Multiple intracellular pathogen infections with ocular pathologies associated with adult-onset immunodeficiency due to anti-interferon-γ autoantibodies: a case report.

BACKGROUND: Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus-negative patient. CASE PRESENTATION: A middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders. CONCLUSIONS: High-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels.

Clinical Characteristics, Course, and Long-Term Outcomes in Patients with Talaromyces marneffei Infection: A 10-Year Retrospective Cohort Study.

INTRODUCTION: Talaromyces marneffei (T. marneffei), a dimorphic fungus, causes local or disseminated infection in humans. We aimed to analyze the clinical characteristics, prognostic factors, and survival outcomes of patients with T. marneffei infection and compare the differences between human immunodeficiency virus (HIV)-positive and HIV-negative subgroups. METHODS: We retrospectively analyzed 241 patients with T. marneffei infection at the First Affiliated Hospital of Guangxi Medical University between January 2012 and January 2022. The overall population was stratified into HIV-positive (n = 98) and HIV-negative (n = 143) groups according to HIV status. Kaplan-Meier analysis and multivariate Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: With a median follow-up time of 58.9 months, 120 patients (49.8%) experienced disease progression and 85 patients (70.8%) died. The 5-year rates of OS and PFS were 61.4% (95% CI 55.0-68.6%) and 47.8% (95% CI 41.5-55.1%), respectively. As an independent factor, patients who were HIV positive had better PFS (HR 0.50, 95% CI 0.31-0.82; p < 0.01) than patients who were HIV negative. Compared with patients who were HIV positive, patients who were HIV negative were older and had more probabilities of underlying diseases, chest involvement, bone destruction, and higher count of neutrophils (all p < 0.05). Hemoglobin (PFS: HR 0.62; 95% CI 0.39-1.00; p < 0.05; OS: HR 0.45; 95% CI 0.22-0.89; p = 0.02) and lymphocyte count (PFS: HR 0.06; 95% CI 0.01-0.26; p < 0.01; OS: HR 0.08; 95% CI 0.01-0.40; p < 0.01) were independent prognostic factors for PFS and OS in patients who were HIV negative. CONCLUSIONS: Patients with T. marneffei infection have a poor prognosis. Patients who are HIV positive and HIV negative have relatively independent clinical characteristics. Multiple organ involvement and disease progression are more common in patients who are HIV negative.

Modified cellulose nanofibers aerogels as a novel air filters; Synthesis and performance evaluation.

Nanofilters made with high adsorption freeze-dried modified cellulose nanofiber (CNF) aerogel were produced. The modification was made using functional groups containing phthalimide, and then their ability to adsorb particulate matter (PM) was evaluated and compared with the control filter (HEPA). The results showed that the highest adsorption of PM2.5 (99.95%) belonged to the nanofilters made of 1.5% phthalimide-modified CNF aerogel, and the lowest adsorption (76.66%) was related to the control samples. Moreover, based on the results, the nanofilter produced from freeze-dried phthalimide-modified CNF aerogel showed high filtration efficiency as well as excellent resistance to temperature and humidity. This modification enables the filter to operate in different environmental conditions, especially for particles less than 0.1 µm that are mainly responsible for reducing air quality, human health, air visibility, and climate change. In conclusion, we developed an environmentally friendly biodegradable nanofilter capable of high-performance filtration functions and structural stability in different environmental conditions.

Preparation and characterization of air nanofilters based on cellulose nanofibers.

