Environmental Factors Associated with Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

BACKGROUND & AIMS: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers. METHODS: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR); gut inflammation via fecal calprotectin (FCP) levels; and fecal microbiome composition through 16S rRNA sequencing. RESULTS: Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5 and 15 (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40-0.96; P = .034), and living with a large family size in the first year of life (HR, 0.43; 95% CI, 0.21-0.85; P = .016) were associated with decreased CD risk, whereas having a bird at the time of recruitment (HR, 2.78; 95% CI, 1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity, whereas bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR. CONCLUSION: This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis.

Associations between long-term night shift work and incidence of chronic obstructive pulmonary disease: a prospective cohort study of 277,059 UK Biobank participants.

BACKGROUND: Little is known about the effects of night shifts and their interactions with genetic factors on chronic obstructive pulmonary disease (COPD). In this study, we aim to investigate relationships between long-term night shift work exposure and COPD risk, and assess modification effects of genetic predisposition. METHODS: A total of 277,059 subjects who were in paid employment or self-employed were included in the UK Biobank. Information on current and lifetime employment was obtained, and a weighted COPD-specific genetic risk score (GRS) was constructed. We used Cox proportional hazard models to investigate associations between night shift work and COPD risk, and their interaction with COPD-specific GRS. RESULTS: The cohort study included 277,059 participants (133,063 men [48.03%]; mean [SD] age, 52.71 [7.08] years). During a median follow-up of 12.87 years, we documented 6558 incidents of COPD. From day work, irregular night shifts to regular night shifts, there was an increased trend in COPD incidence (P for trend < 0.001). Compared with day workers, the hazard ratio (HR) and 95% confidence interval (CI) of COPD was 1.28 (1.20, 1.37) for subjects with rarely/sometimes night shifts and 1.49 (1.35, 1.66) for those with permanent night shifts. Besides, the longer durations (especially in subjects with night shifts ≥ 10 years) and increasing monthly frequency of night shifts (in workers with > 8 nights/month) were associated with a higher COPD risk. Additionally, there was an additive interaction between night shifts and genetic susceptibility on the COPD risk. Subjects with permanent night shifts and high genetic risk had the highest risk of COPD (HR: 1.90 [95% CI: 1.63, 2.22]), with day workers with low genetic risk as a reference. CONCLUSIONS: Long-term night shift exposure is associated with a higher risk of COPD. Our findings suggest that decreasing the frequency and duration of night shifts may offer a promising approach to mitigating respiratory disease incidence in night shift workers, particularly in light of individual susceptibility.

Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis.

OBJECTIVE: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort. DESIGN: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284). Using samples at recruitment, serum protein profiles using the Olink Proximity Extension Assay platform was assessed for association with future development of CD and with other baseline biomarkers as follows: serum antimicrobial antibodies (AS: positive antibody sum) (Prometheus); faecal calprotectin (FCP); gut barrier function using the fractional excretion of lactulose-to-mannitol ratio (LMR) assay. RESULTS: We identified 25 of 446 serum proteins significantly associated with future development of CD. C-X-C motif chemokine 9 (CXCL9) had the highest OR with future risk of CD (OR=2.07 per SD, 95% CI 1.58 to 2.73, q=7.9e-5), whereas matrix extracellular phosphoglycoprotein had the lowest OR (OR 0.44, 95% CI 0.29 to 0.66, q=0.02). Notably, CXCL9 was the only analyte significantly associated with all other CD-risk biomarkers with consistent direction of effect (FCP: OR=2.21; LMR: OR=1.67; AS: OR=1.59) (q<0.05 for all). CONCLUSION: We identified serum proteomic signatures associated with future CD development, reflecting potential early biological processes of immune and barrier dysfunction.

Altered Gut Microbiome Composition and Function Are Associated With Gut Barrier Dysfunction in Healthy Relatives of Patients With Crohn's Disease.

