Tripedal DNA Walker as a Signal Amplifier Combined with a Potential-Resolved Multicolor Electrochemiluminescence Strategy for Ultrasensitive Detection of Prostate Cancer Staging Indicators.

A multicolor electrochemiluminescence (ECL) biosensor based on a closed bipolar electrode (BPE) array was proposed for the rapid and intuitive analysis of three prostate cancer staging indicators. First, [Irpic-OMe], [Ir(ppy)2(acac)], and [Ru(bpy)3]2+ were applied as blue, green, and red ECL emitters, respectively, whose mixed ECL emission colors covered the whole visible region by varying the applied voltages. Afterward, we designed a simple Mg2+-dependent DNAzyme (MNAzyme)-driven tripedal DNA walker (TD walker) to release three output DNAs. Immediately after, three output DNAs were added to the cathodic reservoirs of the BPE for incubation. After that, we found that the emission colors from the anode of the BPE changed as a driving voltage of 8.0 V was applied, mainly due to changes in the interfacial potential and faradaic currents at the two poles of the BPE. Via optimization of the experimental parameters, cutoff values of such three indicators at different clinical stages could be identified instantly with the naked eye, and standard precision swatches with multiple indicators could be prepared. Finally, in order to precisely determine the prostate cancer stage, the multicolor ECL device was used for clinical analysis, and the resulting images were then compared with standard swatches, laying the way for accurate prostate cancer therapy.

Mogroside V reduced the excessive endoplasmic reticulum stress and mitigated the Ulcerative colitis induced by dextran sulfate sodium in mice.

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory condition of the colon, characterized by repeated attacks, a lack of effective treatment options, and significant physical and mental health complications for patients. The endoplasmic reticulum (ER) is a vital intracellular organelle in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is induced when the body is exposed to adverse external stimuli. Numerous studies have shown that ERS-induced apoptosis plays a vital role in the pathogenesis of UC. Mogroside V (MV), an active ingredient of Monk fruit, has demonstrated excellent anti-inflammatory and antioxidant effects. In this study, we investigated the therapeutic effects of MV on dextran sulfate sodium (DSS)-induced UC and its potential mechanisms based on ERS. The results showed that MV exerted a protective effect against DSS-induced UC in mice as reflected by reduced DAI scores, increased colon length, reduced histological scores of the colon, and levels of pro-inflammatory cytokines, as well as decreased intestinal permeability. In addition, the expression of ERS pathway including BIP, PERK, eIF2α, ATF4, CHOP, as well as the apoptosis-related protein including Caspase-12, Bcl-2 and Bax, was found to be elevated in UC. However, MV treatment significantly inhibited the UC and reversed the expression of inflammation signaling pathway including ERS and ERS-induced apoptosis. Additionally, the addition of tunicamycin (Tm), an ERS activator, significantly weakened the therapeutic effect of MV on UC in mice. These findings suggest that MV may be a therapeutic agent for the treatment of DSS-induced UC by inhibiting the activation of the ERS-apoptosis pathway, and may provide a novel avenue for the treatment of UC.

The role of endoplasmic reticulum stress in regulation of intestinal barrier and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease involving the digestive tract, characterized by abdominal pain, diarrhea, rectal bleeding, and so on, which can make patients physically weakened and live difficultly. Although IBD has been recognized for many years, the pathogenesis of IBD has not yet been established and damage to intestinal barrier is thought to be closely associated with IBD. Intestinal barrier is an innate barrier that maintains the homeostasis of the intestinal environment and impedes pathogenic bacteria and toxins, and the endoplasmic reticulum (ER) has recently been found to be involved in maintaining the integrity of intestinal barrier. Endoplasmic reticulum stress (ERS) is a status of endoplasmic reticulum damaged when unfolded or misfolded proteins accumulate in excess of the degradation systematic clearance limit of the misfolded proteins. The regulation of ERS on protein folding synthesis and maintenance of cellular homeostasis is an important factor in influencing the integrity of the intestinal barrier. This paper mainly discusses the relationship between ERS and the intestinal barrier, aiming to understand the regulatory role of ERS on the intestinal barrier and the mechanism and to improve new solutions and notions for the treatment or prevention of IBD.

CUX1 attenuates the apoptosis of renal tubular epithelial cells induced by contrast media through activating the PI3K/AKT signaling pathway.

