Pattern of cooling benefits from ecospaces during urbanization: A case study of the Yangtze River Economic Belt.

Urban ecological spaces are effective thermoregulators under global warming. However, the cooling efficiency of urban ecological spaces during the urbanization has not been studied comprehensively. Here, we investigate the spatio-temporal dynamics of Urban Cold Island (UCI) intensity in 11 typical cities of the Yangtze River Economic Belt (YREB). We determined the impact of ecological landscape trends on these dynamics by using GlobalLand and MODIS 8 d mean land surface temperature (LST) data for three periods (2000, 2010, and 2020), and the landscape pattern index and diversity index. We found that in the past 20 years, the built-up area has increased by sixfold; 62.53 % and 37.47 % of YREB were warming or cooling, with 71.22 % of the daytime cooling and 93 % of the nighttime warming. The average UCI intensity of YREB has increased from 0.518 to 0.847 and is negatively correlated with LST with a decreasing slope. As the UCI intensity of green spaces increased, that of blue spaces decreased. Surface area and landscape pattern are the key determinants of UCI intensity in blue and green spaces, respectively, especially the landscape shape index (LSI). Therefore, maintaining ecological spaces, enriching the structural integrity of green spaces, and improving blue space connectivity can help cities at different development levels cope with heat stress during regional urbanization.

Improve the satisfaction of medical staff on the use of home nursing mobile APP by using a hybrid multi-standard decision model.

OBJECTIVE: To identify critical satisfaction gaps in a home nursing mobile application (APP) using a systematic decision-making model. METHODS: Initially, the decision-making trial and evaluation laboratory method was used to analyze the relationship structure and corresponding weights among the indicators. The Importance-Performance Analysis (IPA) method was used to identify the categories of all indicators and their corresponding strategic directions. Twenty-six home nursing specialists currently providing home nursing services were recruited for this study. RESULTS: The IPA results revealed that "Assurance," "Reliability," and "Personal security protection" are critical satisfaction gaps. From the influence network and weight results, "information quality" and "system quality" were the critical quality factors in the home nursing mobile APP. The influence of the network relationship structure and weight demonstrated a 98.12% significance level, indicating good stability. CONCLUSION: Continuous improvement in information and system quality is recommended to optimize the overall quality of the home nursing mobile APP. Additionally, user demands should be considered, and personal safety guarantee functions should be developed and integrated into the system to ensure the safety of home nursing workers.

PUM2 promoted osteoarthritis progression through PTEN-mediated chondrocyte ferroptosis by facilitating NEDD4 mRNA degradation.

Osteoarthritis (OA) is a prevalent degenerative joint disease with a lack of effective therapeutic. Chondrocyte ferroptosis contributes to the progression of OA. PUM2 is shown to exacerbate ischemia-reperfusion-induced neuroinflammation by promoting ferroptosis, but its role in OA remains unexplored. Here, primary mouse chondrocytes were stimulated with IL-1ß to mimic OA chondrocyte injury in vitro. And PUM2 was upregulated in OA cartilage tissues and IL-1ß-induced chondrocytes. Silencing PUM2 alleviated IL-1ß-induced chondrocyte inflammation and ECM degradation. Mechanistically, PUM2 facilitated the degradation of NEDD4 mRNA by binding to the 3'UTR of NEDD4 mRNA, which in turn inhibited NEDD4 induced PTEN ubiquitination and degradation. Consistently, NEDD4 silencing reversed the ameliorative effect of PUM2 knockdown on chondrocyte injury, and overexpression of PTEN abolished the improved role of NEDD4 in chondrocyte injury. Moreover, PTEN aggravated IL-1ß-induced ferroptosis in chondrocytes through the Nrf2/HO-1 pathway by increasing the levels of Fe2+, ROS, MDA, and ACSL4 protein, decreasing the activity of SOD and the levels of GSH and GPX4 protein, and aggravating mitochondrial damage. Additionally, destabilized medial meniscus (DMM) were conducted to establish the OA mouse model, and adenovirus-mediated PUM2 shRNA was administered intra-articularly. Silencing PUM2 attenuated OA-induced cartilage damage in vivo. In conclusion, PUM2 promoted OA progression through PTEN-mediated chondrocyte ferroptosis by facilitating NEDD4 mRNA degradation.

Establishment and validation of an artificial intelligence-based model for real-time detection and classification of colorectal adenoma.

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.

