Ripretinib inhibits HIV-1 transcription through modulation of PI3K-AKT-mTOR.

Despite the effectiveness of antiretroviral therapy (ART) in prolonging the lifespan of individuals infected with HIV-1, it does not offer a cure for acquired immunodeficiency syndrome (AIDS). The "block and lock" approach aims to maintain the provirus in a state of extended transcriptional arrest. By employing the "block and lock" strategy, researchers endeavor to impede disease progression by preventing viral rebound for an extended duration following patient stops receiving ART. The crux of this strategy lies in the utilization of latency-promoting agents (LPAs) that are suitable for impeding HIV-1 provirus transcription. However, previously documented LPAs exhibited limited efficacy in primary cells or samples obtained from patients, underscoring the significance of identifying novel LPAs that yield substantial outcomes. In this study, we performed high-throughput screening of FDA-approved compound library in the J-Lat A2 cell line to discover more efficacious LPAs. We discovered ripretinib being an LPA candidate, which was validated and observed to hinder proviral activation in cell models harboring latent infections, as well as CD4+ T cells derived from infected patients. We demonstrated that ripretinib effectively impeded proviral activation through inhibition of the PI3K-AKT-mTOR signaling pathway in the HIV-1 latent cells, thereby suppressing the opening states of cellular chromatin. The results of this research offer a promising drug candidate for the implementation of the "block and lock" strategy in the pursuit of an HIV-1 cure.

Prevalence and risk factors of thyroid nodules in breast cancer women with different clinicopathological characteristics: a cross-sectional study.

BACKGROUND: Association between breast cancer (BC) and thyroid nodules (TNs) is still unclear. This research was to estimate the prevalence and risk factors of TN in Chinese BC women at initial diagnosis. METHODS: 1731 Chinese early-stage BC women at initial diagnosis underwent thyroid ultrasound and 1:1 age-matched Chinese healthy women underwent health examination in corresponding period were enrolled for analysis. RESULTS: Prevalence of TN and TI-RADS ≥ 4 TN in BC patients (56.27% and 9.76%) were higher than healthy people (46.04% and 5.49%), respectively, P < 0.001. Among BC patients, prevalence of TN and TI-RADS ≥ 4 TN in hormone receptor (HR)-positive patients (59.57% and 11.81%) were higher than HR-negative patients (48.77% and 5.10%), respectively, P < 0.001, while without difference between HR-negative patients and healthy people. After adjusting for age and BMI, HR-positive patients had higher risk of TN (OR = 1.546, 95%CI 1.251-1.910, P < 0.001) and TI-RADS ≥ 4 TN (OR = 3.024, 95%CI 1.943-4.708, P < 0.001) than HR-negative patients. Furthermore, the risk of TI-RADS ≥ 4 TN was higher in patients with estrogen receptor (ER) positive (OR = 2.933, 95%CI 1.902-4.524), progesterone receptor (PR) positive (OR = 1.973, 95%CI 1.378-2.826), Ki-67 < 20% (OR = 1.797, 95%CI 1.280-2.522), and tumor size < 2 cm (OR = 1.804, 95%CI 1.276-2.552), respectively, P < 0.001. CONCLUSIONS: Prevalence of TN, especially TI-RADS ≥ 4 TN, in Chinese early-stage BC women was higher than healthy people. HR-positive patients had higher prevalence and risk of TN, while without difference between HR-negative patients and healthy people. The increased risk of TN was correlated with ER-positive, PR-positive, lower Ki-67 expression, and smaller tumor size.

Diagnosis of bone marrow involvement in angioimmunoblastic T-cell lymphoma should be based on both [18F]FDG-PET/CT and bone marrow biopsy findings.

