Carbonate uranium isotopes record global expansion of marine anoxia during the Toarcian Oceanic Anoxic Event.

The Toarcian Oceanic Anoxic Event (T-OAE; ~183 Mya) was a globally significant carbon-cycle perturbation linked to widespread deposition of organic-rich sediments, massive volcanic CO2 release, marine faunal extinction, sea-level rise, a crisis in carbonate production related to ocean acidification, and elevated seawater temperatures. Despite recognition of the T-OAE as a potential analog for future ocean deoxygenation, current knowledge on the severity of global ocean anoxia is limited largely to studies of the trace element and isotopic composition of black shales, which are commonly affected by local processes. Here, we present the first carbonate-based uranium isotope (δ238U) record of the T-OAE from open marine platform limestones of the southeastern Tethys Ocean as a proxy for global seawater redox conditions. A significant negative δ238U excursion (~0.4‰) is recorded just prior to the onset of the negative carbon isotope excursion comprised within the T-OAE, followed by a long-lived recovery of δ238U values, thus confirming that the T-OAE represents a global expansion of marine anoxia. Using a Bayesian inverse isotopic mass balance model, we estimate that anoxic waters covered ~6 to 8% of the global seafloor during the peak of the T-OAE, which represents 28 to 38 times the extent of anoxia in the modern ocean. These data, combined with δ238U-based estimates of seafloor anoxic area for other CO2-driven Phanerozoic OAEs, suggest a common response of ocean anoxia to carbon release, thus improving prediction of future anthropogenically induced ocean deoxygenation.

Machine learning based prediction models for analyzing risk factors in patients with acute abdominal pain: a retrospective study.

Background: Acute abdominal pain (AAP) is a common symptom presented in the emergency department (ED), and it is crucial to have objective and accurate triage. This study aims to develop a machine learning-based prediction model for AAP triage. The goal is to identify triage indicators for critically ill patients and ensure the prompt availability of diagnostic and treatment resources. Methods: In this study, we conducted a retrospective analysis of the medical records of patients admitted to the ED of Wuhan Puren Hospital with acute abdominal pain in 2019. To identify high-risk factors, univariate and multivariate logistic regression analyses were used with thirty-one predictor variables. Evaluation of eight machine learning triage prediction models was conducted using both test and validation cohorts to optimize the AAP triage prediction model. Results: Eleven clinical indicators with statistical significance (p < 0.05) were identified, and they were found to be associated with the severity of acute abdominal pain. Among the eight machine learning models constructed from the training and test cohorts, the model based on the artificial neural network (ANN) demonstrated the best performance, achieving an accuracy of 0.9792 and an area under the curve (AUC) of 0.9972. Further optimization results indicate that the AUC value of the ANN model could reach 0.9832 by incorporating only seven variables: history of diabetes, history of stroke, pulse, blood pressure, pale appearance, bowel sounds, and location of the pain. Conclusion: The ANN model is the most effective in predicting the triage of AAP. Furthermore, when only seven variables are considered, including history of diabetes, etc., the model still shows good predictive performance. This is helpful for the rapid clinical triage of AAP patients and the allocation of medical resources.

Regulatory Mechanism of Proanthocyanidins in Grape Peels Using vvi-miR828a and Its Target Gene VvMYBPA1.

Anthocyanins and proanthocyanidins are considered to be essential secondary metabolites in grapes and are used to regulate metabolic processes, while miRNAs are involved in their synthesis of anthocyanins and proanthocyanidins to regulate metabolic processes. The present research work was carried out to investigate the underlying regulatory mechanism of target genes in the grape cultivars 'Italia' and 'Benitaka'. miRNA and transnscriptomic sequencing technology were employed to characterize both the profiles of miRNAs and the transcripts of grape peels at 10 and 11 weeks post flowering (10 wpf and 11 wpf). The results revealed that the expression level of vvi-miR828a in 'Italia' at 10 and 11 wpf was significantly higher than that in 'Benitaka'. miRNA-seq analysis predicted MYBPA1 to be the target gene of vvi-miR828a. In transcriptome analysis, the expression level of the VvMYBPA1 gene in 'Benitaka' was significantly higher than that in 'Italia'; in addition, the TPM values (expression levels) of VvMYBPA1 and miR828a also showed an evident negative correlation. The determination of the proanthocyanidin (PA) content in 'Italia' and 'Benitaka' peels at 11 wpf demonstrated that the PA content of 'Benitaka' was significantly higher than that of 'Italia'. The outcomes of RT-qRCR analysis exhibited that the expression levels of the VdPAL, VdCHS, VdCHI, VdDFR, VdMYB5b, VdANR, and VdMYBPA1 genes related anthocyanin and proanthocyanidin pathways were reduced, while the expression levels of all of the above genes were increased after the transient expression of the VvMYBPA1 vector into grape leaves. The results of the transient overexpression experiment of vvi-miR828a before the veraison period of strawberry fruits showed that vvi-miR828a can significantly slow down the coloration of strawberries. The vvi-miR828a negatively regulates the accumulation of proanthocyanidins in grape fruits by inhibiting the expression of VvMYBPA1.

