Discovery of a Potent Antiosteoporotic Drug Molecular Scaffold Derived from Angelica sinensis and Its Bioinspired Total Synthesis.

Angelica sinensis, commonly known as Dong Quai in Europe and America and as Dang-gui in China, is a medicinal plant widely utilized for the prevention and treatment of osteoporosis. In this study, we report the discovery of a new category of phthalide from Angelica sinensis, namely falcarinphthalides A and B (1 and 2), which contains two fragments, (3R,8S)-falcarindiol (3) and (Z)-ligustilide (4). Falcarinphthalides A and B (1 and 2) represent two unprecedented carbon skeletons of phthalide in natural products, and their antiosteoporotic activities were evaluated. The structures of 1 and 2, including their absolute configurations, were established using extensive analysis of NMR spectra, chemical derivatization, and ECD/VCD calculations. Based on LC-HR-ESI-MS analysis and DFT calculations, a production mechanism for 1 and 2 involving enzyme-catalyzed Diels-Alder/retro-Diels-Alder reactions was proposed. Falcarinphthalide A (1), the most promising lead compound, exhibits potent in vitro antiosteoporotic activity by inhibiting NF-κB and c-Fos signaling-mediated osteoclastogenesis. Moreover, the bioinspired gram-scale total synthesis of 1, guided by intensive DFT study, has paved the way for further biological investigation. The discovery and gram-scale total synthesis of falcarinphthalide A (1) provide a compelling lead compound and a novel molecular scaffold for treating osteoporosis and other metabolic bone diseases.

The functional role of P2 purinergic receptors in the progression of gastric cancer.

Studies have confirmed that P2 purinergic receptors (P2X receptors and P2Y receptors) expressed in gastric cancer (GC) cells and GC tissues and correlates with their function. Endogenous nucleotides including ATP, ADP, UTP, and UDP, as P2 purinergic receptors activators, participate in P2 purinergic signal transduction pathway. These activated P2 purinergic receptors regulate the progression of GC mainly by mediating ion channels and intracellular signal cascades. It is worth noting that there is a difference in the expression of P2 purinergic receptors in GC, which may play different roles in the progression of GC as a tumor promoting factor or a tumor suppressor factor. Among them, P2 × 7, P2Y2 and P2Y6 receptors have certain clinical significance in patients with GC and may be used as biological molecular markers for the prediction of patients with GC. Therefore, in this paper, we discuss the functional role of nucleotide / P2 purinergic receptors signal axis in regulating the progression of GC and that these P2 purinergic receptors may be used as potential molecular targets for the prevention and treatment of GC.

Assessing Postoperative Motor Risk in Insular Low-Grade Gliomas Patients: The Potential Role of Presurgery MRI Corticospinal Tract Shape Measures.

BACKGROUND: Insular low-grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). PURPOSE: This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. STUDY TYPE: Retrospective. POPULATION: 42 patients (mean age 40.26 ± 10.21 years, 25 male) with insular LGGs. FIELD STRENGTH/SEQUENCE: Imaging was performed using 3.0 Tesla MRI, incorporating T1-weighted magnetization-prepared rapid gradient-echo, T2-weighted space dark-fluid with spin echo (SE), and diffusional kurtosis imaging (DKI) with gradient echo sequences, all integrated with echo planar imaging. ASSESSMENT: Shape metrics of the CST, including span, irregularity, radius, and irregularity of end regions (RER and IER, respectively), were compared between the affected and healthy hemispheres. Total end region radius (TRER) was determined as the sum of RER 1 and RER 2. The relationships between shape metrics and postoperative short-term (4 weeks) and long-term (>8 weeks) motor disturbances assessing by British Medical Research Council grading system, was analyzed using multivariable regression models. STATISTICAL TESTING: Paired t-tests compared CST metrics between hemispheres. Logistic regression identified associations between these metrics and motor disturbances. The models were developed using all available data and there was no independent validation dataset. Significance was set at P < 0.05. RESULTS: Short-term motor disturbance risk was significantly related to TRER (OR = 199.57). Long-term risk significantly correlated with IER 1 (OR = 59.84), confirmed as a significant marker with an AUC of 0.78. Furthermore, the CST on the affected side significantly had the greater irregularity, larger TRER and RER 1, and smaller span compared to the healthy side. DATA CONCLUSION: Preoperative evaluation of TRER and IER 1 metrics in the CST may serve as a tool for assessing the risk of postoperative motor complications in insular LGG patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Enhancing photocatalytic CO2 reduction with TiO2-based materials: Strategies, mechanisms, challenges, and perspectives.