OBJECTIVE: During the initial staging of certain lymphoma subtypes, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) has become an alternative to bone marrow biopsy (BMB) for detecting bone marrow (BM) involvement. However, whether [18F]FDG-PET/CT can accurately detect BM involvement in angioimmunoblastic T-cell lymphoma (AITL) remains unknown. Our study aimed to assess the diagnostic and prognostic capability of [18F]FDG-PET/CT for detecting BM involvement in AITL. Methods: This retrospective study included 84 individuals newly diagnosed with AITL who underwent baseline BMB and [18F]FDG-PET/CT. "BM involvement" was defined as one or both of the following: 1) angioimmunoblastic T-cells detected in the BM; or 2) initially heightened focal uptake having disappeared on follow-up [18F]FDG-PET/CT. The ability of [18F]FDG-PET/CT to detect BM cancerous lesions was respectively analyzed by BM involvement confirmed by BMB or the aforementioned definition as the reference standard. The patients' clinical characteristics and survival and prognostic outcomes were respectively analyzed. RESULTS: Of the 84 participants, five (6.0%) displayed positive BMB and PET/BM results, 17 (20.2%) had BMB-positive but PET/BM-negative results, eight (9.5%) showed BMB-negative but PET/BM-positive outcomes, and 54 (64.3%) displayed negative BMB and PET/BM outcomes. Using pre-defined BM involvement as the reference standard, [18F]FDG-PET/CT exhibited a specificity of 100%, sensitivity of 40%, negative predictive value (NPV) of 75%, and positive predictive value (PPV) of 100%. In contrast, using BMB-detected BM involvement as reference, [18F]FDG-PET/CT exhibited a sensitivity, specificity, PPV, and NPV of 38.5%, 76.1%, 22.7%, and 87.1%, respectively. Among patients with PET/BM-positive and BMB-negative outcomes, 62.5% (5/8) underwent upstaging from III to IV. In 58.8% (10/17) of patients who were initially diagnosed with stage II/III disease based on the [18F]FDG-PET/CT results, repeat BMB resulted in upstaging to IV. PET/BM-negative patients had a higher 3-year progression-free survival rate (38.3% vs. 22.8%, p = 0.018) and 3-year overall survival rate (64.4% vs. 34.6%, p = 0.011) than PET/BM-positive patients. CONCLUSION: In AITL patients, PET/BM-positive results may obviate the necessity for repeat BMB to ascertain confirm BM involvement. PET/BM-negative results do not definitively exclude BM involvement. The combined use of [18F]FDG-PET/CT and BMB can increase the diagnostic accuracy of BM involvement for AITL patients.

Eligibility for knee arthroplasty is associated with increased risk of acquired hallux valgus - a Mendelian randomized study.

OBJECTIVE: Clinically, it has been found that patients undergoing knee replacement have a high incidence of concomitant hallux valgus. In this study, we analyzed whether patients with osteoarthritis who underwent surgery and those patient who did not have surgery had an increased risk of hallux valgus by Mendelian randomization and performed reverse causal analysis. DESIGN: Genomewide association study (GWAS) data for osteoarthritis, categorized by knee arthritis with joint replacement, knee arthritis without joint replacement, hip arthritis with joint replacement, and hip arthritis without joint replacement.And acquired hallux valgus were downloaded for Mendelian randomized studies. MR analysis was performed using inverse variance-weighted (IVW), weighted median, and MR-Egger methods. MR-egger regression, MR pleiotropic residuals and outliers (MR-presso), and Cochran's Q statistical methods were used to evaluate heterogeneity and pleiotropy. RESULTS: The IVW results indicate that, compared to healthy individuals, patients who meet the criteria for knee osteoarthritis joint replacement surgery have a significantly higher risk of acquired hallux valgus. There were no significant causal relationships found for the remaining results. No significant heterogeneity or multiplicity was observed in all the Mr analyses. CONCLUSION: Our study supports the increased risk of acquired hallux valgus in patients eligible for knee replacement. There is necessary for clinicians to be concerned about the hallux valgus status of patients undergoing knee arthroplasty.

