Association between abnormal lipid metabolism and Alzheimer's disease: New research has revealed significant findings on the APOE4 genotype in microglia.

APOE4 is widely recognized as a genetic risk factor for Alzheimer's disease (AD), implicated in 60-80% of all AD cases. Recent research suggests that microglia carrying the APOE4 genotype display abnormal lipid metabolism and accumulate lipid droplets, which may exacerbate the pathology of AD. Microglia play a critical role in immune surveillance within the central nervous system and are responsible for removing harmful particles and preserving neuronal function. The APOE4 genotype causes abnormal lipid metabolism in microglia, resulting in excessive accumulation of lipid droplets. This accumulation not only impairs the phagocytic and clearance capabilities of microglia but also disrupts their interactions with neurons, resulting in disorganization and neurodegenerative alterations at the neuronal network level. In addition, the presence of APOE4 modifies the metabolic landscape of microglia, particularly affecting purinergic signaling and lipid metabolism, thereby exacerbating the pathological processes of AD. In conclusion, the accumulation of lipid droplets and abnormal lipid metabolism may be critical mechanisms in the progression of AD in microglia carrying the APOE4 genotype.

Comprehensive assessment and treatment strategies for dysphagia in the elderly population: Current status and prospects.

As the population ages, the prevalence of dysphagia among older adults is a growing concern. Age-related declines in physiological function, coupled with neurological disorders and structural changes in the pharynx associated with aging, can result in weakened tongue propulsion, a prolonged reaction time of the submental muscles, delayed closure of the laryngeal vestibule, and delayed opening of the upper esophageal sphincter (UES), increasing the risk of dysphagia. Dysphagia impacts the physical health of the elderly, leading to serious complications such as dehydration, aspiration pneumonia, malnutrition, and even life-threatening conditions, and it also detrimentally affects their psychological and social well-being. There is a significant correlation between frailty, sarcopenia, and dysphagia in the elderly population. Therefore, older adults should be screened for dysphagia to identify both frailty and sarcopenia. A reasonable diagnostic approach for dysphagia involves screening, clinical assessment, and instrumental diagnosis. In terms of treatment, multidisciplinary collaboration, rehabilitation training, and the utilization of new technologies are essential. Future research will continue to concentrate on these areas to enhance the diagnosis and treatment of dysphagia, with the ultimate aim of enhancing the quality of life of the elderly population.

Ecosystem service tradeoff and synergistic relationship in the Yellow River Delta High-Efficiency Eco-Economic Zone.

Exploring the tradeoff and synergy relationship among ecosystem services in the Yellow River Delta High-Efficiency Eco-Economic Zone is of great practical significance for regional ecosystem service function zoning and high-quality development. Using the InVEST model, spatial auto-correlation and trade-off synergism (ESTD) model, we analyzed the spatial and temporal variations of five ecosystem services (habitat quality, carbon storage, soil conservation, water conservation, and water purification), as well as their trade-off and synergistic relationships at the township scale from 2000 to 2020. The results showed that habitat quality, carbon storage, and nitrogen and phosphorus output decreased as a whole from 2000 to 2020, and soil conservation and water purification increased. Habitat quality showed a distribution pattern of high in the north and low in the south, and carbon sto-rage, nitrogen and phosphorus output, soil conservation and water purification showed a pattern of low in the north and high in the south. During the study period, synergistic relationships among the five ecosystem services were predominant in both time cross-section and time period, but there were still differences, with synergistic relationships mainly between carbon storage and other services in time cross-section, and between habitat quality and other ser-vices in time period. Our results can provide theoretical guidance and practical reference for the enhancement of ecosystem services and the zoning of ecosystem functions, as well as basic support for the optimization of spatial patterns of national territory.

Neoadjuvant therapies in resectable hepatocellular carcinoma: Exploring strategies to improve prognosis.

