Search

Abstract Objective To compare 18 F-PSMA-1007 PET/CT, 18 F-FDG PET/CT and 68Ga-PSMA PET/CT in the diagnostic value of prostate cancer. Method The Chinese and foreign databases, such as Pubmed, Cochrane Library, Embase, CNKI, VIP, Wanfang, etc., were systematically searched within the period from the establishment of the database to June 1, 2022. Clinical studies related to the diagnosis of prostate cancer by methods such as 18 F-PSMA-1007 PET/CT, 18 F-FDG PET/CTCT, 68Ga-PSMA PET/CT, were researched. Two (2) investigators independently screened literatures, extracted data, and assessed the risk of bias when these data were included in the studies with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Review Manager5.4, Stata 14.0, and Meta-disc 1.4 software were used for meta-analysis to compare the efficacy of different methods in the diagnose of prostate cancer. Results Twenty-seven (27) studies, including 2891 subjects were included in our study. Meta-analysis results showed that the pooled sensitivities of 18 F-PSMA-1007 PET/CT, 18 F-FDG PET/CT, and 68Ga-PSMA PET/CT were 0.912 (95%CI: 0.883–0.936), 0.748 (95%CI: 0.698–0.795), and 0.916 (95%CI: 0.896–0.934), respectively; the pooled specification were 0.878 (0.844–0.907), 0.639 (95%CI: 0.589–0.687), and 0.734 (95%CI: 0.685–0.779), respectively; the positive likelihood ratios were 6.335 (95%CI: 4.288–9.357), 2.282 (95%CI: 1.497–3.477), and 3.593 (95%CI: 2.986–4.323), respectively; the negative likelihood ratios were 0.878 (95%CI: 0.844–0.907), 0.374 (95%CI: 0.280–0.499), and 0.110 (95%CI: 0.083–0.144), respectively; the diagnostic odds ratios were 65.125 (95%CI: 34.059–124.53), 7.094 (95%CI: 4.091–12.301), and 29.722 (95%CI: 20.141–43.863), respectively; the positive posterior probability was 64%, 38%, and 62%, respectively; the area under the SPOC curve was 0.95 (95%CI: 0.93–0.97), 0.81 (95%CI: 0.78–0.84), and 0.96 (95%CI: 0.92–0.98), respectively. The funnel plots indicated that there was no significant publication bias in the included literatures. Conclusion The current evidences showed that 18 F-PSMA-1007 PET/CT and 68Ga-PSMA PET/CT had higher diagnostic efficacy of prostate cancer compared with 18 F-FDG PET/CT, among which 68Ga-PSMA PET/CT was slightly higher in the sensitivity of the diagnosis of prostate cancer, while 18 F-PSMA-1007 PET/CT may have higher efficacy in specificity and confirmed positive rate. Due to the limitations of the quality of the included samples and literatures, the above conclusions should be further validated by expanding the sample size and improving the quality.

Abstract TROP2 antibody drug conjugates (ADCs) are under active development. We seek to determine whether we can enhance activity of TROP2 ADCs by increasing TROP2 expression. In metaplastic breast cancers (MpBC), there is limited expression of TROP2, and downregulating transcription factor ZEB1 upregulates E-cad and TROP2, thus sensitizing cancers to TROP2 ADC sacituzumab govitecan (SG). Demethylating agent decitabine decreases DNA methyltransferase expression and TROP2 promoter methylation and subsequently increases TROP2 expression. Decitabine treatment as well as overexpression of TROP2 significantly enhance SG antitumor activity. Decitabine also increases SLFN11, a biomarker of topoisomerase 1 inhibitor (TOP1) sensitivity and is synergistic with SG which has a TOP1 payload, in TROP2-expressing SLFN11-low BC cells. In conclusion, TROP2 and SLFN11 expression can be epigenetically modulated and the combination of demethylating agent decitabine with TROP2 ADCs may represent a novel therapeutic approach for tumors with low TROP2 or SLFN11 expression.

Chronic diabetic wounds remain a globally recognized clinical challenge. They occur due to high concentrations of reactive oxygen species and vascular function disorders. A promising strategy for diabetic wound healing is the delivery of exosomes, comprising bioactive dressings. Metformin activates the vascular endothelial growth factor pathway, thereby improving angiogenesis in hyperglycemic states. However, multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported, and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear. Here, we engineered dual-loaded hydrogels possessing tissue adhesive, antioxidant, self-healing and electrical conductivity properties, wherein 4-armed SH-PEG cross-links with Ag+, which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair. Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group, creating a stable three-dimensional structure for exosome and metformin loading. The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M + E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury. The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission, thereby protecting F-actin homeostasis and alleviating microvascular dysfunction. Hence, we propose a drug–bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.

Micro-hole aerostatic bearings are important components in micro-low-gravity simulation of aerospace equipment, and the accuracy of micro-low-gravity simulation tests is affected by them. In order to eliminate the influence of air resistance on the attitude control accuracy of remote sensing satellites and achieve high fidelity of micro-low-gravity simulation tests, in this study, a design and parameter optimization method was proposed for micro-hole aerostatic bearings for a vacuum environment. Firstly, the theoretical analysis was conducted to investigate the impact of various bearing parameters and external conditions on the bearing load capacity and mass flow. Subsequently, a function model describing the variation in bearing load capacity and mass flow with bearing parameters was obtained utilizing a BP neural network. The parameters of aerostatic bearings in a vacuum environment were optimized using the non-dominated sorting genetic algorithm (NSGA-II) with the objectives of maximizing the load capacity and minimizing the mass flow. Subsequently, experimental tests were conducted on the optimized bearings in both atmospheric and vacuum conditions to evaluate their load capacity and mass flow. The results show that in a vacuum environment, the load capacity and mass flow of aerostatic bearings are increased compared to those in standard atmospheric conditions. Furthermore, it has been determined that the optimal solution for the bearing’s load capacity and mass flow occurs when the bearing has an orifice aperture of 0.1 mm, 36 holes, and an orifice distribution diameter of 38.83 mm. The corresponding load capacity and mass flow are 460.644 N and 11.816 L/min, respectively. The experimental and simulated errors are within 10%; thus, the accuracy of the simulation is verified.

Porous metallic nanomaterials exhibit interesting physical and chemical properties, and are widely used in various fields. Traditional fabrication techniques are limited to metallurgy, sintering, electrodeposition, etc., which limit the control of pore size and distribution, and make it difficult to achieve materials with high surface areas. On the other hand, the chemical preparation of metallic nanoparticles is usually carried out with strong reducing agents or at high temperature, resulting in the formation of dispersed particles which cannot evolve into porous metal. In this study, we reported the simple fabrication of coral-like mesoporous Pd nanomaterial (Pd NC) with a ligament size of 4.1 nm. The fabrication was carried out by simple solvothermal reduction at a mild temperature of 135 °C, without using any templates. The control experiments suggested that tetrabutylammonium bromide (TBAB) played a critical role in the Pd(II) reduction into Pd nanoclusters and their subsequent aggregation to form Pd NC, and another key point for the formation of Pd NC is not to use a strong reducing agent. In alkaline water electrolysis, the Pd NC outperforms the monodisperse Pd NPs and the state-of-the-art Pt (under large potentials) for H2 evolution reaction, probably due to its mesoporous structure and large surface area. This work reports a simple and novel method for producing porous metallic nanomaterials with a high utilization efficiency of metal atoms, and it is expected to contribute to the practical preparation of porous metallic nanomaterials by solvothermal reductions.

Underwater images suffer from low contrast and color distortion. In order to improve the quality of underwater images and reduce storage and computational resources, this paper proposes a lightweight model Rep-UWnet to enhance underwater images. The model consists of a fully connected convolutional network and three densely connected RepConv blocks in series, with the input images connected to the output of each block with a Skip connection. First, the original underwater image is subjected to feature extraction by the SimSPPF module and is processed through feature summation with the original one to be produced as the input image. Then, the first convolutional layer with a kernel size of 3 × 3, generates 64 feature maps, and the multi-scale hybrid convolutional attention module enhances the useful features by reweighting the features of different channels. Second, three RepConv blocks are connected to reduce the number of parameters in extracting features and increase the test speed. Finally, a convolutional layer with 3 kernels generates enhanced underwater images. Our method reduces the number of parameters from 2.7 M to 0.45 M (around 83% reduction) but outperforms state-of-the-art algorithms by extensive experiments. Furthermore, we demonstrate our Rep-UWnet effectively improves high-level vision tasks like edge detection and single image depth estimation. This method not only surpasses the contrast method in objective quality, but also significantly improves the contrast, colorimetry, and clarity of underwater images in subjective quality.

