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Currently, immune checkpoint inhibitors (ICIs) have changed the treatment paradigm for many malignant tumors. As the most common digestive tract malignancy, colorectal cancer (CRC) shows a good response to ICIs only in a small subset of patients with MSI-H/dMMR CRC. In contrast, patients with MSS/pMMR CRC show minimal response to ICIs. The results of the REGONIVO study suggest that targeting the tumor microenvironment (TME) to improve immunotherapy outcomes in MSS/pMMR CRC patients is a feasible strategy. Therefore, this article focuses on exploring the feasibility of targeting the TME to enhance immunotherapy outcomes in CRC, collecting recent basic research on targeting the TME to enhance immunotherapy outcomes in CRC and analyzing ongoing clinical trials to provide a theoretical basis and future research directions for improving immunotherapy outcomes in MSS/pMMR CRC.

Abstract In the distribution network planning work, taking into account the constraints of funds and construction annual plan, there is always the prioritization problem of multiple MVDC distribution networks. Aiming at the problem, this paper proposes a method for the optimization analysis of MVDC distribution network planning objects. Firstly, a comprehensive evaluation index system of urban MVDC distribution network planning and optimization is established from three aspects of improving power supply reliability and the quality of voltage, MVDC distribution network scenario types and distribution network social benefits. Then, the qualitative indexes are quantified based on the cloud model, and the comprehensive evaluation values of each distribution network are calculated and sorted by the hierarchical additive weighting of Delphi entropy weight method. Taking the maximum comprehensive evaluation value of the scheme as objective function and the annual total investment as constraint, the construction priority of multiple MVDC distribution networks is determined. Finally, taking several distribution networks in Guangzhou, Guangdong Province, China as examples, the simulation results show that the optimal objects of distribution network based on the urban scenario demands are X4, X8 and X1, with the lowest total investment cost of 19,180 yuan, thus verifying the effectiveness of the proposed method.

Objective To explore the characteristics and the cause of variance of pharmacokinetics (PK) of docetaxel (DTX) in patients with solid tumors. Methods Between January 1 of 2018 and December 31 of 2020, 374 patients at two research centers—oncology, breast and thyroid surgery, thoracic surgery, the Third Affiliated Hospital of Chongqing Medical University, and oncology, breast and thyroid surgery, obstetrics and gynecology, Henan Provincial People's Hospital—provided a total of 772 docetaxel plasma samples. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to determine docetaxel plasma concentrations. Nonlinear mixed-effects model (NONMEM) software was used to establish the population phar macokinetics(PPK) model. Using bootstrap and visual predictive check(VPC) for internal validation of the model. Results The current study established a three-compartment PPK model with first-order elimination of docetaxel in patients with solid tumors. DTX blood concentrations ranged from 3.53 ng/mL to 2 491 ng/mL, with a median of 175.5 ng/mL. Albumin (ALB) was identified as a covariate significantly affecting the clearance(CL) of docetaxel, and creatinine(CREA) was a covariate significantly affecting Q3. The model-estimated CL, V2, Q2, and Q3 of docetaxel were 57.2 L/h, 11.8 L, 14.1 L/h, and 8.63 L/h, respectively. Conclusion A three-compartment PPK model with multicenter data is established in patients with solid tumors. ALB is the main factor affecting CL variation. The internal validation results show that the model is stable and reliable.

Lithium-rich manganese-based cathode material is a promising next-generation lithium-ion battery cathode material, however, it exhibits significant differences in electrochemical performance at different temperatures, which severely limits the application in practical environments. A variety of electrochemical measures were used to characterize the difference in electrochemical performance of lithium-rich material within the temperature range of 5-45℃. The influencing factors of material properties and temperature dependence were analyzed from the perspective of polarization. The results show that the charge/discharge capacity of lithium-rich material decreases with decreasing temperature, which is mainly due to the significant increase in the polarization of the oxygen/manganese ion reaction in the high-voltage and low-voltage ranges with decreasing temperature, resulting in a severe decrease in its capacity contribution.The significantly increased polarization is mainly caused by the poor intrinsic kinetic performance of oxygen/manganese ions, which leading to high apparent activation energy of the charge transfer process. In addition, the participation of oxygen and manganese ions in the charge compensation reaction changes the structure of the material seriously.It induces changes in the composition of the interface film, which increases the apparent activation energy of lithium ion transmission at the interface in the low voltage interval. Moreover, it causes bulk diffusion of lithium ions at the end of the charge and discharge process having higher apparent activation energy. Therefore, improving the oxygen/manganese ion reaction kinetics of lithium-rich material is the main method to enhance its environmental adaptability.

