Impact of Oil Bodies on Structure, Rheology and Function of Acid-Mediated Soy Protein Isolate Gels.

Oil bodies (OBs) are naturally occurring pre-emulsified oil droplets that have broad application prospects in emulsions and gels. The main purpose of this research was to examine the impact of the OB content on the structure and functional aspects of acid-mediated soy protein isolate (SPI) gel filled with OBs. The results indicated that the peanut oil body (POBs) content significantly affected the water holding capacity of the gel. The rheological and textural analyses showed that POBs reduced the gel strength and hardness. The scanning electron and confocal laser scanning microscopy analyses revealed that POBs aggregated during gel formation and reduced the gel network density. The Fourier transform infrared spectrum (FTIR) analysis demonstrated that POBs participated in protein gels through hydrogen bonds, steric hindrance and hydrophobic interactions. Therefore, OBs served as inactive filler in the acid-mediated protein gel, replaced traditional oils and provided alternative ingredients for the development of new emulsion-filled gels.

Efficacy and safety of ultrasound-assisted wound debridement in the treatment of diabetic foot ulcers: a systematic review and meta-analysis of 11 randomized controlled trials.

Objective: Research data suggests that ultrasound-assisted wound debridement (UAWD) can effectively promote the healing of diabetic foot ulcers (DFU). However, existing research is not consistent with this viewpoint. Therefore, we conducted this study to investigate the effect of UAWD on the healing of diabetic foot ulcers. Methods: From the establishment of the database to January 2024, we searched 8 databases to study the effectiveness and safety of UAWD in the treatment of DFU. Two authors independently screened the qualifications of the articles, while two authors extracted relevant data. Statistical analysis was conducted using Review Manager 5.4 and STATA 18.0 software. Results: A total of 11 randomized controlled studies were included, with 6 countries and 696 participants participating. Our findings showed that UAWD was associated with a significant benefit in healing rate (OR = 2.60, 95% CI: [1.67, 4.03], P < 0.0001, I2 = 25%), wound healing time (MD = -11.94, 95% CI: [-23.65, -0.23], P = 0.05, I2 = 99%), percentage reduction in wound size (MD = 14.2, 95% CI: [10.8, 17.6], P = 0.47, I2 = 32%), effectiveness of treatment (OR = 10.3, 95% CI: [4.68, 22.66], P < 0.00001, I2 = 0%). Moreover, UAWD did not cause any significant adverse reactions. However, there was no obvious difference in wound blood perfusion (MD = 0.25, 95% CI: [-0.01, 0.52], P = 0.06, I2 = 90%), transcutaneous oxygen partial pressure (MD = 14.34, 95% CI: [-10.03, 38.71], P = 0.25, I2 = 98%). Conclusion: UAWD can significantly improve wound healing rate, shorten wound healing time, accelerate wound area reduction, and improve clinical treatment effectiveness without significant adverse reactions. Although there is no significant difference in transcutaneous oxygen pressure and wound blood flow perfusion between UAWD and SWC. So we look forward to more scientifically blinded, placebo-controlled, high-quality studies in the future, to enable researchers to obtain more complete and accurate analytical data, in order to improve the scientific and credibility of the evidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024501198.

Investigating the thermal stability and calcium resistance of O/W emulsions prepared with glycosylated whey protein hydrolysates modified by different saccharides.

The poor thermal stability and ion tolerance of whey protein hydrolysates (WPH) restrict its application in emulsions, while glycosylation shows potential benefits in improving WPH stability. However, the relationship between saccharides with different Mw and the glycosylation behavior of WPH rich in short peptides is unclear. In response, the effect of different saccharides on glycosylated WPH rich in short peptides and its emulsion stability were investigated. Grafted small Mw saccharides were more beneficial to the emulsion stability of WPH. Specifically, grafting xylose effectively inhibited 121 °C sterilization and 5 mM CaCl2-induced coalescence of WPH emulsion (687.50 nm) by comprehensively enhancing steric hindrance, conformational flexibility and electrostatic repulsion, and dissociating large aggregates into small aggregates. Conversely, grafting maltodextrin (30,590 Da) reduced thermal stability of WPH emulsion (4791.80 nm) by steric shielding and bridging flocculation. These findings provide new sights into glycosylation mechanism for WPH and achieving its application in nutritional emulsions.

Colonoscopy-assisted removal of an impaction foreign body at the rectosigmoid junction: A case report.

