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Zhi-Feng Liu,* Yang Zhang,* Jing Liu, Yu-Yan Wang, Mo Chen, Er-Yang Liu, Jun-Ming Guo, Yan-Hua Wang, Zhi-Wen Weng, Chang-Xin Liu, Chang-He Yu, Xi-You Wang Tuina and Pain Management Department, Beijing University of Chinese Medicine Affilliated Dongzhimen Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-He Yu; Xi-You Wang, Email yakno2@163.com; dwxy658@163.comAbstract: Knee osteoarthritis (KOA) stands as a degenerative ailment with a substantial and escalating prevalence. The practice of traditional Chinese non-pharmacological therapy has become a prevalent complementary and adjunctive approach. A mounting body of evidence suggests its efficacy in addressing KOA. Recent investigations have delved into its underlying mechanism, yielding some headway. Consequently, this comprehensive analysis seeks to encapsulate the clinical application and molecular mechanism of traditional Chinese non-pharmacological therapy in KOA treatment. The review reveals that various therapies, such as acupuncture, electroacupuncture, warm needle acupuncture, tuina, and acupotomy, primarily target localized knee components like cartilage, subchondral bone, and synovium. Moreover, their impact extends to the central nervous system and intestinal flora. More perfect experimental design and more comprehensive research remain a promising avenue in the future.Keywords: knee osteoarthritis, traditional Chinese non-pharmacological therapy, mechanism, acupuncture, tuina, acupotomy

Phytochemical study on the stems and leaves of Artocarpus tonkinensis led to the isolation of a new 2-arylbenzofuran, artocartone ( 1 ), as well as seven known 2-arylbenzofurans ( 2-8 ). The chemical structure of 1 was established by means of comprehensive spectroscopic analyses and the known compounds were determined by comparing their MS and NMR data with those reported data in literature. The antiproliferative activities of all isolates 1-8 against five human cancer cell lines: HL-60, SMMC-7721, A-375, MCF-7 and SW480 in vitro were evaluated. As a result, compounds 1- 8 displayed notable antiproliferative activities against various human cancer cell lines with IC 50 values in the range of 0.28 ± 0.05-26.89 ± 0.18 μM.

Anoikis is a distinct type of programmed cell death and a unique mechanism for tumor progress. However, its exact function in gastric cancer (GC) remains unknown. This study aims to investigate the function of anoikis-related lncRNA (ar-lncRNA) in the prognosis of GC and its immunological infiltration. The ar-lncRNAs were derived from RNA sequencing data and associated clinical information obtained from The Cancer Genome Atlas. Pearson correlation analysis, differential screening, LASSO and Cox regression were utilized to identify the typical ar-lncRNAs with prognostic significance, and the corresponding risk model was constructed, respectively. Comprehensive methods were employed to assess the clinical characteristics of the prediction model, ensuring the accuracy of the prediction results. Further analysis was conducted on the relationship between immune microenvironment and risk features, and sensitivity predictions were made about anticancer medicines. A risk model was built according to seven selected ar-lncRNAs. The model was validated and the calibration plots were highly consistent in validating nomogram predictions. Further analyses revealed the great accuracy of the model and its ability to serve as a stand-alone GC prognostic factor. We subsequently disclosed that high-risk groups display significant enrichment in pathways related to tumors and the immune system. Additionally, in tumor immunoassays, notable variations in immune infiltrates and checkpoints were noted between different risk groups. This study proposes, for the first time, that prognostic signatures of ar-lncRNA can be established in GC. These signatures accurately predict the prognosis of GC and offer potential biomarkers, suggesting new avenues for basic research, prognosis prediction and personalized diagnosis and treatment of GC.

Pheromone receptor (PR)-mediated transduction of sex pheromones to electrophysiological signals is the basis for sex pheromone communication. Orthaga achatina , a serious pest of the camphor tree, uses a mixture of four components (Z11-16:OAc, Z11-16:OH, Z11-16:Ald, and Z3,Z6,Z9,Z12,Z15-23:H) as its sex pheromone. In this study, we identified five PR genes ( OachPR 1-5) by phylogenetic analysis. Further RT-PCR and qPCR experiments showed that PR 1-3 were specifically expressed in male antennae, while PR 4 was significantly female-biased in expression. Functional characterization using the XOE-TEVC assay demonstrated that PR1 and PR3 both responded strongly to Z11-16:OH, while PR1 and PR3 had a weak response to Z3,Z6,Z9,Z12,Z15-23:H and Z11-16:Ald, respectively. Finally, two key amino acid residues (N78 and R331) were confirmed to be essential for binding of PR3 with Z11-16:OH by molecular docking and site-directed mutagenesis. This study helps understand the sex pheromone recognition molecular mechanism of O. achatina .

The chemical constituents from the stems and leaves of Artocarpus tonkinensis in Artocarpus of Moraceae were systematically studied by means of silica gel, octadecylsilyl(ODS), and Sephadex LH-20 gel column chromatographies, as well as preparative high-performance liquid chromatography(Pre-HPLC) and a variety of chromatographic separation techniques. The spectral data and physicochemical properties of the compounds were obtained from separation and compared with those of the compounds reported in the literature. As a result, 11 compounds isolated from the 90% ethanol extract of the stems and leaves of A. tonkinensis were identified as artocatonkine(1), 5,6,7,4'-tetramethoxyflavone(2), apigenin-4'-O-β-D-glucoside(3), rayalinol(4), psorachalcone A(5), 4-ketopinoresinol(6), ficusesquilignan B(7), pinnatifidanin AI(8), pinnatifidanin A(9), O-methylmellein(10), and trans-4-hydroxymellein(11). Among these compounds, compound 1 was a new prenylated flavone, and compounds 2-11 were isolated from the plants belonging to the genus Artocarpus for the first time. Furthermore, all compounds 1-11 were evaluated for their anti-rheumatoid arthritis activities, and the MTS method was used to measure their inhibitory effects on the proliferation of synovioblasts in vitro. The results of activity evaluation showed that flavonoid compounds 1-3, 5, and lignan compounds 8 and 9 displayed significant anti-rheumatoid arthritis activities, showing the IC_(50) values in inhibiting the proliferation of synovioblasts MH7A from(6.38±0.06) μmol·L~(-1) to(168.58±0.28)μmol·L~(-1).

