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Introduction: Cross-sectional evidence suggests that sleep problems increased the risk of suicide during the 2019 coronavirus disease (COVID-19) pandemic. However, a lack of longitudinal studies examined the relationship between pre-COVID-19 sleep duration, chronotype and incident suicide during the COVID-19 pandemic. Thus, we examined these associations in a longitudinal study of medical students. Methods: From the Shantou College Student Sleep Cohort, a total of 333 first and second grade medical students (age 19.41 ± 0.82 years, female 61.26%), without suicidal ideation (SI) at pre-COVID-19 period, were followed up during the COVID-19 pandemic. Incident SI was defined by their response to the 9th question from the Beck Depression Inventory. Short sleep duration was defined as less than 7 h/night. The Morningness-Eveningness Questionnaire was used to evaluate the participants' chronotype. Logistic regression with adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) was used to examine the association between sleep and SI. Results: The incidence of SI during the COVID-19 pandemic was 5.71%. Logistic regressions with confounding factors adjustment showed that both short sleep duration (AOR = 4.91, 95% CI = 1.16-20.74) and eveningness (AOR = 3.80, 95% CI = 1.08-13.30) in the pre-COVID-19 period were associated with increased risk of incident SI during the COVID-19 pandemic. Conclusion: Pre-COVID-19 short sleep duration and eveningness predict incident SI during the COVID-19 pandemic in medical students. Prolonging sleep duration may help to decrease SI during major public health crises.
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COVID-19 , Duração do Sono , Estudantes de Medicina , Ideação Suicida , Adolescente , Feminino , Humanos , Masculino , Adulto Jovem , Cronotipo , COVID-19/epidemiologia , COVID-19/psicologia , Incidência , Estudos Longitudinais , Pandemias , Estudos Retrospectivos , Fatores de Risco , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
Neck pain is among the most prevalent musculoskeletal disorders affecting the general population. During the 2019 coronavirus disease 2019 (COVID-19) pandemic, students have increasingly resorted to online learning, requiring prolonged use of electronic devices. This study aimed to investigate the prevalence of and factors influencing neck pain during online learning. The study employed a cross-sectional design. Eligible participants were nursing students who had been receiving online instruction for a duration exceeding 3 months. To develop the study instrument, the researchers integrated the study objectives with insights from an extensive literature review. This process culminated in the creation of a comprehensive online questionnaire designed to capture relevant data. The prevalence of neck pain among students was analyzed for both the pre-COVID-19 and during COVID-19 periods. The chi-square test was utilized to compare the occurrence of neck pain between these 2 periods, while binary logistic regression was employed to examine the association between various influencing factors and neck pain. This study revealed that out of the 426 students who participated in the study, 391 were female (91.8%) and 35 were male (8.2%). The prevalence of neck pain during online learning (62.7%) was significantly higher than before online learning (37.3%) (Pâ <â .05). A significant correlation was also found between neck pain and learning while lying on a bed or table, duration of use of electronic devices, and exercising habits (Pâ <â .05). The prevalence of neck pain among students has significantly increased during the COVID-19 pandemic. Future research should focus on evaluating the long-term impact of distance learning on undergraduate students. Additionally, it is imperative to develop and implement targeted intervention programs based on the identified influencing factors to mitigate the prevalence of neck pain and alleviate neck discomfort.
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COVID-19 , Educação a Distância , Cervicalgia , Humanos , Cervicalgia/epidemiologia , Feminino , Masculino , Prevalência , Estudos Transversais , COVID-19/epidemiologia , Educação a Distância/métodos , Adulto Jovem , Estudantes de Enfermagem/estatística & dados numéricos , Adulto , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints [CNS failure-free survival (cFFS), overall survival (OS)] were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months). Patients were categorized into early and non-early progression (EP, NEP) groups depending on SD status before LMs. Median survivals from LM were assessed with Kaplan Meier plots, compared with Log-Rank test. EP was associated with worse median cFFS and OS vs NEP in both LM analyses (cFFS- LM1: 3.6 vs. 9.7 months, p = 0.0016; LM2: 2.3 vs. 12.5 months, p < 0.0001; OS- LM1: 3.6 vs. 24.3 months, p < 0.0001; LM2: 5.3 vs. 30.2 months, p < 0.0001). In multivariate analyses, EP was associated with shorter cFFS [LM1: Hazard Ratio (HR) with 95% confidence interval (CI) 3.16, 1.46-6.83, p = 0.0034; LM2: 5.32, 2.33-12.15, p = <0.0001] and shorter OS (LM1: HR with 95% CI 4.28, 1.98-9.12, p = 0.0002; LM2: 7.40, 3.10-17.63, p = <0.0001) vs NEP. Early systemic disease progressions after 1st SRS to brain is associated with worse cFFS and OS in patients with BCBM.
