Heterogeneous knowledge spillover channels in universities and green technology innovation in local firms: Stimulating quantity or quality?

Sluggish status of green technology development has stimulated research into new incentives and pathways. Beyond the traditional regulatory-push and demand-pull approaches, we reposition the strength of the technology push. Based on the innovation diffusion theory, a multidimensional path model of knowledge spillover in universities is constructed, and the impact of heterogeneous knowledge spillover channels on green innovation activities of local firms is discussed. We find that R&D collaboration has a significant effect on local firms' quality but not the quantity of green innovation. Contrarily, patent citations and technology transfer have unequal positive effects on the quantity of green innovation of local firms, while there is no evidence that they can also improve the quality of green innovation. Despite regional disparities, strict environmental regulations are pushing companies to cite university patents in some regions. The university knowledge stock has largely contributed to both quantitative and qualitative advances in subsequent green innovation in local firms. Our conclusions provide a precise and objective evaluation of the impact mechanism of multiple knowledge spillover channels in universities on firms' green innovation, as well as a reference for the selection of the form of industry-university-research collaboration.

Biomarkers of PEGylated Liposomal Doxorubicin-Induced Hypersensitivity Reaction in Breast Cancer Patients Based on Metabolomics.

This study aimed to analyze and discuss the biomarkers of PEGylated liposomal doxorubicin (PLD) injection-induced hypersensitivity reactions (HSRs) in advanced breast cancer patients. Fourteen patients from Sun Yat-sen Memorial Hospital were included in the study between April 15th, 2020 and April 14th, 2021. Patient plasma was collected 30 min before PLD injection. HSRs were found to occur in a total of 9 patients (64.3%). No association was found between HSRs and various patient characteristics such as age, body surface area, anthracycline treatment history, IgE, and complement 3 and 4 (p > 0.05). Non-targeted metabolomics analysis of patient plasma was performed, and several metabolites showed significant association with HSRs. In particular, l-histidine (fold change = 91.5, p = 0.01) showed significantly higher levels in the immediate HSR group, while myristicin (fold change = 0.218, p = 0.003), urocanic acid (fold change = 0.193, p = 0.007), and d-aldose (fold change = 0.343, p = 0.003) showed significantly lower levels in the same group. In vivo experiments showed that exogenous histidine aggravated HSRs and increased IgE plasma levels in rats following the injection of PLD. Histidine can be decarboxylated to histamine by histidine decarboxylase. Histidine decarboxylase inhibitor 4-bromo-3-hydroxybenzoic acid improved symptoms and IgE levels in vivo. These findings suggested that l-histidine can be a potential biomarker for PLD-induced HSR. Moreover, an antihistamine drug, histidine decarboxylase inhibitor, or dietary histidine management could be used as potential preventive measures. Furthermore, metabolomics research could serve as a powerful method to explore biomarkers or uncover mechanisms of drug side effects.

First-in-human HER2-targeted Bispecific Antibody KN026 for the Treatment of Patients with HER2-positive Metastatic Breast Cancer: Results from a Phase I Study.

PURPOSE: KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. This first-in-human phase I study evaluated the safety/tolerability, pharmacokinetics, preliminary efficacy, and potential predictive biomarker activity of KN026 administered as monotherapy to patients with HER2-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: Female patients with HER2-positive MBC who had progressed on prior anti HER2 therapies received intravenous KN026 monotherapy at 5 mg/kg (once weekly), 10 mg/kg (once weekly), 20 mg/kg (once every 2 weeks), or 30 mg/kg (once every 3 weeks). Dose escalation was guided by a "3+3" dose escalation rule followed by dose expansion. RESULTS: Sixty-three patients were enrolled. The most common treatment-related adverse events (TRAE) were pyrexia (23.8%), diarrhea (22.2%), aspartate aminotransferase increased (22.2%), alanine aminotransferase increased (22.2%). Only 4 patients reported grade 3 TRAEs. Results from exposure-response analysis supported the selection of the recommended phase II doses at 20 mg/kg once every 2 weeks or 30 mg/kg once every 3 weeks, which had objective response rates (ORR) of 28.1% and median progression-free survival (PFS) of 6.8 months (95% confidence interval: 4.2-8.3) in 57 patients. Translational research in 20 HER2-amplified patients further confirmed that co-amplification (vs. no co-amplification) of CDK12 was a promising biomarker in predicting better response to KN026 (ORR of 50% vs. 0% and median PFS of 8.2 vs. 2.7 months, P = 0.05 and 0.04, respectively). CONCLUSIONS: KN026, a HER2 bispecific antibody, was well tolerated and achieved comparable efficacy as trastuzumab and pertuzumab doublet even in the more heavily pretreated patients. Co-amplification of HER2/CDK12 may define patients who benefit more from KN026.

An Open-Label, Randomized, 2-Way, Crossover Bioequivalence Study of Cefradine Capsules in Healthy Chinese Volunteers.

The purpose of this study was to evaluate whether test cefradine capsules and reference cefradine capsules were bioequivalent in healthy Chinese volunteers. An open-label, randomized, biperiodic, crossover design was used. In each of the 2 study periods (separated by a 1-week washout period), 250-mg single doses of either the test or reference cefradine capsule were administered to study participants under fasted and fed conditions. Blood samples were collected at intervals from predose to 8 hours afterward. In the fasting study, the 90% confidence intervals (90%CI) of the Cmax , AUC0-8h , and AUC0-∞ for the test and reference preparations were 93.7%-112.2%, 94.6%-100.8%, and 94.7%-100.9%, respectively. In the fed study, the 90%CI of the Cmax , AUC0-8h , and AUC0-∞ for the test and reference preparations was 81.0%-99.1%, 100.5%-106.3%, and 100.5%-105.9%, respectively. The results showed that the test cefradine capsules and the reference formulation are bioequivalent under both fasting and fed conditions.

Initial allocation of flood drainage rights based on a PSR model and entropy-based matter-element theory in the Sunan Canal, China.

The pursuit of flood prevention safety and the mitigation of drainage contradiction against an unnecessary influx of floodwater require a modern and efficient model to optimize the management of the initial allocation of flood drainage rights. We attempted to formulate a framework for initial flood drainage rights allocation to promote the sustainable drainage of the Sunan Canal, China. The Pressure-State-Response (PSR) model was constructed using a literature review and interviews with experts and directors using 18 key indicators being determined from field surveys and library studies. We then assessed the flood status of Zhenjiang City, Changzhou City, Wuxi City and Suzhou City in the Sunan Canal zone using an entropy-based matter-element model. The flood drainage rights for a total of 400m3/s was allocated to the four cities in accordance with their flood status. Our research demonstrated that, overall, the four cities may gain the flood drainage rights of 106.67m3/s,120.40m3/s, 118.22m3/s and 54.71m3/s, respectively. Specifically, the calculation of the flood drainage for Wuxi was very close to the actual allocation in 2016, whereas there were differences in the other cities that should not be neglected.