Dielectric capacitors offer great potential for advanced electronics due to their high power densities, but their energy density still needs to be further improved. High-entropy strategy has emerged as an effective method for improving energy storage performance, however, discovering new high-entropy systems within a high-dimensional composition space is a daunting challenge for traditional trial-and-error experiments. Here, based on phase-field simulations and limited experimental data, we propose a generative learning approach to accelerate the discovery of high-entropy dielectrics in a practically infinite exploration space of over 10 11 combinations. By encoding-decoding latent space regularities to facilitate data sampling and forward inference, we employ inverse design to screen out the most promising combinations via a ranking strategy. Through only 5 sets of targeted experiments, we successfully obtain a Bi(Mg 0.5 Ti 0.5 )O 3 -based high-entropy dielectric film with a significantly improved energy density of 156 J cm -3 at an electric field of 5104 kV cm -1 , surpassing the pristine film by more than eight-fold. This work introduces an effective and innovative avenue for designing high-entropy dielectrics with drastically reduced experimental cycles, which could be also extended to expedite the design of other multicomponent material systems with desired properties., (© 2024. The Author(s).)

Artificial intelligence (AI) represents a recent major breakthrough in technology development and, in recent years, generative AI has emerged as another trendsetter. The application of generative AI technologies in the healthcare sector has not only opened new possibilities for improving the efficiency of medical diagnoses but also provided healthcare professionals with more-accurate patient monitoring capabilities and optimized care processes. Combining generative AI with nursing expertise holds out the potential of creating a more valuable model of nursing care. The impact of generative AI on the nursing profession poses both challenges and opportunities. By applying appropriate strategies, it is possible to create more advanced and humane nursing values that enhance overall nursing efficiencies and align the nursing field with modern technological advancements. In this article, the development of AI and generative AI is reviewed, and the potential for their application to nursing care is discussed, with the goal of stimulating innovative thinking and new strategies for interdisciplinary collaboration between technology and nursing.

Background: Mythimna loreyi is an important agricultural pest with a sensitive sex pheromone communication system. To clarify the pheromone binding proteins (PBPs) and pheromone receptors (PRs) involved in sex pheromone perception is important for both understanding the molecular olfactory mechanism and developing a new pest control strategy in M. loreyi., Results: First, the electroantennogram (EAG) assay showed that male M. loreyi displayed the highest response to the major sex pheromone component Z9-14:Ac, and higher responses to two minor components, Z7-12:Ac and Z11-16:Ac. Second, the fluorescence competition binding assay showed that PBP1 bound all three pheromones and other tested compounds with high or moderate affinity, while PBP2 and PBP3 each bound only one pheromone component and few other compounds. Third, functional study using the Xenopus oocyte system demonstrated that, of the six candidate PRs, PR2 was weakly sensitive to the major pheromone Z9-14:Ac, but was strongly sensitive to pheromone analog Z9-14:OH; PR3 was strongly and specifically sensitive to a minor component Z7-12:Ac; PR4 and OR33 were both weakly sensitive to another minor component, Z11-16:Ac. Finally, phylogenetic relationship and ligand profiles of PRs were compared among six species from two closely related genera Mythimna and Spodoptera, suggesting functional shifts of M. loreyi PRs toward Spodoptera PRs., Conclusion: Functional differentiations were revealed among three PBPs and six PRs in sex pheromone perception, laying an important basis for understanding the molecular mechanism of sex pheromone perception and for developing new control strategies in M. loreyi. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC., Patients and Methods: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety., Results: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group., Conclusion: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975., (Copyright © 2023 X. Yan, M. Ye, Q. Zou, P. Chen, Z. He, B. Wu, D. He, C. He, X. Xue, Z. Ji, H. Chen, S. Zhang, Y. Liu, X. Zhang, C. Fu, D. Xu, M. Qiu, J. Lv, J. Huang, X. Ren, Y. Cheng, W. Qin, X. Zhang, F. Zhou, L. Ma, J. Guo, D. Ding, S. Wei, Y. He, H. Guo, B. Shi, L. Liu, F. Liu, Z. Hu, X. Jin, L. Yang, S. Zhu, J. Liu, Y. Huang, T. Xu, B. Liu, T. Sun, Z. Wang, H. Jiang, D. Yu, A. Zhou, J. Jiang, G. Luan, C. Jin, J. Xu, J. Hu, Y. H, Jun, W. Zhai, X. Sheng, Shanghai Junshi Biosciences Co. LTD, Shanghai Junshi Biosciences Co. LTD., a. Published by Elsevier Ltd.. All rights reserved.)

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus , thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.

Ionotropic receptors (IRs) play an important role in olfaction, but little is known in nondrosophila insects. Here, we report in vitro and in vivo functional characterization of IR75q.2 in the invasive moth pest Spodoptera frugiperda . First, 13 IRs (including four coreceptor IRs) were found specifically or highly expressed in adult antennae. Second, these IRs were tested for responding profiles to 59 odorants using the Xenopus oocyte expression system, showing that only SfruIR75q.2 responded to 8-10C fatty acids and their corresponding aldehydes, with SfruIR8a as the only coreceptor. Third, the three acids (especially nonanoic acid) showed repellent effects on moth's behavior and oviposition, but the repellence significantly reduced to the insects with IR75q.2 knockout by CRISPR/Cas9. Taken together, our study reveals the function of SfruIR75q.2 in perception of acid and aldehyde odorants and provides the first in vivo evidence for olfactory function of an odor-specific IR in Lepidoptera.

