Tumor-derived IL-6 promotes chordoma invasion by stimulating tumor-associated macrophages M2 polarization and TNFα secretion.

AIMS: Chordoma is a rare and aggressive bone tumor with high-recurrence and lack of effective treatment methods. Tumor associated macrophages (TAMs) are abundant in tumor microenvironment (TME) and polarize toward M2 in chordoma. It has been observed that the high proportion of M2 cells is associated with chordoma rapid progression. However, the mechanism of TAMs polarization and promotion to tumor progression in chordoma is still unclear. The is an urgent need for further research. MATERIALS AND METHODS: Flow cytometry and immunohistochemical staining was used to detect the degree of macrophages infiltration in chordoma. A co-culture model of chordoma cells and macrophages was established in vitro to investigate the effects of their interaction on cell function, cytokine secretion, and RNA transcriptome expression. KEY FINDINGS: In this study, we found M2 macrophage was predominantly abundant immune cell population in chordoma, and its proportion was associated with the degree of bone destruction. We demonstrated that interleukin 6 (IL-6) derived from chordoma cells could induce TAMs polarization by activating STAT3 phosphorylation, and TAMs could enhance chordoma cells migration and invasion through TNFα/NF-κB pathway. The interaction of chordoma cells and TAMs could promote the bone destruction-related factor Cathepsin B (CTSB) and inhibitory immune checkpoints expression. We also confirmed blocking IL-6/STAT3 pathway could significantly attenuate the M2 polarization of TAMs and decrease the secretion of TNFα. SIGNIFICANCE: This study illustrates the dynamics between chordoma cells and TAMs in promoting chordoma invasion and suggests that IL-6/STAT3 pathway is a potential therapeutic target to reduce TAM-induced chordoma invasion.

Wrinkled Rhenium Disulfide for Anisotropic Nonvolatile Memory and Multiple Artificial Neuromorphic Synapses.

Two-dimensional materials are emerging as potential solutions for high-density nonvolatile memory and efficient neuromorphic computing. However, integrating multidimensional memory and an ideal linear weight updating synapse in a simple device configuration to achieve versatile biomimetic neuromorphic systems remains challenging. Here, we introduce a wrinkled rhenium disulfide (ReS2) transistor, where the wrinkled structure facilitates the carrier trapping/detrapping at the dielectric interface, thus enabling the fusion of nonvolatile memory and both electronic and optoelectronic synaptic functionalities. As a nonvolatile memory, anisotropic wrinkled ReS2 can yield three distinct sets of data across three crystal orientations under identical programming operations. Each set demonstrates exceptional retention and endurance properties. As a neuromorphic synapse, it realizes the linear and symmetric updates of conductance states up to 9 bits and 8 bits, the ultra-low-energy consumption of 75 fJ and 2.5 pJ under the electrical and optical stimuli, respectively. The artificial neural network (ANN) based on electronic synapses gives a superior recognition accuracy of 92.9% for the original handwritten digits. The anisotropic synaptic responses and multiwavelength sensitivities of optoelectronic synapses enable them to execute advanced memory and recognition functions for complex images that encompass a variety of pattern features or color information. This underscores its substantial potential for integration into efficient biomimetic visual systems.

Relationship between illness perception and self-management behaviors among women with gestational diabetes mellitus in China during the COVID-19 pandemic: A mediating role of depression.

OBJECTIVE: Describe the current status of illness perception, depression, and self-management behaviors among women with gestational diabetes mellitus (GDM) during the COVID-19 pandemic, and explore the role of depression in the relationship between illness perception and self-management behaviors among women with GDM. METHODS: Pregnant women diagnosed with GDM were recruited at the obstetrics clinic of a Grade-A tertiary hospital in Wuhan, through convenience sampling. Self-reported questionnaires including basic information, illness perception, depression, and self-management behaviors were used to collect data from April 2021 to February 2022. Mediation analysis was performed by SPSS Process macro. RESULTS: Among GDM pregnant women, the mean self-management behaviors score was 73.89 (SD = 12.21), the mean illness perception score was 31.80 (SD = 8.77), and 44.3% had depression scores of 10 or higher. The indirect effect of illness perception on self-management behaviors mediated by depression was significant (path a * b, ß = -0.045), accounting for 26.6% of the total effect. CONCLUSION: GDM pregnant women have a certain negative illness perception of GDM, and the detection rate of depression symptoms is relatively high. The level of self-management behaviors among GDM pregnant women is notably suboptimal and warrants improvement. Depression partially mediates the relationship between illness perception and self-management behaviors. Improving positive illness perception and decreasing depression are important strategies to improve self-management behaviors in women with GDM.