BACKGROUND: When an anorectal foreign body is found, its composition and shape should be evaluated, and a timely and effective treatment plan should be developed based on the patient's symptoms to avoid serious complications such as intestinal perforation caused by displacement of the foreign body. CASE SUMMARY: A 54-year-old male was admitted to our outpatient clinic on June 3, 2023, due to a rectal foreign body that had been embedded for more than 24 h. The patient reported using a glass electrode tube to assist in the recovery of prolapsed hemorrhoids, however, the electrode tube was inadvertently inserted into the anus and could not be removed by the patient. During hospitalization, the patient underwent surgery, and the foreign body was dragged into the rectum with the aid of colonoscopy. The anus was dilated with a comb-type pulling hook and an anal fistula pulling hook to widen the anus and remove the foreign body, and the local anal symptoms were then relieved with topical drugs. The patient was allowed to eat and drink, and an entire abdominal Computed tomography (CT) and colonoscopy were reviewed 3 d after surgery. CT revealed no foreign body residue and colonoscopy showed no metal or other residues in the colon and rectum, and no apparent intestinal tract damage. CONCLUSION: The timeliness and rationality of the surgical and therapeutic options for this patient were based on a literature review of the clinical signs and conceivable conditions in such cases. The type, material and the potential risks of rectal foreign bodies should be considered.

USP15 facilitates the progression of bladder cancer by amplifying the activation of the NF-κB signaling pathway.

USP15, a pivotal member of the deubiquitinase family, plays a crucial role in orchestrating numerous vital biological processes, including the regulation of NF-κB signaling pathway and deubiquitination of proto-oncogenes. In various cancers, USP15 has been validated to exhibit up-regulated expression, impacting the initiation and progression of cancer. However, its precise mechanism in bladder cancer remains elusive. Our study shed light on the significant overexpression of USP15 in bladder cancer cells compared to normal bladder cells, correlating with a poorer prognosis for bladder cancer patients. Strikingly, attenuation of USP15 expression greatly attenuated the proliferation, migration, and invasion of bladder cancer cells. Moreover, upregulation of USP15 was found to drive cancer progression through the activation of the NF-κB signaling pathway. Notably, USP15 directly deubiquitinates BRCC3, heightening its expression level, and subsequent overexpression of BRCC3 counteracted the antitumoral efficacy of USP15 downregulation. Overall, our findings elucidated the carcinogenic effects of USP15 in bladder cancer, primarily mediated by the excessive activation of the NF-κB signaling pathway, thereby promoting tumor development. These results underscore the potential of USP15 as a promising therapeutic target for bladder cancer in the future.

An ultrasound-triggered injectable sodium alginate scaffold loaded with electrospun microspheres for on-demand drug delivery to accelerate bone defect regeneration.

Biological processes, such as bone defects healing are precisely controlled in both time and space. This spatiotemporal characteristic inspires novel therapeutic strategies. The sustained-release systems including hydrogels are commonly utilized in the treatment of bone defect; however, traditional hydrogels often release drugs at a consistent rate, lacking temporal precision. In this study, a hybrid hydrogel has been developed by using sodium alginate, sucrose acetate isobutyrate, and electrospray microspheres as the base materials, and designed with ultrasound response, and on-demand release properties. Sucrose acetate isobutyrate was added to the hybrid hydrogel to prevent burst release. The network structure of the hybrid hydrogel is formed by the interconnection of Ca2+ with the carboxyl groups of sodium alginate. Notably, when the hybrid hydrogel is exposed to ultrasound, the ionic bond can be broken to promote drug release; when ultrasound is turned off, the release returned to a low-release state. This hybrid hydrogel reveals not only injectability, degradability, and good mechanical properties but also shows multiple responses to ultrasound. And it has good biocompatibility and promotes osteogenesis efficiency in vivo. Thus, this hybrid hydrogel provides a promising therapeutic strategy for the treatment of bone defects.

Single dual-specific anti-PD-L1/TGF-ß antibody synergizes with chemotherapy as neoadjuvant treatment for pancreatic ductal adenocarcinoma: a preclinical experimental study.

