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1.
Adv Sci (Weinh) ; : e2404756, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39377228

ABSTRACT

Hepatocellular carcinoma (HCC) often occurs in the context of fibrosis or cirrhosis. Methylation of histone is an important epigenetic mechanism, but it is unclear whether histone methyltransferases are potent targets for fibrosis-associated HCC therapy. ASH1L, an H3K4 methyltransferase, is found at higher levels in activated hepatic stellate cells (HSCs) and hepatoma cells. To determine the role of ASH1L in vivo, transgenic mice with conditional Ash1l depletion in the hepatocyte cell lineage (Ash1lflox/floxAlbcre) or HSCs (Ash1lflox/floxGFAPcreERT2) are generated, and these mice are challenged in a diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced model of liver fibrosis and HCC. Depleting Ash1l in both hepatocytes and HSCs mitigates hepatic fibrosis and HCC development. Multicolor flow cytometry, bulk, and single-cell transcriptomic sequencing reveal that ASH1L creates an immunosuppressive microenvironment. Mechanically, ASH1L-mediated H3K4me3 modification increases the expression of CCL2 and CSF1, which recruites and polarizes M2-like pro-tumorigenic macrophages. The M2-like macrophages further enhance tumor cell proliferation and suppress CD8+ T cell activation. AS-99, a small molecule inhibitor of ASH1L, demonstrates similar anti-fibrosis and tumor-suppressive effects. Of pathophysiological significance, the increased expression levels of mesenchymal ASH1L and M2 marker CD68 are associated with poor prognosis of HCC. The findings reveal ASH1L as a potential small-molecule therapeutic target against fibrosis-related HCC.

2.
Front Oncol ; 14: 1389468, 2024.
Article in English | MEDLINE | ID: mdl-39267837

ABSTRACT

Leukemia is a malignant tumor with high heterogeneity and a complex evolutionary process. It is difficult to resolve the heterogeneity and clonal evolution of leukemia cells by applying traditional bulk sequencing techniques, thus preventing a deep understanding of the mechanisms of leukemia development and the identification of potential therapeutic targets. However, with the development and application of single-cell sequencing technology, it is now possible to investigate the gene expression profile, mutations, and epigenetic features of leukemia at the single-cell level, thus providing a new perspective for leukemia research. In this article, we review the recent applications and advances of single-cell sequencing technology in leukemia research, discuss its potential for enhancing our understanding of the mechanisms of leukemia development, discovering therapeutic targets and personalized treatment, and provide reference guidelines for the significance of this technology in clinical research.

3.
Angew Chem Int Ed Engl ; : e202414493, 2024 Sep 08.
Article in English | MEDLINE | ID: mdl-39245630

ABSTRACT

The adhesion of H2 bubbles on the electrode surface is one of the main factors limiting the performance of H2 evolution of electrolytic water, especially at high current density. To overcome this problem, here a "quasi-gas phase" electrolytic water reaction system based on capillary effect is proposed for the first time to improve the mass transfer efficiency of H2. The typical feature of this reaction system is that the main site of H2 evolution reaction is transferred from the bulk aqueous solution to the gas phase environment above the bulk aqueous solution, thus effectively inhibiting the aggregation of H2 bubbles and reducing the resistance of their diffusion away. Electrochemical test results show that the proposed quasi-gas phase system can significantly reduce the potential required in H2 evolution reaction process at high current density compared with the conventional electrolytic reaction system. Specifically, the overpotential potential is reduced by 0.31 V when the H2 evolution current density of 250 mA cm-2 is achieved.

4.
J Interferon Cytokine Res ; 44(10): 467-475, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39269813

ABSTRACT

Interferons (IFNs) are universally acknowledged for their pivotal role in antiviral and anticancer responses. Thus, the primary aim of our study was to explore the expressions of IFN-α1b, α2b, and gamma in tobacco leaves via agrobacterium-mediated transient transformation and investigate their possible activities. Briefly, fusion with green fluorescent protein tags aided in detecting the expressed IFN proteins in the foliar tissues. The genetic constructs encoding these fusion proteins were inserted into the MagnICON plant transient expression vector, followed by transformation into the Agrobacterium strain GV3101. The transformed bacteria were then used to infiltrate tobacco leaves. After post-infiltration, protein expression was confirmed within 72 h via sodium dodecyl sulfate polyacrylamide gel electrophoresis, and the fusion proteins were subsequently purified using high-performance liquid chromatography for identification. Both the antiviral and anticancer potencies of these IFN fusion proteins were evaluated using the WISH/VSV (WISH cells/Vesicular stomatitis virus) microneutralization and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, respectively. Results indicated robust expression of the targeted IFN genes in plant tissues and significant biological activities against pathogens and cancer cells. Consequently, this study substantiated the viability of producing these therapeutic proteins in plants, potentially revolutionizing the manufacture of interferons biologically.


