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In this paper, a three-electrode electrochemical detection system was designed. Platinum electrode was used as the counter electrode, saturated KCl electrode as reference electrode, and copper film material as working electrode, respectively. Cyclic voltammetry (CV) and chronoamperometry (i-t) methods were used for d-psicose scanning. CV results indicated that d-psicose presented the oxidation-reduction reacting procedure on the surface of copper film electrode. Testing parameters optimization was conducted using CV scanning in different scanning rates. d-psicose quantitative determination model was developed by i-t scanning results. The sensitivity was9419.1A×cm -2 ·mol/L, the detection limit was1.04311×10 -8 mol/L. The proposed method has some advantages including high sensitivity, low detection line, and fast response speed. Negative control testing results by using glucose, sucrose, and NaCl solutions demonstrated that the proposed method had good selectivity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Oculocutaneous albinism (OCA) could be either non-syndromic or syndromic. There are significant challenges in clinically recognizing and differentiating Hermansky-Pudlak syndrome (HPS) from non-syndromic OCA., Materials and Methods: In a prospective consecutive case series, 63 patients (less than 18 years old) with a molecular genetic diagnosis of albinism (except OCA1A ), Ocular albinism (OA) and Hermansky-Pudlak syndrome seen over a 3-year period were evaluated and analyzed. Hair colour, iris colour was graded, compared and correlated with the degree of fundus pigmentation and foveal development., Results: A total of 63 patients were evaluated. Forty-five patients had non-syndromic OCA (11 OCA1B, 24 OCA2, 9 OCA4, and 1 OCA6), 5 patients had OA and 13 patients had HPS. All 3 BLOC-related HPS categories were seen (1 with BLOC1, 7 with BLOC-2 and 5 with BLOC-3 related HPS). All patients with OA were hyperopic, had darker fundus pigmentation, but had poor foveal development. All HPS patients had lighter fundus pigmentation. The degree of fundus pigmentation correlated positively with the iris pigmentation and also with the foveal development only in OCA2., Conclusions: Careful observation of the phenotype by comparison of the skin, hair, iris colour, with the degree of fundus pigmentation and foveal development may help clinically differentiate HPS from OCA patients of Chinese ethnicity even in the absence of any bleeding tendency.

Arbuscular mycorrhizal fungi (AMF) form mutualistic symbiotic relationships with many land plants and play a key role in nitrogen (N) acquisition. NO 3 - -N and NH 4 + -N are the main sources of soil mineral N, but how extraradical mycelial transfer affects the different N forms and levels available to tomato plants is not clear. In the present study, we set up hyphal compartments (HCs) to study the efficiency of N transfer from the extramycelium to tomato plants treated with different N forms and levels of fertilization. Labeled 15 NO 3 - -N or 15 NH 4 + -N was placed in hyphal compartments under high and low N application levels. 15 N accumulation in shoots and the expression of LeNRT2.3 , LeAMT1.1 , and LeAMT1.2 in the roots of tomato were measured. According to our results, both 15 NO 3 - -N and 15 NH 4 + -N were transported via extraradical mycelia to the shoots of plants. 15 N accumulation in shoots was similar, regardless of the N form, while a higher 15 N concentration was found in shoots with low N application. Compared with the control, inoculation with AMF significantly increased the expression of LeAMT1.1 under high N and LeNRT2.3 under low N. The expression of LeAMT1.1 under high N was significantly increased when NO 3 - N was added, while the expression of LeNRT2.3 was significantly increased when NH 4 + -N was added under low N. Taken together, our results suggest that the N transfer by extraradical mycelia is crucial for the acquisition of both NO 3 - -N and NH 4 + -N by the tomato plant; however, partial N accumulation in plant tissue is more important with N deficiency compared with a higher N supply. The expression of N transporters was influenced by both the form and level of N supply.

There is significant racial disparity in thoracic malignancies in terms of epidemiology and outcomes. We analyzed race reporting and racial diversity in the registration trials of drugs approved by the FDA for thoracic malignancies from 2006 to 2020. We found a significant under-representation of non-white participants in FDA drug registration trials in thoracic malignancies. Furthermore, though almost all trials report some race information, FDA guidelines are not universally followed. There is a disproportionate disease burden of lung cancer in under-represented race communities, and clinical trials should prioritize racial diversity and inclusion efforts.

Objective: High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility., Research Design and Methods: HDL subclasses by nuclear magnetic resonance spectroscopy were determined in sera from 1991 fasted adults with type 2 diabetes (T2D) consecutively recruited from March 2014 to February 2015 in Hong Kong. HDL was divided into small, medium, large and very large subclasses. Associations (per SD increment) with outcomes were evaluated using multivariate Cox proportional hazards models. C-statistic, integrated discrimination index (IDI), and categorial and continuous net reclassification improvement (NRI) were used to assess predictive value., Results: Over median (IQR) 5.2 (5.0-5.4) years, 125 participants developed incident CVD and 90 participants died. Small HDL particles (HDL-P) were inversely associated with incident CVD [hazard ratio (HR) 0.65 (95% CI 0.52, 0.81)] and all-cause mortality [0.47 (0.38, 0.59)] (false discovery rate < 0.05). Very large HDL-P were positively associated with all-cause mortality [1.75 (1.19, 2.58)]. Small HDL-P improved prediction of mortality [C-statistic 0.034 (0.013, 0.055), IDI 0.052 (0.014, 0.103), categorical NRI 0.156 (0.006, 0.252), and continuous NRI 0.571 (0.246, 0.851)] and CVD [IDI 0.017 (0.003, 0.038) and continuous NRI 0.282 (0.088, 0.486)] over the RECODe model., Conclusion: Small HDL-P were inversely associated with incident CVD and all-cause mortality and improved risk stratification for adverse outcomes in people with T2D. HDL-P may be used as markers for residual risk in people with T2D., (© 2022. The Author(s).)

