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1.
Nano Lett ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856230

ABSTRACT

Lithium metal batteries utilizing lithium metal as the anode can achieve a greater energy density. However, it remains challenging to improve low-temperature performance and fast-charging features. Herein, we introduce an electrolyte solvation chemistry strategy to regulate the properties of ethylene carbonate (EC)-based electrolytes through intermolecular interactions, utilizing weakly solvated fluoroethylene carbonate (FEC) to replace EC, and incorporating the low-melting-point solvent 1,2-difluorobenzene (2FB) as a diluent. We identified that the intermolecular interaction between 2FB and solvent can facilitate Li+ desolvation and lower the freezing point of the electrolyte effectively. The resulting electrolyte enables the LiNi0.8Co0.1Mn0.1O2||Li cell to operate at -30 °C for more than 100 cycles while delivering a high capacity of 154 mAh g-1 at 5.0C. We present a solvation structure and interfacial model to analyze the behavior of the formulated electrolyte composition, establishing a relationship with cell performance and also providing insights for the electrolyte design under extreme conditions.

2.
Appl Opt ; 63(12): 3178-3185, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38856464

ABSTRACT

Silicon photonics devices benefit greatly from a partially etched platform and inverse design. Herein, we propose a bi-layer polarization splitter and rotator with a topology pattern and demonstrate it on a silicon-on-insulator platform. Our device exhibits a significantly reduced physical footprint of only 2µm×6µm, compared to traditional directional couplers and tapered waveguides. The device accomplishes the functions of polarization conversion and separation in such a compact design without redundant tapered or bending waveguides. The tested minimum insertion loss with the fabrication batch reaches 0.57 and 0.67 dB for TE and TM modes, respectively. The TE mode demonstrates a wider bandwidth and lower ILs than the TM modes, averaging around 1 dB from 1530 to 1565 nm. The M modes exhibit approximately 2 dB ILs at the same wavelength range, decreasing to about 1 dB between 1565 and 1580 nm. Improved designs and fabrication conditions strongly suggest the potential for further performance enhancement in the device. This successful initiative validates the exceptional performance resulting from the integration of the partially etched platform and inverse design, providing valuable insights for future photonic integrated device designs.

3.
J Immunol ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856712

ABSTRACT

Bats are the natural reservoir hosts of some viruses, some of which may spill over to humans and cause global-scale pandemics. Different from humans, bats may coexist with high pathogenic viruses without showing symptoms of diseases. As one of the most important first defenses, bat type I IFNs (IFN-Is) were thought to play a role during this virus coexistence and thus were studied in recent years. However, there are arguments about whether bats have a contracted genome locus or constitutively expressed IFNs, mainly due to species-specific findings. We hypothesized that because of the lack of pan-bat analysis, the common characteristics of bat IFN-Is have not been revealed yet. In this study, we characterized the IFN-I locus for nine Yangochiroptera bats and three Yinpterochiroptera bats on the basis of their high-quality bat genomes. We also compared the basal expression in six bats and compared the antiviral and antiproliferative activity and the thermostability of representative Rhinolophus bat IFNs. We found a dominance of unconventional IFNω-like responses in the IFN-I system, which is unique to bats. In contrast to IFNα-dominated IFN-I loci in the majority of other mammals, bats generally have shorter IFN-I loci with more unconventional IFNω-like genes (IFNω or related IFNαω), but with fewer or even no IFNα genes. In addition, bats generally have constitutively expressed IFNs, the highest expressed of which is more likely an IFNω-like gene. Likewise, the highly expressed IFNω-like protein also demonstrated the best antiviral activity, antiproliferative activity, or thermostability, as shown in a representative Rhinolophus bat species. Overall, we revealed pan-bat unique, to our knowledge, characteristics in the IFN-I system, which provide insights into our understanding of the innate immunity that contributes to a special coexistence between bats and viruses.

