Sleep-wake changes and incident depressive symptoms in midlife women.

Our study aimed to investigate the relationship between sleep-wake changes and depressive symptoms events among midlife women. We enrolled 1579 women aged 44-56 years who had no clinically relevant depressive symptoms at baseline. Depressive symptoms were assessed at each visit using the Center for Epidemiologic Studies Depression scale. At the third and fourth follow-up visits, women reported their sleep habits. The sleep midpoint was defined as the time to fall asleep plus one-half of the sleep duration. Sleep-wake changes were determined by the difference in the midpoint of sleep between the third and fourth visits, which were 1 year apart. The median follow-up time was 7 years (range 1-7 years). Cox proportional hazard models were fitted to calculate hazard ratios and 95% confidence intervals for the incidence of depressive symptoms associated with sleep-wake changes. After adjusting for potential confounding factors, the hazard ratio (95% confidence interval) of depressive symptoms for severe sleep midpoint changes was 1.51 (1.12, 2.05) compared with mild sleep midpoint changes. This relationship remained statistically significant and changed little when additionally controlling for sleep duration, sleep quality, insomnia symptoms, use of sleep medications, use of nervous medications, glucose, insulin, lipids, dietary energy intake, and C-reactive protein. Our findings indicate that exposure to long-term severe sleep-wake changes increases the risk of depressive symptoms in midlife women.

Association Between Systemic Immune Inflammation Index and Diabetes Mellitus in the NHANES 2003-2018 Population.

Objects: This study aimed to explore the association between the Systemic Immune-Inflammation Index (SII) and diabetes mellitus (DM) and to assess its influence on the prognosis of the DM and no-DM groups. Methods: The study used data from the National Health and Nutrition Examination Survey; 9643 participants were included. Logistic regression analysis was employed to evaluate connections between SII and DM. We used the Cox proportional hazards model, restricted cubic spline, and Kaplan-Meier curve to analyze the relationship between SII and mortality. Results: The logistic regression analysis indicated that a significant increase in the likelihood of developing DM with higher SII levels (odds ratio, 1.31; 95% CI, 1.09-1.57, P = .003). The Cox model showed that there is a positive association between increased SII and higher all-cause mortality. The hazard ratios for SII were 1.53 (1.31, 1.78), 1.61 (1.31, 1.98), and 1.41 (1.12, 1.78) in the total, DM and non-DM groups, respectively. We observed a linear correlation between SII and all-cause mortality in DM participants, whereas non-DM participants and the total population showed a nonlinear correlation. Conclusion: Elevated SII levels are linked to an augmented risk of DM. Those with DM and higher SII levels demonstrated an elevated risk of mortality.

Antioxidant, Antimicrobial, and Anti-Inflammatory Effects of Liriodendron chinense Leaves.

Liriodendron chinense has been widely utilized in traditional Chinese medicine to treat dispelling wind and dampness and used for alleviating cough and diminishing inflammation. However, the antioxidant, antimicrobial, and anti-inflammatory effects of L. chinense leaves and the key active constituents remained elusive. So, we conducted some experiments to support the application of L. chinense in traditional Chinese medicine by investigating the antioxidant, antibacterial, and anti-inflammatory abilities, and to identify the potential key constituents responsible for the activities. The ethanol extract of L. chinense leaves (LCLE) was isolated and extracted, and assays measuring ferric reducing antioxidant power, total reducing power, DPPH•, ABTS•+, and •OH were used to assess its in vitro antioxidant capacities. Antimicrobial activities of LCLE were investigated by minimal inhibitory levels, minimum antibacterial concentrations, disc diffusion test, and scanning electron microscope examination. Further, in vivo experiments including macro indicators examination, histopathological examination, and biochemical parameters measurement were conducted to investigate the effects of LCLE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LCLE was further isolated and purified through column chromatography, and LPS-induced RAW264.7 cells were constructed to assess the diminished inflammation potential of the identified chemical composites. ABTS•+ and •OH radicals were extensively neutralized by the LCLE treatment. LCLE administration also presented broad-spectrum antimicrobial properties, especially against Staphylococcus epidermidis by disrupting cell walls. LPS-induced ALI in mice was significantly ameliorated by LCLE intervention, as evidenced by the histological changes in the lung and liver tissues as well as the reductions of nitric oxide (NO), TNF-α, and IL-6 production. Furthermore, three novel compounds including fragransin B2, liriodendritol, and rhamnocitrin were isolated, purified, and identified from LCLE. These three compounds exhibited differential regulation on NO accumulation and IL-10, IL-1ß, IL-6, TNF-α, COX-2, and iNOS mRNA expression in RAW264.7 cells induced by LPS. Fragransin B2 was more effective in inhibiting TNF-α mRNA expression, while rhamnocitrin was more powerful in inhibiting IL-6 mRNA expression. LCLE had significant antioxidant, antimicrobial, and anti-inflammatory effects. Fragransin B2, liriodendritol, and rhamnocitrin were probably key active constituents of LCLE, which might act synergistically to treat inflammatory-related disorders. This study provided a valuable view of the healing potential of L. chinense leaves in curing inflammatory diseases.