AIMS: Chemotherapy resistance is an important cause of neoadjuvant therapy failure in pancreatic ductal adenocarcinoma (PDAC). BiTP (anti-PD-L1/TGF-ß bispecific antibody) is a single antibody that can simultaneously and dually target transforming growth factor-beta (TGF-ß) and programmed cell death ligand 1 (PD-L1). We attempted in this study to investigate the efficacy of BiTP in combination with first-line chemotherapy in PDAC. METHODS: Preclinical assessments of BiTP plus gemcitabine and nab-paclitaxel were completed through a resectable KPC mouse model (C57BL/6J). Spectral flow cytometry, tissue section staining, enzyme-linked immunosorbent assays, Counting Kit-8, transwell, and Western blot assays were used to investigate the synergistic effects. RESULTS: BiTP combinatorial chemotherapy in neoadjuvant settings significantly downstaged PDAC tumors, enhanced survival, and had a higher resectability for mice with PDAC. BiTP was high affinity binding to targets and reverse chemotherapy resistance of PDAC cells. The combination overcame immune evasion through reprogramming tumor microenvironment via increasing penetration and function of T cells, natural killer cells, and dendritic cells and decreasing the function of immunosuppression-related cells as regulatory T cells, M2 macrophages, myeloid-derived suppressor cells, and cancer-associated fibroblasts. CONCLUSION: Our results suggest that the BiTP combinatorial chemotherapy is a promising neoadjuvant therapy for PDAC.

Synthesizing Knowledge-Enhanced Features for Real-World Zero-Shot Food Detection.

Food computing brings various perspectives to computer vision like vision-based food analysis for nutrition and health. As a fundamental task in food computing, food detection needs Zero-Shot Detection (ZSD) on novel unseen food objects to support real-world scenarios, such as intelligent kitchens and smart restaurants. Therefore, we first benchmark the task of Zero-Shot Food Detection (ZSFD) by introducing FOWA dataset with rich attribute annotations. Unlike ZSD, fine-grained problems in ZSFD like inter-class similarity make synthesized features inseparable. The complexity of food semantic attributes further makes it more difficult for current ZSD methods to distinguish various food categories. To address these problems, we propose a novel framework ZSFDet to tackle fine-grained problems by exploiting the interaction between complex attributes. Specifically, we model the correlation between food categories and attributes in ZSFDet by multi-source graphs to provide prior knowledge for distinguishing fine-grained features. Within ZSFDet, Knowledge-Enhanced Feature Synthesizer (KEFS) learns knowledge representation from multiple sources (e.g., ingredients correlation from knowledge graph) via the multi-source graph fusion. Conditioned on the fusion of semantic knowledge representation, the region feature diffusion model in KEFS can generate fine-grained features for training the effective zero-shot detector. Extensive evaluations demonstrate the superior performance of our method ZSFDet on FOWA and the widely-used food dataset UECFOOD-256, with significant improvements by 1.8% and 3.7% ZSD mAP compared with the strong baseline RRFS. Further experiments on PASCAL VOC and MS COCO prove that enhancement of the semantic knowledge can also improve the performance on general ZSD. Code and dataset are available at https://github.com/LanceZPF/KEFS.

DADS Inhibits the Proliferation of MDCC-MSB-1 Cells by Inducing Autophagy via the MEK/ERK Signalling Pathway.

Diallyl disulfide (DADS) is effective at suppressing tumour cell growth and proliferation. This study verified the morphology and growth activity of MDCC-MSB-1 cells by using an MTT assay to detect the effect of DADS on the proliferation of MDCC-MSB-1 cells and a CCK8 assay to detect the effect of DADS on the viability and proliferation of MDCC-MSB-1 cells. We found that the viability and proliferation of MDCC-MSB-1 cells decreased with increasing DADS concentrations. MDC staining and Western blotting were used to analyse autophagy, the associated protein LC3 and the MEK/ERK pathway proteins MEK and ERK and to investigate changes in cellular autophagy based on cell morphology and molecular biology. With increasing concentrations of DADS, MDCC-MSB-1 cell autophagy increased in a gradient manner. Additionally, the conversion of the autophagy marker protein LC3-I increased with increasing drug concentrations, and the relative expression of LC3-II steadily increased, as did the expression of key protein components of the MEK/ERK signalling pathway, including P-MEK1/2 and P-ERK1/2. These results suggest that DADS induces autophagy through the MEK/ERK pathway, thereby inhibiting the proliferation of MDCC-MSB-1 cells.

A novel montmorillonite clay-cetylpyridinium chloride material for reducing PFAS leachability and bioavailability from soils.

