Novel Alkaloids from Aspergillus fumigatus VDL36, an Endophytic Fungus Associated with Vaccinium dunalianum.

Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.

Bioactive Compounds from Vicia sativa L. and Vicia monantha Retz. with Unveiling Antiviral Potentials in Newly Green Synthesized CdO Nanoparticles.

BACKGROUND: in the current study, a comparative phytochemical analysis was carried out to explore the phenolic and flavonoid contents in the aerial parts of Vicia sativa L and Vicia monantha Retz growing in cultivated, reclaimed, and desert habitats. METHODS: High-performance liquid chromatography (HPLC) was used to detect Vicia methanolic extracts' individual phenolic and flavonoid constituents. The first-time synthesis of cadmium oxide nanoparticles (CdO NPs) using the aqueous extract of V. monantha has been developed using a green approach. Also, the cytotoxicity of V. monantha extract and CdO NPs was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for unveiling them as anti-HAV and anti-AdV. RESULTS: Our results indicated that in the case of desert habitat, the contents of total phenolics (76.37 mg/g) and total flavonoids (65.23 mg/g) of V. monantha were higher than those of V. sativa (67.35 mg/g and 47.34 mg/g, respectively) and the contents of these secondary metabolites were even increased in V. monantha collected from reclaimed land (phenolics: 119.77 mg/g, flavonoids: 88.61 mg/g). Also, V. monantha surpassed V. sativa in the contents of some individual HPLC constituents, and hence, V. monantha was used to synthesize the green CdO NPs and subsequent antiviral tests. The average size of CdO NPs was determined to be 24.28 nm, and the transmission electron microscopy (TEM) images of CdO NPs clearly showed their spherical form and varying particle sizes, with different diameters in the range of 19-29 nm. MTT assay was positive to the exposure of CdO NPs in the normal cell line, proposing that CdO NPs can reduce cell viability. V. monantha extract showed promising antiviral activity against Hepatitis A virus (HAV) and Adenovirus (AdV) with SI of 16.40 and 10.54. On the other hand, CdONPs had poor antiviral activity against HAV with an SI of 4.74 and moderate antiviral activity against AdV with an SI of 10.54. CONCLUSION: V. monantha is now considered a new, valuable natural resource for phenolics and flavonoids, especially when grown in reclaimed soil. The green CdO NPs based on V. monantha extract showed a promising antiviral effect against HAV and AdV.

Casein kinase 1 AELs promote senescence by enhancing ethylene biosynthesis through phosphorylating WRKY22 transcription factor.

Leaf senescence is a complex process regulated by developmental and environmental factors, and plays a pivotal role in the development and life cycle of higher plants. Casein kinase 1 (CK1) is a highly conserved serine/threonine protein kinase in eukaryotes and functions in various cellular processes including cell proliferation, light signaling and hormone effects of plants. However, the biological function of CK1 in plant senescence remains unclear. Through systemic genetic and biochemical studies, we here characterized the function of Arabidopsis EL1-like (AEL), a CK1, in promoting leaf senescence by stimulating ethylene biosynthesis through phosphorylating transcription factor WRKY22. Seedlings lacking or overexpressing AELs presented delayed or accelerated leaf senescence, respectively. AELs interact with and phosphorylate WRKY22 at Thr57, Thr60 and Ser69 residues to enhance whose transactivation activity. Being consistent, increased or suppressed phosphorylation of WRKY22 resulted in the promoted or delayed leaf senescence. WRKY22 directly binds to promoter region and stimulates the transcription of 1-amino-cyclopropane-1-carboxylate synthase 7 gene to promote ethylene level and hence leaf senescence. Our studies demonstrated the crucial role of AEL-mediated phosphorylation in regulating ethylene biosynthesis and promoting leaf senescence by enhancing WRKY22 transactivation activity, which helps to elucidate the fine-controlled ethylene biosynthesis and regulatory network of leaf senescence.

Asprosin contributes to vascular remodeling in hypertensive rats via superoxide signaling.

