The oxygen reduction reaction (ORR) is catalyzed by manganese­(II) porphyrins in the presence of Brønsted acids (HAs). Analyses of the catalytic cyclic voltammetric profiles have permitted the ORR mechanism to be constructed and rate constants to be extracted for both the formation of the initial oxygen adduct and the O–O bond cleavage event for a series of HAs. The dependence of the formation rate constant of the oxygen adduct on reactant concentrations reveals a rate law that is first order in Mn porphyrin and oxygen substrate. A second order dependence in HA is observed for unadorned Mn porphyrin platforms whereas with Mn hangman porphyrin, a proton is provided intramolecular to the oxygen adduct and consequently the HA order is reduced to unity. The stabilization of the oxygen adduct with an additional hydrogen bond from HA engenders a rate-determining step involving O–O bond cleavage, resulting in the rare instance where the activation of the O–O bond is directly observed.

Increased ethnic diversity of physicians is associated with increased access to health care for underserved communities, better anticipation of patient needs, and acceleration of medical research. 1 Similarly, sex concordance between physicians and patients can improve communication and patient satisfaction. 2 Although sex and ethnic diversity of US physicians have both increased over the past several decades, not all clinical specialties have been impacted equally. To better characterize the dermatology field's evolution during this time period, we analyzed sex and ethnicity trends among dermatology residents and compared them with other specialties and medical school graduates over multiple decades. Methods | Thirty-six years of self-reported ethnicity and 19 years of self-reported sex composition data of American College of Graduate Medical Education (ACGME)-registered dermatology, internal medicine, emergency medicine, obstetrics/ gynecology, ophthalmology, general surgery, and orthopedic surgery residents were obtained from the National Graduate Medical Education Census. 3 Similar ethnic and sex composition data of graduating medical school classes were obtained from the Association of American Medical Colleges (AAMC) Data Book. 4 Ethnic groups were defined as white, Asian, African American, Hispanic, or other. Respondents could choose more than 1 category. The categories for sex were male or female. Changes in sex and ethnic compositions were analyzed across the periods for which data were available. Institutional review board approval was waived by the Beth Israel Deaconess Medical Center, because only publicly accessible data was used. Using Stata 14 statistical software (StataCorp), specialtyspecific logistic regression models were constructed to evaluate the proportion of residents across ethnicity and sex groups over time. Demographic differences over time between specialties were evaluated with the likelihood ratio test. To assess recent differences between specialties in sex and ethnic compositions, data from 2011 to 2013 were averaged and binomial proportions were compared using a 2-sample z test. All 2-sided P values <.05 were considered statistically significant.

Background: Although regulatory T cells (Tregs) play crucial roles in the maintenance of immune hemostasis, the numbers of peripheral Tregs in patients with psoriatic arthritis (PsA) remain unclear. We measured these numbers and the efficacy and safety of low-dose interleukin-2 (IL-2) therapy. Methods: We recruited 95 PsA patients, of whom 22 received subcutaneous low-dose IL-2 [0.5 million international units (MIU) per day for 5 days] combined with conventional therapies. The absolute numbers of cells in peripheral CD4+ T cell subsets were measured via modified flow cytometry. Clinical and laboratory indicators were compared before and after treatment. Results: PsA patients had lower peripheral Treg numbers than healthy controls ( p < 0.01), correlating significantly and negatively with the levels of disease indicators ( p < 0.05). Although low-dose IL-2 significantly increased the Th17 and Treg numbers in PsA patients compared with the baseline values, the Treg numbers rose much more rapidly than those of Th17 cells, re-balancing the Th17 and Treg proportions. Low-dose IL-2 combination therapy rapidly reduced PsA disease activities as indicated by the DAS28 instrument, thus the number of tender joints, visual analog scale pain, physician global assessment, the dermatology life quality index score, and the health assessment questionnaire score (all p < 0.05). Conclusion: PsA patients exhibited low Treg numbers. Low-dose IL-2 combination treatment increased these numbers and relieved disease activity without any apparent side effects. Additional studies are required to explore the long-term immunoregulatory utility of IL-2 treatment.

