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1.
Redox Biol ; 76: 103349, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39260061

RESUMO

Chemoresistance remains a principal culprit for the treatment failure in colorectal cancer (CRC), especially for patients with recurrent or metastatic disease. Deciphering the molecular basis of chemoresistance may lead to novel therapeutic strategies for this fatal disease. Here, UBR5, an E3 ubiquitin ligase frequently overexpressed in human CRC, is demonstrated to mediate chemoresistance principally by inhibiting ferroptosis. Paradoxically, UBR5 shields oxaliplatin-activated Smad3 from proteasome-dependent degradation via Lys 11-linked polyubiquitination. This novel chemical modification of Smad3 facilitates the transcriptional repression of ATF3, induction of SLC7A11 and inhibition of ferroptosis, contributing to chemoresistance. Consequently, targeting UBR5 in combination with a ferroptosis inducer synergistically sensitizes CRC to oxaliplatin-induced cell death and control of tumor growth. This study reveals, for the first time, a major clinically relevant chemoresistance mechanism in CRC mediated by UBR5 in sustaining TGFß-Smad3 signaling and tuning ferroptosis, unveiling its potential as a viable therapeutic target for chemosensitization.

2.
Small ; : e2405126, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39106227

RESUMO

Biomass-encapsulated liquid metals (LMs) composite gels have aroused tremendous attention as epidermal smart materials due to their biocompatibility and sustainability. However, they can still not simultaneously possess toughness, adhesion, and recoverability. In this work, the tough, sticky, and recyclable protein-encapsulated LMs organogels (GLMx) are fabricated through the micro-interfacial stabilization of LMs by lignin and the following preparation of food-making inspired gels. With the help of lignin modification, the LMs micro-drops demonstrated uniform dispersion in the protein matrix, as well as dense non-covalent interactions (e.g., H─bond and hydrophobic interaction) with amino acid residues in peptide chains, which endowed the GLMx with high conductivity (≈5.4 S m-1), toughness (≈738.2 kJ m-3), self-adhesiveness (a maximal lap-shear strength of ≈58.3 kPa), and recoverability. By tightly adhering onto human skin, the GLMx can act as epidermal sensors to detect drastic (e.g., joint bending) and subtle body movements (e.g., swallowing) and even recognize handwriting and speaking in real-time. Moreover, the organogels can also harvest solar energy and convert it into heat and electricity, which is promising in self-powered intelligent devices. Thus, this work paves a facile way to prepare protein/LMs composite organogels that are suitable for multiple applications like healthcare, human-robot interactions, and solar energy conversion.

3.
Microorganisms ; 12(8)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39203406

RESUMO

Engineering acid-tolerant microbial strains is a cost-effective approach to overcoming acid stress during industrial fermentation. We previously constructed an acid-tolerant strain (Escherichia coli SC3124) with enhanced growth robustness and productivity under mildly acidic conditions by fine-tuning the expression of synthetic acid-tolerance module genes consisting of a proton-consuming acid resistance system (gadE), a periplasmic chaperone (hdeB), and ROS scavengers (sodB, katE). However, the precise acid-tolerance mechanism of E. coli SC3124 remained unclear. In this study, the growth of E. coli SC3124 under mild acid stress (pH 6.0) was determined. The final OD600 of E. coli SC3124 at pH 6.0 was 131% and 124% of that of the parent E. coli MG1655 at pH 6.8 and pH 6.0, respectively. Transcriptome analysis revealed the significant upregulation of the genes involved in oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and lysine-dependent acid-resistance system in E. coli SC3124 at pH 6.0. Subsequently, a weighted gene coexpression network analysis was performed to systematically determine the metabolic perturbations of E. coli SC3124 with mild acid treatment, and we extracted the gene modules highly associated with different acid traits. The results showed two biologically significant coexpression modules, and 263 hub genes were identified. Specifically, the genes involved in ATP-binding cassette (ABC) transporters, oxidative phosphorylation, the TCA cycle, amino acid metabolism, and purine metabolism were highly positively associated with mild acid stress responses. We propose that the overexpression of synthetic acid-tolerance genes leads to metabolic changes that confer mild acid stress resistance in E. coli. Integrated omics platforms provide valuable information for understanding the regulatory mechanisms of mild acid tolerance in E. coli and highlight the important roles of oxidative phosphorylation and ABC transporters in mild acid stress regulation. These findings offer novel insights to better the design of acid-tolerant chasses to synthesize value-added chemicals in a green and sustainable manner.

