Genetic variants and down-regulation of CACNA1H in pheochromocytoma.

Pheochromocytoma (PCC) and abdominal paraganglioma (aPGL) (together abbreviated PPGL) frequently present with an underlying genetic event in a PPGL driver gene, and additional susceptibility genes are anticipated. Here we re-analysed whole-exome sequencing data for PCC patients and identified two patients with rare missense variants in the calcium voltage-gated channel subunit 1H gene (CACNA1H). CACNA1H variants were also found in the clinical setting in PCC patients using targeted sequencing and from analysis of The Cancer Genome Atlas database. In total, CACNA1H variants were found in six PCC cases. Three of these were constitutional and two are known to have functional consequences on hormone production and gene expression in primary aldosteronism and aldosterone-producing adrenocortical adenoma. In general, PPGL exhibited reduced CACNA1H mRNA expression as compared to normal adrenal. Immunohistochemistry showed strong CACNA1H (CaV3.2) staining in adrenal medulla while PPGL typically had weak or negative staining. Reduced CACNA1H gene expression was especially pronounced in PCC as compared to aPGL and in PPGL with Cluster 2 kinase signalling phenotype. Furthermore, CACNA1H levels correlated with HIF1A and HIF2A. Moreover, TCGA data revealed a correlation between CACNA1H methylation density and gene expression. Expression of rCacna1h in PC12 cells induced differential protein expression profiles determined by mass spectrometry as well as a shift in the membrane potential where maximum calcium currents were observed as determined by electrophysiology. The findings suggest the involvement of CACNA1H/CaV3.2 in pheochromocytoma development and establish a potential link between the aetiology of adrenomedullary and adrenocortical tumor development.

Raspberry-shaped ZIF-8/Au nanozymes with excellent peroxidase-like activity for simple and visual detection of glutathione.

Artificial enzymes with high stability, adjustable catalytic activity, controllable preparation, and good reproducibility have been widely studied. Noble metal nanozymes, particularly gold nanoparticles (Au NPs), exhibit good catalytic activity, but their stability is poor. In this study, zeolitic imidazolate framework-8 (ZIF-8) was used as a carrier for Au NPs, thus improving the utilization efficiency and conservation stability of the nanozymes. A ZIF-8/Au nanocomposite with peroxidase activity and a raspberry-shaped structure was synthesized. In the assay, ZIF-8/Au catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to a blue product oxidized TMB (oxTMB). Glutathione (GSH) selectively inhibited this reaction, with a detection limit of 0.28 µM and linear range of 0.5-60 µM. Using the photo and chromaticity analysis functions, we developed a portable analysis method using a smartphone equipped with a camera module as a detection terminal for a wide range of rapid screening techniques for GSH. Preparation of raspberry-shaped ZIF-8/Au improved the catalytic activity of Au NPs and good results were demonstrated in serum, which suggests their promising application under physiological conditions.

A novel score for predicting falls in community-dwelling older people: a derivation and validation study.

BACKGROUND: Early detection of patients at risk of falling is crucial. This study was designed to develop and internally validate a novel risk score to classify patients at risk of falls. METHODS: A total of 334 older people from a fall clinic in a medical center were selected. Least absolute shrinkage and selection operator (LASSO) regression was used to minimize the potential concatenation of variables measured from the same patient and the overfitting of variables. A logistic regression model for 1-year fall prediction was developed for the entire dataset using newly identified relevant variables. Model performance was evaluated using the bootstrap method, which included measures of overall predictive performance, discrimination, and calibration. To streamline the assessment process, a scoring system for predicting 1-year fall risk was created. RESULTS: We developed a new model for predicting 1-year falls, which included the FRQ-Q1, FRQ-Q3, and single-leg standing time (left foot). After internal validation, the model showed good discrimination (C statistic, 0.803 [95% CI 0.749-0.857]) and overall accuracy (Brier score, 0.146). Compared to another model that used the total FRQ score instead, the new model showed better continuous net reclassification improvement (NRI) [0.468 (0.314-0.622), P < 0.01], categorical NRI [0.507 (0.291-0.724), P < 0.01; cutoff: 0.200-0.800], and integrated discrimination [0.205 (0.147-0.262), P < 0.01]. The variables in the new model were subsequently incorporated into a risk score. The discriminatory ability of the scoring system was similar (C statistic, 0.809; 95% CI, 0.756-0.861; optimism-corrected C statistic, 0.808) to that of the logistic regression model at internal bootstrap validation. CONCLUSIONS: This study resulted in the development and internal verification of a scoring system to classify 334 patients at risk for falls. The newly developed score demonstrated greater accuracy in predicting falls in elderly people than did the Timed Up and Go test and the 30-Second Chair Sit-Stand test. Additionally, the scale demonstrated superior clinical validity for identifying fall risk.