Spatiotemporal evolution characteristics and driving forces of vegetation cover variations in the Chengdu-Chongqing region of China under the background of rapid urbanization.

The research on the spatiotemporal changes and driving factors of ecosystems in rapidly urbanizing regions has always been a topic of widespread concern. As the fourth pole of China's economic development, the research on the Chengdu-Chongqing region has reference significance for the urbanization process of developing countries such as India, Brazil, and South Africa.The normalized difference vegetation index (NDVI) has been widely applied in studies of plant and ecosystem changes. Based on MODIS NDVI data from 2001 to 2020 and meteorological data of the same period, this study reveals the evolution of NDVI in the Chengdu-Chongqing region from three aspects: the spatiotemporal variation characteristics of NDVI, the prediction of future trends in vegetation coverage, and the response of vegetation to climate change and human activities. During the period of plant growth, the mean NDVI achieved a value of 0.78, and the vegetation coverage rate is increasing year by year. According to the Hurst index, the future NDVI in Chengdu-Chongqing region will tend to decrease, and its trend is opposite to that of the past period of time. The Chengdu-Chongqing region vegetation positively affected by human activities is greater than those negatively affected, and in terms of vegetation degradation, the impact of human activities is greater than climate change.

Grass carp peroxiredoxin 5 and 6-mediated autophagy inhibit grass carp reovirus replication and mitigate oxidative stress.

Peroxiredoxins (Prxs) are a family of antioxidant enzymes crucial for shielding cells against oxidative damage from reactive oxygen species (ROS). In this study, we cloned and analyzed two grass carp peroxiredoxin genes, CiPrx5 and CiPrx6. These genes exhibited ubiquitous expression across all sampled tissues, with their expression levels significantly modulated upon exposure to grass carp reovirus (GCRV). CiPrx5 was localized in the mitochondria, while CiPrx6 was uniformly distributed in the whole cells. Transfection or transformation of CiPrx5 and CiPrx6 into fish cells or E. coli significantly enhanced host resistance to H2O2 and heavy metals, leading to increased cell viability and reduced cell apoptosis rates. Furthermore, purified recombinant CiPrx5 and CiPrx6 proteins effectively protected DNA against oxidative damage. Notably, overexpression of both peroxiredoxins in fish cells effectively inhibited GCRV replication, reduced intracellular ROS levels induced by GCRV infection and H2O2 treatment, and induced autophagy. Significantly, these functions of CiPrx5 and CiPrx6 in GCRV replication and ROS mitigation were abolished upon treatment with an autophagy inhibitor. In summation, our findings suggest that grass carp Prx5 and Prx6 promote autophagy to inhibit GCRV replication, decrease intracellular ROS, and provide protection against oxidative stress.

Triphenylamine Spirofunctionalized Light-Emitting Conjugated Polymer with an Ultradeep-Blue Narrowband Emission for Large-Area Printed Display.

Emerging printed large-area polymer light-emitting diodes (PLEDs) are essential for manufacturing flat-panel displays and solid lighting devices. However, it is challenging to obtain large-area and stable ultradeep-blue PLEDs because of the lack of light-emitting conjugated polymers (LCPs) with robust deep-blue emissions, excellent morphological stabilities, and high charging abilities. Here, a novel unsymmetrically substituted polydiarylfluorene (POPSAF) is obtained with stable narrowband emission for large-area printed displays via triphenylamine (TPA) spirofunctionalization of LCPs. POPSAF films show narrowband and stable ultradeep-blue emission with a full width at half maximum (FWHM) of 36 nm, associated with their intrachain excitonic behavior without obvious polaron formation. Compared to controlled poly[4-(octyloxy)-9,9-diphenylfluoren-2,7-diyl]-co-[5-(octyloxy)-9,9-diphenylfluoren-2,7-diyl] (PODPF), excellent charge transport is observed in the POPSAF films because of the intrinsic hole transport ability of the TPA units. Large-area PLEDs are fabricated via blade-coating with an emission area of 9 cm2 , which exhibit uniform ultradeep-blue emission with an FWHM of 36 nm and corresponding Commission internationale de l'éclairage (CIE) coordinates of (0.155, 0.072). These findings are attributed to the synergistic effects of robust emission, stable morphology, and printing capacity. Finally, preliminary printed passive matrix (PM) PLED displays with 20 × 20 pixels monochromes are fabricated, confirmed the effectiveness of spirofunctionalization in optoelectronics.

