Self-assembled high-entropy Prussian blue analogue nanosheets enabling efficient sodium storage.

High entropy material (HEM) has emerged as an appealing material platform for various applications, and specifically, the electrochemical performances of HEM could be further improved through self-assembled structure design. However, it remains a big challenge to construct such high-entropy self-assemblies primarily due to the compositional complexity. Herein, we propose a bottom-up directional freezing route to self-assemble high-entropy hydrosols into porous nanosheets. Taking Prussian blue analogue (PBA) as an example, the simultaneous coordination-substitution reactions yield stable high-entropy PBA hydrosols. During subsequent directional freezing process, the anisotropic growth of ice crystals could guide the two-dimensional confined assembly of colloidal nanoparticles, resulting in high-entropy PBA nanosheets (HE-PBA NSs). Thanks to the high-entropy and self-assembled structure design, the HE-PBA NSs manifests markedly enhanced sodium storage kinetics and performances in comparison with medium/low entropy nanosheets and high entropy nanoparticles.

Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease.

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore, bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico-striato-pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease, particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremor-dominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia-thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity, and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

Evaluation of the nutritional quality of yeast protein in comparison to animal and plant proteins using growing rats and INFOGEST model.

Yeast, identified as a microorganism, boasts a considerable protein content, positioning yeast protein as a highly promising alternative in the quest for sustainable protein sources. The primary aim of this study is to evaluate the protein quality of yeast protein and compare it with animal proteins (whey concentrate/isolate proteins) and plant proteins (soy, wheat, pea proteins). Notably, yeast protein exhibits the highest ratio of indispensable/dispensable amino acids (IAAs/DAAs, 0.91). However, in both in vivo and in vitro digestion experiments, yeast protein demonstrated lower true protein digestibility (TPD) and true ileal digestibility (TID) compared to other proteins. Despite this, the yeast protein's amino acid score (AAS, 1.37 for >3 years), protein digestibility-corrected amino acid score (PDCAAS, 100 % for >3 years), and digestibility-corrected amino acid score (DIAAS, 82.42 % for >3 years) of yeast protein surpassed those of plant proteins, yet remained lower than animal proteins primarily due to its lower digestibility.

Bubble-based electrochemical chip integrated with cobalt-nickel bimetallic hybrid for enhanced detection of dopamine.

Transition metal-based miniaturized electrochemical platforms for dopamine (DA) detection are highly desirable for screening neurological diseases due to their portability, fast response, and low cost. However, mass transfer in these miniaturized platforms remains a challenge for electrochemical sensing performance. Herein, we report a bubble-based chip integrated with a cobalt-nickel hybrid-modified screen-printed electrode for enhanced detection of DA. A simple piezoelectric transducer was employed to produce bulk acoustic waves (BAWs) to actuate the oscillation of air bubbles captured within the chip. The generated strong microstreaming facilitated the diffusion of the analyte to the electrode surface, enhancing the response signal. With the optimized actuating frequency and voltage, the bubble-based electrochemical platform exhibits two linear detection ranges for DA (1-10 µM, and 10-70 µM), with sensitivities approximately 2 times and 2.6 times larger than those without BAW in the lower and higher linear detection ranges, respectively. The detection limit is calculated to be 0.06 µM (S/N = 3) under BAW, which is significantly lower than that achieved without BAW assistance (0.16 µM, S/N = 3). The feasibility of using this chip for DA determination in real serum samples has also been validated. This miniaturized device shows great promise in point-of-care testing (POCT) fields.

Long-term follow-up of methotrexate and cytarabine in adult patients with Langerhans cell histiocytosis.