The concentration of atmospheric CO2 has exceeded 400 ppm, surpassing its natural variability and raising concerns about uncontrollable shifts in the carbon cycle, leading to significant climate and environmental impacts. A promising method to balance carbon levels and mitigate atmospheric CO2 rise is through photocatalytic CO2 reduction. Titanium dioxide (TiO2), renowned for its affordability, stability, availability, and eco-friendliness, stands out as an exemplary catalyst in photocatalytic CO2 reduction. Various strategies have been proposed to modify TiO2 for photocatalytic CO2 reduction and improve catalytic activity and product selectivity. However, few studies have systematically summarized these strategies and analyzed their advantages, disadvantages, and current progress. Here, we comprehensively review recent advancements in TiO2 engineering, focusing on crystal engineering, interface design, and reactive site construction to enhance photocatalytic efficiency and product selectivity. We discuss how modifications in TiO2's optical characteristics, carrier migration, and active site design have led to varied and selective CO2 reduction products. These enhancements are thoroughly analyzed through experimental data and theoretical calculations. Additionally, we identify current challenges and suggest future research directions, emphasizing the role of TiO2-based materials in understanding photocatalytic CO2 reduction mechanisms and in designing effective catalysts. This review is expected to contribute to the global pursuit of carbon neutrality by providing foundational insights into the mechanisms of photocatalytic CO2 reduction with TiO2-based materials and guiding the development of efficient photocatalysts.

Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis.

OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.

Research Progress in Composite Materials for Photocatalytic Nitrogen Fixation.

Ammonia is an essential component of modern chemical products and the building unit of natural life molecules. The Haber-Bosch (H-B) process is mainly used in the ammonia synthesis process in the industry. In this process, nitrogen and hydrogen react to produce ammonia with metal catalysts under high temperatures and pressure. However, the H-B process consumes a lot of energy and simultaneously emits greenhouse gases. In the "double carbon" effect, to promote the combination of photocatalytic technology and artificial nitrogen fixation, the development of green synthetic reactions has been widely discussed. Using an inexhaustible supply of sunlight as a power source, researchers have used photocatalysts to reduce nitrogen to ammonia, which is energy-dense and easy to store and transport. This process completes the conversion from light energy to chemical energy. At the same time, it achieves zero carbon emissions, reducing energy consumption and environmental pollution in industrial ammonia synthesis from the source. The application of photocatalytic technology in the nitrogen cycle has become one of the research hotspots in the new energy field. This article provides a classification of and an introduction to nitrogen-fixing photocatalysts reported in recent years and prospects the future development trends in this field.

Phase noise suppression technique based on an improved reference interferometer scheme.

The reference interferometer scheme is an effective noise reduction method, but the optical path length difference (OPD) of the two interferometers must be strictly equal, which limits its application in practical environments. In this paper, an improved reference interferometer demodulation technique without strictly equal OPDs is proposed to suppress phase noise. By introducing a reference interferometer, the phase noise can be removed from the demodulation results. The combination of the differential self-multiplication algorithm and the fitted phase modulation depth calculation formula can evaluate the phase modulation depth of both interferometers in real time and simultaneously eliminate the nonlinear distortion caused by phase modulation depth drift and the effect of different OPDs on the reference interferometer scheme. The experimental results show that the technique can obtain highly stable and accurate demodulation results even if the OPDs of the two reference interferometers are different. The phase modulation depth calculation error is less than 0.57%, the maximum phase noise reduction is 15 dB, the average reduction is 9 dB, the minimum total harmonic distortion is 0.17%, and the SINAD reaches 35.90 dB.

A dense SERS substrate of the AgNPs@GO compound film for detecting homocysteine molecules.

This study focuses on the development of a highly sensitive surface-enhanced Raman scattering (SERS) sensor for detecting homocysteine (Hcy) molecules. The Hcy sensor was created by depositing silver nanoparticles (AgNPs) onto the surface of graphene oxide (GO) film to form a dense AgNPs@GO composite film. The AgNPs on the composite film interacted with sulfur atoms (S) of Hcy molecules to form Ag-S bonds, which boosted the chemisorption of Hcy molecules and enabled them to be specifically recognized. The SERS sensor exhibited a maximum enhancement factor of up to 1.1 × 104, with a reliable linear response range from 1 to 60 ng mL-1. The limit of detection (LOD) for Hcy molecules was as low as 1.1 × 10-9 M. Moreover, Hcy molecules were successfully distinguished in a mixed solution of γ-aminobutyric acid and Hcy molecules. In this study, a simple preparation process of SERS substrate and a novel detection method for Hcy molecules provided a new pathway for the rapid and effective detection of Hcy molecules in the food and biomedicine fields.