Burst firing in Output-Defined Parallel Habenula Circuit Underlies the Antidepressant Effects of Bright Light Treatment.

Research highlights the significance of increased bursting in lateral habenula (LHb) neurons in depression and as a focal point for bright light treatment (BLT). However, the precise spike patterns of LHb neurons projecting to different brain regions during depression, their roles in depression development, and BLT's therapeutic action remain elusive. Here, LHb neurons are found projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and median raphe nucleus (MnR) exhibit increased bursting following aversive stimuli exposure, correlating with distinct depressive symptoms. Enhanced bursting in DRN-projecting LHb neurons is pivotal for anhedonia and anxiety, while concurrent bursting in LHb neurons projecting to the DRN, VTA, and MnR is essential for despair. Remarkably, reducing bursting in distinct LHb neuron subpopulations underlies the therapeutic effects of BLT on specific depressive behaviors. These findings provide valuable insights into the mechanisms of depression and the antidepressant action of BLT.

Discovery of Novel Ortho-Aminophenol Derivatives Targeting Lipid Peroxidation with Potent Antiferroptotic Activities.

The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho-aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho-aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho-amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.

Prophylactic nicotinamide mononucleotide (NMN) mitigates CSDS-induced depressive-like behaviors in mice via preserving of ATP level in the mPFC.

Depression is a prevalent psychiatric disorder with accumulating evidence implicating dysregulation of extracellular adenosine triphosphate (ATP) levels in the medial prefrontal cortex (mPFC). It remains unclear whether facilitating endogenous ATP production and subsequently increasing extracellular ATP level in the mPFC can exert a prophylactic effect against chronic social defeat stress (CSDS)-induced depressive-like behaviors and enhance stress resilience. Here, we found that nicotinamide mononucleotide (NMN) treatment effectively elevated nicotinamide adenine dinucleotide (NAD+) biosynthesis and extracellular ATP levels in the mPFC. Moreover, both the 2-week intraperitoneal (i.p.) injection and 3-week oral gavage of NMN prior to exposure to CSDS effectively prevented the development of depressive-like behavior in mice. These protective effects were accompanied with the preservation of both NAD+ biosynthesis and extracellular ATP level in the mPFC. Furthermore, catalyzing ATP hydrolysis by mPFC injection of the ATPase apyrase negated the prophylactic effects of NMN on CSDS-induced depressive-like behaviors. Prophylactic NMN treatment also prevented the reduction in GABAergic inhibition and the increase in excitability in mPFC neurons projecting to the lateral habenula (LHb). Collectively, these findings demonstrate that the prophylactic effects of NMN on depressive-like behaviors are mediated by preventing extracellular ATP loss in the mPFC, which highlights the potential of NMN supplementation as a novel approach for protecting and preventing stress-induced depression in susceptible individuals.

Subventricular zone-associated classification in isocitrate dehydrogenase-wildtype glioblastomas: improved prognostic value through integration of FLAIR with contrast-enhanced imaging.

