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1.
Environ Sci Technol ; 58(15): 6825-6834, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38567993

RESUMO

Hg(I) may control Hg redox kinetics; however, its metastable nature hinders analysis. Herein, the stability of Hg(I) during standard preparation and analysis was studied. Gravimetric analysis showed that Hg(I) was stable in its stock solution (1000 mg L-1), yet completely disproportionated when its dilute solution (10 µg L-1) was analyzed using liquid chromatography (LC)-ICPMS. The Hg(I) dimer can form through an energetically favorable comproportionation between Hg(0) and Hg(II), as supported by density functional theory calculation and traced by the rapid isotope exchange between 199Hg(0)aq and 202Hg(II). However, the separation of Hg(0) and Hg(II) (e.g., LC process) triggered its further disproportionation. Polypropylene container, increasing headspace, decreasing pH, and increasing dissolved oxygen significantly enhanced the disproportionation or redox transformations of Hg(I). Thus, using a glass container without headspace and maintaining a slightly alkaline solution are recommended for the dilute Hg(I) stabilization. Notably, we detected elevated concentrations of Hg(I) (4.4-6.1 µg L-1) in creek waters from a heavily Hg-polluted area, accounting for 54-70% of total dissolved Hg. We also verified the reductive formation of Hg(I) in Hg(II)-spiked environmental water samples, where Hg(I) can stably exist in aquatic environments for at least 24 h, especially in seawater. These findings provide mechanistic insights into the transformation of Hg(I), which are indicative of its further environmental identification.


Assuntos
Mercúrio , Poluentes Químicos da Água , Mercúrio/análise , Água do Mar/análise , Água do Mar/química , Isótopos/análise , Poluentes Químicos da Água/análise
2.
J Cancer Res Clin Oncol ; 150(4): 176, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575793

RESUMO

PURPOSE: Residual lymph node metastases (RLNM) remained a great concern in the implementation of organ-preserving strategies and led to poor prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to identify the clinicopathological factors correlated with RLNM in LARC patients with ypT0-2 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 417 patients histologically diagnosed middle-low LARC after NCRT and total mesorectal excision (TME), whose pathological staging was ypT0-2. All patients received pelvic magnetic resonance imaging (MRI) before NCRT. The radiation doses were 50-50.6 Gy for the planning gross tumor volume and 41.8-45 Gy for the planning target volume, respectively. A nomogram for predicting RLNM was constructed using a binary logistic regression. Nomogram performance was assessed by receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: After surgery, 191 patients (45.8%) were ypT0, 43 patients (10.3%) were ypT1 and 183 patients (43.9%) were ypT2, and a total of 49 patients (11.8%) were found the presence of RLNM. Multivariable analyses identified MRI-defined mesorectal fascia (MRF)-positive, high-grade histopathology at biopsy, advanced ypT-category, and the presence of perineural invasion (PNI) as the predictive factors. The nomogram, incorporating all these predictors, showed good discrimination and calibration efficacy, with the areas under the ROC curve of 0.690 (95% CI: 0.610-0.771). Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. CONCLUSION: The nomogram model can predict RLNM in patients with ypT0-2 tumors. It can help select suitable patients for performing organ-preserving strategies after NCRT.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Terapia Neoadjuvante , Metástase Linfática , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Quimiorradioterapia , Quimiorradioterapia Adjuvante , Segunda Neoplasia Primária/patologia
4.
Environ Sci Technol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647522

