Comparative genomics of the primary endosymbiont Buchnera aphidicola in aphid hosts and their coevolutionary relationships.

BACKGROUND: Coevolution between modern aphids and their primary obligate, bacterial endosymbiont, Buchnera aphidicola, has been previously reported at different classification levels based on molecular phylogenetic analyses. However, the Buchnera genome remains poorly understood within the Rhus gall aphids. RESULTS: We assembled the complete genome of the endosymbiont Buchnera in 16 aphid samples, representing 13 species in all six genera of Rhus gall aphids by shotgun genome skimming method. We compared the newly assembled genomes with those from GenBank to comprehensively investigate patterns of coevolution between the bacteria Buchnera and their aphid hosts. Buchnera genomes were mostly collinear, and the pan-genome contained 684 genes, in which the core genome contained 256 genes with some lineages having large numbers of tandem gene duplications. There has been substantial gene-loss in each Buchnera lineage. We also reconstructed the phylogeny for Buchnera and their host aphids, respectively, using 72 complete genomes of Buchnera, along with the complete mitochondrial genomes and three nuclear genes of 31 corresponding host aphid accessions. The cophylogenetic test demonstrated significant coevolution between these two partner groups at individual, species, generic, and tribal levels. CONCLUSIONS: Buchnera exhibits very high levels of genomic sequence divergence but relative stability in gene order. The relationship between the symbionts Buchnera and its aphid hosts shows a significant coevolutionary pattern and supports complexity of the obligate symbiotic relationship.

Enhancing radiosensitivity in osteosarcoma via CDKN2C overexpression: A mechanism involving G1 phase arrest mediated by inhibition of CDK4 expression and Thr172 phosphorylation.

BACKGROUND: The limited radiosensitivity of osteosarcoma poses a challenge in applying radiotherapy, necessitating the search for effective radiosensitizing targets. METHODS: The lentiviral vectors were employed to establish CDKN2C-overexpressing (CDKN2C-OE) and CDKN2C-negative control (CDKN2C-NC) HOS and U2OS osteosarcoma cells. Cells were treated with or without irradiation (IR) to assess radiosensitization via viability, proliferation, apoptosis, and cell cycle analysis. A mouse model with subcutaneous tumors from CDKN2C-OE and CDKN2C-NC HOS cells evaluated tumor growth post-IR. Immunohistochemical staining and Western blot analysis were conducted to confirm model establishment and explore mechanisms. RESULTS: CDKN2C-OE combined with IR inhibited cell viability and proliferation, promoting apoptosis in vitro and inhibiting tumor growth in vivo. CDKN2C-OE inhibited G1 phase progression post-IR by suppressing Cyclin-dependent kinase 4 (CDK4) expression and Thr172 phosphorylation, reducing retinoblastoma protein (RB) phosphorylation at Ser807/811. CDKN2C-OE did not primarily impact the cell cycle by regulating the expression of CDK6 and Cyclin D1. Furthermore, when CDKN2C-OE was combined with IR, the expression of BAX, Caspase-3, and its active cleavage product, cleaved Caspase-3, was upregulated. CONCLUSIONS: Our research results indicate that overexpression of CDKN2C enhances radiosensitivity in osteosarcoma through the induction of G1 phase arrest and subsequent apoptosis. G1 phase arrest is mediated by the suppression of CDK4 expression and Thr172 phosphorylation, which consequently affects the expression of phosphorylated RB at the Ser807/811 sites.

Enhancement of Cu2ZnSn(S, Se)4 device performance using an IPA/MOE hybrid solvent system in ambient air.

In this work, a mixed precursor solvent system comprising isopropyl alcohol (IPA) and 2-methoxy ethanol (MOE) is introduced for the fabrication of Cu2ZnSn(S, Se)4 (CZTSSe) thin films under ambient conditions. The effects of different IPA/(MOE + IPA) ratios on the characteristics of CZTSSe films and the corresponding devices were investigated. Our research results indicate that the addition of IPA enhances the wettability of Cu-Zn-Sn-S precursor solution on the substrate, reduces Sn loss in the film during high-temperature annealing, and diminishes band tail states. Additionally, adding IPA leads to effective enlargement of grain size, improved crystallinity, and enhanced light absorption. However, excessive content of IPA negatively impacts CZTSSe film properties and the device's performance. Notably, when substituting 20% of MOE with IPA, the short-circuit current density (JSC) increased from 30.84 mA cm-2 to 35.55 mA cm-2 in the resulting CZTSSe device, and the efficiency improved from 9.19% to 10.63%. This work provides a new method of a solvent system for preparing efficient kesterite-based solar cells.