The optimal treatment strategy for adult Langerhans cell histiocytosis (LCH) remains unclear. Our previous study demonstrated the remarkable efficacy of combined methotrexate and cytarabine (Ara-C) [MA] therapy in patients newly diagnosed with LCH, with a median follow-up of 2 years. The present article reports long-term follow-up data spanning a median of 78 months (6.5 years) from a single-arm, single-centre, prospective phase 2 clinical trial (NCT02389400) conducted between January 2014 and December 2020. Ninety-five adults with newly diagnosed LCH exhibiting multisystem disease or multifocal single-system involvement underwent MA therapy every 35 days for six cycles. Methotrexate (1 g/m2) was administered by 24 h infusion on day 1 and AraC (0.1 g/m2) by 24 h infusion for 5 days. The primary end-point was event-free survival (EFS). The median patient age was 32 years (range 18-65 years). The overall response rate was 89.5%. Seven patients in this cohort died, and 38 experienced disease reactivation. No degenerative central nervous system diseases were observed. The estimated 6-year overall survival (OS) and EFS rates were 93.2% and 55.2% respectively. Multivariate analysis revealed that risk organ (RO) involvement at baseline (hazard ratio [HR] 6.135 [95% confidence interval (CI) 1.185-32.259]; p = 0.031) and age >40 years at diagnosis (HR 7.299 [95% CI 1.056-21.277]; p = 0.042) were associated with inferior OS. RO (HR 2.604 [95% CI 1.418-4.762]; p = 0.002) and skin (HR 2.232 [95% CI 1.171-4.255]; p = 0.015) involvement at baseline were poor prognostic factors for EFS. Regarding adverse events, four patients developed a second primary malignancy. In conclusion, the MA regimen was a valid and safe therapeutic approach for adult patients newly diagnosed with LCH.

Dictionary Learning Method Based on K-Sparse Approximation and Orthogonal Procrustes Analysis for Reconstruction in Bioluminescence Tomography.

Bioluminescence tomography (BLT) is one kind of noninvasive optical molecular imaging technology, widely used to study molecular activities and disease progression inside live animals. By combining the optical propagation model and inversion algorithm, BLT enables three-dimensional imaging and quantitative analysis of light sources within organisms. However, challenges like light scattering and absorption in tissues, and the complexity of biological structures, significantly impact the accuracy of BLT reconstructions. Here, we propose a dictionary learning method based on K-sparse approximation and Orthogonal Procrustes analysis (KSAOPA). KSAOPA uses an iterative alternating optimization strategy, enhancing solution sparsity with k-coefficients Lipschitzian mappings for sparsity(K-LIMAPS) in the sparse coding stage, and reducing errors with Orthogonal Procrustes analysis in the dictionary update stage, leading to stable and precise reconstructions. We assessed the method performance through simulations and in vivo experiments, which showed that KSAOPA excels in localization accuracy, morphological recovery, and in vivo applicability compared to other methods.

Incorporating Implicit Information to Disentangle the Impacts of Hydropower Dams and Climate Change on Basin-Scale Fish Habitat Distribution.

The loss of freshwater fish habitats, exacerbated by climate change and dam constructions, poses a critical environmental concern. The upper Yangtze River basin, noted for its abundant fish fauna and concentrated dam development, serves as a crucial locale for investigating the impacts of climate shifts and dam construction. This study aims to disentangle the impacts of hydroelectric dams and climate change on fish habitat distribution by analyzing species presence data across different periods. Species distribution models were constructed using Maxent for Coreius guichenoti (a warm-water endangered fish) and Schizopygopsis malacanthus (a cold-water endangered fish). The model accuracy was assessed using the area under the curve of the receiver operating characteristic. Habitat distribution modeling and prediction for the pre-dam period (1970-2000) and post-dam period (2001-2020), as well as future climate change under two shared socioeconomic pathways scenarios, were conducted. The impacts of climate change and dam construction on the habitat suitability of two fish species were quantified. The results revealed dam construction predominantly diminished habitat suitability and range, with high-suitability habitats in the post-dam period decreasing by 56.3% (720.18 km) and 67.0% (1665.52 km) for the two fishes, respectively. Climate change would enhance the habitat suitability of Coreius guichenoti, while it would decrease the habitat suitability of Schizopygopsis malacanthus. The impact of dam construction is greater that of climate change for them. This study underscores the profound impacts of dam construction on fish habitats, particularly for cold-water species, and highlights the critical need for habitat restoration in sustainable hydropower development. Our method of disentangling these factors also provides a new approach to evaluating environmental impacts in large river basins.

Development of a novel nomogram for patients with SCLC and comparison with other models.