A double-emission molecularly imprinted ratiometric fluorescent sensor based on carbon quantum dots and fluorescein isothiocyanate for visual detection of p-nitroaniline.

A novel molecularly imprinted ratiometric fluorescent sensor CQDs@MIP/FITC@SiO2 for the detection of p-nitroaniline (p-NA) was constructed through the mixture of CQDs@MIP and FITC@SiO2 in the ratio of 1:1 (VCQDs@MIP:VFITC@SiO2). The polymers of CQDs@MIP and FITC@SiO2 were prepared by sol-gel method and reversed-phase microemulsion method, respectively. CQDs@MIP was used as the auxiliary response signal and FITC@SiO2 was used as the reference enhancement signal. The signal was measured at excitation/emission wavelengths of 365/438, 512 nm. The sensor showed good linearity in the concentration range 0.14-40.00 µM (R2 = 0.998) with a detection limit of 0.042 µM for p-NA. The color change of "blue-cyan-green" could be observed by the naked eye under 365 nm UV light, thus realizing the visual detection of p-NA. The sensor presented comparable results compared with high-performance liquid chromatography (HPLC) method for the detection of p-NA in hair dye paste and aqueous samples with recoveries of 96.8-103.7% and 95.8-104.4%, respectively. It was demonstrated that the constructed sensor possesses the advantages of simplicity, excellent selectivity, superior sensitivity, and outstanding stability.

Characteristics and risk assessment of potentially toxic elements pollution in river water and sediment in typical gold mining areas of Northwest China.

To assess the concentration characteristics and ecological risks of potential toxic elements (PTEs) in water and sediment, 17 water samples and 17 sediment samples were collected in the Xiyu River to analyze the content of Cr, Ni, As, Cu, Zn, Pb, Cd and Hg, and the environmental risks of PTEs was evaluated by single-factor pollution index, Nemerow comprehensive pollution index, potential ecological risk, and human health risk assessment. The results indicated that Hg in water and Pb, Cu, Cd in sediments exceeded the corresponding environmental quality standards. In the gold mining factories distribution river section (X8-X10), there was a significant increase in PTEs in water and sediments, indicating that the arbitrary discharge of tailings during gold mining flotation is the main cause of PTEs pollution. The increase in PTEs concentration at the end of the Xiyu River may be related to the increased sedimentation rate, caused by the slowing of the riverbed, and the active chemical reactions at the estuary. The single-factor pollution index and Nemerow pollution index indicated that the river water was severely polluted by Hg. Potential ecological risk index indicated that the risk of Hg in sediments was extremely high, the risk of Cd was high, and the risk of Pb and Cu was moderate. The human health risk assessment indicated that As in water at point X10 and Hg in water at point X9 may pose non-carcinogenic risk to children through ingestion, and As at X8-X10 and Cd at X14 may pose carcinogenic risk to adults through ingestion. The average HQingestion value of Pb in sediments was 1.96, indicating that the ingestion of the sediments may poses a non-carcinogenic risk to children, As in the sediments at X8-X10 and X15-X17 may pose non-carcinogenic risk to children through ingestion.

Microglial apolipoprotein E particles contribute to neuronal senescence and synaptotoxicity.

Apolipoprotein E (apoE) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Microglia exhibit a substantial upregulation of apoE in AD-associated circumstances, despite astrocytes being the primary source of apoE expression and secretion in the brain. Although the role of astrocytic apoE in the brain has been extensively investigated, it remains unclear that whether and how apoE particles generated from astrocytes and microglia differ in biological characteristic and function. Here, we demonstrate the differences in size between apoE particles generated from microglia and astrocytes. Microglial apoE particles impair neurite growth and synapses, and promote neuronal senescence, whereas depletion of GPNMB (glycoprotein non-metastatic melanoma protein B) in microglial apoE particles mitigated these deleterious effects. In addition, human APOE4-expressing microglia are more neurotoxic than APOE3-bearing microglia. For the first time, these results offer concrete evidence that apoE particles produced by microglia are involved in neuronal senescence and toxicity.