Subject(s)
Antiviral Agents , Interferon-alpha , Nicotiana , Nicotiana/genetics , Nicotiana/metabolism , Humans , Interferon-alpha/genetics , Interferon-alpha/metabolism , Interferon-alpha/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/metabolism , Interferon-gamma/metabolism , Interferon alpha-2/pharmacology , Interferon alpha-2/metabolism , Recombinant Proteins/pharmacology , Recombinant Proteins/biosynthesis , Recombinant Proteins/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/isolation & purification , Recombinant Fusion Proteins/pharmacology , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism , Gene Expression , Plants, Genetically Modified
5.
Diabetes Obes Metab ; 2024 Sep 26.
Article in English | MEDLINE | ID: mdl-39323371

ABSTRACT

AIM: To assess the global and regional burden of hip fractures associated with type 1 diabetes (T1D) from 1990 to 2021. MATERIALS AND METHODS: The population attributable fraction was calculated by combining the published risk ratio with T1D prevalence (age ≥ 20 years) from the Global Burden of Disease study to estimate the T1D-associated hip-fracture burden. Trends were assessed using the age-standardized incidence rate (ASIR) and estimated annual percentage change (EAPC). RESULTS: The global incidence of T1D-related hip fractures was 290 180 in 2021 with an ASIR of 3.96 (95% confidence interval: 1.92-5.87) per 100 000 population and a male-to-female ratio of 0.54. At the super-regional level, the highest incidence (204 610) and ASIR (13.09 per 100 000 population; 6.40-25.53) were observed in high-income regions, in particular in Australasia and Western Europe. Notably, Australasia exhibited the highest EAPC, 2.90% in T1D-associated ASIR, followed by East Asia (2.73%). The incidence among those aged 45-64 years grew significantly in 14 regions over the past decade. Nationally, the ASIR increased in 166 countries from 1990 to 2021. CONCLUSIONS: High-income regions experienced the greatest burden of T1D-associated hip fracture, while Australasia and East Asia witnessed the largest increase over the last 32 years. Prioritizing the promotion of T1D treatment and hip-fracture screening for middle-aged females living with T1D is crucial in these regions.

6.
Explore (NY) ; 20(5): 103037, 2024.
Article in English | MEDLINE | ID: mdl-39163704

ABSTRACT

OBJECTIVE: To explore the effect of the mindfulness-based stress reduction (MBSR) practice on sleep quality and perceived stress in patients with spinal cord injury (SCI). METHOD: A total of 104 patients with SCI (diagnosed via imaging and clinical symptoms) admitted to our hospital between January 2020 and December 2022 were selected as the study participants. The patients were randomly divided into two groups: the MBSR (observation) group and the control group. The observation group received MBSR therapy and routine nursing, and the control group received music training therapy and routine nursing. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and the perceived stress score was used to evaluate stress experienced by the patients at three timepoints: before intervention, 4 weeks and 8weeks after intervention. RESULTS: Compared with before intervention, the PSQI scores of both the control group and intervention group participants significantly decreased after intervention(P < 0.01). Compared with the 4 weeks after intervention, the PSQI scores of both groups of participants decreased in the 8 weeks after intervention(P < 0.01). There was a significant difference in PSQI scores between the two groups of participants at 4 and 8 weeks after intervention(P < 0.01). Compared with before intervention, the average perceived stress score of both the control group and intervention group participants significantly decreased after intervention(P < 0.05). Compared with the 4 weeks after intervention, the average perceived stress score of both groups of participants decreased in the 8 weeks after intervention(P < 0.01). There was a significant difference in average perceived stress score between the two groups of participants at 4(P < 0.05) and 8 weeks(P < 0.01) after intervention(P < 0.01). CONCLUSION: The use of MBSR therapy could effectively improve patient sleep quality and reduce perceived stress.