One of the most important environmental issues in the world today is the problem of air pollution, which includes particulate matter (PM) and greenhouse gases (mainly CO2). The production of efficient sustainable filters to overcome this concern as well as to provide an alternative to synthetic petroleum-based filters remains a demanding challenge. The purpose of this research was to first produce novel cellulose nanofibers (CNF) based nanofilter from a combination of CNF and chitosan (CS) and then evaluate its applicability for air purification. A number of structural and chemical properties as well as CO2 and PM adsorption efficiency of the modified CNF, were determined using advanced characterization techniques. After pretests, we determined the optimum loading for the CS was 1 wt%, and upon producing the samples, the CNF loadings (1, 1.5, and 2 wt%) were chosen as one variable. For particle absorption, the PM sizes (0.1, 0.3, 0.5, and 2.5 µm) were kept as other variables. Based on SEM results, we concluded the higher the concentration of CNF the higher the specific surface area and the lower the porosity and the diameter of the pores, which was confirmed by the BET test. Furthermore, the results showed that increasing the concentration of modified CNFs increases the adsorption rate of CO2 and PM and that the highest adsorption of CO2 and PM belonged to the 2% modified CNF.

Polyethersulfone membrane embedded with amine functionalized microcrystalline cellulose.

In this investigation, microcrystalline cellulose (MCC) was functionalized with metformin HCl using (3-chloropropyl)triethixysilane (CPTES) as a coupling agent. Polyethersulfone (PES) membranes were incorporated with different concentrations of modified MCC (MMCC) to enhance its affinity for heavy metals during filtration of aqueous solutions. The composite membranes were characterized via fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), atomic force microscopy (AFM), Brunauer-Emmett-Teller (BET) method, porosity and contact angle measurements and mechanical analysis. The presence of MMCC in the host matrix was confirmed by FTIR. Although composites decomposed at lower temperatures, their thermal stability was sufficient to meet their performance requirements. DSC showed enhanced glass transition temperature (Tg) due to the interfacial interactions between membrane constituents which restrict the mobility of polymer chains. Microscopic imaging revealed higher surface roughness of composites compared to neat PES. Inclusion of MMCC increased the porosity and hydrophilicity of the membrane which consequently, higher permeability can be achieved.

Enhancing the Freeze-Thaw Durability of Concrete through Ice Recrystallization Inhibition by Poly(vinyl alcohol).

Frost weathering of porous materials caused by seasonal temperature changes is a major source of damage to the world's infrastructure and cultural heritage. Here we investigate poly(vinyl alcohol) (PVA) addition as a means to enhance the freeze-thaw durability of concrete without compromising its structural or mechanical integrity. We evaluate the ice recrystallization inhibition activity of PVA in a cementitious environment and the impact of PVA on key structural and mechanical properties, such as cement hydration (products), microstructure, strength, as well as freeze-thaw resistance. We find that a low amount of PVA significantly reduces the surface scaling of concrete and displays excellent ice recrystallization inhibition in the saturated Ca(OH)2 solution, which has a similar pH value as cement pore solution, while it does not affect cement hydration, microstructure, nor its mechanical properties. These findings contribute to new insights on the freeze-thaw damage mechanism, and more importantly, we disclose a new direction for the design of concrete with excellent freeze-thaw resistance.

Stromal score as a prognostic factor in primary gastric cancer and close association with tumor immune microenvironment.

BACKGROUND: Gastric cancer remains one of the major causes for tumor-related deaths worldwide. Our study aimed to provide an understanding of primary gastric cancer and prompt its clinical diagnosis and treatment. METHODS: We integrated the expression profiles and overall survival information of primary gastric cancer in TCGA and GEO database and estimated the stromal score of each sample by the estimate R package. Stromal score and clinicopathologic characteristics associated with overall survival were analyzed by using Cox regression and the Kaplan-Meier method. Gene set enrichment analysis (GSEA) and KEGG analysis were performed to explore the potential molecular mechanism in TCGA dataset. The relationship between immunotherapy-associated markers or immune cell types and stromal score was explored by using Pearson correlation analysis. RESULTS: A total of 796 samples were collected for the analysis. Patients with stromal score-high showed poor overall survival (P < .01, HR: 1.407, 95% CI: 1.144-1.731) and identified as an independent prognostic factor. KEGG analysis revealed that stromal score actively involved in diverse tumor-associated pathways. GSEA analysis also revealed stromal score associated with diverse immune-related biological processes. Furthermore, stromal score was related with immunotherapy-associated markers and multiple immune cells. CONCLUSION: Our results showed that stromal score could serve as a potential prognostic biomarker in primary gastric cancer and play an important role in the recognition, surveillance, and prognosis of gastric cancer.

