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Previously, two men were cured of HIV-1 through CCR5Δ32 homozygous (CCR5Δ32/Δ32) allogeneic adult stem cell transplant. We report the first remission and possible HIV-1 cure in a mixed-race woman who received a CCR5Δ32/Δ32 haplo-cord transplant (cord blood cells combined with haploidentical stem cells from an adult) to treat acute myeloid leukemia (AML). Peripheral blood chimerism was 100% CCR5Δ32/Δ32 cord blood by week 14 post-transplant and persisted through 4.8 years of follow-up. Immune reconstitution was associated with (1) loss of detectable replication-competent HIV-1 reservoirs, (2) loss of HIV-1-specific immune responses, (3) in vitro resistance to X4 and R5 laboratory variants, including pre-transplant autologous latent reservoir isolates, and (4) 18 months of HIV-1 control with aviremia, off antiretroviral therapy, starting at 37 months post-transplant. CCR5Δ32/Δ32 haplo-cord transplant achieved remission and a possible HIV-1 cure for a person of diverse ancestry, living with HIV-1, who required a stem cell transplant for acute leukemia.

Oxidative stress is closely linked to tumor initiation and development, conferring a survival advantage to cancer cells. Therefore, understanding cancer cells’ antioxidant molecular mechanisms is crucial to cancer therapy. In this study, we discovered that H2O2-induced oxidative stress increased Nrf3 expression in colon cancer cells. Overexpression of Nrf3 decreased H2O2-mediated cytotoxicity and apoptosis. Furthermore, Nrf3 reduced reactive oxygen species levels and malondialdehyde concentrations after H2O2 treatment. Mechanistically, H2O2-mediated cell apoptosis involves multiple signaling proteins, including Akt, bcl-2, JNK, and p38. An increase in Nrf3 expression in colon cancer cells treated with H2O2 partly reversed Akt/Bcl-2 inhibition, whereas it decreased activation of p38 and JNK. In addition, we found that increasing Nrf3 decreased stress-associated chemical-induced cell death, resulting in drug resistance. According to these results, Nrf3 is critical for drug resistance and oxidant adaptation.

Plectin is a cytoskeletal linker of intermediate filaments, encoded by the PLEC gene. Recently, plectin mutations have been identified in a pair of siblings with progressive familial intrahepatic cholestasis. Here, we reported two unrelated infants with plectinopathy causing cholestatic jaundice with novel variants in the PLEC gene. Trio exome sequencing identified compound heterozygous variants in the PLEC gene for each patient: c.71‐11768C>T and c.4331G>T (p.Arg1444Leu) in Patient 1, and c.592C>T (p.Arg198Trp) and c.4322G>A (p.Arg1441His) in Patient 2. Immunofluorescence staining of liver samples from both patients revealed scattered signals of plectin in the cytoplasm of hepatocytes and reduced colocalization of plectin and cytokeratin 8. This study not only underscores the involvement of plectin in cholestasis but also highlights the utility of exome sequencing as a powerful diagnostic tool in identifying genetic underpinnings of infantile cholestasis. [ABSTRACT FROM AUTHOR]

Innovation is vital for sustainable competitiveness and a process that can be trained and managed. Design thinking is an effective approach that helps create innovative solutions and contributes to new product development (NPD). When applied to NPD, how the involvement and intensity of design thinking offers benefits to firms with distinct organisational cultures remained unclear. This study investigates the effect of the use of design thinking in NPD. A hybrid method approach is adopted. First, 35 senior managers from diverse industries in Taiwan are participated in a set of design thinking workshops hosted by the present study. The participants were interviewed after the workshops to investigate design thinking's influences on organisational creativity capacity. This study highlights two key successful factors to enable an effective NPD by design thinking: 1) clarifying bottlenecks against innovation and 2) establishing an open cooperate culture of innovation. Further, a quantitative study was conducted to validate the proposition, stating that by adopting design thinking, firms can improve their innovation in NPD. The correlation between design thinking and organisational culture by industrial types is examined. [ABSTRACT FROM AUTHOR]

Cervical cancer ranks as the fourth most prevalent form of cancer and is a significant contributor to female mortality on a global scale. Pitavastatin is an anti-hyperlipidemic medication and has been demonstrated to exert anticancer and anti-inflammatory effects. Thus, the purpose of this study was to evaluate the anticancer effect of pitavastatin on cervical cancer and the underlying molecular mechanisms involved. The results showed that pitavastatin significantly inhibited cell viability by targeting cell-cycle arrest and apoptosis in Ca Ski, HeLa and C-33 A cells. Pitavastatin caused sub-G1- and G0/G1-phase arrest in Ca Ski and HeLa cells and sub-G1- and G2/M-phase arrest in C-33 A cells. Moreover, pitavastatin induced apoptosis via the activation of poly-ADP-ribose polymerase (PARP), Bax and cleaved caspase 3; inactivated the expression of Bcl-2; and increased mitochondrial membrane depolarization. Furthermore, pitavastatin induced apoptosis and slowed the migration of all three cervical cell lines, mediated by the PI3K/AKT and MAPK (JNK, p38 and ERK1/2) pathways. Pitavastatin markedly inhibited tumor growth in vivo in a cancer cell-originated xenograft mouse model. Overall, our results identified pitavastatin as an anticancer agent for cervical cancer, which might be expanded to clinical use in the future. [ABSTRACT FROM AUTHOR]

