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Liver fibrosis, mainly arising from chronic viral or metabolic liver diseases, is a significant global health concern. There is currently only one FDA-approved drug (Resmetirom) in the market to combat liver fibrosis. Both galectin-3 and epidermal growth factor receptor (EGFR) play important roles in liver fibrosis, while galectin-3 may interact with EGFR. Galectin-3 inhibitors, typically lactose or galactose derivatives may inhibit liver fibrosis. We hypothesized that targeting both galectin-3 and EGFR may have better effect against liver fibrosis. Here, EGFR inhibitor erlotinib was used in a series of designed galectin-3 inhibitors after hybridization with the pharmacophore structure in reported galectin-3 inhibitors to impede hepatic stellate cells (HSCs) activation by a typical method of click chemistry. Bioactivity test results showed that compound 29 suppressed TGF-β-induced upregulation of fibrotic markers (α-SMA, fibronectin-1, and collagen I). The preferred compound 29 displayed better binding to galectin-3 (K D =52.29 μM) and EGFR protein (K D =3.31 μM) by SPR assay. Further docking studies were performed to clarify the possible binding mode of compound 29 with galectin-3 and EGFR. Taken together, these results suggested that compound 29 could be a potential dual galectin-3 and EGFR inhibitor as leading compound for anti-liver fibrosis new drug development., (© 2024 Wiley-VCH GmbH.)

The flower of Gomphrena globosa (G. globosa.) is used as Chinese traditional medicine and functional food. Extractions from G. globosa. have been reported to exert hepatoprotective effects. We further hypothesized that the polysaccharide components, as a bioactive ingredient, might have anti-fatty and hepatitis function. Here, a novel homogeneous arabinoglucan GGL0.05S1 (Mw = 83.9 kDa) from this flower, was characterized by monosaccharide composition analysis, methylation analysis, and NMR. Structural analysis showed that the backbone of GGL0.05S1 consists of →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1→ residues, and the branched chain linked to the main chain via C-6 of →4,6)-α-Glcp-(1→ in the form α-Araf-(1→[4)-α-Glcp-(1] b → (b > 2). In vitro experiments demonstrated that GGL0.05S1 could inhibit lipid deposition and ROS overload in free fatty acid-induced hepatocytes, meanwhile in vivo tests showed that GGL0.05S1 effectively protected against liver injury, steatohepatitis, and fibrosis in a CDA-HFD-fed MASH model. Mechanism study further uncovered that GGL0.05S1 augmented the expression and antioxidant ability of thioredoxin protein that ameliorated oxidative stress, promoted fatty acid β-oxidation and mitophagy, up to reducing lipotoxicity and alleviating inflammation via inhibiting NLRP3 signaling pathway. Overall, GGL0.05S1 might be a potential novel active compound with liver-protective effect from G. globosa., and which is informative for anti-MASH new drug development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Liver fibrosis may lead to cirrhosis and even cancer without effective clinical medicine available. Previous studies demonstrated that galactan-containing pectins or pectin-like polysaccharides might target Galectin-3 (Gal-3) to impede fibrosis. This research aims to discover novel pectin-like galactan to interfere with fibrosis for potential new drug development. Thus, we purify a novel homogeneous Rhamnogalacturonan-I like polysaccharide with galactan input, XHH2, from the Crocus sativus flower. XHH2 (MW: 35.7 kDa) consists of rhamnose, galacturonic acid, galactose, and arabinose in ratios of 6.6: 6.1: 25.2: 12.1. The backbone of XHH2 comprises 1, 3, 6-Gal and 1, 3, 4-GalA, with branches at O-3 of 1, 3, 6-Gal and O-4 of 1, 3, 4-GalA. O-3 branches include 1, 3-Gal, 1, 4-Gal, 1, 6-Gal, T-Gal, and T-Glc, while O-4 branches consist of 1, 2, 4-Rha, 1, 4-GalA, 1, 5-Ara, T-Ara, T-Gal, and T-α-HexA. Surface plasmon resonance measurement shows that XHH2 binds to both Gal-3 and integrin β1 to block Gal-3/integrin β1 interaction. Mechanism studies further suggest that XHH2 inactivates hepatic stellate cells (HSCs) via disturbing the Gal-3/Integrin-β1/FAK pathway to alleviate liver injury and fibrosis in vitro & in vivo. XHH2 shows a favorable drug safety in the acute toxicity test of oral administration of XHH2 in mice. Overall, XHH2 is an active ingredient against liver fibrosis by targeting the interaction between Gal-3 and Integrin-β1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Kidney diseases are characterized by their intricate nature and complexity, posing significant challenges in their treatment and diagnosis. Nanoparticles (NPs), which can be further classified as synthetic and biomimetic NPs, have emerged as promising candidates for treating various diseases. In recent years, the development of engineered nanotherapeutics has focused on targeting damaged tissues and serving as drug delivery vehicles. Additionally, these NPs have shown superior sensitivity and specificity in diagnosis and imaging, thus providing valuable insights for the early detection of diseases. This review aims to focus on the application of engineered synthetic and biomimetic NPs in kidney diseases in the aspects of treatment, diagnosis, and imaging. Notably, the current perspectives and challenges are evaluated, which provide inspiration for future research directions, and encourage the clinical application of NPs in this field., (© 2024 Wiley‐VCH GmbH.)

Synthetic dye production and the consequent generation of dye-rich wastewater are major concerns of water quality in many countries. We developed a sustainable approach with deep eutectic solvent (DES) treatment to enhance the efficiency of mixed cellulose ester (MCE) membrane-based dye removal material. The DES composition and treatment conditions were optimized, and the treated membranes were comprehensively characterized. DES-treated membranes exhibited improved morphology, surface properties, and superior dye adsorption capabilities. Our study revealed that the adsorption process was chemically controlled and driven by electrostatic and hydrogen bond interactions. Thermodynamic analysis confirmed the endothermic and spontaneous nature of the adsorption process. Moreover, the treated membranes exhibited good separation performance for dye/salt mixtures. Additionally, we demonstrated selective adsorption of cationic dyes over anionic dyes using these treated membranes. This selectivity enabled the development of a membrane solid-phase extraction (MSPE) method for quantification of trace amount of dyes. Compared with other methods, DES-treated MCE membranes present a promising solution for efficient dye quantification and removal, offering a green and effective strategy to address water pollution stemming from synthetic dyes. Additionally, this study provides a novel strategy for green chemistry modification of cellulose-based materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. Despite recent advancements, clinical outcomes for GC remain unsatisfactory. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have shown promise in inhibiting tumor progression, but their role in GC, specifically human umbilical cord MSC-derived small EVs (hucMSC-sEVs), is not well understood. This study investigates the therapeutic potential of hucMSC-sEVs in GC treatment. We found that hucMSC-sEVs are captured by GC cells, substantially inhibiting their proliferation and inducing apoptosis. MiRNA sequencing revealed that hucMSC-sEVs were enriched with miRNAs having anticancer properties. Among these, miR-13896, a new miRNA, was identified as a potent inhibitor of GC cell proliferation and a promoter of apoptosis. Mechanistic studies revealed that miR-13896 targets and down-regulates the ATG2A-mediated autophagy pathway, suppressing GC cell growth and metastasis. Furthermore, we enriched hucMSC-sEVs with miR-13896 through electroporation. These engineered EVs specifically targeted tumor sites and significantly reduced GC cell growth and migration in vitro and in vivo. MiR-13896 emerged as a promising therapeutic target for GC. The delivery of miR-13896 via hucMSC-sEVs represents a novel and effective strategy for GC treatment, highlighting the potential of EV-based therapies to combat this malignancy., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Peipei Wu et al.)