Rationale: Epstein-Barr virus (EBV) infection is associated with a variety of diseases and can involve multiple organs and systems, with complex and nonspecific clinical manifestations that are easily misdiagnosed. Chronic EBV infection with persistent erythema multiforme (EM) on the cheek as the main manifestation is very rare and has been reported rarely., Patient Concerns: This article reports a case of an adolescent female with chronic EBV infection who presented with chronic symmetrical erythema lesions on the face for 4 years, exacerbated with photophobia, lacrimation, Henoch-Schonlein purpura (HSP)-like rash, decline in granulocyte and erythrocyte lineages, hematuria, and proteinuria for 1 week., Diagnoses: The disease was initially misdiagnosed as systemic lupus erythematosus (SLE) and later confirmed as chronic EBV infection by skin biopsy. In the case, EBV infection not only caused chronic facial EM, but also induced acute HSP and purpura nephritis (hematuria and proteinuria type)., Interventions: The child was treated with 1 week of glucocorticosteroids in adequate doses combined with acyclovir antiviral therapy and 3 sessions of hemoperfusion. After discharge, she took prednisone acetate (15 mg twice a day) orally for 1 month and then discontinued., Outcomes: She was discharged with her rash relieved and normal blood routine test and urine routine test. After 13 months of long-term follow-up, her facial erythema and hyperpigmentation became lighter, and there was no new rash on the whole body, and no abnormality in continuous monitoring of complete blood count and urine test., Lessons: This case suggests the need to be alert for chronic EBV infection in adolescent females with chronic facial EM rash and multiple organs and systems injury, in addition to connective tissue diseases such as SLE., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To study the effect and underlying mechanisms of Chinese medicine Yanghe decoction on pain relief in a rat model of bone metastasis of breast cancer induced by michigan cancer foundation-7 (MCF-7)., Methods: Bone pain was induced in the tibia of rats injected with MCF-7 cells. The Chinese herbal remedy was used to decoct Yanghe decoction for the treatment of bone pain rats. The behavior study was carried out to evaluate the paw mechanical withdraw threshold and thermal withdraw latency. Liquid chromatography-mass spectrometry, Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), immunohistochemical (IHC) staining were performed for analysis., Results: Yanghe decoction could improve the defensive behavior similar to the transient receptor potential ankyrin 1 (TRPA1) inhibitor. In morphology study, Yanghe decoction could attenuate the cellular growth as well as inflammatory infiltration in the metastasis group. Furthermore, Yanghe decoction downregulated the TRPA1 expression on the dorsal root ganglion from the metastatic rats at both transcriptional and protein level. Yanghe decoction alleviated the inflammation in metastatic tissues by hematoxylin-eosin and IHC analysis, and Yanghe decoction also reduced the inflammatory cytokines production in the serum including tumor necrosis factor-α and interleukin-6, interleukin-1 beta by ELISA. As the cytochromec oxidase subunit II/prostaglandin E2 (PGE2) is required for cancer development, Yanghe decoction reduced the expression of PGE2 in the tissue and serum., Conclusion: Taken together, Yanghe decoction protected the rats from breast cancer bone metastasis through TRPA1 signaling mediated neuropathic pain and additional immune modulation in tumor microenvironment.

Metastasis, as one of major challenges in the cancer treatment, is responsible for the high mortality of breast cancer. It has been reported that breast cancer cell invasion and metastasis are related to aquaporin 3 (AQP3), which is the transmembrane transport channel for H 2 O 2 molecules. Moreover, there is agreement that preventing the metastasis of breast tumor cells in combination with inhibiting the tumor growth is a promising strategy for cancer chemotherapy. Herein, we constructed a flexible photothermal crosslinked polymeric nanovehicle for the delivery of the AQP3 inhibitor, [AuCl 2 (phen)] + Cl - (Auphen). The polymeric nanovehicle (pOMPC-Dex) is comprised of three modules: 1) pOEGMA-co-pMEO 2 MA serves as the temperature-responsive segment; 2) pCyanineMA acts as the near-infrared (NIR) optical absorbing motif for photothermal therapy and is conjugated with pOEGMA-co-pMEO 2 MA to obtain NIR light stimuli-responsive drug release; and 3) pPBAMA-Dex functions as an acidic tumor microenvironment-responsive unit. Auphen was encapsulated into a nanovehicle (Auphen@pOMPC-Dex) through electrostatic interactions. The designed nanoplatform showed a pH- and NIR light stimuli-responsive drug release profile and exhibited the strong inhibition of intracellular H 2 O 2 uptake by breast cancer cells, which led to the inhibition of breast cancer cell migration and invasion in vitro. In a breast cancer mouse model, Auphen@pOMPC-Dex markedly reduced the number of lung metastases in tumor-bearing mice due to the combined suppression of tumor growth and metastasis. Consequently, the fabricated Auphen@pOMPC-Dex may provide a new strategy for the development of comprehensive oncotherapies. STATEMENT OF SIGNIFICANCE: High mortality due to metastasis-induced breast cancer has been a key issue that needs to be addressed. It has been reported that aquaporin 3 (AQP3), a transmembrane transport channel for H 2 O 2 molecules was found to have an accelerated effect on breast cancer cell migration. Hence, a flexible crosslinked polymeric nanoplatform with the inhibition of AQP3 was designed to inhibit metastasis of breast cancer cells. At the same time, we combined suppression of tumor growth with photothermal therapy to enhance the anticancer therapy effect., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Phthalic acid esters (PAEs) are commonly used as plasticizer and are emerging concern worldwide for potent adverse effects of aquatic organisms. Certain PAEs were often detected in different environmental matrices but related toxicity data were still lacking to support their risk assessment. The study investigated the acute toxicity of Diisobutyl phthalate (DiBP) and Di-n-octyl phthalate (DnOP) using 6 Chinese resident aquatic organisms from 3 phyla and 6 species and constructed the species sensitivity distribution (SSD) models for ecological risk assessment. Lethal concentration 50% (LC 50 ) ranges of DiBP and DnOP were 4.89-21.45 mg/L and 1.45-1200 mg/L, respectively. The derived acute and chronic predicted no-effect concentrations (PNECs) based on log-normal model of water were 0.54 and 0.04 mg/L for DiBP and 0.23 and 0.05 mg/L for DnOP, respectively. The ERA for DiBP and DnOP in the surface water and sediment of China was conducted. Water samples of Haihe Rive (RQ = 0.41) and Hun River (RQ = 0.16) of DiBP showed medium risk. And sediment samples of Yellow River (RQ = 0.71) and Chao Hu Lake (RQ = 0.42) of DiBP showed medium risk. Meanwhile, the above water and sediment samples (RQ＜0.1) of DnOP showed low risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Orthostatic hypotension (OH) is a common autonomic disorder. This study aimed to investigate the influencing factors and hemodynamic mechanisms of initial and sustained OH in middle-aged and elderly patients. The authors analyzed the clinical characteristics and hemodynamic variables of patients aged ≥ 50 years according to the various forms of OH, diagnosed by an active orthostatic test using the CNAP monitor. The study included 473 participants; 119 (25.2%) patients had initial (54, 45.4%) or sustained (65, 54.6%) OH. Age, comorbidities, or medications did not differ significantly between the initial OH and non-OH groups. Sustained OH was associated with age and diabetes (p = .003 and p = .015, respectively). Hemodynamic analysis revealed higher cardiac output (CO) in the sustained OH group within 15 s than in the non-OH and initial OH groups (both p < .001); no difference in CO was observed between the initial OH and non-OH groups. The systemic vascular resistance (SVR) in both initial OH and sustained OH groups within 15 s was lower than that in the non-OH group (both p < .001). No differences in SVR at 3 min were observed between the initial OH and non-OH groups. The SVR at 3 min in the sustained OH group was significantly lower than in non-OH and initial OH groups (both p < .001). Age and diabetes emerged as the independent risk factors associated with sustained OH. Initial OH is associated with a mismatch of increase in CO and decrease in SVR. Sustained OH is mainly associated with sustained inadequate adjustment in SVR., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Androgens are released by humans and livestock into the environment and which cause potent endocrine disruptions even at nanogram per liter levels. In this article, we reviewed updated research results on the structure, source, distribution characteristics and the fate of androgens in ecological systems; and emphasized the potential risk of androgens in aquatic organism. Androgens have moderately solubility in water (23.6-58.4 mg/L) and moderately hydrophobic (log Kow 2.75-4.40). The concentration of androgens in surface waters were mostly in ng/L ranges. The removal efficiencies of main wastewater treatment processes were about 70-100%, except oxidation ditch and stabilization ponds. Sludge adsorption and microbial degradation play important role in the androgens remove. The conjugated androgens were transformed into free androgens in environmental matrices. Global efforts to provide more toxicity data and establish standard monitoring methods need a revisit. Of the day available, there is an urgent need for comprehensive consideration of the impact of androgens on the environment and ecology., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Anesthetics, commonly used in preclinical and fundamental scientific research, have a depressive influence on the metabolic, neuronal, and vascular functions of the brain and can adversely influence neurophysiological results. The use of awake animals for research studies is advantageous but poses the major challenge of keeping the animals calm and stationary to minimize motion artifacts throughout data acquisition. Awake imaging in smaller-sized rodents (e.g., mice) is very common but remains scant in rats as rats are bigger, stronger, and have a greater tendency to oppose movement restraints and head fixation over the long durations required for imaging. A new model of neuroimaging of awake, head-fixed rats using customized hand-sewn slings, 3D-printed head implants, head caps, and a headframe is described. The results acquired following a single trial of single-whisker stimulation suggest an increase in the intensity of the evoked functional response. The acquisition of the evoked functional response from awake, head-fixed rats is faster than that from anesthetized rats, reliable, reproducible, and can be used for repeated longitudinal studies.