OBJECTIVE: Contrast media (CM) is a commonly applied drug in medical examination and surgery. However, contrast-induced acute kidney injury (CIAKI) poses a severe threat to human life and health. Notably, the CUT-like homeobox 1 (CUX1) gene shows protective effects in a variety of cells. Therefore, the objective of this study was to provide a new target for the treatment of CIAKI through exploring the role and possible molecular mechanism of CUX1 in CIAKI. METHOD: Blood samples were collected from 20 patients with CIAKI and healthy volunteers. Human kidney 2 (HK-2) cells were incubated with 200 mg/mL iohexol for 6 h to establish a contrast-induced injury model of HK-2 cells. Subsequently, qRT-PCR was used to detect the relative mRNA expression of CUX1; CCK-8 and flow cytometry to assess the proliferation and apoptosis of HK-2 cells; the levels of IL(interleukin)-1ß, tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) in cells and lactate dehydrogenase (LDH) activity in cell culture supernatant were detect; and western blot to observe the expression levels of CUX1 and the PI3K/AKT signaling pathway related proteins [phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, phosphorylated Akt (p-AKT), AKT]. RESULTS: CUX1 expression was significantly downregulated in blood samples of patients with CIAKI and contrast-induced HK-2 cells. Contrast media (CM; iohexol) treatment significantly reduced the proliferation of HK-2 cells, promoted apoptosis, stimulated inflammation and oxidative stress that caused cell damage. CUX1 overexpression alleviated cell damage by significantly improving the proliferation level of HK-2 cells induced by CM, inhibiting cell apoptosis, and reducing the level of LDH in culture supernatant and the expression of IL-1ß, TNF-α and MDA in cells. CM treatment significantly inhibited the activity of PI3K/AKT signaling pathway activity. Nevertheless, up-regulating CUX1 could activate the PI3K/AKT signaling pathway activity in HK-2 cells induced by CM. CONCLUSION: CUX1 promotes cell proliferation, inhibits apoptosis, and reduces inflammation and oxidative stress in CM-induced HK-2 cells to alleviate CM-induced damage. The mechanism of CUX1 may be correlated with activation of the PI3K/AKT signaling pathway.

Functional divergence of a pair of Arabidopsis phospho-base methyltransferases, PMT1 and PMT3, conferred by distinct N-terminal sequences.

In seed plants, phospho-base N-methyltransferase (PMT) catalyzes a key step in the biosynthesis pathway of phosphatidylcholine (PC), the most abundant phospholipid class. Arabidopsis thaliana possesses three copies of PMT, with PMT1 and PMT3 play a primary role because the pmt1 pmt3 double mutant shows considerably reduced PC content with a pale seedling phenotype. Although the function of PMT1 and PMT3 may be redundant because neither of the parental single mutants showed a similar mutant phenotype, major developmental defects and possible functional divergence of these PMTs underlying the pale pmt1 pmt3 seedling phenotype are unknown. Here, we show the major developmental defect of the pale seedlings in xylem of the hypocotyl with partial impairments in chloroplast development and photosynthetic activity in leaves. Although PMT1 and PMT3 are localized at the endoplasmic reticulum, their tissue-specific expression pattern was distinct in hypocotyls and roots. Intriguingly, the function of PMT3 but not PMT1 requires its characteristic N-terminal sequence in addition to the promoter because truncation of the N-terminal sequence of PMT3 or substitution with PMT1 driven by the PMT3 promoter failed to rescue the pale pmt1 pmt3 seedling phenotype. Thus, PMT3 function requires the N-terminal sequence in addition to its promoter, whereas the PMT1 function is defined by the promoter.

A comprehensive review of matcha: production, food application, potential health benefits, and gastrointestinal fate of main phenolics.