Effectiveness of virtual reality in preventing falls in non-disabled older adults: A meta-analysis and systematic review.

OBJECTIVE: This study was conducted to evaluate the effectiveness of virtual reality interventions in preventing falls among non-disabled older adults. METHODS: We conducted a librarian-designed database search. Two researchers independently screened eligible studies. The Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias in the included studies. RESULTS: Virtual reality interventions can effectively improve gait and dynamic and static balance function, enhance lower limb muscle strength, and reduce the risk of falls in the non-disabled elderly. However, the effect of virtual reality on reducing the fear of falling remains controversial. CONCLUSION: Virtual reality interventions can effectively prevent falls in nondisabled elderly individuals. Higher quality, larger sample size, and long-term follow-up studies are needed to further verify the long-term effectiveness of virtual reality training in preventing falls in non-disabled elderly individuals.

Sediment resuspension as a driving force for organic carbon transference and rebalance in marginal seas.

The transfer of particulate organic carbon (POC) to dissolved organic carbon (DOC; OC transferP-D) is crucial for the marine carbon cycle. Sediment resuspension driven by hydrodynamic forcing can affect the burial of sedimentary POC and benthic biological processes in marginal sea. However, the role of sediment grain size fraction on OC transferP-D and the subsequent impact on OC cycling remain unknown. Here, we conduct sediment resuspension simulations by resuspending grain-size fractionated sediments (< 20, 20-63, and > 63 µm) into filtered seawater, combined with analyses of OC content, optical characteristics, 13C and 14C isotope compositions, and molecular dynamics simulations to investigate OC transferP-D and its regulations on OC bioavailability under sediment resuspension. Our results show that the relative intensities of terrestrial humic-like OC (refractory DOC) increase in resuspension experiments of < 20, 20-63, and > 63 µm sediments by 0.14, 0.01, and 0.03, respectively, likely suggesting that sediment resuspension drives refractory DOC transfer into seawater. The variations in the relative intensities of microbial protein-like DOC are linked to the change of terrestrial humic-like OC, accompanied by higher DOC content and reactivity in seawater, particularly in finer sediments resuspension experiments. This implies that transferred DOC likely fuels microbial growth, contributing to the subsequent enhancement of DOC bioavailability in seawater. Our results also show that the POC contents increase by 0.35 %, 0.66 %, and 0.93 % in < 20, 20-63, and > 63 µm resuspension experiments at the end of incubation, respectively. This suggests that the re-absorption of OC on particles may be a significant process, but previously unrecognized during sediment resuspension. Overall, our findings suggest that sediment resuspension promotes the OC transferP-D, and the magnitudes of OC transferP-D further influence the DOC and POC properties by inducing microbial production and respiration. These processes significantly affect the dynamics and recycling of biological carbon pump in shallow marginal seas.

WO3-x as an activation medium to prompt overall water splitting of NiFe-based electrocatalyst.

The efficient oxygen evolution reaction (OER) is crucial for various electrochemical processes, especially for overall water splitting (OWS). In this study, we focus on the utilization of WO3-x as an activation medium to enhance the OER performance of NiFe-based electrocatalysts. Firstly, we synthesize WO3-x nanowires supported on nickel foam (NF) and then incorporate NiFe on WO3-x nanowires by a simple hydrothermal method. The WO3-x self-supported NiFe (Oxy)hydroxide (denoted as NiFe-W-O/NF) shows a three-dimensional stereostructure composed of ultrathin nanosheets (∼ 4.0 nm). This unique structure provides a large open surface for fuller diffusion of the electrolyte while exposing more active sites. The electronic interaction of tri-centers of NiFeW accelerates the surface reconstruction process of γ-NiOOH and FeOOH, which are converted into the main active species in a short time. The electrochemical measurements confirm that the NiFe-W-O/NF has low OER overpotentials (233 mV at 10 mA cm-2, 298 mV at 100 mA cm-2) and excellent stability (100 h in total) in 1 M KOH electrolyte. In addition, the NiFe-W-O/NF || NiFe-W-O/NF battery also exhibits a low cell voltage (1.52 V at 10 mA cm-2) with a stable lifetime (50 h) under alkaline conditions. These results highlight the great potential of NiFe-W-O/NF for practical applications.

Hydrodeoxygenation of Oxygen-Containing Aromatic Plastic Wastes into Cycloalkanes and Aromatics.

