The MdHSC70-MdWRKY75 module mediates basal apple thermotolerance by regulating the expression of heat shock factor genes.

Heat stress severely restricts the growth and fruit development of apple (Malus domestica). Little is known about the involvement of WRKY proteins in the heat tolerance mechanism in apple. In this study, we found that the apple transcription factor MdWRKY75 responds to heat and positively regulates basal thermotolerance. Apple plants that overexpressed MdWRKY75 were more tolerant to heat stress, while silencing MdWRKY75 caused the opposite phenotype. RNA-seq and reverse transcription quantitative PCR showed that heat shock transcription factor genes (MdHsfs) could be the potential targets of MdWRKY75. Electrophoretic mobility shift, yeast one-hybrid, ß-glucuronidase, and dual-luciferase assays showed that MdWRKY75 can bind to the promoters of MdHsf4, MdHsfB2a, and MdHsfA1d and activate their expression. Apple plants that overexpressed MdHsf4, MdHsfB2a, and MdHsfA1d exhibited heat tolerance and rescued the heat sensitive phenotype of MdWRKY75-Ri3. In addition, apple heat shock cognate 70 (MdHSC70) interacts with MdWRKY75, as shown by yeast two-hybrid, split luciferase, bimolecular fluorescence complementation, and pull-down assays. MdHSC70 acts as a negative regulator of the heat stress response. Apple plants that overexpressed MdHSC70 were sensitive to heat, while virus-induced gene silencing of MdHSC70 enhanced heat tolerance. Additional research showed that MdHSC70 exhibits heat sensitivity by interacting with MdWRKY75 and inhibiting MdHsfs expression. In summary, we proposed a mechanism for the response of apple to heat that is mediated by the 'MdHSC70/MdWRKY75-MdHsfs' molecular module, which enhances our understanding of apple thermotolerance regulated by WRKY transcription factors.

Age-dependent changes in leaf size in apple are governed by a cytokinin-integrated module.

Plants undergo various age-dependent changes in leaf morphology during juvenile to adult vegetative stage. However, the precise molecular mechanisms governing these changes in apple (Malus domestica) remain unknown. Here, we showed that CYTOKININ OXIDASE/DEHYDROGENASE5 (MdCKX5), an age-dependent gene, encodes a functional CKX enzyme and serves as the common downstream target of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor MdSPL14 and WRKY transcription factor MdWRKY24 to control the degradation of cytokinin (CK). As the target of mdm-microRNA156a, MdSPL14 interacts with MdWRKY24 to coordinately repress the transcription of MdCKX5 by forming the age-mediated mdm-miR156a-MdSPL14-MdWRKY24 module, which regulates age-dependent changes in CK during the juvenile-to-adult phase transition. We further demonstrated that MdARR6, a type-A ARABIDOPSIS RESPONSE REGULATOR (ARR), is a negative feedback regulator in the CK signaling pathway. Silencing of MdARR6 in apple resulted in large leaves with smaller epidermal cells and a greater number of epidermal cells. Biochemical analysis showed that the mdm-miR156a-MdSPL14-MdWRKY24 module acts as a transcriptional repressor to directly regulate MdARR6 expression, thus controlling the age-dependent changes in leaf size by reducing CK responses. These findings established a link between the age pathway and CK signaling and revealed the molecular mechanism underlying age-dependent changes during the juvenile-to-adult phase transition; our results also provide targets for the genetic improvement of the vegetative phase transition in apple.

Novel Structure-Driven Predict-to-Hit Strategy for PC Double Bond Positional Isomer Identification Based on Negative LC-MRM Analysis.

