Structure and activity of the septal peptidoglycan hydrolysis machinery crucial for bacterial cell division.

The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria.

V-Based MXene/MAX Heterostructure Composites with Enhancing Dielectric Loss for Broadband Microwave Absorption.

Electromagnetic wave absorption performance is strictly dependent on attenuation and impedance matching, which are directly influenced by the ratio of MXene/MAX in the multilayer structured MXene/MAX composites. However, there is still a challenge to achieve collaborative optimization of dielectric loss and impedance matching by precisely regulating the proportional relationship of MXene/MAX. Herein, V-based MXene/MAX heterostructure composites with different V2C/V2AlC ratios were successfully synthesized by rationally controlling the temperature and time of the hydrothermal reaction. Experimental results indicated that V2C-100 °C-1 harvested the balance between reduced impedance matching and enhanced dielectric losses, which was attributed to the mildly enhanced conduction loss and polarization loss. The first principles indicated that abundant electrons migrate from the V atoms of the MXene to the C atoms of the MAX phase. The charge redistributed and accumulated at the interface, exciting the increase in the dielectric loss of V2C-100 °C-1. As a result, the V2C-100 °C-1 heterostructure composite had an excellent electromagnetic absorption effect with a minimum reflection loss of -50.06 dB and a wide effective absorption bandwidth of 4.0 GHz (12.72-16.72 GHz). This work provides a valuable experience for the development of efficient MXene-based microwave absorbing materials.

Functional characterization and structural basis of a reversible glycosyltransferase involves in plant chemical defence.

Plants experience numerous biotic stresses throughout their lifespan, such as pathogens and pests, which can substantially affect crop production. In response, plants have evolved various metabolites that help them withstand these stresses. Here, we show that two specialized metabolites in the herbaceous perennial Belamcanda chinensis, tectorigenin and its glycoside tectoridin, have diverse defensive effects against phytopathogenic microorganisms and antifeeding effects against insect pest. We further functionally characterized a 7-O-uridine diphosphate glycosyltransferase Bc7OUGT, which catalyses a novel reversible glycosylation of tectorigenin and tectoridin. To elucidate the catalytic mechanisms of Bc7OUGT, we solved its crystal structure in complex with UDP and UDP/tectorigenin respectively. Structural analysis revealed the Bc7OUGT possesses a narrow but novel substrate-binding pocket made up by plentiful aromatic residues. Further structure-guided mutagenesis of these residues increased both glycosylation and deglycosylation activities. The catalytic reversibility of Bc7OUGT was also successfully applied in an one-pot aglycon exchange reaction. Our findings demonstrated the promising biopesticide activity of tectorigenin and its glycosides, and the characterization and mechanistic study of Bc7OUGT could facilitate the design of novel reversible UGTs to produce valuable glycosides with health benefits for both plants and humans.

A novel model for predicting prolonged stay of patients with type-2 diabetes mellitus: a 13-year (2010-2022) multicenter retrospective case-control study.

BACKGROUND: Length of stay (LOS) is an important metric for evaluating the management of inpatients. This study aimed to explore the factors impacting the LOS of inpatients with type-2 diabetes mellitus (T2DM) and develop a predictive model for the early identification of inpatients with prolonged LOS. METHODS: A 13-year multicenter retrospective study was conducted on 83,776 patients with T2DM to develop and validate a clinical predictive tool for prolonged LOS. Least absolute shrinkage and selection operator regression model and multivariable logistic regression analysis were adopted to build the risk model for prolonged LOS, and a nomogram was taken to visualize the model. Furthermore, receiver operating characteristic curves, calibration curves, and decision curve analysis and clinical impact curves were used to respectively validate the discrimination, calibration, and clinical applicability of the model. RESULTS: The result showed that age, cerebral infarction, antihypertensive drug use, antiplatelet and anticoagulant use, past surgical history, past medical history, smoking, drinking, and neutrophil percentage-to-albumin ratio were closely related to the prolonged LOS. Area under the curve values of the nomogram in the training, internal validation, external validation set 1, and external validation set 2 were 0.803 (95% CI [confidence interval] 0.799-0.808), 0.794 (95% CI 0.788-0.800), 0.754 (95% CI 0.739-0.770), and 0.743 (95% CI 0.722-0.763), respectively. The calibration curves indicated that the nomogram had a strong calibration. Besides, decision curve analysis, and clinical impact curves exhibited that the nomogram had favorable clinical practical value. Besides, an online interface ( https://cytjt007.shinyapps.io/prolonged_los/ ) was developed to provide convenient access for users. CONCLUSION: In sum, the proposed model could predict the possible prolonged LOS of inpatients with T2DM and help the clinicians to improve efficiency in bed management.

