CELLULOSE SYNTHASE-LIKE C proteins modulate cell wall establishment during ethylene-mediated root growth inhibition in rice.

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.

Maintenance of persistent transmission of a plant arbovirus in its insect vector mediated by the Toll-Dorsal immune pathway.

Throughout evolution, arboviruses have developed various strategies to counteract the host's innate immune defenses to maintain persistent transmission. Recent studies have shown that, in addition to bacteria and fungi, the innate Toll-Dorsal immune system also plays an essential role in preventing viral infections in invertebrates. However, whether the classical Toll immune pathway is involved in maintaining the homeostatic process to ensure the persistent and propagative transmission of arboviruses in insect vectors remain unclear. In this study, we revealed that the transcription factor Dorsal is actively involved in the antiviral defense of an insect vector (Laodelphax striatellus) by regulating the target gene, zinc finger protein 708 (LsZN708), which mediates downstream immune-related effectors against infection with the plant virus (Rice stripe virus, RSV). In contrast, an antidefense strategy involving the use of the nonstructural-protein (NS4) to antagonize host antiviral defense through competitive binding to Dorsal from the MSK2 kinase was employed by RSV; this competitive binding inhibited Dorsal phosphorylation and reduced the antiviral response of the host insect. Our study revealed the molecular mechanism through which Toll-Dorsal-ZN708 mediates the maintenance of an arbovirus homeostasis in insect vectors. Specifically, ZN708 is a newly documented zinc finger protein targeted by Dorsal that mediates the downstream antiviral response. This study will contribute to our understanding of the successful transmission and spread of arboviruses in plant or invertebrate hosts.

P3N-PIPO but not P3 is the avirulence determinant in melon carrying the Wmr resistance against watermelon mosaic virus, although they contain a common genetic determinant.

Viruses employ a series of diverse translational strategies to expand their coding capacity, which produces viral proteins with common domains and entangles virus-host interactions. P3N-PIPO, which is a transcriptional slippage product from the P3 cistron, is a potyviral protein dedicated to intercellular movement. Here, we show that P3N-PIPO from watermelon mosaic virus (WMV) triggers cell death when transiently expressed in Cucumis melo accession PI 414723 carrying the Wmr resistance gene. Surprisingly, expression of the P3N domain, shared by both P3N-PIPO and P3, can alone induce cell death, whereas expression of P3 fails to activate cell death in PI 414723. Confocal microscopy analysis revealed that P3N-PIPO targets plasmodesmata (PD) and P3N associates with PD, while P3 localizes in endoplasmic reticulum in melon cells. We also found that mutations in residues L35, L38, P41, and I43 of the P3N domain individually disrupt the cell death induced by P3N-PIPO, but do not affect the PD localization of P3N-PIPO. Furthermore, WMV mutants with L35A or I43A can systemically infect PI 414723 plants. These key residues guide us to discover some WMV isolates potentially breaking the Wmr resistance. Through searching the NCBI database, we discovered some WMV isolates with variations in these key sites, and one naturally occurring I43V variation enables WMV to systemically infect PI 414723 plants. Taken together, these results demonstrate that P3N-PIPO, but not P3, is the avirulence determinant recognized by Wmr, although the shared N terminal P3N domain can alone trigger cell death.IMPORTANCEThis work reveals a novel viral avirulence (Avr) gene recognized by a resistance (R) gene. This novel viral Avr gene is special because it is a transcriptional slippage product from another virus gene, which means that their encoding proteins share the common N-terminal domain but have distinct C-terminal domains. Amazingly, we found that it is the common N-terminal domain that determines the Avr-R recognition, but only one of the viral proteins can be recognized by the R protein to induce cell death. Next, we found that these two viral proteins target different subcellular compartments. In addition, we discovered some virus isolates with variations in the common N-terminal domain and one naturally occurring variation that enables the virus to overcome the resistance. These results show how viral proteins with common domains interact with a host resistance protein and provide new evidence for the arms race between plants and viruses.

