Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.322
Filtrar
1.
Medicine (Baltimore) ; 103(16): e37884, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640323

RESUMO

INTRODUCTION: Trigeminal herpes zoster, which comprises 10% to 20% of cases of herpes zoster, often leads to severe pain in the ophthalmic branches. Current treatments, including drug therapy and minimally invasive interventions, have limitations; accordingly, there is a need to explore alternative approaches. This study aimed to evaluate the efficacy and safety of computerized tomography (CT)-guided pulsed radiofrequency of the sphenopalatine ganglion in patients with intractable trigeminal herpetic pain. PATIENT CONCERNS: Three patients with intractable trigeminal ophthalmic zoster neuralgia were studied. All patients complained of bursts of headache, which occurred at least 10 times a day, usually in the periorbital and frontal regions. Conventional treatments, including oral medications and radiofrequency therapy targeting the trigeminal-semilunar ganglion and supraorbital nerve, could not sufficiently provide relief. DIAGNOSIS: Two patients were diagnosed with herpes zoster in the ocular branch of the trigeminal nerve with conjunctivitis, while one patient was diagnosed with postherpetic neuralgia in the ocular branch of the trigeminal nerve. INTERVENTIONS: This study employed a novel approach that involved CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion. OUTCOMES: In all three patients, pain relief was achieved within 1 to 3 days after treatment. During the follow-up, one patient had pain recurrence; however, its severity was ≈ 40% lower than the pretreatment pain severity. The second patient had sustained and effective pain relief. However, the pain of the third patient worsened again after 2 months. The average follow-up duration was 3 months. None of the enrolled patients showed treatment-related adverse reactions or complications. CONCLUSION: Our findings indicated that CT-guided radiofrequency regulation of the pterygopalatine fossa sphenopalatine ganglion was a safe and effective intervention for pain in patients with trigeminal ophthalmic zoster neuralgia, suggesting that it may be a therapeutic option if other treatments fail.


Assuntos
Herpes Zoster Oftálmico , Herpes Zoster , Neuralgia Pós-Herpética , Neuralgia , Dor Intratável , Tratamento por Radiofrequência Pulsada , Neuralgia do Trigêmeo , Humanos , Herpes Zoster Oftálmico/complicações , Herpes Zoster Oftálmico/terapia , Tratamento por Radiofrequência Pulsada/métodos , Neuralgia/etiologia , Neuralgia/terapia , Neuralgia Pós-Herpética/terapia , Neuralgia Pós-Herpética/complicações , Neuralgia do Trigêmeo/terapia , Neuralgia do Trigêmeo/complicações , Herpes Zoster/complicações , Resultado do Tratamento
2.
Cancer Manag Res ; 16: 325-336, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654718

RESUMO

Background: Lung cancer (LC) remains a leading cause of cancer-related mortality worldwide, with its prognosis influenced by complex biological factors. Objective: This study delves into the clinical relevance of circulating tumor cells (CTCs) and their Epithelial-Mesenchymal Transition (EMT) status in LC patients. Methods: We enrolled 30 newly diagnosed LC patients and utilized the CanPatrol technique for the separation and categorization of CTCs from peripheral blood samples. Immunofluorescent staining identified epithelial (CK8/18/19, EpCAM), mesenchymal (Vimentin, Twist), and leukocyte (CD45) markers in these cells. Fluorescence microscopy analyzed the slides, and RECIST 1.1 criteria assessed treatment response. Spearman's method was used to correlate CTCs' EMT states with their count and clinical characteristics. Results: Our findings reveal three distinct CTC groups: epithelial (E-CTCs), hybrid epithelial/mesenchymal (E/M-CTCs), and mesenchymal (M-CTCs). Significant statistical differences were observed in stages III-IV vs I-II, tumor sizes T3-T4 vs T1-T2, and in the presence or absence of distant metastasis and lymph node involvement. Notably, the count of E/M-CTCs was positively correlated with TNM staging, tumor size, lymph node, and distant metastasis. Changes in M-CTC count pre- and post-treatment closely mirrored disease progression and control, showing considerable consistency with RECIST criteria. Conclusion: In conclusion, the EMT status of CTCs, especially E/M-CTCs, holds predictive value for LC staging, tumor size, and metastasis. Dynamic monitoring of M-CTCs can accurately reflect disease progression.

