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1.
J Health Care Poor Underserved ; 35(3): 962-977, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39129613

RESUMO

Emergency medical retrieval services (EMRS) in remote Indigenous islands is rarely investigated. We analyzed the characteristics of patients who underwent EMRS in Lanyu, an offshore island of Taiwan, from January 1, 2014 to December 31, 2021. The need for EMRS for Lanyu Indigenous residents (N=132, 3.83‰) was almost 1.5-fold and 100-fold for non-Indigenous residents (N=16, 2.64‰) and tourists (N=40, 0.04‰), respectively. The resident group had a longer hospitalization (12.0 ± 12.9 vs. 5.9 ± 11.7 days, p=.007). The tourist group had more near-drowning or decompression sickness (44.0% vs. 3.0%, p<.001) and secondary transfers (20.0% vs. 5.4%, p=.003). All the patients (N=12) that required multiple retrievals were Lanyu Indigenous residents. The Lanyu Indigenous residents, compared with the non-Indigenous residents, had fewer admissions to intensive care units (47.7% vs. 80.0%) and more in-hospital mortalities (10.6% vs. 0.0%). Multifaceted approaches should be initiated to improve the health care system in remote Indigenous islands.


Assuntos
Serviços Médicos de Emergência , Humanos , Taiwan , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Serviços Médicos de Emergência/estatística & dados numéricos , Adulto Jovem , Adolescente , Serviços de Saúde do Indígena/organização & administração , Povos Indígenas
2.
Nat Commun ; 15(1): 6812, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39122741

RESUMO

Photosystem II (PSII) catalyzes the light-driven charge separation and water oxidation reactions of photosynthesis. Eukaryotic PSII core is usually associated with membrane-embedded light-harvesting antennae, which greatly increase the absorbance cross-section of the core. The peripheral antennae in different phototrophs vary considerably in protein composition and arrangement. Photosynthetic cryptophytes possess chlorophyll a/c binding proteins (CACs) that serve as their antennae. How these CACs assemble with the PSII core remains unclear. Here, we report the 2.57-Å resolution structure of cryptophyte PSII-CAC purified from cells at nitrogen-limited stationary growth phase. We show that each monomer of the PSII homodimer contains a core complex, six chlorophyll a/c binding proteins (CACs) and a previously unseen chlorophyll-binding protein (termed CAL-II). Six CACs are arranged as a double-layered arc-shaped non-parallel belt, and two such belts attach to the dimeric core from opposite sides. The CAL-II simultaneously interacts with a number of core subunits and five CACs. The distinct organization of CACs and the presence of CAL-II may play a critical role in stabilizing the dimeric PSII-CAC complex under stress conditions. Our study provides mechanistic insights into the assembly and function of the PSII-CAC complex as well as the possible adaptation of cryptophytes in response to environmental stresses.


Assuntos
Criptófitas , Complexo de Proteína do Fotossistema II , Complexo de Proteína do Fotossistema II/metabolismo , Complexo de Proteína do Fotossistema II/química , Criptófitas/metabolismo , Proteínas de Ligação à Clorofila/metabolismo , Proteínas de Ligação à Clorofila/química , Fotossíntese , Modelos Moleculares , Complexos de Proteínas Captadores de Luz/metabolismo , Complexos de Proteínas Captadores de Luz/química
3.
Front Immunol ; 15: 1452078, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144141

RESUMO

Lung cancer (LC) is one of the most common cancer worldwide. Tumor-associated macrophages (TAMs) are important component of the tumor microenvironment (TME) and are closely related to the stages of tumor occurrence, development, and metastasis. Macrophages are plastic and can differentiate into different phenotypes and functions under the influence of different signaling pathways in TME. The classically activated (M1-like) and alternatively activated (M2-like) represent the two polarization states of macrophages. M1 macrophages exhibit anti-tumor functions, while M2 macrophages are considered to support tumor cell survival and metastasis. Macrophage polarization involves complex signaling pathways, and blocking or regulating these signaling pathways to enhance macrophages' anti-tumor effects has become a research hotspot in recent years. At the same time, there have been new discoveries regarding the modulation of TAMs towards an anti-tumor phenotype by synthetic and natural drug components. Nanotechnology can better achieve combination therapy and targeted delivery of drugs, maximizing the efficacy of the drugs while minimizing side effects. Up to now, nanomedicines targeting the delivery of various active substances for reprogramming TAMs have made significant progress. In this review, we primarily provided a comprehensive overview of the signaling crosstalk between TAMs and various cells in the LC microenvironment. Additionally, the latest advancements in novel drugs and nano-based drug delivery systems (NDDSs) that target macrophages were also reviewed. Finally, we discussed the prospects of macrophages as therapeutic targets and the barriers to clinical translation.