OBJECTIVE: Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling. Asprosin, a newly discovered protein hormone, is involved in metabolic diseases. Little is known about the roles of asprosin in cardiovascular diseases. This study focused on the role and mechanism of asprosin on VSMC proliferation and migration, and vascular remodeling in a rat model of hypertension. METHODS AND RESULTS: VSMCs were obtained from the aortic media of 8-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Asprosin was upregulated in the VSMCs of SHR. For in vitro studies, asprosin promoted VSMC proliferation and migration of WKY and SHR, and increased Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, NOX1/2/4 protein expressions and superoxide production. Knockdown of asprosin inhibited the proliferation, migration, NOX activity, NOX1/2 expressions and superoxide production in the VSMCs of SHR. The roles of asprosin in promoting VSMC proliferation and migration were not affected by hydrogen peroxide scavenger, but attenuated by superoxide scavenger, selective NOX1 or NOX2 inhibitor. Toll-like receptor 4 (TLR4) was upregulated in SHR, TLR4 knockdown inhibited asprosin overexpression-induced proliferation, migration and oxidative stress in VSMCs of WKY and SHR. Asprosin was upregulated in arteries of SHR, and knockdown of asprosin in vivo not only attenuated oxidative stress and vascular remodeling in aorta and mesentery artery, but also caused a subsequent persistent antihypertensive effect in SHR. CONCLUSIONS: Asprosin promotes VSMC proliferation and migration via NOX-mediated superoxide production. Inhibition of endogenous asprosin expression attenuates VSMC proliferation and migration, and vascular remodeling of SHR.

GLP-1 in hypothalamic paraventricular nucleus promotes sympathetic activation and hypertension.

Glucagon-like peptide-1 (GLP-1) and its analogs are widely used for treatment of diabetes. Paraventricular nucleus (PVN) is crucial for regulating cardiovascular activity. This study aims to determine the roles of GLP-1 and its receptors (GLP-1R) in PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male normotensive rats and spontaneously hypertensive rats (SHR). Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. GLP-1 and GLP-1R expression was present in the PVN. PVN microinjection of GLP-1R agonist recombinant human GLP-1 (rhGLP-1) or EX-4 increased RSNA and MAP, which were prevented by GLP-1R antagonist EX9-39 or GLP-1R antagonist 1, superoxide scavenger tempol, antioxidant N-acetylcysteine, NADPH oxidase inhibitor apocynin, adenylyl cyclase inhibitor SQ22536 or protein kinase A (PKA) inhibitor H89. PVN microinjection of rhGLP-1 increased superoxide production, NADPH oxidase activity, cAMP level, adenylyl cyclase and PKA activity, which were prevented by SQ22536 or H89. GLP-1 and GLP-1R were upregulated in the PVN of SHR. PVN microinjection of GLP-1 agonist increased RSNA and MAP in both WKY and SHR, but GLP-1 antagonists caused greater effects in reducing RSNA and MAP in SHR than in WKY. The increased superoxide production and NADPH oxidase activity in the PVN of SHR were augmented by GLP-1R agonists, but attenuated by GLP-1R antagonists. These results indicate that activation of GLP-1R in PVN increased sympathetic outflow and blood pressure via cAMP-PKA-mediated NADPH oxidase activation and subsequent superoxide production. GLP-1 and GLP-1R upregulation in the PVN partially contribute to sympathetic overactivity and hypertension.Significance Statement Activation of GLP-1 receptors in paraventricular nucleus (PVN) increases sympathetic activity and blood pressure, which are mediated by cAMP-PKA-NADPH oxidase-superoxide production. Intervention of GLP-1 receptors in the PVN may play beneficial roles in attenuating sympathetic overactivity and hypertension. The central effects may have a major impact during GLP-1 receptor agonist therapy in patients with hypertension.

FNDC5 inhibits malignant growth of human cervical cancer cells via restraining PI3K/AKT pathway.

