Molecular mechanisms, targets and clinical potential of berberine in regulating metabolism: a review focussing on databases and molecular docking studies.

Background: Metabolic imbalance is the common basis of many diseases. As natural isoquinoline alkaloid, berberine (BBR) has shown great promise in regulating glucose and lipids metabolism and treating metabolic disorders. However, the related mechanism still lacks systematic research. Aim: To discuss the role of BBR in the whole body's systemic metabolic regulation and further explore its therapeutic potential and targets. Method: Based on animal and cell experiments, the mechanism of BBR regulating systemic metabolic processes is reviewed. Potential metabolism-related targets were summarized using Therapeutic Target Database (TTD), DrugBank, GeneCards, and cutting-edge literature. Molecular modeling was applied to explore BBR binding to the potential targets. Results: BBR regulates the whole-body metabolic response including digestive, circulatory, immune, endocrine, and motor systems through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), sirtuin (SIRT)1/forkhead box O (FOXO)1/sterol regulatory element-binding protein (SREBP)2, nuclear factor erythroid 2-related factor (Nrf) 2/heme oxygenase (HO)-1, and other signaling pathways. Through these reactions, BBR exerts hypoglycemic, lipid-regulating, anti-inflammatory, anti-oxidation, and immune regulation. Molecular docking results showed that BBR could regulate metabolism targeting FOXO3, Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), glutathione peroxidase (Gpx) 4 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Evaluating the target clinical effects, we found that BBR has the therapeutic potential of anti-aging, anti-cancer, relieving kidney disease, regulating the nervous system, and alleviating other chronic diseases. Conclusion: This review elucidates the interaction between potential targets and small molecular metabolites by exploring the mechanism of BBR regulating metabolism. That will help pharmacologists to identify new promising metabolites interacting with these targets.

Krüppel-like factor 12 decreases progestin sensitivity in endometrial cancer by inhibiting the progesterone receptor signaling pathway.

OBJECTIVE: This study aimed to clarify the mechanism by which Krüppel-like factor 12 (KLF12) affects progesterone sensitivity in endometrial cancer (EC) through the progesterone receptor PGR signaling pathway. METHODS: The relationship of KLF12 with PGR in EC patients was examined by immunohistochemistry, and the expression of KLF12 and PGR in EC cell lines was detected by real-time PCR and western blotting. Cell proliferation assay, plate clone formation, cell apoptosis assay, and cell cycle analysis were conducted to determine the impact of KLF12 intervention on progesterone therapy. CUT&Tag analysis and the dual-luciferase reporter experiment were used to determine the underlying regulatory effect of KLF12 on the PGR DNA sequence. A subcutaneous xenograft nude mouse model was established to validate the in vivo effect of KLF12 on progesterone sensitivity via PGR expression modulation. RESULTS: KLF12 demonstrated decreased progesterone sensitivity and a negative correlation with PGR expression in EC tissues. Progesterone sensitivity was increased by KLF12 deficiency through PGR overexpression, a result that could be significantly reversed by PGR downregulation. PGR was identified as a target gene of KLF12, which could directly bind to the PGR promotor region and inhibit its expression. CONCLUSION: This study is the first to investigate the effect of KLF12 expression on EC cell resistance to progesterone. Our results offer important mechanistic insight into the direct regulation of the PGR promoter region, demonstrating that KLF12 expression strongly suppressed the PGR signaling pathway and, as a result, reduced progesterone sensitivity in EC patients.

Efficacy of GnRH Pulses in Hypogonadism Secondary to Primary Empty Sella: Case Report.