Background: Coronary heart disease (CHD) represents a significant global health concern, arising from an intricate interplay between genetic predisposition and environmental influences, with a pivotal involvement of oxidized low-density lipoprotein (ox-LDL) in the pathophysiology of it. We aimed to elucidate the synergistic dynamics of B cell activating transcription factor (BATF) and Sirtuin 1 (SIRT1) in cell injury caused by ox-LDL, reveal potential therapeutic strategies for CHD., Methods: The GSE42148 dataset was used to analyze Differentially expressed genes (DEGs) to construct a gene co-expression network. Then bioinformatics analysis was performed on key modules to select the BATF gene. In vitro experiments were conducted to investigate the protective impact of BATF against human coronary artery endothelial cells (HCAEC) injury induced by ox-LDL. Further investigations probed the synergistic impact of BATF and SIRT1 modulation on cellular apoptosis and damage in the presence of ox-LDL., Results: BATF was significantly down-regulated in the CHD sample of the GSE42148 dataset. In vitro assays have proven that BATF alleviates ox-LDL-induced HCAEC injury. Notably, BATF emerged as a pivotal regulator of SIRT1 expression post ox-LDL exposure. Subsequent experiments underscored the interplay between BATF and SIRT1 in mitigating ox-LDL-induced apoptosis and Lactate Dehydrogenase (LDH) activity elevation, highlighting their collaborative role in cellular protection., Conclusion: The research findings suggested a prospective protective function of BATF in HCAEC injury induced by ox-LDL, likely through the mediation of SIRT1 regulation. These results could offer fresh perspectives on the etiology of CHD and possible treatment avenues., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Commelina communis L., a functional food and herbal plant in Asia, has been used against obesity, diabetes, and infections for centuries. A growing body of studies has demonstrated that indigestible polysaccharides are significant in obesity management. However, the structures and bioactivities of homogeneous polysaccharides from C. communis remain unclear. This study presented the structural characterization, simulated digestion, and human gut Bacteroides proliferation promotion activity of a novel homogeneous polysaccharide (CCB-3) from C. communis. The results showed that CCB-3 was an arabinoglucuronoxylan, primarily composed of arabinose, galactose, xylose, glucuronic acid (GlcA), and 4-O-methyl GlcA with a molecular weight (Mw) of 58.8 kDa. Following a 6-hour exposure to simulated gastrointestinal fluid, the Mw of CCB-3 remained unchanged, revealing that CCB-3 was an indigestible polysaccharide. Notably, CCB-3 could promote the proliferation of B. thetaiotaomicron, B. ovatus, and B. cellulosilyticus and produce short-chain fatty acids (SCFAs) and 1,2-propanediol. These findings might shed light on the discovery of polysaccharide-based leading compounds from C. communis against obesity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: The relationship between preoperative inflammation status and tumorigenesis as well as tumor progression is widely acknowledged., Aim: To assess the prognostic significance of preoperative inflammatory biomarkers in patients with distal cholangiocarcinoma (dCCA) who underwent pancreatoduodenectomy (PD)., Methods: This single-center study included 216 patients with dCCA after PD between January 1, 2011, and December 31, 2022. The individuals were categorized into two sets based on their systemic inflammatory response index (SIRI) levels: A low SIRI group (SIRI < 1.5, n = 123) and a high SIRI group (SIRI ≥ 1.5, n = 93). Inflammatory biomarkers were evaluated for predictive accuracy using receiver operating characteristic curves. Both univariate and multivariate Cox proportional hazards analyses were performed to estimate SIRI for overall survival (OS) and recurrence-free survival (RFS)., Results: The study included a total of 216 patients, with 58.3% being male and a mean age of 65.6 ± 9.6 years. 123 patients were in the low SIRI group and 93 were in the high SIRI group after PD for dCCA. SIRI had an area under the curve value of 0.674 for diagnosing dCCA, showing better performance than other inflammatory biomarkers. Multivariate analysis indicated that having a SIRI greater than 1.5 independently increased the risk of dCCA following PD, leading to lower OS [hazard ratios (HR) = 1.868, P = 0.006] and RFS (HR = 0.949, P < 0.001). Additionally, survival analysis indicated a significantly better prognosis for patients in the low SIRI group ( P < 0.001)., Conclusion: It is determined that a high SIRI before surgery is a significant risk factor for dCCA after PD., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In the classic molecular model of nacreous layer formation, unusual acidic matrix proteins rich in aspartic acid (Asp) residues are essential for nacre nucleation due to their great affinity for binding calcium. However, the acidic matrix proteins discovered in the nacreous layer so far have been weakly acidic with a high proportion of glutamate. In the present study, several silk-like matrix proteins, including the novel matrix protein HcN57, were identified in the ethylenediaminetetraacetic acid-soluble extracts of the nacreous layer of Hyriopsis cumingii. HcN57 is a highly repetitive protein that consists of a high proportion of alanine (Ala, 34.4%), glycine (Gly, 22.5%), and serine (Ser, 11.4%). It forms poly Ala blocks, Gly n X repeats, an Ala-Gly repeat, and a Ser-Ala-rich region, exhibiting significant similarity to silk proteins found in spider species. The expression of HcN57 was specifically located in the dorsal epithelial cells of the mantle pallium and mantle center. Notably, expression of HcN57 was relatively high during nacreous layer regeneration and pearl nacre deposition, suggesting HcN57 is a silk matrix protein in the nacreous layer. Importantly, HcN57 also contains a certain content of Asp residues, making it an unusual acidic matrix protein present in the nacreous layer. These Asp residues are mainly distributed in three large hydrophilic acidic regions, which showed inhibitory activity against aragonite deposition and morphological regulation of calcite in vitro. Moreover, HcN57-dsRNA injection resulted in failure of nacre nucleation in vivo. Taken together, our results show that HcN57 is a bifunctional silk protein with poly Ala blocks and Gly-rich regions that serve as space fillers within the chitinous framework to prevent crystallization at unnecessary nucleation sites and Asp-rich regions that create a calcium ion supersaturated microenvironment for nucleation in the center of nacre tablets. These observations contribute to a better understanding of the mechanism by which silk proteins regulate framework construction and nacre nucleation during nacreous layer formation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A novel RG-I pectin-like polysaccharide, YJ3A1, was purified from the flowers of Rosa chinensis and its structure and hepatoprotective effect in vivo and in vitro were investigated. The backbone of this polysaccharide is mainly composed of 1, 4-galactan, 1, 4-linked α-GalpA and 1, 2-linked α-Rhap disaccharide repeating unit attached by 1, 6-linked β-Galp or 1, 5-linked α-Araf on C-4 of the Rhap. Interestingly, oral administration of YJ3A1 significantly ameliorates NASH-associated inflammation, oxidative stress and fibrosis and does not affect the liver morphology of normal mice at a dose of 50 mg/kg. The mechanism study suggests that the biological activity may associate to inactivating of high-mobility group box 1 protein (HMGB1)/TLR4/NF-κB and Akt signaling pathways by restraining the expression and release of HMGB1, thereby impeding the effect of NASH. The current findings outline a novel leading polysaccharide for new drug candidate development against NASH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Sinistral portal hypertension (SPH) may occurs in patients with pancreatic carcinoma after pancreaticoduodenectomy (PD) with spleno-mesenterico-portal (S-M-P) cofluence resection. This study aimed to evaluate outcomes with the bifurcated allogeneic vein replacement in the prevention of SPH in pancreatic carcinoma patients., Materials and Methods: A total of 81 patients were included. We retrospectively collected clinicopathological data from 66 patients underwent PD with S-M-P confluence resection in our hospital from Jan. 2011 to Dec. 2021, compared the correlation between different venous reconstruction methods using log-rank tests and clinical outcomes through univariate and multivariate analyses. Secondly, we prospectively collected clinical data and outcomes of 15 patients who underwent splenic vein reconstruction from Jan. 2021 to Jan. 2023., Results: In the retrospective study, 43 cases received reconstruction by bifurcated allogeneic vein (Reconstruction group) and 23 cases received simply SV ligation (Ligation group). The preoperative platelet counts and spleen volume were similar between two groups (P>0.05). Nevertheless, at 1 month, 3 months and 6 months after operation, the related indexes of SPH such as platelet count, spleen volume, spleen volume ratio and esophagogastric varices (EGV) grade in Reconstruction group were better than those in Ligation group (P<0.05). 6 months after surgery, the incidence of SPH in Ligation group was significantly higher than in Reconstruction group (36.4% vs. 8.1%, respectively). In the prospective study, the incidence of SPH in patients undergoing SV reconstruction was 6.7% (1/15)., Conclusion: Without compromising surgical outcomes, reconstruction of the S-M-P confluence by bifurcated allogeneic vein is a better method to avoid SPH in patients with advanced pancreatic carcinoma., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders., (© 2024. The Author(s).)