Quantitative Evaluation of the Contribution of Each Aldo-Keto Reductase and Short-Chain Dehydrogenase/Reductase Isoform to Reduction Reactions of Compounds Containing a Ketone Group in the Human Liver.

Enzymes of the aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase superfamilies are involved in the reduction of compounds containing a ketone group. In most cases, multiple isoforms appear to be involved in the reduction of a compound, and the enzyme(s) that are responsible for the reaction in the human liver have not been elucidated. The purpose of this study was to quantitatively evaluate the contribution of each isoform to reduction reactions in the human liver. Recombinant cytosolic isoforms were constructed, i.e., AKR1C1, AKR1C2, AKR1C3, AKR1C4, and carbonyl reductase 1 (CBR1), and a microsomal isoform, 11ß-hydroxysteroid dehydrogenase type 1 (HSD11B1), and their contributions to the reduction of 10 compounds were examined by extrapolating the relative expression of each reductase protein in human liver preparations to recombinant systems quantified by liquid chromatography-mass spectrometry. The reductase activities for acetohexamide, doxorubicin, haloperidol, loxoprofen, naloxone, oxcarbazepine, and pentoxifylline were predominantly catalyzed by cytosolic isoforms, and the sum of the contributions of individual cytosolic reductases was almost 100%. Interestingly, AKR1C3 showed the highest contribution to acetohexamide and loxoprofen reduction, although previous studies have revealed that CBR1 mainly metabolizes them. The reductase activities of bupropion, ketoprofen, and tolperisone were catalyzed by microsomal isoform(s), and the contributions of HSD11B1 were calculated to be 41%, 32%, and 104%, respectively. To our knowledge, this is the first study to quantitatively evaluate the contribution of each reductase to the reduction of drugs in the human liver. SIGNIFICANCE STATEMENT: To our knowledge, this is the first study to determine the contribution of aldo-keto reductase (AKR)-1C1, AKR1C2, AKR1C3, AKR1C4, carbonyl reductase 1, and 11ß-hydroxysteroid dehydrogenase type 1 to drug reductions in the human liver by utilizing the relative expression factor approach. This study found that AKR1C3 contributes to the reduction of compounds at higher-than-expected rates.

A novel imaging scoring method for identifying facial canal dehiscence: an ultra-high-resolution CT study.

OBJECTIVES: Facial canal dehiscence (FCD), typically found in the tympanic segment, is a risk factor for facial nerve injury. An imaging scoring method was proposed to identify FCD based on ultra-high-resolution CT. METHODS: Forty patients (21 females and 19 males, mean age 44.3 ± 17.4 years), whose tympanic facial canal (FC) was examined during otological surgery, were divided into the FCD group (n = 29) and the control group (n = 11) based on surgical findings. Imaging appearance of tympanic FC was scored 0-3: 0 = no evident bony covering, 1 = discontinuous bony covering with linear deficiency, 2 = discontinuous bony covering with dotted deficiency, and 3 = continuous bony covering. Both lateral and inferior walls were assigned a score as LFCD and IFCD, respectively. An FCD score was calculated as LFCD + IFCD. The diagnostic value of the FCD score was tested using the ROC curve. RESULTS: The inter-observer agreement was moderate for the lateral wall (Cohen's κ coefficient 0.416, 95% CI 0.193-0.639), and good for the inferior wall (Cohen's κ coefficient 0.702, 95% CI 0.516-0.888). In the FCD group, the most common appearance for both walls was discontinuous bony covering with linear deficiency (LFCD = 1, 22/29, 75.9%; IFCD = 1, 15/29, 51.7%). An FCD score of less than 4 was associated with high sensitivity (0.82) and specificity (0.93) for identifying FCD, with an AUC of 0.928. CONCLUSIONS: Using the proposed scoring method, FCD score < 4 could identify FCD of the tympanic segment with high concordance with surgical findings. KEY POINTS: • Imaging appearance of the tympanic facial canal (FC) is divided into four types based on ultra-high-resolution CT images. • The most common appearance of FC with facial canal dehiscence (FCD) is discontinuous bony covering with linear deficiency. • An FCD score, consisting of scores of the lateral and inferior walls, less than 4 is highly indicative of FCD.