Targeting RNA G-quadruplex with repurposed drugs blocks SARS-CoV-2 entry.

The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment.

Extrachromosomal circular MiR-17-92 amplicon promotes HCC.

BACKGROUND AND AIMS: Extrachromosomal circular DNAs (eccDNAs) are prevalent in cancer genomes and emerge as a class of crucial yet less characterized oncogenic drivers. However, the structure, composition, genome-wide frequency, and contribution of eccDNAs in HCC, one of the most fatal and prevalent cancers, remain unexplored. In this study, we provide a comprehensive characterization of eccDNAs in human HCC and demonstrate an oncogenic role of microRNA (miRNA)-17-92-containing eccDNAs in tumor progression. APPROACH AND RESULTS: Using the circle-sequencing method, we identify and characterize more than 230,000 eccDNAs from 4 paired samples of HCC tumor and adjacent nontumor liver tissues. EccDNAs are highly enriched in HCC tumors, preferentially originate from certain chromosomal hotspots, and are correlated with differential gene expression. Particularly, a series of eccDNAs carrying the miRNA-17-92 cluster are validated by outward PCR and Sanger sequencing. Quantitative PCR analyses reveal that miRNA-17-92-containing eccDNAs, along with the expression of their corresponding miRNAs, are elevated in HCC tumors and associated with poor outcomes and the age of HCC patients. More intriguingly, exogenous expression of artificial DNA circles harboring the miR-17-92 cluster, which is synthesized by the ligase-assisted minicircle accumulation method, can significantly accelerate HCC cell proliferation and migration. CONCLUSIONS: These findings delineate the genome-wide eccDNAs profiling of HCC and highlight the functional significance of miRNA-containing eccDNAs in tumorigenesis, providing insight into HCC pathogenesis and cancer therapy, as well as eccDNA and miRNA biology.

Potato virus Y viral protein 6K1 inhibits the interaction between defense proteins during virus infection.

14-3-3 proteins play vital roles in plant defense against various pathogen invasions. To date, how 14-3-3 affects virus infections in plants remains largely unclear. In this study, we found that Nicotiana benthamiana 14-3-3h interacts with TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (TCTP), a susceptibility factor of potato virus Y (PVY). Silencing of Nb14-3-3h facilitates PVY accumulation, whereas overexpression of Nb14-3-3h inhibits PVY replication. The antiviral activities of 3 Nb14-3-3h dimerization defective mutants are significantly decreased, indicating that dimerization of Nb14-3-3h is indispensable for restricting PVY infection. Our results also showed that the mutant Nb14-3-3hE16A, which is capable of dimerizing but not interacting with NbTCTP, has reduced anti-PVY activity; the mutant NbTCTPI65A, which is unable to interact with Nb14-3-3h, facilitates PVY replication compared with the wild-type NbTCTP, indicating that dimeric Nb14-3-3h restricts PVY infection by interacting with NbTCTP and preventing its proviral function. As a counter-defense, PVY 6K1 interferes with the interaction between Nb14-3-3h and NbTCTP by competitively binding to Nb14-3-3h and rescues NbTCTP to promote PVY infection. Our results provide insights into the arms race between plants and potyviruses.

Exploring CYP2D6 polymorphisms and angiotensin receptor blocker response in the Bai hypertensive population.

