Two Novel Diterpenoid Alkaloids from Aconitum pendulum.

Two previously uncharacterized compounds, an aconitine-type C19-diterpenoid alkaloid (1) and a napelline-type diterpenoid alkaloid C20-diterpenoid alkaloid (2), as well as ten known compounds (3-12), were isolated from Aconitum pendulum. Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction analysis. The anti-insecticidal activities of these compounds were evaluated by contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 9 showed moderate contact toxicity, with LC50 values of 0.86±0.09, 0.95±0.23, and 0.89±0.19 mg/mL, respectively. This study highlights the potential use of diterpenoid alkaloids as natural plant-derived pesticides for the management of plant pests.

Myeloid cannabinoid CB1 receptor deletion confers atheroprotection in male mice by reducing macrophage proliferation in a sex-dependent manner.

AIMS: Although the cannabinoid CB1 receptor has been implicated in atherosclerosis, its cell-specific effects in this disease are not well understood. To address this, we generated a transgenic mouse model to study the role of myeloid CB1 signaling in atherosclerosis. METHODS AND RESULTS: Here, we report that male mice with myeloid-specific Cnr1 deficiency on atherogenic background developed smaller lesions and necrotic cores than controls, while only minor genotype differences were observed in females. Male Cnr1 deficient mice showed reduced arterial monocyte recruitment and macrophage proliferation with less inflammatory phenotype. The sex-specific differences in proliferation were dependent on estrogen receptor (ER)α-estradiol signaling. Kinase activity profiling identified a CB1-dependent regulation of p53 and cyclin-dependent kinases. Transcriptomic profiling further revealed chromatin modifications, mRNA processing and mitochondrial respiration among the key processes affected by CB1 signaling, which was supported by metabolic flux assays. Chronic administration of the peripherally-restricted CB1 antagonist JD5037 inhibited plaque progression and macrophage proliferation, but only in male mice. Finally, CNR1 expression was detectable in human carotid endarterectomy plaques and inversely correlated with proliferation, oxidative metabolism and inflammatory markers, suggesting a possible implication of CB1-dependent regulation in human pathophysiology. CONCLUSION: Impaired macrophage CB1 signaling is atheroprotective by limiting their arterial recruitment, proliferation and inflammatory reprogramming in male mice. The importance of macrophage CB1 signaling appears to be sex-dependent.

Recent advances in C(sp3)-N bond formation via metallaphoto-redox catalysis.

The C(sp3)-N bond is ubiquitous in natural products, pharmaceuticals, biologically active molecules and functional materials. Consequently, the development of practical and efficient methods for C(sp3)-N bond formation has attracted more and more attention. Compared to the conventional ionic pathway-based thermal methods, photochemical processes that proceed through radical mechanisms by merging photoredox and transition-metal catalyses have emerged as powerful and alternative tools for C(sp3)-N bond formation. In this review, recent advances in the burgeoning field of C(sp3)-N bond formation via metallaphotoredox catalysis have been highlighted. The contents of this review are categorized according to the transition metals used (copper, nickel, cobalt, palladium, and iron) together with photocatalysis. Emphasis is placed on methodology achievements and mechanistic insight, aiming to inspire chemists to invent more efficient radical-involved C(sp3)-N bond-forming reactions.

Realization of monolayer ZrTe5 topological insulators with wide band gaps.

Two-dimensional topological insulators hosting the quantum spin Hall effect have application potential in dissipationless electronics. To observe the quantum spin Hall effect at elevated temperatures, a wide band gap is indispensable to efficiently suppress bulk conduction. Yet, most candidate materials exhibit narrow or even negative band gaps. Here, via elegant control of van der Waals epitaxy, we have successfully grown monolayer ZrTe5 on a bilayer graphene/SiC substrate. The epitaxial ZrTe5 monolayer crystalizes in two allotrope isomers with different intralayer alignments of ZrTe3 prisms. Our scanning tunneling microscopy/spectroscopy characterization unveils an intrinsic full band gap as large as 254 meV and one-dimensional edge states localized along the periphery of the ZrTe5 monolayer. First-principles calculations further confirm that the large band gap originates from strong spin-orbit coupling, and the edge states are topologically nontrivial. These findings thus provide a highly desirable material platform for the exploration of the high-temperature quantum spin Hall effect.

