A Noncentrosymmetric Metal-Free Borophosphate: Achieving a Large Birefringence and Excellent Stability by Covalent-Linkage.

Organic-inorganic hybrid linear and nonlinear optical (NLO) materials have received increasingly wide spread attention in recent years. Herein, the first hybrid noncentrosymmetric (NCS) borophosphate, (C5H6N)2B2O(HPO4)2 (4PBP), is rationally designed and synthesized by a covalent-linkage strategy. 4-pyridyl-boronic acid (4 PB) is considered as a bifunctional unit, which may effectively improve the optical properties and stability of the resultant material. On the one hand, 4 PB units are covalently linked with PO3(OH) groups via strong B-O-P connections, which significantly enhances the thermal stability of 4PBP (decomposition at 321, vs lower 200 °C of most of hybrid materials). On the other hand, the planar π-conjugated C5H6N units and their uniform layered arrangements represent large structural anisotropy and hyperpolarizability, achieving the largest birefringence (0.156 @ 546 nm) in the reported borophosphates and a second-harmonic generation response (0.7 × KDP). 4PBP also exhibits a wide transparency range (0.27-1.50 µm). This work not only provides a promising birefringent material, but also offers a practical covalent-attachment strategy for the rational design of new high-performance optical materials.

Efficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

Purpose: This study aimed to assess the efficacy and safety of Panax notoginseng saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI). Methods: Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131). Result: Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, p < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, p < 0.05]; (3) reduction in myocardial infarct size [MD = -6.53, p < 0.05]; (4) lower ST segment elevation amplitude [MD = -0.48, p < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = -11.19, p < 0.05], cardiac troponin T [MD = -3.01, p < 0.05], and cardiac troponin I [MD = -10.72, p < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = -91.57, p < 0.05], left ventricular ejection fraction [MD = 5.91, p < 0.05], left ventricular end-diastolic dimension [MD = -3.08, p < 0.05], and cardiac output [MD = 0.53, p < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = -2.99, p < 0.05], tumor necrosis factor-α [MD = -6.47, p < 0.05], interleukin-6 [MD = -24.46, p < 0.05], and pentraxin-3 [MD = -2.26, p < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = -20.56, p < 0.05] and increased nitric oxide [MD = 1.33, p < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, p < 0.05]; (10) no significant difference in adverse events [OR = 1.00, p = 1.00]. Conclusion: This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131).

Association between PEMT rs7946 and blood pressure levels in Chinese adolescents.

OBJECTIVES: This study was to explore blood pressure levels in Chinese adolescents with different genotypes of phosphatidylethanolamine N-methyltransferase (PEMT) gene (PEMT) rs7946, as well as effects of dietary intake on blood pressure levels with different genders and different genotypes of PEMT rs7946. METHODS: PEMT rs7946 genotypes were identified by PCR-restriction fragment length polymorphism and verified by DNA sequencing. Blood pressure was measured using a standard mercury sphygmomanometer. Dietary intakes were analyzed based on a 3-day diet diary, and dietary components were calculated using computer software. RESULTS: A total of 721 high school students (314 males and 407 females) at the age of 16.86 ±â€…0.59 years were included. The A allele carriers of PEMT rs7946 had increased levels of SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP) than the GG homozygotes in the female subjects. There were significant interactions between PEMT rs7946 and gender on SBP and MAP levels, regardless of whether an unadjusted or adjusted model was used. When dietary intake was taken into account, fat intake was positively associated with SBP and PP in the male GG homozygotes, while protein intake was positively associated with PP in the female A allele carriers of PEMT rs7946. CONCLUSION: This study suggests that PEMT rs7946 is significantly associated with blood pressure levels in human being. There might be interactions among PEMT rs7946, gender, and dietary intake on blood pressure levels in the adolescent population.

Granulocyte-Macrophage Colony-Stimulating Factor in Combination With Chemoradiation for Recurrent or Metastatic Cervical Cancer.