Matcha, a powder processed from tea leaves, has a unique green tea flavor and appealing color, in addition to many other sought after functional properties for a wide range of formulated food applications (e.g., dairy products, bakery products, and beverage). The properties of matcha are influenced by cultivation method and processing post-harvest. The transition from drinking tea infusion to eating whole leaves provides a healthy option for the delivery of functional component and tea phenolics in various food matrix. The aim of this review is to describe the physico-chemical properties of matcha, the specific requirements for tea cultivation and industrial processing. The quality of matcha mainly depends on the quality of fresh tea leaves, which is affected by preharvest factors including tea cultivar, shading treatment, and fertilization. Shading is the key measure to increase greenness, reduce bitterness and astringency, and enhance umami taste of matcha. The potential health benefits of matcha and the gastrointestinal fate of main phenolics in matcha are covered. The chemical compositions and bioactivities of fiber-bound phenolics in matcha and other plant materials are discussed. The fiber-bound phenolics are considered promising components which endow matcha with boosted bioavailability of phenolics and health benefits through modulating gut microbiota.

Comprehensive Analysis of Alternative Polyadenylation Events Associated with the Tumor Immune Microenvironment in Colon Adenocarcinoma.

Objective: Colon adenocarcinoma (COAD) is one of the leading causes of cancer death worldwide. Alternative polyadenylation (APA) is relevant to the variability of the 3'-UTR of mRNA. However, the posttranscriptional dysregulation of APA in COAD is poorly understood. Methods: We collected APA data from The Cancer Genome Atlas (TCGA) COAD (n =7692). APA events were evaluated using PDUI values, and the prognostically significant APA events were screened by LASSO Cox regression to construct a prognostic model. Then, prognostic model functions and possible regulatory genes of characteristic APA events were analyzed. Finally, the immune regulatory network based on APA regulatory genes was analyzed and established. Results: A total of 95 APA events were found to influence the COAD outcomes. Among them, 39 genes were screened as characteristic prognostic APA events by LASSO Cox regression to construct a COAD prognostic signature. The analysis results suggested that a high signature score was associated with poor prognosis and was significantly correlated with a variety of immune cells, including NK and Th1, 2 and 17 cells. Further analysis showed that APA regulators mainly served roles in the prognosis of COAD. Based on the above results, we constructed an immunoregulatory network for APA regulatory genes-APA genes-immune cells. Conclusion: Our study revealed that APA events in COAD may regulate tumor progression by influencing immune cells, which provides a new direction for exploring the influencing mechanism of the tumor immune microenvironment and is expected to provide a potential new target for COAD immunotherapy.

Atorvastatin reduces contrast media-induced pyroptosis of renal tubular epithelial cells by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure. However, there is no effective treatment of CI-AKI, and its mechanism is unknown. Interestingly, atorvastatin has been reported to be effective in renal injury. Therefore, the aim of this study was to explore the effect and possible molecular mechanism of atorvastatin in CI-AKI. METHODS: On the CI-AKI in vitro model, rat tubular epithelial cells (NRK-52E) were treated with 18 mg I/ml meglumine diatrizoate (MEG) and then pretreated with atorvastatin. pcDNA3.1-TLR4 treatment was performed to overexpress toll-like receptor 4 (TLR4) in NRK-52E cells. Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) kits were used to detect NRK-52E cell viability as well as LDH release in each group, respectively; qRT-PCR to determine mRNA expression of TLR4 in cells; western blot to detect protein expression levels of pyroptosis-related proteins (NLRP3, caspase-1, ASC, and GSDMD) and TLR4/MyD88/NF-κB signaling pathway-related proteins (TLR4, MyD88, NF-κBp65, and p-NF-κB p65) in cells. RESULTS: MEG treatment significantly inhibited the viability of NRK-52E cells, increased pro-inflammatory factor levels and promoted pyroptosis, representing successful establishment of a rat tubular epithelial cell (NRK-52E) CI-AKI in vitro model. Notably, atorvastatin increased the activity of MEG-treated NRK-52E cells and alleviated cell injury in a concentration-dependent manner. In addition, atorvastatin significantly down-regulated the expression of TLR4 in MEG-treated NRK-52E cells. However, overexpression of TLR4 inhibited the effects of atorvastatin on increasing cell viability, alleviating cell injury, reducing pro-inflammatory factors (IL-1ß, IL-6, and TNF-α) levels, and inhibiting apoptosis (by down-regulating the expression of NLRP3, caspase-1, ASC, and GSDMD). Furthermore, atorvastatin also inhibited the expression of TLR4/MyD88/NF-κB pathway-related proteins (TLR4, MyD88, and p-NF-κB p65). CONCLUSION: Atorvastatin can attenuate CI-AKI through increasing the activity of MEG-treated renal tubular epithelial cells, relieving cell injury, as well as inhibiting pyroptosis and inflammation. More importantly, the mechanism was achieved by inhibiting the TLR4//MyD88/NF-κB signaling pathway.

