Influencing factors and risk prediction model for emergence agitation after general anesthesia for primary liver cancer.

BACKGROUND: General anesthesia is commonly used in the surgical management of gastrointestinal tumors; however, it can lead to emergence agitation (EA). EA is a common complication associated with general anesthesia, often characterized by behaviors, such as crying, struggling, and involuntary limb movements in patients. If treatment is delayed, there is a risk of incision cracking and bleeding, which can significantly affect surgical outcomes. Therefore, having a proper understanding of the factors influencing the occurrence of EA and implementing early preventive measures may reduce the incidence of agitation during the recovery phase from general anesthesia, which is beneficial for improving patient prognosis. AIM: To analyze influencing factors and develop a risk prediction model for EA occurrence following general anesthesia for primary liver cancer. METHODS: Retrospective analysis of clinical data from 200 patients who underwent hepatoma resection under general anesthesia at Wenzhou Central Hospital (January 2020 to December 2023) was conducted. Post-surgery, the Richmond Agitation-Sedation Scale was used to evaluate EA presence, noting EA incidence after general anesthesia. Patients were categorized by EA presence postoperatively, and the influencing factors were analyzed using logistic regression. A nomogram-based risk prediction model was constructed and evaluated for differentiation and fit using receiver operating characteristics and calibration curves. RESULTS: EA occurred in 51 (25.5%) patients. Multivariate analysis identified advanced age, American Society of Anesthesiologists (ASA) grade III, indwelling catheter use, and postoperative pain as risk factors for EA (P < 0.05). Conversely, postoperative analgesia was a protective factor against EA (P < 0.05). The area under the curve of the nomogram was 0.972 [95% confidence interval (CI): 0.947-0.997] for the training set and 0.979 (95%CI: 0.951-1.000) for the test set. Hosmer-Lemeshow test showed a good fit (χ 2 = 5.483, P = 0.705), and calibration curves showed agreement between predicted and actual EA incidence. CONCLUSION: Age, ASA grade, catheter use, postoperative pain, and analgesia significantly influence EA occurrence. A nomogram constructed using these factors demonstrates strong predictive accuracy.

Long-term liver-related outcomes and liver stiffness progression of statin usage in steatotic liver disease.

BACKGROUND: Statins have multiple benefits in patients with metabolic-associated steatotic liver disease (MASLD). AIM: To explore the effects of statins on the long-term risk of all-cause mortality, liver-related clinical events (LREs) and liver stiffness progression in patients with MASLD. METHODS: This cohort study collected data on patients with MASLD undergoing at least two vibration-controlled transient elastography examinations at 16 tertiary referral centres. Cox regression analysis was performed to examine the association between statin usage and long-term risk of all-cause mortality and LREs stratified by compensated advanced chronic liver disease (cACLD): baseline liver stiffness measurement (LSM) of ≥10 kPa. Liver stiffness progression was defined as an LSM increase of ≥20% for cACLD and from <10 kPa to ≥10 or LSM for non-cACLD. Liver stiffness regression was defined as LSM reduction from ≥10 kPa to <10 or LSM decrease of ≥20% for cACLD. RESULTS: We followed up 7988 patients with baseline LSM 5.9 kPa (IQR 4.6-8.2) for a median of 4.6 years. At baseline, 40.5% of patients used statins, and cACLD was present in 17%. Statin usage was significantly associated with a lower risk of all-cause mortality (adjusted HR=0.233; 95% CI 0.127 to 0.426) and LREs (adjusted HR=0.380; 95% CI 0.268 to 0.539). Statin usage was also associated with lower liver stiffness progression rates in cACLD (HR=0.542; 95% CI 0.389 to 0.755) and non-cACLD (adjusted HR=0.450; 95% CI 0.342 to 0.592), but not with liver stiffness regression (adjusted HR=0.914; 95% CI 0.778 to 1.074). CONCLUSIONS: Statin usage was associated with a relatively lower long-term risk of all-cause mortality, LREs and liver stiffness progression in patients with MASLD.

Aristolochic acids-hijacked p53 promotes liver cancer cell growth by inhibiting ferroptosis.