A meta-analysis of the association between inflammatory cytokine polymorphism and neonatal sepsis.

OBJECTIVE: The purpose of this study is to investigate the relationship between single nucleotide polymorphisms of inflammatory cytokines and neonatal sepsis through meta-analysis. METHODS: We collected research literature on the correlation between inflammatory cytokine polymorphisms and neonatal sepsis published before August 2023 through computer searches of databases such as PubMed, Embase, etc. The Stata 14.0 software was utilized for Meta-analysis. To assess heterogeneity, the chi-squared Q-test and I2 statistics were used. The Egger and Begg tests were conducted to determine the possibility of publication bias. RESULTS: After reviewing 1129 articles, 29 relevant articles involving 3348 cases and 5183 controls were included in the study. The meta-analysis conducted on IL-1ßrs1143643 polymorphism revealed significant findings: the T allele genotype has a lower risk of neonatal sepsis(P = 0.000, OR = 0.224, 95% CI: 0.168-0.299), while the TC and TT genotypes showed an increased risk(TC: P = 0.000,OR = 4.251, 95% CI: 2.226-8.119; TT: P = 0.019,OR = 2.020, 95% CI: 1.122-3.639). Similarly, newborns with the IL-6-174 CC genotype had a significantly higher risk of sepsis(P = 0.000,OR = 1.591, 95% CI: 1.154-2.194), while those with the IL-8-rs4073 TT (P = 0.003,OR = 0.467, 95% CI: 0.280-0.777)and TT + AA(P = 0.003,OR = 0.497, 95% CI: 0.315-0.785) genotypes had a significantly lower risk of sepsis. For the IL-10-1082 gene, newborns with the AA genotype(P = 0.002,OR = 1.702, 95% CI: 1.218-2.377), as well as those with the AA + GA genotype(P = 0.016,OR = 1.731, 95% CI: 1.108-2.705), had a significantly higher risk of sepsis. Lastly, newborns carrying the TNF-α-308 A allele (P = 0.016,OR = 1.257, 95% CI: 1.044-1.513)or the AA genotype(P = 0.009,OR = 1.913, 95% CI: 1.179-3.10) have a significantly increased risk of sepsis. Notwithstanding, additional studies must be included for validation. Applying these cytokines in clinical practice and integrating them into auxiliary examinations facilitates the early detection of susceptible populations for neonatal sepsis, thereby providing a new diagnostic and therapeutic approach for neonatal sepsis.

Application of Liposuction and Superior Pedicle Vertical Mammoplasty for Severe Breast Hypertrophy.

BACKGROUND: Vertical mammoplasty techniques have been widely used for breast reduction. The authors present the combination of superior pedicle vertical mammoplasty with liposuction in different regions in the treatment of severe breast hypertrophy in obese patients. We also propose some innovative methods in terms of surgical approach, breast parenchymal anatomy pattern and liposuction. METHODS: A retrospective study of 50 female patients with severe hypertrophic breasts and obesity who underwent breast reduction in our department from February 2019 to February 2022 was performed. Pre- and postoperative photographs, breast parenchyma distribution and postoperative patient satisfaction were recorded. RESULTS: Fifty patients underwent breast reduction. Through clinical examination, patient photo evaluation and satisfaction survey results. Good breast shape and projection, full upper pole of the breast, and high satisfaction results were obtained. There were no serious complications. CONCLUSION: This technique is acceptable and reproducible. It is suitable for patients with varying degrees of breast hypertrophy, especially those with severe hypertrophic breasts and obesity. There are fewer associated complications and a lower rate of re-repair. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Decoding transcriptomic signatures of cysteine string protein alpha-mediated synapse maintenance.