ATP ion channel P2X7 receptor as a regulatory molecule in the progression of colorectal cancer.

Large amounts of adenosine triphosphate (ATP), a natural P2X7 receptor activator, are released during colorectal carcinogenesis. P2X7 receptor activation regulates the activity of colorectal cancer (CRC) cells by mediating intracellular signal transduction. Importantly, the opening and activation of membrane pores of P2X7 receptor are different, which can play a dual role in promoting or inhibiting the progression of CRC. These can also depend on P2X7 receptor to regulate the activities of immune cells in the microenvironment, play the functions of immune regulation, immune escape and immune monitoring. While the use of P2X7 receptor antagonists (such as BBG, A438079 and A740003) can play a certain inhibitory pharmacological role on the activity of CRC. Therefore, in this paper, the mechanism and immunomodulatory function of P2X7 receptor involved in the progression of CRC were discussed. Moreover, we discussed the effect of antagonizing the activity of P2X7 receptor on the progression of CRC. So P2X7 receptor may be a new pharmacological molecular target for the treatment of CRC.

A preliminary study on corticospinal tract morphology in incidental and symptomatic insular low-grade glioma: implications for post-surgical motor outcomes.

OBJECTIVE: Our study aimed to investigate the shape and diffusion properties of the corticospinal tract (CST) in patients with insular incidental and symptomatic low-grade gliomas (LGGs), especially those in the incidental group, and evaluate their association with post-surgical motor function. METHODS: We performed automatic fiber tracking on 41 LGG patients, comparing macroscopic shape and microscopic diffusion properties of CST between ipsilateral and contralateral tracts in both incidental and symptomatic groups. A correlation analysis was conducted between properties of CST and post-operative motor strength grades. RESULTS: In the incidental group, no significant differences in mean diffusion properties were found between bilateral CST. While decreased anisotropy of the CST around the superior limiting sulcus and increased axial diffusivity of the CST near the midbrain level were noted, there was no significant correlation between pre-operative diffusion metrics and post-operative motor strength. In comparison, we found significant correlations between the elongation of the affected CST in the preoperative scans and post-operative motor strength in short-term and long-term follow ups (p = 1.810 × 10-4 and p = 9.560 × 10-4, respectively). CONCLUSIONS: We found a significant correlation between CST shape measures and post-operative motor function outcomes in patients with incidental insular LGGs. CST morphology shows promise as a potential prognostic factor for identifying functional deficits in this patient population.

Improved topography measurement with a high dynamic range using phase difference sensing technology.

Phase difference sensing technology (PDST) is employed for topography measurement, and two interference structures are proposed to achieve upper-limit adjustment and high resolution in the measurement range: a dual-wavelength system with a single Fabry-Perot (FP) cavity and a single-wavelength system with dual FP cavities. The phase difference between the two interference signals is determined by an elliptic fitting algorithm (EFA), and this change in phase difference is utilized to characterize the step height. Experimental results indicate that the measurement upper-limit can be adjusted to either 410 µm, 187 µm, or 108 µm by varying the wavelength difference in the dual-wavelength system, which gives a measurement error of 2.96%. In contrast, while offering a measurement resolution of 3.47 nm, the single-wavelength system exhibits a measurement error of 5.38%. The proposed method is capable of satisfying the measurement requirements during micro-electromechanical system (MEMS) processing with proficiency.

Chitosan biomaterial enhances the effect of OECs on the inhibition of sciatic nerve injury-induced neuropathic pain.