OBJECTIVE: The CYP2D6 enzyme is crucial for the metabolism and disposition of a variety of drugs. This study was conducted to examine the relationship between CYP2D6 gene polymorphisms and the response to angiotensin receptor blocker (ARB)-based treatment in patients of Chinese Bai ethnicity with hypertension. METHODS: Seventy-two hypertensive adults from the Chinese Bai ethnic group, exhibiting systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg, were recruited. Targeted regional sequencing was utilized to genotype single nucleotide polymorphisms in the CYP2D6 gene, aiming to assess their frequency and to evaluate their influence on the therapeutic efficacy of ARB medications. RESULTS: Our research identified nine significant CYP2D6 polymorphisms associated with the efficacy of ARB treatment in the Bai hypertensive cohort. Specifically, patients possessing certain mutant genotype at rs111564371 exhibited substantially greater reductions in SBP and DBP, with P -values of 0.021 and 0.016, respectively, compared to those carrying the wild genotype. Additionally, these mutant genotype at rs111564371 and rs112568578 were linked to approximately 20% higher overall efficacy rates and a 10% increased achievement rate relative to the wild genotype. CONCLUSION: Our research with the Bai hypertensive group shows that certain CYP2D6 polymorphisms significantly influence ARB treatment outcomes. Mutations at rs111564371 led to better blood pressure control ( P -values: 0.021 for SBP, 0.016 for DBP), improving ARB efficacy by appromixately 20% and increasing treatment goal achievement by 10% over the wild-type genotype. STATEMENTS: Our investigation into CYP2D6 polymorphisms within the Bai hypertensive cohort marks a substantial advancement towards personalized healthcare, underscoring the pivotal influence of genetic constitution on the effectiveness of ARB therapy.

First-in-human study to evaluate the safety, tolerability, and population pharmacokinetic/pharmacodynamic target attainment analysis of FL058 alone and in combination with meropenem in healthy subjects.

FL058 is a novel diazabicyclooctane ß-lactamase inhibitor. This first-in-human study evaluated the safety, tolerability, and population pharmacokinetic (PK)/pharmacodynamic target attainment analysis of FL058 alone and in combination with meropenem in healthy subjects. The results showed that the maximum tolerated dose of FL058 was 3,000 mg after single-dose infusion. FL058 in combination with meropenem did not cause any grade 3 or higher adverse event when the dose was escalated up to 1,000 mg/2,000 mg. FL058 exposure PK parameters showed dose proportionality. FL058 was excreted primarily in urine. No significant PK interaction was found between FL058 and meropenem. Population PK model analysis indicated that the PK profiles of FL058 and meropenem were consistent with the two-compartment model. The impact of covariates, creatinine clearance, concomitant use of meropenem, body weight, sex, and FL058 dose, on FL058 exposure was less than 10%. FL058/meropenem combination was safe and well tolerated up to a 1,000-mg/2,000-mg dose in healthy adults. The recommended minimum dose of FL058/meropenem combination was 500 mg/1,000 mg by intravenous infusion over 2 h every 8 h based on target attainment analysis. The good safety, tolerability, and satisfactory PK profiles of FL058 alone and in combination with meropenem in this first-in-human study will support further clinical development of FL058 in combination with meropenem in patients with target infections (ClinicalTrials.gov identifiers: NCT05055687, NCT05058118, and NCT05058105).

Carbon Corrosion Induced by Surface Defects Accelerates Degradation of Platinum/Graphene Catalysts in Oxygen Reduction Reaction.

Graphene supported electrocatalysts have demonstrated remarkable catalytic performance for oxygen reduction reaction (ORR). However, their durability and cycling performance are greatly limited by Oswald ripening of platinum (Pt) and graphene support corrosion. Moreover, comprehensive studies on the mechanisms of catalysts degradation under 0.6-1.6 V versus RHE (Reversible Hydrogen Electrode) is still lacking. Herein, degradation mechanisms triggered by different defects on graphene supports are investigated by two cycling protocols. In the start-up/shutdown cycling (1.0-1.6 V vs. RHE), carbon oxidation reaction (COR) leads to shedding or swarm-like aggregation of Pt nanoparticles (NPs). Theoretical simulation results show that the expansion of vacancy defects promotes reaction kinetics of the decisive step in COR, reducing its reaction overpotential. While under the load cycling (0.6-1.0 V vs. RHE), oxygen containing defects lead to an elevated content of Pt in its oxidation state which intensifies Oswald ripening of Pt. The presence of vacancy defects can enhance the transfer of electrons from graphene to the Pt surface, reducing the d-band center of Pt and making it more difficult for the oxidation state of platinum to form in the cycling. This work will provide comprehensive understanding on Pt/Graphene catalysts degradation mechanisms.