3.
Front Mol Neurosci ; 17: 1365978, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660385

RESUMO

Non-coding RNAs (ncRNAs) play essential regulatory functions in various physiological and pathological processes in the brain. To systematically characterize the ncRNA profile in cortical cells, we downloaded single-cell SMART-Seq v4 data of mouse cerebral cortex. Our results revealed that the ncRNAs alone are sufficient to define the identity of most cortical cell types. We identified 1,600 ncRNAs that exhibited cell type specificity, even yielding to distinguish microglia from perivascular macrophages with ncRNA. Moreover, we characterized cortical layer and region specific ncRNAs, in line with the results by spatial transcriptome (ST) data. By constructing a co-expression network of ncRNAs and protein-coding genes, we predicted the function of ncRNAs. By integrating with genome-wide association studies data, we established associations between cell type-specific ncRNAs and traits related to neurological disorders. Collectively, our study identified differentially expressed ncRNAs at multiple levels and provided the valuable resource to explore the functions and dysfunctions of ncRNAs in cortical cells.

4.
Int J Biol Macromol ; : 131682, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38643914

RESUMO

This study aimed to prepare a new bio-based chromium-free tanning agent. The green epoxide monocase ethylene glycol diglycidyl ether (EGDE) was grafted with tannic acid (TA) derived from natural plant using the one-pot method to synthesize new plant polyphenol-derived tannic acid-based chromium-free tanning agents (TA-EGDE) with abundant terminal epoxides. FTIR, 1H NMR, XPS, GPC, SEM, and other analytical techniques were used to characterize tanning agents. These consequences manifested that EGDE was successfully grafted with the phenol hydroxyl group of TA. The epoxide value of TA-EGDE showed a tendency to increase and then decrease with increasing EGDE dosage, and the epoxide value of TA-EGDE-2 attained a maximum of 0.262 mol/100 g. GPC analysis showed that the formula weight of the prepared TA-EGDE was partially distributed above 5000 Da. The tanning experiment demonstrated that the shrinkage temperatures (Ts) of the TA-EGDE-tanned leathers were all higher than 81.5 °C. Compared with the traditional commercial chromium-free tanning agent (F-90, TWS), TA-EGDE-tanned leathers exhibited higher Ts and better mechanical properties. The TA-EGDE prepared in this study not only has ecological environmental protection but also provides finished leather with good moisture, heat resistance, and mechanical properties.

5.
BMC Pulm Med ; 24(1): 177, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622607

RESUMO

OBJECTIVES: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. METHODS: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. RESULTS: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47-32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20-12.70, P = 0.024). CONCLUSIONS: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.


Assuntos
Tuberculose Latente , Silicose , Tuberculose , Humanos , Tuberculose Latente/epidemiologia , Tuberculose Latente/diagnóstico , Estudos Transversais , Fatores de Risco , China/epidemiologia , Silicose/epidemiologia , Testes de Liberação de Interferon-gama , Teste Tuberculínico
6.
Work ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38578914

RESUMO

BACKGROUND: The effects of traffic sign information volume (TSIV) on the visual characteristics and workload of novice and experienced drivers were investigated in this study. TSIV plays a crucial role in road traffic safety, and understanding its impact on drivers is essential for designing effective traffic sign systems. OBJECTIVE: This research aimed to compare the visual characteristics and workload of novice and experienced drivers under varying TSIV doses through simulated driving tests. The objective was to provide insights for optimizing the design of road TSIV. METHODS: Six TSIV levels were considered: S0, S1, S2, S3, S4, and S5, representing different workload levels. Participants, including both novice and experienced drivers, were involved in simulated driving scenarios with varying TSIV levels. Eye movement data was collected using an eye tracker device. The study was conducted in China, and appropriate driving simulators and equipment were utilized. RESULTS: The findings revealed several valuable results. Experienced drivers exhibited a higher proportion of saccade behavior in the 30-90 ms time period and did not show rapid saccade behavior during the 0-30 ms period, indicating superior visual search strategies. Both novice and experienced drivers demonstrated improved visual cognitive abilities at the S3 level of TSIV, which corresponds to normal and safe driving conditions. Furthermore, a majority of both groups had saccade amplitudes in the range of 0°-4°, with experienced drivers showing a slightly higher proportion. About 82% of experienced drivers had saccade behavior within the range of 0°-2°, compared to 75% of novice drivers. CONCLUSIONS: The study concludes that the S3 level of TSIV, corresponding to 30 bits/km, is optimal for both novice and experienced drivers. This level promotes better visual performance and reduces visual workload, indicating that drivers' information acquisition capacity and visual search strategies are maximized while keeping the workload associated with driving at a minimum. These findings have significant implications for enhancing driving safety.