As the predominant phospholipids in mammalian cells, phosphatidylcholines (PCs) have been demonstrated to play a crucial role in a multitude of vital biological processes. Research has highlighted the significance of the diversity in PC isomers as instigators of both physiological and pathological responses, particularly those with variations in the position of double bonds within their fatty chains. Profiling these PC isomers is paramount to advancing our understanding of their biological functions. Despite the availability of analytical methods utilizing high-resolution secondary mass spectrometry (MS2) fragmentation, a novel approach was imperative to facilitate large-scale profiling of PC isomers while ensuring accessibility, facility, and reliability. In this study, an innovative strategy centered around structure-driven predict-to-hit profiling of the double bond positional isomers for PCs was meticulously developed, employing negative reversed-phase liquid chromatography-multiple reaction monitoring (RPLC-MRM). This novel methodology heightened the sensitivity. The analysis of rat lung tissue samples resulted in the identification of 130 distinct PC isomers. This approach transcended the confines of available PC isomer standards, thereby broadening the horizons of PC-related biofunction investigations. By optimizing the quantitation reliability, the scale of sample analysis was judiciously managed. This work pioneers a novel paradigm for the exploration of PC isomers, distinct from the conventional methods reliant on high-resolution mass spectrometry (HRMS). It equips researchers with potent tools to further explore the biofunctional aspects of lipids.

Prussian blue nanoparticles coated with tumor cell membranes for precise photothermal therapy and subsequent inflammation reduction.

The utilization of photothermal agents (PTAs) in photothermal therapy (PTT) is faced with challenges such as immune clearance and inadequate concentration, which consequently result in residual tumors and an increased risk of recurrence and metastasis. Conversely, excessive treatment can lead to heightened inflammation and inevitable harm to adjacent healthy tissues. To address these issues, we developed a nanosystem (M@PB) consisting of Prussian blue coated with tumor cell membrane for precise photothermal therapy (PTT) and subsequent reduction of inflammation. This system not only evades immune attack due to the homologous biological characteristics of the encapsulating cell membrane but also exhibits active targeting capabilities towards homologous tumors. Furthermore, it effectively reduces excessive phototoxicity by leveraging the distinctive photothermal and anti-inflammatory characteristics of PB nanoparticles. The resulting M@PB nanosystem demonstrates effective photothermal ablation under 808 nm laser irradiation while mitigating the inflammatory response through inhibiting of local production of inflammatory mediators. Our study provides valuable insights into achieving targeted PTT with high efficiency while minimizing post-treatment inflammatory responses.

Genome-wide analysis of the KNOX gene family in Moso bamboo: insights into their role in promoting the rapid shoot growth.

BACKGROUND: KNOTTED1-like homeobox (KNOX) genes, plant-specific homologous box transcription factors (TFs), play a central role in regulating plant growth, development, organ formation, and response to biotic and abiotic stresses. However, a comprehensive genome-wide identification of the KNOX genes in Moso bamboo (Phyllostachys edulis), the fastest growing plant, has not yet been conducted, and the specific biological functions of this family remain unknown. RESULTS: The expression profiles of 24 KNOX genes, divided into two subfamilies, were determined by integrating Moso bamboo genome and its transcriptional data. The KNOX gene promoters were found to contain several light and stress-related cis-acting elements. Synteny analysis revealed stronger similarity with rice KNOX genes than with Arabidopsis KNOX genes. Additionally, several conserved structural domains and motifs were identified in the KNOX proteins. The expansion of the KNOX gene family was primarily regulated by tandem duplications. Furthermore, the KNOX genes were responsive to naphthaleneacetic acid (NAA) and gibberellin (GA) hormones, exhibiting distinct temporal expression patterns in four different organs of Moso bamboo. Short Time-series Expression Miner (STEM) analysis and quantitative real-time PCR (qRT-PCR) assays demonstrated that PeKNOX genes may play a role in promoting rapid shoot growth. Additionally, Gene Ontology (GO) and Protein-Protein Interaction (PPI) network enrichment analyses revealed several functional annotations for PeKNOXs. By regulating downstream target genes, PeKNOXs are involved in the synthesis of AUX /IAA, ultimately affecting cell division and elongation. CONCLUSIONS: In the present study, we identified and characterized a total of 24 KNOX genes in Moso bamboo and investigated their physiological properties and conserved structural domains. To understand their functional roles, we conducted an analysis of gene expression profiles using STEM and RNA-seq data. This analysis successfully revealed regulatory networks of the KNOX genes, involving both upstream and downstream genes. Furthermore, the KNOX genes are involved in the AUX/IAA metabolic pathway, which accelerates shoot growth by influencing downstream target genes. These results provide a theoretical foundation for studying the molecular mechanisms underlying the rapid growth and establish the groundwork for future research into the functions and transcriptional regulatory networks of the KNOX gene family.