Recurrent or metastatic cervical cancer carries a bleak prognosis and presents a formidable challenge in terms of treatment. Granulocyte-macrophage colony-stimulating factor (GM-CSF) increases the body's immune response by enhancing antigen presentation, which has been rarely reported in recurrent or metastatic cervical cancer. A 44-year-old woman presented to the hospital with vaginal bleeding four years after radical hysterectomy for stage IB2 squamous cell carcinoma (SCC) of the cervix (grade II-III). Gynecological examination and imaging revealed a vaginal mass, and the biopsy confirmed the recurrence of grade III SCC. The patient was treated with chemoradiation (CRT) combined with immunoadjuvant GM-CSF and achieved complete remission and a progression-free survival of two years.

Design, synthesis, and biological evaluation of selective covalent inhibitors of FGFR4.

Aberrant signaling via fibroblast growth factor 19 (FGF19)/fibroblast growth factor receptor 4 (FGFR4) has been identified as a driver of tumorigenesis and the development of many solid tumors, making FGFR4 is a promising target for anticancer therapy. Herein, we designed and synthesized a series of bis-acrylamide covalent FGFR4 inhibitors and evaluated their inhibitory activity against FGFRs, FGFR4 mutants, and their antitumor activity. CXF-007, verified by mass spectrometry and crystal structures to form covalent bonds with Cys552 of FGFR4 and Cys488 of FGFR1, exhibited stronger selectivity and potent inhibitory activity for FGFR4 and FGFR4 cysteine mutants. Moreover, CXF-007 exhibited significant antitumor activity in hepatocellular carcinoma cell lines and breast cancer cell lines through sustained inhibition of the FGFR4 signaling pathway. In summary, our study highlights a novel covalent FGFR4 inhibitor, CXF-007, which has the potential to overcome drug-induced FGFR4 mutations and might provide a new strategy for future anticancer drug discovery.

[Medium and Long-term Carbon Emission Projections and Emission Reduction Potential Analysis of the Lingang Special Area Based on the LEAP Model].

Based on the existing statistical data of the Lingang Special Area in Shanghai and considering its future socio-economic development， industrial structure， and technological development， a LEAP-Lingang model was developed to analyze the evolution trends of energy demand and carbon emissions under the baseline scenario， low-carbon scenario， and enhanced low-carbon scenario. To enhance the prediction accuracy of the model， the Logistic population growth model was used to predict future population data， and the learning curve model was used to simulate the cost evolution trend of related carbon reduction technologies. In addition， an economic evaluation model for carbon reduction technologies was developed， and the economic costs and emission reduction potential of typical carbon reduction technologies were evaluated by drawing a marginal emission reduction cost curve. The results showed that under the enhanced low-carbon scenario， the renewable energy accounted for 69% of the primary energy consumption， and the electric energy accounted for 91% of the terminal energy demand in 2060. The Lingang Special Area could achieve carbon peak by 2030， and the carbon emissions in 2060 were predicted to decrease by 94% compared to that in the baseline scenario. In terms of contribution to emission reduction， clean energy substitution， industrial structure optimization， and terminal energy efficiency improvement played a key role in reducing carbon emissions near the port. In the medium term （until 2035）， they were predicted to contribute 35.1%， 27.3%， and 16.2% of carbon emissions， respectively， and in the long term （until 2060）， they should contribute 50.6%， 8.75%， and 7.7% of carbon emissions， respectively. Regarding specific carbon reduction technologies， hydrogen power generation； water electrolysis for hydrogen； and carbon capture， utilization， and storage （CCUS） technology were of great significance for achieving net-zero emissions， but the costs of emission reduction were relatively high. The research results can provide ideas and references for the low-carbon and green development of the Lingang Special Area and related areas.

Repeat DNA methylation is modulated by adherens junction signaling.

