Smoking behavior associated upregulation of SERPINB12 promotes proliferation and metastasis via activating WNT signaling in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. METHODS: Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. RESULTS: In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of ß-catenin, which explained the molecular mechanism underlying tumor progression. CONCLUSIONS: In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target.

A novel approach has been developed to produce pure plant-based gel soy yogurt by combining soy proteins (7S/11S), high pressure homogenization, and glycation reaction.

This research sought to examine how the physicochemical characteristics of soy globulins and different processing techniques influence the gel properties of soy yogurt. The goal was to improve these gel properties and rectify any texture issues in soy yogurt, ultimately aiming to produce premium-quality plant-based soy yogurt. In this research study, the investigation focused on examining the impact of 7S/11S, homogenization pressure, and glycation modified with glucose on the gel properties of soy yogurt. A plant-based soy yogurt with superior gel and texture properties was successfully developed using a 7S/11S globulin-glucose conjugate at a 1:3 ratio and a homogenization pressure of 110 MPa. Compared to soy yogurt supplemented with pectin or gelatin, this yogurt demonstrated enhanced characteristics. These findings provide valuable insights into advancing plant protein gels and serve as a reference for cultivating new soybean varieties by soybean breeding experts.

The Relevance, Predictability, and Utility of Annexin A5 for Human Physiopathology.

As an important functional protein molecule in the human body, human annexin A5 (hAnxA5) is widely found in human cells and body fluids. hAnxA5, the smallest type of annexin, performs a variety of biological functions by reversibly and specifically binding phosphatidylserine (PS) in a calcium-dependent manner and plays an important role in many human physiological and pathological processes. The free state hAnxA5 exists in the form of monomers and usually forms a polymer in a specific self-assembly manner when exerting biological activity. This review systematically discusses the current knowledge and understanding of hAnxA5 from three perspectives: physiopathological relevance, diagnostic value, and therapeutic utility. hAnxA5 affects the occurrence and development of many physiopathological processes. Moreover, hAnxA5 can be used independently or in combination as a biomarker of physiopathological phenomena for the diagnosis of certain diseases. Importantly, based on the properties of hAnxA5, many novel drug candidates have been designed and prepared for application in actual medical practice. However, there are also some gaps and shortcomings in hAnxA5 research. This in-depth study will not only expand the understanding of structural and functional relationships but also promote the application of hAnxA5 in the field of biomedicine.

Improving the beam quality of single-grating spectrally combined fiber lasers with adaptive optics.

Spectral combination is promising for diffraction-limited beam quality and single aperture beams. Unfortunately, beamlet deviations, linewidth broadening, and thermal aberrations inevitably degrade the beam quality. Many high-power laser systems integrate adaptive optics systems to maintain beam qualities. However, owing to the nature of incoherent combination, there is no well-defined wavefront in the spectrally combined beam, and whether phase compensations can enhance beam quality has not been discussed yet. We present the feasibility of improving the beam quality of spectral combined fiber lasers by adaptive optics. Simulations indicate that common path aberrations can be effectively corrected by adaptive optics, while beam quality degraded by displacement deviations and linewidth broadening cannot be improved. Additionally, the combined beam could be directly used as the beacon light in the propagation tunnel. To our knowledge, this study is the first to demonstrate that adaptive optics can improve the beam quality of spectrally combined fiber lasers and enable a further step toward diffraction-limited beam quality.

An in vitro analog of learning that food is inedible in Aplysia: decreased responses to a transmitter signaling food after pairing with transmitters signaling failed swallowing.

An in vitro analog of learning that a food is inedible provided insight into mechanisms underlying the learning. Aplysia learn to stop responding to a food when they attempt but fail to swallow it. Pairing a cholinergic agonist with an NO donor or histamine in the Aplysia cerebral ganglion produced significant decreases in fictive feeding in response to the cholinergic agonist alone. Acetylcholine (ACh) is the transmitter of chemoreceptors sensing food touching the lips. Nitric oxide (NO) and histamine (HA) signal failed attempts to swallow food. Reduced responses to the cholinergic agonist after pairing with NO or HA indicate that learning partially arises via a decreased response to ACh in the cerebral ganglion.