Subject(s)
Mindfulness , Sleep Quality , Spinal Cord Injuries , Stress, Psychological , Humans , Mindfulness/methods , Spinal Cord Injuries/complications , Spinal Cord Injuries/psychology , Spinal Cord Injuries/therapy , Female , Male , Stress, Psychological/therapy , Adult , Middle Aged , Music Therapy/methods
7.
Front Nutr ; 11: 1365587, 2024.
Article in English | MEDLINE | ID: mdl-39166135

ABSTRACT

Introduction: This study aimed to investigate the individual and composite associations of different indices of obesity on osteoporotic fractures at three different sites among individuals affected by conditions influencing bone metabolism. Methods: Participants were included from the National Health and Nutrition Examination Survey (NHANES), a national cross-sectional survey. BMI and WC were used separately and in combination to evaluate the presence of obesity. Obesity was defined as BMI ≥ 30 kg/m2, WC ≥ 88 cm in females, and WC ≥ 102 cm in males. Associations between obesity and osteoporotic fractures were assessed using multivariable logistic regression and OR curves. Associations modified by age, sex, race, and alcohol consumption were also evaluated. Results: A total of 5377 participants were included in this study. In multivariable logistic regression analyses, we found that BMI, WC, BMI defining obesity, and WC defining obesity were negatively associated with hip fracture (all p < 0.05). However, harmful associations between WC and BMI defining obesity and spine fracture were found (all p < 0.05). OR curves revealed that BMI and WC had a linear relationship with hip and spine fractures (all P for non-linearity >0.05). Further analyses showed that the highest WC quartile was harmfully associated with a higher risk of spine fractures (p < 0.05). Obese participants diagnosed by both BMI and WC were less likely to have hip fractures but more likely to have spine fractures (all P for trend <0.05). A significant interaction between age (Ref: age < 50 years) and BMI and WC was detected for hip fractures (all P for interaction <0.05). Discussion: In people with conditions influencing bone metabolism, obesity diagnosed by BMI and WC was associated with a lower risk of hip fracture, while obesity diagnosed by BMI and the highest WC quartile were associated with a higher risk of spine fracture.

8.
BMC Pulm Med ; 24(1): 391, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138459

ABSTRACT

INTRODUCTION: ARDS (acute respiratory distress syndrome) is the most severe form of acute hypoxic respiratory failure. Most studies related to ARDS have excluded patients with hematologic diseases, let alone allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Numerous patients experiencing severe hypoxic respiratory failure do not meet the Berlin definition due to the limitations of diagnosis and treatment. A new definition of ARDS, remove some diagnosis restrictions, was proposed in 2023. Based on the 2023 new definition of ARDS, we investigated the clinical features of ARDS in allo-HSCT recipients and reported risk factors for in-hospital mortality in allo-HSCT recipients defined by the Berlin definition and the new definition of ARDS respectively. METHODS: From Jan 2016 to Dec 2020, 135 allo-HSCT recipients identified with the new definition and 87 identified with the Berlin definition at three teaching hospitals were retrospectively included in this study. Variables (demographic information, characteristics of hematologic disease and ARDS episode, laboratory tests and SOFA score) with P < 0.05 in univariate logistic regression analysis were included in multivariate stepwise logistic regression analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported. RESULTS: Under the new definition, SOFA score (OR = 1.351, 95% CI: 1.146-1.593, P < 0.01) were found as an independent risk factor for in-hospital mortality in ARDS after allo-HSCT, while SpO2/FiO2 (OR = 0.984, 95% CI: 0.972-0.996, P < 0.01) was a protective factor. The infusion of peripheral-derived stem cells was found to be a protective factor against in-hospital mortality in post-transplantation ARDS compared with the infusion of bone marrow-derived stem cells (OR = 0.726, 95% CI: 0.164-3.221, P = 0.04). Under the Berlin definition, PaO2/FiO2 (OR = 0.977, 95% CI: 0.961-0.993, P = 0.01, lactate (OR = 7.337, 95% CI: 1.313-40.989, P < 0.01) and AST (OR = 1.165, 95% CI: 1.072-1.265, P < 0.01) were independently associated with in-hospital mortality. CONCLUSION: These prognostic risk factors we found in allo-HSCT recipients may contribute to closer monitoring and ARDS prevention strategies. These findings require confirmation in prospective, large sample size studies.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hospital Mortality , Respiratory Distress Syndrome , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Male , Retrospective Studies , Female , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Middle Aged , Risk Factors , Adult , Transplantation, Homologous/adverse effects , Aged , Logistic Models , Young Adult
9.
Small Methods ; : e2400892, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39180257