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Pancreatic adenocarcinoma (PAAD) is a life-threatening cancer. Exploring new diagnosis and treatment targets helps improve its prognosis. tRNA-derived small non-coding RNAs (tsRNAs) are a novel type of gene expression regulators and their dysregulation is closely related to many human cancers. Yet the expression and functions of tsRNAs in PAAD are not well understood. Our study used RNA sequencing to identify tsRNA expression profiles in PAAD cells cultured in no or high glucose media and found tRF-18-8R6546D2 was an uncharacterized tsRNA, which has significantly high expression in PAAD cells and tissues. Clinically, tRF-18-8R6546D2 is linked to poor prognosis in PAAD patients and can be used to distinguish them from healthy populations. Functionally, in vitro and vivo, tRF-18-8R6546D2 over-expression promoted PAAD cell proliferation, migration and invasion, inhibited apoptosis, whereas tRF-18-8R6546D2 knock-down showed opposite effects. Mechanistically, tRF-18-8R6546D2 promoted PAAD malignancy partly by directly silencing ASCL2 and further regulating its downstream genes such as MYC and CASP3. These findings show that tRF-18-8R6546D2 is a novel oncogenic factor and can be a promising diagnostic or prognostic biomarker and therapeutic target for PAAD.
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Adenocarcinoma , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas , RNA de Transferência , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Linhagem Celular Tumoral , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proliferação de Células/genética , Camundongos , Animais , Movimento Celular/genética , Apoptose/genética , Progressão da Doença , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo , Prognóstico , Masculino , Feminino , Camundongos NusRESUMO
BACKGROUND AND PURPOSE: There is heterogeneity of white matter damage in Parkinson's disease patients with different cognitive states. Our aim was to find sensitive diffusional kurtosis imaging biomarkers to differentiate the white matter damage pattern of mild cognitive impairment and dementia. MATERIALS AND METHODS: Nineteen patients with Parkinson disease with mild cognitive impairment and 18 patients with Parkinson disease with dementia were prospectively enrolled. All participants underwent MR examination with 3D-T1-weighted image and diffusional kurtosis imaging sequences. Demographic data were compared between the 2 groups. Voxelwise statistical analyses of diffusional kurtosis imaging parameters were performed using tract-based spatial statistics. The receiver operator characteristic curve of significantly different metrics was graphed. The correlation of significantly different metrics with global cognitive status was analyzed. RESULTS: Compared with the Parkinson disease with mild cognitive impairment group, the fractional anisotropy and mean kurtosis values decreased in 4 independent clusters in the forceps minor, forceps major, inferior fronto-occipital fasciculus, and the inferior and superior longitudinal fasciculus in patients with Parkinson disease with dementia; the mean diffusivity decreased in 1 cluster in the forceps minor. The fractional anisotropy value in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus would be the diffusional kurtosis imaging marker for the differential diagnosis of Parkinson disease with mild cognitive impairment and patients with Parkinson disease with dementia, with the best diagnostic efficiency of 0.853. The fractional anisotropy values in the forceps minor (ß = 84.20, P < .001) and years of education (ß = 0.38, P = .014) were positively correlated with the Montreal Cognitive Assessment. CONCLUSIONS: The diffusional kurtosis imaging-derived fractional anisotropy and mean kurtosis can detect the different white matter damage patterns of Parkinson disease with mild cognitive impairment and Parkinson disease with dementia. Fractional anisotropy is more sensitive than mean kurtosis in the differential diagnosis; fractional anisotropy derived from diffusional kurtosis imaging could become a promising imaging marker for the differential diagnosis of Parkinson disease with mild cognitive impairment and Parkinson disease with dementia.