A novel immune-related genes prognosis biomarker for melanoma: associated with tumor microenvironment.

BACKGROUND: Melanoma is a cancer of the skin with potential to spread to other organs and is responsible for most deaths due to skin cancer. It is imperative to identify immune biomarkers for early melanoma diagnosis and treatment. RESULTS: 63 immune-related genes of the total 1039 unique IRGs retrieved were associated with overall survival of melanoma. A multi-IRGs classifier constructed using eight IRGs showed a powerful predictive ability. The classifier had better predictive power compared with the current clinical data. GSEA analysis showed multiple signaling differences between high and low risk score group. Furthermore, biomarker was associated with multiple immune cells and immune infiltration in tumor microenvironment. CONCLUSIONS: The immune-related genes prognosis biomarker is an effective potential prognostic classifier in the immunotherapies and surveillance of melanoma. METHODS: Melanoma samples of genes were retrieved from TCGA and GEO databases while the immune-related genes (IRGs) were retrieved from the ImmPort database. WGCNA, Cox regression analysis and LASSO analysis were used to classify melanoma prognosis. ESTIMATE and CIBERSORT algorithms were used to explore the relationship between risk score and tumor immune microenvironment. GSEA analysis was performed to explore the biological signaling pathway.

A promising process to modify cellulose nanofibers for carbon dioxide (CO2) adsorption.

A novel process of using phthalimide to modify cellulose nanofibers (CNF) for CO2 adsorption was studied. The effectiveness of the modification was confirmed by ATR-IR. Phthalimide incorporation onto CNF was confirmed with the characteristic peaks of NH2, C-N, and ester bonding COO- was observable. The XPS analyses confirmed the presence of N1s peak in Ph-CNF, meaning that the hydroxyl groups reacted with the amino groups (NH2) of phthalimide on the CNF surface. Based on the results, surface modification and addition of phthalimide increased the specific surface area, but also decreased the overall porosity, size of pores and volume of pores. When the temperature, humidity, pressure, and airflow rate increased, the CO2 adsorption significantly increased. The CO2 adsorption of phthalimide-modified CNF was confirmed by ATR-IR spectroscopy as the characteristic peaks of HCO3-,NH3+ and ester bonding NCOO- were visible on the spectra.

Photocatalytic performance and dispersion stability of nanodispersed TiO2 hydrosol in electrolyte solutions with different cations.

The existence of electrolytes in aquatic environment on the photocatalytic performance and coagulation of nanodispersed TiO2 hydrosol and the corresponding photocatalytic alteration were investigated by studying cations (Na+, K+, Ca 2+, Mg2+, and Al3+). The photocatalysis reactions of nano TiO2 with different dosages of electrolytes were measured by monitoring the degradation of Rhodamine B (RhB) under ultraviolet A (UV-A) irradiation over time. The results showed that the photocatalytic performance of TiO2 was improved by the presence of Al3+, while the performance was impaired by the other tested cations. The negative influences of divalent ions on the photocatalytic performance of TiO2 were more significant than monovalent ions. The TiO2 sol dispersed stable at nano scale at low concentration of electrolyte (<0.01 mol/L) with slight change of pH, and coagulated into micro sizes at high concentration of electrolytes (>0.1 mol/L) with larger increase or decrease of pH. The positive effects of Al3+ on the photodegradation rate of RhB might relate to the strong hydrolytic action of Al3+ in aquatic solutions. The photocatalytic processes of TiO2 in the presence of all ions followed the Langmuir-Hinshelwood model, and the reaction kinetic constant was increased with the decrease of pH caused by different cations. These work suggested a new perspective about the relationship between coagulation and photocatalytic performance of TiO2 hydrosols in electrolyte with hydrolysable cations, which demonstrated that TiO2 hydrosols may be suitable as photocatalysts in aquatic environments.

