Isolated Partial Anomalous Pulmonary Veins: A 10-Year Experience at a Single Center.

INTRODUCTION: Isolated partial anomalous pulmonary venous connection (PAPVC) is difficult to diagnose, and surgical indications remain controversial. We reviewed 10 y of isolated PAPVC cases. METHODS: The data of patients with isolated PAPVC admitted to the Anzhen Congenital Heart Disease Department from 2010 to 2019 were reviewed retrospectively. RESULTS: Thirty patients, aged between 4 mo and 32 y, were included in this study. Significant correlations were found between the right ventricle (RV), end-diastolic dimension Z-score (RVED-z) and age (r = 0.398, P = 0.03), and between estimated pulmonary pressure and age (r = 0.423, P = 0.02). However, no significant correlations were found between the RVED-z and the number of anomalous pulmonary veins (r = 0.347, P = 0.061), between estimated pulmonary pressure and the RVED-z (r = 0.218, P = 0.248), and between estimated pulmonary pressure and the number of anomalous veins (r = 0.225, P = 0.232). Transthoracic echocardiography (TTE) confirmed 90% of isolated PAPVC cases. Surgical repair was performed in 29 patients with RV enlargement, persistent low weight, pulmonary hypertension, or respiratory symptoms. Among the surgical patients, nine had elevated pulmonary pressure before surgery, which decreased postoperatively; no mortality or reintervention was observed. The mean duration of echocardiographic follow-up was 1.9 y. CONCLUSIONS: TTE is recommended for routine assessments, and further clarification can be obtained with computed tomography when TTE proves inconclusive for diagnosis. Transesophageal echocardiography and computed tomography are further recommended for adult patients if TTE fails to provide clear results. PAPVC should be considered as an underlying cause when unexplained RV enlargement is observed. Surgery is recommended for patients with RV enlargement, pulmonary hypertension, or respiratory symptoms.

Research progress of flexible pressure sensor based on MXene materials.

Flexible pressure sensors overcome the limitations of traditional rigid sensors on the surface of the measured object, demonstrating broad application prospects in fields such as sports health and vital sign monitoring due to their excellent flexibility and comfort in contact with the body. MXene, as a two-dimensional material, possesses excellent conductivity and abundant surface functional groups. Simultaneously, MXene's unique layered structure and large specific surface area offer a wealth of possibilities for preparing sensing elements in combination with other materials. This article reviews the preparation methods of MXene materials and their performance indicators as sensing elements, discusses the controllable preparation methods of MXene materials and the impact of their physical and chemical properties on their functions, elaborates on the pressure sensing mechanism and evaluation mechanism of MXene materials. Starting from the four specific application directions: aerogel/hydrogel, ink printing, thin film/electronic skin, and fiber fabric, we introduce the research progress of MXene flexible pressure sensors from an overall perspective. Finally, a summary and outlook for developing MXene flexible pressure sensors are provided.

Persistence of peripheral CD8 + CD28- T cells indicates a favourable outcome and tumour immunity in first-line HER2-positive metastatic breast cancer.

BACKGROUND: The contradictory role of CD8 + CD28- T cells in tumour immunity has been reported, while their biological and clinical significance in HER2-positive metastatic breast cancer (MBC) is still unknown. METHODS: HER2-positive MBC patients with no prior therapy in the metastatic setting were retrospectively recruited at two medical centres. Peripheral CD8 + CD28- T cells (pTCD8+CD28-) were detected at baseline and following therapeutic intervals. Progression-free survival (PFS) was compared according to pTCD8+CD28- levels. The molecular features of pTCD8+CD28- and its correlation with tumour immunity were also investigated. RESULTS: A total of 252 patients were enrolled, and the median follow-up time was 29.6 months. pTCD8+CD28- high at baseline has prolonged PFS compared to pTCD8+CD28- low (P = 0.001). Patients who maintained pTCD8+CD28- high had a longer PFS than those who kept pTCD8+CD28- low (P < 0.001). The enhanced pTCD8+CD28- level also indicates a longer PFS compared to pTCD8+CD28- low (P = 0.025). Here, pTCD8+CD28- was demonstrated as an antigen-experienced effector T cell. Higher IL-2 level (P = 0.034) and lower TGF-ß level (P = 0.016) in the serum and highly infiltrated CD8 + CD28- T cells (P = 0.037) were also connected to pTCD8+CD28- high. CONCLUSIONS: High pTCD8+CD28- level is associated with a favourable tumour immunity and a better PFS of HER2-targeting therapy in MBC patients.

