Design of a recombinant asparaginyl ligase for site-specific modification using efficient recognition and nucleophile motifs.

Asparaginyl ligases have been extensively utilized as valuable tools for site-specific bioconjugation or surface-modification. However, the application is hindered by the laborious and poorly reproducible preparation processes, unstable activity and ambiguous substrate requirements. To address these limitations, this study employed a structure-based rational approach to obtain a high-yield and high-activity protein ligase called OaAEP1-C247A-aa55-351. It was observed that OaAEP1-C247A-aa55-351 exhibits appreciable catalytic activities across a wide pH range, and the addition of the Fe3+ metal ion effectively enhances the catalytic power. Importantly, this study provides insight into the recognition and nucleophile peptide profiles of OaAEP1-C247A-aa55-351. The ligase demonstrates a higher recognition ability for the "Asn-Ala-Leu" motif and an N-terminus "Arg-Leu" as nucleophiles, which significantly increases the reaction yield. Consequently, the catalytic activity of OaAEP1-C247A-aa55-351 with highly efficient recognition and nucleophile motif, "Asn-Ala-Leu" and "Arg-Leu" under the buffer containing Fe3+ is 70-fold and 2-fold higher than previously reported OaAEP1-C247A and the most efficient butelase-1, respectively. Thus, the designed OaAEP1-C247A-aa55-351, with its highly efficient recognition and alternative nucleophile options, holds promising potential for applications in protein engineering, chemo-enzymatic modification, and the development of drugs.

Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients.

BACKGROUND: Early and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR). METHODS: This study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization. RESULTS: 53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0-63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 - 84.1%), 76.0% (95%CI: 56.6 - 88.5%), 77.8% (59.2 - 89.4%) and 85.2% (95%CI: 67.5 - 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay. CONCLUSIONS: NTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

PARP-1 inhibitor alleviates cerebral ischemia/reperfusion injury by reducing PARylation of HK-1 and LDH in mice.

Poly (ADP-ribose) polymerase-1 (PARP-1) activity significantly increases during cerebral ischemia/reperfusion. PARP-1 is an NAD+-consumption enzyme. PARP-1 hyperactivity causes intracellular NAD+ deficiency and bioenergetic collapse, contributing to neuronal death. Besides, the powerful trigger of PARP-1 causes the catalyzation of poly (ADP-ribosyl)ation (PARylation), a posttranslational modification of proteins. Here, we found that PARP-1 was activated in the ischemic brain tissue during middle-cerebral-artery occlusion and reperfusion (MCAO/R) for 24 h, and PAR accumulated in the neurons in mice. Using immunoprecipitation, Western blotting, liquid chromatography-mass spectrometry, and 3D-modeling analysis, we revealed that the activation of PARP-1 caused PARylation of hexokinase-1 and lactate dehydrogenase-B, which, therefore, caused the inhibition of these enzyme activities and the resulting cell energy metabolism collapse. PARP-1 inhibition significantly reversed the activity of hexokinase and lactate dehydrogenase, decreased infarct volume, and improved neuronal deficiency. PARP-1 inhibitor combined with pyruvate further alleviated MCAO/R-induced ischemic brain injury in mice. As such, we conclude that PARP-1 inhibitor alleviates neuronal death partly by inhibiting the PARylation of metabolic-related enzymes and reversing metabolism reprogramming during cerebral ischemia/reperfusion injury in mice. PARP-1 inhibitor combined with pyruvate might be a promising therapeutic approach against brain ischemia/reperfusion injury.

Nicotinamide phosphoribose transferase facilitates macrophage-mediated pulmonary fibrosis through the Sirt1-Smad7 pathway in mice.

