Identification and functional characterization of bidirectional gene pairs and their intergenic regions in cotton.

BACKGROUND: In research to improve the quality of transgenic crops, it is often necessary to introduce multiple functionally related genes into recipient plants simultaneously to improve crop genetic traits effectively. Compared with unidirectional promoters, bidirectional promoters simultaneously regulate the expression of multiple genes and improve the efficiency of biotechnology. Therefore, in this study, bidirectional gene pairs were systematically analyzed in Gossypium hirsutum TM-1, and the structure, function and evolutionary relationships of the bidirectional genes were analyzed. The endogenous bidirectional promoters of cotton were mined, and their specific regulatory elements and biological functions were explored to provide useful promoter resources and a theoretical basis for cultivating new cotton germplasms with excellent fiber quality. RESULTS: Using an improved search model, a total of 1,383 bidirectional transcript pairs were identified in the Gossypium hirsutum TM-1 genome, and their gene structure and functional annotations were systematically analyzed. Thirty bidirectional intergenic sequences were randomly screened for promoter activity analysis via a transient expression system, and 25 intergenic sequences were found to have bidirectional promoter activity. Comparative analysis of the bidirectional gene profiles of the four cotton subspecies revealed that these subspecies presented abundant bidirectional gene pairs with high homology and that the bidirectional genes in the cotton subspecies were more similar in terms of their molecular functions, cellular components and biological processes. In addition, parallel analysis of bidirectional genes in dicotyledons and monocotyledons revealed that abundant bidirectional gene pairs exist in different species. Although the total number of orthologous bidirectional genes was similar, there was a significant difference in the number of orthologous bidirectional gene pairs between dicotyledons and monocotyledons. This evolutionary analysis of the function and structure of homologous bidirectional gene pairs in different varieties and different subspecies of the same species revealed potential pathways by which these gene pairs originated, which may be necessary for the evolution of a new species. CONCLUSION: In this study, many bidirectional gene pairs in Gossypium hirsutum TM-1 were identified using computer programming, and systematic analysis was conducted to explore their functions and evolutionary relationships. In addition, the promoter activity of the bidirectional intergenic sequences was verified. The combination of computer programming screening, experimental validation and other methods is expected to provide preferred bidirectional promoters for transgenic breeding work via multigene cotransformation methods, and this information is valuable for genetic engineering research and applications.

Diversified humoral immunity and impacts of booster vaccines: SARS-CoV-2 antibody profile and Omicron BA.2 neutralization before and after first or second boosters.

This study aims to investigate humoral immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and assess the impact of booster vaccines. We recruited individuals scheduled to receive either the first (original formula) or the second (bivalent) booster following the initial two-dose SARS-CoV-2 vaccination. We tested for IgG antibodies targeting the spike protein receptor-binding domain (RBD), S1, S2, and nucleocapsid protein, as well as for neutralizing antibodies against Omicron BA.2, before and 14-28 days after receiving the boosters. One year after receiving the initial series of vaccinations, all participants maintained anti-RBD/S1 antibodies. However, levels were lower in individuals who were vaccinated only compared to those who had both vaccination and prior infection (hybrid immunity). Participants with hybrid immunity also showed higher retention of neutralizing antibodies (93% compared to 24% in vaccine-only individuals). Even before receiving any booster shots, participants with hybrid immunity had antibody levels similar to those of vaccine-only individuals after their first booster. After receiving booster shots, antibody levels at 14-28 days were similar regardless of the number of boosters or the type of immunity. About 1 year after the first booster, all participants maintained neutralizing antibodies, and vaccine-only individuals retained about 10 times higher levels of binding antibodies than those without a booster. Humoral immunity varies widely among individuals, and vaccination planning should consider both vaccination and infection history. Boosters are beneficial for increasing antibody levels to ensure sufficient protection against infection and helping bridge the immunity gap between vaccine-only and hybrid immunity.IMPORTANCEAs we move into the era of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine boosters and shifting from pandemic to endemic, the landscape has changed for both the circulating SARS-CoV-2 variants and population immunity. Even though recent waves of infection have been clinically milder than earlier variants due to the high levels of population immunity and the properties of the Omicron subvariants, vaccination remains crucial for managing COVID-19 in the post-pandemic era. Our study unveils significant variations in the retention of anti-SARS-CoV-2 binding antibody profiles and neutralizing antibody levels 1 year after the primary and the first booster mRNA vaccination. It adds new information regarding how boosters change antibody levels and durability in individuals with hybrid (vaccination plus infection) or vaccine-only (never-infected) immunity. The findings can shed light on future vaccination planning.