Technological Vanguard: the outstanding performance of the LTY-CNN model for the early prediction of epileptic seizures.

BACKGROUND: Epilepsy is a common neurological disorder that affects approximately 60 million people worldwide. Characterized by unpredictable neural electrical activity abnormalities, it results in seizures with varying intensity levels. Electroencephalography (EEG), as a crucial technology for monitoring and predicting epileptic seizures, plays an essential role in improving the quality of life for people with epilepsy. METHOD: This study introduces an innovative deep learning model, a lightweight triscale yielding convolutional neural network" (LTY-CNN), that is specifically designed for EEG signal analysis. The model integrates a parallel convolutional structure with a multihead attention mechanism to capture complex EEG signal features across multiple scales and enhance the efficiency achieved when processing time series data. The lightweight design of the LTY-CNN enables it to maintain high performance in environments with limited computational resources while preserving the interpretability and maintainability of the model. RESULTS: In tests conducted on the SWEC-ETHZ and CHB-MIT datasets, the LTY-CNN demonstrated outstanding performance. On the SWEC-ETHZ dataset, the LTY-CNN achieved an accuracy of 99.9%, an area under the receiver operating characteristic curve (AUROC) of 0.99, a sensitivity of 99.9%, and a specificity of 98.8%. Furthermore, on the CHB-MIT dataset, it recorded an accuracy of 99%, an AUROC of 0.932, a sensitivity of 99.1%, and a specificity of 93.2%. These results signify the remarkable ability of the LTY-CNN to distinguish between epileptic seizures and nonseizure events. Compared to other existing epilepsy detection classifiers, the LTY-CNN attained higher accuracy and sensitivity. CONCLUSION: The high accuracy and sensitivity of the LTY-CNN model demonstrate its significant potential for epilepsy management, particularly in terms of predicting and mitigating epileptic seizures. Its value in personalized treatments and widespread clinical applications reflects the broad prospects of deep learning in the health care sector. This also highlights the crucial role of technological innovation in enhancing the quality of life experienced by patients.

Inhibition of OGFOD1 by FG4592 confers neuroprotection by activating unfolded protein response and autophagy after ischemic stroke.

BACKGROUND: Acute ischemic stroke is a common neurological disease with a significant financial burden but lacks effective drugs. Hypoxia-inducible factor (HIF) and prolyl hydroxylases (PHDs) participate in the pathophysiological process of ischemia. However, whether FG4592, the first clinically approved PHDs inhibitor, can alleviate ischemic brain injury remains unclear. METHODS: The infarct volumes and behaviour tests were first analyzed in mice after ischemic stroke with systemic administration of FG4592. The knockdown of HIF-1α and pretreatments of HIF-1/2α inhibitors were then used to verify whether the neuroprotection of FG4592 is HIF-dependent. The targets predicting and molecular docking methods were applied to find other targets of FG4592. Molecular, cell biological and gene knockdown methods were finally conducted to explore the potential neuroprotective mechanisms of FG4592. RESULTS: We found that the systemic administration of FG4592 decreased infarct volume and improved neurological defects of mice after transient or permanent ischemia. Meanwhile, FG4592 also activated autophagy and inhibited apoptosis in peri-infarct tissue of mice brains. However, in vitro and in vivo results suggested that the neuroprotection of FG4592 was not classical HIF-dependent. 2-oxoglutarate and iron-dependent oxygenase domain-containing protein 1 (OGFOD1) was found to be a novel target of FG4592 and regulated the Pro-62 hydroxylation in the small ribosomal protein s23 (Rps23) with the help of target predicting and molecular docking methods. Subsequently, the knockdown of OGFOD1 protected the cell against ischemia/reperfusion injury and activated unfolded protein response (UPR) and autophagy. Moreover, FG4592 was also found to activate UPR and autophagic flux in HIF-1α independent manner. Blocking UPR attenuated the neuroprotection, pro-autophagy effect and anti-apoptosis ability of FG4592. CONCLUSION: This study demonstrated that FG4592 could be a candidate drug for treating ischemic stroke. The neuroprotection of FG4592 might be mediated by inhibiting alternative target OGFOD1, which activated the UPR and autophagy and inhibited apoptosis after ischemic injury. The inhibition of OGFOD1 is a novel therapy for ischemic stroke.