Biocontrol Mechanisms of Three Plant Essential Oils Against Phytophthora infestans Causing Potato Late Blight.

Late blight, caused by the notorious pathogen Phytophthora infestans, poses a significant threat to potato (Solanum tuberosum) crops worldwide, impacting their quality as well as yield. Here, we aimed to investigate the potential use of cinnamaldehyde, carvacrol, and eugenol as control agents against P. infestans and to elucidate their underlying mechanisms of action. To determine the pathogen-inhibiting concentrations of these three plant essential oils (PEOs), a comprehensive evaluation of their effects using gradient dilution, mycelial growth rate, and spore germination methods was carried out. Cinnamaldehyde, carvacrol, and eugenol were capable of significantly inhibiting P. infestans by hindering its mycelial radial growth, zoospore release, and sporangium germination; the median effective inhibitory concentration of the three PEOs was 23.87, 8.66, and 89.65 µl/liter, respectively. Scanning electron microscopy revealed that PEOs caused the irreversible deformation of P. infestans, resulting in hyphal shrinkage, distortion, and breakage. Moreover, propidium iodide staining and extracellular conductivity measurements demonstrated that all three PEOs significantly impaired the integrity and permeability of the pathogen's cell membrane in a time- and dose-dependent manner. In vivo experiments confirmed the dose-dependent efficacy of PEOs in reducing the lesion diameter of potato late blight. Altogether, these findings provide valuable insight into the antifungal mechanisms of PEOs vis-à-vis late blight-causing P. infestans. By utilizing the inherent capabilities of these natural compounds, we could effectively limit the harmful impacts of late blight on potato crops, thereby enhancing agricultural practices and ensuring the resilience of global potato food production.

A qualitative study on patients' and health care professionals' perspectives regarding care delivered during CIED operation.

BACKGROUND: Cardiac implantable electronic devices (CIEDs) has proven to be an invaluable tool in the practice of cardiology. Patients who have undergone CIED surgery with local anesthesia may result in fear, insecurity and suffering. Some studies have put efforts on ways to improve intraoperative experience of patients with local anesthesia, but researches concerning experiences of CIED patients during surgery is in its infancy. METHODS: Based on semi-structured and in-depth interviews, a qualitative design was conducted in a tertiary general hospital in China from May 2022 to July 2023.Purposeful sampling of 17 patients received CIED surgery and 20 medical staff were interviewed. Thematic analysis with an inductive approach was used to identify dominant themes. RESULTS: Four themes emerged from the data: (1) Safety and success is priority; (2) Humanistic Caring is a must yet be lacking; (3) Paradox of surgery information given; (4) Ways to improve surgery experiences in the operation. CONCLUSIONS: Intraoperative care is significant for CIED surgery. To improve care experience during surgery, healthcare professionals should pay attention to patients' safety and the factors that affecting humanistic caring in clinical practice. In addition, information support should consider information-seeking styles and personal needs. Besides, the four approaches presented in this study are effective to improve the intraoperative care experience.

Characterizing the Pathogenicity and Mycotoxin Production Capacity of Fusarium spp. Causing Root Rot of Angelica sinensis in China.

Root rot is a very destructive soil-borne disease, which severely affects the quality and yield of Angelica sinensis in major planting areas of Gansu Province, China. Twelve Fusarium strains were identified from root rot tissue and infected soil in the field by comparing each isolate strain internal transcribed spacer, translation elongation factor 1-α sequence and RNA polymerase second largest subunit gene with the sequences of known fungal species in the NCBI database. Of these isolates, four were F. acuminatum, followed by three F. solani, two F. oxysporum, and one each of F. equiseti, F. redolens, and F. avenaceum. Under greenhouse conditions, pathogenicity testing experiment was carried out using five strains: two F. acuminatum, one F. solani, one F. oxysporum, and one F. equiseti. Among them, the incidence of F. acuminatum-induced root rot on A. sinensis was 100%; hence, it was the most aggressive. Liquid chromatography was used to show that F. acuminatum could produce neosolaniol (NEO), deoxynivalenol, and T-2 toxins. Of these, the level of NEO produced by F. acuminatum was high compared with the other two toxins. By isolating Fusarium spp. and characterizing their toxin-producing capacity, this work provides new information for effectively preventing and controlling A. sinensis root rot in the field as well as improving the quality of its medicinal materials.