Conventional ultrasonography enabled with augmented reality needle guidance for percutaneous kidney access: An innovative methodologies randomized controlled trial.

IMPORTANCE: Successful needle puncture of the renal collecting system is a critical but difficult procedure in percutaneous nephrolithotomy (PCNL). Although fluoroscopy and ultrasound are the standard imaging techniques to guide puncture during PCNL, both have known limitations. OBJECTIVE: To assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. DESIGN: This study employed a single-center randomized controlled trial (RCT) design to assess the feasibility and safety of a new navigation system for needle puncture in ultrasound-guided PCNL. Conducted between May 2021 and November 2021, the trial utilized computer-generated random numbers for participant allocation to control for selection bias. SETTING: The trial was executed at the *********, which serves as an academic medical center. PARTICIPANTS: All patients who met the inclusion criteria were randomly divided into two groups, with 29 patients in each group. One group underwent PCNL procedures using the new navigation system, while the control group underwent standard ultrasound-guided PCNL procedures. Included patients had renal pelvis or caliceal calculi larger than 2.0 cm in diameter or had multiple or staghorn stones. The puncture procedure was performed with the support of real-time ultrasound imaging and visual guidance displayed on the screen. MAIN OUTCOMES AND MEASURES: The primary outcome was system feasibility and puncture success rate. Secondary outcomes included puncture time, total surgical time, number of attempts, post-procedure complications, and one-year and three-year stone recurrence rates. Stone clearance was defined by postoperative CT. Descriptive statistics summarized patient demographics, stone size, and location. Independent samples t-tests analyzed puncture time and total surgical time. Chi-square or Fisher's exact tests compared stone clearance, complications, socioeconomic status, renal hydronephrosis, stone location, race, and medical history. Linear regression examined the correlation between BMI and puncture time. Significance was set at P<0.05. RESULTS: For all 58 patients undergoing PCNL, needle punctures of the renal collecting system were completed with a success rate of 100%. The average time from planning the puncture protocol to successful puncture was significantly shorter in the AcuSee guidance system group (3.12 min, range 0.2-6.88 min) compared to the standard ultrasound-guided group (7.58 min, range 5.41-10.68 min), representing a reduction of approximately 59%. The total surgical time was also shorter in the AcuSee group for patients with no and mild hydronephrosis (P<0.05). Complication rates were lower in the AcuSee group, with no major complications observed. However, 3 patients in the standard ultrasound-guided group have adverse effects after the PCNL procedure. The one-year stone recurrence rate was significantly lower in the AcuSee group (3.4%) compared to the standard group (24.1%), and the three-year recurrence rate was also lower (6.9% vs. 41.4%). Patient-specific factors such as BMI, renal morphology, and prior surgical history did not significantly affect the performance of the AcuSee system. CONCLUSIONS AND RELEVANCE: We report the first clinical application of a new navigation system for needle puncture in ultrasound-guided PCNL. It has been demonstrated that it is feasible and safe compared to the standard ultrasound-guided group in percutaneous renal puncture. This technology provides intuitive and easy-to-use visual guidance, which may facilitate safe, accurate and fast needle puncture of the kidney.

Mendelian randomization study on causal association of TEF and circadian rhythm with pulmonary arterial hypertension.