BACKGROUND: Though several nomograms have been established to predict the survival probability of patients with small-cell lung cancer (SCLC), none involved enough variables. This study aimed to construct a novel prognostic nomogram and compare its performance with other models. METHODS: Seven hundred twenty-two patients were pathologically diagnosed with SCLC in Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University from January 2016 to December 2018. We input Forty-one factors by reviewing the medical records. The nomogram was constructed based on the variables identified by univariate and multivariate analyses in the training set and validated in the validation set. Then we compared the performance of the models in terms of discrimination, calibration, and clinical net benefit. RESULTS: There were eight variables involved in the nomogram: gender, monocyte (MON), neuron-specific enolase (NSE), cytokeratin 19 fragments (Cyfra211), M stage, radiotherapy (RT), chemotherapy cycles (CT cycles), and prophylactic cranial irradiation (PCI). The calibration curve showed a good correlation between the nomogram prediction and actual observation for overall survival (OS). The area under the curve (AUC) of the nomogram was higher, and the Integrated Brier score (IBS) was lower than other models, indicating a more accurate prediction. Decision curve analysis (DCA) showed a significant improvement in the clinical net benefit compared to the other models. CONCLUSIONS: We constructed a novel nomogram to predict OS for patients with SCLC using more comprehensive and objective variables. It performed better than existing models and would assist clinicians in individually estimating risk and making a therapeutic regimen.

Eimeria tenella rhoptry neck protein 2 plays a key role in the process of invading the host intestinal epithelium.

The Apicomplexa parasitic phylum rhoptry neck protein 2 (RON2) plays a key role in the process of invading host cells. Eimeria tenella, an intracellular protozoan shares a similar conserved invasion pattern. However, whether E. tenella RON2 participates in the process of invading the host intestinal epithelium is poorly understood. In this study, the sequence of EtRON2 was analyzed and expressed. The expression of the truncated extracellular N-terminal fragment of EtRON2 (403-700 aa, designated EtRON2403-700) with a molecular mass of 38.3 kDa. EtRON2 in the sporozoite protein was detected at 151.4 kDa by rabbit anti-rEtRON2403-700 antibody. Immunofluorescence results showed that EtRON2 was mainly localized to the nucleus and apex of the E. tenella sporozoite. qPCR results showed that the highest expression level of EtRON2 was detected in sporulated oocysts compared with other developmental stages of E. tenella. In vitro invasion inhibition assays showed that the capacity of sporozoites to invade DF-1 cells was significantly inhibited after pretreatment with the rabbit anti-rEtRON2403-700 antibody. Silencing the EtRON2 gene by RNA interference (RNAi) significantly inhibited EtRON2 expression and significantly reduced the invasion of DF-1 cells by sporozoites. In vivo experiments revealed a significant decrease parasite burden and oocyst outputs in chicks after infection with EtRON2 gene-silenced sporozoites by cloacal inoculation. Recombinant EtRON2403-700 (rEtRON2403-700) immunizes chicks effectively against E. tenella infection by inducing humoral immunity and upregulating IFN-γ and CD8+ T lymphocytes. Furthermore, chicks exhibited increased relative weight gain rates, lower cecum lesion scores, and reduced oocyst outputs during the E. tenella challenge. H&E staining showed that the cecum tissue of chicks immunized with rEtRON2403-700 showed relatively mild histopathological changes. In conclusion, the results of this study demonstrated that EtRON2 plays a key role in E. tenella invasion of the host intestinal epithelium and provides a potential target for vaccines against E. tenella infection.