Crystal structure of Ti4Ni2C.

Single crystals of the inter-metallic phase with composition Ti4Ni2C were serendipitously obtained by high-pressure sinter-ing of a mixture with initial chemical composition Ti2Ni. The Ti4Ni2C phase crystallizes in the Fd m space group and can be considered as a partially filled Ti2Ni structure with the C atom occupying an octa-hedral void. Ti4Ni2C is isotypic with Ti4Ni2O, Nb4Ni2C and Ta4Ni2C, all of which were studied previously by means of powder diffraction.

Computed tomography-guided microwave ablation for right middle lobe pulmonary nodules: a retrospective, single-center, case-control study.

PURPOSE: This retrospective, single-center, case-control study evaluated the safety and efficacy of Computed tomography (CT)-guided microwave ablation (MWA) for pulmonary nodules located in the right middle lobe (RML), a challenging location associated with a high frequency of complications. METHODS: Between May 2020 and April 2022, 71 patients with 71 RML pulmonary nodules underwent 71 MWA sessions. To comparison, 142 patients with 142 pulmonary nodules in non-RML were selected using propensity score matching. The technical success, technique efficacy, complications, and associated factors were analyzed. The duration of the procedure and post-ablation hospital stay were also recorded. RESULTS: Technical success was achieved in 100% of all patients. There were no significant differences in technique efficacy rates between the RML and non-RML groups (97.2% vs. 95.1%, p = 0.721). However, both major (47.9% vs. 19.7%, p < 0.001) and minor (26.8% vs. 11.3%, p = 0.004) pneumothorax were more common in the RML group than non-RML group. MWA for RML pulmonary nodules was identified as an independent risk factor for pneumothorax (p < 0.001). The duration of procedures (51.7 min vs. 35.3 min, p < 0.001) and post-ablation hospital stays (4.7 days vs. 2.8 days, p < 0.001) were longer in the RML group than non-RML group. CONCLUSIONS: CT-guided MWA for RML pulmonary nodules showed comparable efficacy compared with other lobes, but posed a higher risk of pneumothorax complications, necessitating longer MWA procedure times and extended hospital stays.

Extreme precipitation accelerates nitrate leaching in the intensive agricultural region with thick unsaturated zones.

Nitrate accumulation in the soil profile in the intensive agricultural region has been widely concerned in the world. However, the changes in nitrate accumulation characteristics caused by climate change, such as extremely high precipitation, are not well quantified, particularly for the regions with thick unsaturated zones. Here, we resampled the soil profiles taken in normal year (2020) after extreme precipitation year (2021) (>800 cm) in three regions in the southern Loess Plateau (LP) with three different water managements including rainfed orchards (n = 10), well-irrigated orchards (n = 4) and canal-irrigated orchards (n = 8). The accumulation amounts, peak depths, and accumulation depths of nitrate soil profiles of the different regions of two years were compared. The results showed that average nitrate accumulation in normal year at the rainfed region (800-cm depth), well-irrigated region (800-cm depth) and canal-irrigated region (1400-cm depth) were 5995 kg N ha-1, 9765 kg N ha-1, and 19,608 kg N ha-1, respectively. Compared with 2020, extreme precipitation in 2021 led to 56-91% reductions (2060-3702 kg N ha-1) in nitrate accumulation in 0-200 cm soil layer, and average nitrate leaching into the aquifer was >1390 kg N ha-1 in the canal-irrigated region. Average migration depths of nitrate peak in rainfed, well-irrigated and canal-irrigated regions were 92 cm, 115 cm, and 188 cm, respectively; as for nitrate accumulation depths, they were 10 cm, 80 cm and 108 cm, respectively. Vertically, the dried soil layer and paleosol layer (high clay content) in the canal-irrigated region significantly hindered nitrate deep migration caused by the extreme precipitation. The result highlights that extreme precipitation significantly accelerated nitrate leaching in the deep soil profiles, and future vulnerability and risk assessment studies must account for the impacts of extreme precipitation on nitrate leaching.