Short-chain fatty acids (SCFAs) have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiota–gut–brain axis. However, the precise mechanism by which brain SCFAs extert multiple beneficial effects is not completely understood. Our previous research has demonstrated that the acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is a novel target of the rapid and long-lasting antidepressant responses. Here, we show that micromolar SCFAs significantly augment both total cellular and nuclear ACSS2 to trigger tryptophan hydroxylase 2 (TPH2) promoter histone acetylation and its transcription in SH-SY5Y cells. In chronic-restraint-stress-induced depression mice, neuronal ACSS2 knockdown by stereotaxic injection of adeno-associated virus in the hippocampus abolished SCFA-mediated improvements in depressive-like behaviors of mice, supporting that ACSS2 is required for SCFA-mediated antidepressant responses. Mechanistically, the peroxisome-proliferator-activated receptor gamma (PPARγ) is identified as a novel partner of ACSS2 to activate TPH2 transcription. Importantly, PPARγ is also responsible for SCFA-mediated antidepressant-like effects via ACSS2–TPH2 axis. To further support brain SCFAs as a therapeutic target for antidepressant effects, d-mannose, which is a naturally present hexose, can significantly reverse the dysbiosis of gut microbiota in the chronic-restraint-stress-exposure mice and augment brain SCFAs to protect against the depressive-like behaviors via ACSS2–PPARγ–TPH2 axis. In summary, brain SCFAs can activate ACSS2–PPARγ–TPH2 axis to play the antidepressive-like effects, and d-mannose is suggested to be an inducer of brain SCFAs in resisting depression.

Background Lung adenocarcinoma (LUAD) is a major pathological subtype of malignant lung cancer with a poor prognosis. Necroptosis is a caspase-independent programmed cell death mode that plays a pivotal role in cancer oncogenesis and metastasis. Here, we explore the prognostic values of different necroptosis-related genes (NRGs) in LUAD. Methods mRNA expression data and related clinical information for LUAD samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. NRGs were identified using the GeneCards database. Least absolute shrinkage and selection operator Cox regression and multivariate Cox analysis were used to construct a prognostic risk model. Time-dependent receiver-operating characteristic curves and a nomogram were constructed to validate the predictive values of the prognostic signatures. A necroptosis-related protein–protein interaction network was visualised using the STRING database and Cytoscape software. Functional analyses, including Gene Ontology, Kyoto Encyclopaedia of Genes and Genomes pathway enrichment, gene set enrichment, and gene set variation analyses, were conducted to explore the underlying molecular mechanisms. Finally, the mRNA expression of the prognostic signatures in LUAD cell lines was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. Results A prognostic model was established for eight NRGs (CALM1, DDX17, FPR1, OGT, PGLYRP1, PRDX1, TUFM, and CPSF3) based on TCGA-cohort data and validated with the GSE68465 cohort. Patients with low-risk scores had better survival outcomes than those with high-risk scores (p = 0.00013). The nomogram was used to predict the prognosis of patients with LUAD. The prediction curves for 1-, 3-, and 5-year OS showed good predictive performance and the accuracy of the nomograms increased over time. RT-qPCR results demonstrated that these eight genes, especially CALM1, PRDX1, and PGLYRP1, were differentially expressed in LUAD cells. Conclusion We constructed a reliable eight-NRG signature that provides new insights for guiding clinical practice in the prognosis and treatment of LUAD.

Abstract High‐latitude winter warming was observed following strong tropical volcanism, which has long been believed to be due to the volcanic‐induced positive North Atlantic Oscillation (NAO) phase. However, recent works argue that this warming is caused by El Niño–Southern Oscillation (ENSO) variability instead of volcanoes. Moreover, some studies further argue that El Niño and volcanoes work together to produce this post‐volcanic NAO winter warming. To better understand these arguments on post‐volcanic high‐latitude winter warming, we conducted ENSO‐preconditioned volcanic experiments. Our simulations strongly suggest that the post‐eruption Eurasian winter warming is caused by a post‐eruption positive NAO phase and not by coexisting ENSO‐preconditioned variability. Additionally, we find that the El Niño‐preconditioned volcanic eruption enhances the El Niño phase; however, the neutral and La Niña‐preconditioned eruptions do not lead to an ENSO–like response. These findings are helpful to better understand volcanic‐induced circulation impacts and have important implications for the interpretation of model results and post‐volcanic prediction.

The therapeutic mechanism for the treatment of Alzheimer's disease (AD) is mainly by inhibiting the activity of cholinesterase (ChE) and increasing the transmission of choline and the function of neurons. In this study, two series of ChE inhibitors (CA1–CA8 and CB1–CB7) were designed and synthesized by the acylation of a cannabinoid (CBD) with bromoacetyl bromide, or the esterification of a CBD with an amino acid. All the synthesized compounds were tested for in vitro activity to evaluate the compounds as AD therapies. Compound CB7 was identified as a potential butyrylcholinesterase (BuChE) inhibitor (IC50 = 0.31 ± 0.09 μM), which did not display toxicity against HepG2 or PC12 cells at 6.25 μM. Compound CB7 showed good antioxidant behavior, effective anti-tyrosinase activity (IC50 = 0.037 ± 0.003 μM), and anti-acetylcholinesterase (AChE) activity (IC50 = 19.73 ± 0.79 μM). Kinetic studies also showed that CB7 can act as a dual inhibitor. These results provide a theoretical basis for the use of the natural product CBD in the design and development of anti-AD drugs.

A novel polysaccharide (WAMPa) was purified from Atractylodis macrocephala Koidz. WAMPa was characterized with molecular weight (MW) distribution, infrared spectrum, monosaccharide composition, methylation and nuclear magnetic resonance spectra. The backbone of WAMPa was → 2)-β-D-Glcp-(1 → interspersed with a small amount of → 5)-α-D-Araf-(1→, and the branches were the terminal α-D-Glcp-(1 → and β-D-Glcp-(1→. The immunomodulatory activities of WAMPa were investigated on two levels experiments including in vitro RAW264.7 cells and in vivo zebrafish. Meanwhile, the immune-mediated antitumor activity was evaluated by the inhibitory effect of the culture medium from WAMPa-treated RAW264.7 cells on human breast cancer cell line MCF-7. Bioactivity assays showed that WAMPa increased mRNA expression levels of TNF-α, IL-6 and iNOS, enhanced the levels of NO, and promoted the phosphorylation of ERK, p38 and JNK. Taken together, these findings revealed that WAMPa exhibited immunomodulatory effects by regulating MAPK signaling pathway. The antitumor experiments showed that WAMPa did not show a significant growth inhibition ratio on MCF-7 cells, but WAMPa-treated RAW264.7 macrophages could significantly inhibit the growth of MCF-7 cells. Thus, the antitumor activity of WAMPa was mediated mainly through the activation of macrophages. These results suggested that WAMPa could be considered as potential immunomodulatory and antitumor supplements.