Background: A bioprosthetic valve is recommended for women of childbearing age who require cardiac valve replacement in order to minimize the risk of blood clot formation. However, it should be noted that compared to mechanical valves, bioprosthetic valves have a shorter lifespan and a higher likelihood of requiring reoperation during follow-up. To assess the long-term postoperative results, including the incidence of structural valve deterioration (SVD) and other clinical outcomes, in female patients aged 50 years and younger who underwent BalMedic bovine pericardial bioprosthetic valve replacement, a multicenter retrospective study was implemented in China., Methods: Between 2004 and 2015, a cohort of 86 female patients across three medical centers underwent the implantation of 97 bioprosthetic valves. The primary outcome measure was overall survival (OS), while the secondary outcome measures were preliminary evidence of reoperation, SVD incidence, and bioprosthetic valve-related complications., Results: In this cohort study, 21 patients (24.4%, 21/86) died, while 37 patients (43.0%, 37/86) underwent a second valve replacement. The OS rates at 5 and 10 years were 97.56% and 71.93%, respectively. Additionally, the reoperation-free rates at 5 and 10 years were 92.83% and 80.68%, respectively. Similarly, the rates of freedom from SVD at 5 and 10 years were 95.65% and 51.82%, respectively, and the average duration of bioprosthetic valve replacement in our study was 9.34±3.31 years., Conclusions: Despite the recruitment of younger female patients of child-bearing age in our cohort, the OS, reoperation-free survival, and SVD-free rates of the BalMedic bovine pericardial bioprosthetic valve were not inferior to those of the other age groups in the study or those reported in the literature., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-441/coif). A.M.Q. is a consultant for W. L. Gore and Associates, Medtronic Inc. and B. Braun, and has received consulting fees and support for attending meetings from them, not related to the submitted article. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Herein, a straightforward protocol was developed for the one-pot synthesis of N-doped lignosulfonate-derived carbons (NLDCs) with a tunable porous structure using natural amino acids-templated self-assembly strategy. Specifically, histidine was employed as a template reagent, leading to the preparation of 10-NLDC-21 with remarkable characteristics, including the large specific surface area (S BET  = 1844.5 m 2 /g), pore volume (V mes  = 1.22 cm 3 /g) and efficient adsorption for atrazine (ATZ) removal. The adsorption behavior of ATZ by NLDCs followed the Langmuir and pseudo-second-order models, suggesting a monolayer chemisorption nature of ATZ adsorption with the maximum adsorption capacity reached up to 265.77 mg/g. Furthermore, NLDCs exhibited excellent environmental adaptability and recycling performance. The robust affinity could be attributed to multi-interactions including pore filling, electrostatic attraction, hydrogen bonding and π-π stacking between the adsorbents and ATZ molecules. This approach offers a practical method for exploring innovative bio-carbon materials for sewage treatment., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Isolated partial anomalous pulmonary venous connection (PAPVC) is difficult to diagnose, and surgical indications remain controversial. We reviewed 10 y of isolated PAPVC cases., Methods: The data of patients with isolated PAPVC admitted to the Anzhen Congenital Heart Disease Department from 2010 to 2019 were reviewed retrospectively., Results: Thirty patients, aged between 4 mo and 32 y, were included in this study. Significant correlations were found between the right ventricle (RV), end-diastolic dimension Z-score (RVED-z) and age (r = 0.398, P = 0.03), and between estimated pulmonary pressure and age (r = 0.423, P = 0.02). However, no significant correlations were found between the RVED-z and the number of anomalous pulmonary veins (r = 0.347, P = 0.061), between estimated pulmonary pressure and the RVED-z (r = 0.218, P = 0.248), and between estimated pulmonary pressure and the number of anomalous veins (r = 0.225, P = 0.232). Transthoracic echocardiography (TTE) confirmed 90% of isolated PAPVC cases. Surgical repair was performed in 29 patients with RV enlargement, persistent low weight, pulmonary hypertension, or respiratory symptoms. Among the surgical patients, nine had elevated pulmonary pressure before surgery, which decreased postoperatively; no mortality or reintervention was observed. The mean duration of echocardiographic follow-up was 1.9 y., Conclusions: TTE is recommended for routine assessments, and further clarification can be obtained with computed tomography when TTE proves inconclusive for diagnosis. Transesophageal echocardiography and computed tomography are further recommended for adult patients if TTE fails to provide clear results. PAPVC should be considered as an underlying cause when unexplained RV enlargement is observed. Surgery is recommended for patients with RV enlargement, pulmonary hypertension, or respiratory symptoms., (Copyright © 2023. Published by Elsevier Inc.)