ZmPHR1 contributes to drought resistance by modulating phosphate homeostasis in maize.

As an essential macronutrient, phosphorus (P) is often a limiting nutrient because of its low availability and mobility in soils. Drought is a major environmental stress that reduces crop yield. How plants balance and combine P-starvation responses (PSRs) and drought resistance is unclear. In this study, we identified the transcription factor ZmPHR1 as a major regulator of PSRs that modulates phosphate (Pi) signaling and homeostasis. We found that maize zmphr1 mutants had reduced P concentration and were sensitive to Pi starvation, whereas ZmPHR1-OE lines displayed elevated Pi concentration and yields. In addition, 57% of PSR genes and nearly 70% of ZmPHR1-regulated PSR genes in leaves were transcriptionally responsive to drought. Under moderate and early drought conditions, the Pi concentration of maize decreased, and PSR genes were up-regulated before drought-responsive genes. The ZmPHR1-OE lines exhibited drought-resistant phenotypes and reduced stomatal apertures, whereas the opposite was true of the zmphr1 mutants. ZmPT7-OE lines and zmspx3 mutants, which had elevated Pi concentration, also exhibited drought resistance, but zmpt7 mutants were sensitive to drought. Our results suggest that ZmPHR1 plays a central role in integrating Pi and drought signals and that Pi homeostasis improves the ability of maize to combat drought.

Dissecting the genetic basis of heterosis in elite super-hybrid rice.

Y900 is one of the top hybrid rice (Oryza sativa) varieties, with its yield exceeding 15 t·hm-2. To dissect the mechanism of heterosis, we sequenced the male parent line R900 and female parent line Y58S using long-read and Hi-C technology. High-quality reference genomes of 396.41 Mb and 398.24 Mb were obtained for R900 and Y58S, respectively. Genome-wide variations between the parents were systematically identified, including 1,367,758 single-nucleotide polymorphisms, 299,149 insertions/deletions, and 4,757 structural variations. The level of variation between Y58S and R900 was the lowest among the comparisons of Y58S with other rice genomes. More than 75% of genes exhibited variation between the two parents. Compared with other two-line hybrids sharing the same female parent, the portion of Geng/japonica (GJ)-type genetic components from different male parents increased with yield increasing in their corresponding hybrids. Transcriptome analysis revealed that the partial dominance effect was the main genetic effect that constituted the heterosis of Y900. In the hybrid, both alleles from the two parents were expressed, and their expression patterns were dynamically regulated in different tissues. The cis-regulation was dominant for young panicle tissues, while trans-regulation was more common in leaf tissues. Overdominance was surprisingly prevalent in stems and more likely regulated by the trans-regulation mechanism. Additionally, R900 contained many excellent GJ haplotypes, such as NARROW LEAF1, Oryza sativa SQUAMOSA PROMOTER BINDING PROTEIN-LIKE13, and Grain number, plant height, and heading date8, making it a good complement to Y58S. The fine-tuned mechanism of heterosis involves genome-wide variation, GJ introgression, key functional genes, and dynamic gene/allele expression and regulation pattern changes in different tissues and growth stages.

N6-methyladenosine mRNA methylation positively regulated the response of poplar to salt stress.

