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1.
Artigo em Inglês | MEDLINE | ID: mdl-39303004

RESUMO

Although poly(vinyl alcohol) (PVA) hydrogel has high elasticity and is suitable for cartilage tissue engineering, it is difficult to have both high strength and toughness. In this study, a simple and universal strategy is proposed to prepare strong and tough PVA hydrogels by in situ forming nanofibers on the original network structure induced by a molecular chain rearrangement. Quenching-tempering alteratively in ethanol and water several times is carried out to strengthen PVA hydrogels (PVA-Etn hydrogels) due to the advantages of noncovalent bonds in adjustability and reversibility. The results show that, after three quenching-tempering cycles, PVA-Et3 hydrogel with water content up to 79 wt % shows comprehensive improved mechanical properties. The compression modulus, tensile modulus, fracture strength, tensile strain, and tear energy of the PVA-Et3 hydrogel are 270, 250, 260, 130, and 180% of the initial PVA hydrogel, respectively. The improved mechanical properties of the PVA-Et3 hydrogel are attributed to the strong cross-linked PVA chains and hydrogen bond-reinforced nanofibers. This study not only provides a simple and efficient solution for the preparation of strong and tough polymer scaffolds in tissue engineering but also provides new insights for understanding the mechanism of improving the mechanical properties of polymer hydrogels by adjusting the molecular structure.

2.
Cancer Lett ; 602: 217214, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39218291

RESUMO

Protein arginine methylation is a common post-translational modification (PTM) catalyzed by nine protein arginine methyltransferases (PRMTs). As the major symmetric arginine methyltransferase that methylates both histone and non-histone substrates, PRMT5 plays key roles in a number of biological processes critical for development and tumorigenesis. PRMT5 overexpression has been reported in multiple cancer types including prostate cancer (PCa), but the exact biological and mechanistic understanding of PRMT5 in aggressive PCa remains ill-defined. Here, we show that PRMT5 is upregulated in PCa, correlates with worse patient survival, promotes corrupted RNA splicing, and functionally cooperates with an array of pro-tumorigenic pathways to enhance oncogenesis. PRMT5 inhibition via either genetic knockdown or pharmacological inhibition reduces stemness with paralleled differentiation and arrests cell cycle progression without causing appreciable apoptosis. Strikingly, the severity of antitumor effect of PRMT5 inhibition correlates with disease aggressiveness, with AR+ PCa being less affected. Molecular characterization pinpoints MYC, but not (or at least to a lesser degree) AR, as the main partner of PRMT5 to form a positive feedback loop to exacerbate malignancy in both AR+ and AR- PCa cells. Inspired by the surprising finding that PRMT5 negatively correlates with tumor immune infiltration and transcriptionally suppresses an immune-gene program, we further show that although PRMT5 inhibitor (PRMT5i) EPZ015666 or anti-PD-1 immunotherapy alone exhibits limited antitumor effects, combination of PRMT5i with anti-PD-1 displays superior efficacy in inhibiting castration-resistant PCa (CRPC) in vivo. Finally, to expand the potential use of PRMT5i through a synthetic lethality concept, we also perform a global CRISPR/Cas9 knockout screen to unravel that many clinical-grade drugs of known oncogenic pathways can be repurposed to target CRPC when used in combination with PRMT5i at low doses. Collectively, our findings establish a rationale to exploit PRMT5i in combination with immunotherapy or other targeted therapies to treat aggressive PCa.


Assuntos
Neoplasias da Próstata , Proteína-Arginina N-Metiltransferases , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Masculino , Humanos , Animais , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/tratamento farmacológico , Linhagem Celular Tumoral , Camundongos , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Imunoterapia/métodos , Regulação Neoplásica da Expressão Gênica
3.
Int Immunopharmacol ; 142(Pt A): 113024, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39217875

RESUMO

The incidence of aging-related neurodegenerative disorders and neurocritical care diseases is increasing worldwide. Microglia, the main inflammatory cells in the brain, could be potential viable therapeutic targets for treating neurological diseases. Interestingly, mitochondrial functions, including energy metabolism, mitophagy and transfer, fission and fusion, and mitochondrial DNA expression, also change in activated microglia. Notably, mitochondria play an active and important role in the pathophysiology of neurodegenerative disorders and neurocritical care diseases. This review briefly summarizes the current knowledge on mitochondrial dysfunction in microglia in neurodegenerative disorders and neurocritical care diseases and comprehensively discusses the prospects of the application of neurological injury prevention and treatment targets by mitochondria.

