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1.
Cell ; 187(11): 2717-2734.e33, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653239

RESUMO

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.


Assuntos
Akkermansia , Bacteroides , Ácidos e Sais Biliares , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Simbiose , Animais , Humanos , Masculino , Camundongos , Akkermansia/metabolismo , Bacteroides/metabolismo , beta-Lactamases/metabolismo , Ácidos e Sais Biliares/metabolismo , Vias Biossintéticas/genética , Fígado Gorduroso/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Verrucomicrobia/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia
2.
Phys Rev Lett ; 132(5): 056301, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38364160

RESUMO

Recent experiments reported an antisymmetric planar Hall effect, where the Hall current is odd in the in plane magnetic field and scales linearly with both electric and magnetic fields applied. Existing theories rely exclusively on a spin origin, which requires spin-orbit coupling to take effect. Here, we develop a general theory for the intrinsic planar Hall effect (IPHE), highlighting a previously unknown orbital mechanism and connecting it to a band geometric quantity-the anomalous orbital polarizability (AOP). Importantly, the orbital mechanism does not request spin-orbit coupling, so sizable IPHE can occur and is dominated by an orbital contribution in systems with weak spin-orbit coupling. Combined with first-principles calculations, we demonstrate our theory with quantitative evaluation for bulk materials TaSb_{2}, NbAs_{2}, and SrAs_{3}. We further show that AOP and its associated orbital IPHE can be greatly enhanced at topological band crossings, offering a new way to probe topological materials.

3.
Future Oncol ; 20(3): 121-129, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38353107

RESUMO

Immune checkpoint inhibitors (ICIs) plus chemotherapy has demonstrated efficacy in resectable non-small-cell lung cancer (NSCLC), yet the optimal period of neoadjuvant immunochemotherapy is undetermined. In a phase II study (neoSCORE, NCT04459611), more neoadjuvant therapy cycles appeared to provide greater pathological remission, and patients with squamous NSCLC had a better major pathological response rate than those with nonsquamous NSCLC. Sintilimab, a monoclonal anti-PD-1 antibody, has shown encouraging antitumor activity and safety in multiple cancers, including NSCLC. Here, we describe the study design of neoSCORE II (NCT05429463), a randomized, open-label, multicenter phase III trial comparing the efficacy and safety of three cycles with four cycles of neoadjuvant sintilimab plus platinum-based chemotherapy in resectable stage IIA-IIIB squamous NSCLC. Trial registration number: NCT05429463 (ClinicalTrials.gov).


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Terapia Neoadjuvante , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como Assunto
4.
Environ Res ; 248: 118342, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38295980

RESUMO

Biodegradable mulch films (BDMs) are increasingly used in agricultural production as desirable alternatives to the current widespread use of polyethylene (PE) mulch films in China. However, potential effects of different colors of BDMs on field crop production and microbiomes remain unexplored. Here, the differences in bacterial communities of peanut rhizosphere soil (RS) and bulk soil (BS) under non-mulching (CK), PE, and three different colors of BDMs were studied. The results indicated that all treatments could increase the soil temperature, which positively affected the growth of the peanut plants. Moreover, mulching affected the bacterial community structure in RS and BS compared to CK. Furthermore, certain BDM treatments significantly enriched N-fixing bacteria (Bradyrhizobium and Mesorhizobium) and functional groups, increased the closeness of bacterial networks, and harbored more beneficial bacteria as keystone taxa in the RS. This in turn facilitated the growth and development of the peanut plants under field conditions. Our study provides new insights into the micro-ecological effects of mulch films, which can be affected by both the mulch type and color. The observed effects are likely caused by temperature and prevalence of specific microbial functions under the employed films and could guide the development of optimized mulching materials.