Assuntos
Neoplasias Pulmonares , Transdução de Sinais , Microambiente Tumoral , Macrófagos Associados a Tumor , Microambiente Tumoral/imunologia , Humanos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Animais , Ativação de Macrófagos/imunologia
4.
Transl Cancer Res ; 13(7): 3182-3199, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39145097

RESUMO

Background: Gliomas are the most prevalent primary brain tumors, and patients typically exhibit poor prognoses. Increasing evidence suggests that telomere maintenance mechanisms play a crucial role in glioma development. However, the prognostic value of telomere-related genes in glioma remains uncertain. This study aimed to construct a prognostic model of telomere-related genes and further elucidate the potential association between the two. Methods: We acquired RNA-seq data for low-grade glioma (LGG) and glioblastoma (GBM), along with corresponding clinical information from The Cancer Genome Atlas (TCGA) database, and normal brain tissue data from the Genotype-Tissue Expression (GTEX) database for differential analysis. Telomere-related genes were obtained from TelNet. Initially, we conducted a differential analysis on TCGA and GTEX data to identify differentially expressed telomere-related genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on these genes. Subsequently, univariate Cox analysis and log-rank tests were employed to obtain prognosis-related genes. Least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis were sequentially utilized to construct prognostic models. The model's robustness was demonstrated using receiver operating characteristic (ROC) curve analysis, and multivariate Cox regression of risk scores for clinical characteristics and prognostic models were calculated to assess independent prognostic factors. The aforementioned results were validated using the Chinese Glioma Genome Atlas (CGGA) dataset. Finally, the CIBERSORT algorithm analyzed differences in immune cell infiltration levels between high- and low-risk groups, and candidate genes were validated in the Human Protein Atlas (HPA) database. Results: Differential analysis yielded 496 differentially expressed telomere-related genes. GO and KEGG pathway analyses indicated that these genes were primarily involved in telomere-related biological processes and pathways. Subsequently, a prognostic model comprising ten telomere-related genes was constructed through univariate Cox regression analysis, log-rank test, LASSO regression analysis, and multivariate Cox regression analysis. Patients were stratified into high-risk and low-risk groups based on risk scores. Kaplan-Meier (K-M) survival analysis revealed worse outcomes in the high-risk group compared to the low-risk group, and establishing that this prognostic model was a significant independent prognostic factor for glioma patients. Lastly, immune infiltration analysis was conducted, uncovering notable differences in the proportion of multiple immune cell infiltrations between high- and low-risk groups, and eight candidate genes were verified in the HPA database. Conclusions: This study successfully constructed a prognostic model of telomere-related genes, which can more accurately predict glioma patient prognosis, offer potential targets and a theoretical basis for glioma treatment, and serve as a reference for immunotherapy through immune infiltration analysis.

5.
Food Res Int ; 192: 114811, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39147508

RESUMO

Advanced glycation end products (AGEs), a heterogeneous compound existed in processed foods, are related to chronic diseases when they are accumulated excessively in human organs. Protein-bound Nε-(carboxymethyl) lysine (CML) as a typical AGE, is widely determined to evaluate AGEs level in foods and in vivo. This study investigated the intestinal absorption of three protein-bound CML originated from main food raw materials (soybean, wheat and peanut). After in vitro gastrointestinal digestion, the three protein-bound CML digests were ultrafiltered and divided into four fractions: less than 1 kDa, between 1 and 3 kDa, between 3 and 5 kDa, greater than 5 kDa. Caco-2 cell monolayer model was further used to evaluate the intestinal absorption of these components. Results showed that the absorption rates of soybean protein isolate (SPI)-, glutenin (Glu)-, peanut protein isolate (PPI)-bound CML were 30.18%, 31.57% and 29.5%, respectively. The absorption rates of components with MW less than 5 kDa accounted for 19.91% (SPI-bound CML), 22.59% (Glu-bound CML), 23.64% (PPI-bound CML), respectively, and these samples were absorbed by paracellular route, transcytosis route and active route via PepT-1. Taken together, these findings demonstrated that all three protein-bound CML digests with different MW can be absorbed in diverse absorption pathways by Caco-2 cell monolayer model. This research provided a theoretical basis for scientific evaluation of digestion and absorption of AGEs in food.