BACKGROUND: Previous research has revealed the potential impact of circadian rhythms on pulmonary diseases; however, the connection between circadian rhythm-associated Thyrotroph Embryonic Factor (TEF) and Pulmonary Arterial Hypertension (PAH) remains unclear. We aim to assess the genetic causal relationship between TEF and PAH by utilizing two sets of genetic instrumental variables (IV) and publicly available Pulmonary Arterial Hypertension Genome-Wide Association Studies (GWAS). METHODS: Total of 23 independent TEF genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Gain- and loss-of-function experiments were used to demonstrate the role of TEF in PAH. RESULTS: Our analysis revealed that as TEF levels increased genetically, there was a corresponding increase in the risk of PAH, as evidenced by IVW (OR = 1.233, 95% CI: 1.054-1.441; P = 0.00871) and weighted median (OR = 1.292, 95% CI for OR: 1.064-1.568; P = 0.00964) methods. Additionally, the up-regulation of TEF expression was associated with a significantly higher likelihood of abnormal circadian rhythm (IVW: P = 0.0024733, ß = 0.05239). However, we did not observe a significant positive correlation between circadian rhythm and PAH (IVW: P = 0.3454942, ß = 1.4980398). In addition, our in vitro experiments demonstrated that TEF is significantly overexpressed in pulmonary artery smooth muscle cells (PASMCs). And overexpression of TEF promotes PASMC viability and migratory capacity, as well as upregulates the levels of inflammatory cytokines. CONCLUSION: Our analysis suggests a causal relationship between genetically increased TEF levels and an elevated risk of both PAH and abnormal circadian rhythm. Consequently, higher TEF levels may represent a risk factor for individuals with PAH.

Predictive model for prolonged hospital stay risk after gastric cancer surgery.

Background: Prolonged postoperative hospital stay following gastric cancer (GC) surgery is an important risk factor affecting patients' mood and increasing complications. We aimed to develop a nomogram to predict risk factors associated with prolonged postoperative length of stay (PLOS) in patients undergoing gastric cancer resection. Methods: Data were collected from 404 patients. The least absolute shrinkage and selection operator (LASSO) was used for variable screening, and a nomogram was designed. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC). The consistency between the predicted and actual values was evaluated via a calibration map, and the clinical application value was evaluated via decision curve analysis (DCA) and clinical impact curve analysis (CICA). Results: A total of 404 patients were included in this study. Among these patients, 287 were assigned to the training cohort, and 117 were assigned to the validation cohort. According to the PLOS quartile distance, 103 patients were defined as having prolonged PLOS. LASSO regression and logistic multivariate analysis revealed that 4 clinical characteristics, the neutrophil-lymphocyte ratio (NLR) on postoperative day one, the NLR on postoperative day three, the preoperative prognostic nutrition index and the first time anal exhaust was performed, were associated with the PLOS and were included in the construction of the nomogram. The AUC of the nomogram prediction model was 0.990 for the training set and 0.983 for the validation set. The calibration curve indicated good correlation between the predicted results and the actual results. The Hosmer-Lemeshow test revealed that the P values for the training and validation sets were 0.444 and 0.607, respectively, indicating that the model had good goodness of fit. The decision curve analysis and clinical impact curve of this model showed good clinical practicability for both cohorts. Conclusion: We explored the risk factors for prolonged PLOS in GC patients via the enhanced recovery after surgery (ERAS) program and developed a predictive model. The designed nomogram is expected to be an accurate and personalized tool for predicting the risk and prognosis of PLOS in GC patients via ERAS measures.

Densification of Genetic Map and Stable Quantitative Trait Locus Analysis for Amino Acid Content of Seed in Soybean (Glycine max L.).

Soybean, a primary vegetable protein source, boasts favorable amino acid profiles; however, its composition still falls short of meeting human nutritional demands. The soybean amino acid content is a quantitative trait controlled by multiple genes. In this study, an F2 population of 186 individual plants derived from the cross between ChangJiangChun2 and JiYu166 served as the mapping population. Based on the previously published genetic map of our lab, we increased the density of the genetic map and constructed a new genetic map containing 518 SSR (simple sequence repeats) markers and 64 InDel (insertion-deletion) markers, with an average distance of 5.27 cm and a total length of 2881.2 cm. The content of eight essential amino acids was evaluated in the F2:5, F2:6, and BLUP (best linear unbiased prediction). A total of 52 QTLs (quantitative trait loci) were identified, and 13 QTL clusters were identified, among which loci02.1 and loci11.1 emerged as stable QTL clusters, exploring candidate genes within these regions. Through GO enrichment and gene annotation, 16 candidate genes associated with soybean essential amino acid content were predicted. This study would lay the foundation for elucidating the regulatory mechanisms of essential amino acid content and contribute to germplasm innovation in soybeans.

Optimal nitrogen management for high yield and N use efficiency of ratoon sorghum.