Psychological and Brain Responses to Artificial Intelligence's Violation of Community Ethics.

Human moral reactions to artificial intelligence (AI) agents' behavior constitute an important aspect of modern-day human-AI relationships. Although previous studies have mainly focused on autonomy ethics, this study investigates how individuals judge AI agents' violations of community ethics (including betrayals and subversions) compared with human violations. Participants' behavioral responses, event-related potentials (ERPs), and individual differences were assessed. Behavioral findings reveal that participants rated AI agents' community-violating actions less morally negative than human transgressions, possibly because AI agents are commonly perceived as having less agency than human adults. The ERP N1 component showed the same pattern with moral rating scores, indicating the modulation effect of human-AI differences on initial moral intuitions. Moreover, the level of social withdrawal correlated with a smaller N1 in the human condition but not in the AI condition. The N2 and P2 components were sensitive to the difference between the loyalty/betrayal and authority/subversion domains but not human/AI differences. Individual levels of moral sense and autistic traits also influenced behavioral data, especially on the loyalty/betrayal domain. In our opinion, these findings offer insights for predicting moral responses to AI agents and guiding ethical AI development aligned with human moral values.

Successful allogeneic fecal microbiota transplantation for severe diversion colitis: a case report.

Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding.

Impact of sequential (first- to third-generation) EGFR-TKI treatment on corrected QT interval in NSCLC patients.

Objective: To evaluate the impact of sequential (first- to third-generation) epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment on top-corrected QT interval (top-QTc) in non-small cell lung cancer (NSCLC) patients. Methods: We retrospectively reviewed the medical records of NSCLC patients undergoing sequential EGFR-TKI treatment at Shanghai Chest Hospital between October 2016 and August 2021. The heart rate (HR), top-QT interval, and top-QTc of their ECGs were extracted from the institutional database and analyzed. Logistic regression was performed to identify predictors for top-QTc prolongation. Results: Overall, 228 patients were enrolled. Compared with baseline (median, 368 ms, same below), both first-generation (376 ms vs. 368 ms, p < 0.001) and sequential third-generation EGFR-TKIs (376 ms vs. 368 ms, p = 0.002) prolonged top-QT interval to a similar extent (p = 0.635). Top-QTc (438 ms vs. 423 ms, p < 0.001) and HR (81 bpm vs.79 bpm, p = 0.008) increased after first-generation EGFR-TKI treatment. Further top-QTc prolongation (453 ms vs. 438 ms, p < 0.001) and HR increase (88 bpm vs. 81 bpm, p < 0.001) occurred after treatment advanced. Notably, as HR elevated during treatment, top-QT interval paradoxically increased rather than decreased, and the top-QTc increased rather than slightly fluctuated. Moreover, such phenomena were more significant after treatment advanced. After adjusting for confounding factors, pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation during sequential third-generation EGFR-TKI treatment. Conclusion: First-generation EGFR-TKI could prolong top-QTc, and sequential third-generation EGFR-TKI induced further prolongation. Top-QT interval paradoxically increased and top-QTc significantly increased as HR elevated, which was more significant after sequential EGFR-TKI treatment. Pericardial effusion and lower serum potassium levels were independent predictors of additional QTc prolongation after sequential EGFR-TKI treatment.