CircRNA SEC24A promotes osteoarthritis through miR-107-5p/CASP3 axis.

Background: Osteoarthritis (OA) is the most frequently diagnosed chronic joint disease. CircSEC24A is significantly elevated in OA chondrocytes upon IL-1ß stimulation. However, its biological function in OA is still not fully understood. Methods: The circRNAs-miRNA-mRNA network was predicted by bioinformatics analysis. An in vitro OA chondrocytes model was established by IL-1ß stimulation. The expression of circSEC24A, miR-107-5p, CASP3, apoptosis-related molecules and extracellular matrix (ECM) components were detected by Western blot and qRT-PCR. MTT assay and Annexin V/PI staining were employed to monitor cell viability and apoptosis, respectively. The interaction between circSEC24A and miR-107-5p, as well as the binding between miR-107-5p and CASP3 3' UTR were detected by luciferase reporter and RIP assays. Cytokine secretion was monitored by ELISA assay. The role of circSEC24A was also explored in anterior cruciate ligament transection (ACLT) rat models. Results: CircSEC24A and CASP3 were increased, but miR-107-5p was decreased in rat OA cartilage tissues and OA chondrocytes. CircSEC24A acted as a sponge of miR-107-5p. Knockdown of circSEC24A promoted chondrocyte proliferation, but suppressed chondrocyte apoptosis, ECM degradation and inflammation via sponging miR-107-5p. CASP3 was identified as a miR-107-5p target gene. MiR-107-5p mimics protected against OA progression via targeting CASP3. Silencing of circSEC24A alleviated OA progression in ACLT model. Conclusion: CircSEC24A promotes OA progression through miR-107-5p/CASP3 axis.

Systematic investigation of the material basis, effectiveness and safety of Thesium chinense Turcz. and its preparation Bairui Granules against lung inflammation.

BACKGROUND: Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute mastitis, lobar pneumonia, tonsillitis, coronavirus disease 2019 (COVID-19), and upper respiratory tract infection. However, the material basis, pharmacological efficiency, and safety have not been illustrated. METHODS: Anti-inflammatory activity-guided isolation of constituents has been performed using multiple column chromatography, and their structures were elucidated by NMR spectroscopy and ECD calculations. The inhibitory effects on lung inflammation and safety of the crude ethanol extract (CE), Bairui Granules (BG), and the purified active constituents were evaluated using lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) mice model or normal mice. RESULTS: Seven new compounds (1-7) and fifty-six known compounds (8-63) were isolated from T. chinense, and fifty-four were reported from this plant for the first time. The new flavonoid glycosides 1-2, new fatty acids 4-5, new alkaloid 7 as well as the known constituents including flavonoid aglycones 8-11, lignans 46-54, alkaloids 34 and 45, coumarins 57, phenylpropionic acids 27, and simple aromatic compounds 39, 44 and 58 exhibited anti-inflammatory activity. Network pharmacology analysis indicated that anti-inflammation of T. chinense was attributed to flavonoids and alkaloids by regulating inflammation-related proteins (e.g., TNF, NF-κB, TGF-ß). Furthermore, constituents of T. chinense including kaempferol-3-O-glucorhamnoside (KN, also named as Bairuisu I, 19), astragalin (AG, Bairuisu II, 12), and kaempferol (KF, Bairuisu III, 8), as well as CE and BG could alleviate lung inflammation caused by LPS in mice by preventing neutrophils infiltration and the expression of the genes for pro-inflammatory cytokines NLRP3, caspase-1, IL-1ß, and COX-2. After a 28-day subacute toxicity test, BG at doses of 4.875 g/kg and 9.750 g/kg (equivalent to onefold and twofold the clinically recommended dose) and CE at a dose of 11.138 g/kg (equivalent to fourfold the clinical dose of BG) were found to be safe and non-toxic. CONCLUSIONS: The discovery of sixty-three constituents comprehensively illustrated the material basis of T. chinense. T. chinense and Bairui Granules could alleviate lung inflammation by regulating inflammation-related proteins and no toxicity was observed under the twofold of clinically used doses.

Treatment of Moderate-to-Severe Pain in Hepatocellular Carcinoma with Transcutaneous Electrical Acupoint Stimulation: A Randomized Controlled Trial.