4.
Org Lett ; 26(28): 5917-5922, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38958598

RESUMO

Rh-catalyzed asymmetric hydrogenation of 2-substituted 4H-thiochromenes and 4H-chromenes was successfully developed. This method provided highly efficient access to a series of chiral 2-substituted thiochromanes and chromanes in high yields with excellent enantioselectivities (up to 99% yield, 86-99% ee). The obtained chiral 2-substituted thiochromane products were also successfully transformed to corresponding chiral α-substituted sulfoxides and sulfones with excellent enantioselectivities. Furthermore, this highly enantioselective hydrogenation process could be successfully applied to the concise and practical synthesis of the chiral pharmaceutical BW683C.

5.
BMC Infect Dis ; 24(1): 732, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054428

RESUMO

AIM: To analyze the clinicopathological features of schistosomal and non-schistosomal colorectal cancer in Central China and compare them with other areas of the Yangtze River Basin. METHOD: The 501 cases of colorectal cancer (CRC) were retrospectively analyzed from 2020 to 2022. They were divided into two groups: 406 cases of colorectal cancer without schistosomiasis (CRC-NS) and 95 cases of colorectal cancer with schistosomiasis (CRC-S).The clinicopathological characteristics included the distribution of schistosomiasis eggs, patient age, sex, tumor differentiation, lymph node metastasis, and clinical stage. By retrieving the database, this study compared the clinicopathological differences of colorectal cancer with schistosomiasis in other areas of the Yangtze River basin. RESULTS: The cases of colorectal cancer with schistosomiasis accounted for 18.9%(95/501) in the study. The patients of CRC-S were older than the patients of CRC-NS (P = 0.002, P < 0.05). There was a statistical difference in the location of occurrence (P = 0.000, P < 0.05) between the two groups. There were no significant differences between CRC-S and CRC-NS in other clinicopathological features, such as sex (P = 0.054), Type(P = 0.242), histological type(P = 0.654), infiltrative depth(P = 0.811), differentiation(P = 0.837), lymph node metastasis(P = 0.574), intravascular tumor thrombus(P = 0.698), T stage(P = 0.354). In other areas of the Yangtze River Basin, there were statistical differences in the age of occurrence and T stage (P < 0.05) between colorectal cancer with schistosomiasis and non-schistosomal colorectal cancer. CONCLUSION: In Central China, colorectal cancer with chronic schistosomiasis infection occurs more in the rectum and sigmoid colon. It is more common in individuals over 60 years old, consistent with the findings in the Yangtze River Basin. Additionally, schistosomal colorectal cancer had a higher T stage in the Yangtze River Basin. This may be related to the malignant biological behavior of colorectal cancer and could result in a relatively poor prognosis. Therefore, the elderly population in schistosomiasis endemic areas should pay more attention to early screening and tumor prevention.