Cervical cancer (CxCa) is the fourth most frequent cancer in women. This study aimed to determine the role and underlying mechanism of fibronectin type III domain-containing protein 5 (FNDC5) in inhibiting CxCa growth. Experiments were performed in human CxCa tissues, human CxCa cell lines (HeLa and SiHa), and xenograft mouse model established by subcutaneous injection of SiHa cells in nude mice. Bioinformatics analysis showed that CxCa patients with high FNDC5 levels have a longer overall survival period. FNDC5 expression was increased in human CxCa tissues, HeLa and SiHa cells. FNDC5 overexpression or FNDC5 protein not only inhibited proliferation, but also restrained invasion and migration of HeLa and SiHa cells. The effects of FNDC5 were prevented by inhibiting integrin with cilengitide, activating PI3K with recilisib or activating Akt with SC79. FNDC5 inhibited the phosphorylation of PI3K and Akt, which was attenuated by recilisib. PI3K inhibitor LY294002 showed similar effects to FNDC5 in HeLa and SiHa cells. Intravenous injection of FNDC5 (20 µg/day) for 14 days inhibited the tumor growth, and reduced the proliferation marker Ki67 expression and the Akt phosphorylation in the CxCa xenograft mouse model. These results indicate that FNDC5 inhibits the malignant phenotype of CxCa cells through restraining PI3K/Akt signaling. Upregulation of FNDC5 may play a beneficial role in retarding the tumor growth of CxCa.

50% efficacy dose of intravenous lidocaine in supressing sufentanil-induced cough in children: a randomised controlled trial.

BACKGROUND: Opioids such as sufentanil are used as anaesthetics due to their rapid action and superior analgesic effect. However, sufentanil induces a huge cough in paediatric patients. In contrast, intravenous (IV) lidocaine suppresses opioid-induced cough in children, but its use is limited due to anaesthetists' concern about its toxicity. Therefore, this study aimed to evaluate the effect of dose-dependent IV lidocaine on sufentanil-induced cough (SIC) in paediatric patients. METHODS: A total of 188 patients aged 3-12 years scheduled for elective tonsillectomy with or without adenoidectomy were enrolled and divided into four groups depending on different dose of lidocaine: A (0 mg.kg-1), B (1 mg.kg-1), C (1.5 mg.kg-1), and D (2 mg.kg-1). The primary outcome was the SIC grade observed during the induction of general anaesthesia. The secondary outcomes were the incidence of SIC, mean arterial pressure, and heart rate at T0, T1, T2, T3, T4, and T5. RESULTS: The SIC grade was significantly different between groups A and D (P = 0.04) and between groups B and D (P = 0.03). Moreover, the incidence of SIC in groups A, B, C, and D was 81%, 87%, 68%, and 64%, respectively, and the difference between groups B and C (P = 0.03) and between groups B and D (P = 0.0083) was statistically significant. No statistical differences were observed in the hemodynamic parameters between the groups. The incidence of severe cough was statistically different between group D and group A (P < 0.0001), between group D and group B (P < 0.0001), and between group D and group C (P < 0.0001) respectively. CONCLUSIONS: Lidocaine suppresses SIC in a dose-dependent manner without severe adverse events. IV lidocaine can be used in paediatric patients safely and efficiently, and the median effective dose was 1.75 mg/kg. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of Yichang Central People's Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006).

Toonanoronoids A-E, five new limonoids from Toona ciliata var. yunnanensis.

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

Young osteocyte-derived extracellular vesicles facilitate osteogenesis by transferring tropomyosin-1.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can undergo inadequate osteogenesis or excessive adipogenesis as they age due to changes in the bone microenvironment, ultimately resulting in decreased bone density and elevated risk of fractures in senile osteoporosis. This study aims to investigate the effects of osteocyte senescence on the bone microenvironment and its influence on BMSCs during aging. RESULTS: Primary osteocytes were isolated from 2-month-old and 16-month-old mice to obtain young osteocyte-derived extracellular vesicles (YO-EVs) and senescent osteocyte-derived EVs (SO-EVs), respectively. YO-EVs were found to significantly increase alkaline phosphatase activity, mineralization deposition, and the expression of osteogenesis-related genes in BMSCs, while SO-EVs promoted BMSC adipogenesis. Neither YO-EVs nor SO-EVs exerted an effect on the osteoclastogenesis of primary macrophages/monocytes. Our constructed transgenic mice, designed to trace osteocyte-derived EV distribution, revealed abundant osteocyte-derived EVs embedded in the bone matrix. Moreover, mature osteoclasts were found to release osteocyte-derived EVs from bone slices, playing a pivotal role in regulating the functions of the surrounding culture medium. Following intravenous injection into young and elderly mouse models, YO-EVs demonstrated a significant enhancement of bone mass and biomechanical strength compared to SO-EVs. Immunostaining of bone sections revealed that YO-EV treatment augmented the number of osteoblasts on the bone surface, while SO-EV treatment promoted adipocyte formation in the bone marrow. Proteomics analysis of YO-EVs and SO-EVs showed that tropomyosin-1 (TPM1) was enriched in YO-EVs, which increased the matrix stiffness of BMSCs, consequently promoting osteogenesis. Specifically, the siRNA-mediated depletion of Tpm1 eliminated pro-osteogenic activity of YO-EVs both in vitro and in vivo. CONCLUSIONS: Our findings suggested that YO-EVs played a crucial role in maintaining the balance between bone resorption and formation, and their pro-osteogenic activity declining with aging. Therefore, YO-EVs and the delivered TPM1 hold potential as therapeutic targets for senile osteoporosis.