Objective: Preoperative levels of cognition-related biomarkers and intraoperative cerebral ischemia and hypoxia might cause postoperative neurocognitive dysfunction (PND). The aim of this study was to evaluate the predictive ability of preoperative plasma biomarkers along with cerebral oxygen saturation (SctO2) for the incidence of PND in elderly patients with mild cognitive impairment (MCI).Methods: A total of 210 patients aged 65–80 years undergoing spinal surgery were randomly assigned to three groups (n = 70 each): propofol, sevoflurane, and propofol/sevoflurane as anesthesia maintenance protocols. Propofol was administrated target-controlled infusion of 4 μg/ml (group P), the minimum alveolar concentration (MAC) of inhalation anesthetic sevoflurane was 1.3 (group S), and propofol was injected with a target-controlled plasma concentration of 1.2 μg/ml, accompanied by sevoflurane inhalation 0.7 MAC (group PS). Cognitive function was evaluated 1 day preoperatively and on the 7th day postoperatively. Preoperative levels of amyloidβ-40 (Aβ-40), Aβ-42, total tau protein (T-tau), phosphorylated tau protein (P-tau), and triggering receptors on myeloid cells-2 (TREM2) were investigated. SctO2 was monitored intraoperatively.Results: Aβ-42 had the strongest significant correlation with preoperative MoCA score. The value of Aβ-42 associated with a high risk of PND was 28.34 pg/ml, and the area under the curve (AUC) was predicted to be 0.711. When the preoperative level of Aβ-42 was 28.34 pg/ml, SctO2max% was 9.92%. The AUC was predicted to be 0.872, and the sensitivity and specificity were 0.833 and 0.841, respectively.Conclusion: Under the conditions of preoperative Aβ-42 less than 28.34 pg/ml, the intraoperative fluctuation range of cerebral oxygen saturation should be maintained within 9.92% to reduce the occurrence of PND in geriatric patients with MCI.

Background: Neurofibromatosis type 2 (NF2) is a rare genetic syndrome that predisposes individuals to develop bilateral vestibular schwannomas (VSs) causing a high risk of life-threatening neurological complications. Traditional treatment options for NF2-associated VS usually cause neurological damage, and to date, there are no FDA-approved pharmacotherapies for NF2. The aim of this study was to evaluate the antitumor efficacy of Qu-Du-San-Jie (QDSJ) decoction, a traditional Chinese medicine formula, on NF2-associated VS and to investigate the potential underlying mechanisms.Methods: Ultra high-performance liquid chromatography-mass spectroscopy (UHPLC-MS) analysis was performed to identify the components of QDSJ and their targets. To determine the relationships between the putative targets of QDSJ and the differential genes of NF2-associated VS, the drug-disease crossover genes were screened using the UHPLC-MS data combined with our previous gene expression profiling data. The differentially expressed genes were imported into the STRING database to generate a PPI network. Differentially expressed gene targets and pathways were identified using GO and KEGG pathway enrichment analyses. The in vitro and in vivo drug efficacy of QDSJ decoction was tested using a patient-derived schwannoma cell line and a patient-derived xenograft mouse model, respectively. H&E staining, immunochemistry, and immunofluorescence staining were used to evaluate the cell proliferation and tumor vessels.Results: A total of 133 compounds were identified in QDSJ decoction using UHPLC-MS analysis. Network pharmacology showed that the regulation of necroptosis, apoptosis, cell cycle, angiogenesis, adherens junction, and neuroactive ligand-receptor interaction could be associated with the efficacy of QDSJ in treating NF2-associated VS. Treatment with QDSJ induced necrotic cell death and apoptosis of schwannoma cells in vitro and suppressed the tumor growth in vivo. Histopathological analysis revealed areas of cell necrosis and enlarged tumor blood vessels in the QDSJ-treated tumors. The numbers of cells positive for Cyclin D1 and Ki-67 were significantly reduced in QDSJ-treated tumors compared to control tumors. Immunofluorescence staining of CD31 and αSMA showed a decreased number and density of tumor vessels and normalized vessel structure in QDSJ-treated tumors.Conclusion: Our study demonstrates that QDSJ decoction shows significant antitumor activity against NF2-associated schwannoma and is a possible candidate for future clinical trials.