Background: Olgotrelvir is an oral antiviral with dual mechanisms of action targeting severe acute respiratory syndrome coronavirus 2 main protease (i.e., M pro ) and human cathepsin L. It has potential to serve as a single-agent treatment of coronavirus disease 2019 (Covid-19)., Methods: We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of olgotrelvir in 1212 nonhospitalized adult participants with mild to moderate Covid-19, irrespective of risk factors, who were randomly assigned to receive orally either 600 mg of olgotrelvir or placebo twice daily for 5 days. The primary and key secondary end points were time to sustained recovery of a panel of 11 Covid-19-related symptoms and the viral ribonucleic acid (RNA) load. The safety end point was incidence of treatment-emergent adverse events., Results: The baseline characteristics of 1212 participants were similar in the two groups. In the modified intention-to-treat population (567 patients in the placebo group and 558 in the olgotrelvir group), the median time to symptom recovery was 205 hours in the olgotrelvir group versus 264 hours in the placebo group (hazard ratio, 1.29; 95% confidence interval [CI], 1.13 to 1.46; P<0.001). The least squares mean (95% CI) changes of viral RNA load from baseline were -2.20 (-2.59 to -1.81) log 10 copies/ml in olgotrelvir-treated participants and -1.40 (-1.79 to -1.01) in participants receiving placebo at day 4. Skin rash (3.3%) and nausea (1.5%) were more frequent in the olgotrelvir group than in the placebo group; there were no treatment-related serious adverse events, and no deaths were reported., Conclusions: Olgotrelvir as a single-agent treatment significantly improved symptom recovery. Adverse effects were not dose limiting. (Funded by Sorrento Therapeutics, a parent company of ACEA Therapeutics; ClinicalTrials.gov number, NCT05716425.).

Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs., (© 2024. The Author(s).)

Objectives: This study aimed to explore the relationship between red blood cell distribution width (RDW) and all-cause mortality in critically ill patients undergoing intra-aortic balloon pumping (IABP) in the intensive care unit (ICU)., Methods: This study retrospectively analyzed data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The primary endpoint was the 30-day mortality rate, while the secondary endpoint was the in-hospital mortality rate. Restricted cubic splines were used to assess the dose-response relationship. The receiver operating characteristic (ROC) curve and Kaplan-Meier curve analysis were carried out to evaluate the predictive performance of RDW. Moreover, multiple logistic regression analyses and subgroup analyses were conducted to investigate the relationship between RDW and 30-day mortality. Finally, propensity score matching (PSM) was performed to adjust for the imbalance of covariates., Results: In total, 732 patients were finally identified from the MIMIC-IV database in this study. The RDW of patients in the non-survivor group was significantly higher compared with those in the survivor group (P < 0.01). Multiple logistic regression analyses corroborated RDW was an independent predictor of all-cause 30-day mortality in critically ill patients post-IABP. Meanwhile, ROC analysis identified an RDW cutoff of 14.2%. High RDW patients exhibited a 131% (OR = 2.31, 95% CI: 1.49-3.61) elevated risk of 30-day mortality after adjusting for confounders in multivariable logistic regression. After PSM, 412 patients were included in the matched cohort. In the original and matched cohorts, the high RDW group had higher 30-day and in-hospital mortality rates, as well as longer ICU stays. Lastly, the area under the ROC curve for 30-day mortality was 0.686, with an optimal cutoff point of 14.2 for RDW (sensitivity: 69.09 % and specificity: 63.32%)., Conclusion: RDW could be a simple and valuable prognostic tool to predict mortality in critically ill patients after IABP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end-stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the "gut-kidney axis," therefore, although clinical intervention to modulate the "gut-kidney axis" imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non-absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD-triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain-containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor-β (TGF-β) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4-regulated TGF-β pathway., (© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