Variable task switching in the feeding network of Aplysia is a function of differential command input.

Command systems integrate sensory information and then activate the interneurons and motor neurons that mediate behavior. Much research has established that the higher-order projection neurons that constitute these systems can play a key role in specifying the nature of the motor activity induced, or determining its parametric features. To a large extent, these insights have been obtained by contrasting activity induced by stimulating one neuron (or set of neurons) to activity induced by stimulating a different neuron (or set of neurons). The focus of our work differs. We study one type of motor program, ingestive feeding in the mollusc Aplysia californica, which can either be triggered when a single projection neuron (CBI-2) is repeatedly stimulated or can be triggered by projection neuron coactivation (e.g., activation of CBI-2 and CBI-3). We ask why this might be an advantageous arrangement. The cellular/molecular mechanisms that configure motor activity are different in the two situations because the released neurotransmitters differ. We focus on an important consequence of this arrangement, the fact that a persistent state can be induced with repeated CBI-2 stimulation that is not necessarily induced by CBI-2/3 coactivation. We show that this difference can have consequences for the ability of the system to switch from one type of activity to another.NEW & NOTEWORTHY We study a type of motor program that can be induced either by stimulating a higher-order projection neuron that induces a persistent state, or by coactivating projection neurons that configure activity but do not produce a state change. We show that when an activity is configured without a state change, it is possible to immediately return to an intermediate state that subsequently can be converted to any type of motor program.

Persistent modulatory actions and task switching in the feeding network of Aplysia.

The activity of multifunctional networks is configured by neuromodulators that exert persistent effects. This raises a question, does this impact the ability of a network to switch from one type of activity to another? We review studies that have addressed this question in the Aplysia feeding circuit. Task switching in this system occurs "asymmetrically." When there is a switch from egestion to ingestion neuromodulation impedes switching (creates a "negative bias"). When there is a switch from ingestion to egestion the biasing is "positive." Ingestion promotes subsequent egestion. We contrast mechanisms responsible for the two types of biasing and show that the observed asymmetry is a consequence of the fact that there is more than one set of egestive circuit parameters.

Design, Synthesis and Anti-Melanoma Activity of Novel Annexin V Derivative with ß3-Integrin Affinity.

Tumor tissues often exhibit unique integrin receptor presentation during development, such as high exposures of αvß3 and αIIbß3 integrins. These features are not present in normal tissues. The induction of selective thrombosis and infarction in the tumor-feeding vessels, as well as specific antagonism of αvß3 integrin on the surface of tumor endothelial cells, is a potential novel antitumor strategy. The Echistatin-Annexin V (EAV) fusion protein is a novel Annexin V (ANV) derivative that possesses a high degree of αvß3 and αIIbß3 integrin receptor recognition and binding characteristics while retaining the specific binding ability of the natural ANV molecule for phosphatidylserine (PS). We systematically investigated the biological effects of this novel molecule with superimposed functions on mouse melanoma. We found that EAV inhibited the viability and migration of B16F10 murine melanoma cells in a dose-dependent manner, exhibited good tumor suppressive effects in a xenograft mouse melanoma model, strongly induced tumor tissue necrosis in mice, and targeted the inhibition of angiogenesis in mouse melanoma tumor tissue. EAV exhibited stronger biological effects than natural ANV molecules in inhibiting melanoma in mice. The unique biological effects of EAV are based on its high ß3-type integrin receptor-specific recognition and binding ability, as well as its highly selective binding to PS molecules. Based on these findings, we propose that EAV-mediated tumor suppression is a novel and promising antitumor strategy that targets both PS- and integrin ß3-positive tumor neovascularization and the tumor cells themselves, thus providing a possible mechanism for the treatment of melanoma.

Molecular Characterization of Two Wamide Neuropeptide Signaling Systems in Mollusk Aplysia.

