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Perchlorate, nitrate, and thiocyanate are common thyroid disruptors, but it is not clear whether they are related to depression. In this study, we aimed to investigate the association between perchlorate, nitrate, and thiocyanate and depression, and to explore the potential role of sleep in this process. We used data from the National Health and Nutrition Examination Survey (NHANES). From 2005 to 2016, 6 cycles cross-sectional data were combined. Urinary perchlorate, nitrate, and thiocyanate came from laboratory test; depression was diagnosed by the Nine-item Patient Health Questionnaire (PHQ-9). Weighted generalized liner models, restricted cubic splines, and mediation analysis were used in this study. Totally, 16,715 participants were involved in this study, of which 8295 (49.63%) were male and 8420 (50.37%) were female, with an average age of 46.19 ± 0.32 years. We found that urinary thiocyanate concentration was positively associated with depression (Odds ratios [ORs]: 1.49; 95% confidence intervals [95% CIs]: 1.16, 1.91), but not perchlorate (ORs: 0.71; 95% CIs: 0.52, 0.97) or nitrate (ORs: 0.89, 95% CIs: 0.66, 1.19). Sleep may play a potential mediating role between thiocyanate and depression (9.55%). In conclusion, higher concentrations of thiocyanate exposure may be associated with a higher risk of depression, and the sleep duration may be an important mediating factor.

Obesity is a major risk factor for cancers including hepatocellular carcinoma (HCC) that develops from a background of non-alcoholic fatty liver disease (NAFLD). Hypercholesterolemia is a common comorbidity of obesity. Although cholesterol biosynthesis mainly occurs in the liver, its role in HCC development of obese people remains obscure. Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models, we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T (NKT) cell-mediated antitumor immunosurveillance. Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients. Notably, cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development. Moreover, suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin (mTOR) inhibitor vistusertib preceded tumor regression, which was abolished by NKT inactivation but not CD8(+) T cell depletion. Mechanistically, sterol regulatory element-binding protein 2 (SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells, which were supported by findings in people with obesity, NAFLD and NAFLD-HCC. This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment, providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic.

Previous observational studies reported associations between non-steroidal anti-inflammatory drugs (NSAIDs) and major depressive disorder (MDD), however, these associations are often inconsistent and underlying biological mechanisms are still poorly understood. We conducted a two-sample Mendelian randomisation (MR) study to examine relationships between genetic variants and NSAID target gene expression or DNA methylation (DNAm) using publicly available expression, methylation quantitative trait loci (eQTL or mQTL) data and genetic variant-disease associations from genome-wide association studies (GWAS of MDD). We also assessed drug exposure using gene expression and DNAm levels of NSAID targets as proxies. Genetic variants were robustly adjusted for multiple comparisons related to gene expression, DNAm was used as MR instrumental variables and GWAS statistics of MDD as the outcome. A 1-standard deviation (SD) lower expression of NEU1 in blood was related to lower C-reactive protein (CRP) levels of −0.215 mg/L (95% confidence interval (CI): 0.128–0.426) and a decreased risk of MDD (odds ratio [OR] = 0.806; 95% CI: 0.735–0.885; p = 5.36 × 10−6). A concordant direction of association was also observed for NEU1 DNAm levels in blood and a risk of MDD (OR = 0.886; 95% CI: 0.836–0.939; p = 4.71 × 10−5). Further, the genetic variants associated with MDD were mediated by NEU1 expression via DNAm (β = −0.519; 95% CI: −0.717 to −0.320256; p = 3.16 × 10−7). We did not observe causal relationships between inflammatory genetic marker estimations and MDD risk. Yet, we identified a concordant association of NEU1 messenger RNA and an adverse direction of association of higher NEU1 DNAm with MDD risk. These results warrant increased pharmacovigilance and further in vivo or in vitro studies to investigate NEU1 inhibitors or supplements for MDD.