Synapse maintenance is essential for generating functional circuitry, and decrement in this process is a hallmark of neurodegenerative disease. Yet, little is known about synapse maintenance in vivo. Cysteine string protein α (CSPα), encoded by the Dnajc5 gene, is a synaptic vesicle chaperone that is necessary for synapse maintenance and linked to neurodegeneration. To investigate the transcriptional changes associated with synapse maintenance, we performed single-nucleus transcriptomics on the cortex of young CSPα knockout (KO) mice and littermate controls. Through differential expression and gene ontology analysis, we observed that both neurons and glial cells exhibit unique signatures in the CSPα KO brain. Significantly, all neuronal classes in CSPα KO brains show strong signatures of repression in synaptic pathways, while up-regulating autophagy-related genes. Through visualization of synapses and autophagosomes by electron microscopy, we confirmed these alterations especially in inhibitory synapses. Glial responses varied by cell type, with microglia exhibiting activation. By imputing cell-cell interactions, we found that neuron-glia interactions were specifically increased in CSPα KO mice. This was mediated by synaptogenic adhesion molecules, with the classical Neurexin1-Neuroligin 1 pair being the most prominent, suggesting that communication of glial cells with neurons is strengthened in CSPα KO mice to preserve synapse maintenance. Together, this study provides a rich dataset of transcriptional changes in the CSPα KO cortex and reveals insights into synapse maintenance and neurodegeneration.

Immune responses and reinfection of SARS-CoV-2 Omicron variant in patients with lung cancer.

A significant Omicron wave emerged in China in December 2022. To explore the duration of humoral and cellular response postinfection and the efficacy of hybrid immunity in preventing Omicron reinfection in patients with lung cancer, a total of 447 patients were included in the longitudinal study after the Omicron wave from March 2023 to August 2023. Humoral responses were measured at pre-Omicron wave, 3 months and 7 months postinfection. The detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies including total antibodies, anti-receptor binding domain (RBD) specific IgG, and neutralizing antibodies against SARS-CoV-2 wild type (WT) and BA.4/5 variant. T cell responses against SARS-CoV-2 WT and Omicron variant were evaluated in 101 patients by ELISpot at 3 months postinfection. The results showed that Omicron-infected symptoms were mild, while fatigue (30.2%), shortness of breath (34.0%) and persistent cough (23.6%) were long-lasting, and vaccines showed efficacy against fever in lung cancer patients. Humoral responses were higher in full or booster vaccinated patients than those unvaccinated (p < .05 for all four antibodies), and the enhanced response persisted for at least 7 months. T cell response to Omicron was higher than WT peptides (21.3 vs. 16.0 SFUs/106 PBMCs, p = .0093). Moreover, 38 (9.74%) patients were reinfected, which had lower antibody responses than non-reinfected patients (all p < .05), and those patients of unvaccinated at late stage receiving anti-cancer immunotherapy alone were at high risk of reinfection. Collectively, these data demonstrate the Omicron infection induces a high and durable immune response in vaccinated patients with lung cancer, which protects vaccinated patients from reinfection.

An automated hybrid approach via deep learning and radiomics focused on the midbrain and substantia nigra to detect early-stage Parkinson's disease.

Objectives: The altered neuromelanin in substantia nigra pars compacta (SNpc) is a valuable biomarker in the detection of early-stage Parkinson's disease (EPD). Diagnosis via visual inspection or single radiomics based method is challenging. Thus, we proposed a novel hybrid model that integrates radiomics and deep learning methodologies to automatically detect EPD based on neuromelanin-sensitive MRI, namely short-echo-time Magnitude (setMag) reconstructed from quantitative susceptibility mapping (QSM). Methods: In our study, we collected QSM images including 73 EPD patients and 65 healthy controls, which were stratified into training-validation and independent test sets with an 8:2 ratio. Twenty-four participants from another center were included as the external validation set. Our framework began with the detection of the brainstem utilizing YOLO-v5. Subsequently, a modified LeNet was applied to obtain deep learning features. Meanwhile, 1781 radiomics features were extracted, and 10 features were retained after filtering. Finally, the classified models based on radiomics features, deep learning features, and the hybrid of both were established through machine learning algorithms, respectively. The performance was mainly evaluated using accuracy, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The saliency map was used to visualize the model. Results: The hybrid feature-based support vector machine (SVM) model showed the best performance, achieving ACC of 96.3 and 95.8% in the independent test set and external validation set, respectively. The model established by hybrid features outperformed the one radiomics feature-based (NRI: 0.245, IDI: 0.112). Furthermore, the saliency map showed that the bilateral "swallow tail" sign region was significant for classification. Conclusion: The integration of deep learning and radiomic features presents a potent strategy for the computer-aided diagnosis of EPD. This study not only validates the accuracy of our proposed model but also underscores its interpretability, evidenced by differential significance across various anatomical sites.