This study aims to assess the effectiveness of pulsed gonadotropin-releasing hormone (GnRH) micropump replacement therapy in the treatment of hypogonadotropic hypogonadism (HH) caused by primary empty sella (PES).The efficacy of pulsed GnRH replacement therapy using the micropump was evaluated in a middle-aged male patient with HH who had experienced the loss of his only child. Relevant literature was also consulted to compare the differences between pulse GnRH treatment and conventional treatment in terms of the development of secondary sexual characteristics, sex hormone levels, sperm production rate, and sperm activity rate in male patient with HH.In this report, a 45-year-old male diagnosed with HH and PES presented with fatigue and decreased libido. The main characteristics included decreased follicle stimulating hormone (FSH) levels of 0.03 mIU/mL, luteinizing hormone (LH) levels of 0.02 mIU/mL, and testosterone (T) levels of 0.72 nmol/L. Magnetic resonance imaging (MRI) revealed an empty sella. Semen analysis showed a small number of normal sperm with reduced motility. During treatment with the micropump pulse GnRH, the patient experienced no side effects and showed improvements in fatigue, reduced libido, sexual urge, anxiety, and feelings of inferiority. LH, FSH, and T levels returned to normal, while sperm activity rate increased to 79.9%. Ultimately, the patient's spouse achieved a natural pregnancy.Pulsed gonadotropin delivery using the micropump demonstrates good efficacy and tolerability, and aligns more closely with the physiological rhythm of GnRH secretion in the human body.

[Notch1/Akt/Foxo1 Pathway Regulated by Kisspeptin Is Involved in Endometrial Decidualization in Patients With Recurrent Spontaneous Abortion]. / kisspeptin调控Notch1/Akt/Foxo1é€šè·¯å‚ä¸Žå¤å‘æ€§æµäº§æ‚£è€ å­å®«å† è†œèœ•è†œåŒ–.

Objective: Kisspeptin, a protein encoded by the KISS1 gene, functions as an essential factor in suppressing tumor growth. The intricate orchestration of cellular processes such as proliferation and differentiation is governed by the Notch1/Akt/Foxo1 signaling pathway, which assumes a central role in maintaining cellular homeostasis. In the specific context of this investigation, the focal point lies in a meticulous exploration of the intricate mechanisms underlying the regulatory effect of kisspeptin on the process of endometrial decidualization. This investigation delves into the interplay between kisspeptin and the Notch1/Akt/Foxo1 signaling pathway, aiming to elucidate its significance in the pathophysiology of recurrent spontaneous abortion (RSA). Methods: We enrolled a cohort comprising 45 individuals diagnosed with RSA, who were admitted to the outpatient clinic of the Reproductive Center at the Second Affiliated Hospital of Soochow University between June 2020 and December 2020. On the other hand, an additional group of 50 women undergoing elective abortion at the outpatient clinic of the Family Planning Department during the same timeframe was also included. To comprehensively assess the molecular landscape, Western blot and RT-qPCR were performed to analyze the expression levels of kisspeptin (and its gene KISS1), IGFBP1 (an established marker of decidualization), Notch1, Akt, and Foxo1 within the decidua. Human endometrial stromal cells (hESC) were given targeted interventions, including treatment with siRNA to disrupt KISS1 or exposure to kisspeptin10 (the bioactive fragment of kisspeptin), and were subsequently designated as the siKP group or the KP10 group, respectively. A control group comprised hESC was transfected with blank siRNA, and cell proliferation was meticulously evaluated with CCK8 assay. Following in vitro induction for decidualization across the three experimental groups, immunofluorescence assay was performed to identify differences in Notch1 expression and decidualization morphology between the siKP and the KP10 groups. Furthermore, RT-qPCR and Western blot were performed to gauge the expression levels of IGFBP1, Notch1, Akt, and Foxo1 across the three cell groups. Subsequently, decidualization was induced in hESC by adding inhibitors targeting Notch1, Akt, and Foxo1. The expression profiles of the aforementioned proteins and genes in the four groups were then examined, with hESC induced for decidualization without adding inhibitors serving as the normal control group. To establish murine models of normal pregnancy (NP) and RSA, CBA/J×BALB/c and CBA/J×DBA/2 mice were used. The mice were respectively labeled as the NP model and RSA model. The experimental groups received intraperitoneal injections of kisspeptin10 and kisspeptin234 (acting as a blocker) and were designated as RSA-KP10 and NP-KP234 groups. On the other hand, the control groups received intraperitoneal injections of normal saline (NS) and were referred to as RSA-NS and NP-NS groups. Each group comprised 6 mice, and uterine tissues from embryos at 9.5 days of gestation were meticulously collected for observation of embryo absorption and examination of the expression of the aforementioned proteins and genes. Results: The analysis revealed that the expression levels of kisspeptin, IGFBP1, Notch1, Akt, and Foxo1 were significantly lower in patients diagnosed with RSA compared to those in women with NP (P<0.01 for kisspeptin and P<0.05 for IGFBP1, Notch1, Akt, and Foxo1). After the introduction of kisspeptin10 to hESC, there was an observed enhancement in decidualization capability. Subsequently, the expression levels of Notch1, Akt, and Foxo1 showed an increase, but they decreased after interference with KISS1. Through immunofluorescence analysis, it was observed that proliferative hESC displayed a slender morphology, but they transitioned to a rounder and larger morphology post-decidualization. Concurrently, the expression of Notch1 increased, suggesting enhanced decidualization upon the administration of kisspeptin10, but the expression decreased after interference with KISS1. Further experimentation involved treating hESC with inhibitors specific to Notch1, Akt, and Foxo1 separately, revealing a regulatory sequence of Notch1/Akt/Foxo1 (P<0.05). In comparison to the NS group, NP mice administered with kisspeptin234 exhibited increased fetal absorption rates (P<0.001) and decreased expression of IGFBP1, Notch1, Akt, and Foxo1 (P<0.05). Conversely, RSA mice administered with kisspeptin10 demonstrated decreased fetal absorption rates (P<0.001) and increased expression levels of the aforementioned molecules (P<0.05). Conclusion: It is suggested that kisspeptin might exert its regulatory influence on the process of decidualization through the modulation of the Notch1/Akt/Foxo1 signaling cascade. A down-regulation of the expression levels of kisspeptin could result in suboptimal decidualization, which in turn might contribute to the development or progression of RSA.

