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1.
Environ Pollut ; 357: 124467, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38950850

ABSTRACT

The 31st FISU Summer World University Games (SWUG) was held in Chengdu, southwestern China, from July 22 to August 8, 2023. A series of control measures were carried out to ensure good air quality during the SWUG, providing an opportunity to investigate the atmospheric behaviors of light-absorbing aerosols under such a substantial disturbance caused by the control measures. To assess the impacts of emission controls on primary pollutants, a field campaign was conducted at a rural site in Chengdu to investigate the characterization of equivalent black carbon (eBC). The changes of eBC concentrations before, during, and after the SWUG were characterized. The sources of eBC were resolved, and the impacts of atmospheric processes on the absorption capacity were also investigated. During the SWUG, the eBC concentration decreased by 12.1 % and 25.3 % compared with those before and after the SWUG. A fossil fuel combustion (eBCff) and a biomass burning (eBCbb) originated eBC were resolved using the aethalometer model. Both eBCff and eBCbb decreased during the SWUG, indicating the effectiveness of control measures. After the SWUG, the influence of biomass burning emissions became more and more significant, and the contribution of brown carbon (BrC) to light absorption at 370-660 nm increased by 52, 19, 7, 6, and 17 % compared to those during the SWUG. As the biomass burning emitted aerosols aged, the absorption Ångström exponent and babs(BrC370nm) decreased gradually, which was mainly due to the photobleaching of the chromophores during the daytime. eBCff was mainly affected by strong wind, while high eBCbb concentration was mainly attributed to the gradual accumulation of biomass-burning emissions near the observation site. The results show the significant reduction of eBC with the implementation of the air pollution mitigation campaign, and provide insights on the impacts of atmospheric processes on BC optical properties during summertime.

2.
Environ Int ; 190: 108863, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38959566

ABSTRACT

Atmospheric fine particulate matter (PM2.5) can harm various systems in the human body. Due to limitations in the current understanding of epidemiology and toxicology, the disease types and pathogenic mechanisms induced by PM2.5 in various human systems remain unclear. In this study, the disease types induced by PM2.5 in the respiratory, circulatory, endocrine, and female and male urogenital systems have been investigated and the pathogenic mechanisms identified at molecular level. The results reveal that PM2.5 is highly likely to induce pulmonary emphysema, reperfusion injury, malignant thyroid neoplasm, ovarian endometriosis, and nephritis in each of the above systems respectively. The most important co-existing gene, cellular component, biological process, molecular function, and pathway in the five systems targeted by PM2.5 are Fos proto-oncogene (FOS), extracellular matrix, urogenital system development, extracellular matrix structural constituent conferring tensile strength, and ferroptosis respectively. Differentially expressed genes that are significantly and uniquely targeted by PM2.5 in each system are BTG2 (respiratory), BIRC5 (circulatory), NFE2L2 (endocrine), TBK1 (female urogenital) and STAT1 (male urogenital). Important disease-related cellular components, biological processes, and molecular functions are specifically induced by PM2.5. For example, response to wounding, blood vessel morphogenesis, body morphogenesis, negative regulation of response to endoplasmic reticulum stress, and response to type I interferon are the top uniquely existing biological processes in each system respectively. PM2.5 mainly acts on key disease-related pathways such as the PD-L1 expression and PD-1 checkpoint pathway in cancer (respiratory), cell cycle (circulatory), apoptosis (endocrine), antigen processing and presentation (female urogenital), and neuroactive ligand-receptor interaction (male urogenital). This study provides a novel analysis strategy for elucidating PM2.5-related disease types and is an important supplement to epidemiological investigation. It clarifies the risks of PM2.5 exposure, elucidates the pathogenic mechanisms, and provides scientific support for promoting the precise prevention and treatment of PM2.5-related diseases.