The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers of different carbon chain lengths. The haptens were then used to immunize mice. The antibodies obtained were evaluated systematically, and a colloidal gold immunochromatographic strip was developed based on an anti-aldicarb monoclonal antibody. The 50% inhibition concentration and linear range of anti-aldicarb monoclonal antibody immunized with Hapten 1 were 0.432 ng/mL and 0.106-1.757 ng/mL, respectively. The cross-reactivities for analogs of aldicarb were all <1%. The limit of detection of the colloidal gold immunochromatographic strip was 30 μg/kg, and the average recoveries of aldicarb ranged from 80.4 to 110.5% in spiked samples. In the analysis of spiked samples, the test strip could accurately identify positive samples detected by the instrumental method in the GB 23200.112-2018 standard but produced some false positives for negative samples. This assay provides a rapid and accurate preliminary screening method for the determination of aldicarb in agricultural products and environments., Competing Interests: YW, XW, YZ, TC, HC, GH, XC, and GL were employed by the Beijing Kwinbon Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Wan, Wu, Zhang, Li, Cui, Sun, Cui, He, Hui, Chen, Liu and Du.)

Rationale & Objective: Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing DKD phenotype. We compared the risks of adverse outcomes among patients with this phenotype compared with other DKD phenotypes., Study Design: Multicenter prospective cohort study., Settings & Participants: 19,025 Chinese adults with type 2 diabetes enrolled in the Hong Kong Diabetes Biobank., Exposures: DKD phenotypes defined by baseline estimated glomerular filtration rate (eGFR) and albuminuria: no DKD (no decreased eGFR or albuminuria), albuminuria without decreased eGFR, decreased eGFR without albuminuria, and albuminuria with decreased eGFR., Outcomes: All-cause mortality, cardiovascular disease (CVD) events, hospitalization for heart failure (HF), and chronic kidney disease (CKD) progression (incident kidney failure or sustained eGFR reduction ≥40%)., Analytical Approach: Multivariable Cox proportional or cause-specific hazards models to estimate the relative risks of death, CVD, hospitalization for HF, and CKD progression. Multiple imputation was used for missing covariates., Results: Mean participant age was 61.1 years, 58.3% were male, and mean diabetes duration was 11.1 years. During 54,260 person-years of follow-up, 438 deaths, 1,076 CVD events, 298 hospitalizations for HF, and 1,161 episodes of CKD progression occurred. Compared with the no-DKD subgroup, the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (hazard ratio [HR], 1.59 [95% CI, 1.04-2.44]), hospitalization for HF (HR, 3.08 [95% CI, 1.82-5.21]), and CKD progression (HR, 2.37 [95% CI, 1.63-3.43]), but the risk of CVD was not significantly greater (HR, 1.14 [95% CI, 0.88-1.48]). The risks of death, CVD, hospitalization for HF, and CKD progression were higher in the setting of albuminuria with or without decreased eGFR. A sensitivity analysis that excluded participants with baseline eGFR <30 mL/min/1.73 m 2 yielded similar findings., Limitations: Potential misclassification because of drug use., Conclusions: Nonalbuminuric DKD was associated with higher risks of hospitalization for HF and of CKD progression than no DKD, regardless of baseline eGFR., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The recent remarkable increase in induced seismicity in Western Canada has been largely attributed to hydraulic fracturing in unconventional reservoirs. The nucleation of large magnitude events has been demonstrated to be closely linked to site-specific geological and operational factors. A mitigation strategy of fracturing-induced seismicity concerning both factors has not been well investigated. In this paper, a comprehensive investigation of risk mitigations from induced seismicity is conducted based on the formation overpressure, distance to Precambrian basement, proximity to faults, fracturing job size and safe hydraulic fracture-fault distance. It is found that the middle-south region near Crooked Lake is an optimal region for fracturing operations with low formation pressure, a great distance to the basement and relatively fewer pre-existing faults. A field case study suggests that fracturing operations of three new horizontal wells are successful with low magnitude induced events and with high production performance, demonstrating the applicability of a comprehensive approach of seismicity risk mitigations. Such an approach can be applied to other field cases to mitigate the potential fracturing-induced seismicity in unconventional reservoirs., (© 2022. The Author(s).)

Objective: Osteoarthritis (OA) is a degenerative joint disease. Excessive nitric oxide (NO) mediates the chondrocyte inflammatory response, apoptosis, and extracellular matrix (ECM) degradation during the occurrence and development of OA. NO in chondrocytes is mainly produced by inducible nitric oxide synthase (iNOS). The aim of this study was to design and synthesize an iNOS dimerization inhibitor and evaluate its effects on chondrocyte inflammation and articular cartilage injury in OA via in vitro and in vivo experiments. Design: The title compound 22o was designed, synthesized, and screened based on a previous study. The effects of different concentrations (5, 10, and 20 μM) of compound 22o on chondrocyte inflammatory response and ECM anabolism or catabolism were evaluated by Western blot and real-time quantitative reverse transcription-polymerase chain reaction using the rat chondrocyte model of IL-1β-induced OA. Furthermore, different doses (40 and 80 mg/kg) of compound 22o were administered by gavage to a rat OA model induced by anterior cruciate ligament transection (ACLT), and their protective effects on the articular cartilage were evaluated by histopathology and immunohistochemistry. Results: Compound 22o showed effective iNOS inhibitory activity by inhibiting the dimerization of iNOS. It inhibited the IL-1β-induced expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase 3 (MMP3) in the chondrocytes, decreased NO production, and significantly increased the expression levels of the ECM anabolic markers, aggrecan (ACAN), and collagen type II (COL2A1). Gavage with compound 22o was found to be effective in the rat OA model induced by ACLT, wherein it regulated the anabolism and catabolism and exerted a protective effect on the articular cartilage. Conclusions: Compound 22o inhibited the inflammatory response and catabolism of the chondrocytes and reduced articular cartilage injury in the rat OA model, indicating its potential as a disease-modifying OA drug., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xian Bo, Yan Jie, De Chao, Sai, Zhe, Ya Kun, Hui Hui, Chen, Xiao, Zhong Yao, Hao Ran, Ji Sen and Wen Dan.)