Hepatocellular carcinoma (HCC), a challenging malignancy, often necessitates surgical intervention, notably liver resection. However, the high recurrence rate, reaching 70% within 5 years post-resection, significantly impacts patient outcomes. Neoadjuvant therapies aim to preoperatively address this challenge, reducing lesion size, improving surgical resection rates, deactivating potential micro-metastases, and ultimately lowering postoperative recurrence rates. This review concentrates on advances in research on and clinical use of neoadjuvant therapies for HCC, with particular attention to the use of immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4). Ongoing clinical studies exploring immunotherapy combined with a tyrosine kinase inhibitor (TKI), interventional therapy, radiotherapy, and other modalities offer promising insights into overcoming resistance to monotherapies. In summary, neoadjuvant therapies hold significant promise in terms of improving the prognosis for patients with HCC and enhancing long-term survival, particularly through innovative combination strategies.

Conversion therapy for initially unresectable hepatocellular carcinoma: Current status and prospects.

Research has shown that locoregional and/or systemic treatments can reduce the tumor stage, enabling radical surgical resection in patients with initially unresectable hepatocellular carcinoma. This is referred to as conversion therapy. Patients who undergo conversion therapy followed by curative surgery experience a significant survival benefit compared to those who receive chemotherapy alone, those who are successfully downstaged with conversion therapy but not treated with surgery, or those who are treated with upfront surgery. Several treatments have been studied as conversion therapy. However, the success rate of conversion varies greatly, ranging from 0.8% to 60%. Combined locoregional plus systemic conversion therapy has demonstrated significant clinical advantages, with a conversion rate of up to 60%, an objective remission rate of 96% for patients, and a disease control rate of up to 100%. However, patients who underwent conversion therapy experienced significantly more complications than those who underwent direct LR without conversion therapy. Conversion therapy can cause hepatotoxicity, bone marrow suppression, local adhesions, increased fragility of blood vessels and liver tissues, and hepatic edema, which can increase the difficulty of surgery. In addition, criteria need to be established to evaluate the efficacy of conversion therapy and subsequent treatment. Further clinical evidence in this area is urgently needed.

Real-Time Detection of an Undercarriage Based on Receptive Field Blocks and Coordinate Attention.

Currently, aeroplane images captured by camera sensors are characterized by their small size and intricate backgrounds, posing a challenge for existing deep learning algorithms in effectively detecting small targets. This paper incorporates the RFBNet (a coordinate attention mechanism) and the SIOU loss function into the YOLOv5 algorithm to address this issue. The result is developing the model for aeroplane and undercarriage detection. The primary goal is to synergize camera sensors with deep learning algorithms, improving image capture precision. YOLOv5-RSC enhances three aspects: firstly, it introduces the receptive field block based on the backbone network, increasing the size of the receptive field of the feature map, enhancing the connection between shallow and deep feature maps, and further improving the model's utilization of feature information. Secondly, the coordinate attention mechanism is added to the feature fusion network to assist the model in more accurately locating the targets of interest, considering attention in the channel and spatial dimensions. This enhances the model's attention to key information and improves detection precision. Finally, the SIoU bounding box loss function is adopted to address the issue of IoU's insensitivity to scale and increase the speed of model bounding box convergence. Subsequently, the Basler camera experimental platform was constructed for experimental verification. The results demonstrate that the AP values of the YOLOv5-RSC detection model for aeroplane and undercarriage are 92.4% and 80.5%, respectively. The mAP value is 86.4%, which is 2.0%, 5.4%, and 3.7% higher than the original YOLOv5 algorithm, respectively, with a detection speed reaching 89.2 FPS. These findings indicate that the model exhibits high detection precision and speed, providing a valuable reference for aeroplane undercarriage detection.

Highly Stable Amide-Functionalized Zirconium-Organic Frameworks: Synthesis, Structure, and Methane Storage Capacity.