Dexamethasone Induced Osteocyte Apoptosis in Steroid-Induced Femoral Head Osteonecrosis through ROS-Mediated Oxidative Stress.

OBJECTIVE: Glucocorticoid (GC) overuse is strongly associated with steroid-induced osteonecrosis of the femoral head (SINFH). However, the underlying mechanism of SINFH remains unclear. This study aims to investigate the effect of dexamethasone (Dex)-induced oxidative stress on osteocyte apoptosis and the underlying mechanisms. METHODS: Ten patients with SINFH and 10 patients with developmental dysplasia of the hips (DDH) were enrolled in our study. Sixty rats were randomly assigned to the Control, Dex, Dex + N-Acetyl-L-cysteine (NAC), Dex + Dibenziodolium chloride (DPI), NAC, and DPI groups. Magnetic resonance imaging (MRI) was used to examine edema in the femoral head of rats. Histopathological staining was performed to assess osteonecrosis. Immunofluorescence staining with TUNEL and 8-OHdG was conducted to evaluate osteocyte apoptosis and oxidative damage. Immunohistochemical staining was carried out to detect the expression of NOX1, NOX2, and NOX4. Viability and apoptosis of MLO-Y4 cells were measured using the CCK-8 assay and TUNEL staining. 8-OHdG staining was conducted to detect oxidative stress. 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining was performed to measure reactive oxygen species (ROS). The expression of NOX1, NOX2, and NOX4 in MLO-Y4 cells was analyzed by Western blotting. Multiple comparisons were performed using one-way analysis of variance (ANOVA). RESULTS: In patients and the rat model, hematoxylin-eosin (HE) staining revealed a significantly higher rate of empty lacunae in the SINFH group than in the DDH group. Immunofluorescence staining indicated a significant increase in TUNEL-positive cells and 8-OHdG-positive cells in the SINFH group compared to the DDH group. Immunohistochemical staining demonstrated a significant increase in the expression of NOX1, NOX2, and NOX4 proteins in SINFH patients compared to DDH patients. Moreover, immunohistochemical staining showed a significant increase in the proportion of NOX2-positive cells compared to the Control group in the femoral head of rats. In vitro, Dex significantly inhibited the viability of osteocyte cells and induced apoptosis. After Dex treatment, the intracellular ROS level increased. However, Dex treatment did not alter the expression of NOX proteins in vitro. Additionally, NAC and DPI inhibited the generation of intracellular ROS and partially alleviated osteocyte apoptosis in vivo and in vitro. CONCLUSION: This study demonstrates that GC promotes apoptosis of osteocyte cells through ROS-induced oxidative stress. Furthermore, we found that the increased expression of NOXs induced by GC serves as an important source of ROS generation.

An effective treatment for diabetic foot necrosis with traditional Chinese and Western medicine: a case report.