Objective: Moderate-to-severe pain is the most common clinical symptom in patients with hepatocellular carcinoma (HCC).This trial aimed to analyze the clinical efficacy of Transcutaneous electrical acupoint stimulation (TEAS) in patients of HCC with severe pain and provide a reliable reference for optimizing the clinical diagnostic and therapeutic strategies of HCC. Methods: A total of 104 eligible patients were randomly allocated to experimental and control groups in a ratio of 1:1.The treatment was administered for 1 week continuously. Patients in both groups were followed up 1 week after the end of the treatment.The primary outcome measure was the Numerical Rating Scale (NRS) score, whereas the secondary outcome measures included Brief Pain Inventory BPI-Q3, Q4, Q5 scores, analgesic dose, frequency of opioid-induced gastrointestinal side effects, Karnofsky Performance Status (KPS), Quality of Life Scale - Liver Cancer (QOL-LC), and Brief Fatigue Inventory (BFI) scores. Results: The NRS scores of experimental group was significantly lower after treatment and at the follow-up than baseline (average P<0.01), there were also statistical differences between the groups at the above time points (average P<0.01). BPI-Q3, -Q4, and -Q5 scores in the experimental group were decreased after treatment when compared with those before treatment (average P<0.01). Furthermore, there were significant improvements of gastrointestinal side effects, KPS, QOL-LC and BPI in the experimental group after treatment, and the above results were statistically significant compared to the control group. Conclusion: 7-day TEAS treatment can significantly enhance the analgesic effect and maintain for the following week, also reduce the incidence of gastrointestinal side effects caused by opioids, and improve the quality of life of patients with moderate-to-severe HCC-related pain, which has reliable safety and certain clinical promotion value.

Four new species of Russula from the Xizang Autonomous Region and other provinces of China.

Russula is the largest genus in the Russulales and is widespread throughout the world. Almost all Russula species are known to be ectomycorrhizal with high ecological and edible values, and some are lethal poisonous. In this study, four new species belonging to the subgenus Russula crown clade are identified based on morphological and phylogenetic evidence from the Xizang Autonomous Region and other provinces of China. Morphologically, Russula paragraveolens (sect. Polychromae, subsect. Xerampelinae) is mainly characterised by a cherry red to blood red pileus centre, a reddish orange pileus margin; R. pseudograveolens (sect. Polychromae, subsect. Xerampelinae) is characterised by a violet brown to brownish red pileus centre, a pale red to pastel red pileus margin and short basidia; R. shigatseensis (sect. Flavisiccantes, subsect. Lepidinae) is characterised by a brownish orange to madder red pileus centre, pinkish red pileus margin, and having lateral branches or branches of hyphal terminations in pileipellis; R. yadongensis (sect. Tenellae, subsect. Laricinae) is characterised by a dark purplish red pileus centre with brownish purple tints and having isolated to clustered spines of spore ornamentations. Their distinct taxonomic status is confirmed by the positions of the four new species in both the ITS and 4-locus (nucLSU, mtSSU, rpb2, tef1) phylogenetic trees.

Mitochondrial quality control in human health and disease.

Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable in vital life processes such as cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, a sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key processes like mitochondrial biogenesis, mitochondrial dynamics, and mitophagy, which have garnered increasing attention from researchers to unveil their specific molecular mechanisms. In this review, we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC. Furthermore, the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail. We also discuss agonists or antagonists targeting MQC, aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.

Cross-Linking CdSO4-Type Nets with Hexafluorosilicate Anions to Form an Ultramicroporous Material for Efficient C2H2/CO2 and C2H2/C2H4 Separation.

A 44.610.8 topology hybrid ultramicroporous material (HUM), {[Cu1.5F(SiF6)(L)2.5]·G}n, (L = 4,4'-bisimidazolylbiphenyl, G = guest molecules), 1, formed by cross-linking interpenetrated 3D four-connected CdSO4-type nets with hexafluorosilicate anions is synthesized and evaluated in the context of gas sorption and separation herein. 1 is the first HUM functionalized with two different types of fluorinated sites (SiF6 2- and F- anions) lining along the pore surface. The optimal pore size (≈5 Å) combining mixed and high-density electronegative fluorinated sites enable 1 to preferentially adsorb C2H2 over CO2 and C2H4 by hydrogen bonding interactions with a high C2H2 isosteric heat of adsorption (Qst) of ≈42.3 kJ mol-1 at zero loading. The pronounced discriminatory sorption behaviors lead to excellent separation performance for C2H2/CO2 and C2H2/C2H4 that surpasses many well-known sorbents. Dynamic breakthrough experiments are conducted to confirm the practical separation capability of 1, which reveal an impressive separation factor of 6.1 for equimolar C2H2/CO2 mixture. Furthermore, molecular simulation and density functional theory (DFT) calculations validate the strong binding of C2H2 stems from the chelating fix of C2H2 between SiF6 2- anion and coordinated F- anion.

