Radiotherapy in Preclinical Models of Brain Metastases: A Review and Recommendations for Future Studies.

Brain metastases (BMs) frequently occur in primary tumors such as lung cancer, breast cancer, and melanoma, and are associated with notably short natural survival. In addition to surgical interventions, chemotherapy, targeted therapy, and immunotherapy, radiotherapy (RT) is a crucial treatment for BM and encompasses whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS). Validating the efficacy and safety of treatment regimens through preclinical models is imperative for successful translation to clinical application. This not only advances fundamental research but also forms the theoretical foundation for clinical study. This review, grounded in animal models of brain metastases (AM-BM), explores the theoretical underpinnings and practical applications of radiotherapy in combination with chemotherapy, targeted therapy, immunotherapy, and emerging technologies such as nanomaterials and oxygen-containing microbubbles. Initially, we provided a concise overview of the establishment of AM-BMs. Subsequently, we summarize key RT parameters (RT mode, dose, fraction, dose rate) and their corresponding effects in AM-BMs. Finally, we present a comprehensive analysis of the current research status and future directions for combination therapy based on RT. In summary, there is presently no standardized regimen for AM-BM treatment involving RT. Further research is essential to deepen our understanding of the relationships between various parameters and their respective effects.

CTGF regulates mineralization in human mature chondrocyte by controlling Pit-1 and modulating ANK via the BMP/Smad signalling.

OBJECTIVE: Connective tissue growth factor (CTGF) exhibits potent proliferative, differentiated, and mineralizing effects, and is believed to be contribute to cartilage mineralization in Osteoarthritis (OA). However, the underlying mechanism of chondrocyte mineralization induced by CTGF remains obscure. As a key regulator of mineral responses, type III phosphate transporter 1 (Pit-1) has been associated with the pathogenesis of articular mineralization. Therefore, the primary objective of this study was to investigate whether CTGF influences the development of mature chondrocyte mineralization and the underlying mechanisms governing such mineralization. METHODS: The effect of Connective tissue growth factor (CTGF) on human C-28/I2 chondrocytes were investigated. The chondrocytes were treated with CTGF or related inhibitors, and transfected with Overexpression and siRNA transfection of Type III Phosphate Transporter 1(Pit-1). Subsequently, the cells were subjected to Alizarin red S staining, PiPer Phosphate Assay Kit, Alkaline Phosphatase Diethanolamine Activity Kit, ELISA, RT-PCR or Western blot analysis. RESULTS: Stimulation with Connective tissue growth factor (CTGF) significantly upregulated the expression of the Type III Phosphate Transporter 1(Pit-1) and mineralization levels in chondrocytes through activation of α5ß1 integrin and BMP/Samd1/5/8 signaling pathways. Furthermore, treatment with overexpressed Pit-1 markedly increased the expression of Multipass Transmembrane Ankylosis (ANK) transporter in the cells. The inhibitory effect of CTGF receptor blockade using α5ß1 Integrin blocking antibody was demonstrated by significantly suppressed the expression of Pit-1 and ANK transporter, as well as chondrocyte mineralization. CONCLUSIONS: Our data indicate that Connective tissue growth factor (CTGF) plays a critical role inchondrocyte mineralization, which is dependent on the expression of the Type III Phosphate Transporter 1(Pit-1) and Multipass Transmembrane Ankylosis (ANK) transporter. Consequently, inhibition of CTGF activity may represent a novel therapeutic approach for the management of Osteoarthritis (OA).

Naringin inhibits P2X4 receptor expression on satellite glial cells in the neonatal rat dorsal root ganglion.

Naringin inhibits inflammation and oxidative stress, the P2 purinoreceptor X4 receptor (P2X4R) is associated with glial cell activation and inflammation, the purpose of this study is to investigate the effects of naringin on P2X4 receptor expression on satellite glial cells (SGCs) and its possible mechanisms. ATP promoted the SGC activation and upregulated P2X4R expression; naringin inhibited SGC activation, decreased expression of P2X4R, P38 MAPK/ERK, and NF-κB, and reduced levels of Ca2+, TNF-α, and IL-1ß in SGCs in an ATP-containing environment. These findings suggest that naringin attenuates the ATP-induced SGC activation and reduces P2X4R expression via the Ca2+-P38 MAPK/ERK-NF-κB pathway.