In this study, a simple and eco-friendly method was used to treat alkaline lignin with an acidic deep eutectic solvent (DES) to obtain regenerated lignin for the efficient adsorption of pollutant dyes from aqueous environment. Based on the yield and adsorption capacity of the sorbent for these dyes, conditions such as the type and concentration of DES component, solid-to-liquid ratio, reaction time, and temperature were optimized. By characterizing and comparing alkali lignin with regenerated lignin, a series of reactions were demonstrated to occur during the DES treatment process. The performance and mechanism of methylene blue and rhodamine B adsorption on regenerated lignin were studied systematically, and the maximum adsorbed amounts were 348.29 and 551.05 mg/g at 323 K, respectively. This study provides a new strategy for the green preparation of functionalized lignin and its use in the water pollutant treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Studies have shown that terrestrial acidic polysaccharides containing carboxyl groups and seaweed sulfated polysaccharides have strong potential in anti-liver fibrosis. However, there is no investigation on the anti-liver fibrosis of fructan, a ubiquitous natural polysaccharide. The present study aimed to understand the effect of fructan in ameliorating carbon tetrachloride (CCl 4 )-induced liver fibrosis in mice. Here, an inulin-like fructan ABWW from Achyranthes bidentata Bl. was characterized by fructose enzymatic hydrolysis, methylation analysis, ESI-MS, and NMR. It was composed of →2)-β-d-Fruf-(1→ and →2)-β-d-Fruf-(1, 6→, terminated with →1)-α-d-Glcp and →2)-β-d-Fruf residues. The biological studies showed that ABWW could improve liver damage and liver fibrosis induced by CCl 4 in vivo and inhibit hepatic stellate cell (HSC) activation and migration in vitro. We further demonstrated that ABWW inhibited LX2 activation via suppressing the FAK/PI3K/AKT signaling pathway. Hence, ABWW might be a potential novel active compound for anti-fibrosis new drug development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The potential effect of removing danger-associated molecular patterns (DAMPs) from gut lymph on reducing acute lung injury (ALI) induced by gut ischemia-reperfusion injury (GIRI) is uncertain. This study aimed to investigate whether gut lymph purification (GLP) could improve GIRI-induced acute lung injury in rats by clearing danger-associated molecular patterns., Materials and Methods: Rats were divided into four groups: Sham, GIRI, GIRI + gut lymph drainage (GLD), and GIRI + GLP. After successful modeling, lung tissue samples were collected from rats for hematoxylin-eosin (HE) staining and detection of apoptotic indexes. We detected the DAMPs levels in blood and lymph samples. We observed the microstructure of AEC Ⅱ and measured the expression levels of apoptosis indexes., Results: The GIRI group showed destruction of alveolar structure, thickened alveolar walls, and inflammatory cell infiltration. This was accompanied by significantly increased levels of high mobility group protein-1 (HMGB-1) and Interleukin-6 (IL-6), while reduced levels of heat shock protein 70 (HSP 70) and Interleukin-10 (IL-10) in both lymph and serum. In contrast, the lung tissue damage in the GIRI + GLP group was significantly improved compared to the GIRI group. This was evidenced by a reduction in the expression levels of HMGB-1 and IL-6 in both lymph and serum and an increase in HSP 70 and IL-10 levels. Additionally, organelle structure of AEC II was significantly improved in the GIRI + GLP group compared to the GIRI group., Conclusions: GLP inhibits inflammation and cell apoptosis in GIRI-induced ALI by blocking the link between DAMPs and mononuclear phagocytes, reducing the severity of ALI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Serine protease inhibitors (SPIs) are abundantly reported for its inhibition against specific proteases involved in the immune responses, but SPI data related to calcareous shells are scarce. Previously, our research group has reported the proteome analysis of non-nucleated pearl powder, and a candidate matrix protein containing two Kunitz domains in the acid soluble fraction caught our attention. In the present study, the full-length cDNA sequence of HcKuSPI was obtained from Hyriopsis cumingii. HcKuSPI was specifically expressed in the mantle, with hybridization signals mainly concentrated to dorsal epithelial cells at the mantle edge and weak signals at the mantle pallium, suggesting HcKuSPI was involved in shell formation. HcKuSPI expression in the mantle was upregulated after Aeromonas hydrophila and Staphylococcus aureus challenge to extrapallial fluids (EPFs). A glutathione S transferase (GST)-HcKuSPI recombinant protein showed strong inhibitory activity against the proteases, trypsin and chymotrypsin. Moreover, HcKuSPI expression in an experimental group was significantly higher when compared with a control group during pellicle growth and crystal deposition in shell regeneration processes, while the organic shell framework of newborn prisms and nacre tablets was completely destroyed after HcKuSPI RNA interference (RNAi). Therefore, HcKuSPI secreted by the mantle may effectively neutralize excess proteases and bacterial proteases in the EPF during bacterial infection and could prevent matrix protein extracellular degradation by suppressing protease proteolytic activity, thereby ensuring a smooth shell biomineralization. In addition, GST-HcKuSPI was also crucial for crystal morphology regulation. These results have important implications for our understanding of the potential roles of SPIs during shell biomineralization., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A series of novel waterborne lignin-based epoxy resin emulsions (WLEPs) were successfully synthesized, and then the WLEPs were cured with polyamide (PA) to give formaldehyde-free wood adhesives with high-performance. The chemical structures and properties of WLEP emulsions were determined. The effects of the emulsifiers on thermal and mechanical properties of the adhesives were investigated, and the potential application of WLEPs in the formulation of plywood were also evaluated. The results demonstrated that the WLEP dispersions presented excellent storage stability (>180 days) with their viscosities range from 110 mPa·s to 470 mPa·s and particle sizes in the range of 321-696 nm, which were beneficial for the fluidity and permeability of the wood adhesives. Furthermore, the thermal and mechanical properties of adhesives could be tuned effectively by controlling the length of PEG chains. The adhesive bearing PEG 6000 exhibited the highest tensile strength of 24.0 MPa and Young's modulus of 1439 MPa. Notably, the plywood prepared with the resulting adhesives displayed good bonding performance, especially water resistance, which were much higher than the national standard requirement for exterior-grade plywood type I. These results indicated that the WLEPs could be used as sustainable alternatives for traditional formaldehyde-based wood adhesives in practical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Daedaleopsis sinensis is a fungus that grows on wood and secretes a series of enzymes to degrade cellulose, hemicellulose, and lignin and cause wood rot decay. Wood-decaying fungi have ecological, economic, edible, and medicinal functions. Furthermore, the use of microorganisms to biodegrade lignocellulose has high application value. Genome sequencing has allowed microorganisms to be analyzed from the aspects of genome characteristics, genome function annotation, metabolic pathways, and comparative genomics. Subsequently, the relevant information regarding lignocellulosic degradation has been mined by bioinformatics. Here, we sequenced and analyzed the genome of D. sinensis for the first time. A 51.67-Mb genome sequence was assembled to 24 contigs, which led to the prediction of 12,153 protein-coding genes. Kyoto Encyclopedia of Genes and Genomes database analysis of the D. sinensis data revealed that 3,831 genes are involved in almost 120 metabolic pathways. According to the Carbohydrate-Active Enzyme database, 481 enzymes are found in D. sinensis , of which glycoside hydrolases are the most abundant. The genome sequence of D. sinensis provides insights into its lignocellulosic degradation and subsequent applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ma, Wang, Jin, Ye, Tang, Si and Song.)

Background: Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance., Methods: Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (M pro ), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells., Findings: Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115. The dual mechanism of action of olgotrelvir and AC1115 was confirmed by enzyme activity inhibition assays and co-crystal structures of AC1115 with SARS-CoV-2 M pro and human CTSL. AC1115 displayed antiviral activity by inhibiting replication of all tested SARS-CoV-2 variants in cell culture systems. Olgotrelvir also inhibited viral entry into cells using SARS-CoV-2 Spike-mediated pseudotypes by inhibition of host CTSL. In the K18-hACE2 transgenic mouse model of SARS-CoV-2-mediated disease, olgotrelvir significantly reduced the virus load in the lungs, prevented body weight loss, and reduced cytokine release and lung pathologies. Olgotrelvir demonstrated potent activity against the nirmatrelvir-resistant M pro E166 mutants. Olgotrelvir showed enhanced oral bioavailability in animal models and in humans with significant plasma exposure without ritonavir. In phase I studies (ClinicalTrials.gov: NCT05364840 and NCT05523739), olgotrelvir demonstrated a favorable safety profile and antiviral activity., Conclusions: Olgotrelvir is an oral inhibitor targeting M pro and CTSL with high antiviral activity and plasma exposure and is a standalone treatment candidate for COVID-19., Funding: Funded by Sorrento Therapeutics., Competing Interests: Declaration of interests L.M., C.J., Y.K., J.L., Z.Z., L.D., and X.X. are shareholders of Sorrento Therapeutics, Inc. and employees of ACEA Therapeutics, Inc., which is a wholly owned subsidiary of Sorrento Therapeutics, Inc. N.S., C.P., K.S., H.X., L.K., M.R., M.B., and H.J. are employees and shareholders of Sorrento Therapeutics., Inc. X.Z., W.X., C.X., Y.B., L.X., Y.Z., H.Y., S.Q., Y.H., J.S., C.Z., T.L., Y. Li, N.L., Z.L., S.W., C.W., and W.S. are employees of ACEA Pharmaceutical Co. Ltd., a wholly owned subsidiary of ACEA Therapeutics, Inc. R.A. was an employee of Sorrento Therapeutics during the study. Sorrento Therapeutics has filed a PCT application (WO 2022/256434 Al) of the compound structures and the synthesis and the pre-clinical properties of olgotrelvir along with its potential treatment of COVID-19 as an antiviral agent., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Tea (Camellia sinensis) has been consumed for centuries as a traditional remedy for various metabolic diseases. The pharmacological mechanisms of many conventional medicines, including tea, often need to be clarified. Chin brick tea is a unique Chinese black tea grown in Hubei, China, rich in tea elements such as tea polyphenols and tea polysaccharides., Aim of the Study: We focus on the effects of commercial chin brick tea on non-alcoholic fatty liver disease by altering intestinal flora and its metabolite, bile acids., Materials and Methods: Targeted UPLC-MS/MS was employed to quantify the tea elements in commercial chin brick tea. In this study, we performed an integrated approach of animal experiments, 16 S rDNA, and ultra-performance liquid chromatography-tandem mass spectrometry to explore the potential mechanism of action of chin brick tea in preventing non-alcoholic fatty liver disease (NAFLD)., Results: After 14 weeks of administration, CBT extract could signiffcantly decrease the levels of body weight, liver weight, LDL-C, TC, ALT, IL-1β and IL-18, and slight increase HDL-C levels in NAFLD mice. The results indicated that the interventional impact of CBT with high-fat diet-induced NAFLD might depend on intestinal flora and its metabolites bile acids. Moreover, sequencing of 16 S rRNA genes demonstrated that CBT could signiffcantly improve the intestinal flora disorder of NAFLD mice. Speciffcally, CBT increased the levels of Lactobacillus, Alloprevotella, and Ruminococcaceae, while reducing the levels of Bacteroides in NAFLD mice. Then, a total of 23 bile acids were identified, 17 differential bile acids were obtained by screening, and CBT increase the primary bile acids/secondary bile acids ratio in NAFLD mice. Additionally, correlation analysis revealed that Bacteroides was negatively correlated with DCA and ωMCA, Lactobacillus was positively correlated with DCA and ωMCA, Bacteroides was positively correlated with NAFLD, Lactobacillus was negatively associated with NAFLD, and DCA and ωMCA were negatively correlated with NAFLD., Conclusion: CBT extract has a good interventional impact on NAFLD mice. The mechanism by which this extract exerts its action is, at least partly, related to its regulation of intestinal flora and its metabolites bile acids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Sanghuangporus , also known as "Sanghuang" in China, is a well-known genus of traditional Chinese medicinal macrofungi. To make more effective use of Sanghuangporus resources, we completed the first genome assembly and annotation of a monokaryon strain of S. weigelae in the present study. A 33.96-Mb genome sequence was assembled as 13 contigs, leading to prediction of 9377 protein-coding genes. Phylogenetic and average nucleotide identity analyses indicated that the S. weigelae genome is closely related to those of other Sanghuangporus species in evolutionary tree, which clustered in one clade. Collinearity analysis revealed a high level of collinearity of S. weigelae with S. baumii , S. vaninii , and S. sanghuang . Biosynthesis pathways potentially involved in medicinal properties, including terpenoid and polysaccharide synthesis, were identified in S. weigelae , while polysaccharides were identified as the main medicinal metabolites in S. weigelae , with flavonoids more important in Sanghuangporus than other medicinal mushroom groups. Genes encoding 332 carbohydrate-active enzymes were identified in the S. weigelae genome, including major glycoside hydrolases and glycosyltransferases predicted, revealing the robust lignocellulose degradation capacity of S. weigelae . Further, 130 genes, clustered in seven classes were annotated to encode cytochromes P450 in the S. weigelae genome. Overall, our results reveal the remarkably medicinal capacity of S. weigelae and provide new insights that will inform the study of evolution and medicinal application of S. weigelae . The data are a reference resource for the formulation of scientific and rational ecological protection policies for Sanghuangporus species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jin, Ma, Wang, Tang, Ye, Li and Si.)

