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Abstract Leptomeningeal metastasis (LM), a spread of cancer to the cerebrospinal fluid and meninges, is universally and rapidly fatal due to poor detection and no effective treatment. Breast cancers account for a majority of LMs from solid tumors, with triple-negative breast cancers (TNBCs) having the highest propensity to metastasize to LM. The treatment of LM is challenged by poor drug penetration into CNS and high neurotoxicity. Therefore, there is an urgent need for new modalities and targeted therapies able to overcome the limitations of current treatment options. Quadriga has discovered a novel, brain-permeant chemotherapeutic agent that is currently in development as a potential treatment for glioblastoma (GBM). Recently, we have demonstrated dose-dependent in vitro and in vivo anti-tumor activity with various breast cancer cell lines including the human TNBC cell line MDA-MB-231. To evaluate the in vivo antitumor activity of the compound on LM, we used the mouse model of LM based on the internal carotid injection of luciferase-expressing MDA-MB-231-BR3 cells. Once the bioluminescence signal intensity from the metastatic spread reached (0.2 - 0.5) x 106photons/sec, mice were dosed i.v. (8 mg/kg once a week for nine weeks) or i.p. (4 or 8 mg/kg twice a week for nine weeks). Tumor growth was monitored by bioluminescence. The compound was well tolerated and caused a significant delay in metastatic growth resulting in significant extension of survival. Tumors regressed completely in ~ 28 % of treated animals in the i.p. group. Given that current treatments for LM are palliative with only few studies reporting a survival benefit, Quadriga’s new agent could be effective as a therapeutic for both primary and metastatic brain tumors such as LM. REF: https://onlinelibrary.wiley.com/doi/full/10.1002/pro6.43

Background: Meningioma represents the most common intracranial tumor in adults. However, it is rare in pediatric patients. We aimed to demonstrate the clinicopathological characteristics and long-term outcome of pediatric meningiomas (PMs). Method: We enrolled 74 patients with intracranial PMs and analyzed their clinicopathological characteristics. Targeted next generation sequencing was used to detect alterations in meningioma relevant genes. Progression-free survival (PFS) was compared between PMs and adult meningiomas (AMs). Univariate and multivariate Cox analyses were employed to evaluate the predictive values of clinicopathological characteristics. A nomogram was constructed and its predictive accuracy evaluated. Result: 40 females (54.1%) and 34 males (45.9%) patients, with the gender ratio of 1.18:1, were identified. 9 (12.2%) cases were clinically diagnosed as NF2-related Schwannomatosis (NF2-SWN), while 65 (87.8%) were sporadic. Ventricular location was found in 16 patients (21.6%). 19 patients (25.7%) experienced recurrence during a median follow-up period of 33 months (range 2 -145.25 months). The 3-, 5-, and 8-year PFS rates was 74.74%, 74.74%, and 59.38%, respectively. The PFS of the PM and AM cohorts were not significantly different, with or without propensity score matching. NF2 mutation was observed in 33 sporadic PMs (52.4%), whereas alterations in other genes (AKT1, TRAF7, SMO, PIK3CA, KLF4) frequently mutated in AMs, were not identified. The proportion of NF2 mutation in PMs was significantly lower in the skull base than other locations (p = 0.02). One anaplastic PM harbored TERT promoter mutation. Of note, in sporadic PMs, NF2 mutations were not significantly associated with PFS (p = 0.434) or overall survival (OS) (p = 0.60). The multivariate Cox analysis showed NF2-SWN (p < 0.001) and extent of resection (p = 0.013) to be independently associated with the PFS of PMs. Our prognostic model showed predictive accuracy for long-term PFS in PMs as the 3-, 5- and 8-year Area Under the Curve (AUC) was 0.927, 0.930, and 0.870, respectively. Conclusion: PM was characterized by its relative male predominance, ventricular location, NF2-SWN, and NF2 mutation. Of note, PMs had similar prognosis to AMs and NF2 alteration was not significantly associated with PFS in PMs. [ABSTRACT FROM AUTHOR]

Photodegradation is considered as a universal contributing factor to litter decomposition and carbon (C) cycling within the Earth's biomes. Identifying how solar radiation modifies the molecular structure of litter is essential to understand the mechanism controlling its decomposition and reaction to shifts in climatic conditions and land-use. In this study, we performed a spectral-attenuation experiment following litter decomposition in an understory and gap of a temperate deciduous forest. We found that short-wavelength visible light, especially blue light, was the main factor driving variation in litter molecular structure of Fagus crenata Blume, Quercus crispula Blume, Acer carpinifolium Siebold & Zuccarini and Betula platyphylla Sukaczev, explaining respectively 56.5%, 19.4%, 66.3%, and 16.7% of variation in its chemical composition. However, the variation also depended on canopy openness: Only in the forest gap was lignin aromatic C negatively associated with C-oxygen (C–O) bonding in polysaccharides receiving treatments containing blue light of the full spectrum of solar radiation. Regardless of species, the decomposition index of litter that explained changes in mass and lignin loss was driven by the relative content of C–O stretching in polysaccharides and lignin aromatic C. The results suggest that the availability of readily degradable polysaccharides produced by the reduction in lignin aromatic C most plausibly explains the rate of litter photodegradation. Photo-products of photodegradation might augment the C pool destabilized by the input of readily degradable organic compounds (i.e., polysaccharides). [ABSTRACT FROM AUTHOR]