Aristolochic acids (AAs) have been identified as a significant risk factor for hepatocellular carcinoma (HCC). Ferroptosis is a type of regulated cell death involved in the tumor development. In this study, we investigated the molecular mechanisms by which AAs enhanced the growth of HCC. By conducting bioinformatics and RNA-Seq analyses, we found that AAs were closely correlated with ferroptosis. The physical interaction between p53 and AAs in HepG2 cells was validated by bioinformatics analysis and SPR assays with the binding pocket sites containing Pro92, Arg174, Asp207, Phe212, and His214 of p53. Based on the binding pocket that interacts with AAs, we designed a mutant and performed RNA-Seq profiling. Interestingly, we found that the binding pocket was responsible for ferroptosis, GADD45A, NRF2, and SLC7A11. Functionally, the interaction disturbed the binding of p53 to the promoter of GADD45A or NRF2, attenuating the role of p53 in enhancing GADD45A and suppressing NRF2; the mutant did not exhibit the same effects. Consequently, this event down-regulated GADD45A and up-regulated NRF2, ultimately inhibiting ferroptosis, suggesting that AAs hijacked p53 to down-regulate GADD45A and up-regulate NRF2 in HepG2 cells. Thus, AAs treatment resulted in the inhibition of ferroptosis via the p53/GADD45A/NRF2/SLC7A11 axis, which led to the enhancement of tumor growth. In conclusion, AAs-hijacked p53 restrains ferroptosis through the GADD45A/NRF2/SLC7A11 axis to enhance tumor growth. Our findings provide an underlying mechanism by which AAs enhance HCC and new insights into p53 in liver cancer. Therapeutically, the oncogene NRF2 is a promising target for liver cancer.

New resorcylic acid derivatives of Lysimachia tengyuehensis against MRSA and VRE by interfering with bacterial metabolic imbalance.

The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1-4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4-8 µg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time.

Global burden of metabolic diseases, 1990-2021.

BACKGROUND: Common metabolic diseases, such as type 2 diabetes mellitus (T2DM), hypertension, obesity, hypercholesterolemia, and metabolic dysfunction-associated steatotic liver disease (MASLD), have become a global health burden in the last three decades. The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) data enables the first insights into the trends and burdens of these metabolic diseases from 1990 to 2021, highlighting regional, temporal and differences by sex. METHODS: Global estimates of disability-adjusted life years (DALYs) and deaths from GBD 2021 were analyzed for common metabolic diseases (T2DM, hypertension, obesity, hypercholesterolemia, and MASLD). Age-standardized DALYs (mortality) per 100,000 population and annual percentage change (APC) between 1990 and 2021 were estimated for trend analyses. Estimates are reported with uncertainty intervals (UI). RESULTS: In 2021, among five common metabolic diseases, hypertension had the greatest burden (226 million [95 % UI: 190-259] DALYs), whilst T2DM (75 million [95 % UI: 63-90] DALYs) conferred much greater disability than MASLD (3.67 million [95 % UI: 2.90-4.61]). The highest absolute burden continues to be found in the most populous countries of the world, particularly India, China, and the United States, whilst the highest relative burden was mostly concentrated in Oceania Island states. The burden of these metabolic diseases has continued to increase over the past three decades but has varied in the rate of increase (1.6-fold to 3-fold increase). The burden of T2DM (0.42 % [95 % UI: 0.34-0.51]) and obesity (0.26 % [95 % UI: 0.17-0.34]) has increased at an accelerated rate, while the rate of increase for the burden of hypertension (-0.30 % [95 % UI: -0.34 to -0.25]) and hypercholesterolemia (-0.33 % [95 % UI: -0.37 to -0.30]) is slowing. There is no significant change in MASLD over time (0.05 % [95 % UI: -0.06 to 0.17]). CONCLUSION: In the 21st century, common metabolic diseases are presenting a significant global health challenge. There is a concerning surge in DALYs and mortality associated with these conditions, underscoring the necessity for a coordinated global health initiative to stem the tide of these debilitating diseases and improve population health outcomes worldwide.

Publication trends of Leber congenital amaurosis researches: a bibliometric study during 2002-2022.