4.
J Chem Theory Comput ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39236257

RESUMO

The free energy perturbation (FEP) method is a powerful technique for accurate binding free energy calculations, which is crucial for identifying potent ligands with a high affinity in drug discovery. However, the widespread application of FEP is limited by the high computational cost required to achieve equilibrium sampling and the challenges in obtaining converged predictions. In this study, we present the convergence-adaptive roundtrip (CAR) method, which is an enhanced adaptive sampling approach, to address the key challenges in FEP calculations, including the precision-efficiency tradeoff, sampling efficiency, and convergence assessment. By employing on-the-fly convergence analysis to automatically adjust simulation times, enabling efficient traversal of the important phase space through rapid propagation of conformations between different states and eliminating the need for multiple parallel simulations, the CAR method increases convergence and minimizes computational overhead while maintaining calculation accuracy. The performance of the CAR method was evaluated through relative binding free energy (RBFE) calculations on benchmarks comprising four diverse protein-ligand systems. The results demonstrated a significant speedup of over 8-fold compared to conventional FEP methods while maintaining high accuracy. The overall R2 values of 0.65 and 0.56 were obtained using the combined-structure FEP approach and the single-step FEP approach, respectively, in conjunction with the CAR method. In-depth case studies further highlighted the superior performance of the CAR method in terms of convergence acceleration, improved predicted correlations, and reduced computational costs. The advancement of the CAR method makes it a highly effective approach, enhancing the applicability of FEP in drug discovery.

5.
Int J Biol Macromol ; 278(Pt 3): 134692, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39154693

RESUMO

The preparation of biodegradable and antibacterial hydrogels has important clinical value. In this work, a novel strategy has been developed to prepare degradable hydrogel dressings without chemical crosslinking agent using methacrylate anhydride (MA)-modified amylopectin (APMA) and polyacrylamide (PAM). After introducing CC bonds, APMA/PAM hydrogels can be formed under light irradiation. This strategy improves the gelling ability of AP and degradation properties of the hydrogel by avoiding the addition of crosslinking agent. The degradation rate of APMA/PAM hydrogel is 74.04 ± 0.69 % within 12 weeks, while that of APMA/PAM hydrogel containing crosslinking agent is only 38.5 ± 0.1 %. The APMA/PAM hydrogel loading curcumin (Cur) (APMA/PAM-Cur) exhibits high antibacterial efficiency of 98.29 ± 0.41 % and 97.18 ± 0.81 % against S. aureus and E. coli, respectively, with light irradiation. Animal experiments show that the APMA/PAM-Cur hydrogel reduces the infiltration of inflammatory factors, increases the density of collagen, and makes the newly formed granulation tissue thicker and tighter. This study not only proves the promising potential of the APMA/PAM-Cur hydrogel as degradable and antibacterial wound dressing for clinical treatment, but also provides a new strategy for developing low-cost, degradable, and antibacterial wound dressings and reducing antibiotic abuse and environmental pollution caused by medical waste.


Assuntos
Resinas Acrílicas , Antibacterianos , Bandagens , Curcumina , Hidrogéis , Cicatrização , Curcumina/farmacologia , Curcumina/química , Curcumina/administração & dosagem , Resinas Acrílicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Metacrilatos/química , Escherichia coli/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Camundongos , Injeções
6.
J Transl Int Med ; 12(3): 263-273, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39081280