4.
AIDS Behav ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856846

ABSTRACT

Pre-exposure prophylaxis (PrEP) is pivotal in curbing HIV transmission and is integral to the national plan to end the HIV epidemic in the United States (US). Nonetheless, widespread PrEP adoption faces barriers. Telehealth delivery models for PrEP, or telePrEP, can enhance PrEP access and adherence by providing flexible care remotely. This study presents a systematic review of telePrEP programs in the US, aiming to describe model characteristics and summarize clinical, implementation, and equity outcomes. We reviewed studies published from 2012 to 2023. We included articles that described telePrEP systems in the US and measured PrEP care continuum outcomes (awareness, initiation, uptake, adherence) or acceptability of the intervention by program users. Eight articles describing six distinct telePrEP initiatives met our inclusion criteria. Studies described models implemented in community-based, academic, and commercial settings, with most programs using a direct-to-client telePrEP model. Across studies, clients reported high acceptability of the telePrEP programs, finding them easy to use, convenient, and helpful as a tool for accessing HIV prevention services. No programs were offering injectable PrEP at the time these studies were conducted. Data was limited in measuring PrEP retention rates and the reach of services to underserved populations, including Black and Latinx communities, transgender individuals, and cis-gender women. Findings underscore the potential of telePrEP to bolster the reach of PrEP care and address structural barriers to access. As telehealth models for PrEP care gain prominence, future research should concentrate on refining implementation strategies, enhancing equity outcomes, and expanding services to include injectable PrEP.

5.
Biomed Chromatogr ; : e5931, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38881185

ABSTRACT

As a result of the lack of modern techniques, the study of Tibetan medicine has been hindered in identifying bioactive compounds. Herein, we established a chromatographic approach using an immobilized angiotensin II type 1 receptor (AT1R) via a one-step method triggered by haloalkane dehalogenase. The bioactive compounds from Choerospondias axillaris (Guangzao) were screened and identified using the immobilized AT1R followed by MS. Frontal analysis (FA) and adsorption energy distribution (AED) were used to evaluate the association constants. Molecular docking was used to investigate the binding configurations, and the surface efficiency index, binding efficiency index, and ligand-lipophilicity efficiency (LLE) were calculated to assess the drug-like properties. The results identified naringenin, pinocembrin, and chrysin as the compounds that specifically bind to AT1R in Guangzao. FA and AED confirmed that there is only one type of binding site between these compounds and AT1R. The association constants were (2.40 ± 0.02) × 104 M-1 for naringenin (5.22 ± 0.26) × 104 M-1 for pinocembrin, and (4.27 ± 0.14) × 104 M-1 for chrysin, respectively. These compounds can bind with AT1R through the orthosteric binding pocket. Naringenin exhibited better LLE than pinocembrin and chrysin. These results confirmed the feasibility of using the immobilized AT1R column for screening and analyzing bioactive compounds in Tibetan medicines.

6.
Front Vet Sci ; 11: 1426377, 2024.
Article in English | MEDLINE | ID: mdl-38872794

ABSTRACT

Excessive fat deposition due to impaired fat metabolism in chickens is a major problem in the poultry industry. Nutritional interventions are effective solutions, but current options are limited. A safe phytochemical, rutin, has shown positive effects in animals, but its effect on lipid metabolism in poultry remains unknown. Hence, this study is to investigate the effects of rutin on egg quality, serum biochemistry, fat deposition, lipid peroxidation and hepatic lipid metabolism in post-peak laying hens. A total of 360 Taihang laying hens (49-week-old) were randomly divided into five groups and fed a basal diet (control group, 0%) and a basal diet supplemented with 300 (0.03%), 600 (0.06%), 900 (0.09%), and 1,200 (0.12%) mg rutin/kg feed, respectively. The results showed that eggshell strength was significantly (p < 0.05) higher in the dietary rutin groups, whereas yolk percentage (p < 0.05), total cholesterol (TC) (p < 0.01) and yolk fat ratio (p < 0.01) decreased linearly (p < 0.05) in the dietary rutin groups. Importantly, dietary rutin reduced serum triglyceride (TG) and TC levels, decreased abdominal lipid deposition and liver index (p < 0.05), and which concomitantly decreased hepatic lipid (TG, TC, and free fatty acid) accumulation (p < 0.05). An increase (p < 0.05) in total antioxidant capacity and superoxide dismutase activity and a decrease (p < 0.05) in malondialdehyde levels were also found. At the same time, the activities of hepatic lipase, acetyl-CoA carboxylase and malic enzyme in the liver were decreased (p < 0.05). Dietary rutin also increased (p < 0.05) the expression of fatty acid oxidation-related genes (carnitine palmitoyl transferase 1, peroxisome proliferator-activated receptor α, farnesoid X receptor). Additionally, it decreased fatty acid synthesis genes (sterol regulatory element binding protein-1c, acetyl-CoA carboxylase α, stearoyl-CoA desaturase 1) (p < 0.05). In conclusion, the addition of rutin (0.06-0.12%) to the diet improved the fat metabolism and increased liver antioxidant capacity in post-peak laying hens, and these positive changes improved egg quality to some extent.