AIM: To analyze the changes in scientific output relating to Leber congenital amaurosis (LCA) and forecast the study trends in this field. METHODS: All of the publications in the field of LCA from 2002 to 2022 were collected from Web of Science (WOS) database. We analyzed the quantity (number of publications), quality (citation and H-index) and development trends (relative research interest, RRI) of published LCA research over the last two decades. Moreover, VOSviewer software was applied to define the co-occurrence network of keywords in this field. RESULTS: A total of 2158 publications were ultimately examined. We found that the focus on LCA kept rising and peaked in 2015 and 2018, which is consistent with the development trend of gene therapy. The USA has contributed most to this field with 1162 publications, 56 674 citations and the highest H-index value (116). The keywords analysis was divided into five clusters to show the hotspots in the field of LCA, namely mechanism-related, genotype-related, local phenotype-related, system phenotype-related, and therapy-related. We also identified gene therapy and anti-retinal degeneration therapy as a major focus in recent years. CONCLUSION: Our study illustrates historical research process and future development trends in LCA field. This may help to guide the orientation for further clinical diagnosis, treatment and scientific research.

Nonmetal Doping Modulates Fe Single-Atom Catalysts for Enhancement in Peroxidase Mimicking via Symmetry Disruption, Distortion, and Charge Transfer.

Developing biomimetic catalysts with excellent peroxidase (POD)-like activity has been a long-standing goal for researchers. Doping nonmetallic atoms with different electronegativity to boost the POD-like activity of Fe-N-C single-atom catalysts (SACs) has been successfully realized. However, the introduction of heteroatoms to regulate the coordination environment of the central Fe atom and thus influence the activation of the H2O2 molecule in the POD-like reaction has not been extensively explored. Herein, the effect of different doping sites and numbers of heteroatoms (P, S, B, and N) on the adsorption and activation of H2O2 molecules of Fe-N sites is thoroughly investigated by density functional theory (DFT) calculations. In general, alternation in the catalytic efficiency directly depends on the transfer of electrons and the geometrical shifts near the Fe-N site. First, the symmetry disruption of the Fe-N4 site by P, S, and B doping is beneficial to the activation of H2O2 due to a significant reduction in the adsorption energies. In some cases, without Fe-N4 site disruption, the configurations fail to modulate the adsorption behavior of H2O2. Second, Fe-N-P/S configurations exhibit a stronger affinity for H2O2 molecules due to the significant out-of-plane distortions induced by larger atomic radii of P and S. Moreover, the synergistic effects of Fe and doping atoms P, S, and B with weaker electronegativity than that of N atoms promote electron donation to generated oxygen-containing intermediates, thus facilitating subsequent electron transfer with other substrates. This work demonstrates the critical role of tuning the coordinating environment of Fe-N active centers by heteroatom doping and provides theoretical guidance for controlling the types by breaking the symmetry of SACs to achieve optimal POD-like catalytic activity and selectivity.

[Analysis of the therapeutic effect of trochanteric flip osteotomy combined with Kocher-Langenbeck approach for high acetabular posterior wall fracture].

OBJECTIVE: Evaluation of the clinical efficacy of f trochanteric flip osteotomy combined with Kocher-Langenbeck approach for high acetabular posterior wall fracture. METHODS: Between January 2020 and December 2022, 20 patients with high acetabular posterior wall fractures were retrospectively analyzed, including 12 males and 8 females, aged 18 to 75 years old. They were divided into two groups according to the different surgical methods. Ten patients were treated with greater trochanteric osteotomy combined with Kocher-Langenbeck approach as the observation group, including 5 males and 5 females, aged from 18 to 75 years old. Ten patients were treated with Kocher-Langenbeck approach alone as the control group, including 7 males and 3 females, aged from 18 to 71 years old. Matta reduction criteria were used to evaluate the reduction quality of the two groups, and Harris score was used to compare the hip function of the two groups at the latest follow-up. The operation time, blood loss and postoperative complications of the two groups were analyzed. RESULTS: All patients were followed up for 10 to 24 months. According to the Matta fracture reduction quality evaluation criteria, the observation group achieved anatomical reduction in 6 cases, satisfactory reduction in 3 cases, and unsatisfactory reduction in 1 case, while the control group only achieved anatomical reduction in 3 cases, satisfactory reduction in 3 cases, and unsatisfactory reduction in 4 cases. At the final follow-up, the Harris hip score ranged from 71.4 to 96.6 in the observation group and 65.3 to 94.5 in the control group. According to the results of Harris score. The hip joint function of the observation group was excellent in 6 cases, good in 3 cases, and fair in 1 case. The hip joint function of the control group was excellent in 2 cases, good in 3 cases, fair in 3 cases, and poor in 2 cases. In the observation group, the intraoperative blood loss ranged from 300 to 700 ml, and the operation duration ranged from 120 to 180 min;in the control group, the intraoperative blood loss ranged from 300 to 650 ml, and the operation duration ranged from 100 to 180 min. Complications in the observation group included 1 case of traumatic arthritis and 1 case of heterotopic ossification, while complications in the control group included 3 cases of traumatic arthritis, 3 cases of heterotopic ossification and 1 case of hip abduction weakness. CONCLUSION: Trochanteric flip osteotomy combined with the Kocher-Langenbeck approach significantly improved anatomical fracture reduction rates, enhanced excellent and good hip joint function outcomes, and reduced surgical complication incidence compared to the Kocher-Langenbeck approach alone. Clinical application of this combined approach is promising, although larger studies are needed for further validation.

