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RAS mutations occur in approximately 30% of tumors worldwide and have a poor prognosis due to limited therapies. Covalent targeting of KRAS G12C has achieved significant success in recent years, but there is still a lack of efficient therapeutic approaches for tumors with non-G12C KRAS mutations. A highly promising approach is to target the MAPK pathway downstream of RAS, with a particular focus on RAF kinases. First-generation RAF inhibitors have been authorized to treat BRAF mutant tumors for over a decade. However, their use in RAS-mutated tumors is not recommended due to the paradoxical ERK activation mainly caused by RAF dimerization. To address the issue of RAF dimerization, type II RAF inhibitors have emerged as leading candidates. Recent clinical studies have shown the initial effectiveness of these agents against RAS mutant tumors. Promisingly, type II RAF inhibitors in combination with MEK or ERK inhibitors have demonstrated impressive efficacy in RAS mutant tumors. This review aims to clarify the importance of RAF dimerization in cellular signaling and resistance to treatment in tumors with RAS mutations, as well as recent progress in therapeutic approaches to address the problem of RAF dimerization in RAS mutant tumors.

Abstract A high-fat diet (HFD) may be linked to an increased colorectal cancer (CRC) risk. Stem cell proliferation and adipokine release under inflammatory and obese conditions are the main factors regulating CRC progression. Furthermore, alterations in intestinal flora have been linked to tumorigenesis and tumour progression. However, whether a HFD can promote CRC occurrence by altering intestinal flora remains unclear. The objective of this study was to identify bacterial strains enriched by a HFD and investigate the association and mechanism by which a HFD and bacterial enrichment promote CRC occurrence and development. In this study, the intestinal microbiota of mice was assessed using 16S rRNA and metagenomic sequencing. Serum metabolites of HFD-fed mice were assessed using tandem liquid chromatography-mass spectrometry. CRC cell lines and organoids were co-cultured with Coriobacteriaceae to evaluate the effect of these bacteria on the CPT1A-ERK signalling pathway. We found that Coriobacteriaceae were enriched in the colons of HFD-fed mice. An endogenous Coriobacteriaceae strain, designated as Cori.ST1911, was successfully isolated and cultured from the stools of HFD-fed mice, and the tumorigenic potential of Cori.ST1911 in CRC was validated in several CRC mouse models. Furthermore, Cori.ST1911 increased acylcarnitine levels by activating CPT1A, demonstrating the involvement of the CPT1A-ERK axis. We also found that the endogenous Lactobacillus strain La.mu730 can interfere with Cori.ST1911 colonisation and restore gut barrier function. In conclusion, we identified a novel endogenous intestinal Coriobacteriaceae, Cori.ST1911, which might lead to a new gut microbiota intervention strategy for the prevention and treatment of CRC.

Abstract The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence‐based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti‐angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)‐positive and deficient DNA mismatch repair (dMMR)/microsatellite instability‐high (MSI‐H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

ObjectiveProgrammed cell death protein-1 (PD-1) inhibitor-based therapy has demonstrated promising results in metastatic gastric cancer (MGC). However, the previous researches are mostly clinical trials and have reached various conclusions. Our objective is to investigate the efficacy of PD-1 inhibitor-based treatment as first-line therapy for MGC, utilizing real-world data from China, and further analyze predictive biomarkers for efficacy.MethodsThis retrospective study comprised 105 patients diagnosed with MGC who underwent various PD-1 inhibitor-based treatments as first-line therapy at West China Hospital of Sichuan University from January 2018 to December 2022. Patient characteristics, treatment regimens, and tumor responses were extracted. We also conducted univariate and multivariate analyses to assess the relationship between clinical features and treatment outcomes. Additionally, we evaluated the predictive efficacy of several commonly used biomarkers for PD-1 inhibitor treatments.ResultsOverall, after 28.0 months of follow-up among the 105 patients included in our study, the objective response rate (ORR) was 30.5%, and the disease control rate (DCR) was 89.5% post-treatment, with two individuals (1.9%) achieving complete response (CR). The median progression-free survival (mPFS) was 9.0 months, and the median overall survival (mOS) was 22.0 months. According to both univariate and multivariate analyses, favorable OS was associated with patients having Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–1. Additionally, normal baseline levels of carcinoembryonic antigen (CEA), as well as the combination of PD-1 inhibitors with chemotherapy and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive MGC, independently predicted longer PFS and OS. However, microsatellite instability/mismatch repair (MSI/MMR) status and Epstein-Barr virus (EBV) infection status were not significantly correlated with PFS or OS extension.ConclusionAs the first-line treatment, PD-1 inhibitors, either as monotherapy or in combination therapy, are promising to prolong survival for patients with metastatic gastric cancer. Additionally, baseline level of CEA is a potential predictive biomarker for identifying patients mostly responsive to PD-1 inhibitors.