The insect olfaction plays crucial roles in many important behaviors, in which ORs are key determinants for signal transduction and the olfactory specificity. Spodoptera litura is a typical polyphagous pest, possessing a large repertoire of ORs tuning to broad range of plant odorants. However, the specific functions of those ORs remain mostly unknown. In this study, we functionally characterized one S. litura OR (OR51) that was highly expressed in the adult antennae. First, by using Xenopus oocyte expression and two-electrode voltage clamp recording system (XOE-TEVC), OR51 was found to be strongly and specifically responsive to vanillin (a volatile of S. litura host plants) among 77 tested odorants. Second, electroantennogram (EAG) and Y-tube behavioral experiment showed that vanillin elicited significant EAG response and attraction behavior especially of female adults. This female attraction was further confirmed by the oviposition experiment, in which the soybean plants treated with vanillin were significantly preferred by females for egg-laying. Third, 3D structural modelling and molecular docking were conducted to explore the interaction between OR51 and vanillin, which showed a high affinity (-4.46 kcal/mol) and three residues (Gln163, Phe164 and Ala305) forming hydrogen bonds with vanillin, supporting the specific binding of OR51 to vanillin. In addition, OR51 and its homologs from other seven noctuid species shared high amino acid identities (78-97%) and the same three hydrogen bond forming residues, suggesting a conserved function of the OR in these insects. Taken together, our study provides some new insights into the olfactory mechanisms of host plant finding and suggests potential applications of vanillin in S. litura control., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bottle palm (Hyophorbe lagenicaulis) is a picturesque evergreen plant in the family Aceraceae, ubiquitously cultivated as an ornamental tree throughout the tropics and subtropics due its attractive shape and small stature. During 2016-2022, brown spots were observed on the leaves of bottle palm on both sides of a campus road in Mazhang, Zhanjiang, Guangdong province (N21°8' 59.9" E110°17' 51.4"). Symptoms appeared as circular, light yellow to brownish red, slightly sunken spots, and brown to black in the center (Fig 1 A-C). The spots expanded to big irregular blotches, which finally led leaves to wither. 0ne hundred percent of 50 plants were infected and 90% of the leaves each plant were covered with brown patches of different sizes. Tissues (5 × 5 mm) from the diseased-healthy junction of the leaf spots were surface disinfected with 75% ethanol for 30 s and 3.5% hydrogen peroxide solution for 5 min, rinsed three times with sterile water and placed on potato dextrose agar (PDA) at 25-28℃ in the dark for 3 days. Fungi with the similar morphology grew from 100% of these inoculated tissues. Hyphal tips from the colony edges were transferred to PDA. Single isolates were obtained by plate dilution method after sporogenesis. Colonies with sparse aerial mycelium were flat, grey. Conidiomata were superficial, black, solitary, scattered. Conidiophores were cylindrical, densely aggregated. Alpha conidia with bi-multiguttulate were hyaline, smooth, ellipsoidal, aseptate, 4.7-7.9×1.6-3.4 µm (Av. 6.4×2.3µm, n>50). Beta conidia were filiform, slightly curved, 15.9-28.3× 0.7-1.1 μm (20.1 × 0.9 μm, n>50) (Fig 1 E-H). Gamma conidia were not observed. The internal transcribed spacer (ITS) regions, large subunit (LSU) rRNA sequence, translation elongation factor (TEF), actin (ACT), calmodulin (CAL), histone H3 (HIS), and beta tubulin (TUB2) genes were amplified using the primers ITS4/ITS1 (White et al. 1990), LR0R/LR5, EF1-728F/EF-2, ACT-512F/ACT-783R, CAL228F/ CAL737R, CYLH3F/ H3-1b, and TUB2Fd /TUB4Rd (Aveskamp et al. 2009; Carbone and Kohn 1999; Crous et al. 2004; O'Donnell et al. 2000), respectively. All seven sequences of the isolate CCAS-JPYZ-4B (ACCC 35493) were submitted to NCBI (OR430112-3, OR451702-6). BLAST search result showed high sequence identity with several Diaporthe ueckeri isolates (Tab1). Phylogenetic analysis of the concatenated data of CAL, HIS, ITS, TEF and TUB genes using Maximum Likelihood method placed CCAS-JPYZ-4B in the D. ueckeri clade. Thus, the isolate was identified as D. ueckeri (Udayanga et al. 2015). Pathogenicity tests were performed on three 5-year-old plants, one healthy new leaf per plant and 10 sites on per leaf were slightly wounded and inoculated with 5-mm mycelial plugs from 10-day-old culture on PDA. The control sites were treated with PDA plugs. Each inoculated leaf was covered with a plastic bag to maintain high humidity and kept at natural temperatures (25-28 ℃). The experiment was repeated once. Symptoms appeared as those described as above 5 to 10 days after inoculation (Fig 1 D). Controls were asymptomatic. The fungus was reisolated from diseased leaves and identified as D. ueckeri. D. ueckeri may infect Arachis hypogaea, Cucumis melo, Camellia sinensis, Glycine max, Mangifera indica and Michelia shiluensis, and this is first report causing brown blotch on bottle palm in China. This disease occurred all year round, which seriously affected plants growth and ornamental value; it is necessary to develop an effective management strategy.

Aim: To investigate the aqueous vein in vivo by using enhanced depth imaging optical coherence tomography (EDI-OCT) and optical coherence tomography angiography (OCTA)., Methods: In this cross-sectional comparative study, 30 healthy participants were enrolled. Images of the aqueous and conjunctival veins were captured by EDI-OCT and OCTA before and after water loading. The area, height, width, location depth and blood flow of the aqueous vein and conjunctival vein were measured by Image J software., Results: In the static state, the area of the aqueous vein was 8166.7±3272.7 µm 2 , which was smaller than that of the conjunctival vein (13 690±7457 µm 2 , P <0.001). The mean blood flow density of the aqueous vein was 35.3%±12.6%, which was significantly less than that of the conjunctival vein (51.5%±10.6%, P <0.001). After water loading, the area of the aqueous vein decreased significantly from 8725.8±779.4 µm 2 (baseline) to 7005.2±566.2 µm 2 at 45min but rose to 7863.0±703.2 µm 2 at 60min ( P =0.032). The blood flow density of the aqueous vein decreased significantly from 41.2%±4.5% (baseline) to 35.4%±3.2% at 30min but returned to 45.6%±3.6% at 60min ( P =0.021)., Conclusion: The structure and blood flow density of the aqueous vein can be effectively evaluated by OCT and OCTA. These may become biological indicators to evaluate aqueous vein changes and aqueous outflow resistance under different interventions in glaucoma patients., (International Journal of Ophthalmology Press.)