Assuntos
Arachis , Solo , Solo/química , Agricultura/métodos , Bactérias , Polietileno
5.
BMC Geriatr ; 24(1): 284, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532326

RESUMO

BACKGROUND: Dyadic coping resources have been considered a potential explanatory mechanism of spousal interdependence in health, but the mediation of spousal collaboration for the relationship between self-rated health and depressive symptoms has yet to be examined. This study aimed to investigate the within- (actor effect) and between-partner effects of self-rated health on depressive symptoms in community-dwelling older couples facing physical functioning limitations and to examine the role of spousal collaboration in mediating the actor and cross-partner effects of self-rated health on depressive symptoms. METHOD: Data from 185 community-dwelling older Chinese married couples were analyzed using the actor-partner interdependence mediation model (APIMeM). Couples were interviewed through trained research assistants using the 5-item common dyadic coping subscale of the Dyadic Coping Inventory (DCI), the Visual Analog Scale (VAS) of the QoL questionnaire EQ-5D and the Patient Health Questionnaire-9 (PHQ-9). RESULTS: Husbands' self-rated health had an actor effect on their own depressive symptoms and a partner effect on their wives' depressive symptoms. Wives' self-rated health had an actor effect on their own depressive symptoms. The actor effects between self-rated health and depressive symptoms were partially mediated by their own perception of spousal collaboration. Furthermore, husbands' self-rated health not only affects wives' depressive symptoms directly but also indirectly by influencing wives' perceptions of spousal collaboration. DISCUSSION: The findings from this study underscored the importance of viewing couples' coping processes from a dyadic and gender-specific perspective, since more (perceived) collaborative efforts have beneficial effects on both partners' mental health outcomes.


Assuntos
Depressão , Qualidade de Vida , Humanos , Depressão/psicologia , Cônjuges/psicologia , Inquéritos e Questionários , China
6.
J Asian Nat Prod Res ; : 1-8, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963349

RESUMO

The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/ß, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.

7.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38892292

RESUMO

Cuticular waxes are essential for protecting plants from various environmental stresses. Allium fistulosum serves as an excellent model for investigating the regulatory mechanisms underlying cuticular wax synthesis with notable epidermal wax characteristics. A combination of gas chromatography-mass spectrometry (GC-MS) metabolite analysis and transcriptomics was used to investigate variations in metabolites and gene expression patterns between the wild type (WT) and glossy mutant type (gl2) of A. fistulosum. The WT surface had a large number of acicular and lamellar waxy crystals, whereas the leaf surface of gl2 was essentially devoid of waxy crystals. And the results revealed a significant decrease in the content of 16-hentriacontanone, the principal component of cuticular wax, in the gl2 mutant. Transcriptomic analysis revealed 3084 differentially expressed genes (DEGs) between WT and gl2. Moreover, we identified 12 genes related to fatty acid or wax synthesis. Among these, 10 DEGs were associated with positive regulation of wax synthesis, whereas 2 genes exhibited negative regulatory functions. Furthermore, two of these genes were identified as key regulators through weighted gene co-expression network analysis. Notably, the promoter region of AfisC5G01838 (AfCER1-LIKE1) exhibited a 258-bp insertion upstream of the coding region in gl2 and decreased the transcription of the AfCER1-LIKE1 gene. This study provided insights into the molecular mechanisms governing cuticular wax synthesis in A. fistulosum, laying the foundation for future breeding strategies.


Assuntos
Allium , Cromatografia Gasosa-Espectrometria de Massas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Transcriptoma , Ceras , Ceras/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Perfilação da Expressão Gênica/métodos , Allium/genética , Allium/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
8.
Ecol Lett ; 26(8): 1370-1381, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37278184

RESUMO

Shifts in plant phenology influence ecosystem structures and functions, yet how multiple global change drivers interact to affect phenology remains elusive. We conducted a meta-analysis of 242 published articles to assess interactions between warming (W) and other global change drivers including nitrogen addition (N), increased precipitation (IP), decreased precipitation (DP) and elevated CO2 (eCO2 ) on multiple phenophases in experimental studies. We show that leaf out and first flowering were most strongly affected by warming, while warming and decreased precipitation were the most pronounced drivers for leaf colouring. Moreover, interactions between warming and other global change drivers were common and both synergistic and antagonistic interactions were observed: interactions W + IP and W + eCO2 were frequently synergistic, whereas interactions W + N and W + DP were mostly antagonistic. These findings demonstrate that global change drivers often affect plant phenology interactively. Incorporating the multitude of interactions into models is crucial for accurately predicting plant responses to global changes.