Textile Bandwidth-Enhanced Half-Mode Substrate-Integrated Cavity Antenna Based on Embroidered Shorting Vias.

A textile bandwidth-enhanced half-mode substrate-integrated cavity (HMSIC) antenna based on embroidered shorting vias is designed. Based on the simulated results of the basic HMSIC antenna, two embroidered hollow posts with square cross-sections are added as shorting vias at the intersections of the zero-E traces of the TM210HM and TM020HM modes to shift the TM010HM-mode band to merge with the bands of the higher-order modes for bandwidth enhancement. A prototype is practically fabricated based on computerized embroidery techniques. Measurement results show that the prototype is of an expanded -10 dB impedance band of 4.87~6.17 GHz (23.5% fractional bandwidth), which fully covers the 5 GHz wireless local area network (WLAN) band. The simulated radiation efficiency and maximum gain of the proposed antenna are above 97% and 7.6 dBi, respectively. Furthermore, simulations and measurements prove its robust frequency response characteristic in the proximity of the human tissues or in bending conditions, and the simulations of the specific absorption rate (SAR) prove its electromagnetic safety on the human body.

Unconjugated bilirubin promotes uric acid restoration by activating hepatic AMPK pathway.

Hyperuricemia and its development to gout have reached epidemic proportions. Systemic hyperuricemia is facilitated by elevated activity of xanthine oxidase (XO), the sole source of uric acid in mammals. Here, we aim to investigate the role of bilirubin in maintaining circulating uric acid homeostasis. We observed serum bilirubin concentrations were inversely correlated with uric acid levels in humans with new-onset hyperuricemia and advanced gout in a clinical cohort consisting of 891 participants. We confirmed that bilirubin biosynthesis impairment recapitulated traits of hyperuricemia symptoms, exemplified by raised circulating uric acid levels and accumulated hepatic XO, and exacerbated mouse hyperuricemia development. Bilirubin administration significantly decreased circulating uric acid levels in hyperuricemia-inducing (HUA) mice receiving potassium oxonate (a uricase inhibitor) or fed with a high fructose diet. Finally, we proved that bilirubin ameliorated mouse hyperuricemia by increasing hepatic autophagy, restoring antioxidant defense and normalizing mitochondrial function in a manner dependent on AMPK pathway. Hepatocyte-specific AMPKα knockdown via adeno-associated virus (AAV) 8-TBG-mediated gene delivery compromised the efficacy of bilirubin in HUA mice. Our study demonstrates the deficiency of bilirubin in hyperuricemia progression, and the protective effects exerted by bilirubin against mouse hyperuricemia development, which may potentiate clinical management of hyperuricemia.

Investigating vertical distributions and photochemical indications of formaldehyde, glyoxal, and NO2 from MAX-DOAS observations in four typical cities of China.

