A Mechanistic Spectrum of O-H Bond Cleavage Observed for Reactions of Phenols with a Manganese Superoxo Complex.

Reaction of a rare and well-characterized MnIII-superoxo species, Mn(BDPBrP)(O2•) (1, H2BDPBrP = 2,6-bis((2-(S)-di(4-bromo)phenylhydroxylmethyl-1-pyrrolidinyl)methyl)pyridine), with 4-dimethylaminophenol at -80 °C proceeds via concerted proton electron transfer (CPET) to produce a MnIII-hydroperoxo complex, Mn(BDPBrP)(OOH) (2), alongside 4-dimethylaminophenoxy radical; whereas, upon treatment with 4-nitrophenol, complex 1 undergoes a proton transfer process to afford a MnIV-hydroperoxo complex, [Mn(BDPBrP)(OOH)]+ (3). Intriguingly, the reactions of 1 with 4-chlorophenol and 4-methoxyphenol follow two routes of CPET and sequential proton and electron transfer to furnish complex 2 in the end. UV-vis and EPR spectroscopic studies coupled with DFT calculations provided support for this wide mechanistic spectrum of activating various phenol O-H bonds by a single MnIII-superoxo complex, 1.

Advances in Synthesis and Applications of Single-Atom Catalysts for Metal Oxide-Based Gas Sensors.

As a stable, low-cost, environment-friendly, and gas-sensitive material, semiconductor metal oxides have been widely used for gas sensing. In the past few years, single-atom catalysts (SACs) have gained increasing attention in the field of gas sensing with the advantages of maximized atomic utilization and unique electronic and chemical properties and have successfully been applied to enhance the detection sensitivity and selectivity of metal oxide gas sensors. However, the application of SACs in gas sensors is still in its infancy. Herein, we critically review the recent advances and current status of single-atom catalysts in metal oxide gas sensors, providing some suggestions for the development of this field. The synthesis methods and characterization techniques of SAC-modified metal oxides are summarized. The interactions between SACs and metal oxides are crucial for the stable loading of single-atom catalysts and for improving gas-sensitive performance. Then, the current application progress of various SACs (Au, Pt, Cu, Ni, etc.) in metal oxide gas sensors is introduced. Finally, the challenges and perspectives of SACs in metal oxide gas sensors are presented.

ß-Sitosterol Reduces the Content of Triglyceride and Cholesterol in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Zebrafish (Danio rerio) Model.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with hyperlipidemia, which is closely related to high levels of sugar and fat. ß-sitosterol is a natural product with significant hypolipidemic and cholesterol-lowering effects. However, the underlying mechanism of its action on aquatic products is not completely understood. METHODS: A high-fat diet (HFD)-induced NAFLD zebrafish model was successfully established, and the anti-hyperlipidemic effect and potential mechanism of ß-sitosterol were studied using oil red O staining, filipin staining, and lipid metabolomics. RESULTS: ß-sitosterol significantly reduced the accumulation of triglyceride, glucose, and cholesterol in the zebrafish model. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that differential lipid molecules in ß-sitosterol mainly regulated the lipid metabolism and signal transduction function of the zebrafish model. ß-sitosterol mainly affected steroid biosynthesis and steroid hormone biosynthesis in the zebrafish model. Compared with the HFD group, the addition of 500 mg/100 g of ß-sitosterol significantly inhibited the expression of Ppar-γ and Rxr-α in the zebrafish model by at least 50% and 25%, respectively. CONCLUSIONS: ß-sitosterol can reduce lipid accumulation in the zebrafish model of NAFLD by regulating lipid metabolism and signal transduction and inhibiting adipogenesis and lipid storage.

A Prospective Randomized Controlled Trial Assessing the Impact of Preoperative Combined with Postoperative Progressive Resistance Training on Muscle Strength, Gait, Balance and Function in Patients Undergoing Total Hip Arthroplasty.