OBJECTIVE: Controversy surrounds the prognostic value of contrast-enhanced T1-weighted (T1CE) imaging-based subventricular zone (SVZ) classification in isocitrate dehydrogenase (IDH)-wildtype glioblastomas (GBMs). In this study, the authors aimed to assess the potential of incorporating FLAIR imaging into T1CE imaging-based classification for improving prognostic accuracy. METHODS: A retrospective analysis was conducted on 281 patients with IDH-wildtype GBM. T1CE imaging-based classification was performed, and T2-weighted/FLAIR imaging was integrated to evaluate its prognostic estimation ability. Based on the relationship between the tumors and SVZ, patients were categorized into SVZ+ and SVZ- cohorts based on T1CE and T2-weighted/FLAIR imaging findings. Kaplan-Meier and Cox proportional hazards regression analyses were used to assess progression-free survival (PFS) and overall survival (OS), respectively. Patients were then categorized into three subgroups based on their combined classifications: group 1 (SVZ+ on T1CE and T2-weighted/FLAIR imaging), group 2 (SVZ- on T1CE but SVZ+ on T2-weighted/FLAIR imaging), and group 3 (SVZ- on T1CE and T2-weighted/FLAIR imaging). Subgroup analysis was used to evaluate differences in clinical and molecular factors as well as in prognoses. RESULTS: The T1CE imaging-based classification failed to stratify OS between SVZ+ and SVZ- cohorts (16.0 vs 20.0 months, p = 0.36). Survival analysis revealed similar prognoses for patients in groups 1 and 2, and patients in group 2 exhibited worse OS compared with those in group 3 (19.0 vs 23.5 months, p = 0.024). Logistic regression identified lower Karnofsky Performance Status (KPS) (p = 0.011), tumor diameter (p = 0.002), and telomerase reverse transcriptase (TERT) promoter mutation (p = 0.003) to be associated with a higher incidence of group 2 GBMs. Additionally, T2-weighted/FLAIR imaging-based classification provided significant prognostic value (17.0 vs 23.5 months p = 0.021) and was found to be an independent prognostic factor in the Cox multivariate analysis (HR 1.79, 95% CI 1.08-2.96; p = 0.024). CONCLUSIONS: This study underscores the limitations of T1CE imaging-based SVZ-associated classification in predicting prognosis for IDH-wildtype GBMs. The authors therefore propose an integrated approach that involves T2-weighted/FLAIR imaging that can provide improved prognostic ability. Notably, the presence of TERT promoter mutation was identified as a critical factor in nonenhancing tumor infiltration into the SVZ. Further validation through extensive cohort studies is recommended to confirm these findings.

PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

A visual circuit related to the parabrachial nucleus for the antipruritic effects of bright light treatment.

In addition to its role in vision, light also serves non-image-forming visual functions. Despite clinical evidence suggesting the antipruritic effects of bright light treatment, the circuit mechanisms underlying the effects of light on itch-related behaviors remain poorly understood. In this study, we demonstrate that bright light treatment reduces itch-related behaviors in mice through a visual circuit related to the lateral parabrachial nucleus (LPBN). Specifically, a subset of retinal ganglion cells (RGCs) innervates GABAergic neurons in the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), which subsequently inhibit CaMKIIα+ neurons in the LPBN. Activation of both the vLGN/IGL-projecting RGCs and the vLGN/IGL-to-LPBN projections is sufficient to reduce itch-related behaviors induced by various pruritogens. Importantly, we demonstrate that the antipruritic effects of bright light treatment rely on the activation of the retina-vLGN/IGL-LPBN pathway. Collectively, our findings elucidate a visual circuit related to the LPBN that underlies the antipruritic effects of bright light treatment.

Alteration of the gut microbiome in patients with heart failure: A systematic review and meta-analysis.

