Low-viscosity hydroxypropyl methylcellulose obtained by electron beam irradiation and its performance in spray drying.

Low-viscosity hydroxypropyl methylcellulose (HPMC) was obtained by electron beam irradiation, and its use as an excipient for improving the properties of spray dried pharmaceutical powders was investigated. The minimum molecular weight of HPMC which could maintain the capacity of encapsulation and powder modification was explored. As the irradiation dose was increased from 10 to 200 kGy, the molecular weight and viscosity of HPMC decreased linearly. However, its main structure and degrees of methoxy and hydroxypropyl substitution were not significantly affected. The irradiated HPMC could encapsulate particles during spray drying and, thus, modify powder properties. Furthermore, the water content of spray-dried powders with irradiated HPMC was lower than that with parent HPMC. After the spray-dried powder with irradiated HPMC was prepared into granules, their dissolution rate was also faster. However, in order to achieve high encapsulation, the molecular weight of HPMC should be ensured to be above 7.5 kDa. The designated low-viscosity HPMC obtained by electron beam irradiation is a suitable powder-modification material for use in spray drying, and it shows promise as a superior excipient in medicine, food, paint industries, among others.

Prominent response to savolitinib monotherapy in high-grade fetal adenocarcinoma with MET amplification and concurrent brain metastasis: a case report.

Background: Mesenchymal-epithelial transition (MET) represents a potential therapeutic target in various cancers, with amplification of the MET gene identified in a subset of patients with pulmonary adenocarcinomas. However, MET gene amplification is rarely observed in high-grade fetal adenocarcinoma (H-FLAC). Case Description: Here we present a novel case of a patient diagnosed with stage IV H-FLAC harboring MET amplifications and treated with savolitinib. The 69-year-old male patient, who presented with a primary complaint of cough and white sputum, had a history of hypertension for over 10 years and a 45-year smoking history. The patient received savolitinib monotherapy treatment due to brain metastases. Despite the omission of radiotherapy for asymptomatic brain metastases, a notable response to savolitinib therapy was observed, with a partial response (PR) achieved after 4 weeks and a reduction in the brain tumor. At the time of the submission of this report, the patient received over 24 weeks of savolitinib treatment, and was maintained PR. The patient was still undergoing treatment. This highlights the potential clinical benefits of targeted therapy against MET amplification in H-FLAC. Conclusions: H-FLAC harboring MET amplification and brain metastasis is rare. Treatment with savolitinib monotherapy resulted in a PR, providing preliminary insights to the efficacy of savolitinib for H-FLAC with MET amplification.

Integration of Proteomic and Metabolomic Data Reveals the Lipid Metabolism Disorder in the Liver of Rats Exposed to Simulated Microgravity.

Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among astronauts. However, the reasons for this persistence of symptoms remain insufficiently investigated. In this study, we used tandem mass tag (TMT)-based quantitative proteomics techniques, as well as non-targeted metabolomics techniques based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), to comprehensively analyse the relative expression levels of proteins and the abundance of metabolites associated with lipid accumulation in rat liver tissues under simulated microgravity conditions. The differential analysis revealed 63 proteins and 150 metabolites between the simulated microgravity group and the control group. By integrating differentially expressed proteins and metabolites and performing pathway enrichment analysis, we revealed the dysregulation of major metabolic pathways under simulated microgravity conditions, including the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, steroid hormone biosynthesis and butanoate metabolism, indicating disrupted liver metabolism in rats due to weightlessness. Finally, we examined differentially expressed proteins associated with lipid metabolism in the liver of rats exposed to stimulated microgravity. These findings contribute to identifying the key molecules affected by microgravity and could guide the design of rational nutritional or pharmacological countermeasures for astronauts.

Fingerprinting of physical manufacturing properties of different acids for effervescent systems.

