Phytochrome B interacts with LIGULELESS1 to control plant architecture and density tolerance in maize.

Over the past few decades, significant improvements in maize yield have been largely attributed to increased plant density of upright hybrid varieties rather than increased yield per plant. However, dense planting triggers shade avoidance responses (SAR) that optimize light absorption but impair plant vigor and performance, limiting yield improvement through increasing plant density. In this study, we demonstrated that high-density induced leaf angle narrowing and stem/stalk elongation are largely dependent on phytochrome B (phyB1/B2), the primary photoreceptor responsible for perceiving red (R) and far-red (FR) light in maize. Maize phyB physically interacts with the LIGULELESS1 (LG1), a classical key regulator of leaf angle, to coordinately regulate plant architecture and density tolerance. The abundance of LG1 is significantly increased by phyB under high R:FR light (low density) but rapidly decreases under low R:FR light (high density), correlating with variations in leaf angle and plant height under various densities. Additionally, we identified the homeobox transcription factor HB53 as a target co-repressed by both phyB and LG1 but rapidly induced by canopy shade, indicating its central role in response to varying densities. Notably, HB53 regulates plant architecture by controlling the elongation and division of ligular adaxial and abaxial cells. These findings uncover the phyB-LG1-HB53 regulatory module as a key molecular mechanism governing plant architecture and density tolerance, providing potential genetic targets for breeding maize hybrid varieties optimized for high-density planting.

Dual-earner couples' sharing of work-related experiences: Effects on relational and personal well-being.

Personal growth and self-expressive goals have become increasingly important in modern marriages. In dual-earner couples, sharing work-related experiences with the partner can be particularly important in promoting mutual support for each other's personal growth. The current study examined dual-earner couples' sharing of work-related experiences and how it influenced both partners' relationship satisfaction and personal well-being. A total of 102 heterosexual dual-earner couples were recruited from communities in Hong Kong. They completed a pretest survey, a 14-day daily diary study, and a follow-up survey 1 year later. The Actor-Partner Interdependence Model was adopted to analyze the dyadic effects of sharing positive and negative work-related experiences on relationship satisfaction and personal well-being on the same day and 1 year later. In general, the sharing of both positive and negative work-related experiences had beneficial effects on the outcomes. Specifically, wives' sharing had more immediate effects on both partners' relational and personal well-being, whereas husbands' sharing had more long-term effects on the partner's personal well-being. The findings highlight the importance of work-related sharing in dual-earner couples. Practical implications are discussed.

Associations of E-proteinoid 3 receptor genetic polymorphisms with salt sensitivity, longitudinal blood pressure changes, and hypertension incidence in Chinese adults.

The E-proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G-protein-coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt-Sensitivity Study Cohort in northern China. These participants followed a 3-day regular baseline diet, followed by a 7-day low-salt diet (3.0 g/d) and a 7-day high-salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14-year follow-up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

C-H-activated Csp2-Csp3 diastereoselective gridization enables ultraviolet-emitting stereo-molecular nanohydrocarbons with mulitple H···H interactions.

Gridization is an emerging molecular integration technology that enables the creation of multifunctional organic semiconductors through precise linkages. While Friedel-Crafts gridization of fluorenols is potent, direct linkage among fluorene molecules poses a challenge. Herein, we report an achiral Pd-PPh3-cataylized diastereoselective (>99:1 d.r.) gridization based on the C-H-activation of fluorene to give dimeric and trimeric windmill-type nanogrids (DWGs and TWGs). These non-conjugated stereo-nanogrids showcase intramolecular multiple H…H interactions with a low field shift to 8.51 ppm and circularly polarized luminescence with high luminescent dissymmetry factors (|gPL | = 0.012). Significantly, the nondoped organic light-emitting diodes (OLEDs) utilizing cis-trans-TWG1 emitter present an ultraviolet electroluminescent peak at ~386 nm (CIE: 0.17, 0.04) with a maximum external quantum efficiency of 4.17%, marking the highest record among nondoped ultraviolet OLEDs based on hydrocarbon compounds and the pioneering ultraviolet OLEDs based on macrocycles. These nanohydrocarbon offer potential nanoscafflolds for ultraviolet light-emitting optoelectronic applications.

Radical enhanced intersystem crossing mechanism, electron spin dynamics of high spin states and their applications in the design of heavy atom-free triplet photosensitizers.