Clinical features and prognostic model for viral encephalitis after allogeneic haematopoietic stem cell transplantation.

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.

[Phytic Acid Modification Enhanced Cadmium Sorption and Immobilization of Sludge-based Hydrochar].

Phytic acid-assisted sludge hydrothermal carbonization was employed to synthesize phytic acid-modified hydrochar via a one-step method. The surface morphology, pore structure, elemental composition, functional groups, and thermal stability of the phytic acid-modified hydrochar were characterized. Sorption kinetics and isotherm experiments were conducted to investigate the effects of humic acid, temperature, and pH on the sorption process of cadmium （Cd） onto the phytic acid-modified hydrochar. The Cd fixation ability was evaluated through soil passivation experiments. The results demonstrated that the surface of the phytic acid-modified hydrochar exhibited an abundance of phosphoric acid groups, enhanced electronegativity, and thermal stability. Furthermore, both the sorption rate and maximum sorption capacity for Cd increased by 1.88 times and 1.22 times compared to that in unmodified hydrochar, respectively, owing to the presence of phosphoric acid groups that enhanced complexation and electrostatic interaction with Cd. Elevated temperatures, higher pH values, and coexistence with humic acids were beneficial for enhancing Cd sorption onto phytic acid-modified hydrochar. When heavy metals such as Cu, Zn, and Pb coexisted, the sorption capacity of phytic acid-modified hydrochar for Cd was 0.77-6.88 times higher than that for other metals. Phyic acid-modified hydrochar exhibited excellent efficiency in fixing Cd （56.1%-81.l%）, mitigating the loss of available nutrients in soil and significantly increasing the AP content in the soil. In conclusion, the use of phytic acid-modified hydrochar could effectively remove Cd from water and serve as a promising soil amendment for stabilizing soil Cd content.

Natriuretic peptide receptor-C perturbs mitochondrial respiration in white adipose tissue.

Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues, and regulates obesity related diseases, however the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein 1 (UCP1) and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1 and mitochondrial complex expression. These findings demonstrate that NPR-C deficiency enhances metabolic health by boosting energy expenditure in WAT, emphasizing the potential of NPR-C inhibition for treating obesity and related metabolic disorders.

Targeting AGTPBP1 inhibits pancreatic cancer progression via regulating microtubules and ERK signaling pathway.

BACKGROUND: AGTPBP1 is a cytosolic carboxypeptidase that cleaves poly-glutamic acids from the C terminus or side chains of α/ß tubulins. Although its dysregulated expression has been linked to the development of non-small cell lung cancer, the specific roles and mechanisms of AGTPBP1 in pancreatic cancer (PC) have yet to be fully understood. In this study, we examined the role of AGTPBP1 on PC in vitro and in vivo. METHODS: Immunohistochemistry was used to examine the expression of AGTPBP1 in PC and non-cancerous tissues. Additionally, we assessed the malignant behaviors of PC cells following siRNA-mediated AGTPBP1 knockdown both in vitro and in vivo. RNA sequencing and bioinformatics analysis were performed to identify the differentially expressed genes regulated by AGTPBP1. RESULTS: We determined that AGTPBP1 was overexpressed in PC tissues and the higher expression of AGTPBP1 was closely related to the location of tumors. AGTPBP1 inhibition can significantly decrease cell progression in vivo and in vitro. Moreover, the knockdown of AGTPBP1 inhibited the expression of ERK1/2, P-ERK1/2, MYLK, and TUBB4B proteins via the ERK signaling pathway. CONCLUSION: Our research indicates that AGTPBP1 may be a putative therapeutic target for PC.