RESUMO

Algae are an entry point for mercury (Hg) into the food web. Bioconcentration of Hg by algae is crucial for its biogeochemical cycling and environmental risk. Herein, considering the cell heterogeneity, we investigated the bioconcentration of coexisting isotope-labeled inorganic (199IHg) and methyl Hg (201MeHg) by six typical freshwater and marine algae using dual-mass single-cell inductively coupled plasma mass spectrometry (scICP-MS). First, a universal pretreatment procedure for the scICP-MS analysis of algae was developed. Using the proposed method, the intra- and interspecies heterogeneities and the kinetics of Hg bioconcentration by algae were revealed at the single-cell level. The heterogeneity in the cellular Hg contents is largely related to cell size. The bioconcentration process reached a dynamic equilibrium involving influx/adsorption and efflux/desorption within hours. Algal density is a key factor affecting the distribution of Hg between algae and ambient water. Cellular Hg contents were negatively correlated with algal density, whereas the volume concentration factors almost remained constant. Accordingly, we developed a model based on single-cell analysis that well describes the density-driven effects of Hg bioconcentration by algae. From a novel single-cell perspective, the findings improve our understanding of algal bioconcentration governed by various biological and environmental factors.

5.
J Hazard Mater ; 470: 134113, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38565021

RESUMO

Photo-induced degradation of dimethylmercury (DMHg) is considered to be an important source for the generation of methylmercury (MMHg). However, studies on DMHg photodegradation are scarce, and it is even debatable about whether DMHg can be degraded in natural waters. Herein, we found that both DMHg and MMHg could be photodegraded in three natural waters collected from the Yellow River Delta, while in pure water only DMHg photodegradation occurred under visible light irradiation. The effects of different environmental factors on DMHg photodegradation were investigated, and the underlying mechanisms were elucidated by density functional theory calculations and a series of control experiments. Our findings revealed that the DMHg degradation rate was higher in the tidal creek water compared to Yellow River, Yan Lake, and purified water. NO3-, NO2-, and DOM could promote the photodegradation with DOM and NO3- showing particularly strong positive effects. Different light sources were employed, and UV light was found to be more effective in DMHg photodegradation. Moreover, MMHg was detected during the photodegradation of DMHg, confirming that the photochemical demethylation of DMHg is a source of MMHg in sunlit water. This work may provide a novel mechanistic insight into the DMHg photodegradation in natural waters and enrich the study of the global biogeochemical cycle of Hg.


Assuntos
Compostos de Metilmercúrio , Fotólise , Poluentes Químicos da Água , Compostos de Metilmercúrio/química , Compostos de Metilmercúrio/análise , Compostos de Metilmercúrio/efeitos da radiação , Poluentes Químicos da Água/química , Poluentes Químicos da Água/efeitos da radiação , Poluentes Químicos da Água/análise , Luz , Raios Ultravioleta , Nitratos/química , Nitratos/análise , Rios/química
6.
Oncol Lett ; 27(4): 172, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38455661

RESUMO

Malignant mesothelioma of the tunica vaginalis testis is a rare, highly invasive urogenital malignant tumor with no specific clinical manifestations. Reported cases of this disease are limited. Therefore, an early preoperative diagnosis is difficult. The current study presents a case of malignant mesothelioma of the tunica vaginalis testis and a literature review. A 52-year-old man was admitted to Xiaoshan Affiliated Hospital of Wenzhou Medical University (Hangzhou, China) in December 2022 and underwent radical resection of the right testicle and epididymis but did not undergo radiotherapy or chemotherapy. The patient was followed up for 5 months, and no recurrence or metastasis was found. The rarity of testicular mesothelioma poses a challenge to its etiology and diagnosis, which is rarely achieved preoperatively. Malignant mesothelioma of the testicular tunica vaginalis has a poor prognosis and is not sensitive to radiotherapy or chemotherapy, requiring close postoperative follow-up. This condition is rare in clinical practice; therefore, it needs to be reported to aid clinicians' decision-making regarding diagnosis and treatment.