Heavy atom-free triplet photosensitizers (PSs) can overcome the high cost and biological toxicity of traditional molecular systems containing heavy atoms (such as Pt(II), Ir(III), Ru(II), Pd(II), Lu(III), I, or Br atoms) and, therefore, are developing rapidly. Connecting a stable free radical to the chromophore can promote the intersystem crossing (ISC) process through electron spin exchange interaction to produce the triplet state of the chromophore or the doublet (D) and quartet (Q) states when taking the whole spin system into account. These molecular systems based on the radical enhanced ISC (REISC) mechanism are important in the field of heavy atom-free triplet PSs. The REISC system has a simple molecular structure and good biocompatibility, and it is especially helpful for building high-spin quantum states (D and Q states) that have the potential to be developed as qubits in quantum information science. This review introduces the molecular structure design for the purpose of high-spin states. Time-resolved electron paramagnetic resonance (TREPR) is the most important characterization method to reveal the properties of these molecular systems, generation mechanism and electron spin polarization (ESP) of the high spin states. The spin polarization manipulation of high spin states and potential application in the field of quantum information engineering are also summarized. Moreover, molecular design principles of the REISC system to obtain long absorption wavelength, high triplet state quantum yield and long triplet state lifetime are introduced, as well as applications of the compounds in triplet-triplet annihilation upconversion, photodynamic therapy and bioimaging. This review is useful for the design of heavy atom-free triplet PSs based on the radical-chromophore molecular structure motif and the study of the photophysics of the compounds, as well as the electron spin dynamics of the multi electron system upon photoexcitation.

Progress on the role of LIN28A/B in tumor development and progression.

LIN28A and its homolog LIN28B are highly conserved RNA-binding proteins that play important roles in early embryonic development, somatic cell reprogramming, metabolism and tumorigenesis. LIN28A/B are highly expressed in a variety of malignant tumors such as breast cancer. They play important roles in the initiation, maintenance, and metastasis of tumors and are associated with poor prognosis. Previous studies have shown that the main regulatory mechanisms of LIN28A/B include let-7s dependent ways and let-7s independent ways, such as directly targeting mRNA. In this review, we summarize the function and molecular regulatory mechanisms of LIN28A/B in malignant tumors such as liver cancer, breast cancer and colorectal cancer, in order to provide references for further exploring the function and mechanism of LIN28A/B and their possible roles in clinical applications.

Sources and formation characteristics of particulate nitrate in the Pearl River Delta region of China: Insights from three-year online observations.

Nitrate (NO3-) has been identified as a key component of particulate matter (PM2.5) in China. However, there is still a lack of understanding regarding its sources and how it forms, especially in the context of high-frequency and long-term data. In this study, NO3- levels were observed on an hourly basis over an almost three-year period at an urban site in the Pearl River Delta (PRD) region, China, from January 2019 to December 2021. The results reveal an average daily NO3- concentration ranging from 0.08 µg m-3 to 61.69 µg m-3, constituting 11.9 ± 12.5 % of PM2.5. This percentage rose to as high as 57 % during pollution episodes, highlighting NO3-'s significant role in pollution formation. The ammonia-rich environment was found to be the most important factor in promoting NO3- formation. Positive Matrix Factorization (PMF) analysis indicates that the primary sources of NO3- in the PRD region were vehicle emissions (43.8 ± 21.2 %) and coal combustion (39.1 ± 21.5 %), with shipping emissions, sea salt, soil dust and industrial emissions + biomass burning following in importance. Regarding source areas, the primary contributor of vehicle emissions was predominantly from the PRD region, whereas the coal combustion, aside from local contributions, also originates from the northern region. From a long-term perspective, NO3- pollution has remained relatively stable since the summer of 2020. Concurrently, coal combustion source has shown a localization trend. These insights derived from the extensive, high-frequency observation presented in this study serve as a valuable reference for devising strategies to control NO3- and PM2.5 in the PRD region and China.

Physiological and molecular mechanism of Populus pseudo-cathayana × Populus deltoides response to Hyphantria cunea.