Manifestations and outcomes of digestive tract involvement in adult Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a heterogeneous histiocytosis characterized by proliferation of Langerhans cells. While less common, manifestations of digestive tract involvement in LCH remain largely unrevealed. We conducted a retrospective analysis of demographics, clinical, endoscopic, genetic and follow-up data from 13 adult patients with pathologically confirmed gastrointestinal involvement of LCH (LCH-GI), in a single-center cohort of 465 patients. Digestive tract involvement was observed in 2.80% of LCH patients. At LCH-GI diagnosis, 7 patients (53.8%) had unifocal lesions, and 6 patients (46.2%) had multisystem disease. 6 patients (46.2%) experienced no gastrointestinal symptoms at LCH-GI onset, while others were symptomatic. Stomach was most commonly affected (61.5%), followed by esophagus (23.1%), colon (7.7%) and anus (7.7%). Endoscopic findings varied among 12 patients, including submucosal bulge (8 patients, 66.7%) and non-bulging lesions (4 patients, 33.3%) such as erosions, coarse granular mucosa, and regional abnormal coloration. Among 8 patients with genetic analysis, BRAFV600E mutation was detected in 5 patients (62.5%). The estimated 1-year overall survival rate was 91.7%. Progression-free survival of patients with submucosal bulges under endoscopy was significantly better than those with non-bulging lesions. This study presents 13 cases of LCH with digestive tract involvement. We emphasize the importance of endoscopy and biopsy for pathological examination of lesions such as submucosal bulges and erosions under endoscopy to assist in early detection of LCH. Comprehensive systemic assessment and regular endoscopic monitoring are essential in patient management. Treatment should be individualized with dynamic adjustments during follow-up.

Neuromelanin-MRI identifies locus coeruleus and substantia nigra degeneration as key differentiators in isolated rapid eye movement sleep behavior disorder.

To explore the neuromelanin depigmentation of locus coeruleus (LC) and substantia nigra pars compacta (SNc) in the isolated rapid eye movement sleep behavior disorder (iRBD) using neuromelanin-sensitive MRI (NM-MRI), and to evaluate its utility for iRBD diagnosis. A total of 25 iRBD patients and 25 healthy controls were recruited and underwent NM-MRI. The contrast-to-noise ratio (CNR) of SNc and LC, and the volume of SNc were compared between groups and evaluated visually. The power of NM measures in discriminating iRBD patients from healthy controls were performed with receiver operating characteristic (ROC) curves and the area under curve (AUC) was calculated. The CNR of SNc and LC, the volume of SNc, the SNc/midbrain volume ratio as well as the visual scores of SNc and LC in iRBD patients were significantly decreased than those in controls (all P < 0.05). For quantitative analysis, the LC CNR acquired the highest accuracy in predicting iRBD (AUC 0.95, sensitivity 80%, specificity 100%), followed by SNc volume (AUC 0.93, sensitivity 88%, specificity 96%) and SNc CNR (AUC 0.74, sensitivity 92%, specificity 44%). For visual analysis, the accuracy of the visual score for SNc and LC were 78% (sensitivity 68%, specificity 88%) and 86% (sensitivity 88%, specificity 84%), respectively. The NM in the SNc and LC regions were significantly reduced in iRBD patients. NM measures showed good capability in discriminating iRBD from controls, suggesting that NM-MRI may be a valuable screening tool for iRBD.

Gelation embolism agents suppress clinical TACE-incited pro-metastatic microenvironment against hepatocellular carcinoma progression.