Dandelion inspired microparticles with highly efficient drug delivery to deep lung.

Active pharmaceutical ingredient (API) embedded dry powder for inhalation (AeDPI) shows higher drug loading and delivery dose for directly treating various lung infections. Inspired by the dandelion, we propose a novel kind of AeDPI microparticle structure fabricated by spray freeze drying technology, which would potentially enhance the alveoli deposition efficiency. When inhaling, such microparticles are expected to be easily broken-up into fragments containing API that acts as 'seed' and could be delivered to alveoli aided by the low density 'pappus' composed of excipient. Herein, itraconazole (ITZ), a first-line drug for treating pulmonary aspergillosis, was selected as model API. TPGS, an amphiphilic surfactant, was used to achieve stable primary ITZ nanocrystal (INc) suspensions for spray freeze drying. A series of microparticles were prepared, and the dandelion-like structure was successfully achieved. The effects of feed liquid compositions and freezing parameters on the microparticle size, morphology, surface energy, crystal properties and in vitro aerosol performance were systematically investigated. The optimal sample (SF(-50)D-INc7Leu3-2) in one-way experiment showed the highest fine particle fraction of ∼ 68.96 % and extra fine particle fraction of ∼ 36.87 %, equivalently ∼ 4.60 mg and ∼ 2.46 mg could reach the lung and alveoli, respectively, when inhaling 10 mg dry powders. The response surface methodology (RSM) analysis provided the optimized design space for fabricating microparticles with higher deep lung deposition performance. This study demonstrates the advantages of AeDPI microparticle with dandelion-like structure on promoting the delivery efficiency of high-dose drug to the deep lung.

Gasdermin-E-mediated pyroptosis drives immune checkpoint inhibitor-associated myocarditis via cGAS-STING activation.

Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, is activated in myocardial tissue of mice and cancer patients with ICI-induced myocarditis. Deficiency of GSDME in male mice alleviates ICI-induced cardiac infiltration of T cells, macrophages, and monocytes, as well as mitochondrial damage and inflammation. Restoration of GSDME expression specifically in cardiomyocytes, rather than myeloid cells, in GSDME-deficient mice reproduces ICI-induced myocarditis. Mechanistically, quantitative proteomics reveal that GSDME-dependent pyroptosis promotes cell death and mitochondrial DNA release, which in turn activates cGAS-STING signaling, triggering a robust interferon response and myocardial immune/inflammation activation. Pharmacological blockade of GSDME attenuates ICI-induced myocarditis and improves long-term survival in mice. Our findings may advance the understanding of ICI-induced myocarditis and suggest that targeting the GSDME-cGAS-STING-interferon axis may help prevent and manage ICI-associated myocarditis.

A robust ensemble deep learning framework for accurate diagnoses of tuberculosis from chest radiographs.