Background Extensive attention has been given to the role of myeloid-derived suppressor cells (MDSCs) in driving tumor progression and treatment failure. Preclinical studies have identified multiple agents that eliminate MDSCs. However, none have been authorized in the cliniccal ues due to the safety reasons. In the present study, we investigated the efficacy and mechanism of sulforaphane (SFN) to eliminate MDSCs in the tumor microenvironment (TME).Methods We monitored SFN effect on tumor growth and the percents or apoptosis of immune cell subsets in mice models bearing LLC or B16 cells. Flow cytometry, quantitative reverse transcription-PCR, immunohistochemistry, ELISA, immunofluorescence, imaging flow cytometry and western blot were performed to validate the role of SFN on MDSCs function in vivo and in vitro. RNA sequencing was then used to interrogate the mechanisms of how SFN regulated MDSCs function. Tumor xenograft models were established to evaluate the involvement of IL-12RB2/MMP3/FasL induced MDSCs apoptosis in vivo. We verified the effect of SFN on MDSCs and CD8+ T cells in the blood samples from a phase I clinical trial (KY-2021–0350).Results In this study, we elucidated that SFN liberated CD8+ T-cell antitumor ability by reducing MDSCs abundance, leading to repressed tumor growth. SFN treatment suppressed MDSCs accumulation in the peripheral blood and tumor sites of mice, but had no effect on the bone marrow. Mechanistically, SFN activates IL-12RB2, which stimulates the MMP3/FasL signaling cascade to trigger caspase 3 cleavage and induce apoptosis in MDSCs. Clinically, SFN treatment eliminates peripheral MDSCs and increases the percentage and activation of CD8+ T cells.Conclusions Collectively, we uncovered the role of SFN in eliminating MDSCs to emancipate CD8+ T cells through IL-12RB2/MMP3/FasL induced apoptosis, thus providing a strategy for targeting MDSCs to control tumors and improve clinical efficacy.

Abstract With the advantage of fast charge transfer, heterojunction engineering is identified as a viable method to reinforce the anodes' sodium storage performance. Also, vacancies can effectively strengthen the Na+ adsorption ability and provide extra active sites for Na+ adsorption. However, their synchronous engineering is rarely reported. Herein, a hybrid of Co0.85Se/WSe2 heterostructure with Se vacancies and N‐doped carbon polyhedron (CoWSe/NCP) has been fabricated for the first time via a hydrothermal and subsequent selenization strategy. Spherical aberration‐corrected transmission electron microscopy confirms the phase interface of the Co0.85Se/WSe2 heterostructure and the existence of Se vacancies. Density functional theory simulations reveal the accelerated charge transfer and enhanced Na+ adsorption ability, which are contributed by the Co0.85Se/WSe2 heterostructure and Se vacancies, respectively. As expected, the CoWSe/NCP anode in sodium‐ion battery achieves outstanding rate capability (339.6 mAh g−1 at 20 A g−1), outperforming almost all Co/W‐based selenides.

In order to evaluate the effects of sizing agents on the wettability, strength loss, and properties of final filament wound structures during filament winding of carbon fibers, three types of sizing agent based on epoxy, epoxy + polyester, and epoxy + polyurethane were used to treat carbon fibers, the surface properties of carbon fiber samples after treatment were evaluated using SEM, infrared spectroscopy, dynamic contact angle analysis, and interlaminar shear strength (ILSS) test, the strength loss caused by fiber damage during filament winding was quantitatively analyzed, and the strength properties of the filament wound structures were characterized by NOL ring test. The results showed that the sizing agent treatment only slightly improved the surface free energy and ILSS of carbon fibers, but it had obvious influence on the strength loss rate of carbon fiber bundles. Added polyester or polyurethane in epoxy-based sizing may improve its protective effect for carbon fiber, and thus decrease strength loss during winding process, result in better tensile properties of carbon fiber filament wound structures.

Background: Sorafenib is a classic molecular targeted drug approved for hepatocellular carcinoma (HCC) therapy. However, a poor response rate and increasing resistance to sorafenib make its therapeutic efficacy suboptimal. Combination treatment with an agent capable of potentiating sorafenib sensitivity may be a promising solution. Aim: The aim of this study was to determine the synergistic effect of ellagic acid (EA), a natural polyphenol, and sorafenib on HCC. Methods: CCK-8, EdU incorporation and colony formation assays were used to study the effect of EA on HCC cell proliferation. Apoptosis was detected by flow cytometry in HCC cells and TUNEL assay in xenograft tumors. Transcriptome analysis was utilized to investigate alterations in signaling pathways with EA treatment. A xenograft mouse model was used to confirm the synergistic effect of sorafenib and EA on HCC tumors in vivo. Results: We found that EA inhibited growth and induced apoptosis in both HCC cells and xenograft tumors. Mechanistically, EA treatment reduced the activation of the MAPK and Akt/mTOR signaling pathways in HCC cells. Furthermore, combined EA and sorafenib treatment further inhibited the MAPK and Akt/mTOR signaling pathways compared to EA or sorafenib alone. EA synergistically potentiated the anticancer activity of sorafenib against HCC both in vitro and in vivo. Conclusion: EA inhibits HCC growth by inducing apoptosis through attenuation of the MAPK and Akt/mTOR signaling pathways. EA potentiates the response of HCC tumors to sorafenib both in vitro and in vivo, an effect that may be attributed to further inhibition of the MAPK and Akt/mTOR signaling pathways. These results suggest that EA is an effective adjuvant option for sorafenib therapy.

ABSTRACT The mosquito immune system limits Plasmodium infection and malaria transmission. Plasmodium falciparum evades the mosquito defense response by expressing the surface protein P. falciparum P47 (Pfs47) that inhibits midgut epithelial nitration by interacting with the mosquito midgut P47 receptor (P47Rec). However, the mechanism by which P47Rec suppresses caspase-mediated nitration is unknown. Here, we show that epithelial invasion by Pfs47 knockout parasites is followed by an extrusion of cells undergoing caspase-mediated apoptosis, which triggers the release of hemocyte-derived microvesicles (HdMv’s), known to promote complement activation and ookinete lysis. In contrast, invasion by P. falciparum parasites that express Pfs47 accelerates the extrusion of damaged cells and disrupts caspase activation and HdMv release. The Anopheles gambiae heat shock protein 70 cognate 3 (Hsc70-3), the ortholog of Drosophila binding immunoglobulin protein, was identified as a molecular partner of P47Rec. Silencing of Hsc70-3 promotes lysis of Pfs47 wild-type parasites through a caspase S2-dependent mechanism. The interaction of P47Rec activates a Hsc70-3-mediated anti-apoptotic response that prevents caspase activation. The interaction of P47Rec with Hsc70-3 is necessary for P. falciparum to evade the mosquito early immune responses that target the ookinete stage. IMPORTANCE Malaria transmission by Anopheles gambiae mosquitoes is very effective, in part because the parasite expresses a surface protein called Pfs47 that allows it to evade the mosquito immune system. Here we investigate how this protein changes the response of mosquito midgut epithelial cells to invasion by the parasite. Pfs47 is known to interact with P47Rec, a mosquito midgut receptor. We found that Pf47Rec inhibits caspase-mediated apoptosis by interacting with the Hsc70-3. This disrupts nitration of midgut epithelial cells invaded by the parasite and the release of hemocyte-derived microvesicles, which are critical for effective activation of the mosquito complement system that eliminates the parasite.

“Ancient tea plants” are defined as tea trees > 100 years old, or with a trunk diameter > 25 cm; their leaves are manufactured to high - quality, valuable ancient plants pu-erh tea (APPT). In this study, a fermentation of APPT were developed, and outstanding sweetness of APPT infusion was observed. During fermentation, the content of soluble sugars, theabrownins (p 1.0; p 2]; While relative levels of 72 metabolites were decreased (VIP > 1.0, p

Background: Ischemia‒reperfusion (IR) is a pathological process that causes secondary damage to blood vessels. However, whether IR can further worsen neointima formation after balloon injury and the detailed mechanism are unclear. Methods: An in vivo model of balloon injury to the rat carotid artery was established to study the effect of IR following balloon injury on neointima formation. Smooth muscle cells (SMCs) were isolated from rat aortas and exposed to hypoxia-reoxygenation to mimic the IR process in vitro. The in vitro cell model was used to investigate the mechanism of IR-mediated neointima formation after balloon injury, which was further confirmed in an in vivo rat model. Results: IR aggravated neointima formation in the rat carotid artery 2 weeks after balloon injury compared with that observed in the absence of balloon injury (P

Skin diseases are global health issues caused by multiple pathogenic factors, in which epigenetics plays an invaluable role. Post-transcriptional RNA modifications are important epigenetic mechanism that regulate gene expression at the genome-wide level. N6-methyladenosine (m6A) is the most prevalent modification that occurs in the messenger RNAs (mRNA) of most eukaryotes, which is installed by methyltransferases called “writers”, removed by demethylases called “erasers”, and recognised by RNA-binding proteins called “readers”. To date, m6A is emerging to play essential part in both physiological processes and pathological progression, including skin diseases. However, a systematic summary of m6A in skin disease has not yet been reported. This review starts by illustrating each m6A-related modifier specifically and their roles in RNA processing, and then focus on the existing research advances of m6A in immune homeostasis and skin diseases.