Formaldehyde (HCHO), glyoxal (CHOCHO), and nitrogen dioxide (NO2) are crucial in atmospheric photochemical processes at both surface and elevated altitudes. This study presents synchronous multi-axis differential optical absorption spectroscopy (MAX-DOAS) measurements of the vertical distributions of summertime HCHO, CHOCHO and NO2 in four representative megacities within the Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD), Sichuan Basin (SB), and Pearl River Delta (PRD) regions of China. The vertical distributions of HCHO and CHOCHO tended to occur at higher altitudes compared to NO2, influenced by both primary emissions near the ground and photochemical oxidation processes at elevated altitudes. Source separation regression analysis using the CO-CHOCHO trace pair identified secondary formation as the predominant source of ambient HCHO. In urban areas, the ratio of CHOCHO to secondary HCHO (RGFsec) serves as a more reliable metric at ground level for diagnosing VOC precursor sources, excluding the interference of primary and background HCHO. The increase in RGF values at higher altitudes highlights the relative contribution of VOCs favoring CHOCHO production. Moreover, four indicators (e.g. FNR, FNRsec, GNR, and MNR) were utilized to characterize O3 formation sensitivity at different altitudes. The range of FNR, FNRsec, GNR, and MNR marking the O3 formation sensitivity regime varies regionally, highlighting the need for localized assessments. The VOC-limited regime dominated at the ground level, whereas the contribution of the NOx-limited regime increased with altitude. Therefore, a comprehensive control strategy addressing both VOC and NOx emissions across different altitudes is essential for effectively mitigating photochemical pollution in urban areas of China.

Effects and mechanisms of Polygonati Rhizoma polysaccharide on potassium oxonate and hypoxanthine-induced hyperuricemia in mice.

Hyperuricemia, a prevalent metabolic disturbance intricately linked to gout and chronic kidney disease (CKD), may be relieved by traditional Chinese medicine Polygonati Rhizoma. It is derived from the rhizomes of Polygonatum sibiricum, Polygonatum kingianum, and Polygonatum cyrtonema, which are rich in polysaccharides and are effective hyperuricemia alleviators. This study investigated the potential of Polygonatum sibiricum polysaccharide (PSP) in managing hyperuricemia. PSP (125, 250, and 500 mg/kg, i.g.) or allopurinol was administered to hyperuricemia mice treated with potassium oxonate and hypoxanthine for two weeks. PSP effectively decreased serum uric acid levels by inhibiting xanthine oxidase and adenosine deaminase activity and expression in the liver and modulating uric acid-related transporters (URAT1, OAT1, and OAT3) in the kidney. PSP lowered serum creatinine and blood urea nitrogen levels, alleviating hyperuricemia-induced renal tubular epithelial-mesenchymal fibrosis. In vitro, PSP promoted mitochondrial biogenesis via the PGC-1α/NRF1/TFAM pathway, suppressed reactive oxygen species production, and prevented cytochrome C and dynamin-related protein 1 dysregulation in HK-2 cells. Furthermore, PSPA (Mw 4.0 kDa) and PSPB (Mw 112.2 kDa) isolated from PSP exhibit different uric acid-lowering mechanisms. In conclusion, our findings highlight the therapeutic potential of PSP and its nephroprotective effects in hyperuricemia, thereby supporting its development as a therapeutic agent for hyperuricemia.

HLA Alleles Associate with Insulin Autoimmune Syndrome.

In recent years, there have been hundreds of reports on insulin autoimmune syndrome (IAS) globally; however, fewer than a hundred patients have undergone genetic testing. Our objective is to examine the background of IAS and the variations in drugs that trigger it among patients who have been genetically tested, aiming to deepen our understanding of this condition. HLA Analysis of 68 cases showed that DR4 is predominant, especially in individuals of East Asian descent, notably in DRB1 *0406. Methimazole was the primary drug associated with IAS in these populations, while in Caucasian individuals, the emphasis was on DRB1 *0403, with lipoic acid being the common inducer. The key factor determining disease risk is the combination of chromosomal allele variations, with HLA class II allele DR4 positive patients showing a strong association with DQA1 *0301/DQB1 *0302.

The lipid-metabolism enzyme ECI2 reduces neutrophil extracellular traps formation for colorectal cancer suppression.