MdASMT9-mediated melatonin biosynthesis enhances basal thermotolerance in apple plants.

High temperatures negatively impact the yield and quality of fruit crops. Exogenous melatonin (MT) application has been shown to enhance heat tolerance, but the response of endogenous MT to heat stress, particularly in perennial fruit trees, remains unclear. The present study investigated the effects of high temperatures on transgenic apple plants overexpressing the MT biosynthesis gene N-acetylserotonin methyltransferase 9 (MdASMT9). Endogenous MT protected transgenic plants from heat stress by increasing antioxidant enzyme activity and scavenging reactive oxygen species (ROS), and protecting the chloroplasts from damage. Application of MT and overexpression of MdASMT9 also reduced abscisic acid accumulation through promoting MdWRKY33-mediated transcriptional inhibition of MdNCED1 and MdNCED3, thus inducing stomatal opening for better heat dissipation. Furthermore, MT-enhanced autophagic activity through promoting MdWRKY33-mediated transcriptional enhancement of MdATG18a under heat stress. These findings provide new insights into the regulation of endogenous MT and its role in improving basal thermotolerance in perennial fruit trees.

Selecting non-metal doped FeS2 as efficient sulfur cathode host for enhanced Li-S redox chemistry.

Lithium-sulfur batteries (LSBs) are considered as the development direction of the new generation energy storage system due to their high energy density and low cost. The slow redox kinetics of sulfur and the shuttle effect of lithium polysulfide (LiPS) are considered to be the main obstacles to the practical application of LSBs. Transition-metal sulfide as the cathode host can improve the Li-S redox chemistry. However, there has been no investigation of the application of FeS2 host in Li-S redox chemistry. Applying the first-principles calculations, we investigated the formation energy, band gap, Li+ diffusion, adsorption energy, catalytic performance and Li2 S decomposition barrier of FeAx S2-x (A=N, P, O, Se; x=0, 0.125, 0.25, 0.375) to explore the Li-S redox chemistry and finally select excellent host material. FeA0.25 S1.75 (A=P, Se) has a low Li+ diffusion barrier and superior electronic conductivity. FeO0.25 S1.75 is more favorable for LiPS adsorption, followed by FeP0.25 S1.75 . FeP0.25 S1.75 (001) shows a low overpotential for the Li-S redox chemistry. In summary, FeP0.25 S1.75 has more application potential in LSBs due to its physical and chemical properties, followed by FeSe0.25 S1.75 . This work provides theoretical guidance for the design and selection of the sulfur cathode host materials in LSBs.

Development of generic metabolic Raman calibration models using solution titration in aqueous phase and data augmentation for in-line cell culture analysis.