Integrated Serum Pharmacochemistry and Network Pharmacological Analysis Used To Explore Possible Anti-Aging Mechanisms of the Ginsenosides

BACKGROUND: Although constitutive ginsenosides are credited with ginseng's remarkable anti-aging efficacy, the mechanism of action and bioactive components of ginsenosides are unclear. OBJECTIVE: The goal of the study was to examine the effect of ginsenosides on D-galactose (D-gal)-induced aging in rats and to figure out the underlying molecular mechanism using serum pharmacochemistry and network pharmacology. METHODS: Using behavioral, biochemical indexes, and histological analysis, ginsenosides were evaluated for their anti-aging effects in rats induced by D-gal, and effective ingredients absorbed in the blood were examined by ultra-performance liquid chromatography quadrupole time of flight coupled with mass spectrometry (UPLC-Q/TOF-MS) before being subjected to network pharmacology analysis. RESULTS: As well as improving spatial learning and memory skills, Ginsenosides are known to regulate malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity. In addition, it improved the ultrastructure of neurons in D-gal-induced rats' hippocampus. Seventy-four absorption components and metabolites of ginsenosides were identified in aging rat serum. According to a network pharmacology study, ginsenosides have anti-aging properties by modulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPK) signaling pathways. CONCLUSION: The potential mechanisms of the anti-aging effect of ginsenosides involve multiple components, targets, and pathways. These findings serve as a foundation for further research into the processes behind ginsenoside's anti-aging impact.

Dietary fats and the APOE-e4 risk allele in relation to cognitive decline: a longitudinal investigation in a biracial population sample.

BACKGROUND: APOE-e4 is the strongest genetic risk factor for Alzheimer's disease. However, the influence of APOE-e4 on dietary fat intake and cognition has not been investigated. OBJECTIVE: We aim to examine the association of types of dietary fat and their association to cognitive decline among those with and without the APOE-e4 allele. METHODS: The study included 3,360 Chicago Health and Aging Project (CHAP) participants from four Southside Chicago communities. Global cognition was assessed using a composite score of episodic memory, perceptual speed, MMSE, and diet using a 144-item food frequency questionnaire. APOE genotype was assessed by the hME Sequenom mass-array platform. Longitudinal mixed-effect regression models were used to examine the association of dietary fat and the APOE-e4 allele with cognitive decline, adjusted for age, sex, education, smoking status, and calorie intake. RESULTS: The present study involved 3,360 participants with a mean age of 74 at baseline, 62% African Americans, 63% females, and a mean follow-up of 7.8 years. Among participants with the APOE-e4 risk allele, higher intakes of total and saturated fat (SFA) were associated with a faster decline in global cognition. Among individuals with the APOE-e4 risk allele, a 5% increase in calories from SFA was associated with a 21% faster decline (ß = -0.0197, P = 0.0038). In contrast, a higher intake of long-chain n-3 polyunsaturated fatty acids (LC-n3 PUFA) was associated with a slower rate of decline in global cognition among APOE-e4 carriers. Specifically, for every 1% energy increment from LC-n3 PUFA, the annual rate of global cognitive decline was slower by 0.024 standardized unit (SD 0.010, P = 0.023), about 30.4% slower annual cognitive decline. Higher SFA or other types of dietary fat were not associated with cognitive decline among APOE-e4 non-carriers. CONCLUSIONS: Our study found a significant association between SFA and faster cognitive decline, LC-n3 PUFA and slower cognitive decline among those with the APOE-e4 allele. Our findings suggested that higher intake of SFA might contribute faster cognitive decline in combination with APOE-e4 whereas LC-n3 PUFA might compensate the adverse effects of APOE-e4. The interaction between intakes of different types of dietary fat and APOE-e4 on cognitive function warrants further research.