Assuntos
Neoplasias Colorretais , Esquistossomose , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/parasitologia , Neoplasias Colorretais/epidemiologia , Masculino , Feminino , China/epidemiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Esquistossomose/epidemiologia , Esquistossomose/complicações , Esquistossomose/parasitologia , Esquistossomose/patologia , Adulto , Idoso de 80 Anos ou mais , Metástase Linfática , Adulto Jovem
6.
PeerJ ; 12: e17459, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827311

RESUMO

Background: Engaging in appropriate physical activity can significantly lower the risk of various diseases among middle-aged and older adults. Investigating optimal levels of physical activity (PA) is crucial for enhancing the health of this demographic. This study aims to explore the dose-response relationship between weekly PA levels and the frequency of colds among Chinese middle-aged and elderly individuals, identifying the necessary PA level to effectively diminish the risk of colds. Methods: We conducted a cross-sectional study using a web-based survey targeting individuals aged 40 and older (n = 1, 683) in China. The survey collected information on PA and the frequency of colds. Data was analyzed using Kruskal-Wallis test and the χ2 test. We explored the dose-response relationship between weekly PA and cold frequency over the past year through an ordered multivariate logistic regression model and a restricted cubic spline model. Results: (1) Brisk walking emerged as the preferred physical exercise for those over 40. The findings suggest that engaging in moderate (odds ratio (OR) = 0.64, P < 0.001, 95% confidence interval (CI) [0.50-0.81]) and high (OR = 0.64, P < 0.001, 95% CI [0.51-0.79]) levels of PA weekly significantly reduces the risk of catching a cold. Individuals with one (OR = 1.47, P < 0.001, 95% CI [1.20-1.80]) or multiple chronic diseases (OR = 1.56, P < 0.001, 95% CI [1.21-2.00]) were at increased risk. Those residing in central (OR = 1.64, P < 0.001, 95% CI [1.33-02.01]) and western China (OR = 1.49, P = 0.008, 95% CI [1.11-02.00]) faced a higher risk compared to their counterparts in eastern China. (2) According to the restricted cubic spline model, adults who experienced one cold in the past year had a weekly PA level of 537.29 metabolic equivalent-minutes per week (MET-min/wk) with an OR value of 1. For those reporting two or more colds, the PA level was 537.76 MET-min/wk with an OR of 1. Conclusions: (1) Brisk walking is the most favored exercise among the Chinese middle-aged and elderly, with the prevalence of colds being affected by the number of chronic diseases and the geographic location. (2) Regular, moderate exercise is linked to a lower risk of colds. To effectively reduce cold frequency, it is recommended that middle-aged and elderly Chinese individuals engage in a minimum of 538 MET-min/wk of exercise.


Assuntos
Exercício Físico , Humanos , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Idoso , Exercício Físico/fisiologia , Adulto , Caminhada/estatística & dados numéricos , Resfriado Comum/epidemiologia , Resfriado Comum/prevenção & controle , População do Leste Asiático
7.
Clin Transl Med ; 14(7): e1750, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38943041

RESUMO

BACKGROUND: Serotonin (5-hydroxytryptamine) is a multifunctional bioamine serving as a neurotransmitter, peripheral hormone and mitogen in the vertebrate system. It has pleiotropic activities in central nervous system and gastrointestinal function via an orchestrated action of serotonergic elements, particularly serotonin receptor-mediated signalling cascades. The mitogenic properties of serotonin have garnered recognition for years and have been exploited for repurposing serotonergic-targeted drugs in cancer therapy. However, emerging conflicting findings necessitate a more comprehensive elucidation of serotonin's role in cancer pathogenesis. MAIN BODY AND CONCLUSION: Here, we provide an overview of the biosynthesis, metabolism and action modes of serotonin. We summarise our current knowledge regarding the effects of the peripheral serotonergic system on tumourigenesis, with a specific emphasis on its immunomodulatory activities in human cancers. We also discuss the dual roles of serotonin in tumour pathogenesis and elucidate the potential of serotonergic drugs, some of which display favourable safety profiles and impressive efficacy in clinical trials, as a promising avenue in cancer treatment. KEY POINTS: Primary synthesis and metabolic routes of peripheral 5-hydroxytryptamine in the gastrointestinal tract. Advanced research has established a strong association between the serotonergic components and carcinogenic mechanisms. The interplay between serotonergic signalling and the immune system within the tumour microenvironment orchestrates antitumour immune responses. Serotonergic-targeted drugs offer valuable clinical options for cancer therapy.