Biotransformation characteristics of tetracycline by strain Serratia marcescens MSM2304 and its mechanism evaluation based on products analysis and genomics.

Microbial biotransformation is a recommended and reliable method in face of formidable tetracycline (TC) with broad-spectrum antibacterial activity. Herein, comprehensive characteristics of a newfound strain and its molecular mechanism in process of TC bioremediation were involved in this study. Specifically, Serratia marcescens MSM2304 isolated from pig manure sludge grew well in presence of TC and achieved optimal removal efficiency of 61% under conditions of initial TC concentration of 10 mg/L, pH of 7.0, cell inoculation amount of 5%, and tryptone of 10 g/L as additional carbon. The pathways of biotransformation include EPS biosorption, cell surface biosorption and biodegradation, which enzymatic processes of biodegradation were occurred through TC adsorbed by biofilms was firstly broken down by extracellular enzymes and part of TC migrated towards biofilm interior and degraded by intracellular enzymes. Wherein extracellular polysaccharides in extracellular polymeric substances (EPS) from biofilm of strain MSM2304 mainly performed extracellular adsorption, and changes in position and intensity of CO, =CH and C-O-C/C-O of EPS possible further implied TC adsorption by it. Biodegradation accounting for 79.07% played a key role in TC biotransformation and could be fitted well by first-order model that manifesting rapid and thorough removal. Potential biodegradation pathway including demethylation, dihydroxylation, oxygenation, and ring opening possibly involved in TC disposal process of MSM2304, TC-degrading metabolites exhibited lower toxicity to indicator bacteria relative to parent TC. Whole genome sequencing as underlying molecular evidence revealed that TC resistance genes, dehydrogenases-encoding genes, monooxygenase-encoding genes, and methyltransferase-encoding genes of strain MSM2304 were positively related to TC biodegradation. Collectively, these results favored a theoretical evaluation for Serratia marcescens MSM2304 as a promising TC-control agent in environmental bioremediation processes.

Platinum-Metformin Conjugates Acting as Promising PD-L1 Inhibitors through the AMP-Activated Protein Kinase Mediated Lysosomal Degradation Pathway.

With the development of metalloimmunology, the potential of platinum drugs in cancer immunotherapy has attracted extensive attention. Although immunochemotherapy combining PD-1/PD-L1 antibodies with platinum drugs has achieved great success in the clinic, combination therapy commonly brings new problems. Herein, we have developed a platinum-metformin conjugate as a promising alternative to antibody-based PD-L1 inhibitors, not only disrupting PD-1/PD-L1 axis on cell surface but also down-regulating the total PD-L1 levels in non-small cell lung cancer (NSCLC) cells comprehensively, thus achieving highly efficient immunochemotherapy by a single small molecule. Mechanism studies demonstrate that Pt-metformin conjugate can selectively accumulate in lysosomes, promote lysosomal-dependent PD-L1 degradation via the AMPK-TFEB pathway, and modulate the upstream regulatory proteins related to PD-L1 expression (e.g. HIF-1α and NF-κB), eventually decreasing the total abundance of PD-L1 in NSCLC, overcoming tumor hypoxia, and activating anti-tumor immunity in vivo. This work suggests an AMPK-mediated lysosomal degradation pathway of PD-L1 for the first time and provides a unique design perspective for the development of novel platinum drugs for immunochemotherapy.

A phase I, single-sequence, open-label study to evaluate the drug-drug interaction between hetrombopag and cyclosporine in healthy Chinese subjects.