In order to accurately measure the flight trajectory of the projectile in a long-distance target range, it is important to establish a vertical target measurement system with a two-line array camera at several positions along the range. In the present work, a calibration system using dual theodolites is proposed to calibrate the vertical target measurement system of a dual linear array camera at different positions along a long target range. The present study investigates the principle of intersection measurement in the vertical target measurement system with a double linear array camera and presents the projectile’s target coordinate measurement formula. The calibration method of the measurement system is developed based on an analysis of the parameters in the projectile coordinate measurement formula. The calibration method only requires calibration of the camera’s distortion coefficient, the optical axis angle, and the principal point, ensuring a simplified and expedited calibration process. After calibration, the vertical target measurement system with a 3 m × 3 m measurement area is simulated and analyzed, yielding an error distribution diagram and identifying the factors that influence the measurement accuracy of the projectile’s target coordinates.

Based on engineered cell/exosome technology and various skin-related animal models, exosomal microRNA (miRNA)-based therapies derived from natural exosomes have shown good therapeutic effects on nine skin diseases, including full-thickness skin defects, diabetic ulcers, skin burns, hypertrophic scars, psoriasis, systemic sclerosis, atopic dermatitis, skin aging, and hair loss. Comparative experimental research showed that the therapeutic effect of miRNA-overexpressing exosomes was better than that of their natural exosomes. Using a dual-luciferase reporter assay, the targets of all therapeutic miRNAs in skin cells have been screened and confirmed. For these nine types of skin diseases, a total of 11 animal models and 21 exosomal miRNA-based therapies have been developed. This review provides a detailed description of the animal models, miRNA therapies, disease evaluation indicators, and treatment results of exosomal miRNA therapies, with the aim of providing a reference and guidance for future clinical trials. There is currently no literature on the merits or drawbacks of miRNA therapies compared with standard treatments.

Photovoltaic power generation and photothermal power generation are two forms of solar power generation. The development cost of photovoltaic is relatively lower than photothermal, but a certain proportion of energy storage and distributed synchronous condensers are needed to ensure the safe and stable operation of the system. As a result the cost of photovoltaic power generation rises. Photothermal comes with heat storage and output friendliness, so currently there is still a great dispute about the technical route of photovoltaic and photothermal. This paper takes Haixi area of Qinghai province as an example. Firstly, based on the characteristics of solar irradiation resources and output in the same time and space, the power guarantee capabilities of photovoltaic+energy storage and photothermal is compared. Then this paper compares photovoltaic+energy storage+condenser with photothermal from the perspective of power grid security and stability support ability. Finally, this paper compares the economics of solar thermal and photovoltaic based on the forecast of their cost declining trend. Photothermal has both thermal storage and conventional generator functions, providing short circuit capacity, reactive power compensation and moment of inertia support for the system. The results show the economy of photothermal is basically equivalent to, or even better than photovoltaic+energy storage+condenser after the cost reduction in the case of technical equivalence.

Islet transplantation may be the most efficient therapeutic technique for patients with type 1 diabetes mellitus (T1DM). However, the clinical application of this method is faced with numerous limitations, including isolated islet apoptosis, recipient rejection, and graft vascular reconstruction. Mesenchymal stem cells (MSCs) possess anti-apoptotic, immunomodulatory, and angiogenic properties. Here, we review recent studies on co-culture and co-transplantation of islets with MSCs. We have summarized the methods of preparation of co-transplantation, especially the merits of co-culture, and the effects of co-transplantation. Accumulating experimental evidence shows that co-culture of islets with MSCs promotes islet survival, enhances islet secretory function, and prevascularizes islets through various pretransplant preparations. This review is expected to provide a reference for exploring the use of MSCs for clinical islet co-transplantation.