Sorghum ratooning, a time and labor-saving cultivation practice, is increasingly being adopted by farmers in Southwest China as an alternative. Efficient N fertilizer management is critical for economical production of sorghum and the long-term protection of the environment. To investigate the impact of N management on grain yield and nitrogen use efficiencies (NUEs) of ratoon sorghum system, a three-year field experiment was conducted for Jinyunuo3 (a hybrid cultivar) and Guojiaohong1 (an inbred cultivar) using 12 combinations of N rates and splitting ratios. The results showed that increasing N rate and splitting application times led to improvements in various growth parameters such as dry matter weight, crop growth rate (CGR), leaf area index (LAI), and photosynthetic potential (PP). The main, ratoon, and annual yields increased with N rate increase, but there was no significant difference between 225 and 150 kg N ha-1 in the ratoon and annual yields. Splitting the application of N fertilizer enhanced grain yield compared to a single dose application method, especially three-split applications yielded higher than two-split applications. Compared with N rates of 225 and 150 kg ha-1, N rate of 75 kg ha-1 increased apparent recovery rate of applied nitrogen (REN), agronomic efficiency of applied nitrogen (AEN), and partial factor productivity from applied nitrogen (PFPN) in both main season and whole year. But through splitting application methods at high N rates could achieve similar or even higher levels of NUEs compared to all applied as basal fertilizer at low N rates. Therefore, it could be recommended that applying 150 kg N ha-1 with a basal-jointing-heading fertilizer ratio of 2:4:4 represented an efficient N management practice to synchronously obtain high grain yield and NUEs in ratoon sorghum system in Southwest China.

Force Analysis Using Self-Expandable Valve Fluoroscopic Imaging: a way Through Artificial Intelligence.

This study aimed to develop a force analysis model correlating fluoroscopic images of self-expandable valves with stress distribution. For this purpose, a nonmetallic measuring device designed to apply diverse forces at specific positions on a valve stent while simultaneously measuring force magnitude was manufactured, obtaining 465 sets of fluorescent films under different force conditions, resulting in 5580 images and their corresponding force tables. Using the XrayGLM, a mechanical analysis model based on valve fluorescence images was trained. The accuracy of the image force analysis using this model was approximately 70% (50-88.3%), with a relative accuracy of 93.3% (75-100%). This confirms that fluoroscopic images of transcatheter aortic valve replacement (TAVR) valve stents contain a wealth of mechanical information, and machine learning can be used to train models to recognize the relationship between stent images and force distribution, enhancing the understanding of TAVR complications.

Natural triterpenoid-aided identification of the druggable interface of HMGB1 occupied by TLR4.

HMGB1 interacts with TLR4 to activate the inflammatory cascade response, contributing to the pathogenesis of endogenous tissue damage and infection. The immense importance of HMGB1-TLR4 interaction in the immune system has made its binding interface an area of significant interest. To map the binding interface of HMGB1 occupied by TLR4, triterpenoids that disrupt the HMGB1-TLR4 interaction and interfere with HMGB1-induced inflammation were developed. Using the unique triterpenoid PT-22 as a probe along with photoaffinity labeling and site-directed mutagenesis, we found that the binding interface of HMGB1 was responsible for the recognition of TLR4 located on the "L" shaped B-box with K114 as a crucial hot-spot residue. Amazingly, this highly conserved interaction surface overlapped with the antigen-recognition epitope of an anti-HMGB1 antibody. Our findings propose a novel strategy for better understanding the druggable interface of HMGB1 that interacts with TLR4 and provide insights for the rational design of HMGB1-TLR4 PPI inhibitors to fine tune immune responses.

ATF family members as therapeutic targets in cancer: From mechanisms to pharmacological interventions.

The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) transcription factors (TFs) with a variety of physiological functions, such as endoplasmic reticulum (ER) stress, amino acid stress, heat stress, oxidative stress, integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF family has been increasingly implicated in autophagy and ferroptosis in recent years. Thus, the ATF family is important for homeostasis and its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate the ATF family include direct modulators, upstream modulators, post-translational modifications (PTMs) modulators. This review summarizes the structural domain and the PTMs feature of the ATF/CREB family and comprehensively explores the molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, and drug resistance in various types of cancer cells are sorted out and discussed. We then systematically summarize the status of the therapeutic applications of existing ATF family modulators and finally look forward to the future prospect of clinical applications in the treatment of tumors by modulating the ATF family.