Assuntos
Arachis , Digestão , Glutens , Absorção Intestinal , Lisina , Proteínas de Soja , Humanos , Células CACO-2 , Lisina/análogos & derivados , Lisina/metabolismo , Arachis/química , Absorção Intestinal/fisiologia , Proteínas de Soja/metabolismo , Proteínas de Soja/química , Glutens/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Proteínas de Plantas/metabolismo , Triticum/química
6.
Artigo em Inglês | MEDLINE | ID: mdl-39148418

RESUMO

CONTEXT: Hereditary distal renal tubular acidosis caused by SLC4A1 gene mutation (SLC4A1-dRTA) is a rare hereditary form of renal tubular acidosis. Rickets or osteomalacia is a common complication of SLC4A1-dRTA, and seriously affects patients' daily life. However, studies on the bone microstructure in SLC4A1-dRTA are limited. OBJECTIVE: This work aimed to evaluate the bone microstructure of SLC4A1-dRTA patients, compared to age- and sex-matched healthy controls and X-linked hypophosphatemic rickets (XLH) patients. METHODS: This was a retrospective study on eleven SLC4A1-dRTA patients. Clinical manifestations, biochemical and radiographical examinations were characterized. Bone microstructure was examined in seven SLC4A1-dRTA patients, seven healthy controls and twenty-one XLH patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: Skeletal symptoms, including fracture, bone pain, and lower limb deformity, were presented in 72.7% of SLC4A1-dRTA patients. Short stature was presented in 63.6% of the patients. SLC4A1-dRTA patients had significantly lower volumetric BMD in the distal tibia, and more severe deteriorated trabecular bone in the distal radius and tibia than healthy controls. SLC4A1-dRTA patients had significantly more severe deteriorated trabecular bone in the distal radius and distal tibia compared to XLH patients. With long-term alkaline therapy, SLC4A1-dRTA patients had alleviation in bone pain, increase in height. CONCLUSIONS: Skeletal lesions were common clinical manifestations in SLC4A1-dRTA patients. Compared with XLH, another common type of rickets, SLC4A1-dRTA patients had more severe trabecular bone microstructure damage, further supporting the necessity of early diagnosis and timely treatment of the disease.

7.
Bioresour Technol ; : 131291, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153698

RESUMO

Overexpression of Dunaliella parva (D. parva) malic enzyme (ME) gene (DpME) significantly increased DpME expression and ME enzyme activity in transgenic D. parva. Nitrogen limitation had an inhibitory effect on protein content, and DpME overexpression could improve protein content. Nitrogen limitation increased carbohydrate content, and Dunaliella parva overexpressing malic enzyme gene under nitrogen limitation (DpME-N-) group showed the lowest starch content among all groups. Dunaliella parva overexpressing malic enzyme gene under nitrogen sufficient condition (DpME) and DpME-N- groups showed considerably high mRNA levels of DpME. ME activity was significantly enhanced by DpME overexpression, and nitrogen limitation caused a smaller increase. DpME overexpression and nitrogen limitation obviously enhanced lipid accumulation, and DpME overexpression had more obvious effect. Compared with control (wild type), lipid content (68.97%) obviously increased in DpME-N- group. This study indicated that the combination of DpME overexpression and nitrogen limitation was favorable to the production of microalgae biodiesel.