Four new xanthones, cratocochinones A-D ( 1 - 4 ), together with eight known analogues ( 5 - 12 ), were isolated from the stems and leaves of Cratoxylum cochinchinense . The chemical structures of cratocochinones A-D ( 1 - 4 ) were elucidated by comprehensive spectroscopic analyses and the known compounds were identified by comparisons with the spectral data reported in the literature. All isolated compounds 1 - 12 were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1 - 12 showed remarkable inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro, with IC 50 values in the range of 0.86 ± 0.05 to 18.36 ± 0.21 µM. Meanwhile, compounds 1 - 12 exhibited significant anti-HIV-1 activities with EC 50 which ranged from 0.22 to 11.23 µM. These findings indicate that the discoveries of these xanthones, isolated from the stems and leaves of C. cochinchinense, showing significant anti-inflammatory and anti-HIV-1 effects could be of great importance to the research and development of new natural anti-inflammatory and anti-HIV agents.

The Brewster effect has been previously reported as an essential mechanism for terahertz (THz) wave sensing application. However, generally in a sensing application, a complex rotation apparatus is required for detecting the slight change in Brewster angle. Here, we propose a graphene-based Brewster angle device operating at a specific terahertz frequency capable of sensing the refractive index at a fixed incident angle. In other words, our sensing device could avoid the impact of Brewster angle shift and eliminate the need for high-precision rotating equipment, which is usually required in traditional sensing applications. The conversion from the refractive index to a Volt-level detectable voltage roots from the tunability of graphene's Fermi level in the external electrical field. A linear correlation between the output voltage and the background refractive index is observed and theocratically analyzed. Furthermore, we present the improvement of our device in terms of sensing range and sensitivity by adjusting the permittivity of the dielectric substrate. As a demonstration of our proposed device, a detection range of 1.1-2.4 and a sensitivity of 20.06 V/RIU for refractive index is achieved on a high-resistance silicon substrate operating at 0.3 THz.

For post-menopausal women, stroke is complicated by the variable effects of estrogen therapy and the age-related therapeutic consequences involved. Estrogen therapy has been shown to have an age-dimorphic effect, which is neuroprotective in young females, but non-neuroprotective, even neurotoxic in acyclic females. We hypothesized that arterial baroreflex (ABR) and its downstream acetylcholine-α7 nicotinic acetylcholine receptor (α7nAChR) anti-inflammatory pathways are involved in estrogen efficacy toward cerebral ischemic damage. Our data showed that estrogen supplements contributed to ABR improvement and neuroprotection in adult, not aged, ovariectomized (OVX) rats. In adult rats, OVX-induced estrogen deficiency aggravated middle cerebral artery occlusion (MCAO), which induced brain infarction and reduced ABR function, with decreased α7nAChR expression of the brain and exaggerated inflammation following MCAO; these effects were significantly prevented by supplementation with estrogen. ABR impairment by sinoaortic denervation partly attenuated the estrogen effect on baroreflex sensitivity (BRS) and ischemic damage in adult rats, as well as α7nAChR expression and inflammatory response. These data suggested that ABR and acetylcholine-α7nAChR anti-inflammatory pathways are involved in the neuroprotection of estrogen in adult OVX rats. In contrast, aged rats exhibited more severe ischemic damage and inflammatory response than adult rats, as well as poorer baroreflex function and lower α7nAChR expression. Estrogen supplements did not improve BRS or confer neuroprotection in aged rats without affecting brain α7nAChR and post-ischemic inflammation. Most importantly, ketanserin restored ABR function and significantly postponed the onset of stroke in aged female strokeprone spontaneously hypertensive rats, whereas estrogen treatment failed to delay the development of stroke. Our findings reveal that estrogen is protective against ischemic stroke (IS) in adult female rats and that ABR played a role in this beneficial action. Dysfunction of ABR and unresponsiveness to estrogen in aged female rats may contribute to a reduced estrogen efficacy against cerebral ischemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Wang, Shan, Shu and Guo.)

Bradina is a species-rich genus that differs from most other Spilomelinae genera because of its distinctive wing venation. Most species of this genus are very similar in appearance. In this study, we have studied morphological characteristics of the genus and eight closely related species from China. Among them, B.falciculata Guo & Du, sp. nov. , B.fusoidea Guo & Du, sp. nov. , B.spirella Guo & Du, sp. nov. , B.ternifolia Guo & Du, sp. nov. and B.torsiva Guo & Du, sp. nov. are described as new to science. Bradinamegesalis (Walker, 1859), B.translinealis Hampson, 1896 and B.subpurpurescens (Warren, 1896) are redescribed based on their holotypes and additional material, and the latter two are newly recorded from China and their genitalia are described for the first time. The images of the habitus and genitalia of these eight species are provided, with a key to their identification., (Jia-Ming Guo, Xi-Cui Du.)

A quantitative analysis method for corrosion products based on terahertz spectroscopy is proposed in this paper. Mixture samples consisting of three major corrosion products (magnetite, hematite, and goethite) were prepared in 51 different concentrations. The refractive index spectra measured by terahertz time-domain spectroscopy were projected to the 2D score diagram by performing principal component analysis. The Euclidean distances between the mixtures and pure analyte on the diagram were used to build a concentration prediction model. The results indicate that the established model can precisely predict the concentration of magnetite, which is essential for a stability evaluation of the corrosion system.

An efficient approach to access chiral N-α indole substituted pyrrolidine and piperidine skeletons has been developed through a AgSbF 6 -catalyzed N-α aza -Friedel-Crafts alkylation of N , O -acetals 6a, 6b, 9, and 11a-11d with indoles. As a result, a series of 2,3- trans N-α indole substituted pyrrolidines 8a-8x and piperidines 10a-10j were prepared in moderate to excellent yields and with excellent diastereoselectivities ( dr up to 99 : 1). Moreover, several 2,5- cis-N-α indole substituted pyrrolidine derivatives 12a-12k were synthesized according to this strategy with moderate to good yields and diastereoselectivities ( dr up to 99 : 1).