Correction: Yi et al. An Innovative Inducer of Platelet Production, Isochlorogenic Acid A, Is Uncovered through the Application of Deep Neural Networks. Biomolecules 2024, 14, 267.

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A novel inherited CARD9 deficiency in an otherwise healthy woman with CNS candidiasis.

Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.

Investigation of the differential susceptibility of extraocular muscles in patients diagnosed with ocular myasthenia gravis based on the computerized diplopia test and the Ocular Motor Nerve Palsy Scale.

Introduction: The pattern of extraocular muscle involvement in ocular myasthenia gravis varies across different reports, diverging from our own observations. Thus, we employed two novel tools to discern this pattern. Methods: A retrospective analysis was conducted to collect and organize clinical data from 43 patients diagnosed with ocular myasthenia gravis. Each patient underwent both the computerized diplopia test and the Ocular Motor Nerve Palsy Scale assessment to evaluate the involvement of extraocular muscles. Results: Among the patients, there were 30 male and 13 female individuals, with a total of 113 affected extraocular muscles identified. Among all the affected extraocular muscles, the involvement of the levator palpebrae superioris muscle accounted for 35.40%, medial rectus muscle 7.7%, lateral rectus muscle 16.81%, superior rectus muscle 13.27%, inferior rectus muscle 12.39%, superior oblique muscle 1.77%, and inferior oblique muscle 2.65% of the total affected extraocular muscles. The positivity rates of the Neostigmine test were 89.19%, AChR antibody detection was 59.38%, and repetitive nerve stimulation was 34.38%. The AChR antibody positive rate among patients with only diplopia was 100%; among those with only ptosis, it was 80%; and among those with both diplopia and ptosis, it was 86.67%. Conclusion: The involvement of the extraocular muscles is not uniform. The levator palpebrae superioris exhibits the highest incidence rate, followed by the four rectus muscles and two oblique muscles. The inferior oblique involvement typically occurs when four or more EOMs are affected. Moreover, the levator palpebrae superioris and medial rectus show a higher tendency for bilateral involvement compared with other extraocular muscles.

