Preparation and characterization of zein-caseinate-pectin complex nanoparticles for encapsulation of curcumin: pectin extracted by high-speed shearing from passion fruit (Passiflora edulis f. flavicarpa) peel.

BACKGROUND: Pectin extracted by high-speed shearing from passion fruit peel (HSSP) is a potentially excellent wall material for encapsulating curcumin, which has multiple advantages over pectin prepared by heated water extraction. HSSP was used to fabricate complex nanoparticles of zein-sodium caseinate-pectin for encapsulation of curcumin in this study. The influence of heating on the physicochemical properties of the composite nanoparticles was also investigated, as well as the effect of composite nanoparticles on the encapsulation efficiency, antioxidant activity and release characteristics of curcumin. RESULTS: The nanoparticles were formed through electrostatic interactions, hydrogen bonds and hydrophobic interactions between the proteins and HSSP. A temperature of 50 °C was more favorable for generating compact and small-sized nanoparticles, which could effectively improve the encapsulation efficiency and functional properties. Moreover, compared to other pectin used in the study, the nanoparticles prepared with HSSP showed the best functionality with a particle size of 234.28 ± 0.85 nm, encapsulation rate of 90.22 ± 0.54%, free radical scavenging rate of 78.97% and strongest protective capacity in simulated gastric fluid and intestinal release effect. CONCLUSION: Zein-sodium caseinate-HSSP is effective for encapsulating and delivering hydrophobic bioactive substances such as curcumin, which has potential applications in the functional food and pharmaceutical industries. © 2024 Society of Chemical Industry.

Gestational diabetes mellitus combined with fulminant type 1 diabetes mellitus, four cases of double diabetes: A case report.

BACKGROUND: Fulminant type 1 diabetes mellitus (FT1DM) that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM (PF), always without history of abnormal glucose metabolism. Here, we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus (GDM). CASE SUMMARY: The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected, and the patients and their infants were followed up. All patients were diagnosed with GDM during the second trimester and were treated. The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM. Two patients had an insulin allergy, and two had symptoms of upper respiratory tract infection before onset. One patient developed ketoacidosis, and three developed ketosis. Two patients had cesarean section deliveries, and two had vaginal deliveries. The growth and development of the infants were normal. C-peptide levels were lower than those at onset, suggesting progressive impairment of islet function. The frequencies of the DRB1 09:01, DQB1 03: 03, DQA1 03:02, DPA1 01:03, DPA1 02:02, DPB1 05:01, DRB4 01:03, G 01:01, and G 01:04 human leukocyte antigen (HLA)-G alleles were high in the present study. CONCLUSION: In comparison with pregnancy-associated FT1DM (PF), patients with GDM combined with FT1DM had an older age of onset, higher body mass index, slower onset, fewer prodromal symptoms, and less acidosis. The pathogenesis may be due to various factors affecting the already fragile ß-cells of GDM patients with genetically susceptible class II HLA genotypes. We speculate that GDM combined with FT1DM during pregnancy, referred to as "double diabetes," is a subtype of PF with its own unique characteristics that should be investigated further.

A strategy to boost xanthine oxidase and angiotensin converting enzyme inhibitory activities of peptides via molecular docking and module substitution.

Molecular docking and activity evaluation screened the dipeptide module GP with low xanthine oxidase (XOD) inhibitory activity and modules KE and KN with high activity, and identified them as low- and high-contribution modules, respectively. We hypothesized the substitution of low-contribution modules in peptides with high contributions would boost their XOD inhibitory activity. In the XOD inhibitory peptide GPAGPR, substitution of GP with both KE and KN led to enhanced affinity between the peptides and XOD. They also increased XOD inhibitory activity (26.4% and 10.3%) and decreased cellular uric acid concentrations (28.0% and 10.4%). RNA sequencing indicated that these improvements were attributable to the inhibition of uric acid biosynthesis. In addition, module substitution increased the angiotensin-converting enzyme inhibitory activity of GILRP and GAAGGAF by 84.8% and 76.5%. This study revealed that module substitution is a feasible strategy to boost peptide activity, and provided information for the optimization of hydrolysate preparation conditions.