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Disfunção Cognitiva , Imagem de Tensor de Difusão , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/complicações , Feminino , Masculino , Disfunção Cognitiva/diagnóstico por imagem , Idoso , Anisotropia , Imagem de Tensor de Difusão/métodos , Pessoa de Meia-Idade , Demência/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Estudos Prospectivos , Sensibilidade e Especificidade , Diagnóstico Diferencial , Biomarcadores , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
Intrathoracic airway segmentation in computed tomography is a prerequisite for various respiratory disease analyses such as chronic obstructive pulmonary disease, asthma and lung cancer. Due to the low imaging contrast and noises execrated at peripheral branches, the topological-complexity and the intra-class imbalance of airway tree, it remains challenging for deep learning-based methods to segment the complete airway tree (on extracting deeper branches). Unlike other organs with simpler shapes or topology, the airway's complex tree structure imposes an unbearable burden to generate the "ground truth" label (up to 7 or 3 hours of manual or semi-automatic annotation per case). Most of the existing airway datasets are incompletely labeled/annotated, thus limiting the completeness of computer-segmented airway. In this paper, we propose a new anatomy-aware multi-class airway segmentation method enhanced by topology-guided iterative self-learning. Based on the natural airway anatomy, we formulate a simple yet highly effective anatomy-aware multi-class segmentation task to intuitively handle the severe intra-class imbalance of the airway. To solve the incomplete labeling issue, we propose a tailored iterative self-learning scheme to segment toward the complete airway tree. For generating pseudo-labels to achieve higher sensitivity (while retaining similar specificity), we introduce a novel breakage attention map and design a topology-guided pseudo-label refinement method by iteratively connecting breaking branches commonly existed from initial pseudo-labels. Extensive experiments have been conducted on four datasets including two public challenges. The proposed method achieves the top performance in both EXACT'09 challenge using average score and ATM'22 challenge on weighted average score. In a public BAS dataset and a private lung cancer dataset, our method significantly improves previous leading approaches by extracting at least (absolute) 6.1% more detected tree length and 5.2% more tree branches, while maintaining comparable precision.
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Purpose: Major depressive disorder (MDD) is associated with cognitive impairment through unclear mechanisms. We examined the relationship between sleep electroencephalogram (EEG) power and attention level in MDD. Patients and Methods: Forty-seven untreated patients with MDD and forty-seven age- and sex-matched controls were included. We examined relative EEG power during non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep by fast Fourier transform. The Attention Network Test (ANT) was performed to evaluate attention levels. Results: Compared to controls, patients with MDD had lower theta power during NREM (P = 0.018) and REM (P = 0.002) sleep, while higher beta power (P = 0.050) during NREM sleep and delta power (P = 0.018) during REM sleep. Regarding attention level, patients with MDD had lower levels of accuracy (P = 0.021), longer mean reaction time (P < 0.001), poorer manifestations of the alerting effect (P = 0.038) and worse executive control (P = 0.048). Moreover, decreased theta power during NREM sleep was correlated with worsened accuracy (ß = 0.329, P = 0.040), decreased theta power during REM sleep was correlated with worsened alerting effect (ß = 0.355, P = 0.020), and increased delta power during REM sleep was correlated with longer mean reaction time (ß = 0.325, P = 0.022) in patients with MDD. No association between ANT performance and other frequency bands was observed in patients with MDD. Conclusion: Our findings suggest that patients with MDD manifest impaired selective attention function that is associated with decreased theta power during NREM/REM sleep and increased delta power during REM sleep.
