Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

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

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

NADPH oxidase 2 mediates cardiac sympathetic denervation and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced cardiomyopathy.

Doxorubicin has been used extensively as a potent anticancer agent, but its clinical use is limited by its cardiotoxicity. However, the underlying mechanisms remain to be fully elucidated. In this study, we tested whether NADPH oxidase 2 (Nox2) mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced heart failure. Nox2 knockout (KO) and wild-type (WT) mice were randomly assigned to receive a single injection of doxorubicin (15 mg/kg, i.p.) or saline. WT doxorubicin mice exhibited the decreases in survival rate, left ventricular (LV) wall thickness and LV fractional shortening and the increase in the lung wet-to-dry weight ratio 1 week after the injections. These alterations were attenuated in Nox2 KO doxorubicin mice. In WT doxorubicin mice, myocardial oxidative stress was increased, myocardial noradrenergic nerve fibers were reduced, myocardial expression of PGP9.5, GAP43, tyrosine hydroxylase and norepinephrine transporter was decreased, and these changes were prevented in Nox2 KO doxorubicin mice. Myocyte autophagy was increased and myocyte size was decreased in WT doxorubicin mice, but not in Nox2 KO doxorubicin mice. Nox2 mediates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy-both of which contribute to cardiac atrophy and failure after doxorubicin treatment.

Delivery Strategies, Structural Modification, and Pharmacological Mechanisms of Honokiol: A Comprehensive Review.

Honokiol (HK) is a traditional Chinese herbal bioactive compound that originates mainly from the Magnolia species, traditionally used to treat anxiety and stroke, as well as alleviation of flu symptoms. This natural product and its derivatives displayed diverse biological activities, including anticancer, antioxidant, anti-inflammatory, neuroprotective, and antimicrobial activities. However, its poor bioavailability and pharmacological activity require primary consideration in the development of HK-based drugs. Recent innovative HK formulations based on the nanotechnology approach allowed for improvement in both bioavailability and therapeutic efficacy. Chemical derivation and drug combination are also effective strategies to ameliorate the drawbacks of HK. In recent years, studies on HK derivatives and compositions have made great progress in the treatment of cancer, inflammation, bacterial infection, cardiovascular, and cerebrovascular diseases, demonstrating better activity than HK. The objective of this review is an examination of the recent developments in the field of pharmacological activity of HK and its drug-related issues, and approaches to improve its physicochemical and biological properties, including solubility, stability, and bioavailability. Recent patents and the ongoing clinical trials in HK are also summarized.

Role of miRNAs in glucose metabolism of mouse cumulus cells†.

It is known that the oocyte has a limited capacity to acquire and metabolize glucose, and it must rely on cumulus cells (CCs) to take up glucose and produce pyruvate for use to produce ATP through oxidative phosphorylation. We therefore propose that miRNAs might regulate glucose metabolism (GM) in CCs and might be used as markers for oocyte quality assessment. Here, mouse CC models with impaired glycolysis or pentose phosphate pathway (PPP) were established, and miRNAs targeting the key enzymes in glycolysis/PPP were predicted using the miRNA target prediction databases. Expression of the predicted miRNAs was compared between CCs with normal and impaired glycolysis/PPP to identify candidate miRNAs. Function of the candidate miRNAs was validated by transfecting CCs or cumulus-oocyte-complexes (COCs) with miRNA inhibitors and observing effects on glucose metabolites of CCs and on competence of oocytes. The results validated that miR-23b-3p, let-7b-5p, 34b-5p and 145a-5p inhibited glycolysis, and miR-24-3p, 3078-3p,183-5p and 7001-5p inhibited PPP of CCs. Our observation using a more physiologically relevant model (intact cultured COCs) further validated the four glycolysis-targeting miRNAs we identified. Furthermore, miR-let-7b-5p, 34b-5p and 145a-5p may also inhibit PPP, as they decreased the production of glucose-6-phosphate. In conclusion, miRNAs play critical roles in GM of CCs and may be used as markers for oocyte quality assessment. Summary sentence:  We identified and validated eight new miRNAs that inhibit glycolysis and/or pentose phosphate pathways in cumulus cells (CCs) suggesting that miRNAs play critical roles in glucose metabolism of CCs and may be used for oocyte quality markers.