Abnormalities in ether lipid metabolism as well as the formation of neutrophil extracellular traps have recently been recognized as detrimental factors affecting tumorigenesis and progression. However, the role of abnormal ether lipid metabolism in colorectal cancer (CRC) evolution has not been reported. Here we show that the lipid metabolism-related gene enoyl-CoA δ-isomerase 2 (ECI2) plays a tumor-suppressor role in CRC and is negatively associated with poor prognosis in CRC patients. We mechanistically demonstrate that ECI2 reduces ether lipid-mediated Interleukin 8 (IL-8) expression leading to decreased neutrophil recruitment and neutrophil extracellular traps formation for colorectal cancer suppression. In particular, ECI2 inhibits ether lipid production in CRC cells by inhibiting the peroxisomal localization of alkylglycerone phosphate synthase (AGPS), the rate-limiting enzyme for ether lipid synthesis. These findings not only deepen our understanding of the role of metabolic reprogramming and neutrophil interactions in the progression of CRC, but also provide ideas for identifying potential diagnostic markers and therapeutic targets for CRC.

Von Willebrand factor exacerbates heart failure through formation of neutrophil extracellular traps.

BACKGROUND AND AIMS: Heart failure (HF) is a leading cause of mortality worldwide and characterized by significant co-morbidities and dismal prognosis. Neutrophil extracellular traps (NETs) aggravate inflammation in various cardiovascular diseases; however, their function and mechanism of action in HF pathogenesis remain underexplored. This study aimed to investigate the involvement of a novel VWF-SLC44A2-NET axis in HF progression. METHODS: NET levels were examined in patients with HF and mouse models of transverse aortic constriction (TAC) HF. PAD4 knockout mice and NET inhibitors (GSK-484, DNase I, NEi) were used to evaluate the role of NETs in HF. RNA sequencing was used to investigate the downstream mechanisms. Recombinant human ADAMTS13 (rhADAMTS13), ADAMTS13, and SLC44A2 knockouts were used to identify novel upstream factors of NETs. RESULTS: Elevated NET levels were observed in patients with HF and TAC mouse models of HF. PAD4 knockout and NET inhibitors improved the cardiac function. Mechanistically, NETs induced mitochondrial dysfunction in cardiomyocytes, inhibiting mitochondrial biogenesis via the NE-TLR4-mediated suppression of PGC-1α. Furthermore, VWF/ADAMTS13 regulated NET formation via SLC44A2. Additionally, sacubitril/valsartan amplifies the cardioprotective effects of the VWF-SLC44A2-NET axis blockade. CONCLUSIONS: This study established the role of a novel VWF-SLC44A2-NET axis in regulating mitochondrial homeostasis and function, leading to cardiac apoptosis and contributing to HF pathogenesis. Targeting this axis may offer a potential therapeutic approach for HF treatment.

Synthesis of Mo-Pt/CeO2 Dual Single-Atom Nanozyme for Multifunctional Biochemical Detection Applications.

Elaborated structural modulation of Pt-based artificial nanozymes can efficiently improve their catalytic activity and expand their applications in clinical diagnosis and biochemical sensing. Herein, a highly efficient dual-site peroxidase mimic composed of highly dispersed Pt and Mo atoms is reported. The obtained Mo-Pt/CeO2 exhibits exceptional peroxidase-like catalytic activity, with a Vmax as high as 34.16 × 10-8 m s-1, which is 37.5 times higher than that of the single-site counterpart. Mechanism studies suggest that the Mo atoms can not only serve as adsorption and activation sites for the H2O2 substrate but also regulate the charge density of Pt centers to promote the generation ability of •OH. As a result, the synergistic effect between the dual active sites significantly improves the catalytic efficiency. Significantly, the application of the Mo-Pt/CeO2 catalyst's excellent peroxidase-like activity is extended to various biochemical detection applications, including the trace detection of glucose and cysteine, as well as the assessment of antioxidants' antioxidant capacity. This work reveals the great potential of rational design dual-site active centers for constructing high-performance artificial nanozymes.

Protosappanin A Protects DOX-Induced Myocardial Injury and Cardiac Dysfunction by Targeting ACSL4/FTH1 Axis-Dependent Ferroptosis.