Neuropeptides with the C-terminal Wamide (Trp-NH2) are one of the last common ancestors of peptide families of eumetazoans and play various physiological roles. In this study, we sought to characterize the ancient Wamide peptides signaling systems in the marine mollusk Aplysia californica, i.e., APGWamide (APGWa) and myoinhibitory peptide (MIP)/Allatostatin B (AST-B) signaling systems. A common feature of protostome APGWa and MIP/AST-B peptides is the presence of a conserved Wamide motif in the C-terminus. Although orthologs of the APGWa and MIP signaling systems have been studied to various extents in annelids or other protostomes, no complete signaling systems have yet been characterized in mollusks. Here, through bioinformatics, molecular and cellular biology, we identified three receptors for APGWa, namely, APGWa-R1, APGWa-R2, and APGWa-R3. The EC50 values for APGWa-R1, APGWa-R2, and APGWa-R3 are 45, 2100, and 2600 nM, respectively. For the MIP signaling system, we predicted 13 forms of peptides, i.e., MIP1-13 that could be generated from the precursor identified in our study, with MIP5 (WKQMAVWa) having the largest number of copies (4 copies). Then, a complete MIP receptor (MIPR) was identified and the MIP1-13 peptides activated the MIPR in a dose-dependent manner, with EC50 values ranging from 40 to 3000 nM. Peptide analogs with alanine substitution experiments demonstrated that the Wamide motif at the C-terminus is necessary for receptor activity in both the APGWa and MIP systems. Moreover, cross-activity between the two signaling systems showed that MIP1, 4, 7, and 8 ligands could activate APGWa-R1 with a low potency (EC50 values: 2800-22,000 nM), which further supported that the APGWa and MIP signaling systems are somewhat related. In summary, our successful characterization of Aplysia APGWa and MIP signaling systems represents the first example in mollusks and provides an important basis for further functional studies in this and other protostome species. Moreover, this study may be useful for elucidating and clarifying the evolutionary relationship between the two Wamide signaling systems (i.e., APGWa and MIP systems) and their other extended neuropeptide signaling systems.

Identification of three elevenin receptors and roles of elevenin disulfide bond and residues in receptor activation in Aplysia californica.

Neuropeptides are ubiquitous intercellular signaling molecules in the CNS and play diverse roles in modulating physiological functions by acting on specific G-protein coupled receptors (GPCRs). Among them, the elevenin signaling system is now believed to be present primarily in protostomes. Although elevenin was first identified from the L11 neuron of the abdominal ganglion in mollusc Aplysia californica, no receptors have been described in Aplysia, nor in any other molluscs. Here, using two elevenin receptors in annelid Platynereis dumerilii, we found three putative elevenin GPCRs in Aplysia. We cloned the three receptors and tentatively named them apElevR1, apElevR2, and apElevR3. Using an inositol monophosphate (IP1) accumulation assay, we demonstrated that Aplysia elevenin with the disulfide bond activated the three putative receptors with low EC50 values (ranging from 1.2 to 25 nM), supporting that they are true receptors for elevenin. In contrast, elevenin without the disulfide bond could not activate the receptors, indicating that the disulfide bond is required for receptor activity. Using alanine substitution of individual conserved residues other than the two cysteines, we showed that these residues appear to be critical to receptor activity, and the three different receptors had different sensitivities to the single residue substitution. Finally, we examined the roles of those residues outside the disulfide bond ring by removing these residues and found that they also appeared to be important to receptor activity. Thus, our study provides an important basis for further study of the functions of elevenin and its receptors in Aplysia and other molluscs.

Characterization of an Aplysia vasotocin signaling system and actions of posttranslational modifications and individual residues of the ligand on receptor activity.