7.
Traffic Inj Prev ; : 1-8, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656910

RESUMO

OBJECTIVES: This research aims to (1) study the visual and psychological characteristics of drivers in foggy tunnel entrances, (2) compare driver behavior inside and outside foggy tunnels, and (3) propose improvement ideas based on the study results. METHODS: A realistic vehicle trial was conducted. Eight participants completed trials in both foggy and clear zones on the same roadway. Drivers' physiological and psychological properties were analyzed using gaze, saccade, pupil, and heart rate as primary indicators. Pupil area change rate and heart rate variability (HRV) were used as secondary indicators. RESULTS: Visibility and tunnel area had a significant impact on drivers' visual and psychological traits. For instance, drivers in the foggy zone exhibited longer fixation duration, larger pupil area, faster heart rate, and greater HRV. Moreover, the foggy zone inside the tunnel heightened drivers' visual discomfort and psychological tension. CONCLUSION: The study suggests a high risk associated with driving in the entrance area of highway tunnels during foggy conditions, particularly after entering the tunnel. This situation significantly increases drivers' visual and psychological load. Furthermore, the effectiveness of retro-reflective facilities diminishes. Therefore, employing more self-illuminated or actively illuminated visual guiding facilities is recommended to aid drivers in acquiring traffic information.

8.
Biol Pharm Bull ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38631865

RESUMO

Nonalcoholic steatohepatitis (NASH) is a subtype of nonalcoholic fatty liver disease (NAFLD) characterized by hepatic steatosis and evidence of hepatocyte injury (ballooning) and inflammation, with or without liver fibrosis. In this study, after 12 weeks of induction, the mice were treated with emodin succinyl ethyl ester (ESEE) for four weeks at doses of 10/30/90 mg/kg/day. The blood analysis of experimental endpoints showed that ESEE exhibited significant therapeutic effects on the progression of disorders of glycolipid metabolism and the induced liver injury in the model animals. Histopathological diagnosis of the liver and total triglyceride measurements revealed that ESEE had a significant therapeutic effect on the histopathological features of nonalcoholic fatty liver disease/hepatitis, such as cellular steatosis and activation of intrahepatic inflammation. Additionally, ESEE was able to improve hepatocyte fat deposition, steatosis, and the course of intrahepatic inflammatory activity. Furthermore, it showed some inhibitory effect on liver fibrosis in the model animals. In summary, this study confirms the therapeutic effects of ESEE on the NAFLD/NASH model in C57BL/6J mice induced by a high-fat, high cholesterol, and fructose diet. These effects were observed through improvements in liver function, inhibition of fibrosis, and inflammatory responses. Changes in blood glucose levels, blood lipid metabolism, liver histopathological staining, liver fibrosis staining, and related pathological scores further supported the therapeutic effects of ESEE. Therefore, this study has important implications for the exploration of novel drugs for nonalcoholic fatty liver disease.

9.
Traffic Inj Prev ; : 1-9, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634777

RESUMO

OBJECTIVE: This study aimed to investigate the effects of visual attraction in the entrance areas of highway tunnels on drivers' saccade behavior and driving safety, with the objective of providing insights for tunnel entrance design and driver education. METHODS: Fifty participants were recruited for the naturalistic driving experiment. Four different visually attractive driving scenarios (baseline, landscape-style architecture, tip slogan, and billboard) were selected. Eye-tracking technology was utilized to record and analyze the scanning behavior of participating drivers. Various metrics, including saccade duration, frequency, amplitude, velocity, and the peak-to-average ratio of saccade velocity (PARSV), were measured and compared across different scenarios. RESULTS: The results revealed different patterns of visual scanning dynamics among the four experimental scenarios, reflecting the different levels of visual-cognitive demands and situation awareness of drivers. The visual attraction in the tunnel entrance area resulted in prolonged saccade duration, increased saccade amplitude, reduced saccade frequency, and slower, less stable saccade velocity. Among these, drivers exhibited the most intricate and unstable scanning behavior, accompanied by the lowest level of situational awareness, particularly under the influence of visual attraction of tip slogan. CONCLUSIONS: The findings highlight the importance of considering visual attraction in tunnel entrance design. Minimizing unnecessary visual attraction can help reduce distractions and maintain driver attention, ultimately enhancing driving safety. Driver education programs should emphasize the significance of adapting to visual attraction at tunnel entrances to promote safer driving practices. Overall, this study contributes valuable insights into the effects of visual attraction on driver scanning behavior, facilitating the development of strategies to improve tunnel design and driver education.