7.
Food Chem ; 457: 140046, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38901342

ABSTRACT

The extraction of active ingredients from traditional Chinese medicine has received considerable attentions. In this study, 16 kinds of natural deep eutectic solvent (NADES) with ultrasonic were selected to extract saponins from purple yam root and the extraction mechanism was investigated. The results showed that chloride/acrylic acid (1:2; n/n) had the highest extraction yield for saponins. The optimal extraction process parameters were 24% water content, 20 mL/g liquid-solid ratio, and ultrasonic extraction for 85 min (81 °C, 600 W). The extraction rate (ER) of purple yam saponins was 0.935%, close to the fitted result of 96.5 mg/g. Molecular dynamics simulations and FT-IR results showed that the NADES may extract the saponin constituents from purple yam through hydrogen bonding. Compared with traditional extraction methods and molecularly imprinted polymer methods, NADES has a higher ER and lower cost (1.53 $/g), which provides a reference for subsequent industrial quantitative production.

8.
Photodiagnosis Photodyn Ther ; : 104255, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901715

ABSTRACT

BACKGROUND: Chromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. METHODS: In vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10mM KI, 2 mM MB +100 J/cm² and 10mM KI+2mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. RESULTS: KI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. CONCLUSION: KI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.

9.
Sci Rep ; 14(1): 14005, 2024 06 18.
Article in English | MEDLINE | ID: mdl-38890351

ABSTRACT

Although decreasing body mass index (BMI) is associated with higher mortality risk in patients undergoing hemodialysis (HD), BMI neither differentiates muscle and fat mass nor provides information about the variations of fat distribution. It remains unclear whether changes over time in fat and muscle mass are associated with mortality. We examined the prognostic significance of trajectory in the triceps skinfold (TSF) thickness and mid-upper arm circumference (MUAC). In this multicenter prospective cohort study, 972 outpatients (mean age, 54.5 years; 55.3% men) undergoing maintenance HD at 22 treatment centers were included. We calculated the relative change in TSF and MUAC over a 1-year period. The outcome was all-cause mortality. Kaplan-Meier, Cox proportional hazard analyses, restricted cubic splines, and Fine and Gray sub-distribution hazards models were performed to examine whether TSF and MUAC trajectories were associated with all-cause mortality. During follow-up (median, 48.0 months), 206 (21.2%) HD patients died. Compared with the lowest trajectory group, the highest trajectories of TSF and MUAC were independently associated with lower risk for all-cause mortality (HR = 0.405, 95% CI 0.257-0.640; HR = 0.537; 95% CI 0.345-0.837; respectively), even adjusting for BMI trajectory. Increasing TSF and MUAC over time, measured as continuous variables and expressed per 1-standard deviation decrease, were associated with a 55.7% (HR = 0.443, 95% CI 0.302-0.649), and 97.8% (HR = 0.022, 95% CI 0.005-0.102) decreased risk of all-cause mortality. Reduction of TSF and MUAC are independently associated with lower all-cause mortality, independent of change in BMI. Our study revealed that the trajectory of TSF thickness and MUAC provides additional prognostic information to the BMI trajectory in HD patients.