ABSTRACT

2D platinum diselenide (PtSe2), a novel member of the transition metal dichalcogenides (TMDCs) family, possesses many excellent properties, including a layer-dependent bandgap, high carrier mobility, and broadband response, making it promise for applications in technologies like field-effect transistors and room-temperature photodetectors. Doping represents an effective method to modify the electrical properties of 2D TMDCs and to bestow upon them additional functions. However, to date, little research has been conducted on the successful doping of 2D PtSe2 for modification. In this study, sulfur (S) powder is utilized during the chemical vapor deposition growth process of 2D PtSe2 ribbons and successfully integrated into the PtSe2 lattice through substitutional doping. The Au substrate significantly decreases the substitution energy of Se atoms in the lower layer of PtSe2, resulting in the formation of the Janus PtSSe structure. S-doped PtSe2 ribbons demonstrate significant symmetry breaking and enhanced electrical properties, showcasing a strong nonlinear optical response and certain synaptic plasticity, further simulating some neuromorphological processes. This study not only demonstrates a viable method for controllable doping and modification of 2D PtSe2 but also establishes a platform for exploring the characteristics of Janus TMDCs.

10.
Nat Commun ; 15(1): 6215, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043664

ABSTRACT

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Neoplasm Recurrence, Local , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Female , Neoplasm Recurrence, Local/genetics , Middle Aged , Aged , Prognosis , Genomics/methods , Adult , Neoplasm Staging , Deep Learning , Disease-Free Survival
11.
Nanoscale ; 16(29): 13938-13944, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38979605

ABSTRACT

A novel breakthrough has been achieved in gas detection through the innovative application of surface-enhanced Raman scattering (SERS) to hydrogen (H2) detection for the first time. This study capitalizes on the unique SERS effects of gold nanoparticles coupled with the redox interaction between hydrogen and crystal violet, allowing for the development of a magnetic SERS probe that demonstrated enhanced sensitivity and specificity. This new probe can detect hydrogen concentrations as low as 1% by volume in gaseous environments, offering a substantial improvement over the detection limits of traditional hydrogen alarms. Further, this report comprehensively detailed the synthesis of the FA-CV materials, instrumental analysis, and an in-depth evaluation of the SERS performance of the FA-CV substrate, underlining the outstanding sensitivity, stability, and recyclability of the probe. The introduction of SERS in this novel capacity not only contributes a valuable approach to gas sensing technologies, but also suggests promising avenues for the application of SERS in environmental monitoring and energy security. This illustrates the adaptability and potential impact of this powerful technique.

12.
Microbiol Spectr ; 12(8): e0334023, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-38980024

ABSTRACT

Vibrio vulnificus (Vv) is known to cause life-threatening infections, particularly septicemia. These patients often exhibit elevated levels of pro-inflammatory cytokines. While it is established that mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) contributes to the production of pro-inflammatory cytokines, the role of MNK in macrophages during Vv infection remains unclear. In this study, we investigate the impact of MNK on macrophages. We demonstrate that the inhibition of MNK in J774A.1 cells, when treated with lipopolysaccharide or Vv, resulted in decreased production of tumor necrosis factor alpha and interleukin-6, without affecting their transcription. Interestingly, treatment with MNK inhibitor CGP57380 led to enhanced phosphorylation of MNK1 but decreased phosphorylation of eIF4E. Moreover, MNK1 knockout cells exhibited an increased capacity for phagocytosis and clearance of Vv, with more acidic phagosomes than the parental cells. Notably, CGP57380 did not impact phagocytosis, bacterial clearance, or phagosome acidification in Vv-infected J774A.1 cells. Considering the reported association between MNK and mammalian target of rapamycin complex 1 (mTORC1) activation, we investigated the mTORC1 signaling in MNK1 knockout cells infected with Vv. Our results revealed that attenuation of the mTORC1 signaling in these cells and treatment with the mTORC1 inhibitor rapamycin significantly enhanced bacterial clearance in J774A.1 cells following Vv infection. In summary, our findings suggest that MNK promotes the Vv-induced cytokine production in J774A.1 cells without affecting their transcription levels. MNK1 appears to impair the phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected J774A.1 cells through the MNK1-mTORC1 signaling pathway rather than the MNK1-eIF4E signaling pathway. Our findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection. IMPORTANCE: Mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) plays a role in promoting the production of tumor necrosis factor alpha and interleukin-6 in macrophages during Vibrio vulnificus (Vv) infection. Inhibition or knockout of MNK1 in J774A.1 cells resulted in reduced cytokine production without affecting their transcription levels. MNK1 also impairs phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected cells through the MNK1-mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection.