Assuntos
Neoplasias , Serotonina , Transdução de Sinais , Humanos , Serotonina/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo
8.
Adv Mater ; 36(32): e2403818, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38794816

RESUMO

Lithium-ion batteries (LIBs) are rapidly developing into attractive energy storage technologies. As LIBs gradually enter retirement, their sustainability is starting to come into focus. The utilization of recycled spent LIBs as raw materials for battery manufacturing is imperative for resource and environmental sustainability. The sustainability of spent LIBs depends on the recycling process, whereby the cycling of battery materials must be maximized while minimizing waste emissions and energy consumption. Although LIB recycling technologies (hydrometallurgy and pyrometallurgy) have been commercialized on a large scale, they have unavoidable limitations. They are incompatible with circular economy principles because they require toxic chemicals, emit hazardous substances, and consume large amounts of energy. The direct regeneration of degraded electrode materials from spent LIBs is a viable alternative to traditional recycling technologies and is a nondestructive repair technology. Furthermore, direct regeneration offers advantages such as maximization of the value of recycled electrode materials, use of sustainable, nontoxic reagents, high potential profitability, and significant application potential. Therefore, this review aims to investigate the state-of-the-art direct LIB regeneration technologies that can be extended to large-scale applications.

9.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124383, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38772177

RESUMO

Recently, synthesized N-linked-disalicylaldehyde H2QJI probes have been used to detect heavy metal ions in the experiment conveniently. Nevertheless, there needs to be a more in-depth examination of the excited state intramolecular proton transfer (ESIPT) mechanism and photophysical properties of the probe. This work remedied it based on quantum chemistry calculations. We contained due hydrogen bond (O1-H2 ⋯ N3 and O4-H5 ⋯ O6) and then analyzed bond parameters, IR vibration spectra, and non-covalent interaction. The bond strength is enhanced under photoexcitation, and the former is significantly stronger. The calculated electron spectra are in agreement with the experimental values. The results of the S0 and S1 potential energy curves and IRC calculations also confirm the unique ESIPT behavior, which isan excited stated stepwise double proton transfer. The fluorescence, internal conversion, and intersystem crossing rate of KD molecules (twisted-, double proton transfer) were calculated respectively to reveal the radiative and non-radiative pathways. It proved that the corresponding spectra are not obtained since the electrons are mainly deactivated by the ISC (S1->T1). Furthermore, the interfragment charge transfer (IFCT) approach indicates that the molecule possesses twisted intramolecular charge transfer (TICT) characteristics, which lead to the quenching of fluorescence introduction.

10.
Burns ; 50(5): 1341-1348, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38472001

RESUMO

BACKGROUND: A considerable number of burn patients have greater psychological stress due to the special trauma site. In clinical practice, it is found that medical staff pay more attention to the rehabilitation of physical function, while the mental health status of patients is greatly neglected. In contact with patients, we found that attention should be paid to the levels of stigma and self-esteem. However, there are few studies on stigma and self-esteem in patients with facial burns. Therefore, this study aimed to describe the stigma and self-esteem levels of facial burns, investigate the relationship between these two variables, and explore the influencing factors of stigma in patients with facial burns, in order to provide evidence for follow-up interventions to improve this population. METHODS: From August 2020 to June 2021, we recruited patients with facial burns who met the inclusion criteria in one burn specialist clinic and three burn units of a tertiary A hospital in Guangzhou, China. The survey tools of this study include sociodemographic and disease-related information questionnaires, the Chinese version of the Social Impact Scale, and the self-esteem scale (these scales were validated). SPSS 25.0 software was used for data analysis through t test, analysis of variance, correlation analysis, multiple linear regression method for data statistics. RESULTS: The total stigma score of facial burn patients was (58.01 ± 7.57), which was at a medium level; the self-esteem score was (19.72 ± 2.43), which was at a low level. Correlation analysis showed that there was a positive correlation between the self-esteem score and the total score of stigma (r = 0.286, P < 0.01). The family per capita monthly income, education level, way of medical expenses expenditure, and self-esteem of facial burn patients were the influencing factors of their stigma, and these factors explained 33.7% of the variation in stigma (F=8.659, P<0.01). CONCLUSIONS: Patients with facial burns have low levels of stigma and self-esteem, which requires our efforts. In particular, there is a positive correlation between stigma and self-esteem, and self-esteem is an independent risk factor affecting stigma. Our findings suggest that interventions aimed at enhancing self-esteem have the potential to positively impact the reduction of stigma in this patient population.