Mobile microrobots are of great scientific significance. However, external actuation and control methods are still challenging to conduct. We present a single carbon nanocoil (CNC) microrobot induced by an NIR laser beam, capable of light-driven locomotion and photothermal actuation. This research demonstrates that CNC-based microrobots roll away from the focal spot when the laser beam is focused near the CNC. The maximum translational distance of a CNC microrobot increases with an increase in laser power, and the direction of motion is guided by controlling the focusing position of NIR. CNC-based microrobots can load and transport multiple cells under NIR light irradiation, resulting from the temperature gradient generated by photothermal conversion, which causes thermophoresis. The hydrophobic surface and unique helical structure of CNCs are beneficial to the underwater drag reduction in CNC microrobots' motion and the adhesion of cells on CNC microrobots. Therefore, CNC microrobots, as cell vectors driven by a laser beam, may find applications in a wide range of biomedical applications. In addition, the rotation of a CNC powered by a laser beam provides promising prospects for the future of nanomechanical devices using a carbon nanocoil as a micro/nanomotor. [ABSTRACT FROM AUTHOR]

The trend of DC development in the medium voltage AC distribution network is obvious. However, due to the constraints of reliability, cost, and power quality, not every AC distribution network is suitable for DC transformation. As for the AC distribution network suitable for DC transformation, it is necessary to solve the problems of multivariable constraint solutions and the demand for sorting and optimizing multi-schemes in DC transformation. Therefore, this study proposes a comprehensive decision-making method for the DC transformation object of the medium voltage AC distribution network. Firstly, a comprehensive evaluation index system for DC transformation is established from four aspects: improving power supply reliability, technical requirements, social benefits, and economic benefits. Among them, the reliability of power supply mainly examines the completion degree of the target. In terms of the technical requirements of DC transformation, it is necessary to consider the constraints of AC transformation and the driving force of DC transformation. As for the social benefits, it reflects the indirect demand for DC transformation, which reflects social development. In terms of economic benefits, it pays attention to the transformation cost and input–output ratio. Then, the combined optimization model is used to solve the index’s comprehensive weight based on the subjective and objective weight model. Moreover, the comprehensive evaluation value of the transformation object is determined by the double-base point method. The scheme optimization model is used to determine the final transformation scheme to guide the power grid enterprises to prioritize the DC transformation projects. Finally, several medium-voltage distribution networks in Guangzhou, Guangdong province, China, are taken as examples to verify the effectiveness of the proposed method.

Dielectric elastomer generators (DEGs) provide a new solution for vibrational energy harvesting. Currently, a type of impact-based DEGs, which can harvest energy from ambient vibrations, has been proposed and studied through simulations. However, the energy conversion mechanism and the performance evaluation approach of such impact-based DEGs have not been fully studied yet, thus limiting the reliability of the research on the system design/optimization and performance evaluation. In this paper, a single-sided impact (SSI) model is proposed to reveal the impact-based energy conversion mechanism. Based on this model, a complete four-stage impact process is analyzed to reveal the energy conversion mechanism, and the electrical outputs and energy conversion efficiency are derived as the energy harvesting performance evaluation indexes. To use the developed analytical model to predict the system electrical response accurately, some important parameters including the coefficient of restitution (COR) and largest deflection of the membrane at impacts were obtained experimentally, and the system output voltages at impacts were measured to verify the theoretical approaches in calculating the system electrical outputs and studying the parameters' influences. Furthermore, the influences of the pre-stretched ratio, impact velocity, and input voltage on the system energy harvesting performance are studied through simulations. The research results can provide guidelines to improve the energy harvesting performance of the impact-based DEGs in real applications.