Assuntos
Clima , Ecossistema , Plantas , Folhas de Planta/fisiologia , Reprodução , Mudança Climática
9.
J Cell Biochem ; 124(9): 1324-1345, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37475541

RESUMO

Upper tract urothelial carcinoma (UTUC), including renal, pelvic, and ureteral carcinoma, has a high incidence rate in Taiwan, which is different from that in Western countries. Therefore, it is imperative to elucidate the mechanisms underlying UTUC growth and metastasis. To explore the function of miR-145-5p in UTUC, we transfected the BFTC909 cell line with miR-145-5p mimics and analyzed the differences in protein levels by performing two-dimensional polyacrylamide gel electrophoresis. Real-time polymerase chain reaction and Western blot analysis were used to analyze 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inositol monophosphate cyclohydrolase (ATIC) messenger RNA and protein levels. A dual-luciferase assay was performed to identify the target of miR-145-5p in ATIC. The effects of miR-145-5p and ATIC expression by cell transfection on cell proliferation, migration, and invasion were also assessed. miR-145-5p downregulated ATIC protein expression. High ATIC expression is associated with tumor stage, metastasis, recurrence, and a poor prognosis in patients with UTUC. Cell function assays revealed that ATIC knockdown inhibited the proliferation, migration, and invasive abilities of UTUC cells. In contrast, miR-145-5p affected the proliferation, migration, and invasive abilities of UTUC cells by directly targeting the 3'-untranslated regions of ATIC. Furthermore, we used RNA sequencing and Ingenuity Pathway Analysis to identify possible downstream genes regulated by ATIC and found that miR-145-5p regulated the protein levels of fibronectin 1, Slug, cyclin A2, cyclin B1, P57, and interferon-induced transmembrane 1 via ATIC. ATIC may be a valuable predictor of prognosis and a potential therapeutic target for UTUC.


Assuntos
Carcinoma de Células de Transição , Hidroximetil e Formil Transferases , MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , MicroRNAs/genética , Carcinoma de Células de Transição/genética , Linhagem Celular Tumoral , Neoplasias da Bexiga Urinária/genética , Hidroximetil e Formil Transferases/genética , Proliferação de Células/genética , Ribonucleotídeos , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica
10.
Phys Rev Lett ; 130(1): 016301, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36669212

RESUMO

Berry curvature dipole plays an important role in various nonlinear quantum phenomena. However, the maximum symmetry allowed for nonzero Berry curvature dipole in the transport plane is a single mirror line, which strongly limits its effects in materials. Here, via probing the nonlinear Hall effect, we demonstrate the generation of Berry curvature dipole by applied dc electric field in WTe_{2}, which is used to break the symmetry constraint. A linear dependence between the dipole moment of Berry curvature and the dc electric field is observed. The polarization direction of the Berry curvature is controlled by the relative orientation of the electric field and crystal axis, which can be further reversed by changing the polarity of the dc field. Our Letter provides a route to generate and control Berry curvature dipole in broad material systems and to facilitate the development of nonlinear quantum devices.


Assuntos
Eletricidade , Frutas
11.
Phys Rev Lett ; 130(16): 166302, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37154629

RESUMO

We propose a time-reversal-even spin generation in second order of electric fields, which dominates the current induced spin polarization in a wide class of centrosymmetric nonmagnetic materials, and leads to a novel nonlinear spin-orbit torque in magnets. We reveal a quantum origin of this effect from the momentum space dipole of the anomalous spin polarizability. First-principles calculations predict sizable spin generations in several nonmagnetic hcp metals, in monolayer TiTe_{2}, and in ferromagnetic monolayer MnSe_{2}, which can be detected in experiment. Our work opens up the broad vista of nonlinear spintronics in both nonmagnetic and magnetic systems.