Recent research has revealed that alterations of the gut microbiome (GM) play a comprehensive role in the pathophysiology of HF. However, findings in this field remain controversial. In this study, we focus on differences in GM diversity and abundance between HF patients and non-HF people, based on previous 16 S ribosomal RNA (16rRNA) gene sequencing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search of PubMed, Web of Science, Embase, Cochrane Library, and Ovid databases using the keyword "Heart failure" and "Gastrointestinal Microbiome". A significant decrease in alpha diversity was observed in the HF patients (Chao1, I2 = 87.5 %, p < 0.001; Shannon index, I2 = 62.8 %, p = 0.021). At the phylum level, the HF group exhibited higher abundances of Proteobacteria (I2 = 92.0 %, p = 0.004) and Actinobacteria (I2 = 82.5 %, p = 0.010), while Bacteroidetes (I2 = 45.1 %, p = 0.017) and F/B ratio (I2 = 0.0 %, p＜0.001) were lower. The Firmicutes showed a decreasing trend but did not reach statistical significance (I2 = 82.3 %, p = 0.127). At the genus level, the relative abundances of Streptococcus, Bacteroides, Alistipes, Bifidobacterium, Escherichia-Shigella, Enterococcus and Klebsiella were increased in the HF group, whereas Ruminococcus, Faecalibacterium, Dorea and Megamona exhibited decreased relative abundances. Dialister, Blautia and Prevotella showed decreasing trends but without statistical significance. This observational meta-analysis suggests that GM changes are associated with HF, manifesting as alterations in GM abundance, disruptions in the production of short-chain fatty acids (SCFAs) bacteria, and an increase in trimethylamine N-oxide (TMAO) producing bacteria.

Tailored different sizes of quantum dot nanobeads for sensitive and quantitative detection based on the competition fluorescence-linked immunosorbent assay platform.

Highly stable and multicolor photoluminescent (PL) quantum dots (QDs) have attracted widespread attention as ideal probe materials in the field of in vitro diagnostics (IVD), especially the fluorescence-linked immunosorbent assay (FLISA), due to their advantages of high-throughput, high stability, and high sensitivity. However, the size of QDs as fluorescent probes have significant effects on antigen-antibody performance. Therefore, it is critical to design suitable QDs for obtain excellent quantitative detection-based biosensors. In this paper, we prepared different sizes of aqueous QDs (30 nm, 116 nm, 219 nm, and 320 nm) as fluorescent probes to optimize the competitive FLISA platform. The SARS-CoV-2 neutralizing antibody (NTAB) assay was used as an example, and it was found that the size of the QDs has a significant impact on the antigen-antibody binding efficiency and detection sensitivity in competitive FLISA platform. The results showed that these QD nanobeads (QBs, ∼219 nm) could be used as a labeled probe for competitive FLISA, with half-maximal inhibitory concentration (IC50) of 1.34 ng/mL and limit of detection (LOD) of 0.21 pg/mL for NTAB detection. More importantly, the results showed good specificity and accuracy, and the QB219 probe was able to efficiently bind NTAB without interference from other substances in the serum. Given the above advantages, the nanoprobe material (∼200 nm) offers considerable potential as a competitive FLISA platform in the field of IVD.

Identifying optimal surgical approach among T1N2-3M0 non-small cell lung cancer patients: a population-based analysis.

Background: Whether stage T1N2-3M0 non-small cell lung cancer (NSCLC) patients could benefit from surgery and the optimal surgical procedure have remained controversial and unclear. This study aimed to investigate whether stage T1N2-3M0 NSCLC can benefit from different surgery types and develop a tool for survival prediction. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with stage T1N2-3M0 NSCLC between 2000 and 2015. A 1:1 propensity score-matched (PSM) analysis was used to balance the distribution of clinical characteristics. Survival analyses were performed by using the Kaplan-Meier (KM) curves and Cox proportional hazards regression. All patients were randomly split at a ratio of 7:3 into training and validation cohorts. The nomogram was constructed by integrating all independent predictors for overall survival (OS) and cancer-specific survival (CSS). The model's performance was evaluated by discrimination, calibration ability, and risk stratification ability. Results: A total of 4,671 patients were enrolled. After 1:1 PSM, the distribution proportions of clinical characteristics in 1,146 patients were balanced (all P>0.05). The non-surgical approach was associated with worse survival compared with sublobectomy and lobectomy in the unmatched and matched cohorts. The multivariate Cox analysis showed that sublobectomy and lobectomy were both related to better OS and CSS rates compared with no surgery (P<0.001). Moreover, the results of subgroup analyses based on age, N stage, and radiotherapy or chemotherapy strategy were consistent. A total of 801 patients were included in the training cohort and 345 cases constituted the validation cohort. The nomogram constructed for the 1-, 3-, and 5-year OS and CSS prediction showed good discrimination, performance, and calibration both in the training and validation sets. Significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed (all P<0.001). Conclusions: Stage T1N2-3M0 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provides better survival benefits. We developed and validated nomograms, which could offer clinicians instructions for strategy making.