BACKGROUND: Current embolic agents in transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) encounter instability and easy leakage, discounting TACE efficacy with residual HCC. Moreover, clinical TACE aggravates hypoxia and pro-metastatic microenvironments, rendering patients with HCC poor prognosis. METHODS: Herein, we developed Zein-based embolic agents that harness water-insoluble but ethanol-soluble Zein to encompass doxorubicin (DOX)-loaded mesoporous hollow MnO2 (HMnO2). The conditions and capacity of HMnO2 to generate reactive oxygen species (ROS) were assayed. Mechanical examinations of Zein-HMnO2@DOX were performed to evaluate its potential as the embolic agent. In vitro experiments were carried out to evaluate the effect of Zein-HMnO2@DOX on HCC. The subcutaneous HCC mouse model and rabbit VX2 HCC model were established to investigate its anti-tumor and anti-metastasis efficacy and explore its potential anti-tumor mechanism. FINDINGS: The high adhesion and crosslinking of Zein with HMnO2@DOX impart Zein-HMnO2@DOX with strong mechanical strength to resist deformation and wash-off. Zein gelation and HMnO2 decomposition in response to water and acidic tumor microenvironment, respectively, enable continuous DOX release and Fenton-like reaction for reactive oxygen species (ROS) production and O2 release to execute ROS-enhanced TACE. Consequently, Zein-based embolic agents outperform clinically-used lipiodol to significantly inhibit orthotopic HCC growth. More significantly, O2 release down-regulates hypoxia inducible factor (HIF-1α), vascular endothelial growth factor (VEGF) and glucose transporter protein 1 (GLUT1), which thereby re-programmes TACE-aggravated hypoxic and pro-metastatic microenvironments to repress HCC metastasis towards lung. Mechanistic explorations uncover that such Zein-based TACE agents disrupt oxidative stress, angiogenesis and glycometabolism pathways to inhibit HCC progression. INTERPRETATION: This innovative work not only provides a new TACE agent for HCC, but also establishes a new strategy to ameliorate TACE-aggravated hypoxia and metastasis motivation against clinically-common HCC metastasis after TACE operation. FUNDING: Excellent Young Science Fund for National Natural Science Foundation of China (82022033); National Natural Science Foundation of China (Grant No. 82373086, 82102761); Major scientific and technological innovation project of Wenzhou Science and Technology Bureau (Grant No. ZY2021009); Shanghai Young Top-Notch Talent.

Recent Advances in Nanozyme-Based Sensing Technology for Antioxidant Detection.

Antioxidants are substances that have the ability to resist or delay oxidative damage. Antioxidants can be used not only for the diagnosis and prevention of vascular diseases, but also for food preservation and industrial production. However, due to the excessive use of antioxidants, it can cause environmental pollution and endanger human health. It can be seen that the development of antioxidant detection technology is important for environment/health maintenance. It is found that traditional detection methods, including high performance liquid chromatography, gas chromatography, etc., have shortcomings such as cumbersome operation and high cost. In contrast, the nanozyme-based detection method features advantages of low cost, simple operation, and rapidity, which has been widely used in the detection of various substances such as glucose and antioxidants. This article focuses on the latest research progress of nanozymes for antioxidant detection. Nanozymes for antioxidant detection are classified according to enzyme-like types. Different types of nanozyme-based sensing strategies and detection devices are summarized. Based on the summary and analysis, one can find that the development of commercial nanozyme-based devices for the practical detection of antioxidants is still challenging. Some emerging technologies (such as artificial intelligence) should be fully utilized to improve the detection sensitivity and accuracy. This article aims to emphasize the application prospects of nanozymes in antioxidant detection and to provide new ideas and inspiration for the development of detection methods.

Immunoprotective effect of recombinant Lactobacillus plantarum expressing largemouth bass virus MCP on largemouth bass.

Largemouth bass virus (LMBV) is an infectious pathogen that causes high mortality rates in largemouth bass, and outbreaks of this virus can significantly harm the aquaculture industry. Currently, no vaccine has been developed that can effectively prevent the transmission of LMBV. In this study, we constructed a recombinant Lactobacillus plantarum (L. plantarum) strain capable of expressing the MCP gene of LMBV and displaying this protein on its surface; then, we evaluated the immunoprotective effect of this recombinant bacterium on largemouth bass. Western blotting, immunofluorescence, and flow cytometry confirmed that MCP was successfully expressed and anchored on the surfaces of NC8 cells. Immunization of largemouth bass with NC8-pSIP409-pgsA'-MCP via the oral feeding route induced CD4, CD8, IL-1ß, and IL-6 gene expression. In addition, NC8-pSIP409-pgsA'-MCP at different CFUs increased the survival of largemouth bass after LMBV infection; in particular, NC8-pSIP409-pgsA'-MCP (109 CFU) resulted in approximately 30% survival. NC8-pSIP409-pgsA'-MCP immunization alleviated the pathological changes in the liver and spleen, exerting a more advantageous protective effect. These data suggest that the recombinant L. plantarum strain NC8-pSIP409-pgsA'-MCP can increase the resistance of largemouth bass to LMBV infection and that this strain is a promising candidate oral vaccine for the prevention of LMBV infection.

EIDU-Net: edge-preserved inception DenseGCN U-Net for LiDAR point cloud segmentation.