3.
Inorg Chem ; 63(26): 12073-12080, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946340

ABSTRACT

Luminescent materials typically emit their fluorescence or phosphorescence at a specific wavelength with different excitation energies via the so-called Kasha's rule. If fluorescence or phosphorescence emission via anti-Kasha's rule could be achieved, it will hold great promise for applications in many fields. In this work, we report the synthesis and characterization of new metal-organic halide materials with dual emission of efficient room-temperature phosphorescence and fluorescence, which obey anti-Kasha's rule. Here, three emitting metal-organic halides with formula [ZnX2(bidpe)] (X = Cl for 1, X = Br for 2, X = I for 3, bidpe = 4,4'-bis(imidazol-1-yl)diphenyl ether) were prepared and their photophysical properties were investigated. The complexes exhibit dual emission of fluorescence and phosphorescence via anti-Kasha's rule, and their RTP properties of resultant products are modulated by halide substitution synthesis. DFT calculations indicate that the singlet states exhibit a halide-ligand charge transfer (XLCT) character while the triplet states are dominated by the intraligand π-π* transitions. Furthermore, the multilevel information encryption and anticounterfeiting applications are developed by virtue of anti-Kasha's rule emission.

4.
Theranostics ; 14(9): 3470-3485, 2024.
Article in English | MEDLINE | ID: mdl-38948063

ABSTRACT

Background: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC), but acquired resistance during the treatment greatly limits its clinical efficiency. Lipid metabolic disorder plays an important role in hepatocarcinogenesis. However, whether and how lipid metabolic reprogramming regulates sorafenib resistance of HCC cells remains vague. Methods: Sorafenib resistant HCC cells were established by continuous induction. UHPLC-MS/MS, proteomics, and flow cytometry were used to assess the lipid metabolism. ChIP and western blot were used to reflect the interaction of signal transducer and activator of transcription 3 (STAT3) with glycerol-3-phosphate acyltransferase 3 (GPAT3). Gain- and loss-of function studies were applied to explore the mechanism driving sorafenib resistance of HCC. Flow cytometry and CCK8 in vitro, and tumor size in vivo were used to evaluate the sorafenib sensitivity of HCC cells. Results: Our metabolome data revealed a significant enrichment of triglycerides in sorafenib-resistant HCC cells. Further analysis using proteomics and genomics techniques demonstrated a significant increase in the expression of GPAT3 in the sorafenib-resistant groups, which was found to be dependent on the activation of STAT3. The restoration of GPAT3 resensitized HCC cells to sorafenib, while overexpression of GPAT3 led to insensitivity to sorafenib. Mechanistically, GPAT3 upregulation increased triglyceride synthesis, which in turn stimulated the NF-κB/Bcl2 signaling pathway, resulting in apoptosis tolerance upon sorafenib treatment. Furthermore, our in vitro and in vivo studies revealed that pan-GPAT inhibitors effectively reversed sorafenib resistance in HCC cells. Conclusions: Our data demonstrate that GPAT3 elevation in HCC cells reprograms triglyceride metabolism which contributes to acquired resistance to sorafenib, which suggests GPAT3 as a potential target for enhancing the sensitivity of HCC to sorafenib.


Subject(s)
Carcinoma, Hepatocellular , Drug Resistance, Neoplasm , Liver Neoplasms , STAT3 Transcription Factor , Sorafenib , Sorafenib/pharmacology , Sorafenib/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Humans , Drug Resistance, Neoplasm/drug effects , Cell Line, Tumor , Animals , STAT3 Transcription Factor/metabolism , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mice, Nude , Xenograft Model Antitumor Assays , Lipid Metabolism/drug effects , Apoptosis/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Signal Transduction/drug effects
5.
Front Endocrinol (Lausanne) ; 15: 1385167, 2024.
Article in English | MEDLINE | ID: mdl-38948526

ABSTRACT

Background: Thyroid nodules, increasingly prevalent globally, pose a risk of malignant transformation. Early screening is crucial for management, yet current models focus mainly on ultrasound features. This study explores machine learning for screening using demographic and biochemical indicators. Methods: Analyzing data from 6,102 individuals and 61 variables, we identified 17 key variables to construct models using six machine learning classifiers: Logistic Regression, SVM, Multilayer Perceptron, Random Forest, XGBoost, and LightGBM. Performance was evaluated by accuracy, precision, recall, F1 score, specificity, kappa statistic, and AUC, with internal and external validations assessing generalizability. Shapley values determined feature importance, and Decision Curve Analysis evaluated clinical benefits. Results: Random Forest showed the highest internal validation accuracy (78.3%) and AUC (89.1%). LightGBM demonstrated robust external validation performance. Key factors included age, gender, and urinary iodine levels, with significant clinical benefits at various thresholds. Clinical benefits were observed across various risk thresholds, particularly in ensemble models. Conclusion: Machine learning, particularly ensemble methods, accurately predicts thyroid nodule presence using demographic and biochemical data. This cost-effective strategy offers valuable insights for thyroid health management, aiding in early detection and potentially improving clinical outcomes. These findings enhance our understanding of the key predictors of thyroid nodules and underscore the potential of machine learning in public health applications for early disease screening and prevention.