12.
Phys Chem Chem Phys ; 25(24): 16559-16569, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37309184

RESUMO

The coexistence of spin-orbit coupling and piezoelectricity in a single material may have potential application in multifunctional devices, including spintronics, nanorobotics and piezotronics. Spin-orbit coupling provides a new means to manipulate electron's spin without an additional external magnetic field, while piezoelectricity refers to the interplay between mechanical stresses and electric polarization. Using first-principles calculations, the structural, electronic, optical, spin, and piezoelectric properties of the Janus Ge2XY (X ≠ Y = P, As, Sb, and Bi) monolayers were systematically investigated. All the Ge2XY are energetically and dynamically stable in the α phase. At the GW level, Ge2AsSb, Ge2AsBi, and Ge2SbBi have direct fundamental band gaps of 0.65, 0.64, and 0.91 eV. At the GW + BSE level, their optical gaps are 0.42, 0.45, and 0.63 eV, and the optical absorption coefficients can reach about 10-5 cm-1 in the infrared light region, which reveals that they have potential for application in infrared photodetectors. For Ge2PBi, Ge2AsBi, and Ge2SbBi containing the heavy Bi element, the lowermost conduction band and uppermost valence band have large spin splitting along the M-K and K-Γ lines, and the bands near the Fermi level possess Rashba spin splitting at the Γ point. Ge2PBi and Ge2SbBi have both large in-plane piezoelectric coefficients d11 (-0.75 and -3.18 pm V-1) and out-of-plane piezoelectric coefficients d31 (0.37 and 0.30 pm V-1). Our findings are helpful to understand the mechanism of the spin-orbit physics and piezoelectricity of Janus Ge2XY monolayers and guide experiments in exploring novel multifunctional materials.

13.
Aging Ment Health ; 27(7): 1266-1273, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35758023

RESUMO

OBJECTIVES: With sociodemographic changes, men are increasingly taking responsibility for spousal caregiving. Previous studies have described gender differences in the psychological outcomes of caregiving; however, few have focused exclusively on husband caregivers. This study investigates the influence of starting spousal caregiving on the psychological well-being of older husbands in rural areas and examines whether living arrangements can moderate this relationship. METHODS: A total of 1,167 baseline non-caregiver husbands aged 60 and above in rural areas were taken from the 2011-2015 China Health and Retirement Longitudinal Study (CHARLS). The generalized estimating equation (GEE) was employed to examine the effects of spousal caregiving transitions and living arrangement changes on depressive symptoms over four years. RESULTS: Compared with rural husbands who remained non-caregivers, those transitioning into activities of daily living (ADL) caregiving reported higher depressive symptoms at follow-up (B = 1.67, p < 0.05). Moreover, the increase in depressive symptoms when transitioning into ADL caregiving was significantly lower among participants who changed from living with spouse alone to living with spouse and other family members together (B = - 5.37, p < 0.05). CONCLUSION: There was an association between transitioning into ADL caregiving and an elevated level of depression over four years among older husbands, which could be alleviated by living with family members. Co-residence with family members could serve as a natural support resource, buffering adverse mental health outcomes when older husbands start a demanding caregiving role.

14.
Aging Ment Health ; 27(10): 2027-2033, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36995262

RESUMO

OBJECTIVES: Previous research has identified that unmet needs are associated with adverse mental health outcomes in older adults. However, the unmet needs of older adults' spousal caregivers are unknown. The present study examined the association between unmet needs and depression among spousal caregivers, and whether marital satisfaction mediated this association. METHODS: We included 1,856 participants who provided care to their spouses with difficulties in activities of daily living (ADL) and instrumental activities of daily living (IADL) from the 2018 China Health and Retirement Longitudinal Survey. Unmet needs of spousal caregivers were assessed as the total number of ADL/IADL tasks with which respondents had unmet needs. Path models were conducted to evaluate the associations between unmet needs, marital satisfaction, and depression. Subgroup analyses by sex were conducted to examine the sex differences regarding the associations. RESULTS: Spousal caregivers with more unmet ADL/IADL needs reported higher levels of depression (p < 0.001). Additionally, for wife caregivers, unmet ADL/IADL needs were associated with lower marital satisfaction, and lower marital satisfaction was associated with higher degrees of depression, indicating that marital satisfaction partially mediated the association between unmet needs and depression (p < 0.01). However, marital satisfaction did not mediate the association between unmet needs and depression among husband caregivers. CONCLUSIONS: The mediating effect of marital satisfaction on the association between unmet needs and depression only existed in wife caregivers. Social services should be provided to meet the needs of caregivers with ADL/IADL difficulties, and interventions should be implemented to promote the marital satisfaction of wife caregivers.