With the development of crystalline porous materials toward methane storage, the stability issue of metal-organic framework (MOF) materials has caused great concern despite high working capacity. Considering the high stability of zirconium-based MOFs and effective functions of amide groups toward gas adsorption, herein, a series of UiO-66 type of Zr-MOFs, namely, Zr-fcu-H/F/CH3/OH, were successfully designed and synthesized by virtue of amide-functionalized dicarboxylate ligands bearing distinct side groups (i.e., -H, -F, -CH3, and -OH) and ZrCl4 in the presence of trifluoroacetic acid as the modulator. Single-crystal X-ray diffraction and topology analyses reveal that these compounds are archetypal fcu MOFs encompassing octahedral and tetrahedral cages, respectively. The N2 sorption isotherms and acid-base stability tests demonstrate that the materials possess not only relatively high surface areas, pore volumes, and appropriate pore sizes but also great hydrolytic stabilities ranging pH = 3-11. Furthermore, the volumetric methane storage working capacities of Zr-fcu-H, Zr-fcu-F, Zr-fcu-CH3, and Zr-fcu-OH at 298/273 K and 80 bar are 187/217, 175/193, 167/187, and 154/171 cm3 (STP) cm-3, respectively, which indicate that the zirconium-based crystalline porous materials are capable of storing relatively high amounts of methane.

Comprehensive analysis of ceRNA network composed of circRNA, miRNA, and mRNA in septic acute kidney injury patients based on RNA-seq.

Background: Sepsis is a complex, life-threatening clinical syndrome that can cause other related diseases, such as acute kidney injury (AKI). Circular RNA (circRNA) is a type of non-coding RNA with a diverse range of functions, and it plays essential roles in miRNA sponge. CircRNA plays a huge part in the development of various diseases. CircRNA and the competing endogenous RNA (ceRNA) regulatory network are unknown factors in the onset and progression of septic AKI (SAKI). This study aimed to clarify the complex circRNA-associated regulatory mechanism of circRNAs in SAKI. Methods: We collected 40 samples of whole blood of adults, including 20 cases of SAKI and 20 cases of healthy controls. Moreover, five cases were each analyzed by RNA sequencing, and we identified differentially expressed circRNA, miRNA, and mRNA (DEcircRNAs, DEmiRNAs, and DEmRNAs, respectively). All samples were from SAKI patients with intraperitoneal infection. Results: As a result, we screened out 236 DEcircRNAs, 105 DEmiRNAs, and 4065 DEmRNAs. Then, we constructed two co-expression networks based on RNA-RNA interaction, including circRNA-miRNA and miRNA-mRNA co-expression networks. We finally created a circRNA-miRNA-mRNA regulation network by combining the two co-expression networks. Functional and pathway analyses indicated that DEmRNAs in ceRNA were mostly concentrated in T cell activation, neutrophils and their responses, and cytokines. The protein-protein interaction network was established to screen out the key genes participating in the regulatory network of SAKI. The hub genes identified as the top 10 nodes included the following: ZNF727, MDFIC, IFITM2, FOXD4L6, CIITA, KCNE1B, BAGE2, PPIAL4A, USP17L7, and PRSS2. Conclusion: To our knowledge, this research is the first study to describe changes in the expression profiles of circRNAs, miRNAs, and mRNAs in patients with SAKI. These findings provide a new treatment target for SAKI treatment and novel ideas for its pathogenesis.

Influence of intermittent fasting on autophagy in the liver.

