Combination therapy with probiotics and anti-PD-L1 antibody synergistically ameliorates sepsis in mouse model.

The study investigated the protective effects and mechanisms of probiotics in conjunction with an anti-PD-L1 antibody on the immune functions of septic mice. Sixty-four mice were assigned to sepsis groups receiving vehicle, probiotics, and anti-PD-L1 antibody individually or in combination, with healthy mice as controls. Sepsis was induced by cecal ligation and puncture (CLP), followed by intraperitoneal Lipopolysaccharide (LPS) injection. Blood and tissues were collected one day post-injection for detecting inflammation-related cytokines, Treg, PI3K/Akt pathway-related protein expression, and lung tissue pathology. The survival time of the remaining ten mice was recorded over seven days. Compared to healthy mice, septic mice given PBS exhibited significantly different serum levels of IL-6, IL-8, IL-17, IL-10, and IFN-γ (all p < 0.001). Treatment with anti-PD-L1 antibody combined with probiotics significantly increased the 7-day survival rate in septic mice, accompanied by decreased pro-inflammatory cytokines, increased anti-inflammatory cytokines, improved oxidative stress, reduced lung injury, and enhanced Th17/Treg balance. This combined therapy demonstrated superior efficacy compared to antibodies or probiotics alone. Additionally, it facilitated peripheral blood polymorphonuclear neutrophil apoptosis, enhancing protection by blocking PD-L1 function and inhibiting PI3K-dependent AKT phosphorylation. In conclusion, combining probiotics with an anti-PD-L1 antibody enhances protective effects in septic mice by reducing serum inflammatory factors, promoting neutrophil apoptosis, regulating Th17/Treg balance, and inhibiting the PI3K/Akt pathway.

Preparation of NIR-II Polymer Nanoprobe Through Twisted Intramolecular Charge Transfer and Förster Resonance Energy Transfer of NIR-I Dye.

Near-infrared-II (NIR-II) fluorescence imaging is pivotal in biomedical research. Organic probes exhibit high potential in clinical translation, due to advantages such as precise structure design, low toxicity, and post-modifications convenience. In related preparation, enhancement of NIR-II tail emission from NIR-I dyes is an efficient method. In particular, the promotion of twisted intramolecular charge transfer (TICT) of relevant NIR-I dyes is a convenient protocol. However, present TICT-type probes still show disadvantages in relatively low emission, large particle sizes, or limited choice of NIR-I dyes, etc. Herein, the synthesis of stable small-sized polymer NIR-II fluoroprobes (e.g., 7.2 nm), integrating TICT and Förster resonance energy transfer process to synergistically enhance the NIR-II emission is reported. Strong enhanced emissions can be obtained from various NIR-I dyes and lanthanide elements (e.g., twelvefold at 1250 nm from Nd-DTPA/IR-808 sample). The fluorophore provides high-resolution angiography, with high-contrast imaging on middle cerebral artery occlusion model mice for distinguishing occlusion. The fluorophore can be rapidly excreted from the kidney (urine ≈65% within 4 h) in normal mice and exhibits long-term renal retention on acute kidney injury mice, showing potential applications in the prognosis of kidney diseases. This development provides an effective strategy to design and synthesize effective NIR-II fluoroprobes.

The composition and function of bacterial communities in Bombyx mori (Lepidoptera: Bombycidae) changed dramatically with infected fungi: A new potential to culture Cordyceps cicadae.