As the most abundant form of methylation modification in messenger RNA (mRNA), the distribution of N6-methyladenosine (m6A) has been preliminarily revealed in herbaceous plants under salt stress, but its function and mechanism in woody plants were still unknown. Here, we showed that global m6A levels increased during poplar response to salt stress. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that m6A significantly enriched in the coding sequence region and 3'-untranslated regions in poplar, by recognising the conserved motifs, AGACU, GGACA and UGUAG. A large number of differential m6A transcripts have been identified, and some have been proved involving in salt response and plant growth and development. Further combined analysis of MeRIP-seq and RNA-seq revealed that the m6A hypermethylated and enrich in the CDS region preferred to positively regulate expression abundance. Writer inhibitor, 3-deazaneplanocin A treatment increased the sensitivity of poplar to salt stress by reducing mRNA stability to regulate the expression of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Furthermore, we verified that the methyltransferase PagFIP37 plays a positively role in the response of poplar to salt stress, overexpressed lines have stronger salt tolerance, while RNAi lines were more sensitive to salt, which relied on regulating mRNA stability in an m6A manner of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Collectively, these results revealed the regulatory role of m6A methylation in poplar response to salt stress, and revealed the importance and mechanism of m6A methylation in the response of woody plants to salt stress for the first time.

Dual-trajectory of TyG levels and lifestyle scores and their associations with ischemic stroke in a non-diabetic population: a cohort study.

BACKGROUND: The Triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, has been implicated in the risk of ischemic stroke. However, the interplay between TyG levels, lifestyle factors, and their collective impact on stroke risk in non-diabetic populations remains inadequately explored. This study aims to evaluate the association of ischemic stroke with the joint development of the TyG index and lifestyle in the non-diabetic population. METHODS: In this prospective cohort study, data was collected across three consecutive biennial surveys of the Kailuan Study from 2006 to 2011. The dual-trajectory model was used to determine the temporal development of TyG levels and lifestyle scores. Statistical analysis involved Cox regression models to evaluate the association between TyG-lifestyle trajectories and ischemic stroke risk, adjusting for potential confounders. RESULTS: A total of 44,403 participants were included, with five distinct TyG levels and lifestyle scores trajectory subtypes identified. In the multivariable-adjusted analyses, significant differences in ischemic stroke risk among the trajectory subtypes. Group 5, characterized by the highest TyG levels and moderate lifestyle scores, exhibited the greatest ischemic stroke risk (HR = 1.81, 95% CI: 1.51-2.18), while group 4, with moderate TyG levels and higher lifestyle scores, demonstrated the lowest risk (HR = 1.19, 95% CI: 1.04-1.37), compared with group 3. Participants with elevated TyG levels were at an increased risk of ischemic stroke in cases of pronounced insulin resistance, even with a healthy lifestyle. CONCLUSIONS: This study reveals the significant associations between the identified TyG and lifestyle trajectories and the stratification of ischemic stroke risk among non-diabetics. The TyG index is a valuable indicator for assessing insulin resistance. However, the potential benefits of lifestyle changes for those with significantly high TyG levels need to be clarified by more research to develop more effective stroke prevention strategies.

Metabolic syndrome parameters' variability and stroke incidence in hypertensive patients: evidence from a functional community cohort.

BACKGROUND: Stroke is a common complication of hypertension, but the predictive value of metabolic syndrome parameters' variability on stroke risk in individuals with hypertension remains unclear. Therefore, our objective was to investigate the relationship between metabolic syndrome parameters' variability and the risk of total stroke and its subtypes in hypertensive patients. METHODS: This prospective cohort study included 17,789 individuals with hypertension from the Kailuan study since 2006. Metabolic syndrome parameters, including waist circumference (WC), fasting blood glucose (FBG), systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), were collected at three follow-up visits in the 2006, 2008, and 2010 surveys. We assess the variability utilizing the coefficient of variation (CV), standard deviation (SD), average real variation (ARV), and variability independent of the mean (VIM), with CV initially assessed. Participants were categorized based on the number of high-variability metabolic syndrome parameters (0, 1, 2, ≥ 3). Stroke cases were identified by reviewing medical records. The associations between variability in metabolic syndrome parameters and the risk of total stroke and its subtypes were analyzed using Cox proportional hazard regression models. RESULTS: During a median follow-up of 9.32 years, 1223 cases of stroke were recorded. Participants with ≥ 3 high-variability metabolic syndrome parameters had an increased risk of total stroke (HR: 1.29, 95%CI 1.09-1.52), as well as an increased risk of ischemic stroke (HR: 1.31, 95%CI 1.05-1.63) compared to those without high-variability parameters. The study also examined variability in each metabolic syndrome parameter, and significant associations with an increased risk of total stroke were observed for variability in SBP (HR: 1.24, 95%CI 1.05-1.46) and HDL-C (HR: 1.34, 95%CI 1.09-1.64). CONCLUSIONS: Long-term fluctuations in metabolic syndrome parameters significantly increase the risk of total stroke, especially ischemic stroke. Maintaining low variability in metabolic syndrome parameters could benefit health, and hypertensive individuals must be regularly monitored.