Studies have found that intermittent fasting (IF) can prevent diabetes, cancer, heart disease, and neuropathy, while in humans it has helped to alleviate metabolic syndrome, asthma, rheumatoid arthritis, Alzheimer's disease, and many other disorders. IF involves a series of coordinated metabolic and hormonal changes to maintain the organism's metabolic balance and cellular homeostasis. More importantly, IF can activate hepatic autophagy, which is important for maintaining cellular homeostasis and energy balance, quality control, cell and tissue remodeling, and defense against extracellular damage and pathogens. IF affects hepatic autophagy through multiple interacting pathways and molecular mechanisms, including adenosine monophosphate (AMP)-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), silent mating-type information regulatory 2 homolog-1 (SIRT1), peroxisomal proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR), as well as signaling pathways and molecular mechanisms such as glucagon and fibroblast growth factor 21 (FGF21). These pathways can stimulate the pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), play a cytoprotective role, downregulate the expression of aging-related molecules, and prevent the development of steatosis-associated liver tumors. By influencing the metabolism of energy and oxygen radicals as well as cellular stress response systems, IF protects hepatocytes from genetic and environmental factors. By activating hepatic autophagy, IF has a potential role in treating a variety of liver diseases, including non-alcoholic fatty liver disease, drug-induced liver injury, viral hepatitis, hepatic fibrosis, and hepatocellular carcinoma. A better understanding of the effects of IF on liver autophagy may lead to new approaches for the prevention and treatment of liver disease.

Lipid accumulation product is a better predictor of metabolic syndrome in Chinese adolescents: a cross-sectional study.

Aim: Confirm and compare the degree of associations of non-traditional lipid profiles and metabolic syndrome (MetS) in Chinese adolescents, determine the lipid parameter with better predictive potential, and investigate their discriminatory power on MetS. Methods: Medical measurements, including anthropometric measurements and biochemical blood tests, were undergone among a total sample of 1112 adolescents (564 boys and 548 girls) aged from 13 to 18 years. Univariate and multivariate logistic regression analyses were applied for assessing the relationships between the levels of traditional/non-traditional lipid profiles and MetS. We performed Receiver Operating Characteristic (ROC) analyses to mensurate the effectiveness of lipid accumulation product (LAP) on the diagnosis of MetS. Meanwhile, areas under the ROC curve and the cut-off values were calculated for MetS and its components. Results: Univariate analysis showed that all our lipid profiles were closely associated with MetS (P< 0.05). LAP index showed the closest association with MetS than the other lipid profiles. Additionally, ROC analyses indicated that the LAP index showed sufficient capabilities to identify adolescents with MetS and its components. Conclusion: The LAP index is a simple and efficient tool to identify individuals with MetS in Chinese adolescents.

Serum Cystatin C Levels Are Associated With Obesity in Adolescents Aged 14-17 Years.

Background: The association between serum cystatin C levels and obesity has not been fully explored in adolescents. This study aimed to explore the association between serum cystatin C levels and obesity in adolescents of different sexes. Methods: We conducted a cross-sectional study including 481 adolescents aged 14-17 years. Cystatin C level was measured by immunoassay. Health examinations data, biochemical parameters, and questionnaire information were collected. The restricted cubic spline model analyzed the association between cystatin C levels and obesity in boys and girls. Results: Boys exhibited significantly higher cystatin C levels than girls, with a mean level of 0.97 ± 0.10 mg/L in boys and 0.86 ± 0.09 mg/L in girls (P < 0.001). The restricted cubic spline model suggested that low or high cystatin C levels were associated with an increased risk of obesity in boys, whereas only higher cystatin C levels were associated with an increased risk of obesity in girls. Conclusions: A U-shaped correlation was observed between serum cystatin C levels and the risk of obesity in boys. However, in girls, the risk of obesity showed a trend of initially increase and then decrease with increasing cystatin C levels. Longitudinal studies should be conducted to further investigate the diagnostic potential of cystatin C in the progression of early obesity in adolescents of different sexes.

Trapping integrated molecular devices via local transport circulation.

Interactions between quantum systems and their environments may always result in inevitable decoherence. Isolation of the quantum system from the undesired environmental noise is a great challenge for ideal quantum information processing. Herein, based on a parallelly shaped control-target molecular nanomagnet structure, we report a novel strategy which decouples the target molecular device from its surrounding conduction baths. By tuning the level differences between the control and target orbitals through external gate voltages, one manipulates both, neither or only the target subsystem to contribute to the quantum transport in sequence, corresponding to an "on-off-on" behavior in the linear conductance. In the off window, a local transport circulation develops, preventing the target device from being disturbed by the itinerant electrons. This finding provides a prospective method for confining integrated quantum devices with high intrinsic fidelity, remarkable tunability, and universal suitability.