Benefit finding among family caregivers of patients with advanced cancer in a palliative treatment: a qualitative study.

BACKGROUND: Benefit finding is the search for positive meaning from traumatic events, such as cancer. It can help caregivers have a positive experience in the caregiving process, relieve negative emotions, and reduce caregiving stress. The aim of this study was to explore benefit finding among caregivers of patients with advanced cancer in their palliative caregiving journey. METHODS: An exploratory qualitative design of phenomenology was used. Semistructured interviews were conducted with 19 caregivers of palliative care patients with advanced cancer. The Colaizzi 7-step analysis was used to analyse, summarize, and extract themes from the interview data. RESULTS: The study identified five themes of caregiver benefit finding in the caregiving process: personal growth, strengthened relationships with patients, adjustment and adaptation, perceived social support, and perceived meaning in life. Most caregivers reported a closer, more dependent relationship with the patient, and only one caregiver did not report any positive changes. CONCLUSIONS: Caregivers of palliative care patients with advanced cancer can have positive experiences in their care. Healthcare professionals should focus on supporting caregivers and helping them find positive experiences to cope with the challenges of caregiving and improve their quality of life.

Exposure of pregnant women to neonicotinoids in Wenzhou City, East China: A biomonitoring study.

BACKGROUND: China produces and consumes a large amount of neonicotinoids. A non-negligible exposure to neonicotinoids might occur for Chinese pregnant women, but relevant data remain limited. OBJECTIVE: To investigate the exposure to neonicotinoids by urinary biomonitoring in pregnant women from Wenzhou City, East China. METHODS: We selected 432 pregnant women in Wenzhou City in 2022. A total of eight parent neonicotinoids and four metabolites were determined in single spot urine by liquid chromatography coupled to mass spectrometry. Basic characteristics, physical activity, pre-pregnant body mass index, and intake of drinking water and food were investigated by the questionnaire. Health risk was assessed by hazard quotient (HQ) and hazard index (HI) based on human safety thresholds derived from different health endpoints. RESULTS: Neonicotinoids and their metabolites in urine had a detection frequency between 0 % and 80.1 %. At least one neonicotinoid or metabolite was detected in 93.5 % of urine samples. Except for clothianidin (51.2 %) and N-desmethyl-acetamiprid (80.1 %), the detection frequencies of other neonicotinoids and metabolites ranged from 0 % to 43.8 %. The summed concentrations of all neonicotinoids and their metabolites ranged from < LOD to 222.83 µg/g creatinine with the median concentration of 2.58 µg/g creatinine. Maternal age, educational level, occupation, household income, screen time, and pre-pregnant body mass index were associated with detection frequencies or concentrations of neonicotinoids and their metabolites. Pregnant women with higher consumption frequencies of wheat, fresh vegetable, shellfish, fresh milk, and powdered milk had higher detection frequencies of neonicotinoids and their metabolites. Both HQ and HI were less than one. CONCLUSIONS: Overall, pregnant women in Wenzhou City showed a notable frequency of exposure to at least one neonicotinoid, although the exposure frequency for each specific neonicotinoid was generally low. Several food items derived from plants and animals were potential exposure sources. A low health risk was found based on current safety thresholds.

A enzyme-free fluorescence quenching sensor for amplified detection of kanamycin in milk based on competitive triggering strategies.

In this work, we constructed a FAM fluorescence quenching biosensor based on an aptamer competition recognition and enzyme-free amplification strategy. We design a competing unit consisting of an aptamer chain and a complementary chain, and a catalytic hairpin self-assembly (CHA) unit consisting of two hairpins in which the complementary chain can trigger the catalytic hairpin self-assembly. In the initial state, the aptamer chain is combined with the complementary chain, the catalytic hairpin self-assembly unit is inhibited, the FAM fluorescence group was far away from the BHQ1 quenching group, and the fluorescence is turn-on. In the presence of kanamycin, the aptamer chain recognizes kanamycin and doesn't form double chains, resulting in the free complementary chain triggering hairpin 1 (H1), and then H1 triggering hairpin 2 (H2), FAM fluorophore is close to the BHQ1 quenching group, and the fluorescence is off-on. When H1 and H2 form a cyclic reaction, enzyme-free amplification is achieved and there is significant output of the fluorescence signal. Therefore, the biosensor has good performance in detecting kanamycin, the detection line is 54 nM, the linear range is 54 nM-0.9 µM, and it can achieve highly selective detection of kanamycin. Kanamycin residue may cause serious harm to human health. The high sensitivity detection of kanamycin is urgent, so this project has a great application potential for food detection.