Pulmonary fibrosis is a challenging lung disease characterized by a bleak prognosis. A pivotal element in the progression of this disease is the dysregulated recruitment of macrophages. Nicotinamide phosphoribose transferase (NAMPT), secreted by alveolar epithelial cells and inflammatory cells, has been previously identified to influence macrophage inflammation in acute lung injury through the nicotinamide adenine dinucleotide (NAD) rescue synthesis pathway. Nonetheless, the exact role of NAMPT in the regulation of lung fibrosis is yet to be elucidated. In our research, we employed bleomycin (BLM) to induce pulmonary fibrosis in Namptflox/flox;Cx3cr1CreER mice, using Namptflox/flox mice as controls. Our findings revealed an augmented expression of NAMPT concurrent with a marked increase in the secretion of NAD and inflammatory cytokines such as IL-6, TNF-α, and TGF-ß1 post-BLM treatment. Furthermore, an upsurge in NAMPT-positive macrophages was observed in the lungs of BLM-treated Namptflox/flox mice. Notably, a conditional knockout of NAMPT (NAMPT cKO) in lung macrophages curtailed the BLM-induced inflammatory responses and significantly mitigated pulmonary fibrosis. This was associated with diminished phospho-Sirt1 (p-Sirt1) expression levels and a concomitant rise in mothers against decapentaplegic homolog 7 (Smad7) expression in BLM-treated mouse lungs and murine RAW 264.7 macrophage cells. Collectively, our data suggests that NAMPT exacerbates macrophage-driven inflammation and pulmonary fibrosis via the Sirt1-Smad7 pathway, positioning NAMPT as a promising therapeutic target for pulmonary fibrosis intervention.

Regular nutrition consultations reduced risk factors for cardiovascular diseases in adults.

OBJECTIVES: This study investigated the effects of regular nutrition consultations on reducing risk factors, including body mass index, body composition, blood pressure, blood lipid profile, blood glucose-related markers, and inflammatory factors for cardiovascular diseases. METHODS: Data were collected from participants (n = 129) who completed eight dietary consultations and were divided into two groups according to the regularity of the consultations: an irregular group (with irregular consultation intervals; n = 39) and a regular group (accepted consultation once every 3 wk; n = 90). RESULTS: Compared with the irregular group, the regular group had more significant reductions in cardiovascular disease risk factors, such as body mass index, body fat, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and insulin levels. Moreover, participants with a body mass index ≥ 27 kg/m2 presented significantly obvious improvements in cardiovascular risk factors, such as body weight; body mass index; visceral fat weight; and triglyceride, total cholesterol, low-density lipoprotein cholesterol, glycated hemoglobin, and insulin levels. CONCLUSION: There is a proven benefit to regular nutrition consultation for adults with risk factors of cardiovascular diseases, particularly those who are obese.

Changes in carbohydrate metabolism and soil microorganisms under the stress of polyamide and polyethylene nanoplastics during rice (Oryza sativa L.) growth.

Nanoplastics (NPs) presence in agricultural soils can affect plant growth and impact the quality of agricultural products. To investigate the effect of polyamide (PA) NPs and polyethylene (PE) NPs on carbohydrate metabolism and soil microorganisms during rice growth, rice seedlings were exposed to soil containing 2 g/kg of 100 nm PA or 100 nm PE powder for 33 d. The results revealed that 100 nm PE reduced shoot length and dry weight of rice by 4.14 % and 15.68 %, respectively. Analyzing the expression of hexokinase-2 (HXK), phosphofructokinase-1 (PFK), pyruvate kinase (PK) and isocitrate dehydrogenase (IDH), which are four genes related to carbohydrate metabolism, 100 nm PA decreased the expression of PFK and increased the expression of PK and IDH. 100 nm PE increased the expression of HXK, PFK, PK, and IDH. The results of soil microorganisms showed that 100 nm PA significantly effects on 3 bacterial phyla (Bacteroidota, Deinococcota, and Desulfobacterota), whereas 100 nm PE significantly effects on phylum Rozellomycota, class Umbelopsidomycetes, and an unclassified Firmicutes. Our study provides direct evidence of the negative effects of PA and PE on rice, which may be important for assessing the risk of NPs on agroecosystems.

Consumption of a Taiwanese cafeteria diet induces metabolic disorders and fecal flora changes in obese rats.