Subject(s)
Macrophages , Mechanistic Target of Rapamycin Complex 1 , Phagocytosis , Protein Serine-Threonine Kinases , Vibrio vulnificus , Vibrio vulnificus/metabolism , Vibrio vulnificus/genetics , Macrophages/microbiology , Macrophages/immunology , Macrophages/metabolism , Animals , Mice , Mechanistic Target of Rapamycin Complex 1/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Cell Line , Vibrio Infections/immunology , Vibrio Infections/microbiology , Signal Transduction , Cytokines/metabolism , Tumor Necrosis Factor-alpha/metabolism , Phosphorylation , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Humans , Aniline Compounds , Purines
13.
J Inorg Biochem ; 259: 112664, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39018747

ABSTRACT

HIV-1 reverse transcriptase (RT) inhibitors play a crucial role in the treatment of HIV by preventing the activity of the enzyme responsible for the replication of the virus. The HIV-1 Tat protein binds to transactivation response (TAR) RNA and recruits host factors to stimulate HIV-1 transcription. We have created a small library consisting of 4 × 6 polypyridyl Ru(II) complexes that selectively bind to TAR RNA, with targeting groups specific to HIV-1 TAR RNA. The molecule design was conducted by introducing hydroxyl or methoxy groups into an established potent TAR binder. The potential TAR binding ability was analysis from nature charge population and electrostatic potential by quantum chemistry calculations. Key modifications were found to be R1 and R3 groups. The most potent and selective TAR RNA binder was a3 with R1 = OH, R2 = H and R3 = Me. Through molecular recognition of hydrogen bonds and electrostatic attraction, they were able to firmly and selectively bind HIV-1 TAR RNA. Furthermore, they efficiently obstructed the contact between TAR RNA and Tat protein, and inhibited the reverse transcription activity of HIV-1 RT. The polypyridyl Ru(II) complexes were chemical and photo-stable, and sensitive and selective spectroscopic responses to TAR RNA. They exhibited little toxicity towards normal cells. Hence, this study might offer significant drug design approaches for researching AIDS and other illnesses associated with RT, including HCV, EBOV, and SARS-CoV-2. Moreover, it could contribute to fundamental research on the interactions of inorganic transition metal complexes with biomolecules.


Subject(s)
Coordination Complexes , HIV Reverse Transcriptase , HIV-1 , RNA, Viral , Reverse Transcriptase Inhibitors , Ruthenium , Ruthenium/chemistry , HIV-1/drug effects , HIV-1/enzymology , Humans , HIV Reverse Transcriptase/antagonists & inhibitors , HIV Reverse Transcriptase/metabolism , HIV Reverse Transcriptase/chemistry , Structure-Activity Relationship , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , RNA, Viral/metabolism , Anti-HIV Agents/pharmacology , Anti-HIV Agents/chemistry , HIV Long Terminal Repeat/drug effects
14.
Adv Sci (Weinh) ; 11(33): e2400500, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38884208

ABSTRACT

For several decades after Moore's Law is proposed, there is a continuous effort to reduce the feature-size of transistors. However, as the size of transistors continues to decrease, numerous challenges and obstacles including severe short channel effects (SCEs) are emerging. Recently, low-dimensional materials have provided new opportunities for constructing small feature-size transistors due to their superior electrical properties compared to silicon. Here, state-of-the-art low-dimensional materials-based transistors with small feature-sizes are reviewed. Different from other works that mainly focus on material characteristics of a specific device structure, the discussed topics are utilizing device structure design including vertical structure and nano-gate structure, and nanofabrication techniques to achieve small feature-sizes of transistors. A comprehensive summary of these small feature-size transistors is presented by illustrating their operation mechanism, relevant fabrication processes, and corresponding performance parameters. Besides, the role of small feature-size transistors based on low-dimensional materials in further reducing the small footprint is also clarified and their cutting-edge applications are highlighted. Finally, a comparison and analysis between state-of-art transistors is made, as well as a glimpse into the future research trajectory of low dimensional materials-based small feature-size transistors is briefly outlined.