Subject(s)
Body Mass Index , Renal Dialysis , Subcutaneous Fat , Humans , Renal Dialysis/mortality , Male , Female , Middle Aged , Prospective Studies , Skinfold Thickness , Arm/anatomy & histology , Aged , Prognosis , Adult , Muscle, Skeletal/pathology , Proportional Hazards Models , Kaplan-Meier Estimate
10.
BMC Psychol ; 12(1): 357, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38890704

ABSTRACT

BACKGROUND: The mental health of university students during the COVID-19 pandemic has attracted the attention of researchers. For the present study researchers constructed a mediation model to explore the relationship between psychological resilience and post-traumatic growth, the mediating role of negative emotions and the moderating role of deliberate rumination in students. METHODS: The Psychological Resilience Scale, Posttraumatic Growth Inventory, Depression-Anxiety-Stress Scale (DASS-21) and Event Related Rumination Inventory were used in a survey of 881 college students. The data were analyzed using SPSS 26.0 and the PROCESS plugin (version 3.3). RESULTS: (1) Psychological resilience is positively related with post-traumatic growth. Deliberate rumination is positively related to psychological resilience, posttraumatic growth, and negative emotions. Psychological resilience, post-traumatic growth and negative emotions are negatively related. (2) Negative emotions mediated the relationship between psychological resilience and post-traumatic growth. (3) Deliberate rumination plays a moderating role in psychological resilience affecting negative emotions. Deliberate rumination plays a moderating role in the extent to which psychological resilience influences PTG through negative emotions. CONCLUSIONS: Psychological resilience affects post-traumatic growth directly and also indirectly through negative emotions. With the increase of mental resilience, the level of negative emotion tended to decrease. When individuals are experiencing negative emotions, high levels of active rumination are more likely to promote post-traumatic growth. This study helps to explore the factors affecting the mental health of college students during the epidemic, thus providing guidance for appropriate mental health interventions.


Subject(s)
COVID-19 , Emotions , Posttraumatic Growth, Psychological , Resilience, Psychological , Rumination, Cognitive , Students , Humans , COVID-19/psychology , Students/psychology , Female , Male , Young Adult , Universities , Adult , Adolescent , Mental Health , Depression/psychology
11.
bioRxiv ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38895273

ABSTRACT

Rationale: The role of MUC5B mucin expression in IPF pathogenesis is unknown. Bleomycin-exposed rodent models do not exhibit sustained fibrosis or airway remodeling. Unlike mice, ferrets have human-like distribution of MUC5B expressing cell types and natively express the risk-conferring variant that induces high MUC5B expression in humans. We hypothesized that ferrets would consequently exhibit aberrant repair to propagate fibrosis similar to human IPF. Methods: Bleomycin (5U/kg) or saline-control was micro-sprayed intratracheally then wild-type ferrets were evaluated through 22 wks. Clinical phenotype was assessed with lung function. Fibrosis was assessed with µCT imaging and comparative histology with Ashcroft scoring. Airway remodeling was assessed with histology and quantitative immunofluorescence. Results: Bleomycin ferrets exhibited sustained restrictive physiology including decreased inspiratory capacity, decreased compliance, and shifted Pressure-Volume loops through 22 wks. Volumetric µCT analysis revealed increased opacification of the lung bleomycin-ferrets. Histology showed extensive fibrotic injury that matured over time and MUC5B-positive cystic structures in the distal lung suggestive of honeycombing. Bleomycin ferrets had increased proportion of small airways that were double-positive for CCSP and alpha-tubulin compared to controls, indicating an aberrant 'proximalization' repair phenotype. Notably, this aberrant repair was associated with extent of fibrotic injury at the airway level. Conclusions: Bleomycin-exposed ferrets exhibit sustained fibrosis through 22 wks and have pathologic features of IPF not found in rodents. Ferrets exhibited proximalization of the distal airways and other pathologic features characteristic of human IPF. MUC5B expression through native cell types may play a key role in promoting airway remodeling and lung injury in IPF.