Artificial intelligence technology will be increasingly applied in the oil and gas industry. The rapid development of artificial intelligence technology can solve problems such as high environmental sensitivity and complex production processes in the oil and gas industry. In recent years, emerging technologies represented by artificial intelligence have developed rapidly, assisting petroleum enterprises in digital transformation and intelligent upgrading. This article elaborates on the development trend of artificial intelligence technology. Based on the business scenarios and characteristics of the oil and gas industry, the application status of artificial intelligence technology in domestic and foreign petroleum technology service enterprises was summarized and analyzed. The application scenarios of artificial intelligence technology in the fields of dynamic analysis of oil and gas reservoirs, intelligent historical fitting, numerical simulation proxy models, and production plan optimization were analyzed with emphasis. Based on the problems and challenges faced in the development process of oil and gas reservoirs, it is proposed that petroleum enterprises should attach importance to the "three modernizations" innovation of data standardization, oil and gas field intelligence, and platform collaboration, in order to achieve more refined intelligent analysis and management of oil and gas reservoirs and quickly develop more targeted oil and gas reservoir development plans to assist in the intelligent transformation of oil and gas reservoir development. On this basis, prospects for future artificial intelligence technology are proposed, pointing out that the development of artificial intelligence technology will be faster and faster, and there will be higher demand for artificial intelligence technology in the construction of digital oil and gas fields in China in the future. The research results have important reference value for the development of the oil and gas industry., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Gualou Guizhi Decoction (GGD) has long been used as a folk medicine for the treatment of rheumatic diseases, but its bioactive components and therapeutic mechanisms are still unclear., Methods: An integrated approach using network pharmacology and molecular docking and using methotrexate as a positive control drug., Results: We obtained 157 active ingredients of GGD, 7542 RA disease targets and 49 intersecting targets. GO and KEGG enrichment analysis revealed that their functions were mainly related to cytokine active metal ion binding, enzyme binding and DNA binding, and enriched in TNF signaling pathway, T cell receptor signaling pathway, Toll-like receptor signaling pathway, RA pathway and other signaling pathways that are closely related to RA. The molecular docking results show that the effector components of GGD bind better to the core targets of RA, and some are even better than methotrexate., Conclusion: The therapeutic effect of GGD for RA is achieved by affecting the core targets such as VEGFA, IL-1β, IL6, CXCL8, CCL2, and JUN, which together interfere with the tumor necrosis factor signaling pathway and RA pathway to treat RA. The above study provides new ideas for further exploration of this classic formula in the future., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The development of atomically dispersed iron-nitrogen-carbon (Fe─N─C) catalysts as an alternative to precious platinum holds great potential for the substantial progress of a variety of oxygen reduction reaction (ORR)-associated energy conversion technologies. Nevertheless, the precise synthesis of Fe─N─C single atomic catalysts (SACs) with a high density of accessible active sites and pronounced electrocatalytic performance still remains an enormous challenge. Herein, an innovative extended Stöber method is designed for the controllable preparation of monodisperse small-sized N-doped carbon colloidal nanospheres (≈40 nm) anchoring atomically isolated Fe─N 4 sites (abbreviated as Fe-SA@N-CNSs hereafter) with a narrow size distribution and high uniformity. Benefiting from the single Fe─N 4 moieties and the unique spherical carbon substrate, the resultant Fe-SA@N-CNSs exhibit excellent ORR activity, outstanding long-term durability, and methanol tolerance in KOH electrolyte. More impressively, when further assembled into a flexible solid-state rechargeable zinc-air battery (ZAB), the Fe-SA@N-CNSs-driven ZAB delivers a higher open circuit voltage, a larger power density, and robust cycling/mechanical stability, outperforming the state-of-the-art Pt/C-based counterpart and further testifying the great potential of the as-prepared Fe-SA@N-CNSs in diverse ORR-related practical energy devices. The developed extended Stöber method provides an efficient and versatile avenue toward the preparation of a series of well-defined SACs for diverse electrocatalytic systems., (© 2023 Wiley-VCH GmbH.)