Cordyceps cicadae (Hypocreales: Cordycipitaceae) is a renowned entomopathogenic fungus used as herbal medicine in China. However, wild C. cicadae resources have been threatened by heavy harvesting. We hypothesised that Bombyx mori L. (Lepidoptera: Bombycidae) could be a new alternative to cultivate C. cicadae due to the low cost of rearing. Bacterial communities are crucial for the formation of Cordyceps and for promoting the production of metabolites. To better understand the bacterial community structure associated with Cordyceps, three Claviciptaceae fungi were used to explore the pathogenicity of the silkworms. Here, fifth-instar silkworms were infected with C. cicadae, Cordyceps cateniannulata (Hypocreales: Cordycipitaceae) and Beauveria bassiana (Hypocreales: Cordycipitaceae). Subsequently, we applied high-throughput sequencing to explore the composition of bacterial communities in silkworms. Our results showed that all three fungi were highly pathogenic to silkworms, which suggests that silkworms have the potential to cultivate Cordyceps. After fungal infection, the diversity of bacterial communities in silkworms decreased significantly, and the abundance of Staphylococcus increased in mummified larvae, which may play a role in the death process when the host suffers infection by entomopathogenic fungi. Furthermore, there were high similarities in the bacterial community composition and function in the C. cicadae and C. cateniannulata infected samples, and the phylogenetic analysis suggested that these similarities may be related to the fungal phylogenetic relationship. Our findings reveal that infection with different entomopathogenic fungi affects the composition and function of bacterial communities in silkworms and that the bacterial species associated with Cordyceps are primarily host dependent, while fungal infection affects bacterial abundance.

Tribuloside: Mechanisms and Efficacy in Treating Acute Lung Injury Revealed by Network Pharmacology and Experimental Validation.

Background: Acute lung injury (ALI) is a serious illness that has few treatment options available. Tribuloside, a natural flavonoid extracted from the Tribulus Terrestris plant in China, is potent in addressing many health issues such as headaches, dizziness, itching, and vitiligo. Objective: This study intends to explore the mechanisms of action of Tribuloside in treating ALI through a combination of network pharmacology and experimental validation. Methods: We obtained the 2D structure and SMILES number of Tribuloside from the PubChem database. We used the SwissTargetPrediction database to identify pharmacological targets. We found 1215 targets linked to ALI by examining the GeneCards database. We used the String database and Cytoscape software to create the "drug or disease-target" network as well as the protein-protein interactions (PPI). Key targets were identified by evaluating associated biological processes and pathway enrichment. A Venny Diagram showed 49 intersection points between Tribuloside and ALI. Molecular docking with AutoDockTools found that Tribuloside had a high affinity for IL6, BCL2, TNF, STAT3, IL1B, and MAPK3, the top 6 targets in the PPI network by Degree values. To test Tribuloside's therapeutic efficacy in ALI, an acute lung damage model in mice was constructed using lipopolysaccharide. Tribuloside treatment reduced inflammatory cell infiltration, decreased fibrotic area, repaired damaged alveoli, and suppressed inflammatory factors IL-6, TNF-α, and IL-1ß in the lungs through many pathways and targets. Conclusion: This study reveals that Tribuloside has the potential to treat ALI by targeting various pathways and targets, according to network pharmacology predictions and experimental confirmation.

Development and validation of the osteoporosis scale among the system of quality of life instruments for chronic diseases QLICD-OS (V2.0).

BACKGROUND: Quality of life of osteoporosis patients had caused widespread concern, due to high incidence and difficulty to cure. Scale specifics for osteoporosis and suitable for Chinese cultural background lacked. This study aimed to develop an osteoporosis scale in Quality of Life Instruments for Chronic Diseases system, namely QLICD-OS (V2.0). METHODS: Procedural decision-making approach of nominal group, focus group and modular approach were adopted. Our scale was developed based on experience of establishing scales at home and abroad. In this study, Quality of life measurements were performed on 127 osteoporosis patients before and after treatment to evaluate the psychometric properties. Validity was evaluated by qualitative analysis, item-domain correlation analysis, multi-scaling analysis and factor analysis; the SF-36 scale was used as criterion to carry out correlation analysis for criterion-related validity. The reliability was evaluated by the internal consistency coefficients Cronbach's α, test-retest reliability Pearson correlation r. Paired t-tests were performed on data of ​​the scale before and after treatment, with Standardized Response Mean (SRM) being calculated to evaluate the responsiveness. RESULTS: The QLICD-OS, composed of a general module (28 items) and an osteoporosis-specific module (14 items), had good content validity. Correlation analysis and factor analysis confirmed the construct, with the item having a strong correlation (most > 0.40) with its own domains/principle components, and a weak correlation (< 0.40) with other domains/principle components. Correlation coefficient between the similar domains of QLICD-OS and SF-36 showed reasonable criterion-related validity, with all coefficients r being greater than 0.40 exception of physical function of SF-36 and physical domain of QLICD-OS (0.24). Internal consistency reliability of QLICD-OS in all domains was greater than 0.7 except the specific module. The test-retest reliability coefficients (Pearson r) in all domains and overall score are higher than 0.80. Score changes after treatment were statistically significant, with SRM ranging from 0.35 to 0.79, indicating that QLICD-OS could be rated as medium responsiveness. CONCLUSION: As the first osteoporosis-specific quality of life scale developed by the modular approach in China, the QLICD-OS showed good reliability, validity and medium responsiveness, and could be used to measure quality of life in osteoporosis patients.