The vasopressin/oxytocin signaling system is present in both protostomes and deuterostomes and plays various physiological roles. Although there were reports for both vasopressin-like peptides and receptors in mollusc Lymnaea and Octopus, no precursor or receptors have been described in mollusc Aplysia. Here, through bioinformatics, molecular and cellular biology, we identified both the precursor and two receptors for Aplysia vasopressin-like peptide, which we named Aplysia vasotocin (apVT). The precursor provides evidence for the exact sequence of apVT, which is identical to conopressin G from cone snail venom, and contains 9 amino acids, with two cysteines at position 1 and 6, similar to nearly all vasopressin-like peptides. Through inositol monophosphate (IP1) accumulation assay, we demonstrated that two of the three putative receptors we cloned from Aplysia cDNA are true receptors for apVT. We named the two receptors as apVTR1 and apVTR2. We then determined the roles of post-translational modifications (PTMs) of apVT, i.e., the disulfide bond between two cysteines and the C-terminal amidation on receptor activity. Both the disulfide bond and amidation were critical for the activation of the two receptors. Cross-activity with conopressin S, annetocin from an annelid, and vertebrate oxytocin showed that although all three ligands can activate both receptors, the potency of these peptides differed depending on their residue variations from apVT. We, therefore, tested the roles of each residue through alanine substitution and found that each substitution could reduce the potency of the peptide analog, and substitution of the residues within the disulfide bond tended to have a larger impact on receptor activity than the substitution of those outside the bond. Moreover, the two receptors had different sensitivities to the PTMs and single residue substitutions. Thus, we have characterized the Aplysia vasotocin signaling system and showed how the PTMs and individual residues in the ligand contributed to receptor activity.

A Single Central Pattern Generator for the Control of a Locomotor Rolling Wave in Mollusc Aplysia.

Locomotion in mollusc Aplysia is implemented by a pedal rolling wave, a type of axial locomotion. Well-studied examples of axial locomotion (pedal waves in Drosophila larvae and body waves in leech, lamprey, and fish) are generated in a segmented nervous system via activation of multiple coupled central pattern generators (CPGs). Pedal waves in molluscs, however, are generated by a single pedal ganglion, and it is unknown whether there are single or multiple CPGs that generate rhythmic activity and phase shifts between different body parts. During locomotion in intact Aplysia, bursting activity in the parapedal commissural nerve (PPCN) was found to occur during tail contraction. A cluster of 20 to 30 P1 root neurons (P1Ns) on the ventral surface of the pedal ganglion, active during the pedal wave, were identified. Computational cluster analysis revealed that there are 2 phases to the motor program: phase I (centered around 168°) and phase II (centered around 357°). PPCN activity occurs during phase II. The majority of P1Ns are motoneurons. Coactive P1Ns tend to be electrically coupled. Two classes of pedal interneurons (PIs) were characterized. Class 1 (PI1 and PI2) is active during phase I. Their axons make a loop within the pedal ganglion and contribute to locomotor pattern generation. They are electrically coupled to P1Ns that fire during phase I. Class 2 (PI3) is active during phase II and innervates the contralateral pedal ganglion. PI3 may contribute to bilateral coordination. Overall, our findings support the idea that Aplysia pedal waves are generated by a single CPG.

Multiple exposures to heavy metals and changes in steroid hormones production in 4-year-old children.

BACKGROUND: Prenatal exposure to multiple heavy metals can interfere with early neurodevelopment, lead to changes in sex hormone concentrations in children, and affect female reproductive health. To date, the influence of prenatal exposure to heavy metals on the endocrine system of children in Chinese electronic waste (e-waste) recycling areas has not been elucidated. METHODS: Four weeks after delivery, 10 mL of human milk was collected for analysis of three heavy metals (lead (Pb), cadmium (Cd), and mercury (Hg)) via inductively coupled plasma mass spectrometry (ICP-MS). Four serum steroid hormones, including progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA), were analyzed in 4-year-old children (25 boys and 17 girls). A multiple linear regression (MLR) model was implemented to investigate the association between each individual metal and serum steroid hormone. The exposure-response relationships were explored by generalized additive models (GAMs). Additionally, a Bayesian kernel machine regression (BKMR) model was used to assess the effects of multiple heavy metal exposures on each steroid hormone. RESULTS: The MLR results show a significant positive association between a natural log unit increase in Hg and DHEA levels after adjusting for confounders (ß = 65.50, 95% confidence interval (CI) = 4.37, 126.62). According to the GAM, the univariate exposure-response relationship of Hg on DHEA was almost linear. However, this association was attenuated based on the multiple metal MLR and BKMR results after accounting for multiple heavy metal exposures. SIGNIFICANCE: Prenatal Hg exposure may affect sex hormones in children by affecting DHEA levels. IMPACT STATEMENT: Prenatal maternal exposure to Hg may have long-term effects on the next generation. Hence, regulatory measures to reduce Hg exposure and long-term monitoring of children's health in e-waste areas are needed.