Dysfunction of CCT3-associated network signals for the critical state during progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and is a serious threat to human health; thus, early diagnosis and adequate treatment are essential. However, there are still great challenges in identifying the tipping point and detecting early warning signals of early HCC. In this study, we aimed to identify the tipping point (critical state) of and key molecules involved in hepatocarcinogenesis based on time series transcriptome expression data of HCC patients. The phase from veHCC (very early HCC) to eHCC (early HCC) was identified as the critical state in HCC progression, with 143 genes identified as key candidate molecules by combining the DDRTree (dimensionality reduction via graph structure learning) and DNB (dynamic network biomarker) methods. Then, we ranked the candidate genes to verify their mRNA levels using the diethylnitrosamine (DEN)-induced HCC mouse model and identified five early warning signals, namely, CCT3, DSTYK, EIF3E, IARS2 and TXNRD1; these signals can be regarded as the potential early warning signals for the critical state of HCC. We identified CCT3 as an independent prognostic factor for HCC, and functions of CCT3 involving in the "MYCtargets_V1" and "E2F-Targets" are closely related to the progression of HCC. The predictive method combining the DDRTree and DNB methods can not only identify the key critical state before cancer but also determine candidate molecules of critical state, thus providing new insight into the early diagnosis and preemptive treatment of HCC.

Variant allele frequency in circulating tumor DNA correlated with tumor disease burden and predicted outcomes in patients with advanced breast cancer.

PURPOSE: In patients with first-line advanced breast cancer (ABC), the correlation between ctDNA variant allele frequency (VAF) and tumor disease burden, and its prognostic value remains poorly investigated. METHODS: This study included patients with ABC diagnosed at Peking University Cancer Hospital who performed ctDNA test before receiving first-line treatment. Baseline plasma samples were collected for assessing ctDNA alterations and VAF with next-generation sequencing. The sum of tumor target lesion diameters (SLD) was measured with imaging methods according to RECIST 1.1 criteria. RESULTS: The final cohort included 184 patients. The median age of the cohort was 49.4 (IQR: 42.3-56.8) years. The median VAF was 15.6% (IQR: 5.4%-33.7%). VAF showed positive correlation with SLD in patients with relatively large tumor lesions (r = 0.314, p = 0.003), but not in patients with small tumor lesions (p = 0.226). VAF was associated with multiple metastasis sites (p = 0.001). Multivariate Cox regression analysis showed that high VAF was associated with shorter overall survival (OS) (HR: 3.519, 95% confidence interval (CI): 2.149-5.761), and first-line progression-free survival (PFS) (HR: 2.352, 95%CI: 1.462-3.782). Combined VAF and SLD improved prediction performance, both median OS and PFS of patients in VAF(H)/SLD(H) group were significantly longer than VAF(L)/SLD(L) group (mOS: 49.3 vs. 174.1 months; mPFS: 9.6 vs. 25.3 months). CONCLUSION: ctDNA VAF associated with tumor disease burden, and was a prognostic factor for patients with ABC. A combination of ctDNA test and radiographic imaging might enhance tumor burden evaluation, and improve prognosis stratification in patients with ABC.

Endocrine therapy plus HER2-targeted therapy, another favorable option for HR+/HER2+ advanced breast cancer patients.