Diet Quality, Sedentary Time, and Blood Pressure in the POUCHmoms Study.

BACKGROUND: Elevated blood pressure (BP) is a major contributor to cardiovascular disease in womens; diet and sedentary time (ST) are modifiable lifestyle factors thought to influence BP. OBJECTIVES: The aim of this study was to examine 2 diet-quality measures and ST in relation to BP among parous womens. METHODS: This cross-sectional analysis uses data from 677 womens (age 25-55 y) enrolled in the Pregnancy Outcomes and Community Health (POUCH) Study and followed up in the POUCHmoms study 7-15 y after delivery (2011 and 2014). Follow-up measures included a food-frequency questionnaire (FFQ), self-report of ST (occupational and leisure), and systolic and diastolic blood pressure (SBP and DBP, respectively). The FFQ was used to calculate 2 diet-quality measures, Alternative Healthy Eating Index-2010 (AHEI) and Dietary Approaches to Stop Hypertension (DASH). Total ST h/wk was dichotomized at the median and labeled "low" or "high." In weighted unadjusted and adjusted regression models, BP was assessed in relation to diet scores (linear and threshold associations) and combinations of dichotomized diet-quality scores ("poor" = lowest quartile compared with "not poor" = upper 3 quartiles) and ST. RESULTS: Higher mean SBP and DBP occurred mainly in women with a '"poor" diet-quality score (AHEI and DASH). Among womens with a "poor"-quality diet (on the basis of the AHEI score) and "high" ST, (N = 93) adjusted mean SBP and DBP were 4.5 mmHg and 4.4 mmHg higher, respectively, than that of the counterparts who did not have a poor-quality diet and had "low" ST (N = 275). Results were similar in analyses using the DASH diet score. CONCLUSIONS: Women with poor-quality diets and more ST may need closer BP monitoring. Even modest improvements in womens' diet quality and reductions in ST might help lower their BP, but this observation needs testing in prospective studies..

Crystal-Rigidifying Strategy in Hybrid Manganese Halide to Achieve Narrow Green Emission and High Structural Stability.

Although organic-inorganic hybrid Mn2+ halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C-H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4 [BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4 display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor ß-SiAlON:Eu2+ and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2- units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron-phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4 realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+ halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.

Predictors of outcome in large vessel occlusion stroke patients with intravenous tirofiban treatment: a post hoc analysis of the RESCUE BT clinical trial.

OBJECTIVE: The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. METHODS: Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. RESULTS: A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0-2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947-0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807-0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869-0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665-0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991-0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705-25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CONCLUSION: Younger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CHINESE CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-IOR-17014167.

The impact of stress hyperglycemia ratio on short-term and long-term outcomes for acute basilar artery occlusion underwent endovascular treatment.