The SMARCA4R1157W mutation facilitates chromatin remodeling and confers PRMT1/SMARCA4 inhibitors sensitivity in colorectal cancer.

Genomic studies have demonstrated a high frequency of genetic alterations in components of the SWI/SNF complex including the core subunit SMARCA4. However, the mechanisms of tumorigenesis driven by SMARCA4 mutations, particularly in colorectal cancer (CRC), remain largely unknown. In this study, we identified a specific, hotspot mutation in SMARCA4 (c. 3721C>T) which results in a conversion from arginine to tryptophan at residue 1157 (R1157W) in human CRC tissues associated with higher-grade tumors and controls CRC progression. Mechanistically, we found that the SMARCA4R1157W mutation facilitated its recruitment to PRMT1-mediated H4R3me2a (asymmetric dimethylation of Arg 3 in histone H4) and enhanced the ATPase activity of SWI/SNF complex to remodel chromatin in CRC cells. We further showed that the SMARCA4R1157W mutant reinforced the transcriptional expression of EGFR and TNS4 to promote the proliferation of CRC cells and patient-derived tumor organoids. Importantly, we demonstrated that SMARCA4R1157W CRC cells and mutant cell-derived xenografts were more sensitive to the combined inhibition of PRMT1 and SMARCA4 which act synergistically to suppress cell proliferation. Together, our findings show that SMARCA4-R1157W is a critical activating mutation, which accelerates CRC progression through facilitating chromatin recruitment and remodeling. Our results suggest a potential precision therapeutic strategy for the treatment of CRC patients carrying the SMARCA4R1157W mutation.

Integrin Targeting Enhances the Antimelanoma Effect of Annexin V in Mice.

Malignant melanoma, an increasingly common form of skin cancer, is a major threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. Targeted drug development is an effective strategy for the treatment of malignant melanoma. In this work, a new antimelanoma tumor peptide, the lebestatin-annexin V (designated LbtA5) fusion protein, was developed and synthesized by recombinant DNA techniques. As a control, annexin V (designated ANV) was also synthesized by the same method. The fusion protein combines annexin V, which specifically recognizes and binds phosphatidylserine, with the disintegrin lebestatin (lbt), a polypeptide that specifically recognizes and binds integrin α1ß1. LbtA5 was successfully prepared with good stability and high purity while retaining the dual biological activity of ANV and lbt. MTT assays demonstrated that both ANV and LbtA5 could reduce the viability of melanoma B16F10 cells, but the activity of the fusion protein LbtA5 was superior to that of ANV. The tumor volume growth was slowed in a mouse xenograft model treated with ANV and LbtA5, and the inhibitory effect of high concentrations of LbtA5 was significantly better than that of the same dose of ANV and was comparable to that of DTIC, a drug used clinically for melanoma treatment. The hematoxylin and eosin (H&E) staining test showed that ANV and LbtA5 had antitumor effects, but LbtA5 showed a stronger ability to induce melanoma necrosis in mice. Immunohistochemical experiments further showed that ANV and LbtA5 may inhibit tumor growth by inhibiting angiogenesis in tumor tissue. Fluorescence labeling experiments showed that the fusion of ANV with lbt enhanced the targeting of LbtA5 to mouse melanoma tumor tissue, and the amount of target protein in tumor tissue was significantly increased. In conclusion, effective coupling of the integrin α1ß1-specific recognition molecule lbt confers stronger biological antimelanoma effects of ANV, which may be achieved by the dual effects of effective inhibition of B16F10 melanoma cell viability and inhibition of tumor tissue angiogenesis. The present study describes a new potential strategy for the application of the promising recombinant fusion protein LbtA5 in the treatment of various cancers, including malignant melanoma.

Nickel Foam Coated by Ni Nanoparticle-Decorated 3D Nanocarbons as a Freestanding Host for High-Performance Lithium-Sulfur Batteries.