Physiological Regulation of Photosynthetic-Related Indices, Antioxidant Defense, and Proline Anabolism on Drought Tolerance of Wild Soybean (Glycine soja L.).

Wild soybean (Glycine soja L.), drought-tolerant cultivar Tiefeng 31 (Glycine max L.), and drought-sensitive cultivar Fendou 93 (Glycine max L.) were used as materials to investigate the drought tolerance mechanism after 72 h 2.5 M PEG 8000 (osmotic potential -0.54 MPa)-simulated drought stress at the seedling stage. The results indicated that the leaves of the G. soja did not wilt under drought stress. However, both the drought-tolerant and drought-sensitive cultivated soybean cultivars experienced varying degrees of leaf wilt. Notably, the drought-sensitive cultivated soybean cultivars exhibited severe leaf wilt after the drought stress. Drought stress was determined to have a significant impact on the dry matter of the above-ground part of the drought-sensitive cultivar Fendou 93, followed by the drought-tolerant cultivar Tiefeng 31, with the lowest reduction observed in G. soja. Furthermore, the presence of drought stress resulted in the closure of leaf stomata. G. soja exhibited the highest proportion of stomatal opening per unit area, followed by the drought-tolerant cultivar Tiefeng 31, while the drought-sensitive cultivar Fendou 93 displayed the lowest percentage. Photosynthesis-related indexes, including photosynthetic rate, intercellular CO2, transpiration rate, and stomatal conductance, decreased in Fendou 93 and Tiefeng 31 after drought stress, but increased in G. soja. In terms of the antioxidant scavenging system, lower accumulation of malondialdehyde (MDA) was observed in G. soja and Tiefeng 31, along with higher activities of superoxide dismutase (SOD, EC 1.15.1.1) and catalase (CAT, EC 1.11.1.6) to counteract excess reactive oxygen species and maintain cell membrane integrity. In contrast, the drought-sensitive cultivar Fendou 93 had higher MDA content and higher activities of ascorbate peroxidase (APX, EC 1.11.1.11) and peroxidase (POD, 1.11.1.7). G. soja and Tiefeng 31 also exhibited less accumulation of osmolytes, including soluble sugar, soluble protein, and free proline content. The activities of δ-OAT, ProDH, and P5CS, key enzymes in proline anabolism, showed an initial increase under drought stress, followed by a decrease, and then an increase again at the end of drought stress in G. soja. Before drought stress, Tiefeng 31 had higher activities of ProDH and P5CS, which decreased with prolonged drought stress. Fendou 93 experienced an increase in the activities of δ-OAT, ProDH, and P5CS under drought stress. The δ-OAT gene expression levels were up-regulated in all three germplasms. The expression levels of the P5CS gene in Fendou 93 and Tiefeng 31 were down-regulated, while G. soja showed no significant change. The expression of the P5CR gene and ProDH gene was down-regulated in Fendou 93 and Tiefeng 31, but up-regulated in G. soja. This indicates that proline content is regulated at both the transcription and translation levels.

Reproductive factors and risk of cardiovascular diseases and all-cause and cardiovascular mortality in American women: NHANES 2003-2018.

BACKGROUND: The evidence regarding the association of reproductive factors with cardiovascular diseases (CVDs) is limited. AIMS: To investigate the relationship of reproductive factors with the risk of CVDs, as well as all-cause and cardiovascular mortality. METHODS: This study included 16,404 adults with reproductive factors from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2019. Logistic models and restricted cubic spline models were used to assess the association of reproductive factors with CVDs. COX proportional hazards models and restricted cubic spline models, with adjustment for potential confounding, were employed to analyze the relation between reproductive factors and cardiovascular and all-cause death. RESULTS: There is a nonlinear relationship between age at menarche and CVDs. Age at menopause ≤ 11(OR 1.36, 95% CI 1.10-1.69) was associated with an increased risk of CVDs compared to ages 12-13 years. Age at Menopause ≤ 44 (OR 1.69, 95% CI 1.40-2.03) was associated with increased CVDs compared to age 35-49 years. Number of pregnancies ≥ 5(OR 1.26, 95% CI 1.02-1.55) was associated with an increased risk of CVDs compared to one pregnancy. In continuous variable COX regression models, a later age at menopause (HR 0.98, 95% CI 0.97-0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97-0.99) were associated with a decreased risk of all-cause death. A later age at menopause (HR 0.98, 95% CI 0.97-0.99) and a longer reproductive lifespan (HR 0.98, 95% CI 0.97-0.99) were associated with a decreased risk of cardiac death. CONCLUSIONS: Female reproductive factors are significant risk factors for CVDs American women.