This study presents a novel approach for developing generic metabolic Raman calibration models for in-line cell culture analysis using glucose and lactate stock solution titration in an aqueous phase and data augmentation techniques. First, a successful set-up of the titration method was achieved by adding glucose or lactate solution at several different constant rates into the aqueous phase of a bench-top bioreactor. Subsequently, the in-line glucose and lactate concentration were calculated and interpolated based on the rate of glucose and lactate addition, enabling data augmentation and enhancing the robustness of the metabolic calibration model. Nine different combinations of spectra pretreatment, wavenumber range selection, and number of latent variables were evaluated and optimized using aqueous titration data as training set and a historical cell culture data set as validation and prediction set. Finally, Raman spectroscopy data collected from 11 historical cell culture batches (spanning four culture modes and scales ranging from 3 to 200 L) were utilized to predict the corresponding glucose and lactate values. The results demonstrated a high prediction accuracy, with an average root mean square errors of prediction of 0.65 g/L for glucose, and 0.48 g/L for lactate. This innovative method establishes a generic metabolic calibration model, and its applicability can be extended to other metabolites, reducing the cost of deploying real-time cell culture monitoring using Raman spectroscopy in bioprocesses.

Disturbed nutrient accumulation and cell wall metabolism in panicles are responsible for rice straighthead disease.

Rice straighthead disease substantially reduces crop yield, posing a significant threat to global food security. Dimethylarsinic acid (DMA) is the causal agent of straighthead disease and is highly toxic to the reproductive tissue of rice. However, the precise physiological mechanism underlying DMA toxicity remains unknown. In this study, six rice varieties with varying susceptibility to straighthead were utilized to investigate the growth performance and element distribution in rice panicles under DMA stress through pot experiments, as well as to explore the physiological response to DMA using transcriptomic methods. The findings demonstrate significant variations in both DMA accumulation and straighthead sensitivity among cultivars. The susceptible varieties exhibited higher DMA accumulation indices and displayed typical symptoms of straighthead disease, including erect panicles, deformed rachides and husks, and reduced seed setting rate and grain yield when compared to the resistant varieties. Moreover, DMA addition promoted mineral nutrients to accumulate in rachides and husks but less in grains. DMA showed preferential accumulation in rice grains with a distribution pattern similar to that of Copper (Cu) and zinc (Zn) within the panicle. Transcriptome analyses underscored the substantial impact of DMA on gene expression related to mineral metabolism. Notably, DMA addition significantly up-regulated the expression of pectin methylesterase, pectin lyase, polygalacturonase, and exogalacturonase genes in Nanjingxiangzhan, while these genes were down-regulated or weakly expressed in Ruanhuayou 1179. The alteration of pectin metabolic pathways induced by DMA may lead to abnormality of cell wall assembly and modification, thereby resulting in deformed rice panicles.

Diabatic Potential Energy Surfaces of SrH2+ and Dynamics Studies of the Sr+(5s2S) + H2 Reaction.

Based on the ab initio energy points of both ground and excited states, a neural network fitting method combined with a specific function was successfully used to construct the diabatic potential energy surfaces (PESs) of the SrH2+ system. The topographical features of the diabatic PESs were examined in detail. The results indicate that the nonadiabatic transition characteristics between ground and excited states are accurately described by the newly constructed diabatic PESs. To verify the validity and applicability of the diabatic PESs, as well as the nonadiabatic effects during the reaction process, the quantum dynamics studies of the Sr+(5s2S) + H2 reaction were performed based on both adiabatic and diabatic PESs. The dynamics results indicate that adiabatic dynamics results are dozens of times larger than those of nonadiabatic. This illustrates the significant effect of nonadiabaticity, indicating that adiabatic dynamics results often overestimate the actual values. The integral cross sections (ICSs) were calculated and compared with the experimental data. The diabatic ICSs are in good agreement with the experimental results. The reasonable dynamics results indicate that the newly constructed diabatic PESs are suitable for the relevant dynamics studies.

Identification of Aggregation Pheromone as an Attractant for Odontothrips loti, A Serious Thrips Pest on Alfalfa.

