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The application of renewable energy has become increasingly widespread worldwide because of its advantages of resource abundance and environmental friendliness. However, the deployment of hybrid renewable energy systems (HRESs) varies greatly from city to city due to large differences in economic endurance, social acceptance and renewable energy endowment. Urban policymakers thus face great challenges in promoting local clean renewable energy utilization. To address these issues, this paper proposes a combined multi-objective optimization method, and the specific process of this method is described as follows. The Hybrid Optimization Model for electric energy was first used to examine five different scenarios of renewable energy systems. Then, the Technique for Order Preference by Similarity to an Ideal Solution was applied using eleven comprehensive indicators to determine the best option for the target area using three different weights. To verify the feasibility of this method, Xiongan New District (XND) was selected as an example to illustrate the process of selecting the optimal HRES. The empirical results of simulation tools and multi-objective decision-making show that the Photovoltaic-Diesel-Battery off-grid energy system (option III) and PV-Diesel-Hydrogen-Battery off-grid energy system (option V) are two highly feasible schemes for an HRES in XND. The cost of energy for these two options is 0.203 and 0.209 $/kWh, respectively, and the carbon dioxide emissions are 14,473 t/yr and 345 t/yr, respectively. Our results provide a reference for policymakers in deploying an HRES in the XND area.

We present new 1.5–8.5 GHz Very Long Baseline Array (VLBA) observations and 0.32–1.26 GHz Giant Meterwave Radio Telescope (GMRT) observations of J0354−1340, which is the only known radio-quiet (RQ) or radio-intermediate (RI) narrow-line Seyfert 1 galaxy with a 100 kpc, two-sided radio jet. A parsec-scale, one-sided jet in the southeastern direction from the core emission is found in the VLBA observations, while the kiloparsec-scale jet observed with the Karl G. Jansky Very Large Array (VLA) and GMRT is in the south–north direction. Core spectra on parsec and kiloparsec scales are presented in combination with archival VLA Sky Survey observations at 3.0 GHz and VLA C-configuration observations at 5.5 GHz. The parsec-scale emission dominates the kiloparsec-scale emission above ∼5 GHz, and the spectrum is inverted due to synchrotron self-absorption. This indicates a compact synchrotron source with a size of ∼0.04 pc, which is associated with either the jet base or the corona. A subkiloparsec-scale jet, which is unresolved on scales of ∼3″, probably dominates the emission below ∼5 GHz. Future radio observations can explore the jet structure between the parsec and 100 kpc scales, the origin of their direction mismatch, and the parsec-scale jet proper motion. It remains to be explored how common such large-scale jets are in RQ or RI active galactic nuclei.

Objective Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) and endovascular therapy (EVT) are established treatments for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. This study aimed to compare the safety and efficacy of bridging therapy (rt-PA before EVT) versus direct EVT in a real-world, multicenter setting. Methods In this retrospective multicenter cohort study, 724 patients with anterior circulation AIS treated with EVT within 8 h of symptom onset were analyzed. Patients received either pre-EVT rt-PA (n = 314) or direct EVT without rt-PA (n = 410). Primary outcomes included 3-month functional independence (modified Rankin Scale (mRS) 0–2), excellent outcome (mRS 0–1), and mortality. Secondary outcomes included hemorrhagic transformation, parenchymal hematoma, and successful reperfusion (mTICI ≥ 2b). Multivariate logistic regression was adjusted for key clinical confounders. Results Baseline characteristics were comparable, except for higher median NIHSS scores in the direct EVT group (16 vs. 15, p < 0.001). No significant differences were observed in 3-month functional independence (43.0% vs. 50.3%, p = 0.051), excellent outcome (36.8% vs. 42.0%, p = 0.155), or mortality (22.9% vs. 20.1%, p = 0.354). Hemorrhagic transformation and parenchymal hematoma rates were similar. Although successful reperfusion was higher in the rt-PA group (93.6% vs. 88.5%, p = 0.019), this did not remain significant after adjustment. Conclusion Pre-EVT rt-PA did not improve functional outcomes or reduce mortality in AIS patients. While rt-PA showed a trend toward higher reperfusion rates, this did not translate to clinical benefit. Hemorrhage risks were similar between groups.

This study investigates the daily age and growth characteristics of Sepia esculenta along the East coast of China, aiming to provide essential data for population dynamics and sustainable fisheries management. A total of 360 specimens were collected from September to November 2021. Among these, 178 individuals (81 females and 97 males) were successfully aged by analyzing growth increments in the sagittal section of the upper beak rostrum (RSS) using beak microstructure analysis. The mantle length (ML) of S. esculenta ranged from 55 to 201 mm and body weight (BW) from 30 to 667 g, with no significant sex differences. Age estimates ranged from 59 to 152 days, averaging 106.44 ± 17.35 days for females and 103.86 ± 19.70 days for males. The ML-age relationship fitted a linear growth model, while BW-age relationships followed an exponential model for females and a power function model for males. Growth rate analysis showed varied growth trajectories with age, with the highest absolute growth rate (AGR) of ML observed at 120–150 days for females (1.23 mm/d) and at 60–90 days for males (1.93 mm/d). These findings provide crucial insights into the growth patterns and population dynamics of S. esculenta in the East coast of China, supporting resource assessment and sustainable management efforts.