Background: Excessive doses of electromagnetic radiation pose a negative impact on the central nervous system and lead to mental disorders. Molecular hydrogen can scavenge intracellular hydroxyl radicals, acting as an antioxidant, anti-apoptotic and anti-inflammatory agent. We seek to assess the capability of molecular hydrogen to ameliorate brain damage induced by electromagnetic radiation., Methods: NEMP (nuclear electromagnetic pulse), a subset of electromagnetic pulse with high voltage value that could cause severe brain injury, was applied to this study. Male wild-type rats were divided into four groups: the control group, the H 2 (Molecular hydrogen) group, the NEMP group and the NEMP+H 2 group. Rats in the H 2 group and the NEMP+H 2 group were fed with saturated hydrogen-rich water from 3 days before NEMP exposure (electromagnetic field intensity 400 kV/m, rising edge 20 ns and pulse width 200 ns) to the day of sacrifice. One day after exposure, animal behavior experiments were performed, and samples for transcriptomics and metabolomics analysis were collected. Seven days after exposure, histopathological experiments were conducted., Results: The data from the elevated plus maze and the open field test showed that NEMP exposure elicited anxiety-like behavior in rats, which could be alleviated by H 2 treatment. Histopathological results manifested that NEMP exposure-induced injuries of the neurons in the hippocampus and amygdala could be attenuated by H 2 treatment. Transcriptomic results revealed that NEMP exposure had a profound effect on microtubule structure in the brain. And the combined analysis of transcriptomics and metabolomics showed that H 2 has a significant impact on the neuroactive ligand-receptor interaction, synaptic vesicle cycle and synapse etc. Moreover, it was indicated that the glutathione metabolic pathway played a vital role in the NEMP exposure-induced damage and the protective activity of H 2 ., Conclusions: H 2 is identified as a potent agent against NEMP exposure-induced brain damage and has the potential to be a promising electromagnetic radiation protectant., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ma, Tian, Zhang, Wang, Wang, Yan, Hu, Shao and Guo.)

Inflammatory bowel disease (IBD) is a recurrent disease associated with a potential risk of colorectal cancer. Abelmoschus manihot (AM), a Chinese herbal medicine, is known to alleviate IBD. However, its mechanism of action requires further clarification. Here, we focused on the role of IL-10 and the gut microbiota in the mechanism of action of AM. The effects of AM on intestinal inflammation, mucus production, and gut microbes were evaluated in dextran sodium sulfate (DSS)-induced acute and chronic IBD models and in IL-10-deficient mice (IL-10[Formula: see text]). AM exhibited protective effects on acute and chronic models of IBD in wild-type mice by restoring body weight and colon length, promoting IL-10 secretion, and decreasing TNF-[Formula: see text] levels. Moreover, AM alleviated inflammatory infiltration, increased mucin 2 transcription, and increased the number of goblet cells in the colon. On the contrary, these effects were diminished in IL-10[Formula: see text] mice, which implied that the effect of AM on intestinal inflammation is IL-10-dependent. A gut microbial sequencing analysis showed that gut microbial dysbiosis was modulated by AM intervention. The regulatory effects of AM on Eggerthellaceae , Sutterellaceae , Erysipelotrichaceae , Burkholderiaceae , Desulfovibrionaceae , and Enterococcaceae were dependent on IL-10. These results revealed that AM ameliorated IBD and modulated gut microbes by promoting IL-10 secretion, indicating that AM has the potential to improve IBD and that AM is IL-10-dependent.

Intercropping a Cd-accumulator with economically valuable crops is common in slightly or moderately Cd-polluted farmland soils. A field experiment was conducted to evaluate the effects of water-soluble chitosan (WSC) on the growth and Cd uptake of the Cd-accumulator Hylotelephium spectabile and soybean ( Glycine max ) during a co-cultivation in Cd-contaminated agricultural soil (WSC, 0 and 10 g·m -2 ). The results indicated that soybean yields were highest in response to the intercropping and WSC treatment. The results from the field trials generally showed that intercropping and WSC treatments significantly decreased Cd concentrations in inedible parts of soybean by 42.9-72.1% (except for stems), in the meantime, increased 95.8%-334.6% in shoot and root tissues of H. spectabile compared with the control ( p  < 0.05). The data revealed that Cd uptake was highest for H. spectabile during the intercropping and WSC treatment. The application of WSC in the intercropping system significantly increased the uptake of Cd by H. spectabile , but not by soybean. The findings of this study suggest that combining an intercropping system with a WSC treatment may be better for remediating Cd-contaminated soils than other methods involving the growth of a single hyperaccumulator.

Background: In insects, the chemosensory system is crucial in guiding their behaviors for survival. Plagiodera versicolora (Coleoptera: Chrysomelidae), is a worldwide leaf-eating forest pest in salicaceous trees. There is little known about the chemosensory genes in P. versicolora. Here, we conducted a transcriptome analysis of larvae heads in P. versicolora., Results: In this study, 29 odorant binding proteins (OBPs), 6 chemosensory proteins (CSPs), 14 odorant receptors (ORs), 13 gustatory receptors (GRs), 8 ionotropic receptors (IRs) and 4 sensory neuron membrane proteins (SNMPs) were identified by transcriptome analysis. Compared to the previous antennae and foreleg transcriptome data in adults, 12 OBPs, 2 CSPs, 5 ORs, 4 IRs, and 7 GRs were newly identified in the larvae. Phylogenetic analyses were conducted and found a new candidate CO 2 receptor (PverGR18) and a new sugar receptor (PverGR23) in the tree of GRs. Subsequently, the dynamic expression profiles of various genes were analyzed by quantitative real-time PCR. The results showed that PverOBP31, OBP34, OBP35, OBP38, and OBP40 were highly expressed in larvae, PverOBP33 and OBP37 were highly expressed in pupae, and PverCSP13 was highly expressed in eggs, respectively., Conclusions: We identified a total of 74 putative chemosensory genes based on a transcriptome analysis of larvae heads in P. versicolora. This work provides new information for functional studies on the chemoreception mechanism in P. versicolora., (© 2022. The Author(s).)

