Cardiac-Oxidized Antigens Are Targets of Immune Recognition by Antibodies and Potential Molecular Determinants in Chagas Disease Pathogenesis

Trypanosoma cruzi elicits reactive oxygen species (ROS) of inflammatory and mitochondrial origin in infected hosts. In this study, we examined ROS-induced oxidative modifications in the heart and determined whether the resultant oxidized cardiac proteins are targets of immune response and of pathological significance in Chagas disease. Heart biopsies from chagasic mice, rats and human patients exhibited, when compared to those from normal controls, a substantial increase in protein 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), carbonyl, and 3-nitrotyrosine (3-NT) adducts. To evaluate whether oxidized proteins gain antigenic properties, heart homogenates or isolated cardiomyocytes were oxidized in vitro and one- or two-dimensional gel electrophoresis (2D-GE)/Western blotting (WB) was performed to investigate the proteomic oxidative changes and recognition of oxidized proteins by sera antibodies in chagasic rodents (mice, rats) and human patients. Human cardiomyocytes exhibited LD50 sensitivity to 30 µM 4-HNE and 100 µM H2O2 at 6 h and 12 h, respectively. In vitro oxidation with 4-HNE or H2O2 resulted in a substantial increase in 4-HNE- and carbonyl-modified proteins that correlated with increased recognition of cardiac (cardiomyocytes) proteins by sera antibodies of chagasic rodents and human patients. 2D-GE/Western blotting followed by MALDI-TOF-MS/MS analysis to identify cardiac proteins that were oxidized and recognized by human chagasic sera yielded 82 unique proteins. We validated the 2D-GE results by enzyme-linked immunosorbent assay (ELISA) and WB and demonstrated that oxidation of recombinant titin enhanced its immunogenicity and recognition by sera antibodies from chagasic hosts (rats and humans). Treatment of infected rats with phenyl-α-tert-butyl nitrone (PBN, antioxidant) resulted in normalized immune detection of cardiac proteins associated with control of cardiac pathology and preservation of heart contractile function in chagasic rats. We conclude that ROS-induced, cardiac-oxidized antigens are targets of immune recognition by antibodies and molecular determinants for pathogenesis during Chagas disease

Determination of the number of J/ψ events with J/ψ → inclusive decays

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Two-photon widths of the χ c0,2 states and helicity analysis for χ c2→γγ

Based on a data sample of 106×106 ψ ′ events collected with the BESIII detector, the decays ψ ′→γχ c0,2, χ c0,2→γγ are studied to determine the two-photon widths of the χ c0,2 states. The two-photon decay branching fractions are determined to be B(χ c0→γγ)=(2. 24±0.19±0.12±0.08)×10 -4 and B(χ c2→γγ)=(3.21±0.18±0. 17±0.13)×10 -4. From these, the two-photon widths are determined to be Γ γγ(χ c0)=(2. 33±0.20±0.13±0.17)keV, Γ γγ(χ c2)=(0.63±0.04±0. 04±0.04)keV, and R=Γ γγ(χ c2)/ Γ γγ(χ c0)=0.271±0. 029±0.013±0.027, where the uncertainties are statistical, systematic, and those from the PDG B(ψ ′→γχ c0,2) and Γ(χ c0,2) errors, respectively. The ratio of the two-photon widths for helicity λ=0 and helicity λ=2 components in the decay χ c2→γγ is measured for the first time to be f 0/2=Γγγλ= 0(χ c2)/Γγγλ=2(χ c2)=0. 00±0.02±0.02. © 2012 American Physical Society.published_or_final_versio

Search for a light exotic particle in J/psi radiative decays

Using a data sample containing 1.06x10^8 psi' events collected with the BESIII detector at the BEPCII electron-positron collider, we search for a light exotic particle X in the process psi' -> pi^+ pi^- J/psi, J/psi -> gamma X, X -> mu^+ mu^-. This light particle X could be a Higgs-like boson A^0, a spin-1 U boson, or a pseudoscalar sgoldstino particle. In this analysis, we find no evidence for any mu^+mu^- mass peak between the mass threshold and 3.0 GeV/c^2. We set 90%-confidence-level upper limits on the product-branching fractions for J/psi -> gamma A^0, A^0 -> mu^+ mu^- which range from 4x10^{-7} to 2.1x10^{-5}, depending on the mass of A^0, for M(A^0)<3.0 GeV/c^2. Only one event is seen in the mass region below 255 MeV/c^2 and this has a mu^+mu^- mass of 213.3 MeV/c^2 and the product branching fraction upper limit 5x10^{-7}.Comment: 7 pages, 3 figures, submitted to Physical Review

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

The number of resected lymph nodes is associated with the long-term survival outcome in patients with T2 N0 non-small cell lung cancer