Bottom-Up Construction of Ni(II)-Incorporated Covalent Organic Framework for Metallaphotoredox Catalysis.

The construction of an all-in-one catalyst, in which the photosensitizer and the transition metal site are close to each other, is important for improving the efficiency of metallaphotoredox catalysis. However, the development of convenient synthetic strategies for the precise construction of an all-in-one catalyst remains a challenging task due to the requirement of precise installation of the catalytic sites. Herein, we have successfully established a facile bottom-up strategy for the direct synthesis of Ni(II)-incorporated covalent organic framework (COF), named LZU-713@Ni, as a versatile all-in-one metallaphotoredox catalyst. LZU-713@Ni showed excellent activity and recyclability in the photoredox/nickel-catalyzed C-O, C-S, and C-P cross-coupling reactions. Notably, this catalyst displayed a better catalytic activity than its homogeneous analogues, physically mixed dual catalyst system, and, especially, LZU-713/Ni which was prepared through post-synthetic modification. The improved catalytic efficiency of LZU-713@Ni should be attributed to the implementation of bottom-up strategy, which incorporated the fixed, ordered, and abundant catalytic sites into its framework. This work sheds new light on the exploration of concise and effective strategies for the construction of multifunctional COF-based photocatalysts.

Acute exacerbation of postoperative idiopathic pulmonary fibrosis in a patient with lung cancer caused by invasive mechanical ventilation: A case report.

Study design and objection: Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disease characterized by damage to alveolar epithelial cells and abnormal deposition of the extracellular matrix. Although the disease course for most patients with IPF is progressive, in some cases the disease may appear as an acute exacerbation. Mechanical ventilation life support plays an important role in the treatment of patients with IPF but is associated with an increased risk of acute exacerbation of IPF (AE-IPF). Treatment is controversial and is not supported by sufficient clinical evidence. AE-IPF after lung cancer surgery is extremely rare, and the etiology and mechanism remain unclear, and its clinical manifestations are very similar to acute pulmonary edema and are easily misdiagnosed. Summaryof background data: We describe a 66-year-old male patient with IPF complicated with lung cancer who underwent thoracoscopic resection of the right upper lobe of the lung. Seventy-two hours after surgery, chest computed tomography indicated that AE-IPF in the mechanically ventilated lung was significantly greater than that in the operated lung. The patient's own lung was used as a control and proved that mechanical ventilation can lead to AE-IPF. Results and conclusions: By highlighting the clinical characteristics of patients with acute exacerbation of idiopathic pulmonary fibrosis, this article will enhance the vigilance of clinicians on AE-IPF caused by mechanical ventilation. Importantly, preoperative nintedanib therapy should be applied in advance to prevent AE-IPF on in patients with mild IPF. Precise pulmonary protective ventilation strategies need to be formulated for patients with IPF to reduce mortality.

Novel hydrophilic bistriazolyl-phenanthroline ligands with improved solubility and performance in An/Ln separations.

Two novel bistriazolyl-phenanthroline (BTrzPhen) ligands, bearing benzene-sulphonate (DS-BTrzPhen) and amino-acidic (DAA-BTrzPhen) hydrophilizing moieties were developed and found to be more soluble in aqueous acidic media with improved selectivity for Am(iii) over Eu(iii) in solvent extraction studies having SFEu/Am values reaching >300. The remarkable activities of both ligands suggest that BTrzPhen ligands are generally still worth exploring and improving.

Valorization of the pelagic Sargassum horneri for co-production of erythritol and alginate oligosaccharides.

Pelagic Sargassum is invasive macroalgae with huge biomass. To produce bulk chemicals with profit from the biomass, innovative strategies need to be developed. In this study, maximum saccharification yield of Sargassum horneri biomass was obtained with the combined use of 3% alginate lyase and 3% cellulase, releasing 20.83 g/L glucose and 1.73 g/L mannitol at a 1:6 feed ratio. Subsequently, the crude S. horneri hydrolysate (pH 3.0) was proved most suitable for erythritol production of Yarrowia lipolytica strain. After 60 h fermentation in a 10-L fermenter, the erythritol concentration reached 18.42 g/L with a yield of 0.82 g/g; while the concentration of alginate oligosaccharides (AOS) was 37.56 g/L. Finally, AOS with a purity of 93.4% were obtained by ethanol precipitation, and erythritol was harvested via crystallization. This proposed strategy demonstrates the feasibility of transforming invasive Sargassum into two high-value chemicals for the first time.