Shell Modulation of Hollow Metal Sulfide Nanocomposite for Stable Potassium Storage at Room and High Temperature.

The large size of K-ion makes the pursuit of stable high-capacity anodes for K-ion batteries (KIBs) a formidable challenge, particularly for high temperature KIBs as the electrode instability becomes more aggravated with temperature climbing. Herein, we demonstrate that a hollow ZnS@C nanocomposite (h-ZnS@C) with a precise shell modulation can resist electrode disintegration to enable stable high-capacity potassium storage at room and high temperature. Based on a model electrode, we identify an interesting structure-function correlation of the h-ZnS@C: with an increase in the shell thickness, the cyclability increases while the rate and capacity decreases, shedding light on the design of high-performance h-ZnS@C anodes via engineering the shell thickness. Typically, the h-ZnS@C anode with a shell thickness of 60 nm can deliver an impressive comprehensive performance at room temperature; the h-ZnS@C with shell thickness increasing to 75 nm can achieve an extraordinary stability (88.6% capacity retention over 450 cycles) with a high capacity (450 mAh g-1) and a superb rate even at an extreme temperature of 60 ℃, which is much superior than those reported anodes. This contribution envisions new perspectives on rational design of functional metal sulfides composite toward high-performance KIBs with insights into the significant structure-function correlation.

Boswellianols A-I, Structurally Diverse Diterpenoids from the Oleo-Gum Resin of Boswellia carterii and Their TGF-ß Inhibition Activity.

Olibanum, a golden oleo-gum resin from species in the Boswellia genus (Burseraceae family), is a famous traditional herbal medicine widely used around the world. Previous phytochemical studies mainly focused on the non-polar fractions of olibanum. In this study, nine novel diterpenoids, boswellianols A-I (1-9), and three known compounds were isolated from the polar methanolic fraction of the oleo-gum resin of Boswellia carterii. Their structures were determined through comprehensive spectroscopic analysis as well as experimental and calculated electronic circular dichroism (ECD) data comparison. Compound 1 is a novel diterpenoid possessing an undescribed prenylmaaliane-type skeleton with a 6/6/3 tricyclic system. Compounds 2-4 were unusual prenylaromadendrane-type diterpenoids, and compounds 5-9 were new highly oxidized cembrane-type diterpenoids. Compounds 1 and 5 showed significant transforming growth factor ß (TGF-ß) inhibitory activity via inhibiting the TGF-ß-induced phosphorylation of Smad3 and the expression of fibronectin and N-cadherin (the biomarker of the epithelial-mesenchymal transition) in a dose-dependent manner in LX-2 human hepatic stellate cells, indicating that compounds 1 and 5 should be potential anti-fibrosis agents. These findings give a new insight into the chemical constituents of the polar fraction of olibanum and their inhibitory activities on the TGF-ß/Smad signaling pathway.

[A multi-center epidemiological study on pneumococcal meningitis in children from 2019 to 2020]. / 2019­2020å¹´160ä¾‹å„¿ç«¥è‚ºç‚Žé“¾çƒèŒè„‘è†œç‚Žä¸´åºŠæµè¡Œç— å­¦å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

An aquaporin and an aquaglyceroporin have roles in low temperature adaptation of mosquitoes (Anopheles sinensis).