Purpose: The aim of this study is to investigate the effects of a preoperative combined with postoperative moderate-intensity progressive resistance training (PRT) of the operative side in patients with hip osteoarthritis (HOA) who are undergoing total hip arthroplasty (THA). The study seeks to evaluate the impact of this combined intervention on muscle strength, gait, balance, and hip joint function in a controlled, measurable, and objective manner. Additionally, the study aims to compare the outcomes of this combined intervention with those of preoperative or postoperative muscle strength training conducted in isolation. Methods: A total of 90 patients with HOA scheduled for unilateral primary THA were randomly assigned to three groups: Pre group (preoperative PRT), Post group (postoperative PRT), and Pre& Post group (preoperative combined with postoperative PRT) focusing on hip flexion, extension, adduction, and abduction of operated side. Muscle strength, gait parameters, balance, and hip function were assessed at specific time points during a 12-month follow-up period. Results: All three groups showed significant improvements in muscle strength, with the Pre& Post group demonstrating the most pronounced and sustained gains. Gait velocity and cadence were significantly improved in the Pre& Post group at 1-month and 3-month postoperative follow-ups compared to the other groups. Similarly, the Pre& Post group exhibited superior balance performance at 3-month and 12-month postoperative follow-ups. The Harris Hip Score also showed better outcomes in the Pre& Post group at all follow-up intervals. Conclusion: Preoperative combined with postoperative moderate-intensity PRT in HOA patients undergoing THA led to superior improvements in muscle strength, gait, balance, and hip joint function compared to preoperative or postoperative PRT alone. This intervention shows significant promise in optimizing postoperative rehabilitation and enhancing patient outcomes following THA.

Perioperative outcomes of robotic versus video-assisted thoracoscopic surgery in non-small cell lung cancer patients after neoadjuvant chemoimmunotherapy.

Background: Limited data are available regarding perioperative outcomes in patients with non-small cell lung cancer (NSCLC) who undergo robotic-assisted thoracic surgery (RATS) after neoadjuvant chemoimmunotherapy. This study aimed to compare the perioperative outcomes of RATS and video-assisted thoracic surgery (VATS) in NSCLC patients after neoadjuvant chemoimmunotherapy. Methods: The study involved consecutive NSCLC patients treated with minimally invasive surgery (MIS) after neoadjuvant chemoimmunotherapy at a high-volume single center from September 2020 to October 2022. Short-term effects, including demographic, perioperative and pathological parameters, were compared between the RATS group and the VATS group. Results: A total of 119 patients were included in this study. Of these, 33 (27.7%) patients received RATS and 86 (72.3%) patients received VATS. Major pathological response (MPR) and pathological complete response (pCR) rates were comparable between the two groups. The RATS group had a higher number of dissected lymph nodes (21 vs. 18, P=0.03) and lymph node stations (7 vs. 6, P=0.004) compared with the VATS group but no differences were found in perioperative outcomes. Conclusions: These findings suggest that both RATS and VATS are safe and feasible options for NSCLC patients who have received neoadjuvant chemoimmunotherapy. Furthermore, RATS may offer advantages over VATS in patients who require a more extensive lymph node dissection.

The effect of cognitive impairment based on Mini-Mental State Examination (MMSE) on suicidal tendency in patients with schizophrenia: A large cross-sectional study.

BACKGROUND: The effect of cognitive function on suicidal tendency in patients with schizophrenia is still inconclusive. This study aimed to explore the effect of cognitive impairment on suicidal tendency in schizophrenia patients and the risk factors of suicidal tendency in schizophrenia patients with cognitive impairment. METHODS: A total of 988 subjects were recruited for this study and finally 517 patients were included in the statistical analysis. Sociodemographic information was collected for each subject. Mini-Mental State Examination (MMSE) was used to assess patients' cognitive functioning. In addition, the Positive and Negative Syndrome Scale (PANSS) positive subscale, Insomnia Severity Index (ISI), and Beck Scale for Suicide Ideation (BSI) were used to assess psychotic symptoms, severity of insomnia, and intensity of suicidal ideation, respectively. RESULTS: Schizophrenia patients with cognitive dysfunction were significantly less likely to develop suicidal tendencies than those without cognitive dysfunction (P < 0.05, OR = 0.58, 95%CI: 0.39-0.81). In patients with cognitive impairment, those with suicidal tendency had substantially higher scores on BSI, ISI, EC, PD, IRI, F1, and PANSS positive subscale, and took more types of antipsychotic drugs than those without suicidal tendency (all P < 0.05), and the results of binary logistic regression analysis showed that, PANSS positive subscale score (B = 0.06, p = 0.04, OR = 1.07, 95%CI: 1.00-1.13) was a risk factor for suicidal tendencies. CONCLUSIONS: Our findings suggest that schizophrenia patients with cognitive dysfunction are significantly less likely to develop suicidal tendencies. Moreover, positive symptom is a risk factor for suicidal tendencies in schizophrenia patients with cognitive dysfunction.