BACKGROUND & AIMS: The gut microbiome has been suggested to play a role in gut barrier hemostasis, but data are scarce and limited to animal studies. We therefore aimed to assess whether alterations in gut microbial composition and functional pathways are associated with gut barrier function in a cohort of healthy first-degree relatives of patients with Crohn's disease. METHODS: We used the Crohn's and Colitis Canada Genetic Environmental Microbial (CCC-GEM) cohort of healthy first-degree relatives of patients with Crohn's disease. Gut barrier function was assessed using the urinary fractional excretion of lactulose-to-mannitol ratio (LMR). Microbiome composition was assessed by sequencing fecal 16S ribosomal RNA. The cohort was divided into a discovery cohort (n = 2472) and a validation cohort (n = 655). A regression model was used to assess microbial associations with the LMR. A random forest classifier algorithm was performed to assess microbial community contribution to barrier function. RESULTS: Individuals with impaired barrier function (LMR >0.025) had reduced alpha-diversity (Chao1 index, P = 4.0e-4) and altered beta-diversity (Bray-Curtis dissimilarity index, R2 = 0.001, P = 1.0e-3) compared with individuals with an LMR ≤0.025. When taxa were assessed individually, we identified 8 genera and 52 microbial pathways associated with an LMR >0.025 (q < 0.05). Four genera (decreased prevalence of Adlercreutzia, Clostridia UCG 014, and Clostridium sensu stricto 1 and increased abundance of Colidextribacter) and 8 pathways (including decreased biosynthesis of glutamate, tryptophan, and threonine) were replicated in the validation cohort. The random forest approach revealed that the bacterial community is associated with gut barrier function (area under the curve, 0.63; P = 1.4e-6). CONCLUSIONS: The gut microbiome community and pathways are associated with changes in gut barrier function. These findings may identify potential microbial targets to modulate gut barrier.

An observational study of the effects of smoking cessation earlier on the clinical characteristics and course of acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Previous studies have focused on the negative effects of continued smoking on chronic obstructive pulmonary disease (COPD). However, few studies have investigated the positive effects of long-term smoking cessation on patients suffering from acute exacerbations of COPD. METHODS: The study recruited and followed current or former smokers who had been hospitalized and diagnosed with AECOPD. An in-depth analysis of clinical and laboratory indicators was conducted. RESULTS: 125 patients were covered, including 72 short-term quitters and 53 long-term quitters. The results showed that long-term smoking cessation may result in milder dyspnea and cough, a higher oxygenation index, a lower arterial partial pressure of carbon dioxide, and milder pulmonary hypertension, airflow restriction, and gas retention in patients with AECOPD. However, despite the lower treatment intensity for long-term quitters, improvement in dyspnea and an increase in oxygenation index were comparable to those achieved by short-term quitters. Furthermore, patients with mild phlegm, which accounted for 84% of all subjects, showed greater improvement in phlegm in AECOPD patients with long-term cessation of smoking. CONCLUSION: It was found that in patients with AECOPD who quit smoking for a long period of time, there was a reduction in symptoms, improvement in lung function, reduction in treatment intensity, and better improvement in phlegm symptoms after therapy. It is beneficial and necessary to quit smoking early, even if you smoke a small amount of cigarettes.

Influence of age, stigma and social support on male temporary ejaculation failure on IVF oocyte retrieval day.

OBJECTIVE: To explore the social and psychological factors associated with male Temporary Ejaculation Failure (TEF) during In Vitro Fertilization (IVF), with the goal of providing a theoretical basis for clinical intervention and treatment. METHODS: The study included 75 TEF patients and 223 non-TEF patients undergoing IVF treatment at the center of reproduction and genetics of Integrated Chinese and Western medicine in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2019 to May 2020. A questionnaire survey was then administered to the study subjects. The questionnaires included general information, Perceived Stress Scale (PSS), Stigma Questionnaire, Perceived Social Support Scale (PSSS), and Positive Psychological Capital Questionnaire (PPQ). Logistic regression analysis was then used to analyze the social psychological factors associated with the research objectives. RESULTS: Comparison of social demographic factors and clinical data between TEF group and non-TEF group: there were significant differences in the age and educational level between the two groups (P< 0.05), and the average age of the TEF group (37.01±7.11) was significantly higher than that of the non-TEF group (34.89±6.24). In addition, patients with high school or technical secondary school education levels had the lowest probability of TEF(X2=7.662, P=0.022). 2. The difference of related social and psychological factors between the two groups: the scores of perceived stress (17.57±6.51) and stigma (4.52±3.87) in the TEF group were significantly higher than those in the non-TEF group, which were (15.50±5.00, P< 0.05) and (2.61±3.52, P< 0.05), respectively. On the other hand, the scores of social support (55.31±14.04) and psychological capital (121.73±25.93) in the TEF group were significantly lower than those in the non-TEF group, which were (60.74±10.93, P< 0.05) and (130.31±17.32, P< 0.05), respectively. Results Obtained after conducting univariate logistic regression analysis indicated that age (OR=1.051, P=0.016), perceived stress (OR=1.073, P=0.005), stigma (OR=1.139, P< 0.001), family support (OR=0.901, P< 0.001), friend support (OR=0.932, P=0.023), other support (OR=0.915, P=0.004), self-efficacy (OR=0.947, P=0.009), resilience (OR=0.947, P=0.013), hope (OR=0.930, P=0.002), and optimism (OR=0.953, P=0.032) can all significantly affect male TEF.4. Moreover, the multivariate logistic regression analysis results indicated that age (OR=1.071, P=0.002) and stigma (OR=1.132, P=0.003) can positively predict TEF, while family support (OR=0.877, P=0.012) can negatively predict TEF. CONCLUSIONS: The results obtained in this study have indicated that age and stigma are independent risk factors for male TEF, while family support is a protective factor of TEF. Analyzing the treatment of TEF from a socio-psychological perspective provides a new intervention target for effectively reducing its incidence, thereby helping to improve the success rate of IVF.