Exploring causal association between circulating inflammatory cytokines and functional outcomes following ischemic stroke: A bidirectional Mendelian randomization study.

OBJECTIVES: Previous observational studies have indicated correlations between various inflammatory cytokines and functional outcomes following ischemic stroke (IS); however, the causality remains unclear. We aimed to further evaluate the causal association between 41 circulating inflammatory cytokines and functional outcomes following IS. METHODS: Two-sample bidirectional Mendelian randomization (MR) analysis was used in this study. The genetic variation of 41 circulating inflammatory cytokines were derived from genome-wide association study (GWAS) data of European ancestry (n = 8293). The corresponding genetic association of functional outcomes following IS were derived from European ancestry GWAS data (n = 6021). RESULTS: Inverse variance weighted (IVW) analysis showed that genetically predicted increased levels of regulation and activation in normal T-cell expression and secretion factor (RANTES/CCL5) and eosinophilic chemotactic factor (EOTAXIN/CCL11) were positively correlated with the increased adverse functional outcomes (modified Rankin Scale [mRS≥3] following IS (OR: 1.40, 95% CI: 1.002-1.96, p = 0.049; OR: 1.33, 95% CI: 1.15-1.54, p = 0.0001). Interleukin 18 (IL-18) level might be the downstream consequence of adverse functional outcomes following IS (ß: -0.09, p = 0.039). Other inflammatory cytokines and functional outcomes following IS did not appear to be causally related. CONCLUSIONS: This study suggests a causality between inflammation and adverse functional outcomes following IS. RANTES (CCL5) and EOTAXIN (CCL11) may be the upstream factors of adverse functional outcomes following IS, while IL-18 may be the downstream effect of adverse functional outcomes following IS. Whether these cytokines can be used to predict or improve adverse functional outcomes after IS requires further researches.

Advanced progress of spatial metabolomics in head and neck cancer research.

Head and neck cancer ranks as the sixth most prevalent malignancy, constituting 5 % of all cancer cases. Its inconspicuous onset often leads to advanced stage diagnoses, prompting the need for early detection to enhance patient prognosis. Currently, research into early diagnostic markers relies predominantly on genomics, proteomics, transcriptomics, and other methods, which, unfortunately, necessitate tumor tissue homogenization, resulting in the loss of temporal and spatial information. Emerging as a recent addition to the omics toolkit, spatial metabolomics stands out. This method conducts in situ mass spectrometry analyses on fresh tissue specimens while effectively preserving their spatiotemporal information. The utilization of spatial metabolomics in life science research offers distinct advantages. This article comprehensively reviews the progress of spatial metabolomics in head and neck cancer research, encompassing insights into cancer cell metabolic reprogramming. Various mass spectrometry imaging techniques, such as secondary ion mass spectrometry, stroma-assisted laser desorption/ionization, and desorption electrospray ionization, enable in situ metabolite analysis for head and neck cancer. Finally, significant emphasis is placed on the application of presently available techniques for early diagnosis, margin assessment, and prognosis of head and neck cancer.

Mechanisms of resveratrol against diabetic wound by network pharmacology and experimental validation.