BACKGROUND: Stress hyperglycemia ratio (SHR) reflects a true acute hyperglycemic state during acute basilar artery occlusion (ABAO). We aimed to investigate the association between SHR and short-term and long-term outcomes in patients with ABAO receiving endovascular treatment (EVT). METHODS: We selected patients treated with EVT from the BASILAR study, a nationwide prospective registry. A total 250 patients with documented glucose and glycated hemoglobin (HbA1C) values at admission were included. SHR was calculated as the ratio of glucose/HbA1C. All 250 patients completed 90 days of follow-up and 234 patients (93.6%) completed 1 year of follow-up. The primary outcome was the favorable outcome defined as modified Rankin Scale (mRS) score ≤ 3 at 90 days. Safety outcomes included mortality at 90 days and 1 year, and intracranial hemorrhage. RESULTS: Among the 250 patients included, patients with higher tertiles of SHR were associated with decreased odds of a favorable functional outcome at 90 days (adjusted OR, 0.26; 95% CI, 0.12-0.56; P = 0.001 and adjusted OR, 0.37; 95% CI, 0.18-0.80; P = 0.01; respectively) and 1 year (adjusted OR, 0.34; 95% CI, 0.16-0.73; P = 0.006 and adjusted OR, 0.38; 95% CI, 0.18-0.82; P = 0.01; respectively) after adjusting for confounding covariates. The mortality was comparable across tertiles of SHR groups at 90 days and 1 year. CONCLUSIONS: Our study showed that SHR was associated with a decreased probability of favorable functional outcome both at 90 days and 1 year after EVT in patients with ABAO. The relationship was more pronounced in non-diabetes patients. TRIAL REGISTRATION: Clinical Trial Registry Identifier: ChiCTR1800014759 (November 12, 2013).

Construction of GSH-responsive polyethyleneimine-based delivery vector for effective gene transfection.

The rise of gene therapy has solved many diseases that cannot be effectively treated by conventional methods. Gene vectors is very important to protect and deliver the therapeutic genes to the target site. Polyethyleneimine (PEI) modified with mannitol could enhance the gene transfection efficiency reported by our group previously. In order to further control and improve the effective gene release to action site, disulfide bonds were introduced into mannitol-modified PEI to construct new non-viral gene vectors PeiSM. The degrees of mannitol linking with disulfide bonds were screened. Among them, moderate mannitol-modified PEI with disulfide bonds showed the best transfection efficiency, and significantly enhanced long-term systemic transgene expression for 72 hin vivoeven at a single dose administration, and could promote caveolae-mediated uptake through up-regulating the phosphorylation of caveolin-1 and increase the loaded gene release from the nanocomplexes in high glutathione intracellular environment. This functionalized gene delivery system can be used as an potential and safe non-viral nanovector for further gene therapy.

Sorting Out the Latest Advances in Separators and Pilot-Scale Microbial Electrochemical Systems for Wastewater Treatment: Concomitant Development, Practical Application, and Future Perspective.

To date, dozens of pilot-scale microbial fuel cell (MFC) devices have been successfully developed worldwide for treating various types of wastewater. The availability and configurations of separators are determining factors for the economic feasibility, efficiency, sustainability, and operability of these devices. Thus, the concomitant advances between the separators and pilot-scale MFC configurations deserve further clarification. The analysis of separator configurations has shown that their evolution proceeds as follows: from ion-selective to ion-non-selective, from nonpermeable to permeable, and from abiotic to biotic. Meanwhile, their cost is decreasing and their availability is increasing. Notably, the novel MFCs configured with biotic separators are superior to those configured with abiotic separators in terms of wastewater treatment efficiency and capital cost. Herein, a highly comprehensive review of pilot-scale MFCs (>100 L) has been conducted, and we conclude that the intensive stack of the liquid cathode configuration is more advantageous when wastewater treatment is the highest priority. The use of permeable biotic separators ensures hydrodynamic continuity within the MFCs and simplifies reactor configuration and operation. In addition, a systemic comparison is conducted between pilot-scale MFC devices and conventional decentralized wastewater treatment processes. MFCs showed comparable cost, higher efficiency, long-term stability, and significant superiority in carbon emission reduction. The development of separators has greatly contributed to the availability and usability of MFCs, which will play an important role in various wastewater treatment scenarios in the future.