Clinical Data based XGBoost Algorithm for infection risk prediction of patients with decompensated cirrhosis: a 10-year (2012-2021) Multicenter Retrospective Case-control study.

OBJECTIVES: To appraise effective predictors for infection in patients with decompensated cirrhosis (DC) by using XGBoost algorithm in a retrospective case-control study. METHODS: Clinical data were retrospectively collected from 6,648 patients with DC admitted to five tertiary hospitals. Indicators with significant differences were determined by univariate analysis and least absolute contraction and selection operator (LASSO) regression. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed infection risk prediction model with simple-tree XGBoost model. Finally, the simple-tree XGBoost model is compared with the traditional logical regression (LR) model. Performances of models were evaluated by area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. RESULTS: Six features, including total bilirubin, blood sodium, albumin, prothrombin activity, white blood cell count, and neutrophils to lymphocytes ratio were selected as predictors for infection in patients with DC. Simple-tree XGBoost model conducted by these features can predict infection risk accurately with an AUROC of 0.971, sensitivity of 0.915, and specificity of 0.900 in training set. The performance of simple-tree XGBoost model is better than that of traditional LR model in training set, internal verification set, and external feature set (P < 0.001). CONCLUSIONS: The simple-tree XGBoost predictive model developed based on a minimal amount of clinical data available to DC patients with restricted medical resources could help primary healthcare practitioners promptly identify potential infection.

High-titer production of staurosporine by heterologous expression and process optimization.

Staurosporine is the most well-known member of the indolocarbazole alkaloid family; it can induce apoptosis of many types of cells as a strong protein kinase inhibitor, and is used as an important lead compound for the synthesis of the antitumor drugs. However, the low fermentation level of the native producer remains the bottleneck of staurosporine production. Herein, integration of multi-copy biosynthetic gene cluster (BGC) in well characterized heterologous host and optimization of the fermentation process were performed to enable high-level production of staurosporine. First, the 22.5 kb staurosporine BGC was captured by CRISPR/Cas9-mediated TAR (transformation-associated recombination) from the native producer (145 mg/L), and then introduced into three heterologous hosts Streptomyces avermitilis (ATCC 31267), Streptomyces lividans TK24 and Streptomyces albus J1074 to evaluate the staurosporine production capacity. The highest yield was achieved in S. albus J1074 (750 mg/L), which was used for further production improvement. Next, we integrated two additional staurosporine BGCs into the chromosome of strain S-STA via two different attB sites (vwb and TG1), leading to a double increase in the production of staurosporine. And finally, optimization of fermentation process by controlling the pH and glucose feeding could improve the yield of staurosporine to 4568 mg/L, which was approximately 30-fold higher than that of the native producer. This is the highest yield ever reported, paving the way for the industrial production of staurosporine. KEYPOINTS: • Streptomyces albus J1074 was the most suitable heterologous host to express the biosynthetic gene cluster of staurosporine. • Amplification of the biosynthetic gene cluster had obvious effect on improving the production of staurosporine. • The highest yield of staurosporine was achieved to 4568 mg/L by stepwise increase strategy.

Development and validation of a risk prediction model for osteoporosis in elderly patients with type 2 diabetes mellitus: a retrospective and multicenter study.