Artificial intelligence-based tools with automated segmentation and measurement on CT images to assist accurate and fast diagnosis in acute pancreatitis.

PURPOSE: To develop an artificial intelligence (AI) tool with automated pancreas segmentation and measurement of pancreatic morphological information on CT images to assist improved and faster diagnosis in acute pancreatitis. METHODS: This study retrospectively contained 1124 patients suspected for AP and received non-contrast and enhanced abdominal CT examination between September 2013 to September 2022. Patients were divided into training (N = 688), validation (N = 145), testing dataset (N = 291, N = 104 for normal pancreas, N = 98 for AP, N = 89 for AP complicated with PDAC (AP&PDAC)). A model based on convolutional neural network (MSAnet) was developed. The pancreas segmentation and measurement were performed via eight open-source models and MSAnet based tools, and the efficacy was evaluated using Dice similarity coefficient (DSC) and Intersection over union (IoU). The DSC and IoU for patients with different ages were also compared. The outline of tumor and edema in the AP and were segmented by clustering. The diagnostic efficacy for radiologists with or without the assistance of MSAnet tool in AP and AP&PDAC was evaluated using receiver operation curve and confusion matrix. RESULTS: Among all models, MSAnet based tool showed best performance on the training and validation dataset, and had high efficacy on testing dataset. The performance was age-affected. With assistance of the AI tool, the diagnosis time was significantly shortened by 26.8% and 32.7% for junior and senior radiologists, respectively. The area under curve in diagnosis of AP was improved from 0.91 to 0.96 for junior radiologist and 0.98 to 0.99 for senior radiologist. In AP&PDAC diagnosis, AUC was increased from 0.85 to 0.92 for junior and 0.97 to 0.99 for senior. CONCLUSION: MSAnet based tools showed good pancreas segmentation and measurement performance, which help radiologists improve diagnosis efficacy and workflow in both AP and AP with PDAC conditions. ADVANCES IN KNOWLEDGE: This study developed an AI tool with automated pancreas segmentation and measurement and provided evidence for AI tool assistance in improving the workflow and accuracy of AP diagnosis.

Enzyme-responsive oncolytic polypeptide for tumor therapy.

Host defense peptide-mimicking cationic oncolytic polymers have attracted increasing attention for cancer treatment in recent years. However, polymers with large amounts of positive charge may cause rapid clearance and severe off-target toxicity. To facilitate in vivo application, an alkaline phosphatase (ALP)-responsive oncolytic polypeptide precursor (C12-PLL/PA) has been reported in this work. C12-PLL/PA could be hydrolyzed into the active form of the oncolytic polypeptide (C12-PLL) by the extracellular alkaline phosphatase within solid tumors, thereby resulting in the conversion of the negative charge to positive charge and restoring its membrane-lytic activity. Detailed mechanistic studies showed that C12-PLL/PA could effectively destroy cancer cell membranes and subsequently result in rapid necrosis of cancer cells. More importantly, C12-PLL/PA significantly inhibited the tumor growth in the 4T1 orthotopic breast tumor model with negligible side effects. In summary, these findings demonstrated that the shielding of the amino groups with phosphate groups represents a secure and effective strategy to develop cationic oncolytic polypeptide, which represents a valuable reference for the design of enzyme-activated oncolytic polymers. STATEMENT OF SIGNIFICANCE: Recently, there has been a growing interest in fabricating host defense peptide-mimicking cationic oncolytic polymers for cancer therapy. However, there remain concerns about the tumor selectivity and off-target toxicity of these cationic polymers. In this study, an alkaline phosphatase-responsive oncolytic polypeptide precursor (C12-PLL/PA) has been developed to selectively target cancer cells while sparing normal cells. Mechanistic investigations demonstrated that C12-PLL/PA effectively disrupted cancer cell membranes, leading to rapid necrosis. Both in vitro and in vivo experiments showed promising anticancer activity and reliable safety of C12-PLL/PA. The findings suggest that this synthetic enzyme-responsive polypeptide holds potential as a tumor-specific oncolytic polymer, paving the way for future applications in cancer therapy.

Discovery of superconductivity in technetium borides at moderate pressures.