Subject(s)
Machine Learning , Thyroid Nodule , Thyroid Nodule/diagnosis , Thyroid Nodule/epidemiology , Thyroid Nodule/diagnostic imaging , Humans , Female , Male , China/epidemiology , Cross-Sectional Studies , Middle Aged , Adult , Early Detection of Cancer/methods , Aged , Mass Screening/methods , Ultrasonography/methods
6.
World J Gastrointest Surg ; 16(6): 1660-1669, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38983352

ABSTRACT

BACKGROUND: Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment. Chemoradiotherapy, as one of the important treatment methods for gastric cancer, is of great significance for improving the survival rate of patients. However, the tumor recurrence and survival prognosis of gastric cancer patients after radiotherapy and chemotherapy are still uncertain. AIM: To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians. METHODS: A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023. The Kaplan-Meier method was used to calculate the recurrence rate and survival rate; the log-rank method was used to analyze the single-factor prognosis; and the Cox model was used to analyze the prognosis associated with multiple factors. RESULTS: The median follow-up time of the whole group was 63 months, and the follow-up rate was 93.6%. Stage II and III patients accounted for 31.0% and 66.7%, respectively. The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8% and 9.9%, respectively. A total of 166 patients completed the entire chemoradiotherapy regimen, during which no adverse reaction-related deaths occurred. In terms of the recurrence pattern, 17 patients had local recurrence, 29 patients had distant metastasis, and 12 patients had peritoneal implantation metastasis. The 1-year, 3-year, and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, respectively. The 1-year, 3-year, and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. Multivariate analysis revealed that T stage, peripheral nerve invasion, and the lymph node metastasis rate (LNR) were independent prognostic factors for OS. CONCLUSION: Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects, which is beneficial for local tumor control and can improve the long-term survival of patients. The LNR was an independent prognostic factor for OS. For patients with a high risk of local recurrence, postoperative adjuvant chemoradiation should be considered.

7.
Cancer Lett ; 598: 217095, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964728

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has optimized the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacies of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategies. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC.

8.
Adv Sci (Weinh) ; : e2405050, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38973148

ABSTRACT

Transition metal disulfide compounds (TMDCs) emerges as the promising candidate for new-generation flexible (opto-)electronic device fabrication. However, the harsh growth condition of TMDCs results in the necessity of using hard dielectric substrates, and thus the additional transfer process is essential but still challenging. Here, an efficient strategy for preparation and easy separation-transfer of high-uniform and quality-enhanced MoS2 via the precursor pre-annealing on the designed graphene inserting layer is demonstrated. Based on the novel strategy, it achieves the intact separation and transfer of a 2-inch MoS2 array onto the flexible resin. It reveals that the graphene inserting layer not only enhances MoS2 quality but also decreases interfacial adhesion for easy separation-transfer, which achieves a high yield of ≈99.83%. The theoretical calculations show that the chemical bonding formation at the growth interface has been eliminated by graphene. The separable graphene serves as a photocarrier transportation channel, making a largely enhanced responsivity up to 6.86 mA W-1, and the photodetector array also qualifies for imaging featured with high contrast. The flexible device exhibits high bending stability, which preserves almost 100% of initial performance after 5000 cycles. The proposed novel TMDCs growth and separation-transfer strategy lightens their significance for advances in curved and wearable (opto-)electronic applications.

9.
Adv Sci (Weinh) ; : e2400066, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38973154

ABSTRACT

The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer.

10.
BMC Plant Biol ; 24(1): 632, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38970019

ABSTRACT

BACKGROUND: The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. RESULTS: In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. CONCLUSION: The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.