Circulating TP73-AS1 and CRNDE serve as diagnostic and prognostic biomarkers for non-small cell lung cancer.

BACKGROUND: Circulating long noncoding RNAs (lncRNAs) are considered a new class of biomarkers for the diagnosis and prognosis of various malignancies. We aimed to identify circulating lncRNAs as biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). METHODS: The expression of 14 candidate lncRNAs was measured in matched cancer and ipsilateral normal lung tissues of 20 patients with NSCLC using quantitative reverse-transcription PCR. In plasma samples from training and testing sets, significantly and aberrantly expressed lncRNAs, TA73-AS1 and CRNDE, were further analyzed. Receiver operating characteristic (ROC) curves were constructed, and the areas under the ROC curves (AUC) were obtained to assess diagnostic performance. The Kaplan-Meier survival analysis was used to assess the impact of plasma TA73-AS1 and CRNDE expression on tumor-free survival (TFS) of patients with NSCLC. The effect of TP73-AS1 expression on NSCLC cells was investigated in vitro. RESULTS: AUC values of plasma TA73-AS1 and CRNDE were 0.822 and 0.815 in the training set and 0.843 and 0.804 in the testing set, respectively, to distinguish NSCLC from healthy controls. The combination of plasma TP73-AS1, CRNDE, and two classical tumor markers, carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1), showed excellent diagnostic performance for NSCLC (AUC =0.927 in the training set; AUC = 0.925 in the testing set). Furthermore, the high expression of the two plasma lncRNAs correlated with worse TFS in patients with NSCLC. In vitro cell model studies revealed that TP73-AS1 overexpression facilitated NSCLC cell survival, invasion, and migration. CONCLUSION: Circulating TP73-AS1 and CRNDE could be potential biomarkers for the diagnosis and prognostic prediction of NSCLC.

Regional location of lymph node metastases predicts survival in patients with de novo metastatic prostate cancer.

To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases in men with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients between November 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classified into 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymph node (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and liver metastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane (below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostate cancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showed that patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, and patients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those in G5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015; median OS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC, and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicate that the farther the NRLNs are located, the more aggressive the disease is.

Use self-gravitation traction to treat lumbar disc herniation: Study protocol for a double-center, single-blind randomized controlled trial.

BACKGROUND: Self-gravitation traction is 1 of the most popular treatments for lumbar disc herniation (LDH). This study aims to evaluate the effectiveness and safety of the self-gravitation traction device in the treatment of LDH and to confirm its positive treatment effect. METHODOLOGY: This trial is designed as a pragmatic double-center, single-blind, and 3-arm (1:1:1 ratio) randomized controlled trial. The recruited patients with LDH will be randomly allocated to the intervention (traction weight is 40% or 60% of its body weight) or control (traction weight is 20% of its body weight) group. Traction will be completed within 6 consecutive weeks (3 times a week), with 10 minutes of traction for the first 3 weeks, 20 minutes of traction for the next 3 weeks. After the experiment is completed, we will establish an experiment-related database. The software of SPSS, version 21 (SPSS Inc. Chicago, IL) will be used for statistical analysis, and measurement data will be expressed via mean and standard deviation (mean ±â€…SD). DISCUSSION: Once the trial is completed, we will publish the study in journals in both Chinese and English to promote the dissemination and use of the results. In addition, we also plan to promote the research results at various academic conferences both domestically and internationally.

Corynebacterium striatum Endocarditis After Renal Transplantation Confirmed by Metagenomic Next-Generation Sequencing: Case Report and Literature Review.