8.
Heliyon ; 10(14): e33890, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39108873

RESUMO

Context: Ultrasound (US) is the most economical and widely used method for detecting lesions in parathyroid regions. Identifying typically parathyroid adenomas as hypoechoic nodules with clear margins. However, 10 % of lesions exhibit atypical features, such as the dual concentric sign, and the cognition of them still needs to be improved. Objective: To promote understanding of clinical and histopathological features for parathyroid lesions with the dual concentric echo sign and to investigate its pathogenesis and methods for distinguishing from cervical lymph nodes to improve US diagnostic accuracy. Methods: Retrospectively, patients were categorized into three groups: Group 1, with 36 patients showing parathyroid lesions with dual concentric echo signs; Group 2, with 40 patients displaying classic hypoechoic parathyroid lesions; and Group 3, comprising 36 patients with identified lymph nodes, which were all examined from January 2018 to December 2019. The clinical data on demographics, clinical symptoms, serum levels, histopathologic findings, and US image characteristics were thoroughly reviewed. Results: According to the clinical data, no significant differences in demographics or lesion sizes were observed in Group 1 and Group 2 (p > 0.05). No significant variances were noted in biochemical markers, including PTH, T-25OHD, and ALP. However, a notable difference was identified in adjusted serum calcium levels, which were significantly lower in Group 1 compared to Group 2 (p < 0.05). Additionally, the proportion of asymptomatic patients was significantly higher in Group 1 compared to Group 2 (p < 0.05). Pathological examination revealed that all lesions with dual concentric echo signs were parathyroid adenomas. The isoechoic central region predominantly corresponded to areas of loose edema, while the hypoechoic peripheral layer was primarily associated with chief and/or oncocytic cells. By comparing the ultrasonography of Groups 1 and 3, the parathyroid lesions with dual concentric echo signs exhibited significant distinctions from lymph nodes in size, blood flow classification, vascular distribution, and anatomical location (p < 0.05). Conclusion: The parathyroid lesions with dual concentric echo signs in US corresponded to specific histopathological manifestations and relatively mild clinical features in the patients, this finding may increase the likelihood of incidental detection of parathyroid lesions by US. Attention to the details of size, location, and blood flow, especially, may aid US physicians in differentiating parathyroid adenomas from cervical lymph nodes.

9.
EMBO Mol Med ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39122888

RESUMO

Collecting duct carcinoma (CDC) is an aggressive rare subtype of kidney cancer with unmet clinical needs. Little is known about its underlying molecular alterations and etiology, primarily due to its rarity, and lack of preclinical models. This study aims to comprehensively characterize molecular alterations in CDC and identify its therapeutic vulnerabilities. Through whole-exome and transcriptome sequencing, we identified KRAS hotspot mutations (G12A/D/V) in 3/13 (23%) of the patients, in addition to known TP53, NF2 mutations. 3/13 (23%) patients carried a mutational signature (SBS22) caused by aristolochic acid (AA) exposures, known to be more prevalent in Asia, highlighting a geologically specific disease etiology. We further discovered that cell cycle-related pathways were the most predominantly dysregulated pathways. Our drug screening with our newly established CDC preclinical models identified a CDK9 inhibitor LDC000067 that specifically inhibited CDC tumor growth and prolonged survival. Our study not only improved our understanding of oncogenic molecular alterations of Asian CDC, but also identified cell-cycle machinery as a therapeutic vulnerability, laying the foundation for clinical trials to treat patients with such aggressive cancer.

10.
Abdom Radiol (NY) ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150544

RESUMO

PURPOSE: The purpose of this study was to evaluate the ability of the mRENAL score to identify patients at risk of either major adverse events (AEs) and/or local tumor recurrence (LR) after percutaneous cryoablation (PCA) in an external patient population. METHODS: Patient demographic data were recorded. The RENAL and mRENAL nephrometry scores were calculated. Clinical outcomes such as AEs, LR, cancer-specific survival (CSS), and overall survival (OS) were collected. AEs were classified according to SIR criteria. Continuous variables and categorical variables were analyzed using the Wilcoxon rank sum test and chi-square test, respectively. Logistic regression analysis was performed to identify variables associated with major AEs or LR. RESULTS: The study included 207 patients (Males: n = 117 (56.5%)) with a mean age of 65.8 (± 11.2) years (range:27-90). Overall, the mean tumor diameter, RENAL score, and mean mRENAL score were 30.1 mm (± 11.4), 6.3 (± 1.7), and 6.8 (± 1.9), respectively. 14 patients (6.8%) and 13 patients (6.3%) experienced a major AE or LR after PCA, respectively. CSS and OS were 98.6% and 90.3%, respectively. For patients with major AEs after PCA, the mean tumor diameter (p < 0.0001), mean RENAL score (p = 0.03), and mean mRENAL score (p = 0.009) were all higher than those for patients without a major AE. Multi-variate regression analysis showed that only mean tumor diameter (p = 0.005) was predictive of a major AE. There were no statistically significant differences between patients with LR and patients without LR after PCA with regards to tumor size (p = 0.07), mean RENAL score (p = 0.32), or mean mRENAL score (p = 0.07). Multi-variate regression analysis showed that only mean tumor diameter (p = 0.01) was predictive of LR. CONCLUSION: The mRENAL score did not accurately identify patients at risk for either major AEs or LR. Maximum tumor diameter alone was predictive of both major AEs and LR, and should be the primary focus during patient selection.

