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1.
Dalton Trans ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739029

RESUMEN

C-H carboxylation of furoic acid (FA) with CO2 is an atom-efficient strategy to produce 2,5-furandicarboxylic acid (2,5-FDCA) from lignocellulose. The existing carbonate-promoted CO2 carboxylation processes rely on the use of large amounts of expensive Cs2CO3 as a deprotonating reagent and molten salt. Substitution of Cs with other cheap and abundant alkali ions (such as K and Na) can reduce the use of Cs, but it faces the problem of a low yield of 2,5-FDCA. This study found that the addition of catalytic amounts of ZnCl2 as a Lewis acid can increase the yield of 2,5-FDCA in the CO2 carboxylation reaction of Na/K-FA in a molten salt reaction system. 1H NMR analysis and DFT calculations confirmed that ZnCl2 coordinates with the furan ring through electron transfer from the conjugated furan ring to Zn2+, thereby activating the H at the C5 position of Na/K-FA. This coordination lengthened the C5-H bond and lowered its heterolytic dissociation energy, making it more susceptible to being deprotonated by CO32- and subsequently carboxylated by CO2. The developed Lewis acid coordination strategy provides a new idea for the efficient construction of C-C bonds between CO2 and aromatics through carbonate-promoted C-H carboxylation.

2.
Inorg Chem ; 63(19): 8919-8924, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38698558

RESUMEN

The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.

3.
Analyst ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38716512

RESUMEN

Extracellular vesicles (EVs) in urine are a promising source for developing non-invasive biomarkers. However, urine concentration and content are highly variable and dynamic, and actual urine collection and handling often is nonideal. Furthermore, patients such as those with prostate diseases have challenges in sample collection due to difficulties in holding urine at designated time points. Here, we simulated the actual situation of clinical sample collection to examine the stability of EVs in urine under different circumstances, including urine collection time and temporary storage temperature, as well as daily urine sampling under different diet conditions. EVs were isolated using functionalized EVtrap magnetic beads and characterized by nanoparticle tracking analysis (NTA), western blotting, electron microscopy, and mass spectrometry (MS). EVs in urine remained relatively stable during temporary storage for 6 hours at room temperature and for 12 hours at 4 °C, while significant fluctuations were observed in EV amounts from urine samples collected at different time points from the same individuals, especially under certain diets. Sample normalization with creatinine reduced the coefficient of variation (CV) values among EV samples from 17% to approximately 6% and facilitated downstream MS analyses. Finally, based on the results, we applied them to evaluate potential biomarker panels in prostate cancer by data-independent acquisition (DIA) MS, presenting the recommendation that can facilitate biomarker discovery with nonideal handling conditions.

4.
Inorg Chem ; 63(19): 8889-8898, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38693871

RESUMEN

Phosphor-in-glass represents a promising avenue for merging the luminous efficiency of high-quality phosphor and the thermal stability of a glass matrix. Undoubtedly, the glass matrix system and its preparation are pivotal factors in achieving high stability and preserving the original performance of embedded phosphor particles. In contrast to the well-established commercial Y3Al5O12:Ce3+ oxide phosphor, red nitride phosphor, which plays a critical role in high-quality lighting, exhibits greater structural instability during the high-temperature synthesis of inorganic glasses. A telluride glass with a refractive index (RI = 2.15@615 nm) akin to that of nitride phosphor (∼2.19) has been devised, demonstrating high efficiency in photon utilization. The lower glass-transition temperature plays a crucial role in safeguarding phosphor particles against erosion resulting from exposure to high-temperature melts. Phosphor-in-glass retains 93% of the quantum efficiency observed for pure phosphor. The assembled white light-emitting diodes module has precise color tuning capabilities, achieving an optimal color rendering index of 93.7, a luminous efficacy of 80.4 lm/W, and a correlated color temperature of 5850 K. These outcomes hold potential for advancing the realm of inorganic package and high-quality white light illumination.