Assuntos
Queimaduras , Traumatismos Faciais , Autoimagem , Estigma Social , Humanos , Queimaduras/psicologia , Feminino , Masculino , Adulto , Traumatismos Faciais/psicologia , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia , Inquéritos e Questionários , Adolescente
11.
Int J Biol Macromol ; 264(Pt 2): 130670, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38453108

RESUMO

Liquid free ion-conductive elastomers (ICEs) have demonstrated promising potential in various advanced application scenarios including sensor, artificial skin, and human-machine interface. However, ICEs that synchronously possess toughness, adhesiveness, stability, and anti-bacterial capability are still difficult to achieve yet highly demanded. Here, a one-pot green and sustainable strategy was proposed to fabricate multifunctional ICEs by extracting non-cellulose components (mainly lignin and hemicellulose) from lignocellulose with polymerizable deep eutectic solvents (PDES) and the subsequent in-situ photo-polymerization process. Ascribing to the uniform dispersion of non-cellulose components in PDES, the resultant ICEs demonstrated promising mechanical strength (a tensile strength of ~1200 kPa), high toughness (~9.1 MJ m-3), favorable adhesion (a lap-shear strength up to ~61.5 kPa toward metal), conducive stabilities, and anti-bacterial capabilities. With the help of such advantages, the ICEs exhibited sensitive (a gauge factor of ~23.5) and stable (~4000 cycles) performances in human motion and physiological signal detection even under sub-zero temperatures (e.g., -20 °C). Besides, the residue cellulose can be mechanically isolated into nanoscale fibers, which matched the idea of green chemistry.


Assuntos
Solventes Eutéticos Profundos , Dietilestilbestrol/análogos & derivados , Lignina , Humanos , Celulose , Elastômeros
12.
Int J Biol Macromol ; 263(Pt 1): 130305, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382788

RESUMO

Protein-based hydrogels with promising biocompatibility and biodegradability have attracted considerable interest in areas of epidermal sensing, whereas, which are still difficult to synchronously possess high mechanical strength, self-adhesion, and recoverability. Hence, the bio-polymer lignosulfonate-reinforced gluten organohydrogels (GOHLx) are fabricated through green and simple food-making processes and the following solvent exchange with glycerol/water binary solution. Ascribing to the uniform distribution of lignosulfonate in gluten networks, as well as the noncovalent interactions (e.g., H-bond) between them, the resultant GOHLx exhibit favorable conductivity (∼14.3 × 10-4 S m-1), toughness (∼711.0 kJ m-3), self-adhesion (a maximal lap-shear strength of ∼33.5 kPa), high sensitivity (GF up to ∼3.04), and durability (∼3000 cycles) toward shape deformation, which are suitable for the detection of both drastic (e.g., elbow and wrist bending) and subtle (e.g., swallowing and speaking) human movements even under -20 °C. Furthermore, the GOHLx is also biocompatible, degradable, and recoverable (by a simple kneading process). Thus, this work may pave a simple, green, and cheap way to prepare all-biomass-based, tough, sticky, and recoverable protein-based organohydrogels for epidermal strain sensing even in harsh environments.