15.
Inorg Chem ; 63(26): 12342-12349, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38904258

ABSTRACT

As a typical RNA virus, the genetic information on HIV-1 is entirely stored in RNA. The reverse transcription activity of HIV-1 reverse transcriptase (RT) plays a crucial role in the replication and transmission of the virus. Non-nucleoside RT inhibitors (NNRTIs) block the function of RT by binding to the RNA binding site on RT, with very few targeting viral RNA. In this study, by transforming planar conjugated ligands into a spiro structure, we convert classical Ru(II) DNA intercalators into a nonintercalator. This enables selective binding to HIV-1 transactivation response (TAR) RNA on the outer side of nucleic acids through dual interactions involving hydrogen bonds and electrostatic attraction, effectively inhibiting HIV-1 RT and serving as a selective fluorescence probe for TAR RNA.


Subject(s)
HIV Reverse Transcriptase , HIV-1 , Reverse Transcriptase Inhibitors , Ruthenium , HIV Reverse Transcriptase/antagonists & inhibitors , HIV Reverse Transcriptase/metabolism , Reverse Transcriptase Inhibitors/chemistry , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/metabolism , Ligands , HIV-1/enzymology , HIV-1/drug effects , Ruthenium/chemistry , Ruthenium/pharmacology , RNA, Viral/metabolism , RNA, Viral/chemistry , Spiro Compounds/chemistry , Spiro Compounds/pharmacology , Spiro Compounds/metabolism , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemical synthesis , Intercalating Agents/chemistry , Intercalating Agents/pharmacology , Molecular Structure , Humans , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , HIV Long Terminal Repeat , Binding Sites
16.
J Blood Med ; 15: 265-273, 2024.
Article in English | MEDLINE | ID: mdl-38895162

ABSTRACT

Purpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China. Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and ß - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis. Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and ß globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes. Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin.

17.
Toxics ; 12(6)2024 May 27.
Article in English | MEDLINE | ID: mdl-38922071

ABSTRACT

Insecticide exposure may affect childhood asthma/wheezing, but evidence is scarce in low- and middle-income countries. We conducted a population-based cross-sectional study in Sanya, China. Generalized linear models were adopted to assess the associations of insecticide exposure with childhood asthma/wheezing, reported as odds ratios (ORs) and 95% confidence intervals (CIs). A subgroup analysis was performed to explore the possible effects of sociodemographic and environmental factors on these associations. The median age of the 9754 children was 6.7 years, and 5345 (54.8%) were boys. The prevalences of ever asthma (EA), ever wheezing (EW), and current wheezing (CW) were 7.4%, 5.3%, and 2.9%, respectively. We found a greater prevalence of childhood EA with insecticide exposure (OR = 1.18, 95% CI: 1.00, 1.38). Outdoor insecticide exposure was associated with elevated ORs for EA (1.24, 95% CI: 1.03, 1.50), EW (1.27, 95% CI: 1.03, 1.57), and CW (1.38, 95% CI: 1.04, 1.81). The p for the trend in insecticide exposure frequency was significant for EA (p = 0.001) and CW (p = 0.034). These adverse impacts were pronounced in girls who were exposed to low temperatures. Our findings suggest adverse effects of insecticide use, especially outdoors, on childhood asthma/wheezing. Further studies are warranted to verify this association and develop tailored prevention measures.

18.
Opt Express ; 32(9): 15645-15657, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38859210

ABSTRACT

The spectral emission of laser-induced plasma in water has a broadband continuum containing ultraviolet light, which can be used as a novel light source for the degradation of organic compounds. We studied the degradation process of the organic dye Rhodamine B (RhB) using plasma light source excited by the "Laser + Fe" mode. Spectral analysis and reaction kinetics modelling were used to study the degradation mechanism. The degradation process using this light source could be divided into two stages. The initial stage was mainly photocatalytic degradation, where ultraviolet light broke the chemical bond of RhB, and then RhB was degraded by the strong oxidising ability of ·OH. As the iron and hydrogen ion concentrations increased, the synergistic effect of photocatalysis and the Fenton reaction further enhanced the degradation rate in the later stage. The plasma excited by the "Laser + Fe" mode achieved photodegradation by effectively enhancing the ultraviolet wavelength ratio of the emission spectrum and triggered the Fenton reaction to achieve rapid organic matter degradation. Our findings indicate that the participation of the Fenton reaction can increase the degradation rate by approximately 10 times. Besides, the impact of pH on degradation efficiency demonstrates that both acidic and alkaline environments have better degradation effects than neutral conditions; this is because acidic environments can enhance the Fenton reaction, while alkaline environments can provide more ·OH.