AIMS: This study aims to evaluate the drug-drug interaction (DDI) between hetrombopag and cyclosporine in healthy Chinese subjects. METHODS: Twenty-six eligible subjects enrolled in this single-centre, single-sequence, open-label, DDI study with 3 treatment periods, receiving 5 mg hetrombopag once on Day 1, 100 mg cyclosporine twice daily from Day 11 to Day 15 and 5 mg hetrombopag + 100 mg cyclosporine on Day 16. Serial blood samples were collected for pharmacokinetic evaluation. Adverse events were monitored throughout the study. RESULTS: The plasma hetrombopag geometric mean ratios (90% confidence interval) of maximum plasma concentration, area under the plasma concentration-time curve (AUC) from predose to time of last quantifiable sample and AUC to infinity of coadministration of hetrombopag with cyclosporine vs. hetrombopag alone were 95.97% (70.08-131.43%), 105.75% (75.04-149.04%) and 104.19% (74.71-145.32%), respectively, indicating multiple doses of cyclosporine had minimal effects on hetrombopag exposure. The geometric mean ratios (90% confidence interval) of maximum blood concentration and AUC at steady state during a dosing interval for blood cyclosporine of coadministration vs. cyclosporine alone were 100.49% (91.89-109.89%) and 100.81% (107.88-103.82%), respectively, suggesting a single dose of hetrombopag had no impact on the exposure of cyclosporine. Coadministration of hetrombopag with cyclosporine was generally well tolerated. CONCLUSION: No clinically significant DDI was observed when coadministration of hetrombopag with cyclosporine. The results of this study will inform the appropriate use of this combination therapy both in clinical trials and clinical settings.

Metabolic Defects of Peripheral T Cells in COVID-19 Patients.

The relatively low partial pressure of oxygen, reduced oxygen saturation, and aberrant plasma metabolites in COVID-19 may alter energy metabolism in peripheral immune cells. However, little is known regarding the immunometabolic defects of T cells in COVID-19 patients, which may contribute to the deregulated immune functions of these cells. In this study, we longitudinally characterized the metabolic profiles of resting and activated T cells from acutely infected and convalescent COVID-19 patients by flow cytometry and confirmed the metabolic profiles with a Seahorse analyzer. Non-COVID-19 and healthy subjects were enrolled as controls. We found that ex vivo T cells from acutely infected COVID-19 patients were highly activated and apoptotic and displayed more extensive mitochondrial metabolic dysfunction, especially cells in CD8+ T cell lineages, than those from convalescent COVID-19 patients or healthy controls, but slightly disturbed mitochondrial metabolic activity was observed in non-COVID-19 patients. Importantly, plasma IL-6 and C-reactive protein (CRP) levels positively correlated with mitochondrial mass and negatively correlated with fatty acid uptake in T cells from COVID-19 patients. Additionally, compared with those from healthy controls, in vitro-activated T cells from acutely infected COVID-19 patients showed signs of lower glycolysis, a reduced glycolytic capacity, and a decreased glycolytic reserve, accompanied by lower activation of mTOR signaling. Thus, newly identified defects in T cell mitochondrial metabolic functions and metabolic reprogramming upon activation might contribute to immune deficiency in COVID-19.

Antifungal activity and mechanism of palmarosa essential oil against pathogen Botrytis cinerea in the postharvest onions.

AIMS: Botrytis cinerea is a pathogenic fungus that infests multiple crops, which causes a severe decrease in yield and generates substantial losses in the economy. Palmarosa essential oil (PEO) is a primary aromatic compound extracted from palmarosa that is commonly used for scent, medicine, and flavoring foods due to its diverse bioactive properties. In this study, we explored the antifungal activity and the main mechanism of action of PEO against B. cinerea. In addition, the components and control effects of PEO were also studied. METHODS AND RESULTS: The antifungal assay was tested using the mycelial growth rate method and colony morphology. The constituents of PEO were identified according to gas chromatography/mass spectrometry (GC-MS). The main mechanism of action of PEO was evaluated by measuring representative indicators, which consist of cell contents leakage, excess reactive oxygen species (ROS), and other related indicators. The results indicated that at a concentration of 0.60 ml l-1, PEO exhibits strong antifungal activity against B. cinerea. The PEO mainly included 13 compounds, of which citronellol (44.67%), benzyl benzoate (14.66%), and acetyl cedrene (9.63%) might be the main antifungal ingredients. The study elucidated the main mechanism of action of PEO against B. cinerea, which involved the disruption of cell membrane structure, resulting in altered the cell membrane permeability, leakage of cell contents, and accumulation of excess ROS. CONCLUSIONS: PEO is a satisfactory biological control agent that inhibits B. cinerea in postharvest onions. PEO (0.60 ml l-1) exhibited strong antifungal activity by disrupting the cell membrane structure, altering cell membrane permeability, leading to the cell contents leakage, accumulation of excess ROS and increased level of Malondialdehyde (MDA) compared to the control group.