As an autoimmune disease, systemic lupus erythematosus (SLE) can affect multiple organs and systems. Whether SLE can increase the risk of coeliac disease (CeD) was not evaluated until now. We performed a two-sample Mendelian randomisation study to evaluate the relationship between SLE and CeD, and found that SLE can significantly increase the risk of CeD, suggesting the association between SLE and abnormal intestinal immune microenvironment.

Background: Deletion/insertion polymorphisms (DIPs), a novel class of biomarker, have been widely utilized in forensic areas for individual identification, paternity tests, and ancestral origin inference due to its applicability to degraded samples and low mutation rates. Despite the availability of a well-established commercial kit, the Investigator® DIPplex kit (Qiagen), certain loci exhibit limited levels of polymorphisms in East Asian populations, particularly in Chinese populations. Objective: This dissertation seeks to undertake a comprehensive evaluation about the forensic efficiency of a self-developed multiplex amplification system in high-altitude adaptive ethnic groups of China. Healthy unrelated Tibetan individuals residing in Tibet Autonomous Region and Qinghai Province were genotyped using previously reported 43 deletion/insertion polymorphism loci. Forensic statistical analyses including allele frequencies and forensic parameters were conducted in the two Tibetan groups, and the genetic relatedness of the studied groups with reference populations from the 1000 Genomes Project Phase 3 were investigated. Results: Forensic statistical results showed that the polymorphism information content values of the 43 deletion/insertion polymorphism loci in the two Tibetan groups exceeded 0.35. Moreover, the combined power of discrimination using the 43 deletion/insertion polymorphism loci was calculated to be 0.9999999999999999984 in the Qinghai Tibetan group and 0.9999999999999999921 in the Tibet Tibetan group. The cumulative power of exclusion using the 43 deletion/insertion polymorphism loci was calculated to be 0.999782512 in the Qinghai Tibetan group and 0.999886205 in the Tibet Tibetan group. Analysis of population genetics demonstrated that the two studied Tibetan groups shared close genetic relationships with East Asia populations. Conclusion: The set of 43 deletion/insertion polymorphism loci exhibited remarkable forensic efficacy, rendering it a promising tool for forensic practice. Population genetic analyses indicated that the two Tibetan groups had closer genetic affinities to East Asian populations.

Backgrounds G-protein-coupled receptor 84 (GPR84) marks a subset of myeloid-derived suppressor cells (MDSCs) with stronger immunosuppression in the tumor microenvironment. Yet, how GPR84 endowed the stronger inhibition of MDSCs to CD8+ T cells function is not well established. In this study, we aimed to identify the underlying mechanism behind the immunosuppression of CD8+ T cells by GPR84+ MDSCs.Methods The role and underlying mechanism that MDSCs or exosomes (Exo) regulates the function of CD8+ T cells were investigated using immunofluorescence, fluorescence activating cell sorter (FACS), quantitative real-time PCR, western blot, ELISA, Confocal, RNA-sequencing (RNA-seq), etc. In vivo efficacy and mechanistic studies were conducted with wild type, GPR84 and p53 knockout C57/BL6 mice.Results Here, we showed that the transfer of GPR84 from MDSCs to CD8+ T cells via the Exo attenuated the antitumor response. This inhibitory effect was also observed in GPR84-overexpressed CD8+ T cells, whereas depleting GPR84 elevated CD8+ T cells proliferation and function in vitro and in vivo. RNA-seq analysis of CD8+ T cells demonstrated the activation of the p53 signaling pathway in CD8+ T cells treated with GPR84+ MDSCs culture medium. While knockout p53 did not induce senescence in CD8+ T cells treated with GPR84+ MDSCs. The per cent of GPR84+ CD8+ T cells work as a negative indicator for patients’ prognosis and response to chemotherapy.Conclusions These data demonstrated that the transfer of GPR84 from MDSCs to CD8+ T cells induces T-cell senescence via the p53 signaling pathway, which could explain the strong immunosuppression of GPR84 endowed to MDSCs.

ObjectiveThe aim of this study is to discuss the postpartum anxiety disorder and influencing factors in puerperae with gestational diabetes mellitus (GDM) to provide a clinical basis for better early identification and intervention of adverse mood.MethodsConvenient sampling method was adopted to investigate 205 pregnant women as the observation group and 201 normal healthy pregnant women in the same period as the control group. The self-rating anxiety scale (SAS) was used to investigate and observe the respondents, evaluate the postpartum anxiety status of patients with GDM, and analyze the related influencing factors. Statistical analysis of the data was performed using SAS 3.0 software. A proposed P < 0.05 was considered as statistically significant.ResultsPatients with GDM had a higher risk than normal maternal anxiety, related to years of education, triglycerides, 1-h postprandial blood glucose, and a history of induced abortion.ConclusionGDM can lead to the occurrence of postpartum anxiety, and the poor psychological state is not conducive to the maternal and infant health. Early identification and early intervention can reduce the harm caused by anxiety and promote the progress of maternal and infant health and clinical research.

IntroductionBrain glioma segmentation is a critical task for medical diagnosis, monitoring, and treatment planning.DiscussionAlthough deep learning-based fully convolutional neural networks have shown promising results in this field, their unstable segmentation quality remains a major concern. Moreover, they do not consider the unique genomic and basic data of brain glioma patients, which may lead to inaccurate diagnosis and treatment planning.MethodsThis study proposes a new model that overcomes this problem by improving the overall architecture and incorporating an innovative loss function. First, we employed DeepLabv3+ as the overall architecture of the model and RegNet as the image encoder. We designed an attribute encoder module to incorporate the patient’s genomic and basic data and the image depth information into a 2D convolutional neural network, which was combined with the image encoder and atrous spatial pyramid pooling module to form the encoder module for addressing the multimodal fusion problem. In addition, the cross-entropy loss and Dice loss are implemented with linear weighting to solve the problem of sample imbalance. An innovative loss function is proposed to suppress specific size regions, thereby preventing the occurrence of segmentation errors of noise-like regions; hence, higher-stability segmentation results are obtained. Experiments were conducted on the Lower-Grade Glioma Segmentation Dataset, a widely used benchmark dataset for brain tumor segmentation.ResultsThe proposed method achieved a Dice score of 94.36 and an intersection over union score of 91.83, thus outperforming other popular models.

Objectives We aimed to estimate the genotype distribution of persistent human papillomavirus (HPV) infection in females worldwide, and provided a scientific basis for the prevention strategies of cervical cancer (CC) and the development of HPV vaccines. Methods Both English and Chinese databases were researched from the inception to July 2023. The pooled persistent HPV infection prevalence was calculated using a random effects model. The subgroup analysis was performed to explore the heterogeneity. Publication bias was evaluated using funnel plot, Egger’s and Begg’s test. Results Twenty-eight studies with 27,335 participants were included. The pooled prevalence of persistent HPV infection was 29.37% (95% CI [24.05%∼35.31%]), and the genotypes with the persistent infection prevalence were HPV16 (35.01%), HPV52 (28.19%), HPV58 (27.06%), HPV18 (25.99%), HPV33 (24.37%), HPV31 (23.35%), HPV59 (21.87%), HPV39 (19.54%), HPV68 (16.61%) and HPV45 (15.05%). The prevalence of multiple and single HPV persistent infection were 48.66% and 36.71%, respectively; the prevalence of persistent HPV infection in different age groups (50) were 29.83%, 28.39%, 22.24% and 30.22%, respectively. The follow-up time was significantly associated with heterogeneity by subgroup analysis (P

To investigate the embryonic development of the mud crab Scylla paramamosain, we analyzed three critical parameters: egg color of, embryo morphology (through conventional and laser scanning confocal microscopy), and the distribution of cell divisions. During embryonic development, the egg color exhibited a progressive transition, shifting from orange to reddish-orange, then to brown, before ultimately darkening to black. Each embryo displayed a spherical shape, measuring approximately 280 μm in diameter, characterized by a smooth surface devoid of any depressions. The embryonic cell division was in the form of mixed oogenesis, comprised of complete division in the early stage, spiral oogenesis in the middle stage and surface division in the late stage. It is noteworthy that the blastopore appeared at the position where the transparent area and cell aggregation just appeared under the microscope, and the blastomere was a characteristic of the embryo entering the gastrulation stage. After entering the gastrulation stage, the cells aggregated towards the blastopore and formed two symmetrical cell clusters, which formed a V-shape with the void of the classic blastopore. When the transparent region occupied approximately 1/5 of the embryo’s volume, the embryo entered the nauplius stage, and the thoracic and abdominal armor, as well as the optic lobe and abdominal limb primordia, could be clearly distinguished. The appearance of the compound eye pigment band indicated the stage of compound eye pigment formation. At this time, the transparent area accounted for 1/4 of the embryo and a large number of ganglia appeared. The change of the compound eye pigment band from red to black was also one of the reasons for the blackening of the egg color of the crabs. The data obtained through this study have potential applications in the determination of embryonic development status and obtaining of high-quality seeds for S. paramamosain culture.