7.
Maturitas ; 184: 107965, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38460416

RESUMO

BACKGROUND: Sexual and reproductive health (SRH) is critical to the overall health of older adults. We assessed the utilization of SRH services and its correlates among older adults in China. METHODS: We recruited community-dwelling adults aged 50 and above in five Chinese cities between June 2020 and December 2022. In this study SRH services included reproductive health examination, cervical cancer screening, and sexual life counselling. Logistic regression was used to assess correlates of SRH services utilization. RESULTS: A total of 3001 older adults (1819 men and 1182 women) were enrolled. Among them, 11.4 % (343/3001) of participants received a reproductive health examination, 35.4 % (418/1182) of female participants received cervical cancer screening, and 30.1 % (401/1332) of sexually active participants sought help for their sexual lives. Older men with an annual income of USD 7500 or more (aOR = 3.21, 95%CI: 1.39-7.44), two or more chronic conditions (2.38, 1.39-4.08), and reproductive health problems (2.01, 1.18-3.43) were more likely to receive a urological examination. For older women, individuals who were younger (aged 50-59 years: 5.18, 2.84-9.43; aged 60-69 years: 2.67, 1.49-4.79), lived in an urban area (1.88, 1.31-2.71), were employed (1.73, 1.21-2.47), had two or more chronic conditions (2.04, 1.37-3.05), were sexually active (1.72, 1.15-2.58) and talked about sex (1.69, 1.21-2.36) were more likely to receive a gynecological examination. CONCLUSION: SRH services utilization among older adults was low, with urological examination among older men particularly low. SRH messages and services tailored for older adults are needed to enhance their utilization of SRH services.

8.
Medicine (Baltimore) ; 103(13): e37526, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552093

RESUMO

The role of serum albumin (ALB) has been extensively studied in patients with cancer; however, research on its effect on bone metastasis in these patients remains limited. This study aimed to investigate the relationship between serum ALB and alkaline phosphatase (ALP) levels in patients with tumors. Using data from the National Health and Nutrition Examination Survey 2011 to 2018, we assessed the correlation between serum ALB and ALP levels using a weighted multivariate linear regression model, whereas a weighted generalized additive model and smooth curve fitting were used to address potential nonlinearities. A total of 1876 patients with cancer were included in our study. In the subgroup analysis stratified by sex, race/ethnicity, and liver disease, the negative correlation of ALB with ALP remained for most groups, except in blacks (ß = -1.755, 95%CI: [-3.848, 0.338], P = .103) and patients with gout (ß = -0.676, 95%CI: [-2.061, 0.709], P = .340). In black people and patients with gout, the relationship between ALB and ALP showed an inverted U-shaped curve, with an inflection point at approximately 42 g/dL. Our study showed an inverse correlation between ALB and ALP levels in most patients with tumors, but not in black patients and those with gout. The measurement of ALB levels can serve as a screening tool for bone metastases while guiding therapeutic intervention strategies.


Assuntos
Neoplasias Ósseas , Gota , Humanos , Albumina Sérica/análise , Fosfatase Alcalina , Inquéritos Nutricionais
9.
J Hazard Mater ; 469: 133979, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38492396

RESUMO

Riverine mercury (Hg) is mainly transported to coastal areas in suspended particulate matter (SPM)-bound form, posing a potential threat to human health. Water discharge and SPM characteristics in rivers vary naturally with seasonality and can also be arbitrarily disrupted by anthropogenic regulation events, but their effects on Hg transport remain unresolved. Aiming to understand the confounding effects of seasonality and anthropogenic river regulation on Hg and SPM transport, this study selected the highly sediment-laden Yellow River as a representative conduit. Significant variations in SPM concentrations (108 - 7097 mg/L) resulted in fluctuations in total mercury (THg, 3.79 - 111 ng/L) in river water corresponding to seasonality and anthropogenic water/sediment regulation. Principal component analysis and structural equation model revealed that SPM was the essential factor controlling THg and particulate Hg (PHg) in river water. While SPM exhibited equilibrium state in the dry season, a net resuspension during the anthropogenic regulation and net deposition in the wet season demonstrated the impact of SPM dynamics on Hg distribution and transport to coastal regions. Combining water discharge, SPM, and Hg concentrations, a modified model was developed to quantify Hg flux (2256 kg), over 98% of which was in particulate phase.