Advanced breast cancer (ABC) that is positive for hormone receptors (HRs) and human epidermal growth factor receptor 2 (HER2) is a cancer subtype with distinctive characteristics. The primary treatment guidelines suggest that a combination therapy comprising anti-HER2 therapy and chemotherapy should be administered as the initial treatment for HR-positive/ HER2-positive (HR+/HER2+) ABC. However, crosstalk between the HR and HER2 pathways can partially account for the resistance of HR+/HER2+ disease to HER2-targeted therapy. This, in turn, provides a rationale for the concomitant administration of HER2-targeted therapy and endocrine therapy (ET). Many clinical studies have confirmed that the combination of HER2-targeted therapy and ET as a first-line treatment is not inferior to the combination of HER2-targeted therapy and chemotherapy, and support its use as a first-line treatment choice for HR+/HER2+ ABC. Other drugs, such as antibody-drug conjugates, cyclin-dependent kinase 4/6 inhibitors, phosphatidylinositol 3-kinase-protein kinase B (AKT)-mammalian target of rapamycin inhibitors, and programmed cell death protein 1 or programmed cell death ligand 1 inhibitors, may also improve the prognosis of patients with breast cancer by blocking signaling pathways associated with tumor proliferation and break new ground for the treatment of HR+/HER2+ ABC.

Analysis of abnormal expression of signaling pathways in PQ-induced acute lung injury in SD rats based on RNA-seq technology.

Background: Paraquat (PQ) plays an important role in agricultural production due to its highly effective herbicidal effect. However, it has led to multiple organ failure in those who have been poisoned, with damage most notable in the lungs and ultimately leading to death. Because of little research has been performed at the genetic level, and therefore, the specific genetic changes caused by PQ exposure are unclear.Methods: Paraquat poisoning model was constructed in Sprague Dawley (SD) rats, and SD rats were randomly divided into Control group, paraquat (PQ) poisoning group and Anthrahydroquinone-2,6-disulfonate (AH2QDS) treatment group. Then, the data was screened and quality controlled, compared with reference genes, optimized gene structure, enriched at the gene expression level, and finally, signal pathways with significantly different gene enrichment were screened.Results: This review reports on lung tissues from paraquat-intoxicated Sprague Dawley (SD) rats that were subjected to RNA-seq, the differentially expressed genes were mainly enriched in PI3K-AKT, cGMP-PKG, MAPK, Focal adhesion and other signaling pathways.Conclusion: The signaling pathways enriched with these differentially expressed genes are summarized, and the important mechanisms mediated through these pathways in acute lung injury during paraquat poisoning are outlined to identify important targets for AH2QDS treatment of acute lung injury due to paraquat exposure, information that will be used to support a subsequent in-depth study on the mechanism of PQ action.

Long-term Outcome Analysis of Pyrotinib in Patients With HER2-Positive Metastatic Breast Cancer and Brain Metastasis: A Real-World Study.

BACKGROUND: Pyrotinib is currently approved for the treatment of HER2-positive advanced breast cancer in China. Data on the overall survival (OS) and efficacy in patients with brain metastasis (BM) remain scarce. This study evaluated the effectiveness of pyrotinib in a real-world setting, especially in patients with BM. METHODS: We reviewed patients with metastatic breast cancer treated with pyrotinib-based therapy between June 2018 and June 2022. Progression-free survival (PFS), OS, objective response rate, and safety were analyzed following the administration of pyrotinib. RESULTS: A total of 239 patients were included. The median PFS in patients who received pyrotinib-based therapy as first-line (15/239), second-line (115/239), or third-or-higher-line (109/239) treatment was 14.00, 9.33, and 8.20 months, respectively, and the median OS was not reached, 29.07 and 22.23 months, respectively. The median PFS in patients who pretreated with trastuzumab (214/239), trastuzumab plus pertuzumab (22/239), lapatinib (68/239), or trastuzumab emtansine (14/239) was 9.33, 6.87, 7.20, and 7.20 months, respectively. In 61 patients with BM, the median PFS was 7.50 months, the median central nervous system (CNS)-PFS was 11.17 months, and the median OS was 21.27 months. Furthermore, 19 patients with concomitant brain radiotherapy tended to achieve a longer OS than 42 patients without radiation (34.17 vs. 20.70 months, P = .112). CONCLUSIONS: Long-term outcomes of pyrotinib-based therapy are promising for patients with HER2-positive metastatic breast cancer in real world and in patients with BM, regardless of the treatment lines and prior anti-HER2 therapies.