Through its involvement in gene transcription and heterochromatin formation, DNA methylation regulates how cells interact with their environment. Nevertheless, the extracellular signaling cues that modulate the distribution of this central chromatin modification are largely unclear. DNA methylation is highly abundant at repetitive elements, but its investigation in live cells has been complicated by methodological challenges. Utilizing a CRISPR/dCas9 biosensor that reads DNA methylation of human α-satellite repeats in live cells, we here uncover a signaling pathway linking the chromatin and transcriptional state of repetitive elements to epithelial adherens junction integrity. Specifically, we find that in confluent breast epithelial cell monolayers, α-satellite repeat methylation is reduced by comparison to low density cultures. This is coupled with increased transcriptional activity at repeats. Through comprehensive perturbation experiments, we identify the junctional protein E-cadherin, which links to the actin cytoskeleton, as a central molecular player for signal relay into the nucleus. Furthermore, we find that this pathway is impaired in cancer cells that lack E-cadherin and are not contact-inhibited. This suggests that the molecular connection between cell density and repetitive element methylation could play a role in the maintenance of epithelial tissue homeostasis.

Comparison of the efficacy of steroid-free versus classic steroid-containing regimens in primary membranous nephropathy.

Objective: To compare the efficacy of a steroid-free regimen with steroid-based treatment in managing primary membranous nephropathy (PMN) and investigate the potential benefits of steroid-free regimens in PMN therapy. Methods: This was a single-centre prospective cohort study. A total of 81 patients were divided into two groups according to their medication regimen: a rituximab (RTX)/tacrolimus (TAC) group (low-dose RTX combined with low-dose TAC group, without steroids, n = 31) and a prednisone (P)/TAC group (P combined with TAC group, n = 61). The changes in 24-h urine protein quantification, levels of blood albumin, blood creatinine, total cholesterol, triglyceride and fasting blood glucose as well as anti-phospholipase A2 receptor antibody titres were observed in both groups before treatment and after 1, 3, 6 and 12 months of treatment. Clinical remission (complete and partial remission), serological remission and recurrence were assessed in both groups after treatment, and the occurrence of adverse reactions was observed. Results: 1) Before treatment, there was no significant difference in baseline values between the two groups (p > 0.05). 2) After 12 months of treatment, the 24-h proteinuria and total cholesterol levels in the RTX/TAC group were significantly lower than those in the P/TAC group (p < 0.05). 3) After 6 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). After 12 months of treatment, the clinical remission rate of the RTX/TAC group was significantly higher than that of the P/TAC group (p < 0.05). (4) After 3, 6 and 12 months of treatment, serological remission rates in the RTX/TAC group were significantly higher than those in the P/TAC group (p < 0.05). During treatment, the anti-PLA2R antibody titres in the RTX/TAC group remained lower than those in the P/TAC group (p < 0.05). Conclusion: The low-dose RTX combined with low-dose TAC steroid-free regimen induces serological remission in patients with PMN earlier than the classic regimen of P combined with TAC, and there was no significant difference in adverse effects between the two groups. Besides, the long-term clinical remission effect of low-dose RTX combined with low-dose TAC is better than that of P combined with TAC.

Bacillus licheniformis ameliorates Aflatoxin B1-induced testicular damage by improving the gut-metabolism-testis axis.