Overexpression of Calcineurin B-like Interacting Protein Kinase 31 Promotes Lodging and Sheath Blight Resistance in Rice.

A breakthrough "Green Revolution" in rice enhanced lodging resistance by using gibberellin-deficient semi-dwarf varieties. However, the gibberellic acid (GA) signaling regulation on rice disease resistance remains unclear. The resistance test showed that a positive GA signaling regulator DWARF1 mutant d1 was more susceptible while a negative GA signaling regulator Slender rice 1 (SLR1) mutant was less susceptible to sheath blight (ShB), one of the major rice diseases, suggesting that GA signaling positively regulates ShB resistance. To isolate the regulator, which simultaneously regulates rice lodging and ShB resistance, SLR1 interactors were isolated. Yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC), and Co-IP assay results indicate that SLR1 interacts with Calcineurin B-like-interacting protein kinase 31 (CIPK31). cipk31 mutants exhibited normal plant height, but CIPK31 OXs showed semi-dwarfism. In addition, the SLR1 level was much higher in CIPK31 OXs than in the wild-type, suggesting that CIPK31 OX might accumulate SLR1 to inhibit GA signaling and thus regulate its semi-dwarfism. Recently, we demonstrated that CIPK31 interacts and inhibits Catalase C (CatC) to accumulate ROS, which promotes rice disease resistance. Interestingly, CIPK31 interacts with Vascular Plant One Zinc Finger 2 (VOZ2) in the nucleus, and expression of CIPK31 accumulated VOZ2. Inoculation of Rhizoctonia solani AG1-IA revealed that the voz2 mutant was more susceptible to ShB. Thus, these data prove that CIPK31 promotes lodging and ShB resistance by regulating GA signaling and VOZ2 in rice. This study provides a valuable reference for rice ShB-resistant breeding.

Rotating Sonotrode Design for Ultrasonic-Assisted Arc Welding of Metal Materials.

In the process of the ultrasonic-assisted arc welding of metal materials, traditional ultrasonic application methods, such as the low-frequency impact of ultrasonic horns on a base material, can easily cause the non-fusion defect. In order to solve this problem, a rotating sonotrode with a groove and double thin ends was designed in this study. The ultrasonic vibration is transmitted into the weld pool by the rolling of the sonotrode on both sides of the weld. The resonant frequency was set at 50 kHz. Firstly, based on the Mindlin theory, a rotating sonotrode without a groove was designed by solving the frequency equation and by conducting a finite element simulation. Secondly, the effects of the groove, perforation, and transition mode on the resonant frequency, stress distribution, and amplification factor were investigated by finite element simulation. Finally, the optimum rotating sonotrode with a groove was obtained. The results show that the size of a rotating sonotrode that has a small frequency error can be obtained by using the discrete interval solver method combined with finite element simulation. The groove can significantly reduce the resonant frequency. The stress concentration can be effectively reduced by using the elliptical transition mode. The resonant frequency and amplification factor of a rotating sonotrode with a groove could be effectively adjusted by a method of double-position joint perforation. The final resonant frequency was 49.721 kHz and the amplification factor was 3.02. This study provides an effective design method for a sonotrode with double thin ends and a groove structure.

Circulating Immune Landscape Profiling in Psoriasis Vulgaris and Psoriatic Arthritis by Mass Cytometry.

Background: Psoriasis, a systemic disorder mediated by the immune system, can appear on the skin, joints, or both. Individuals with cutaneous psoriasis (PsC) have an elevated risk of developing psoriatic arthritis (PsA) during their lifetime. Despite this known association, the cellular and molecular mechanisms underlying this progression remain unclear. Methods: We performed high-dimensional, in-depth immunophenotyping of peripheral blood mononuclear cells (PBMCs) in patients with PsA and psoriasis vulgaris (PsV) by mass cytometry. Blood samples were collected before and after therapy for a longitudinal study. Then three sets of comparisons were made here: active PsA vs. active PsV, untreated PsV vs. treated PsV, and untreated PsA vs. treated PsA. Results: Marked differences were observed in multiple lymphocyte subsets of PsA related to PsV, with expansion of CD4+ T cells, CD16- NK cells, and B cells. Notably, two critical markers, CD28 and CD127, specifically differentiated PsA from PsV. The expression levels of CD28 and CD127 on both Naïve T cells (TN) and central memory CD4+ T cells (TCM) were considerably higher in PsA than PsV. Meanwhile, after treatment, patients with PsV had higher levels of CD28hi CD127hi CD4+ TCM cells, CD28hi CD127hi CD4+ TN cells, and CD16- NK cells. Conclusion: In the circulation of PsA patients, the TN and CD4+ TCM are characterized with more abundant CD28 and CD127, which effectively distinguished PsA from PsV. This may indicate that individuals undergoing PsV could be stratified at high risk of developing PsA based on the circulating levels of CD28 and CD127 on specific cell subsets.