Aiming at the problem of complex internal structure and difficult monitoring of the distribution room, a new monitoring method for the distribution room based on a digital twin is studied. Firstly, a 3D model design method for the distribution room is proposed by combining visualization technology and 3D Max software to complete the modeling. The 3D laser technology is used to scan the entity to get the texture photos of the 3D laser points and the raw data, then a complete model is obtained by modeling the details, and finally, the texture photos are mapped with the model to get the final model. To enhance the model’s accuracy, the optimal minimum spanning tree model optimization method is proposed, and the power distribution room’s three-dimensional model design is now finished. On the basis of the feature extraction of the sensor data of the distribution room, the digital twin technology is used to realize the matching of the information model architecture from the real entity of the distribution room to the virtual model, digital conversion, correlation of the operating data features and real-time monitoring, and then the monitoring method of the distribution room based on the digital twin is obtained. The experimental analysis yields a 3D Max modeling time of 9.98s and a fineness of 90%, which is more suitable for the construction of complex 3D models of distribution rooms than the other two methods. The accuracy of digital twin wireless communication is kept at 98% or above, and the system operation is disturbed to a small extent. It shows that digital twin technology is suitable for monitoring the complex structure inside the distribution room.

With the development of multimedia, the flipped classroom is deeply loved by educators with its unique, flexible and efficient features, which meet the requirements of physical education reform from a multimedia perspective. In this paper, we first use a genetic algorithm to arrange the physical education course information in a real number coding way to form chromosomes and initial populations. Then the individual fitness F is determined, the outstanding parent individuals are selected, the chaotic crossover and chaotic mutation operations are performed, and the end conditions are judged. According to the calculation of the fitness function, this ensures the diversity of the population and also eliminates the conflicting course plan programs. Then, 83 students from two classes at Guizhou Normal University were used as experimental subjects to explore the effect of integrating flipped classroom teaching into physical education, and the volleyball skills of students in the experimental and control groups were tested in the form of teaching-examination separation. The results showed that there was a significant difference between the volleyball skill test results of students in the experimental and control groups t=2.071, p=0.042, less than 0.05, indicating that the volleyball skill level of the experimental group was better than that of the control group after experiencing 32 credit hours of volleyball teaching. This study promotes the reform of physical education teaching and is of great significance to the development of physical education.

Coal water slurry is an advanced and efficient coal utilization technology, prepare coal water slurry by gasification wastewater can realize the recycling of wastewater and improve the combustion or gasification efficiency of the slurry. Stabilizer is an important component to ensure fluidity and stability in industrial applications of coal water slurry, and the complex substances in wastewater for coal water slurry preparation have a great influence on the stabilizer. Therefore, in this paper, the influence of the major substances in gasification wastewater on the stabilizer is studied. Results show that (a) Ammonia nitrogen substances have adverse effects on stabilizers, because the ionized NH4+ in the solution will bond with the polar groups on the stabilizer, which will affect the stabilizer to lose its effectiveness and reduce the stability of the slurry. (b) Small organic molecules have little effect on stabilizers, this is because the binding strength and quantity of stabilizer to water molecules is much larger than that of organic matters such as phenolic substances. (c) Highvalent metal ions have a greater impact on stabilizers, the metal ions easily form gels or precipitates with the stabilizer, causing it to lose its effectiveness, and also have an electrostatic effect with the carboxyl group on the side chain of the stabilizer, which makes the stabilizer easy to aggregate together and lose the steric hindrance effect, finally cause the stability of the slurry reduced. The conclusion of the influence of substances in wastewater on stabilizer can provide a technical reference for the selection of suitable wastewater and stabilizer to prepare coal water slurry, then promoting the efficient use of energy.