5.
PLoS One ; 19(5): e0299696, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38728335

RESUMEN

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 disease, which represents a new life-threatening disaster. Regarding viral infection, many therapeutics have been investigated to alleviate the epidemiology such as vaccines and receptor decoys. However, the continuous mutating coronavirus, especially the variants of Delta and Omicron, are tended to invalidate the therapeutic biological product. Thus, it is necessary to develop molecular entities as broad-spectrum antiviral drugs. Coronavirus replication is controlled by the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme, which is required for the virus's life cycle. In the cases of severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), 3CLpro has been shown to be a promising therapeutic development target. Here we proposed an attention-based deep learning framework for molecular graphs and sequences, training from the BindingDB 3CLpro dataset (114,555 compounds). After construction of such model, we conducted large-scale screening the in vivo/vitro dataset (276,003 compounds) from Zinc Database and visualize the candidate compounds with attention score. geometric-based affinity prediction was employed for validation. Finally, we established a 3CLpro-specific deep learning framework, namely GraphDPI-3CL (AUROC: 0.958) achieved superior performance beyond the existing state of the art model and discovered 10 molecules with a high binding affinity of 3CLpro and superior binding mode.


Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , Aprendizaje Profundo , SARS-CoV-2 , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/metabolismo , SARS-CoV-2/genética , Antivirales/farmacología , Antivirales/uso terapéutico , Humanos , Proteasas 3C de Coronavirus/metabolismo , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Unión Proteica , COVID-19/virología , Simulación del Acoplamiento Molecular
6.
Artículo en Inglés | MEDLINE | ID: mdl-38744448

RESUMEN

The use of metaphors to talk about cancer experiences has attracted much research and debate, especially in the case of military metaphors. However, questions remain about what metaphors are used by different populations for different aspects of the cancer experience. This scoping review aims to answer them.We searched PubMed, PsycINFO, CINAHL, Scopus and Web of Science databases. Eligible sources include peer-reviewed scientific research published in English between 2013 and 2023, investigating patterns of metaphor use from adult populations (age ≥18) for cancer-related topics, such as cancer itself, the general experience of being ill, treatment, and people and relationships.Out of 1929 articles identified, 30 met the criteria, spanning over different populations. While most papers focused on cancer in general, some focused on specific cancer types, such as breast cancer. Both spontaneous and elicited data were collected in ten languages: mostly English (N=12), Swedish (N=3) and Arabic (N=3). The identified metaphors were subsumed under various broad categories, including particularly violence and journey. Other categories include education and non-human animate entity for the cancer itself, confinement and deprivation and cleanliness for the general experience of being ill with cancer, Poison and gardening for cancer treatment, and distance for patients' social relationships.It was found that metaphors help to identify how patients describe experiences of vulnerability and empowerment. To provide patient-centred care, clinicians and researchers should avoid blanket conclusions about helpful or unhelpful metaphors, but consider the ways in which different metaphors are used by different populations in different contexts.

7.
Food Chem ; 450: 139285, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38631203

RESUMEN

Theaflavins are beneficial to human health due to various bioactivities. Biosynthesis of theaflavins using polyphenol oxidase (PPO) is advantageous due to cost effectiveness and environmental friendliness. In this review, studies on the mechanism of theaflavins formation, the procedures to screen and prepare PPOs, optimization of reaction systems and immobilization of PPOs were described. The challenges associated with the mass biosynthesis of theaflavins, such as poor enzyme activity, undesirable subproducts and inclusion bodies of recombinant PPOs were presented. Further strategies to solve these challenges and improve theaflavins production, including enzyme engineering, immobilization enzyme technology, water-immiscible solvent-water biphasic systems and recombinant enzyme technology, were proposed.

8.
J Control Release ; 369: 493-505, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582335

RESUMEN

Osteoarthritis (OA) is the most prevalent degenerative cartilage disease, but no effective treatment is currently available to ameliorate the dysregulation of cartilage catabolism. Cartilage degeneration is closely related to the change in the physiology of chondrocytes: for example, chondrocytes of the OA patients overexpress matrix metallopeptidase 13 (MMP13), a.k.a. collagenase 3, which damages the extracellular matrix (ECM) of the cartilage and deteriorate the disease progression. Inhibiting MMP13 has shown to be beneficial for OA treatments, but delivering therapeutics to the chondrocytes embedded in the dense cartilage is a challenge. Here, we engineered the exosome surface with the cartilage affinity peptide (CAP) through lipid insertion to give chondrocyte-targeting exosomes, CAP-Exo, which was then loaded with siRNA against MMP13 (siMMP13) in the interior to give CAP-Exo/siMMP13. Intra-articular administration of CAP-Exo/siMMP13 reduced the MMP13 level and increased collagen COL2A1 and proteoglycan in cartilage in a rat model of anterior cruciate ligament transection (ACLT)-induced OA. Proteomic analysis showed that CAP-Exo/siMMP13 treatment restored the altered protein levels in the IL-1ß-treated chondrocytes. Taken together, a facile exosome engineering method enabled targeted delivery of siRNA to chondrocytes and chondrocyte-specific silencing of MMP13 to attenuate cartilage degeneration.