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PURPOSE: CBCT-guided online-adaptive radiotherapy (oART) systems have been made possible by using artificial intelligence and automation to substantially reduce treatment planning time during on-couch adaptive sessions. Evaluating plans generated during an adaptive session presents significant challenges to the clinical team as the planning process gets compressed into a shorter window than offline planning. We identified MU variations up to 30% difference between the adaptive plan and the reference plan in several oART sessions that caused the clinical team to question the accuracy of the oART dose calculation. We investigated the cause of MU variation and the overall accuracy of the dose delivered when MU variations appear unnecessarily large. METHODS: Dosimetric and adaptive plan data from 604 adaptive sessions of 19 patients undergoing CBCT-guided oART were collected. The analysis included total MU per fraction, planning target volume (PTV) and organs at risk (OAR) volumes, changes in PTV-OAR overlap, and DVH curves. Sessions with MU greater than two standard deviations from the mean were reoptimized offline, verified by an independent calculation system, and measured using a detector array. RESULTS: MU variations relative to the reference plan were normally distributed with a mean of -1.0% and a standard deviation of 11.0%. No significant correlation was found between MU variation and anatomic changes. Offline reoptimization did not reliably reproduce either reference or on-couch total MUs, suggesting that stochastic effects within the oART optimizer are likely causing the variations. Independent dose calculation and detector array measurements resulted in acceptable agreement with the planned dose. CONCLUSIONS: MU variations observed between oART plans were not caused by any errors within the oART workflow. Providers should refrain from using MU variability as a way to express their confidence in the treatment planning accuracy. Clinical decisions during on-couch adaptive sessions should rely on validated secondary dose calculations to ensure optimal plan selection.
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MOTIVATION: ADP-ribosylation is a critical modification involved in regulating diverse cellular processes, including chromatin structure regulation, RNA transcription, and cell death. Bacterial ADP-ribosyltransferase toxins (bARTTs) serve as potent virulence factors that orchestrate the manipulation of host cell functions to facilitate bacterial pathogenesis. Despite their pivotal role, the bioinformatic identification of novel bARTTs poses a formidable challenge due to limited verified data and the inherent sequence diversity among bARTT members. RESULTS: We proposed a deep learning-based model, ARTNet, specifically engineered to predict bARTTs from bacterial genomes. Initially, we introduced an effective data augmentation method to address the issue of data scarcity in training ARTNet. Subsequently, we employed a data optimization strategy by utilizing ART-related domain subsequences instead of the primary full sequences, thereby significantly enhancing the performance of ARTNet. ARTNet achieved a Matthew's correlation coefficient (MCC) of 0.9351 and an F1-score (macro) of 0.9666 on repeated independent test datasets, outperforming three other deep learning models and six traditional machine learning models in terms of time efficiency and accuracy. Furthermore, we empirically demonstrated the ability of ARTNet to predict novel bARTTs across domain superfamilies without sequence similarity. We anticipate that ARTNet will greatly facilitate the screening and identification of novel bARTTs from bacterial genomes. AVAILABILITY AND IMPLEMENTATION: ARTNet is publicly accessible at http://www.mgc.ac.cn/ARTNet/. The source code of ARTNet is freely available at https://github.com/zhengdd0422/ARTNet/.
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ADP Ribose Transferases , Biologia Computacional , Aprendizado Profundo , ADP Ribose Transferases/metabolismo , ADP Ribose Transferases/química , ADP Ribose Transferases/genética , Biologia Computacional/métodos , Toxinas Bacterianas/química , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Genoma Bacteriano , Bactérias/genéticaRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) is associated with hypertension. However, the differential mechanisms underlying OSA-related hypertension between normal-weight vs. obese patients is limited. METHODS: We studied 92 patients with OSA and 24 patients with continuous positive airway pressure (CPAP) treatment. Blood pressure (BP) was measured twice during awake and continuously monitored during sleep. Obesity was defined as body mass index ≥28 kg/m2. Serum metabolite levels were assessed by metabolomics. RESULTS: Among 59 normal-weight and 33 obese patients, 651 and 167 metabolites showed differences between hypertension and normotension or were associated with systolic and diastolic BP (SBP, DBP) after controlling confounders. These metabolites involved 16 and 12 Kyoto Encyclopedia of Genes and Genomes enrichment pathways in normal-weight and obese patients respectively, whereas 6 pathways overlapped. Among these 6 overlapping pathways, 4 were related to homocysteine metabolism and 2 were non-specific pathways. In homocysteine metabolism pathway, 13 metabolites were identified. Interestingly, the change trends of 7 metabolites associated with SBP (all interaction-p≤0.083) and 8 metabolites associated with DBP (all interaction-p≤0.033) were opposite between normal-weight and obese patients. Specifically, increased BP was associated with down-regulated folate-dependent remethylation and accelerated transsulfuration in normal-weight patients, whereas associated with enhanced betaine-dependent remethylation and reduced transsulfuration in obese patients. Similar findings were observed in ambulatory BP during sleep. After CPAP treatment, baseline low homocysteine levels predicted greater decrease in DBP among normal-weight but not obese patients. CONCLUSIONS: Mechanisms in OSA-related hypertension differ between normal-weight and obese patients, which are explained by different changes in homocysteine metabolism.