Trigonelline hydrochloride attenuates silica-induced pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation.

BACKGROUND: Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it's unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear. METHODS: To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions. RESULTS: In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-ß/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts. CONCLUSION: In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.

The causal associations of inflammatory cytokines with obesity and systemic lupus erythematosus: A Mendelian randomization study.

OBJECTIVE: Previous studies have partly discussed the roles of inflammatory cytokines in obesity and systemic lupus erythematosus (SLE), but the causal relationship among inflammatory cytokines, obesity, and SLE is unclear. It is challenging to comprehensively evaluate the causal relationship between these variables. This study aimed to investigate the role of cytokines as intermediates between obesity and SLE. METHODS: The inverse-variance weighted method (IVW) of mendelian randomization (MR) is mainly used to explore the causal relationship between exposure and outcome by using the genetic variation of the open large genome-wide association studies (GWAS), namely single-nucleotide polymorphisms (SNPs) related to obesity (more than 600 000 participants), inflammatory cytokines (8293 healthy participants) and SLE (7219 cases). Methods such as weighted median, MR-Egger are used to evaluate the reliability of causality. Reverse analysis is performed for each MR analysis to avoid reverse causality. Cochran's Q statistic and funnel chart are used to detect heterogeneity, MR-Egger intercept test and leave-one-out sensitivity analyses evaluated pleiotropy. RESULTS: Obesity was associated with 25 cytokines, and 3 cytokines were associated with SLE, including CTACK (OR = 1.19, 95% CI: 1.06, 1.33, p = .002), IL-18 (OR = 1.13, 95% CI: 1.01, 1.26, p = .027), SCGFb (OR = 0.89, 95% CI: 0.79, 0.99, p = .044). In the opposite direction, SLE was associated with 18 cytokines, and 2 cytokines were associated with obesity, including IP-10 (ßIVW = -.03, 95% CI: -0.05, -0.01, p = .002), MIP-1B (ßIVW = -.03, 95% CI: -0.05, -0.01, p = .004). CONCLUSION: Our MR study suggested that CTACK, IL-18 and SCGFb may play an intermediary role in obesity to SLE, while IP-10 and MIP-1B may play an intermediary role in SLE to obesity.

RNA Sequencing Analyses Reveal the Potential Anti-Inflammatory Mechanisms of Acacetin Against ODG/R Injuries in Microglia.

Background: Acacetin is a natural flavonoid known for its anti-tumor, antioxidant, and anti-inflammatory properties. Our previous studies have shown its protective effects against cerebral ischemia-reperfusion injury (IRI), but the underlying molecular mechanisms remain unclear. Purpose: The study delves into acacetin's mechanism in mitigating cerebral IRI, with a focus on transcriptomic insights. Methods: We established the oxygen-glucose deprivation/re-oxygenation (OGD/R) model in BV2 microglia, treating them with 10µM acacetin. Then we assessed cell proliferation using CCK-8 and measured Lactate Dehydrogenase (LDH) release. High-throughput RNA sequencing (RNA-seq) underpinned the analysis of differentially expressed genes (DEGs) and long non-coding RNAs (lncRNAs), functional enrichment, and alternative splicing events (ASEs), validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: OGD/R injury significantly impaired cell proliferation and increased LDH release, effects mitigated by acacetin. RNA-seq identified 2148 upregulated and 2135 downregulated DEGs post-OGD/R. In contrast, the acacetin-treated group showed 248 upregulated and 240 downregulated DEGs compared to the OGD/R group. All DEGs were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Overlapping analysis indicated that acacetin treatment reversed the expression of 203 genes affected by OGD/R, including inflammation-related genes such as Isg15, Fcgr1, Il1b, and Parp12. Moreover, the oxidative stress-related gene, Mt2, was downregulated post-OGD/R but upregulated following acacetin treatment. We further found that OGD/R and acacetin treatment could modulate gene splicing events, impacting cell apoptosis or inflammatory responses, such as the A3SS splicing event in the Trim47 gene. RNA-seq also highlighted differential expression of numerous lncRNAs, particularly the upregulation of lncRNA Rmrp and Terc post-OGD/R and their subsequent downregulation post-acacetin treatment. These lncRNAs might regulate cell proliferation through mediating target gene expressions. RT-qPCR validation confirmed these findings. Conclusion: Significant upregulation of genes and ASEs linked to oxidative stress and inflammatory response is observed in cerebral IRI. Acacetin intervention reverses these effects, highlighting its mechanism in alleviating the injury by modulating gene expression and splicing events.

Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice.

Kv1.3 belongs to the voltage-gated potassium (Kv) channel family, which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders. Kv1.3 is highly expressed in the olfactory bulb and piriform cortex and involved in the process of odor perception and nutrient metabolism in animals. Previous studies have explored the function of Kv1.3 in olfactory bulb, while the role of Kv1.3 in piriform cortex was less known. In this study, we investigated the neuronal changes of piriform cortex and feeding behavior after smell stimulation, thus revealing a link between the olfactory sensation and body weight in Kv1.3 KO mice. Coronal slices including the anterior piriform cortex were prepared, whole-cell recording and Ca2+ imaging of pyramidal neurons were conducted. We showed that the firing frequency evoked by depolarization pulses and Ca2+ influx evoked by high K+ solution were significantly increased in pyramidal neurons of Kv1.3 knockout (KO) mice compared to WT mice. Western blotting and immunofluorescence analyses revealed that the downstream signaling molecules CaMKII and PKCα were activated in piriform cortex of Kv1.3 KO mice. Pyramidal neurons in Kv1.3 KO mice exhibited significantly reduced paired-pulse ratio and increased presynaptic Cav2.1 expression, proving that the presynaptic vesicle release might be elevated by Ca2+ influx. Using Golgi staining, we found significantly increased dendritic spine density of pyramidal neurons in Kv1.3 KO mice, supporting the stronger postsynaptic responses in these neurons. In olfactory recognition and feeding behavior tests, we showed that Kv1.3 conditional knockout or cannula injection of 5-(4-phenoxybutoxy) psoralen, a Kv1.3 channel blocker, in piriform cortex both elevated the olfactory recognition index and altered the feeding behavior in mice. In summary, Kv1.3 is a key molecule in regulating neuronal activity of the piriform cortex, which may lay a foundation for the treatment of diseases related to piriform cortex and olfactory detection.

Recognition of apnea and hypopnea by non-contact optical fiber mattress and its application in the diagnosis of obstructive sleep apnea hypopnea syndrome: a retrospective study.