Objective SLE is a common multisystem autoimmune disease with chronic inflammation. Many efficacy evaluation indicators of randomised clinical trials (RCTs) for SLE have been proposed but the comparability remains unknown. We aim to explore the preference and comparability of indicators reporting response rate and provide basis for primary outcome selection when evaluating the efficacy of SLE pharmaceutical treatment.Methods We systematically searched three databases and three registries to identify pharmacological intervention-controlled SLE RCTs. Relative discriminations between indicators were assessed by the Bayesian hierarchical linear mixed model.Results 33 RCTs met our inclusion criteria and we compared eight of the most commonly used indicators reporting response rate. SLE Disease Activity Index 4 (SLEDAI-4) and SLE Responder Index 4 were considered the best recommended indicators reporting response rate to discriminate the pharmacological efficacy. Indicator preference was altered by disease severity, classification of drugs and outcome of trials, but SLEDAI-4 had robust efficacy in discriminating ability for most interventions. Of note, BILAG Index-based Combined Lupus Assessment showed efficacy in trials covering all-severity patients, as well as non-biologics RCTs. The British Isles Lupus Assessment Group response and Physician’s Global Assessment response were more cautious in evaluating disease changes. Serious adverse event was often applied to evaluate the safety and tolerability of treatments rather than efficacy.Conclusions The impressionable efficacy discrimination ability of indicators highlights the importance of flexibility and comprehensiveness when choosing primary outcome(s). As for trials that are only evaluated by SLEDAI-4, attention should be paid to outcome interpretation to avoid the exaggeration of treatment efficacy. Further subgroup analyses are limited by the number of included RCTs.PROSPERO registration number CRD42022334517.

The mining disturbance causes the rock mass in a certain range of the coal seam floor to be in a post-peak state. Due to the excavation of adjacent roadways and the mining of coal seams, the post-peak rock mass undergoes a cyclic loading-unloading process. In order to explore the influence of post-peak cyclic loading on rock mass structure under different in-situ stress environments and clarify the gestation process of disasters such as water inrush from coal seam floor, post-peak cyclic loading tests of sandstone under 5,10,15,20,25 MPa confining pressure were carried out based on Rock Top multi-field coupling tester. The results show that: ① Before the post-peak cyclic loading, the unit permeability of rock shows a rapid decline-tend to be stable-sudden rise-sudden decline-tend to be stable. In the post-peak cycle stage, the unit permeability of rock is almost inverted with the axial load. ② Rock elastic modulus, crack closure stress, crack initiation stress, damage stress, peak stress and residual stress are positively correlated with confining pressure, while Poisson 's ratio increases first and then decreases with the increase of confining pressure. ③ Under the confining pressure of 5 and 10 MPa, the intermittent failure of rock occurs, and the brittle failure characteristics are weakened. Under the confining pressure of 15, 20 and 25 MPa, the brittle failure characteristics of rock are obvious, and the failure characteristics of rock are determined by the properties of rock itself. ④ The post-peak axial load mainly promotes the increase of rock permeability, but the promotion effect is weaker than that of confining pressure on rock permeability, and confining pressure is the dominant factor affecting the post-peak permeability change of rock. ⑤ Under different confining pressures, a through-shear crack occurs in all rocks, but with the increase of confining pressure, the degree of rock failure gradually weakens and the failure mode tends to be simple.

An extraction process of terpenoids from stigma maydis was discussed in this paper. Firstly, a UPLC analytical method was established based on the three standard substances tigmene F(1), 3β-hydroxy- ent-kaur-15-en-17-oic acid-18-ester(2), and 4α-hydroxy-19-nor-ent-kaur-15-en-17-oic acid (3) from stigma maydis. The chromatography condition was determined as C18 100Ȧ column (4.6 mm×150 mm, 2.6 µm) eluted with MeOH (A)-0.1% phosphoric acid (B) in gradient with the 1.0 mL/min flow rate. The column temperature was 40 ℃ with a 10 μL injection volume. The detection wavelength was set at 220 nm. Results showed that, three terpenoids had good linearity (r>0.9993) in the concentration range of 0.96~192.0 μg/mL (stigmene F) and 5.0~200.0 μg/mL (3β-hydroxy-ent-kaur-15-en-17-oic acid-18-ester and 4α-hydroxy-19-nor-ent-kaur-15-en-17-oic acid), respectively. They showed the same limits of quantitation (LOQ, S/N=10) ranged from 5.0 μg/g to 10.0 μg/g, similar average recovery rate of 89.1%~105.8%, and with could be used for quantitative analysis and provided research reference for terpenoids in stigma maydis. Finally, guided by the optimized analytical method, the extraction process for the three terpenoids from stigma maydis was determined as follows: The extract solvent was 20% MeOH-H2O, which was 25 times weight of stigma maydis, and with refluxed extraction for 1 h.

Acupuncture is widely used in China for various conditions. Recently, due to the limitations of conventional treatment, many patients with psychogenic erectile dysfunction (ED) tend to choose acupuncture therapy, which is more commonly applied in countries such as China. The present clinical trial protocol aimed to initially verify the efficacy and safety of acupuncture in the treatment of psychogenic ED. Our study is a prospective, randomized control trial (RCT). The protocol for this RCT is based on the standard protocol items: recommendations for interventional trials (SPIRIT) 2013 statement. After the participants who met the inclusion and exclusion criteria sign an informed consent form, the investigator will schedule them for the trial. Patients will be randomly divided into two groups (acupuncture and sham acupuncture). Both groups will receive 18 sessions of interventions for 6 continuous weeks and will be followed up for 10 weeks. At five time points (0, 2, 4, 6 and 10 weeks), We will measure the primary and secondary outcomes. Emerging evidence support acupuncture therapy for improving male sexual function and its application in andrology. However, its efficacy on patients diagnosed with psychogenic ED has not been extensively studied. With our study, we anticipate to fill the knowledge gap in acupuncture as treatment for psychogenic ED.

Abstract Tacrolimus is an important immunosuppressant used in the treatment of myasthenia gravis (MG). However, the population pharmacokinetic (PK) characteristics together with the exposure‐response of tacrolimus in the treatment of MG remain largely unknown. In this study, we aimed to develop a population PK/pharmacodynamic (PK/PD) model of tacrolimus in patients with MG, in order to explore the relationships among tacrolimus dose, exposure, and its therapeutic efficacy. The genotype of CYP3A5, Osserman's classification, and status of thymus, as well as demographic characteristics and other biomarkers from laboratory testing were tested as covariate, and simulations were performed based on the final model. The population PK model was described using a one‐compartment model with first‐order elimination and fixed absorption parameters. CYP3A5 genotype significantly influenced the apparent clearance, and total protein (TP) influenced the apparent volume of distribution as covariates. The quantitative MG scores were characterized by the cumulated area under curve of tacrolimus in a maximum effect function. Osserman's classification was a significant covariate on the initial score of patients with MG. The simulations demonstrated that tacrolimus showed an unsatisfying effect possibly due to insufficient exposure in some patients with MG. A starting dose of 2 mg/d and even higher dose for patients with CYP3A5 *1/*1 and *1/*3 and lower TP level were required for the rapid action of tacrolimus. The population PK/PD model quantitatively described the relationships among tacrolimus dose, exposure, and therapeutic efficacy in patients with MG, which could provide reference for the optimization of tacrolimus dosing regimen at the individual patient level.