Subject(s)
Avena , Droughts , Homeostasis , Phylogeny , Plant Proteins , Reactive Oxygen Species , Transcription Factors , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Reactive Oxygen Species/metabolism , Avena/genetics , Avena/metabolism , Gene Expression Regulation, Plant , Polyethylene Glycols/pharmacology , Multigene Family , Stress, Physiological/genetics , Genome-Wide Association Study , Genome, Plant
11.
Neurosci Bull ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976218

ABSTRACT

Endocytosis is a fundamental biological process that couples exocytosis to maintain the homeostasis of the plasma membrane and sustained neurotransmission. Super-resolution microscopy enables optical imaging of exocytosis and endocytosis in live cells and makes an essential contribution to understanding molecular mechanisms of endocytosis in neuronal somata and other types of cells. However, visualization of exo-endocytic events at the single vesicular level in a synapse with optical imaging remains a great challenge to reveal mechanisms governing the synaptic exo-endocytotic coupling. In this protocol, we describe the technical details of stimulated emission depletion (STED) imaging of synaptic endocytosis at the single-vesicle level, from sample preparation and microscopy calibration to data acquisition and analysis.

12.
J Environ Pathol Toxicol Oncol ; 43(4): 81-93, 2024.
Article in English | MEDLINE | ID: mdl-39016143

ABSTRACT

Acute pancreatitis (AP) is a common digestive emergency, needs early prediction and recognition. The study examined the clinical value of long non-coding RNA SNHG1 in AP, and explored its related mechanism for AP. A total of 288 AP cases and 150 healthy persons were recruited, the AP patients were grouped based on AP severity. AR42J cells were treated with 100nM caerulein to stimulate AP in vitro. qRT-PCR was performed for mRNA detection. Receiver operating characteristic (ROC) curve was drawn for diagnostic significance evaluation. The relationship of SNHG1 and miR-140-3p was verified via luciferase reporter and RNA immunoprecipitation (RIP) assay. AP cases had high expression of SNHG1, and it can differentiate AP cases from healthy people with the area under the curve (AUC) of 0.899. Severe AP cases had high values of SNHG1, which was independently related to AP severity. SNHG1 knockdown relieved caerulein-induced AR42J cell apoptosis and inflammatory response. miR-140-3p interacted with SNHG1, and reversed the role of SNHG1 in caerulein-induced AR42J cell injury. RAB21 was a candidate target of miR-140-3p, and was at high expression in AP cell models. SNHG1 may be a promising biomarker for the detection of AP, and serves as a potential biological marker for further risk stratification in the management of AP. SNHG1 knockdown can relieve inflammatory responses and pancreatic cell apoptosis by absorbing miR-140-3p.


Subject(s)
Apoptosis , Pancreatitis , RNA, Long Noncoding , RNA, Long Noncoding/genetics , Pancreatitis/genetics , Humans , Apoptosis/genetics , Male , Female , Middle Aged , Pancreas/pathology , Adult , MicroRNAs/genetics , Inflammation/genetics , Cell Line
13.
Opt Lett ; 49(14): 4030-4033, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008769

ABSTRACT

In this work, we propose a highly reflective Ni/Pt/Al p-electrode for AlGaN-based deep ultraviolet (DUV) light-emitting diodes (LEDs) with a wavelength of 276 nm. AlGaN-based DUV LEDs with traditional Al-based reflectivity electrodes suffer from device degradation and wall-plug efficiency (WPE) droop due to the Al diffusion during electrode annealing. By inserting a Pt layer between the Ni contact layer and the Al reflective layer, the contact characteristics of the p-electrode can be optimized by blocking the diffusion of the O and Al atoms, maintaining a high reflectivity of over 80% near 280 nm. Compared to the AlGaN-based DUV LEDs with Ni/Au traditional p-electrodes and Ni/Al traditional reflective p-electrodes, the WPE of the LED with a highly reflective Ni/Pt/Al p-electrode is improved by 10.3% and 30.5%, respectively. Besides, compared to the other novel reflective p-electrodes using multiple annealing or evaporation processes reported for the AlGaN-based DUV LEDs, we provide a new, to the best of our knowledge, optimization method for single evaporation and annealing p-type reflective electrodes, featured with a simpler and more convenient process flow.

