Pathogen spectrum and immunotherapy in patients with anti-IFN-γ autoantibodies: A multicenter retrospective study and systematic review

BackgroundAnti-interferon-γ autoantibody (AIGA) positivity is an emerging immunodeficiency syndrome closely associated with intracellular infection in individuals without human immunodeficiency virus (HIV). However, the information on epidemiology, pathogen spectrum, and immunotherapy among these patients lack a systematic description of large data.MethodsThis systematic literature review and multicenter retrospective study aimed to describe the pathogen spectrum and review treatment strategies among patients with AIGA positivity.ResultsWe included 810 HIV-negative patients with AIGA positivity infected with one or more intracellular pathogens. Excluding four teenagers, all the patients were adults. The most common pathogen was nontuberculous mycobacteria (NTM) (676/810, 83.5%). A total of 765 NTM isolates were identified in 676 patients with NTM, including 342 (44.7%) rapid-grower mycobacteria, 273 (35.7%) slow-grower mycobacteria, and 150 (19.6%) unidentified NTM subtype. Even with long-term and intensive antimicrobial treatments, 42.6% of patients with AIGA positivity had recurrence and/or persistent infection. Sixty-seven patients underwent immunoregulatory or immunosuppressive therapy, and most (60) achieved remission. The most common treatment strategy was rituximab (27/67, 40.3%) and cyclophosphamide (22/67, 32.8%), followed by cyclophosphamide combined with glucocorticoids (8/67, 11.9%).ConclusionsIntracellular pathogen was the most common infection in patients with AIGA positivity. The predominant infection phenotypes were NTM, varicella-zoster virus, Talaromyces marneffei, and Salmonella spp., with or without other opportunistic infections. AIGA immunotherapy, including rituximab or cyclophosphamide, has yielded good preliminary results in some cases

The complete chloroplast genome of Rhus punjabensis var. sinica

Rhus punjabensis var. sinica belongs to the family Anacardiaceae in the order Sapindales. In this study, we first reported the complete chloroplast genome sequence of R. punjabensis var. sinica. The cp genome was sequenced on Illumina Hiseq 2000 platform. The sequence was found to be 159,617 bp in length with 37.9% GC contents, including a large single-copy region of 87,694 bp, a small single-copy region of 18,971 bp, and a pair of inverted repeats of 26,476 bp. The chloroplast genome of R. punjabensis var. sinica contains 133 genes, including 86 protein-coding genes, 8 rRNA genes, and 2 pseudogenes identified by CPGAVAS2 and BLAST search, and 37 tRNA genes annotated by tRNAscan-SE. Maximum-likelihood (ML) phylogenetic analysis showed that R. punjabensis var. sinica was sister to Rhus potaninii

The complete chloroplast genome sequence of Iris tectorum

The complete chloroplast genome sequence of Iris tectorum Maximowicz, assembled with Illumina NovaSeq 6000 system platform sequencing data, was reported. The total length of the chloroplast genome of I. tectorum is 153,253 bp and its GC content is 37.89%. The complete chloroplast genome has four distinct parts a large single copy region (82,833 bp), a small single copy region (18,562 bp), and a pair of inverted repeats (25,929 bp). The chloroplast genome includes 86 protein-coding genes, 8 rRNAs and 38 tRNAs genes. A phylogenetic tree showed that I. tectorum is close to Iris missouriensis

The complete chloroplast genome sequence of Rhus potaninii

We reported the complete chloroplast genome sequences of Rhus potaninii which was characterized by de novo assembly with Illumina sequencing data. The size of R. potaninii complete chloroplast genome is 159,620 bp in length and includes a large single copy region of 87,722 bp, a small single copy region of 18,948 bp, and a pair of inverted repeats of 26,475 bp. Its GC content is 37.9%. A total of 133 genes were predicted, including 86 protein-coding genes, 8 rRNA genes, 37 tRNA genes, and 2 pseudogenes. Maximum-likelihood (ML) phylogenetic tree indicates that R. potaninii is sister to R. chinensis

ATR and p-ATR are emerging prognostic biomarkers and DNA damage response targets in ovarian cancer