Mosquitoes (Anopheles sinensis), widely geographically distributed in Asia including China, are the primary vector of the malaria parasite Plasmodium vivax and other parasitic diseases such as Malayan filariasis. An. sinensis can survive through low winter temperatures. Aquaporin channels are found in all life forms, where they facilitate environmental adaptation by allowing rapid trans-cellular movement of water (classical aquaporins) or water and solutes such as glycerol (aquaglyceroporins). Here, we identified and characterized 2 aquaporin (AQP) homologs in An. sinensis: AsAQP2 (An. sinensis aquaglyceroporin) and AsAQP4 (An. sinensis aquaporin). When expressed in frog (Xenopus laevis) oocytes, AsAQP2 transported water, glycerol, and urea; AsAQP4 transported only water. Water permeation through AsAQP2 and AsAQP4 was inhibited by mercuric chloride. AsAQP2 expression was slightly higher in adult female mosquitoes than in males, and AsAQP4 expression was significantly higher in adult males. The 2 AsAQPs were highly expressed in Malpighian tubules and midgut. AsAQP2 and AsAQP4 expression was up-regulated by blood feeding compared with sugar feeding. At freezing point (0 °C), the AsAQP4 expression level increased and An. sinensis survival time reduced compared with those at normal temperature (26 °C). At low temperature (8 °C), the AsAQP2 and AsAQP4 expression levels decreased and survival time was significantly longer compared with those at 26 °C. These results suggest that AsAQP2 and AsAQP4 have roles in water homeostasis during blood digestion and in low temperature adaptation of A. sinensis. Together, our results show that the 2 AQPs are important for mosquito diuresis after blood feeding and when exposed to low temperatures.

Nano-Interfacial Supramolecular Adhesion of Metal-Organic Framework-Based Separator Enables High-Safety and Wide-Temperature-Range Lithium Batteries.

Polyolefin separators are the most commonly used separators for lithium batteries; however, they tend to shrink when heated, and their Li+ transference number (t Li +) is low. Metal-organic frameworks (MOFs) are expected to solve the above problems due to their high thermal stability, abundant pore structure, and open metal sites. However, it is difficult to prepare high-porosity MOF-based membranes by conventional membrane preparation methods. In this study, a high-porosity free-standing MOF-based safety separator, denoted the BCM separator, is prepared through a nano-interfacial supramolecular adhesion strategy. The BCM separator has a large specific surface area (450.22 m2 g-1) and porosity (62.0%), a high electrolyte uptake (475 wt%), and can maintain its morphology at 200 °C. The ionic conductivity and t Li + of the BCM separator are 1.97 and 0.72 mS cm-1, respectively. Li//LiFePO4 cells with BCM separators have a capacity retention rate of 95.07% after 1100 cycles at 5  C, a stable high-temperature cycling performance of 300 cycles at 80 °C, and good capacity retention at -40 °C. Li//NCM811 cells with BCM separators exhibit significantly improved rate performance and cycling performance. Pouch cells with BCM separators can work at 120 °C and have good safety at high temperature.

Omentin-1 inhibits the development of benign prostatic hyperplasia by attenuating local inflammation.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. METHODS: Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1-/-) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. RESULTS: In vivo, Itln-1-/- mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. CONCLUSION: The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.

Single centre analysis of factors influencing surgical treatment of splenic trauma in children.