Soils contaminated by per- and polyfluoroalkyl substances (PFAS) present a significant threat to both ecological and human health. Extensive research efforts are currently underway to develop effective strategies for immobilizing these chemicals in soils. In this study, calcium montmorillonite was modified with cetylpyridinium chloride (CPC-CM) to enhance its electrostatic and hydrophobic interactions with PFAS. CPC-CM exhibited high adsorption for perfluorooctanoate acid (PFOA), perfluorooctane sulfonate (PFOS) and 8:2 fluorotelomer sulfonic acids (8:2 FTSA) across initial concentrations of 50-1000 µg/L, outperforming both the parent CM and L-carnitine modified CM. Soil leaching tests demonstrated the superior immobilization capabilities of the CPC-CM, maintaining an average PFAS leaching rate below 7% after 120-day incubation. In the context of human exposure scenarios, the in vitro bioaccessibility and in vivo bioavailability of PFAS in soils were measured by gastrointestinal extraction and mouse assay. CPC-CM treatment effectively reduced the bioaccessibility (by up to 84%) and bioavailability (by up to 76%) of PFAS in soils. Furthermore, the safety and efficacy of CPC-CM were evaluated using enteric microorganisms of mice. CPC-CM treatment mitigated PFAS-induced changes in the abundance of Bacteroidetes and Firmicutes, thereby reducing PFAS-induced health risks for humans. Overall, CPC-CM synthesized in this study demonstrated superior adsorption performance and application safety, offering a highly promising approach for remediating PFAS-contaminated soil.

A machine learning and experimental-based model for prediction of soil sorption capacity toward phenanthrene.

Sorption by soil is the fundamental basis for environment fate of hydrophobic organic contaminants (HOCs), which varies significantly depending on diverse properties of soils. Therefore, a generalized approach to predict HOC sorption by soils is required. In this study, 488 data points were extracted from references and adopted to develop models for estimating the sorption capacities of phenanthrene in soils using six different machine learning (ML) approaches. The extreme gradient boosting (XGBT) model demonstrated the most favorable performance, achieving a coefficient of determination of 0.91 and root-mean-square errors of 0.24 for the testing dataset. The XGBT model's performance was further demonstrated by comparing with experimental data from batch sorption tests conducted on 20 soil samples collected from 17 provinces of China. The differences between the predicted values and the experimental values were statistically equal to zero (p = 0.14). Leveraging the XBGT model together with soil properties from the Harmonized World Soil Database, the distribution of sorption capacities in Chinese soils was successfully depicted on a national scale. This research is expected to contribute to a deeper understanding of the migration of persistent organic pollutants in terrestrial system. Furthermore, the established model holds implications for more precise and scientific soil environmental management.

Triggering efficient reconstructions of Co/Fe dual-metal incorporated Ni hydroxide by phosphate additives for electrochemical hydrogen and oxygen evolutions.

Alkaline electrochemical water splitting has been considered as an efficient way for the green hydrogen production in industry, where the electrocatalysts play the critical role for the electricity-to-fuel conversion efficiency. Phosphate salts are widely used as additives in the fabrication of electrocatalysts with improved activity, but their roles on the electrocatalytic performance have not been fully understood. Herein, we fabricate Co, Fe dual-metal incorporated Ni hydroxide on Ni foam using NaH2PO4 ((Co, Fe)NiOxHy-pi) and NaH2PO2 ((Co, Fe)NiOxHy-hp) as additive, respectively. We find that (Co, Fe)NiOxHy-hp with NaH2PO2 in the fabrication shows high activity and stability for both HER and OER (a overpotential of -0.629 V and 0.65 V at 400 mA cm-2 for HER and OER, respectively). Further experiment reveals that the reconstructed structures of electrocatalyst by using NaH2PO2 (hp) endow high electrocatalytic performances: (1) in-situ generated active metal improves the accumulation, transportation and activity of hydrogen species in the HER process; and (2) in-situ generated poor-crystalline hydroxide endows superior charge/mass transportation and kinetics improvements in the OER process. Our study may provide an insightful understanding on the catalytic performance of non-precious metal electrocatalysts by controlling additives and guidance for the design and synthesis of novel electrocatalysts.

Effects of natural products on functional constipation: analysis of active ingredient and mechanism.