Lung adenocarcinoma is a malignancy with a low overall survival and a poor prognosis. Studies have shown that lung adenocarcinoma progression relates to locus-specific/global changes in histone modifications. To explore the relationship between histone modification and gene expression changes, we focused on 11 histone modifications and quantitatively analyzed their influences on gene expression. We found that, among the studied histone modifications, H3K79me2 displayed the greatest impact on gene expression regulation. Based on the Shannon entropy, 867 genes with differential H3K79me2 levels during tumorigenesis were identified. Enrichment analyses showed that these genes were involved in 16 common cancer pathways and 11 tumors and were target-regulated by trans -regulatory elements, such as Tp53 and WT1. Then, an open-source computational framework was presented (https://github.com/zlq-imu/Identification-of-potential-LUND-driver-genes). Twelve potential driver genes were extracted from the genes with differential H3K79me2 levels during tumorigenesis. The expression levels of these potential driver genes were significantly increased/decreased in tumor cells, as assayed by RT-qPCR. A risk score model comprising these driver genes was further constructed, and this model was strongly negatively associated with the overall survival of patients in different datasets. The proportional hazards assumption and outlier test indicated that this model could robustly distinguish patients with different survival rates. Immune analyses and responses to immunotherapeutic and chemotherapeutic agents showed that patients in the high and low-risk groups may have distinct tendencies for clinical selection. Finally, the regions with clear H3K79me2 signal changes on these driver genes were accurately identified. Our research may offer potential molecular biomarkers for lung adenocarcinoma treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

An efficient approach to access α-arylacetylene-substituted pyrrolidine and piperidine derivatives has been developed through a samarium diiodide-mediated addition-elimination process of pyrrolidine and piperidine N -α-radicals with arylacetylene sulfones.

Infertility has got to be a broadly concerned social issue these days, in which the malefactor cannot be overlooked. Numerous studies have shown that electromagnetic pulse (EMP) radiation may have seriously damaging effects on reproductive health, through nonthermal effects and oxidative stress. Molecular hydrogen, a selective hydroxyl radical scavenger, explains the protective effects against many diseases closely associated with oxidative damage, such as ionizing radiation (IR). We sought to characterize the beneficial effects of molecular hydrogen on the male reproductive system in a rodent EMP exposure model. The 8-week-old male Sprague-Dawley rats were exposed to EMP (peak intensity 1000 kV/m, pulse edge 20 ns, pulse width 200 ns, 1 Hz, and 200 pulses), with or without hydrogen-rich water. The pathological structure of the testis, the rate of apoptosis of the testis, the serum testosterone level, the sperm parameters, and the activity of the antioxidant enzymes of the testis were measured. Then, transcriptomic and untargeted metabolomic analyses were applied to uncover the underlying mechanism. Exposure to EMP increased testicular apoptosis rate and apoptosis protein level, decreased sperm viability and motility, decreased serum testosterone levels, and diminished testicular antioxidant capacity. Molecular hydrogen-alleviated damage decreased the testicular apoptosis rate and apoptosis protein level, increased sperm motility, increased serum testosterone levels, and improved antioxidative capacity. Omics results showed that molecular hydrogen has a strong influence on metabolic pathways, and EMP affects mainly oxidative phosphorylation, TNF signaling pathways, and cytokine-receptor interactions. The mechanism of molecular hydrogen's effect may be related to the reversal of some metabolite levels. These observations warrant molecular hydrogen as an innovative approach for potential protection against EMP., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Long Ma et al.)

In order to explore the distribution characteristics of heavy metal contamination of farmland soil surrounding Luancheng town, Shijiazhuang City, Henan province, the concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the surface soil and crops were determined and assessed. The principal components were also analyzed for source apportionment. The heavy metal concentrations in crops were further detected, and the non-carcinogenic health risks in the study area were evaluated using the probabilistic risk assessment method, as to provide a theoretical basis for the treatment, prevention, and control of heavy metal pollution in farmland soil in Luancheng. According to the results, ω (Cd), ω (Cr), ω (Cu), ω (Pb), and ω (Zn) in the soils were 0.06-1.08, 22.14-473.47, 12.83-150.74, 10.75-577.72, and 62.23-652.78 mg·kg -1 , which exceeded the standard with over-standard rates reaching 1.83%, 1.22%, 0.61%, 0.61%, and 1.22%, respectively. Further, Cd and Pb were transported into crops, in which Cd concentrations exceeded the standard in some corn samples, and Cd and Pb concentrations exceeded the standard in some wheat samples. The total non-carcinogenic health risks (TTHQ) to the human body caused by the consumption of heavy metals in corn grown in the study area were all less than 1, with no obvious negative effects, and TTHQ was higher than 1 in wheat, increasing the likelihood of negative impacts on the human body. With the influence of the distribution of pollution-related enterprises in the industrial zone, heavy metal concentrations were higher in the south, west, and middle directions of the study area. Among them, the study area soil was slightly contaminated by Cd (Level 1). Cd and Hg had a slight potential ecological risk (Level 2), whereas other heavy metals had low potential ecological risk (Level 1). In general, most of the surface cultivated soil was not obviously polluted by heavy metals in the study area. According to the PMF results and survey, we speculated that soil heavy metals mainly came from soil parent material (52.05%), artificial pollution sources (historical sewage irrigation and industrial manufacture) (32.98%), and atmospheric deposition (14.97%). To summarize, the study area should be divided into a priority protection category and safe utilization category. The input of pollution sources should be strictly controlled for the priority protection category, and alternative planting, rotating, and fallow should be implemented for the safe utilization category to reduce the risk of standard-exceeding agricultural products.