Global aflatoxin B1 (AFB1) contamination is inevitable, and it can significantly damage testicular development. However, the current mechanism is confusing. Here, by integrating the transcriptome, microbiome, and serum metabolome, we comprehensively explain the impact of AFB1 on testis from the gut-metabolism-testis axis. Transcriptome analysis suggested that AFB1 exposure directly causes abnormalities in testicular inflammation-related signalling, such as tumor necrosis factor (TNF) pathway, and proliferation-related signalling pathways, such as phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT) pathway, which was verified by immunofluorescence. On the other hand, we found that upregulated inflammatory factors in the intestine after AFB1 exposure were associated with intestinal microbial dysbiosis, especially the enrichment of Bacilli, and enrichment analysis showed that this may be related to NLR family pyrin domain containing 3 (NLRP3)-mediated NOD-like receptor signalling. Also, AFB1 exposure caused blood metabolic disturbances, manifested as decreased hormone levels and increased oxidative stress. Significantly, B. licheniformis has remarkable AFB1 degradation efficiency (> 90%). B. licheniformis treatment is effective in attenuating gut-testis axis damage caused by AFB1 exposure through the above-mentioned signalling pathways. In conclusion, our findings indicate that AFB1 exposure disrupts testicular development through the gut-metabolism-testis axis, and B. licheniformis can effectively degrade AFB1.

Methyltransferase METTL3-mediated maturation of miR-4654 facilitates high glucose-induced apoptosis and oxidative stress in lens epithelial cells via decreasing SOD2.

N6-methyladenosine (m6 A) modification has been reported to have roles in modulating the development of diabetic cataract (DC). Methyltransferase-like 3 (METTL3) is a critical m6 A methyltransferase involving in m6 A modification activation. Here, we aimed to explore the action and mechanism of METTL3-mediated maturation of miR-4654 in DC progression. Human lens epithelial cells (HLECs) were exposed to high glucose (HG) to imitate DC condition in vitro. Levels of genes and proteins were tested via qRT-PCR and western blotting assays. The proliferation and apoptosis of HLECs were evaluated by cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays, respectively. Oxidative stress was analyzed by detecting the contents of reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA). The binding of miR-4654 and SOD2 was confirmed by dual-luciferase reporter assay. The m6 A-RNA immunoprecipitation (MeRIP) assay detected the m6 A modification profile. Thereafter, we found that miR-4654 expression was elevated in DC samples and HG-induced HLECs. MiR-4654 knockdown reversed HG-mediated apoptosis and oxidative stress in HLECs. Mechanistically, miR-4654 directly targeted SOD2, silencing of SOD2 abolished the protective effects of miR-4654 knockdown on HLECs under HG condition. In addition, METTL3 induced miR-4654 maturation through promoting pri-miR-4654 m6 A modification, thereby increasing miR-4654 content in HLECs. METTL3 was highly expressed in DC samples and HG-induced HLECs, METTL3 deficiency protected HLECs against HG-mediated apoptotic and oxidative injury via down-regulating miR-4654. In all, METTL3 induced miR-4654 maturation in a m6 A-dependent manner, which was then reduced SOD2 expression, thus promoting apoptosis and oxidative stress in HLECs, suggesting a novel path for DC therapy.

Relationship between bedtime, nighttime sleep duration, and anxiety symptoms in preschoolers in China.

Background: Sleep problems in preschoolers are becoming increasingly prominent, and the association between sleep status and anxiety symptoms has attracted growing attention. However, studies investigating the relationship between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms remain scant. We used the large sample data from the Longhua Cohort Study of Children in Shenzhen, China (LCCS) to analyze the association between bedtime and sleep in preschoolers and their anxiety symptoms. Methods: A cross-sectional study of 69,138 preschoolers in Longhua District, Shenzhen, China was conducted in 2022. Data on sociodemographic characteristics of families, bedtime, nighttime sleep duration of preschoolers, and their anxiety symptoms (measured by the Spence Preschool Children Anxiety Scale) were collected through a structured questionnaire completed by the parents. Using binary logistic regression models, the relationship between bedtime, nighttime sleep duration, and childhood anxiety symptoms was examined. Results: The bedtimes of preschoolers were concentrated between 21:01-22:00 (52.41%). Among the preschoolers, 38.70% had bedtimes later than 22:00, and 75.49% had insufficient nighttime sleep duration. The positive screening rate for anxiety symptoms among preschoolers was 3.50%. After adjusting for confounding factors using binary logistic regression models, compared with preschoolers with bedtime ≤21:00, The OR (95%CI) values of anxiety in preschoolers with bedtime ≥23:01, 22:01-23:00 and 21:01-22:00 were 2.86 (2.21-3.69), 1.51 (1.27-1.79) and 1.48 (1.26-1.76), respectively. Compared with those with sufficient nighttime sleep duration, the OR (95%CI) of children with nighttime sleep duration less than 9 h was 1.36 (1.23-1.51). Conclusion: An association exists between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms. Preschoolers with 21:00 for bedtime and a nighttime sleep duration of 10 h may have lower anxiety symptoms. These findings support the importance of adequate sleep for preventing anxiety symptoms in children.