CircNCX1 modulates cardiomyocyte proliferation through promoting ubiquitination of BRG1.

In mammal, the myocardium loss cannot be recovered spontaneously due to the negligible proliferation ability of mature mammalian cardiomyocyte. However, accumulated evidence has shown that terminally differentiated mammalian cardiomyocyte also has proliferation potency, which can be mediated by several mechanisms. Here, we reported that circNCX1, the most abundant circular RNA in mammalian hearts, can affect the proliferation of murine cardiomyocytes. The level of circNCX1 is significantly elevated during heart development. Forced expression of circNCX1 inhibits cardiomyocyte proliferation, while silencing of endogenous circNCX1 in cardiomyocyte shows reversed effect in vitro. Mechanistically, circNCX1 functions via negatively regulating transcription activator BRG1. It bridges BRG1 and FBXW7 to enhance the ubiquitination and degradation of BRG1, decreasing the expression of BMP10 to lead cell cycle arrest. In summary, our study first revealed that circNCX1 is a modulator of cardiomyocyte proliferation.

Multimodal phototherapy agents target lipid droplets for near-infrared imaging-guided type I photodynamic/photothermal therapy.

The construction and optimization of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) functions remain challenging. In this study, we aimed to design and synthesize four donor-acceptor (D-A) type aggregation-induced emission molecules: PSI, TPSI, PSSI, and TPSSI. We employed phenothiazine as an electron donor and 1,3-bis(dicyanomethylidene)indan as a strong electron acceptor in the synthesis process. Among them, TPSSI exhibited efficient type I reactive oxygen species generation, high photothermal conversion efficiency (45.44 %), and near-infrared emission. These observations can be attributed to the introduction of a triphenylamine electron donor group and a thiophene unit, which resulted in increased D-A strengths, a reduced singlet-triplet energy gap, and increased free intramolecular motion. TPSSI was loaded into bovine serum albumin to prepare biocompatible TPSSI nanoparticles (NPs). Our results have indicated that TPSSI NPs can target lipid droplets with negligible dark toxicity and can efficiently generate O2•- in hypoxic tumor environments. Moreover, TPSSI NPs selectively targeted 4T1 tumor tissues and exhibited a good PDT-PTT synergistic effect in vitro and in vivo. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technologies. STATEMENT OF SIGNIFICANCE: The construction of a single phototherapeutic agent with photoluminescence, type I photodynamic therapy, and photothermal therapy functions, and its optimization remain challenging. In this study, we construct four donor-acceptor aggregation-induced emission molecules using phenothiazine as an electron donor and 1,3-Bis(dicyanomethylidene)indan as a strong electron acceptor. By optimizing the molecular structure, an integrated phototherapy agent with fluorescence imaging ability and high photodynamic / photothermal therapy performance was prepared. We believe that the successful preparation of multifunctional phototherapeutic agents will promote the development of efficient tumor diagnosis and treatment technology.

Extracellular ATP Is a Homeostatic Messenger That Mediates Cell-Cell Communication in Physiological Processes and Psychiatric Diseases.