10.
Heliyon ; 10(7): e28769, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38590908

RESUMO

Objective: To investigate the effectiveness of a multimodal deep learning model in predicting tumor budding (TB) grading in rectal cancer (RC) patients. Materials and methods: A retrospective analysis was conducted on 355 patients with rectal adenocarcinoma from two different hospitals. Among them, 289 patients from our institution were randomly divided into an internal training cohort (n = 202) and an internal validation cohort (n = 87) in a 7:3 ratio, while an additional 66 patients from another hospital constituted an external validation cohort. Various deep learning models were constructed and compared for their performance using T1CE and CT-enhanced images, and the optimal models were selected for the creation of a multimodal fusion model. Based on single and multiple factor logistic regression, clinical N staging and fecal occult blood were identified as independent risk factors and used to construct the clinical model. A decision-level fusion was employed to integrate these two models to create an ensemble model. The predictive performance of each model was evaluated using the area under the curve (AUC), DeLong's test, calibration curve, and decision curve analysis (DCA). Model visualization Gradient-weighted Class Activation Mapping (Grad-CAM) was performed for model interpretation. Results: The multimodal fusion model demonstrated superior performance compared to single-modal models, with AUC values of 0.869 (95% CI: 0.761-0.976) for the internal validation cohort and 0.848 (95% CI: 0.721-0.975) for the external validation cohort. N-stage and fecal occult blood were identified as clinically independent risk factors through single and multivariable logistic regression analysis. The final ensemble model exhibited the best performance, with AUC values of 0.898 (95% CI: 0.820-0.975) for the internal validation cohort and 0.868 (95% CI: 0.768-0.968) for the external validation cohort. Conclusion: Multimodal deep learning models can effectively and non-invasively provide individualized predictions for TB grading in RC patients, offering valuable guidance for treatment selection and prognosis assessment.

11.
Int J Psychol ; 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38616135

RESUMO

Social comparison is a universal social phenomenon that profoundly influences aggressive behaviours among young adults. Based on the general aggression model, this study investigated the relationship between social comparison and aggression, and the mediating role of relative deprivation. To further explore the mechanism underlying this influence, covert narcissism was examined as a moderator in this relationship, based on relative deprivation theory. The results from the current study using a total of 726 Chinese college students showed that social comparison was positively correlated with aggression, which was mediated by relative deprivation. Specifically, more frequent social comparison was associated with higher relative deprivation, which was, in turn, associated with higher aggression. Covert narcissism acted as a moderator in this model. Covert narcissism exacerbated the relationships between social comparison and relative deprivation and relative deprivation and aggression. Specifically, compared to individuals with low levels of covert narcissism, those with high levels of covert narcissism exhibited greater relative deprivation when subjected to the same social comparisons, subsequently displaying increased levels of aggression. This study deepens the understanding of the relationship between social comparison and aggression and provides an intervention direction and a theoretical basis for effectively preventing aggression in young adults.

12.
J Agric Food Chem ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619332

RESUMO

The present work was conducted to research the potential mechanism of palmatine (PAL) on lipopolysaccharide (LPS)-caused acute lung injury (ALI). Network pharmacology and bioinformatic analyses were carried out. Mice were intragastrically treated with PAL and intratracheally stimulated with LPS. LPS-induced RAW264.7 cells were employed for the in vitro model. The MPO activity, W/D ratio, neutrophils, total cell number in BALF, and histopathological alteration were examined. The levels of TNF-α, IL-1ß, IL-6, IL-18, IL-4, and IL-10 in serum, BALF, and supernatant were examined by ELISA. The mRNA expressions of iNOS, CD68, Arg1, Ym1, and CD206 and protein expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome were detected by PCR, WB, and immunofluorescence. The NAMPT inhibitor FK866, TLR2 inhibitor C29, CCR1 inhibitor BX471, NAMPT-overexpression (OE) plasmid, and TLR2-OE plasmid were used for mechanism research. As a result, PAL relieved the symptoms of ALI. PAL inhibited M1 phenotype indices and promoted M2 phenotype indices in both LPS-induced mice and RAW264.7 cells. PAL also inhibited the expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome. The treatments with FK866, NAMPT-OE plasmid, C29, TLR2-OE plasmid, and BX471 proved that PAL exerted its effect via NAMPT/TLR2/CCR1. Molecular docking suggested that PAL might combine with NAMPT. In conclusion, PAL ameliorated LPS-induced ALI by inhibiting M1 phenotype macrophage polarization via NAMPT/TLR2/CCR1 signaling.