Antifungal Peptide P852 Effectively Controls Fusarium oxysporum, a Wilt-Causing Fungus, by Affecting the Glucose Metabolism and Amino Acid Metabolism as well as Damaging Mitochondrial Function.

Fusarium oxysporum causes wilt disease, which causes huge economic losses to a wide range of agricultural cash crops. Antifungal peptide P852 is an effective biocide. However, the mechanism of direct inhibition of pathogenic fungus needs to be explored. The proteomics and transcriptomics results showed that P852 mainly affected intracellular pathways such as glucose metabolism, amino acid metabolism, and oxidoreductase activity in F. oxysporum. P852 disrupts the intracellular oxidative equilibrium in F. oxysporum, and transmission electron microscopy observed mitochondrial swelling, disruption of membrane structure, and leakage of contents. Decreased mitochondrial membrane potential, mitochondrial cytochrome c leakage, and reduced ATP production were also detected. These results suggest that P852 is able to simultaneously inhibit intracellular metabolism and disrupt the mitochondrial function of F. oxysporum, exerting its inhibitory effects in multiple pathways together. The present study provides some insights into the multitargeted mechanism of fungus inhibition of antifungal lipopeptide substances produced by Bacillus spp.

First Report of Fungal Pathogens Causing Leaf Spot on Sorghum-Sudangrass Hybrids and Their Interactions with Plants.

The sorghum-sudangrass hybrid is the main high-quality forage grass in Southwest China, but, in recent years, it has suffered from leaf spot disease, with a prevalence of 88% in Bazhong, Sichuan, China, seriously affecting yield and quality. The causal agents were obtained from symptomatic leaves by tissue isolation and verified by pathogenicity assays. A combination of morphological characterization and sequence analysis revealed that strains SCBZSL1, SCBZSX5, and SCBZSW6 were Nigrospora sphaerica, Colletotrichum boninense, and Didymella corylicola, respectively, and the latter two were the first instance to be reported on sorghum-sudangrass hybrids in the world. SCBZSX5 significantly affected the growth of the plants, which can reduce plant height by 25%. The biological characteristics of SCBZSX5 were found to be less sensitive to the change in light and pH, and its most suitable culture medium was Potato Dextrose Agar (PDA), with the optimal temperature of 25 °C and lethal temperature of 35 °C. To clarify the interactions between the pathogen SCBZSX5 and plants, metabolomics analyses revealed that 211 differential metabolites were mainly enriched in amino acid metabolism and flavonoid metabolism. C. boninense disrupted the osmotic balance of the plant by decreasing the content of acetyl proline and caffeic acid in the plant, resulting in disease occurrence, whereas the sorghum-sudangrass hybrids improved tolerance and antioxidant properties through the accumulation of tyrosine, tryptophan, glutamic acid, leucine, glycitein, naringenin, and apigetrin to resist the damage caused by C. boninense. This study revealed the mutualistic relationship between sorghum-sudangrass hybrids and C. boninense, which provided a reference for the control of the disease.

Stable antiferromagnetic property and tunable electronic structure of two-dimensional MnPX3(X = S and Se) from pristine structure to Janus phase.

Transition-metal phosphorus trichalcogenides have been considered as very promising two-dimensional (2D) magnetic candidates up-to-date. We performed a systematical first-principles study on the electronic structures and magnetic properties of pristine MnPX3(X = S and Se) and Janus Mn2P2S3Se3monolayers. All monolayers behave as a direct-band-gap semiconductor in antiferromagnetic ground state which is caused by strong direct and indirect exchange interactions. It is found that the electronic structures and magnetic properties can be manipulated by Janus phase. The calculated band gap is 2.44 eV, 1.80 eV and 1.86 eV for MnPS3, MnPSe3and Mn2P2S3Se3with a valley polarization with consideration of spin-orbital coupling (SOC), respectively. In particular, significant energy-splittings emerge in the SOC-band structures of Janus Mn2P2S3Se3due to its broken-inversion-symmetry. Estimated by Monte Carlo simulations, the Néel temperature is 96 K, 71 K and 79 K based on Ising model while halved down to 41 K, 33 K and 36 K on the basis ofXYmodel for MnPS3, MnPSe3and Mn2P2S3Se3, respectively, indicating theXYmodel should be more reliable to describe the spin dynamics. Our research offers an insight into the magnetic mechanism and paves a feasible path to modulate the magnetism for 2D magnets in realistic applications on spintronics.