Shading-Dependent Greening Process of the Leaves in the Light-Sensitive Albino Tea Plant 'Huangjinya': Possible Involvement of the Light-Harvesting Complex II Subunit of Photosystem II in the Phenotypic Characteristic.

The light-sensitive albino tea plant can produce pale-yellow shoots with high levels of amino acids which are suitable to process high-quality tea. In order to understand the mechanism of the albino phenotype formation, the changes in the physio-chemical characteristics, chloroplast ultrastructure, chlorophyll-binding proteins, and the relevant gene expression were comprehensively investigated in the leaves of the light-sensitive albino cultivar 'Huangjinya' ('HJY') during short-term shading treatment. In the content of photosynthetic pigments, the ultrastructure of the chloroplast, and parameters of the photosynthesis in the leaves of 'HJY' could be gradually normalized along with the extension of the shading time, resulting in the leaf color transformed from pale yellow to green. BN-PAGE and SDS-PAGE revealed that function restoration of the photosynthetic apparatus was attributed to the proper formation of the pigment-protein complexes on the thylakoid membrane that benefited from the increased levels of the LHCII subunits in the shaded leaves of 'HJY', indicating the low level of LHCII subunits, especially the lack of the Lhcb1 might be responsible for the albino phenotype of the 'HJY' under natural light condition. The deficiency of the Lhcb1 was mainly subject to the strongly suppressed expression of the Lhcb1.x which might be modulated by the chloroplast retrograde signaling pathway GUN1 (GENOMES UNCOUPLED 1)-PTM (PHD type transcription factor with transmembrane domains)-ABI4 (ABSCISIC ACID INSENSITIVE 4).

Dihydropyrimidone Derivatives as Thymidine Phosphorylase Inhibitors: Inhibition Kinetics, Cytotoxicity, and Molecular Docking.

Overexpression of the thymidine phosphorylase (TP) enzyme induces angiogenesis, which eventually leads to metastasis and tumor growth. The crucial role of TP in cancer development makes it an important target for anticancer drug discovery. Currently, there is only one US-FDA-approved drug, i.e., Lonsurf, a combination of trifluridine and tipiracil, for the treatment of metastatic colorectal cancer. Unfortunately, numerous adverse effects are associated with its use, such as myelosuppression, anemia, and neutropenia. Since the last few decades, the discovery of new, safe, and effective TP inhibitory agents has been rigorously pursued. In the present study, we evaluated a series of previously synthesized dihydropyrimidone derivatives 1-40 for their TP inhibitory potential. Compounds 1, 12, and 33 showed a good activity with IC50 = 314.0 ± 0.90, 303.5 ± 0.40, and 322.6 ± 1.60 µM, respectively. The results of mechanistic studies revealed that compounds 1, 12, and 33 were the non-competitive inhibitors. These compounds were also evaluated for cytotoxicity against 3T3 (mouse fibroblast) cells and were found to be non-cytotoxic. Finally, the molecular docking suggested the plausible mechanism of non-competitive inhibition of TP. The current study thus identifies some dihydropyrimidone derivatives as potential inhibitors of TP, which can be further optimized as leads for cancer treatment.

Activation of the P2X7 receptor in the dental pulp tissue contributes to the pain in rats with acute pulpitis.

Treatment of acute pulpitis (AP) is beneficial for pain relief and pulp regeneration. The purinergic P2X7 receptor activation is responsible for the formation and maintenance of inflammation and pain. This study aims to determine the role of the pulp tissue P2X7 receptor to activate the mechanisms of the AP in rats. The Sprague-Dawley rats were divided into groups, namely, normal, normal saline (NS), and lipopolysaccharide (LPS) groups. Alterations in pain behavior were detected through head-withdrawal thresholds (HWTs), and the pathological changes in pulp tissue were studied through hematoxylin and eosin staining. The expression of the P2X7 receptor in pulp tissue was observed through immunohistochemistry and Western Blotting. The effect of the P2X7 receptor antagonist A-740003 on HWTs was also observed. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the pulp tissue of rats were analyzed through enzyme-linked immunosorbent assay. The HWTs were reduced in the rats with AP. Inflammation is formed but was found more severe in the LPS group than the NS group, and the expression levels of the P2X7 receptors in the NS and LPS groups were higher than in the normal group. The periodontal ligament injection of the A-740003 dose-dependant increases the HWTs in rats with AP. The IL-6 and TNF-α levels in the pulp in the NS and LPS groups were increased but reversed by A-740003 injection. In rats with AP, the expression level of the P2X7 receptor and IL-6/TNF-α release was upregulated. The A-740003 can relieve pain and reduce the inflammation progression in rats with AP.

