RESUMEN

To investigate the variation and fractionation of stable isotopes from irrigation water to soil, grapes, and wine, δ2H, δ18O, and δ17O in different samples from 10 regions in China were determined using a water isotope analyser. The values were significantly different among regions according to the chemometric analysis. All isotopes were significantly and positively correlated with irrigation water-soil and grape-wine. A significant water isotopic fractionation effect was observed from the irrigation water to the soil, grapes, and wine. Stable isotope distribution characteristics correlated with longitude, latitude, altitude, temperature, precipitation, station pressure and wind speed. The linear discriminant analysis (LDA), random forest (RF), support vector machine (SVM), and feed-forward neural network (FNN) models 58.33-100 %, 80-100 %, 53.33-100 %, and 73.33-100 % accurate for distinguishing the geographical origins of all samples from training and test data, respectively. These findings provide a theoretical basis for authenticating the geographic origin of Chinese wines using stable isotope analysis.

Asunto(s)

RESUMEN

Tubocapsicum anomalum, a Chinese medicinal plant rich in anti-tumor withanolides, requires efficient extraction methods. In this paper, an HPLC method was first established for the detection of withanolides, and gradient elution was carried out using a methanol-water solvent system. It was found that the content of withanolides was the highest in the leaves of T. anomalum, followed by the stems and fruits, and almost none in the roots. During the actual picking process, the quantity of leaves collected was relatively small, while the number of stems was the highest. Therefore, the Box-Behnken response surface method was used to optimize the ultrasonic-assisted extraction process of withanolides from the stems of T. anomalum. The optimal extraction conditions were determined as follows: the liquid-solid ratio was 20:1, the extraction solvent was 70 % ethanol, the ultrasonic power was 250 W, the ultrasonic time was 40 min, and the ultrasonic temperature was 50 °C. Under these conditions, the average yields of tubocapsenolide A (Te-A) and tubocapsanolide A (Ta-A) can reach 2.87 ± 0.12 mg/g and 1.18 ± 0.05 mg/g, respectively. We further compared extraction rates of two withanolides from different parts of T. anomalum using ultrasonic and traditional extraction methods. Ultrasonic extraction significantly increased rates, with the highest yields from leaves, followed by stems and fruits. The results show that ultrasonic optimization can improve extraction rate, reduce time, lower costs, enhance quality, and increase yield. Therefore, the optimized ultrasonic-assisted extraction process was adopted to extract the aerial parts of T. anomalum and separate the components. After optimization, the extract underwent several chromatographic separations to isolate eight previously undescribed withanolides (1-8) and two artificial withanolides (9-10), in addition to fifteen known compounds (11-25). Their structures were established through extensive spectroscopic data analysis. The compounds were evaluated for their antiproliferative effects against multiple cancer cell lines, including human hepatocellular carcinoma cells (HepG2, Hep3B, and MHCC97-H), human lung cancer cells (A549), human fibro-sarcoma cancer cells (HT1080), human chronic myeloid leukemia cells (K562), and human breast cancer cells (MDA-MB-231 and MCF7). Compounds 1-3, 5, 7, 11, 13, 15-16, and 22 displayed significant activity with IC50 values of 5.14-19.87 µM. The above results indicate that ultrasonic-assisted extraction technology can be used to obtain new withanolides more efficiently from T. anomalum, thereby enhancing the utilization rate of T. anomalum resources.

RESUMEN

Biofouling has been persisting as a global problem due to the difficulties in finding efficient and environmentally friendly antifouling coatings for long-term applications. Initial attachment of bacteria on material surface and subsequent formation of biofilm are the predominate phenomena accounting for subsequent occurrence of biofouling. Among the various factors influencing the bacterial attachment, conditioning layer formed by organic macromolecules usually plays the key role in mediating bacterial attachment through altering physicochemical properties of substrate surface. In this study, a guanidine-modified polysaccharide conditioning layer with the capability of tuning the bacterial attachment is constructed and characterized. Dextran, a polysaccharide widespread in bacteria extracellular polymeric substances (EPS), is oxidized by sodium periodate, and cationic polymer polyhexamethylene guanidine hydrochloride (PHMG) is anchored to oxidized dextran (ODEX) by Schiff base reaction. AFM characterization reveals morphological changes of the polysaccharide conditioning layer from tangled chain to island conformation after the PHMG modification. The guanidine-based dextran conditioning layer promotes attachment of both P. aeruginosa and S. aureus and disrupted bacterial cytomembranes are seen for the attached bacteria due to electrostatic interaction of the electropositive guanidine group with the electronegative bacteria. The guanidine-based dextran conditioning layer shows a low survival ratio of 22 %-34 % and 1 %-4 % for P. aeruginosa and S. aureus respectively after incubation in the bacterial suspension for 72 hours. The results would give insight into further exploring the potential applications of the newly designed polysaccharides conditioning layer for combating occurrence of biofouling.