Constipation is a prevalent clinical ailment of the gastrointestinal system, yet its pathogenesis remains ambiguous. Despite the availability of numerous treatment modalities, they are insufficient in resolving the issue for patients. This work conducted a comprehensive review of the existing literature pertaining to the utilization of natural products for the treatment of constipation, with a focus on the efficacy of natural products in treating constipation, and to provide a comprehensive summary of their underlying mechanisms of action. Upon conducting a thorough review of the extant literature, we found that natural products can effectively treat constipation as modern synthetic drugs and compounded drugs with acetylcholinesterase (AChE) effects, rich in fiber and mucus, and the effects of increasing the tension of the ileum and gastrointestinal tract muscle, mediating signaling pathways, cytokine, excitability of the smooth muscle of the gastrointestinal tract, and regulating the homeostasis of intestinal flora. However, there is a wide variety of natural products, and there are still relatively few studies; the composition of natural products is complex, and the mechanism of action of natural products cannot be clarified. In the future, we need to further improve the detailed mechanism of natural products for the treatment of constipation.

Synthesis, crystal structures, and biological activity of aroylhydrazone di-m-chlorobenzyltin complexes.

Six aroylhydrazone di-m-chlorobenzyltin complexes {[X-C6H4(O)C=N-N=C(Me)COO](MeOH)(m-Cl-C6H4CH2)2Sn}2 (X = p-Me- (1), p-MeO- (2), p-t-Bu- (3), p-NO2- (4), p-OH- (5) or o-OH- (6)) were synthesized and characterized by HRMS (high-resolution mass spectrometry), NMR (nuclear magnetic resonance spectroscopy), IR (Fourier transform infrared spectroscopy), and TGA (thermogravimetric analysis) techniques. The molecular structure of complexes 1-6 was confirmed by single-crystal X-ray crystallography. The structure of complexes showed a distorted pentagonal bipyramidal configuration around the tin atom center, and the ligands adopted a tridentate chelating mode. Fascinatingly, either one-dimensional infinite chain structures or two-dimensional network structures were observed in the complexes through hydrogen bonds. Complex 2 has the strongest inhibitory effect on MCF7 and HepG2 cell proliferation, its effect was superior to that of the positive control drug cisplatin. The interaction of ct-DNA (calf-thymus DNA) with complex 2 was explored using UV absorption (ultraviolet absorption) and fluorescence spectroscopy. Complex 2 exhibited a moderate affinity for ct-DNA through intercalation modes. The interaction of complex 2 with ct-DNA has also been supported by molecular docking studies.

Saponins from Momordica charantia exert hypoglycemic effect in diabetic mice by multiple pathways.

The antidiabetic activity of saponins extracted from Momordica charantia (MCS) on streptozotocin-induced diabetic mice was investigated in order to elucidate the mechanism of MCS for exerting hypoglycemic effects. Saponins were first extracted from M. charantia L. and their composition was analyzed. The diabetic Kunming mice were fed low-dose saponins from M. charantia L. and high-dose MCS, using normal mice and diabetic mice as controls. Body weight, blood glucose level, oral glucose tolerance, serum C-peptide level, hepatic antioxidant capacity, hepatic glycogen and hexokinase in liver tissues, serum blood lipid level, and alpha-glucosidase activity in small intestines were measured, and microstructure of pancreatic islet was analyzed. The results showed that the total content of seven triterpenoid compounds in MCS was 18.24 µg/mg, with Momordicoside K having the highest content at 11.66 µg/mg. Diabetic mice treated with MCS at 100 and 200 mg/kg body weight daily for 30 days showed a maximum glucose reduction (p < .05) of 12.63% and 26.47%, respectively. MCS significantly decreased levels of postprandial hyperglycemia, serum lipid, α-glucosidase activity, and liver malondialdehyde. Additionally, levels of serum C-peptide and liver glycogen, as well as hexokinase and antioxidant enzyme activity, were significantly increased compared to the diabetic control groups. Histopathological results showed that MCS markedly reduced degenerative changes in islet ß-cells. It is concluded that MCS exerts antidiabetic effects by improved hypoglycemic, hypolipidemic, and antioxidant effects, increased hexokinase activity and glycogen synthesis, and enhanced reparative effects on the histological architecture and insulin secretion function of the pancreas.

IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis.

Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.

Enhancing Solubility and Reducing Thermal Aggregation in Pea Proteins through Protein Glutaminase-Mediated Deamidation.