Doxorubicin (DOX) is an effective anticancer agent, but its clinical utility is constrained by dose-dependent cardiotoxicity, partly due to cardiomyocyte ferroptosis. However, the progress of developing cardioprotective medications to counteract ferroptosis has encountered obstacles. Protosappanin A (PrA), an anti-inflammatory compound derived from hematoxylin, shows potential against DOX-induced cardiomyopathy (DIC). Here, it is reported that PrA alleviates myocardial damage and dysfunction by reducing DOX-induced ferroptosis and maintaining mitochondrial homeostasis. Subsequently, the molecular target of PrA through proteome microarray, molecular docking, and dynamics simulation is identified. Mechanistically, PrA physically binds with ferroptosis-related proteins acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferritin heavy chain 1 (FTH1), ultimately inhibiting ACSL4 phosphorylation and subsequent phospholipid peroxidation, while also preventing FTH1 autophagic degradation and subsequent release of ferrous ions (Fe2+) release. Given the critical role of ferroptosis in the pathogenesis of ischemia-reperfusion (IR) injury, this further investigation posits that PrA can confer a protective effect against IR-induced cardiac damage by inhibiting ferroptosis. Overall, a novel pharmacological inhibitor is unveiled that targets ferroptosis and uncover a dual-regulated mechanism for cardiomyocyte ferroptosis in DIC, highlighting additional therapeutic options for chemodrug-induced cardiotoxicity and ferroptosis-triggered disorders.

Immune microenvironment and immunotherapy for chordoma.

Chordoma, as a rare, low-grade malignant tumor that tends to occur in the midline of the body, grows slowly but often severely invades surrounding tissues and bones. Due to the severe invasion and damage to the surrounding tissues, chordoma is difficult to be gross totally resected in surgery, and the progression of the residual tumor is often unavoidable. Besides, the tumor is insensitive to conventional radiotherapy and chemotherapy, thus finding effective treatment methods for chordoma is urgent. Nowadays, immunotherapy has made a series of breakthroughs and shown good therapeutic effects in kinds of tumors, which brings new insights into tumors without effective treatment strategies. With the deepening of research on immunotherapy, some studies focused on the immune microenvironment of chordoma have been published, most of them concentrated on the infiltration of immune cells, the expression of tumor-specific antigen or the immune checkpoint expression. On this basis, a series of immunotherapy studies of chordoma are under way, some of which have shown encouraging results. In this review, we reviewed the research about immune microenvironment and immunotherapy for chordoma, combined with the existing clinical trials data, hoping to clarify the frontiers and limitations of chordoma immune research, and provide reference for follow-up immunotherapy research on chordoma.

Differences in gas exchange, chlorophyll fluorescence, and modulated reflection of light at 820 nm between two rhododendron cultivars under aluminum stress conditions.

Aluminum (Al) toxicity is an important factor restricting the normal growth of plants in acidic soil. Rhododendron (Ericaceae) can grow relatively well in acidic soil. To uncover the adaptive mechanisms of photosynthesis under Al stress, the influence of Al stress on the photosynthetic activities of Al-sensitive (Baijinpao) and Al-resistant (Kangnaixin) rhododendron cultivars was examined by measuring gas exchange, chlorophyll fluorescence, and the modulated reflection of light at 820 nm. Under Al stress conditions, the net photosynthetic rate and stomatal conductance of the rhododendron leaves decreased, whereas the intercellular CO2 concentration increased. The Al stress treatment damaged the oxygen-evolving complex of the rhododendron seedlings, while also inhibiting electron transport on the photosystem II (PSII) donor side. In addition, the exposure to Al stress restricted the oxidation of plastocyanin (PC) and the photosystem I (PSI) reaction center (P700) and led to the re-reduction of PC+ and P700+. The comparison with Kangnaixin revealed an increase in the PSII connectivity in Baijinpao. Additionally, the donor-side electron transport efficiency was more inhibited and the overall activity of PSII, PSI, and the intersystem electron transport chain decreased more extensively in Baijinpao than in Kangnaixin. On the basis of the study findings, we concluded that Al stress adversely affects photosynthesis in rhododendron seedlings by significantly decreasing the activity of PSII and PSI. Under Al stress, Kangnaixin showed stronger tolerance compared with Baijinpao.

Fatty acid composition in erythrocytes and coronary artery disease risk: a case-control study in China.