Ying-Sheng Wen,1,2,* Ke-Xing Xi,3,* Ke-Xiang Xi,4 Ru-Si Zhang,1,2 Gong-Ming Wang,1,2 Zi-Rui Huang,1,2 Lan-Jun Zhang1,5 1State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People&rsquo;s Republic of China; 2Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, People&rsquo;s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510630, People&rsquo;s Republic of China; 4Department of Obstetrics, Jieyang People&rsquo;s Hospital (Jieyang Affiliated Hospital, Sun Yat-sen University), Jieyang 522000, People&rsquo;s Republic of China; 5Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, People&rsquo;s Republic of China *These authors have contributed equally to this work Objective: For the patients with pathologic T2 N0 non-small cell lung cancer (NSCLC), the extent of lymph node (LN) removal required for survival is controversial. We aimed to explore the prognostic significance of examined LNs and to identify how many nodes should be examined.Methods: We reviewed 549 patients who underwent pulmonary or pneumonectomy surgery or plus lymphadenectomy who were confirmed as T2 stage and LN negative by postoperative pathological diagnosis. According to Martingale residuals of the Cox model, the patients were classified into four groups by the number of examined LNs (1&ndash;2 LNs, 3&ndash;7 LNs, 8&ndash;11 LNs, and &ge;12 LNs). Kaplan&ndash;Meier analysis and Cox regression analysis were used to evaluate the association between survival and the number of examined LNs.Result: Compared with the 1&ndash;2 LNs, 3&ndash;7 LNs, and 8&ndash;11 LNs groups, the survival was significantly better in the &ge;12 LNs group. The 5-year cancer-specific survival rate was 60.5% for patients with 1&ndash;2 negative LNs, compared with 68.7%, 72.6%, and 78.4% for those with 3&ndash;7, 8&ndash;11, and &gt;11 LNs examined, respectively. The 7-year cancer-specific survival rate was 52.9% for patients with 1&ndash;2 negative LNs, compared with 63.7%, 63.8%, and 70.8% for those with 3&ndash;7, 8&ndash;11, and &gt;11 LNs examined, respectively (P=0.045). There was a significant drop in mortality risk with the examination of more LNs. The lowest mortality risk occurred in those with 32 or more LNs examined. Multivariate analysis showed that age and the number of examined LNs were strong independent predictors of survival.Conclusion: The number of examined LNs is a strong independent prognostic factor. Our study demonstrates that patients with T2 N0 NSCLC should have at least 12 LNs examined and that the results of this study may provide information for the optimal number of resected LNs in surgery. Keywords: number of resected lymph nodes, non-small cell lung cancer, survival outcom

Epidemiology and Clinical Characteristics of Seasonal Human Coronaviruses in Children Hospitalized in Hebei Province, China Before and During the COVID-19 Pandemic

Meng-Chuan Zhao,1 Chan Wen,2 Ling Sun,2 Su-xia Duan,1 Ke-xin Zang,3 Le Wang,1 Xiao-Wei Cui4 1Department of Laborotory Medicine, Children’s Hospital of Hebei Province, Shijiazhuang, People’s Republic of China; 2Department of Medical, Children’s Hospital of Hebei Province, Shijiazhuang, People’s Republic of China; 3Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Children’s Hospital of Hebei Province, Shijiazhuang, People’s Republic of ChinaCorrespondence: Xiao-Wei Cui, Children’s Hospital of Hebei Province, No. 133 of JianHua Street, Shijiazhuang, 050031, People’s Republic of China, Tel +86 18503292016, Fax +86 031185911109, Email [email protected]: This study aimed to assess the impact of the COVID-19 pandemic on the prevalence and clinical characteristics of seasonal human coronavirus (HCoV) infections among children hospitalized in Hebei, China.Methods: We examined nasopharyngeal aspirate (NPA) specimens for seasonal HCoVs from January 2018 to December 2021, at the Children’s Hospital of Hebei Province. We used a GeXP-based multiplex reverse transcription PCR assay for the detection of 11 common respiratory viruses (including seasonal HCoVs), chlamydia, and Mycoplasma pneumoniae. The demographic and clinical characteristics of children who tested positive for seasonal HCoVs were recorded and analyzed.Results: A total of 377 (1.96%) of the 19,248 specimens from 2018 to 2019 and 263 (1.96%) of the 13,426 specimens from 2020 to 2021 exhibited seasonal HCoVs. Compared to 2018 and 2019, the positive rate of seasonal HCoVs was lower from January to July of 2020 and increased beginning in August 2020, peaking in the autumn and winter. In 2020– 2021, nasal blockage and swollen adenoids were detected more frequently in children who tested positive for seasonal HCoVs. During 2018– 2019, however, the duration of fever was significantly longer, and cough and dyspnea were more prominent among children who had fallen ill. In addition, seasonal HCoV-positive patients in 2018– 2019 were more likely to experience complications, had a higher risk of severe community-acquired pneumonia (CAP), and had a tendency to require a longer hospital stay than patients in 2020– 2021.Conclusion: According to our findings, there were significant changes in the epidemiology of seasonal HCoVs in Hebei, China during the COVID-19 pandemic, and children infected with seasonal HCoVs usually experienced milder clinical symptoms during the pandemic than before it.Keywords: children, clinical characteristics, COVID-19 pandemic, epidemiology, Seasonal human coronaviru