Background: Although ataxia-telangiectasia and Rad3 related (ATR) has an established role in the DNA damage response of various cancers, its clinical and prognostic significance in ovarian cancer remains largely unknown. The aims of this study were to assess the expression, function, and clinical prognostic relationship of ATR and phospho-ATR ser428 (p-ATR) in ovarian cancer. Methods: We confirmed ATR and p-ATR expression by immunohistochemistry (IHC) in a unique ovarian cancer tissue microarray constructed of paired primary, recurrent, and metastatic tumor tissues from 26 individual patients. ATR-specific small interfering RNA (siRNA) and ATR inhibitor VE-822 were applied to determine the effects of ATR inhibition on ovarian cancer cell proliferation, apoptosis, and DNA damage. ATR expression and the associated proteins of the ATR/Chk1 pathway in ovarian cancer cell lines were evaluated by Western blotting. The clonogenicity was also examined using clonogenic assays. A three dimensional (3D) cell culture model was performed to mimic the in vivo ovarian cancer environment to further validate the effects of ATR inhibition on ovarian cancer cells. Results: We show recurrent ovarian cancer tissues express higher levels of ATR and p-ATR than their patient-matched primary tumor counterparts. Additionally, higher expression of p-ATR correlates with decreased survival in ovarian cancer patients. Treatment of ovarian cancer cells with ATR specific siRNA or ATR inhibitor VE-822 led to significant apoptosis and inhibition of cellular proliferation, with reduced phosphorylation of Chk1 (p-Chk1), Cdc25c (p-Cdc25c), Cdc2 (p-Cdc2), and increased expression of cleaved PARP and γH2AX. Inhibition of ATR also suppressed clonogenicity and spheroid growth of ovarian cancer cells. Conclusion: Our results support the ATR and p-ATR pathway as a prognostic biomarker, and targeting the ATR machinery is an emerging therapeutic approach in the treatment of ovarian cancer

Uniform Carbon Coating on Silicon Nanoparticles by Dynamic CVD Process for Electrochemical Lithium Storage

A uniform carbon layer was coated on Si nanoparticles by the dynamic chemical vapor deposition (CVD) process with toluene as the carbon source. The carbon layer thickness could easily be adjusted by controlling the preparation conditions. Samples selected from different positions of the reaction tube showed a small deviation in carbon content. As an anode material for a lithium-ion battery, the resulting Si@C composites exhibited better cycle reversibility and rate capability than pristine Si. The Si@C-2 sample (carbon layer thickness ≈ 12 nm) delivered a relatively stable specific capacity of ca. 1600 mA h g^–1 at 0.3 A g^–1 for 70 cycles. Its capacity remained at 750 mA h g^–1 at 5 A g^–1, compared with 240 mA h g^–1 for pristine Si. Acetylene as a carbon source can also lead to superior cycle stability. This reformative CVD process provides an avenue for the large-scale production of uniform carbon coating materials used for batteries and other devices

Patients with advanced cancer were treated with immune checkpoint inhibitors and injected with COVID-19 vaccine to improve their prognosis without increasing pancreatic related adverse events

To investigate immune checkpoint inhibitors (ICIs) induced pancreatic injury (ICIPI), the prognostic effect of COVID-19 vaccine on cancer patients, and whether COVID-19 vaccine increases the incidence of ICIPI. We conducted a retrospective study of 256 stage IV cancer patients treated with ICIs at The First Affiliated Hospital of Anhui Medical University from January 2020 to November 2022. Data collected included pancreatic enzyme levels, treatment outcomes, and vaccination status. Statistical significance was determined using the χ2 test and Kaplan-Meier method (p < .05). Compared to the control group, the vaccinated group (p < .0001) and the group with elevated pancreatic enzyme levels (p = .044) demonstrated higher disease control rates, indicating a direct benefit of vaccination and enzyme monitoring on treatment outcomes. Additionally, vaccinated patients demonstrated longer overall survival versus unvaccinated patients (23.9 months [95% CI, 22.3–25.5] vs 23.6 months [95% CI, 21.1–26.2], HR = 0.45 [95% CI, 0.24–0.86], p = .015) and progression-free survival (17.2 months [95% CI, 14.3–20.1] vs 13.7 months [95% CI, 11.3–16.1], HR = 0.54 [95% CI, 0.36–0.82], p = .004). Importantly, the analysis revealed no significant association between vaccination and pancreatic injury (p = .46). Monitoring pancreatic enzymes can effectively evaluate the therapeutic impact in patients using ICIs. Patients vaccinated against COVID-19 experience better immunotherapy outcomes without an increased risk of ICIPI

Decreased Expression of TGR5 in Vogt-Koyanagi-Harada (VKH) Disease

Purpose: To investigate the role of G-protein-coupled bile acid receptor-1, Gpbar1 (TGR5) in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. Methods: The mRNA level of TGR5, iNOS, Arg1, CD16, and CD206 in macrophages was assayed by real-time PCR. ELISA was used to detect the production of cytokines in cell culture supernatants. The frequencies of CD4+IFN-γ+ and CD4+ IL-17+ T cells were tested by flow cytometry. Results: A decreased expression of TGR5 in M1 macrophages was observed in active VKH patients as compared with normal controls. TGR5 stimulation of M1 macrophages with INT-777 caused a shift of the inflammatory M1 toward the anti-inflammatory M2 macrophage subtype. TGR5 activation of macrophages co-cultured with CD4+ T cells inhibited Th1 and Th17 polarization, as well as the release of IFN-γ and IL-17 in the culture supernatant. Conclusion: Our results show that a decreased TGR5 expression might contribute to the pathogenesis of VKH disease.</p