Neuropathic pain is a common symptom experienced by most clinical diseases at different levels, and its treatment has always been a clinical difficulty. Therefore, it is particularly important to explore new and effective treatment methods. The role of olfactory ensheathing cells (OECs) in nerve injury and pain is recognized by different studies. Our previous study found that transplantation of OECs alleviated hyperalgesia in rats. However, single-cell transplantation lacks medium adhesion and support, and exerts limited analgesic effect. Therefore, on the basis of the previous study, this study investigated the effect of pain relief by co-transplanting OECs with chitosan (CS) (a biological tissue engineering material, as OECs were transplanted into the host medium) to the injured sciatic nerve. The results showed that the pain threshold of sciatic nerve injury of rats was significantly reduced, and the expression level of P2×4 receptor in the spinal cord was significantly increased. While olfactory ensheathing cells combined with chitosan (OECs+CS) transplantation could significantly relieve pain, and the analgesic effect was stronger than that of OECs transplantation alone. OECs+CS transplantation promoted the formation of sciatic nerve remyelination, improved the changes of demyelination, and promoted the repair of sciatic nerve injury more significantly. In addition, the effect of OECs+CS to down-regulate the expression of P2×4 receptor was significantly stronger than that of OECs transplantation, and exerted a better analgesic effect. These data reveal that OECs+CS have a better analgesic effect in relieving neuropathic pain induced by sciatic nerve injury, and provide a new therapeutic strategy for pain treatment.

Potential role of Schwann cells in neuropathic pain.

Neuropathic pain (NPP) is a common syndrome associated with most forms of disease, which poses a serious threat to human health. NPP may persist even after the nociceptive stimulation is eliminated, and treatment is extremely challenging in such cases. Schwann cells (SCs) form the myelin sheaths around neuronal axons and play a crucial role in neural information transmission. SCs can secrete trophic factors to nourish and protect axons, and can further secrete pain-related factors to induce pain. SCs may be activated by peripheral nerve injury, triggering the transformation of myelinated and non-myelinated SCs into cell phenotypes that specifically promote repair. These differentiated SCs provide necessary signals and spatial clues for survival, axonal regeneration, and nerve regeneration of damaged neurons. They can further change the microenvironment around the regions of nerve injury, and relieve the pain by repairing the injured nerve. Herein, we provide a comprehensive overview of the biological characteristics of SCs, discuss the relationship between SCs and nerve injury, and explore the potential mechanism of SCs and the occurrence of NPP. Moreover, we summarize the feasible strategies of SCs in the treatment of NPP, and attempt to elucidate the deficiencies and defects of SCs in the treatment of NPP.

A Review on Cu2O-Based Composites in Photocatalysis: Synthesis, Modification, and Applications.

Photocatalysis technology has the advantages of being green, clean, and environmentally friendly, and has been widely used in CO2 reduction, hydrolytic hydrogen production, and the degradation of pollutants in water. Cu2O has the advantages of abundant reserves, a low cost, and environmental friendliness. Based on the narrow bandgap and strong visible light absorption ability of Cu2O, Cu2O-based composite materials show infinite development potential in photocatalysis. However, in practical large-scale applications, Cu2O-based composites still pose some urgent problems that need to be solved, such as the high composite rate of photogenerated carriers, and poor photocatalytic activity. This paper introduces a series of Cu2O-based composites, based on recent reports, including pure Cu2O and Cu2O hybrid materials. The modification strategies of photocatalysts, critical physical and chemical parameters of photocatalytic reactions, and the mechanism for the synergistic improvement of photocatalytic performance are investigated and explored. In addition, the application and photocatalytic performance of Cu2O-based photocatalysts in CO2 photoreduction, hydrogen production, and water pollution treatment are discussed and evaluated. Finally, the current challenges and development prospects are pointed out, to provide guidance in applying Cu2O-based catalysts in renewable energy utilization and environmental protection.

Improved ellipse-fitting phase demodulation technique to suppress the effect of light source intensity noise in interferometric system.

An improved ellipse-fitting algorithm phase demodulation (EFAPD) technique is proposed to reduce the influence of light source intensity noise on a system. In the original EFAPD, the sum of the intensities of coherent light (ICLS) is an important part of the interference signal noise, which makes the demodulation results suffer. The improved EFAPD corrects the ICLS and fringe contrast quantity of the interference signal by an ellipse-fitting algorithm, and then calculates the ICLS based on the structure of pull-cone 3 × 3 coupler, so as to remove it in the algorithm. Experimental results show that the noise of the improved EFAPD system is significantly reduced compared with that of the original EFAPD, with a maximum reduction of 35.57 dB. The improved EFAPD makes up for the deficiency of the original EFAPD in suppressing light source intensity noise, and promotes the application and popularization of EFAPD.

Advances in the Application of Bi-Based Compounds in Photocatalytic Reduction of CO2.

