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1.
Am J Cancer Res ; 14(5): 2072-2087, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859866

RESUMO

Heat shock factor 1 (HSF1), an essential transcription factor for stress response, is exploited by various tumors to facilitate their initiation, progression, invasion, and migration. Amplification of HSF1 is widely regarded as an indicator in predicting cancer severity, the likelihood of treatment failure and reduced patient survival. Notably, HSF1 is markedly amplified in 40% of pancreatic cancer (PC), which typically have limited treatment options. HSF1 has been proven to be a promising therapeutic target for multiple cancers. However, a direct small molecule HSF1 inhibitor with sufficient bioactivity and reliable safety has not been developed clinically. In this study, we successfully established a high-throughput screening system utilizing luciferase reporter assay specifically designed for HSF1, which leads to the discovery of a potent small molecule inhibitor targeting HSF1. Homoharringtonine (HHT) selectively inhibited PC cell viability with high HSF1 expression and induced a markedly stronger tumor regression effect in the subcutaneous xenograft model than the comparator drug KRIBB11, known for its direct action on HSF1. Moreover, HHT shows promise in countering the resistance encountered with HSP90 inhibitors, which have been observed to increase heat shock response intensity in clinical trials. Mechanistically, HHT directly bound to HSF1, suppressing its expression and thereby inhibiting transcription of HSF1 target genes. In conclusion, our work presents a preclinical discovery and validation for HHT as a HSF1 inhibitor for PC treatment.

2.
Phytomedicine ; 131: 155765, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38851105

RESUMO

BACKGROUND: Infection by Toxoplasma gondii can lead to severe pneumonia, with current treatments being highly inadequate. The NLRP3 inflammasome is one member of the NOD-like receptor family with a pyrin domain, which is crucial in the innate immune defense against T. gondii. Research has shown that resveratrol (RSV) prevents lung damage caused by this infection by inhibiting the T. gondii-derived heat shock protein 70/TLR4/NF-κB pathway, thus reducing the macrophage-driven inflammatory response. However, it should be mentioned that the participation of NLRP3 inflammasome in the immune response to the lung injuries caused by T. gondii infections is not entirely clear. PURPOSE: This study aims to clarify how RSV ameliorates lung damage triggered by Toxoplasma gondii infection, with a particular focus on the pathway involving TLR4, NF-κB, and the NLRP3 inflammasome. METHODS: Both in vitro and in vivo models of infection were developed by employing the RH strain of T. gondii in BALB/c mice and RAW 264.7 macrophage cell lines. The action mechanism of RSV was explored using techniques such as molecular docking, surface plasmon resonance, ELISA, Western blot, co-immunoprecipitation, and immunofluorescence staining. RESULTS: Findings indicate that the suppression of TLR4 or NF-κB impacts the levels of proteins associated with the NLRP3 inflammasome pathway. Additionally, a significant affinity for binding between RSV and NLRP3 was observed. Treatment with RSV led to a marked reduction in the activation and formation of the NLRP3 inflammasome within lung tissues and RAW 264.7 cells, alongside a decrease in IL-1ß concentrations in the bronchoalveolar lavage fluid. These outcomes align with those seen when using the NLRP3 inhibitor CY-09. Moreover, the application of CY-09 prior to RSV negated the latter's anti-inflammatory properties. CONCLUSION: Considering insights from previous research alongside the outcomes of the current investigation, it appears that the TLR4/NF-κB/NLRP3 signaling pathway emerges as a promising target for immunomodulation to alleviate lung injury from T. gondii infection. The evidence gathered in this study lays the groundwork for the continued exploration and potential future clinical deployment of RSV as a therapeutic agent with anti-Toxoplasma properties and the capability to modulate the inflammatory response.