OBJECTIVES: Among diet-induced obesity animal models, the cafeteria diet, which contains human junk food and processed foods, is a popular experimental animal diets in Western countries. Consumption of a cafeteria diet can lead to the development of obesity and non-alcoholic liver disease in as soon as 2 mo, which more accurately reflects human eating patterns. The aim of this study was to establish a Taiwanese cafeteria diet and compare it with a traditional lard-based, 60% high-fat diet in a 12-wk animal model. METHODS: Six-wk-old male Wistar rats were assigned to the following three groups: control diet (C; LabDiet 5001); high-fat diet (HFD; 60% HFD); and the Taiwanese cafeteria diet (CAF). RESULTS: At the end of the study, weight gain and steatosis were observed in the HF and CAF groups. Compared with the HFD group, rats in the CAF group showed significantly higher plasma triacylglycerol concentrations and insulin resistance, which may have been correlated with increased inflammatory responses. Significantly lower hepatic sterol regulatory element-binding protein-1c and insulin receptor substrate-1 protein expressions were observed in the CAF group compared with the HFD group. Additionally, disruption of the microbiotic composition followed by increased obesity-related bacteria was observed in the CAF group. CONCLUSIONS: The present study confirmed that the Taiwanese cafeteria diet-induced rat model provided a potential platform for investigating obesity-related diseases.

Genetically engineered virus-like particle-armoured and multibranched DNA scaffold-corbelled ultra-sensitive hierarchical hybridization chain reaction for targeting-enhanced imaging in living biosystems under spatiotemporal light powering.

Although nucleic acids-based fluorescent biosensors, exemplified by the hybridization chain reaction (HCR), have exhibited promise as an imaging tool for detecting disease-related biomolecular makers in living biosystems, they still face certain challenges. These include the need for improved sensitivity, poor bio-targeting capability, the absence of signal enrichment interface and the uncontrollable biosensing initiation. Herein, we present a range of effective solutions. First, a stacking design resembling building blocks is used to construct a special hierarchical HCR (termed H-HCR), for which a hierarchical bridge is employed to graft multiunit HCR products. Furthermore, the H-HCR components are encapsulated into a virus-like particle (VLP) endowed with a naturally peptide-mediated targeting unit through genetic engineering of plasmids, after which the biosensor can specifically identify cancer cytomembranes. By further creating a multibranched DNA scaffold to enrich the H-HCR produced detection signals, the biosensor's analyte recognition module is inserted with a photocleavage-linker, allowing that the biosensing process can be spatiotemporally initiated via a light-powered behavior. Following these innovations, this genetically engineered VLP-armoured and multibranched DNA-scaffold-corbelled H-HCR demonstrates an ultra-sensitive and specific biosensing performance to a cancer-associated microRNA marker (miRNA-155). Beyond the worthy in vitro analysis, our method is also effective in performing imaging assays for such low-abundance analyte in living cells and even bodies, thus providing a roust platform for disease diagnosis.

Consistency and Accuracy of Artificial Intelligence for Providing Nutritional Information.

This cross-sectional study analyzes the accuracy of nutrition information from artificial intelligence (AI) in comparison with a nutritionist.

Effects of dietary adjustment of n-3:n-6 fatty-acid ratio to 1:2 on anti-inflammatory and insulin-signaling pathways in ovariectomized mice with high fat diet-induced obesity.