Introduction: Tuberculosis (TB) stands as a paramount global health concern, contributing significantly to worldwide mortality rates. Effective containment of TB requires deployment of cost-efficient screening method with limited resources. To enhance the precision of resource allocation in the global fight against TB, this research proposed chest X-ray radiography (CXR) based machine learning screening algorithms with optimization, benchmarking and tuning for the best TB subclassification tasks for clinical application. Methods: This investigation delves into the development and evaluation of a robust ensemble deep learning framework, comprising 43 distinct models, tailored for the identification of active TB cases and the categorization of their clinical subtypes. The proposed framework is essentially an ensemble model with multiple feature extractors and one of three fusion strategies-voting, attention-based, or concatenation methods-in the fusion stage before a final classification. The comprised de-identified dataset contains records of 915 active TB patients alongside 1,276 healthy controls with subtype-specific information. Thus, the realizations of our framework are capable for diagnosis with subclass identification. The subclass tags include: secondary tuberculosis/tuberculous pleurisy; non-cavity/cavity; secondary tuberculosis only/secondary tuberculosis and tuberculous pleurisy; tuberculous pleurisy only/secondary tuberculosis and tuberculous pleurisy. Results: Based on the dataset and model selection and tuning, ensemble models show their capability with self-correction capability of subclass identification with rendering robust clinical predictions. The best double-CNN-extractor model with concatenation/attention fusion strategies may potentially be the successful model for subclass tasks in real application. With visualization techniques, in-depth analysis of the ensemble model's performance across different fusion strategies are verified. Discussion: The findings underscore the potential of such ensemble approaches in augmenting TB diagnostics with subclassification. Even with limited dataset, the self-correction within the ensemble models still guarantees the accuracies to some level for potential clinical decision-making processes in TB management. Ultimately, this study shows a direction for better TB screening in the future TB response strategy.

Ce12V6 Clusters with Multi-Enzymatic Activities for Sepsis Treatment.

Artificial enzymes, especially nanozymes, have attracted wide attention due to their controlled catalytic activity, selectivity, and stability. The rising Cerium-based nanozymes exhibit unique SOD-like activity, and Vanadium-based nanozymes always hold excellent GPx-like activity. However, most inflammatory diseases involve polymerase biocatalytic processes that require multi-enzyme activities. The nanocomposite can fulfill multi-enzymatic activity simultaneously, but large nanoparticles (>10 nm) cannot be excreted rapidly, leading to biosafety challenges. Herein, atomically precise Ce12V6 clusters with a size of 2.19 nm are constructed. The Ce12V6 clusters show excellent glutathione peroxidase (GPx) -like activity with a significantly lower Michaelis-Menten constant (Km, 0.0125 mM versus 0.03 mM of natural counterpart) and good activities mimic superoxide dismutase (SOD) and peroxidase (POD). The Ce12V6 clusters exhibit the ability to scavenge the ROS including O2 ·- and H2O2 via the cascade reactions of multi-enzymatic activities. Further, the Ce12V6 clusters modulate the proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) and consequently rescue the multi-organ failure in the lipopolysaccharide (LPS)-induced sepsis mouse model. With excellent biocompatibility, the Ce12V6 clusters show promise in the treatment of sepsis.

Application of fecal immunochemical test in colorectal cancer screening: A community-based, cross-sectional study in average-risk individuals in Hainan.

BACKGROUND: The incidence of colorectal cancer (CRC) in China is steadily rising, with a high proportion of advanced-stage diagnoses. This highlights the significance of early detection and prevention measures to enhance survival rates. Fecal immunochemical testing (FIT) is a globally recommended CRC screening method; however, limited research has been conducted on its application in Hainan. AIM: To assess the efficacy and adherence of FIT screening among average-risk individuals in Hainan, while also examining the risk factors associated with positive FIT results. METHODS: This population-based cross-sectional study implemented FIT screening for CRC in 2000 asymptomatic participants aged 40-75 years from five cities and 21 community health centers in Hainan Province. The study was conducted from August 2022 to April 2023, employing a stratified sampling method to select participants. Individuals with positive FIT results subsequently underwent colonoscopy. Positive predictive values for confirmed CRC and advanced adenoma were calculated, and the relationship between relevant variables and positive FIT results was analyzed using χ 2 tests and multivariate logistic regression. RESULTS: A total of 1788 participants completed the FIT screening, with a median age of 57 years (interquartile range: 40-75). Among them, 503 (28.1%) were males, and 1285 (71.9%) were females, resulting in an 89.4% compliance rate for FIT screening. The overall positivity rate of FIT was 4.4% [79 out of 1788; 95% confidence interval (CI): 3%-5%]. The specific positivity rates for Haikou, Sanya, Orient City, Qionghai City, and Wuzhishan City were 9.6% (45 of 468; 95%CI: 8%-11%), 1.3% (6 of 445; 95%CI: 0.1%-3.1%), 2.7% (8 of 293; 95%CI: 1.2%-4.3%), 3.3% (9 of 276; 95%CI: 1.0%-6.3%), and 4.2% (11 of 406; 95%CI: 1.2%-7.3%), respectively. Significant associations were found between age, dietary habits, and positive FIT results. Out of the 79 participants with positive FIT results, 55 underwent colonoscopy, demonstrating an 82.2% compliance rate. Among them, 10 had a clean gastrointestinal tract, 43 had polyps or adenomas, and 2 were confirmed to have CRC, yielding a positive predictive value of 3.6% (95%CI: 0.9%-4.2%). Among the 43 participants with polyps or adenomas, 8 were diagnosed with advanced adenomas, resulting in an advanced adenoma rate of 14.5% (95%CI: 10.1%-17.7%). CONCLUSION: In the Hainan region, FIT screening for CRC among asymptomatic individuals at average risk is feasible and well-received.