Ferroptosis is an iron‐dependent form of programmed cell death governed by redox homeostasis. Although Ezrin, Radixin, and Moesin (ERM) proteins are established membrane‐actin cytoskeleton linkers, their role in ferroptosis remains unexplored. Here, ERM proteins are identified as modulators of erastin‐induced ferroptosis. In human fibrosarcoma HT‐1080 cells, pharmacological inhibition of ERM phosphorylation, knockdown of individual ERM members, or overexpression of a phospho‐deficient Ezrin mutant (T567A) consistently attenuated ferroptosis, whereas wild‐type ERM overexpression enhances ferroptosis susceptibility. Mechanistically, ERM inhibition leads to F‐actin depolymerization accompanied by a modest rise in reactive oxygen species (ROS). F‐actin stabilization prevents this ROS surge and restores ferroptotic sensitivity, whereas its depolymerization mimics the protective effect of ERM inhibition. ROS elevation triggers KEAP1 degradation, stabilizing NRF2 and promoting its nuclear translocation. Activated nuclear NRF2 induces antioxidant genes, particularly HMOX1, a key effector of heme catabolism that enhances redox buffering and limits lipid peroxidation, ultimately conferring resistance to ferroptosis. The protective effects of ERM inhibition are further validated in ferroptosis‐relevant ex vivo and in vivo models. Notably, other pro‐oxidants similarly attenuate ferroptosis at appropriate concentrations. Together, these results establish ERM proteins as regulators of ferroptosis and reveal an underappreciated group of ferroptosis inhibitors that engage ROS‐NRF2‐mediated redox‐adaptation. ERM inhibition disrupts ERM‐actin interactions, elevating ROS and triggering KEAP1 degradation, which stabilizes and activates NRF2. Nuclear NRF2 induces cytoprotective genes, notably HMOX1, enhancing redox buffering and suppressing lipid peroxidation to resist erastin‐induced ferroptosis. ERM inhibitors thus act as pro‐oxidants that paradoxically promote ferroptosis resistance, with protective effects observed in ex vivo and in vivo models.

BackgroundThe efficacy of systemic treatment for primary central nervous system lymphoma (PCNSL) is limited because of the blood–brain barrier (BBB) and the ineffectiveness of chemotherapy. The dual PI3K/HDAC inhibitor BEBT-908 has exhibited favorable in vivo distribution and activity in various cancers.ObjectivesThe aims of this study were to assess the efficacy of BEBT-908 in brain orthotopic mouse models of hematological malignancies, to investigate its pharmacologic properties, and to elucidate the underlying mechanism of action.MethodsWe evaluated the anticancer activity of BEBT-908 in various hematological malignancies through cell viability assays. The impact of BEBT-908 on c-Myc expression and ferroptosis signaling pathways was assessed using Western blotting, qPCR, ROS detection, GSH/GSSG detection, and IHC. Pharmacokinetic and pharmacodynamic profiles were assessed through LC–MS/MS and Western blotting. The effects of BEBT-908 in vivo were examined using xenografts and brain orthotopic mouse models.ResultsOur findings demonstrate that BEBT-908 exhibits promising anti-tumor activity in vitro and in vivo across multiple subtypes of hematological malignancies. Furthermore, BEBT-908 exhibits excellent BBB penetration and inhibits tumor growth in a brain orthotopic lymphoma model with prolonged survival of host mice. Mechanistically, BEBT-908 downregulated c-Myc expression, which contributed to ferroptosis, ultimately leading to tumor shrinkage.ConclusionOur study provides robust evidence for the dual PI3K/HDAC inhibitor BEBT-908 as an effective anti-cancer agent for PCNSL.

Studies investigating the impact of polymorphisms on monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor (CCR2) on the susceptibility of Parkinson’s disease (PD) have reported inconsistent results. Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two gene polymorphisms and PD risk. We performed a meta-analysis of five eligible studies to summarize the data describing the association between PD risk and polymorphisms in MCP-1 A2518G and CCR2 V64I. The association was evaluated by calculating the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). A significant increased risk of PD was observed in the MCP-1 A2518G polymorphism in allele model (G vs. A: OR 1.12, 95% CI 1.01–1.25, p  = 0.03). The dominant model of MCP-1 A2518G genotype showed no significant association with PD risk, while the risk tendency was increased (AG + GG vs. AA: OR 1.20, 95% CI 1.00–1.42, p  = 0.05). In addition, CCR2 V64I polymorphism showed no significant association with PD risk (I vs. V: OR 0.33, 95% CI 0.06–1.92, p  = 0.22; VI + II vs. VV: OR 1.00, 95% CI 0.83–1.21, p  = 0.99). In subgroup analysis by ethnicity, no significant difference was found in both Caucasians and Asians between CCR2 V64I polymorphism and PD risk, while a significant statistical association was identified in Asians between MCP-1 A2518G polymorphism and PD risk. When the data were stratified by study area, the increased risk of PD was observed only in studies conducted in China. In summary, the present meta-analysis suggests that genetic polymorphisms of MCP-1 A2518G may influence the susceptibility of PD in Asian countries, especially in China. However, CCR2 V64I polymorphism is not correlated with PD risk. The results should be interpreted with caution due to limited sample and heterogeneity. Large scale and well-designed studies are needed to validate our findings.