Assuntos
Atividades Cotidianas , Cuidadores , Humanos , Masculino , Feminino , Idoso , Cuidadores/psicologia , Depressão/epidemiologia , Casamento , Cônjuges/psicologia , Satisfação Pessoal
15.
Phytother Res ; 37(9): 4042-4058, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37165703

RESUMO

Lentinan, a natural drug with wide-ranging pharmacological activities, can regulate autophagy-the process through which Schwann cells (SCs) eliminate myelin fragments after peripheral nerve injury (PNI). However, the effect of lentinan after PNI and the role of accelerated myelin debris removal via autophagy in this process are unclear. This study examined the effect of lentinan on rat sciatic nerve repair following crush injury and the underlying mechanisms. After the successful establishment of the sciatic nerve compression injury model, group-specific treatments were performed. The treatment group received 20 mg/kg lentinan via intraperitoneal injection, while the model group was treated with normal saline. The recovery in each group was then evaluated. Further, a rat SC line (RSC96) was cultured in medium with/without lentinan after supplementation with homogenous myelin fractions to evaluate the removal of myelin particles. Our results showed that lentinan promotes autophagic flux in vivo via the AMPK/mTOR signaling pathway, accelerates the clearance of myelin debris by SCs, and inhibits neuronal apoptosis, thereby promoting neurological recovery. Similarly, in vitro experiments showed that lentinan promotes the phagocytosis of myelin debris by SCs. In conclusion, our results suggest that lentinan primarily promotes nerve regeneration by accelerating the autophagic clearance of myelin debris in SCs, and this process is likely regulated by the AMPK/mTOR signaling pathway. Therefore, this study provides compelling evidence that lentinan may be a cost-effective and natural treatment agent for PNI.


Assuntos
Bainha de Mielina , Traumatismos dos Nervos Periféricos , Ratos , Animais , Bainha de Mielina/metabolismo , Lentinano/metabolismo , Lentinano/farmacologia , Traumatismos dos Nervos Periféricos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Nervo Isquiático , Serina-Treonina Quinases TOR/metabolismo
16.
J Formos Med Assoc ; 2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38044211

RESUMO

OBJECTIVE: This study aimed to assess the impact of preoperative chronic kidney disease (CKD) on the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who underwent standard radical nephroureterectomy (RNU). METHODS: A total of 1172 UTUC patients who received RNU at a single center in Taiwan between February 2005 and August 2019 were included. The patients were categorized into two groups based on their preoperative CKD stage: CKD stage ≤3 (811 patients) and CKD stage >3 (361 patients). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. The study investigated the oncological outcomes, including intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality, stratified by preoperative CKD status. RESULTS: The main findings indicated that UTUC patients with CKD stage >3 in Taiwan exhibited a higher proportion of females (p < 0.001), a greater history of concurrent bladder cancer (p = 0.003), more multifocal tumor behavior (p < 0.001), a higher incidence of carcinoma in situ (p = 0.008), increased rates of intravesical recurrence (p < 0.001), a lower prevalence of smoking history (p = 0.003), lower utilization of adjuvant chemotherapy (p < 0.001), reduced occurrence of non-urothelial recurrence (p < 0.001), and lower cancer-specific mortality (p = 0.006) compared to patients with CKD stage ≤3. Multivariate Cox regression analysis revealed significant differences in intravesical recurrence (p = 0.014) and non-urothelial recurrence (p = 0.006) between the CKD stage >3 and CKD stage ≤3 groups. The study also demonstrated that patients with concurrent bladder cancer and variant histology had higher rates of intravesical recurrence, non-urothelial recurrence, and cancer-specific mortality. The CKD stage >3 group exhibited lower rates of intravesical recurrence (p = 0.0014), higher rates of non-urothelial recurrence (p < 0.0001), and increased cancer-specific mortality (p = 0.0091) compared to the CKD stage ≤3 group in the 5-year free survival analysis. CONCLUSION: In Taiwan, UTUC patients with CKD stage >3 exhibit distinct characteristics compared to the general population with urothelial carcinoma. They are associated with a non-smoking status, a higher proportion of females, and less aggressive pathological features. Additionally, CKD stage >3 can serve as a clinical indicator for intravesical and non-urothelial recurrence. Further investigation into molecular aspects and treatment modifications for these patients is warranted.

17.
Int J Mol Sci ; 24(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37108649

RESUMO

Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial cancer (UTUC) is not well understood. In this study, we collected tissues from 10 patients with UTUC, including 6 with and 4 without lymphovascular invasion (LVI), a pathological feature that plays a significant role in determining metastasis. Results from RNA sequencing revealed that the most differentially expressed genes were involved in extracellular matrix organization. Using the TCGA database for clinical correlation, VCAN was identified as a target for study. A chromosome methylation assay showed that VCAN was hypomethylated in tumors with LVI. In our patient samples, VCAN expression was also found to be high in UTUC tumors with LVI. In vitro analysis showed that knocking down VCAN inhibited cell migration but not proliferation. A heatmap analysis also confirmed a significant correlation between VCAN and migration genes. Additionally, silencing VCAN increased the effectiveness of cisplatin, gemcitabine and epirubicin, thus providing potential opportunities for clinical application.


Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias da Bexiga Urinária , Sistema Urinário , Humanos , Carcinoma de Células de Transição/patologia , Versicanas/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias Renais/patologia , Biomarcadores Tumorais/genética , Sistema Urinário/patologia
18.
Bioconjug Chem ; 33(6): 1179-1191, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35543724

RESUMO

Antibody-drug conjugates (ADCs) hold great promise for targeted cancer cell killing. Site-specific antibody-drug conjugation is highly desirable for synthesizing homogeneous ADCs with optimal safety profiles and high efficacy. We have recently reported that azide-functionalized disaccharide oxazolines of the Manß1,4GlcNAc core were an efficient substrate of wild-type endoglycosidase Endo-S2 for Fc glycan remodeling and conjugation. In this paper, we report the synthesis and evaluation of new disaccharide oxazolines as enzyme substrates for examining the scope of the site-specific conjugation. Thus, azide-functionalized disaccharide oxazolines derived from Manß1,4GlcNAc, Glcß1,4GlcNAc, and Galß1,4GlcNAc (LacNAc) were synthesized. Enzymatic evaluation revealed that wild-type Endo-S2 demonstrated highly relaxed substrate specificity and could accommodate all the three types of disaccharide derivatives for transglycosylation to provide site-specific azide-tagged antibodies, which were readily clicked with a payload to generate homogeneous ADCs. Moreover, we also found that Endo-S2 was able to accommodate drug-preloaded minimal disaccharide oxazolines as donor substrates for efficient glycan transfer, enabling a single-step and site-specific antibody-drug conjugation without the need of an antibody click reaction. The ability of Endo-S2 to accommodate simpler and more easily synthesized disaccharide oxazoline derivatives for Fc glycan remodeling further expanded the scope of this bioconjugation method for constructing homogeneous antibody-drug conjugates in a single-step manner. Finally, cell-based assays indicated that the synthetic homogeneous ADCs demonstrated potent targeted cancer cell killing.


Assuntos
Azidas , Imunoconjugados , Anticorpos , Dissacarídeos , Fragmentos Fc das Imunoglobulinas , Polissacarídeos
19.
Phys Rev Lett ; 129(8): 086602, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36053706

RESUMO

We propose an intrinsic nonlinear electric spin generation effect, which can dominate in centrosymmetric magnets. We reveal the band geometric origin of this effect and clarify its symmetry characters. As an intrinsic effect, it is determined solely by the material's band structure and represents a material characteristic. Combining our theory with first-principle calculations, we predict sizable nonlinear spin generation in single-layer MnBi_{2}Te_{4}, which can be detected in experiment. Our theory opens a new route for all-electric controlled spintronics in centrosymmetric magnets which reside outside of the current paradigm based on linear spin response.

20.
Phys Chem Chem Phys ; 24(7): 4425-4436, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35113108

RESUMO

Vertically stacking two-dimensional materials into van der Waals (vdW) heterostructures (HS) is deemed to be an effective strategy to tailor their physical properties and enrich their applications in modern nanoelectronics. Here, we study the geometry, electronic, and optical properties of Janus Ga2SeTe/In2SSe heterostructures by using first-principles calculations. We consider four models of Ga2SeTe/In2SSe heterostructures with an alternative chalcogen atom layer sequence and five potential stacking configurations, and find that the most energy favorable stacking pattern is AB stacking for each model. The heterostructures form type II alignment with a direct band gap. Moreover, the band gap values are highly dependent on the magnitude of the electric dipole, which is related to the sublayer intrinsic dipole direction and interface charge transfer. Additionally, the optical absorption of the heterostructures is intensified in the visible and ultraviolet regime. Furthermore, we predict two heterostructures with the band edge straddling the water redox potential level. These findings can help in understanding the tailored properties of the heterostructures based on Janus two-dimensional materials, and guide experiments in designing novel optoelectronic devices.

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