RESUMO

Background and objectives: Comprehensive data analyses in heart failure research can provide academics with information and help policymakers formulate relevant policies. We collected data from reports published between 1945 and 2021 to identify research topics, trends, and cross-domains in the heart failure disease literature. Methods: Text fragments were extracted and clustered from the titles and abstracts in 270617 publications using artificial intelligence techniques. Two algorithms were used to corroborate the results and ensure that they were reliable. Experts named themes and document clusters based on the results of these semiautomated methods. Using consistent methods, we identified and flagged 107 heart failure topics and 16 large document clusters (divided into two groups by time). The annual vocabularies of research hotspots were calculated to draw attention to niche research fields. Results: Clinical research is an expanding field, followed by basic research and population research. The most frequently raised issues were intensive care treatment for heart failure, applications of artificial intelligence technologies, cardiac assist devices, stem cells, genetics, and regional distribution and use of heart failure-related health care. Risk scoring and classification, care for patients, readmission, health economics of treatment and care, and cell regeneration and signaling pathways were among the fastest-growing themes. Drugs, signaling pathways, and biomarkers were all crucial issues for clinical and basic research in the entire population. Studies on intelligent medicine and telemedicine, interventional therapy for valvular disease, and novel coronavirus have emerged recently. Conclusion: Clinical and population research is increasingly focusing on the customization of intelligent treatments, improving the quality of patients' life, and developing novel treatments. Basic research is increasingly focusing on regenerative medicine, translational medicine, and signaling pathways. Additionally, each research field exhibits mutual fusion characteristics. Medical demands, new technologies, and social support are all potential drivers for these changes.

7.
J Environ Manage ; 366: 121744, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38971072

RESUMO

The continuous excessive application of phosphorus (P) fertilizers in intensive agricultural production leads to a large accumulation of P in surface soils, increasing the risk of soil P loss by runoff and leaching. However, there are few studies on the accumulation and loss of P from surface soil to deep soil profiles driven by shallow groundwater table (SGT) fluctuations. This study used the intensive cropland around 7 plateau lakes in Yunnan Province as an example and conducted in situ monitoring of P storage in the soil profile and SGT during the rainy season (RS) and dry season (DS) as well as simulation experiments on soil P loss. The aim was to study the spatiotemporal variation in P accumulation in the soil profile of cropland driven by SGT fluctuations in the RS and DS and estimate the P loss in the soil profile driven by SGT fluctuations. The results showed that fluctuations in the SGT promoted P accumulation from the surface soil to deeper soil. The proportions of P stored in various forms in the 30-60 cm and 60-100 cm soil layers in the RS were greater than those in the DS, while the average proportion in the 0-30 cm soil layer in the DS was as high as 48%. Compared with those in the DS, the maximum decreases in the proportion of P stored as TP and Olsen-P in the 0-100 cm soil layer in the RS were 16% and 58%, respectively, due to the rise in the SGT (SGT <30 cm), while the soil TP storage decreased by only 1% when the SGT was maintained at 60-100 cm. The critical thresholds for soil Olsen-P and TP gradually decreased with increasing soil depth, and the risk of P loss in deeper soil increased. The loss of soil P was increased by fluctuations in the SGT. Based on the cropland area around the 7 plateau lakes, P storage, and SGT fluctuations, the average loss intensity and loss amount of TP in the 0-100 cm soil layer around the 7 plateau lakes were estimated to be 25 kg/ha and 56 t, respectively. Therefore, reducing exogenous P inputs, improving soil endogenous P utilization efficiency and maintaining deep soil P retention are the basic strategies for preventing and controlling P accumulation and loss in deep soil caused by SGT fluctuations.


Assuntos
Água Subterrânea , Lagos , Fósforo , Solo , Fósforo/análise , Solo/química , China , Água Subterrânea/química , Agricultura , Fertilizantes/análise
8.
Nat Commun ; 15(1): 6259, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39048559