ROS at the Tipping Point This image depicts pro‐oxidant‐induced reactive oxygen species (ROS) as a double‐edged blade or shield that fine‐tunes cellular fate at the tipping point between protection and destruction, with the ERM inhibitors NSC305787 and NSC668394 representing a class of pro‐oxidant ferroptosis inhibitors. More details can be found in the Research Article by Junqi Huang, Ting Gang Chew, Yunmiao Guo, Lijuan Pang, and co‐workers (DOI: 10.1002/advs.202513310).

Taxus yunnanensis is a paclitaxel-containing herb with traditional usage in cancer treatment, and its extract possesses great oral bioavailability of paclitaxel. However, it is elusive whether paclitaxel-containing extract (HDS-1) can exert anti-tumor effect through oral administration and how other components contribute to its efficacy. Therefore, we investigate the oral-route anti-tumor effect of HDS-1 in A549-bearing mice. HDS-1-derived flavonoids (HDS-2) and lignoids (HDS-3) are hypothesized to contribute to HDS-1’s efficacy, and their effects of enhancing enterocytic absorption and cytotoxicity of paclitaxel are validated in 2 permeability experiments and apoptosis-related assay, respectively. In vivo, A549 growth is significantly inhibited by 86.1 ± 12.94% (P<0.01) at 600 mg/kg of HDS-1 and 65.7 ± 38.71% (P<0.01) at 200 mg/kg. HDS-2 and HDS-3 significantly reduce the efflux ratio of paclitaxel to 2.33 and 3.70, respectively, in Caco-2 permeability experiment and reduce paclitaxel reflux in MDCK-MDR1 experiment. Furthermore, HDS-2 and HDS-3 potentiated paclitaxel-induced cytotoxicity by 19.1–22.45% (P<0.05) and 10.52–18.03% (P<0.05), respectively, inhibited the expression of cyclinB1, Bcl-2, and pMCL-1, and increased the percentage of necrosis cell in the condition of paclitaxel exposure. Conclusively, paclitaxel-containing extracts exert anti-cancer effects through oral administration, and flavonoid and lignoids contribute to its anti-cancer effect through simultaneously improving enterocytic absorption of paclitaxel and the cytotoxic effect of paclitaxel.

Introduction Activation of the PI3K/AKT pathway is a common phenomenon in cancer due to multiple mechanisms, including mutation of PI3KCA, loss or mutation of PTEN, or over-expression of receptor tyrosine kinases. We recently developed a novel AKT kinase inhibitor, AZD5363, and demonstrated that HGC27, a cell line harboring both PI3KCA mutation and PTEN loss, displayed the greatest sensitivity to this AKT inhibitor in vitro and in vivo . Case preparation To further elucidate the correlation between AZD5363 response and genetic alterations in gastric cancer (GC) and identify GC patients with both PI3KCA mutations and PTEN loss, we investigated the effects of pharmacological inhibition of AKT on a panel of 20 GC cell lines and genetic aberrations in tumor samples from a cohort of Chinese GC patients. We demonstrated that GC cells with PI3KCA mutations were selectively sensitive to AZD5363. Disease linkage studies showed that PI3KCA activating mutations or PTEN loss were found in 2.7% (4/150) and 23% (14/61) of Chinese GC patients respectively. To further dissect the role of PI3KCA mutation and PTEN loss in response to AKT inhibition, we tested the antitumor activity of AZD5363 in two patient-derived GC xenograft (PDGCX) models harboring either PI3KCA mutation or PTEN loss. Our data indicated that AZD5363 monotherapy treatment led to a moderate response in the PI3KCA mutant PDGCX model. Whilst monotherapy AZD5363 or Taxotere were ineffective in the PTEN negative PDGCX model, significant anti-tumor activity was observed when AZD5363 was combined with Taxotere. Conclusion Our results indicated that PI3KCA mutation is an important determinant of response to AKT inhibition in GC and combination with AZD5363 can overcome innate resistance to Taxotere in a PTEN loss PDGCX model. It is suggested that AKT inhibitor is an attractive option for treatment of a new segment of GC patients with aberrant PI3K/AKT signaling.