[Socio-psychological factors related to temporary ejaculation failure in male patients undergoing IVF: Results of logistic regression analyses].

OBJECTIVE: To explore the socio-psychological factors associated with male temporary ejaculation failure (TEF) during in vitro fertilization (IVF) and provide some theoretical evidence for the clinical intervention and treatment of the condition. METHODS: We conducted a questionnaire investigation among 298 males undergoing IVF, 75 with and 223 without TEF. The questionnaires covered general information, Perceived Stress Scale (PSS), Stigma Questionnaire, Perceived Social Support Scale (PSSS), and Positive Psychological Capital Questionnaire (PPQ). We subjected the relevant social psychological factors found in the investigation to logistic regression analysis and compared them between the patients in the TEF and non-TEF groups. RESULTS: Statistically significant differences were found between the two groups in age, education level, perceived stress, stigma, social support and psychological capital (P < 0.05). Univariate logistic regression analysis indicated that age, perceived stress, stigma, family support, friend support, other supports, self-efficacy, resilience, hope and optimism in psychological capital significantly affected the incidence of TEF. Multivariate logistic regression analysis showed age (OR = 1.071, 95% CI: 1.025－1.119) and stigma (OR = 1.132, 95% CI: 1.044－1.227) to be independent risk factors for TEF, capable of positively predicting the condition, and family support (OR = 0.877, 95% CI: 0.791－0.971) to be an independent protective factor against TEF, capable of negatively predicting the disorder. CONCLUSIONS: Age, stigma and family support are associated with the incidence of TEF during IVF. The social psychology-related influencing factors may help provide a new intervention target for effectively reducing the incidence of TEF and improving the success rate of IVF.

Effects of selenium combined with zinc amendment on zinc fractions and bioavailability in calcareous soil.

Selenium (Se) and zinc (Zn) are two important trace elements for human being and animals. The interaction between Se and Zn on the bioavailability of Zn in soil is still unclear. Therefore, pot experiments exposed to different dosages of zinc sulfate (ZnSO4) (0, 20, and 50 mg/kg soil) and sodium selenite (Na2SeO3) (0, 0.5, 1.0, and 2.5 mg/kg soil) were conducted to investigate the effects of selenite application on Zn bioavailability in calcareous soil and its related mechanisms. The total Zn content of different tissues (roots and shoots) of pak choi (Brassica chinensis L.) and the changes in Zn fraction distribution in soil before planting and after harvest were determined, and the mobility factor (MF) and distribution index (DI) of Zn in soils were calculated. In addition, the Pearson correlation and path analysis were conducted to clarify the relationships between Zn fractions in soil and the Zn uptake of pak choi. Results showed that Se amendment elevated soil Zn bioavailability at appropriate levels of Se and Zn. When 1.0 and 2.5 mg/kg of Se and 20 mg/kg of Zn were applied in soil, the proportion of exchangeable Zn (Ex-Zn) and Zn weakly bound to organic matter (Wbo-Zn) to the total content of Zn was significantly increased by 28.14%-82.52% compared with that of the corresponding single Zn treatment. Therefore, the Zn concentration in the shoots of pak choi was significantly increased by 27.2%-31.1%. High Zn (50 mg/kg) and Se co-amended treatments showed no significantly beneficial effect on the bioavailability of Zn. In addition, the potential available Zn content in soil (weakly bound to organic matter and carbonate bound Zn) and MF and DI values were all positively correlated with the Zn concentrations in pak choi, indicating that these indexes can be used to predict the bioavailability of Zn in soil. This study can provide a good reference for Se and Zn biofortification of plants in calcareous soil.