13.
Commun Biol ; 7(1): 427, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589700

RESUMO

Aging is a global challenge, marked in the lungs by function decline and structural disorders, which affects the health of the elderly population. To explore anti-aging strategies, we develop a dynamic atlas covering 45 cell types in human lungs, spanning from embryonic development to aging. We aim to apply the discoveries of lung's development to address aging-related issues. We observe that both epithelial and immune cells undergo a process of acquisition and loss of essential function as they transition from development to aging. During aging, we identify cellular phenotypic alternations that result in reduced pulmonary compliance and compromised immune homeostasis. Furthermore, we find a distinctive expression pattern of the ferritin light chain (FTL) gene, which increases during development but decreases in various types of lung cells during the aging process.


Assuntos
Envelhecimento , Pulmão , Idoso , Humanos , Pulmão/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Homeostase
14.
Front Pharmacol ; 15: 1375112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38666025

RESUMO

IDH wild-type glioblastoma (GBM) intrinsic subtypes have been linked to different molecular landscapes and outcomes. Accurate prediction of molecular subtypes of GBM is very important to guide clinical diagnosis and treatment. Leveraging machine learning technology to improve the subtype classification was considered a robust strategy. Several single machine learning models have been developed to predict survival or stratify patients. An ensemble learning strategy combines several basic learners to boost model performance. However, it still lacked a robust stacking ensemble learning model with high accuracy in clinical practice. Here, we developed a novel integrative stacking ensemble model framework (ecGBMsub) for improving IDH wild-type GBM molecular subtype classification. In the framework, nine single models with the best hyperparameters were fitted based on extrachromosomal circular DNA (eccDNA) molecular profiling. Then, the top five optimal single models were selected as base models. By randomly combining the five optimal base models, 26 different combinations were finally generated. Nine different meta-models with the best hyperparameters were fitted based on the prediction results of 26 different combinations, resulting in 234 different stacked ensemble models. All models in ecGBMsub were comprehensively evaluated and compared. Finally, the stacking ensemble model named "XGBoost.Enet-stacking-Enet" was chosen as the optimal model in the ecGBMsub framework. A user-friendly web tool was developed to facilitate accessibility to the XGBoost.Enet-stacking-Enet models (https://lizesheng20190820.shinyapps.io/ecGBMsub/).

15.
Biomed Pharmacother ; 174: 116565, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38603888

RESUMO

Neural cell adhesion molecule L1 (L1CAM) is a cell-surface glycoprotein involved in cancer occurrence and migration. Up to today, L1CAM-targeted therapy appeared limited efficacy in clinical trials although quite a few attempts by monoclonal antibody (mAb) or chimeric antigen receptor T-cell therapy (CAR-T) have been reported. Therefore, the development of new effective therapies targeting L1CAM is highly desirable. It has been demonstrated that T cell-engaging bispecific antibody (TCE) plays an effective role in cancer immunotherapy by redirecting the cytotoxic activity of CD3+ T cells to tumor cells, resulting in tumor cell death. In this study, we designed and characterized a novel bispecific antibody (CE7-TCE) based on the IgG-(L)-ScFv format, which targets L1CAM and CD3 simultaneously. In vitro, CE7-TCE induced specific killing of L1CAM-positive tumor cells through T cells. In vivo, CE7-TCE inhibited tumor growth in human peripheral blood mononuclear cell/tumor cell co-grafting models. To overcome the adaptive immune resistance (AIR) that impairs the efficacy of TCEs, we conducted a combination therapy of CE7-TCE with Pembrolizumab (anti-PD1 mAb), which enhanced the anti-tumor activity of CE7-TCE. Our results confirmed the feasibility of using L1CAM as a TCE target for the treatment of solid tumors and revealed the therapeutic potential of CE7-TCE combined with immune checkpoint inhibitors.