Molecular basis of human noradrenaline transporter reuptake and inhibition.

Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types1. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter (NET) located in the presynaptic membrane2. Here we report the cryo-electron microscopy (cryo-EM) structures of the human NET in both its apo state and when bound to substrates or antidepressant drugs, with resolutions ranging from 2.5 Å to 3.5 Å. The two substrates, noradrenaline and dopamine, display a similar binding mode within the central substrate binding site (S1) and within a newly identified extracellular allosteric site (S2). Four distinct antidepressants, namely, atomoxetine, desipramine, bupropion and escitalopram, occupy the S1 site to obstruct substrate transport in distinct conformations. Moreover, a potassium ion was observed within sodium-binding site 1 in the structure of the NET bound to desipramine under the KCl condition. Complemented by structural-guided biochemical analyses, our studies reveal the mechanism of substrate recognition, the alternating access of NET, and elucidate the mode of action of the four antidepressants.

Discovery of JNJ-74856665: A Novel Isoquinolinone DHODH Inhibitor for the Treatment of AML.

Acute myelogenous leukemia (AML), a heterogeneous disease of the blood and bone marrow, is characterized by the inability of myeloblasts to differentiate into mature cell types. Dihydroorotate dehydrogenase (DHODH) is an enzyme well-known in the pyrimidine biosynthesis pathway and preclinical findings demonstrated that DHODH is a metabolic vulnerability in AML as inhibitors can induce differentiation across multiple AML subtypes. As a result of virtual screening and structure-based drug design approaches, a novel series of isoquinolinone DHODH inhibitors was identified. Further lead optimization afforded JNJ-74856665 as an orally bioavailable, potent, and selective DHODH inhibitor with favorable physicochemical properties selected for clinical development in patients with AML and myelodysplastic syndromes (MDS).

SUVmean ratios of liver/muscle and lung/muscle from 13N-NH3 PET perfusion outperformed traditional myocardial viability parameters in predicting survival after CABG.

PURPOSE: Myocardial viability evaluation in predicting survival after coronary artery bypass graft (CABG) remains debatable. Thus, this study aimed to investigate the role of 13N-NH3/18F-FDG PET myocardial viability scan in predicting treatment outcomes and survival. METHODS: 90 patients with CABG and pre-surgical PET-based myocardial viability scan were retrospectively reviewed. Perfusion-metabolism features, myocardium motion parameters, and patient characteristics were recorded. Additionally, the SUVmean of blood pool, lung, liver, spleen, and muscle were measured and the SUVmean ratios were calculated. Factors associated with treatment outcomes and survival were analyzed by Logistic and Cox regressions. Nomogram models were subsequently established to predict ejection fraction (EF) improvement and survival outcomes. RESULTS: The mean EF of these 90 patients was 38.1 ± 9.5% and 46.0 ± 9.2% before and after CABG surgery, and 35 patients (38.9%) achieved EF improvement ≥ 10%. EF measurements by PET and echocardiogram showed a reasonable linear correlation (R = 0.752). Sex, pre-surgical EF, mismatch of the left ventricle, total perfusion deficit (TPD), and peak ejection rate (PER) were independent predictive factors of EF improvements. Surgery waiting time, valve damage, and SUVmean ratio of Liver/Muscle were independently predictive of event-free survival (EFS), while valve damage, together with SUVmean ratio of either Liver/Muscle or Lung/Muscle, were independently predictive of overall survival (OS). CONCLUSION: Although traditional cardiac parameters from PET-based myocardial viability can effectively predict EF improvements after CABG, SUVmean ratios of liver/muscle and lung/muscle from 13N-NH3 PET perfusion outperformed these parameters in predicting survival.

Accurate prediction of CDR-H3 loop structures of antibodies with deep learning.