RESUMO

Pityriasis rubra pilaris (PRP) is an inflammatory papulosquamous dermatosis, characterized by hyperkeratotic follicular papules and erythematous desquamative plaques. The precise pathogenic mechanism underlying PRP remains incompletely understood. Herein, we conduct a case-control study involving a cohort of 102 patients with sporadic PRP and 800 healthy controls of Han Chinese population and identify significant associations (P = 1.73 × 10-6) between PRP and heterozygous mutations in the Keratin 32 gene (KRT32). KRT32 is found to be predominantly localized in basal keratinocytes and exhibits an inhibitory effect on skin inflammation by antagonizing the NF-κB pathway. Mechanistically, KRT32 binds to NEMO, promoting excessive K48-linked polyubiquitination and NEMO degradation, which hinders IKK complex formation. Conversely, loss-of-function mutations in KRT32 among PRP patients result in NF-κB hyperactivation. Importantly, Krt32 knockout mice exhibit a PRP-like dermatitis phenotype, suggesting compromised anti-inflammatory function of keratinocytes in response to external pro-inflammatory stimuli. This study proposes a role for KRT32 in regulating inflammatory immune responses, with damaging variants in KRT32 being an important driver in PRP development. These findings offer insights into the regulation of skin immune homeostasis by keratin and open up the possibility of using KRT32 as a therapeutic target for PRP.


Assuntos
Queratinócitos , Pitiríase Rubra Pilar , Pele , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Adulto Jovem , Estudos de Casos e Controles , Homeostase , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Queratinócitos/imunologia , Queratinócitos/metabolismo , Queratinas/metabolismo , Queratinas/genética , Mutação com Perda de Função , Camundongos Knockout , NF-kappa B/metabolismo , Pitiríase Rubra Pilar/genética , Pitiríase Rubra Pilar/imunologia , Pitiríase Rubra Pilar/patologia , Pitiríase Rubra Pilar/metabolismo , Transdução de Sinais , Pele/patologia , Pele/imunologia , Pele/metabolismo , Ubiquitinação
9.
Eur J Med Chem ; 276: 116646, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972080

RESUMO

Cycloicaritin (CICT), a bioactive flavonoid derived from the genus Epimedium, exhibits a variety of beneficial biological activities, including promising anticancer effects. However, its poor oral bioavailability is attributed to its extremely low aqueous solubility and rapid elimination via phase II conjugative metabolism. To overcome these limitations, we designed and synthesized a series of carbamate-bridged prodrugs, protecting the hydroxyl group at the 3-position of cycloicaritin by binding with the N-terminus of a natural amino acid. The optimal prodrug 4b demonstrated a significant increase in aqueous solubility as compared to CICT, as well as improved stability in phase II metabolism, while allowing for a rapid release of CICT in the blood upon gastrointestinal absorption. The prodrug 4b also facilitated oral absorption through organic anion-transporting polypeptide 2B1-mediated transport and exhibited moderate cytotoxicity. Importantly, the prodrug enhanced the oral bioavailability of CICT and displayed dose-dependent antitumor activity with superior safety. In summary, the prodrug 4b is a novel potential antitumor drug candidate, and the carbamate-bridged amino acid prodrug approach is a promising strategy for the oral delivery of CICT.


Assuntos
Aminoácidos , Antineoplásicos , Carbamatos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Pró-Fármacos , Solubilidade , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Humanos , Carbamatos/química , Carbamatos/farmacologia , Carbamatos/síntese química , Carbamatos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Animais , Relação Estrutura-Atividade , Aminoácidos/química , Aminoácidos/farmacologia , Aminoácidos/síntese química , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Água/química , Linhagem Celular Tumoral , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/síntese química , Flavonoides/farmacocinética , Masculino
10.
Polymers (Basel) ; 16(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38891525

RESUMO

Rubber concrete has been applied to a certain extent in fatigue-resistant structures due to its good durability. Based on a cohesive model of rubber composed of a five-phase material containing mortar, aggregate, rubber, aggregate-mortar interfacial transition zone (ITZ), and rubber-mortar ITZ, this paper studies the influence of the cohesive parameters in the rubber-mortar ITZ on the fatigue problem of rubber concrete on the mesoscopic scale. As the weak part of cement-based composite materials, the ITZ has a great influence on the mechanical properties and durability of concrete, but the performance of the ITZ is difficult to test in macro experiments, resulting in difficulties in determining its simulation parameters. Based on the cohesive model with a rubber content of 5%, this study uses Monofactor analysis and the Plackett-Burman test to quickly and effectively determine the primary and secondary influences of the cohesive model parameters in the rubber-mortar ITZ; further, the response surface method is used to optimize the cohesive parameters in the rubber-mortar ITZ, and the numerical simulation results after optimizing the cohesive parameters are compared and analyzed with the simulation results before optimization. The results show that, under the setting of the optimized parameters, the simulation results of each item of the optimal cohesive model parameters in the rubber-mortar ITZ are in line with the reality and closer to the experimental data, and they are also applicable to rubber concrete models with different rubber dosing.