Ethnopharmacological Relevance: Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Chaenomeles speciosa (CSP) (Chinese Pinyin: mugua) is a medicinal and food herb that has long been used as a folk medicine for rheumatic diseases, yet its bioactive components and therapeutic mechanisms are not clear., Aim of the Study: Exploring anti-inflammatory and chondroprotective effects of CSP on rheumatoid arthritis (RA) and its possible targets of action., Materials and Methods: In this study, we performed an integrated approach of network pharmacology, molecular docking and experimental studies to explore the potential mechanism of action of CSP in the treatment of cartilage damage in RA., Results: Studies have shown that Quercetin, ent-Epicatechin and Mairin may be the main active compounds of CSP in the treatment of RA, while AKT1, VEGFA, IL-1β, IL-6, MMP9 etc. are considered as core target proteins to which the main active compounds in CSP bind, as further confirmed by molecular docking. In addition, the potential molecular mechanism of CSP for the treatment of cartilage damage in RA predicted by network pharmacology analysis was validated by in vivo experiments. CSP was found to downregulate the expression of AKT1, VEGFA, IL-1β, IL-6, MMP9, ICAM1, VCAM1, MMP3, MMP13 and TNF-α and increase the expression of COL-2 in the joint tissue of Glucose-6-Phosphate Isomerase (G6PI) model mice. Thus CSP contributes to the treatment of rheumatoid arthritis cartilage destruction., Conclusion: This study showed that CSP has multi-component, multi-target and multi-pathway characteristics in treating cartilage damage in RA, which can achieve the effect of treating RA by inhibiting the expression of inflammatory factors, reducing neovascularization and alleviating the damage to cartilage caused by the diffusion of synovial vascular opacities, and reducing the degradation of cartilage by MMPs to play a protective role in RA cartilage damage. In conclusion, this study indicates that CSP is a candidate Chinese medicine for further research in treating cartilage damage in RA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Correctly distinguishing mass-forming chronic pancreatitis (MFCP) from pancreatic cancer (PC) is of clinical significance to determine optimal therapy and improve the prognosis of patients. According to research, inflammation status in PC is different from that in MFCP. Mean platelet volume/platelet ratio (MPR) is a platelet-related inflammation index which has been proven to be valuable in the diagnosis and prognosis of various malignant cancers due to the change in mean platelet volume and platelet count under abnormal inflammatory conditions caused by tumors. Thus, we conducted this study to investigate the clinical value of MPR in distinguishing MFCP from PC., Methods: We retrospectively analyzed the data of 422 patients who were suspected to have PC during imaging examination at our department from January 2012 to December 2021. Included patients were divided into the PC ( n = 383) and MFCP groups ( n = 39), according to their pathological diagnosis. Clinical data including MPR were compared within these two groups and the diagnostic value was explored using logistic regression. The ROC curve between MPR and PC occurrence was drawn and an optimal cut-off value was obtained. Propensity score matching was applied to match MFCP patients with PC patients according to their age and carbohydrate antigen 19-9 (CA19-9). Differences in MPR between groups were compared to verify our findings., Results: The area under the ROC curve between MPR and PC occurrence was 0.728 (95%CI: 0.652-0.805) and the optimal cut-off value was 0.045 with a 69.2% sensitivity and 68.0% accuracy. For all the included patients, MPRs in the MFCP and PC groups were 0.04 (0.04, 0.06) and 0.06 (0.04, 0.07), respectively ( p = 0.005). In patients with matching propensity scores, MPRs in the MFCP and PC groups were 0.04 (0.03, 0.06) and 0.06 (0.05, 0.08), respectively ( p = 0.005). Multiple logistic regression in all included patients and matched patients confirmed MPR and CA19-9 as independent risk markers in distinguishing PC. Combining CA19-9 with MPR can increase the sensitivity and accuracy in diagnosing PC to 93.2% and 89.5%, respectively., Conclusion: MPR in PC patients is significantly higher than that in MFCP patients and may be adopted as a potential indicator to distinguish MFCP and PC. Its differential diagnosis capacity can be improved if combined with CA19-9.

A visible-light-driven desaturative β-alkoxyoxalyation of N-aryl cyclic amines with difluoromethyl bromides and H 2 O has been reported. This tandem reaction is triggered by homolysis of the C-Br bond to produce the difuoroalkyl radical, which undergoes the subsequent defluorinated β-alkoxyoxalylation cascades to afford a wide range of β-ketoester/ketoamides substituted enamines. The prominent feature of this reaction contains photocatalyst-free, transition-metal free, and mild conditions. The 18 O labeling experiment disclosed that H 2 O is the oxygen source of the carbonyl unit.

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a &quot;traditional Chinese medicine-active component-common target-disease&quot; network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P&lt;0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P&lt;0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.

Opioids, such as morphine, are the most potent drugs used to treat pain. Long-term use results in high tolerance to morphine. High mobility group box-1 (HMGB1) has been shown to participate in neuropathic or inflammatory pain, but its role in morphine tolerance is unclear. In this study, we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days. We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1. HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4 receptor expression in microglia, thereby inducing morphine tolerance. Glycyrrhizin, an HMGB1 inhibitor, markedly attenuated chronic morphine tolerance in the mouse model. Finally, compound C (adenosine 5'-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin (heme oxygenase-1 inhibitor) alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tolerance, and alleviated morphine tolerance in the mouse model. These findings suggest that morphine induces HMGB1 release via the adenosine 5'-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway, and that inhibiting this signaling pathway can effectively reduce morphine tolerance., Competing Interests: None

The accumulation of amyloid β (Aβ) containing senile plaques is one of the key histopathological hallmarks of Alzheimer's disease (AD). Increasing evidences demonstrated the important role of autophagy in Aβ clearance. Recent studies implied that extracts from Semiaquilegia adoxoides (DC.) Makino could ameliorate the memory of D-galactose induced aging mice. However, the bioactive substance and underlying mechanism remains unknown. Thus, the present study sought to explore the effects of a novel homogenous peptidoglycan on Aβ 42 secretion and the underlying mechanism. Briefly, we extracted a novel peptidoglycan named SA02C using hot water extraction and alcohol precipitation with the Mw of 13.72 kDa. SA02C contains 73.33% carbohydrate and 27.83% protein. The structure characterization revealed that its glycan part might mainly composed of galacturonic acid with minor rhamnose in backbone, and branched with glucose, galactose, arabinose, xylose and galacturonic acid. The protein or peptide moiety in SA02C was bonded to the polysaccharide via threonine. Bioactivities test showed that SA02C could reduce Aβ 42 production in a dose dependent manner with no obvious cytotoxicity. Mechanism study demonstrated that SA02C could modulate APP processing by upregulating the expression of ADAM10, sAPPα and downregulating BACE1, sAPPβ. Furthermore, SA02C also could stimulate autophagy by promoting the expression of the markers of autophagy such as LC3B and ATG5, resulting in the promotion of Aβ 42 phagocytosis., Competing Interests: Declaration of Competing Interest The authors indicated no conflicts of interest with regard to the content of this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Achyranthes bidentata (A. bidentata) is a famous traditional Chinese medicine (TGM) for treatment osteoporosis. Polysaccharides, a major factor for shaping the gut microbiota, are the primary ingredients of A. bidentata. However, bioactivity of A. bidentata polysaccharide on human gut microbiota (HGM) remains unknown. Here, a homogeneous pectic polysaccharide A23-1 with average molecular weight of 93.085 kDa was extracted and purified from A. bidentata. And A23-1 was compsed of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 7.26: 0.76: 5.12: 2.54: 23.51: 60.81. GC-MS, partial acid hydrolysis and NMR results indicated the backbone of A23-1 was composed of 1, 2, 4-Rhap and 1, 4-GlapA, while the branches were composed of galactose, arabinose, glucose and glucuronic acid. Further, A23-1 was found to be degraded into monosaccharides and fragments. Taking Bacteroides thetaiotaomicron (BT) as a model, we suggested three polysaccharide utilization loci (PULs) might be involved in the A23-1 degradation. Degraded products generated by BO might not support the growth of probiotics. Besides, acetate and propionate as the main end products were generated by Bacteroides spp. and probiotics utilizing A23-1. These findings suggested A23-1 was possible one of food sources of human gut Bacteroides spp., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Crystallization selectivity is an important principle in polymorph control. Ribavirin Form I, Form II, DMSO solvate, and amorphous ribavirin are prepared, and the short-range order similarities between these solid forms and ribavirin aqueous solution and DMSO solution are compared via mid-frequency Raman difference spectra (MFRDS). The crystallization process from amorphous ribavirin to Form I and from solution to amorphous phase is explained. Reasons for the difficulty in preparing the DMSO solvate are proposed. The rationale provided for the crystallization selectivity provides a foundation for the synthesis of metastable phases with a robust and convenient method.