First Report of Powdery Mildew Caused by Erysiphe cruciferarum on Orychophragmus violaceus in China.

Orychophragmus violaceus is an annual or perennial herb in the Brassicaceae family. It is widely planted in China and used as an ornamental and green manure plant (Luo et al. 2022). In September 2022, a survey conducted in a 600 m2 garden in Lanzhou (36°06'N, 103°43'E) found that over 70% of O. violaceus plants were infected with powdery mildew, with 80% of the leaf area on the upper surface of infected leaves was infected. The white colonies on the upper surface of the leaves gradually expanded, thickened, and spread to cover the stem surface. In severe cases, entire foliage withered and the plants died. Fungal structures were taken from the leaves with adhesive tape and placed in sterile water for microscopic observation. The conidiophores were upright, cylindrical, composed of 3 to 4 cells, and measured 92.3 ± 12.9 × 9.2 ± 0.6 µm (n=30). Conidial pedicels had 21.6 ± 3.4 µm (n=50) long cylindrical podocytes. Monoconidia were cylindrical or oval in shape, 32.9 ± 6.1 µm long and 15.1 ± 2.1 µm wide (n=80). Conidia lacked an obvious cellulose body. The bud tubes formed from the end of conidia, and papillary appressoria developed on the epiphytic mycelia. Based on these morphological characteristics, the pathogen was initially identified as Erysiphe cruciferarum (Braun et al. 2012). To validate the identity, the internal transcribed spacer (ITS) region of an isolate EYL was amplified by PCR and sequenced using both ITS1/ITS4 and ITS5/PM6 primers (Takamatsu et al. 2001). The resulting sequences were deposited at GenBank (accession nos: OR437967 and OR437969). The ITS sequence of the isolate EYL (OR437967) is 99% (451/453) identical to E. cruciferarum (KP730001) on Brassica napus in China and that of the isolate EYL (OR437969) is 100% (509/509) identical to E. cruciferarum (KM260718) on B. juncea in Vietnam. Pathogenicity experiments were performed on six-week-old plants with an average of 10 ± 0.8 leaves. In the inoculated group, five healthy plants were inoculated by gently pressing the upper surface of diseased leaves against the upper surface of leaves of healthy plants for about 5 to 10 seconds. In the control group, the leaves of five healthy plants were treated with asymptomatic using the same method as described above. The plants were maintained in a greenhouse set at 25℃, 14-h photoperiod, and ≥ 70% humidity. After 13 days, all inoculated plants showed symptoms of powdery mildew, while the plants in the control group had no symptoms. The fungus on the inoculated plant was re-isolated and identified as E. cruciferarum based on its morphological characteristics and ITS sequence. Powdery mildew caused by E. cruciferarum has been reported on Cleome hassleriana in Italy and B. juncea in Australia (Garibaldi et al. 2009; Kaur et al. 2008). To our knowledge, this is the first time that powdery mildew caused by E. cruciferarum have been reported on O. violaceus in China. This disease poses a potential threat to the quality and yield of O. violaceus plants, which may warrant the development of preventative and management strategies in the future.

Method of Building Detection in Optical Remote Sensing Images Based on SegFormer.

An appropriate detection network is required to extract building information in remote sensing images and to relieve the issue of poor detection effects resulting from the deficiency of detailed features. Firstly, we embed a transposed convolution sampling module fusing multiple normalization activation layers in the decoder based on the SegFormer network. This step alleviates the issue of missing feature semantics by adding holes and fillings, cascading multiple normalizations and activation layers to hold back over-fitting regularization expression and guarantee steady feature parameter classification. Secondly, the atrous spatial pyramid pooling decoding module is fused to explore multi-scale contextual information and to overcome issues such as the loss of detailed information on local buildings and the lack of long-distance information. Ablation experiments and comparison experiments are performed on the remote sensing image AISD, MBD, and WHU dataset. The robustness and validity of the improved mechanism are demonstrated by control groups of ablation experiments. In comparative experiments with the HRnet, PSPNet, U-Net, DeepLabv3+ networks, and the original detection algorithm, the mIoU of the AISD, the MBD, and the WHU dataset is enhanced by 17.68%, 30.44%, and 15.26%, respectively. The results of the experiments show that the method of this paper is superior to comparative methods such as U-Net. Furthermore, it is better for integrity detection of building edges and reduces the number of missing and false detections.