11.
Mol Cancer ; 23(1): 124, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849840

RESUMO

BACKGROUND: Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. METHODS: In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. RESULTS: Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3ß and resulted in increased ß-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. CONCLUSIONS: OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.


Assuntos
Progressão da Doença , Glicogênio Sintase Quinase 3 beta , Metaplasia , Cadeias Pesadas de Miosina , beta Catenina , Humanos , Metaplasia/metabolismo , Metaplasia/patologia , Metaplasia/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Animais , beta Catenina/metabolismo , beta Catenina/genética , Camundongos , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Feminino , Via de Sinalização Wnt , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Modelos Animais de Doenças , Masculino , Organoides/metabolismo , Organoides/patologia
12.
Zhongguo Gu Shang ; 37(6): 5465-52, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38910375

RESUMO

OBJECTIVE: To explore clinical efficacy of osteoplasty combined with percutaneous vertebroplasty(PVP) and percutaneous kyphoplasty (PKP) alone in treating osteoporosis vertebral compression fractures (OVCFs). METHODS: The clinical data of 80 patients with single-level OVCFs treated from January 2021 to June 2022 were retrospectively analyzed, and were divided into treatment group and control group according to different surgical methods, 40 patients in each group. In treatment group, there were 24 males and 16 females, aged from 60 to 83 years old with an average of (70.43±7.31) years old;bone mineral density ranged from -3.30 to -2.50 SD with an average of(-2.84±0.24) SD;1 patient with T10, 4 patients with T11, 11 patients with T12, 7 patients with L1, 7 patients with L2, 5 patients with L3, 3 patients with L4, 2 patients with L5;bone setting technique combined with PVP were performed. In control group, there were 27 males and 13 females, aged from 60 to 82 years old with an average of (68.98±6.94) years old;bone mineral density ranged from -3.40 to -2.50 SD with an average of (-2.76±0.23) SD;2 patients with T10, 3 patients with T11, 13 patients with T12, 11 patients with L1, 5 patients with L2, 3 patients with L3, 2 patients with L4, 1 patient with L5;simple PKP were peformed. Visual analogue scale (VAS) and lumbar Oswestry disability index (ODI) were compared between two groups before operation, 3 days, 3 and 12 months after operation. The changes of local kyphotic angle, vertebral wedge angle and vertebral anterior margin height ratio were compared between two groups before operation, 3 days and 12 months after operation. RESULTS: All patients were successfully completed operation. Treatment group were followed up from 13 to 22 months with an average of (16.82±2.14) months, and control group were followed up from 13 to 23 months with an average of (16.45±2.56) months. Three patients were occurred bone cement leakage in treatment group, while 1 patient were occurred bone cement leakage and 1 patient occurred sensory disturbance of lower limb skin in control group;there were no significant difference in complications between two groups (P>0.05). There were no significant difference in preoperative VAS and ODI between two groups (P>0.05). At 3 days after operation, VAS of treatment group 3.68±0.62 was significantly higher than that of control group 4.00±0.72 (P<0.05). There were no significant difference in VAS and ODI between two groups at 3 and 12 months after operation (P>0.05). There were no significant difference in local kyphotic angle, vertebral wedge angle and vertebral anterior margin height between two groups at 3 days and 12 months after operation (P>0.05). CONCLUSION: Compared with PKP, bone setting manipulation combined with PVP for the treatment of OVCFs has advantages in early postoperative pain relief. In terms of vertebral height recovery, bone setting manipulation combined with PVP and PKP alone have similar clinical effects.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Feminino , Masculino , Idoso , Fraturas por Compressão/cirurgia , Pessoa de Meia-Idade , Cifoplastia/métodos , Vertebroplastia/métodos , Idoso de 80 Anos ou mais , Fraturas da Coluna Vertebral/cirurgia , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos
13.
Toxins (Basel) ; 16(6)2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38922158