The importance of Arabidopsis PHOSPHOLIPID N-METHYLTRANSFERASE in glycerolipid metabolism and plant growth.

Phosphatidylcholine (PC) is a major class of phospholipids that are essential for post-embryonic growth in plants. In Arabidopsis, three copies of the phospho-base N-methyltransferase, PMT1, PMT2, and PMT3, are known to account for PC biosynthesis because the triple-knockout mutant is devoid of biosynthesis and shows lethality in post-embryonic but not embryonic growth. Arabidopsis also contains a distinct phospholipid N-methyltransferase (PLMT) that is homologous with yeast and animal PLMT that methylates phospholipids to produce PC. However, the knockout mutant of PLMT does not show morphological phenotypes or decreased PC content, so the role of PLMT remains unclear. Here, we show that PLMT is ubiquitously expressed in different organs and localized at the endoplasmic reticulum, where PC is produced. Overexpression of PLMT in planta increased the content of phospholipids including PC and affected vegetative but not reproductive growth. Although silique lengths were shorter, pollen remained viable and mature seeds were produced. Intriguingly, seed triacylglycerol content was increased with altered fatty acid composition. We conclude that PLMT might be a functional enzyme in PC biosynthesis and play an organ-specific role in developing seeds, where rapid accumulation of triacylglycerol dominates the entire glycerolipid metabolic flux.

PRDX6 alleviates lipopolysaccharide-induced inflammation and ferroptosis in periodontitis.

OBJECTIVE: Periodontitis is a progressive and inflammatory oral disease and results in the damage of the supporting tissues of teeth. Peroxiredoxin 6 (PRDX6) is an antioxidant enzyme identified as a regulator in ferroptosis. This study aimed to investigate whether PRDX6 could protect human gingival fibroblasts (HGFs) from lipopolysaccharide (LPS)-induced inflammation and its mechanisms. MATERIAL AND METHODS: Both inflamed and non-inflamed human gingival tissues were collected to assess the expression of PRDX6 and nuclear factor erythropoietin 2-related factor 2 (NRF2) by Immunohistochemistry and Western blotting. Furthermore, the molecular mechanisms of PRDX6 have been clarified in PRDX6 silenced cells. The inflammatory cytokines in HGFs were measured by RT-qPCR and ELISA. The lipid hydroperoxide (LOOH) was detected by C11-BODIPY. RESULTS: The expression of PRDX6 and NRF2 were decreased in gingival tissues of severe periodontitis patients. The increased LPS-induced LOOH and inflammatory cytokines were found in PRDX6 knockdown HGFs. Besides, the inhibition of ferroptosis or PRDX6 phospholipase A2 activity (PLA2) alleviated LPS-induced inflammatory cytokines and LOOH. However, inhibiting NRF2 signalling upregulated those in HGFs. CONCLUSIONS: Therefore, this study provided a new mechanistic insight that PRDX6, regulated by the NRF2 signalling, alleviates LPS-induced inflammation and ferroptosis in human gingival fibroblasts.

High-Light-Induced Degradation of Photosystem II Subunits' Involvement in the Albino Phenotype in Tea Plants.

