Explore the vast range of titles available.

Optical imaging probes allow us to detect and uncover the physiological and pathological functions of an analyte of interest at the molecular level in a non-invasive, longitudinal manner. By virtue of simplicity, low cost, high sensitivity, adaptation to automated analysis, capacity for spatially resolved imaging and diverse signal output modes, optical imaging probes have been widely applied in biology, physiology, pharmacology and medicine. To build a reliable and practically/clinically relevant probe, the design process often encompasses multidisciplinary themes, including chemistry, biology and medicine. Within the repertoire of probes, dual-locked systems are particularly interesting as a result of their ability to offer enhanced specificity and multiplex detection. In addition, chemiluminescence is a low-background, excitation-free optical modality and, thus, can be integrated into dual-locked systems, permitting crosstalk-free fluorescent and chemiluminescent detection of two distinct biomarkers. For many researchers, these dual-locked systems remain a ‘black box’. Therefore, this Review aims to offer a ‘beginner’s guide’ to such dual-locked systems, providing simple explanations on how they work, what they can do and where they have been applied, in order to help readers develop a deeper understanding of this rich area of research. Dual-locked optical probes change their optical signals when they respond to two biomarkers of interest. This facilitates real-time imaging of multiple interrelated biomarkers in living systems and, thus, provides opportunities to better understand pathological events and enhanced diagnostic specificity.

In light of this, our study endeavors to illuminate the distinctions in COVID-19 severity between ART-experienced and ART-naïve PLWH through a retrospective case–control analysis. The average age of the ART-naïve group was younger than that of the ART-experienced group (41.52 years old vs. 47.46 years old, t = 2.164, P = 0.032), while there was no significant difference in gender distribution between the two groups. [...]the clinical classification of the two groups also showed significant differences, with a lower percentage of mild and asymptomatic cases (20 [45.45%] vs. 67 [76.14%], χ2 = 12.38, P = 0.001) in ART-naïve group [Supplementary Table 1, http://links.lww.com/CM9/B782]. Ordinal logistic regression indicated that the absence of ART, but not age, SARS-CoV-2 vaccination, comorbidities, and low CD4+ T cell count was a risk factor for the severity of COVID-19 among PLWH, with an OR of 5.06 (95% confidence interval [CI] 1.71–14.92, P = 0.003) [Figure 1A].

HIV-associated cryptococcosis is marked by unpredictable disease trajectories and persistently high mortality rates worldwide. Although improved risk stratification and tailored clinical management are urgently needed to enhance patient survival, such strategies remain limited. We analyzed clinical and immunological data from 98 HIV-related cryptococcosis cases, employing machine learning techniques to model disease severity and predict survival outcomes. Our approach included unsupervised clustering, elastic net regularized Cox regression, and random survival forests. Model performance was rigorously assessed using the C-index, Brier score, Calibration and time-dependent AUC, with validation executed through a comprehensive, multi-replicated nested cross-validation framework. Through cytokine profiling, we identified an immune phenotype characterized by excessive inflammatory response (EXC), associated with greater disease severity, more frequent neurological symptoms, and poorer survival outcomes compared to the other two immune phenotypes, highlighting its potential significance in risk stratification. To further support clinical decision-making, we developed an elastic net regularized Cox regression model, achieving superior predictive accuracy with a mean C-index of 0.78 for 36-month outcomes and a mean Brier score of 0.13, outperforming both random survival forest and traditional Cox models. Time-dependent AUC analysis validated the model's robustness, with AUC values of 0.84 at 12 months and 0.79 at 36 months, indicating its reliability and potential clinical utility. This study presents comprehensive and multidimensional approaches to overcome the challenges commonly encountered in real-world clinical settings. By applying cytokine-based clustering, we illustrate the potential for more nuanced severity stratification, offering a fresh perspective on disease progression. In parallel, our penalized survival model provides a step forward in personalized risk assessment, supporting informed clinical decisions and customized patient management. These findings suggest promising directions for individualized healthcare solutions, leveraging machine learning to enhance survival predictions in HIV-related cryptococcosis.