Trastuzumab Biosimilar (HLX02), Pertuzumab Plus Chemotherapy in Patients with HER2-Positive Metastatic Breast Cancer after Progression of Trastuzumab: A Prospective, Phase II Study.

Purpose: This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with HER2-positive metastatic breast cancer (MBC) after progression of trastuzumab. Materials and Methods: In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of tratuzumab received pertuzuamb, HLX02 and chemotherapy (PTC) in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495). Results: A total of 45 patients were included in this study. 12(26.7%) patients were treated in second line and 33(73.3%) patients were in third-line and later setting. 80% and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range: 1.2-43.9), the median PFS was 7.6 months (95% confidence interval [CI],4.3- 10.9m), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated. Conclusion: The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond line treatment in HER2-positive metastatic breast cancer.

AZF microdeletion affects semen parameters, sex hormone levels, and chromosome karyotypes in infertile men in Xinjiang.

This study aimed to analyze the correlation between the microdeletion of different regions of the azoospermia factor (AZF) gene and semen parameters, sex hormone levels, and karyotypes in infertile males by retrospective study. This was performed to obtain a comprehensive understanding of the clinical data of AZF microdeletion in infertile males, to guide clinical diagnoses and treatments, and to improve the efficacy and safety of assisted reproductive technology. For this purpose, Fifty-seven patients with AZF microdeletions and complete data were selected from 1916 patients with AZF microdeletions in our hospital from January 2020 to August 2022. The correlation between semen parameters, sex hormone levels, and chromosome karyotypes of these 57 patients was analyzed. Results showed that among the 57 patients with AZF microdeletions, the region with the highest microdeletion rate was AZFc with 57.89%; single or combined deletions in AZFa and AZFb regions resulted in azoospermia. The deletion frequency of AZFc in the oligospermia group was significantly higher than that in the azoospermia group, and the deletion frequencies of AZFb and AZFb + c in the azoospermia group were significantly higher than those in the oligospermia group (P<0.05). There were statistically significant differences in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and chromosome karyotypes between patients with azoospermia and oligospermia (P<0.05). Statistically significant differences were observed in prolactin (PRL), FSH, testosterone (T), LH levels, and chromosome karyotypes of patients in different AZF microdeletion regions (P<0.05). In conclusion, AZF microdeletions can lead to a decline in semen quality in men, and different types of deletions have different effects on semen parameters, sex hormone levels, and karyotype analysis. Further treatments should be selected based on the AZF microdeletion area.

Association of Vitamin E and Cognitive Decline in Older Adults with and without the APOEɛ4 Allele: A Biracial Population-Based Community Study.

BACKGROUND: The association of different types of tocopherols (vitamin E) with cognition might vary by the APOEɛ4 allele status. OBJECTIVE: We examined the association of dietary tocopherols with cognitive decline among participants with and without the APOEɛ4 allele over a median of 12 years. METHODS: 2,193 participants from the Chicago Health and Aging Project were included in the analyses. Global cognition was assessed in three-year cycles. We used a 144-item FFQ to assess dietary intakes of tocopherols and hME Sequenom mass-array platform to assess APOE genotype. We used linear mixed effects models to examine the relationship between tocopherol from food sources and global cognitive decline. RESULTS: The mean baseline age was 74.1 (SD = 5.9) years. Among APOEɛ4 carriers, participants in the highest quintile of intakes of dietary vitamin E had a slower cognitive decline of 0.022 SDU (95% CI: 0.000, 0.043) compared to those in the lowest quintile. A higher intake of dietary α-tocopherol from food sources only was associated with slower cognitive decline in APOEɛ4 carriers (p for trend 0.002) but not among the non-carriers (p for trend 0.937). Among APOEɛ4 carriers, those in the highest quintile of intake of α-tocopherol had a 16.4% slower rate of decline of global cognition compared to those in the lowest quintile (ß= 0.034, 95% CI: 0.013, 0.054). CONCLUSIONS: Individuals consuming high α-tocopherol from food sources had slower cognitive decline among APOEɛ4 carriers. In older adults, different forms of vitamin E might moderate the relationship of APOEɛ4 with global cognition.