Quality of life and its related-influencing factors in patients with cervical cancer based on the scale QLICP-CE(V2.0).

BACKGROUND: Quality of life research can guide clinical workers to adopt more targeted treatment and intervention measures, so as to achieve the purpose of improving patients' quality of life. The objective of this study was to evaluate health-related quality of life in Chinese patients with cervical cancer and to explore its influencing factors. METHODS: A total of 186 patients with cervical cancer were investigated by using the QLICP-CE (V2.0) scale (Quality of Life Instruments for Cancer Patients-Cervical Cancer) developed by our group in China. The data were analyzed by t-test, one-way ANOVA, univariate analysis, and multivariate linear regression. RESULTS: The total score of quality of life scale for cervical cancer patients was (62.58 ± 12.69), Univariate analysis of objective clinical indexes showed that creatinine concentration was a negative influence factor in the psychological domain, potassium ion concentration was a negative influence factor in the common symptoms and side effect domain, erythrocyte content was a positive influence factor physical domain and common general domain. Multiple linear regression results suggested that clinical staging was the influencing factor of common symptom and side effect domain, common general module and total score of scale. Marital status has different degrees of influence on the psychological, social, and common general domains. The level of education also influenced scores in the social domain. CONCLUSION: The total score of quality of life in patients with cervical cancer who received active treatment was acceptable. Marital status, clinical staging, and educational level are the factors that affect the quality of life of patients with cervical cancer. At the same time, potassium ion concentration, red blood cell count and creatinine concentration also have important effects on quality of life in patients with cervical cancer. Therefore, it is very important to give personalized treatment and nursing to patients based on various factors.

Evaluation of osteogenic properties of a novel injectable bone-repair material containing strontium in vitro and in vivo.

Objective: This study aims to develop and evaluate the biocompatibility and osteogenic potential of a novel injectable strontium-doped hydroxyapatite bone-repair material. Methods: The properties of strontium-doped hydroxyapatite/chitosan (Sr-HA/CS), hydroxyapatite/chitosan (HA/CS) and calcium phosphate/chitosan (CAP/CS) were assessed following their preparation via physical cross-linking and a one-step simplified method. Petri dishes containing Escherichia coli and Staphylococcus epidermidis were inoculated with the material for in vitro investigations. The material was also co-cultured with stem cells derived from human exfoliated deciduous teeth (SHEDs), to assess the morphology and proliferation capability of the SHEDs, Calcein-AM staining and the Cell Counting Kit-8 assay were employed. Osteogenic differentiation of SHEDs was determined using alkaline phosphatase (ALP) staining and Alizarin Red staining. For in vivo studies, Sr-HA/CS was implanted into the muscle pouch of mice and in a rat model of ovariectomy-induced femoral defects. Hematoxylin-eosin (HE) staining was performed to determine the extent of bone formation and defect healing. The formation of new bone was determined using Masson's trichrome staining. The osteogenic mechanism of the material was investigated using Tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical studies. Results: X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) showed that strontium was successfully doped into HA. The Sr-HA/CS material can be uniformly squeezed using a syringe with a 13% swelling rate. Sr-HA/CS had a significant antibacterial effect against both E. coli and S. epidermidis (p < 0.05), with a stronger effect observed against E. coli. The Sr-HA/CS significantly improved cell proliferation and cell viability in vitro studies (p < 0.05). Compared to CAP/CS and CS, Sr-HA/CS generated a substantially greater new bone area during osteoinduction experiments (p < 0.05, p < 0.001). The Sr-HA/CS material demonstrated a significantly higher rate of bone repair in the bone defeat studies compared to the CAP/CS and CS materials (p < 0.01). The OCN-positive area and TRAP-positive cells in Sr-HA/CS were greater than those in control groups (p < 0.05). Conclusion: A novel injectable strontium-doped HA bone-repair material with good antibacterial properties, biocompatibility, and osteoinductivity was successfully prepared.