Chemical recycling and upcycling offer promising approaches for the management of plastic wastes. Hydrodeoxygenation (HDO) is one of the appealing ways for conversion of oxygen-containing plastic wastes, including PET, PBT, PC, PPO, and PEEK, into cyclic alkanes and aromatics in high yields under mild reaction conditions. The challenge lies in achieving C-O activation while preserving C-C bonds. In this review, we highlight the recent advancements in catalytic strategies and catalysts for the conversion of these oxygen-containing plastic wastes into cycloalkanes and aromatics. The reaction systems, including multi-step routes, direct HDO and transfer HDO methods, are exemplified. The design and performance of HDO catalysts are systematically summarized and compared. We comprehensively discuss the functions of the catalysts' components, reaction pathway and mechanism to gain insights into the HDO process for efficient valorization of oxygen-containing plastic wastes. Finally, we provide perspectives for this field, with specific emphasis on the non-noble metal catalyst design, selectivity control, reaction network and mechanism studies, mixed plastic wastes management and product functionalization. We anticipate that this review will inspire innovations on the catalytic process development and rational catalyst design for the HDO of oxygen-containing aromatic plastics to establish a low-emission circular economy.

Reverse remodeling of mitral leaflets after medical treatment in recent-onset dilated cardiomyopathy.

BACKGROUND: The growth of mitral leaflets (MLs) adaptive to left ventricluar (LV) remodeling has been observed. However, the elasticity of MLs upon mechanical stimuli would be supposed if it shrinks with LV reverse remodeling (LVRR). MATERIAL AND METHODS: Patients with idiopathic recent-onset dilated cardiomyopathy (RODCM) (n = 82) and 50 matched normal controls (NC) were prospectively enrolled. Echocardiography was performed at baseline and 6 months of follow-up for the anterior and posterior mitral leaflet (AML and PML) length, mitral annular dimension (MAD), and tenting height (TH). LVRR was measured as a ≥ 15% reduction in LV end-diastolic volume (LVEDV). RESULTS: After 6 months, LVRR was achieved in 69.5% of patients. The AML (28 ± 3 vs. 26 ± 3 mm, p = 0.004) and PML (19 ± 4 vs. 17 ± 3 mm, p < 0.001) decreased in length, as well as the MAD (31 ± 5 vs. 28 ± 5 mm, p = 0.001) and TH (10 ± 3 vs. 8 ± 2 mm, p < 0.001). Compared with the NC group, the AML and PML of the RODCM group were 16.7% and 35.7% longer at baseline and remained 8.3% and 21.2% longer at follow-up, respectively. The change in AML or PML correlated moderately with that in LVEDV (r = 0.487, p < 0.001; r = 0.516, p < 0.001, respectively). The AML and PML length decreased in the LVRR (+) subgroup (AML, 28 ± 3 vs. 26 ± 3 mm, p = 0.001; PML, 20 ± 4 vs. 16 ± 3 mm, p < 0.001), but remained the same in the LVRR (-) subgroup (27 ± 4 vs. 28 ± 4 mm, p = 0.318; 17 ± 3 vs. 17 ± 3 mm, p = 0.790). CONCLUSIONS: Enlarged MLs could reverse accompanied by LV reverse remodeling. This study provided the other facet of ML plasticity adaptive to mechanical stretching.

Enhancement of vincristine sensitivity in retinoblastoma through Janus kinase inhibition by ruxolitinib.

Chemotherapy remains the main approach conserving vision during the treatment of retinoblastoma, the most prevalent eye cancer in children. Unfortunately, the development of chemoresistance stands as the primary reason for treatment failure. Within this study, we showed that prolonged exposure to vincristine led to heightened expression of JAK1 and JAK2 in retinoblastoma cells, while the other members of the JAK family exhibited no such changes. Employing a genetic intervention, we demonstrated the efficacy of depleting either JAK1 or JAK2 in countering vincristine-resistant retinoblastoma cells. In addition, the dual depletion of both JAK1 and JAK2 produced a more potent inhibitory outcome compared to the depletion of either gene alone. We further demonstrated that ruxolitinib, a small molecular inhibitor of JAK1/2, effectively reduced viability and colony formation in vincristine-resistant retinoblastoma cells. It also acts synergistically with vincristine in retinoblastoma cells regardless of inherent cellular and genetic heterogeneity. The effectiveness of ruxolitinib as standalone treatment against chemoresistant retinoblastoma, as well as its combination with vincristine, was validated in multiple retinoblastoma mouse models. Importantly, mice exhibited favorable tolerance to ruxolitinib administration. We confirmed that the underlying mechanism of ruxolitinib's action in chemoresistant retinoblastoma cells is the inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling. Our study reveals that the underlying mechanism driving ruxolitinib's impact on chemoresistant retinoblastoma cells is the inhibition of JAK/STAT signaling. This study reveals the contribution of JAK1/2 to the development of chemoresistance in retinoblastoma and underscores the effectiveness of targeting JAK1/2 as a strategy to sensitize retinoblastoma to chemotherapy.