Assuntos
Mercúrio , Poluentes Químicos da Água , Humanos , Rios/química , Material Particulado/análise , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Mercúrio/análise , Água/análise , Poeira/análise , Oceanos e Mares , Sedimentos Geológicos/análise
10.
Eur J Med Chem ; 269: 116341, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38518523

RESUMO

Protein arginine methyltransferase 5 (PRMT5) and epidermal growth factor receptor (EGFR) are both involved in the regulation of various cancer-related processes, and their dysregulation or overexpression has been observed in many types of tumors. In this study, we designed and synthesized a series of 1-phenyl-tetrahydro-ß-carboline (THßC) derivatives as the first class of dual PRMT5/EGFR inhibitors. Among the synthesized compounds, 10p showed the most potent dual PRMT5/EGFR inhibitory activity, with IC50 values of 15.47 ± 1.31 and 19.31 ± 2.14 µM, respectively. Compound 10p also exhibited promising antiproliferative activity against A549, MCF7, HeLa, and MDA-MB-231 cell lines, with IC50 values below 10 µM. Molecular docking studies suggested that 10p could bind to PRMT5 and EGFR through hydrophobic, π-π, and cation-π interactions. Furthermore, 10p displayed favorable pharmacokinetic properties and oral bioavailability (F = 30.6%) in rats, and administrated orally 10p could significantly inhibit the growth of MCF7 orthotopic xenograft tumors. These results indicate that compound 10p is a promising hit compound for the development of novel and effective dual PRMT5/EGFR inhibitors as potential anticancer agents.


Assuntos
Antineoplásicos , Carbolinas , Humanos , Ratos , Animais , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Proliferação de Células , Antineoplásicos/química , Receptores ErbB , Inibidores de Proteínas Quinases/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Proteína-Arginina N-Metiltransferases
11.
Small Methods ; : e2400067, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38494754

RESUMO

Wide-bandgap (WBG) perovskite solar cells (PSCs) have been widely used as the top cell of tandem solar cells. However, photoinduced phase segregation and high open-circuit voltage loss pose significant obstacles to the development of WBG PSCs. Here, a two-step small-size A-site and large-size X-site incorporation strategy is reported to modulate the lattice distortion and improve the film quality of WBG formamidinium-methylammonium (FAMA) perovskite films for photostable PSCs based on two-step deposition method. First, CsI with content of 0-20% is introduced to tune the lattice distortion and film quality of FAMA perovskite with a bandgap of 1.70 eV. Then, 4% RbI is incorporated to further modulate the perovskite growth and lattice distortion, leading to the suppression of photoinduced phase segregation in the resultant RbCsFAMA quadruple cation perovskites. As a result, the 20%CsI/4%RbI-doped device obtains a promising efficiency of 20.6%, and the corresponding perovskite film shows good photothermal stability. Even without encapsulation, the device can maintain 92% of its initial efficiency after 1000 h of continuous operation under 1 sun equivalent white light-emitting diode illumination.

13.
BJPsych Open ; 10(2): e41, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38297498

RESUMO

BACKGROUND: COVID-19 carriers experience psychological stresses and mental health issues such as varying degrees of stigma. The Social Impact Scale (SIS) can be used to measure the stigmatisation of COVID-19 carriers who experience such problems. AIMS: To evaluate the reliability and validity of the Chinese version of the SIS, and the association between stigma and depression among asymptomatic COVID-19 carriers in Shanghai, China. METHOD: A total of 1283 asymptomatic COVID-19 carriers from Shanghai Ruijin Jiahe Fangcang Shelter Hospital were recruited, with a mean age of 39.64 ± 11.14 years (59.6% male). Participants completed questionnaires, including baseline information and psychological measurements, the SIS and Self-Rating Depression Scale. The psychometrics of the SIS and its association with depression were examined through exploratory factor analysis, confirmatory factor analysis and receiver operating characteristic analysis. RESULTS: The average participant SIS score was 42.66 ± 14.61 (range: 24-96) years. Analyses suggested the model had four factors: social rejection, financial insecurity, internalised shame and social isolation. The model fit statistics of the four-factor SIS were 0.913 for the comparative fit index, 0.902 for the Tucker-Lewis index and 0.088 for root-mean-square error of approximation. Standard estimated factor loadings ranged from 0.509 to 0.836. After controlling for demographic characteristics, the total score of the 23-item SIS predicted depression (odds ratio: 1.087, 95% CI 1.061-1.115; area under the curve: 0.84, 95% CI 0.788-0.892). CONCLUSIONS: The Chinese version of the SIS showed good psychometric properties and can be used to assess the level of perceived stigma experienced by asymptomatic COVID-19 carriers.