11.
Int J Biol Macromol ; 278(Pt 1): 134610, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39128737

RESUMO

Multifunctional green food packaging films were developed by incorporating Koelreuteria paniculata Laxm. bract extract (KBE) and bio-waste-derived Ti-doped carbon dots (Ti-CDs) into a chitosan/locust bean gum (CG) matrix for the first time. Results from FTIR and XRD demonstrated the precise bonding of Ti-CDs to CG through a Schiff base reaction and hydrogen bonding, while KBE was effectively immobilized within the film matrix via hydrogen bonding. SEM and TGA analysis demonstrated enhanced thermal stability and density of the films. Addition of Ti-CDs synergistically improved the barrier properties and mechanical strength of the films through enhanced hydrogen bonding and Schiff base reactions. Specifically, the incorporation of 3 wt% Ti-CDs increased the oxygen barrier properties, tensile strength, water resistance, and vapor permeability of CG films by approximately 1.18, 0.75, and 1.51 times, respectively. Furthermore, the antimicrobial and antioxidant capabilities were significantly improved with the addition of KBE to films. The CG-3%CDs-KBE film coating effectively prolonged the shelf life of strawberries. Additionally, these films exhibited superior pH responsiveness and ammonia-sensitivity, enabling visual monitoring of shrimp freshness during storage. Importantly, CG-3%CDs-KBE films exhibited biodegradability in soil and displayed good biosafety. Overall, these findings underscore the promising potential of CG-3%CDs-KBE films as multifunctional green food packaging materials.

12.
Osteoporos Int ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093437

RESUMO

Vertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate. PURPOSE: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods. METHODS: This was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center. RESULTS: Vertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (ß-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis. CONCLUSION: 68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

13.
Zhongguo Zhen Jiu ; 44(8): 966-74, 2024 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-39111798

RESUMO

OBJECTIVE: To evaluate the reporting quality of randomized controlled trials (RCTs) of acupuncture for depression. METHODS: Systematic searches were performed in PubMed, the Cochrane Library, EMbase, CNKI, Wanfang, SinoMed and VIP Database for RCTs of acupuncture in treatment of depression. The search time was from the establishment of database to December 1, 2023, and the language restriction was Chinese and English. The reporting quality of RCTs of acupuncture for depression was evaluated using the CONSORT statement, the international standardization for trial reporting, STRICTA, the international standard for clinical trial interventions of acupuncture, and SHARE, the guideline and checklist for reporting sham acupuncture controls. RESULTS: According to the CONSORT statement items, the items with the reporting rate less than 50% was accounted for 54.05% of all of the items for Chinese articles, and there were 8 and 1 items with a reporting rate of 0% and 100%, respectively. For the English articles, the items with the reporting rate less than 50% was accounted for 35.14% of all of the items, and there were 3 and 7 items with a reporting rate of 0% and 100%, respectively. The reporting rate of 15 items in Chinese and English articles was greater than 50%, e.g. structured abstract, background and purpose. Based on STRICTA criteria, the reporting rate of either Chinese or English articles was relatively high. The items for Chinese articles with the reporting rate less than 50% was accounted for 23.53% of all of the items, and there were 1 and 4 items with a reporting rate of 0% and 100%, respectively. For English articles, the items with the reporting rate less than 50% was accounted for 11.76% of all of the items, and there was 1 item with a reporting rate of either 0% or 100%. In compliance with SHARE checklist, the reporting rate was low for either Chinese or English articles. The items with the reporting rate less than 50% was accounted for 57.89% of all of the items for Chinese articles, and there were 2 and 0 items with a reporting rate of 0% and 100%, respectively. For English articles, the items with the reporting rate less than 50% was accounted for 52.63% of all of the items, and there was 1 item with a reporting rate of 0% and 100%, respectively. CONCLUSION: The overall reporting quality of RCTs of acupuncture for depression is low currently. It is urgent to enhance the reporting of the details on sham acupuncture control especially. It is suggested that RCTs should be reported strictly in compliance with the CONSORT statement, STRICTA criteria, and SHARE checklist in the future.