Association between coronary artery calcification and cognitive function in a Chinese community-based population.

BACKGROUND: Coronary atherosclerosis and cognitive impairment are both age-related diseases, with similar risk factors. Coronary artery calcium (CAC), a marker of coronary atherosclerosis, may play a role in early detection of individuals prone to cognitive decline. This study aimed to investigate the relationship between CAC and cognitive function, and the capability of CAC to identify participants with a high risk of dementia in a Chinese community-based population. METHODS: A total of 1332 participants, aged 40-80 years and free of dementia from a community located in Beijing were included. All participants completed neurocognitive questionnaires and noncontrast CT examinations. Cognitive performance tests (including verbal memory, semantic fluency, executive function, and global cognitive function tests), the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CIDE) risk score, and the CAC score (CACS) were evaluated by questionnaires and CT. A CAIDE score ≥ 10 was considered to indicate a high risk of dementia in late-life. Participants were divided into three groups according to CACS (0, 1-399, ≥ 400). RESULTS: After adjusting for risk factors, CACS was significantly associated with verbal memory (r = -0.083, P = 0.003) and global cognitive function (r = -0.070, P = 0.012). The prevalence of a high risk of dementia in the subgroups of CACS = 0, 1-399, and ≥ 400 was 4.67%, 13.66%, and 24.79%, respectively (P < 0.001). Individuals with CACS ≥ 400 had a higher risk of CAIDE score ≥ 10 [OR = 2.30 (1.56, 4.56), P = 0.014] than those with CACS = 0. The receiver-operating characteristic curves showed that the capability of CACS to identify participants with a high risk of dementia was moderate (AUC = 0.70, 95% CI: 0.67-0.72,P < 0.001). CONCLUSIONS: CAC, a marker of subclinical atherosclerosis, was significantly associated with cognitive performance in verbal memory and global cognitive function. CAC had a moderate capability to identify participants with a high risk of dementia, independent of age, education, and other risk factors.

Transcriptome-Wide Identification and Characterization of the JAZ Gene Family in Mentha canadensis L.

Jasmonate ZIM-domain (JAZ) proteins are the crucial transcriptional repressors in the jasmonic acid (JA) signaling process, and they play pervasive roles in plant development, defense, and plant specialized metabolism. Although numerous JAZ gene families have been discovered across several plants, our knowledge about the JAZ gene family remains limited in the economically and medicinally important Chinese herb Mentha canadensis L. Here, seven non-redundant JAZ genes named McJAZ1-McJAZ7 were identified from our reported M. canadensis transcriptome data. Structural, amino acid composition, and phylogenetic analysis showed that seven McJAZ proteins contained the typical zinc-finger inflorescence meristem (ZIM) domain and JA-associated (Jas) domain as conserved as those in other plants, and they were clustered into four groups (A-D) and distributed into five subgroups (A1, A2, B1, B2, and D). Quantitative real-time PCR (qRT-PCR) analysis showed that seven McJAZ genes displayed differential expression patterns in M. canadensis tissues, and preferentially expressed in flowers. Furthermore, the McJAZ genes expression was differentially induced after Methyl jasmonate (MeJA) treatment, and their transcripts were variable and up- or down-regulated under abscisic acid (ABA), drought, and salt treatments. Subcellular localization analysis revealed that McJAZ proteins are localized in the nucleus or cytoplasm. Yeast two-hybrid (Y2H) assays demonstrated that McJAZ1-5 interacted with McCOI1a, a homolog of Arabidopsis JA receptor AtCOI1, in a coronatine-dependent manner, and most of McJAZ proteins could also form homo- or heterodimers. This present study provides valuable basis for functional analysis and exploitation of the potential candidate McJAZ genes for developing efficient strategies for genetic improvement of M. canadensis.