Patients with diabetes who undergo a kidney transplant are at a great risk of undergoing amputations, usually associated with severe infection and necrosis. The treatment of severe diabetic foot necrosis is challenging in clinic, and the function of the limb is often hugely compromised. A 74-year-old male who had been diagnosed with severe post-renal transplant diabetic foot necrosis refused the option of below-knee amputation from previous surgeons, and requested to keep his left foot. The patient was treated with integrated traditional Chinese medicine (TCM) and Western medicine, with positive results. TCM therapeutic principles included 'clearing heat, removing toxicity, regulating Qi, resolving dampness, activating stagnant blood and nourishing yin as well as tonifying Qi and blood'. Treatment with Western medicine included wound debridement, internal fixation or joint fusion, and use of insulin, antibiotics and vasodilators. The patient was treated with a staged and diverse approach (i.e., a combination of TCM and Western medicine, surgical management and education for diabetic foot care), which ultimately helped the patient achieve limb salvage and regain normal function. A combination therapy of Western medicine and TCM may be a promising approach to heal diabetic foot ulcers.

Overdiagnosis and overtreatment of ground-glass nodule-like lung cancer.

Lung cancer has had one of the highest incidences and mortality in the world over the last few decades, which has aided in the promotion and popularization of screening for lung ground-glass nodules (GGNs). People have great psychological anxiety about GGN because of the chance that it will develop into lung cancer, which makes clinical treatment of GGN a generally excessive phenomenon. Overdiagnosis in screening has recently been mentioned in the literature. An important research emphasis of screening is how to reduce the incidence of overdiagnosis and overtreatment. This paper discusses from different aspects how to characterize the occurrence of overdiagnosis and overtreatment, how to reduce overdiagnosis and overtreatment, and future screening, follow-up, and treatment approaches.

Grass carp superoxide dismutases exert antioxidant function and inhibit autophagy to promote grass carp reovirus (GCRV) replication.

Superoxide dismutases (SODs) are potent antioxidants crucial for neutralizing reactive oxygen species (ROS) and protecting organisms from oxidative damage. In this study, we successfully cloned and analyzed two SOD genes, CiSOD1 and CiSOD2, from grass carp (Ctenopharyngodon idellus). CiSOD1 consists of two CuZn signature motifs and two conserved cysteine residues, while CiSOD2 contains a single Mn signature motif. The expression of CiSODs was found to be ubiquitous across all examined tissues, with their expression levels significantly altered after stimulation by grass carp reovirus (GCRV) or pathogen-associated molecular patterns (PAMPs). CiSOD1 was observed to be uniformly distributed in the cytoplasm, whereas CiSOD2 localized in the mitochondria. Escherichia coli transformed with both CiSODs demonstrated enhanced host resistance to H2O2 and heavy metals. Additionally, purified recombinant CiSOD proteins effectively protected DNA against oxidative damage. Furthermore, overexpression of CiSODs in fish cells reduced intracellular ROS, inhibited autophagy, and then resulted in the promotion of GCRV replication. Knockdown of CiSODs showed opposite trends. Notably, these roles of CiSODs in autophagy and GCRV replication were reversed upon treatment with an autophagy inducer. In summary, our findings suggest that grass carp SODs play an important role in decreasing intracellular ROS levels, inhibiting autophagy, and subsequently promoting GCRV replication.

Causal Effects of Basal Metabolic Rate on Cardiovascular Disease: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Despite the health effects of basal metabolic rate (BMR), the causal effect of BMR on cardiovascular diseases (CVDs) remains undetermined. To elucidate the causal nature, Mendelian randomization (MR) analyses were performed. METHODS AND RESULTS: Summary genome-wide association statistics regarding BMR and 5 CVDs were obtained from European databases. A 2-sample bidirectional MR was performed to assess the causal association between BMR and CVDs. The causal effects were estimated using inverse variance weighting. Simultaneously, multiple sensitivity analyses were performed to validate the robustness and reliability of the results. Our results indicated that genetically predicted BMR was significantly positively associated with the risk of heart failure (odds ratio, 1.53 [95% CI, 1.39-1.67]; P<0.001), atrial fibrillation and flutter (odds ratio, 2.12 [95% CI, 1.87-2.40]; P<0.001), and aortic aneurysm (odds ratio, 1.64 [95% CI, 1.41-1.92]; P<0.001). Genetically predicted BMR may not be causally associated with coronary artery disease and ischemic stroke risk. Furthermore, a significant causal effect of CVDs on BMR was not found in the reverse MR analysis. Multivariable MR was applied to further assess the direct effect of BMR on CVDs. Multivariable MR indicated that a high level of BMR still increased the risk of heart failure and atrial fibrillation and flutter after adjustment independent of possible confounders. However, the P value of aortic aneurysm was not significant. CONCLUSIONS: The present study provides robust evidence that genetically predicted BMR is independently causally associated with heart failure and atrial fibrillation and flutter but not vice versa. These findings have implications for the prevention and treatment of CVDs in clinical practice.