Objective: The purpose of this trial was to explore the effects of the ultrasound-guided transverse abdominal plane block (TAPB) on the systemic immune-inflammatory index (SII), peripheral blood neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) in patients undergoing radical resection of endometrial carcinoma. Methods: This trail was registered in the Chinese Clinical Trial Registry (ChiCTR2300072186, www.chictr.org/; approval date: 2023-06-06). In the study, a total of 90 patients who were scheduled for radical resection of endometrial carcinoma were selected, and they were randomized to receive ultrasound-guided TAPB combined with general anesthesia (GA) or either GA. The primary outcomes were the values of NLR、PLR and SII which were obtained at postoperative 24 hours and 72 hours. Other observational indicators included: the counts of neutrophil, lymphocyte, and platelet; the numbers of effective press of the analgesic pump; postoperative pain intensity; remifentanil consumption; and adverse reactions. Results: The values of preoperative peripheral blood neutrophil, platelet, lymphocyte, NLR, PLR, and SII did not differ between the two groups (P>0.05). The TAP+GA group exhibited significantly reduced levels of neutrophil, NLR, and SII at 24 and 72 hours post-surgery than the GA group (P<0.05). However, there were no significant differences in the values of PLR between the two groups (P>0.05). Compared with the GA group, the VAS scores at 6 hours, 12 hours, and 24 hours after surgery in the TAP+GA group were significantly decreased, and the intraoperative consumption of remifentanil and the numbers of postoperative analgesic pump presses were significantly reduced (P<0.05). Moreover, the incidence of postoperative nausea and vomiting was reduced considerably in the TAP+GA group (P<0.05). Conclusions: Ultrasound-guided TAPB can effectively lower the values of postoperative neutrophil, NLR, and SII, improve postoperative pain intensity, decrease opioid consumption, and reduce the incidence of postoperative nausea and vomiting. [ABSTRACT FROM AUTHOR]

Summary statement: High solar radiation exacerbated the negative effects of extreme drought on plant growth and fine root traits. Ectomycorrhizae did not compensate for fine roots under drought stress. Fine roots biomass determined the role of ectomycorrhizal fungi, supporting the energy limitation hypothesis. [ABSTRACT FROM AUTHOR]

High-voltage initial anode-free lithium metal batteries (AFLMBs) promise the maximized energy densities of rechargeable lithium batteries. However, the reversibility of the high-voltage cathode and lithium metal anode is unsatisfactory in sustaining their long lifespan. In this research, a concentrated electrolyte comprising dual salts of LiTFSI and LiDFOB dissolved in mixing solvents of dimethyl carbonate (DMC) and fluoroethylene carbonate (FEC) with a LiNO3 additive was formulated to address this challenge. FEC and LiNO3 regulate the anion-rich solvation structure and help form a LiF, Li3N-rich solid electrolyte interphase (SEI) with a high lithium plating/stripping Coulombic efficiency of 98.3%. LiDFOB preferentially decomposes to effectively suppress the side reaction at the high-voltage operation of the Li-rich Li1.2Mn0.54Ni0.13Co0.13O2 cathode. Moreover, the large irreversible capacity during the initial charge/discharge cycle of the cathode provides supplementary lithium sources for cycle life extension. Owing to these merits, the as-fabricated AFLMBs can operate stably for 80 cycles even at an ultrahigh voltage of 4.6 V. This study sheds new insights on the formulation of advanced electrolytes for highly reversible high-voltage cathodes and lithium metal anodes and could facilitate the practical application of AFLMBs. [ABSTRACT FROM AUTHOR]