Assuntos
Adesivos , Dispositivos Eletrônicos Vestíveis , Humanos , Lignina , Temperatura , Glutens , Condutividade Elétrica , Hidrogéis
13.
Psychol Health Med ; : 1-14, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053313

RESUMO

This study aimed to identify group variations in adolescent impulsivity and explore the connections between latent categories of impulsivity and psychological symptoms, social anxiety, and internet addiction. The research involved 2,378 participants from three middle schools in Guangdong Province, China. We assessed the impact of impulsivity levels (measured by BBIS) on depression (measured by KADS-11), anxiety (measured by SCARED), social anxiety (measured by SASC), and internet addiction (measured by YDQ). Latent profile analysis was employed to examine the diversity in adolescent impulsivity, establish latent classifications, and investigate the variances in psychological symptoms, social anxiety, and internet addiction. The middle school students were categorized into five latent groups based on their BBIS scores. Statistical analysis revealed five impulsivity categories, strongly linked to psychological symptoms and social anxiety but less strongly associated with internet addiction. The high impulsivity group (C5) exhibited higher scores in psychological symptoms and social anxiety compared to other groups, whereas the poor self-regulation group (C3) displayed greater psychological symptoms, social anxiety scores, and internet addiction than the impulsive behavior group (C4). Future investigations should investigate the underlying factors contributing to the observed differences among these groups.

14.
J Org Chem ; 88(22): 15726-15738, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37921031

RESUMO

A Rh-catalyzed highly chemo- and enantioselective hydrogenation of 2-CF3-chromen/thiochromen-4-ones was successfully established achieving excellent selectivity and high turnover numbers. Under mild conditions, a series of 2-CF3-chromen-4-ones were hydrogenated to provide the corresponding chiral 2-CF3-chroman-4-ones with excellent enantioselectivities (up to 99.9% ee) and achieve high turnover numbers (TON of up to 11,800). Moreover, the obtained hydrogenation products were also successfully transformed into other derivatives including the important intermediate of plasmepsin inhibitors with maintained enantiopurity.

15.
Chem Sci ; 14(34): 9048-9054, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37655036

RESUMO

A highly enantioselective rhodium-catalyzed reductive dearomatization of 7-substituted pyrazolo[1,5-a]pyrimidines has been realized for the first time by two strategies to afford chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidines with excellent enantioselectivities of up to 98% ee. This method also provides an efficient approach for the synthesis of the powerful BTK inhibitor, zanubrutinib.

16.
Org Lett ; 25(37): 6858-6862, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37703279

RESUMO

Rh-(R,R)-f-spiroPhos complex-catalyzed asymmetric hydrogenation of α-substituted alkenyl sulfones has been achieved, affording the chiral γ-keto sulfones and simple α-alkyl-substituted sulfones in high yields (96-99%) with excellent chemo-/enantioselectivities (86-96% ee) and high turnover numbers (TONs) of up to 4000. The method provides an efficient and high-enantioselectivity strategy for chiral γ-keto sulfones and simple α-substituted sulfones under mild conditions. Moreover, the obtained hydrogenation product was transformed into other important chiral α-substituted sulfones.

17.
Redox Biol ; 67: 102891, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37734229

RESUMO

As an essential micronutrient for humans, the metabolism of copper is fine-tuned by evolutionarily conserved homeostatic mechanisms. Copper toxicity occurs when its concentration exceeds a certain threshold, which has been exploited in the development of copper ionophores, such as elesclomol, for anticancer treatment. Elesclomol has garnered recognition as a potent anticancer drug and has been evaluated in numerous clinical trials. However, the mechanisms underlying elesclomol-induced cell death remain obscure. The discovery of cuproptosis, a novel form of cell death triggered by the targeted accumulation of copper in mitochondria, redefines the significance of elesclomol in cancer therapy. Here, we provide an overview of copper homeostasis and its associated pathological disorders, especially copper metabolism in carcinogenesis. We summarize our current knowledge of the tumor suppressive mechanisms of elesclomol, with emphasis on cuproptosis. Finally, we discuss the strategies that may contribute to better application of elesclomol in cancer therapy.