BACKGROUND: Resveratrol (RSV) that possesses anti-oxidative, anti-inflammatory, and pro-angiogenic effects is an effective drug for diabetic wound (DW), while its pharmacological mechanism remains to be elucidated. In this study, we apply network pharmacology and experimental validation approach to reveal the potential mechanism of RSV against DW. METHODS: We obtained potential targets for RSV and DW from the publicly available database. Using interaction networks and conducting GO and KEGG pathway enrichment analyses, we constructed target-pathway networks to explore the relationship between RSV and DW. To validate the pharmacological mechanism of RSV, we induced the DW model. RESULTS: Ninety overlapped targets between RSV and DW were obtained, and the hub genes of the PPI network included TNF, IL-6, CASP3, MAPK3, VEGFA, IL-1ß, AKT1, and JUN. Based on target-pathway networks, the AGE-RAGE signalling pathway was involved in the RSV treatment of DW. Furthermore, in vivo experiments revealed that RSV significantly promoted wound healing in diabetic mice and attenuated the expression of pro-inflammatory cytokines in wound tissue. Meanwhile, RSV could inhibit the AGE-RAGE signalling pathway and thus reduce the activation of NF-κB. CONCLUSION: This study initially revealed the biological mechanism of RSV for treating DW through multi-target and multi-pathway. AGE-RAGE, FoxO, MAPK, PI3K-AKT and other signalling pathways may be the main pathways of RSV in treating DW. RSV reduces the inflammatory response by inhibiting the AGE-RAGE signalling pathway, which in turn promotes DW healing.

Impacts of climate change on climatically suitable regions of two invasive Erigeron weeds in China.

Introduction: Erigeron philadelphicus and Erigeron annuus are two ecologically destructive invasive plants from the Asteraceae family. Predicting the potential distribution pattern of two invasive alien Erigeron weeds can provide a scientific basis for prevent the further spread of these two weeds in China under climate change. Methods: Based on historical occurrence datasets and environmental variables, we optimized a MaxEnt model to predict the potential suitable habitats of E. philadelphicus and E. annuus. We also analyzed the shifts of distribution centroids and patterns under climate change scenarios. Results: The key variables that affect the potential geographical distribution of E. annuus and E. philadelphicus, respectively, are temperature seasonality and precipitation of the driest month. Moreover, topsoil sodicity and topsoil salinity also influence the distribution of E. philadelphicus. Under climate change, the overall suitable habitats for both invasive alien Erigeron weeds are expected to expand. The potential geographical distribution of E. annuus exhibited the highest expansion under the SSP245 climate scenario (medium forcing scenarios), whereas E. philadelphicus had the highest expansion under the SSP126 climate scenario (lower forcing scenarios) globally. The future centroid of E. annuus is projected to shift to higher latitudes specifically from Hubei to Hebei, whereas E. philadelphicus remains concentrated primarily in Hubei Province. The overlapping suitable areas of the two invasive alien Erigeron plants mainly occur in Jiangsu, Zhejiang, Fujian, Jiangxi, Hunan, Guizhou, and Chongqing, within China. Discussion: Climate change will enable E. annuus to expand into northeastern region and invade Yunnan Province whereas E. philadelphicus was historically the only suitable species. E. annuus demonstrates a greater potential for invasion and expansion under climate change, as it exhibits higher environmental tolerance. The predictive results obtained in this study can serve as a valuable reference for early warning systems and management strategies aimed at controlling the spread of these two invasive plants.

Tryptophan residue of plasmid-encoded Pgp3 is important for Chlamydia muridarum to induce hydrosalpinx in mice.

The crucial role of plasmid-encoded protein Pgp3 in Chlamydia pathogenesis has been demonstrated in various animal models. Previous studies have revealed that the Pgp3-deficient C. muridarum mutant fails to induce hydrosalpinx after vaginal inoculation in mice. Structural analysis of C. trachomatis Pgp3 trimer has indicated that Trp234 may play a critical role in trimeric crystal packing interactions and that Tyr197 is involved at predominant cation-binding sites. In this study, we constructed C. muridarum transformants harboring Pgp3, Trp234, or Tyr197 point mutations (Pgp3W234A and Pgp3Y197A). C3H/HeJ mice infected with Pgp3W234A mutant failed to induce severe hydrosalpinx in the oviduct tissue, which largely phenocopied the full-length Pgp3-deficient C. muridarum. The Pgp3Y197A variant induced an intermediate severity of pathology. The attenuated pathogenicity caused by the Pgp3W234A mutant may be due to its decreased survival in the lower genital tracts of mice, reduced ascension to the oviduct, and milder induction of inflammatory cell infiltration in the oviduct tissue. Thus, our results point to an important amino acid residue involved in Pgp3 virulence, providing a potential therapeutic target for chlamydial infection.