Radiating blood flow signal: A new ultrasound feature of thyroid carcinoma.

OBJECTIVE: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated. RESULTS: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001). CONCLUSION: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score.

Association between quality of discharge teaching and self-management in patients after percutaneous coronary intervention: A chain mediation model.

AIMS: To examine chain mediating effect of discharge readiness and self-efficacy between quality of discharge teaching and self-management in patients after percutaneous coronary intervention (PCI). BACKGROUND: Although self-management after PCI has significant benefits in controlling risk factors and delaying disease progression, the status of self-management remains unoptimistic. A large number of studies have explored the close relationship between the quality of discharge teaching and patients self-management, but little is known about the underlying mechanisms. METHODS: The cross-sectional samples was collected from a tertiary hospital in China. Self-reported questionnaires were used to assess quality of discharge teaching, discharge readiness, self-efficacy and self-management. Pearson correlation analysis and mediation effect analysis were used for statistical analysis. REPORTING METHOD: The study used the STROBE checklist for reporting. RESULTS: A total of 198 patients with a mean age of 64.99 ± 11.32 (34-85) were included. The mean score of self-management was 88.41 ± 11.82. Quality of discharge teaching, discharge readiness, self-efficacy and self-management were all positively correlated. Mediation effect analysis showed that the mediating effects of discharge readiness, self-efficacy, discharge readiness and self-efficacy between quality of discharge teaching and self-management were 0.157, 0.177 and 0.049, respectively, accounting for 21.96%, 24.76% and 6.85% of the total effect. CONCLUSION: The quality of discharge teaching for patients after PCI not only directly affects self-management, but also can indirectly affect self-management through discharge readiness and self-efficacy. RELEVANCE TO CLINICAL PRACTICE: To improve the life quality of patients after PCI, medical staff should pay attention to the influence of self-management of quality of discharge teaching, and develop intervention strategies based on the path of discharge readiness and self-efficacy. PATIENT OR PUBLIC CONTRIBUTION: Questionnaires filled out by patients were used to understand the association between quality of discharge teaching, discharge readiness, self-efficacy and self-management.

Design, synthesis, and ex vivo anti-drug resistant cervical cancer activity of novel molecularly targeted chalcone derivatives.

Chemotherapy toxicity and tumor multidrug resistance remain the main reasons for clinical treatment failure in cervical cancer. In this study, 79 novel chalcone derivatives were designed and synthesized using the principle of active substructure splicing with the parent nucleus of licorice chalcone as the lead compound and VEGFR-2 and P-gp as the target of action and their potentials for anticervical cancer activity were preliminarily evaluated. The results showed that the IC50 values of candidate compound B20 against HeLa and HeLa/DDP cells were 3.66 ± 0.10 and 4.35 ± 0.21 µΜ, respectively, with a resistance index (RI) of 1.18, which was significantly higher than that of the positive drug cisplatin (IC50:13.60 ± 1.63, 100.03 ± 7.94 µΜ, RI:7.36). In addition, B20 showed significant inhibitory activity against VEGFR-2 kinase and P-gp-mediated rhodamine 123 efflux, as well as the ability to inhibit the phosphorylation of VEGFR-2 and downstream PI3K/AKT signaling pathway proteins, inducing apoptosis, blocking cells in the S-phase, and inhibiting invasive migration and tubule generation by HUVEC cells. Acceptable safety was demonstrated in acute toxicity tests when B20 was at 200 mg/kg. In the nude mouse HeLa/DDP cell xenograft tumor model, the inhibition rate of transplanted tumors was 39.2 % and 79.2 % when B20 was at 10 and 20 mg/kg, respectively. These results suggest that B20 is a potent VEGFR-2 and P-gp inhibitor with active potential for treating cisplatin-resistant cervical cancer.