A Golgi-Targeted Platinum Complex Plays a Dual Role in Autophagy Regulation for Highly Efficient Cancer Therapy.

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus is a substrate of autophagy but the Golgi-autophagy (Golgiphagy) mediated antitumor pathway is rarely reported. Herein, we have developed a novel Golgi-targeted platinum (II) complex Pt3, which is ca. 20 times more cytotoxic to lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano-encapsulated system for tail vein administration also features a good anti-tumor effect. Mechanism studies indicate that Pt3 induces substantial Golgi stress, indicated by the fragmentation of Golgi structure, down-regulation of Golgi proteins (GM130, GRASP65/55), loss of Golgi-dependent transport and glycosylation. This triggers Golgiphagy but blocks the subsequent fusion of autophagosomes with lysosomes, that is a dual role in autophagy regulation, resulting in loss of proteostasis and apoptotic cell death. As far as we know, Pt3 is the first Golgi-targeted Pt complex that can trigger Golgi stress-mediated dual-regulation of autophagic flux and autophagy-apoptosis crosstalk for highly efficient cancer therapy.

CYP4CJ6-mediated resistance to two neonicotinoid insecticides in Sitobion miscanthi (Takahashi).

The wheat aphid Sitobion miscanthi (CWA) is an important harmful pest in wheat fields. Insecticide application is the main method to effectively control wheat aphids. However, CWA has developed resistance to some insecticides due to its extensive application, and understanding resistance mechanisms is crucial for the management of CWA. In our study, a new P450 gene, CYP4CJ6, was identified from CWA and showed a positive response to imidacloprid and thiamethoxam. Transcription of CYP4CJ6 was significantly induced by both imidacloprid and thiamethoxam, and overexpression of CYP4CJ6 in the imidacloprid-resistant strain was also observed. The sensitivity of CWA to these two insecticides was increased after the knockdown of CYP4CJ6. These results indicated that CYP4CJ6 could be associated with CWA resistance to imidacloprid and thiamethoxam. Subsequently, the posttranscriptional regulatory mechanism was assessed, and miR-316 was confirmed to participate in the posttranscriptional regulation of CYP4CJ6. These results are crucial for clarifying the roles of P450 in the resistance of CWA to insecticides.

MicroRNA-190-5p confers chlorantraniliprole resistance by regulating CYP6K2 in Spodoptera frugiperda (Smith).

The fall armyworm Spodoptera frugiperda (Smith) (FAA) is responsible for considerable losses in grain production, and chemical control is the most effective strategy. However, frequent insecticide application can lead to the development of resistance. In insects, cytochrome P450 plays a crucial role in insecticide metabolism. CYP6K2 is related to FAA resistance to chlorantraniliprole. However, the regulatory mechanism of CYP6K2 expression is poorly understood. In this study, a conserved target of isolated miRNA-190-5p was located in the 3' UTR of CYP6K2 in FAA. A luciferase reporter analysis showed that in FAA, miRNA-190-5p can combine with the 3'UTR of CYP6K2 to suppress its expression. Injected miRNA-190-5p agomir significantly reduced CYP6K2 abundance by 54.6% and reduced tolerance to chlorantraniliprole in FAA larvae, whereas injected miRNA-190-5p antagomir significantly increased CYP6K2 abundance by 1.77-fold and thus improved chlorantraniliprole tolerance in FAA larvae. These results provide a basis for further research on the posttranscriptional regulatory mechanism of CYP6K2 and will facilitate further study on the function of miRNAs in regulating tolerance to chlorantraniliprole in FAA.

The effect of PCSK9 inhibitors on brain stroke prevention: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention. METHODS AND RESULTS: We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67-0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84-1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66-1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81-1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times. CONCLUSIONS: PCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment.