Nanocarbons (NCs) consisting of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) were coated on the surface of nickel foam (NF) via a chemical vapor deposition method. The CNFs formed conductive networks on NF, while the CNTs grew perpendicular to the surface of the CNFs, accompanied with the formation of Ni nanoparticles (Ni NPs) at the end of CNTs. The unique Ni-NCs-coated NF with a porous structure was applied as the three-dimensional (3D) current collector of lithium-sulfur (Li-S) batteries, which provided enough space to accommodate the electrode materials inside itself. Therefore, the 3D interconnected conductive framework of the coated NF collector merged in the electrode materials shortened the path of electron transport, and the generated Ni NPs could adsorb lithium polysulfides (LiPSs) and effectively accelerated the conversion kinetics of LiPSs as well, thereby suppressing the "shuttle effect". Moreover, the rigid framework of NF would also constrain the movement of the electrode compositions, which benefited the stability of the Li-S batteries. As a matter of fact, the Li-S battery based on the Ni-NCs-coated NF collector delivered an initial discharge capacity as high as 1472 mAh g-1 at 0.1C and outstanding high rate capability at 3C (802 mAh g-1). Additionally, low decay rates of 0.067 and 0.08% at 0.2C (300 cycles) and 0.5C (500 cycles) have been obtained, respectively. Overall, our prepared Ni-NCs-coated NF collector is promising for the application in high-performance Li-S batteries.

Effects of abdominal breathing exercises at different periods on the gastrointestinal symptoms in patients with gastroesophageal reflux disease / 中国实用护理杂志

Objective:To explore the effect of abdominal breathing exercises at different periods on the gastrointestinal symptoms, quality of life and proton pump inhibitor dependency in patients with gastroesophageal reflux disease (GERD). To provide reference for patients to choose the best time for abdominal breathing exercises.Methods:This was a prospective study. From March 2020 to December 2021, totally 108 GERD patients were collected in digestive outpatient clinic of Yibin Hospital of Chinese Medicine Hospital by convenient sampling method, they were randomly divided into pre meal group, 1 h postprandial group and 2 h postprandial group with 36 cases in each group. All patients in the three groups were given abdominal breathing training for 8 weeks on the basis of conventional acid suppression drug treatment and nursing. The training time of pre meal group, 1 h postprandial group and 2 h postprandial group was at 30 min before meal, 1 h after meal, 2 h after meal, respectively. Before and after 8 weeks of intervention, the difference of gastrointestinal symptoms and quality of life were assessed by Reflux Disease Ouestionnaire (RDQ) and the MOS 36 Item Short Form Health Survey (SF-36). Patients followed up for 12 weeks after drug withdrawal, the medication of proton pump inhibitor (PPI) between three groups were compared.Results:There was no significant difference in RDQ score and SF-36 score among the three groups before intervention ( P>0.05). After intervention, the symptom scores were (7.89 ± 1.86) in the 1 h postprandial group, lower than in the pre meal group (10.38 ± 1.81) and in the 2 h postprandial group (9.64 ± 1.65), the difference was statistically significant ( t = 5.83, 4.06, both P<0.01). The scores of each demensions in SF-36 were higher in the 1 h postprandial group compared to the pre meal group and the 2 h postprandial group, the differences were statistically significant ( t values were 2.04-3.70, all P<0.05). After followed up for 12 weeks, the PPI discontinuation rate was 71.43% in the 1 h postprandial group, higher than in the pre meal group 44.12% and in the 2 h postprandial group 45.45%, the differences were statistically significant ( χ2 = 5.28, 4.73, both P<0.05). Conclusions:Abdominal breathing exercises at 1 hour after meal can effectively alleviate gastrointestinal symptoms, promote quality of life and decrease the proton pump inhibitor dependency of GERD patients.