Estrogen deficiency increases the secretion of inflammatory mediators and can lead to obesity. Consequently, estrogen deficiency can cause metabolic syndrome, particularly insulin resistance during menopause. Both fish oil and perilla oil contain n-3 fatty acids, which may regulate several inflammatory cytokines. Additionally, adjusting the dietary n-3:n-6 fatty-acid ratio to 1:2 may help treat or prevent chronic diseases. Therefore, we investigated the effect of anti-inflammatory and insulin-signaling pathways, not solely in relation to the (n-3:n-6 fatty-acid ratio at 1:2), but also considering the origin of n-3 fatty acids found in fish oil and perilla oil, in a mouse model of estrogen deficiency induced by ovariectomy and obesity induced by a high-fat diet (HFD). Female C57BL/6J mice were divided into five groups: sham mice on a normal diet; ovariectomized (OVX) mice on a normal diet (OC); OVX mice on a HFD plus lard oil (OL), fish oil (OF), or perilla oil (OP). The dietary n-3:n-6 ratio in the OF and OP groups was adjusted to 1:2. The results showed OF group exhibited significantly lower abdominal adipose tissue weight, fewer liver lipid droplets, and smaller uterine adipocytes, compared with the OL group. Compared with the OL group, the OF and OP groups exhibited higher oral glucose tolerance and lower serum alanine aminotransferase activity, triacylglycerol levels, and total cholesterol levels. Hepatic JAK2, STAT3, and SOCS3 mRNA expression and p-NF-κB p65 and IL-6 levels were significantly lower in the OF and OP groups than in the OL group. Only the OF group exhibited an increase in PI3K and Akt mRNA expression, decrease in GLUT2 mRNA expression, and considerable elevation of p-Akt. Both fish and perilla oil reduced inflammatory signaling markers. However, only fish oil improved insulin signaling (PI3K, Akt, and GLUT2). Our data suggest that fish oil can alleviate insulin signaling through activating the PI3K-Akt-GLUT2 cascade signaling pathway.

MicroRNA2871b of Dongxiang Wild Rice (Oryza rufipogon Griff.) Negatively Regulates Cold and Salt Stress Tolerance in Transgenic Rice Plants.

Cold and salt stresses are major environmental factors that constrain rice production. Understanding their mechanisms is important to enhance cold and salt stress tolerance in rice. MicroRNAs (miRNAs) are a class of non-coding RNAs with only 21-24 nucleotides that are gene regulators in plants and animals. Previously, miR2871b expression was suppressed by cold stress in Dongxiang wild rice (DXWR, Oryza rufipogon Griff.). However, its biological functions in abiotic stress responses remain elusive. In the present study, miR2871b of DWXR was overexpressed to investigate its function under stress conditions. When miR2871b of DWXR was introduced into rice plants, the transgenic lines were more sensitive to cold and salt stresses, and their tolerance to cold and salt stress decreased. The increased expression of miR2871b in rice plants also increased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA); however, it markedly decreased the activities of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) and the contents of proline (Pro) and soluble sugar (SS). These data suggested that miR2871b of DXWR has negative regulatory effects on cold and salt stress tolerance. Meanwhile, 412 differentially expressed genes (DEGs) were found in rice transgenic plants using transcriptome sequencing, among which 266 genes were up-regulated and 146 genes were down-regulated. Furthermore, the upstream cis-acting elements and downstream targets of miR2871b were predicted and analyzed, and several critical acting elements (ABRE and TC-rich repeats) and potential target genes (LOC_Os03g41200, LOC_Os07g47620, and LOC_Os04g30260) were obtained. Collectively, these results generated herein further elucidate the vital roles of miR2871b in regulating cold and salt responses of DXWR.

The Influence of Oral Terbinafine on Gut Fungal Microbiome Composition and Microbial Translocation in People Living with HIV Treated for Onychomycosis.

People living with HIV (PLWH) display altered gut epithelium that allows for the translocation of microbial products, contributing to systemic immune activation. Although there are numerous studies which examine the gut bacterial microbiome in PLWH, few studies describing the fungal microbiome, or the mycobiome, have been reported. Like the gut bacterial microbiome, the fungal microbiome and its by-products play a role in maintaining the body's homeostasis and modulating immune function. We conducted a prospective study to assess the effects of oral terbinafine, an antifungal agent widely used against onychomycosis, on gut permeability and microbiome composition in ART-treated PLWH (trial registration: ChiCTR2100043617). Twenty participants completed all follow-up visits. During terbinafine treatment, the levels of the intestinal fatty acid binding protein (I-FABP) significantly increased, and the levels of interleukin-6 (IL-6) significantly decreased, from baseline to week 12. Both markers subsequently returned to pre-treatment levels after terbinafine discontinuation. After terbinafine treatment, the abundance of fungi decreased significantly, while the abundance of the bacteria did not change. After terbinafine discontinuation, the abundance of fungi returned to the levels observed pre-treatment. Moreover, terbinafine treatment induced only minor changes in the composition of the gut bacterial and fungal microbiome. In summary, oral terbinafine decreases fungal microbiome abundance while only slightly influencing gut permeability and microbial translocation in ART-treated PLWH. This study's findings should be validated in larger and more diverse studies of ART-treated PLWH; our estimates of effect size can be used to inform optimal sample sizes for future studies.