The study aimed to fingerprint the physical manufacturing properties of five commonly used acid sources in effervescent systems for designing the formulation and process of such systems. The hygroscopicity, texture properties, rheological torque, compressibility, tabletability, etc., were investigated to inspect 'powder direct compression (DC)' and 'wet granulation and compression' properties of citric (CA), tartaric (TA), malic (MA), fumaric (FA), and adipic acid (AA). The DC ability was evaluated by the SeDeM expert system. The results indicated that all acid powders failed to meet flowability requirements for DC, and plastic deformation dominated during compression. Furthermore, CA exhibited strong hygroscopicity and punch sticking, while MA demonstrated the best tabletability. TA had a large wet granulation space and was relatively the most suitable for DC. AA was extremely hygroscopic, and its flowability improved significantly as particle size increased. Finally, FA displayed the lowest hygroscopicity and ejection force as well as great compressibility and wet granulation space, and did not exhibit punch sticking, while the granule fragments dissolved slowly during disintegration. Generally speaking, the formulation or granulation affected the tabletability, indicating that pairing with other acids or suitable fillers could potentially improve its disadvantages. These multidimensional assessments effectively reduce the pre-exploration and enhance the efficiency of the development of effervescent systems.

Self-healing, antioxidant, and antibacterial Bletilla striata polysaccharide-tannic acid dual dynamic crosslinked hydrogels for tissue adhesion and rapid hemostasis.

Biomaterials capable of achieving effective sealing and hemostasis at moist wounds are in high demand in the clinical management of acute hemorrhage. Bletilla striata polysaccharide (BSP), a natural polysaccharide renowned for its hemostatic properties, holds promising applications in biomedical fields. In this study, a dual-dynamic-bonds crosslinked hydrogel was synthesized via a facile one-pot method utilizing poly(vinyl alcohol) (PVA)-borax as a matrix system, followed by the incorporation of BSP and tannic acid (TA). Chemical borate ester bonds formed around borax, coupled with multiple physical hydrogen bonds between BSP and other components, enhanced the mechanical properties and rapid self-healing capabilities. The catechol moieties in TA endowed the hydrogel with excellent adhesive strength of 30.2 kPa on the surface of wet tissues and facilitated easy removal without residue. Benefiting from the synergistic effect of TA and the preservation of the intrinsic properties of BSP, the hydrogel exhibited outstanding biocompatibility, antibacterial, and antioxidant properties. Moreover, it effectively halted acute bleeding within 31.3 s, resulting in blood loss of 15.6 % of that of the untreated group. As a superior hemostatic adhesive, the hydrogel in this study is poised to offer a novel solution for addressing future acute hemorrhage, wound healing, and other biomedical applications.

[Reflections on good manufacturing practice and quality control system of personalized traditional Chinese medicine preparations].

Personalized traditional Chinese medicine(TCM) preparations have entered a stage of rapid development. The key to the healthy development of this industry is to establish a sound manufacturing standard and quality control system. This paper analyzed the characteristics of personalized TCM preparations and drew reference from the quality management standards in the production of commissioned decoctions and oral pastes, on the basis of which the production quality management scheme and cautions for the safe production of personalized TCM preparations was put forward with consideration to various problems that may exist and occur in the production of such preparations. It provided references for formulating the production standards and quality management system of personalized TCM preparations. The production standards and quality control system should develop with the times. In the future, modern technologies such as big data and artificial intelligence should be employed to achieve the automated and intelligent production and establish a sound quality traceability system, online control strategy, and safety management mode of personalized TCM preparations, which will ensure the healthy development of this industry under requirement of good manufacturing practice(GMP).

[Research practice and development direction of intelligent manufacturing of presonalized traditional Chinese medicine preparations].