Objectives: This study sought to evaluate the diagnostic value of a non-contact optical fiber mattress for apnea and hypopnea and compare it with traditional polysomnography (PSG) in adult obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: To determine the value of a non-contact optical fiber mattress for apnea and hypopnea, six healthy people and six OSAHS patients were selected from Tongji Hospital to design a program to identify apnea or hypopnea. A total of 108 patients who received polysomnography for drowsiness, snoring or other suspected OSAHS symptoms. All 108 patients were monitored with both the non-contact optical fiber mattress and PSG were collected. Results: Six healthy controls and six patients with OSAHS were included. The mean apnea of the six healthy controls was 1.22 times/h, and the mean hypopnea of the six healthy controls was 2 times/h. Of the six patients with OSAHS, the mean apnea was 12.63 times/h, and the mean hypopnea was 19.25 times/h. The non-contact optical fiber mattress results showed that the mean apnea of the control group was 3.17 times/h and the mean hypopnea of the control group was 3.83 times/h, while the mean apnea of the OSAHS group was 11.95 times/h and the mean hypopnea of the OSAHS group was 17.77 times/h. The apnea index of the non-contact optical fiber mattress was positively correlated with the apnea index of the PSG (P < 0.05, r = 0.835), and the hypopnea index of the non-contact optical fiber mattress was also positively correlated with the hypopnea index of the PSG (P < 0.05, r = 0.959). The non-contact optical fiber mattress had high accuracy (area under curve, AUC = 0.889), specificity (83.4%) and sensitivity (83.3%) for the diagnosis of apnea. The non-contact fiber-optic mattress also had high accuracy (AUC = 0.944), specificity (83.4%) and sensitivity (100%) for the diagnosis of hypopnea. Among the 108 patients enrolled, there was no significant difference between the non-contact optical fiber mattress and the polysomnography monitor in total recording time, apnea hypopnea index (AHI), average heart rate, tachycardia index, bradycardia index, longest time of apnea, average time of apnea, longest time of hypopnea, average time of hypopnea, percentage of total apnea time in total sleep time and percentage of total hypopnea time in total sleep time. The AHI value of the non-contact optical fiber mattress was positively correlated with the AHI value of the PSG (P < 0.05, r = 0.713). The specificity and sensitivity of the non-contact optical fiber mattress AHI in the diagnosis of OSAHS were 95% and 93%, with a high OSAHS diagnostic accuracy (AUC = 0.984). Conclusion: The efficacy of the non-contact optical fiber mattress for OSAHS monitoring was not significantly different than PSG monitoring. The specificity of the non-contact optical mattress for diagnosing OSAHS was 95% and its sensitivity was 93%, with a high OSAHS diagnostic accuracy.

Characterization of YABBY transcription factors in Osmanthus fragrans and functional analysis of OfYABBY12 in floral scent formation and leaf morphology.

BACKGROUND: The plant-specific YABBY transcription factor family plays important roles in plant growth and development, particularly leaf growth, floral organ formation, and secondary metabolite synthesis. RESULTS: Here, we identified a total of 13 OfYABBY genes from the Osmanthus fragrans genome. These 13 OfYABBY genes were divided into five subfamilies through phylogenetic analysis, and genes in the same subfamily showed similar gene structures and conserved protein motifs. Gene duplication promoted the expansion of the OfYABBY family in O. fragrans. Tissue-specific expression analysis showed that the OfYABBY family was mainly expressed in O. fragrans leaves and floral organs. To better understand the role of OfYABBY genes in plant growth and development, OfYABBY12 was selected for heterologous stable overexpression in tobacco, and OfYABBY12-overexpressing tobacco leaves released significantly fewer volatile organic compounds than wild-type tobacco leaves. Overexpression of OfYABBY12 led to the downregulation of NtCCD1/4 and decreased ß-ionone biosynthesis. Correspondingly, a dual-luciferase assay showed that OfYABBY12 negatively regulated the expression of OfCCD4, which promotes ß-ionone synthesis. Furthermore, tobacco leaves overexpressing OfYABBY12 were curled and wrinkled and had significantly reduced leaf thickness and leaf inclusions and significantly extended flower pistils (styles). CONCLUSION: Overall, the results suggest that the OfYABBY gene family may influence the biosynthesis of the floral scent (especially ß-ionone) in O. fragrans and may regulate leaf morphogenesis and lateral organs.

Three-Dimensional Location of the Facial Artery in Relation to the Nasolabial Fold in Asian People: A Cadaveric CTA Study.