Progress of uric acid in cardiovascular disease.

Due to the global prevalence of hyperuricemia (HUA), there is growing interest in research on uric acid (UA). HUA is a common condition that has various adverse consequences, including gout and kidney disease. However, recent studies have also implicated UA in the development of cardiovascular diseases (CVD) such as atrial fibrillation (AF) and coronary heart disease (CHD). Experimental and clinical research has extensively demonstrated the detrimental effects of elevated serum UA levels on cardiovascular health. Furthermore, serum UA levels have been identified as predictors of CVD outcomes following percutaneous coronary intervention (PCI) and catheter ablation. Additionally, the use of UA-lowering therapy holds important implications for the management of CVD. This review aims to consolidate the current evidence on the relationship between serum UA and CVD.

A peptide selectively recognizes Gram-negative bacteria and forms a bacterial extracellular trap (BET) through interfacial self-assembly.

An innate immune system intricately leverages unique mechanisms to inhibit colonization of external invasive Bacteria, for example human defensin-6, through responsive encapsulation of bacteria. Infection and accompanying antibiotic resistance stemming from Gram-negative bacteria aggregation represent an emerging public health crisis, which calls for research into novel anti-bacterial therapeutics. Herein, inspired by naturally found host-defense peptides, we design a defensin-like peptide ligand, bacteria extracellular trap (BET) peptide, with modular design composed of targeting, assembly, and hydrophobic motifs with an aggregation-induced emission feature. The ligand specifically recognizes Gram-negative bacteria via targeting cell wall conserved lipopolysaccharides (LPS) and transforms from nanoparticles to nanofibrous networks in situ to trap bacteria and induce aggregation. Importantly, treatment of the BET peptide was found to have an antibacterial effect on the Pseudomonas aeruginosa strain, which is comparable to neomycin. Animal studies further demonstrate its ability to trigger aggregation of bacteria in vivo. This biomimetic self-assembling BET peptide provides a novel approach to fight against pathogenic Gram-negative bacteria.

Can green funds improve corporate environmental, social, and governance performance? Evidence from Chinese-listed companies.

Green funds play pivotal roles in driving corporate sustainable development. Utilizing data from Chinese publicly listed companies from 2010 to 2021, we examine the impact of green funds on corporate environmental, social, and governance (ESG) performance and the underlying mechanisms. The research findings claim that green funds positively affect corporate ESG performance. Mechanism analysis systematically demonstrates that green funds contribute to elevated corporate ESG performance by alleviating financial constraints, enhancing managerial efficiency, and fostering green innovation. Heterogeneity analysis further underscores that the effect of green funds is particularly potent in companies with high external attention. Furthermore, green funds also play significant roles in production capabilities and economic value. This research enriches the micro-level evidence on the development of green funds and furnishes substantial implications for sustainable development.

Canagliflozin regulates metabolic reprogramming in diabetic kidney disease by inducing fasting-like and aestivation-like metabolic patterns.