Populus pseudo-cathayana × Populus deltoides is a crucial artificial forest tree species in Northeast China. The presence of the fall webworm (Hyphantria cunea) poses a significant threat to these poplar trees, causing substantial economic and ecological damage. This study conducted an insect-feeding experiment with fall webworm on P. pseudo-cathayana × P. deltoides, examining poplar's physiological indicators, transcriptome, and metabolome under different lengths of feeding times. Results revealed significant differences in phenylalanine ammonia-lyase activity, total phenolic content, and flavonoids at different feeding durations. Transcriptomic analysis identified numerous differentially expressed genes, including AP2/ERF, MYB, and WRKY transcription factor families exhibiting the highest expression variations. Differential metabolite analysis highlighted flavonoids and phenolic acid compounds of poplar's leaves as the most abundant in our insect-feeding experiment. Enrichment analysis revealed significant enrichment in the plant hormone signal transduction and flavonoid biosynthetic pathways. The contents of jasmonic acid and jasmonoyl-L-isoleucine increased with prolonged fall webworm feeding. Furthermore, the accumulation of dihydrokaempferol, catechin, kaempferol, and naringenin in the flavonoid biosynthesis pathway varied significantly among different samples, suggesting their crucial role in response to pest infestation. These findings provide novel insights into how poplar responds to fall webworm infestation.

A facile and on-site sensing strategy for phenolic compounds based on a novel nanozyme with high polyphenol oxidase-like activity.

Phenolic compounds (PCs) are diverse in nature and undergo complex migration and transformations in the environment, making it challenging to use techniques such as chromatography and other traditional methods to determine the concentration of PCs by separation, individual monitoring and subsequent addition. To address this issue, a facile and on-site strategy was developed to measure the concentration of PCs using a novel nanozyme with polyphenol oxidase-like activity. First, the nanozyme was designed by coordinating the asymmetric ligand nicotinic acid with copper to mimic the structure of mononuclear and trinuclear copper clusters of natural laccases. Subsequently, by introducing 2-mercaptonicotinic acid to regulate the valence state of copper, the composite nanozyme CuNA10S was obtained with significantly enhanced activity. Interestingly, CuNA10S was shown to have a broad substrate spectrum capable of catalyzing common PCs. Building upon the superior performance of this nanozyme, a method was developed to determine the concentration of PCs. To enable rapid on-site sensing, we designed and prepared CuNA10S-based test strips and developed a tailored smartphone sensing platform. Using paper strip sensors combined with a smartphone sensing platform with RGB streamlined the sensing process, facilitating rapid on-site analysis of PCs within a range of 0-100 µM. Our method offers a solution for the quick screening of phenolic wastewater at contaminated sites, allowing sensitive and quick monitoring of PCs without the need for standard samples. This significantly simplifies the monitoring procedure compared to more cumbersome large-scale instrumental methods.

Engineered low-pathogenic Helicobacter pylori as orally tumor immunomodulators for the stimulation of systemic immune response.

Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori (H. pylori) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori. H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori-based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy.

Tailoring the ion storage of MXene by aramid nanofibers towards self-standing electrodes for flexible solid-state supercapacitors.

Two-dimensional (2D) transition metal carbides and nitrides (MXenes) are a class of 2D nanomaterials that can offer excellent properties for high-performance supercapacitors. Nevertheless, irreversible restacking of MXene sheets decreases the interlayer spacing, which inhibits the ion intercalation between the MXene nanosheets and finally deteriorates the electrochemical performance of supercapacitors. Herein, aramid nanofibers (ANFs) are mixed with Ti3C2TxMXene to prepare MXene/ANFs composite films. The restacking of MXene sheets is inhibited by the electrostatic repulsion between ANFs and MXene. The ANFs act as intercalation agents to increase the interlayer spacing of the composite films, which can improve the ion storage ability of supercapacitors. Furthermore, the ANFs enhance the mechanical strength of the composite films due to the strong hydrogen bonding interaction and nanomechanical interlocking between ANFs and MXene, endowing the composite films with self-standing property. The resultant composite films are used as electrodes for flexible solid-state supercapacitors to achieve high specific capacitance (996.5 mF cm-2at 5 mV s-1) and outstanding cycling stability. Thus, this work provides a potential strategy to regulate the properties of 2D nanomaterials, which may expand the application of them in energy storage, ionic separation, osmotic energy conversion and beyond.

New insights into how freeze-drying and cryo-milling affects the fine structure and digestibility of gelatinized starch.