Genetic Analysis of Novel Fertility Restoration Genes (qRf3 and qRf6) in Dongxiang Wild Rice Using GradedPool-Seq Mapping and QTL-Seq Correlation Analysis.

The improvement of grain yield, quality, and resistance can be achieved through the utilization of heterosis. The combination of cytoplasmic male sterility (CMS) and fertility restoration (Rf) gene(s) greatly facilitates the commercial development of three-line hybrid rice based on heterosis. The basis for investigating the relationship between CMS and Rf genes lies in the rapid localization of wild rice fertility restoration genes. A set of the BC4F5 population derived from interspecific crosses between Xieqingzao B (XB) and the BC1F9 XB//Dongxiang wild rice (DWR)/XB line L5339 was used to detect quantitative trait loci (QTL) for fertility restoration. The population was then crossed with two male sterile lines, Zhong9A (Z9A) and DongB11A (DB11A), in order to generate a testcrossing population for investigating spikelet fertility. Based on the linkage mapping, seven QTLs were detected on chromosomes 1, 3, 5, 6, 8, and 10, explaining 2.76 to 12.46% of the phenotypic variation. Of them, two novel fertility restoration QTLs, qRf3 and qRf6, can restore fertility of the CMS-DWR line DB11A by 16.56% and 15.12%, respectively. By employing joint QTL-seq and GradedPool-Seq methods, two novel Rf QTLs for DB11A, qRf3 and qRf6, were identified at the physical locations of 10,900,001-11,700,000 bp and 28,016,785-31,247,556 bp, respectively. These findings are useful for exploring the natural variations of Rf genes in rice. Therefore, rice's new genetic resources for the selection and breeding of rice restorer lines provide promising candidates for QTL fine localization and clarification.

Controlled Growth of Highly Oriented Perovskite Crystals in Polymer Solutions via Selective Solvent Vapor Diffusion.

Organic-inorganic hybrid perovskites have garnered significant attention in optoelectronics owing to their outstanding tunable optical characteristics. Controlled growth of perovskite nanocrystals from solutions is key for controlling the emission intensity and photoluminescence lifetime of perovskites. In particular, most studies have focused on controlling the crystallization of perovskite through chemical treatment using chelating ligands or physical treatment via antisolvent diffusion, and there exists a trade-off between the photoluminescence intensity and lifetime of perovskites. Herein, a selective solvent vapor-assisted crystallization with the aid of a functional polymer, which nanoscale perovskite crystals are grown andante from precursor solution, is presented for tuning the crystallization and optical properties of a common halide perovskite, methylammonium lead bromide (MAPbBr3 ). The proposed method here produces perovskite nanocrystals in the range of 200-300 nm. The spin-coated thin film formed from the perovskite solution exhibits strong green photoluminescence with a long lifetime. The effects of the functional group and polymer dosage on the crystallization of MAPbBr3 are systematically investigated, and the crystallization mechanism is explained based on a modified LaMer model. This study provides an advanced solution process for precisely controlling perovskite crystallization to enhance their optical properties for next-generation optoelectronic devices.

Focal lymphoblastic transformation of chronic myelogenous leukemia develops into erythroid leukemia: A case report.