3.
BMC Biotechnol ; 24(1): 37, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38825715

RESUMO

BACKGROUND: As part of a publicly funded initiative to develop genetically engineered Brassicas (cabbage, cauliflower, and canola) expressing Bacillus thuringiensis Crystal (Cry)-encoded insecticidal (Bt) toxin for Indian and Australian farmers, we designed several constructs that drive high-level expression of modified Cry1B and Cry1C genes (referred to as Cry1BM and Cry1CM; with M indicating modified). The two main motivations for modifying the DNA sequences of these genes were to minimise any licensing cost associated with the commercial cultivation of transgenic crop plants expressing CryM genes, and to remove or alter sequences that might adversely affect their activity in plants. RESULTS: To assess the insecticidal efficacy of the Cry1BM/Cry1CM genes, constructs were introduced into the model Brassica Arabidopsis thaliana in which Cry1BM/Cry1CM expression was directed from either single (S4/S7) or double (S4S4/S7S7) subterranean clover stunt virus (SCSV) promoters. The resulting transgenic plants displayed a high-level of Cry1BM/Cry1CM expression. Protein accumulation for Cry1CM ranged from 5.18 to 176.88 µg Cry1CM/g dry weight of leaves. Contrary to previous work on stunt promoters, we found no correlation between the use of either single or double stunt promoters and the expression levels of Cry1BM/Cry1CM genes, with a similar range of Cry1CM transcript abundance and protein content observed from both constructs. First instar Diamondback moth (Plutella xylostella) larvae fed on transgenic Arabidopsis leaves expressing the Cry1BM/Cry1CM genes showed 100% mortality, with a mean leaf damage score on a scale of zero to five of 0.125 for transgenic leaves and 4.2 for wild-type leaves. CONCLUSIONS: Our work indicates that the modified Cry1 genes are suitable for the development of insect resistant GM crops. Except for the PAT gene in the USA, our assessment of the intellectual property landscape of components presents within the constructs described here suggest that they can be used without the need for further licensing. This has the capacity to significantly reduce the cost of developing and using these Cry1M genes in GM crop plants in the future.


Assuntos
Arabidopsis , Toxinas de Bacillus thuringiensis , Proteínas de Bactérias , Endotoxinas , Proteínas Hemolisinas , Plantas Geneticamente Modificadas , Plantas Geneticamente Modificadas/genética , Arabidopsis/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas Hemolisinas/genética , Animais , Endotoxinas/genética , Regiões Promotoras Genéticas/genética , Bacillus thuringiensis/genética , Mariposas/genética , Brassica/genética , Controle Biológico de Vetores/métodos , Inseticidas/farmacologia
4.
Plant J ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38824648

RESUMO

Gibberellins (GAs) play crucial roles in regulating plant architecture and grain yield of crops. In rice, the inactivation of endogenous bioactive GAs and their precursors by GA 2-oxidases (GA2oxs) regulates stem elongation and reproductive development. However, the regulatory mechanisms of GA2ox gene expression, especially in rice reproductive organs, are unknown. The BEL1-like homeodomain protein OsBLH4, a negative regulatory factor for the rice OsGA2ox1 gene, was identified in this study. Loss of OsBLH4 function results in decreased bioactive GA levels and pleiotropic phenotypes, including reduced plant height, decreased grain number per panicle, and delayed heading date, as also observed in OsGA2ox1-overexpressing plants. Consistent with the mutant phenotype, OsBLH4 was predominantly expressed in shoots and young spikelets; its encoded protein was exclusively localized in the nucleus. Molecular analysis demonstrated that OsBLH4 directly bound to the promoter region of OsGA2ox1 to repress its expression. Genetic assays revealed that OsBLH4 acts upstream of OsGA2ox1 to control rice plant height, grain number, and heading date. Taken together, these results indicate a crucial role for OsBLH4 in regulating rice plant architecture and yield potential via regulation of bioactive GA levels, and provide a potential strategy for genetic improvements of rice.

5.
Org Lett ; 26(23): 4857-4862, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38838191

RESUMO

The efficient construction of π-conjugated polycyclic heteroarenes represents a significant task in the field of functional materials. A one-step oxidative tandem cyclization of aromatic acids with (benzo)thiophenes was developed to access planar sulfur-containing polycyclic heteroarenes. This protocol undergoes intermolecular cross-dehydrogenative coupling followed by intramolecular Friedel-Crafts acylation and provides a facile pathway to planar polycyclic compounds from inexpensive reactants. The synthesized heteroarenes serving as lipid-droplet-targeted probes exhibit outstanding performance with favorable biocompatibility and photostability.

6.
Ren Fail ; 46(2): 2359033, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38836372

RESUMO

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.


Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.


Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Nefropatias Diabéticas , Quimioterapia Combinada , Sistema Renina-Angiotensina , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Astrágalo , Ensaios Clínicos Controlados Aleatórios como Assunto , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Resultado do Tratamento , Creatinina/sangue , Hemoglobinas Glicadas , Proteinúria/tratamento farmacológico
7.
Proc Natl Acad Sci U S A ; 121(25): e2400546121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38857407

RESUMO

Reduction of carbon dioxide (CO2) by renewable electricity to produce multicarbon chemicals, such as ethylene (C2H4), continues to be a challenge because of insufficient Faradaic efficiency, low production rates, and complex mechanistic pathways. Here, we report that the rate-determining steps (RDS) on common copper (Cu) surfaces diverge in CO2 electroreduction, leading to distinct catalytic performances. Through a combination of experimental and computational studies, we reveal that C─C bond-making is the RDS on Cu(100), whereas the protonation of *CO with adsorbed water becomes rate-limiting on Cu(111) with a higher energy barrier. On an oxide-derived Cu(100)-dominant Cu catalyst, we reach a high C2H4 Faradaic efficiency of 72%, partial current density of 359 mA cm-2, and long-term stability exceeding 100 h at 500 mA cm-2, greatly outperforming its Cu(111)-rich counterpart. We further demonstrate constant C2H4 selectivity of >60% over 70 h in a membrane electrode assembly electrolyzer with a full-cell energy efficiency of 23.4%.

9.
Radiother Oncol ; 197: 110344, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38806113

RESUMO

BACKGROUND: Accurate segmentation of lung tumors on chest computed tomography (CT) scans is crucial for effective diagnosis and treatment planning. Deep Learning (DL) has emerged as a promising tool in medical imaging, particularly for lung cancer segmentation. However, its efficacy across different clinical settings and tumor stages remains variable. METHODS: We conducted a comprehensive search of PubMed, Embase, and Web of Science until November 7, 2023. We assessed the quality of these studies by using the Checklist for Artificial Intelligence in Medical Imaging and the Quality Assessment of Diagnostic Accuracy Studies-2 tools. This analysis included data from various clinical settings and stages of lung cancer. Key performance metrics, such as the Dice similarity coefficient, were pooled, and factors affecting algorithm performance, such as clinical setting, algorithm type, and image processing techniques, were examined. RESULTS: Our analysis of 37 studies revealed a pooled Dice score of 79 % (95 % CI: 76 %-83 %), indicating moderate accuracy. Radiotherapy studies had a slightly lower score of 78 % (95 % CI: 74 %-82 %). A temporal increase was noted, with recent studies (post-2022) showing improvement from 75 % (95 % CI: 70 %-81 %). to 82 % (95 % CI: 81 %-84 %). Key factors affecting performance included algorithm type, resolution adjustment, and image cropping. QUADAS-2 assessments identified ambiguous risks in 78 % of studies due to data interval omissions and concerns about generalizability in 8 % due to nodule size exclusions, and CLAIM criteria highlighted areas for improvement, with an average score of 27.24 out of 42. CONCLUSION: This meta-analysis demonstrates DL algorithms' promising but varied efficacy in lung cancer segmentation, particularly higher efficacy noted in early stages. The results highlight the critical need for continued development of tailored DL models to improve segmentation accuracy across diverse clinical settings, especially in advanced cancer stages with greater challenges. As recent studies demonstrate, ongoing advancements in algorithmic approaches are crucial for future applications.

10.
Ecotoxicol Environ Saf ; 279: 116453, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38772139

RESUMO

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.


Assuntos
Inflamassomos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Placenta , Animais , Feminino , Gravidez , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Placenta/efeitos dos fármacos , Placenta/patologia , Camundongos , Inflamassomos/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/patologia , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Fluorocarbonos/toxicidade , Transdução de Sinais/efeitos dos fármacos
11.
Mol Pharm ; 21(6): 2993-3005, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38722865