The mining area in northwest China is located in the arid and semi-arid zone, in which the surface water resource is sparse and the ecological environment is fragile. Coupled with the exploitation of mineral resources, the land has been degraded seriously. How to realize the efficient reclamation of soil and the effective utilization of soil water is an urgent scientific and technical problem. In this study, the layered soil with different configurations is set up for water transport and infiltration test to monitor the moisture changes in the soil profile. Hydrus-1D is used to simulate the rainfall infiltration process and reveal the water transport characteristics of layered soil from three aspects: soil moisture, water potential and water flux. The scenario simulation is conducted based on the optimized model to explore the effect of interlayer characteristics on shallow soil water. The results show that the interlayer significantly changes the distribution and transport of soil water, and the soil water potential is continuously distributed at the interlayer interface, while the soil water abruptly changes at the interlayer interface. Although loess interlayer and weathered sandstone interlayer both block the infiltration of soil water, the principle and the source of water increase are different. The former is the retention of soil water above the interlayer due tothe poor permeability of loess, while the latter is the retention of water above the interlayer due to the small matrix potential of the coarser interlayer. According to the results of the model, it is suggested that setting loess interlayer of 20 cm thick at the depth of 40 cm of aeolian sand is conducive to increase soil moisture above the interlayer for vegetation utilization. Summarily, the results can provide a theoretical basis for understanding and mastering the layered soil hydrological process in arid regions and optimizing the soil reconstruction mode in the process of land reclamation and ecological restoration.

China's economy has entered a new stage of high-quality development, and the high-quality development of the marine economy requires a more scientific and reasonable index system to reflect the development of the marine economy in a comprehensive and accurate manner. The paper used the subjective and objective assignment method to combine the relevant data of Qingdao City's marine economy from 2015 to 2020, and conducted a comprehensive research and empirical analysis on the level of Qingdao City's high-quality development of marine economy. The results showed that innovation-driven, green development and people's livelihood were important supporting forces for the high-quality development of Qingdao City's marine economy. Open development and comprehensive quality and efficiency played an important driving role for the high-quality development of Qingdao City's marine economy. Coordinated development was the main problem facing the high-quality development of Qingdao City's marine economy in recent years. Finally, countermeasures and suggestions to promote the high-quality development of Qingdao City's marine economy were further discussed and put forward.

In arid and semiarid regions, lake-basin ecosystems are an important part of watershed security barriers, playing an important role in maintaining the stability of ecological patterns. However, the ecological environment of the lake-basin system has been gradually degraded in recent years, and its change process is accompanied by a complex dynamic mechanism. In the present study, we explored the spatial variability of the ecological environment of the lake-basin system and its drivers by taking Baozhainao Lake in the Mu Us Sandy Land of the Ordos Basin as the study area.In-situ dynamic monitoring, sample survey, statistical analysis and numerical simulation were employed. The distribution patterns of typical vegetation in the basin were determined and the mechanisms underlying the mutual feedbacks between subsurface hydrological process and lakeshore ecosystem was explored. The results show that the Baozhainao lake-basin ecosystem consists of four zoning types, namely, the lake zone, the lake nearshore fluctuation zone, the lakeshore beach zone, and the lakeshore wind beach zone. From the lake to the beach zone, the depth of water table increased gradually and the vegetation type transitions from water-loving and salt-tolerant to drought-tolerant. It was further found that the presence of vegetation on the lake shore significantly affects the circulation mode of the groundwater flow system. The conversion between lake and groundwater occurs mainly in the local groundwater flow system, resulting in a significant reduction in groundwater recharge to the lake.The results of this study can provide a scientific basis for the restoration and conservation of plant species diversity and vegetated ecosystems in the lake nearshore fluctuation zoneand lakeshore wind beach zone in arid regions.

Abstract Introduction Cigarette smoking is usually more prevalent among those with a lower socioeconomic status (SES), which can be driven by inequalities in the initiation and cessation of smoking, giving rise to SES disparities in health. This study aimed to gauge the SES inequalities in smoking related behaviours and their evolving trends based on a nationally representative database. Method Data were extracted from repeated cross-sectional China Family Panel Studies (CFPS) of adults aged ≥18 and

In the study of atmospheric wind fields from the upper troposphere to the stratosphere (10 km to 50 km), direct detection wind LiDAR is considered a promising method that offers high-precision atmospheric wind field data. In 2020, Xie et al. of the Anhui Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, developed an innovative rotating Rayleigh Doppler wind LiDAR (RRDWL). The system aims to achieve single-LiDAR detection of atmospheric wind fields by rotating the entire device cabin. In 2022, the feasibility of the system was successfully validated in laboratory conditions, and field deployment was completed. Due to the structural differences between this system and traditional direct-detection wind LiDAR, performance tests were conducted to evaluate its continuous detection capability in outdoor environments. Subsequently, based on the test results and error analysis, further analysis was carried out to identify the main factors affecting the system’s detection performance. Finally, the error analysis and traceability of the detection results were conducted, and corresponding measures were discussed to provide a theoretical foundation for optimizing the performance of RRDWL.

Exploring the ocean’s resources requires finding underwater objects, which is a challenging task due to blurry images and small, densely packed targets. To improve the accuracy of underwater target detection, we propose an enhanced version of the YOLOv7 network called YOLOv7-SN. Our goal is to optimize the effectiveness and accuracy of underwater target detection by introducing a series of innovations. We incorporate the channel attention module SE into the network’s key part to improve the extraction of relevant features for underwater targets. We also introduce the RFE module with dilated convolution behind the backbone network to capture multi-scale information. Additionally, we use the Wasserstein distance as a new metric to replace the traditional loss function and address the challenge of small target detection. Finally, we employ probe heads carrying implicit knowledge to further enhance the model’s accuracy. These methods aim to optimize the efficacy of underwater target detection and improve its ability to deal with the complexity and challenges of underwater environments. We conducted experiments on the URPC2020, and RUIE datasets. The results show that the mean accuracy (mAP) is improved by 5.9% and 3.9%, respectively, compared to the baseline model.

Traditional methods for harvesting medicinal materials with long roots, like Astragalus membranaceus, require extensive soil excavation, leading to problems like inefficient soil separation, low stemming rates, and blockages in conveyor chains. To address these challenges, this study introduces a prototype machine capable of digging, separating soil, crushing soil, and collecting the medicinal materials in one continuous process. The paper focuses on the machine’s design and working principle, with theoretical analysis and calculations for key components like the digging shovel, multi-stage conveyor, and soil-crushing device. Specific structural parameters were determined, and the screening efficiency of the roller screen was analyzed using EDEM 2020 software, comparing scenarios with and without rollers. A motion model for the medicinal materials during conveyance was established, allowing for the determination of optimal linear velocity and mounting angle for the conveyor. Additionally, a motion model for the second-stage conveyor chain and rear soil-crushing device was used to optimize their placement, ensuring efficient soil crushing without affecting the thrown Astragalus. Compared to traditional Chinese medicine diggers, this machine boasts superior resistance reduction and soil-crushing capabilities. Compared with traditional harvesters, the drag-reducing and soil-crushing device of this machine is more efficient, reducing the damage to Astragalus during the harvesting process, reducing the labor intensity of farmers, and improving the quality and efficiency of Astragalus harvesting. Field experiments have shown that when the operating speed of the prototype is 1.0 m/s and the roller-screen speed is 130~150 rpm, the operating performance is optimal, and comparative experiments can be conducted under the optimal parameters. From the experimental results, it can be seen that the improved equipment has increased the bright-stem rate by about 4%, the digging and loosening rate by 97.42%, and the damage rate by 2.44%. The equipment design meets the overall design requirements, and all experimental indicators meet national and industry standards. This provides a reference for the optimization and improvement of the soil-crushing device and the structure of the Astragalus membranaceus harvester.