Jasmonate- and abscisic acid-activated AaGSW1-AaTCP15/AaORA transcriptional cascade promotes artemisinin biosynthesis in Artemisia annua.

Artemisinin, a sesquiterpene lactone widely used in malaria treatment, was discovered in the medicinal plant Artemisia annua. The biosynthesis of artemisinin is efficiently regulated by jasmonate (JA) and abscisic acid (ABA) via regulatory factors. However, the mechanisms linking JA and ABA signalling with artemisinin biosynthesis through an associated regulatory network of downstream transcription factors (TFs) remain enigmatic. Here we report AaTCP15, a JA and ABA dual-responsive teosinte branched1/cycloidea/proliferating (TCP) TF, which is essential for JA and ABA-induced artemisinin biosynthesis by directly binding to and activating the promoters of DBR2 and ALDH1, two genes encoding enzymes for artemisinin biosynthesis. Furthermore, AaORA, another positive regulator of artemisinin biosynthesis responds to JA and ABA, interacts with and enhances the transactivation activity of AaTCP15 and simultaneously activates AaTCP15 transcripts. Hence, they form an AaORA-AaTCP15 module to synergistically activate DBR2, a crucial gene for artemisinin biosynthesis. More importantly, AaTCP15 expression is activated by the multiple reported JA and ABA-responsive TFs that promote artemisinin biosynthesis. Among them, AaGSW1 acts at the nexus of JA and ABA signalling to activate the artemisinin biosynthetic pathway and directly binds to and activates the AaTCP15 promoter apart from the AaORA promoter, which further facilitates formation of the AaGSW1-AaTCP15/AaORA regulatory module to integrate JA and ABA-mediated artemisinin biosynthesis. Our results establish a multilayer regulatory network of the AaGSW1-AaTCP15/AaORA module to regulate artemisinin biosynthesis through JA and ABA signalling, and provide an interesting avenue for future research exploring the special transcriptional regulation module of TCP genes associated with specialized metabolites in plants.

Synchronously voltage-manipulable spin reversing and selecting assisted by exchange coupling in a monomeric dimer with magnetic interface.

The use of the molecular spin state as a quantum of next-generation information technology is receiving impressive research attention, within which the fundamental issues include manipulating the phase transition between the spin-up and -down states and generating spin polarized current. The spinterface between ferromagnetic electrodes and a molecular bridge represents one of the most intriguing elements in this context. Herein, by means of the celebrated numerical renormalization group technique, we present an original way to realize spin reversal in a monomeric dimer. Our scheme is based on the exchange interactions between electronic spins on one monomer and those on the other one or on the electrodes, which could be easily controlled through purely electronic technology. Through a careful engineering of the interfacial parameters, one of the monomers is devoted to the spin reversing, whereas the other one contributes to the spin selecting. The charge numbers of spin-up and -down electrons swap their respective occupancies at some particular points, indicating charge sensing between different spins. The competition between the spinterface and the molecular energy level results in charge oscillating in a single spin channel, which is unfavorable to the spin selecting. The observation may provide a prospective example for a multifunctional magnetoelectronics molecular device, which works without any external magnetic field.

Sugar-Acetic Acid-Ethanol-Water Mixture as a Potent Attractant for Trapping the Oriental Fruit Moth (Lepidoptera: Tortricidae) in Peach-Apple Mixed-Planting Orchards.

Sugar-acetic acid-ethanol-water mixture (SAEWM) trapping has initially shown the potential efficacy for monitoring or trapping insects. It is unknown how SAEWM-baited traps affect field number of oriental fruit moth (OFM), Grapholita molesta (Busck) (Lepidoptera: Tortricidae), the female/male ratio trapped, and the type of natural-enemy insects captured. This study investigated changes in seasonal population dynamics and diurnal flight rhythm of OFM, the number and female/male ratio of OFM and the numbers of Coccinellidae and Chrysopidae trapped by SAEWM in peach-apple mixed-planting orchards. The SAEWM performed well in trapping OFM, most of which were adult females, with the maximum trapping at 2.5 m above ground. The daily trapping peak occurred between 18:00 and 20:00, during each continuous monitoring period, with another peak occurring at 4:00-8:00, after the second monitoring period (2-5 July). However, the use of SAEWM also resulted in the trapping of Coccinellidae and Chrysopidae, of which peak trapping time partially overlapped with the second and third peak trapping times of OFM. We suggest the cessation of SAEWM trapping during the peak activity time of Coccinellidae and Chrysopidae, or application of alternative attractive mixture that do not trap the natural enemy insects, in order to protect the ecological balance in the field.