Gold-catalyzed regioselective hydrofluorination of alkynes using aqueous HF has been achieved by employing an amide directing group. For both aryl- and alkyl-substituted propargylamines, the fluorination occurred at the site distal to the amino group.

Gardenia jasminoides (GJ) is a classic edible medicine in China of which the fruit has been proved to alleviate liver damage. We hypothesized whether polysaccharide in the fruit could have comparable bioactivity. To address this, a novel polysaccharide GJE0.2-2, is purified from the fruit of Gardenia jasminoides. Indeed, GJE0.2-2 may attenuate CCl 4 -induced liver fibrosis in mice and impede the expression of critical fibrogenesis associated molecules such as α-SMA, FN1, and Collagen I induced by TGF-β in human hepatic stellate LX-2 cells. Mechanism studies suggest that this bioactivity may be implicated in TLR4/NF-κB signaling pathway via directly binding to TLR4. The structure characterization shows that the backbone of this polysaccharide is mainly composed of galacturonic acid with minor rhamnose, branched with galactose and arabinose, galacturonic acid, and esterified hexenuronic acid (HexpA). These findings provide evidence for a novel pectin-linked polysaccharide-based new drug candidate development for liver fibrosis therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Glutamine (Gln) is the most widely acting and abundant amino acid in the body and has anti-inflammatory properties, regulates body metabolism, and improves immune function. However, the mechanism of Gln's effect on hyperoxic lung injury in neonatal rats is unclear. Therefore, this work focused on examining Gln's function in lung injury of newborn rats mediated by hyperoxia and the underlying mechanism. We examined body mass and ratio of wet-to-dry lung tissue weights of neonatal rats. Hematoxylin and eosin (HE) staining was performed to examine histopathological alterations of lung tissues. In addition, enzyme-linked immunoassay (ELISA) was conducted to measure pro-inflammatory cytokine levels within bronchoalveolar lavage fluid (BALF). Apoptosis of lung tissues was observed using TUNEL assay. Western blotting was performed for detecting endoplasmic reticulum stress (ERS)-associated protein levels. The results showed that Gln promoted body weight gain, significantly reduced pathological damage and oxidative stress in lung tissue, and improved lung function in neonatal rats. Gln reduced pro-inflammatory cytokine release as well as inflammatory cell production in BALF and inhibited apoptosis in lung tissue cells. Furthermore, we found that Gln could downregulate ERS-associated protein levels (GRP78, Caspase-12, CHOP) and inhibit c-Jun N-terminal kinase (JNK) and inositol-requiring enzyme 1 alpha (IRE1α) phosphorylation. These results in an animal model of bronchopulmonary dysplasia (BPD) suggest that Gln may have a therapeutic effect on BPD by reducing lung inflammation, oxidative stress, and apoptosis and improving lung function; its mechanism of action may be related to the inhibition of the IRE1α/JNK pathway., (© 2023. The Author(s) under exclusive licence to University of Navarra.)

Objective: To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier., Methods: Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed., Results: The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months., Conclusion: Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery., (Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

A facile and novel strategy has been developed for synthesis of 24-(R)-hydroxycholesterol, a key intermediate of tacalcitol, starting from 24-dehydrocholesterol in seven steps with 48.2% overall yield and high diastereomer ratio. Photocatalytic oxidation of olefins by employing inexpensive Rose Bengal as photosensitizer and air as the sole oxidant for the preparation of Δ 5,25 -3β-Hydroxycholestadiene-24-one-3-acetate is the key step in this synthetic route. This developed strategy features mild conditions, satisfied total yield and excellent stereoselectivity (24-R/S = 97.7:2.3), providing a novel access to the 24-(R)-hydroxycholesterol., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Phylogenetic and morphological analyses on Rigidoporus were carried out. The genus Rigidoporus ( Hymenochaetales , Basidiomycota ), typified by R. microporus (Fr.) Overeem. (synonym Polyporus micromegas Mont.), was established by Murrill in 1905. The genus is mainly characterized by annual to perennial, resupinate, effused-reflexed to pileate or stipitate basidiomata with azonate or concentrically zonate and sulcate upper surface, a monomitic to pseudo-dimitic hyphal structure, simple-septate generative hyphae, and ellipsoid to globose basidiospores. Phylogeny on species of the genus is reconstructed with two loci DNA sequences including the internal transcribed spacer regions and the large subunit. Three new species in Rigidoporus are described and illustrated from Asia, and one new combination in the genus is proposed. The main morphological characteristics of the currently accepted species of Rigidoporus are provided., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Vlasák, Jin and Si.)

Age-related bone loss is unavoidable and effective safe drugs are in great need. The fruit of Lycium barbarum was recorded to strengthen bones in the "Ben Cao Gang Mu (Compendium of Materia Medica)". However, there lacks scientific explanation. Herein, we investigated L. barbarum water extract (LBE), L. barbarum polysaccharides (LBP) and the homogeneous polysaccharide LBP1C-2 on the bone loss in adult mouse, aging mouse and ovariectomized mouse models. LBE, LBP and LBP1C-2 all markedly increased bone mass and bone strength in these models and promoted osteoblast proliferation, differentiation and ossification. Mechanistic studies showed that LBP1C-2 binds directly to the BMP receptors (BMPRIA and BMPRII) and noggin, activates the phosphorylation of Smad and disrupts the interaction between noggin and BMPs. Our results clearly elucidate the mechanism, the critical component and the direct targets of L. barbarum and provide potentially safe natural products and new drug candidate against age-related bone loss., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)