It is widely known that mold is one of important indices in assessing the quality of stored wheat. First, mold will decrease the quality of wheat kernels; the wheat kernels infected by mold can produce secondary metabolites, such as aflatoxins, ochratoxin A, zearalenone, fumonisins and so on. Second, the mycotoxins metabolized by mycetes are extremely harmful to humans; once the food or feed is made of by those wheat kernels infected by mold, it will cause serious health problems on human beings as well as animals. Therefore, the effective and accurate detection of wheat mold is vitally important to evaluate the storage and subsequent processing quality of wheat kernels. However, traditional methods for detecting wheat mold mainly rely on biochemical methods, which always involve complex and long pretreatment processes, and waste part of wheat samples for each detection. In view of this, this paper proposes a type of eco-friendly and nondestructive wheat mold detection method based on ultra weak luminescence. The specific implementation process is as follows: firstly, ultra weak luminescence signals of the healthy and the moldy wheat subsamples are measured by a photon analyzer; secondly, the approximate entropy and multiscale approximate entropy are introduced as the main classification features separately; finally, the detection model has been established based on the support vector machine in order to classify two types of wheat subsamples. The receiver operating characteristic curve of the newly established detection model shows that the highest classification accuracy rate can reach 93.1%, which illustrates that our proposed detection model is feasible and promising for detecting wheat mold., (© 2022. The Author(s).)

Numerous immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), have been approved for the treatment of genitourinary (GU) malignancies. While ICIs have improved treatment outcomes and expanded treatment options, they can cause immune-related adverse events (irAEs). The scope of irAEs is broad, and this paper aims to review the rheumatologic side effects associated with immunotherapy drugs approved for bladder cancer and renal cell carcinoma. IrAEs are graded by the common terminology criteria for adverse events (CTCAE), which ranges from 1 to 5. The management of irAEs includes corticosteroids or other immunosuppressive therapies, and it may require discontinuation of immunotherapy. Several real world experience studies suggest that most patients with pre-existing autoimmune diseases treated with ICI did not have to discontinue treatment due to immune-mediated side effects. While data suggest autoimmune side effects are manageable, patients with pre-existing autoimmune diseases are often excluded from immunotherapy clinical trials. Better understanding of these irAEs will improve its safety and expand its use in those with underlying autoimmune disease.

Exosomes participate in many physiological and pathological processes by regulating cell-to-cell communication. This affects the etiology and development of diseases, such as osteoarthritis (OA). Although exosomes in the OA tissue microenvironment are involved in the progression of OA, exosomes derived from therapeutic cells represent a new therapeutic strategy for OA treatment. Recent studies have shown that exosomes participate in OA treatment by regulating the proliferation, apoptosis, inflammation, and extracellular matrix synthesis of chondrocytes. However, studies in this field are scant. This review summarizes the therapeutic properties of exosomes on chondrocytes in OA and their underlying molecular mechanisms. We also discuss the challenges and prospects of exosome-based OA treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xian Bo, Chen, Chang, Hao Ran, Hui Hui, Ya Kun, Wu Kun, Hai Tao and Wen Dan.)

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) remain a matter of concern, as the clinical use of multiple antibiotics induces antibiotic resistance in bacteria, resulting in the failure of treatments. Despite the emergence of anti-adhesion strategies that can prevent the development of bacterial drug resistance, these strategies are mainly used for disease prevention rather than effective treatment. Photothermal therapy (PTT) has emerged as an efficient alternative for the elimination of bacteria. Nevertheless, high local temperatures related to PTT probably cause damage to surrounding healthy tissue. Herein, a biomimetic nonantibiotic nanoplatform for low-temperature photothermal treatment of UTIs is developed. The nanoplatform comprises polydopamine (PDA) photothermal core and biphenyl mannoside (Man) shell with multivalent high-affinity to UPEC. Scanning electron microscope (SEM) shows PDA-Man possessed ultra-strong targeting binding ability toward UPEC. It is the fact that this impulse UPEC to form a large bacterial cluster. Consequently, the high photothermal energy of the PDA-Man appears predominantly in the affected bacterial area, while the overall environment remains at a low temperature. The fabricated nanoplatform shows excellent photothermal bactericidal effects, approximately 100% in a UTI model. Overall, this low-temperature photothermal nanoplatform provides an appropriate strategy for the elimination of bacteria in clinical applications., (© 2022 Wiley-VCH GmbH.)

Data pertaining to risk factor analysis in coronavirus disease 2019 (COVID-19) is confounded by the lack of data from an ethnically diverse population. In addition, there is a lack of data for young adults. This study was conducted to assess risk factors predicting COVID-19 severity and mortality in hospitalized young adults. A retrospective observational study was conducted at two centers from China and India on COVID-19 patients aged 20-50 years. Regression analysis to predict adverse outcomes was performed using parameters including age, sex, country of origin, hospitalization duration, comorbidities, lymphocyte count, and National Early Warning Score 2 (NEWS2) score at admission. A total of 420 patients (172 East Asians and 248 South Asians) were included. The predictive model for intensive care unit (ICU) admission with variables NEWS2 Category II and higher, diabetes mellitus, liver dysfunction, and low lymphocyte counts had an area under the curve (AUC) value of 0.930 with a sensitivity of 0.931 and a specificity of 0.784. The predictive model for mortality with NEWS2 Category III, cancer, and decreasing lymphocyte count had an AUC value of 0.883 with a sensitivity of 0.903 and a specificity of 0.701. A combined predictive model with bronchial asthma and low lymphocyte count, in contrast, had an AUC value of 0.768 with a sensitivity of 0.828 and a specificity of 0.719 for NEWS2 score (5 or above) at presentation. NEWS2 supplemented with comorbidity profile and lymphocyte count could help identify hospitalized young adults at risk of adverse COVID-19 outcomes., (© 2021 Wiley Periodicals LLC.)

Background: Reducing stigma is a perennial target of mental health advocates, but effectively addressing stigma relies on the ability to correctly understand and accurately measure culture-specific and location-specific components of stigma and discrimination., Methods: We developed two culture-sensitive measures that assess the core components of stigma. The 40-item Interpersonal Distance Scale (IDS) asks respondents about their willingness to establish four different types of relationships with individuals with 10 target conditions, including five mental health-related conditions and five comparison conditions. The 40-item Occupational Restrictiveness Scale (ORS) asks respondents how suitable it is for individuals with the 10 conditions to assume four different types of occupations. The scales - which take 15 min to complete - were administered as part of a 2013 survey in Ningxia Province, China to a representative sample of 2425 adult community members., Results: IDS and ORS differentiated the level of stigma between the 10 conditions. Of the total, 81% of respondents were unwilling to have interpersonal relationships with individuals with mental health-related conditions and 91% considered them unsuitable for various occupations. Substantial differences in attitudes about the five mental health-related conditions suggest that there is no community consensus about what constitutes a 'mental illness'., Conclusions: Selection of comparison conditions, types of social relationships, and types of occupations considered by the IDS and ORS make it possible to develop culture-sensitive and cohort-specific measures of interpersonal distance and occupational restrictiveness that can be used to compare the level and type of stigma associated with different conditions and to monitor changes in stigma over time.