An efficient approach to functionalized ( E )-3-cinnamyl-3-methyl-2,3-dihydrobenzofurans and ( E )-(3-methyl-2,3-dihydrobenzofuran-3-yl)but-2-enones has been developed through a Pd-catalyzed one-pot cascade process involving two sequential Heck reactions, that is, an intramolecular Heck reaction of olefin-tethered aryl iodides and an intermolecular Heck reaction with substituted styrenes and α,β-unsaturated ketones. As a result, a series of desired products were obtained in moderate to good yields and with exclusive E -form selectivities.

The present study established a determination method of Psoraleae Fructus by quantitative analysis of multi-components by the single marker(QAMS) and further improved the thin-layer chromatography(TLC) method. The QAMS method was established by UPLC with psoralen as the internal marker, and the content of psoralenoside, isopsoralenoside, psoralen, and isopsoralen was simultaneously determined. As revealed by the comparison with results of the external standard method, the QAMS method was accurate and feasible. According to the current quality standards of Psoraleae Fructus, the TLC method was further optimized and improved, and bakuchiol was added for identification based on the original TLC method with psoralen and isopsoralen as indicators. This study provides a reference for improving the quality control method of Psoraleae Fructus.

Observational findings achieved that gut microbes mediate human metabolic health and disease risk. The types of intestinal microorganisms depend on the intake of food and drugs and are also related to their metabolic level and genetic factors. Recent studies have shown that chronic inflammatory pain is closely related to intestinal microbial homeostasis. Compared with the normal intestinal flora, the composition of intestinal flora in patients with chronic inflammatory pain had significant changes in Actinomycetes , Firmicutes , Bacteroidetes , etc. At the same time, short-chain fatty acids and amino acids, the metabolites of intestinal microorganisms, can regulate neural signal molecules and signaling pathways, thus affecting the development trend of chronic inflammatory pain. Glucocorticoids and non-steroidal anti-inflammatory drugs in the treatment of chronic inflammatory pain, the main mechanism is to affect the secretion of inflammatory factors and the abundance of intestinal bacteria. This article reviews the relationship between intestinal microorganisms and their metabolites on chronic inflammatory pain and the possible mechanism., Competing Interests: Competing interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

A catalyzed process for the synthesis of the 4,6-substituted 3,4-dihydro-1,3-oxazin-2-one skeleton has been developed through cycloaddition of in situ generated acyliminium intermediates with alkynes. A range of chain N , O -acetals and terminal alkynes were amenable for this mild transformation. As a result, a series of desired cycloaddition products were obtained in moderate to good yields.

Pheromone-binding proteins (PBPs) play important roles in perception of insect sex pheromones, functioning to recognize and transport pheromone components onto the olfactory receptors of the odorant sensing neurons. Orthaga achatina, a serious pest of camphor trees, uses a mixture of three Type I (Z11-16:OAc, Z11-16:OH and Z11-16:Ald) and one Type II (Z3,Z6,Z9,Z12,Z15-23:H) sex pheromone components in its sex communication, in which Z11-16:OAc is the major component and others are minor components. In this study, we for the first time demonstrated that the three PBPs differentiated in recognition among pheromone components in a moth using mixed-type sex pheromones. First, tissue expression study showed that all three PBPs of O. achatina were expressed only in antennae and highly male-biased, suggesting their involvement in perception of the sex pheromones. Second, the three PBPs were expressed in Escherichia coli and the binding affinities of PBPs to four sex pheromone components and some pheromone analogs were determined by the fluorescence competition binding assays. The results showed that OachPBP1 bound all four sex pheromone components with high binding affinity, while OachPBP2 had high or moderate binding affinity only to three Type I components, and OachPBP3 had high binding affinity only to three minor pheromone components. Furthermore, key amino acid residues that bind to sex pheromone components were identified in three PBPs by 3-D structure modeling and ligand molecular docking, predicting the interactions between PBPs and pheromone components. Our study provides a fundamental insight into the olfactory mechanism in moths that use mixed-type sex pheromones., (Copyright © 2022. Published by Elsevier Inc.)

Falling is a major cause of personal injury and accidental death worldwide, in particular for the elderly. For aged care, a falling alarm system is highly demanded so that medical aid can be obtained immediately when the fall accidents happen. Previous studies on fall detection lacked practical considerations to deal with real-world situations, including the camera's mounting angle, lighting differences between day and night, and the privacy protection for users. In our experiments, IR-depth images and thermal images were used as the input source for fall detection; as a result, detailed facial information is not captured by the system for privacy reasons, and it is invariant to the lighting conditions. Due to the different occurrence rates between fall accidents and other normal activities, supervised learning approaches may suffer from the problem of data imbalance in the training phase. Accordingly, in this study, anomaly detection is performed using unsupervised learning approaches so that the models were trained only with the normal cases while the fall accident was defined as an anomaly event. The proposed system takes sequential frames as the inputs to predict future frames based on a GAN structure, and it provides (1) multi-subject detection, (2) real-time fall detection triggered by motion, (3) a solution to the situation that subjects were occluded after falling, and (4) a denoising scheme for depth images. The experimental results show that the proposed system achieves the state-of-the-art performance and copes with the real-world cases successfully.

Accurate glioma subtype classification is critical for the treatment management of patients with brain tumors. Developing an automatically computer-aided algorithm for glioma subtype classification is challenging due to many factors. One of the difficulties is the label constraint. Specifically, each case is simply labeled the glioma subtype without precise annotations of lesion regions information. In this paper, we propose a novel hybrid fully convolutional neural network (CNN)-based method for glioma subtype classification using both whole slide imaging (WSI) and multiparametric magnetic resonance imagings (mpMRIs). It is comprised of two methods: a WSI-based method and a mpMRIs-based method. For the WSI-based method, we categorize the glioma subtype using a 2D CNN on WSIs. To overcome the label constraint issue, we extract the truly representative patches for the glioma subtype classification in a weakly supervised fashion. For the mpMRIs-based method, we develop a 3D CNN-based method by analyzing the mpMRIs. The mpMRIs-based method consists of brain tumor segmentation and classification. Finally, to enhance the robustness of the predictions, we fuse the WSI-based and mpMRIs-based results guided by a confidence index. The experimental results on the validation dataset in the competition of CPM-RadPath 2020 show the comprehensive judgments from both two modalities can achieve better performance than the ones by solely using WSI or mpMRIs. Furthermore, our result using the proposed method ranks the third place in the CPM-RadPath 2020 in the testing phase. The proposed method demonstrates a competitive performance, which is creditable to the success of weakly supervised approach and the strategy of label agreement from multi-modality data., (© 2022. The Author(s).)