Effects of sarpogrelate hydrochloride on peripheral arterial disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of our study was to assess the efficacy and safety of sarpogrelate hydrochloride by comparing the effects of sarpogrelate with conventional treatment on the improvement of symptoms in PAD patients. METHODS: The search was conducted in PubMed, Embase, Cochrane library database, CNKI, CBM for relevant randomized controlled trials (RCTs) before January 1st, 2019. Inclusion and exclusion of studies, assessment of quality, outcome measures, data extraction and synthesis were completed by two reviewers independently. The meta-analysis was performed with RevMan 5.3. RESULTS: Totally, 12 eligible RCTs were included in our analysis. Comparing the results of sarpogrelate group and control group, sarpogrelate significantly improved ankle-brachial index (ABI) levels (SMD = 0.05, [95%CI 0.20 to 0.74, P = .0005]), dorsalis pedis artery blood flow (MD = 0.16, [95%CI 0.09 to 0.23, P < .001]) and pain-free walking distance (PFWD) (MD = 201.86, [95%CI 9.34 to 394.38, P = .04]). The pooled analysis showed that a significant decrease in hsCRP (MD = -0.57, [95%CI -1.12 to -0.02, P = .04]) and IL-6 (MD = 1.48,[95%CI 0.39 to 2.56, P = .008]) was observed in the sarpogrelate treatment. CONCLUSION: Sarpogrelate was effective for improving the symptoms of PAD and showed good tolerability without significant adverse events.

Clinical outcomes of BRAF plus MEK inhibition in melanoma: A meta-analysis and systematic review.

BACKGROUND: Melanoma is a potentially fatal malignancy with poor prognosis. Several recent studies have demonstrated that combination therapy of BRAF and MEK inhibition achieved better curative effect and appeared less toxic effects. We conducted a meta-analysis to evaluate the efficacy and safety between BRAF inhibition plus MEK inhibition combination therapy and BRAF inhibition monotherapy in melanoma patients. METHODS: We performed the search in PubMed, EMBASE, and the Cochrane Library from January 2010 to January 2019. Inclusion and exclusion of studies, assessment of quality, outcome measures, data extraction, and synthesis were independently accomplished by two reviewers. Revman 5.3 software was used for the meta-analysis. RESULTS: Totally, seven randomized controlled trials involving 3146 patients met our inclusion criteria. Comparing the results of combination therapy and monotherapy, combination therapy significantly improved OS (RR = 1.13; 95% CI, 1.08, 1.19; P < 0.00001), ORR (RR = 1.36; 95% CI, 1.28, 1.45; P < 0.00001), PFS (RR = 0.57; 95% CI, 0.52, 0.63; P < 0.00001) and reduced deaths (RR = 0.78; 95% CI, 0.69, 0.88; P < 0.0001). Skin-related adverse events such as hyperkeratosis, cutaneous squamous-cell carcinoma were less compared with monotherapy. However, gastrointestinal events like nausea, diarrhea, and vomiting were at a higher frequency. CONCLUSION: Doublet BRAF and MEK inhibition achieved better survival outcomes over single-agent BRAF inhibition and occurred less skin-related events, but gastrointestinal events were more in combination therapy.

Amine functionalization of microcrystalline cellulose assisted by (3-chloropropyl)triethoxysilane.

To improve the heavy metal adsorption of microcrystalline cellulose (MCC), two successive grafting reactions of silylation by (3-chloropropyl)triethoxysilane (CPTES) and amine-functionalization with metformin HCl were performed and the modified MCC from the first and second steps were denoted as MMCC-1 and MMCC-2, respectively. MMCCs were characterized by fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) and compared to MCC. The presence of the amine group on the MMCC-2 surface was confirmed by FT-IR analysis. According to the XRD results, the crystallinity index (CI) of MMCC-1 increased very slightly compared to that of MCC that can be attributed to the partial hydrolysis of amorphous parts because of acidic conditions used for MCC silylation but CI of MMCC-2 decreased due to the high temperature and long time in the 2nd step of modification. TGA revealed the lower thermal stability of MMCC-2 than the corresponding MCC.