Smoking status affects clinical characteristics and disease course of acute exacerbation of chronic obstructive pulmonary disease: A prospectively observational study.

Existing studies primarily explored chronic obstructive pulmonary disease (COPD) in smokers, whereas the clinical characteristics and the disease course of passive or nonsmokers have been rarely described. In the present study, patients hospitalized and diagnosed as acute exacerbation of COPD (AECOPD) were recruited and followed up until being discharged. Clinical and laboratory indicators were ascertained and delved into. A total of 100 patients were covered, namely, 52 active smokers, 34 passive smokers, and 14 nonsmokers. As revealed from the results here, passive or nonsmokers developed less severe dyspnea (patients with modified Medical Research Council scale (mMRC) <2, 0.0% vs. 8.8% vs. 14.3%, p < 0.05, active, passive, and nonsmokers, respectively), higher oxygenation index (206.4 ± 45.5 vs. 241.2 ± 51.1 vs. 242.4 ± 41.8 mmHg, p < 0.01), as well as lower arterial partial pressure of carbon dioxide (70.8 ± 12.7 vs. 58.85 ± 9.9 vs. 56.6 ± 6.5 mmHg, p < 0.001). Despite lower treatment intensity over these patients, amelioration of dyspnea, mitigation of cough, and elevation of oxygenation index were comparable to those of active smokers. However, in terms of patients exhibiting mMRC ≥2 and type 2 respiratory failure, amelioration of dyspnea was more common in nonsmokers as compared with passive smokers (46.4% vs. 83.3%, p < 0.05, passive and nonsmokers, respectively). In terms of patients exhibiting Global Initiative for COPD severity <3, mMRC ≥2, and type 2 respiratory failure, active smokers achieved the least mitigation of cough symptom (8.7% vs. 35.0% vs. 44.4%, p < 0.05). Similar results could be achieved after the effects of confounders were excluded, with the most prominent amelioration of dyspnea (odds ratio (OR) 3.8, 95% confidence interval (CI) 1.1-13.6, p < 0.05, as compared with active smokers) and cough (OR 3.3, 95% CI 1.0-10.7, p < 0.05) in nonsmokers, and relatively better amelioration of hypoxemia in passive smokers (oxygenation index change, 39.0 ± 34.6 vs. 51.5 ± 32.4 vs. 45.3 ± 25.4 mmHg, p < 0.05). In brief, passive or nonsmokers with AECOPD were subjected to less severe disease, and nonsmokers, especially patients with more severe disease, might achieve the optimal enhancement of clinical presentation after treatment.

Leaching behaviors and chemical fraction distribution of exogenous selenium in three agricultural soils through simulated rainfall.

To clarify the leaching risk of selenium (Se) in agricultural soils, a laboratory column experiment was conducted to study the characteristics of leaching and chemical fractions of Se in three different soils treated with different levels of exogenous selenate under simulated local rainfall. Results demonstrated that the Se concentration in leachates of all tested soils decreased rapidly at the beginning of leaching and slowly decreased thereafter. After leaching, Se concentrations in leachates of all tested soils at 1, 3, and 6 mg/kg exogenous Se concentrations were 0.06-0.24, 0.25-0.84, and 0.60-1.65 mg/L, respectively, which exceeded the standard limit of the Chinese Environmental Quality Standards for Groundwater (<0.01 mg/L) (GB/T 14848-2017). The cumulative leached Se amount accounted for 51.27-86.22% of the total Se. Those results indicated the high risk of Se leaching in the tested soils. The Elovich model could better describe Se leaching processes in krasnozem, while the leaching processes of Se in black soil and loess soil accorded with the power function model. Se mainly existed in soluble fraction (61.33-81.05%) before leaching and residual fraction (48.91-68.04%) after leaching. The soluble and exchangeable Se fractions were the main contributors of Se in leachates. In addition, the parameters of the Uts and IR values could well describe the distribution of Se fractions in soil during leaching. In general, more attention should be placed on the assessment of Se leaching in soil.