RESUMEN

The compound 2,4,6-trichlorophenol poses significant risks to both the aquatic environment and human health. Its inherent persistence and stability present challenges in achieving complete purification, thus warranting its inclusion as a priority pollutant. The present study reports the development of an amphiphilic small-molecule compound that self-assembles into nanovesicles exhibiting remarkable adsorption and photodegradation capabilities. Through the synergistic effects of hydrogen bonding, van der Waals forces, π-π interactions, and electrostatic interactions, these vesicles efficiently adsorb 2,4,6-trichlorophenol from aqueous solutions within 1 min while demonstrating exceptional environmental stability and broad applicability. Upon self-assembly into vesicles, not only are more adsorption sites exposed, but charge separation and migration within the vesicles are also facilitated. Through the synergistic effects of adsorption and photodegradation, complete removal of 2,4,6-trichlorophenol in aqueous solution can be achieved within 8 h while exhibiting excellent recycling capability. This approach offers a viable strategy for designing and synthesizing pure organic photodegradable materials.

RESUMEN

Reactor pressure vessel (RPV) studs are key components of nuclear reactors, and their connection with flange ensures the sealing of the RPV under high-pressure and high-temperature conditions. In the present work, the external threads of the RPV stud were prepared by triaxial rolling, and the texture evolution of the external thread root material of an RPV stud was predicted by finite element analysis coupled with viscoplastic self-consistent simulations. The microstructure of the external thread root material of RPV stud was characterized by scanning electron microscope and electron back-scattered diffraction. The installation characteristics of the turned and rolled parts of the RPV stud were tested by installation and pretightening tests. It was found that the dynamic recrystallization at the external thread root formed ultrafine tempered sorbite grains, high-angle grain boundaries (47%), and strong {111} <110> and {111} <112> textures. In the installation and pretightening test, the residual elongation of rolled parts was reduced by 6% under the same loading pressure. The triaxial rolling process distributed the microstructure of the external thread root of the RPV stud in a gradient manner, resulting in improved stud installation characteristics.

RESUMEN

OBJECTIVE: To explore the effectiveness of HPV 16/18 E7 oncoprotein in detecting high-grade cervical intraepithelial neoplasia (CIN) and predicting disease outcomes in HPV 16/18-positive patients. METHODS: The present study was a cross-sectional study with a 2-year follow up. We collected 915 cervical exfoliated cell samples from patients who tested positive for HPV 16/18 in gynecologic clinics of three tertiary hospitals in Beijing from March 2021 to October 2022 for HPV 16/18 E7 oncoprotein testing. Subsequently, 2-year follow up of 408 patients with baseline histologic CIN1 or below were used to investigate the predictive role of HPV 16/18 E7 oncoprotein in determining HPV persistent infection and disease progression. RESULTS: The positivity rate of the HPV 16/18 E7 oncoprotein assay was 42.06% (249/592) in the inflammation/CIN 1 group and 85.45% (277/324) in the CIN2+ group. For CIN2+ detection, using the HPV 16/18 E7 oncoprotein assay combined with HPV 16/18 testing, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.45%, 57.94%, 52.57%, and 87.95%, respectively. During the 2-year follow up, the sensitivity, specificity, PPV, and NPV for predicting persistent HPV infection were 48.44%, 58.21%, 34.64%, and 71.18% in the baseline inflammation and CIN1 group. CONCLUSIONS: As a triage method for high-grade CIN screening in HPV 16/18-positive patients, HPV 16/18 E7 oncoprotein demonstrated a relatively high NPV, making it suitable for clinical use in triaging HPV 16/18-positive cases and potentially reducing the colposcopic referral rate. HPV 16/18 E7 oncoprotein exhibited a preferably predictive value in determining HPV infection outcomes and disease progression.