Phytocannabinoid-like meroterpenoids from twigs and leaves of Rhododendron spinuliferum.

Six pairs of previously undescribed enantiomeric phytocannabinoid-like meroterpenoids, (±)-spinulinoids A‒F, and two naturally occurring compounds, (+)-rhododaurichromanic acid A and (E)-4-((3,7-dimethylocta-2,6-dien-1-yl)oxy)benzoic acid, together with one known congener, (-)-rhododaurichromanic acid A, were obtained from the twigs and leaves of Rhododendron spinuliferum. Their structures were established by their extensive spectral data (NMR and HRESIMS), ECD calculations, and single-crystal X-ray diffraction data. Spinulinoids A and B are unprecedented phytocannabinoid-like meroterpenoids constructed by the resorcinol moiety and a ß-bisabolene unit, whereas spinulinoid C represents a rare adduct of quinone and ß-bisabolene with a tricyclic 6/6/6 ring system.

Clinical characteristics and prognostic importance of anticoagulant use in ischemic left ventricular aneurysm: a retrospective cohort study.

There is insufficient data on systemic embolic events (SSEs) in patients with ischemic left ventricular aneurysm (LVA) concerning the impact of anticoagulation therapy. In this retrospective cohort study with 1043 patients with ischemic LVA, SSEs occurred in 7.2% over 2.4 years. After adjusting for relevant factors, the use of anticoagulants was independently associated with a lower incidence of SSE (3.1% vs. 9.0%, P < 0.001; subdistribution hazard ratios (SHR) 0.21, 95% confidence intervals (CI) 0.10-0.44, P < 0.001), with no significant difference in net adverse clinical events (NACEs) (10.6% vs. 13.3%, P = 0.225). Specifically, anticoagulation in patients with apical segment akinesis significantly reduced SSEs (3.9% vs. 13.6%, P = 0.002) and NACE rates (7.8% vs. 19.4%, P = 0.002). Major bleeding rates did not significantly differ between groups (5.6% vs. 3.5%, P = 0.111). These findings highlight the SSE risk in ischemic LVA and suggest potential benefits of anticoagulation, particularly in those with apical segment akinesis. These findings need to be validated in independent datasets.

Microscopic in situ observation of electromechanical instability in a dielectric elastomer actuator utilizing transparent carbon nanotube electrodes.

Electromechanical instability (EMI) restricts the performance of dielectric elastomer actuators (DEAs), leading to premature electrical breakdown at a certain voltage. However, macro-level observations using traditional carbon grease electrodes have failed to capture the detailed features of EMI. In this study, we investigated EMI at the microscopic scale by fabricating transparent and conductive single-walled carbon nanotube (SWCNT) electrodes. Our findings reveal that EMI predominantly occurs in highly localized regions with dimensions on the order of tens of micrometers. This snap-through instability is likely induced by pre-existing defects within the elastomer, such as air voids or conductive particles, which reduce the critical voltage required for EMI in the flawed areas. From the perspective of phase transition principles, these defects act as heterogeneous nucleation sites for new phase embryos, thereby lowering the energy barrier for the electromechanical phase transition (i.e., EMI) compared to homogeneous nucleation in an ideally impurity-free elastomer. This study clarifies the longstanding discrepancy between theoretically predicted deformation bursts and the experimentally observed macroscopic continuous expansion of DEAs under low pre-stretch conditions. Additionally, it underscores the critical importance of material purity in mitigating electromechanical instability.