9.
Nat Commun ; 15(1): 3132, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605051

RESUMEN

Surface condensation control strategies are crucial but commonly require relatively tedious, time-consuming, and expensive techniques for surface-chemical and topographical engineering. Here we report a strategy to alter surface condensation behavior without resorting to any molecule-type or topographical transmutations. After ultrafast contact of liquids with and removal from surfaces, the condensation rate and density of water droplets on the surfaces decrease, the extent of which is positively correlated with the polarity of the liquid and the duration of contact. The liquid contact-induced condensation rate/density decrease (LCICD) can be attributed to the decrease of nucleation site density resulted from the liquid contact-induced adaption of surface molecular conformation. Based on this, we find that LCICD is applicable to various surfaces, on condition that there are flexible segments capable of shielding at least part of nucleation sites through changing the conformation under liquid contact induction. Leveraging the LCICD effect, we achieve erasable information storage on diverse substrates. Furthermore, our strategy holds promise for controlling condensation of other substances since LCICD is not specific to the water condensation process.

10.
One Health ; 18: 100723, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38623498

RESUMEN

Blastocystis is a parasitic protist that can infect humans and various domestic and wild animals. However, there is limited research on the prevalence of this parasite among rodents, particularly those living in pig farm settings. Therefore, to investigate the occurrence, molecular characterization, and zoonotic potential of Blastocystis among rodents within pig farm environments, we conducted an investigation of 227 rodents and shrews from 34 pig farms located in Henan, Shaanxi, and Shanxi provinces of China using nested PCR of the SSU rRNA gene of Blastocystis. The potential transmission and public health implications were also assessed from a One Health perspective. Blastocystis was detected in 86 (37.9%) fecal samples. The highest infection rate was observed among Ruttus norvegicus (73.7%, 42/58), followed by Ruttus tanezumi (30.1%, 41/136), and Mus musculus (12.0%, 3/25). However, it was not detected among individuals with Apodemus agrarius (n = 1) and Crocidura shantungensis (n = 7). Five known zoonotic Blastocystis subtypes (ST1-ST5) were identified, with ST4 (51.2%, 44/86) and ST5 (40.7%, 35/86) being the predominant ones, followed by ST1 (3.5%, 3/86), ST3 (3.5%, 3/86), and ST2 (1.2%, 1/86). ST4 was prevalent among R. norvegicus (83.3%, 35/42), while ST5 dominated R. tanezumi (70.7%, 29/41). Furthermore, ST5 exhibited the widest distribution at pig farm level, accounting for 65.0% (13/20) of Blastocystis-positive pig farms. This investigation presents the first documented Blastocystis infection in R. tanezumi and M. musculus, highlighting the predominant presence of the zoonotic ST5 subtype in rodents for the first time. The results demonstrate that sympatric rodents can serve as natural reservoirs for Blastocystis and play a role in its transmission. These findings provide information on the dynamics of rodent transmission and emphasize the potential public health threat posed by zoonotic Blastocystis subtypes spillover from pig farms.

11.
Heliyon ; 10(8): e29164, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38644881

RESUMEN

Gypenosides (Gyp) are bioactive components of Gynostemma pentaphyllum that have a variety of pharmacological properties. Extracts of G. pentaphyllum have been found to be effective in the reduction of blood sugar and lipids and prevention of atherosclerosis. Here, the functions of Gyp and the mechanisms underlying their effects on atherosclerosis were investigated. Mice were allocated to three groups, namely, the control (C57BL/6), atherosclerosis model (ApoE-/- mice with high-fat diet), and Gyp-treated groups. Differentially expressed mRNAs, miRNAs, circRNA, and differential metabolites among the groups were analyzed. The results showed that "Fatty acid metabolism", "Fatty acid elongation", "Cytokine-cytokine receptor interaction", and "PI3K-Akt signaling pathway", amongst others, were involved in treatment process. Differentially expressed genes, including Fabp1, Apoe, FADS1, ADH1, SYNPO2, and Lmod1were also identified. Mmu-miR-30a and mmu-miR-30e showed reduced expression in atherosclerosis models but were increased following Gyp treatment, suggesting involvement in the effects of Gyp. In addition, chr5:150604177-150608440 were found to interact with mmu-miR-30a and mmu-miR-30e to regulate their abundance. In terms of metabolomics, Gyp may regulate biological processes involving PGD2 and PGJ2, potentially alleviating atherosclerosis. In conclusion, Gyp appeared to have complex effects on atherosclerosis, most of which were positive. These results support the use of Gyp in the treatment of atherosclerosis.