RESUMEN

Puberty onset through hypothalamic-pituitary-gonad (HPG) axis as an important reproductive event in postnatal development is initiated from hypothalamic arcuate nucleus (ARC). The growing evidence indicates that translational control also plays an essential role in the final expression of gonadotropin genes. To investigate the role of protein translation and behavior of ribosomes in pubertal onset, the global profiles of transcriptome, single ribosome (monosome), polysome, and tandem mass tag proteome were comprehensively investigated in rat hypothalamic ARCs of different pubertal stages using RNA sequencing, polyribo sequencing, and mass spectrum. Transcriptome-wide enrichments of N6-methyladenosine and IGF2BP2 were investigated using meRIP and RIP sequencing. Monosome was robustly enriched on a large proportion of mRNA in early puberty rats (postnatal day (PND)-25) compared to late puberty (PND-35 and PND-45). Monosome-enriched mRNAs, including HPG axis-related genes, had a large number of upstream ORFs (uORF, < 100 nt) and displayed translational repression in early puberty. Furthermore, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could particularly interact with and facilitate monosome to bind with mRNA in early puberty. Finally, ectopic over-expression of IGF2BP2 in hypothalamic ARC via lateral ventricle injection in vivo could recruit monosome to aggregate on mRNA and delay puberty onset. We uncovered a novel regulatory mechanism of IGF2BP2 and monosome for translational control in puberty onset, which shed light on the neuroendocrine regulatory network involved in HPG axis activation.

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The Danshen-Shanzha Decoction (DSD) is a renowned herbal combination consisting of the root of Salvia miltiorrhiza Bunge (known as Danshen in Chinese) and the fruits of Crataegus pinnatifida Bunge (known as Shanzha in Chinese), which has exhibited remarkable clinical efficacy in the treatment of coronary heart disease (CHD) in traditional Chinese medicine, with its earliest recorded application dating to around 202 BCE during the Han Dynasty. Despite significant advancements in the fundamental research and clinical applications of DSD over the past few decades, the precise bioactive components as well as the underlying mechanisms responsible for its protective effect on CHD remain unelucidated. AIM OF THE STUDY: The present study was designed to elucidate the bioactive components and potential mechanism of DSD in the treatment of CHD using in silico technologies integrated with pharmacoinformatic methods and experimental validation. MATERIALS AND METHODS: The chemical components of DSD were analyzed and identified using UPLC-Q-TOF-MS. Pharmacoinformatic-based methods were employed to comprehensively investigate the principal active components and targets of DSD for treating CHD. GO and KEGG pathway analyses were utilized to elucidate the underlying mechanism responsible for DSD's efficacy against CHD. Molecular docking and molecular dynamics simulation were performed to assess the binding affinity between active components and putative targets. Furthermore, surface plasmon resonance (SPR) was carried out to verify the affinity and kinetic characteristics of major components to STAT3 protein. Subsequently, a series of in vitro experiments, including cell viability test, flow cytometric analysis, ELISA and western blotting, were conducted to validate the predicted results in an oxygen-glucose deprivation (OGD)-stimulated H9c2 model. RESULTS: A total of 96 compounds were characterized by UPLC-Q-TOF-MS, and 281 overlapping targets were identified through pharmacoinformatic-based methods. Among these, ten critical compounds were determined as the core active components of DSD. The core targets associated with the development of CHD included STAT3, SRC, TP53, JUN, and AKT1. Notably, Dihydrotanshinone I and (+)-Epicatechin exhibited strong binding affinity towards STAT3. The potential mechanisms by which DSD modulates the pathological progression of CHD were predicted to involve inflammation, oxidative stress, and apoptosis. Importantly, the cytoprotective effect of DSD against apoptosis was confirmed in OGD-stimulated H9c2 cells, as evidenced by the upregulation of Bcl-2 expression and downregulation of both Bax and cleaved caspase-3 expressions upon DSD treatment. Furthermore, DSD significantly enhanced the phosphorylated protein expressions of JAK2 and STAT3 compared to the OGD group, suggesting its potential role in modulating related signaling pathways. CONCLUSIONS: The current study successfully fills the gap in the understanding of the chemical profiles of DSD, predicting its active components, potential targets, and molecular mechanisms in the treatment of CHD. These findings not only provide a valuable strategy but also robust data support for future investigations into DSD, thereby facilitating the identification of novel therapeutic targets for traditional Chinese medicines in the battle against CHD.