Odontothrips loti (Haliday) (Thysanoptera: Thripidae) is one of the most serious pests on alfalfa, causing direct damage by feeding and indirect damage by transmitting plant viruses. This damage causes significant loss in alfalfa production. Semiochemicals offer opportunities to develop new approaches to thrips management. In this study, behavioral responses of female and male adults of O. loti to headspace volatiles from live female and male conspecifics were tested in a Y-tube olfactometer. The results showed that both male and female adults of O. loti were attracted to the odors released by conspecific males but not those released by females. Headspace volatiles released by female and male adults were collected using headspace solid-phase microextraction (HS-SPME). The active compound in the volatiles was identified by gas chromatography-mass spectrometry (GC-MS). The analysis showed that there was one major compound, (R)-lavandulyl (R)-2-methylbutanoate. The attractive activity of the synthetic aggregation pheromone compound was tested under laboratory and field conditions. In an olfactometer, both male and female adults showed significant preference for synthetic (R)-lavandulyl (R)-2-methylbutanoate at certain doses. Lures with synthetic (R)-lavandulyl (R)-2-methylbutanoate significantly increased the trap catches of sticky white traps at doses of 40-80 µg in the field. This study confirmed the production of aggregation pheromone by O. loti male adults and identified its active compound as (R)-lavandulyl (R)-2-methylbutanoate, providing a basis for population monitoring and mass trapping of this pest.

Biologically active isoquinoline alkaloids covering 2019-2022.

Isoquinoline alkaloids are an important class of natural products that are abundant in the plant kingdom and exhibit a wide range of structural diversity and biological activities. With the deepening of research in recent years, more and more isoquinoline alkaloids have been isolated and identified and proved to contain a variety of biological activities and pharmacological effects. In this review, we introduce the research progress of isoquinoline alkaloids from 2019 to 2022, mainly in the part of biological activities, including antitumor, antimicrobial, antidiabetic, antiviral, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, analgesic, and other activities. This study provides a clear direction for the rational development and utilization of isoquinoline alkaloids, suggesting that these alkaloids have great potential in the field of drug research.

SARS-CoV-2 Infection Increases High Risk Rate of Down Syndrome Screening Test by Reducing Alpha-Fetoprotein.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a significant global health issue in recent years. Numerous studies indicate that COVID-19 during pregnancy is associated with an increased likelihood of pregnancy complications. Additionally, pregnancy itself is known to elevate the risk of severe SARS-CoV-2 infection. To explore the potential impact of SARS-CoV-2 infection on the probability of Down syndrome in fetuses, we conducted serological testing of Down syndrome markers in pregnant women who had contracted the virus. METHODS: Serological experiments were conducted utilizing a particle chemiluminescence test. The cohort of pregnant women was categorized into three groups: a control group with no infection, a group infected with SARS-CoV-2 Omicron within the first six weeks of gestation, and a group infected beyond the sixth week of gestation. RESULTS: In the group of individuals infected within 6 gestational weeks, the infection resulted in a decrease in alpha-fetoprotein (AFP) levels and a higher positive rate of Down syndrome screening tests (p ˂ 0.05). However, in this study, SARS-CoV-2 infection did not lead to an increase in the occurrence of Down syndrome in the fetus. The positive rate of women infected beyond 6 gestational weeks was slightly higher than the non-infected group (6.2% vs. 5.7%), but these differences were not statistically significant (p > 0.05). Within the group infected beyond 6 gestational weeks, there was, compared to the control group, a decrease in free beta human chorionic gonadotropin (ß-hCG) levels (p < 0.05). CONCLUSIONS: This study presents a novel investigation into the impact of SARS-CoV-2 infection on AFP and ß-hCG levels. It has been observed that pregnant women who contract SARS-CoV-2 may exhibit an increased likelihood of positive results in serum tests conducted for Down syndrome screening. However, it is important to note that the occurrence of Down syndrome in the developing fetus does not appear to be elevated. To validate these findings, additional research involving larger and diverse cohorts is necessary.