Background and aims: There is limited and conflicting evidence about the association of erythrocyte fatty acids with coronary artery disease (CAD), particularly in China where the CAD rates are high. Our study aimed to explore the association between erythrocyte fatty acid composition and CAD risk in Chinese adults. Methods: Erythrocyte fatty acids of 314 CAD patients and 314 matched controls were measured by gas chromatography. Multivariable conditional logistic regression and restricted cubic spline models were used to explore the odds ratio with 95% confidence interval (OR, 95% CI) and potential association between erythrocyte fatty acids and CAD risk. Principal component analysis (PCA) was used to analyze further the potential role of various erythrocyte fatty acid patterns in relation to CAD risk. Results: Significant inverse associations were observed between high levels of erythrocyte total n-3 polyunsaturated fatty acids (n-3 PUFA) [ORT3-T1 = 0.18 (0.12, 0.28)], monounsaturated fatty acids (MUFA) [ORT3-T1 = 0.21 (0.13, 0.32)], and the risk of CAD. Conversely, levels of saturated fatty acids (SFAs) and n-6 polyunsaturated fatty acids (n-6 PUFAs) were positively associated with CAD risk [ORT3-T1 = 3.33 (2.18, 5.13), ORT3-T1 = 1.61 (1.06, 2.43)]. No significant association was observed between CAD risk and total trans fatty acids. Additionally, the PCA identifies four new fatty acid patterns (FAPs). The risk of CAD was significantly positively associated with FAP1 and FAP2, while being negatively correlated with FAP3 and FAP4. Conclusion: The different types of erythrocyte fatty acids may significantly alter susceptibility to CAD. Elevated levels of n-3-PUFAs and MUFAs are considered as protective biomarkers against CAD, while SFAs and n-6 PUFAs may be associated with higher CAD risk in Chinese adults. The risk of CAD was positively associated with FAP1 and FAP2, and negatively associated with FAP3 and FAP4. Combinations of erythrocyte fatty acids may be more important markers of CAD development than individual fatty acids or their subgroups.

Effect of Bright Light Therapy on Perinatal Depression: A Systematic Review and Meta-Analysis: Effet de la luminothérapie sur la dépression périnatale: une revue systématique et une méta-analyse.

OBJECTIVE: This study represents the inaugural attempt to systematically review and analyse the efficacy of bright light therapy on depression among women experiencing major depressive disorder or depressive symptoms during the perinatal period, encompassing its efficacy on depression scores, remission rates, and response rates. METHODS: We searched 10 databases for randomized controlled trials examining bright light therapy's efficacy on perinatal depression up to January 2024. Data extraction was performed independently by 2 investigators. The Cochrane Handbook guidelines appraised the study quality, and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach assessed evidence certainty. RESULTS: We incorporated 6 studies, encompassing 151 participants. When contrasted with dim light therapy, bright light therapy did not significantly alter depression scores (standard mean difference = -0.29, 95% confidence interval [CI], -0.62 to 0.04, P = 0.08, I² = 34%) or response rates (risk ratio [RR] = 1.56, 95% CI, 0.98 to 2.49, P = 0.06, I² = 0%) in women experiencing perinatal depression. Conversely, bright light therapy was associated with a substantial increase in remission rates (RR = 2.63, 95% CI, 1.29 to 5.38, P = 0.008, I² = 2%). CONCLUSION: Bright light therapy did not show efficacy in treating perinatal depression in terms of depression scores and response rates. However, regarding the remission rate, bright light did show efficacy compared to control conditions. Due to the limited sample size in the included studies, type II err or may occur. To obtain more conclusive evidence, future studies must employ larger sample sizes.

Pre- and postpartum fear of childbirth and its predictors among rural women in China.