RESUMEN

Prostate cancer rarely metastasizes to the stomach and kidneys. We report a 73-year-old male with such spread, highlighting significant clinical challenges. Initially diagnosed via biopsy and imaging, he received hormone therapy and cytoreductive radical prostatectomy. Despite initial management, the cancer progressed to metastatic castration-resistant prostate cancer, with gastric and renal metastases confirmed by imaging and biopsy. This case emphasizes the need for awareness of rare metastatic sites, comprehensive diagnostic evaluations, and further research into these atypical metastases to improve patient outcomes and develop better treatment strategies for managing advanced prostate cancer effectively.

RESUMEN

Pine wilt disease (PWD) is caused by pine wood nematode (PWN, Bursaphelenchus xylophilus) and significantly impacts pine forest ecosystems globally. This study focuses on Pinus massoniana, an important timber and oleoresin resource in China, and is highly susceptible to PWN. However, the defense mechanism of pine trees in response to PWN remains unclear. Addressing the complexities of PWD, influenced by diverse factors like bacteria, fungi, and environment, we established a reciprocal system between PWN and P. massoniana seedlings under aseptic conditions. Utilizing combined second and third-generation sequencing technologies, we identified 3,718 differentially expressed genes post-PWN infection. Transcript analysis highlighted the activation of defense mechanisms via stilbenes, salicylic acid and jasmonic acid pathways, terpene synthesis, and induction of pathogenesis-related proteins and resistance genes, predominantly at 72 hours post-infection. Notably, terpene synthesis pathways, particularly the mevalonate pathway, were crucial in defense, suggesting their significance in P. massoniana's response to PWN. This comprehensive transcriptome profiling offers insights into P. massoniana's intricate defense strategies against PWN under aseptic conditions laid a foundation for future functional analyses of key resistance genes.

RESUMEN

OBJECTIVES: To investigate the incidence and risk factors for acute kidney injury (AKI) in children with primary nephrotic syndrome (PNS), as well as the role of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in the early identification of AKI in these children. METHODS: A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted. The children were divided into two groups based on the presence of AKI: the AKI group (47 cases) and the non-AKI group (169 cases). The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis. Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups, as well as among the different stages of AKI. RESULTS: The incidence of AKI in children with PNS was 21.8%. Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome, gastrointestinal infections, and heavy proteinuria were independent risk factors for AKI in these children with PNS (P<0.05). Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group (P<0.05), and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup (P<0.017). CONCLUSIONS: KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS. Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.

Asunto(s)

RESUMEN

BACKGROUND: Adenocarcinoma is the most common subtype of prostate cancer. Prostatic urothelial carcinoma (UC) typically originates from the prostatic urethra. The concurrent occurrence of adenocarcinoma and UC of the prostate gland is uncommon. CASE SUMMARY: We present the case of an 82-year-old male patient with simultaneous adenocarcinoma and UC of the prostate gland. The patient underwent a transrectal ultrasound-guided biopsy, and the pathology test revealed UC. Subsequently, transurethral laser prostatectomy was performed, and the pathology test indicated adenocarcinoma of the prostate with a Gleason score of 3 + 4 and high-grade UC. Therefore, the patient was treated with androgen deprivation therapy, systemic chemotherapy, and immunotherapy. Magnetic resonance imaging performed during follow-up revealed a prostate tumor classified as cT2cN1M0, stage IVA. Therefore, the patient underwent robotic-assisted radical prostatectomy and bilateral pelvic lymph node dissection. The final pathology test of the prostate gland revealed acinar-type adenocarcinoma, Gleason pattern 4 + 3, pT2N0M0, and high-grade UC. The patient regularly presented to the clinic for postoperative follow-up evaluations. He did not experience any urinary discomfort. CONCLUSION: According to our literature review, this is the first reported case of coexisting adenocarcinoma and UC of the prostate gland.