Neuronal activity is the basis of information encoding and processing in the brain. During neuronal activation, intracellular ATP (adenosine triphosphate) is generated to meet the high-energy demands. Simultaneously, ATP is secreted, increasing the extracellular ATP concentration and acting as a homeostatic messenger that mediates cell-cell communication to prevent aberrant hyperexcitability of the nervous system. In addition to the confined release and fast synaptic signaling of classic neurotransmitters within synaptic clefts, ATP can be released by all brain cells, diffuses widely, and targets different types of purinergic receptors on neurons and glial cells, making it possible to orchestrate brain neuronal activity and participate in various physiological processes, such as sleep and wakefulness, learning and memory, and feeding. Dysregulation of extracellular ATP leads to a destabilizing effect on the neural network, as found in the etiopathology of many psychiatric diseases, including depression, anxiety, schizophrenia, and autism spectrum disorder. In this review, we summarize advances in the understanding of the mechanisms by which extracellular ATP serves as an intercellular signaling molecule to regulate neural activity, with a focus on how it maintains the homeostasis of neural networks. In particular, we also focus on neural activity issues that result from dysregulation of extracellular ATP and propose that aberrant levels of extracellular ATP may play a role in the etiopathology of some psychiatric diseases, highlighting the potential therapeutic targets of ATP signaling in the treatment of these psychiatric diseases. Finally, we suggest potential avenues to further elucidate the role of extracellular ATP in intercellular communication and psychiatric diseases.

A guide to troubleshooting metal sacrificial anodes for organic electrosynthesis.

The development of reductive electrosynthetic reactions is often enabled by the oxidation of a sacrificial metal anode, which charge-balances the reductive reaction of interest occurring at the cathode. The metal oxidation is frequently assumed to be straightforward and innocent relative to the chemistry of interest, but several processes can interfere with ideal sacrificial anode behavior, thereby limiting the success of reductive electrosynthetic reactions. These issues are compounded by a lack of reported observations and characterization of the anodes themselves, even when a failure at the anode is observed. Here, we weave lessons from electrochemistry, interfacial characterization, and organic synthesis to share strategies for overcoming issues related to sacrificial anodes in electrosynthesis. We highlight common but underexplored challenges with sacrificial anodes that cause reactions to fail, including detrimental side reactions between the anode or its cations and the components of the organic reaction, passivation of the anode surface by an insulating native surface film, accumulation of insulating byproducts at the anode surface during the reaction, and competitive reduction of sacrificial metal cations at the cathode. For each case, we propose experiments to diagnose and characterize the anode and explore troubleshooting strategies to overcome the challenge. We conclude by highlighting open questions in the field of sacrificial-anode-driven electrosynthesis and by indicating alternatives to traditional sacrificial anodes that could streamline reaction optimization.

[Chemical Speciation, Influencing Factors, and Regression Model of Heavy Metals in Farmland of Typical Carbonate Area with High Geological Background, Southwest China].

The speciation of heavy metals in soil is an important factor determining their bioavailability and toxicity, and it is crucial for the scientific assessment of ecological risks posed by heavy metals in soils of typical carbonate areas with high geological background in southwest China. In order to investigate the distribution of speciation of heavy metals in soils of carbonate rock with high geological background, we selected a typical carbonate rock distribution area in Guizhou Province and used the second national soil survey plots as sampling units. A total of 309 topsoil samples were collected from farmland. The improved Tessier seven-step sequential extraction method was used to analyze the seven chemical forms of heavy metals:water-soluble (F1); exchangeable (F2); carbonate-bound (F3); weakly organic-bound (F4); iron-manganese oxide-bound (F5); strongly organic-bound (F6); and residual (F7) forms of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn). The study found that the residual forms of heavy metals As, Cu, Hg, Ni, Pb, and Zn in the soil accounted for more than 50%, the effective components (F1-F3) accounted for less than 5%, and the potential biological effective components (F4-F6) were less than 45%, indicating low reactivity and low ecological risk. The effective and potentially bioavailable components of Cd accounted for 55.49% and 29.37%, respectively, which were much higher than those of other heavy metals. The ecological risk based on the speciation of heavy metals in the soil was much lower than that based on the total content of heavy metals. The stepwise regression equations could effectively establish the relationship between the bioavailable and potentially bioavailable fractions of Cd, Cu, and Pb and their influencing factors. Total heavy metal contents and pH value were important factors influencing the speciation of heavy metals in soils of carbonate rock with high geological background areas. The enrichment of heavy metal elements in the residual fraction was influenced by long-term zinc smelting activities and the weathering of carbonate rocks into soil. Soil organic matter (OM) and oxide content had a relatively small influence on the speciation of heavy metals in the soil.

A young woman with Mycobacterium chelonae complex infection caused by facial stem cell injection.

In outpatient settings, Mycobacterium chelonae complex infection brought on by cosmetic injections are rather uncommon. We came across a case of infection brought on by a commercial stem cell injection.