Spatial and Cross-Sectoral Transfer of Air Pollutant Emissions from the Fleet Electrification in China by 2030.

Fleet electrification shifts emission sources from the tailpipe to electricity generation and automotive supply chains subsequently, with emission transfer among regions. Such a spatial and cross-sectoral transfer of air pollutant emissions might embody uncertain environmental benefits spatially, which has not been comprehensively quantified, mainly due to the complexity of manufacturing processes of electric vehicle (EV) components (e.g., battery). We developed a hybrid life cycle assessment by combining inventory data of major processes and cross-sectoral input-output information and identified how China's EV deployment would influence the spatial redistribution of air pollutant emissions currently (2017) and in the future (2030). The results indicate that fleet electrification could readily reduce life cycle nitrogen oxides (NOx) and nonmethane volatile organic compound (NMVOC) emissions by 12-93%, and the reductions are estimated to be concentrated in major cities and urban agglomerations. However, increased demand for electricity and power battery production could increase PM2.5 and SO2 emissions in 17-55% of grids under all the scenarios, which emerge in coal-rich (e.g., Inner Mongolia, Shanxi) and industrial (e.g., Shandong, Henan, Jiangsu) provinces. By tracing the upstream, 31-55% of vehicle-cycle emissions are from deep supply chains but exhibit diverse sources. It suggests the necessity to relieve emissions leakage of fleet electrification by synchronizing effective environmental management across multiple sectors through EV supply chains.

Line Laser Scanning Combined with Machine Learning for Fish Head Cutting Position Identification.

Fish head cutting is one of the most important processes during fish pre-processing. At present, the identification of cutting positions mainly depends on manual experience, which cannot meet the requirements of large-scale production lines. In this paper, a fast and contactless identification method of cutting position was carried out by using a constructed line laser data acquisition system. The fish surface data were collected by a linear laser scanning sensor, and Principal Component Analysis (PCA) was used to reduce the dimensions of the dorsal and abdominal boundary data. Based on the dimension data, Least Squares Support Vector Machines (LS-SVMs), Particle Swarm Optimization-Back Propagation (PSO-BP) networks, and Long and Short Term Memory (LSTM) neural networks were applied for fish head cutting position identification model establishment. According to the results, the LSTM model was considered to be the best prediction model with a determination coefficient (R2) value, root mean square error (RMSE), mean absolute error (MAE), and residual predictive deviation (RPD) of 0.9480, 0.2957, 0.1933, and 3.1426, respectively. This study demonstrated the reliability of combining line laser scanning techniques with machine learning using LSTM to identify the fish head cutting position accurately and quickly. It can provide a theoretical reference for the development of intelligent processing and intelligent cutting equipment for fish.

Causal association of epigenetic aging and osteoporosis: a bidirectional Mendelian randomization study.