14.
Environ Pollut ; 346: 123554, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38395130

RESUMO

In the past few decades, mercury (Hg) discharged into the coastal bays of China has significantly increased; however, long-term trends regarding the pollution status and sources of Hg in these bays have yet to be clear. Focusing on this issue, surface sediments and core sediments were collected in the Jiaozhou Bay (JZB), a typical bay highly affected by human activities in China, to analyze the concentrations and stable isotopic composition of Hg. Total mercury (THg) concentrations in surface sediment varied from 7 to 163 ng/g, with higher levels located in the eastern JZB, possibly attributed to intensive industrial and population density. THg in sediment cores 14 and 20 displayed fluctuating increasing trends from 1936 to 2019, reflecting the deterioration of Hg pollution. In contrast, THg in sediment core 28 near the river mouth exhibited a declining trend, possibly due to the river dam construction. Using a stable isotope mixing model, contributions of various sources (atmospheric, riverine, and industrial emissions) to Hg in the JZB were estimated. The results showed that industrial emissions were the main source (over 50%) of mercury in the JZB in 2019. Sediment cores recorded an increase in industrial Hg due to early industrialization and Reform and Opening-up before 2000. In addition, sediment core 20 demonstrated a rise in the percentage of riverine Hg due to land reclamation at the bay's mouth during 2000-2007.


Assuntos
Mercúrio , Poluentes Químicos da Água , Humanos , Mercúrio/análise , Baías , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Isótopos , China
15.
J Am Geriatr Soc ; 72(4): 1122-1135, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38319006

RESUMO

BACKGROUND: Sexual function is an important yet understudied aspect of overall health and well-being in older adults. We aimed to examine sexual function and its correlates among people 50 years and older in China. METHODS: We enrolled people aged 50 years and older recruited from four regions in China between September 2021 and July 2022 in a multicenter cross-sectional study. Data were collected through an investigator-administered questionnaire about demographic characteristics, health characteristics, and sexual function status. Logistic regression was used to assess correlates of lower sexual function (the highest quintile of the sex-specific population distribution of Natsal-SF scores [i.e., lower functioning compared with the remaining]). RESULTS: A total of 465 women and 832 men who were sexually active in the past year were included in the analysis (mean age: 60.4 ± 7.2) [Correction added after first online publication on 12 Feb 2024. The word "years" has been changed to "year" in this sentence.]. Over a quarter of all participants were dissatisfied with their sex life. Notably, 92 women and 167 men were categorized as having a lower sexual function. Age (in men only), living in urban areas, general health status, being underweight or overweight (in men only), and having depressive symptoms were associated with lower sexual function. Among all participants, 43.1% of men and 54.0% of women experienced sexual response problems lasting 3 months or more. Less than one-third of all participants had sought help or advice for sex life in the past year. CONCLUSIONS: Sexual dysfunction and sexual dissatisfaction are prevalent among older adults in China and are associated with self-assessed poor health. More efforts are needed to better understand sexual health needs and tailor service provision.