Association of Whole Grain Consumption and Cognitive Decline: An Investigation From a Community-Based Biracial Cohort of Older Adults.

BACKGROUND AND OBJECTIVES: To examine the association of whole grain consumption and longitudinal change in global cognition, perceptual speed, and episodic memory by different race/ethnicity. METHODS: We included 3,326 participants from the Chicago Health and Aging Project who responded to a Food Frequency Questionnaire (FFQ), with 2 or more cognitive assessments. Global cognition was assessed using a composite score of episodic memory, perceptual speed, and the Mini Mental State Examination (MMSE). Diet was assessed by a 144-item FFQ. Linear mixed-effects models were used to estimate the association of intakes of whole grains and cognitive decline. RESULTS: This study involved 3,326 participants (60.1% African American [AA], 63.7% female) with a mean age of 75 years at baseline and a mean follow-up of 6.1 years. Higher consumption of whole grains was associated with a slower rate of global cognitive decline. Among AA participants, those in the highest quintile of whole grain consumption had a slower rate of decline in global cognition (ß = 0.024, 95% CI [0.008-0.039], p = 0.004), perceptual speed (ß = 0.023, 95% CI [0.007-0.040], p = 0.005), and episodic memory (ß = 0.028, 95% CI [0.005-0.050], p = 0.01) compared with those on the lowest quintile. Regarding the amount consumed, in AA participants, those who consumed >3 servings/d vs those who consumed <1 serving/d had a slower rate of decline in global cognition (ß = 0.021, 95% CI [0.005-0.036], p = 0.0093). In White participants, with >3 servings/d, we found a suggestive association of whole grains with global cognitive decline when compared with those who consumed <1 serving/d (ß = 0.025, 95% CI [-0.003 to 0.053], p = 0.08). DISCUSSION: Among AA participants, individuals with higher consumption of whole grains and more frequent consumption of whole grain had slower decline in global cognition, perceptual speed, and episodic memory. We did not see a similar trend in White adults.

Dietary Sugar Intake Associated with a Higher Risk of Dementia in Community-Dwelling Older Adults.

BACKGROUND: We have limited evidence for the relationship of high sugar intake with dementia risk. OBJECTIVE: To determine whether high sugar intake is associated with an increased risk of dementia in community-dwelling older adultsMethods:This study included 789 participants of the Rush Memory and Aging Project (community-based longitudinal cohort study of older adults free of known dementia at enrollment), with annual clinical assessments and complete nutrient data (obtained by validated food frequency questionnaire). Clinical diagnosis of dementia is based on the criteria of the joint working group of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. We used Cox proportional hazard models. RESULTS: 118 participants developed dementia during 7.3±3.8 years of follow-up. Those in the highest quintile of total sugar intake were twice as likely to develop dementia than those in the lowest quintile (Q5 versus Q1:HR=2.10 (95% CI: 1.05, 4.19) when adjusted for age, sex, education, APOEɛ4 allele, calories from sources other than sugar, physical activity, and diet score. Higher percent calories from sugar were positively associated with dementia risk (ß=0.042, p = 0.0009). In exploratory analyses, the highest versus lowest quintile of fructose and sucrose in the diet had higher dementia risk by 2.8 (95% CI: 1.38, 5.67) and 1.93 (95% CI: 1.05, 3.54) times, respectively. CONCLUSIONS: A higher intake of total sugar or total calories from sugar is associated with increased dementia risk in older adults. Among simple sugars, fructose (e.g., sweetened beverages, snacks, packaged desserts) and sucrose (table sugar in juices, desserts, candies, and commercial cereals) are associated with higher dementia risk.