Toona ciliata var. pubescens, known as “Chinese mahogany”, has high commercial value and is classified as a level II priority protected wild plant in China. However, due to overexploitation and its poor natural regeneration capacity, natural T. ciliata var. pubescens forests show varying degrees of decline in habitat adaptability. Arbuscular mycorrhizal fungi (AMF) symbiosis presents a potential strategy to enhance its regeneration. In this study, T. ciliata var. pubescens seedlings were inoculated with Septoglomus viscosum, followed by RNA-Seq analysis to compare gene expression differences between AMF-inoculated (AMI) and non-mycorrhizal (NM) treatments three months post-inoculation. A total of 16,163 differentially expressed genes (DEGs) were upregulated by AMF colonization, constituting 96.46% of the total DEGs. Specifically, 14,420 DEGs were exclusively expressed in the AMI treatment, while 35 DEGs were completely silenced. Most of the upregulated DEGs were located on the cell membrane, nucleus, and cytoskeleton and functioned in protein binding, S-adenosylmethionine-dependent methyltransferase activity, and lipid binding during cellular/macromolecule/protein localization, intracellular/protein transport, the cell cycle, and signal transduction. Additionally, lots of key genes related to oxidative stress responses, nutrient transport, and small GTPase-mediated signal transduction were found to be upregulated. These results suggest that AMF inoculation may enhance root cell growth by activating genes involved in nutrient uptake, stress responses, signal transduction, and substance transportation. This study elucidates the molecular mechanisms underlying the growth promotion of T. ciliata var. pubescens through AMF symbiosis, laying a foundation for the future application of AMF in its natural forest regeneration.

Phytophthora root rot is a devastating disease of soybean caused by Phytophthora sojae. However, the resistance mechanism is not yet clear. Our previous studies have shown that GmAP2 enhances sensitivity to P. sojae in soybean, and GmMYB78 is downregulated in the transcriptome analysis of GmAP2-overexpressing transgenic hairy roots. Here, GmMYB78 was significantly induced by P. sojae in susceptible soybean, and the overexpressing of GmMYB78 enhanced sensitivity to the pathogen, while silencing GmMYB78 enhances resistance to P. sojae, indicating that GmMYB78 is a negative regulator of P. sojae. Moreover, the jasmonic acid (JA) content and JA synthesis gene GmAOS1 was highly upregulated in GmMYB78-silencing roots and highly downregulated in overexpressing ones, suggesting that GmMYB78 could respond to P. sojae through the JA signaling pathway. Furthermore, the expression of several pathogenesis-related genes was significantly lower in GmMYB78-overexpressing roots and higher in GmMYB78-silencing ones. Additionally, we screened and identified the upstream regulator GmbHLH122 and downstream target gene GmbZIP25 of GmMYB78. GmbHLH122 was highly induced by P. sojae and could inhibit GmMYB78 expression in resistant soybean, and GmMYB78 was highly expressed to activate downstream target gene GmbZIP25 transcription in susceptible soybean. In conclusion, our data reveal that GmMYB78 triggers soybean sensitivity to P. sojae by inhibiting the JA signaling pathway and the expression of pathogenesis-related genes or through the effects of the GmbHLH122-GmMYB78-GmbZIP25 cascade pathway.

Lycopene represents one of the central compounds in the carotenoid pathway and it exhibits a potent antioxidant ability with wide potential applications in medicine, food, and cosmetics. The microbial production of lycopene has received increasing concern in recent years. Corynebacterium glutamicum (C. glutamicum) is considered to be a safe and beneficial industrial production platform, naturally endowed with the ability to produce lycopene. However, the scarcity of efficient genetic tools and the challenge of identifying crucial metabolic genes impede further research on C. glutamicum for achieving high-yield lycopene production. To address these challenges, a novel genetic editing toolkit, CRISPR/MAD7 system, was established and developed. By optimizing the promoter, ORI and PAM sequences, the CRISPR/MAD7 system facilitated highly efficient gene deletion and exhibited a broad spectrum of PAM sites. Notably, 25 kb of DNA from the genome was successfully deleted. In addition, the CRISPR/MAD7 system was effectively utilized in the metabolic engineering of C. glutamicum, allowing for the simultaneous knockout of crtEb and crtR genes in one step to enhance the accumulation of lycopene by blocking the branching pathway. Through screening crucial genes such as crtE, crtB, crtI, idsA, idi, and cg0722, an optimal carotenogenic gene combination was obtained. Particularly, cg0722, a membrane protein gene, was found to play a vital role in lycopene production. Therefore, the CBIEbR strain was obtained by overexpressing cg0722, crtB, and crtI while strategically blocking the by-products of the lycopene pathway. As a result, the final engineered strain produced lycopene at 405.02 mg/L (9.52 mg/g dry cell weight, DCW) in fed-batch fermentation, representing the highest reported lycopene yield in C. glutamicum to date. In this study, a powerful and precise genetic tool was used to engineer C. glutamicum for lycopene production. Through the modifications between the host cell and the carotenogenic pathway, the lycopene yield was stepwise improved by 102-fold as compared to the starting strain. This study highlights the usefulness of the CRISPR/MAD7 toolbox, demonstrating its practical applications in the metabolic engineering of industrially robust C. glutamicum.

SPL (SQUAMOSA promoter binding protein-like), as one family of plant transcription factors, plays an important function in plant growth and development and in response to environmental stresses. Despite SPL gene families having been identified in various plant species, the understanding of this gene family in peanuts remains insufficient. In this study, thirty-eight genes (AhSPL1-AhSPL38) were identified and classified into seven groups based on a phylogenetic analysis. In addition, a thorough analysis indicated that the AhSPL genes experienced segmental duplications. The analysis of the gene structure and protein motif patterns revealed similarities in the structure of exons and introns, as well as the organization of the motifs within the same group, thereby providing additional support to the conclusions drawn from the phylogenetic analysis. The analysis of the regulatory elements and RNA-seq data suggested that the AhSPL genes might be widely involved in peanut growth and development, as well as in response to environmental stresses. Furthermore, the expression of some AhSPL genes, including AhSPL5, AhSPL16, AhSPL25, and AhSPL36, were induced by drought and salt stresses. Notably, the expression of the AhSPL genes might potentially be regulated by regulatory factors with distinct functionalities, such as transcription factors ERF, WRKY, MYB, and Dof, and microRNAs, like ahy-miR156. Notably, the overexpression of AhSPL5 can enhance salt tolerance in transgenic Arabidopsis by enhancing its ROS-scavenging capability and positively regulating the expression of stress-responsive genes. These results provide insight into the evolutionary origin of plant SPL genes and how they enhance plant tolerance to salt stress.

The Heshui area within the Ordos Basin holds significant strategic importance for the extraction and development of tight oil resources in the Changqing Oilfield. This study extensively explored the geochemical features and distribution tendencies of source rocks in the Chang 7 member, utilizing core samples and logging data for a comprehensive analysis. A more advanced model was utilized to predict the dispersion of Total Organic Carbon (TOC) in the Chang 7 member source rock. The properties and hydrocarbon generation potential of source rocks were thoroughly assessed through a comprehensive analysis that involved evaluating their total organic carbon content, pyrolysis parameters, and reflectance (Ro) values. The research concluded that the source rocks boast substantial organic matter, predominantly categorized as type II-I organic material. The thermal maturation levels span from low maturity to maturity, signifying significant potential for oil generation. Generally, the source rock quality falls within the range of good to excellent. Sedimentary patterns notably influence the distribution of hydrocarbon-source rocks. The northeastern sector of the study area is situated in an area characterized by deep to semi-deep lake sedimentation, making it the primary location for the presence of Chang 7 member hydrocarbon source rocks. With a thickness ranging from 40 to 70 m, this zone becomes a pivotal focus for the potential exploration of tight oil resources in the future. The results of this study offer crucial insights for understanding the geochemical characteristics of hydrocarbon source rocks, evaluating their potential for hydrocarbon generation, and forecasting favorable zones for oil and gas exploration in similar regions.