Relationship between bone mineral density and the risk of breast cancer: a systematic review and dose-response meta-analysis of ten cohort studies.

PURPOSE: The evidence from recent epidemiological studies investigating the relationship between bone mineral density (BMD) and the risk of breast cancer (BC) remains inconsistent. MATERIALS AND METHODS: The PubMed, EMBASE, and Web of Science databases were comprehensively searched by two independent authors to identify related cohort studies from the inception of the databases through January 31, 2018. Similarly, two researchers separately extracted the data from the selected studies, and any differences were resolved by discussion. Summarized relative risks (RRs) and 95% CIs were summarized via inverse variance weighted random-effects meta-analysis. Heterogeneity among studies was assessed with the I 2 statistic. RESULTS: Ten studies with 1,522 BC patients among 81,902 participants were included in this meta-analysis. Compared to the participants with the lowest BMD at the lumbar spine, those with the highest BMD had a significantly lower RR for BC (RR =0.75; 95% CI =0.60-0.93; I 2=23.0%). In the subgroup analyses, although the directions of the results were consistent with those of the main findings, not all showed statistical significance. We failed to detect an association between BMD at the femoral neck or total hip and the risk of BC (RR =0.94; 95% CI =0.66-1.33; I 2=72.5%). Furthermore, the results of the dose-response analysis did not show a significant association between BMD at the lumbar spine, femoral neck, or total hip and the risk of BC. Funnel plot and statistical analyses showed no evidence of publication bias. CONCLUSION: There is no relationship between BMD and the risk of BC. More prospective cohort studies are warranted to further investigate this issue.

Jasmonate promotes artemisinin biosynthesis by activating the TCP14-ORA complex in Artemisia annua.

Artemisia annua produces the valuable medicinal component, artemisinin, which is a sesquiterpene lactone widely used in malaria treatment. AaORA, a homolog of CrORCA3, which is involved in activating terpenoid indole alkaloid biosynthesis in Catharanthus roseus, is a jasmonate (JA)-responsive and trichome-specific APETALA2/ETHYLENE-RESPONSE FACTOR that plays a pivotal role in artemisinin biosynthesis. However, the JA signaling mechanism underlying AaORA-mediated artemisinin biosynthesis remains enigmatic. Here, we report that AaORA forms a transcriptional activator complex with AaTCP14 (TEOSINTE BRANCHED 1/CYCLOIDEA/PROLIFERATING CELL FACTOR 14), which is also predominantly expressed in trichomes. AaORA and AaTCP14 synergistically bind to and activate the promoters of two genes, double bond reductase 2 (DBR2) and aldehyde dehydrogenase 1 (ALDH1), both of which encode enzymes vital for artemisinin biosynthesis. AaJAZ8, a repressor of the JA signaling pathway, interacts with both AaTCP14 and AaORA and represses the ability of the AaTCP14-AaORA complex to activate the DBR2 promoter. JA treatment induces AaJAZ8 degradation, allowing the AaTCP14-AaORA complex to subsequently activate the expression of DBR2, which is essential for artemisinin biosynthesis. These data suggest that JA activation of the AaTCP14-AaORA complex regulates artemisinin biosynthesis. Together, our findings reveal a novel artemisinin biosynthetic pathway regulatory network and provide new insight into how specialized metabolism is modulated by the JA signaling pathway in plants.