Assessment of speciation and in vitro bioaccessibility of selenium in Se-enriched Pleurotus ostreatus and potential health risks.

Due to the two-dimensional effect of selenium (Se) to health, which form of Se is most effective for increasing the bioaccessible Se content in P. ostreatus and whether these products have potential health risks are worth considering. Three Se supplements were applied at different application rates into substrates for cultivating P. ostreatus. The total content and speciation of Se in P. ostreatus fruit bodies were analyzed, and the bioaccessibility of Se was determined via an in vitro physiologically based extraction test (PBET). Results showed that P. ostreatus had the highest utilization efficiency with selenite, followed by Se yeast and selenate. Organic Se (46%-90%) was the major Se speciation in P. ostreatus regardless applied Se species. Although the Se bioaccessibility of the gastrointestinal digestion of P. ostreatus was high (70%-92%), the estimated daily intake and target hazard quotient values are all within the safe ranges. Se-enriched P. ostreatus can be safely used as a dietary source of Se for increasing Se intake.

Heavy metals and associated health risk of wheat grain in a traditional cultivation area of Baoji, Shaanxi, China.

As a staple food for people worldwide, wheat is one of the major exposure pathways for heavy metals (HMs). Therefore, the safety of the wheat grain directly affects food security and human health. Long-term agricultural activities are sources of heavy metal pollution in farmland ecosystems. This study assessed the pollution situation of HMs in wheat grain from the major wheat-cultivation areas of Baoji, a typical agricultural area in Shaanxi, to assess the dietary health risks caused by consuming wheat grains and to prevent food pollution. The results showed that the mean grain concentration of Cr, Ni, Cu, Zn, Cd and Pb were 0.11, 0.09, 4.41, 26.79, 0.01 and 0.03 mg/kg, respectively. These values were all remarkably lower than the tolerance limits of the Chinese food hygiene standard (GB2762-2017). According to the metal pollution index (MPI) analysis, wheat grain consumption poses no direct threat to human health. The health risk assessment showed that there was a noncarcinogenic risk to adults and children for wheat consumed in the study area. In the study area, no carcinogenic risk was manifested. Principal component analysis (PCA) indicated that the source of Ni was different from that of the other tested HMs and was mainly from industry, where as the others were mainly derived from agricultural activities. Therefore, more attention should be paid to Cu and Zn input through agricultural activities in fields to further prevent the accumulation of these HMs in wheat grains and their related human health risks.

Identification and Validation of PKR as a Direct Target for the Novel Sulfonamide-Substituted Tetrahydroquinoline Nonselective Inhibitor of the NLRP3 Inflammasome.

The NLRP3 inflammasome is a critical component of the innate immune system. The persistent abnormal activation of the NLRP3 inflammasome is implicated in numerous human diseases. Herein, sulfonamide-substituted tetrahydroquinoline derivative S-9 was identified as the most promising NLRP3 inhibitor, without obvious cytotoxicity. In vitro, S-9 inhibited the priming and activation stages of the NLRP3 inflammasome. Incidentally, we also observed that S-9 had inhibitory effects on the NLRC4 and AIM2 inflammasomes. To elucidate the multiple anti-inflammatory activities of S-9, photoaffinity probe P-2, which contained a photoaffinity label and a functional handle, was developed for target identification by chemical proteomics. We identified PKR as a novel target of S-9 in addition to NLRP3 by target fishing. Furthermore, S-9 exhibited a significant anti-neuroinflammatory effect in vivo. In summary, our findings show that S-9 is a promising lead compound targeting both PKR and NLRP3 that could emerge as a molecular tool for treating inflammasome-related diseases.

Ratiometric fluorescence detection of the angiotensin-converting enzyme via single-excitation and double-emission biomass-derived carbon quantum dots.