With the development of laser scanners and machine learning, point cloud semantic segmentation plays a significant role in autonomous driving, scene reconstruction, human-computer interaction, and other fields. In recent years, point cloud semantic segmentation based on deep learning has become one of the key research directions in point cloud processing. Due to the limited ability to exploit geometric details and contextual information in point clouds, most methods that adopt encoder-decoder architecture lose local structural information easily, especially detailed features, and extract features insufficiently. To address this issue, the edge-preserving inception DenseGCN U-Net (entitled as EIDU-Net) is proposed. EIDU-Net makes full use of the complementation between geometric details in the original point cloud and high-level features. The edge-preserved graph pooling (EGP) layer, the key module of the EIDU-Net, is designed to retain additional edge feature information from the original point cloud during pooling operations. Accordingly, the edge-preserved graph unpooling (EGU) layer can restore the feature graph more efficiently based on the additionally retained edge features. Extensive experiments demonstrate that our proposed EIDU-Net has remarkable improvements on semantic segmentation tasks under whatever S3DIS or Terracotta Warrior fragments. Our code is publicly available at https://github.com/caoxin918/EIDU-Net .

Improving Sexual Function through Penis Enlargement: Comparing Silicone Pearls Implantation and Fat Grafting.

BACKGROUND: Although current penile enlargement techniques can improve appearance, it remains unclear whether these procedures increase sexual function. We aimed to systematically compare the surgical outcomes, with a particular focus on sexual function, in patients and their partners following silicone pearls implantation and fat grafting for penis enlargement. METHODS: A single-site, retrospective study reviewed patients who underwent silicone pearls implantation or fat grafting for penis enlargement. In the operation, silicone pears were connected to form a ring-shaped implant, which was then implanted under the dartos fascia. For patients underwent fat grafting, a total of 40-55 ml of fat was injected for penis enlargement. Preoperative and 6-month postoperative data of patients and their partners were collected. The penis diameter, penis appearance score (PAS) and treatment satisfaction scale (TSS) were evaluated. RESULTS: Both pearls implantation (n = 28) and fat grafting (n = 27) led to an increase in penis diameter. The TSS scores of patients who underwent pearls implantation increased by 11.96%, and the partners' scores increased by 9.17%. Specifically, Confidence, Pleasure from Sexual Activity, and Satisfaction with Orgasm scores of partners showed significant improvements. Partners' Satisfaction with Orgasm increased most. The total TSS scores of patients with fat grafting increased by 16.7%; meanwhile, scores of their partners had not obvious improvement. CONCLUSION: Silicone pearls implantation was found to effectively improve the sexual function of men and the sexual satisfaction of their partners compared to fat grafting. Therefore, pearls implantation is possible to enhanced sexual experiences both for man and their partners. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Dachaihu Decoction alleviates chronic pancreatitis by regulating MAPK signaling pathway: Insights from network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic pancreatitis (CP), a syndrome characterized by inflammatory fibrosis, can impair both the internal and external secretory functions of the pancreas. The global incidence of this disease is gradually increasing. However, the exact pathogenesis remains unclear, resulting in a lack of targeted clinical therapies. According to the principles of traditional Chinese medicine, CP can be attributed to Shaoyang and Yangming syndromes, which manifest as abdominal pain and hypochondriac distension. Dachaihu Decoction (DCHD) is a classic formula from the "Treatise on Febrile and Miscellaneous Disease." It is frequently prescribed for conditions associated with combined Shaoyang and Yangming syndromes. However, the specific mechanisms by which DCHD prevents and treats CP remain unclear and require further investigation. AIM OF THE STUDY: Using a holistic methodology, including network pharmacology, molecular docking, transcriptomic profiling, and animal experimentation, we explored the potential therapeutic mechanisms of DCHD in CP. MATERIALS AND METHODS: In a mouse model, caerulein was used to induce CP, and DCHD was administered via gastric lavage to assess its therapeutic effect on pancreatic injury caused by caerulein-induced CP. Subsequently, pancreatic tissues were collected for transcriptomic analysis. Screening of DCHD-active ingredient-target pathways for CP treatment was conducted using network pharmacology and further preliminary validation was performed using molecular docking techniques. Additionally, in vivo and in vitro validation was conducted using animal and cells experiments based on the predicted results. RESULTS: Our findings suggest that DCHD ameliorates pancreatic acinar cell injury, pancreatic inflammation, and fibrosis in mice with CP. Network pharmacology identified 385 potential targets of DCHD associated with CP. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the therapeutic effect of DCHD on CP may be linked to the mitogen-activated protein kinase (MAPK) signaling pathway. Transcriptomic data supported this finding, as it confirmed that DCHD inhibited the pancreatic MAPK signaling pathway in CP. Molecular docking studies further revealed that the top ten active components of DCHD exhibited strong docking activity with key molecules within the MAPK signaling pathway. Finally, animal experiments confirmed that DCHD effectively reduced the phosphorylation of P38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in pancreatic tissues. In addition, the expression of p-P38, p-JNK, and p-ERK was reduced in pancreatic stellate cells and macrophages in the DCHD group. We further treated CP mice, human pancreatic stellate cell line (hPSCs), and macrophage cell line RAW264.7 with the active component baicalin from DCHD, and found that baicalin effectively reduced pancreatic damage in CP. Additionally, the expression of key proteins in the MAPK signaling pathway was significantly decreased in both hPSCs and RAW264.7. CONCLUSION: In summary, DCHD plays an important role in the treatment of chronic pancreatitis, and it may become a promising drug against the progression of CP. The role of DCHD in alleviating pancreatic inflammatory cell infiltration and fibrosis may be related to the regulation of the MAPK signaling pathway.