High-power tapered two-section distributed feedback laser based on a chirped sampled grating.

We propose and theoretically study a two-section high-power distributed feedback (DFB) laser with three equivalent phase shifts (3EPSs). A tapered waveguide with a chirped sampled grating is introduced to amplify the output power and keep a stable single-mode operation. The simulation exhibits the maximum output power and side mode suppression ratio of a 1200 µm length two-section DFB laser as high as 306.5 mW and 40 dB, respectively. Compared with traditional DFB lasers, the proposed laser has a higher output power, which may benefit wavelength division multiplexing transmission systems, gas sensors, and large-scale silicon photonics.

Interfacial molecular regulation of TiO2 for enhanced and stable cocatalyst-free photocatalytic hydrogen production.

On the basis of the inherent property limitations of commercial P25-TiO2, many surface interface modification methods have attracted substantial attention for further improving the photocatalytic properties. However, current strategies for designing and modifying efficient photocatalysts (which exhibit complicated manufacturing processes and harsh conditions) are not efficient for production that is low cost, is nontoxic, and exhibits good stability; and therefore restrict practical applications. Herein, a facile and reliable method is reported for in situ amine-containing silane coupling agent functionalization of commercial P25-TiO2 by covalent surface modification for constructing a highly efficient photocatalyst. As a consequence, a high efficiency of H2 evolution was achieved for TiO2-SDA with 0.95 mmol h-1 g-1 (AQE ∼45.6 % at 365 nm) under solar light irradiation without a co-catalyst. The amination modification broadens the light absorption range of the photocatalyst, inhibits the binding of photogenerated carriers, and improves the photocatalytic efficiency; which was verified by photochemical properties and DFT theoretical calculations. This covalent modification method ensures the stability of the photocatalytic reaction. This work provides an approach for molecularly modified photocatalysts to improve photocatalytic performance by covalently modifying small molecules containing amine groups on the photocatalyst surface.

A Multi-Task Multi-Stage Transitional Training Framework for Neural Chat Translation.

Neural chat translation (NCT) aims to translate a cross-lingual chat between speakers of different languages. Existing context-aware NMT models cannot achieve satisfactory performances due to the following inherent problems: 1) limited resources of annotated bilingual dialogues; 2) the neglect of modelling conversational properties; 3) training discrepancy between different stages. To address these issues, in this paper, we propose a multi-task multi-stage transitional (MMT) training framework, where an NCT model is trained using the bilingual chat translation dataset and additional monolingual dialogues. We elaborately design two auxiliary tasks, namely utterance discrimination and speaker discrimination, to introduce the modelling of dialogue coherence and speaker characteristic into the NCT model. The training process consists of three stages: 1) sentence-level pre-training on large-scale parallel corpus; 2) intermediate training with auxiliary tasks using additional monolingual dialogues; 3) context-aware fine-tuning with gradual transition. Particularly, the second stage serves as an intermediate phase that alleviates the training discrepancy between the pre-training and fine-tuning stages. Moreover, to make the stage transition smoother, we train the NCT model using a gradual transition strategy, i.e., gradually transiting from using monolingual to bilingual dialogues. Extensive experiments on two language pairs demonstrate the effectiveness and superiority of our proposed training framework.

Design of two-dimensional sampled Bragg grating for a curved waveguide.

Due to the ability of changing light propagation path direction, curved waveguide Bragg grating (CWG) plays an important role in photonic integrated circuits. In this paper, we proposed a cascaded sampled Bragg grating on tilted waveguide (CSBG-TW) structure to equivalently realize CWG. As an example, by designing two-dimensional (2D) sampled gratings, the direction of +1st sub-grating vector in CSBG-TW can be changed. Then if a curved waveguide is divided into several sections of tilted waveguide, we can keep the grating direction being always parallel to the longitudinal direction of each section of tilted waveguide, while the basic grating is uniform. Hence, the required CWG can be equivalently realized, and the light responses such as reflection Bragg wavelength shift and backward mode convert caused by the tilted grating in curved waveguide can be compensated for. The results show that the sampling structures of CSBG-TW is micro-scale and the difference between reflection intensity between the CSBG-TW with four section tilted waveguide and CWG as design target is less than 0.1 dB. Compared with CWG, the CSBG-TW allows convenient holographic exposure and the wavelength can be accurately controlled. Therefore, the CSBG-TW can be used in various photonic integrated devices that require changing propagation paths.