12.
Small ; : e2310316, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38895965

ABSTRACT

Following the diverse structural characteristics and primary usage, diamond products include nano-polycrystalline diamond (NPD), micron-polycrystalline diamond (MPD), diamond film, porous diamond, and diamond wire drawing die. Among them, porous diamond possesses a distinctive combination of flexible surface functionality and a remarkably high surface area-to-volume ratio (SA/V) compared to traditional bulk materials, which contributes to cross-cutting applications in catalysis, adsorption, and electrochemistry while retaining the superior traits of diamond, particularly its exceptional chemical inertia. To avoid etching or microwave plasma chemical vapor deposition (MPCVD) techniques, this study proposes a high-temperature and high-pressure method based on a soluble skeleton (HPHT-ss) as an efficient and inexpensive approach for synthesizing millimeter-level porous diamonds. Interestingly, porous diamond synthesized by HPHT-ss exhibits multiscale pores distributed as macropores (average 75 µm) and mesopores (average 19 nm), which gives it a unique feature compared with other methods. Pertinent temperature-pressure conditions, HPHT-ss synthesis, and the formation mechanism of porous diamonds are also thoroughly discussed.

13.
Front Oncol ; 14: 1357419, 2024.
Article in English | MEDLINE | ID: mdl-38863637

ABSTRACT

Purpose: To evaluate the capability of dual-layer detector spectral CT (DLCT) quantitative parameters in conjunction with clinical variables to detect malignant lesions in cytologically indeterminate thyroid nodules (TNs). Materials and methods: Data from 107 patients with cytologically indeterminate TNs who underwent DLCT scans were retrospectively reviewed and randomly divided into training and validation sets (7:3 ratio). DLCT quantitative parameters (iodine concentration (IC), NICP (IC nodule/IC thyroid parenchyma), NICA (IC nodule/IC ipsilateral carotid artery), attenuation on the slope of spectral HU curve and effective atomic number), along with clinical variables, were compared between benign and malignant cohorts through univariate analysis. Multivariable logistic regression analysis was employed to identify independent predictors which were used to construct the clinical model, DLCT model, and combined model. A nomogram was formulated based on optimal performing model, and its performance was assessed using receiver operating characteristic curve, calibration curve, and decision curve analysis. The nomogram was subsequently tested in the validation set. Results: Independent predictors associated with malignant TNs with indeterminate cytology included NICP in the arterial phase, Hashimoto's Thyroiditis (HT), and BRAF V600E (all p < 0.05). The DLCT-clinical nomogram, incorporating the aforementioned variables, exhibited superior performance than the clinical model or DLCT model in both training set (AUC: 0.875 vs 0.792 vs 0.824) and validation set (AUC: 0.874 vs 0.792 vs 0.779). The DLCT-clinical nomogram demonstrated satisfactory calibration and clinical utility in both training set and validation set. Conclusion: The DLCT-clinical nomogram emerges as an effective tool to detect malignant lesions in cytologically indeterminate TNs.

14.
Biomaterials ; 310: 122634, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38823195

ABSTRACT

The hypoxic nature of pancreatic cancer, one of the most lethal malignancies worldwide, significantly impedes the effectiveness of chemoradiotherapy. Although the development of oxygen carriers and hypoxic sensitizers has shown promise in overcoming tumor hypoxia. The heterogeneity of hypoxia-primarily caused by limited oxygen penetration-has posed challenges. In this study, we designed a hypoxia-responsive nano-sensitizer by co-loading tirapazamine (TPZ), KP372-1, and MK-2206 in a metronidazole-modified polymeric vesicle. This nano-sensitizer relies on efficient endogenous NAD(P)H quinone oxidoreductase 1-mediated redox cycling induced by KP372-1, continuously consuming periphery oxygen and achieving evenly distributed hypoxia. Consequently, the normalized tumor microenvironment facilitates the self-amplified release and activation of TPZ without requiring deep penetration. The activated TPZ and metronidazole further sensitize radiotherapy, significantly reducing the radiation dose needed for extensive cell damage. Additionally, the coloaded MK-2206 complements inhibition of therapeutic resistance caused by Akt activation, synergistically enhancing the hypoxic chemoradiotherapy. This successful hypoxia normalization strategy not only overcomes hypoxia resistance in pancreatic cancer but also provides a potential universal approach to sensitize hypoxic tumor chemoradiotherapy by reshaping the hypoxic distribution.