Prophylactic Vitamin C Attenuates Radiation-induced Lung Injury by Modulating Macrophage Polarization and Alveolar Epithelial Cell Apoptosis / 中国生物化学与分子生物学报

With the ongoing epidemic of the Coronavirus disease in China and the widespread development of radiotherapy, radiation-induced lung injury has gradually become a clinical problem that has attracted much attention. The pathogenesis of radiation-induced lung injury is complex, involving an imbalance in the polarization state of alveolar macrophages and an upregulation of alveolar epithelial cell apoptosis. Previous studies have shown that vitamin C is an important antioxidant substance, and preventive use of vitamin C can effectively treat acute lung injury. However, whether prophylactic use of vitamin C can effectively prevent or treat lung injury caused by radioactive substances, and its specific molecular mechanism remains to be studied. The purpose of this study is to investigate whether the prophylactic use of vitamin C to treat the alveolar macrophage cell line RAW 264. 7 and human lung epithelial cells BEAS-2B can effectively control the abnormal polarization of macrophages and the abnormal apoptosis of lung epithelial cells. This study found that after 4 weeks and 8 weeks of radioactive X-ray irradiation, the expression of macrophage M1 polarization state markers such as iNOS was significantly up-regulated (P< 0. 05), and preventive use of vitamin C to treat macrophages and lung epithelial cells can alleviate the polarization state disorder of macrophages and the apoptosis of alveolar epithelial cells caused by external radiation exposure, which is manifested in the down-regulation of the expression of Cleaved Caspase3. In addition, the preventive application of vitamin C treatment can inhibit the MAPK signaling pathway activated by external radiation exposure. Further experimental results showed that the inhibition of the MAPK pathway is the key to inhibiting the M1 polarization of macrophages and the apoptosis of lung epithelial cells. In summary, our findings suggest that vitamin C may play a protective role in acute radiation-induced lung injury by inhibiting macrophage M1 polarization/ promoting macrophage M2 polarization and alleviating alveolar epithelial cell apoptosis. This study will help to better understand the process and mechanism of the preventive effect of vitamin C, a common vitamin, on radiation-induced lung injury.

Electronic structure evolution induced by the charge redistribution during the construction of two-dimensional polymer networks from monomers to crystal frameworks.

Two-dimensional covalent organic frameworks (COFs) are a new type of porous crystalline material constructed by the linkage of organic building units through covalent bonds to produce predetermined structures. Here, the electronic structure evolution induced by the charge redistribution during the construction of two-dimensional polymer networks (sp2c-COF-2 and COF-66) from building units to crystal frameworks is examined theoretically. The calculated results demonstrate that the electronic structure of the framework is controlled by the relative energy level between the frontier orbitals of organic building core and linker units as well as the charge transfer amount between them during the construction of the framework. Moreover, it is observed that a noncoplanar framework becomes more conjugated because the charge transfer amount between core and linker units becomes larger during the construction of 2D frameworks, which leads to a larger charge carrier mobility within the 2D structure of COFs. The charge carrier mobility along the z-direction of the COF crystal is dominated by the interface interaction between COF layers. Thereby, we believed reasonable design or selection of organic building units plays a key role in improving the electronic and optoelectronic properties of such 2D organic frameworks.

Smilax glabra Roxb.: A Review of Its Traditional Usages, Phytochemical Constituents, Pharmacological Properties, and Clinical Applications.

Smilax glabra Roxb. (SGB) is a medicinal plant widely distributed in 17 countries worldwide. It is the primary raw material of the world-famous and best-selling functional food and beneficial tea. SGB was first recorded in Ben Cao Jing Ji Zhu of the Southern and Northern Dynasties (420-589 AD) and was reported for nutritional and medicinal properties for thousands of years. This review searched PubMed, Web of Science, and other databases for relevant literature on SGB species until April 2022. It aims to provide more integrated thinking, detailed awareness, and better knowledge of SGB. More than 200 chemical components have been discovered, including flavonoids, phenolic, phenolic acids, stilbenes, organic acids, phenylpropanoids, and others. Previous studies have demonstrated that SGB and its active ingredients show a wide range of pharmacological effects, including anti-infective, anti-cancer, anti-inflammatory, antioxidant, cardiovascular protection, etc. However, many studies on the biological activity of this plant were mainly based on crude extracts and active ingredients, and there is a lack of clinical studies and toxicity studies to support the development of drug design, development, and therapy. In summary, this review will provide specific and valuable suggestions and guidelines for further research and application of this plant in the medicinal field.