In recent years, as people's living standards continue to improve, and the pace of life accelerates dramatically, the demand and quality of traditional Chinese medicine(TCM) services from patients continue to rise. As an essential supplement to the existing forms of TCM application, such as Chinese patent medicine, decoction, and formulated granules, presonalized TCM preparations is facing an increasing market demand. Currently, manual and semi-mechanized production are the primary production ways in presonalized TCM preparations. However, the production process control level is low, and digitalization and informatization need to be improved, which restricts the automated and intelligent development of presonalized TCM preparations. Presonalized TCM preparations faces a significant opportunity and challenge in integrating with intelligent manufacturing through research and development of intelligent equipment and core technology. This paper overviews the connotation and characteristics of intelligent manufacturing and summarizes the application of intelligent manufacturing technologies such as "Internet of things" "big data", and "artificial intelligence" in the TCM industry. Based on the innovative research and development model of "intelligent classification of TCM materials, intelligent decision making of prescription and process, and online control and intelligent production" of presonalized TCM preparations, the research practice and achievements from our research group in the field of intelligent manufacturing of presonalized TCM preparations are introduced. Ultimately, the paper proposes the direction for developing intelligent manufacturing of presonalized TCM preparations, which will provide a reference for the research and application of automation and intelligence of presonalized TCM preparations.

[Molding matrix formulation of hot-melt pressure-sensitive adhesive plaster of personalized traditional Chinese medicine preparations].

This study aims to optimize the matrix formulation for the hot-melt pressure-sensitive adhesive plaster of personalized traditional Chinese medicine(TCM) preparations and verify the applicability of the formulation. The central composite design in JMP Pro 16.1.0 was employed to optimize the dosages of styrene-isoprene-styrene triblock copolymer(SIS), hydrogenated petroleum resin, and lightweight liquid paraffin, with the fine powder of Yipifang as the model drug(drug loading of 10%) and the sensory score and objective evaluation as the comprehensive evaluation indicators. The quality evaluation system of hot-melt pressure-sensitive adhesive plaster of personalized TCM preparations was established. The applicability of the optimized matrix formulation of hot-melt pressure-sensitive adhesive plaster was verified with 16 TCM preparations for external application. Furthermore, the applicability of the matrix formulation was investigated with different drug loadings. The general molding matrix formulation was SIS∶hydrogenated petroleum resin∶lightweight liquid paraffin 3∶3∶5. The optimized matrix formulation showed good molding properties and high quality scores for 16 TCM preparations and were suitable for the plastering of finely powdered decoction pieces with a loading capacity of 10% to 30%. The results suggest that the optimized matrix formulation has good applicability and is suitable for TCM preparations. The findings lay a foundation for the application and promotion of the hot-melt pressure-sensitive adhesive plasters of personalized TCM preparations.

Non-electrophysiological techniques targeting transient receptor potential (TRP) gene of gastrointestinal tract.

Transient receptor potential (TRP) channels are cation channels related to a wide range of physical and chemical stimuli, they are expressed all along the gastrointestinal system, and a myriad of diseases are often associated with aberrant expression or mutation of the TRP gene, suggesting that TRPs are promising targets for drug therapy. Therefore, a better understanding of the information of TRPs in health and disease could facilitate the development of effective drugs for the treatment of gastrointestinal diseases like IBD. But there are very few generalizations about the experimental techniques studied in this field. In view of the promise of TRP as a therapeutic target, we discuss experimental methods that can be used for TRPs including their distribution, function and interaction with other proteins, as well as some promising emerging technologies to provide experimental methods for future studies.

Non-targeted metabolomic analysis reveals the mechanism of quality formation of citrus flower-green tea.

BACKGROUND: Citrus flower-green tea (CT) is a scented tea processed from green tea (GT) and fresh citrus flower, which is favored by consumers due to its potential health benefits and unique citrus flavor. This study evaluated the quality of CT and revealed the mechanism of its quality formation. RESULTS: The CT had a significant citrus flavor and a good antioxidant activity, and its sensory quality was superior to that of GT. Headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) analysis revealed that the scenting process resulted in a significant increase of alkenes such as ß-pinene, trans-ß-ocimene, α-farnesene, isoterpinolene, and γ-terpinene, as well as a significant decrease of alcohols such as α-terpineol, l-menthol, and linalool in CT in comparison with GT. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis revealed that the levels of flavonoids (such as neohesperidin, hesperidin, tangeritin, hesperetin 5-O-glucoside, and nobiletin) and alkaloids (such as trigonelline and theobromine) in CT increased significantly after scenting process, while the levels of amino acids (such as valine and l-phenylalanine) and organic acids (such as ascorbic acid) decreased significantly. CONCLUSION: These observations showed that the scenting process promoted the absorption of aroma from citrus flowers by GT and the changes in its non-volatile metabolites, leading to the formation of citrus flavor quality in CT. © 2024 Society of Chemical Industry.