Advances in theoretical calculations have boosted the search for high-temperature superconductors, such as sulfur hydrides and rare-earth polyhydrides. However, the required extremely high pressures for stabilizing these superconductors has handicapped further implementation. Based upon thorough structural searches, we identified a series of unprecedented superconducting technetium borides at moderate pressures, including TcB (P63/mmc) with a superconducting transition temperature of Tc = 20.2 K at ambient pressure and TcB2 (P6/mmm) with Tc = 23.1 K at 20 GPa. Superconductivity in these technetium borides mainly originates from the coupling between the low-frequency vibrations of technetium atoms and the dominant technetium-4d electrons at the Fermi level. Our work therefore presents a fresh group in the family of superconducting borides, whose diversified crystal structures suggest rich possibilities in the discovery of other superconducting transition-metal borides.

A systematic mutation analysis of 13 major SARS-CoV-2 variants.

SARS-CoV-2 evolves constantly with various novel mutations. Due to their enhanced infectivity, transmissibility and immune evasion, a comprehensive understanding of the association between these mutations and the respective functional changes is crucial. However, previous mutation studies of major SARS-CoV-2 variants remain limited. Here, we performed systematic analyses of full-length amino acids mutation, phylogenetic features, protein physicochemical properties, molecular dynamics and immune escape as well as pseudotype virus infection assays among thirteen major SARS-CoV-2 variants. We found that Omicron exhibited the most abundant and complex mutation sites, higher indices of hydrophobicity and flexibility than other variants. The results of molecular dynamics simulation suggest that Omicron has the highest number of hydrogen bonds and strongest binding free energy between the S protein and ACE2 receptor. Furthermore, we revealed 10 immune escape sites in 13 major variants, some of them were reported previously, but four of which (i.e. 339/373/477/496) are first reported to be specific to Omicron, whereas 462 is specific to Epslion. The infectivity of these variants was confirmed by the pseudotype virus infection assays. Our findings may help us understand the functional consequences of the mutations within various variants and the underlying mechanisms of the immune escapes conferred by the S proteins.

Potential of metallurgical iron-containing solid waste-based catalysts as activator of persulfate for organic pollutants degradation.

The production of solid wastes in the metallurgical industry has significant implications for land resources and environmental pollution. To address this issue, it is crucial to explore the potential of recycling these solid wastes to reduce land occupation while protecting the environment and promoting resource utilization. Steel slag, red mud, copper slag and steel picking waste liquor are examples of solid wastes generated during the metallurgical process that possess high iron content and Fe species, making them excellent catalysts for persulfate-based advanced oxidation processes (PS-AOPs). This review elucidates the catalytic mechanisms and pathways of Fe2+ and Fe0 in the activation PS. Additionally, it underscores the potential of metallurgical iron-containing solid waste (MISW) as a catalyst for PS activation, offering a viable strategy for its high-value utilization. Lastly, the article provides an outlook towards future challenges and prospects for MISW in PS activation for the degradation of organic pollutants.

Timing Matters: A Longitudinal Study Examining the Effects of Physical Activity Intensity and Timing on Adolescents' Mental Health Outcomes.

Physical activity is universally acknowledged for its benefits to mental health; however, the specific intensities and timings that best benefit adolescents' mental health, crucial due to their significant influence on daily schedules, have not been thoroughly investigated. This study addresses the substantive research gap by exploring the varied effects of physical activity intensity (light versus moderate to vigorous) and timing (weekdays versus weekends and holidays) on adolescent mental health. Utilizing a large-scale longitudinal dataset (NT1 = 84,054; NT2 = 44,623) from 158 schools, this research describes the current state of adolescent physical activity and investigates the effects of physical activity on mental health outcomes, including positive (i.e., life satisfaction, positive mental health) and negative indicators (depression, anxiety), over a 6-month period. Participants were adolescents aged 9-19 years (mean age = 12.73 ± 2.43 years, 48.9% female), with the analysis adjusted for potential confounding factors. Results showed that as adolescents grow older, their engagement in moderate-to-vigorous physical activity during both weekdays and weekends/holidays tends to decrease, while light physical activity during weekdays increases. Multilevel regression analysis indicated that moderate-to-vigorous physical activity during weekends/holidays at Time 1 positively correlated with better mental health outcomes at Time 2 (six months later), featuring enhanced positive indicators and reduced negative ones. Moderate-to-vigorous physical activity on weekdays at Time 1 was positively linked to mental health at Time 2. Light physical activity during weekends/holidays at Time 1 positively predicted life satisfaction and positive mental health at Time 2. In contrast, light physical activity on weekdays at Time 1 negatively correlated with life satisfaction at Time 2. The study underscores the importance of promoting moderate-to-vigorous physical activity, particularly on weekends and holidays, to improve mental health outcomes among adolescents.