BACKGROUND: Fear of childbirth (FOC) can influence both maternal and child health. Research on FOC in China is scarce, especially on rural women. This study aimed to assess pre- and postpartum FOC and its predictors among Chinese rural women. METHODS: This was a prospective correlation study. A total of 569 women completed the prenatal questionnaire in the third trimester, and 477 of them completed the postpartum questionnaire within three days after childbirth. Maternal socio-demographic information, clinical information, childbirth self-efficacy and prenatal and postpartum FOC were investigated. FOC was evaluated using the Wijma Childbirth Expectancy/ Experience Questionnaire (WDEQ). Descriptive, bivariate, multivariate linear regression analysis, univariate and multivariate logistic regression analyses were performed. RESULTS: The mean pre- and postpartum FOC scores were 64.5 (standard deviation: 25.1) and 64.3 (standard deviation: 23.9), respectively, with 20.8% of women reporting severe fear before childbirth and 18.2% after childbirth. Multivariate linear regression analysis revealed predictors for higher levels of prenatal FOC including higher education level, nullipara, higher monthly household income, lower family support, and lower childbirth self-efficacy (p < 0.05) and the predictors for higher levels of postpartum FOC included unemployed status, lower childbirth self-efficacy, and higher prenatal FOC (p < 0.05). Multivariate logistic regression showed that higher childbirth self-efficacy reduced the likelihood of severe prenatal FOC (OR: 0.99, p < 0.001), while severe prenatal FOC increased the likelihood of severe postpartum FOC (OR: 3.57, p < 0.001). CONCLUSION: The rural women have high levels of FOC before and after childbirth, with approximately 20% experiencing severe FOC during both periods. Higher education level, nullipara, higher monthly household income, lower family support, and lower childbirth self-efficacy are predictors of heightened prenatal FOC. Unemployed status, lower childbirth self-efficacy, and higher prenatal FOC are predictors of heightened postpartum FOC. Notably, enhancing childbirth self-efficacy emerges as crucial in mitigating severe prenatal FOC, while severe prenatal FOC significantly increases the likelihood of severe postpartum FOC. The development of targeted intervention strategies for the above factors can help reduce women's FOC level and improve their overall pregnancy and childbirth experience.

TET2-STAT3-CXCL5 nexus promotes neutrophil lipid transfer to fuel lung adeno-to-squamous transition.

Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)-mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3-CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to-cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.

Current status of electronic health literacy among pregnant women with gestational diabetes mellitus and their perceptions of online health information: a mixed-methods study.

BACKGROUND: Women diagnosed with gestational diabetes mellitus often rely on internet-based health information for managing their condition. This study aims to investigate the present state of electronic health literacy among women with gestational diabetes mellitus, analyze the influencing factors, and explore their experiences regarding accessing, comprehending, evaluating, and applying online health information pertinent to gestational diabetes mellitus. METHODS: A sequential explanatory mixed methods research design was adopted in this study. Initially, 235 women with gestational diabetes mellitus participated in a cross-sectional survey. The research tools included general information and the Chinese version of the electronic Health Literacy Scale (eHEALS). Descriptive analyses were conducted to describe the characteristics of the sample, and multiple linear regression analyses were used to explore the factors influencing electronic health literacy among women with gestational diabetes mellitus. Secondly, 11 women with gestational diabetes mellitus joined semi-structured in-depth interviews to obtain their perceptions about online health information. The data were analyzed using inductive content analysis to develop themes. RESULTS: The median score of eHEALS in the Chinese version among 235 women diagnosed with gestational diabetes mellitus was 29 (interquartile range [IQR], 26 to 32). Factors influencing electronic health literacy among these women included accessing health information from medical professionals (ß = 0.137, p = 0.029) and utilizing health information from applications (ß = 0.159, p = 0.013). From the qualitative phase of the study, four thematic categories emerged: reasons and basis for accessing health information from the Internet; address barriers to accessing and applying online health information; desires for a higher level of online health information services; outcomes of accessing and applying online health information. CONCLUSION: The electronic health literacy of women diagnosed with gestational diabetes mellitus remains suboptimal and warrants improvement. The sources of access to health information affect electronic health literacy in women with gestational diabetes mellitus. Moreover, women facing gestational diabetes encounter numerous impediments when attempting to access health-related information online, underscoring the necessity for enhanced online health information services to meet their needs.