Imaging metabolic mechanisms and the binding behavior of nutrients/transporters of edible Matricaria flowers VOCs.

To promote the consumption of flowers and to utilize the nutritional value of proteins, the efficacy of the beneficial components of flowers has been intensively studied. Anthemis nobilis was used as the study object, and all its volatile components (VOCs) were fingerprinted using headspace solid-phase micro-extraction gas-mass spectrometry (HS-SPME/GC-MS). GC-MS fingerprints of five parts of Anthemis nobilis were established using three proteins, bovine lactoferrin (BLF), bovine lactoglobulin (ß-Lg), and human serum albumin (HSA), as nutrient transporters. The interactions between the volatile components from different parts of the mother chrysanthemum plant and the nutrient/transport proteins were investigated. The results of fingerprinting showed that the flavor components were dominated by alkenes. In addition, this study revealed that among the three nutrient transporters, the strongest binding to the adsorbed volatile components was HSA, followed by BLF, and ß-Lg was second. In addition, a characteristic molecule, camphene, was screened. Integrated molecular simulation using fluorescence spectroscopy was used to validate the results of the interaction of the nutrient/transport proteins systems with characteristic molecule. The properties of the characteristic molecules such as absorption, distribution, metabolism, excretion and toxicity in vivo were analyzed using ADMET to provide a theoretical basis for the preparation of flower-flavored dairy products.

Selective disruption of mTORC1 and mTORC2 in VTA astrocytes induces depression and anxiety-like behaviors in mice.

Dysfunction of the mechanistic target of rapamycin (mTOR) signaling pathway is implicated in neuropsychiatric disorders including depression and anxiety. Most studies have been focusing on neurons, and the function of mTOR signaling pathway in astrocytes is less investigated. mTOR forms two distinct complexes, mTORC1 and mTORC2, with key scaffolding protein Raptor and Rictor, respectively. The ventral tegmental area (VTA), a vital component of the brain reward system, is enrolled in regulating both depression and anxiety. In the present study, we aimed to examine the regulation effect of VTA astrocytic mTOR signaling pathway on depression and anxiety. We specifically deleted Raptor or Rictor in VTA astrocytes in mice and performed a series of behavioral tests for depression and anxiety. Deletion of Raptor and Rictor both decreased the immobility time in the tail suspension test and the latency to eat in the novelty suppressed feeding test, and increased the horizontal activity and the movement time in locomotor activity. Deletion of Rictor decreased the number of total arm entries in the elevated plus-maze test and the vertical activity in locomotor activity. These data suggest that VTA astrocytic mTORC1 plays a role in regulating depression-related behaviors and mTORC2 is involved in both depression and anxiety-related behaviors. Our results indicate that VTA astrocytic mTOR signaling pathway might be new targets for the treatment of psychiatric disorders.

Learning Dynamics from Multicellular Graphs with Deep Neural Networks.