Cisplatin-induced Pyroptosis Enhances the Efficacy of PD-L1 Inhibitor in Small-Cell Lung Cancer via GSDME/IL12/CD4Tem Axis.

The combination therapy of platinum-based chemotherapy and PD-L1 inhibitors but not the single anti-PD-L1 therapy has significantly improved the prognosis of patients with small-cell lung cancer (SCLC). However, the synergistic mechanism of combination therapy has not been fully elucidated. In this work, we identified a positive correlation between the expression of pyroptosis-related proteins Gasdermin E (GSDME) and the survival rates of patients with SCLC. Importantly, it was shown that human SCLC cell lines with high expression of GSDME showed more sensitivity to cisplatin, as well as cisplatin plus anti-PD-L1 treatment both in vitro and in vivo. Mechanically, cisplatin induced the activation of GSDME and the release of cytokines including IL-12, which enhance the expression of IFN-γ in T cells in the tumor immune microenvironment (TME) and subsequently improve anti-PD-L1 response. Altogether, our work demonstrates that cisplatin could induce GSDME-dependent cell pyroptosis to improve the response of anti-PD-L1 therapy though switching the TME from "cold" to "hot" in SCLC, indicating GSDME as a response biomarker for combination therapy of anti-PD-L1 and chemotherapy, as well as a potential target to sensitize the response to PD-L1 inhibitor therapy in future.

MR Spectroscopy Assessment of Daily Variations of GABA Levels within the Parietal Lobe and Anterior Cingulate Gyrus Regions of Healthy Young Adults.

BACKGROUND: The changes that occur in the gamma-aminobutyric acid (GABA) levels within specific brain regions throughout the day are less clear. PURPOSE: To evaluate the daily fluctuations of GABA levels within the parietal lobe (PL) and anterior cingulate gyrus (ACC) regions and explore their association with melatonin (MT) levels, heart rate (HR), and blood pressure. STUDY TYPE: Prospective. SUBJECTS: 26 healthy young adults (15 males and 11 females aged 22-27 years). FIELD STRENGTH/SEQUENCE: 3.0T, T1-weighted imaging, Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. ASSESSMENT: The acquired GABA signal contained the overlapping signals of macromolecules and homocarnosine, hence expressed as GABA+. The creatine (Cr) signal was applied as an endogenous reference. The GABA+, GABA+/Cr were measured at six different time points (1:00, 5:00, 9:00, 13:00, 17:00, and 21:00 hours) using MEGA-PRESS. The blood pressure, HR and sputum MT levels, were also acquired. STATISTICAL TESTS: The one-way repeated-measures analysis of variance (ANOVA) was used to evaluate the GABA, blood pressure, HR, and MT levels throughout the day. A general linear model was used to find the correlation between GABA and blood pressure, HR, and MT. P < 0.05 was statistically significant. RESULTS: Significant variations in GABA+/Cr and GABA+ levels were observed throughout the day within the PL region. The lowest levels were recorded at 9:00 hour (GABA+/Cr: 0.100 ± 0.003，GABA+:1.877 ± 0.051 i.u) and the highest levels were recorded at 21:00 hour (GABA+/Cr: 0.115 ± 0.003, GABA+:2.122 ± 0.052 i.u). The MT levels were positively correlated with GABA+/Cr (r = 0.301) and GABA+ (r = 0.312) within the ACC region. DATA CONCLUSION: GABA+/Cr and GABA+ in ACC are positively correlated with MT. GABA levels in the PL have diurnal differences. These findings may indicate that the body's GABA level change in response to the light-dark cycle. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

[Progress in targeted inhibition of aerobic glycolysis combined with immunotherapy for renal cell carcinoma].

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.

Plasma membrane-localized hexose transporter OsSWEET1b, affects sugar metabolism and leaf senescence.