Freeze-drying (FD) and cryo-milling (CM) are common methods for preparing powder gelatinized starch samples. This study investigates the structural characterization of raw/gelatinized maize starches and digestibility after FD/CM processes to elucidate their effect on starch digestibility determination. Results showed that FD slightly increased digestibility, while higher initial glucose content in CM samples, especially for gelatinized samples. Only FD retained the granular morphology and relative crystallinity (RC), while gelatinized-FD decreased RC by 75%. CM decreased RC by 12%, while gelatinized-CM decreased it by 97%. Combined with short-range and chain structural results, FD tended to disrupt internal connected chains through volume stress, while CM cleaved glycosidic bonds in external chain. Stretched chains in gelatinized starch promoted the breakage of chains during shearing and their efficient binding with digestive enzymes. These findings would provide a basis for pre-treatment of powder samples and processes of starch- rich foods.

The Intramolecular Charge Transfer Mechanism by Which Chiral Self-Assembled H8-BINOL Vesicles Enantioselectively Recognize Amino Alcohols.

The chiral H8-BINOL derivatives R-1 and R-2 were efficiently synthesized via a Suzuki coupling reaction, and they can be used as novel dialdehyde fluorescent probes for the enantioselective recognition of R/S-2-amino-1-phenylethanol. In addition, R-1 is much more effective than R-2. Scanning electron microscope images and X-ray analyses show that R-1 can form supramolecular vesicles through the self-assembly effect of the π-π force and strong hydrogen bonding. As determined via analysis, the fluorescence of the probe was significantly enhanced by mixing a small amount of S-2-amino-1-phenylethanol into R-1, with a redshift of 38 nm, whereas no significant fluorescence response was observed in R-2-amino-1-phenylethanol. The enantioselective identification of S-2-amino-1-phenylethanol by the probe R-1 was further investigated through nuclear magnetic titration and fluorescence kinetic experiments and DFT calculations. The results showed that this mechanism was not only a simple reactive probe but also realized object recognition through an ICT mechanism. As the intramolecular hydrogen bond activated the carbonyl group on the probe R-1, the carbonyl carbon atom became positively charged. As a strong nucleophile, the amino group of S-2-amino-1-phenylethanol first transferred the amino electrons to a carbonyl carbocation, resulting in a significantly enhanced fluorescence of the probe R-1 and a 38 nm redshift. Similarly, S-2-amino-1-phenylethanol alone caused severe damage to the self-assembled vesicle structure of the probe molecule itself due to its spatial structure, which made R-1 highly enantioselective towards it.

A new flavonostilbene glycoside and four new stilbene derivatives from the roots of Polygonum multiflorum.

One new flavonostilbene glycoside, polygonflavanol C (1), two new dimeric stilbene glycosides, multiflorumiside M and multiflorumiside N (2-3), one new diphenyl ethanol glycoside, (R)-2,3,5,4'-tetrahydroxy-diphenylethanol 2-O-ß-D-glucopyranoside (4), and one new deoxybenzoin glycoside, 2,4,3',5'-tetrahydroxy-6-methyl-deoxybenzoin 2-O-ß-D-glucopyranoside (5), together with six known ones (6-11), were isolated from the roots of Polygonum multiflorum. Their structures were elucidated by the comprehensive spectroscopic analyses. In addition, compounds 1 and 7 showed significantly in vitro anti-inflammatory activity.

Comprehensive pan-cancer analysis reveals the versatile role of GALNT7 in epigenetic alterations and immune modulation in cancer.

Cancer is a leading cause of mortality globally, characterized by intricate molecular alterations, including epigenetic changes such as glycosylation. This study presents a comprehensive pan-cancer analysis of Polypeptide N-Acetylgalactosaminyltransferase 7 (GALNT7), an enzyme involved in mucin-type O-linked protein glycosylation. GALNT7 has previously been linked to various cancers, but a unified analysis across cancer types is lacking. Leveraging data from TCGA, GTEx, and other sources, we scrutinized GALNT7's expression, prognostic relevance, links to immune-related genes, immune cell infiltration, and its involvement in tumor genetic heterogeneity across 33 cancer types. GALNT7 exhibited diverse expression patterns across cancer types, showcasing its potential as an oncogenic factor, with its expression levels linked to both positive and negative prognoses, highlighting the context-specific nature of its role in cancer progression. We delved into the intricate interplay between GALNT7 and immune genes, unveiling positive and negative correlations, underscoring complex interactions in the tumor microenvironment. GALNT7 was found to impact immune cell infiltration, which could have implications for treatment strategies. Additionally, GALNT7 displayed associations with genetic tumor aspects, encompassing genomic instability, DNA repair issues, and genetic mutations, hinting at its pivotal role in shaping the genetic landscape of diverse cancers. Enrichment analysis uncovered potential functions of GALNT7 beyond glycosylation, such as its participation in signaling pathways and its association with various diseases, notably cancer. This comprehensive analysis elucidates the multifaceted role of GALNT7 in cancer biology, underlining its potential as a therapeutic target and biomarker across various cancer types. These findings provide valuable insights for future research and the development of personalized cancer treatment strategies.