Robotic Right Hepatectomy with En Bloc Caudatectomy for Bismuth IIIa Hilar Cholangiocarcinoma: A Video Demonstration of Left-Liver-First Anterior Radical Modular Orthotopic Right Hemihepatectomy.

BACKGROUND: Minimally invasive resection for perihilar cholangiocarcinoma is a complicated and technically demanding surgical procedure. Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma.1,2 Right hepatectomy with caudate lobe resection is necessary as the treatment for bismuth IIIa hilar cholangiocarcinoma.3 The left-liver-first anterior radical modular orthotopic right hemihepatectomy (LARMORH), which can simplify surgical steps and decrease procedural difficulty, may be a better choice for Bismuth IIIa hilar cholangiocarcinoma.4 However, there are no reports of this approach using robotic technique for this operation. We will provide a detailed introduction to this method through this video. METHODS: A 45-year-old female patient was diagnosed with a hilar cholangiocarcinoma. Following a 7-day percutaneous biliary drainage of the left intrahepatic bile duct and obtaining informed consent, we performed a robotic radical resection of the HCCA using the LARMORH approach. The patient was positioned supine with the entire bed elevated 20° and tilted 15° to the left. Trocars were placed in position (Fig. 1). After entering the abdominal cavity, it was explored for tumor metastasis. The surgery adopted a left approach, initially exploring the left hepatic artery and vein to further assess resectability. After confirming resectability, the right hepatic artery and gastroduodenal artery (GDA) were dissected. The common bile duct was dissected and transected at its distal end, ensuring R0 surgical margins. Lymph nodes were cleared from the foot side to the head side, confirming the metastasis to the lymph node group 13a, so we further cleared the group 16 and 9 lymph nodes.5 Subsequently, we approached the resection of the right half and the entire caudate lobe with the reverse thinking of left hepatic resection mode, preserving only the left branch of the portal vein and left hepatic artery, and dissecting the liver tissue along the resection plane of the left liver. After transection of the left hepatic duct, the activity space of the left liver was larger and the caudate lobe could be better exposed. The Spiegel lobe was lifted to the right in a "turn the page" fashion for in situ resection of the entire caudate lobe and the right half of the liver. Finally, a bilioenteric anastomosis was performed using the Roux-en-Y method. RESULTS: Robotic right hepatectomy with caudate lobectomy was successfully performed in 450 min, with an estimated blood loss of 200 ml. The histological grading was determined as T1aN1M0 (stage IIIB) on the basis of postoperative pathological biopsy results. The patient achieved a satisfactory postoperative recovery and was discharged on the 14th postoperative day without any major complications. Following the operation, the patient received capecitabine chemotherapy according to the Chinese Society of Clinical Oncology (CSCO) criteria. Since September 2022, our team has completed three radical resections for Bismuth IIIa HCCA using this technique. All patients achieved a satisfactory postoperative recovery without any further complications. CONCLUSIONS: Robotic left-liver-first anterior radical modular orthotopic right hemihepatectomy for Bismuth IIIa HCCA is both safe and feasible. This method may provide a new surgical approach for patients with type IIIA HCCA or liver diseases requiring right hemihepatectomy combined with total caudate lobectomy.

Corrigendum: The role of microtubules in pancreatic cancer: therapeutic progress.

[This corrects the article DOI: 10.3389/fonc.2021.640863.].

Suberitolactams A-D and Suberitopyridines A-B: New γ-lactam and Pyridine Alkaloids Isolated from the South China Sea Sponge Pseudospongosorites suberitoides.

Four new γ-lactam alkaloids, suberitolactams A-D (1-4), two new pyridine alkaloids, suberitopyridines A-B (7-8), and two known compounds (5-6) were isolated from the South China Sea sponge Pseudospongosorites suberitoides. The structures were elucidated by detailed 1D and 2D NMR experiments along with HRESIMS analysis and single crystal X-ray diffraction. Compounds 1 and 8 showed moderate to weak antiviral activity against H1N1 virus with IC50 values of 27.6 and 13.3 µM, respectively.