BACKGROUND: Injection cosmetics have become popular in recent years. The nasolabial fold is one of the most important and dangerous regions in the midface, and its three-dimensional relationship with the facial artery remains unclear. METHODS: Fifty-two cadavers infused with lead oxide contrast medium via the external carotid arteries were scanned by computed tomography (CT). The three-dimensional model was reconstructed using Mimics and Origin software, and the relevant data were calculated using validated algorithms. RESULTS: There were three facial artery types according to its course in relation to the nasolabial fold. In the most common type, accounting for 83.7% of specimens, the facial artery evolves into an angular artery, with a horizontal distance between facial artery and nasolabial fold of - 1.90 ± 2.40, - 3.90 ± 2.95, - 5.18 ± 3.42, - 5.59 ± 3.53, - 5.59 ± 3.83, - 6.07 ± 4.10, - 6.92 ± 3.70, - 6.79 ± 3.37, - 4.52 ± 3.20, and - 2.76 ± 3.60 (mm) from the nasal ala to the oral commissure and a vertical distance of - 4.03 ± 2.56, - 3.27 ± 2.27, - 2.81 ± 2.57, - 2.1 ± 2.64, - 1.5 ± 3.32, - 0.71 ± 3.99, 0.92 ± 4.43, 0.4 ± 5.31, - 4.14 ± 5.14, - 7.05 ± 4.74 (mm). CONCLUSIONS: The facial artery is vulnerable to damage when injecting filler in the nasolabial fold. For the upper 1/3 of the nasolabial fold, the supraperiosteal layer is recommended for injection, while for the lower 2/3 of the nasolabial fold, the dermal layer along the nasolabial fold is recommended. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A fabric-based hydrovoltaic electricity generator with multi-component carbon black for sustainable energy output.

Water evaporation-induced electricity generators are considered a promising green energy-harvesting technology to alleviate the increasingly serious fossil energy crisis. Previous water evaporation-induced electricity generators mainly focused on single component carbon black, limiting the improvements in energy output. At present, there are relatively few studies on multi-component carbon black for improving electricity-generation performance. Herein, inspired by plant transpiration, we designed a fabric-based water evaporation-induced electricity generator (FWEG) based on multi-component carbon black, which can maintain a voltage of 0.65 V for more than 48 h. Through the synergistic effect of multi-component carbon black-enhanced oxygen-containing functional density, the FWEG can generate an enhanced output current of 61.61 µA without any additional energy input. Moreover, we show that the FWEG can be integrated readily to charge commercial capacitors or directly power LED lights and calculators for a long time. This work provides new insights for designing high-performance hydrovoltaic electricity generators for sustainable green energy harvesting.

Enhancing diabetic wound healing with a pH/glucose dual-responsive hydrogel for ROS clearance and antibacterial activity.

Currently, the treatment of diabetic wounds in clinical practice is still unsatisfactory due to the risks of oxidative damage and bacterial infection during the healing process. An optimal wound dressing should exhibit robust capabilities in scavenging reactive oxygen species (ROS) and combatting bacterial growth. In this study, we utilized borax as a crosslinker and prepared a pH/glucose dual-responsive composite hydrogel based on poly(vinyl alcohol) (PVA), sodium alginate (SA), and tannic acid (TA). This hydrogel, loaded with cerium dioxide, serves as an effective ROS scavenger, promoting wound closure by reducing the level of ROS in the wound area. Additionally, the hydrogel can release the antibacterial drug ofloxacin in response to the low pH and high glucose microenvironment in infected wounds. Results from skin defect model in diabetic mice demonstrated this ROS-scavenging and antibacterial hydrogel can suppress inflammation and accelerate wound healing. In summary, our work provides a new perspective on a local and stimulus-responsive drug delivery strategy for treating diabetic wounds.

Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2-Amino-bicyclo[2.1.1]hexenes.

Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)3-catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2-amino-bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB-based cycloaddition chemistry.

Fuzzy-set qualitative comparative analysis of factors affecting the use of e-cigarettes among college students in Guangdong province.