The inference of multicellular self-assembly is the central quest of understanding morphogenesis, including embryos, organoids, tumors, and many others. However, it has been tremendously difficult to identify structural features that can indicate multicellular dynamics. Here we propose to harness the predictive power of graph-based deep neural networks (GNN) to discover important graph features that can predict dynamics. To demonstrate, we apply a physically informed GNN (piGNN) to predict the motility of multi-cellular collectives from a snapshot of their positions both in experiments and simulations. We demonstrate that piGNN is capable of navigating through complex graph features of multicellular living systems, which otherwise can not be achieved by classical mechanistic models. With increasing amounts of multicellular data, we propose that collaborative efforts can be made to create a multicellular data bank (MDB) from which it is possible to construct a large multicellular graph model (LMGM) for general-purposed predictions of multicellular organization.

A Novel LDLC Equation is Superior to the NIH LDLC Equation and the Friedewald Equation.

Background: LDLC equations have varying levels of underestimation for the calculated LDLC. Therefore, underestimating LDLC should be avoided as much as possible. We need to establish LDLC equations that underestimate LDLC as little as possible. Methods: We established the equations with a healthy cohort from Shuyang Hospital and validated the equations with an unselected patient cohort from The Second People's Hospital of Lianyungang. We established the novel LDLC equations by using the regression equation. The relationship between two markers was analysed using Pearson's approach. The 95% limits of measuring agreement within ±2 SD for the LDLC equations was performed using Bland‒Altman analysis. ROC curve analysis was used to predict LDLC levels and the accuracy of the LDLC equation for determining the direct LDLC levels at LDLC cut-offs was assessed. Results: We obtained two novel LDLC equations (LDL_nonHDLC equation=-0.899+1.195*nonHDLC-0.00347*nonHDLC2 and LDL_TC(total cholesterol) equation=-2.775+1.29*TC -0.00990* TC 2). The correlation coefficient between the novel LDLC equation and the direct LDLC measurements is not lower than that between the LDL_NIH equation and the direct LDLC measurements. The AUCs of our novel LDLC equations were greater than those of the LDL_NIH equation and the LDL_F equation at the LDLC cut-offs for clinical decision-making. The measuring agreement in the methods of the LDL_nonHDL equation is superior to that of the LDL_NIH equation. Conclusion: LDLC calculated by the novel LDL_nonHDL equation exhibited superiority over the LDL_NIH equation. Combining the LDL_NIH equation and our novel LDLC equation may improve accuracy and avoid undertreatment of high LDLC levels.

Lipid Droplets Accumulation in the Brain of HIV Transgenic Rat: Implication in the Accelerated Aging of HIV Infected Individuals.

Abnormal microglial activation has been suggested as "driven force" promoting brain aging. Lipid droplets accumulating microglia (LDAM), identified as a novel inflammatory phenotype, elevate neuroinflammation and exaggerate neuronal injuries in aging and multiple neurodegenerative diseases. Since chronic HIV (human immunodeficiency virus) (+) individuals show an accelerated brain aging and higher incidence of neurological symptoms compared to age-matched HIV (-) population, we hypothesize that LDAM are also involved in such phenomenon. For validating the hypothesis, we employed HIV transgenic (HIV-Tg) and wilt type (WT) rats to check lipid droplets (LDs) accumulation in the brains at mature (6 months) and middle age (12 months). Our results showed that HIV-Tg rats possess higher levels of LDs formation in the hippocampus (HP) and prefrontal cortex (PFc) than controls at middle age. Increased LDs are mainly presented in microglia in the HP but largely co-localized with astrocytes in the PFc. Interestingly, increased LDs are associated with upregulation on Iba1 but not with GFAP levels. HIV-Tg rats reveal an accelerated LDs accumulation during normal aging. Purified microglia from HIV-Tg rats (12 month) show higher expression of neuroimmune signaling than microglia from controls. HIV-Tg rats showed dysregulation on cholesterol synthesis in the brain HP as well as deficiency on locomotion coordination compared to controls. Overall, our results demonstrate substantial LDs accumulation in the brains of HIV-Tg rats which is associated with abnormal microglial activation and accelerated decline on locomotion coordination during aging. Dysregulation on lipid metabolism might underlie accelerated brain aging in the context of chronic HIV infection.