BACKGROUND: The relationship between aging and osteoporosis is well established. However, the relationship between the body's physiological age, i.e. epigenetic age, and osteoporosis is not known. Our goal is to analyze the bidirectional causal relationship between epigenetic clocks and osteoporosis using a bidirectional Mendelian randomization study. METHODS: We used SNPs closely associated with GrimAge, Hannum, PhenoAge, and HorvathAge in epigenetic age and SNPs closely associated with femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density as instrumental variables, respectively, using the inverse variance weighting method and several other MR methods to assess the bidirectional causal relationship between epigenetic age and osteoporosis. RESULT: There was no evidence of a clear causal relationship of epigenetic age (GrimAge, Hannum, PhenoAge, and HorvathAge) on femoral neck bone mineral density, lumbar spine bone mineral density, and forearm bone mineral density. In reverse Mendelian randomization analysis showed a significant causal effect of lumbar spine bone mineral density on GrimAge: odds ratio (OR) = 0.692, 95% confidence interval (CI) = (0.538-0.890), p = 0.004. The results suggest that a decrease in lumbar spine bone mineral density promotes an acceleration of GrimAge. CONCLUSION: There was no significant bidirectional causal relationship between epigenetic age and osteoporosis A decrease in lumbar spine bone density may lead to an acceleration of the epigenetic clock "GrimAge". Our study provides partial evidence for a bidirectional causal effect between epigenetic age and Osteoporosis.

N-N-Bridged Polynuclear POM-Based Coordination Polymers Based on a V-Type Ligand: Proton Conduction and Magnetism.

The construction of polyoxometalate (POM)-based coordination polymers, in the presence of a nitrogen heterocyclic ligand, is intriguing due to the potential for obtaining diverse structures. These structures exhibit extensive application possibilities in the fields of proton conductivity and magnetism. Herein, four new POM-based polynuclear coordination polymers with the formulas of {[Fe2(btb)3(H2O)2(SiW12O40)]·3H2O}n (1), {[Cd2(btb)2(H2O)6(HPMoVI10MoV2O40)]·2H2O}n (2), {[Co3(OH)2(btb)2(H2O)5(HPMoVI10MoV2O40)]·7H2O}n (3), and {[Cu3(OH)(btb)2(H2O)(HP2Mo5O23)]·6H2O}n (4) have been prepared using the V-type 1,3-bis(4H-1,2,4-triazole-4-yl)benzene (btb) ligand. Compounds 1 and 2 feature similar two-dimensional (2D) structures, derived from the binuclear Fe2N6 and Cd2N4 subunits connected by tridentate btb ligands. Meanwhile, in compound 3, hexanuclear Co6(OH)4 units are bound by quadridentate btb ligands forming a 2D layer with the same 4-c sql topology simplification as compounds 1 and 2. In compound 1, Keggin-type polyoxoanions are monodentate-coordinated to metal ions and suspended on the 2D structure, while, in compounds 2 and 3, they act as discrete counterions residing in the interstitial spaces between two adjacent layers, thereby extending the 2D structures into 3D structures through hydrogen bonding interactions. In compound 4, trinuclear Cu3(OH) subunits are further constructed into a 3D framework through cooperation with four tridentate and quadridentate btb ligands as well as Strandberg-type anions. Furthermore, the proton conduction of the four compounds has been investigated. They display high proton conductivities at 358 K and 98% RH with powdered samples, which are 1.26 × 10-3, 1.24 × 10-3, 3.24 × 10-4, and 2.57 × 10-4 S cm-1, respectively. Interestingly, by mixing with Nafion, the composite membranes of compounds 2 and 4 exhibit enhanced proton conductivities, measuring at 4.87 × 10-2 and 1.28 × 10-2 S cm-1, respectively, at 358 K and 98% RH, which suggests excellent potential for applications. In addition, compounds 1, 3, and 4 display antiferromagnetic behaviors due to similar magnetic interactions. This work can provide research insights into the assembly of 2D POM-based coordination polymers with nitrogen heterocyclic ligands and Keggin-type POMs and further promote their research progress in proton conduction.

Ootheca mantidis mitigates renal fibrosis in mice by the suppression of apoptosis via increasing the gut microbe Akkermansia muciniphila and modulating glutamine metabolism.

Renal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut-renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.