Antimicrobial Peptides Mediate Apoptosis by Changing Mitochondrial Membrane Permeability.

Changes in mitochondrial membrane permeability are closely associated with mitochondria-mediated apoptosis. Antimicrobial peptides (AMPs), which have been found to enter cells to exert physiological effects, cause damage to the mitochondria. This paper reviews the molecular mechanisms of AMP-mediated apoptosis by changing the permeability of the mitochondrial membrane through three pathways: the outer mitochondrial membrane (OMM), inner mitochondrial membrane (IMM), and mitochondrial permeability transition pore (MPTP). The roles of AMPs in inducing changes in membrane permeability and apoptosis are also discussed. Combined with recent research results, the possible application prospects of AMPs are proposed to provide a theoretical reference for the development of AMPs as therapeutic agents for human diseases.

Silencing P2X7R Alleviates Diabetic Neuropathic Pain Involving TRPV1 via PKCε/P38MAPK/NF-κB Signaling Pathway in Rats.

Transient receptor potential vanillic acid 1 (TRPV1) is an ion channel activated by heat and inflammatory factors involved in the development of various types of pain. The P2X7 receptor is in the P2X family and is associated with pain mediated by satellite glial cells. There might be some connection between the P2X7 receptor and TRPV1 in neuropathic pain in diabetic rats. A type 2 diabetic neuropathic pain rat model was induced using high glucose and high-fat diet for 4 weeks and low-dose streptozocin (35 mg/kg) intraperitoneal injection to destroy islet B cells. Male Sprague Dawley rats were administrated by intrathecal injection of P2X7 shRNA and p38 inhibitor, and we recorded abnormal mechanical and thermal pain and nociceptive hyperalgesia. One week later, the dorsal root ganglia from the L4-L6 segment of the spinal cord were harvested for subsequent experiments. We measured pro-inflammatory cytokines, examined the relationship between TRPV1 on neurons and P2X7 receptor on satellite glial cells by measuring protein and transcription levels of P2X7 receptor and TRPV1, and measured protein expression in the PKCε/P38 MAPK/NF-κB signaling pathway after intrathecal injection. P2X7 shRNA and p38 inhibitor relieved hyperalgesia in diabetic neuropathic pain rats and modulated inflammatory factors in vivo. P2X7 shRNA and P38 inhibitors significantly reduced TRPV1 expression by downregulating the PKCε/P38 MAPK/NF-κB signaling pathway and inflammatory factors in dorsal root ganglia. Intrathecal injection of P2X7 shRNA alleviates nociceptive reactions in rats with diabetic neuropathic pain involving TRPV1 via PKCε/P38 MAPK/NF-κB signaling pathway.

Investigations on structural, electronic and optical properties of ZnO in two-dimensional configurations by first-principles calculations.

The electronic structures and optical properties of two-dimensional (2D) ZnO monolayers in a series of configurations were systematically investigated by first-principles calculations with HubbardUevaluated by the linear response approach. Three types of 2D ZnO monolayers, as planer hexagonal-honeycomb (Plan), double-layer honeycomb (Dlhc), and corrugated tetragonal (Tile) structures, show a mechanical and dynamical stability, while the Dlhc-ZnO is the most energetically stable configuration and Plan-ZnO is the second one. Each 2D ZnO monolayer behaves as a semiconductor with that Plan-, Dlhc-ZnO have a direct band gap of 1.81 eV and 1.85 eV at theΓpoint, respectively, while Tile-ZnO has an indirect band gap of 2.03 eV. Interestingly, the 2D ZnO monolayers all show a typical near-free-electron character for the bottom conduction band with a small effective mass, leading to a tremendous optical absorption in the whole visible and ultraviolet window, and this origination was further confirmed by the transition dipole moment. Our investigations suggest a potential candidate in the photoelectric field and provide a theoretical guidance for the exploration of wide-band-gap 2D semiconductors.

Fast Explainable Recommendation Model by Combining Fine-Grained Sentiment in Review Data.