Trends in violent offending among people with schizophrenia: A 10-year ecological study.

Violent offending committed by people with schizophrenia has been a public concern. The present study aims to examine the incidence of violent offending among people with schizophrenia and its correlations with mental health resources and economic factors. In this study, an examination of violent offending by people with schizophrenia and those identified as not criminally responsible on account of mental disorder (NCRMD) between 2010 and 2019 in China's Hunan province was undertaken. Principal component analysis (PCA) and regression analyses were used to explore the association of violent offending in people with schizophrenia and those identified as NCRMD with violent offending in the general population, mental health medical resources, and provincial GDP. Between 2010 and 2019, a total of 2,093 people with schizophrenia committed violent offending in Hunan province, including 1,374 (65.6%) cases identified as NCRMD. Over the period, the incidence of violent offending in people with schizophrenia and those identified as NCRMD has been decreasing. The incidences were positively correlated with the incidence of violent offending in the general population and negatively associated with mental health resources and provincial GDP. These findings may be valuable in helping to develop strategies for violence prevention and risk management for people with schizophrenia.

Identification of the immune repertoire of γδ T-cell receptors in psoriasis.

The γδ T cells are a subpopulation of T cells that are abundantly found in the skin and mucous membranes. Their reactivity to self-antigens and ability to secrete various cytokines make them a key component in psoriasis development. Although the correlation between the immune repertoire (IR) of γδ T-cell receptors and the occurrence and severity of psoriasis remains incompletely explored, high-throughput sequencing of γδ T cells has led to a deeper understanding of IR in psoriasis. This study investigated the differences between γδ T cells in patients with psoriasis and healthy controls. The γδ T cells were identified via immunofluorescence staining and a correlation analysis was performed according to the psoriasis area and severity index (PASI) scores. The IR sequencing method was used to detect IR in the γδ T-cell receptors. The findings demonstrated more skin γδ T cells in patients with psoriasis, which were positively correlated with the PASI score. There were subtle differences in most variable (V), diversity (D) and joining (J) gene segments and VJ/VDJ combination segments between patients with psoriasis and healthy controls. However, a higher diversity of complementarity-determining region 3 (CDR3) was observed in patients with psoriasis. In summary, the IR of skin γδ T cells was significantly altered in patients with psoriasis, and the diversity in the cell's CDR3 population is a promising biomarker for assessment of psoriasis severity.

The mediating effects of hope on the relationships of social support and self-esteem with psychological resilience in patients with stroke.

PURPOSE: To explore the mediating effect of hope in the relationships between social support and self-esteem with psychological resilience among patients with stroke survivors in early rehabilitation. METHODS: A cross-sectional study design was adopted. Data from a cross-sectional survey of 210 patients undergoing early stroke rehabilitation were analyzed using structural equation modeling. The variables of interest were measured using the Connor Davidson Resilience Scale, the Social Support Rating Scale, the Herth Hope Index, and the Self-Esteem Scale. This article reports according to the STROBE checklist. RESULTS: A positive relationship was found between social support and psychological resilience (ß1 = 0.548), which was mediated by hope (ß2 = 0.114), and social support had significant direct effect on resilience (ß3 = 0.434). A positive relationship was also found between self-esteem and psychological resilience (ß4 = 0.380), which was mediated by hope (ß5 = 0.200), and self-esteem had significant direct effect on resilience (ß6 = 0.179). CONCLUSION: According to the results of this study, some strategies can be incorporated into the rehabilitation process to enhance psychological resilience, such as cultivating individual personality characteristics and improving patients' social relationships. In the future, we need to explore methods for improving psychological resilience among patients with stroke in combination with their risk factors to improve their quality of life and reduce the incidence of post-stroke depression.

Genetically optimizing soybean nodulation improves yield and protein content.