Background Anti-PD-1 antibodies have been approved for treating several cancer. However, data regarding the safety and efficacy of these agents in HIV-infected patients with cancer is lacking, because these patients are frequently omitted from clinical trials. Objectives The primary aim of our research is to assess the safety, activity, and long-term outcomes of PD-1 inhibitors in the treatment of HIV-infected patients with advanced cancer. Method We retrospectively analyzed data from HIV-infected patients with advanced cancers who were treated with PD-1 inhibitors at Shanghai Public Health Clinical Center, Shanghai, China. Results Fifteen HIV-infected patients (all are men; asian; median age, 44) with cancer who were treated with chemotherapy and/or combined the other oncology treatments [along with combined antiretroviral therapy (cART)] prior to Sintilimab (12 out of 15) or Nivolumab (1 out of 11) or Camrelizumab (2 out of 11) injection were identified. Eight patients responded to treatment (disease control rate 53.3%), with 1 got partial response (PR) and 7 were stable. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 including anemia, leukopenia, hyperglycemia, granulocytopenia, and thrombocytopenia. Eight patients (53.3%) experienced treatment-related AEs (TRAEs) with grades 3/4including myelosuppression, infection, and neurological disorders. CD4 + T cell count and plasma HIV RNA remained stable throughout the treatment. Conclusions When used in HIV-infected patients with advanced malignancies, PD-1 inhibitors tend to have favorable efficacy, manageable side effects, and no deteriorated impacts on plasma HIV-RNA and CD4 + T cell count.

The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8 + T cells (NCT05129189). 15 participants completed the study. At week 8, CA HIV RNA levels showed a significant increase from baseline, and the values returned to baseline after discontinuing ASC22 and chidamide. The total HIV DNA was only transiently increased at week 4 ( P  = 0.014). In contrast, integrated HIV DNA did not significantly differ from baseline. Increases in the proportions of effector memory CD4 + and CD8 + T cells (T EM ) were observed from baseline to week 24 ( P  = 0.034 and P  = 0.002, respectively). The combination treatment did not succeed in enhancing the function of HIV Gag/Pol- specific CD8 + T cells. Nevertheless, at week 8, a negative correlation was identified between the proportions of HIV Gag-specific T EM cells and alterations in integrated DNA in the T cell function improved group ( P  = 0.042 and P  = 0.034, respectively). Nine adverse events were solicited, all of which were graded 1 and resolved spontaneously. The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs. Further investigations are warranted in the context of analytic treatment interruption.

Herein, we report the evaluation and synthesis of a reaction based fluorescent probe DCM‐Bpin for the detection of peroxynitrite (ONOO−). DCM‐Bpin exhibits selective fluorescence off‐on response for ONOO− over other reactive oxygen species, including H2O2. Moreover, DCM‐Bpin is biocompatible and has been used to visualize exogenous ONOO− in HeLa cells. Turn on the light: A 50‐fold “turn‐on” fluorescence response at 667 nm was observed for DCM‐Bpin upon the addition of ONOO− (0–27 equiv.) using an excitation wavelength of 560 nm.

Background The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. Methods A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. Results Observed plasma cytokine levels before treatment were significantly lower for IL-1RA ( p  < 0.001) and MCP-1 ( p  < 0.05) when in the survivor group. Incorporating plasma levels of IL-1RA, IL-6, and high-risk CURB-65 score demonstrated the highest area under curve (AUC) value (0.96) for predicting 1-year mortality. For 1-, 2- and 3-year predictions, the single-factor model with IL-1RA demonstrated superior performance compared to all multiple-variate models (AUC = 0.95/0.78/0.78). Conclusions IL-1RA is a biomarker for predicting 3-year survival. Further investigations to explore the pathogenetic role of IL-1RA in HIV-associated disseminated cryptococcosis and as a potential therapeutic target are warranted.