INTRODUCTION: In recent years, e-cigarettes as an emerging tobacco product have been favored by college students. Our study aims to explore the factors affecting the use of e-cigarettes among college students and to put forward feasible suggestions for effectively controlling the use of e-cigarettes among college students. METHODS: The participating students were from three undergraduate and three specialized colleges in Guangdong Province, surveyed from January to March 2022. The Fuzzy-set Qualitative Comparative Analysis (fsQCA) method was used to analyze the influence mechanism and path of five antecedents: self-efficacy, social environment, cognition, sales environment, and negative outcome expectation, on the use of e-cigarettes. The fsQCA used in this study is a novel research methodology that combines the strengths of qualitative and quantitative analyses, through which we can determine which conditions are essential to the outcomes that lead to e-cigarette use among college students, and which combinations of conditions are more important than others. RESULTS: The interaction of self-efficacy, social environment, cognition, sales environment, and negative outcome expectation, affected college students' use of e-cigarettes. Through the fsQCA method, it was found that self-efficacy alone constitutes a necessary condition for college students not to use e-cigarettes. There are four possible pathways for college students not to use e-cigarettes, with higher self-efficacy, correct cognition, and a healthy social environment influencing the most important combination of conditions for college students to use e-cigarettes. CONCLUSIONS: The use of e-cigarettes by students in Guangdong Province is the result of the synergistic effect of multiple factors. Tobacco control action suggestions focus on improving students' self-efficacy and paying attention to the combination of different factors to achieve more effective tobacco control.

Obstructive sleep apnea hypopnea syndrome and vascular lesions: An update on what we currently know.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is the most prevalent sleep and respiratory disorder. This syndrome can induce severe cardiovascular and cerebrovascular complications, and intermittent hypoxia is a pivotal contributor to this damage. Vascular pathology is closely associated with the impairment of target organs, marking a focal point in current research. Vascular lesions are the fundamental pathophysiological basis of multiorgan ailments and indicate a shared pathogenic mechanism among common cardiovascular and cerebrovascular conditions, suggesting their importance as a public health concern. Increasing evidence shows a strong correlation between OSAHS and vascular lesions. Previous studies predominantly focused on the pathophysiological alterations in OSAHS itself, such as intermittent hypoxia and fragmented sleep, leading to vascular disruptions. This review aims to delve deeper into the vascular lesions affected by OSAHS by examining the microscopic pathophysiological mechanisms involved. Emphasis has been placed on examining how OSAHS induces vascular lesions through disruptions in the endothelial barrier, metabolic dysregulation, cellular phenotype alterations, neuroendocrine irregularities, programmed cell death, vascular inflammation, oxidative stress and epigenetic modifications. This review examines the epidemiology and associated risk factors for OSAHS and vascular diseases and subsequently describes the existing evidence on vascular lesions induced by OSAHS in the cardiovascular, cerebrovascular, retinal, renal and reproductive systems. A detailed account of the current research on the pathophysiological mechanisms mediating vascular lesions caused by OSAHS is provided, culminating in a discussion of research advancements in therapeutic modalities to mitigate OSAHS-related vascular lesions and the implications of these treatment strategies.

Simulation of stress in a blood vessel due to plaque sediments in coronary artery disease.

Atherosclerosis is a cardiovascular disease mainly caused by plaque deposition in blood vessels. Plaque comprises components such as thrombosis, fibrin, collagen, and lipid core. It plays an essential role in inducing rupture in a blood vessel. Generally, Plaque could be described as three kinds of elastic models: cellular Plaque, hypocellular Plaque, and calcified Plaque. The present study aimed to investigate the behavior of atherosclerotic plaque rupture according to different lipid cores using Fluid-Structure Interaction (FSI). The blood vessel was also varied with different thicknesses (0.05, 0.25, and 0.5 mm). In this study, FSI simulation with a cellular plaque model with various thicknesses was investigated to obtain information on plaque rupture. Results revealed that the blood vessel with Plaque having a lipid core represents higher stresses than those without a lipid core. Blood vessels' thin thickness, like a thin cap, results in more considerable than Von Mises stress. The result also suggests that even at low fracture stress, the risk of rupture due to platelet decomposition at the gap was more significant for cellular plaques.