BACKGROUND: This study aimed to construct a risk prediction model to estimate the odds of osteoporosis (OP) in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate its prediction efficiency. METHODS: This study included 21,070 elderly patients with T2DM who were hospitalized at six tertiary hospitals in Southwest China between 2012 and 2022. Univariate logistic regression analysis was used to screen for potential influencing factors of OP and least absolute shrinkage. Further, selection operator regression (LASSO) and multivariate logistic regression analyses were performed to select variables for developing a novel predictive model. The area under the receiver operating characteristic curve (AUROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to evaluate the performance and clinical utility of the model. RESULTS: The incidence of OP in elderly patients with T2DM was 7.01% (1,476/21,070). Age, sex, hypertension, coronary heart disease, cerebral infarction, hyperlipidemia, and surgical history were the influencing factors. The seven-variable model displayed an AUROC of 0.713 (95% confidence interval [CI]:0.697-0.730) in the training set, 0.716 (95% CI: 0.691-0.740) in the internal validation set, and 0.694 (95% CI: 0.653-0.735) in the external validation set. The optimal decision probability cut-off value was 0.075. The calibration curve (bootstrap = 1,000) showed good calibration. In addition, the DCA and CIC demonstrated good clinical practicality. An operating interface on a webpage ( https://juntaotan.shinyapps.io/osteoporosis/ ) was developed to provide convenient access for users. CONCLUSIONS: This study constructed a highly accurate model to predict OP in elderly patients with T2DM. This model incorporates demographic characteristics and clinical risk factors and may be easily used to facilitate individualized prediction.

Communicating Antibiotic Resistance via Linguistic Agency Assignment.

Antibiotic resistance is a serious health threat that healthcare providers must communicate to the public to decelerate its development. Prior studies have shown that linguistic agency assignment is a viable strategy to frame health threats in a way that both conveys their severity and preserves audience members' sense of self-efficacy. In the current study, we examined this messaging strategy in the context of antibiotic resistance. Individuals' perceptions of the threat and efficacy, behavioral intentions, fear appeals, and evaluations of the educational fact sheet were explored. Participants (N = 449) were randomly assigned to one of the eight conditions crossing threat agency (bacteria/human), temporal agency (antibiotic resistance/human) and imagery agency (taking antibiotics/antibiotics). The results revealed that individuals' perceived severity, susceptibility, response efficacy, and self-efficacy were positively associated with their intentions to use antibiotics judiciously. The interaction effects between perceived threat and efficacy predicted behavioral intentions and the persuasiveness of the fact sheet. Relative to bacteria threat agency, human agency assignment led to significantly higher behavioral intentions. Also, readers of the human temporal agency condition reported higher persuasiveness toward the fact sheet than readers of the resistance condition. The implications, limitations, and future research directions of the study are discussed.

An exploratory study of imaging diagnostic clues for overhanging facial nerve in ultra-high-resolution CT.

PURPOSE: Overhanging facial nerve (FN) may be challenging in imaging diagnosis. The purpose of the study is to investigate the imaging clues for overhanging FN near the oval window on ultra-high-resolution computed tomography (U-HRCT) images. METHODS: Between October 2020 and August 2021, images of 325 ears (276 patients) were included in the analysis obtained by an experimental U-HRCT scanner. On standard reformatted images, the morphology of FN was evaluated and its position was quantitatively measured using the following indices: protrusion ratio (PR), protruding angle (A), position of FN (P-FN), distance between FN and stapes (D-S), and distance between FN and anterior and posterior crura of stapes (D-AC and D-PC). According to the FN morphology in imaging, images were divided into overhanging FN group and non-overhanging FN group. Binary univariate logistic regression analysis was used to identify the imaging indices independently associated with overhanging FN. RESULTS: Overhanging FN was found in 66 ears (20.3%), which manifested as downwards protrusion of either local segment (61 ears, 61/66) or the entire course near the oval window (5 ears, 5/66). D-AC [odds ratio: 0.063, 95% CI 0.012-0.334, P = 0.001) and D-PC (odds ratio: 0.008, 95% CI 0.001-0.050, P = 0.000) were identified as independent predictors of FN overhang (area under the curve: 0.828 and 0.865, respectively). CONCLUSION: Abnormal morphology of the lower margin of FN, D-AC and D-PC on U-HRCT images provide valuable diagnostic clues for FN overhang.

Self-reported sleep disturbance is significantly associated with depression, anxiety, self-efficacy, and stigma in Chinese patients with rheumatoid arthritis.