Accurate prediction of the structurally diverse complementarity determining region heavy chain 3 (CDR-H3) loop structure remains a primary and long-standing challenge for antibody modeling. Here, we present the H3-OPT toolkit for predicting the 3D structures of monoclonal antibodies and nanobodies. H3-OPT combines the strengths of AlphaFold2 with a pre-trained protein language model and provides a 2.24 Å average RMSDCα between predicted and experimentally determined CDR-H3 loops, thus outperforming other current computational methods in our non-redundant high-quality dataset. The model was validated by experimentally solving three structures of anti-VEGF nanobodies predicted by H3-OPT. We examined the potential applications of H3-OPT through analyzing antibody surface properties and antibody-antigen interactions. This structural prediction tool can be used to optimize antibody-antigen binding and engineer therapeutic antibodies with biophysical properties for specialized drug administration route.

Association of in situ thrombus within the patent foramen ovale and patients with migraine: A prospective cohort study.

Background: Patent foramen ovale (PFO) is associated with migraine; however, the mechanism of PFO-associated migraine is not well known; additionally, percutaneous closure is controversial. This study aimed to investigate in situ thrombi within the PFO and explore the possible predictors of the effectiveness of PFO closure in migraineurs. Methods: This prospective cohort study included 48 asymptomatic patients and 92 migraineurs with PFO. Optical coherence tomography (OCT) was used to evaluate the PFO microstructure. Only migraineurs underwent percutaneous closure. Migraineurs were divided into two cohorts based on the presence of a thrombus within the PFO. The symptoms were assessed at the 12-month follow-up visit. Predictors were evaluated employing multivariate logistic regression and receiver operating characteristic curve analyses. Results: In situ thrombi within PFO were identified in 69 migraineurs and in two asymptomatic patients (76.7 % vs. 4.3 %; P < 0.001). Additionally, endocardial irregularity, discontinuity, low signal, and spasm were found in 59 (65.6 %), 15 (16.7 %), 13 (14.4 %), and six (6.7 %) patients, respectively, in the migraine group. In situ thrombus was associated with migraine risk (OR 49.03; 95%CI 8.52-282.18; P < 0.001). At the 12-month follow-up of the migraineur cohort, the primary endpoint, a 50 % reduction in migraine frequency after closure (with or without thrombus in PFO) was met (85.3 % vs. 25.0 %; P < 0.001). In situ thrombus was associated with migraine relief (OR 6.75; 95%CI 1.28-35.56; P = 0.024). Conclusions: In situ thrombus and abnormal endocardium within PFOs were common in migraineurs, and in situ thrombus was a risk factor for migraine. Percutaneous closure was more effective in migraineurs with thrombi within the PFO. OCT imaging improved the understanding of pathogenic PFOs and may be helpful in selecting suitable migraineurs for PFO closure.

A Novel Swine Model for Inducing Functional Tricuspid Valve Regurgitation.

Functional tricuspid regurgitation (FTR) is the most common TR, although experimental models to effectively study it are scarce; therefore, this study aimed to establish a robust experimental swine model. A swine FTR model was developed using radiofrequency ablation, atrial septostomy, and right atrial volume overload. The baseline and follow-up echocardiography was performed to evaluate the progression FTR and changes in the heart. Autopsy was employed to verify the anatomy of tricuspid valve. One-month post intervention, among the subjects, one (8.3%) exhibited severe FTR, eight (66.7%) exhibited moderate TR, and three (25%) exhibited mild FTR. Each pig developed an atrial septal defect (diameter, 1.5 ± 0.5 cm). The tricuspid annular diameter significantly increased with enlargement of right heart (P < 0.05). No significant difference was found on left heart size and mitral regurgitation. We successfully developed a novel swine FTR model, providing a reliable and effective platform for further research on FTR.

Comparisons of noncoronary sinus pivot implantation (NCPI) and conventional method for transcatheter aortic valve replacement with self-expanding valve in pure aortic regurgitation (PAR).