With the rapid development of e-commerce, recommendation system has become one of the main tools that assists users in decision-making, enhances user's experience, and creates economic value. Since it is difficult to explain the implicit features generated by matrix factorization, explainable recommendation system has attracted more and more attention recently. In this paper, we propose an explainable fast recommendation model by combining fine-grained sentiment in review data (FSER, (Fast) Fine-grained Sentiment for Explainable Recommendation). We innovatively construct user-rating matrix, user-aspect sentiment matrix, and item aspect-descriptive word frequency matrix from the review-based data. And the three matrices are reconstructed by matrix factorization method. The reconstructed results of user-aspect sentiment matrix and item aspect-descriptive word frequency matrix can provide explanation for the final recommendation results. Experiments in the Yelp and Public Comment datasets demonstrate that, compared with several classical models, the proposed FSER model is in the optimal recommendation accuracy range and has lower sparseness and higher training efficiency than tensor models or neural network models; furthermore, it can generate explanatory texts and diagrams that have high interpretation quality.

A Novel Progress: Glial Cells and Inflammatory Pain.

Inflammatory pain is the perception of noxious stimuli that occurs during inflammation or an immune response. Glial cells are widespread in the central and peripheral nervous systems, supporting and guiding the migration of neurons, participating in the immune response, forming the myelin sheath and blood-brain barrier, and maintaining the concentration of potassium ions outside nerve cells. Recent studies have shown that glial cells have a significant connection with the production and development of inflammatory pain. This article reviews the relationship, mechanisms, therapeutic targets between five types of glial cells and inflammatory pain, and the medicine composition that can effectively inhibit inflammatory pain. It expands the study on the mechanism of glial cells regulating pain and provides new ideas for the therapy of inflammatory pain.

Environmental regulation, foreign direct investment, and export sophistication of China: an empirical study based on dynamic system GMM and threshold model.

The mechanism of how environmental regulations (ERs) affect export sophistication (ES) is complex, and for many years, it has been a hot topic for researchers. However, few previous studies have focused on whether ERs can promote the upgrading of China's ES through foreign direct investment (FDI). To address this research gap, in this study, ERs, FDI, and ES were incorporated into one novel research framework. Based on the provincial panel data of China for the period ranging from 2004 to 2016, the system generalized method of moments (SYS-GMM) was utilized to analyze the mutual relationship between FDI, ERs, and ES. Then, the panel threshold model was employed to empirically investigate the upgrading of the ES that is determined by FDI under different-intensity ERs. The results were as follows: First, ERs lead the influx of foreign capital to China, as a "pollution shelter" of developed countries, but excessive ERs have negative effects on FDI, resulting in an inverted U-shaped relationship between ERs and FDI. Second, the upgrading of the ES was affected by FDI, with the trend following a U-shaped curve. Third, the ERs have significant direct effects on the upgrading of the ES in the form of a U-shaped relationship, which was determined by the combined "innovation compensation" and "cost offset" effects. Finally, the environmental regulations had indirect influences on the upgrading of the export sophistication through the linkage effect of FDI in the form of an N-shaped relationship. Based on the aforementioned achievements, some policy recommendations were proposed to promote the upgrading of the ES in the future.

Clinical effect of removable partial denture prepared by Saddle-Lock hidden-clasp.

OBJECTIVE: To study the method for preparing removable partial denture using Saddle-Lock hidden-clasp and evaluate its clinical effect. METHOD: Casting process was adopted for the preparation of the clasp, which was fixed at the points on the mesial and distal surfaces of the abutment tooth. The clinical records of 305 patients treated with such removable partial dentures were reviewed. RESULTS: Within a follow-up period of 6 years, 295 of the 305 patients retained good abutment condition and were satisfied with the denture that was capable of easy wearing and removing. CONCLUSIONS: Removable partial denture made by Saddle-lock hidden-clasp exhibits good performance in fixation and stability. As an innovation of traditional design of partial denture clasp, it is simple to prepare and well received by the patients with good clinical effect.

[Restoration of molar residual roots and crowns with multiple canals by unparalleled posts: an evaluation].

OBJECTIVE: To repair the residual roots and crowns of the molars with multi-canals using unparalleled posts and cores and ceramic crowns. METHODS: Unparalleled insertion of the posts and cores was adopted in the casting of the ceramic crown to repair the residual roots and crowns of the molars. RESULTS AND CONCLUSION: Unparalleled insertion of the posts increased the retention strength of the cores, which provided a solid foundation for the restoration of the molars with ceramic crowns, therefore yielding better clinical effect in repairing the molars.