The objective of this article is to assess self-reported sleep disturbance and identify psychological, clinical, and sociodemographic factors that might influence sleep disturbance in patients with rheumatoid arthritis (RA). The study included 141 patients with confirmed RA (84.4% women, mean age 56.87 years). The Pittsburgh Sleep Quality Index, the Chinese version of rheumatoid arthritis self-efficacy scale, the Chinese version of Anxiety Depression Distress Inventory-27, the Chinese version of Stigma Scale for Chronic Illness, Visual Analogue Scale-Pain, disease activity index were used. Sleep disturbance was positively correlated with age, pain, disease activity, depression and anxiety, and stigma, while self-efficacy was correlated negatively with sleep disturbance. Multiple linear regression analysis revealed that depression, anxiety, self-efficacy, and stigma explained 77.4% of sleep quality variance. The data has demonstrated a suggestive relationship between low sleep quality and anxiety, depression, self-efficacy, and stigma. Patients reporting poor sleep, fatigue, and pain might have particular psychological intervention needs focusing on distress or anxiety symptoms, low self-efficacy, and high stigma.

Potential of ultra-high-resolution CT in detecting osseous changes of temporomandibular joint: experiences in temporomandibular disorders.

BACKGROUND: Osseous changes of the temporomandibular joint (TMJ) are related to the progression of temporomandibular disorders (TMD), and computed tomography (CT) plays a vital role in disease evaluation. OBJECTIVE: The aims of this study were to evaluate the image quality and diagnostic value of ultra-high-resolution CT (U-HRCT) in TMD compared to cone-beam CT (CBCT). METHODS: TMD patients who underwent both CBCT and U-HRCT between November 2021 and September 2022 were retrospectively included. Image quality scores were assigned for four osseous structures (the cortical and trabecular bones of the condyle, articular eminence, and glenoid fossa) by two independent observers from Score 1 (unacceptable) to Score 5 (excellent). Diagnostic classification of TMD was categorized as follows: Class A (no evident lesion), Class B (indeterminate condition) and Class C (definitive lesion). Image quality scores and diagnostic classifications were compared between CBCT and U-HRCT. The Cohen's Kappa test, Wilcoxon signed-rank test, Chi-square test and Fisher's exact test were conducted for statistical analysis. RESULTS: Thirty TMD patients (median age, 30 years; interquartile range, 26-43 years; 25 females) with 60 TMJs were enrolled. Image quality scores were higher for U-HRCT than for CBCT by both observers (all Ps < 0.001). Definitive diagnoses (Class A and C) were achieved in more cases with U-HRCT than with CBCT (93.3% vs. 65.0%, Fisher's exact value = 7.959, P = 0.012). Among the 21 cases which were ambiguously diagnosed (Class B) by CBCT, definitive diagnosis was achieved for 17 cases (81.0%) using U-HRCT. CONCLUSIONS: U-HRCT can identify osseous changes in TMD, providing improved image quality and a more definitive diagnosis, which makes it a feasible diagnostic imaging method for TMD.

[Determination of vitamin A, D and E in dishes by two-dimensional liquid chromatography].

OBJECTIVE: To establish a method for the simultaneous determination of vitamins A, D and E in dishes by two-dimensional liquid chromatography. METHODS: The samples were saponified and extracted with a mixture of ethyl acetate and n-hexane(3∶2, V/V)under the protection of antioxidants, and determined by two-dimensional liquid chromatography. The baseline separation of retinol, α-tocopherol, ß-tocopherol, γ-tocopherol, δ-tocopherol, and α-tocotrienols was achieved by using Alphasil pentafluorophenyl column(PFP, 150 mm×4.6 mm, 5 µm) as the one-dimensional column, and using water and methanol as mobile phases for gradient elution under the fluorescence detector. The separation detection of ergocalciferol and cholecalciferol from other impurities was achieved on the UV detector by Alphasil VC-C_(18) column(150 mm×4.6 mm, 3.5 µm) as the two-dimensional column. RESULTS: The baseline separation detection of retinol, ergocalciferol, cholecalciferol and five tocopherols was achieved. The compounds were linearly correlated within the set range, and the correlation coefficients were >0.999. The recovery rate of the method was between 85.4% and 106.4%. The detection limit of all-trans retinol was 0.7 µg/100 g, and the limit of quantitation was 2.4 µg/100 g. The limits of detection and quantification of tocopherols ranged from 1.1 to 2.5 µg/100 g and 3.6 to 8.3 µg/100 g. The detection limit of ergocalciferol and cholecalciferol was 0.3 µg/100 g, and the limit of quantification was 1.0 µg/100 g. In the end, finished dishes such as dry fried hairtail, braised mushroom, steamed egg with soy sauce, sweet and sour ribs were repeatedly measured by this method for six times, and the relative standard deviation was less than 10%. CONCLUSION: The method has the characteristics of simple operation, good repeatability, high accuracy and friendly to operators and ecological environment. It can realize the simultaneous typing detection of vitamins A, D and E in finished dishes.