Urolithin A Alleviates Colitis in Mice by Improving Gut Microbiota Dysbiosis, Modulating Microbial Tryptophan Metabolism, and Triggering AhR Activation.

Urolithin A (UroA) is a microbial metabolite derived from ellagitannins and ellagic acid with good bioavailability. In this study, we explored the anticolitis activity of UroA and clarified the mechanism by 16S rDNA sequencing and metabonomics. UroA alleviated dextran sulfate sodium (DSS)-induced colitis in mice, characterized by a decreased disease activity index, increased colon length, and improved colonic histopathological lesions, along with inhibited phosphorylation of the mitogen-activated protein kinase signaling pathway. In addition, UroA improved gut microbiota dysbiosis and modulated the microbiota metabolome. Furthermore, targeted metabolomics focused on tryptophan catabolites showed that UroA significantly increased the production of indole-3-aldehyde (IAld) and subsequently led to increased colonic expression of aryl hydrocarbon receptor (AhR) and promoted the serum content of IL-22 in mice with colitis. Collectively, our data identified a novel anticolitis mechanism of UroA by improving gut microbiota dysbiosis, modulating microbial tryptophan metabolism, promoting IAld production, and triggering AhR/IL-22 axis activation. However, a limitation noted in this study is that these beneficial effects of UroA were found at 50 µM in vitro and 20 mg/kg in vivo, which were nonphysiological concentrations.

Spatial effects of air pollutants reduction on CO2 emissions.

The sources of air pollutants and CO2 are basically the same, hence the reduction of air pollutants will affect CO2 emissions. Considering the regional integration of economic development as well as air pollution control, it is necessary to analyze the impact of air pollutants reduction in a region on CO2 emissions in its surrounding regions. Furthermore, as different stages of air pollutants reduction have different effects on CO2 emissions, it is also important to study the heterogeneity of this impact. In this article, we took China as the research case and built a spatial panel model based on the data of 240 cities above the prefecture level from 2005 to 2016 to study the impact of two different stages of air pollutants reduction-front reduction of air pollutants (FRAP) and end-of-pipe treatment of air pollutants (EPAP) on CO2 emissions-and their spatial spillover effects. On this basis, we further modified traditional spatial weight matrix and constructed the matrices of cities in the same and different provinces to discuss the influence of provincial administrative boundaries on the spillover effect between cities. The results show that FRAP affects CO2 emissions mainly through the local synergistic effect, and its spatial spillover effect is not significant. The local effect of EPAP on CO2 emissions is antergic, and the spatial spillover effect is significant. The increase of a city's EPAP will increase the CO2 emissions in surrounding regions. Besides, provincial boundaries weaken the spatial spillover effects of FRAP and EPAP on CO2 emissions in prefecture-level cities. There is a significant spatial spillover effect between cities in the same province, but the spillover effect does not exist for cities in different provinces nearby.

Neutrophils extracellular traps and ferroptosis in diabetic wounds.

Wound healing is an extremely complex process involving multiple levels of cells and tissues. It is mainly completed through four stages: haemostasis, inflammation, proliferation, and remodelling. When any one of these stages is impaired, it may lead to delayed healing or even transformation into chronic refractory wounds. Diabetes is a kind of common metabolic disease that affects approximately 500 million people worldwide, 25% of whom develop skin ulcers that break down repeatedly and are difficult to heal, making it a growing public health problem. Neutrophils extracellular traps and ferroptosis are new types of programmed cell death identified in recent years and have been found to interact with diabetic wounds. In this paper, the normal wound healing and interfering factors of the diabetic refractory wound were outlined. The mechanism of two kinds of programmed cell death was also described, and the interaction mechanism between different types of programmed cell death and diabetic refractory wounds was discussed.

PYGL-mediated glucose metabolism reprogramming promotes EMT phenotype and metastasis of pancreatic cancer.