Assuntos
Terapia por Acupuntura , Depressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Acupuntura/normas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Depressão/terapia , Lista de Checagem/normas , Projetos de Pesquisa/normas
14.
Cancer Res ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120596

RESUMO

N6-methyladenosine (m6A) is the most prevalent RNA modification and is associated with various biological processes. Proteins that function as readers and writers of m6A modifications have been shown to play critical roles in human malignancies. Here, we identified KH-type splicing regulatory protein (KHSRP) as an m6A binding protein that contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). High KHSRP levels were detected in PDAC and predicted poor patient survival. KHSRP deficiency suppressed PDAC growth and metastasis in vivo. Mechanistically, KHSRP recognized and stabilized FAK pathway mRNAs, including MET, ITGAV and ITGB1, in an m6A-dependent manner, which led to activation of downstream FAK signaling that promoted PDAC progression. Targeting KHSRP with a PROTAC showed promising tumor suppressive effects in mouse models, leading to prolonged survival. Together, these findings indicate that KHSRP mediates FAK pathway activation in an m6A-dependent manner to support PDAC growth and metastasis, highlighting the potential of KHSRP as a therapeutic target in pancreatic cancer.

15.
Gigascience ; 132024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-39028588

RESUMO

BACKGROUND: Integrative analysis of spatially resolved transcriptomics datasets empowers a deeper understanding of complex biological systems. However, integrating multiple tissue sections presents challenges for batch effect removal, particularly when the sections are measured by various technologies or collected at different times. FINDINGS: We propose spatiAlign, an unsupervised contrastive learning model that employs the expression of all measured genes and the spatial location of cells, to integrate multiple tissue sections. It enables the joint downstream analysis of multiple datasets not only in low-dimensional embeddings but also in the reconstructed full expression space. CONCLUSIONS: In benchmarking analysis, spatiAlign outperforms state-of-the-art methods in learning joint and discriminative representations for tissue sections, each potentially characterized by complex batch effects or distinct biological characteristics. Furthermore, we demonstrate the benefits of spatiAlign for the integrative analysis of time-series brain sections, including spatial clustering, differential expression analysis, and particularly trajectory inference that requires a corrected gene expression matrix.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Aprendizado de Máquina não Supervisionado , Perfilação da Expressão Gênica/métodos , Biologia Computacional/métodos , Humanos , Algoritmos , Animais , Análise por Conglomerados , Encéfalo/metabolismo
16.
J Colloid Interface Sci ; 676: 521-531, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39047379

RESUMO

The sluggish redox reaction kinetics and "shuttle effect" of lithium polysulfides (LPSs) impede the advancement of high-performance lithium-sulfur batteries (LSBs). Transition metal phosphides exhibit distinctive polarity, metallic properties, and tunable electron configuration, thereby demonstrating enhanced adsorption and electrocatalytic capabilities towards LPSs. Consequently, they are regarded as exceptional sulfur hosts for LSBs. Moreover, the introduction of a heterogeneous structure can enhance reaction kinetics and expedite the transport of electrons/ions. In this study, a composite of hollow CoP-FeP cubes with heterostructure modified carbon nanotube (CoFeP-CNTs) was fabricated and utilized as sulfur host in advanced LSBs. The presence of carbon nanotubes (CNTs) facilitates enhanced electron and Li+ transport. Meanwhile, the active sites within the heterogeneous interface of CoP-FeP suppress the "shuttle effect" and enhance the conversion kinetics of LPSs. Therefore, the CoFeP-CNTs/S electrode exhibited exceptional cycling stability and demonstrated a capacity attenuation of merely 0.051 % per cycle over 600 cycles at 1C. This study presents a highly effective tactic for synthesizing dual-acting transition metal phosphides with heterostructure, which will play a pivotal role in advancing the development of efficient LSBs.

17.
Carbohydr Polym ; 342: 122355, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39048218

RESUMO

The application of cellulose derivatives including carboxymethyl cellulose (CMC), polyanionic cellulose (PAC), hydroxyethyl cellulose (HEC), cellulose nanofibrils (CNFs), and cellulose nanocrystals (CNCs) has gained enormous interest, especially as environmentally friendly additives for water-based drilling fluids (WBDFs). This is due to their sustainable, biodegradable, and biocompatible nature. Furthermore, cellulose nanomaterials (CNMs), which include both CNFs and CNCs, possess unique properties such as nanoscale dimensions, a large surface area, as well as unique mechanical, thermal, and rheological performance that makes them stand out as compared to other additives used in WBDFs. The high surface hydration capacity, strong interaction with bentonite, and the presence of a complex network within the structure of CNMs enable them to act as efficient rheological modifiers in WBDFs. Moreover, the nano-size dimension and facilely tunable surface chemistry of CNMs make them suitable as effective fluid loss reducers as well as shale inhibitors as they have the ability to penetrate, absorb, and plug the nanopores within the exposed formation and prevent further penetration of water into the formation. This review provides an overview of recent progress in the application of cellulose derivatives, including CMC, PAC, HEC, CNFs, and CNCs, as additives in WBDFs. It begins with a discussion of the structure and synthesis of cellulose derivatives, followed by their specific application as rheological, fluid loss reducer, and shale inhibition additives in WBDFs. Finally, the challenges and future perspectives are outlined to guide further research and development in the effective utilization of cellulose derivatives as additives in WBDFs.