BACKGROUND: We present a case of focal lymphoblastic transformation to erythroid leukemia following acute myeloblastic transformation in a patient with chronic myelogenous leukemia (CML) and discuss its mechanism of occurrence and development. CASE SUMMARY: The presence of the Philadelphia (Ph) chromosome was identified through karyotype analysis, while the BCR-ABL fusion gene was detected using quantitative real-time polymerase chain reaction of the peripheral blood sample. Fluorescence in situ hybridization was used to detect the expression of the BCR-ABL gene in the lymphoma. Antigen expression and gene mutations in the primitive cells were detected by flow cytometry. The analysis confirmed the presence of CML along with focal lymphoblastic transformation to erythroid leukemia. Additionally, the patient was found to have secondary erythroid leukemia, along with multiple new gene mutations and abnormalities in complex karyotypes of chromosomes. CONCLUSION: Our findings suggest a possible molecular basis for the focal lymphoblastic transformation secondary to myeloblastic transformation in patients with CML.

Caulerpa lentillifera improves ethanol-induced liver injury and modulates the gut microbiota in rats.

Caulerpa lentillifera (CL), also called sea grape, is a type of edible green alga which was reported to have antioxidative and immunomodulatory potential. This study aimed to investigate the hepatoprotective effects of CL in a rat model of chronic ethanol exposure. Wistar rats were assigned to four groups and supplied with an isocaloric control liquid diet (group C), an ethanol liquid diet (group E), a control liquid diet supplemented with 5% CL (group CC), or an ethanol liquid diet supplemented with 5% CL (group EC) for a 12-week experimental period. Ethanol feeding induced steatosis, inflammation, and changes in the gut microbiota by the end of the study, whereas CL supplementation significantly improved liver injuries and decreased circulatory endotoxin levels. Moreover, we also found that CL reversed ethanol-induced elevation of hepatic toll-like receptor 4 (TLR4), MyD88 protein expression, the phosphorylated-nuclear factor (NF)-κB-to-NF-κB ratio, and proinflammatory cytokine concentrations. Additionally, CL also increased the abundance of Akkermansia and tight junction proteins and diminished the Firmicutes-to-Bacteroidetes ratio. Dietary CL inhibited the progression of alcoholic liver disease, and some of the possible mechanisms may be strengthening the intestinal barrier function, alleviating dysbiosis, and modulating the TLR4 pathway.

Light-Driven and Metal-Organic Framework Synergetic Loaded DNA Tetrahedral Amplifier for Exonuclease III-Powered All-in-One Biosensing and Chemotherapy in Live Biosystems.

As a result of inaccurate biosensing and difficult synergetic loading, it is challenging to further impel DNA amplifiers to perform therapeutic application. Herein, we introduce some innovative solutions. First, a smart light-driven biosensing concept based on embedding nucleic acid modules with a simple photocleavage-linker is proposed. In this system, the target identification component is exposed on irradiation with ultraviolet light, thus avoiding an always-on biosensing response during biological delivery. Further, in addition to providing controlled spatiotemporal behavior and precise biosensing information, a metal-organic framework is used for the synergetic loading of doxorubicin in the internal pores, whereafter a rigid DNA tetrahedron-sustained exonuclease III-powered biosensing system is attached to prevent drug leakage and enhance resistance to enzymatic degradation. By selecting a next-generation breast cancer correlative noncoding microRNA biomarker (miRNA-21) as a model low-abundance analyte, a highly sensitive in vitro detection ability even allowing to distinguish single-base mismatching is demonstrated. Moreover, the all-in-one DNA amplifier shows excellent bioimaging competence and good chemotherapy efficacy in live biosystems. These findings will drive research into the use of DNA amplifiers in diagnosis and therapy integrated fields.

Face morphing attack detection based on high-frequency features and progressive enhancement learning.

Face morphing attacks have become increasingly complex, and existing methods exhibit certain limitations in capturing fine-grained texture and detail changes. To overcome these limitation, in this study, a detection method based on high-frequency features and progressive enhancement learning was proposed. Specifically, in this method, first, high-frequency information are extracted from the three color channels of the image to accurately capture the details and texture changes. Next, a progressive enhancement learning framework was designed to fuse high-frequency information with RGB information. This framework includes self-enhancement and interactive-enhancement modules that progressively enhance features to capture subtle morphing traces. Experiments conducted on the standard database and compared with nine classical technologies revealed that the proposed approach achieved excellent performance.