Epithelial-mesenchymal transition (EMT) is closely associated with tumor invasion and metastasis. However, key regulators of EMT in pancreatic ductal adenocarcinoma (PDAC) need to be further studied. Bioinformatics analyses of pancreatic cancer public datasets showed that glycogen phosphorylase L (PYGL) expression is elevated in quasimesenchymal PDAC (QM-PDAC) and positively associated with EMT. In vitro cellular experiments further confirm PYGL as a crucial EMT regulator in PDAC cells. Functionally, PYGL overexpression promotes cell migration and invasion in vitro and facilitates liver metastasis in vivo, while PYGL knockdown has opposite effects. Mechanically, hypoxia induces PYGL expression in a hypoxia inducible factor 1α (HIF1α)-dependent manner and promotes glycogen accumulation. Elevated PYGL mobilizes accumulated glycogen to fuel glycolysis via its activity as a glycogen phosphorylase, thus inducing the EMT process, which could be suppressed by the glycolysis inhibitor 2-deoxy-D-glucose (2-DG). Clinically, PYGL expression is upregulated in PDAC and correlates with its malignant features and poor prognosis. Collectively, the data from our study reveal that the hypoxia/PYGL/glycolysis-induced EMT promotes PDAC metastasis, which establishes the rational for targeting hypoxia/PYGL/glycolysis/EMT signaling pathway against PDAC.

How can Chinese metropolises drive global carbon emissions? Based on a nested multi-regional input-output model for China.

Given metropolises' participation in complex regional and global trade networks, they have huge demands for vast carbon-embodied intermediate and final goods. To clarify embodied carbon transfers of metropolises in regional and international trade, a metropolis-centered model was constructed by nesting the World's multi-regional input-output table and China's multi-regional input-output (CMRIO) table. Based on this model, we analyzed the multi-scale impact of two typical Chinese metropolises, namely Beijing and Shanghai, on global carbon emissions. Structural decomposition analysis and social network analysis (SNA) were used to explore the driving factors of consumption-based carbon (CBC) and the roles of metropolises in the carbon networks. Results showed that both Beijing and Shanghai are net embodied carbon consumers, which respectively drove 231.19 and 219.52 Mt global carbon emissions in 2017. These figures were underestimated by 12.54 % and 15.41 % when using the CMRIO. After China's economy entered a new normal, instead of technological progress, structural adjustment became the prominent factor driving the CBC reduction of metropolises. During 2012-2017, the consumption structure optimization reduced 18.87 and 32.48 Mt CBC in Beijing and Shanghai, respectively. Compared with other domestic regions, the CBC of Beijing has continued to increase, whereas that of Shanghai has declined. At the international scale, the combined net carbon emission imported by the two metropolises was 88.43 Mt in 2017, equivalent to 18.09 % of China's total carbon deficit. This indicates that metropolises have become pioneering regions for China to alleviate the carbon deficit in international trade. By using SNA, we further found that both metropolises are crucial carbon consumers in the global carbon network, with strong stability and obvious hub roles. Furthermore, various urban functions and geographical locations form the heterogeneous structural characteristics of CBC in the two metropolises, highlighting the need for different strategies for embodied carbon mitigation in these metropolises.

DHA inhibits invasion and metastasis in NSCLC cells by interfering with CCL18/STAT3 signaling pathway.