Subject(s)
Chemoradiotherapy , Drug Liberation , Pancreatic Neoplasms , Tirapazamine , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Humans , Tirapazamine/pharmacology , Chemoradiotherapy/methods , Cell Line, Tumor , Animals , Mice, Nude , Heterocyclic Compounds, 3-Ring/pharmacology , Nanoparticles/chemistry , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Tumor Hypoxia/drug effects , Mice, Inbred BALB C , Metronidazole/pharmacology , Metronidazole/therapeutic use , Tumor Microenvironment/drug effects
15.
BMC Nurs ; 23(1): 392, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849821

ABSTRACT

AIM: To explore the views and experiences of formal caregivers caring for older inpatients with physical disabilities. METHODS: It was a qualitative phenomenological study. Using purposive sampling, twelve formal caregivers were chosen in a tertiary comprehensive hospital in Hangzhou, China. Semi-structured, face-to-face interviews were conducted, guided by open-ended questions that focused on gaining rich insights into participants' views and experiences. Coding reliability thematic analysis was used to guide data analysis and categorize, based on Lazarus and Folkman's theory of transactional coping. RESULTS: Four themes emerged from the data analysis: (1) Caregiving Threats. (2) motivations. (3) Responsibility Management. (4) Fear. CONCLUSION: Despite facing significant pressure at work, formal caregivers of elderly inpatients with physical disabilities possess the drive and various coping strategies to excel in their role. Identifying caregivers' experiences of care can be helpful in improving resilience to stress and maintaining stability in formal caregivers.

16.
Emerg Microbes Infect ; 13(1): 2366359, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38855910

ABSTRACT

Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB's hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (Mφ), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ Mφ aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + Mφ highly co-expressed IL6R/pSTAT3, contrasting TB granulomas' high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.


Subject(s)
Coinfection , Granuloma , HIV Infections , Lung , Macrophages , Receptors, Interleukin-6 , STAT3 Transcription Factor , Humans , Coinfection/virology , Coinfection/immunology , Coinfection/microbiology , HIV Infections/complications , HIV Infections/immunology , Macrophages/immunology , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Granuloma/immunology , Lung/pathology , Lung/immunology , Receptors, Interleukin-6/metabolism , Receptors, Interleukin-6/genetics , Suppressor of Cytokine Signaling 3 Protein/metabolism , Suppressor of Cytokine Signaling 3 Protein/genetics , Antigens, Differentiation, Myelomonocytic/metabolism , Antigens, Differentiation, Myelomonocytic/genetics , Antigens, CD/metabolism , Antigens, CD/genetics , Signal Transduction , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/complications , Male , Tuberculosis/immunology , Tuberculosis/microbiology , Tuberculosis/complications , Female , Adult , Interleukin-6/metabolism , Interleukin-6/genetics , CD68 Molecule
17.
Front Med (Lausanne) ; 11: 1382004, 2024.
Article in English | MEDLINE | ID: mdl-38903804

ABSTRACT

Background: Gastric cancer (GC) and type 2 diabetes (T2D) contribute to each other, but the interaction mechanisms remain undiscovered. The goal of this research was to explore shared genes as well as crosstalk mechanisms between GC and T2D. Methods: The Gene Expression Omnibus (GEO) database served as the source of the GC and T2D datasets. The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were utilized to identify representative genes. In addition, overlapping genes between the representative genes of the two diseases were used for functional enrichment analysis and protein-protein interaction (PPI) network. Next, hub genes were filtered through two machine learning algorithms. Finally, external validation was undertaken with data from the Cancer Genome Atlas (TCGA) database. Results: A total of 292 and 541 DEGs were obtained from the GC (GSE29272) and T2D (GSE164416) datasets, respectively. In addition, 2,704 and 336 module genes were identified in GC and T2D. Following their intersection, 104 crosstalk genes were identified. Enrichment analysis indicated that "ECM-receptor interaction," "AGE-RAGE signaling pathway in diabetic complications," "aging," and "cellular response to copper ion" were mutual pathways. Through the PPI network, 10 genes were identified as candidate hub genes. Machine learning further selected BGN, VCAN, FN1, FBLN1, COL4A5, COL1A1, and COL6A3 as hub genes. Conclusion: "ECM-receptor interaction," "AGE-RAGE signaling pathway in diabetic complications," "aging," and "cellular response to copper ion" were revealed as possible crosstalk mechanisms. BGN, VCAN, FN1, FBLN1, COL4A5, COL1A1, and COL6A3 were identified as shared genes and potential therapeutic targets for people suffering from GC and T2D.