12.
Biosens Bioelectron ; 256: 116275, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38603839

RESUMEN

Constructing relatively inexpensive nanomaterials to simulate the catalytic performance of laccase is of great significance in recent years. Although research on improving laccase-like activity by regulating ligands of copper (amino acids or small organic molecules, etc.) have achieved remarkable success. There are few reports on improving laccase-like activity by adjusting the composition of metal Cu. Here, we used perovskite hydroxide AB(OH)6 as a model to evaluate the relationship between Cu based alloys and their laccase-like activity. We found that when the Cu/Mn alloy ratio of the perovskite hydroxide A point is greater than 1, the laccase-like activity of the binary alloy perovskite hydroxide is higher than that of the corresponding single Cu. Based on the measurements of XPS and ICP-MS, we deduced that the improvements of laccase-like activity mainly attribute to the ratio of Cu+/Cu2+and the content of Cu. Moreover, two types of substrates (toxic pollutants and catechol neurotransmitters) were used to successfully demonstrated such nanozymes' excellent environmental protecting function and biosensing property. This work will provide a novel approach for the construction and application of laccase-like nanozymes in the future.


Asunto(s)
Técnicas Biosensibles , Cobre , Lacasa , Óxidos , Titanio , Lacasa/química , Lacasa/metabolismo , Técnicas Biosensibles/métodos , Cobre/química , Titanio/química , Óxidos/química , Hidróxidos/química , Compuestos de Calcio/química , Restauración y Remediación Ambiental/métodos , Catecoles/análisis , Catecoles/química , Materiales Biomiméticos/química , Catálisis
13.
Materials (Basel) ; 17(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38673221

RESUMEN

Heterojunction semiconductors have been extensively applied in various optoelectronic devices due to their unique carrier transport characteristics. However, it is still a challenge to construct heterojunctions based on colloidal quantum dots (CQDs) due to stress and lattice mismatch. Herein, HgSe/CsPbBrxI3-x heterojunctions with type I band alignment are acquired that are derived from minor lattice mismatch (~1.5%) via tuning the ratio of Br and I in halide perovskite. Meanwhile, HgSe CQDs with oleylamine ligands can been exchanged with a halide perovskite precursor, acquiring a smooth and compact quantum dot film. The photoconductive detector based on HgSe/CsPbBrxI3-x heterojunction presents a distinct photoelectric response under an incident light of 630 nm. The work provides a promising strategy to construct CQD-based heterojunctions, simultaneously achieving inorganic ligand exchange, which paves the way to obtain high-performance photodetectors based on CQD heterojunction films.

14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(5): 581-585, 2024 May 10.
Artículo en Chino | MEDLINE | ID: mdl-38684305

RESUMEN

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Central core disease (CCD). METHODS: A child with CCD who was treated at the Children's Hematology Department of the First Affiliated Hospital of Zhengzhou University in February 2022 was selected as the study subject. Muscle biopsy was performed. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing. RESULTS: The child, a 12-year-old boy, had manifested motor retardation, facial weakness, ptosis, pectus carinatum, scoliosis, etc. Muscle biopsy showed that the central nucleus muscle fibers and atrophic muscle fibers were mainly type I. WES revealed that the child has harbored c.10561G>A (p.G3521S) and c.3448T>C (p.C1150R) compound heterozygous variants of the RYR1 gene. Sanger sequencing confirmed that they were inherited from his mother and father, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were considered as likely pathogenic (PS4+PM1+PM2_Supporting+PP3;PM1+PM2_Supporting+PM3+PP3). CONCLUSION: By combining his clinical manifestation and results of muscle pathology and genetic testing, the child was diagnosed with CCD, which may be attributed to the c.10561G>A (p.G3521S) and c.3448T>C (p.C1150R) compound heterozygous variants of the RYR1 gene.