Symbiotic nitrogen fixation in legume nodules requires substantial energy investment from host plants, and soybean (Glycine max (L.) supernodulation mutants show stunting and yield penalties due to overconsumption of carbon sources. We obtained soybean mutants differing in their nodulation ability, among which rhizobially induced cle1a/2a (ric1a/2a) has a moderate increase in nodule number, balanced carbon allocation, and enhanced carbon and nitrogen acquisition. In multi-year and multi-site field trials in China, two ric1a/2a lines had improved grain yield, protein content and sustained oil content, demonstrating that gene editing towards optimal nodulation improves soybean yield and quality.

Changes of RNA m6A/m5C Modification Regulatory Molecules in Ferroptosis of T2DM Rat Pancreas.

N6-methyladenine (m6A) and 5-methylcytosine (m5C) are two common forms of RNA methylation that play an important role in the epigenetics of type 2 diabetes mellitus (T2DM). One type of cell death, ferroptosis, has been implicated in islet ß-cell damage in T2DM. Notably, RNA methylation, an upstream regulatory mechanism of mRNAs, can regulate the expression of ferroptosis signaling molecules, thereby affecting cell proliferation and death. Here, we found that the ferroptosis signaling pathway was activated in pancreas of T2DM rats, followed by significant changes in m6A/m5C modification regulatory molecules. These detection data together with the prediction results that m6A and m5C exist in the mRNAs of ferroptosis molecules, we speculate that m6A and m5C are probably involved in pancreatic cell damage by modifying of ferroptosis signaling molecules. In short, our findings provide a new research idea for future studies on the molecular mechanisms of pancreatic cell damage and point to a new direction for exploring the mechanisms of ferroptosis from the perspective of RNA methylation modification.

Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E2 in the lateral parabrachial nucleus of male rats.

It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.

Fucoidan alleviates the inhibition of protein digestion by chitosan and its oligosaccharides.

Chitosan (CTS) and chitosan oligosaccharides (COS) have been widely applied in food industry due to their bioactivities and functions. However, CTS and COS with positive charges could interact with proteins, such as whey protein isolate (WPI), influencing their digestion. Interaction among CTS/COS, FUC, and WPI/enzymes was studied by spectroscopy, chromatography, and chemical methods in order to reveal the role of FUC in relieving the inhibition of protein digestibility by CTS/COS and demonstrate the action mechanisms. As shown by the results, the addition of FUC increased degree of hydrolysis (DH) and free protein in the mixture of CTS and WPI to 3.1-fold and 1.8-fold, respectively, while raise DH value and free protein in the mixture of COS and WPI to 6.7-fold and 1.2-fold, respectively. The interaction between amino, carboxyl, sulfate, and hydroxyl groups from carbohydrates and protein could be observed, and notably, FUC could interact with CTS/COS preferentially to prevent CTS/COS from combining with WPI. In addition, the addition of FUC could also relieve the combination of CTS to trypsin, increasing the fluorescence intensity and concentration of trypsin by 83.3 % and 4.8 %, respectively. Thus, the present study demonstrated that FUC could alleviate the inhibitory effect of CTS/COS on protein digestion.

The pattern of tumor progression on first-line immune checkpoint inhibitor-based systemic therapy for Chinese advanced hepatocellular carcinoma -CLEAP 004 study.

Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.

Bringing Artificial Intelligence (AI) into Environmental Toxicology Studies: A Perspective of AI-Enabled Zebrafish High-Throughput Screening.

The booming development of artificial intelligence (AI) has brought excitement to many research fields that could benefit from its big data analysis capability for causative relationship establishment and knowledge generation. In toxicology studies using zebrafish, the microscopic images and videos that illustrate the developmental stages, phenotypic morphologies, and animal behaviors possess great potential to facilitate rapid hazard assessment and dissection of the toxicity mechanism of environmental pollutants. However, the traditional manual observation approach is both labor-intensive and time-consuming. In this Perspective, we aim to summarize the current AI-enabled image and video analysis tools to realize the full potential of AI. For image analysis, AI-based tools allow fast and objective determination of morphological features and extraction of quantitative information from images of various sorts. The advantages of providing accurate and reproducible results while avoiding human intervention play a critical role in speeding up the screening process. For video analysis, AI-based tools enable the tracking of dynamic changes in both microscopic cellular events and macroscopic animal behaviors. The subtle changes revealed by video analysis could serve as sensitive indicators of adverse outcomes. With AI-based toxicity analysis in its infancy, exciting developments and applications are expected to appear in the years to come.