Assuntos
Comportamento Sexual , Disfunções Sexuais Fisiológicas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Inquéritos e Questionários , China/epidemiologia
16.
Cell Genom ; 4(2): 100474, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38359790

RESUMO

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/genética , Neoplasias Nasofaríngeas/epidemiologia , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo Único/genética
17.
Brain Inj ; 38(3): 194-201, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38297513

RESUMO

AIM: To explore the potential role of microRNA miR-221-5p on the angiopoietin-1 (Ang-1)/Ang-2/Tie-2 signaling axis after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Aspects of the rat's behavior were measured using the Kaoutzanis scoring system to test neurological responses. This included feeding behavior, body contraction, motor, and eye-opening responses. Brain sections were studied using transmission electron microscopy and Evans blue extravasation. Levels of Ang-1, Ang-2, and Tie-2 were determined by Western blot, while miR-221-5p was quantified using stem-loop real-time quantitative PCR (RT-qPCR). RESULTS: The SAH group responded worse to the neurological response test than the sham-operated group. The intercellular space was widened in the SAH group, but not in the sham-operated group. Evans blue dye leaked significantly more into brain tissue cells of the SAH group. Stem-loop qRT-PCR showed elevated miR-221-5p levels. Additionally, Ang-1 and Tie-2 were reduced but Ang-2 expression was increased after SAH. This led to a significant reduction of the Ang-1/Ang-2 ratio in the brain tissue, which was associated with the destruction of the blood-brain barrier. CONCLUSION: The data indicate that miR-221-5p might regulate blood-brain barrier dysfunction through the Ang-1/Ang-2/Tie-2 signaling axis, suggesting that it should be further investigated as a potential novel biomarker.


Assuntos
MicroRNAs , Hemorragia Subaracnóidea , Ratos , Animais , Barreira Hematoencefálica , Angiopoietina-1/genética , Angiopoietina-1/metabolismo , Azul Evans/metabolismo , MicroRNAs/metabolismo
18.
Cell Death Discov ; 10(1): 91, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378646

RESUMO

Pyroptosis plays a crucial role in sepsis, and the abnormal handling of myocyte calcium (Ca2+) has been associated with cardiomyocyte pyroptosis. Specifically, the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is a Ca2+ release channel in the endoplasmic reticulum (ER). However, the specific role of IP3R2 in sepsis-induced cardiomyopathy (SIC) has not yet been determined. Thus, this study aimed to investigate the underlying mechanism by which IP3R2 channel-mediated Ca2+ signaling contributes to lipopolysaccharide (LPS)-induced cardiac pyroptosis. The SIC model was established in rats by intraperitoneal injection of LPS (10 mg/kg). Cardiac dysfunction was assessed using echocardiography, and the protein expression of relevant signaling pathways was analyzed using ELISA, RT-qPCR, and western blot. Small interfering RNAs (siRNA) and an inhibitor were used to explore the role of IP3R2 in neonatal rat cardiomyocytes (NRCMs) stimulated by LPS in vitro. LPS-induced NLRP3 overexpression and GSDMD-mediated pyroptosis in the rats' heart. Treatment with the NLRP3 inhibitor MCC950 alleviated LPS-induced cardiomyocyte pyroptosis. Furthermore, LPS increased ATP-induced intracellular Ca2+ release and IP3R2 expression in NRCMs. Inhibiting IP3R activity with xestospongin C (XeC) or knocking down IP3R2 reversed LPS-induced intracellular Ca2+ release. Additionally, inhibiting IP3R2 reversed LPS-induced pyroptosis by suppressing the NLRP3/Caspase-1/GSDMD pathway. We also found that ER stress and IP3R2-mediated Ca2+ release mutually regulated each other, contributing to cardiomyocyte pyroptosis. IP3R2 promotes NLRP3-mediated pyroptosis by regulating ER Ca2+ release, and the mutual regulation of IP3R2 and ER stress further promotes LPS-induced pyroptosis in cardiomyocytes.