Mass Spectrometry-Based Approaches for the Analysis of Protein Higher Order Structure.

ARTICLES DISCUSSED: Espino, J. A., Jones, L. M. In vivo hydroxyl radical protein footprinting for the study of protein interactions in Caenorhabditis elegans. Journal of Visualized Experiments. (158), e60910 (2020). Chea, E. E., Rinas, A., Espino, J. A., Jones, L. M. Characterizing cellular proteins with in-cell fast photochemical oxidation of proteins. Journal of Visualized Experiments. (157), e60911 (2020). Moorthy, B. S., Iyer, L. K., Topp, E. M. Mass spectrometric approaches to study protein structure and interactions in lyophilized powders. Journal of Visualized Experiments. (98), e52503 (2015). Habibi, Y., Thibodeaux, C. J. A hydrogen-deuterium exchange mass spectrometry (HDX-MS) platform for investigating peptide biosynthetic enzymes. Journal of Visualized Experiments. (159), e61053 (2020). Kirsch, Z. J., Arden, B. G., Vachet, R. W., Limpikirati, P. Covalent labeling with diethylpyrocarbonate for studying protein higher-order structure by mass spectrometry. Journal of Visualized Experiments. (172), e61983 (2021). Johnson, D., Punshon-Smith, B., Espino, J. A., Gershenson, A., Jones, L. M. Platform incubator with movable XY stage: A new platform for implementing in-cell fast photochemical oxidation of proteins. Journal of Visualized Experiments. (171), e62153 (2021). Haupt, C. et al. Combining chemical cross-linking and mass spectrometry of intact protein complexes to study the architecture of multi-subunit protein assemblies. Journal of Visualized Experiments. (129), e56747 (2017). Lento, C. et al. Time-resolved electrospray ionization hydrogen-deuterium exchange mass spectrometry for studying protein structure and dynamics. Journal of Visualized Experiments. (122), e55464 (2017). Weinberger, S. R., Chea, E. E., Sharp, J. S., Misra, S. K. Laser-free hydroxyl radical protein footprinting to perform higher order structural analysis of proteins. Journal of Visualized Experiments. (172), e61861 (2021). Misra, S. K., Sharp, J. S. Enabling real-time compensation in fast photochemical oxidations of proteins for the determination of protein topography changes. Journal of Visualized Experiments. (163), e61580 (2020). Chaihu, L. et al. Capillary electrophoresis-based hydrogen/deuterium exchange for conformational characterization of proteins with top-down mass spectrometry. Journal of Visualized Experiments. (172), e62672 (2021).

Prevalence and correlates of suicide attempts in young patients with first-episode and drug-naïve major depressive disorder: A large cross-sectional study.

BACKGROUND: Few studies in China have reported factors influencing suicide attempt in young first-episode drug-free (FEDN) MDD patients. This study aimed to investigate the incidence and potential relevant factors of suicide attempt among young Chinese patients with FEDN MDD to prevent suicidal behavior in this population. METHODS: We recruited 1076 FEDN MDD outpatients aged 18-45 years. Patients' mental states were measured by the Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Positive and Negative Syndrome Scale (PANSS) positive subscale, and Clinical Global Impression Severity Scale (CGIS). Fasting blood glucose, lipid levels, and thyroid function parameters were also measured. RESULTS: The prevalence of suicide attempt for FEDN MDD patients was 18.31 %. Compared to patients without suicide attempt, patients with suicide attempt had an older age of onset, higher HAMA, HAMD, PANSS-positive subscale and CGI-S scores, higher blood pressure, fasting blood glucose, thyroid peroxidases antibody (A-TPO), anti-thyroglobulin (A-TG), thyroid stimulating hormone (TSH), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), but lower high-density lipoprotein cholesterol (HDLC) (all p < 0.05). Logistic regression analysis showed that duration of illness, hypertension, PANSS-positive subscale, HAMA and CGI-S scores, and A-TPO, LDL-C, TC, and HDL-C were associated with suicide attempt in patients with MDD. LIMITATIONS: The main limitations are cross-sectional design and inability to control selection bias. CONCLUSIONS: This study suggests that young patients with FEDN MDD have a high rate of suicide attempts. Several clinical and metabolic indicators related to lipids and thyroid function may be involved in suicide attempts in FEDN MDD patients.