Identification of differentially expressed microRNAs under imidacloprid exposure in Sitobion miscanthi.

Imidacloprid is a neonicotinoid that targets sucking pests, such as aphids and the green leaf bug and has been widely applied in wheat fields to control wheat aphids in China. To investigate the involvement of miRNAs in imidacloprid resistance, we sequenced small RNA libraries of Sitobion miscanthi Fabricius, across two different treatments using Illumina short-read sequencing technology. As a result, 265 microRNAs (miRNAs), of which 242 were known and 23 were novel, were identified. Quantitative analysis of miRNA levels showed that 23 miRNAs were significantly up-regulated, and 54 miRNAs were significantly down-regulated in the nymphs of S. miscanthi treated with imidacloprid in comparison with those of the control. Modulation of the abundances of differentially expressed miRNAs, smi-miR-316, smi-miR-1000, and smi-miR-iab-4 by the addition of the corresponding antagomir/inhibitor to the artificial diet significantly changed the susceptibility of S. miscanthi to imidacloprid. Subsequently, the post-transcriptional regulatory mechanism was conducted, smi-miR-278 and smi-miR-316 were confirmed to be participated in the post-transcriptional regulation of nAChRα1A and CYP4CJ6, respectively. The results suggested that miRNAs differentially expressed in response to imidacloprid could play a critical regulatory role in the metabolism of S. miscanthi to imidacloprid.

Regional assemblages shaped by historical and contemporary factors: Evidence from a species-rich insect group.

Understanding diversity patterns requires accounting for the roles of both historical and contemporary factors in the assembly of communities. Here, we compared diversity patterns of two moth assemblages sampled from Taihang and Yanshan mountains in Northern China and performed ancestral range reconstructions using the Multi-State Speciation and Extinction model, to track the origins of these patterns. Further, we estimated diversification rates of the two moth assemblages and explored the effects of contemporary ecological factors. From 7,788 specimens we identified 835 species belonging to 23 families, using both DNA barcode analysis and morphology. Moths in Yanshan mountains showed higher species diversity than in Taihang mountains. Ancestral range analysis indicated Yanshan as the origin, with significant historical dispersals from Yanshan to Taihang. Asymmetrical diversification, population expansion, along with frequent and considerable gene flow were detected between communities. Moreover, dispersal limitation or the joint effect of environment filtering and dispersal limitation were inferred as main driving forces shaping current diversity patterns. In summary, we demonstrate that a multiscale (community, population and species level) analysis incorporating both historical and contemporary factors can be useful in delineating factors contributing to community assembly and patterning in diversity.

Low Aromatase Activity and Estradiol/Sex Hormone Binding Globulin Ratio are Associated with Total Hip Bone Mineral Density and the Presence of Osteoporosis: A Study in Chinese Postmenopausal Women.

Several groups have reported the important role of estradiol (E2) and testosterone (T) in postmenopausal osteoporosis (PMOP). Because aromatase catalyzes the conversion of T to E2, the purpose of this study was to determine the influence of aromatase activity on the bone mineral density (BMD) in postmenopausal women. A total of 344 postmenopausal women were selected for this study. Serum E2, T, sex hormone-binding globulin (SHBG), calcium (Ca), alkaline phosphatase (ALP), C-terminal telopeptide of type I collagen (CTX), and procollagen type I amino-terminal propeptide (PINP) were examined. The E2/T was positively associated with total hip BMD and PINP (p<0.05). When E2/T was divided into quartiles, participants in lower quartiles of E2/T were likely to have higher PINP and lower BMD (p<0.05). The prevalence of osteoporosis significantly increased as E2/T ratio decreased. The receiver operating characteristic (ROC) curves were constructed for serum E2, free E2 index (FEI), and E2/T, to assess their diagnostic accuracy in PMOP. The overall area under the curve (AUC) were 0.83 (95% CI=0.77-0.88) for E2, 0.87 (95% CI=0.82-0.92) for FEI, and 0.89 (95% CI=0.85-0.94), respectively. In conclusion, the study suggests that in postmenopausal women, aromatase activity could be an important determinant of skeletal health. The women with lower aromatase activity may have greater likelihood of PMOP and the E2/T was expected to be a valuable indicator for the prediction of PMOP and to monitor the process of osteoporosis.