The light-sensitive (LS) albino tea plant grows albinic shoots lacking chlorophylls (Chls) under high-light (HL) conditions, and the albinic shoots re-green under low light (LL) conditions. The albinic shoots contain a high level of amino acids and are preferential materials for processing quality green tea. The young plants of the albino tea cultivars are difficult to be cultivated owing to lacking Chls. The mechanisms of the tea leaf bleaching and re-greening are unknown. We detected the activity and composition of photosystem II (PSII) subunits in LS albino tea cultivar "Huangjinya" (HJY), with a normal green-leaf cultivar "Jinxuan" (JX) as control so as to find the relationship of PSII impairment to the albino phenotype in tea. The PSII of HJY is more vulnerable to HL-stress than JX. HL-induced degradation of PSII subunits CP43, CP47, PsbP, PsbR. and light-harvest chlorophyll-protein complexes led to the exposure and degradation of D1 and D2, in which partial fragments of the degraded subunits were crosslinked to form larger aggregates. Two copies of subunits PsbO, psbN, and Lhcb1 were expressed in response to HL stress. The cDNA sequencing of CP43 shows that there is no difference in sequences of PsbC cDNA and putative amino acids of CP43 between HJY and JX. The de novo synthesis and/or repair of PSII subunits is considered to be involved in the impairment of PSII complexes, and the latter played a predominant role in the albino phenotype in the LS albino tea plant.

Identification of Key Aroma Compounds Responsible for the Floral Ascents of Green and Black Teas from Different Tea Cultivars.

Chemicals underlying the floral aroma of dry teas needs multi-dimensional investigations. Green, black, and freeze-dried tea samples were produced from five tea cultivars, and only 'Chunyu2' and 'Jinguanyin' dry teas had floral scents. 'Chunyu2' green tea contained the highest content of total volatiles (134.75 µg/g) among green tea samples, while 'Jinguanyin' black tea contained the highest content of total volatiles (1908.05 µg/g) among black tea samples. The principal component analysis study showed that 'Chunyu2' and 'Jinguanyin' green teas and 'Chunyu2' black tea were characterized by the abundant presence of certain alcohols with floral aroma, while 'Jinguanyin' black tea was discriminated due to the high levels of certain alcohols, esters, and aldehydes. A total of 27 shared volatiles were present in different tea samples, and the contents of 7 floral odorants in dry teas had correlations with those in fresh tea leaves (p < 0.05). Thus, the tea cultivar is crucial to the floral scent of dry tea, and these seven volatiles could be promising breeding indices.

Dihydrochalcones in Sweet Tea: Biosynthesis, Distribution and Neuroprotection Function.

Sweet tea is a popular herbal drink in southwest China, and it is usually made from the shoots and tender leaves of Lithocarpus litseifolius. The sweet taste is mainly attributed to its high concentration of dihydrochalcones. The distribution and biosynthesis of dihydrochaldones in sweet tea, as well as neuroprotective effects in vitro and in vivo tests, are reviewed in this paper. Dihydrochalones are mainly composed of phloretin and its glycosides, namely, trilobatin and phloridzin, and enriched in tender leaves with significant geographical specificity. Biosynthesis of the dihydrochalones follows part of the phenylpropanoid and a branch of flavonoid metabolic pathways and is regulated by expression of the genes, including phenylalanine ammonia-lyase, 4-coumarate: coenzyme A ligase, trans-cinnamic acid-4-hydroxylase and hydroxycinnamoyl-CoA double bond reductase. The dihydrochalones have been proven to exert a significant neuroprotective effect through their regulation against Aß deposition, tau protein hyperphosphorylation, oxidative stress, inflammation and apoptosis.

[Overview of systematic reviews and Meta-analysis of Aidi Injection combined with chemotherapy in treatment of non-small cell lung cancer].