SODL-IR-FISTA: sparse online dictionary learning with iterative reduction FISTA for cone-beam X-ray luminescence computed tomography.

Cone beam X-ray luminescence computed tomography (CB-XLCT) is an emerging imaging technique with potential for early 3D tumor detection. However, the reconstruction challenge due to low light absorption and high scattering in tissues makes it a difficult inverse problem. In this study, the online dictionary learning (ODL) method, combined with iterative reduction FISTA (IR-FISTA), has been utilized to achieve high-quality reconstruction. Our method integrates IR-FISTA for efficient and accurate sparse coding, followed by an online stochastic approximation for dictionary updates, effectively capturing the sparse features inherent to the problem. Additionally, a re-sparse step is introduced to enhance the sparsity of the solution, making it better suited for CB-XLCT reconstruction. Numerical simulations and in vivo experiments were conducted to assess the performance of the method. The SODL-IR-FISTA achieved the smallest location error of 0.325 mm in in vivo experiments, which is 58% and 45% of the IVTCG-L 1 (0.562 mm) and OMP-L 0 (0.721 mm), respectively. Additionally, it has the highest DICE similarity coefficient, which is 0.748. The results demonstrate that our approach outperforms traditional methods in terms of localization precision, shape restoration, robustness, and practicality in live subjects.

Global tendency and frontiers of research on pertussis from 2000 to 2023: A bibliometric and visual analysis.

Pertussis has reemerged globally, with rising incidence in China. Controlling this disease remains a significant public health challenge worldwide. This study applies bibliometric methods to analyze global and Chinese research on pertussis, assessing current trends, identifying hot topics, predicting future research directions, and providing guidance for scientific research and clinical practice. Pertussis-related articles from 2000 to 2023 were retrieved from four major Chinese databases and three English databases. COOC and CiteSpace software were used to analyze publication trends, geographic distribution, institutions, disciplines, and keywords, to visualize through network maps. The study analyzed 2,580 Chinese and 5,311 foreign articles and reviews. Pertussis research publications have increased globally, with foreign research peaking earlier than in China. The United States leads in publication volume, while China showed the highest burst of activity from 2019 to 2023. Research mainly focuses on animal experiments, vaccine development and safety, clinical characteristics and treatment, and pertussis toxin. Pertussis research is thriving globally and in China. Future research should emphasize interdisciplinary collaboration across molecular biology, immunology, and epidemiology to innovate vaccines and control strategies. Additionally, continued development of treatment drugs remains crucial as current vaccines do not fully control pertussis.