RESUMO

The escalating proliferation of cyanobacteria poses significant taste and odor (T/O) challenges, impacting freshwater ecosystems, public health, and water treatment costs. We examined monthly variations in four T/O compounds from September 2011 to August 2012 in Chaohu Lake's eastern drinking water source (DECL). More importantly, we compared the reported T/O occurrence and the related factors in freshwater bodies worldwide. The assessment of T/O issues indicated a severe and widespread problem, with many cases surpassing odor threshold values. Remarkably, China reported the highest frequency and severity of odor-related problems. A temporal analysis revealed variations in odor occurrences within the same water body across different years, emphasizing the need to consider high values in all seasons for water safety. Globally, T/O issues were widespread, demanding attention to variations within the same water body and across different layers. Algae were crucial contributors to odor compounds, necessitating targeted interventions due to diverse odorant sources and properties. A correlation analysis alone lacked definitive answers, emphasizing the essential role of further validation, such as algae isolation. Nutrients are likely to have influenced the T/O, as GSM and MIB correlated positively with nitrate and ammonia nitrogen in DECL, resulting in proposed control recommendations. This study offers recommendations for freshwater ecosystem management and serves as a foundation for future research and management strategies to address T/O challenges.


Assuntos
Água Potável , Lagos , Odorantes , Paladar , Odorantes/análise , China , Água Potável/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Cianobactérias , Estações do Ano , Água Doce
14.
Acta Parasitol ; 69(3): 1352-1358, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38888726

RESUMO

BACKGROUND: In recent years, the trichomonosis in raccoon dogs in China had occurred frequently. Pentatrichomonas hominis had been described in raccoon dogs in China in some previous studies. PURPOSE TO REVEAL: whether raccoon dogs can be infected by other trichomonad species besides P. hominis, and clarify the prevalence and species distribution of trichomonad in raccoon dogs. METHODS: Herein, the 389 fecal samples were collected from farm-raised raccoon dogs in Hebei Province, all the samples were detected using the microscopic examination and several fecal samples containing trichomonad-like organisms were processed, cultured, stained, and photographed. Meanwhile, all the samples were screened by the species-specific nested PCR based on the small subunit rRNA (SSU rRNA) gene of P. hominis,Tritrichomonas foetus and Tetratrichomonas buttreyi, respectively, and all positive secondary PCR amplications obtained in this study were sequenced, aligned and analysed. RESULTS: 62 fecal samples (15.9%,62/389) were trichomonad-positive under light microscopy, and the trichomonad-like cells were clearly observed in the culture contents. The PCR results showed that 100 samples were trichomonad-positive, including 45 P. hominis-positive samples (11.6%,45/389), 32 T. foetus-positive samples (8.2%,32/389), and 33 T. buttreyi-positive samples (8.5%,33/389), respectively. Double mixed infections were observed in 10 samples. The prevalence of T. foetus and P. hominis were both significantly higher in raccoon dogs with diarrhea (13.9%, and 25.0%) than that in raccoon dogs without diarrhea (7.6%, and 9.3%) (p < 0.05).All samples confirmed as trichomonad-positive under microscopy were also found to be trichomonad-positive by PCR analysis. The sequencing and phylogenetic analysis demonstrated the sequences obtained in this study belonged to P. hominis, T. foetus and T. buttreyi SSU rRNA, respectively. Among them, the T. buttreyi SSU rRNA sequences obtained in this study harbored the new sequence polymorphisms. Based on preliminary morphological and molecular analyses, raccoon dogs are considered as the new host of T. foetus and T. buttreyi. CONCLUSION: This is the first report about the identifcation and prevalence of T. foetus and T. buttreyi in raccoon dogs in China, and the results increase our knowledge about the host range and prevalence of trichomonad species.