AIMS/HYPOTHESIS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) are antihyperglycaemic drugs that protect the kidneys of individuals with type 2 diabetes mellitus. However, the underlying mechanisms mediating the renal benefits of SGLT2i are not fully understood. Considering the fuel switches that occur during therapeutic SGLT2 inhibition, we hypothesised that SGLT2i induce fasting-like and aestivation-like metabolic patterns, both of which contribute to the regulation of metabolic reprogramming in diabetic kidney disease (DKD). METHODS: Untargeted and targeted metabolomics assays were performed on plasma samples from participants with type 2 diabetes and kidney disease (n=35, 11 women) receiving canagliflozin (CANA) 100 mg/day at baseline and 12 week follow-up. Next, a systematic snapshot of the effect of CANA on key metabolites and pathways in the kidney was obtained using db/db mice. Moreover, the effects of glycine supplementation in db/db mice and human proximal tubular epithelial cells (human kidney-2 [HK-2]) cells were studied. RESULTS: Treatment of DKD patients with CANA for 12 weeks significantly reduced HbA1c from a median (interquartile range 25-75%) of 49.0 (44.0-57.0) mmol/mol (7.9%, [7.10-9.20%]) to 42.2 (39.7-47.7) mmol/mol (6.8%, [6.40-7.70%]), and reduced urinary albumin/creatinine ratio from 67.8 (45.9-159.0) mg/mmol to 47.0 (26.0-93.6) mg/mmol. The untargeted metabolomics assay showed downregulated glycolysis and upregulated fatty acid oxidation. The targeted metabolomics assay revealed significant upregulation of glycine. The kidneys of db/db mice undergo significant metabolic reprogramming, with changes in sugar, lipid and amino acid metabolism; CANA regulated the metabolic reprogramming in the kidneys of db/db mice. In particular, the pathways for glycine, serine and threonine metabolism, as well as the metabolite of glycine, were significantly upregulated in CANA-treated kidneys. Glycine supplementation ameliorated renal lesions in db/db mice by inhibiting food intake, improving insulin sensitivity and reducing blood glucose levels. Glycine supplementation improved apoptosis of human proximal tubule cells via the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. CONCLUSIONS/INTERPRETATION: In conclusion, our study shows that CANA ameliorates DKD by inducing fasting-like and aestivation-like metabolic patterns. Furthermore, DKD was ameliorated by glycine supplementation, and the beneficial effects of glycine were probably due to the activation of the AMPK/mTOR pathway.

Immune-like sandwich multiple hotspots SERS biosensor for ultrasensitive detection of NDKA biomarker in serum.

Developing the rapid, specific, and sensitive tumor marker NDKA biosensor has become an urgent need in the field of early diagnosis of colorectal cancer (CRC). Surface-enhanced Raman spectroscopy (SERS) with the advantages of high sensitivity, high resolution as well as providing sample fingerprint, enables rapid and sensitive detection of tumor markers. However, many SERS biosensors rely on boosting the quantity of Raman reporter molecules on individual nanoparticle surfaces, which can result in nanoparticle agglomeration, diminishing the stability and sensitivity of NDKA detection. Here, we proposed an immune-like sandwich multiple hotspots SERS biosensor for highly sensitive and stable analysis of NDKA in serum based on molecularly imprinted polymers and NDKA antibody. The SERS biosensor employs an array of gold nanoparticles, which are coated with a biocompatible polydopamine molecularly imprinted polymer as a substrate to specifically capture NDKA. Then the biosensor detects NDKA through Raman signals as a result of the specific binding of NDKA to the SERS nanotag affixed to the capture substrate along with the formation of multiple hotspots. This SERS biosensor not only avoids the aggregation of nanoparticles but also presents a solution to the obstacles encountered in immune strategies for certain proteins lacking multiple antibody or aptamer binding sites. Furthermore, the practical application of the SERS biosensor is validated by the detection of NDKA in serum with the lower limit of detection (LOD) of 0.25 pg/mL, meanwhile can detect NDKA of 10 ng/mL in mixed proteins solution, illustrating high sensitivity and specificity. This immune-like sandwich multiple hotspots biosensor makes it quite useful for the early detection of CRC and also provides new ideas for cancer biomarker sensing strategy in the future.