Background: Potent immune-suppressive therapy has been demonstrated to increase the risk of infective endocarditis (IE) in renal recipients. Reports of Corynebacterium striatum (C. striatum) endocarditis in renal recipients are scarce, thus limiting understanding of the disease. Case Presentation: We describe a case of native valve endocarditis caused by C. striatum in a 35-year-old male patient. The young man with end-stage renal failure underwent kidney transplantation because of autosomal dominant polycystic kidney disease. Ceftazidime was administered after the surgery according to routine procedures, and the patient was discharged on the 14th day after the surgery without any evidence of infection. The patient experienced fever on the 56th day, and Corynebacterium was cultured from the patient's blood, in agreement with the results of testing of the donor kidney preservation solution. On the 64th day, multiple thromboses were found in the right external iliac artery, particularly around the anastomotic orifice of the transplanted renal artery. Vegetation was found in the posterior mitral valve tip on the 65th day. The patient had symptoms of persistent angina pectoris and chest tightness and underwent mitral valve replacement and vegetative resection. The patient eventually died. C. striatum was detected in the mitral valve and vegetation tissue with metagenomic next-generation sequencing. Conclusion: C. striatum may cause endocarditis and endanger patients' lives and thus warrants greater attention. Genotypic assays such as metagenomic next-generation sequencing are demonstrated to be effective in confirming species identity. Adequate anti-infection therapy and early surgery are required after IE is discovered.

Drug Repurposing by Siderophore Conjugation: Synthesis and Biological Evaluation of Siderophore-Methotrexate Conjugates as Antibiotics.

Drug repurposing is considered a promising strategy to fight antimicrobial resistance (AMR). Methotrexate (Mtx), a classical anticancer drug, could strongly inhibit bacterial dihydrofolate reductase (DHFR). However, its poor permeability into bacteria and potent human cytotoxicity make it unsuitable as an antibacterial. Herein, we reported the conjugation of Mtx with a siderophore to construct "Trojan horse" antibacterials. The most potent conjugate 8 with nanomolar minimum inhibitory concentration (MIC) values exhibited over 1.00×103 -fold improved activity against Gram-positive Streptococcus pneumoniae (S. pneumoniae) and Gram-negative Yersinia enterocolitica (Y. enterocolitica) compared with Mtx, while possessing 2.31×103 -fold reduced human cytotoxicity, resulting in 2.08×106 -fold improvements in the therapeutic index. This proof-of-principle study verifies that siderophore conjugation is an effective strategy for developing new antibacterials from anticancer drugs.

Production, Biosynthesis, and Commercial Applications of Fatty Acids From Oleaginous Fungi.

Oleaginous fungi (including fungus-like protists) are attractive in lipid production due to their short growth cycle, large biomass and high yield of lipids. Some typical oleaginous fungi including Galactomyces geotrichum, Thraustochytrids, Mortierella isabellina, and Mucor circinelloides, have been well studied for the ability to accumulate fatty acids with commercial application. Here, we review recent progress toward fermentation, extraction, of fungal fatty acids. To reduce cost of the fatty acids, fatty acid productions from raw materials were also summarized. Then, the synthesis mechanism of fatty acids was introduced. We also review recent studies of the metabolic engineering strategies have been developed as efficient tools in oleaginous fungi to overcome the biochemical limit and to improve production efficiency of the special fatty acids. It also can be predictable that metabolic engineering can further enhance biosynthesis of fatty acids and change the storage mode of fatty acids.

Optimization of the Natural Product Calothrixin A to Discover Novel Dual Topoisomerase I and II Inhibitors with Improved Anticancer Activity.

Calothrixin A (CAA) is a dual Topo I and II inhibitor but exhibits poor antiproliferative activities and water solubility. Herein, a library of novel CAA analogues was synthesized. Among them, compound F16 exhibited superior water solubility (>5 mg/mL) as compared to CAA (<5 µg/mL). The mechanism of action studies confirmed that F16 acted as a dual Topo I and II poison. Furthermore, F16 displayed potent antiproliferative activities against high Topo I and II expression cell lines A375 and HCT116, with IC50 values of 20 and 50 nM, respectively. In xenograft models, F16 reduced the tumor growth at a dose of 10 or 20 mg/kg without apparent effect on the mouse weight, while the clinically used Topo II inhibitor VP-16 dramatically reduced the mouse weight. Collectively, our data demonstrated that F16 could be a promising lead for the development of novel dual Topo I and II antitumor agents.