RESUMO

The susceptibility of lysosomal membranes in tumor cells to cationic amphiphilic drugs (CADs) enables CADs to induce lysosomal membrane permeabilization (LMP) and trigger lysosome-dependent cell death (LDCD), suggesting a potential antitumor therapeutic approach. However, the existence of intrinsic lysosomal damage response mechanisms limits the display of the pharmacological activity of CADs. In this study, we report that low concentrations of QS-21, a saponin with cationic amphiphilicity extracted from Quillaja Saponaria tree, can induce LMP but has nontoxicity to tumor cells. QS-21 and MAP30, a type I ribosome-inactivating protein, synergistically induce apoptosis in tumor cells at low concentrations of both. Mechanistically, QS-21-induced LMP helps MAP30 escape from endosomes or lysosomes and subsequently enter the endoplasmic reticulum, where MAP30 downregulates the expression of autophagy-associated LC3 proteins, thereby inhibiting lysophagy. The inhibition of lysophagy results in the impaired clearance of damaged lysosomes, leading to the leakage of massive lysosomal contents such as cathepsins into the cytoplasm, ultimately triggering LDCD. In summary, our study showed that coadministration of QS-21 and MAP30 amplified the lysosomal disruption and can be a new synergistic LDCD-based antitumor therapy.


Assuntos
Apoptose , Autofagia , Lisossomos , Saponinas , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Saponinas/farmacologia , Apoptose/efeitos dos fármacos , Humanos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Sinergismo Farmacológico , Proteínas Inativadoras de Ribossomos Tipo 1/farmacologia , Camundongos , Quillaja/química , Antineoplásicos/farmacologia
12.
Int Immunopharmacol ; 135: 112304, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38776851

RESUMO

Activating angiotensin-converting enzyme 2 (ACE2) is an important player in the pathogenesis of septic-related acute respiratory distress syndrome (ARDS). Rosmarinic acid (RA) as a prominent polyphenolic secondary metabolite derived from Rosmarinus officinalis modulates ACE2 in sepsis remains unclear, although its impact on ACE inhibition and septic-associated lung injury has been explored. The study investigated the ACE2 expression in lipopolysaccharide (LPS)-induced lungs in mice and BEAS2B cells. Additionally, molecular docking, protein-protein interaction (PPI) network analysis, and western blotting were employed to predict and evaluate the molecular mechanism of RA on LPS-induced ferroptosis in vivo and in vitro. LPS-induced glutathione peroxidase 4 (GPX4) downregulation, ACE/ACE2 imbalance, and alteration of frequency of breathing (BPM), minute volume (MV), and the expiratory flow at 50% expired volume (EF50) were reversed by captopril pretreatment in vitro and in vivo. RA notably inhibited the infiltration into the lungs of neutrophils and monocytes with increased amounts of GPX4 and ACE2 proteins, lung function improvement, and decreased inflammatory cytokines levels and ER stress in LPS-induced ARDS in mice. Molecular docking showed RA was able to interact with ACE and ACE2. Moreover, combined with different pharmacological inhibitors to block ACE and ferroptosis, RA still significantly inhibited inflammatory cytokines Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and C-X-C motif chemokine 2 (CXCL2) levels, as well as improved lung function, and enhanced GPX4 expression. Particularly, the anti-ferroptosis effect of RA in LPS-induced septic ARDS is RAS-dependent.


Assuntos
Enzima de Conversão de Angiotensina 2 , Cinamatos , Depsídeos , Ferroptose , Lipopolissacarídeos , Síndrome do Desconforto Respiratório , Ácido Rosmarínico , Sepse , Animais , Depsídeos/uso terapêutico , Depsídeos/farmacologia , Ferroptose/efeitos dos fármacos , Cinamatos/uso terapêutico , Cinamatos/farmacologia , Síndrome do Desconforto Respiratório/tratamento farmacológico , Humanos , Camundongos , Masculino , Sepse/tratamento farmacológico , Enzima de Conversão de Angiotensina 2/metabolismo , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/metabolismo , Camundongos Endogâmicos C57BL , Brônquios/efeitos dos fármacos , Brônquios/patologia , Linhagem Celular , Captopril/farmacologia , Captopril/uso terapêutico , Modelos Animais de Doenças , Citocinas/metabolismo
13.
J Pharm Biomed Anal ; 246: 116164, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38776585