Omega-3 has been proposed as an antitumor substance that suppresses the growth and metastasis of multiple types of tumor cells, including lung cancer, but the specific mechanisms involved remain obscure. Our previous studies showed that the expression of chemokine ligand 18 was related to the migration and metastasis of non-small cell lung cancer. Here, we aim to explore whether omega-3 inhibits invasion and metastasis of NSCLC by regulating the expression of CCL18. The expression of CCL18, metastasis- and epithelial-mesenchymal transition (EMT)-related genes at mRNA and protein levels in NSCLC cell lines were detected by RT-qPCR and Western blot, respectively. The metastatic and invasive capability of NSCLC cells were evaluated by scratch wound healing and Transwell assays, respectively. Our results showed that the level of CCL18 is positively associated with metastatic ability of NSCLC cells. Docosahexaenoic acid, an important long-chain, polyunsaturated omega-3 (n-3) fatty acid, significantly inhibited invasion and metastasis of NSCLC cells, and concomitantly downregulated the expression of metastasis- and EMT-related genes and p-STAT3 signaling pathway. Additionally, we found that DHA inhibited CCL18 expression in lung cancer cells, while overexpression of CCL18 effectively reversed DHA-mediated downregulation in the expression of metastasis- and EMT-related genes and p-STAT3 signaling as well as DHA-mediated inhibitory effect on metastasis and invasion of NSCLC cells. DHA inhibits NSCLC cell invasion and metastasis possibly through targeted inhibition of CCL18/ STAT3 signaling pathway and EMT process.

Enhancing the effect of biochar ageing on reducing cadmium accumulation in Medicago sativa L.

Biochar (BC) application to farmland soil can reduce the mobility and bioavailability of Cd. Nevertheless, BC is prone to natural ageing in soil, which alters its structure, physicochemical properties, thereby affecting the immobilisation of Cd. We used dry-wet and freeze-thaw cycles to mimic the natural ageing of BC, and used adsorption experiments to explore the changes of Cd adsorption capacity of BC and aged BC (ABC). We conducted a pot experiment to investigate the effects of BC and ABC on soil biotic and abiotic factors, alfalfa growth, and Cd accumulation in agricultural soils with high and low Cd concentrations. The increase of specific surface area, pore size, oxygen containing functional groups and mineral composition leads to better adsorption capacity of ABC. The adsorption of Cd(II) by BC and ABC is mainly by monolayer adsorption and chemical adsorption. Applying BC and ABC to Cd-contaminated soil significantly increased the aboveground biomass and decreased the Cd accumulation by reducing the Cd bioconcentration factor in alfalfa. At high Cd levels, adding BC and ABC reduced the Cd content in alfalfa shoots by 32.8 % and 35.1 %, respectively; the fixing effect of ABC was better than that of BC. Adding BC and ABC significantly increased the microbial biomass and geometric mean of enzymes. BC addition increased soil pH by 0.32-0.36 units and cation exchange capacity (CEC) by 15.5 %. Adding BC and ABC significantly increased soil organic matter (SOM) by 5.7 % and 6.2 %, respectively. Random forest analysis showed that SOM, total organic carbon, and fluorescein diacetate hydrolase were important variables for Cd content in alfalfa shoots. Structural equation modelling showed that BC indirectly affected the Cd content in alfalfa shoots by affecting soil pH, CEC, SOM, microbial biomass, and microbial metabolic activity. BC has a long-term effect on alleviating Cd pollution in farmland.

IER3IP1 is critical for maintaining glucose homeostasis through regulating the endoplasmic reticulum function and survival of ß cells.

Recessive mutations in IER3IP1 (immediate early response 3 interacting protein 1) cause a syndrome of microcephaly, epilepsy, and permanent neonatal diabetes (MEDS). IER3IP1 encodes an endoplasmic reticulum (ER) membrane protein, which is crucial for brain development; however, the role of IER3IP1 in ß cells remains unknown. We have generated two mouse models with either constitutive or inducible IER3IP1 deletion in ß cells, named IER3IP1-ßKO and IER3IP1-ißKO, respectively. We found that IER3IP1-ßKO causes severe early-onset, insulin-deficient diabetes. Functional studies revealed a markedly dilated ß-cell ER along with increased proinsulin misfolding and elevated expression of the ER chaperones, including PDI, ERO1, BiP, and P58IPK. Islet transcriptome analysis confirmed by qRT-PCR revealed decreased expression of genes associated with ß-cell maturation, cell cycle, and antiapoptotic genes, accompanied by increased expression of antiproliferation genes. Indeed, multiple independent approaches further demonstrated that IER3IP1-ßKO impaired ß-cell maturation and proliferation, along with increased condensation of ß-cell nuclear chromatin. Inducible ß-cell IER3IP1 deletion in adult (8-wk-old) mice induced a similar diabetic phenotype, suggesting that IER3IP1 is also critical for function and survival even after ß-cell early development. Importantly, IER3IP1 was decreased in ß cells of patients with type 2 diabetes (T2D), suggesting an association of IER3IP1 deficiency with ß-cell dysfunction in the more-common form of diabetes. These data not only uncover a critical role of IER3IP1 in ß cells but also provide insight into molecular basis of diabetes caused by IER3IP1 mutations.