Asunto(s)
Heterocigoto , Miopatía del Núcleo Central , Canal Liberador de Calcio Receptor de Rianodina , Humanos , Canal Liberador de Calcio Receptor de Rianodina/genética , Masculino , Niño , Miopatía del Núcleo Central/genética , Secuenciación del Exoma , Mutación , Pruebas Genéticas
15.
Neuroimage ; 292: 120609, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38614371

RESUMEN

Current diagnostic systems for Alzheimer's disease (AD) rely upon clinical signs and symptoms, despite the fact that the multiplicity of clinical symptoms renders various neuropsychological assessments inadequate to reflect the underlying pathophysiological mechanisms. Since putative neuroimaging biomarkers play a crucial role in understanding the etiology of AD, we sought to stratify the diverse relationships between AD biomarkers and cognitive decline in the aging population and uncover risk factors contributing to the diversities in AD. To do so, we capitalized on a large amount of neuroimaging data from the ADNI study to examine the inflection points along the dynamic relationship between cognitive decline trajectories and whole-brain neuroimaging biomarkers, using a state-of-the-art statistical model of change point detection. Our findings indicated that the temporal relationship between AD biomarkers and cognitive decline may differ depending on the synergistic effect of genetic risk and biological sex. Specifically, tauopathy-PET biomarkers exhibit a more dynamic and age-dependent association with Mini-Mental State Examination scores (p<0.05), with inflection points at 72, 78, and 83 years old, compared with amyloid-PET and neurodegeneration (cortical thickness from MRI) biomarkers. In the landscape of health disparities in AD, our analysis indicated that biological sex moderates the rate of cognitive decline associated with APOE4 genotype. Meanwhile, we found that higher education levels may moderate the effect of APOE4, acting as a marker of cognitive reserve.


Asunto(s)
Enfermedad de Alzheimer , Apolipoproteínas E , Disfunción Cognitiva , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/fisiopatología , Apolipoproteínas E/genética , Biomarcadores , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Imagen por Resonancia Magnética , Neuroimagen , Tomografía de Emisión de Positrones
16.
Int J Cardiol ; 407: 132029, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38583590

RESUMEN

BACKGROUND: Programmed cell death 1 (PD-1) inhibitors can induce various adverse reactions associated with immunity, of which cardiotoxicity is a serious complication. Limited research exists on the link between PD-1 inhibitor use and pericardial effusion (PE) occurrence and outcomes. METHODS: We conducted a retrospective study at the First Affiliated Hospital of Xi'an Jiaotong University from 2017 to 2019, comparing cancer patients who developed PE within 2 years after PD-1 inhibitor therapy to those who did not. Our primary outcome was the all-cause mortality rate at one year. We applied the Kaplan-Meier method for survival analysis. Multivariate logistic regression was utilized to identify PE risk factors, adjusting for potential confounders. RESULTS: A total of 91 patients were finally included, of whom 39 patients had PE. Compared to non-PE group, one-year all-cause mortality was nearly 5 times higher in PE group (64.10% vs. 13.46%, P < 0.001). Patients who developed PE within 2 years of taking PD-1 inhibitors were significantly associated with increased all-cause mortality compared with those who did not (HR: 6.26, 95%CI: 2.70-14.53, P < 0.001). Multivariable logistic regression showed that use of sintilimab (OR: 14.568, 95%CI: 3.431-61.857, P < 0.001), history of lung cancer (OR: 15.360, 95%CI: 3.276-72.017, P = 0.001), and history of hypocalcemia (OR: 7.076, 95%CI: 1.879-26.649, P = 0.004) were independent risk factors of PE development in patients received PD-1 inhibitors therapy. CONCLUSIONS: In cancer patients receiving PD-1 inhibitors, PE was associated with higher one-year mortality. Use of sintilimab, and history of lung cancer or hypocalcemia were linked to PE occurrence.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias , Derrame Pericárdico , Humanos , Derrame Pericárdico/epidemiología , Derrame Pericárdico/inducido químicamente , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Factores de Riesgo , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Anciano , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Tasa de Supervivencia/tendencias , Resultado del Tratamiento
17.
Stat Sin ; 34(2): 527-546, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38655129

RESUMEN

Multi-modal data are prevalent in many scientific fields. In this study, we consider the parameter estimation and variable selection for a multi-response regression using block-missing multi-modal data. Our method allows the dimensions of both the responses and the predictors to be large, and the responses to be incomplete and correlated, a common practical problem in high-dimensional settings. Our proposed method uses two steps to make a prediction from a multi-response linear regression model with block-missing multi-modal predictors. In the first step, without imputing missing data, we use all available data to estimate the covariance matrix of the predictors and the cross-covariance matrix between the predictors and the responses. In the second step, we use these matrices and a penalized method to simultaneously estimate the precision matrix of the response vector, given the predictors, and the sparse regression parameter matrix. Lastly, we demonstrate the effectiveness of the proposed method using theoretical studies, simulated examples, and an analysis of a multi-modal imaging data set from the Alzheimer's Disease Neuroimaging Initiative.