2020) Reticulocalbin-1 knockdown increases the sensitivity of cells to Adriamycin in nasopharyngeal carcinoma and promotes endoplasmic reticulum stress-induced cell apoptosis,

Background Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy. Methods Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan–Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. Results Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients. Conclusions We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

Chronic pain easily leads to concomitant mood disorders, and the excitability of anterior cingulate cortex (ACC) pyramidal neurons (PNs) is involved in chronic pain-related anxiety. However, the mechanism by which PNs regulate pain-related anxiety is still unknown. The GABAergic system plays an important role in modulating neuronal activity. In this paper, we aimed to study how the GABAergic system participates in regulating the excitability of ACC PNs, consequently affecting chronic inflammatory pain-related anxiety. A rat model of CFA-induced chronic inflammatory pain displayed anxiety-like behaviors, increased the excitability of ACC PNs, and reduced inhibitory presynaptic transmission; however, the number of GAD65/67 was not altered. Interestingly, intra-ACC injection of the GABAAR agonist muscimol relieved anxiety-like behaviors but had no effect on chronic inflammatory pain. Intra-ACC injection of the GABAAR antagonist picrotoxin induced anxiety-like behaviors but had no effect on pain in normal rats. Notably, chemogenetic activation of GABAergic neurons in the ACC alleviated chronic inflammatory pain and pain-induced anxiety-like behaviors, enhanced inhibitory presynaptic transmission, and reduced the excitability of ACC PNs. Chemogenetic inhibition of GABAergic neurons in the ACC led to pain-induced anxiety-like behaviors, reduced inhibitory presynaptic transmission, and enhanced the excitability of ACC PNs but had no effect on pain in normal rats. We demonstrate that the GABAergic system mediates a reduction in inhibitory presynaptic transmission in the ACC, which leads to enhanced excitability of pyramidal neurons in the ACC and is associated with chronic inflammatory pain-related anxiety.

Chronic inflammatory pain is a common clinical disease that tends to be associated with negative emotions such as anxiety and depression. The anterior cingulate cortex (ACC) is involved in pain and pain-related anxiety, and γ-aminobutyric acid (GABA)-ergic interneurons play an important role in chronic pain and anxiety. Electroacupuncture (EA) has good analgesic and antianxiety effect, but the underlying mechanisms have not yet been fully elucidated. In this study, we established a chronic inflammatory pain model and observed that this model induced anxiety-like behaviors and decreased the numbers of parvalbumin (PV) and somatostatin (SOM) positive cells. Activation of PV but not SOM interneurons by chemogenetic techniques alleviated anxiety-like behaviors and pain sensation. EA treatment improved pain sensation, anxiety-like behaviors and increased the number of PV- positive cells in the ACC, but did not affect on the number of SOM-positive cells in the ACC. Moreover, specific inhibition of PV interneurons by chemogenetic methods reversed the analgesic and antianxiety effects of EA. These results suggest that EA ameliorates chronic inflammatory pain and pain-related anxiety by upregulating PV but not SOM interneurons in the ACC.

ObjectivesThe Depression Stigma Scale (DSS) is commonly used to assess depression stigma in the general population and in people with depression. The DSS includes two 9-item subscales assumed to measure personal depression stigma (ie, personal perceptions of depression) and perceived depression stigma (ie, perceptions of how others perceive depression). The aim of the present study was to examine its psychometric properties in terms of validity and reliability in Chinese cancer patients.DesignA cross-sectional study design.Participants and settingsThis study focused on 301 Chinese cancer patients recruited from two hospitals in Xi’an, China.MethodsExploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess the factor structure. Internal consistency was assessed using Cronbach’s alpha. To examine concurrent validity, symptoms of depression were used as the criterion.ResultsFor each subscale of the DSS (ie, personal and perceived depression stigma), the EFA and CFA confirmed a two-factor structure: weak-not-sick (ie, perceiving that depression is not a real illness, but rather a sign of weakness) and discrimination (ie, perceiving that depressed people are discriminated against). The Cronbach’s alphas were adequate, ranging from 0.70 to 0.80. Symptoms of depression were positively but weakly correlated to personal and perceived depression stigma.ConclusionsThe DSS appeared to show satisfactory psychometric properties in our sample of cancer patients. Both personal depression stigma and perceived depression stigma subscales consisted of two underlying aspects.