ImportanceCombination antiretroviral therapy initiated within several weeks of human immunodeficiency virus (HIV) infection in adults limits proviral reservoirs that preclude HIV cure. Biomarkers of restricted proviral reservoirs may aid in the monitoring of HIV remission or cure.ObjectivesTo quantify peripheral blood proviral reservoir size in perinatally HIV-infected (PHIV+) adolescents and to identify correlates of limited proviral reservoirs.Design, setting, and participantsA cross-sectional study including 144 PHIV+ youths (median age, 14.3 years) enrolled in the United States-based Pediatric HIV/AIDS Cohort Study and receiving durable (median duration, 10.2 years) combination antiretroviral therapy, stratified by age at virologic control.Main outcomes and measuresThe primary end point was peripheral blood mononuclear cell (PBMC) proviral load after virologic control at different ages. Correlations between proviral load and markers of active HIV production (ie, HIV-specific antibodies, 2-long terminal repeat circles) and markers of immune activation and inflammation were also assessed.ResultsProviral reservoir size was markedly reduced in the PHIV+ youth who achieved virologic control before 1 year of age (4.2 [interquartile range, 2.6-8.6] copies per 1 million PBMCs) compared with those who achieved virologic control at 1 to 5 years of age (19.4 [interquartile range, 5.5-99.8] copies per 1 million PBMCs) or after 5 years of age (70.7 [interquartile range, 23.2-209.4] copies per 1 million PBMCs; P

BackgroundEarly initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1 replication and reduces mortality.MethodsPlasma viremia (lower limit of detection,

An infant born to a woman with human immunodeficiency virus type 1 (HIV-1) infection began receiving antiretroviral therapy (ART) 30 hours after birth owing to high-risk exposure. ART was continued when detection of HIV-1 DNA and RNA on repeat testing met the standard diagnostic criteria for infection. After therapy was discontinued (when the child was 18 months of age), levels of plasma HIV-1 RNA, proviral DNA in peripheral-blood mononuclear cells, and HIV-1 antibodies, as assessed by means of clinical assays, remained undetectable in the child through 30 months of age. This case suggests that very early ART in infants may alter the establishment and long-term persistence of HIV-1 infection.

Brassica napus L. (B. napus) is one of the most important oil crops in China, and has high risk of waterlogging stress during its production. The objective of this study is to evaluate the field waterlogging tolerance and screen stable waterlog-ging-resistant germplasm resources. The appropriate waterlogging duration for waterlogging tolerance identification was determined under pot conditions first, and then the comprehensive evaluation and comparison of the waterlogging tolerance of 505 germplasm resources of B. napus were carried out. The stable extreme materials were screened in field experiments. The results showed that the growth of B. napus plants began to be affected after four-day-waterlogging, and severely inhibited after about 10-day-waterlogging under pot conditions. In the two-year field experiment, 27 indexes extracted using the UAV phenotype acquisition platform were converted into two common factors by factor analysis. The common factor 1 represented the growth state of B. napus under waterlogging, and the common factor 2 represented the physiological state. The comprehensive evaluation value of waterlogging resistance (D-value), which was calculated according to the load and variance contribution rate of the two common factors, divided the waterlogging resistance of B. napus germplasm resources into four types, including extremely waterlogging resistant type (Cluster I, 99 materials), waterlogging resistant type (Cluster II, 200 materials), sensitive type (Cluster III, 187 materials), and extremely sensitive type (Cluster IV, 19 materials). In the two-year field experiment, nine stable waterlogging sensitive materials and nine resistant materials were identified, and the results were confirmed by the field experiments in 2022. Moreover, in the two-year experiment, the vegetation indexes, MTVI2D, and MCARI2D had high correlations with the D-value, and the correlation coefficients were greater than 0.76, which can be used for rapid and efficient comprehensive evaluation of B. napus waterlogging resistance. In conclusion, the evaluation system and rapid and comprehensive evaluation methods for waterlogging tolerance of B. napus in the field were established, which were applied to analyze the types of waterlogging tolerance of B. napus germplasm resources and identify the stable waterlogging resistant and sensitive materials in this study, providing reliable evaluation methods and important germplasm resources for the research and genetic improvement of waterlogging resistance of B. napus. [ABSTRACT FROM AUTHOR]

Objectives: Otitis media with effusion (OME) is characterized by the presence of fluid in the middle ear without the presentation of signs or symptoms of acute ear infection. The point prevalence of OME reaches as high as 60% in children younger than 2 years of age. We used the National Health Insurance Research Database (NHIRD) to investigate the use of medication in children with OME before receiving ventilation tube insertion (VTI). Methods: Data of pediatric patients (age ≤ 12 years) who had OME and received VTI from January 1, 2011, to December 30, 2012, were retrieved from the Taiwan NHIRD. We surveyed the use of 4 medications to understand whether health care providers achieved the standards of medication use recommended by clinical practice guidelines. Results: This study examines the factors affecting the use of medication for pediatric OME. Overall, according to the study's operational definitions, the use of systemic antibiotics was most common (59.9%), followed by systemic antihistamines (23.4%), systemic steroids (8.8%), and intranasal steroids (9.6%). Systemic antibiotics use was associated with 12 factors. Ten of the 12 factors increase the use of systemic antibiotics, including namely age (age > 2 years), comorbidities, teaching hospital, and community hospital. In contrast, namely catastrophic illness and watchful waiting are the 2 factors that decrease systemic antibiotics use. For the use of systemic antihistamines, systemic steroids, and intranasal steroids were related to 6, 5, and 2 factors, respectively. Conclusions: The rate of drug use differs from the rate of use recommended by commonly used clinical practice guidelines. We found that the higher the number of factors that influenced the patients' drug use, the higher the rate of drug use. According to these results, drafting a treatment guideline for OME patients in accordance with current clinical practices in Taiwan is highly recommended. [ABSTRACT FROM AUTHOR]