Insights into the Formation Mechanism of Reactive Oxygen Species in the Interface Reaction of SO2 on Hematite.

The interplay between sulfur and iron holds significant importance in their atmospheric cycle, yet a complete understanding of their coupling mechanism remains elusive. This investigation delves comprehensively into the evolution of reactive oxygen species (ROS) during the interfacial reactions involving sulfur dioxide (SO2) and iron oxides under varying relative humidity conditions. Notably, the direct activation of water by iron oxide was observed to generate a surface hydroxyl radical (•OH). In comparison, the aging of SO2 was found to markedly augment the production of •OH radicals on the surface of α-Fe2O3 under humid conditions. This augmentation was ascribed to the generation of superoxide radicals (•O2-) stemming from the activation of O2 through the Fe(II)/Fe(III) cycle and its combination with the H+ ion to produce hydrogen peroxide (H2O2) on the acidic surface. Moreover, the identification of moderate relative humidity as a pivotal factor in sustaining the surface acidity of iron oxide during SO2 aging underscores its crucial role in the coupling of iron dissolution, ROS production, and SO2 oxidation. Consequently, the interfacial reactions between SO2 and iron oxides under humid conditions are elucidated as atmospheric processes that enhance oxidation capacity rather than deplete ROS. These revelations offer novel insights into the mechanisms underlying •OH radical generation and oxidative potential within atmospheric interfacial chemistry.

Critical Role of Mineral Fe(IV) Formation in Low Hydroxyl Radical Yields during Fe(II)-Bearing Clay Mineral Oxygenation.

In subsurface environments, Fe(II)-bearing clay minerals can serve as crucial electron sources for O2 activation, leading to the sequential production of O2•-, H2O2, and •OH. However, the observed •OH yields are notably low, and the underlying mechanism remains unclear. In this study, we investigated the production of oxidants from oxygenation of reduced Fe-rich nontronite NAu-2 and Fe-poor montmorillonite SWy-3. Our results indicated that the •OH yields are dependent on mineral Fe(II) species, with edge-surface Fe(II) exhibiting significantly lower •OH yields compared to those of interior Fe(II). Evidence from in situ Raman and Mössbauer spectra and chemical probe experiments substantiated the formation of structural Fe(IV). Modeling results elucidate that the pathways of Fe(IV) and •OH formation respectively consume 85.9-97.0 and 14.1-3.0% of electrons for H2O2 decomposition during oxygenation, with the Fe(II)edge/Fe(II)total ratio varying from 10 to 90%. Consequently, these findings provide novel insights into the low •OH yields of different Fe(II)-bearing clay minerals. Since Fe(IV) can selectively degrade contaminants (e.g., phenol), the generation of mineral Fe(IV) and •OH should be taken into consideration carefully when assessing the natural attenuation of contaminants in redox-fluctuating environments.

Single Dispersion of Fe(H2O)2-based Polyoxometalate on Polymeric Carbon Nitride for Biomimetic CH4 Photooxidation.

Direct methane conversion to value-added oxygenates under mild conditions with in-depth mechanism investigation has attracted wide interest. Inspired by methane monooxygenase, the K9Na2Fe(H2O)2{[γ-SiW9O34Fe(H2O)]}2·25H2O polyoxometalate (Fe-POM) with well-defined Fe(H2O)2 sites is synthesized to clarify the key role of Fe species and their microenvironment towards CH4 photooxidation. The Fe-POM can efficiently drive the conversion of CH4 to HCOOH with a yield of 1570.0 µmol gPOM -1 and 95.8% selectivity at ambient conditions, much superior to that of [Fe(H2O)SiW11O39]5- with Fe(H2O) active site, [Fe2SiW10O38(OH)]2 14- and [P8W48O184Fe16(OH)28(H2O)4]20- with multi-nuclear Fe-OH-Fe active sites. Single-dispersion of Fe-POM on polymeric carbon nitride (PCN) is facilely achieved to provide single-cluster functionalized PCN with well-defined Fe(H2O)2 site, the HCOOH yield can be improved to 5981.3 µmol gPOM -1. Systemic investigations demonstrate that the (WO)4-Fe(H2O)2 can supply Fe = O active center for C-H activation via forming (WO)4-Fea-Ot···CH4 intermediate, similar to that for CH4 oxidation in the monooxygenase. This work highlights a promising and facile strategy for single dispersion of 1 ∼ 2 Å metal center with precise coordination microenvironment by uniformly anchoring nanoscale molecular clusters, which provides a well-defined model for in-depth mechanism research. This article is protected by copyright. All rights reserved.