19.
J Med Virol ; 96(6): e29724, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38837426

ABSTRACT

Although the burden of the human immunodeficiency virus (HIV) in the Asia-Pacific region is increasingly severe, comprehensive evidence of the burden of HIV is scarce. We aimed to report the burden of HIV in people aged 15-79 years from 1990 to 2019 using data from the Global Burden of Disease Study (GBD) 2019. We analyzed rates of age-standardized disability-adjusted life years (ASDR), age-standardized mortality (ASMR), and age-standardized incidence (ASIR) in our age-period-cohort analysis by sociodemographic index (SDI). According to HIV reports in 2019 from 29 countries in the Asia-Pacific region, the low SDI group in Papua New Guinea had the highest ASDR, ASMR, and ASIR. From 1990 to 2019, the ASDR, ASIR, and ASMR of persons with acquired immune deficiency syndrome (AIDS) increased in 21 (72%) of the 29 countries in the Asia-Pacific region. During the same period, the disability-adjusted life years (DALYs) of AIDS patients in the low SDI group in the region grew the fastest, particularly in Nepal. The incidence of HIV among individuals aged 20-30 years in the low-middle SDI group was higher than that of those in the other age groups. In 2019, unsafe sex was the main cause of HIV-related ASDR in the region's 29 countries, followed by drug use. The severity of the burden of HIV/AIDS in the Asia-Pacific region is increasing, especially among low SDI groups. Specific public health policies should be formulated based on the socioeconomic development level of each country to alleviate the burden of HIV/AIDS.


Subject(s)
Global Burden of Disease , HIV Infections , Humans , Adult , Middle Aged , Adolescent , Young Adult , HIV Infections/epidemiology , HIV Infections/mortality , Male , Female , Aged , Global Burden of Disease/trends , Asia/epidemiology , Cohort Studies , Incidence , Disability-Adjusted Life Years , Cost of Illness
20.
Immun Inflamm Dis ; 12(6): e1286, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38860755

ABSTRACT

OBJECTIVE: This study aimed to link intracellular adenosine triphosphate content in CD4+ T lymphocytes (CD4+ iATP) with sepsis patient mortality, seeking a new predictive biomarker for outcomes and enhanced management. METHODS: 61 sepsis patients admitted to the Intensive Care Unit between October 2021 and November 2022 were enrolled. iATP levels were gauged using whole blood CD4+ T cells stimulated with mitogen PHA-L. Based on CD4+ iATP levels (<132.24 and ≥132.24 ng/mL), patients were categorized into two groups. The primary endpoint was all-cause mortality. To identify factors associated with mortality, both univariate and multivariate Cox proportional hazard analyses were conducted. RESULTS: Of the patients, 40 had high CD4+ iATP levels (≥132.24 ng/mL) and 21 had low levels (<132.24 ng/mL). In a 28-day follow-up, 21 (34.4%) patients perished. Adjusting for confounders like SOFA score, APACHE II score, lactic acid, and albumin, those with low CD4+ iATP had three- to fivefold higher mortality risk compared to high CD4+ iATP patients (61.9% vs. 20.0%; hazard ratio [95% confidence interval], Model 1: 4.515 [1.276-15.974], p = .019, Model 2: 3.512 [1.197-10.306], p = .022). CD4+ iATP correlated positively with white blood cell and neutrophil counts but not with lymphocytes, CD3, and CD4 counts. CONCLUSIONS: Low CD4+ iATP levels were associated with a higher risk of mortality in sepsis patients. Measurement of CD4+ iATP may serve as a useful tool for identifying patients at a higher risk of mortality and could potentially provide a basis for clinical treatment. Further research is warranted to fully elucidate the underlying mechanisms of this association.


Subject(s)
Adenosine Triphosphate , CD4-Positive T-Lymphocytes , Sepsis , Humans , Adenosine Triphosphate/metabolism , Sepsis/mortality , Sepsis/immunology , Sepsis/blood , Male , Female , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Middle Aged , Prospective Studies , Aged , Biomarkers , Prognosis , Intensive Care Units/statistics & numerical data , Adult
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