19.
JAMA Surg ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381429

RESUMO

Importance: Total neoadjuvant therapy (TNT) is the standard treatment for locally advanced rectal cancer, especially for patients with high-risk factors. However, the efficacy of TNT combined with immunotherapy for patients with proficient mismatch repair (pMMR) rectal cancer is unknown. Objectives: To evaluate the safety and efficacy of TNT with induction chemoimmunotherapy followed by long-course chemoradiation in patients with high-risk, pMMR rectal cancer and to identify potential molecular biomarkers associated with treatment efficacy. Design, Setting, and Participants: This cohort study was a single-arm phase 2 trial conducted at Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, from June 2020 to October 2021. Biopsies and plasma were collected before treatment for whole-exome sequencing and cell-free DNA sequencing, respectively. Data were analyzed from May 2022 to September 2022. Interventions: Participants received 3 cycles of induction oxaliplatin and capecitabine combined with camrelizumab and radiotherapy (50.6 Gy in 22 fractions) with concurrent capecitabine. Patients without disease progression received 2 cycles of consolidation oxaliplatin/capecitabine. Main Outcomes and Measures: The primary end point was pathologic complete response rate. Results: Of 25 patients enrolled (19 men [76%]; 6 women [24%]; median [IQR] age, 58 [48-64] years), 22 patients (88%) completed the TNT schedule. The pathologic complete response rate was 33.3% (7/21). Twelve patients (48%) achieved clinical complete response, and 4 patients (16%) chose to watch and wait. R0 resection was achieved in 21 of 21 patients, and the major pathologic response rate was 38.1% (8/21). The most common adverse event was nausea (80%, 20/25); grade 3 toxic effects occurred in 9 of 25 patients (36%). Patients with tumor shrinkage of 50% or greater after induction oxaliplatin/capecitabine and camrelizumab or clinical complete response had higher percentages of LRP1B mutation. Mutation of LRP1B was associated with high tumor mutation burden and tumor neoantigen burden. Patients with high tumor mutation burden all benefited from therapy. Conclusions and Relevance: This study found that TNT with induction chemoimmunotherapy followed by long-course chemoradiation was safe and effective for patients with high-risk rectal cancer with pMMR status. Longer follow-up and larger clinical studies are needed to validate this innovative regimen. There is also an urgent need to further validate the predictive value of LRP1B and discover other novel biomarkers with potential predictive value for rectal cancer.

20.
Child Adolesc Psychiatry Ment Health ; 18(1): 11, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243299

RESUMO

BACKGROUND: Longitudinal evidence is lacking on the interplay between lifestyle behaviors and depressive symptoms, especially in the context of the COVID-19 pandemic. This study investigated the changes in physical activity and recreational screen time during the pandemic, along with their reciprocal associations with depressive symptoms among children and adolescents. METHODS: The public health emergency due to the pandemic started in January 2023 and lasted for two months in Shanghai, China. A three-wave longitudinal study was conducted among 1,666 children and adolescents (6-18 years) in January, March, and July 2023. Moderate-to-vigorous intensity physical activity (MVPA), recreational screen time, and depressive symptoms were measured using self-reported questionnaires. Random-intercept cross-lagged panel models were constructed to examine the bidirectional associations between physical activity and recreational screen time with depressive symptoms. RESULTS: Children and adolescents experienced a significant decrease in MVPA and a substantial increase in recreational screen time during the pandemic, which failed to return to pre-pandemic levels post-pandemic. Pre-pandemic MVPA was negatively associated with subsequent depressive symptoms (ß = -0.147). Conversely, pre-pandemic depressive symptoms were positively associated with subsequent recreational screen time (ß = 0.085), which in turn predicted heightened post-pandemic depressive symptoms (ß = 0.076). When stratified by age, significant associations were found in adolescents but not children. CONCLUSIONS: Sustained unhealthy changes in physical activity and recreational screen time were observed during the COVID-19 pandemic among children and adolescents. This study elucidates a potential reciprocal relationship between lifestyle behaviors and mental well-being. Effective interventions are emphasized to counter the negative impacts of insufficient physical activity and excessive screen use on the mental health of children and adolescents.

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