Assuntos
Fezes , Infecções Protozoárias em Animais , Cães Guaxinins , Animais , Cães Guaxinins/parasitologia , China/epidemiologia , Infecções Protozoárias em Animais/parasitologia , Infecções Protozoárias em Animais/epidemiologia , Fezes/parasitologia , Tritrichomonas foetus/isolamento & purificação , Tritrichomonas foetus/genética , Filogenia , Reação em Cadeia da Polimerase/veterinária , Prevalência , Trichomonadida/genética , Trichomonadida/isolamento & purificação , Trichomonadida/classificação , DNA de Protozoário/genética
15.
BMC Cancer ; 24(1): 576, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730348

RESUMO

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Adenoide Cístico/radioterapia , Carcinoma Adenoide Cístico/mortalidade , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Masculino , Feminino , Radioterapia de Intensidade Modulada/métodos , Pessoa de Meia-Idade , Adulto , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Idoso , Estudos Retrospectivos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Adulto Jovem , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento , Seguimentos , Adolescente , Intervalo Livre de Progressão
16.
BMC Womens Health ; 24(1): 307, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783362

RESUMO

BACKGROUND: This study aimed to analyze the relationship between physical activity and the risk of premenstrual syndrome among college students. METHODS: Eligible studies were searched from the PubMed, Web of Science, and Embase databases. The link between physical activity and the risk of premenstrual syndrome was evaluated using odds ratio (OR) and 95% confidence interval (CI). The heterogeneity of the included studies was tested and their sources were explored by subgroup analysis. A sensitivity analysis was performed to assess the effect of a single study on the pooled results. The included studies were evaluated for publication bias. Five moderate-quality studies were included in this meta-analysis. RESULTS: Physical activity levels were negatively associated with risk of premenstrual syndrome among college students (OR [95%CI] = 1.46 [1.09, 1.96], P = .011). The pooled results were not influenced after being stratified by the study region and whether multi-factor correction was performed or not. Publication bias was not observed in the included studies. CONCLUSION: A high level of physical activity is dramatically associated with a reduced risk of premenstrual syndrome among female college students.


Assuntos
Exercício Físico , Síndrome Pré-Menstrual , Estudantes , Humanos , Síndrome Pré-Menstrual/epidemiologia , Feminino , Estudantes/estatística & dados numéricos , Exercício Físico/fisiologia , Universidades , Adulto Jovem , Fatores de Risco , Adulto
17.
Small ; : e2400997, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712477

RESUMO

Dielectric capacitors are widely used in advanced electrical and electronic systems due to the rapid charge/discharge rates and high power density. High comprehensive energy storage properties are the ultimate ambition in the field of application achievements. Here, the high-entropy strategy is proposed to design and fabricate single-phase homogeneous (Bi0.5Ba0.1Sr0.1Ca0.2Na0.1)(Fe0.5Ti0.3Zr0.1Nb0.1)O3 ceramic, the hierarchical heterostructure including rhombohedral-tetragonal multiphase nanoclusters and locally disordered oxygen octahedral tilt can lead to the increased dielectric relaxation, diffused phase transition, diverse local polarization configurations, grain refinement, ultrasmall polar nanoregions, large random field, delayed polarization saturation and improved breakdown field. Accordingly, a giant Wrec ≈13.3 J cm-3 and a high η ≈78% at 66.4 kV mm-1 can be simultaneously achieved in the lead-free high-entropy BiFeO3-based ceramic, showing an obvious advantage in overall energy-storage properties over BiFeO3-based lead-free ceramics. Moreover, an ultrafast discharge rate (t0.9 = 18 ns) can be achieved at room temperature, concomitant with favorable temperature stability in the range of 20-160 °C, due to the enhanced diffuse phase transition and fast polarization response. This work provides a feasible pathway to design and generate dielectric materials exhibiting high comprehensive energy-storage performance.