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Pressão Positiva Contínua nas Vias Aéreas , Homocisteína , Hipertensão , Obesidade , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/terapia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/metabolismo , Homocisteína/sangue , Homocisteína/metabolismo , Masculino , Obesidade/complicações , Obesidade/metabolismo , Feminino , Pessoa de Meia-Idade , Adulto , Pressão Sanguínea/fisiologia , Índice de Massa CorporalRESUMO
Flexible and stretchable electronic devices are subject to failure because of vulnerable circuit interconnections. We develop a low-voltage (1.5 to 4.5 V) and rapid (as low as 5 s) electric welding strategy to integrate both rigid electronic components and soft sensors in flexible circuits under ambient conditions. This is achieved through the design of conductive elastomers composed of borate ester polymers and conductive fillers, which can be self-welded and generate welding effects to various materials including metals, hydrogels, and other conductive elastomers. The welding effect is generated through the electrochemical reaction-triggered exposure of interfacial adhesive promotors or the cleavage/reformation of dynamic bonds. Our strategy can ensure both mechanical compliance and conductivity at the circuit interfaces and easily produce welding strengths in the kilopascal to megapascal range. The as-designed conductive elastomers in combination with the electric welding technique provide a robust platform for constructing standalone flexible and stretchable electronic devices that are detachable and assemblable on demand.
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BACKGROUND: Neoadjuvant immune checkpoint blockade (ICB) combined with chemoradiotherapy offers high pathologic complete response (pCR) rate for patients with locally advanced esophageal squamous cell carcinomas (ESCC). But the dynamic tumor immune microenvironment modulated by such neoadjuvant therapy remains unclear. PATIENTS AND METHODS: A total of 41 patients with locally advanced ESCC were recruited. All patients received neoadjuvant toripalimab combined with concurrent chemoradiotherapy. Matched pre- and post-treatment tissues were obtained for fluorescent multiplex immunohistochemistry (mIHC) and IHC analyses. The densities and spatial distributions of immune cells were determined by HALO modules. The differences of immune cell patterns before and after neoadjuvant treatment were investigated. RESULTS: In the pre-treatment tissues, more stromal CD3 + FoxP3 + Tregs and CD86+/CD163 + macrophages were observed in patients with residual tumor existed in the resected lymph nodes (pN1), compared with patients with pCR. The majority of macrophages were distributed in close proximity to tumor nest in pN1 patients. In the post-treatment tissues, pCR patients had less CD86 + cell infiltration, whereas higher CD86 + cell density was significantly associated with higher tumor regression grades (TRG) in non-pCR patients. When comparing the paired pre- and post-treatment samples, heterogeneous therapy-associated immune cell patterns were found. Upon to the treatment, CD3 + T lymphocytes were slightly increased in pCR patients, but markedly decreased in non-pCR patients. In contrast, a noticeable increase and a less obvious decrease of CD86 + cell infiltration were respectively depicted in non-pCR and pCR patients. Furthermore, opposite trends of the treatment-induced alterations of CD8 + and CD15 + cell infiltrations were observed between pN0 and pN1 patients. CONCLUSIONS: Collectively, our data demonstrate a comprehensive picture of tumor immune landscape before and after neoadjuvant ICB combined with chemoradiotherapy in ESCC. The infiltration of CD86 + macrophage may serve as an unfavorable indicator for neoadjuvant toripalimab combined with chemoradiotherapy.