Correlation between carcinoembryonic antigen (CEA) expression and EGFR mutations in non-small-cell lung cancer: a meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to investigate the relationship between serum carcinoembryonic antigen (CEA) expression and epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer (NSCLC). METHODS: Databases such as PubMed, Cochrane, EMBASE and Google Scholar were systematically searched to identify studies assessing the association of serum CEA expression with EGFR mutations. Across 19 studies, 4168 patients were included between CEA expression and EGFR mutations odds ratio (OR) conjoint analysis of correlations. RESULTS: Compared with CEA-negative NSCLC, CEA-positive tumors had an increased EGFR mutation rate (OR = 1.85, 95% confidence interval: 1.48-2.32, P < 0.00001). This association was observed in both stage IIIB/IV patients (OR = 1.60, 95% CI: 1.18-2.15, P = 0.002) and stage I-IIIA (OR = 1.67, 95% CI: 1.01-2.77, P = 0.05) patients. In addition, CEA expression was associated with exon 19 (OR = 1.97, 95% CI: 1.25-3.11, P = 0.003) and exon 21 (OR = 1.51, 95% CI: 1.07-2.12, P = 0.02) EGFR mutations. In ADC pathological type had also showed the correlation (OR = 1.84, 95% CI: 1.31-2.57, P = 0.0004). CONCLUSIONS: This meta-analysis indicated that serum CEA expression was associated with EGFR mutations in NSCLC patients. The results of this study suggest that CEA level may play a predictive role in the EGFR mutation status of NSCLC patients. Detecting serum CEA expression levels can give a good suggestion to those patients who are confused about whether to undergo EGFR mutation tests. Moreover, it may help better plan of the follow-up treatment.

Canagliflozin improves fatty acid oxidation and ferroptosis of renal tubular epithelial cells via FOXA1-CPT1A axis in diabetic kidney disease.

Impaired fatty acid oxidation (FAO) is a metabolic hallmark of renal tubular epithelial cells (RTECs) under diabetic conditions. Disturbed FAO may promote cellular oxidative stress and insufficient energy production, leading to ferroptosis subsequently. Canagliflozin, an effective anti-hyperglycemic drug, may exert potential reno-protective effects by upregulating FAO and inhibiting ferroptosis in RTECs. However, the mechanisms involved remain unclear. The present study is aimed to characterize the detailed mechanisms underlying the impact of canagliflozin on FAO and ferroptosis. Type 2 diabetic db/db mice were administrated daily by gavage with canagliflozin (20 mg/kg/day, 40 mg/kg/day) or positive control drug pioglitazone (10 mg/kg/day) for 12 weeks. The results showed canagliflozin effectively improved renal function and structure, reduced lipid droplet accumulation, enhanced FAO with increased ATP contents and CPT1A expression, a rate-limiting enzyme of FAO, and relieved ferroptosis in diabetic mice. Moreover, overexpression of FOXA1, a transcription factor related with lipid metabolism, was observed to upregulate the level of CPT1A, and further alleviated ferroptosis in high glucose cultured HK-2 cells. Whereas FOXA1 knockdown had the opposite effect. Mechanistically, chromatin immunoprecipitation assay and dual-luciferase reporter gene assay results demonstrated that FOXA1 transcriptionally promoted the expression of CPT1A through a sis-inducible element located in the promoter region of the protein. In conclusion, these data suggest that canagliflozin improves FAO and attenuates ferroptosis of RTECs via FOXA1-CPT1A axis in diabetic kidney disease.

A Homochiral Fulgide Organic Ferroelectric Crystal with Photoinduced Molecular Orbital Breaking.

Thermally triggered spatial symmetry breaking in traditional ferroelectrics has been extensively studied for manipulation of the ferroelectricity. However, photoinduced molecular orbital breaking, which is promising for optical control of ferroelectric polarization, has been rarely explored. Herein, for the first time, we synthesized a homochiral fulgide organic ferroelectric crystal (E)-(R)-3-methyl-3-cyclohexylidene-4-(diphenylmethylene)dihydro-2,5-furandione (1), which exhibits both ferroelectricity and photoisomerization. Significantly, 1 shows a photoinduced reversible change in its molecular orbitals from the 3 π molecular orbitals in the open-ring isomer to 2 π and 1 σ molecular orbitals in the closed-ring isomer, which enables reversible ferroelectric domain switching by optical manipulation. To our knowledge, this is the first report revealing the manipulation of ferroelectric polarization in homochiral ferroelectric crystal by photoinduced breaking of molecular orbitals. This finding sheds light on the exploration of molecular orbital breaking in ferroelectrics for optical manipulation of ferroelectricity.

Establishment of RNA Interference Genetic Transformation System and Functional Analysis of FlbA Gene in Leptographium qinlingensis.