Efficient and rapid detection of angiotensin-converting enzyme (ACE) activity is important for preventing hypertension and the discovery of new angiotensin-converting enzyme inhibitors (ACEI). In this work, a single-excitation and double-emission biomass-derived carbon quantum dots (CQDs) was prepared and applied for ratiometric fluorescence detection of ACE. Fresh banyan leaves were extracted with ethanol and acetone, and the extracted solution was used as the precursor to produce the carbon quantum dots (BL-CQDs) with single-excitation and double-emission properties. The synthesized BL-CQDs is about 1.7 nm, has a graphene-like structure, contains a variety of hydrophilic functional groups on the surface, and has good fluorescence properties. Its fluorescence intensity ratio (I677/I460) is linear with ACE activity in the range of 0.02-0.8 U l-1. The regression equation is△F=2.5371CACE-0.0311. The method was successfully applied to the determination of ACE activity in pig lung and human serum, and the inhibitory efficiency of the flavonoid extract and captopril tablets on ACE activity was also investigated, which can be applied to the screening of ACEI. The survival rate and fluorescence imaging of Bel-7404 cells under the condition of high concentration BL-CQDs showed BL-CQDs had low cytotoxicity and good biocompatibility. These results indicate that the BL-CQDs can be used as an excellent fluorescent probe, providing a new method for screening ACE activity and plant-derived ACEI.

Differences in selenium concentration and bioavailability between paddy and dryland soils of China: A study based on literature collection and field sampling.

Lack systematic understanding of differences in environmental behavior of selenium between paddy and dryland soils affects Se biofortification and leads to human Se-related health risks. Therefore, this study investigated differences in Se concentration and bioavailability between paddy and dryland soils using data collected from literatures and field sampling. Our analysis showed paddy soil Se concentration in Se-rich area of China was significantly lower than that in dryland soil. Selenium biological concentration factor of rice grain (BCFgrain) in Se-rich area was lower than that in non-Se-rich area attributed to higher percentage of selenite in available Se. Concentration and percentage of available Se were in dryland soil lower than those in paddy soil and this affected BCFgrain of maize, whereas BCFgrain of rice was further influenced by its Se transport capacity. The ranges of Se concentration in Se-rich paddy (0.14-3.63 mg kg-1) and dryland (0.45-1.17 mg kg-1) soils were derived using a linear regression model. The current soil Se concentration evaluation standard was only suitable for dryland but overestimated Se-deficiency and Se-toxicity levels in paddy field. The present study provides theoretical foundations for understanding Se concentrations and bioavailability in soils and selecting efficient and safe approach on cultivated land use.

Rational N,P-Codoped pH-Activatable Red Carbon Dot for In Vitro and In Vivo Tumor Imaging.

Tumor detection and imaging via tumor microenvironmental indicators can have practical value. Here, a low-pH-responsive red carbon dot (CD) was prepared via a hydrothermal reaction for specific tumor imaging in vitro and in vivo. The probe responded to the acidic tumor microenvironment. The CDs are codoped by nitrogen and phosphorene and contain anilines on the surface. These anilines are efficient electron donors and modulate the pH response: Fluorescence is undetectable at common physical pH (>7.0), but red fluorescence (600-720 nm) increases with decreasing pH. The inactivation of fluorescence is due to three aspects: photoinduced electron transfer from anilines, deprotonation-induced energy states changing, and particle aggregation-induced quenching. It is believed that this pH-responsive character of CD is better than other reported CDs. Thus, in vitro images of HeLa cells show strong fluorescence that is 4-fold higher than normal cells. Subsequently, the CDs are used for in vivo imaging of tumors in mice. Tumors can be clearly observed within 1 h, and clearance of CDs will be finished within 24 h due to the small size of the CDs. The CDs offer excellent tumor-to-normal tissue (T/N) ratios and have great potential for biomedical research and disease diagnosis.

Early-life tobacco smoke exposure, genetic susceptibility and the risk of type 2 diabetes in adulthood: A large prospective cohort study.

OBJECTIVES: We aimed to assess the relationships between early-life tobacco smoke exposures and the incident risk of type 2 diabetes (T2D) in later life as well as the joint effects and interactions between genetic susceptibility and early-life tobacco exposures. METHODS: We used data on in utero tobacco exposure and the age of smoking initiation to estimate the status of early-life tobacco exposure in the UK Biobank. Cox proportion hazard models were applied to estimate the associations between early-life tobacco exposure and T2D risk and investigate joint effects and interactions of early-life tobacco smoke exposure with genetic susceptibility. RESULTS: Among 407,943 subjects from the UK Biobank, 17,115 incident cases were documented during a median follow-up of 12.80 years. Compared with subjects without prenatal tobacco exposure, those with in utero tobacco exposure had a higher risk of T2D with a hazard ratio (HR) (95 % confidence interval [CI]) of 1.11 (1.08, 1.15). Besides, the HRs (95 % CIs) of incident T2D for smoking initiation in adulthood, adolescence, and childhood (vs. never smokers) were 1.36 (1.31, 1.42), 1.44 (1.38, 1.50), and 1.78 (1.69, 1.88), respectively (P trend <0.001). No interaction between early-life tobacco exposure and genetic susceptibility was observed. In addition, participants with prenatal (HR 4.67 [95 % CI 4.31, 5.06]) or childhood (6.91 [6.18, 7.72]) tobacco exposure combined with high genetic risk showed the highest risk of T2D, compared to low genetic risk subjects without early-life smoke exposure. CONCLUSION: Early-life tobacco exposure was associated with an increased risk of T2D later in life regardless of genetic background. This highlights the significance of education campaigns aimed at reducing smoking among children, adolescents, and pregnant women as an effective measure to combat the T2D epidemic.