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Quimiorradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidores de Checkpoint Imunológico , Terapia Neoadjuvante , Microambiente Tumoral , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/patologia , Terapia Neoadjuvante/métodos , Masculino , Feminino , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/patologia , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Microambiente Tumoral/imunologia , Idoso , Adulto , Macrófagos/imunologia , Macrófagos/metabolismoRESUMO
Key Clinical Message: A patient presented with cardiogenic shock, requiring the implantation of a left ventricular assist device (LVAD), and acute myeloblastic leukemia. This necessitated total body irradiation (TBI) while balancing dose reduction to the LVAD components to avoid potential radiation damage. Here we outline our treatment approach and dose estimates to the LVAD. Abstract: This case report discusses the delivery of TBI to a patient with an LVAD. This treatment required radiation-dose determinations and consequential reductions for the heart, LVAD, and an external controller connected to the LVAD. The patient was treated using a traditional 16MV anterior posterior (AP)/posterior anterior (PA) technique at a source-to-surface-distance of 515 cm for 400 cGy in two fractions. A 3 cm thick Cerrobend block was placed on the beam spoiler to reduce dose to the heart and LVAD to 150 cGy. The external controller was placed in a 1 cm thick acrylic box to reduce neutron dose and positioned as far from the treatment fields as achievable. In vivo measurements were made using optically stimulated luminescence dosimeters (OSLDs) placed inside the box at distances of 2 cm, 8.5 cm, and 14 cm from the field edge, and on the patient along the central axis and centered behind the LVAD block. Further ion chamber measurements were made using a solid water phantom to more accurately estimate the dose delivered to the LVAD. Neutron dose measurements were also conducted. The total estimated dose to the controller ranged from 135.3 cGy to 91.5 cGy. The LVAD block reduced the surface dose to the patient to 271.6 cGy (68.1%). The block transmission factors of the 3 cm Cerrobend block measured in the phantom were 45% at 1 cm depth and decreased asymptotically to around 30% at 3 cm depth. Applying these transmission factors to the in vivo measurements yielded a dose of 120 cGy to the implanted device. The neutron dose the LVAD region is estimated around 0.46 cGy. Physical limitations of the controller made it impossible to completely avoid dose. Shielding is recommended. The block had limited dose reduction to the surface, due to secondary particles, but appropriately reduced the dose at 3 cm and beyond. More research on LVADs dose limits would be beneficial.
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Owing to the global health crisis of resistant pathogenic infections, researchers are emphasizing the importance of novel prevention and control strategies. Existing antimicrobial drugs predominantly target a few pathways, and their widespread use has pervasively increased drug resistance. Therefore, it is imperative to develop new antimicrobial drugs with novel targets and chemical structures. The de novo cysteine biosynthesis pathway, one of the microbial metabolic pathways, plays a crucial role in pathogenicity and drug resistance. This pathway notably differs from that in humans, thereby representing an unexplored target for developing antimicrobial drugs. Herein, we have presented an overview of cysteine biosynthesis pathways and their roles in the pathogenicity of various microorganisms. Additionally, we have investigated the structure and function of enzymes involved in these pathways as well as have discussed drug design strategies and structure-activity relationships of the enzyme inhibitors. This review provides valuable insights for developing novel antimicrobials and offers new avenues to combat drug resistance.
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Cisteína , Descoberta de Drogas , Cisteína/metabolismo , Cisteína/química , Cisteína/biossíntese , Humanos , Relação Estrutura-Atividade , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Estrutura Molecular , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/biossíntese , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Testes de Sensibilidade Microbiana , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/metabolismoRESUMO
Hydrogen peroxide (H2O2) plays a crucial role in various applications, such as green oxidation processes and the production of high-quality fuels. Currently, H2O2 is primarily manufactured using the indirect anthraquinone method, known for its significant energy consumption and the generation of intensive by-products. Extensive research has been conducted on the photocatalytic production of H2O2 via oxygen reduction reaction (ORR), with polymeric carbon nitride (PCN) emerging as a promising catalyst for this conversion. This review article is organized around two approaches. The first part main consists of the chemical optimization of the PCN structure, while the second focuses on the physical integration of PCN with other functional materials. The objective is to clarify the correlation between the physicochemical properties of PCN photocatalysts and their effectiveness in H2O2 production. Through a thorough review and analysis of the findings, this article seeks to stimulate new insights and achievements, not only in the domain of H2O2 production via ORR but also in other redox reactions.