At present, many systematic reviews(SRs)/Meta-analysis of Aidi Injection combined with chemotherapy in the treatment of non-small cell lung cancer(NSCLC) have been published, and the effectiveness has been proved.However, the methodological quality and evidence quality of these SRs/Meta-analysis have not been evaluated, and their guiding role in the clinical practice needs to be further verified.In this study, SRs/Meta-analysis of Aidi Injection combined with chemotherapy in the treatment of NSCLC were assessed to provide evidence overview and basis for the application and decision-making of this drug in clinical practice.PubMed, Cochrane Library, EMbase, CNKI, VIP, Wanfang, and SinoMed databases were searched for research articles on SRs/Meta-analysis of Aidi Injection combined with chemotherapy in the treatment of NSCLC.The methodological quality and evidence quality of included 15 articles on SRs/Meta-analysis were evaluated by using the AMSTAR-2 and GRADE system.The results of SRs/Meta-analysis suggested that Aidi Injection combined with chemotherapy had certain advantages over chemotherapy alone in improving short-term efficacy, improving quality of life, and reducing leukopenia, thrombocytopenia, and the incidence of gastrointestinal adverse events.The results of the AMSTAR-2 checklist showed low quality for 11 SRs/Meta-analysis and extremely low quality for another four SRs/Meta-analysis.The top problems included failure to provide the preliminary protocol or guide, unreported funding sources, and non-assessed risk of bias in the included articles on the results.According to the results of the GRADE assessment, 32 of the 148 outcome indicators were of intermediate quality, 40 were of low quality, and 76 were of extremely low quality.The critical factor leading to the downgrade was the risk of bias, followed by imprecision and publication bias.Aidi Injection combined with chemotherapy in the treatment of NSCLC can enhance efficacy and reduce toxicity.However, due to the low methodological quality and evidence quality of the included research articles, the efficacy and safety of Aidi Injection combined with chemotherapy in the treatment of NSCLC still need to be further confirmed by high-quality studies.In the follow-up original research and SRs/Meta-analysis, the corresponding quality evaluation standards should be strictly followed to improve the quality of evidence.

Synthesis and Near-Infrared Photothermal Conversion of Discrete Supramolecular Topologies Featuring Half-Sandwich [Cp*Rh] Units.

Although a large number of novel supramolecular topologies featuring half-sandwich [Cp*Rh] units have been reported, investigations into the properties of these architectures are astoundingly rare. In addition, the bidentate ligands employed to prepare these species have remained relatively homogeneous (i.e., symmetrical bis(pyri-4-dyl) ligands). To address these paucities in the field, the novel unsymmetrical ligand L2 and the rarely reported pyri-3-dyl ligand L3, all bearing aromatic phenazine groups (an N-heterocyclic analog of anthracene), were synthesized in addition to the common symmetrical pyri-4-dyl L1. [3]Catenane, [2]catenane, and Borromean rings assemblies were constructed successfully by the self-assembly of L1 with different building blocks. Afterward, ligand L2 was applied to prepare two novel molecular-tweezer-like compounds. Lastly, a twisted [2]catenane (relative to the [2]catenane constructed using L1) and a sandwiched metallarectangle were obtained using L3. π-π stacking interactions were observed to play a significant role in stabilizing these topologies, which also promoted nonradiative migration and triggered photothermal conversion in both the solution and the solid state. In the solution state, a clear rule of thumb was derived whereby the NIR photothermal conversion efficiency increased as the π-π stacking increased, and a very high photothermal conversion efficiency (35.5-62.4%) was observed. In addition, this family of half-sandwich-based assemblies also exhibited good photothermal conversion properties in the crystalline and noncrystal powder states. This research provides a novel method to synthesize excellent NIR photothermal conversion materials featuring half-sandwich [Cp*Rh] units and points to potential applications in the near future.

Antiviral Effects of Green Tea EGCG and Its Potential Application against COVID-19.

(-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant component of catechins in tea (Camellia sinensis (L.) O. Kuntze), plays a role against viruses through inhibiting virus invasiveness, restraining gene expression and replication. In this paper, the antiviral effects of EGCG on various viruses, including DNA virus, RNA virus, coronavirus, enterovirus and arbovirus, were reviewed. Meanwhile, the antiviral effects of the EGCG epi-isomer counterpart (+)-gallocatechin-3-O-gallate (GCG) were also discussed.

Optimal designs for discrete-time survival models with random effects.

This paper considers the optimal design for the frailty model with discrete-time survival endpoints in longitudinal studies. We introduce the random effects into the discrete hazard models to account for the heterogeneity between experimental subjects, which causes the observations of the same subject at the sequential time points being correlated. We propose a general design method to collect the survival endpoints as inexpensively and efficiently as possible. A cost-based generalized D ([Formula: see text])-optimal design criterion is proposed to derive the optimal designs for estimating the fixed effects with cost constraint. Different computation strategies based on grid search or particle swarm optimization (PSO) algorithm are provided to obtain generalized D ([Formula: see text])-optimal designs. The equivalence theorem for the cost-based D ([Formula: see text])-optimal design criterion is given to verify the optimality of the designs. Our numerical results indicate that the presence of the random effects has a great influence on the optimal designs. Some useful suggestions are also put forward for future designing longitudinal studies.