Bi-based semiconductor materials have special layered structure and appropriate band gap, which endow them with excellent visible light response ability and stable photochemical characteristics. As a new type of environment-friendly photocatalyst, they have received extensive attention in the fields of environmental remediation and energy crisis resolution and have become a research hotspot in recent years. However, there are still some urgent issues that need to be addressed in the practical large-scale application of Bi-based photocatalysts, such as the high recombination rate of photogenerated carriers, limited response range to visible spectra, poor photocatalytic activity, and weak reduction ability. In this paper, the reaction conditions and mechanism of photocatalytic reduction of CO2 and the typical characteristics of Bi-based semiconductor materials are introduced. On this basis, the research progress and application results of Bi-based photocatalysts in the field of reducing CO2, including vacancy introduction, morphological control, heterojunction construction, and co-catalyst loading, are emphasized. Finally, the future prospects of Bi-based photocatalysts are prospected, and it is pointed out that future research directions should be focused on improving the selectivity and stability of catalysts, deeply exploring reaction mechanisms, and meeting industrial production requirements.

G protein-coupled P2Y12 receptor is involved in the progression of neuropathic pain.

The pathological mechanism of neuropathic pain is complex, which seriously affects the physical and mental health of patients, and its treatment is also difficult. The role of G protein-coupled P2Y12 receptor in pain has been widely recognized and affirmed. After nerve injury, stimulated cells can release large amounts of nucleotides into the extracellular matrix, act on P2Y12 receptor. Activated P2Y12 receptor activates intracellular signal transduction and is involved in the development of pain. P2Y12 receptor activation can sensitize primary sensory neurons and receive sensory information. By transmitting the integrated information through the dorsal root of the spinal cord to the secondary neurons of the posterior horn of the spinal cord. The integrated information is then transmitted to the higher center through the ascending conduction tract to produce pain. Moreover, activation of P2Y12 receptor can mediate immune cells to release pro-inflammatory factors, increase damage to nerve cells, and aggravate pain. While inhibits the activation of P2Y12 receptor can effectively relieve pain. Therefore, in this article, we described P2Y12 receptor antagonists and their pharmacological properties. In addition, we explored the potential link between P2Y12 receptor and the nervous system, discussed the intrinsic link of P2Y12 receptor and neuropathic pain and as a potential pharmacological target for pain suppression.

S-Scheme 2D/2D Heterojunction of ZnTiO3 Nanosheets/Bi2WO6 Nanosheets with Enhanced Photoelectrocatalytic Activity for Phenol Wastewater under Visible Light.

The pollution of phenol wastewater is becoming worse. In this paper, a 2D/2D nanosheet-like ZnTiO3/Bi2WO6 S-Scheme heterojunction was synthesized for the first time through a two-step calcination method and a hydrothermal method. In order to improve the separation efficiency of photogenerated carriers, the S-Scheme heterojunction charge-transfer path was designed and constructed, the photoelectrocatalytic effect of the applied electric field was utilized, and the photoelectric coupling catalytic degradation performance was greatly enhanced. When the applied voltage was +0.5 V, the ZnTiO3/Bi2WO6 molar ratio of 1.5:1 had highest degradation rate under visible light: the degradation rate was 93%, and the kinetic rate was 3.6 times higher than that of pure Bi2WO6. Moreover, the stability of the composite photoelectrocatalyst was excellent: the photoelectrocatalytic degradation rate of the photoelectrocatalyst remained above 90% after five cycles. In addition, through electrochemical analysis, XRD, XPS, TEM, radical trapping experiments, and valence band spectroscopy, we found that the S-scheme heterojunction was constructed between the two semiconductors, which effectively retained the redox ability of the two semiconductors. This provides new insights for the construction of a two-component direct S-scheme heterojunction as well as a feasible new solution for the treatment of phenol wastewater pollution.

Research Progress on Propylene Preparation by Propane Dehydrogenation.

At present, the production of propylene falls short of the demand, and, as the global economy grows, the demand for propylene is anticipated to increase even further. As such, there is an urgent requirement to identify a novel method for producing propylene that is both practical and reliable. The primary approaches for preparing propylene are anaerobic and oxidative dehydrogenation, both of which present issues that are challenging to overcome. In contrast, chemical looping oxidative dehydrogenation circumvents the limitations of the aforementioned methods, and the performance of the oxygen carrier cycle in this method is superior and meets the criteria for industrialization. Consequently, there is considerable potential for the development of propylene production by means of chemical looping oxidative dehydrogenation. This paper provides a review of the catalysts and oxygen carriers employed in anaerobic dehydrogenation, oxidative dehydrogenation, and chemical looping oxidative dehydrogenation. Additionally, it outlines current directions and future opportunities for the advancement of oxygen carriers.