Highlights: NaTFSI/SUL:OTE:FEC facilitates the formation of S, N-rich, dense and robust cathode–electrolyte interphase on NaNMF cathode, which improves the cycling stability under high voltage. By utilizing NaTFSI/SUL:OTE:FEC, the Na||NaNMF batteries achieved an impressive retention of 81.15% after 400 cycles at 2 C with the cutoff voltage of 4.2 V. The study offers a reference for the utilization of sulfolane-based electrolytes in sodium-ion batteries (SIBs), while the nonflammability of the NaTFSI/SUL:OTE:FEC enhances the safety of SIBs. Sodium-ion batteries hold great promise as next-generation energy storage systems. However, the high instability of the electrode/electrolyte interphase during cycling has seriously hindered the development of SIBs. In particular, an unstable cathode–electrolyte interphase (CEI) leads to successive electrolyte side reactions, transition metal leaching and rapid capacity decay, which tends to be exacerbated under high-voltage conditions. Therefore, constructing dense and stable CEIs are crucial for high-performance SIBs. This work reports localized high-concentration electrolyte by incorporating a highly oxidation-resistant sulfolane solvent with non-solvent diluent 1H, 1H, 5H-octafluoropentyl-1, 1, 2, 2-tetrafluoroethyl ether, which exhibited excellent oxidative stability and was able to form thin, dense and homogeneous CEI. The excellent CEI enabled the O3-type layered oxide cathode NaNi1/3Mn1/3Fe1/3O2 (NaNMF) to achieve stable cycling, with a capacity retention of 79.48% after 300 cycles at 1 C and 81.15% after 400 cycles at 2 C with a high charging voltage of 4.2 V. In addition, its nonflammable nature enhances the safety of SIBs. This work provides a viable pathway for the application of sulfolane-based electrolytes on SIBs and the design of next-generation high-voltage electrolytes. [ABSTRACT FROM AUTHOR]

The shared energy storage device acts as an energy hub between multiple microgrids to better play the complementary characteristics of the microgrid power cycle. In this paper, the cooperative operation process of shared energy storage participating in multiple island microgrid systems is researched, and the two-stage research on multi-microgrid operation mode and shared energy storage optimization service cost is focused on. In the first stage, the output of each subject is determined with the goal of profit optimization and optimal energy storage capacity, and the modified grey wolf algorithm is used to solve the problem. In the second stage, the income distribution problem is transformed into a negotiation bargaining process. The island microgrid and the shared energy storage are the two sides of the game. Combined with the non-cooperative game theory, the alternating direction multiplier method is used to reduce the shared energy storage service cost. The simulation results show that shared energy storage can optimize the allocation of multi-party resources by flexibly adjusting the control mode, improving the efficiency of resource utilization while improving the consumption of renewable energy, meeting the power demand of all parties, and realizing the sharing of energy storage resources. Simulation results show that compared with the traditional PSO algorithm, the iterative times of the GWO algorithm proposed in this paper are reduced by 35.62%, and the calculation time is shortened by 34.34%. Compared with the common GWO algorithm, the number of iterations is reduced by 18.97%, and the calculation time is shortened by 22.31%. [ABSTRACT FROM AUTHOR]

The extended diamond model of green building was constructed to clarify the key elements of green building industry development and the core effectiveness of government. On this basis, a two-dimensional analysis framework of green building with policy tools and life cycle was further developed, and 62 policy texts were coded and analyzed by using Nvivo12 software. It is found that the existing policy tools have limited impact on demand conditions, production factors, enterprise strategies and supporting industries. According to the results, this paper provides the following advice: expand the use of policies in the operation and maintenance phase, increase incentives on the demand side, improve the supply capacity and quality of production factors, pay attention to talent training and enterprise capacity building, improve the overall process precision control system, increase financial incentives for enterprises, implement technological innovation support, and improve the policy system of the whole industry chain. [ABSTRACT FROM AUTHOR]

Organosulfur materials containing sulfur–sulfur bonds are an emerging class of high‐capacity cathodes for lithium storage. However, it remains a great challenge to achieve rapid conversion reaction kinetics at practical testing conditions of high cathode mass loading and low electrolyte utilization. In this study, a Li‐rich pyrolyzed polyacrylonitrile/selenium disulfide (pPAN/Se2S3) composite cathode is synthesized by deep lithiation to address the above challenges. The Li‐rich molecular structure significantly boosts the lithium storage kinetics by accelerating lithium diffusivity and improving electronic conductivity. Even under practical test conditions requiring a lean electrolyte (Electrolyte/sulfur ratio of 4.1 μL mg−1) and high loading (7 mg cm−2 of pPAN/Se2S3), DL‐pPAN/Se2S3 exhibits a specific capacity of 558 mAh g−1, maintaining 484 mAh g−1 at the 100th cycle with an average Coulombic efficiency of near 100%. Moreover, it provides (electro)chemically stable Li resources to offset Li consumption over charge–discharge cycles. As a result the as‐fabricated anode‐free cell shows a superior cycling stability with 90% retention of the initial capacity over 45 cycles. This study provides a novel approach for fabricating high‐energy and stable Li–SPAN cells. [ABSTRACT FROM AUTHOR]