Inhibition of microelement accumulation and disorder of saccharide and amino acid metabolism explain rice grain empty under dimethylarsinic acid stress.

KEY MESSAGE: Metabolomic and transcriptomic analyses revealed an intensification of energy metabolism in rice grains under DMA stress, possibly causing the consumption of sugars or non-sugars and the development of unfilled grains Excessive dimethylarsinic acid (DMA) causes rice straighthead disease, a physiological disorder typically with erect panicle due to empty grain at maturity. Although the toxicity of DMA and its uptake and transport in rice are well recognized, the underlying mechanism of unfilled grains remains unclear. Therefore, a pot experiment was conducted using a susceptible variety (Ruanhuayou1179, RHY) and a resistant one (Nanjingxiangzhan, NJXZ) via the metabolomic and transcriptomic approaches to explore the mechanisms of empty grains in diseased rice under DMA stress. The results demonstrate an increase in total and methylated As in grains of RHY and NJXZ under DMA addition, with RHY containing higher levels of DMA. DMA addition increased the soluble sugar content in grains of RHY and NJXZ by 17.1% and 14.3% compared to the control, respectively, but significantly reduced the levels of amino acid, soluble protein, and starch. The decrease of grain Zn and B contents was also observed, and inadequate Zn might be a key factor limiting rice grain yield under DMA stress. Notably, DMA addition altered the expression levels of genes involved in the transport of sugar, amino acids, nitrates/peptides, and mineral ions. In sugar and amino acid metabolism, the reduction of metabolites and the upregulated expression of genes reflect positive regulation at the level of energy metabolism, implying that the reduction of grain starch and proteins might be ascribed to generate sufficient energy to resist the stress. This study provides a useful reference for understanding the molecular mechanism of grain emptying under DMA stress.

The Chemistry and Biology of Lycopodium Alkaloids.

Lycopodiales, an order comprising 388 distinct species, is the source of Lycopodium alkaloids (LAs), a group of naturally occurring alkaloids that share a common biosynthesis and structural attributes. These remarkable organisms are considered vestiges of ancient ferns, with fossil evidence dating their existence back to an impressive 300 million years. LAs usually are tricyclic or tetracyclic compounds with C16N or C16N2 skeleton. But then there are also have a few C11N, C15N, C15N2, C22N2, and C27N3 skeleton. LAs have attracted much scientific attention because of their important biological activities related to acetylcholinesterase and unique structural characteristics. From 1881 to December 2023, there are 593 LAs from 49 species of Lycopodiales have been reported. Because the total amount of LAs is nearly five times that of 1994, the classification and group allocation of some newly isolated LAs is often challenging and not unambiguous by Ayer's simple classification. This review makes a more systematic and detailed classification for it and provides extensive coverage of naturally occurring LAs discovered from 1881 to December 2023. Until now, there is no comprehensively summary of biological activity of the LAs. This review is the first time covered the biological activity of the all LAs.

Flavonoids From the Aerial Parts of Sophora tonkinensis and Their Potential Anti-Inflammatory Activities.

Four undescribed prenylated flavonoids, sophoratones A-D (1-4), and 17 known flavonoids, were obtained from the aerial parts of Sophora tonkinensis. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and ECD calculations. Meanwhile, the ability of these compounds to inhibit the release of nitric oxide (NO) by a lipopolysaccharide induced mouse in RAW 264.7 cells was assayed. The results indicated that some compounds exhibited clear inhibitory effects, with IC50 ranging from 19.91±1.08 to 35.72±2.92 µM. These results suggest that prenylated flavonoids from the aerial parts of S. tonkinensis could potentially be used as a latent source of anti-inflammatory agents.

Surgical treatment for recurrent patellar dislocation with severe torsional deformities: Double-level derotational osteotomy may not have a clear advantage over single-level derotational osteotomy in improving clinical and radiological outcomes.