18.
Environ Sci Pollut Res Int ; 31(21): 31240-31258, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38630395

RESUMO

Sub-Saharan Africa (SSA) is seeing exceptional urbanization and economic expansion rates. Therefore, the STIRPAT (Stochastic Impacts by Regression on Population, Affluence, and Technology) parameters and the spatial econometric framework are used in this work to examine the influence of economic growth and urbanization on SSA's CO2 emissions. Likewise, to determine the spatial effect and understand how factors influence the spatial dependence of carbon emissions, the study builds a spatial Durbin model (SDM). In line with the findings, the spatial correlation test revealed the spatial correlations across various countries. This indicates that the changes in sub-Saharan African country's CO2 emissions impacted nearby countries and the countries themselves. Additionally, the findings reveal that, in the SSA's countries, urbanization, economic growth, industrial structure, trade, and population, excluding energy intensity, which failed the significant test, all positively influence CO2 outflows, in line with the spatial econometric model's findings. Thus, energy intensity shares an adverse impact on carbon emissions. As an outcome, energy intensity reduces carbon dioxide emissions in nearby nations and the entire region. Thus, the study recommends that policymakers account for the effects of spatial spillover when establishing low-carbon policies, encouraging a low-carbon lifestyle, promoting environmentally friendly technologies, and improving regional collaboration.


Assuntos
Dióxido de Carbono , Desenvolvimento Econômico , Urbanização , Dióxido de Carbono/análise , África Subsaariana , Poluentes Atmosféricos/análise , Humanos , Poluição do Ar
19.
Oncogene ; 43(21): 1594-1607, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38565944

RESUMO

Prostate cancer (PCa) remains a significant cause of morbidity and mortality among men worldwide. A number of genes have been implicated in prostate tumorigenesis, but the mechanisms underlying their dysregulation are still incompletely understood. Evidence has established the competing endogenous RNA (ceRNA) theory as a novel regulatory mechanism for post-transcriptional alterations. Yet, a comprehensive characterization of ceRNA network in PCa lacks. Here we utilize stringent in-silico methods to construct a large ceRNA network across different PCa stages, and provide experimental demonstration for the competing regulation among protumorigenic SEC23A, PHTF2, and their corresponding ceRNA pairs. Using machine learning, we establish a ceRNA-based signature (ceRNA_sig) predictive of androgen receptor (AR) activity, tumor aggressiveness, and patient outcomes. Importantly, we identify miR-375 as a key node in PCa ceRNA network, which is upregulated in PCa relative to normal tissues. Forced expression of miR-375 significantly inhibits, while its inhibition promotes, aggressive behaviors of both AR+ and AR- PCa cells in vitro and in vivo. Mechanistically, we show that miR-375 predominantly targets genes possessing oncogenic roles (e.g., proliferation, DNA repair, and metastasis), and thus release targets with tumor suppressive functions. This action model well clarifies why an upregulated miRNA plays a tumor suppressive role in PCa. Together, our study provides new insights into understanding of transcriptomic aberrations during PCa evolution, and nominates miR-375 as a potential therapeutic target for combating aggressive PCa.


Assuntos
Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs , Neoplasias da Próstata , MicroRNAs/genética , Humanos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Masculino , Camundongos , Animais , Regulação para Cima/genética , Linhagem Celular Tumoral , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Genes Supressores de Tumor , Proliferação de Células/genética , RNA Endógeno Competitivo
20.
Adv Sci (Weinh) ; 11(24): e2309303, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582516

RESUMO

The development of highly active, reusable catalysts for aqueous-phase reactions is challenging. Herein, metallic nickel is encapsulated in a nitrogen-doped carbon-silica composite (SiO2@Ni@NC) as a catalyst for the selective hydrogenation of vanillin in aqueous media. The constructed catalyst achieved 99.8% vanillin conversion and 100% 4-hydroxymethyl-2-methoxyphenol selectivity at room temperature. Based on combined scanning transmission electron microscopy, X-ray photoelectron spectroscopy, and Raman analyses, the satisfactory catalytic performance is attributed to the composite structure consisting of an active metal, carbon, and silica. The hydrophilic silica core promoted dispersion of the catalyst in aqueous media. Moreover, the external hydrophobic NC layer has multiple functions, including preventing oxidation or leaching of the internal metal, acting as a reducing agent to reduce the internal metal, regulating the active-site microenvironment by enriching the concentrations of H2 and organic reactants, and modifying the electronic structure of the active metal via metal-support interactions. Density functional theory calculations indicated that NC facilitates vanillin adsorption and hydrogen dissociation to promote aqueous-phase hydrogenation. This study provides an efficient strategy for constructing encapsulated Ni-based amphiphilic catalysts to upgrade biomass-derived compounds.

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