Background: Central poststroke pain (CPSP) is one of the primary sequelae following stroke, yet its underlying mechanisms are poorly understood. Methods: By lesioning the lateral thalamic nuclei, we first established a CPSP model that exhibits mechanical and thermal hypersensitivity. Innocuous mechanical stimuli following the thalamic lesion evoked robust neural activation in somatosensory corticospinal neurons (CSNs), as well as in the deep dorsal horn, where low threshold mechanosensory afferents terminate. In this study, we used viral‐based mapping and intersectional functional manipulations to decipher the role of somatosensory CSNs and their spinal targets in the CPSP pathophysiology. Results: We first mapped the post‐synaptic spinal targets of lumbar innervating CSNs using an anterograde trans‐synaptic AAV1‐based strategy and showed these spinal interneurons were activated by innocuous tactile stimuli post‐thalamic lesion. Functionally, tetanus toxin‐based chronic inactivation of spinal neurons targeted by CSNs prevented the development of CPSP. Consistently, transient chemogenetic silencing of these neurons alleviated established mechanical pain hypersensitivity and innocuous tactile stimuli evoked aversion linked to the CPSP. In contrast, chemogenetic activation of these neurons was insufficient to induce robust mechanical allodynia typically observed in the CPSP. Conclusion: The CSNs and their spinal targets are required but insufficient for the establishment of CPSP hypersensitivity. Our study provided novel insights into the neural mechanisms underlying CPSP and potential therapeutic interventions to treat refractory central neuropathic pain conditions. [ABSTRACT FROM AUTHOR]

In order to comprehensively reflect the current status, research hotspots and evolutionary trends of research on construction projects from a social network perspective, 143 HJrelevant papers in the WoS database from 1999 to 2020 were taken as the research objects, and the bibliometric method and CiteSpace V were used to reveal the research development and evolution of the field during the 20 years and explore the future research trends. The study shows that the hotspots of construction project research from social network perspective include performance, governance, stakeholder management, risk management, and communication; research on construction project organizational network innovation, stakeholder risk and governance, BIM technology application, and social capital perspective to improve project organization become future research trends.

Meningioma is one of the most common primary neoplasms in the central nervous system, but no specific molecularly targeted therapy has been approved for the clinical treatment of aggressive meningiomas. There is hence an urgent demand to decrypt the biological and molecular landscape of malignant meningioma. Here, through the in-silica prescreening and 10-year follow-up studies of 445 meningioma patients, we uncovered that CBX7 expression progressively decreases with malignancy grade and neoplasia stage in meningioma, and a high CBX7 expression level predicts a favorable prognosis in meningioma patients. CBX7 restoration significantly induces cell cycle arrest and inhibits meningioma cell proliferation. iTRAQ-based proteomics analysis indicated that CBX7 restoration triggers the metabolic shift from glycolysis to oxidative phosphorylation. The mechanistic study demonstrated that CBX7 promotes the proteasome-dependent degradation of c-MYC protein by transcriptionally inhibiting the expression of a c-MYC deubiquitinase, USP44, consequently attenuates c-MYC-mediated transactivation of LDHA transcripts, and further inhibits glycolysis and subsequent cell proliferation. More importantly, the functional role of CBX7 was further confirmed in subcutaneous and orthotopic meningioma xenograft mouse models and meningioma patients. Altogether, our results shed light on the critical role of CBX7 in meningioma malignancy progression and identify the CBX7/USP44/c-MYC/LDHA axis as a promising therapeutic target against meningioma progression. [ABSTRACT FROM AUTHOR]

The development of cooperative relationships among project participants makes relationship norms an important governance mechanism to promote cooperative behavior. However, the research on relationship norms mostly ignored the project network environment established by project participants. A static project network cannot accurately reflect the actual project network state from the perspective of network embeddedness, but the research on the mechanism of cooperative behavior from the perspective of dynamic network embeddedness is limited. Therefore, this study overcame the limitation of static analysis. This paper divided the implementation process of construction projects into early, middle, and late phases. The theoretical model of network embeddedness, relationship norms, and cooperative behavior was tested using sample data from 716 surveys regarding the three phases from China to determine the mechanism of the effect of network embeddedness on cooperative behavior. The research results show that network embeddedness (including structural embeddedness and relational embeddedness) has a direct impact on cooperative behavior. The results also indicate that network embeddedness has an indirect impact on cooperative behavior through relationship norms. Additionally, the results further indicate that the direct and indirect effects of network embeddedness on cooperative behavior are different in different phases of construction projects. With the advance of construction projects, the influence of relational embeddedness increases, whereas the effect of structural embeddedness decreases. The research results deepen the understanding of relationship norms in construction projects and make up for the lack of research on cooperative behavior in construction projects from the perspective of dynamic networks. The research results also provide enlightenment for project participants to fully utilize the network relationships in different phases of construction projects, stimulate the establishment of relationship norms, and promote cooperation. This is helpful to improve the cooperative construction management mode. [ABSTRACT FROM AUTHOR]