Altering Brain Amyloidosis by Intra-Lingual and Extra-Nasal Exposure of Aß Aggregates.

Extensive experimental and human-derived evidence suggest that misfolded Aß particles spread similarly to infectious prions. Moreover, peripheral administration of Aß seeds accelerates brain amyloidosis in both susceptible experimental animals and humans. The mechanisms and elements governing the transport of misfolded Aß from the periphery to the brain are not fully understood, although circulation and retrograde axonal transport have been proposed. Here, we demonstrate that injection of Aß seeds in the tongue, a highly innervated organ, substantially accelerates the appearance of plaques in Tg2576 mice. In addition, the extra-nasal exposure of Aß aggregates increased amyloid pathology in the olfactory bulb. Our results show that exposing highly innervated tissues to Aß seeds accelerates AD-like pathological features, and suggest that Aß seeds can be transported from peripheral compartments to the brain by retrograde axonal transport. Research in this direction may be relevant on different fronts, including disease mechanisms, diagnosis, and risk-evaluation of potential iatrogenic transmission of Aß misfolding.

Prognostic value of receptor tyrosine kinases in malignant melanoma patients: A systematic review and meta-analysis of immunohistochemistry.

Background: Substantial evidence suggests that receptor tyrosine kinases (RTKs) are overexpressed in tumors; however, few studies have focused on the prognostic value of RTKs in melanoma. Objectives: The objective of this study is to evaluate the association between overexpression of RTKs and survival in melanoma patients based on immunohistochemistry (IHC) analysis. Methods: Our review is registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42021261460. Seven databases were searched, and data were extracted. We used IHC to measure the association between overexpression of RTKs and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and clinicopathology in melanoma patients. Pooled analysis was conducted to assess the differences between Hazard Ratios along with 95% confidence intervals. Results: Of 5,508 publications examined following the database search, 23 publications were included in this study, which included data from a total of 2,072 patients. Vascular endothelial growth factor receptor 2 (VEGF-R2) overexpression was associated with worse OS and DFS in melanoma. Furthermore, there was an association between OS and the expression of several RTKs, including epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition factor (MET), vascular endothelial growth factor receptor 1 (VEGF-R1), and insulin-like growth factor 1 receptor (IGF-1R). There were no significant correlations between EGFR overexpression and worse DFS or PFS. EGFR overexpression was associated with worse OS cutaneous and nasal melanoma, but not uveal melanoma. However, MET overexpression was related to worse OS in both cutaneous and uveal melanoma. Furthermore, EGFR overexpression was associated with a worse OS in Europe compared to other geographic areas. Moreover, EGFR and MET overexpression showed significant prognostic value in patients with the cut-off "≥10% staining". Conclusions: Our findings build concrete evidence that overexpression of RTKs is associated with poor prognosis and clinicopathology in melanoma, highlighting RTK expression has the potential to inform individualized combination therapies and accurate prognostic evaluation.

Higher than predicted resting energy expenditure and lower physical activity in healthy underweight Chinese adults.

Contrary to popular opinion that lean individuals "eat what they want" and exercise more, Hu et al. study a cohort of healthy underweight volunteers and reveal them to have reduced physical activity relative to normal BMI controls and lower food intake. This cohort is also shown to have higher than expected resting energy expenditure, which is associated with elevations in thyroid hormones.