An inversion method for calculating formation and borehole parameters in X-ray lithology density logging.

The use of X-ray sources in place of the 137Cs sources used in traditional lithology density logging methods has become a new trend in the development of nuclear logging techniques. How to eliminate the effects of drilling fluids or mudcake in the measurement process is a key question that determines the accuracy of measurement. In order to reduce the effects of mudcake and improve the accuracy of measurement of formation parameters, this paper presents an inversion method that can accurately calculate formation and borehole parameters and is suitable for X-ray lithology density logging. The general process of this inversion method is described below. First, a response model for broad-beam attenuation during X-ray lithology density logging is derived. Subsequently, the responses of four detectors under various formation and borehole conditions are studied by means of Monte Carlo simulation, and the energy spectra measured by each detector are divided into four energy windows (ranges) depending on the correlation with formation parameters. Finally, accurate values of formation and borehole parameters are obtained through iterative inversion using the Levenberg-Marquardt (LM) algorithm. The results of this study show that compared with previously established analysis methods, the inversion method based on forward modeling can effectively improve the accuracy of measurement of formation density and lithology index during X-ray lithology density logging, reduce the influence of the borehole environment, and overcome the deficiencies of data processing techniques based on the spine and ribs plot.

Investigating the effects of species niche shifts on the potential distribution of Tuta absoluta (Lepidoptera: Gelechiidae) by using global occurrence data.

Invasive species may occupy quite different environments in their invaded areas to native ones, which may intensively interfere with predicting potential distribution through ecological niche modeling (ENM). Here, we take the tomato leafminer Tuta absoluta Meyrick (Lepidoptera: Gelechiidae), a tomato pest, as an example to investigate this topic. We analyzed niche expansion, stability, unfilling, and Schoener's D by principal component analysis (PCA) ordination method to examine its realized niche shifts and to explore how ENM approaches are affected by niche shifts. We used 5 datasets: Asian, African, European, South American, and global occurrence records in this study. Results showed that high niche unfilling for the species' invaded areas in Asia (20%), Africa (12%), and Europe (37%), possibly due to T. absoluta being in the early stages of invasion. High niche expansion was observed in Asia (38%) and Europe (19%), implying that some European and Asian populations had reached new climatic areas. African niche had the most niche stability (94%) and was equivalent to the native one in climate space (PCA ordination method), but the n-dimensional climate space framework showed that they were different. When projecting the native model to Asia and Europe, the native model performed poorly, implying that the niche shifts affected the transferability of the native model. ENM based on global data outperformed than other models, and our results suggested that T. absoluta has a large potential distribution in Asia, Mexico, South Europe, the United States, and Australia. Meanwhile, we recommend updating ENMs based on the species' invasion stage.

Diagnosis and Treatment of Varus Posteromedial Rotational Instability of the Elbow Joint in Children: Re-Understanding of the Injury Mechanism Associated With Coronoid Process Fractures.