Characterization of extrachromosomal circular DNAs in plasma of patients with clear cell renal cell carcinoma.

BACKGROUND AND PURPOSE: Extrachromosomal circular DNAs (eccDNAs) have been recognized for their significant involvement in numerous biological processes. Nonetheless, the existence and molecular characteristics of eccDNA in the peripheral blood of patients diagnosed with clear cell renal cell carcinoma (ccRCC) have not yet been reported. Our aim was to identify potentially marked plasma eccDNAs in ccRCC patients. METHODS AND MATERIALS: The detection of plasma eccDNA in ccRCC patients and healthy controls was performed using the Tn5-tagmentation and next-generation sequencing (NGS) method. Comparisons were made between ccRCC patients and healthy controls regarding the distribution of length, gene annotation, pattern of junctional nucleotide motif, and expression pattern of plasma eccDNA. RESULTS: We found 8,568 and 8,150 plasma eccDNAs in ccRCC patients and healthy controls, respectively. There were no statistical differences in the length distribution, gene annotation, and motif signature of plasma eccDNAs between the two groups. A total of 701 differentially expressed plasma eccDNAs were identified, and 25 plasma eccDNAs with potential diagnostic value for ccRCC have been successfully screened. These up-regulated plasma eccDNAs also be indicated to originate from the genomic region of the tumor-associated genes. CONCLUSION: This work demonstrates the characterization of plasma eccDNAs in ccRCC and suggests that the up-regulated plasma eccDNAs could be considered as a promising non-invasive biomarker in ccRCC.

Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction.

OBJECTIVE: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). METHODS: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. RESULTS: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). CONCLUSION: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

Peripheral inflammation and trajectories of depressive symptomology after ischemic stroke: A prospective cohort study.

BACKGROUND: Understanding the association of peripheral inflammation and post-stroke depressive symptomology (PSDS) might provide further insights into the complex etiological mechanism of organic depression. However, studies focusing on the longitudinal patterns of PSDS were limited and it remained unclear whether peripheral inflammation influences the occurrence and development of PSDS. METHODS: A total of 427 prospectively enrolled and followed ischemic stroke patients were included in the analytical sample. Depressive symptomology was assessed on four occasions during 1 year after ischemic stroke. Peripheral inflammatory proteins on admission and repeated measures of peripheral immune markers in three stages were collected. Latent class growth analysis (LCGA) was employed to delineate group-based trajectories of peripheral immune markers and PSDS. Multinomial regression was performed to investigate the association of peripheral inflammation with PSDS trajectories. RESULTS: Four distinct trajectories of PSDS were identified: stable-low (n = 237, 55.5 %), high-remitting (n = 120, 28.1 %), late-onset (n = 44, 10.3 %), and high-persistent (n = 26, 6.1 %) PSDS trajectories. The elevation of peripheral fibrinogen on admission increased the risk of high-persistent PSDS in patients with early high PSDS. Additionally, chronic elevation of innate immune levels might not only increase the risk of high-persistent PSDS in patients with early high PSDS but also increase the risk of late-onset PSDS in patients without early high PSDS. The elevation of adaptive immune levels in the convalescence of ischemic stroke may contribute to the remission of early high PSDS. CONCLUSIONS: Peripheral immunity could influence the development of PSDS, and this influence might have temporal heterogeneity. These results might provide vital clues for the inflammation hypothesis of PSD.

Enhanced quantum secret sharing protocol for anonymous secure communication utilizing W states.

Quantum secret sharing (QSS) represents the fusion of quantum mechanics principles with secret information sharing, allowing a sender to distribute a secret among receivers for collective recovery. This paper introduces the concept of quantum anonymous secret sharing (QASS) to enhance the practicality of such protocols. We propose a QASS protocol leveraging W states, ensuring both recover-security and anonymity of shared secrets. Our protocol undergoes rigorous evaluation verifying their accuracy and fortifying their security against scenarios involving the active adversary. Additionally, acknowledging the imperfections inherent in real-world communication channels, we conduct a comprehensive analysis of protocol security and efficacy in noisy quantum networks. Our investigations reveal that W states exhibit good performance in mitigating noise interference, making them apt for practical applications.