Nobiletin inhibits de novo FA synthesis to alleviate gastric cancer progression by regulating endoplasmic reticulum stress.

BACKGROUND: Gastric cancer (GC) is a common malignant tumor with limited treatment options. The natural flavonoid nobiletin (NOB) is a beneficial antioxidant that possesses anticancer activity. However, the mechanisms by which NOB inhibits GC progression remain unclear. METHODS: A CCK-8 assay was performed to determine cytotoxicity. Cell cycle and apoptosis analyses were performed by flow cytometry. RNA-seq was performed to detect differential gene expression after NOB treatment. RT‒qPCR, Western blot and immunofluorescence staining were used to examine the underlying mechanisms of NOB in GC. Xenograft tumor models were constructed to verify the effect of NOB and its specific biological mechanism in GC. RESULTS: NOB inhibited cell proliferation, caused cell cycle arrest and induced apoptosis in GC cells. KEGG classification identified that the inhibitory effect of NOB on GC cells mainly involved the lipid metabolism pathway. We further showed that NOB reduced de novo fatty acid (FA) synthesis, as evidenced by the decreased levels of neutral lipids and the expression levels of ACLY, ACACA and FASN, and ACLY abrogated the effect of NOB on lipid deposits in GC cells. In addition, we also found that NOB triggered endoplasmic reticulum (ER) stress by activating the IRE-1α/GRP78/CHOP axis, but overexpression of ACLY reversed ER stress. Mechanistically, inhibiting ACLY expression with NOB significantly reduced neutral lipid accumulation, thereby inducing apoptosis by activating IRE-1α-mediated ER stress and inhibiting GC cell progression. Finally, in vivo results also demonstrated that NOB inhibited tumor growth by decreasing de novo FA synthesis. CONCLUSION: NOB could inhibit the expression of ACLY to activate IRE-1α-induced ER stress, which ultimately led to GC cell apoptosis. Our results provide novel insight into the use of de novo FA synthesis for GC treatment and are the first to reveal that NOB inhibits GC progression by ACLY-dependent ER stress.

Individualized 3D-printed navigation template-assisted tension band wiring for olecranon fractures.

PURPOSE: 3D printing techniques guide precision medicine and show great development potential in clinical applications. The purpose of this study was to compare the clinical outcomes of 3D-printed navigation templates versus free-hand in tension band wiring (TBW) procedures for olecranon fractures. METHODS: Patients who underwent TBW due to Mayo type II olecranon fractures between January 2019 and December 2021 in our hospital were prospectively enrolled in the study. The patients were divided into the 3D printed navigation template guiding TBW group (3D printed group) and the free-hand TBW group (free-hand group). The primary endpoint of this study was the success rate of the bicortical placement of Kirschner wires (K-wires). Times of intraoperative fluoroscopy, operation times, complications, VAS scores, and Mayo Elbow Performance Scores (MEPS) were analyzed as the secondary outcomes measure. RESULTS: The success rate of the bicortical placement of K-wires was 85.7% in the 3D Printed group was significantly higher than the free-hand group (60%). There were fewer times of intraoperative fluoroscopy in the 3D Printed group (1.43 ± 0.51) than that in the free-hand group (2.60 ± 1.00) with statistical significance (P < 0.05). At the date of the last follow-up, four patients suffer from pain and skin injury at the K-wires insertion site in the 3D Printed group and 14 patients in the free-hand group, a significant difference between the two groups (P < 0.05). No statistically significant differences were found in operation time, VAS scores, and MEPS between the two groups. CONCLUSIONS: The individualized 3D-printed navigation template-assisted TBW demonstrated good accuracy and resulted in reduced times of intraoperative fluoroscopy and complication compared to the free-hand TBW for olecranon fractures.