PURPOSE: To investigate the injury mechanism, diagnosis, and treatment of varus-posteromedial rotational instability of the elbow joint in children. METHODS: According to the diagnostic criteria of varus posteromedial rotational instability of elbow joint, 16 children with coronoid process fractures treated in our department from July 2013 to July 2017 were re-evaluated. There were 14 males and 2 females, aged 7 to 14 years, with an average age of 11.6 years. Eight cases on left and 8 cases on right side. An associated elbow dislocation occurred in 8 of 16 cases. Nine patients were treated with a lateral soft tissue repair only. In 7 other patients in addition to the lateral soft tissue repair, the coronoid process fractures were treated with open reduction and fixation. At the last clinical follow-up, each elbow joint range of motion was recorded, radiographs were obtained, and functional performance was evaluated by the Mayo elbow performance score (MEPS). RESULTS: The average follow-up time was 81.9 months for the 9 patients treated with lateral elbow soft tissue repair. At the last follow-up, 2 of the patients had MEPS scores as excellent, 1 was good, and 6 were rated as moderate or poor. Four patients had a cubitus varus deformity. The average follow-up time was 30.3 months for the 7 patients treated with both soft tissue repair and coronoid fracture stabilization. The elbow joint MEPS scores for each of these 7 patients was excellent at the last follow-up, and no complications such as cubitus varus occurred. CONCLUSION: The results of the study suggest that children could also develop elbow varus-posterior medial rotational instability injuries under the same mechanism. Although the morbidity rate is low, due to insufficient understanding of the injury mechanism, it is prone to missed diagnosis, misdiagnosis, and delayed treatment, resulting in severe complications such as elbow instability, dislocation, traumatic arthritis, and elbow stiffness. On the contrary, according to the treatment principle of the posterior medial rotational instability of the elbow joint in adult, while the lateral repair is carried out, strong and effective reduction and fixation of the coronoid process fractures are adopted, it is expected that such children with rare elbow injuries can obtain excellent treatment outcomes.

Extracellular vesicles derived from bone marrow mesenchymal stem cells ameliorate chronic liver damage via microRNA-136-5p.

Chronic liver damage (CLD) encompasses a spectrum of conditions and poses a significant global health challenge, affecting millions of individuals. Currently, there is a deficiency of clinically validated therapeutics with minimal side effects. Emerging evidence underscores the significant potential of extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) as a promising therapeutic method for CLD. This study aimed to evaluate the influence of BMSC-EVs containing microRNA-136-5p (BMSC-EVs-miR-136-5p) on macrophage polarization during chronic liver injury and elucidate the mechanisms associated with the GNAS/PI3K/ERK/STAT3 axis. Surface markers of BMSCs were detected via Immunofluorescent Staining. Subsequently, EVs were harvested from the BMSC culture medium. In vivo fluorescence imaging was employed to locate the BMSC-EVs. Additionally, fluorescence microscopy was used to visualize the uptake of DIR-labeled BMSC-EVs by RAW264.7 cells. Various methods were employed to assess the impact of BMSC-EVs on the expression levels of inflammatory factors (IL-1ß, IL-6, IL-10, and TNF-α), M1/M2 macrophage markers (iNOS and Arg-1), and members of inflammation-related signaling pathways (GNAS, PI3K, ERK, and STAT3) in RAW264.7 cells co-cultured with BMSC-EVs. Loss-of-function approaches targeting miR-136-5p in RAW264.7 cells were subsequently utilized to validate the role of BMSC-EVs-miR-136-5p. The Luciferase Reporter Assay indicates that GNAS was identified to be a target of miR-136-5p, and miR-136-5p demonstrating increased within BMSC-EVs compared to Raw264.7-EVs. BMSC-EVs-miR-136-5p mitigated CCl4-induced liver inflammation and improved liver function by Suppressing the GNAS/STAT3 Signaling. Notably, miR-136-5p suppressed lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. BMSC-EVs-miR-136-5p alleviates CLD by activating M2 polarization through the GNAS-mediated PI3K/ERK/STAT3 axis. Accordingly, the members of this axis may serve as therapeutic targets.

Research on collaborative innovation optimization strategies for digitally enabled higher education ecosystems.

Digitally enabled higher education involves the in-depth use of new-generation digital technology, which has subverted and innovated the traditional teaching mode, driven the development of high-quality teaching and learning, and improved teachers' teaching experience, and increased efficiency. Based on ecosystem theory, this paper constructs a higher education ecosystem with the government, enterprises, and universities as the core participating subjects. It considers the participating subjects' effort level and the ecosystem's overall benefits under the three scenarios of noncooperative research and development (R&D), cost sharing, and cooperative R&D. The results show that (1) the service innovation effort level of the three parties increases with increasing human resource level and technology maturity, and the government's benefit decreases with increasing cost of fulfilling social responsibility. (2) The government's cost subsidies to universities and enterprises can enhance the service innovation level of both parties and increase the optimal returns of the three parties and the ecosystem as a whole. (3) In the cooperative R&D game scenario, the effort level of the three parties and the total ecosystem returns are greater than those in the noncollaborative R&D scenario, and after determining the subsidy coefficients of the government, Pareto optimality of the three parties and the ecosystem as a whole can be achieved. The conclusions of this study can aid in understanding the dynamic evolution mechanism of digitally enabled higher education and provide a realistic decision-making reference for higher education ecosystem managers.