14.
Proc Natl Acad Sci U S A ; 121(30): e2319267121, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39008679

ABSTRACT

Migrasomes, vesicular organelles generated on the retraction fibers of migrating cells, play a crucial role in migracytosis, mediating intercellular communication. The cargoes determine the functional specificity of migrasomes. Migrasomes harbor numerous intraluminal vesicles, a pivotal component of their cargoes. The mechanism underlying the transportation of these intraluminal vesicles to the migrasomes remains enigmatic. In this study, we identified that Rab10 and Caveolin-1 (CAV1) mark the intraluminal vesicles in migrasomes. Transport of Rab10-CAV1 vesicles to migrasomes required the motor protein Myosin Va and adaptor proteins RILPL2. Notably, the phosphorylation of Rab10 by the kinase LRRK2 regulated this process. Moreover, CSF-1 can be transported to migrasomes through this mechanism, subsequently fostering monocyte-macrophage differentiation in skin wound healing, which served as a proof of the physiological importance of this transporting mechanism.


Subject(s)
Caveolin 1 , Cell Movement , rab GTP-Binding Proteins , rab GTP-Binding Proteins/metabolism , rab GTP-Binding Proteins/genetics , Humans , Caveolin 1/metabolism , Caveolin 1/genetics , Macrophages/metabolism , Phosphorylation , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Myosin Type V/metabolism , Myosin Type V/genetics , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Mice , Myosin Heavy Chains/metabolism , Myosin Heavy Chains/genetics , Biological Transport , Wound Healing/physiology , Organelles/metabolism
15.
Injury ; 55(10): 111690, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39002323

ABSTRACT

BACKGROUND: Femoral neck fractures (FNF) in young and middle-aged adults are primarily caused by high-energy injuries in traffic accidents. Surgical delays often occur due to transportation issues, preoperative evaluations, and economic burdens. METHODS: A retrospective analysis was conducted on young and middle-aged FNF patients undergoing reduction and internal fixation surgeries from 2010 to 2019 with the use of the National Inpatient Sample database. Logistic regression analysis was used to assess the relationship between surgical delays and complications, and the independent risk factors contributing to delays. Categorical variables were investigated via a chi-square test, while continuous variables including Elixhauser Comorbidity Index (ECI) scores, length of hospital stay (LOS), and total medical costs were analyzed via t-test or rank-sum test. RESULTS: 9,204 patients undergoing reduction and internal fixation surgeries were included. In the delayed group, patients had higher ECI scores, longer hospital stays, higher expenses, and increased inpatient mortality (1.61% vs. 0.28 %, P < 0.0001). Longer surgical delays were associated with higher risks of complications, including femoral head osteonecrosis, internal fixation loosening and breakage, and respiratory complications. Fluid and electrolyte disorders, metastatic cancer, pulmonary circulation disorders, and renal failure were identified as independent risk factors for surgical delays. Except for anemia (OR=2.37, P < 0.0001), no significant differences in early postoperative complications were found between open-reduction and closed-reduction internal fixation (ORIF/CRIF) surgeries. CONCLUSION: Early surgical intervention, within a 2-days period after injury, seems to be crucial for young adults with FNF. If CRIF is challenging in some cases, ORIF can be another choice.