Assembly of AgStBu and PhCOOH ligands with the assistance of soluble silver salt CH3COOAg/CF3SO3Ag in methanol, N, N-dimethylformamide (DMF) and dichloromethane solution, yielded two Ag20 cage isomers co-constructed by thiol and carboxylate/sulfonate ligands encapsulating a CO32– anion template, [(CO32–)@Ag20(StBu)10(PhCOO)4(CH3COO)4(DMF)4] (1) and [(CO32–)@Ag20(StBu)10(PhCOO)6(CF3SO3)2(DMF)4]·2DMF (2). The CO32– anion template was generated in situ by fixing atmospheric CO2. The precise structures of 1 and 2 were confirmed by single-crystal X-ray diffractometry (SCXRD). The thermal stability of compounds 1 and 2 was proved by thermogravimetric (TG) analysis, and their solution stability was characterized by nuclear magnetic resonance hydrogen spectroscopy (1H NMR). The absorption spectra, photocurrent responses, and luminescence of compounds 1 and 2 were investigated. In addition, the photodegradation of methylene blue (MB) and cyclic voltammetry characteristic curves of 1 and 2 were also studied.

Hot air drying (HD), vacuum freeze drying (FD), and pilot-scale freeze drying (PSFD) are extensively used to prepare peach slices. However, the aroma of hot air drying and vacuum freeze-drying is yet to be addressed. In this study, HS-SPME-GC–MS was used to characterize and quantify the volatile compounds in peach slices. First, 33, 36, and 46 volatile compounds were identified and quantified in the HD, FD, and PSFD groups, respectively. PSFD is preferable to HD and FD in terms of the volatile compound types, content, and aroma profiles. PSFD was selected for subsequent permeation and dehydration experiments. The key aroma compounds with an OAV ≥ 1 were found in the PSFD30 group. GC-O analysis was conducted on the PSFD30 group, leading to the preliminary identification of 2-methylbutanal, pentanal, hexanal, 2-hexenal, phenylacetaldehyde, ethyl acetate, 2-methylbutyl acetate, ethyl lactate, linalool, methyl heptenone, and γ-octalactone as distinctive aromas in dried peach slices.

Two silver alkynyl clusters, [(CO32−)@Ag20(tBuC≡C)14(PhCOO)3(CF3COO)] (1) and [(CO32−)@Ag20(tBuC≡C)14(PhCOO)(CF3COO)3] (2), composed of alkynyl Ag20 shell templated by a CO32− anion and supported by carboxyl ligands PhCOO− and CF3COO−, were synthesized successfully by conventional methods. Single crystal X–ray diffractometer (SCXRD) was used to determine the precise structures of 1 and 2. Although compounds 1 and 2 have the [(CO32−)@Ag20(tBuC≡C)14]4+ unit, the numbers of PhCOO− and CF3COO− ligands along with Ag···Ag interactions were affected by the steric hindrance of different carboxyl ligands and their concentrations. That is, compounds 1 and 2 separately contain the [(CO32−)@Ag20(tBuC≡C)14(PhCOO)(CF3COO)]2+ unit, which is involved in the ligand exchange between PhCOO− and CF3COO−. Powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA) were used to characterized compounds 1 and 2. The photocurrent responses, absorption spectra, as well as luminescence of 1 and 2 have been studied. In addition, the reduction of H2O2 for GCE–1 and GCE–2 showed good electrocatalytic activity, and catalysts 1 and 2 showed good photocatalytic degradation efficiency of methylene blue (MB). The results suggest that 1 and 2 can act as new electrocatalysts and photocatalysts to detect and decompose organic pollutants and hazardous materials in wastewater.

Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but there is a lack of experience in using this medicine in China. This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, including a review of related literature. After diagnosis, the patient was treated with GPB, followed by efficacy follow-up and pharmacological monitoring. The 6-year and 6-month-old male patient exhibited poor speech development, disobedience, temper tantrums, and aggressive behavior. Blood ammonia levels peaked at 327 μmol/L; urine organic acid analysis indicated elevated uracil levels; cranial MRI showed extensive abnormal signals in both cerebral hemispheres. Genetic testing revealed de novo mutation in the OTC gene (c.241T>C, p.S81P). Blood ammonia levels were approximately 43, 80, and 56 μmol/L at 1, 2, and 3 months after starting GPB treatment, respectively. During treatment, blood ammonia was well-controlled without drug-related adverse effects. The patient showed improvement in developmental delays, obedience, temperament, and absence of aggressive behavior.