Background: Heavy episodic drinking is common in the United States (US) and causes substantial burden to individuals and the society. The transition from first drinking to first heavy drinking episode is a major milestone in the escalation of drinking. There is limited evidence about whether major depressive symptoms predict the progression from drinking to heavy drinking and potential variations across age, sex, and depressive symptoms. In this study, we aim to estimate the association between history of major depressive symptoms and the risk of first heavy drinking episode among new drinkers in the US., Methods: Study population was US non-institutionalized civilian new drinkers 12 years of age and older who had their first drink during the past 12 months drawn from the National Survey on Drug Use and Health. History of major depressive symptoms and alcohol drinking behaviors were assessed via audio-computer-assisted self-interviews. Logistic regressions and structural equation modeling were used for analysis., Results: Depressed mood and/or anhedonia predicted the transition from the first drink to a heavy drinking episode among underage female new drinkers, whereas null associations were found among males and female new drinkers who had their first drink at 21 and later. Among new drinkers with depressed mood and/or anhedonia, low mood or energy positively predicted the progression to a heavy drinking episode among late-adolescent boys, but negatively among late-adolescent girls; neurovegetative symptoms positively predicted the progression to a heavy drinking episode among young adult new drinkers., Conclusions: The relationships linking major depressive symptoms and the transition from drinking to first heavy drinking episode vary across age, sex, and depressive symptoms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Susceptibility to tobacco use predicts tobacco use onset among youth. The current study aimed to estimate the extent of overlap in susceptibilities across various tobacco products, investigate sociopsychological correlates with susceptibilities, and examine whether the relationship linking susceptibility with the onset of use is product-specific or is accounted for by a general susceptibility-onset relationship., Methods: The study population consisted of US youth 12-17 years old who had never used a tobacco product, sampled in the longitudinal Population Assessment of Tobacco and Health study wave 4 (Dec. 2016-Jan. 2018; n = 10,977). Tobacco product-specific susceptibility at wave 4 was assessed via questions about curiosity, likelihood to try, and likelihood of use if a best friend offered. The onset of use of various tobacco products was defined as first use occurring between the wave 4 and wave 4.5 (Dec. 2017-Dec. 2018) assessments (n = 8841). Generalized linear regression and structural equation models were used for data analysis., Results: There is a large degree of overlap in susceptibilities across tobacco products (65% of tobacco-susceptible youth were susceptible to more than one tobacco product). Tobacco-susceptible youths were more likely to have recently used cannabis, consumed alcohol, or to have been associated with tobacco-using peers. Structural equation models suggest that the susceptibility-onset relationship largely operates in a non-product-specific manner after accounting for the general susceptibility-to-tobacco-onset relationship., Conclusions: Youth susceptibility to tobacco use overlaps widely across different tobacco products and other risky behaviors. Findings from this study support a holistic approach towards the prevention of risk behaviors, supplemented by product-specific strategies when needed., (© 2021. The Author(s).)

Background: This study aimed to describe the prevalence and lifetime criteria profiles of DSM-5 alcohol use disorder (AUD) and the transitions from alcohol use to disorder in Chifeng, China., Methods: Face-to-face interviews were conducted using Composite International Diagnostic Interview-3.0 (CIDI-3.0) among 4528 respondents in Chifeng., Results: The weighted lifetime and 12-month prevalence of DSM-5 AUD were 3.03 and 1.05%, respectively. Mild lifetime AUD was the most prevalent severity level (69.53%). The two most common criteria were "failure to quit/cutdown" and "drinking more or for longer than intended." Lifetime prevalence was 65.59% for alcohol use, and 22.97% for regular drinking. Male and domestic violence were risk factors for the transition from alcohol use to regular drinking or AUD and from regular drinking to AUD. Younger age was risk factor for the transition to AUD from alcohol use or regular drinking. Poverty (OR = 2.49) was risk factor for the transition from alcohol use to regular drinking. The earlier drinkers were more likely to develop to regular drinking (OR = 2.11)., Conclusion: AUD prevalence in Chifeng was not as high as that in Western countries. The study revealed that multiple risk factors might contribute to the transition across different stages of alcohol use. Further research should explore the underlying mechanisms., (© 2021. The Author(s).)

Background: The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear., Methods: We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients., Results: Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10 - 103  < P < 1.3 × 10 - 75 ) and 3-year lipid changes (1.4 × 10 - 6  < P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (β ± SE = 0.052 ± 0.002), 11.7% in TG (β ± SE = 0.111 ± 0.006), 5.8% in HDL-C (β ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (β ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10 - 3  < P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10 - 10  < P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (β ± SE = 0.011 ± 0.005, P trend  = 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC [OR (95% CI) = 1.07 (1.03-1.11)], TG [OR (95% CI) = 1.05 (1.01-1.09)], and LDL-C [OR (95% CI) = 1.05 (1.01-1.09)] were significantly associated with increased risk of CHD in T2D patients (4.8 × 10 - 4  < P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association., Conclusions: The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism has been inconsistently reported to be a risk factor for Childhood immunoglobulin A vasculitis (IgAV) nephritis. We comprehensively searched electronic databases as of Jan 2020. Nineteen studies with 1104 cases and 1589 controls were included. Sensitivity analyses based on different subgroups were performed. Further analyses were conducted for association of ACE polymorphism with disease severity and prognosis. Significant associations were found between ACE I/D polymorphism and childhood IgAV nephritis, with the strongest association in DD vs. II comparison (OR 1.72, 95% CI 1.21-2.46). Subgroup analyses generally showed significant results. Besides, ACE polymorphism was significantly associated with proteinuria (DD + DI vs. II: OR 2.22, 95% CI 1.14-4.33; DI + II vs. DD: OR 0.49, 95% CI 0.30-0.81) and worse prognosis (the strongest effect in DD + DI vs. II: OR 4.43, 95% CI 1.84-10.71) among children with IgAV nephritis. The ACE polymorphism seemed not to be associated with hematuria, hypertension, and renal pathology. This study suggested significant association of ACE gene polymorphism with the risk of IgAV nephritis in children. D allele in the ACE genotype could be a useful genetic marker to predict proteinuria and worse prognosis for childhood IgAV nephritis.

This study brings insight into interpreting forest structural diversity and explore the classification of individuals according to the distribution of the neighbours in natural forests. Natural forest communities with different latitudes and distribution patterns in China were used. Each tree and its nearest neighbours form a structural unit. Random structural units (or random trees) in natural forests were divided into different sub-types based on the uniform angle index (W). The proportions of different random structural units were analysed. (1) There are only two types of random structural units: type R1 looks similar to a dumbbell, and type R2 looks similar to a torch. These two random structural units coexist in natural forests simultaneously. (2) The proportion of type R1 is far less than that of R2, is only approximately 1/3 of all random structural units or random trees; R2 accounts for approximately 2/3. Furthermore, the proportion of basal area presents the same trend for both random structural units and random trees. R2 has approximately twice the basal area of R1. Random trees (structural units) occupy the largest part of natural forest communities in terms of quantity and basal area. Meanwhile, type R2 is the largest part of random trees (structural units). This study finds that the spatial formation mechanism of natural forest communities which is of great significance to the cultivation of planted forests.

Binocular triplopia is a rare symptom and usually has a corneal or lenticular origin. Uniocular diplopia arising from ectopia lentis is quite common in Marfan syndrome. A visual phenomenon related to binocular triplopia due to strabismus was first reported in 1943 by Burian. Both monocular diplopia and binocular triplopia have been reported in concomitant strabismus. Strabismus is also common in Marfan syndrome but congenital superior oblique paresis has never been reported before. We report herein a rare case of binocular triplopia in a patient with Marfan syndrome arising from decompensation of his coexistent congenital superior oblique paresis triggered by his uniocular diplopia. This is the first report of congenital superior oblique paresis in a patient with Marfan syndrome. Though it is unlikely to have any etiological implications and is likely to be a mere coincidental simultaneous occurrence, it had a confounding effect on the clinical interpretation of the signs and symptoms posing an interesting diagnostic and management dilemma. Our case report emphasizes the necessity for careful evaluation of any patient with symptoms of triplopia. We further review and summarize all the causes of binocular triplopia published in English literature and propose an approach to its evaluation and management.