The Fabry–Perot interferometer (FPI) plays a crucial role as the frequency discriminator in the incoherent Doppler wind lidar. However, in the practical receiver system, reflections occurring between optical elements introduce non-normal incident components in the light beams passing through the FPI. This phenomenon results in the deformation of the FPI transmission spectral lines. Based on that, a theoretical model has been developed to describe the transmission spectrum of the FPI when subjected to obliquely incident light beams with a divergence angle. By appropriately adjusting the model parameters, the simulated transmission spectrum of the FPI edge channels can coincide with the experimentally measured FPI spectral line. Subsequently, the impact of deformations in the transmission spectrum of the two edge channels on wind measurements is evaluated. The first implication is a systematic shift of 30.7 m/s in line-of-sight (LOS) wind velocities. This shift is based on the assumption that the lidar echo is solely backscattered from atmospheric molecules. The second consequence is the inconsistency in the response sensitivities of Doppler frequency shift between Rayleigh signals and Mie signals. As a result, the lidar system fails to fully achieve its initial design objectives, particularly in effectively suppressing interference from Mie signals. The presence of aerosols can introduce a significant error of several meters per second in the measurement of LOS wind velocity.

Integrated systems are facing complex and changing environments with the wide application of atmospheric LiDAR in civil, aerospace, and military fields. Traditional analysis methods employ optical software to evaluate the optical performance of integrated systems, and cannot comprehensively consider the influence of optical and mechanical coupling on the optical performance of the integrated system, resulting in the unsatisfactory accuracy of the analysis results. Optical–mechanical integration technology provides a promising solution to this problem. A small-field-of-view LiDAR system with high repetition frequency, low energy, and single-photon detection technology was taken as an example in this study, and the Zernike polynomial fitting algorithm was programmed to enable transmission between optical and mechanical data. Optical–mechanical integration technology was employed to obtain the optical parameters of the integrated system under a gravity load in the process of designing the optical–mechanical structure of the integrated system. The experimental validation results revealed that the optical–mechanical integration analysis of the divergence angle of the transmission unit resulted in an error of 2.586%. The focal length of the telescope increased by 89 μm, its field of view was 244 μrad, and the error of the detector target surface spot was 4.196%. The continuous day/night detection results showed that the system could accurately detect the temporal and spatial variations in clouds and aerosols. The inverted optical depths were experimentally compared with those obtained using a solar photometer. The average optical depth was 0.314, as detected using LiDAR, and 0.329, as detected by the sun photometer, with an average detection error of 4.559%. Therefore, optical–mechanical integration analysis can effectively improve the stability of the structure of highly integrated and complex optical systems.

Abstract Retrosynthesis analysis is an important task in organic chemistry with numerous industrial applications. Previously, machine learning approaches employing natural language processing techniques achieved promising results in this task by first representing reactant molecules as strings and subsequently predicting reactant molecules using text generation or machine translation models. Chemists cannot readily derive useful insights from traditional approaches that rely largely on atom-level decoding in the string representations, because human experts tend to interpret reactions by analyzing substructures that comprise a molecule. It is well-established that some substructures are stable and remain unchanged in reactions. In this paper, we developed a substructure-level decoding model, where commonly preserved portions of product molecules were automatically extracted with a fully data-driven approach. Our model achieves improvement over previously reported models, and we demonstrate that its performance can be boosted further by enhancing the accuracy of these substructures. Analyzing substructures extracted from our machine learning model can provide human experts with additional insights to assist decision-making in retrosynthesis analysis.

In recent years, artificial intelligence technology has exhibited great potential in seismic signal recognition, setting off a new wave of research. Vast amounts of high-quality labeled data are required to develop and apply artificial intelligence in seismology research. In this study, based on the 2013–2020 seismic cataloging reports of the China Earthquake Networks Center, we constructed an artificial intelligence seismological training dataset (“DiTing”) with the largest known total time length. Data were recorded using broadband and short-period seismometers. The obtained dataset included 2,734,748 three-component waveform traces from 787,010 regional seismic events, the corresponding P- and S-phase arrival time labels, and 641,025 P-wave first-motion polarity labels. All waveforms were sampled at 50 Hz and cut to a time length of 180 s starting from a random number of seconds before the occurrence of an earthquake. Each three-component waveform contained a considerable amount of descriptive information, such as the epicentral distance, back azimuth, and signal-to-noise ratios. The magnitudes of seismic events, epicentral distance, signal-to-noise ratio of P-wave data, and signal-to-noise ratio of S-wave data ranged from 0 to 7.7, 0 to 330 km, –0.05 to 5.31 dB, and –0.05 to 4.73 dB, respectively. The dataset compiled in this study can serve as a high-quality benchmark for machine learning model development and data-driven seismological research on earthquake detection, seismic phase picking, first-motion polarity determination, earthquake magnitude prediction, early warning systems, and strong ground-motion prediction. Such research will further promote the development and application of artificial intelligence in seismology.

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disorder in which excessive CD4+ T-cell activation and imbalanced effector T-cell differentiation play critical roles. Recent studies have implied a potential association between posttranscriptional N6-methyladenosine (m6A) modification and CD4+ T-cell-mediated humoral immunity. However, how this biological process contributes to lupus is not well understood. In this work, we investigated the role of the m6A methyltransferase like 3 (METTL3) in CD4+ T-cell activation, differentiation, and SLE pathogenesis both in vitro and in vivo. Methods The expression of METTL3 was knocked down and METTL3 enzyme activity was inhibited using siRNA and catalytic inhibitor, respectively. In vivo evaluation of METTL3 inhibition on CD4+ T-cell activation, effector T-cell differentiation, and SLE pathogenesis was achieved using a sheep red blood cell (SRBC)-immunized mouse model and a chronic graft versus host disease (cGVHD) mouse model. RNA-seq was performed to identify pathways and gene signatures targeted by METTL3. m6A RNA-immunoprecipitation qPCR was applied to confirm the m6A modification of METTL3 targets. Results METTL3 was defective in the CD4+ T cells of SLE patients. METTL3 expression varied following CD4+ T-cell activation and effector T-cell differentiation in vitro. Pharmacological inhibition of METTL3 promoted the activation of CD4+ T cells and influenced the differentiation of effector T cells, predominantly Treg cells, in vivo. Moreover, METTL3 inhibition increased antibody production and aggravated the lupus-like phenotype in cGVHD mice. Further investigation revealed that catalytic inhibition of METTL3 reduced Foxp3 expression by enhancing Foxp3 mRNA decay in a m6A-dependent manner, hence suppressing Treg cell differentiation. Conclusion In summary, our findings demonstrated that METTL3 was required for stabilizing Foxp3 mRNA via m6A modification to maintain the Treg differentiation program. METTL3 inhibition contributed to the pathogenesis of SLE by participating in the activation of CD4+ T cells and imbalance of effector T-cell differentiation, which could serve as a potential target for therapeutic intervention in SLE.

Abstract Background The roles of gut microbiota in the pathogenesis of SLE have been receiving much attention during recent years. However, it remains unknown how fecal microbiota transplantation (FMT) and microbial metabolites affect immune responses and lupus progression. Methods We transferred fecal microbiota from MRL/lpr (Lpr) mice and MRL/Mpj (Mpj) mice or PBS to pristane-induced lupus mice and observed disease development. We also screened gut microbiota and metabolite spectrums of pristane-induced lupus mice with FMT via 16S rRNA sequencing, metagenomic sequencing, and metabolomics, followed by correlation analysis. Results FMT from MRL/lpr mice promoted the pathogenesis of pristane-induced lupus and affected immune cell profiles in the intestine, particularly the plasma cells. The structure and composition of microbial communities in the gut of the FMT-Lpr mice were different from those of the FMT-Mpj mice and FMT-PBS mice. The abundances of specific microbes such as prevotella taxa were predominantly elevated in the gut microbiome of the FMT-Lpr mice, which were positively associated with functional pathways such as cyanoamino acid metabolism. Differential metabolites such as valine and L-isoleucine were identified with varied abundances among the three groups. The abundance alterations of the prevotella taxa may affect the phenotypic changes such as proteinuria levels in the pristane-induced lupus mice. Conclusion These findings further confirm that gut microbiota play an important role in the pathogenesis of lupus. Thus, altering the gut microbiome may provide a novel way to treat lupus.