RESUMO

Evaluating the quality of herbal medicine based on the content and activity of its main components is highly beneficial. Developing an eco-friendly determination method has significant application potential. In this study, we propose a new method to simultaneously predict the total flavonoid content (TFC), xanthine oxidase inhibitory (XO) activity, and antioxidant activity (AA) of Prunus mume using near-infrared spectroscopy (NIR). Using the sodium nitrite-aluminum nitrate-sodium hydroxide colorimetric method, uric acid colorimetric method, and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) free radical scavenging activity as reference methods, we analyzed TFC, XO, and AA in 90 P. mume samples collected from different locations in China. The solid samples were subjected to NIR. By employing spectral preprocessing and optimizing spectral bands, we established a rapid prediction model for TFC, XO, and AA using partial least squares regression (PLS). To improve the model's performance and eliminate irrelevant variables, competitive adaptive reweighted sampling (CARS) was used to calculate the pretreated full spectrum. Evaluation model indicators included the root mean square error of cross-validation (RMSECV) and determination coefficient (R2) values. The TFC, XO, and AA model, combining optimal spectral preprocessing and spectral bands, had RMSECV values of 0.139, 0.117, and 0.121, with RCV2 values exceeding 0.92. The root mean square error of prediction (RMSEP) for the TFC, XO, and AA model on the prediction set was 0.301, 0.213, and 0.149, with determination coefficient (RP2) values of 0.915, 0.933, and 0.926. The results showed a strong correlation between NIR with TFC, XO, and AA in P. mume. Therefore, the established model was effective, suitable for the rapid quantification of TFC, XO, and AA. The prediction method is simple and rapid, and can be extended to the study of medicinal plant content and activity.


Assuntos
Antioxidantes , Flavonoides , Prunus , Espectroscopia de Luz Próxima ao Infravermelho , Xantina Oxidase , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Flavonoides/análise , Prunus/química , Xantina Oxidase/antagonistas & inibidores , Antioxidantes/análise , Análise dos Mínimos Quadrados , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/farmacologia , China
14.
J AOAC Int ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733574

RESUMO

BACKGROUND: The identification of the geographical origin of Polygonatum cyrtonema Hua is of particular importance because the quality and market value of Polygonatum cyrtonema Hua from different production areas are highly variable due to differences in the growing environment and climatic conditions. OBJECTIVE: This study utilized near-infrared spectra (NIR) of Polygonatum cyrtonema Hua (n = 400) to develop qualitative models for effective differentiation of Polygonatum cyrtonema Hua from various regions. METHODS: The models were produced under different conditions to distinguish the origins distinctly. Ten pre-processing methods have been used to pre-process the original spectra (OS) and to select the most optimal spectral pre-processing method. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to determine appropriate models. For simplicity, the pretreated full spectrum was calculated by different wavelength selection methods, and the four most significant variables were selected as discriminant indicator variables. RESULTS: The results show that Polygonatum cyrtonema Hua from different regions can be effectively distinguished using spectra from a series of samples analyzed by OPLS-DA. The accuracy of the OPLS-DA model is also satisfactory, with a good differentiation rate. CONCLUSION: The study findings indicate the feasibility of using spectroscopy in combination with multivariate analysis to identify the geographical origins of Polygonatum cyrtonema Hua. HIGHLIGHTS: The utilization of near-infrared spectroscopy combined with chemometrics exhibits high efficacy in discerning the provenance of herbal medicines and foods, thereby facilitating quality assurance measures.

15.
Ann Hematol ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805037

RESUMO

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

16.
Alpha Psychiatry ; 25(1): 9-14, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38799487

RESUMO

Schizophrenia is a severe mental disorder with a neurodevelopmental origin. Although schizophrenia results from changes in the brain, the underlying biological mechanisms are unknown. Transcriptomics studies quantitative expression changes or qualitative changes of all genes and isoforms, providing a more meaningful biological insight. Magnetic resonance imaging (MRI) techniques play roles in revealing brain structure and function. We give a narrative focused review on the current transcriptome combined with MRI studies related to schizophrenia and summarize the research methodology and content of these studies to identify the research commonalities as well as the implications for future research, in an attempt to provide new insights into the mechanism, clinical diagnosis, and treatments of schizophrenia.