KEY MESSAGE: OsSWEET1b is a hexose transporter protein, which localized in cell membranes and interacting with itself to form homodimer and knockout of OsSWEET1b resulted in reduced leaves sugar content and accelerating leaf senescence. In the rice genome, the SWEET gene family contains 21 homologous members, but the role of some of them in rice growth and development is still unknown. The function of the sugar transporter OsSWEET1b protein in rice was identified in this research. Expression analysis showed that the expression levels of OsSWEET1b in leaves were higher than that in other tissues. The hexose transport experiment confirmed that OsSWEET1b has glucose and galactose transporter activity in yeast. Subcellular localization indicates that OsSWEET1b protein was targeted to the plasma membrane and BiFC analysis showed that OsSWEET1b interacts with itself to form homodimers. Functional analysis demonstrated that the ossweet1b mutant plants were have reduced the sucrose, glucose, fructose, starch and galactose contents, and induced carbon starvation-related gene expression, which might lead to carbon starvation in leaves at filling stage. The ossweet1b knockout plants showed decreased chlorophyll content and antioxidant enzyme activity, and increased ROS accumulation in leaves, leading to leaf cell death and premature senescence phenotype at filling stage. In ossweet1b mutants, the leaf senescence-related gene expression levels were increased and the abundance of photosynthesis-related proteins was decreased. Loss of OsSWEET1b were affected the starch, sucrose metabolism and carbon fixation in photosynthetic organelles pathway by RNA-seq analysis. The destruction of OsSWEET1b function will cause sugar starvation, decreased photosynthesis and leaf senescence, which leading to reduced rice yield. Collectively, our results suggest that the OsSWEET1b plays a key role in rice leaves carbohydrate metabolism and leaf senescence.

GR5 acts in the G protein pathway to regulate grain size in rice.

Grain size is an important determinant of grain yield in rice. Although dozens of grain size genes have been reported, the molecular mechanisms that control grain size remain to be fully clarified. Here, we report the cloning and characterization of GR5 (GRAIN ROUND 5), which is allelic to SMOS1/SHB/RLA1/NGR5 and encodes an AP2 transcription factor. GR5 acts as a transcriptional activator and determines grain size by influencing cell proliferation and expansion. We demonstrated that GR5 physically interacts with five Gγ subunit proteins (RGG1, RGG2, DEP1, GS3, and GGC2) and acts downstream of the G protein complex. Four downstream target genes of GR5 in grain development (DEP2, DEP3, DRW1, and CyCD5;2) were revealed and their core T/CGCAC motif identified by yeast one-hybrid, EMSA, and ChIP-PCR experiments. Our results revealed that GR5 interacts with Gγ subunits and cooperatively determines grain size by regulating the expression of downstream target genes. These findings provide new insight into the genetic regulatory network of the G protein signaling pathway in the control of grain size and provide a potential target for high-yield rice breeding.

GW9 determines grain size and floral organ identity in rice.

Grain weight is an important determinant of grain yield. However, the underlying regulatory mechanisms for grain size remain to be fully elucidated. Here, we identify a rice mutant grain weight 9 (gw9), which exhibits larger and heavier grains due to excessive cell proliferation and expansion in spikelet hull. GW9 encodes a nucleus-localized protein containing both C2H2 zinc finger (C2H2-ZnF) and VRN2-EMF2-FIS2-SUZ12 (VEFS) domains, serving as a negative regulator of grain size and weight. Interestingly, the non-frameshift mutations in C2H2-ZnF domain result in increased plant height and larger grain size, whereas frameshift mutations in both C2H2-ZnF and VEFS domains lead to dwarf and malformed spikelet. These observations indicated the dual functions of GW9 in regulating grain size and floral organ identity through the C2H2-ZnF and VEFS domains, respectively. Further investigation revealed the interaction between GW9 and the E3 ubiquitin ligase protein GW2, with GW9 being the target of ubiquitination by GW2. Genetic analyses suggest that GW9 and GW2 function in a coordinated pathway controlling grain size and weight. Our findings provide a novel insight into the functional role of GW9 in the regulation of grain size and weight, offering potential molecular strategies for improving rice yield.