USFM: A universal ultrasound foundation model generalized to tasks and organs towards label efficient image analysis.

Inadequate generality across different organs and tasks constrains the application of ultrasound (US) image analysis methods in smart healthcare. Building a universal US foundation model holds the potential to address these issues. Nevertheless, the development of such foundation models encounters intrinsic challenges in US analysis, i.e., insufficient databases, low quality, and ineffective features. In this paper, we present a universal US foundation model, named USFM, generalized to diverse tasks and organs towards label efficient US image analysis. First, a large-scale Multi-organ, Multi-center, and Multi-device US database was built, comprehensively containing over two million US images. Organ-balanced sampling was employed for unbiased learning. Then, USFM is self-supervised pre-trained on the sufficient US database. To extract the effective features from low-quality US images, we proposed a spatial-frequency dual masked image modeling method. A productive spatial noise addition-recovery approach was designed to learn meaningful US information robustly, while a novel frequency band-stop masking learning approach was also employed to extract complex, implicit grayscale distribution and textural variations. Extensive experiments were conducted on the various tasks of segmentation, classification, and image enhancement from diverse organs and diseases. Comparisons with representative US image analysis models illustrate the universality and effectiveness of USFM. The label efficiency experiments suggest the USFM obtains robust performance with only 20% annotation, laying the groundwork for the rapid development of US models in clinical practices.

AMPK-a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment?

Immunotherapy has now garnered significant attention as an essential component in cancer therapy during this new era. However, due to immune tolerance, immunosuppressive environment, tumor heterogeneity, immune escape, and other factors, the efficacy of tumor immunotherapy has been limited with its application to very small population size. Energy metabolism not only affects tumor progression but also plays a crucial role in immune escape. Tumor cells are more metabolically active and need more energy and nutrients to maintain their growth, which causes the surrounding immune cells to lack glucose, oxygen, and other nutrients, with the result of decreased immune cell activity and increased immunosuppressive cells. On the other hand, immune cells need to utilize multiple metabolic pathways, for instance, cellular respiration, and oxidative phosphorylation pathways to maintain their activity and normal function. Studies have shown that there is a significant difference in the energy expenditure of immune cells in the resting and activated states. Notably, competitive uptake of glucose is the main cause of impaired T cell function. Conversely, glutamine competition often affects the activation of most immune cells and the transformation of CD4+T cells into inflammatory subtypes. Excessive metabolite lactate often impairs the function of NK cells. Furthermore, the metabolite PGE2 also often inhibits the immune response by inhibiting Th1 differentiation, B cell function, and T cell activation. Additionally, the transformation of tumor-suppressive M1 macrophages into cancer-promoting M2 macrophages is influenced by energy metabolism. Therefore, energy metabolism is a vital factor and component involved in the reconstruction of the tumor immune microenvironment. Noteworthy and vital is that not only does the metabolic program of tumor cells affect the antigen presentation and recognition of immune cells, but also the metabolic program of immune cells affects their own functions, ultimately leading to changes in tumor immune function. Metabolic intervention can not only improve the response of immune cells to tumors, but also increase the immunogenicity of tumors, thereby expanding the population who benefit from immunotherapy. Consequently, identifying metabolic crosstalk molecules that link tumor energy metabolism and immune microenvironment would be a promising anti-tumor immune strategy. AMPK (AMP-activated protein kinase) is a ubiquitous serine/threonine kinase in eukaryotes, serving as the central regulator of metabolic pathways. The sequential activation of AMPK and its associated signaling cascades profoundly impacts the dynamic alterations in tumor cell bioenergetics. By modulating energy metabolism and inflammatory responses, AMPK exerts significant influence on tumor cell development, while also playing a pivotal role in tumor immunotherapy by regulating immune cell activity and function. Furthermore, AMPK-mediated inflammatory response facilitates the recruitment of immune cells to the tumor microenvironment (TIME), thereby impeding tumorigenesis, progression, and metastasis. AMPK, as the link between cell energy homeostasis, tumor bioenergetics, and anti-tumor immunity, will have a significant impact on the treatment and management of oncology patients. That being summarized, the main objective of this review is to pinpoint the efficacy of tumor immunotherapy by regulating the energy metabolism of the tumor immune microenvironment and to provide guidance for the development of new immunotherapy strategies.