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Addressing the significant level of variability exhibited by pancreatic cancer necessitates the adoption of a systems biology approach that integrates molecular data, biological properties of the tumors, medical images, and clinical features of the patients. In this study, a comprehensive multi-omics methodology was employed to examine a distinctive collection of patient dataset containing rapid autopsy tumor and normal tissue samples as well as longitudinal imaging with a focus on pancreatic cancer. By performing a whole exome sequencing analysis on tumor and normal tissues to identify somatic gene variants and a radiomic feature analysis to tumor CT images, the genome-wide association approach established a connection between pancreatic cancer driver genes and relevant radiomic features, enabling a thorough and quantitative assessment of the heterogeneity of pancreatic tumors. The significant association between sets of genes and radiomic features revealed the involvement of genes in shaping tumor morphological heterogeneity. Some results of the association established a connection between the molecular level mechanism and their outcomes at the level of tumor structural heterogeneity. Because tumor structure and tumor structural heterogeneity are related to the patients' overall survival, patients who had pancreatic cancer driver gene mutations with an association to a certain radiomic feature have been observed to experience worse survival rates than cases without these somatic mutations. Furthermore, the association analysis has revealed potential gene mutations and radiomic feature candidates that warrant further investigation in future research endeavors.
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Sequenciamento do Exoma , Mutação , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Fenótipo , Estudo de Associação Genômica Ampla , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodosRESUMO
The role of circular RNAs (circRNAs) in glucose metabolism in pancreatic duct adenocarcinoma (PDAC) remains elusive. Through RNA sequencing of cells cultured under conditions of glucose deprivation, we identified hsa_circ_0007590. Sanger sequencing and RNase R and Act D treatments were performed to confirm the circular RNA features of hsa_circ_0007590. RNA in situ hybridization (RNA-ISH) and quantitative reverse transcription PCR (qRT-PCR) were used to estimate hsa_circ_0007590 expression in PDAC clinical specimens and cell lines. hsa_circ_0007590 expression was higher in PDAC patients and closely related to the clinicopathological characteristics of the disease. Cytoplasmânuclear fractionation and FISH assays demonstrated that hsa_circ_0007590 was located in the nucleus. Gain-of-function and loss-of-function assays were performed to assess the biological behaviors of PDAC cells. Seahorse XF assays were performed to validate the Warburg effect. hsa_circ_0007590 facilitated the proliferation, migration, and invasion of PDAC cells and promoted the Warburg effect. Mass spectrometry, RNA pulldown, RNA immunoprecipitation (RIP), RNA m6A quantification, m6A dot blot, MeRIP, and Western blotting were conducted to investigate the detailed mechanism through which hsa_circ_0007590 produces these effects. Mechanistically, hsa_circ_0007590 targeted PTBP1 and increased the expression of the m6A reader protein YTHDF2, leading to PTEN mRNA degradation and PI3K/AKT/mTOR pathway activation. Overall, hsa_circ_0007590, which targets PTBP1, reprograms glucose metabolism by attenuating the stability of m6A-modified PTEN mRNA and holds potential promise as a therapeutic target for PDAC.
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Carcinoma Ductal Pancreático , Glucose , Ribonucleoproteínas Nucleares Heterogêneas , PTEN Fosfo-Hidrolase , Neoplasias Pancreáticas , Proteína de Ligação a Regiões Ricas em Polipirimidinas , RNA Circular , Humanos , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Glucose/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Camundongos , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Animais , Feminino , Linhagem Celular Tumoral , Estabilidade de RNA , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Empathy is a critical component of nursing care, impacting both nurses' and patients' outcomes. However, perceived empathy from spouses during pregnancy and its impact on health-related quality of life (HRQoL) are unclear. This study aimed to examine pregnant women's perceived empathy from their spouses and assess the relation of perceived empathy on HRQoL. METHODS: This cross-sectional study, performed in the obstetric clinics or wards of four well-known hospitals in Anhui Province, China, included 349 pregnant women in the second or third trimester; participants were recruited by convenience sampling and enrolled from October to December 2021. A general information questionnaire, the Interpersonal Reactivity Index (IRI), a purpose-designed empathy questionnaire and the Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) were used to evaluate the pregnant women's general information, perceptions of empathy and HRQoL. Data were analysed using SPSS 22 at a threshold of P < 0.05. Descriptive analysis, Pearson correlation analysis, Student's t test, ANOVA, and multiple regression analysis were used for analysis. RESULTS: The pregnant women's total empathy, physical component summary (PCS) and mental component summary (MCS) scores were 41.6 ± 9.0, 41.6 ± 7.6, and 47.7 ± 9.1, respectively. Correlation analysis revealed that the purpose-designed empathy questionnaire items were significantly positively correlated with perspective taking and empathic concern but were not correlated with the personal distress dimension and were only partially correlated with the fantasy dimension. Maternal physical condition during pregnancy, planned pregnancy, and occupational stress were predictors of the PCS score (ß = 0.281, P < 0.01; ß = 0.132, P = 0.02; ß = -0.128, P = 0.02). The behavioural empathy item of our purpose-designed empathy questionnaire and empathic concern were important predictors of the MCS score (ß = 0.127, P = 0.02; ß = 0.158, P < 0.01), as well as other demographic and obstetric information, explaining 22.0% of the variance in MCS scores totally (F = 12.228, P < 0.01). CONCLUSIONS: Pregnant women perceived lower empathy from their spouses and reported lower HRQoL. Perceived empathy, particularly behavioural empathy, may significantly impact pregnant women's MCS scores but has no effect on their PCS scores. Strategies that foster perceived empathy from spouses among pregnant women are essential for facilitating healthy pregnancies and potentially improving maternal and child health.