Hericium erinaceus is a traditional edible mushroom. Selenium (Se) is an essential trace element for humans and other mammals. To develop a Se biofortification strategy for H. erinaceus, the effects of selenate, selenite, and selenomethionine (SeMet) on Se uptake and mushroom growth were investigated. Selenium bioaccessibility and the major Se species present in Se-enriched H. erinaceus were tested in vitro . The H. erinaceus growth was efficiently affected by SeMet than by selenite and selenate. Selenium concentrations in fruiting bodies increased with substrate Se concentration and disturbed accumulation of other microelements. Substrate Se was absorbed and transformed into organic forms. The major Se species in Se-enriched fruiting bodies was SeMet (>63.9%). During in vitro gastrointestinal digestion tests, 51% of total Se was released, and selenocystine (SeCys 2 ) (90%) and Se-methylselenocysteine (MeSeCys) (76%) were more easily digested than SeMet (51%). H. erinaceus is suggested as a novel dietary source of supplemental bioavailable Se., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In order to discuss the &quot;entropy weight method&quot; for weighting various indicators in the comprehensive evaluation of Angelicae Sinensis Radix slices(ASR), the quality of ASR was comprehensively evaluated by entropy weight-based gray systematic theory and cluster analysis. In this study, the contents of ferulic acid, volatile oil, polysaccharide, alcohol extract, water extract, moisture, total ash and acid-insoluble ash in 44 batches of ASR from different sources were determined. The entropy weight method was used for objective weighting. With relative correlation(r&#95;i) as a measure, a multi-index comprehensive evaluation model was constructed for the quality of ASR. The results showed that the relative correlation value of 44 batches of ASR ranged from 0.301 9 to 0.662 9. There were certain differences in the quality of ASR from different sources. The ASR S1-S8, traceable and standardized in processing techno-logy, showed a high relative correlation degree and high quality ranking, indicating that the implementation of systemic management of the production chain of Chinese herbal pieces was beneficial to the quality control of ASR. The quality evaluation results of 44 batches of ASR were consistent with those of traditional geo-authentic habitats for ASR and the mainstream varieties of ASR on market, and basically consistent with the results of cluster analysis. This study suggests that the gray systematic theory based on the entropy weighting method can be used for the quality evaluation of ASR. The objective weighting of the entropy weight method improves the reliability of the gray correlation method and the scientificity of ASR quality evaluation.

Heart failure (HF) is a heterogeneous clinical syndrome with a variety of causes, risk factors, and pathology. Clinically, only brain natriuretic peptide (BNP) or its precursor N-terminus proBNP (NTproBNP) has been validated for HF diagnosis, but they are also affected by other conditions, such as female gender, renal disease, and acute coronary syndromes, and false low levels in the setting of obesity or flash pulmonary edema. In addition, there is no one biomarker which could encompass all heart failure phenotypes. Advances in bioinformatics have provided us with large databases that characterize the complex genetic and epigenetic changes associated with human diseases. The use of data mining strategies on public access databases to identify previously unknown disease markers is an innovative approach to identify potential biomarkers or even new therapeutic targets in complex diseases such as heart failure (HF). In this study, we analyzed the genomic and transcription data of HF peripheral blood mononuclear cell (PBMC) samples obtained from the Gene Expression Omnibus data sets using Omicsbean online database (http://www.omicsbean.cn/) and found that the prostaglandin-endoperoxide synthase 2 (PTGS2), also named as cyclooxygenase-2 (COX-2), as well as its related micro RNAs including miR-1297 and miR-4649-3p might be used as potential biomarkers for non-ischemic heart failure. Our result showed that plasma COX-2 and miR-4649-3p were significantly up-regulated, whereas the plasma miR-1297 was significantly decreased, and miR-4649-3p displayed high predictive power for non-ischemic heart failure., (Copyright © 2020 Yan, Song, Zhang, Hui and Wang.)

Background: Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D., Methods and Findings: In 1995-2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 [SD] years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 [IQR: 1-9] years; mean HbA1c 7.4% ± 1.7%; mean body mass index [BMI] 25.3 ± 4.0 kg/m2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c ≥8.5% while on ≥2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8-13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval [CI] 46.3-49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio [HR]: 1.07 [95% CI 1.03-1.12] per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 [95% CI 1.06-1.46] per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta [SE] = 0.312 [0.057] per SD; P = 5.84 × 10-8) but not glycemic progression (HR: 1.01 [95% CI 0.96-1.05] per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort., Conclusions: Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: RCWM acknowledges receiving research support (outside of this work) from AstraZeneca, Bayer, and Pfizer and honoraria or consultancy fees from AstraZeneca and Boehringer Ingelheim, all of which have been donated to the Chinese University of Hong Kong to support diabetes research. CKPL, WYS, JCNC, and RCWM are cofounders of GemVCare, a diabetes genetic testing laboratory, which was established through support from the Technology Start-up Support Scheme for Universities (TSSSU) from the Hong Kong Government Innovation and Technology Commission (ITC). RCWM is a member of the editorial board of PLOS Medicine. JCNC has received research grants and/or honoraria for consultancy or giving lectures, from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Eli-Lilly, GlaxoSmithKline, Merck Serono, Merck Sharp & Dohme, Novo Nordisk, Pfizer, and Sanofi. APSK has received research grants and/or speaker honoraria from Abbott, AstraZeneca, Eli-Lilly, Merck Serono, Nestle, Sanofi, and Novo Nordisk. AOL has served as an advisory committee member for AstraZeneca, Boehringer Ingelheim, Sanofi, and Amgen and has received research grants and travel grants from AstraZeneca, Boehringer Ingelheim, MSD, Novartis, Novo Nordisk, Sanofi, and Amgen.