18.
Front Immunol ; 15: 1380211, 2024.
Article in English | MEDLINE | ID: mdl-38898888

ABSTRACT

Background: Klebsiella pneumoniae is a common Gram-negative bacterium. Blood infection caused by K. pneumoniae is one of the most common causes of human sepsis, which seriously threatens the life of patients. The immune status of peripheral blood mononuclear cells (PBMCs) based on single-cell RNA sequencing (scRNA-seq) in acute stage and recovery stage of sepsis caused by K. pneumoniae bloodstream infection has not been studied. Methods: A total of 13 subjects were included in this study, 3 healthy controls, 7 patients with K. pneumoniae bloodstream infection in the acute stage (4 patients died), and 3 patients in the recovery stage. Peripheral blood of all patients was collected and PBMCs were isolated for scRNA-seq analysis. We studied the changes of PBMCs components, signaling pathways, differential genes, and cytokines in acute and recovery stages. Results: During K. pneumoniae acute infection we observed a decrease in the proportion of T cells, most probably due to apoptosis and the function of T cell subtypes was disorder. The proportion of monocytes increased in acute stage. Although genes related to their phagocytosis function were upregulated, their antigen presentation capacity-associated genes were downregulated. The expression of IL-1ß, IL-18, IFNGR1 and IFNGR2 genes was also increased in monocytes. The proportion of DCs was depleted during the acute stage and did not recover during sepsis recovery. DCs antigen presentation was weakened during the acute stage but recovered fast during the recovery stage. pDCs response to MCP-1 chemokine was weakened, they recovered it quickly during the recovery stage. B cells showed apoptosis both in the acute stage and recovery stage. Their response to complement was weakened, but their antigen presentation function was enhanced. The proportion of NK cells stable during all disease's stages, and the expression of IFN-γ gene was upregulated. Conclusion: The proportion of PBMCs and their immune functions undergo variations throughout the course of the disease, spanning from the acute stage to recovery. These findings provide new insights into the mechanism of PBMCs immune function during K. pneumoniae bloodstream infection sepsis and recovery and sets the basis for further understanding and treatment.


Subject(s)
Klebsiella Infections , Klebsiella pneumoniae , Leukocytes, Mononuclear , Sepsis , Humans , Klebsiella pneumoniae/immunology , Klebsiella Infections/immunology , Klebsiella Infections/blood , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Male , Female , Middle Aged , Sepsis/immunology , Sepsis/microbiology , Sepsis/blood , Sepsis/genetics , Aged , Single-Cell Analysis , Cytokines/blood , Bacteremia/immunology , Bacteremia/microbiology , Bacteremia/genetics , Sequence Analysis, RNA , Adult
20.
Heliyon ; 10(11): e32290, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38882382

ABSTRACT

The emergence of the digital economy has accelerated digital transformation, and digitalization has shown new potential and solutions to increasingly severe environmental challenges. Based on the resource-based view, dynamic capability view, synergy effect and upper echelons theory, the connotation and measurement dimensions of digital capability and green supply chain collaboration are defined and improved. Then, a theoretical model of "digital capability-green supply chain collaboration-green innovation performance" is constructed. The influence mechanism and transmission process of digital capability on green innovation performance from the perspective of green supply chain collaboration is discussed. Meanwhile, the boundary condition of the influence of digital capability on green innovation performance in the view of top management's environmental awareness is explored. Finally, an empirical test is conducted based on the Chinese manufacturing corporates. The results indicate that green innovation performance is significantly and favorably impacted by digital capability, green supply chain collaboration plays a partial mediating role between digital capability and green innovation performance, and top management's environmental awareness can positively moderate the effect of digital capability on green innovation performance. This study offers valuable theoretical and practical enlightenments for manufacturing companies to foster the growth of green innovation through digital capability more effectively.

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