Aptamer based hybrid monolithic pipette tips supported by melamine sponge for enrichment of proteins.

BACKGROUND: The convenient preparation and application of functionalized organic-inorganic hybrid monolithic materials have obtained substantial interest in the pretreatment of complex samples by solid-phase extraction (SPE). Compared to the in-tube solid-phase microextraction in fused-silica capillaries, micro SPE in plastic pipette tips have fascinating merits for the easily operated enrichment of trace target analytes from biological samples. However, the poor compatibility of organic-inorganic hybrid monoliths with plastics leads to the rare appearance of commercial hybrid monolithic pipette tips (HMPTs). Therefore, how to synthesize the organic-inorganic hybrid monolithic materials with better extraction performance in plastic pipette tips becomes a challenge. RESULTS: We develop a facile and cheap strategy to immobilize organic-inorganic hybrid monoliths in pipette tips. Melamine sponge was employed as the supporting skeleton to in situ assemble amine- and thiol-bifunctionalized hybrid monolithic material via "one pot" in a pipette tip, and gold nanoparticles (GNPs) and thiol-modified aptamer against human α-thrombin were sequentially attached to the hybrid monolith within the HMPTs. The average coverage density of the aptamer with GNPs as an intermediary reached as high as 818.5 pmol µL-1. The enriched thrombin concentration was determined by a sensitive enzymatic chromogenic assay with the limit of detection of 2 nM. The extraction recovery of thrombin at 10 nM in human serum was 86.1 % with a relative standard deviation of 6.1 %. This proposed protocol has been applied to the enrichment and determination of thrombin in real serum sample with strong anti-interference ability, low limit of detection and high recovery. SIGNIFICANCE: The amine- and thiol-bifunctionalized HMPTs prepared with sponge as the skeleton frame provided a novel substrate material to decorate aptamers for efficient enrichment of proteins. This enlightens us that we can take advantage of the tunability of sponge assisted HMPTs to produce and tailor a variety of micro SPE pipette tips for broader applications on the analysis of trace targets in complex biological, clinic and environmental samples.

Liquid-based cytology specimens for next-generation sequencing in lung adenocarcinoma: challenges and evaluation of targeted therapy.

BACKGROUND: To explore challenges of liquid-based cytology (LBC) specimens for next-generation sequencing (NGS) in lung adenocarcinoma and evaluate the efficacy of targeted therapy. METHODS: A retrospective analysis was conducted on the NGS test of 357 cases of advanced lung adenocarcinoma LBC specimens and compared with results of histological specimens to assess the consistency. The impact of tumor cellularity on NGS test results was evaluated. The utility of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) was collected. Clinical efficacy evaluation was performed and survival curve analysis was conducted using the Kaplan-Meier method. RESULTS: There were 275 TKI-naive and 82 TKI-treated specimens, the mutation rates of cancer-related genes detected in both groups were similar (86.2% vs. 86.6%). The EGFR mutation rate in the TKI treated group was higher than that in the TKI-naive group (69.5% > 54.9%, P = 0.019). There was no significant difference in the EGFR mutation frequency among different tumor cellularity in the TKI-naive group. However, in the TKI treated group, the frequency of EGFR sensitizing mutation and T790M resistance mutation in specimens with < 20% tumor cellularity was significantly lower than that in specimens with ≥ 20% tumor cellularity. Among 22 cases with matched histological specimens, 72.7% (16/22) of LBC specimens were completely consistent with results of histological specimens. Among 92 patients with EGFR-mutant lung adenocarcinoma treated with EGFR-TKIs in the two cohorts, 88 cases experienced progression, and the median progression-free survival (PFS) was 12.1 months. CONCLUSIONS: Cytological specimens are important sources for gene detection of advanced lung adenocarcinoma. When using LBC specimens for molecular testing, it is recommended to fully evaluate the tumor cellularity of the specimens.