The effects of the plant growth regulator DA-6 and chelator EDDS on the growth, Cd absorption, and soil bacterial community structure of Solanum nigrum L. on Cd-polluted soil were examined through a pot experiment, so as to evaluate the practical application effects of different remediation treatments. The results showed that the addition of DA-6 alone and the combined application of DA-6 and EDDS could promote the growth of S. nigrum L., and the shoot fresh weight increased by 24.58% and 19.57%, respectively, compared with that in the control. At the same time, the chlorophyll content and antioxidant enzyme activity of S. nigrum L. leaves also increased, whereas the content of malondialdehyde decreased. The application of DA-6 and EDDS also significantly increased the content of soil available Cd and promoted the absorption of Cd by S. nigrum L. Compared with that in the control, the extraction amount of Cd from S. nigrum L. shoots was significantly increased by 39.42% (DA-6), 30.17% (EDDS), and 51.04% (DA-6+EDDS), respectively. It was also found that the application of EDDS alone significantly reduced the ACE index of the soil bacterial community and significantly increased the Simpson index, and the abundance of the Lysobacter genus in the soil was significantly reduced. After the combination of DA-6 and EDDS, the diversity and taxonomic composition of the soil bacterial community were improved.

Regioselective C-H alkenylation of N,N -dialkylanilines with ynamides was developed using AgNTf 2 as a catalyst. This approach represents a facile hydroarylation of ynamides, allowing for the introduction of an alkenyl group exclusively at the para position of aniline derivatives. As a result, a series of 4-alkenyl N,N -dialkylanilines were synthesized with excellent regioselectivities.

Pot and field trials were conducted to investigate Cd uptake and phytoremediation efficiency of two Brassica napus cultivars (QY-1 and SYH) with applied water-soluble chitosan (WSC, Pot: 0, 2% and 4%; Field: 0 and 10 g·m -2 ) grown in Cd-contaminated soils. The results from the pot and field trials generally showed that WSC treatments significantly increased Cd concentrations in shoot and root tissues by 33.77-159.71% (except for SYH/JY) and 7.42-168.71% of two B. napus cultivars compared with the control ( p  < 0.05). The uptake of Cd by shoots of SYH was obviously higher than by shoots of QY-1 treated with WSC under pot and field conditions, which was 1.54-2.22 times than that of QY-1 ( p  < 0.05). The results indicated that 2% WSC treatment significantly increased the water-soluble and acid extractable Cd in rhizosphere soils of both B. napus cultivars. Furthermore, Cd concentrations in the oils of two B. napus cultivars with applied WSC (10 g·m -2 ) grown under field conditions were not significantly different from commercial rapeseed oils. Rapeseed oil of B. napus is not only an edible oil with high nutritional value, but it can also be converted into biomass diesel that can be used as a substitute for petroleum diesel.

A unique prenylated bicarbazole alkaloid, clausanisumine ( 1 ), and two biogenetically related known monomer carbazole alkaloids, mukonal ( 2 ) and 3-methylcarbazole ( 3 ), were isolated from the fruits of Clausena anisum-olens . Clausanisumine ( 1 ) was an uncommon prenylated bicarbazole alkaloid, possessing an unprecedented carbon skeleton, which was composed of a simple carbazole alkaloid and a prenylated carbazole alkaloid. The chemical structure of 1 was established by a combination of comprehensive spectral methods. A plausible biosynthetic pathway of 1 was also proposed. Additionally, the potential anti-HIV activities of all isolates 1 - 3 in vitro were evaluated. Compound 1 exhibited remarkable anti-HIV-1 reverse transcriptase effects showing an EC 50 value of 18.58 nM. The discovery of the prenylated bicarbazole alkaloid from C. anisum-olens with notable anti-HIV activity would be meaningful to discovering and developing new anti-HIV drugs.

Recently, experimentalists have developed a green and efficient method to synthesize pyrazole-fused quinones through light-induced tetrazole-quinone 1,3-dipole cycloadditions. However, the underlying microscopic mechanisms remain to be clarified. In this work, we have employed several electronic structure calculation methods (MS-CASPT2, CASSCF, DFT) to systematically explore the microscopic mechanism of related light-induced reactions and deactivation pathways. Upon excitation with ultraviolet light, one of the original reactants 2-(4-fluorophenyl)-5-phenyl-2 H -tetrazole (FPT) reaches its S 1 excited state. After that, due to the ultrahigh energy and the small energy barrier, the FPT molecule breaks the N2-N3 and N4-C5 bonds sequentially, removing the nitrogen atom finally in the S 1 state. Combined with the cleavage of the second N4-C5 bond, the system reaches its conical intersection region and deactivates ultrafast to the ground state, generating the active intermediate ((4-fluorophenyl)diazen-1-ium-1-ylidene) (phenyl)methanide (FPNI). Subsequently, the active intermediate FPIN can react with naphthoquinone in the ground state by overcoming an energy barrier of about 5.7 kcal mol -1 , after which the 1-(4-fluorophenyl)-3-phenyl-1 H -benzo[f]indazole-4,9(3aH, 9aH)-dione (FP2HQ) is formed. The FP2HQ can be oxidized to obtain the 1-(4-fluorophenyl)-3-phenyl-1 H -benzo[ f ]indazole-4,9-dione (PFQ). Due to the high energy and small barrier, the entire reaction process can easily take place, which ultimately leads to the efficient reaction. Our present work not only explains the experimental mechanism in detail but can also be helpful for the future design of related photoinduced reactions with the aid of theoretical calculations., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)