The study assessed the feasibility of merging data acquired from hyperspectral imaging (HSI) and electronic nose (e-nose) to develop a robust method for the rapid prediction of intramuscular fat (IMF) and peroxide value (PV) of pork meat affected by temperature and NaCl treatments. Multivariate calibration models for prediction of IMF and PV using median spectra features (MSF) and image texture features (ITF) from HSI data and mean signal values (MSV) from e-nose signals were established based on support vector machine regression (SVMR). Optimum wavelengths highly related to IMF and PV were selected from the MSF and ITF. Next, recurring optimum wavelengths from the two feature groups were manually obtained and merged to constitute “combined attribute features” (CAF) which yielded acceptable results with (Rc2 = 0.877, 0.891; RMSEC = 2.410, 1.109; Rp2 = 0.790, 0.858; RMSEP = 3.611, 2.013) respectively for IMF and PV. MSV yielded relatively low results with (Rc2 = 0.783, 0.877; RMSEC = 4.591, 0.653; Rp2 = 0.704, 0.797; RMSEP = 3.991, 0.760) respectively for IMF and PV. Finally, data fusion of CAF and MSV was performed which yielded relatively improved prediction results with (Rc2 = 0.936, 0.955; RMSEC = 1.209, 0.997; Rp2 = 0.895, 0.901; RMSEP = 2.099, 1.008) respectively for IMF and PV. The results obtained demonstrate that it is feasible to mutually integrate spectral and image features with volatile information to quantitatively monitor IMF and PV in processed pork meat.

Nature of exosome-secreting cells determines exosome content and function. ALIX, involved in exosome biogenesis, promotes cell degeneration. Here, ALIX was knocked out (iPSC-ALIX-/-) and overexpressed (iPSC-ALIX3+) in induced pluripotent stem cells (iPSCs) using CRISPR-Cas9 and lentiviral transduction, respectively, and the secreted exosomes were analyzed. Exosomes from iPSC-ALIX-/- (exosome-KO), iPSC-ALIX3+ (exosome-over), and their corresponding controls contained 176, 529, 431, and 351 proteins, respectively. Exosome-over showed increased protein levels, while exosome-KO contained fewer protein types without differing in total protein content. ALIX knockout did not affect exosome uptake by endothelial cells. Exosome-over more effectively promoted cell viability than exosome-GFP, in a dose-dependent manner. All exosomes were protective for endothelial cells injured by hydrogen peroxide or cisplatin, as demonstrated by promotion of cell viability, horizontal migration, angiogenic sprouting from aortic rings, and formation of capillary-like structures, inhibition of apoptosis, and maintenance of permeability of endothelial monolayer, although exosome-over and exosome-KO had stronger and weaker effects, respectively. SNX2 was important for ALIX-mediated exosomal function. Beneficial functions of the exosomes were independent of experimental models, targeted cell types, causes of injury, exosome-producing iPSC passages, clones of ALIX knockout, and transfection batches of ALIX overexpression. Thus, we present a novel strategy to manipulate iPSCs for production of exosomes with beneficial ALIX-regulated protein composition for varied exosome functions. KEY MESSAGES: ALIX knockout and overexpression regulate protein profile in iPSC-derived exosome. ALIX knockout decreases therapeutic function of iPSC-derived exosomes. ALIX overexpression increases therapeutic function of iPSC-derived exosomes. Manipulating iPSCs can produce exosomes with more beneficial protein content.

Background Stem cells, including induced pluripotent stem cells (iPSCs), have tremendous potential in health care, though with several significant limitations. Each of the limitations, including immunogenicity, may block most of the therapeutic potentials. Beta2 microglobulin (B2M) and MHC II transactivator (CIITA) are critical for MHC I and II, respectively. MHCs are responsible for immunogenic recognition. Methods B2M and CIITA were knocked out from human iPSCs, either separately or simultaneously. The effects of single or dual knockout of B2M and CIITA on iPSC properties were evaluated in a xenogeneic model of human-to-monkey transplantation. Results B2M or CIITA knockout in human induced pluripotent stem cells (iPSCs) diminishes the expression of MHC I or II alleles, respectively, without changing iPSC pluripotency. Dual knockout was better than either single knockout in preserving the ability of human iPSCs to reduce infiltration of T and B lymphocytes, survive, and promote wound healing in monkey wound lesions. The knockouts did not affect the xenogeneic iPSC-induced infiltration of macrophages and natural killer cells. They, however, decreased the iPSC-promoted proliferation of allogeneic peripheral blood mononuclear cells and T lymphocytes in vitro, although not so for B lymphocytes isolated from healthy human donors. Although the dual knockout cells survived long enough for suiting therapeutic needs, the cells eventually died, possibly due to innate immune response against them, thereby eliminating long-term risks. Conclusions Having these iPSCs with diminished immunogenicity-recognizable to allogeneic recipient may provide unlimited reproducible, universal, standardized “ready-to-use” iPSCs and relevant derivatives for clinical applications.