18.
Adv Sci (Weinh) ; : e2400676, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38460179

RESUMEN

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with a highly immunosuppressive tumor microenvironment and a typical pattern of disturbances in hepatic lipid metabolism. Long non-coding RNAs are shown to play an important role in the regulation of gene expression, but much remains unknown between tumor microenvironment and lipid metabolism as a bridging molecule. Here, long intergenic nonprotein coding RNA 01116 (LINC01116) acts as this molecular which is frequently upregulated in HCC patients and associated with HCC progression in vitro and in vivo is identified. Mechanistically, LINC01116 stabilizes EWS RNA-binding protein 1 (EWSR1) by preventing RAD18 E3 Ubiquitin Protein Ligase (RAD18) -mediated ubiquitination. The enhanced EWSR1 protein upregulates peroxisome proliferator activated receptor alpha (PPARA) and fatty acid binding protein1 (FABP1) expression, a long-chain fatty acid (LCFA) transporter, and thus cancer cells outcompete T cells for LCFAs, especially linoleic acid, for seeding their own growth, leading to T cell malfunction and HCC malignant progression. In a preclinical animal model, the blockade of LINC01116 leads to enhanced efficacy of anti-PD1 treatment accompanied by increased cytotoxic T cell and decreased exhausted T cell infiltration. Collectively, LINC01116 is an immunometabolic lncRNA and the LINC01116-EWSR1-PPARA-FABP1 axis may be targetable for cancer immunotherapy.

19.
Front Bioeng Biotechnol ; 12: 1345163, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38481574

RESUMEN

Peripheral nerve injury (PNI) is a common clinical problem, which due to poor recovery often leads to limb dysfunction and sensory abnormalities in patients. Tissue-engineered nerve guidance conduits (NGCs) that are designed and fabricated from different materials are the potential alternative to nerve autografts. However, translation of these NGCs from lab to commercial scale has not been well achieved. Complete functional recovery with the aid of NGCs in PNI becomes a topic of general interest in tissue engineering and regeneration medicine. Electrical stimulation (ES) has been widely used for many years as an effective physical method to promote nerve repair in both pre-clinical and clinical settings. Similarly, ES of conductive and electroactive materials with a broad range of electrical properties has been shown to facilitate the guidance of axons and enhance the regeneration. Graphene and its derivatives possess unique physicochemical and biological properties, which make them a promising outlook for the development of synthetic scaffolds or NGCs for PNI repair, especially in combination with ES. Considering the discussion regarding ES for the treatment of PNI must continue into further detail, herein, we focus on the role of ES in PNI repair and the molecular mechanism behind the ES therapy for PNI, providing a summary of recent advances in context of graphene-based scaffolds (GBSs) in combination with ES. Future perspectives and some challenges faced in developing GBSs are also highlighted with the aim of promoting their clinical applications.

20.
J Agric Food Chem ; 72(10): 5416-5427, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38477043

RESUMEN

Schizophyllum commune, a fleshy fungus, is an important medicinal and food-homologous mushroom in China. In this work, eight undescribed sesquiterpenes schizomycins A-H (1-8) and one new meroterpenoid schizomycin I (9) together with three known analogues (10-12) were isolated from fruiting bodies of S. commune. Their planar structures were established by extensive spectroscopic and mass spectrometric data. The absolute configurations of compounds 1, 2, and 4 were determined by single crystal X-ray diffraction, and compounds 3 and 5-9 were confirmed by electronic circular dichroism calculations. Anti-inflammatory activities of all isolated compounds were evaluated for their inhibitory effects on IL-6 and IL-1ß production in RAW 264.7 cells. Among them, compound 7 exhibited significant IL-6 inhibitory activity with an IC50 value of 3.6 µM. The results of molecular docking showed that compound 7 interacts with amino acid residues (Gly117, Lys118, Asp120, Thr166, and Try168) of the IL-6 receptor protein through hydrogen bonding.


Asunto(s)
Ascomicetos , Schizophyllum , Sesquiterpenos , Schizophyllum/química , Schizophyllum/metabolismo , Interleucina-6/metabolismo , Simulación del Acoplamiento Molecular , Dicroismo Circular , Cuerpos Fructíferos de los Hongos , Sesquiterpenos/metabolismo , Estructura Molecular
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