Background: There has been mixed evidence about whether major depression predicts drinking onset. Empirical evidence about whether the heterogeneity of major depressive symptoms differentially predicts drinking onset is scarce, and potential sex- and age-variations have not been fully studied. In this study, we estimate sex- and age-specific relationships linking (a) depressed mood and/or anhedonia with drinking onset among all 'at-risk' individuals and (b) three latent depressive constructs, manifested by 13 clinical features, with drinking onset among individuals with depressed mood and/or anhedonia., Methods: Study population was non-institutionalized civilian residents 12 years of age and older living in the United States. Major depressive symptoms and drinking onset were assessed via audio-computer-assisted self-interviews. Logistic regressions and structural equation modeling were used for analysis., Results: Among all 'at risk' individuals, depressed mood or anhedonia strongly predicted early-adolescent drinking onset, whereas they did not predict at-age drinking onset. Among individuals with depressed mood or anhedonia, a 3-factor model provided a good fit to the data for all sex- and age-subgroups. With the exception of early-adolescent boys, neurovegetative symptoms and suicide-related symptoms tended to positively predict underage drinking onset, whereas Low mood or energy tended to inversely predict underage drinking onset; limited evidence was found for at-age and post-21 drinking onset., Limitations: The observational nature precludes causal inference. Few people initiated alcohol drinking later than 21 years of age, which resulted in less precise estimates., Conclusions: Strengths and directions of major depressive symptoms predicting drinking onset vary across age, sex, and depressive symptoms., Competing Interests: Declaration of Competing Interest Authors declare no competing interest related to this study. HGC is a full-time employee of Altria Client Services, LLC. This work is not associated with or sponsored by Altria Client Services, LLC., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Breast cancer is the leading cause of cancer-related disease in women. Cumulative evidence supports a causal role of alcohol intake and breast cancer incidence. In this study, we explore the change on expression of genes involved in the biological pathways through which alcohol has been hypothesized to impact breast cancer risk, to shed new insights on possible mechanisms affecting the survival of breast cancer patients. Here, we performed differential expression analysis at individual genes and gene set levels, respectively, across survival and breast cancer subtype data. Information about postdiagnosis breast cancer survival was obtained from 1977 Caucasian female participants in the Molecular Taxonomy of Breast Cancer International Consortium. Expression of 16 genes that have been linked in the literature to the hypothesized alcohol-breast cancer pathways, were examined. We found that the expression of 9 out of 16 genes under study were associated with cancer survival within the first 4 years of diagnosis. Results from gene set analysis confirmed a significant differential expression of these genes as a whole too. Although alcohol consumption is not analyzed, nor available for this dataset, we believe that further study on these genes could provide important information for clinical recommendations about potential impact of alcohol drinking on breast cancer survival., Competing Interests: The authors have declared that no competing interests exist.

Background: Increasing the pipeline of aspiring minority biomedical/health professionals is a crucial component to diversifying the health science workforce. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) created the High School Short-Term Research Experience for Underrepresented Persons (HS-STEP-UP) to provide introductory biomedical/biobehavioral research experiences to promising high school students, who are traditionally underrepresented in the biomedical/biobehavioral sciences. The program reaches out to African American and Lationo/Hispanic students, as well as Native American students and students from the United States Territories., Methods: HS-STEP-UP provides a stimulating, rigorous 8- to 10-week summer research experience for a national cohort of ~100 high school students each year; the experience is organized through four National Institutes of Health (NIH)-funded coordinating centers. Typically, the program receives about 300 applications a year and about 100 students are accepted. Applicants are reviewed and selected based upon their online application that includes: a high school transcript, list of classes and extracurricular activities, two recommendation letters and a personal statement. The program culminates with a symposium at the NIH where students present their research and attend workshops and seminars., Results: For the 2017 and 2018 HS-STEP-UP programs, the classes included 193 students; 67% were females and 82% were underrepresented minorities. Forty eight percent of students reported a family income <$37,000/year, and 23% were from first generation college families. Ninety percent were very satisfied or satisfied with their research topic and 94% rated the end of the year symposium at NIH as excellent or very good. Only 65% were very satisfied or satisfied with their mentor matching, and 21% stated they were dissatisfied or very dissatisfied with their mentor. All the students successfully completed their summer research projects and presented their research abstracts at the symposium. All participating seniors reported attending college., Conclusion: HS-STEP-UP has been highly successful in recruiting traditionally underrepresented students and supporting underrepresented HS students with a rewarding introductory experience to research. Students are overall satisfied with the program, but mentor matching needs more attention. Longer-term follow-up is needed to determine how participating in STEP UP impacts their decisions to participate in the biomedical workforce in the future., Competing Interests: Competing Interests: None declared., (Copyright © 2020, Ethnicity & Disease, Inc.)

Background: E-cigarettes have become the most commonly used tobacco products among youth in the United States (US) recently. It is not clear whether there is a causal relationship between e-cigarette use and the onset of cigarette smoking. The "common liability" theory postulates that the association between e-cigarette use and cigarette smoking can be attributed to a common risk construct of using tobacco products. This study aims to investigate the relationship between ever e-cigarette use and cigarette smoking onset in the US using a structural equation modeling approach guided by the "common liability" theory. Methods: The study population is non-institutionalized civilian adolescents living in the US, sampled in the longitudinal Population Assessment of Tobacco and Health study. Information about tobacco product use was obtained via confidential self-report. A structural equation modeling approach was used to estimate the relationship between e-cigarette use at wave 1 and the onset of cigarette smoking at wave 2 after controlling for a latent construct representing a "common liability to use tobacco products." Results:  After controlling for a latent construct representing a "common liability to use tobacco products", ever e-cigarette use does not predict the onset of cigarette smoking (β=0.13, 95% CI= -0.07, 0.32, p=0.204). The latent "common liability to use tobacco products" is a robust predictor for the onset of cigarette smoking (β=0.38; 95% CI=0.07, 0.69; p=0.015). Conclusions: Findings from this study provide supportive evidence for the 'common liability' underlying observed associations between e-cigarette use and smoking onset., Competing Interests: Competing interests: All authors are full-time employees of Altria Client Services LLC., (Copyright: © 2020 Cheng HG et al.)

Background: A comprehensive epidemiology of dependence on prescription opioid pain relievers requires evidence about age-specific female-male differences, possibly manifest during adolescent and early adult years. In this study, we identified newly incident extra-medical users of prescription pain relievers (EMPPR), all observed with onsets before the 22 nd birthday. We then quantified female-male differences in clinical features or manifestations of opioid dependence (OD), devised a measurement-equivalent OD dimension, and estimated age-specific female-male differences in OD levels., Method: The population under study included 12-to-21-year-old non-institutionalized civilian community residents of United States sampled for recent nation-scale surveys. Confidential computer-assisted self-interviews identified newly incident EMPPR users (n = 10,188). Analysis-weighted estimation procedures yielded cumulative incidence proportions for each OD feature, evaluated measurement non-equivalence across subgroups, and estimated female-male differences age-by-age., Results: (1) Tolerance and salience ('spending a lot of time') are most common OD features. (2) Measurement non-equivalence (bias) was found across sex- and onset-age groups. (3) With biasing features removed, we can see elevated OD levels for female new initiates, age-by-age. Subsidiary analyses suggested possibly accelerated progression toward higher OD levels when extra-medical PPR use starts before age 18., Conclusions: Dimensional approaches to OD and other drug use disorders have gained popularity but can be fragile when differential measurement biases are left uncontrolled. This study's bias-corrected dimensional view of female-male differences shows elevated OD levels among newly incident female EMPPR users relative to new male initiates. Future studies can check for accelerated progression to higher OD levels when EM use starts before age 18 years., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Auricularia auricular could be useful as a candidate for human selenium supplementation. This study examined the effects of exogenous Se on the growth, yield, nutritive value, and mineral accumulation of A. auricular. Selenate or selenite (0.5-40.0 μg g -1 ) had no effect on mycelium morphology or the yield of fruiting bodies. In some cases, they affected the accumulation of inter-elements and significantly decreased the concentrations of copper, iron, and chromium in the Se-enriched fruiting bodies compared to that with control treatments. The polysaccharide (116.5-131.6 μg g -1 ) and protein (105.2-113.4 μg g -1 ) content in Se-enriched fruiting bodies were not significantly different from those observed in the controls (polysaccharide, 114.1 μg g -1 ; protein, 105.6 μg g -1 ). Thus, A. auricular can absorb inorganic Se from the substrate and convert it to organic Se compounds (selenocystine (≥4.1%), selenomethionine (≥91.9%), and Se-methylselenocysteine (≥2.3%))., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: The present study aims to evaluate the effect of cell phone radiation on neutrophil of mice. Materials and methods: 40 male BALB/C mice were randomly divided into four groups as control, blank control, TD-CDMA, and LTE-advanced groups, respectively. Mice were exposed to cell phone radiation for a period of 6 weeks. Then numbers of neutrophil were detected by fully automatic hematology analyzer. Soft agar diffusion method was performed to assess the chemotaxis of neutrophils while the phagocytosis of neutrophils was determined by measuring the staphylococcus albus phagocytosis percentage. Apoptosis was analyzed by flow cytometry. Results: No significant differences were observed among the control and exposure groups regarding the numbers of neutrophils after 2 weeks' exposure to cell phone radiation, while the numbers of neutrophils in TD-SCDMA and LTE-advanced groups were seen to rise after an exposure of 4 or 6 weeks. No effect was observed on chemotaxis of neutrophils due to phone radiation. The phagocytosis of neutrophils was decreased while the apoptosis were increased both in TD-SCDMA and LTE-advanced groups after 6 weeks exposure. Conclusions: Mobile phone radiation could give rise to increase of neutrophil numbers yet with no effect whatever on neutrophils chemotaxis, and the radiation was likely to cause decrease of phagocytosis and induced apoptosis of neutrophils.