17.
Dig Liver Dis ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38744556

RESUMO

OBJECTIVE: The primary purpose of the study was to explore the clinical efficacy of the novel snare assisted endoscopic resection of extraluminal growing gastric gastrointestinal stromal tumors (gastric GISTs) using external traction, and the secondary purpose was to compare the novel snare assisted endoscopic resection of extraluminal GISTs with the standard laparoscopic procedure. METHODS: We retrospectively analyzed the patients who underwent novel external traction assisted endoscopic resection or laparoscopic resection for their extraluminal gastric GIST ≤5 cm in diameter. RESULTS: A total of 111 patients (27 in the endoscopic group and 84 in the laparoscopic group) were included in this study. There was no significant difference in tumor diameter and complication rate between the two groups. The overall procedure time was slightly higher in the endoscopic group compared to the laparoscopic group (P = 0.034). However, postoperative hospitalization time (P < 0.001) and postoperative fasting time (P = 0.005) were shorter in the endoscopic group compared to the laparoscopic group. CONCLUSION: Snare external traction-assisted endoscopic resection of extraluminal growing gastric GISTs is safe and effective, and it provides a new adjunctive method for endoscopic resection of GIST.

18.
World J Oncol ; 15(3): 521-525, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38751705

RESUMO

Inflammatory myofibroblastic tumors (IMTs), which involve the proliferation of fibroblastic-myofibroblastic cells mixed with inflammatory infiltrates, are exceedingly rare in the extremities. There are no reported IMTs involving the sciatic nerve. This type of involvement may cause entrapment of the sciatic nerve, whose symptoms may mimic lumbar disc herniation (LDH), especially when it occurs in patients with lumbar degenerative disc disease. We describe the case of a 40-year-old male with lumbar degenerative disc disease accompanied by IMT involving the sciatic nerve whose symptoms mimicked LDH and posed a diagnostic challenge. We showed the course of the disease as well as the systematic imaging manifestations of IMTs involving the sciatic nerve and discussed their therapeutic management.

19.
Obes Rev ; : e13760, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697953

RESUMO

A systematic review and meta-analysis was conducted to evaluate the relative effectiveness of different dietary macronutrient patterns on changes in resting energy expenditure (REE) in relation to weight loss, categorized as minimal (<5%) and moderate to high (>5%). Changes in REE were assessed using a DerSimonian and Laird random-effects meta-analysis. A diet lower in carbohydrates (CHO) or higher in fat and protein was associated with smaller reductions in REE, with these trends being more pronounced among participants who experienced moderate to high weight loss. Adjusted meta-regression analysis indicated that, within the participants who experienced moderate to high weight loss, each 1% increase in CHO intake was associated with a reduction of 2.30 kcal/day in REE (95% CI: -4.11 to -0.47, p = 0.013). In contrast, a 1% increase in protein and fat intake was correlated with an increase in REE by 3.00 (95% confidence interval [CI] [1.02, 5.07], p = 0.003) and 0.5 (95% CI [-2.43, 3.41], p = 0.740) kcal/day, respectively. No significant associations were found among participants who experienced minimal weight loss. These findings indicate that, under a caloric deficit, the impact of dietary macronutrient composition on REE may vary depending on the degree of weight loss and individual metabolic responses.

20.
J Am Chem Soc ; 146(19): 12958-12968, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38695595

RESUMO

The discovery of efficient and stable electrocatalysts for oxygen evolution reaction (OER) in acid is vital for the commercialization of the proton-exchange membrane water electrolyzer. In this work, we demonstrate that short-range Ru atom arrays with near-ideal Ru-Ru interatomic distances and a unique Ru-O hybridization state can trigger direct O*-O* radical coupling to form an intermediate O*-O*-Ru configuration during acidic OER without generating OOH* species. Further, the Ru atom arrays suppress the participation of lattice oxygen in the OER and the dissolution of active Ru. Benefiting from these advantages, the as-designed Ru array-Co3O4 electrocatalyst breaks the activity/stability trade-off that plagues RuO2-based electrocatalysts, delivering an excellent OER overpotential of only 160 mV at 10 mA cm-2 in 0.5 M H2SO4 and outstanding durability during 1500 h operation, representing one of the best acid-stable OER electrocatalysts reported to date. 18O-labeled operando spectroscopic measurements together with theoretical investigations revealed that the short-range Ru atom arrays switched on an oxide path mechanism (OPM) during the OER. Our work not only guides the design of improved acidic OER catalysts but also encourages the pursuit of short-range metal atom array-based electrocatalysts for other electrocatalytic reactions.

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