Leptographium qinlingensis is a pathogenic fungus of Pinus armandii that is epidemic in the Qinling Mountains. However, an effective gene interference strategy is needed to characterize the pathogenic genes in this fungus on a functional level. Using the RNA silencing vector pSilent-1 as a template, we established an RNA interference genetic transformation system mediated by Agrobacterium tumefaciens GV3101, which is suitable for the gene study for Leptographium qinlingensis by homologous recombination and strain interference system screening. The LqFlbA gene was silenced using the RNA interference approach described above, and the resulting transformants displayed various levels of silencing with a gene silencing effectiveness ranging from 41.8% to 91.4%. The LqFlbA-RNAi mutant displayed altered colony morphology, sluggish mycelium growth, and diminished pathogenicity toward the host P. armandii in comparison to the wild type. The results indicate that this method provides a useful reverse genetic system for studying the gene function of L. qinlingensis, and that LqFlbA plays a crucial role in the growth, development, and pathogenicity of L. qinlingensis.

Large Phase-Transition Temperature Enhancement Achieved in a Layered Lead Iodide Hybrid Crystal by H/F Substitution.

Organic-inorganic hybrid metal halides with structural flexibility and solution processability have been widely investigated for different application scenarios. However, the effective construction of phase-transition materials with a high phase-transition temperature (Ttr) for potential practical applications remains a great challenge, and reports on the regulation of Ttr with significant enhancement have been rare. In this manuscript, we have realized a large Ttr increase of 148 K in a layered hybrid lead iodide crystal (4-FTMBA)4Pb3I10 (4-FTMBA = 4-fluoro-N,N,N-trimethylbenzenaminium) by the H/F substitution strategy. Compared to the parent (TMBA)4Pb3I10 (TMBA = N,N,N-trimethylbenzenaminium), H/F substitution preserves the structural framework and crystal symmetry in (4-FTMBA)4Pb3I10. The introduction of heavier fluorine will significantly increase the motion barrier for the order-disorder transition, resulting in the remarkably improved Ttr. Temperature-dependent crystal structures, Raman spectra, and dielectric analyses well support the phase-transition behavior. In addition, evident thermochromism with a tunable direct band gap in (4-FTMBA)4Pb3I10 has been observed using UV-vis spectra. To the best of our knowledge, the achieved Ttr enhancement of 148 K by H/F substitution is the highest among the organic-inorganic hybrid lead halide phase-transition materials. This finding would greatly inspire the rational design of functional materials with high performance.

LncRNA GAS5 Attenuates Cardiac Electrical Remodeling Induced by Rapid Pacing via the miR-27a-3p/HOXa10 Pathway.

Previous studies indicated long non-coding RNAs (lncRNAs) participated in the pathogenesis of atrial fibrillation (AF). However, little is known about the role of lncRNAs in AF-induced electrical remodeling. This study aimed to investigate the regulatory effect of lncRNA GAS5 (GAS5) on the electrical remodeling of neonatal rat cardiomyocytes (NRCMs) induced by rapid pacing (RP). RNA microarray analysis yielded reduced GAS5 level in NRCMs after RP. RT-qPCR, western blot, and immunofluorescence yielded downregulated levels of Nav1.5, Kv4.2, and Cav1.2 after RP, and whole-cell patch-clamp yielded decreased sodium, potassium, and calcium current. Overexpression of GAS5 attenuated electrical remodeling. Bioinformatics tool prediction analysis and dual luciferase reporter assay confirmed a direct negative regulatory effect for miR-27a-3p on lncRNA-GAS5 and HOXa10. Further analysis demonstrated that either miR-27a-3p overexpression or the knockdown of HOXa10 further downregulated Nav1.5, Kv4.2, and Cav1.2 expression. GAS5 overexpression antagonized such effects in Nav1.5 and Kv4.2 but not in Cav1.2. These results indicate that, in RP-treated NRCMs, GAS5 could restore Nav1.5 and Kv4.2 expression via the miR-27a-3p/HOXa10 pathway. However, the mechanism of GAS5 restoring Cav1.2 level remains unclear. Our study suggested that GAS5 regulated cardiac ion channels via the GAS5/miR-27a-3p/HOXa10 pathway and might be a potential therapeutic target for AF.