BACKGROUND: As compared to treatment of aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) using the commercially available valves to treat pure aortic regurgitation (PAR) has a lower device success rate and higher complication rates. AIMS: The study compared the acute results between TAVR using a novel noncoronary sinus pivot implantation (NCPI) method and that using the conventional method, aiming to explore a more optimized and effective operation method for TAVR in PAR. METHODS: PAR patients who underwent TAVR with self-expanding valves in our center from September 2021 to September 2023 were enrolled were divided into the NCPI (group A, N = 16) and conventional method (group B, N = 39) groups. We analyzed the pre-operative evaluation parameters and procedural and postoperative data of the two subgroups. RESULTS: The total patients' mean age was 71.2 ± 8.7 years and most were male (61.8%), with a mean Society of Thoracic Surgeons score of 3.4 ± 1.9%. The device success rate of groups A and B was 100% and 71.8%, respectively. In group B, 48.7% had major adverse cardiac events (MACE); 46.2% patients had permanent pacemaker implantation or valve in valve implantation. None had MACE in group A. The noncoronary sinus implantation depth in NCPI was -1.1 + 1.0 and 4.2 + 3.7 mm in groups A and B (p < 0.001), respectively. CONCLUSIONS: TAVR with a self-expanding valve using the NCPI method had a higher procedure success rate and dramatically low complications than that using the conventional method in PAR patients.

Construction of high-performance and sustainable polylactic acid composites for 3D printing applications with plasticizer.

Polylactic acid (PLA) attains much attention because of its biodegradability, biocompatibility, and high strength, but its further application was remarkably hindered by its brittleness. In order to improve the toughness of PLA, a biodegradable composite was prepared by blending ductile polycaprolactone (PCL), stiff microcrystalline cellulose (MCC), and green plasticizer tributyl citrate (TBC) with PLA by melting extrusion. The physicochemical properties and microstructure of PLA composites were thoroughly investigated using FTIR, TGA, DSC, XRD, melting rheology, optical transmittance, 3d printing, tensile tests, and SEM. The tensile tests results show that introduction of TBC exhibited a remarkable improvement effect in the elongation at break of PLA/PCL/MCC (PPM) composite, increasing from 2.9 % of PPM to up to 30 % of PPM/6TBC and PPM/8TBC. Noticeably, the strength of PPM/TBC composites (at least 33.1 MPa) was enhanced compared with that of PPM (28.2 MPa). The plasticization of TBC, enhancing the compatibility of composites, and reinforcing effect of MCC were identified as pivotal factors in toughening and reinforcing PLA. Furthermore, it is observed that the incorporation of TBC contributed to enhanced thermal stability, crystallinity, and rheology property of composites. This research supplies a novel approach to bolstering the toughness of PLA and broaden its potential applications.

Delayed luminescence to monitor growth stages and assess the entropy of Saccharomyces cerevisiae.

Delayed luminescence (DL) refers to the photon-induced ultra-weak luminescence emitted by samples after the light source is switched off. As a noninvasive method for health monitoring and disease diagnosis, DL has attracted increasing attention. The further development of this technology is valuable for the study of complex biological processes, such as different growth stages. If such studies were to be conducted in humans, large numbers of subjects of all ages would need to be recruited, and individual differences would be inevitable. The budding yeast Saccharomyces cerevisiae (S. cerevisiae) has a short population lifespan, and the growth phases can be monitored within dozens of hours. Therefore, S. cerevisiae is an ideal model organism for research. In this study, we investigated the physiological characteristics and DL emission of S. cerevisiae during growth in glucose-based media and entry into stationary phase, and the results showed that DL kinetic curves of yeast cells in the growing phase were obviously separated from those of stationary phase cells. Moreover, the metabolic and physiological characteristics of the yeast cell population were discussed using the DL emission parameters I0, τ and γ. We also discussed the possibility of assessing entropy using DL emission parameters. Our research demonstrates the potential of this technology to be used in wider applications.

MicroRNA-126 (MiR-126): key roles in related diseases.

In eukaryotes such as humans, some non-coding single-stranded RNAs (ncRNAs) help to regulate the pre- and post-transcriptional expression of certain genes, which in turn control many important physiological processes, such as cell proliferation, distinctions, invasion, angiogenesis, and embryonic development. microRNA-126 is an important member of these miRNAs that can be directly or indirectly involved in the control of angiogenesis. Recently, numerous studies have expounded that microRNA-126 can inhibit or promote angiogenesis as well as attenuate inflammatory responses through complex molecular mechanisms. As such, it serves as a biomarker or potential therapeutic target for the prediction, diagnosis, and treatment of relevant diseases. In this review, we present the advancements in research regarding microRNA-126's role in the diagnosis and treatment of related diseases, aiming to provide innovative therapeutic options for the diagnosis and treatment of clinically relevant diseases.