Introduction: Owing to widespread roles of miRs, the dysregulation of their expression in human tissues has been linked with the development of several diseases such as cancer. The study was designed to investigate the role and therapeutic potential of miR-1179 in ovarian cancer., Material and Methods: Proliferation rate was monitored by MTT assay. Transfections were performed using Lipofectamine 2000 reagent. Cell cycle apoptosis was detected by AO/EB and annexin V/PI staining. Expressions analysis was carried out by qRT-PCR and western blotting. In vivo evaluation was carried out in xenografted mouse models., Results: The results revealed that miR-1179 is considerably upregulated in ovarian cancer cell lines. Inhibition of miR-1179 triggers decrease in the viability via initiation of apoptotic cell death of ovarian PA-1 cancer cells. TargetScan analysis showed PTEN to be the main target of miR-1179 in PA-1 cells. Exploration of PTEN expression in ovarian cancer cell lines revealed up to 9-fold downregulation of PTEN. However, inhibition of miR-1179 in PA-1 cells resulted in upregulation of PTEN expression. In addition, overexpression of PTEN caused a reduction of PA-1 cell viability via induction of apoptotic cell death. However, silencing of miR-1179 could rescue the effects of miR-1179 inhibition on the proliferation of miR-1179. The miR-1179 suppression was accompanied by a significant decline in phosphorylation of PI3K and AKT expression in the PA-1 cells. The in vivo study showed that miR-1179 suppression inhibits the xenografted tumor growth., Conclusions: The results of this study indicate that miR-1179 may prove to be an important therapeutic target for ovarian cancer., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Termedia & Banach.)

Acute organophosphorus pesticide poisoning (AOPP) is fairly common in rural areas of Asia. The symptoms of AOPP are mainly caused by acetylcholine accumulation. According to the clinical characteristics, AOPP symptoms can fall into the following three categories: muscarinic, nicotinic, and central. Death from fatal poisoning is caused by respiratory paralysis, and neurological complications are common. However, no case of intestinal necrosis caused by AOPP has been reported. Hepatic portal vein gas and pneumatosis intestinalis are considered typical and early imaging manifestations of intestinal necrosis. In this article, we describe a very rare case of computed tomography imaging-proven intestinal necrosis caused by AOPP.

Currently, wireless sensor network (WSN) protocols are mainly used to achieve low power consumption of the network, but there are few studies on the quality of services (QoS) of these networks. Coverage can be used as a measure of the WSN's QoS, which can further reflect the quality of data information. Additionally, the coverage requirements of regional monitoring target points are different in real applications. On this basis, this paper proposes an energy-efficient clustering routing protocol based on a high-QoS node deployment with an inter-cluster routing mechanism (EECRP-HQSND-ICRM) in WSNs. First, this paper proposes formula definitions for information integrity, validity, and redundancy from the coverage rate and introduces a node deployment strategy based on twofold coverage. Then, in order to satisfy the uniformity of the distribution of cluster heads (CHs), the monitoring area is divided into four small areas centered on the base station (BS), and the CHs are selected in the respective cells. Finally, combined with the practical application of the WSN, this paper optimizes the Dijkstra algorithm, including: (1) nonessential paths neglecting considerations, and (2) a simultaneous introduction of end-to-end weights and path weights, achieving the selection of optimal information transmission paths between the CHs. The simulation results show that, compared with the general node deployment strategies, the deployment strategy of the proposed protocol has higher information integrity and validity, as well as lower redundancy. Meanwhile, compared with some classic protocols, this protocol can greatly reduce and balance network energy consumption and extend the network lifetime.

Objective: To investigate whether there were differences in Th17 cells mediated immunological responses among asthmatics with or without allergic rhinitis., Methods: A case-control comparison was conducted in a cohort of 67 children with asthma (AS), 50 children with allergic rhinitis (AR), 52 children with both AS and AR (ASR), 25 infectious rhinitis (IR), and 55 healthy controls (HC). The percentages of circulating Th17 cells were determined by flow cytometry. The Th2- and Th17-related cytokines in plasma and culture supernatants were measured by enzyme-linked immunosorbent assay. The effect of proinflammation cytokine IL-17E on Th2 cytokines production from human T helper (Th) lymphocytes was analyzed., Results: (1) A inter-group comparison revealed that Th17 cells levels were highest in ASR group [(0.89% ± 0.27) %], following by AS group [(0.82 ± 0.29) %] and AR group[(0.78 ± 0.17) %] (P < 0.05). (2) After in-vitro stimulation with house dust mite (HDM) antigen, the levels of IL-4 and IL-17E in culture supernatants of PBMCs from allergic children (AS group, AR group and ASR group) were significantly enhanced. (3) The release of Th2 cytokines from IL-17E treated Th cells of allergic children (AS group, AR group and ASR group) were significantly induced, no similar result was observed in IR group and HC group. CONCLUSIONonclusion: Our findings preliminarily revealed that Th17 cell and its related cytokines might be involved in pathogenesis of airway inflammation diseases, and also presenting varying immunological characteristics among asthmatic children with or without allergic rhinitis.

While localized penile cancers are typically treated surgically and metastatic penile cancers benefit from standard chemotherapy, there have been studies on the horizon demonstrating immunotherapy as a novel approach to metastatic penile cancers that have failed standard chemotherapy. We report a case series of two patients who improved on immunotherapy after progressing with standard chemotherapy regimens. The first case describes a 64-year-old male with a penile mass and significant lymphadenopathy who had surgical resection and adjuvant chemotherapy prior to continued disease progression. He was started on anti-EGFR treatment and improved initially, but he eventually had progression of disease. The second case describes a 79-year-old male with a penile mass who was treated with surgical resection and started on adjuvant chemoradiation, but he developed recurrence and nodal involvement. Therefore, second-line therapy of the PD-L1 inhibitor was started in this patient. There were no available clinical trials for penile cancer patients who progressed beyond the standard surgical therapy and chemotherapy.