Intracytoplasmic Sperm Injection Improves Normal Fertilization Rate and Clinical Pregnancy Rate in Male Infertility.

The purpose of this study was to investigate the effect of intracytoplasmic sperm injection (ICSI) on the normal fertilization rate of oocytes and the clinical pregnancy rate of cycles in male infertility. Eighty cases of male infertility patients attending our hospital from March 2020 to March 2021 were selected and divided into observation group and control group using the random number table method, with 40 cases in each group. The control group was treated with in vitro fertilization (IVF), and the observation group was treated with ICSI. The normal fertilization rate of oocytes and the clinical pregnancy rate of the cycle were compared between the two groups, and the adverse pregnancy outcome and obstetric and perinatal complications were compared between the two groups The rate of normal fertilization and clinical pregnancy in the cycle was higher in the observation group (P < 0.05). The differences were not statistically significant (P > 0.05) when comparing adverse pregnancy outcomes between the two groups. The difference was not statistically significant (P > 0.05) when comparing obstetrics (5.41%, 10.34%) and perinatal complications (8.33%, 14.81%) between the two groups. ICSI in male infertility is significantly effective in improving the rate of normal oocyte fertilization and the clinical pregnancy rate of the cycle. It also has a low impact on adverse pregnancy outcomes and obstetric and perinatal complications and has a high safety profile.

A Machine Learning Based Framework to Identify and Classify Non-alcoholic Fatty Liver Disease in a Large-Scale Population.

Non-alcoholic fatty liver disease (NAFLD) is a common serious health problem worldwide, which lacks efficient medical treatment. We aimed to develop and validate the machine learning (ML) models which could be used to the accurate screening of large number of people. This paper included 304,145 adults who have joined in the national physical examination and used their questionnaire and physical measurement parameters as model's candidate covariates. Absolute shrinkage and selection operator (LASSO) was used to feature selection from candidate covariates, then four ML algorithms were used to build the screening model for NAFLD, used a classifier with the best performance to output the importance score of the covariate in NAFLD. Among the four ML algorithms, XGBoost owned the best performance (accuracy = 0.880, precision = 0.801, recall = 0.894, F-1 = 0.882, and AUC = 0.951), and the importance ranking of covariates is accordingly BMI, age, waist circumference, gender, type 2 diabetes, gallbladder disease, smoking, hypertension, dietary status, physical activity, oil-loving and salt-loving. ML classifiers could help medical agencies achieve the early identification and classification of NAFLD, which is particularly useful for areas with poor economy, and the covariates' importance degree will be helpful to the prevention and treatment of NAFLD.

A novel dual-channel fluorescent probe for selectively and sensitively imaging endogenous nitric oxide in living cells and zebrafish.

Nitric oxide (NO) plays various physiological and pathological roles in lots of biological processes. It is crucial to detect NO sensitively and selectively in vivo and in vitro as homeostasis of NO is closely related to various diseases. Herein, a novel dual-channel fluorescent dye (ENNH2) based on dicarboxyimide anthracene was developed as a highly sensitive and selective probe to detect NO in living systems using the dual-channel fluorescence. ENNH2 can emit bright red fluorescence due to the intramolecular charge transfer (ICT) from the amino group at the 6-position of 1,2-dicarboxyimide anthracene to the conjugated aromatic ring, and the ICT is effectively inhibited by the reductive deamination of the amino in the presence of NO to obtain the remarkable strong green emission with the excellent sensitivity (5.52 nM). Promisingly, ENNH2 exhibits an excellent performance in endogenous NO dual-channel fluorescence imaging of RAW 264.7 cells and zebrafish.