The limited solubility and stability of pea proteins hinder their utilization in liquid formulations. In this study, protein glutaminase (PG) was employed to modify pea protein isolates (PPIs) and obtain deamidated PPI with varying degrees of deamidation (DD, 10-25%). The solubility and thermal stability of these deamidated PPI samples were assessed, and a comprehensive analysis, including SDS-PAGE, zeta potential, FTIR, surface hydrophobicity, and intrinsic fluorescence, was conducted to elucidate the mechanism behind the improvement in their functional properties. The results reveal that PG modification greatly enhances the solubility and heat stability of PPI, with the most notable improvements observed at higher DD (>20%). PG modification increases the net charge of PPI, leading to the unfolding and extension of the protein structures, thus exposing more hydrophobic groups. These structural changes are particularly pronounced when DD exceeds 20%. This increased electrostatic repulsion between carboxyl groups would promote protein unfolding, enhancing interactions with water and hindering the aggregation of unfolded protein in the presence of salts at elevated temperatures (supported by high-performance size exclusion chromatography and transmission electron microscopy). Accordingly, PG-mediated deamidation shows promise in enhancing the functional properties of PPI.

Risk prediction of the progression of chronic kidney disease stage 1 based on peripheral blood samples: construction and internal validation of a nomogram.

Patients with chronic kidney disease (CKD) have high morbidity and mortality, and the disease progression has a significant impact on their survival and living standards. This research aims to analyze risk factors for CKD stage 1 and provide a reference for clinical decision making. The clinical data and peripheral blood samples of 300 patients with CKD stage 1 were collected retrospectively. Patients were randomly assigned into a training set (n = 210) and a validation set (n = 90). Patients' baseline characteristic levels were subjected to statistical tests for difference. Univariate and multivariate Cox regression analyses were utilized to identify risk factors influencing disease progression. Subsequently, a prediction model for disease progression was developed using a nomogram, and the model's accuracy was assessed using the C-index and calibration curve. The results revealed that hypertension, diabetes, and urinary albumin were essential factors in the progression of CKD stage 1. The nomogram was constructed and then the C-index was calculated. The calibration curve was utilized to assess the risk model. The C-index of the training set was 0.75, and the C-index of the validation set was 0.73, suggesting a good predictive ability of the model. The risk model accurately predicted the progression of CKD stage 1, which is of great significance to developing personalized treatment for patients in clinical practice.

Omics analyses of Rehmannia glutinosa dedifferentiated and cambial meristematic cells reveal mechanisms of catalpol and indole alkaloid biosynthesis.

BACKGROUND: Rehmannia glutinosa is a rich source of terpenoids with a high medicinal reputation. The present study compared dedifferentiated cells (DDCs) and cambial meristematic cells (CMCs) cell cultures of R. glutinosa for terpenoid (catalpol) and indole alkaloid (IA) biosynthesis. In this regard, we used widely targeted metabolomics and transcriptome sequencing approaches together with the comparison of cell morphology, cell death (%), and catalpol production at different time points. RESULTS: We were able to identify CMCs based on their morphology and hypersensitivity to zeocin. CMCs showed higher dry weight content and better catalpol production compared to DDCs. The metabolome analysis revealed higher concentrations of IA, terpenoids, and catalpol in CMCs compared to DDCs. The transcriptome sequencing analysis showed that a total of 27,201 genes enriched in 139 pathways were differentially expressed. The higher catalpol concentration in CMCs is related to the expression changes in genes involved in acetyl-CoA and geranyl-PP biosynthesis, which are precursors for monoterpenoid biosynthesis. Moreover, the expressions of the four primary genes involved in monoterpenoid biosynthesis (NMD, CYP76A26, UGT6, and CYP76F14), along with a squalene monooxygenase, exhibit a strong association with the distinct catalpol biosynthesis. Contrarily, expression changes in AADC, STR, and RBG genes were consistent with the IA biosynthesis. Finally, we discussed the phytohormone signaling and transcription factors in relation to observed changes in metabolome. CONCLUSIONS: Overall, our study provides novel data for improving the catalpol and IA biosynthesis in R. glutinosa.

Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants achieved immune escape and became less virulent and easily transmissible through rapid mutation in the spike protein, thus the efficacy of vaccines on the market or in development continues to be challenged. Updating the vaccine, exploring compromise vaccination strategies, and evaluating the efficacy of candidate vaccines for the emerging variants in a timely manner are important to combat complex and volatile SARS-CoV-2. This study reports that vaccines prepared from the dimeric receptor-binding domain (RBD) recombinant protein, which can be quickly produced using a mature and stable process platform, had both good immunogenicity and protection in vivo and could completely protect rodents from lethal challenge by SARS-CoV-2 and its variants, including the emerging Omicron XBB.1.16, highlighting the value of dimeric recombinant vaccines in the post-COVID-19 era.