Effect of sacubitril-valsartan on left ventricular remodeling in patients with acute myocardial infarction after primary percutaneous coronary intervention: a systematic review and meta-analysis.

Background: Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure (HF). However, the effect of sacubitril-valsartan in patients with acute myocardial infarction (AMI) remains controversial. Therefore, we conducted this meta-analysis to investigate whether sacubitril-valsartan could reverse left ventricular remodeling and reduce cardiovascular adverse events in AMI patients after primary percutaneous coronary intervention (PPCI). Materials and methods: Two researchers independently retrieved the relevant literature from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database. The retrieval time was limited from inception to 1 June 2023. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analyzed. Results: In total, 21 RCTs involving 2442 AMI patients who underwent PPCI for revascularization were included in this meta-analysis. The meta-analysis showed that compared with the angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril-valsartan treatment in AMI patients after PPCI significantly reduced left ventricular end-diastolic dimension (LVEDD) (weighted mean difference (WMD) -3.11, 95%CI: -4.05∼-2.16, p < 0.001), left ventricular end-diastolic volume (LVEDV) (WMD -7.76, 95%CI: -12.24∼-3.27, p = 0.001), left ventricular end-systolic volume (LVESV) (WMD -6.80, 95%CI: -9.45∼-4.15, p < 0.001) and left ventricular end-systolic dimension (LVESD) (WMD -2.53, 95%CI: -5.30-0.24, p < 0.001). Subgroup analysis according to the dose of sacubitril-valsartan yielded a similar result. Meanwhile, PPCI patients using sacubitril-valsartan therapy showed lower risk of major adverse cardiac events (MACE) (OR = 0.36, 95%CI: 0.28-0.46, p < 0.001), myocardial reinfarction (OR = 0.54, 95%CI: 0.30-0.98, p = 0.041) and HF (OR = 0.35, 95%CI: 0.26-0.47, p < 0.001) without increasing the risk of renal insufficiency, hyperkalemia, or symptomatic hypotension. At the same time, the change of LV ejection fraction (LVEF) (WMD 3.91, 95%CI: 3.41-4.41, p < 0.001), 6 min walk test (6MWT) (WMD 43.56, 95%CI: 29.37-57.76, p < 0.001) and NT-proBNP level (WMD -130.27, 95%CI: -159.14∼-101.40, p < 0.001) were statistically significant. Conclusion: In conclusion, our meta-analysis indicates that compared with ACEI/ARB, sacubitril-valsartan may be superior to reverse left ventricular remodeling, improve cardiac function, and effectively reduce the risk of MACE, myocardial reinfarction, and HF in AMI patients after PPCI during follow-up without increasing the risk of adverse reactions including renal insufficiency, hyperkalemia, and symptomatic hypotension.

A Hydrogen-Bonded Organic Framework-Based Mitochondrion-Targeting Bioorthogonal Platform for the Modulation of Mitochondrial Epigenetics.

Bioorthogonal chemistry represents a powerful tool in chemical biology, which shows great potential in epigenetic modulation. As a proof of concept, the epigenetic modulation model of mitochondrial DNA (mtDNA) is selected because mtDNA establishes a relative hypermethylation stage under oxidative stress, which impairs the mitochondrion-based therapeutic effect during cancer therapy. Herein, we design a new biocompatible hydrogen-bonded organic framework (HOF) for a HOF-based mitochondrion-targeting bioorthogonal platform TPP@P@PHOF-2. PHOF-2 can activate a prodrug (pro-procainamide) in situ, which can specifically inhibit DNA methyltransferase 1 (DNMT1) activity and remodel the epigenetic modification of mtDNA, making it more susceptible to ROS damage. In addition, PHOF-2 can also catalyze artemisinin to produce large amounts of ROS, effectively damaging mtDNA and achieving better chemodynamic therapy demonstrated by both in vitro and in vivo studies. This work provides new insights into developing advanced bioorthogonal therapy and expands the applications of HOF and bioorthogonal catalysis.