Mode-Locked Operation of High-Order Transverse Modes in a Vertical-External-Cavity Surface-Emitting Laser.

Understanding the mechanism of mode-locking in a laser with high-order transverse mode is important for achieving an ultrashort pulses train under more complicated conditions. So far, mode-locking with high-order transverse mode has not been reported in other lasers except the multimode fiber laser. This paper demonstrates robust mode-locking with high-order transverse mode in a Kerr-lens mode-locked vertical-external-cavity surface-emitting laser for the first time, to the best of our knowledge. While the longitudinal modes are locked, continuous mode-locking accompanied by high-order transverse mode up to TEM40 is observed. The threshold of the mode-locking is only a little bigger than that of the lasing. After the laser oscillation is built up, the mode-locked pulse train can be obtained almost immediately and maintained until the thermal rollover of the laser. Output powers of 717 mW under fundamental mode and 666 mW under high-order transverse mode are achieved with a 4.3 ps pulse duration and 1.1 GHz pulses repetition rate, and some phenomenological explanations to the related characteristics of the mode-locked operation of high-order transverse mode in the vertical-external-cavity surface-emitting laser are proposed.

Diversity inhibits foliar fungal diseases in grasslands: Potential mechanisms and temperature dependence.

A long-standing debate exists among ecologists as to how diversity regulates infectious diseases (i.e., the nature of diversity-disease relationships); a dilution effect refers to when increasing host diversity inhibits infectious diseases (i.e., negative diversity-disease relationships). However, the generality, strength, and potential mechanisms underlying negative diversity-disease relationships in natural ecosystems remain unclear. To this end, we conducted a large-scale survey of 63 grassland sites across China to explore diversity-disease relationships. We found widespread negative diversity-disease relationships that were temperature-dependent; non-random diversity loss played a fundamental role in driving these patterns. Our study provides field evidence for the generality and temperature dependence of negative diversity-disease relationships in grasslands, becoming stronger in colder regions, while also highlighting the role of non-random diversity loss as a mechanism. These findings have important implications for community ecology, disease ecology, and epidemic control.

Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy.

Objectives: This study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP. Materials and methods: Network pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP. Results: Network pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats. Conclusion: Apoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.

Ultra rapid lispro improves postprandial glucose control versus lispro in combination with basal insulin: a study based on CGM in type 2 diabetes in China.

Aim: To evaluate the efficacy and safety of URLi (ultra rapid lispro insulin) compared to insulin lispro as bolus insulin with basal insulin using CGM in the individuals with type 2 diabetes(T2D) in China. Methods: This was a double-blind, randomized, parallel, prospective, phase 3 study. Subjects with uncontrolled T2D were recruited and randomized 1:2 into the insulin lispro and URLi groups. Subjects received a consistent basal insulin regimen during the study and self-administered insulin lispro or URLi before each meal throughout the treatment period. Subjects underwent a 3-day continuous glucose monitoring (CGM) at the baseline and endpoint respectively, and then CGM data were analyzed. The primary endpoint was to compare the difference in postprandial glucose (PPG) control using CGM between the two groups. Results: A total of 57 subjects with T2D completed the study. Our CGM data showed that postprandial glucose excursions after breakfast (BPPGE) in the URLi group was lower than that in the insulin lispro group (1.59 ± 1.57 mmol/L vs 2.51 ± 1.73 mmol/L, p = 0.046). 1-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.37 ± 3.28 mmol/L vs 0.24 ± 2.58 mmol/L, p = 0.047). 2-hour PPG was observed to decrease more in the URLi group than that in the insulin lispro group (-1.12 ± 4.00 mmol/L vs 1.22 ± 2.90 mmol/L, p = 0.021). The mean HbA1c level decreased by 1.1% in the URLi group and 0.99% in the insulin lispro group, with no treatment difference (p = 0.642). In the CGM profile, TBR was not significantly different between the two groups (p = 0.743). The weight gain also did not differ between the two groups (p = 0.303). Conclusion: URLi can control breakfast PPG better than insulin lispro in adults with T2D in China, while it is non-inferior in improving HbA1c. The incidence of hypoglycemic and weight gain were similar between the two groups.