Exploiting Waste towards More Sustainable Flame-Retardant Solutions for Polymers: A Review.

The development of sustainable flame retardants is gaining momentum due to their enhanced safety attributes and environmental compatibility. One effective strategy is to use waste materials as a primary source of chemical components, which can help mitigate environmental issues associated with traditional flame retardants. This paper reviews recent research in flame retardancy for waste flame retardants, categorizing them based on waste types like industrial, food, and plant waste. The paper focuses on recent advancements in this area, focusing on their impact on the thermal stability, flame retardancy, smoke suppression, and mechanical properties of polymeric materials. The study also provides a summary of functionalization methodologies used and key factors involved in modifying polymer systems. Finally, their major challenges and prospects for the future are identified.

Temperature dependence mechanism of high-temperature oxidation of transition metal silicide MoSi2.

Transition metal silicides represented by MoSi2have excellent oxidation resistance and are widely used as high-temperature anti-oxidation coatings in hot end components of power equipment. However, the mechanism of temperature-dependent growth of MoSi2oxidation products has not been revealed. Therefore, this study investigated the formation characteristics of oxide film and silicide-poor compound on MoSi2at temperatures of 1000 °C-1550 °C through high-temperature oxidation experiments, combined with microscopic Raman spectroscopy, scanning electron microscope, and x-ray diffraction (XRD) characterizations. The result showed that MoSi2underwent high-temperature selective oxidation reactions at 1000 °C-1200 °C, forming MoO2and SiO2oxide film on the substrate. As the oxidation temperature increased to 1550 °C, after 100 h of oxidation, along with the disappearance of MoO2and the phase transformation of SiO2, a continuous Mo5Si3layer with a thickness of approximately 47µm was formed at the SiO2-MoSi2interface. Thermodynamics and kinetic calculations further revealed the mechanism of temperature-dependent growth of oxidation products (MoO2and Mo5Si3) during high-temperature oxidation process of MoSi2. As the temperature increased, the diffusion flux ratio of O and Si decreased, leading to a decrease in oxygen concentration at the interface and promoting the growth of the Mo5Si3layer. Its thickness is an important indicator for evaluating the oxidation resistance of MoSi2coatings during service. This study provides experimental and mechanistic insights into the temperature-dependent growth behavior of Mo5Si3during the high-temperature oxidation of MoSi2coating, and provides guidance for predicting the service life and improving the oxidation resistance of silicide coatings.

Association of maternal mineral status with the risk of preterm birth: a retrospective cohort study.

Background: There has been a gradual increase in the proportion of preterm birth in China during the past several decades. Maternal malnutrition is a significant determinant for preterm birth. Nevertheless, comprehensive studies investigating serum mineral levels during pregnancy associated with preterm birth remain scarce. This study aims to assess the associations between maternal serum mineral levels and the risk of preterm birth. Methods: This retrospective cohort study of 18,048 pregnant women used data from a tertiary hospital in China from January 2016 to December 2022. Demographic data and serum mineral concentrations in the second and third trimesters of mothers were collected from the hospital information system. Analysis was performed using restricted cubic splines and logistic regression models. Results: The proportion of preterm birth in this study was 6.01%. Phosphorus [P for overall = 0.005; P for nonlinear = 0.490; OR (95%CI) = 1.11 (1.04, 1.18)] and chlorine [P for overall = 0.002; P for nonlinear = 0.058; OR (95%CI) = 1.11 (1.03, 1.19)] showed a significant positive correlation with preterm birth in a linear fashion. Furthermore, serum levels of potassium (P for nonlinear <0.001), sodium (P for nonlinear = 0.004), and magnesium (P for nonlinear <0.001) exhibited non-linear relationships with the risk of preterm birth. Conclusion: Serum levels of some minerals during pregnancy were associated with the risk of preterm birth among pregnant women. In addition to commonly recognized micronutrients such as folic acid, iron, and vitamin D, healthcare providers should also pay attention to the levels of these minerals during pregnancy.