Interleukin-1 receptor-associated kinase 2 promotes inflammatory reactions by activating the nuclear factor kappa-B signaling pathway in diabetic nephropathy.

Diabetic nephropathy (DN) is a major complication of diabetes. Interleukin-1 receptor-associated kinase 2 (IRAK2) has been implicated in various diseases. This study aimed to investigate the role of IRAK2 in DN progression and its association with inflammation and the nuclear factor-kappa B (NF-κB) signaling pathway. DN model mice were generated by intraperitoneal injection of streptozotocin. IRAK2 expression was upregulated in the DN model mice. IRAK2 knockdown increased weight and reduced blood glucose levels in DN model mice. In addition, IRAK2 downregulation improved glomerular morphology in DN mice. IRAK2 knockdown reduced the levels of kidney damage biomarkers (24-h urinary protein, urine albumin-creatinine ratio, and plasma creatinine) and inflammatory cytokines (IL-6, tumor necrosis factor [TNF]-α, TNF-1R, and TNF-2R). Moreover, IRAK2 activated the NF-κB signaling pathway in DN model mice. Overexpression of NF-κB exacerbated DN progression, and IRAK2 knockdown reversed these effects. IRAK2 promoted DN progression and inflammation by activating the NF-κB signaling pathway. These findings suggest that IRAK2 is a potential therapeutic target for DN treatment.

Nesfatin-1 exerts protective effects on acidosis-stimulated chondrocytes and rats with adjuvant-induced arthritis by inhibiting ASIC1a expression.

Nesfatin-1, a newly identified energy-regulating peptide, has been reported to possess antioxidant, anti-inflammatory, and antiapoptotic properties; however, to date, its effect on rheumatoid arthritis (RA) has not been previously explored in detail. We previously showed that activation of acid-sensing ion channel 1a (ASIC1a) by acidosis plays an important role in RA pathogenesis. Therefore, in this study, we evaluated the effects of nesfatin-1 on acidosis-stimulated chondrocyte injury in vitro and in vivo and examined the involvement of ASIC1a and the mechanism underlying the effects of nesfatin-1 on RA. Acid-stimulated articular chondrocytes were used to examine one of the several possible mechanisms underlying RA pathogenesis in vitro. The mRNA expression profile of acid-induced chondrocytes treated or not treated with nesfatin-1 was investigated by RNA sequencing. The effects of nesfatin-1 on oxidative stress, inflammation, and apoptosis in acid-induced chondrocytes were measured. The mechanistic effect of nesfatin-1 on ASIC1a expression and intracellular Ca2+ in acid-stimulated chondrocytes was studied. Rats with adjuvant-induced arthritis (AA) were used for in vivo analysis of RA pathophysiology. Cartilage degradation and ASIC1a expression in chondrocytes were detected in rats with AA after intraarticular nesfatin-1 injection. The in vitro experiments showed that nesfatin-1 decreased acidosis-induced cytotoxicity and elevation of intracellular Ca2+ levels in chondrocytes. Moreover, it attenuated acid-induced oxidative stress, inflammation, and apoptosis in chondrocytes. Nesfatin-1 decreased ASIC1a protein levels in acid-stimulated chondrocytes via the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and nuclear factor kappa-B (NF-κB) signaling pathways. In vivo analysis showed that nesfatin-1 ameliorated cartilage degradation and decreased ASIC1a expression in the chondrocytes of rats with AA. Collectively, nesfatin-1 suppressed acidosis-induced oxidative stress, inflammation, and apoptosis in acid-stimulated chondrocytes and alleviated arthritis symptoms in rats with AA, and its mechanism may be related to its ability to decrease ASIC1a protein levels via the MAPK/ERK and NF-κB pathways.

Quinary High-Entropy-Alloy@Graphite Nanocapsules with Tunable Interfacial Impedance Matching for Optimizing Microwave Absorption.