16.
Heliyon ; 10(12): e33077, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38994107

ABSTRACT

Dysfunction of the blood-brain barrier (BBB) has been increasingly recognised as a critical early event in Alzheimer's disease (AD) pathophysiology. Central to this mechanism is the impaired function of brain endothelial cells (BECs), the primary structural constituents of the BBB, the study of which is imperative for understanding AD pathophysiology. However, the published methods to isolate BECs are time-consuming and have a low success rate. Here, we developed a rapid and streamlined protocol for BEC isolation without using transgenic reporters, flow cytometry, and magnetic beads, which are essential for existing methods. Using this novel protocol, we isolated high-purity BECs from cell clusters of cortical microvessels from wild-type and APPswe/PS1dE9 (APP/PS1, a classical AD model) mice at 2, 4 and 9 months of age. Reduced levels of tight junction proteins Claudin-5 and Zonula Occludens-1, as well as glucose transporter 1, were observed in the isolated cortical microvessels from APP/PS1 mice and amyloid-ß (Aß) oligomer-treated BECs from wild-type mice. Trans-well permeability assay showed increased FITC-dextran leakage in BECs treated with Aß, suggesting impaired BBB permeability. BECs obtained using our novel protocol can undergo various experimental analyses, including immunofluorescence staining, western blotting, real-time PCR, and trans-well permeability assay. In conclusion, our novel protocol represents a reliable and valuable tool for in vitro modelling BBB to study AD-related mechanisms and develop targeted therapeutic strategies.

17.
Front Pharmacol ; 15: 1403966, 2024.
Article in English | MEDLINE | ID: mdl-38994198

ABSTRACT

Background: Voriconazole is primarily metabolized by CYP2C19 and CYP3A4. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted voriconazole concentrations. Case summary: In this case report, we describe the case of a 64-year-old man who was treated for non-Hodgkin's lymphoma with continuous glucocorticoids co-administrated with voriconazole against invasive pulmonary aspergillosis. A decrease in trough concentration (Cmin) of voriconazole was observed and related with co-administration of dexamethasone in the patient carrying the CYP2C19 *1*2 genotype: voriconazole Cmin/dose ratios of 0.018 (0.1 mg L-1/5.7 mg kg-1 day-1), 0.18 (1 mg L-1/5.7 mg kg-1 day-1), and 0.23 (2 mg L-1/8.6 mg kg-1 day-1) at dexamethasone doses of 20, 12.5, and 2.5 mg, respectively. Sub-therapeutic voriconazole Cmin was associated with high- and moderate-dose dexamethasone (20 and 12.5 mg), leading to failure of antifungal treatment. Conclusion: The extent of voriconazole-dexamethasone interaction was determined by the dose of dexamethasone and associated with the CYP2C19 *1*2 genotype. Therapeutic drug monitoring of voriconazole is necessary to avoid clinically relevant interactions for optimal antifungal therapy.

18.
Nat Commun ; 15(1): 5774, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38982079

ABSTRACT

Vertical transistors, in which the source and drain are aligned vertically and the current flow is normal to the wafer surface, have attracted considerable attention recently. However, the realization of high-density vertical transistors is challenging, and could be largely attributed to the incompatibility between vertical structures and conventional lateral fabrication processes. Here we report a T-shape lamination approach for realizing high-density vertical sidewall transistors, where lateral transistors could be pre-fabricated on planar substrates first and then laminated onto vertical substrates using T-shape stamps, hence overcoming the incompatibility between planar processes and vertical structures. Based on this technique, we vertically stacked 60 MoS2 transistors within a small vertical footprint, corresponding to a device density over 108 cm-2. Furthermore, we demonstrate two approaches for scalable fabrication of vertical sidewall transistor arrays, including simultaneous lamination onto multiple vertical substrates, as well as on the same vertical substrate using multi-cycle layer-by-layer laminations.

19.
Ecol Evol ; 14(7): e11589, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38979007

ABSTRACT

Beetles have a remote evolutionary history dating back to the Carboniferous, with Mesozoic fossils playing a pivotal role in elucidating the early evolution of extant families. Despite their exceptional preservation in amber, deciphering the systematic positions of Mesozoic trogossitid-like beetles remains challenging. Here, we describe and illustrate a new trogossitid-like lineage from mid-Cretaceous Kachin amber, Foveapeltis rutai Li, Kolibác, Liu & Cai, gen. et sp. nov. Foveapeltis stands out within the Cleroidea due to the presence of a significant large cavity on each hypomeron. While the exact phylogenetic placement of Foveapeltis remains uncertain, we offer a discussion on its potential affinity based on our constrained phylogenetic analyses.

20.
J Crohns Colitis ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980753

ABSTRACT

BACKGROUND AND AIMS: Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis (steroid-refractory (SR) ASUC) requires colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC. METHODS: Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5 mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo. RESULTS: Tofacitinib (odds ratio [OR]: 0.09 [95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates. CONCLUSION: This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.

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