Preparation of SBA-15 supported Ru nanocatalysts by electrostatic adsorption-ultrasonic in situ reduction method and its catalytic performance for hydrogen storage of N-ethylcarbazole.

N-ethylcarbazole (NEC) is an ideal liquid organic hydrogen storage carrier. The development of efficient hydrogen storage catalysts can promote the large-scale application of this process. In this paper, SBA-15 supported Ru nanocatalysts (Ru/S15-SU) were synthesized by strong electrostatic adsorption (SEA)-ultrasonic in situ reduction method (UR). Ru/S15-SU was characterized by N2 adsorption-desorption, TEM, H2 temperature program reduction, FT-IR, XRD, and XPS analysis measures. The results showed that ultrafine Ru NPs were evenly distributed on the surface of SBA-15, and ultrasonic in situ reduction not only reduced Ru3+ to Ru0, but also produced a coordination effect between Ru and O, enhancing the interaction between Ru NPs and the carrier. Ru/S15-SU exhibited excellent catalytic performance in the hydrogenation reaction of NEC, and the hydrogen storage efficiency reached 99.31% at 130°C and 6 MPa H2 pressure, which is superior to that of commercial 5wt%Ru/Al2O3. The excellent catalytic hydrogenation performance can be attributed to the selective anchoring of ruthenium ions on the surface of SBA-15 via electrostatic adsorption, preventing the aggregation of Ru NPs and enhancing the interaction between SBA-15 and Ru NPs by ultrasonic in situ reduction. Ru/S15-SU had a lower NEC hydrogenation apparent activated energy (Ea) of 68.45 kJ/mol than 5wt%Ru/Al2O3 catalyst. This method provides a new approach for the green preparation of nanocatalysts without using any chemical reducing agents.

miR-122-3p Alleviates LPS-Induced Pyroptosis of Macrophages via Targeting NLRP1.

OBJECTIVE: Sepsis, a life-threatening organ dysfunction, is among the leading causes of mortality in intensive care units. Sepsis occurrence is associated with macrophage pyroptosis, and microRNAs (miRNAs) have emerged as key factors in this process. However, the specific role of miR-122-3p in pyroptosis during sepsis progression and its underlying mechanisms remain to be fully elucidated. METHODS: We established an in vitro sepsis model using lipopolysaccharide (LPS)-activated macrophages, followed by transfection of a miR-122-3p mimic into RAW264.7 macrophages. We subsequently determined the effects of miR-122-3p on cell viability and pyroptosis using cell viability, western blot, and qPCR assays. The binding affinity between miR-122-3p and NLR pyrin domain containing 1 (NLRP1) mRNA was then confirmed using a dual-luciferase reporter assay. Finally, the secretion of pro-inflammatory cytokines (interleukin (IL)-2, IL-6, and tumor necrosis factor-α (TNF-α) was determined using ELISA. RESULTS: The results revealed that LPS treatment lead to a significant increase in the production of pro-inflammatory cytokines including IL-2, IL-6, and TNF-α in RAW264.7 cells. We observed that overexpression of miR-122-3p effectively restored cell viability and attenuated the expression of key inflammatory markers promoted by LPS, such as caspase-1, pro-caspase-1, IL-18, IL-1ß, NLRP3, apoptosis-associated speck-like protein containing CARD, and cleaved- gasdermin-D. Our data indicate that miR-122-3p is capable of directly bounding to NLRP1 and inhibiting its expression. CONCLUSIONS: These results confirmed that miR-122-3p plays a crucial role in the inhibition of sepsis by suppressing macrophage pyroptosis in an NLRP1-dependent manner. Therefore, miR-122-3p presents as a promising therapeutic target for sepsis.