RESUMEN

Owing to their limited accuracy and narrow applicability, current antimicrobial peptide (AMP) prediction models face obstacles in industrial application. To address these limitations, we developed and improved an AMP prediction model using Comparing and Optimizing Multiple DEep Learning (COMDEL) algorithms, coupled with high-throughput AMP screening method, finally reaching an accuracy of 94.8% in test and 88% in experiment verification, surpassing other state-of-the-art models. In conjunction with COMDEL, we employed the phage-assisted evolution method to screen Sortase in vivo and developed a cell-free AMP synthesis system in vitro, ultimately increasing AMPs yields to a range of 0.5-2.1 g/L within hours. Moreover, by multi-omics analysis using COMDEL, we identified Lactobacillus plantarum as the most promising candidate for AMP generation among 35 edible probiotics. Following this, we developed a microdroplet sorting approach and successfully screened three L. plantarum mutants, each showing a twofold increase in antimicrobial ability, underscoring their substantial industrial application values.

RESUMEN

BACKGROUND: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.

Respiratory rate ≥22/min demonstrated the most superior diagnostic value.Respiratory rate ≥22/min showed the strongest association with severity.Respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg predicted mortality well, adequately and poorly, respectively.

Asunto(s)

RESUMEN

Prolactin-releasing peptide (PrRP) is an RF-amide neuropeptide that binds and activates its cognate G protein-coupled receptor, prolactin-releasing peptide receptor (PrRPR), also known as GPR10. PrRP and PrRPR are highly conserved across mammals and involved in regulating a range of physiological processes, including stress response, appetite regulation, pain modulation, cardiovascular function, and potentially reproductive functions. Here we present cryo-electron microscopy structures of PrRP-bound PrRPR coupled to Gq or Gi heterotrimer, unveiling distinct molecular determinants underlying the specific recognition of the ligand's C-terminal RF-amide motif. We identify a conserved polar pocket that accommodates the C-terminal amide shared by RF-amide peptides. Structural comparison with neuropeptide Y receptors reveals both similarities and differences in engaging the essential RF/RY-amide motifs. Our findings demonstrate the general mechanism governing RF-amide motif recognition by PrRPR and RF-amide peptide receptors, and provide a foundation for elucidating activation mechanisms and developing selective drugs targeting this important peptide-receptor system.

RESUMEN

BACKGROUND: Differences of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. In more than 50% of human DSD cases, a molecular diagnosis is not available. In intensively farmed pig populations, the incidence of XX DSD pigs is relatively high, leading to economic losses for pig breeders. Interestingly, in the majority of 38, XX DSD pigs, gonads still develop into testis-like structures or ovotestes despite the absence of the testis-determining gene (SRY). However, the current understanding of the molecular background of XX DSD pigs remains limited. METHODS: Anatomical and histological characteristics of XX DSD pigs were analysed using necropsy and HE staining. We employed whole-genome sequencing (WGS) with 10× Genomics technology and used de novo assembly methodology to study normal female and XX DSD pigs. Finally, the identified variants were validated in 32 XX DSD pigs, and the expression levels of the candidate variants in the gonads of XX DSD pigs were further examined. RESULTS: XX DSD pigs are characterised by the intersex reproductive organs and the absence of germ cells in the seminiferous tubules of the gonads. We identified 4,950 single-nucleotide polymorphisms (SNPs) from non-synonymous mutations in XX DSD pigs. Cohort validation results highlighted two specific SNPs, "c.218T > C" in the "Interferon-induced transmembrane protein 1 gene (IFITM1)" and "c.1043C > G" in the "Newborn ovary homeobox gene (NOBOX)", which were found exclusively in XX DSD pigs. Moreover, we verified 14 candidate structural variants (SVs) from 1,474 SVs, identifying a 70 bp deletion fragment in intron 5 of the WW domain-containing oxidoreductase gene (WWOX) in 62.5% of XX DSD pigs. The expression levels of these three candidate genes in the gonads of XX DSD pigs were significantly different from those of normal female pigs. CONCLUSION: The nucleotide changes of IFITM1 (c.218T > C), NOBOX (c.1043 C > G), and a 70 bp deletion fragment of the WWOX were the most dominant variants among XX DSD pigs. This study provides a theoretical basis for better understanding the molecular background of XX DSD pigs. DSD are conditions affecting development of the gonads or genitalia. These disorders can happen in many different types of animals, including pigs, goats, dogs, and people. In people, DSD happens in about 0.02-0.13% of births, and in pigs, the rate is between 0.08% and 0.75%. Pigs have a common type of DSD where the animal has female chromosomes (38, XX) but no SRY gene, which is usually found on the Y chromosome in males. XX DSD pigs may look like both males and females on the outside and have testis-like or ovotestis (a mix of ovary and testis) gonads inside. XX DSD pigs often lead to not being able to have piglets, slower growth, lower chance of survival, and poorer meat quality. Here, we used a method called whole-genome de novo sequencing to look for variants in the DNA of XX DSD pigs. We then checked these differences in a larger group of pigs. Our results reveal the nucleotide changes in IFITM1 (c.218T > C), NOBOX (c.1043 C > G), and a 70 bp deletion fragment in intron 5 of the WWOX, all linked to XX DSD pigs. The expression levels of these three genes were also different in the gonads of XX DSD pigs compared to normal female pigs. These variants are expected to serve as valuable molecular markers for XX DSD pigs. Because pigs are a lot like humans in their genes, physiology, and body structure, this research could help us learn more about what causes DSD in people.