18.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3441-3451, 2024 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-39041116

RESUMO

Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Macrófagos , Obesidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/complicações , Obesidade/tratamento farmacológico , Obesidade/imunologia , Obesidade/metabolismo , Obesidade/complicações , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Animais , Medicina Tradicional Chinesa
19.
Anesthesiology ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39042042

RESUMO

BACKGROUND: As a mechanosensitive cation channel and key regulator of vascular barrier function, endothelial transient receptor potential vanilloid-type 4 (TRPV4) contributes critically to ventilator-induced lung injury (VILI) and edema formation. Ca2+ influx via TRPV4 can activate Ca2+-activated K + (KCa) channels, categorized into small (SK1-3), intermediate (IK1), and big (BK) KCa, which may in turn amplify Ca2+ influx by increasing the electrochemical Ca2+ gradient and thus, promote lung injury. We therefore hypothesized that endothelial KCa channels may contribute to the progression of TRPV4-mediated VILI. METHODS: Male C57Bl/6J mice were ventilated for 2 h with low or high tidal volumes in the presence or absence of the non-selective KCa antagonists apamin, charybdotoxin, or the selective IK1 antagonist TRAM34. Lung injury was similarly assessed in overventilated, endothelial-specific TRPV4-deficient mice or TRAM34-treated C57Bl/6J mice challenged with intratracheal acid installation. Changes in endothelial Ca2+ concentration ([Ca2+]i) were monitored by real-time imaging in isolated-perfused lungs in response to airway pressure elevation or in human pulmonary microvascular endothelial cells (HPMECs) in response to TRPV4 activation with or without inhibition of KCa channels. Analogously, changes in intracellular potassium concentration ([K+]i) and membrane potential (Vm) were imaged in vitro. RESULTS: Endothelial TRPV4 deficiency or inhibition of KCa channels, and most prominently inhibition of IK1 by TRAM34 attenuated VILI as demonstrated by reduced lung edema, protein leak, and by quantitative lung histology. All KCa antagonists reduced the [Ca2+]i response to mechanical stimulation or direct TRPV4 activation in isolated lungs. TRAM34 and charybdotoxin, yet not apamin prevented TRPV4-induced K+ efflux and membrane hyperpolarization in HPMECs. TRAM34 also attenuated the TRPV4 agonist-induced Ca2+ influx in vitro and reduced acid-induced lung injury in vivo. CONCLUSIONS: KCa channels, specifically IK1, act as amplifiers of TRPV4-mediated Ca2+ influx and establish a detrimental feedback that promotes barrier failure and drives the progression of VILI.

20.
Research (Wash D C) ; 7: 0429, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045421

RESUMO

Lung cancer is the second most commonly diagnosed cancer and a leading cause of cancer-related death, with non-small cell lung cancer (NSCLC) being the most prevalent type. Over 70% of lung cancer patients require radiotherapy (RT), which operates through direct and indirect mechanisms to treat cancer. However, RT can damage healthy tissues and encounter radiological resistance, making it crucial to enhance its precision to optimize treatment outcomes, minimize side effects, and overcome radioresistance. Integrating nanotechnology into RT presents a promising method to increase its efficacy. This review explores various nano-assisted RT strategies aimed at achieving precision treatment. These include using nanomaterials as radiosensitizers, applying nanotechnology to modify the tumor microenvironment, and employing nano-based radioprotectors and radiation-treated cell products for indirect cancer RT. We also explore recent advancements in nano-assisted RT for NSCLC, such as biomimetic targeting that alters mesenchymal stromal cells, magnetic targeting strategies, and nanosensitization with high-atomic number nanomaterials. Finally, we address the existing challenges and future directions of precision RT using nanotechnology, highlighting its potential clinical applications.

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