Assuntos
Cobre , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Cobre/metabolismo , Hidrazinas , Neoplasias/tratamento farmacológico
18.
Int Immunopharmacol ; 122: 110602, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37437432

RESUMO

HER2 is an established therapeutic target in breast, gastric, and gastroesophageal junction carcinomas with HER2 overexpression or genomic alterations. The humanized monoclonal antibody trastuzumab targeting HER2 has substantially improved the clinical outcomes of HER2-positive patients, yet the inevitable intrinsic or acquired resistance to trastuzumab limits its clinical benefit, necessitating the elucidation of resistance mechanisms to develop alternate therapeutic strategies. This review presents an overview of trastuzumab resistance mechanisms involving signaling pathways, cellular metabolism, cell plasticity, and tumor microenvironment, particularly discussing the prospects of developing rational combinations to improve patient outcomes.


Assuntos
Antineoplásicos , Neoplasias da Mama , Neoplasias , Humanos , Feminino , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Receptor ErbB-2/genética , Resistencia a Medicamentos Antineoplásicos/genética , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Microambiente Tumoral
19.
Adv Mater ; 35(51): e2301540, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37191036

RESUMO

Lithium (Li)-based batteries are gradually evolving from the liquid to the solid state in terms of safety and energy density, where all solid-state Li-metal batteries (ASSLMBs) are considered the most promising candidates. This is demonstrated by the Bluecar electric vehicle produced by the Bolloré Group, which is utilized in car-sharing services in several cities worldwide. Despite impressive progress in the development of ASSLMBs, their avenues for recycling them remain underexplored, and combined with the current explosion of spent Li-ion batteries, they should attract widespread interest from academia and industry. Here, the potential challenges of recycling ASSLMBs as compared to Li-ion batteries are analyzed and the current progress and prospects for recycling ASSLMBs are summarized and analyzed. Drawing on the lessons learned from Li-ion battery recycling, it is important to design sustainable recycling technologies before ASSLMBs gain widespread market adoption. A battery-recycling-oriented design is also highlighted for ASSLMBs to promote the recycling rate and maximize profitability. Finally, future research directions, challenges, and prospects are outlined to provide strategies for achieving sustainable development of ASSLMBs.

20.
J Cancer Res Ther ; 19(Supplement): S166-S171, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37147994

RESUMO

Background: There is little evidence on the efficacy of external beam radiation (EBR) compared to liver resection (LR) for patients with solitary small (≤5 cm) hepatocellular carcinoma (HCC). Objective: We aimed to investigate this clinical question based on the Surveillance, Epidemiology, and End Results (SEER) database. Method: SEER database was used to identify 416 patients with solitary small HCC who underwent LR or EBR. Survival analysis and Cox proportional hazards model were performed to evaluate overall survival (OS) and identify prognostic factors for OS. Propensity score matching (PSM) method was used to adjust the baseline characteristics of the two groups. Result: Before PSM, the 1- and 2-year OS rates were 92.0% and 85.2% in the LR cohort and 76.0% and 60.3% in the EBR cohort, respectively (P < 0.001). After PSM, LR (n = 62) demonstrated improved OS compared to EBR (n = 62) (1-year OS rate: 96.5% vs. 76.0%; 2-year OS rate: 89.3% vs. 60.3%, P < 0.001), despite stratification on tumor size. Multivariate Cox regression analysis indicated that treatment type was the only factor associated with OS (hazard ratio: 5.297; 95% confidence interval: 1.952-14.371, P = 0.001). Conclusion: For patients with solitary small HCC, LR may offer better survival outcomes than EBR.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Hepatectomia/métodos , Análise de Sobrevida , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Prognóstico
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