Asunto(s)

RESUMEN

Background: In recent years, transcatheter aortic valve replacement (TAVR) has emerged as a pivotal treatment for pure native aortic regurgitation (PNAR). Given patients with severe aortic regurgitation (AR) are prone to suffer from pulmonary hypertension (PH), understanding TAVR's efficacy in this context is crucial. This study aims to explore the short-term prognosis of TAVR in PNAR patients with concurrent PH. Methods: Patients with PNAR undergoing TAVR at Zhongshan Hospital, Affiliated with Fudan University, were enrolled between June 2018 to June 2023. They were categorized based on pulmonary artery systolic pressure (PASP) into groups with or without PH. The baseline characteristics, imaging records, and follow-up data were collected. Results: Among the 103 patients recruited, 48 were afflicted with PH. In comparison to PNAR patients without PH, the PH group exhibited higher rates of renal dysfunction (10.4% vs. 0.0%, p = 0.014), increased Society of Thoracic Surgeons scores (6.4 ± 1.9 vs. 4.7 ± 1.6, p < 0.001), and elevated Nterminal fragment of pro-brain natriuretic peptide (NT-proBNP). Transthoracic ultrasound examination revealed that patients with PH displayed lower left ventricular ejection fraction, larger left ventricle dimension, and more frequent moderate to severe tcuspid regurgitation (TR). Following TAVR, both groups experienced significant reductions in PASP, mitral regurgitation (MR) and TR. There were no significant differences in the incidence of postoperative adverse events in patients with or without PH. Conclusions: We found TAVR to be a safe and effective treatment for patients with PNAR and PH, reducing the degree of aortic regurgitation and PH without increasing the risk of postoperative adverse events.

RESUMEN

Neurodegenerative diseases (NDs) represent a hallmark of numerous incapacitating and untreatable conditions, the incidence of which is escalating swiftly, exemplified by Alzheimer's disease and Parkinson's disease. There is an urgent necessity to create pharmaceuticals that exhibit high efficacy and minimal toxicity in order to address these debilitating diseases. The structural complexity and diversity of natural products confer upon them a broad spectrum of biological activities, thereby significantly contributing to the history of drug discovery. Nevertheless, natural products present challenges in drug discovery, including time-consuming separation processes, low content, low bioavailability, and other related issues. To address these challenges, numerous analogs of natural products have been synthesized. This methodology enables the rapid synthesis of analogs of natural products with the potential to serve as lead compounds for drug development, thereby paving the way for the discovery of novel pharmaceuticals. This paper provides a summary of 127 synthetic analogues featuring various natural product structures, including flavonoids, alkaloids, coumarins, phenylpropanoids, terpenoids, polyphenols, and amides. The compounds are categorized based on their efficacy in treating various diseases. Furthermore, this article delves into the structure-activity relationship (SAR) of certain analogues, offering a thorough point of reference for the systematic development of pharmaceuticals aimed at addressing neurodegenerative conditions.

RESUMEN

This paper presents a novel hierarchical control scheme for solving the data-driven optimal cooperative tracking control problem of heterogeneous multi-agent systems. Considering that followers cannot communicate with the leader, a prescribed-time fully distributed observer is devised to estimate the leader's state for each follower. Then, the data-driven decentralized controller is designed to ensure that the follower's output can track the leader's one. Compared with the existing results, the advantages of the designed distributed observer are that the prescribed convergence time is completely predetermined by the designer, and the design of the observer gain is independent of the global topology information. Besides, the advantages of the designed decentralized controller are that neither the follower's system model nor a known initial stabilizing control policy is required. Finally, simulation results exemplify the advantage of the proposed method.