There is a benefit in characterizing radiation-induced cancer risk in pediatric chest and abdominopelvic CT: a singular metric that represents the whole-body radiation burden while also accounting for age, gender and organ sensitivity. To compute an index of radiation risk for pediatric chest and abdominopelvic CT. Using a protocol approved by our institutional review board, 42 pediatric patients (age: 0-16 years, weight: 2-80 kg) were modeled into virtual whole-body anatomical models. Organ doses were estimated for clinical chest and abdominopelvic CT examinations of the patients using validated Monte Carlo simulations of two major scanner models. Using age-, size- and gender-specific organ risk coefficients, the values were converted to normalized effective dose (by dose length product) (denoted as the k factor) and a normalized risk index (denoted as the q factor). An analysis was performed to determine how these factors are correlated with patient age and size for both males and females to provide a strategy to better characterize individualized risk. The k factor was found to be exponentially correlated with the average patient diameter. For both genders, the q factor also exhibited an exponential relationship with both the average patient diameter and with patient age. For both factors, the differences between the scanner models were less than 8%. The study defines a whole-body radiation risk index for chest and abdominopelvic CT imaging, that incorporates individual estimated organ dose values, organ radiation sensitivity, patient size, exposure age and patient gender. This indexing metrology enables the assessment and potential improvement of chest and abdominopelvic CT performance through surveillance of practice dose profiles across patients and may afford improved informed communication.

1 keV argon ion beam was employed to remove the oxide film of pure aluminum before diffusion bonding. A sound joint of pure aluminum was obtained by ion activation-assisted diffusion bonding at the low temperature of $350~{}^{\circ}\mathrm{C}$ , while the high-quality joining of pure aluminum was infeasible by conventional diffusion bonding at the temperature lower than $500~{}^{\circ}\mathrm{C}$ . The residual oxide film ratios of joints decreased with the increase of ion cleaning time. When the specimens were cleaned for 120 min, the joint with the maximum tensile strength of 62.3 MPa and the elongation of 14.1 % was obtained. The argon ion beam etching surface treatment provides a new route for the low-temperature diffusion bonding. The reliable diffusion bonded joint of pure aluminum indicates that low-temperature diffusion bonding is feasible for bulk materials, especially for materials with the outstanding plasticity.

Unlike most malignancies, chemotherapy but not surgery plays the most important role in treating non-Hodgkin lymphoma (NHL). Currently, liposomes have been widely used to encapsulate chemotherapeutic drugs in treating solid tumors. However, higher in vivo stability owns a much more important position for excellent antitumor efficacy in treating hematological malignancies. In this study, we finely fabricated a rituximab Fab fragment-decorated liposome based on 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC), which can form intermolecular cross-linking through the diacetylenic group by ultra-violet (UV) irradiation. Our experimental results demonstrated that after the UV irradiation, the liposomes exhibit better serum stability and slower drug release with a decreased mean diameter of approximately 285 nm. The cellular uptake of adriamycin (ADR) by this Fab-navigated liposome was about four times of free drugs. Cytotoxicity assays against CD20+ lymphoma cells showed that the half maximal (50%) inhibitory concentration (IC50) of ADR-loaded immunoliposome was only one fourth of free ADR at the same condition. In vivo studies were evaluated in lymphoma-bearing SCID mice. With the high serum stability, finely regulated structure, active targeting strategy via antigen-antibody reaction and passive targeting strategy via enhanced permeability and retention (EPR) effect, our liposome exhibits durable and potent antitumor activities both in the disseminated and localized human NHL xeno-transplant models.