Real-world performance of indobufen versus aspirin after percutaneous coronary intervention: insights from the ASPIRATION registry.

BACKGROUND: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS) and aspirin intolerance were excluded. We aimed to explore this question in a real-world population. METHODS: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM) was adopted for confounder adjustment. RESULTS: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs. 11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS. CONCLUSIONS: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS. TRIAL REGISTRATION: Chinese Clinical Trial Register ( https://www.chictr.org.cn ); Number: ChiCTR2300067274.

Discovery of Hepatitis B Virus Surface Antigen Suppressor GS-8873.

Chronic hepatitis B (CHB) virus infection afflicts hundreds of millions of people and causes nearly one million deaths annually. The high levels of circulating viral surface antigen (HBsAg) that characterize CHB may lead to T-cell exhaustion, resulting in an impaired antiviral immune response in the host. Agents that suppress HBsAg could help invigorate immunity toward infected hepatocytes and facilitate a functional cure. A series of dihydropyridoisoquinolizinone (DHQ) inhibitors of human poly(A) polymerases PAPD5/7 were reported to suppress HBsAg in vitro. An example from this class, RG7834, briefly entered the clinic. We set out to identify a potent, orally bioavailable, and safe PAPD5/7 inhibitor as a potential component of a functional cure regimen. Our efforts led to the identification of a dihydropyridophthalazinone (DPP) core with improved pharmacokinetic properties. A conformational restriction strategy and optimization of core substitution led to GS-8873, which was projected to provide deep HBsAg suppression with once-daily dosing.

Development and validation of the rheumatoid arthritis scale among the system of quality of life instruments for chronic diseases QLICD-RA (V2.0).

Rheumatoid Arthritis is a more serious threatening to people and suitable for QOL measurement. A few specific QOL instruments are available without considering Chinese culture. The present study was aimed to develop and validate the Rheumatoid Arthritis Scale among the System of Quality of Life Instruments for Chronic Diseases (QLICD-RA V2.0). The data collected from 379 patients with RA was used to evaluate the psychometric properties of the scale. The reliability was evaluated by the internal consistency Cronbach's α, test-retest reliability Pearson correlation r and intra-class correlation (ICC). We evaluated the construct validity and criteria-related validity by correlation analysis and structural equation modeling. We compared the differences in scores of QLICD-RA before and after treatment and used the Standard Response Mean (SRM) to assess the responsiveness. The results showed that the internal consistency coefficient Cronbach's α values were greater than 0.70. The correlations r and ICCs were greater than 0.80. The correlation analysis and structural equation modeling confirmed good construct validity and criterion-related validity. The SRM ranges from 0.07 to 0.27 for significant domains/facets. It concluded that QLICD-RA (2.0) is a reliable and valid instrument to measure QOL among patients with RA.

The complete chloroplast genome of Keteleeria evelyniana Mast var. pendula Hsüeh (Pinaceae), a species with extremely small populations in China.

Keteleeria evelyniana Mast var. pendula Hsüeh, a typical plant species of extremely small population, is faced to be endangered. The complete chloroplast (cp) genome of K. evelyniana var. pendula has been assembled and annotated for the first time in this study. The complete genome in length was found to be 117,139 bp. The genome annotation revealed a total of 118 genes, including 34 transfer RNA (tRNA) genes, 4 ribosomal RNA (rRNA) genes, and 80 protein-coding genes. The maximum-likelihood phylogenetic tree supported that K. evelyniana var. pendula, K. fortune, K. evelyniana, and K. davidiana are clustered in one branch. This complete chloroplast genome helped us to understand the evolution of K. evelyniana var. pendula. These results laid the foundation for future studies on the conservation of this species.