16.
Acta Pharmacol Sin ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605180

RESUMO

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs.

17.
Eur J Immunol ; : e2350730, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430202

RESUMO

Sepsis, a multiorgan dysfunction with high incidence and mortality, is caused by an imbalanced host-to-infection immune response. Organ-support therapy improves the early survival rate of sepsis patients. In the long term, those who survive the "cytokine storm" and its secondary damage usually show higher susceptibility to secondary infections and sepsis-induced immunosuppression, in which regulatory T cells (Tregs) are evidenced to play an essential role. However, the potential role and mechanism of Tregs in sepsis-induced immunosuppression remains elusive. In this review, we elucidate the role of different functional subpopulations of Tregs during sepsis and then review the mechanism of sepsis-induced immunosuppression from the aspects of regulatory characteristics, epigenetic modification, and immunometabolism of Tregs. Thoroughly understanding how Tregs impact the immune system during sepsis may shed light on preclinical research and help improve the translational value of sepsis immunotherapy.

18.
Front Bioeng Biotechnol ; 12: 1339135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38476968

RESUMO

Introduction: Bone tissue engineering is considered the ideal approach for bone repair. Mesoporous bioactive glass (MBG) possesses the characteristics of high drug-loading capacity and bioactivity. Low-intensity pulsed ultrasound contributes to promoting fracture healing and bone defect repair, and dimethyloxalyl glycine (DMOG) is a small molecular inhibitor that can suppress prolyl hydroxylase, reducing the degradation of hypoxia-inducible factor. Methods: In this study, we proposed to prepare DMOG-loaded MBG/poly(D,L-lactide) composite scaffolds (DMOG-MBG/PDLLA) for promoting bone repair. The effects of ultrasound stimulation and DMOG release on the cell responses of rat bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) and bone repair in vivo were investigated. Results and Discussion: The results showed that both ultrasound stimulation and DMOG release could promote the proliferation, adhesion and differentiation of BMSCs and HUVECs, respectively. After the implantation of scaffolds in rat cranial bone defect model for 8 weeks, the results indicated that the combined ultrasound stimulation and DMOG release contributed to the highest ability for promoting bone repair. Hence, the DMOG-MBG/PDLLA scaffolds with ultrasound stimulation are promising for application in bone repair.

20.
Theor Appl Genet ; 137(3): 67, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441674

RESUMO

KEY MESSAGE: A major stable QTL, qKl-1BL, for kernel length of wheat was narrowed down to a 2.04-Mb interval on chromosome 1BL; the candidate genes were predicated and the genetic effects on yield-related traits were characterized. As a key factor influencing kernel weight, wheat kernel shape is closely related to yield formation, and in turn affects both wheat processing quality and market value. Fine mapping of the major quantitative trait loci (QTL) for kernel shape could provide genetic resources and a theoretical basis for the genetic improvement of wheat yield-related traits. In this study, a major QTL for kernel length (KL) on 1BL, named qKl-1BL, was identified from the recombinant inbred lines (RIL) in multiple environments based on the genetic map and physical map, with 4.76-21.15% of the phenotypic variation explained. To fine map qKl-1BL, the map-based cloning strategy was used. By using developed InDel markers, the near-isogenic line (NIL) pairs and eight key recombinants were identified from a segregating population containing 3621 individuals derived from residual heterozygous lines (RHLs) self-crossing. In combination with phenotype identification, qKl-1BL was finely positioned into a 2.04-Mb interval, KN1B:698.15-700.19 Mb, with eight differentially expressed genes enriched at the key period of kernel elongation. Based on transcriptome analysis and functional annotation information, two candidate genes for qKl-1BL controlling kernel elongation were identified. Additionally, genetic effect analysis showed that the superior allele of qKl-1BL from Jing411 could increase KL, thousand kernel weight (TKW), and yield per plant (YPP) significantly, as well as kernel bulk density and stability time. Taken together, this study identified a QTL interval for controlling kernel length with two possible candidate genes, which provides an important basis for qKl-1BL cloning, functional analysis, and application in molecular breeding programs.


Assuntos
Locos de Características Quantitativas , Triticum , Humanos , Triticum/genética , Mapeamento Cromossômico , Alelos , Embaralhamento de DNA
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...