PURPOSE: The purpose of this study was to investigate whether double-level (femur + tibia) derotational osteotomy is superior to single-level femoral derotational osteotomy for recurrent patellar dislocation with severe femoral and tibial rotational deformities (femoral anteversion >30° and external tibial torsion >30°). METHODS: Between January 2015 and June 2020, a total of 115 knees with recurrent patellar dislocation treated with combined medial patellofemoral ligament reconstruction (MPFL-R) and derotational osteotomies were evaluated after a minimum follow-up of 2 years. Among these cases, 15 knees that underwent double-level derotational osteotomy were included in the double-level group, which was propensity-matched in a 1:2 ratio to a single-level group of patients who underwent single-level femoral derotational osteotomy (30 knees). The clinical and radiological outcomes were evaluated and compared between the groups. Furthermore, the foot progression angle was measured preoperatively and 2 years after surgery. RESULTS: The patient-specific variables did not differ significantly between the double- and the single-level groups after propensity score matching. The postoperative mean foot progression angle was significantly lower in the double-level group than in the single-level group (9° ± 8° vs. 15° ± 11°; p = 0.014); however, there were no statistically significant differences between the groups in terms of any other clinical and radiological assessments. CONCLUSION: For patients with severe femoral and tibial torsional deformities (femoral anteversion >30° and external tibial torsion >30°), the double-level derotational osteotomy is superior to single-level osteotomy in maintaining normal foot progression angle, but it does not show an advantage in terms of patient-reported outcomes, radiological results and redislocation rate at minimum 2 years of follow-up. Furthermore, concomitant excessive external tibial torsion (>30°) did not have an adverse effect on clinical outcomes in patients who underwent derotational distal femoral osteotomy with MPFL-R due to excessive femoral anteversion. LEVEL OF EVIDENCE: Level III.

Habitual patellar dislocation exhibits less severe rotational deformities but poorer trochlear development and higher incidence of patella baja compared with recurrent patellar dislocation in skeletally mature patients.

PURPOSE: This study compared the radiological characteristics between habitual and recurrent patellar dislocation in skeletally mature patients. METHODS: From 2017 to 2019, 77 skeletally mature patients with habitual patellar dislocation were surgically treated at a single institution and reviewed retrospectively. A total of 55 knees from these patients were included in the habitual patellar dislocation group. During the same period, 55 knees with recurrent patellar dislocation were randomly selected from 242 patients and included in the recurrent patellar dislocation group. Various bony deformities were measured and compared between the two groups. Additionally, a subgroup analysis was conducted among patients with habitual patellar dislocation, comparing those with and without an 'invisible patella' observed on true lateral views with 30° of knee flexion. RESULTS: The femoral anteversion angle (21.8° vs. 26.3°, p = 0.041), tibiofemoral rotation angle (9.7° vs. 12.4°, p = 0.042) and external tibial rotation angle (24.3° vs. 29.6°, p = 0.001) in the habitual patellar dislocation group were significantly lower than those in the recurrent patellar dislocation group. 54% of knees in the habitual patellar dislocation group had a patella baja, and this was in sharp contrast to the recurrent patellar dislocation group in which none of the knees had a patella baja. 49.1% of knees in the habitual patellar dislocation group showed 'invisible patella' at 30° of knee flexion, and knees with 'invisible patella' had significantly higher tibial tubercle-trochlear groove (TT-TG) distance (30.4 vs. 19.8, p < 0.001) and tibiofemoral rotation angle (13.2° vs. 6.4°, p < 0.001) than knees with a visible patella. CONCLUSIONS: A distinct difference in bony anatomical features was observed between habitual and recurrent patellar dislocation in skeletally mature patients. Habitual patellar dislocation exhibited less severe rotational deformities of the lower extremity but showed poorer trochlear and patellar development, a larger TT-TG distance and a higher incidence of patella baja compared with recurrent patellar dislocation. LEVEL OF EVIDENCE: Level III.