Assuntos
Empatia , Cônjuges , Gravidez , Criança , Humanos , Feminino , Estudos Transversais , Gestantes , Qualidade de Vida , ChinaRESUMO
Purpose: To investigate the relationship between normal brain exposure in LINAC-based single-isocenter multitarget multifraction stereotactic radiosurgery or stereotactic radiation therapy (SRT) and the number or volume of treated brain metastases, especially for high numbers of metastases. Methods and Materials: A cohort of 44 SRT patients with 709 brain metastases was studied. Renormalizing to a uniform prescription of 27 Gy in 3 fractions, normal brain dose volume indices, including V23 Gy (volume receiving >23 Gy), V18 Gy (volume receiving >18 Gy), and mean dose, were evaluated on these plans against the number and the total volume of targets for each plan. To compare with exposures from whole-brain radiation therapy (WBRT), the SRT dose distributions were converted to equivalent dose in 3 Gy fractions (EQD3) using an alpha-beta ratio of 2 Gy. Results: With increasing number of targets and increasing total target volume, normal brain exposures to dose ≥18 Gy increases, and so does the mean normal brain dose. The factors of the number of targets and the total target volume are both significant, although the number of targets has a larger effect on the mean normal brain dose and the total target volume has a larger effect on V23 Gy and V18 Gy. The EQD3 mean normal brain dose with SRT planning is lower than conventional WBRT. On the other hand, SRT results in higher hot spot (ie, maximum dose outside of tumor) EQD3 dose than WBRT. Conclusions: Based on clinical SRT plans, our study provides information on correlations between normal brain exposure and the number and total volume of targets. As SRT becomes more greatly used for patients with increasingly extensive brain metastases, more clinical data on outcomes and toxicities is necessary to better define the normal brain dose constraints for high-exposure cases and to optimize the SRT management for those patients.
RESUMO
The programmed death-ligand 1 (PD-L1) is a key mediator of immunosuppression in the tumor microenvironment. The expression of PD-L1 in cancer cells is useful for the clinical determination of an immune checkpoint blockade (ICB). However, the regulatory mechanism of the PD-L1 abundance remains incompletely understood. Here, we integrated the proteomics of 52 patients with solid tumors and examined immune cell infiltration to reveal PD-L1-related regulatory modules. Wiskott-Aldrich syndrome protein (WASP) was identified as a potential regulator of PD-L1 transcription. In two independent cohorts containing 164 cancer patients, WASP expression was significantly associated with PD-L1. High WASP expression contributed to immunosuppressive cell composition, including cells positive for immune checkpoints (PD1, CTLA4, TIGIT, and TIM3), FoxP3+ Treg cells, and CD163+ tumor-associated macrophages. Overexpression of WASP increased, whereas knockdown of WASP decreased the protein level of PD-L1 in cancer cells without alteration of PD-L1 protein stability. The WASP-mediated cell migration and invasion were markedly attenuated by the silence of PD-L1. Collectively, our data suggest that WASP is a potential regulator of PD-L1 and the WASP/PD-L1 axis is responsible for cell migration and an immunosuppressive microenvironment.