Designing heterogeneous interfaces and components at the nanoscale is proven effective for optimizing electromagnetic wave absorption and shielding properties, which can achieve desirable dielectric polarization and ferromagnetic resonances. However, it remains a challenge for the precise control of components and microstructures via an efficient synthesis approach. Here, the arc-discharged plasma method is proposed to synthesize core@shell structural high-entropy-alloy@graphite nanocapsules (HEA@C-NPs), in which the HEA nanoparticles are in situ encapsulated within a few layers of graphite through the decomposition of methane. In particular, the HEA cores can be designed via combinations of various transition elements, presenting the optimized interfacial impedance matching. As an example, the FeCoNiTiMn HEA@C-NPs obtain the minimum reflection loss (RLmin ) of -33.4 dB at 7.0 GHz (3.34 mm) and the efficient absorption bandwidth (≤-10 dB) of 5.45 GHz ranging from 12.55 to 18.00 GHz with an absorber thickness of 1.9 mm. The present approach can be extended to other carbon-coated complex components systems for various applications.

Local-flexible coupling optical-resolution photoacoustic microscopy with enhanced sensitivity.

An acoustic coupling scheme largely determines the performance of optical-resolution photoacoustic microscopy (OR-PAM), including practicability, sensitivity, and stability. In this study, we propose OR-PAM based on a local-flexible acoustic coupling scheme, which includes a well-designed combiner connecting a set of circulating systems. The combiner integrates an objective lens and an ultrasonic transducer, controls the water level, restricts the flow rate, and drains bubbles. The circulating system provides sustained and steady flowing water. The flowing water constrained in the combiner and the circulating system forms a flexible and stable local contact between the sample and the transducer. Phantom experiments demonstrate that the proposed method can maintain high optical resolution but improve the detection sensitivity by approximately 1.9 times in comparison to dry coupling. In vivo imaging experiments of the mouse eyeground are conducted to examine the practicability of the proposed system in biomedicine. Moreover, in vivo experiments show that OR-PAM based on local-flexible coupling can reveal more details of eyeground microvasculatures, benefiting from its enhanced sensitivity. These merits promise that OR-PAM based on local-flexible coupling may have broad applications in biomedical fields.

Tripartite motif-containing protein 46 accelerates influenza A H7N9 virus infection by promoting K48-linked ubiquitination of TBK1.

BACKGROUND: Avian influenza A H7N9 emerged in 2013, threatening public health and causing acute respiratory distress syndrome, and even death, in the human population. However, the underlying mechanism by which H7N9 virus causes human infection remains elusive. METHODS: Herein, we infected A549 cells with H7N9 virus for different times and assessed tripartite motif-containing protein 46 (TRIM46) expression. To determine the role of TRIM46 in H7N9 infection, we applied lentivirus-based TRIM46 short hairpin RNA sequences and overexpression plasmids to explore virus replication, and changes in type I interferons and interferon regulatory factor 3 (IRF3) phosphorylation levels in response to silencing and overexpression of TRIM46. Finally, we used Co-immunoprecipitation and ubiquitination assays to examine the mechanism by which TRIM46 mediated the activity of TANK-binding kinase 1 (TBK1). RESULTS: Type I interferons play an important role in defending virus infection. Here, we found that TRIM46 levels were significantly increased during H7N9 virus infection. Furthermore, TRIM46 knockdown inhibited H7N9 virus replication compared to that in the control group, while the production of type I interferons increased. Meanwhile, overexpression of TRIM46 promoted H7N9 virus replication and decrease the production of type I interferons. In addition, the level of phosphorylated IRF3, an important interferon regulatory factor, was increased in TRIM46-silenced cells, but decreased in TRIM46 overexpressing cells. Mechanistically, we observed that TRIM46 could interact with TBK1 to induce its K48-linked ubiquitination, which promoted H7N9 virus infection. CONCLUSION: Our results suggest that TRIM46 negatively regulates the human innate immune response against H7N9 virus infection.

High efficient freeze-drying technology in food industry.

Freeze-drying technology is an interdisciplinary and complex technology, combined with freezing and vacuum drying, It has become an important technology for heat-sensitive drugs and food preservation. Freeze-dried foods are classified into meat, vegetables, fruits, fungus, and micro-powders, etc. In this paper, the definition, principle, steps, advantages and disadvantages of freeze-drying are summarized, and the research progress of freeze-drying in food industry in recent years is reviewed, including the technological parameters and influencing factors.