The effect of the PDMS/MWNT sheets on the neural cell proliferation and cytotoxicity was evaluated using MTT and alamar blue assays. Our results indicate the viability and proliferation of primary neuronal cells and Schwann cells in PDMS/MWNT sheets increased over twice when compared with a noncoated dish that is not usual in the primary neuronal cell growth control ( p < 0.05). In addition, PDMS/MWNT sheets enhanced the adhesion and viability of the cells compared with poly- l-lysine coated dishes, which are most commonly used for improving cell adherence. Additionally, the PDMS/MWNT sheets exhibited excellent biocompatibility for culturing neuronal and Schwann cells. Overall, all assessments indicate that PDMS/MWNT sheets are ideal candidates for the development of artificial nerve conduits for clinical use following peripheral nerve injury. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1746-1754, 2015. [ABSTRACT FROM AUTHOR]

The influence of biochar amendments on the physical quality of a clayey soil (Vertisol) was evaluated by aggregate-size distribution and stability, water retention, and pore-space structure of biochar-amended soils. Clayey soil was treated with three kinds of biochars (straw biochar, woodchips biochar, and wastewater-sludge biochar) at the rate of 0, 20, 40, and 60 g biochar (kg soil)-1 and incubated for 180 d in glasshouse. The application of straw biochar (SB) and wastewater-sludge biochar (WSB) significantly enhanced the formation of 5-2 and 0.25-0.5 mm macroaggregates in the clayey soil relative to the control treatment, while the < 0.25-cm microaggregate decreased with biochar additions. However, woodchips biochar (WCB) had no obvious effect on the formation of macroaggregate. The application of SB and WSB increased the mean weight diameter (MWD) and geometric mean diameter (GMD) of clayey soil, implying that biochar increased the aggregate stability. They improved the aggregate stability through an enhanced resistance to slaking and increased interparticular cohesion. The SB-amended soils exhibited significant increases in the available water contents of soils. The application of SB significantly increased pore volume in the macropore (> 75 μm) and mesopore (30-75 μm) ranges, which may be the result of the reorganization of pore-size distribution and aggregation processes induced by the addition of biochar. Results indicated that biochar had the potential to improve the physical quality and pore-space status of clayey soil. It is suggested that biochar may be considered as a soil amendment for improving poor physical characteristics of clayey soil. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Acute fever is the most common early clinical symptom of many critical illnesses with a high mortality rate. It is necessary to identify patients with severe acute fever early and accurately. The aim of this study is to identify risk factors for critically ill outpatients with acute fever and formulate activation criteria of adult fever state score (AFSS) to alert outpatient clinic doctors. Methods Retrospectively, 357 adult patients with acute fever were divided into two groups: 180 patients with a severe state and 177 patients with a mild state. Logistic regression was used to determine risk factors for the severe state. Risk factors were weighted and an AFSS was formulated. A receiver operating characteristic (ROC) analysis of weighted cumulative scores was performed to evaluate the diagnostic accuracy of AFSS, and the kappa test was used to confirm diagnostic reliability. A χ2-test for trend was applied to determine the relevance between AFSS and admission rate and in-hospital mortality. A Kruskal-Wallis test was used to examine the relationship between AFSS and length of stay. Results Risk factors for state included: old age, long fever course, past medical history, abnormal temperature, abnormal respiratory rate, abnormal heart rate, abnormal mean arterial pressure and abnormal peripheral white blood cell count. The area under the ROC curve of AFSS was 0.964 and ≥8 points predicted severe state; the Kappa value was 0.801. With an increase in score, there was an increase in admission rate, mortality rate and length of stay. The forecast performance of AFSS was superior to the modified early warning score. Conclusions The AFSS has high diagnostic accuracy and reliability for the early identification of patients with severe acute fever. [ABSTRACT FROM AUTHOR]

Acute fever is the most common clinical symptom for infectious diseases. It is necessary to identify risk factors for infectious patients with acute fever and formulate activation criteria of early warning infectiosity score system (EWIS) to alert outpatient clinic doctors. Logistic regression analysis was used to determine risk factors for infectious diseases from the clinical data of 758 patients with acute fever. Risk factors were weighted and an EWIS was formulated. A receiver operator characteristic (ROC) analysis of weighted cumulative scores was performed to evaluate the diagnostic accuracy of EWIS, and the Kappa test used to confirm diagnostic reliability. A χ-test for trend was applied to determine the relevance between EWIS and incidence of infectious diseases. Risk factors for infections included conjunctival hyperaemia, rash, diarrhoea, increased alanine aminotransferase, splenomegaly and abnormal percentage of peripheral neutrophils (NE%). Risk factors were weighted and tabulated. The areas under the ROC curves of the EWIS was 0.929 and ≥4 points predicted infectious diseases, and the Kappa values were 0.750. As the score increased, the incidence of infectious diseases increased. The areas under the ROC curves of the EWIS predicting on single viral and bacterial infectious diseases were 0.961 and 0.896, and the Kappa values were 0.807 and 0.701, respectively. Risk factors for infections have been identified, quantified and formulated into a table of EWIS that have high diagnostic accuracy and reliability for the early identification of contagious diseases. [ABSTRACT FROM AUTHOR]