OBJECTIVE: This study aims to investigate determinants impacting the surgical management of splenic trauma in paediatric patients by scrutinizing age distribution, etiological factors and concomitant injuries. The analysis seeks to establish a foundation for delineating optimal operative timing. METHODS: A cohort of 262 paediatric cases presenting with splenic trauma at our institution from January 2011 to December 2021 underwent categorization into either the conservative or operative group. RESULTS: Significantly disparate attributes between the two groups included age, time of presentation, blood pressure, haemoglobin levels, blood transfusion requirements, thermal absorption, American Association for the Surgery of Trauma (AAST) classification and associated injuries. Logistic regression analysis revealed age, haemoglobin levels, AAST classification and blood transfusion as autonomous influencers of surgical intervention (OR = 1.024, 95% CI: 1.011-1.037; OR = 1.067, 95% CI: 1.01-1.127; OR = 0.2760, 95% CI: 0.087-0.875; OR = 7.873, 95% CI: 2.442-25.382; OR = 0.016, 95% CI: 0.002-0.153). The AAST type and age demonstrated areas under the receiver operating characteristic (ROC) curve of 0.782 and 0.618, respectively. CONCLUSION: Age, haemoglobin levels, AAST classification and blood transfusion independently influence the decision for surgical intervention in paediatric patients with splenic trauma. Age and AAST classification emerge as viable parameters for assessing and prognosticating the likelihood of surgical intervention in this patient cohort.

Cevanine-type alkaloids from the bulbs of Fritillaria unibracteata var. wabuensis and their antifibrotic activities in vitro.

Steroidal alkaloids are the main bioactive components of the bulbs of Fritillaria, which have been used as traditional Chinese medicine, known as "Beimu", for the treatment of cough for thousands of years in China. Cough and dyspnea are the most common symptoms observed in patients with pulmonary fibrosis. However, the antifibrotic activity of steroidal alkaloids has not been reported yet. In this study, two previously unreported cevanine-type steroidal alkaloids (1 and 2), four previously undescribed cevanine-type alkaloid glycosides (3-6), and 19 known steroidal alkaloids (7-25) were isolated from the bulbs of Fritillaria unibracteata var. wabuensis. The structures of these compounds were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, as well as DP4+ NMR calculations. The biological evaluation showed that compounds 2, 7-10, 14, 15, and 17 downregulated fibrotic markers induced by transforming growth factor-ß (TGF-ß) in MRC-5 cells. Moreover, compounds 14 and 17 dose dependently inhibited TGF-ß-induced epithelial-mesenchymal transition in A549 cells, alleviated TGF-ß-induced migration and proliferation of fibroblasts, and decreased the expression of fibrotic markers, fibronectin, and N-cadherin in TGF-ß-induced MRC-5 cells. The research showed the potential of cevanine-type alkaloids as a class of natural antifibrotic agents.

Atrachinenins D-S, novel meroterpenoids with geranyl hydroquinone moiety from Atractylodes chinensis by the LC/MS-based molecular decoy and targeted isolation.

To mine fascinating molecules from the rhizomes of Atractylodes chinensis, the known molecular formula of atrachinenin A was used as a bait to search LC-HRMS data in different subfractions. Sixteen new meroterpenoids, atrachinenins D-S (1-16) including three unprecedented carbon skeletons (1-5) and eleven new oxygen-bridged hybrids (6-16) were obtained by the targeted isolation. Their structures and absolute configurations were elucidated by the spectroscopic data and electronic circular dichroism (ECD) calculations. The isolated compounds were evaluated for their inhibitory activity of NO production and compounds 1, 4, 8, and 13 showed moderate anti-inflammatory activity. The proposed biosynthetic pathways of 1-5 were also discussed.

Extending the Large Molecule Limit: The Role of Fermi Resonance in Developing a Quantum Functional Group.

Polyatomic molecules equipped with optical cycling centers (OCCs), enabling continuous photon scattering during optical excitation, are exciting candidates for advancing quantum information science. However, as these molecules grow in size and complexity, the interplay of complex vibronic couplings on optical cycling becomes a critical but relatively unexplored consideration. Here, we present an extensive exploration of Fermi resonances in large-scale OCC-containing molecules using high-resolution dispersed laser-induced fluorescence and excitation spectroscopy. These resonances manifest as vibrational coupling leading to intensity borrowing by combination bands near optically active harmonic bands, which require additional repumping lasers for effective optical cycling. To mitigate these effects, we explore altering the vibrational energy level spacing through substitutions on the phenyl ring or changes in the OCC itself. While the complete elimination of vibrational coupling in complex molecules remains challenging, our findings highlight significant mitigation possibilities, opening new avenues for optimizing optical cycling in large polyatomic molecules.

Age-related decline in melatonin contributes to enhanced osteoclastogenesis via disruption of redox homeostasis.

BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.