This study aimed to describe and compare the epidemiological, demographic, clinical, laboratory and radiological characteristics as well as the complications, treatments, and outcomes of these patients. We retrospectively investigated clinical data of patients with infection (psittacosis) in eight Grade IIIA hospitals of Fujian. Metagenomic next-generation sequencing (mNGS) was used identify in clinical samples of all included patients. A total of 74 patients (39 severe/35 non-severe) was diagnosed with psittacosis, 25 (33.8%) of whom had history of poultry exposure. Common symptoms included high fever (98% [37/74]), fatigue (52.7% [39/74]), and dyspnea (51.4% [38/74]). Common manifestations in imaging included consolidation (89.2%), pleural effusion (77.0%), and air bronchogram (66.2%). Common complications included acute respiratory distress syndrome (55.4% [41/74]), type I respiratory failure (52.7% [39/74]), acute liver injury (41.9% [31/74]), and secondary infection (27.0% [20/74]). The in-hospital mortality rate was 8.11% (6/74). C. infection is represents an underestimated cause of CAP. For SCAP patients with poultry and bird contact history, specimens were encouraged to be sended for mNGS test in time. infection can lead to severe, multiple system involvement, and several complications. mNGS facilitate timely diagnosis of infection.

Summary This study examined low bone mineral density (BMD) prevalence and associated factors among Chinese people living with HIV (PLWH), uncovering a persistent high BMD risk in older individuals, even after adjusting for age and body mass index (BMI). Notably, lopinavir/ritonavir (LPV/r) therapy was linked to reduced BMD, highlighting the imperative need for regular BMD monitoring and interventions in older PLWH. Purpose HIV infection and antiretroviral therapy (ART) have been shown to contribute to lower BMD, resulting in an increased susceptibility to osteopenia and osteoporosis. However, there is limited knowledge about the prevalence of reduced BMD and its associated factors among Chinese PLWH. In this cross-sectional study, we aimed to investigate the prevalence and factors associated with low BMD among PLWH in China. Methods We retrospectively enrolled PLWH and non-HIV volunteers who underwent dual-energy X-ray absorptiometry (DXA) scans to measure bone density. Demographic information, laboratory test results, ART regimens, and treatment duration were collected. Univariate and multiple regression analyses were performed to identify factors influencing abnormal bone mass in PLWH. Results A total of 829 individuals were included in this study, comprising the HIV group ( n  = 706) and the non-HIV group ( n  = 123). The prevalence of low BMD among all PLWH was found to be 13.88% (98 out of 706). However, among PLWH aged 50 years and above, the prevalence increased to 65.32% (81 out of 124). In contrast, control subjects in the same age group had a prevalence of 38.21% (47 out of 123). After adjusting for age and BMI, older PLWH still demonstrated a higher prevalence of low BMD compared to the non-HIV group (68.24% vs 34.94%, P  < 0.001). Multivariate analysis revealed that older age was strongly associated with a higher risk of low BMD among PLWH, with an odds ratio (OR) of 6.28 for every 10-year increase in age in the ART-naïve population (95% confidence intervals [CIs], 3.12–12.65; P  < 0.001) and OR of 4.83 in the ART-experienced population (3.20–7.29, P  < 0.001). Within the ART-experienced group, current LPV/r treatment was associated with an increased risk of low BMD (OR = 3.55, 1.24–10.14, P  < 0.05), along with lower BMI (OR = 0.84, 0.75–0.95, P  < 0.05), and elevated alkaline phosphatase (OR = 1.02, 1.01–1.03, P  < 0.01). Conclusion The prevalence of low BMD is higher among PLWH aged 50 years and above compared to non-HIV individuals. The use of LPV/r for ART is associated with reduced BMD. These findings emphasize the importance of regular monitoring of BMD in older PLWH and the need for appropriate interventions to mitigate the risks of osteopenia and osteoporosis in this population.