Fused-Ring-Linked Covalent Organic Frameworks.

The development of linkage chemistry in the research area of covalent organic frameworks (COFs) is fundamentally important for creating robust structures with high crystallinity and diversified functionality. We reach herein a new level of complexity and controllability in linkage chemistry by achieving the first synthesis of fused-ring-linked COFs. A series of bicyclic pyrano[4,3-b]pyridine COFs have been constructed via a cascade protocol involving Schiff-base condensation, intramolecular [4 + 2] cycloaddition, and dehydroaromatization. With a broad scope of Brønsted or Lewis acids as the catalyst, the designed monomers, that is, O-propargylic salicylaldehydes and multitopic anilines, were converted into the fused-ring-linked frameworks in a one-pot fashion. The obtained COFs exhibited excellence in terms of purity, stability, and crystallinity, as comprehensively characterized by solid-state nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction, high-resolution transmission electron microscopy, and so on. Specifically, the highly selective formation (>94%) of pyrano[4,3-b]pyridine linkage was verified by quantitative NMR measurements combined with 13C-labeling synthesis. Moreover, the fused-ring linkage possesses fully locked conformation, which benefits to the high crystallinity observed for these COFs. Advancing the linkage chemistry from the formation of solo bonds or single rings to that of fused rings, this study has opened up new possibilities for the concise construction of sophisticated COF structures with high controllability.

Risk factors of early liver dysfunction after liver transplantation using grafts from donation after citizen death donors.

BACKGROUND: As an early complication after liver transplantation, early allograft dysfunction (EAD) indicates a poor prognosis. This study analyzes the risk factors related to early allograft dysfunction (EAD) after liver transplantation using grafts from donation after citizen death (DCD) to provide a reference for the prevention of EAD after DCD liver transplantation. METHODS: A total of 32 patients who underwent DCD liver transplantation in the organ transplantation center of our hospital from September 2013 to January 2021 were enrolled in this study. The patients were divided into the EAD group and non-EAD group according to whether they developed EAD after transplantation. The general data of the donors and recipients before transplantation, intraoperative conditions, and clinical data within one week after transplantation were compared between the two groups, and related complications were statistically analyzed. The follow-up time was one week postoperatively or, if they died within the first week postoperatively, until the patient died. RESULTS: The subjects included 10 females and 22 males, and the incidence of postoperative EAD was 25% (8/32). Four patients (12%) had primary malignant tumors (primary liver cancer and cholangiocarcinoma), and five donors (15%) had fatty liver. The univariate analysis revealed that the donor BMI (P = 0.005), degree of fatty liver (P = 0.025), aspartate aminotransferase (P = 0.001), alanine aminotransferase (P < 0.001), and total bilirubin (P = 0.009) were related to the occurrence of EAD after DCD liver transplantation. By analyzing the correlation between the incidence EAD and postoperative complications after liver transplantation using grafts from DCD donors, it was shown that the incidence of primary nonfunction (PNF) is related to EAD (P = 0.024). CONCLUSION: Donor BMI, the degree of fatty liver, and preoperative liver function are risk factors for EAD after DCD liver transplantation, and the occurrence of EAD after DCD liver transplantation significantly increases the probability of PNF.

Laminaria japonica hydrolysate promotes fucoxanthin accumulation in Phaeodactylum tricornutum.

Fucoxanthin (Fx) has gained a growing attention due to the remarkable biological activities. The limited biomass of was the restrictive factor for Fx production in Phaeodactylum tricornutum. In this study, Laminaria japonica hydrolysate (LPH) with a low addition proportion of 1.5 ml/L, was proved to promote fucoxanthin accumulation and cell growth simultaneously. Fx topped at 27.9 mg/L after 10-d cultivation in the LPH group, with a biomass of 1.59 g/L and a Fx content of 17.55 mg/g. Three key plant hormones in LPH were screened responsible for promoting fucoxanthin accumulation. Transcriptomic analysis and qRT-PCR results showed that genes related to Fx formation were generally up- regulated. The study demonstrated that LPH addition was a feasible and efficient strategy to enhance production of fucoxanthin, facilitating the scale-up production of Fx in autotrophic culture.