Search

Ying Li1,2 *, Jia-Jing Lu1,2 *, Xiao-Yuan Zhong1,2 *, Ying-Yuan Yu1,2 *, Ning Yu,1,2 Yu Wang,1,2 Xue-Mei Yi,1,2 Yang-Feng Ding,1,2 Yu-Ling Shi1,2 1Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Institute of Psoriasis, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Ling Shi; Yang-Feng Ding, Department of Dermatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, 1278 Road, Shanghai, 200443, People’s Republic of China, Email shiyuling1973@tongji.edu.cn; dingyangfeng@hotmail.comBackground: Data pertaining to biologic agents used for treating psoriasis in real-world settings are lacking at present. To compare drug survival at 52 weeks for a range of biologics used to treat psoriasis under real-world conditions.Methods: This was a retrospective, single-center, observational study of a cohort of patients diagnosed with plaque psoriasis treated using ixekizumab, secukinumab, guselkumab, or adalimumab between January 2020 and December 2021. Baseline demographic characteristics, duration of psoriasis, and prior biological treatments for all patients were recorded. Drug survival rates were analyzed in different patient groups using Kaplan–Meier curves and Log rank tests.Results: In total, this study included 386 plaque psoriasis patients, of whom 70, 175, 36, and 105 were, respectively, treated using ixekizumab, secukinumab, guselkumab, and adalimumab. Over a 52-week period, the overall cumulative drug survival rates for ixekizumab, secukinumab, guselkumab, and adalimumab were 67.1%, 63.0%, 72.2%, and 37.1%, respectively. Lack of efficacy was the primary cause of discontinuation for these biologic therapies, followed by economic burden and adverse event incidence.Conclusion: These results suggest that guselkumab exhibited superior drug survival, drug survival outcomes for ixekizumab and secukinumab were comparable, and significantly better than those of adalimumab in China. Preventing a loss of drug efficacy represents a primary approach to improving biologic drug survival in psoriasis patients.Keywords: biologics, drug survival, real-world, psoriasis, ixekizumab, secukinumab, guselkumab, adalimumab

Caudatin-2,6-dideoxy-3-O-methy-[beta]-d-cymaropyranoside (CDMC), the C-21 steroidal glycoside recently extracted from the traditional Chinese medicinal plant, the root of Cynanchum auriculatum Royle ex Wight (Asclepiadaceae), has been shown to possess potent antitumor properties. However, the bioactivities of CDMC are still largely unknown, especially the antitumor effect and its mechanism. This study investigated the CDMC antitumor effects on human hepatoma cell line SMMC7721 cells by analysis of cell viability, cell cycle phases and apoptosis. The results showed that CDMC inhibited the growth of SMMC7721 cells in a time- and dose-dependent manner and resulted in cell cycle arrest in G(0) /G(1) phase. Furthermore, CDMC induced SMMC7721 cell apoptosis rather than necrosis through caspase 3 activation, and a caspase 3 inhibitor, Ac-DEVD-CHO, could attenuate the apoptosis induced by CDMC. The results suggested that the anticancer activity of CDMC could be attributed partially to its inhibition of cell proliferation and induction of apoptosis associated with caspase 3 activation. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Bicaval dual lumen cannula (DLC) is gaining popularity in veno-venous extracorporeal membrane oxygenation (V-V ECMO) for having less recirculation and facilitating mobilization. It is usually inserted under fluoroscopic or transesophageal echocardiographic guidance to prevent potentially fatal complications. Thus, their utilization was limited during the COVID-19 outbreak due to stringent quarantine policy and manpower shortage, especially when emergency insertion was required., Purpose: To describe our experience on DLC insertion using transthoracic echocardiography alone during the pandemic, with a focus on safety considerations by using detail step-by-step procedural guide., Outcome: Four patients were performed V-V ECMO using the transthoracic echocardiographic-guided DLC cannulation technique during the fifth wave of the COVID-19 outbreak, with no cannulation-related complications., Conclusion: Transthoracic echocardiographic guidance for DLC insertion is feasible and probably safe with a detailed guide, which can be adopted as a supplementary tool during future endemic outbreaks., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials., Objective: We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis., Methods: Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300 mg every 2 weeks up to 52 weeks. Efficacy outcomes included the proportions of patients with ≥ 50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale., Results: In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week 52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥ 2-point reduction was achieved in 39.3% of patients at week 16, increasing to 58.9% at week 52. The proportions of patients with ≥ 3-point and ≥ 4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week 52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events., Conclusions: Long-term treatment with stapokibart for 52 weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021)., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A novel extra-long carbon-chain salamo-like fluorescent chemical probe DNS (named as 2,2'-[1,10-(decanedioxy)bis(nitromethyldyne)]dinaphthol) containing ten methylene groups was synthesized based on the 2-hydroxy-1-naphthylaldehyde unit. Research has shown that the fluorescent probe DNS can achieve efficient and selective recognition of CO 3 2- anions, with a detection limit LOD=1.59 × 10 -8 M. The binding constant Ka = 3.7 × 10 4 M -1 and quantification limit is as low as LOQ=4.31 × 10 -8 M, respectively. The possible identification mechanism of the fluorescent chemosensor DNS was analyzed and studied through fluorescence titration and nuclear magnetic titration. The results showed that the fluorescence chemical sensor DNS is deprotonated by CO 3 2- anions, enhancing its fluorescence and producing a ICT effect., 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.)

Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1β levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

Two new 9,11-secosterols, hipposponols A ( 1 ) and B ( 2 ), together with five known analogues, aplidiasterol B ( 3 ), (3 β ,5 α ,6 β )-3,5,6-triol-cholest-7-ene ( 4 ), (3 β ,5 α ,6 β ,22 E )-3,5,6-triol-ergosta-7,22-diene ( 5 ), and one pair of inseparable C-24 epimers of (3 β ,5 α ,6 β ,22E)-3,5,6-triol-stigmasta-7,22-diene ( 6 / 7 ), were isolated from the marine sponge Hippospongia lachne de Laubenfels. The structures of isolated compounds were extensively elucidated based on HRESIMS and NMR data. Compounds 2  -  5 showed cytotoxicity against PC9 cells with IC 50 values ranging from 34.1 ± 0.9 to 38.9 ± 1.0 µM and compound 4 displayed cytotoxicity against MCF-7 cells with IC 50 value of 39.0 ± 0.4 µM.

Interface modification plays an important role in improving the power conversion efficiency (PCE) of organic solar cells (OSCs). However, the low non-covalent interaction between the cathode interface layer (CIL) and nonfullerene acceptor (NFA) directly affects the charge collection of OSCs. Here, the non-covalent interaction between the CIL and NFA is enhanced by introducing the 2D vermiculite (VML) in the poly(9,9-bis(3'-(N,N-dimethyl)-Nethylammonium-propyl-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)) dibromide (PFN-Br) interface layer to form an efficient electron transport channel. As a result, the electron extraction efficiency from the active layer to the CIL is increased, and the PCE of OSCs based on PBDB-T:ITIC is boosted from 10.87% to 12.89%. In addition, the strategy of CIL doping VML is proven to be universal in different CIL materials, for which the PCE is boosted from 10.21% to 11.57% for OSCs based on PDINN and from 9.82% to 11.27% for OSCs based on PNDIT-F3N. The results provide a viable option for designing efficient CIL for high-performance non-fullerene OSCs, which may promote the commercialization of OSCs., (© 2024 Wiley‐VCH GmbH.)

Objective To investigate the effects of platelet-rich plasma-derived exosomes (PRP-Exos) on the proliferation and migration of tendon stem/progenitor cell (TSPC).Methods PRP-Exos were extracted through the combination of polymer-based precipitation and ultracentrifugation.The morphology,concentration,and particle size of PRP-Exos were identified by transmission electron microscopy and nanoparticle tracking analysis.The expression levels of surface marker proteins on PRP-Exos and platelet membrane glycoproteins were determined by Western blot analysis.Rat TSPC was extracted and cultured,and the expression of surface marker molecules on TSPC was detected using flow cytometry and immunofluorescence staining.The proliferation of TSPC influenced by PRP-Exos was evaluated using CCK-8 assay and EdU assay.The effect of PRP-Exos on the migration of TSPC was evaluated by cell scratch assay and Transwell assay.Results The extracted PRP-Exos exhibit typical saucer-like structures,with a concentration of 4.9×10 11 particles/mL,an average particle size of (132.2±56.8) nm,and surface expression of CD9,CD63 and CD41.The extracted TSPC expressed the CD44 protein.PRP-Exos can be taken up by TSPC,and after co-cultured for 48 h,concentrations of 50 and 100 μg/mL of PRP-Exos significantly promoted the proliferation of TSPC (both P <0.001),with no statistical difference between the two concentrations ( P =0.283).Additionally,after co-cultured for 24 h,50 μg/mL of PRP-Exos significantly promoted the migration of TSPC ( P <0.001).Conclusion Under in vitro culture conditions,PRP-Exos significantly promote the proliferation and migration of rat TSPC.

An innovative salamo-like fluorescent chemical sensor H 2 L, has been prepared that can be utilized to selectively detect Cu 2+ and B 4 O 7 2- ions. Cu 2+ ions can bind to oxime state nitrogen and phenol state oxygen atoms in the chemosensor H 2 L, triggering the LMCT effect leading to fluorescence enhancement. The crystal structure of the copper(II) complex, named as [Cu(L)], has been achieved via X-ray crystallography, and the sensing mechanism has been confirmed by further theoretical calculations with DFT. Besides, the sensor H 2 L recognizes B 4 O 7 2- ions causing an ICT effect resulting in bright blue fluorescence. Moreover, the sensor has relatively high selectivity and sensitivity for Cu 2+ and B 4 O 7 2- ions, and the detection limits are 1.02 × 10 -7 and 2.06 × 10 -7 M, respectively. In addition, the good biocompatibility and excellent water solubility of the sensor H 2 L make it very advantageous in practical applications, using H 2 L powder for fingerprint visualization, using H 2 L to identify the phenomenon of B 4 O 7 2- ions emitting bright blue fluorescence, making it an ink that can print encrypted messages on A4 paper, in addition to this, based on H 2 L, the real water sample was tested for Cu 2+ ion recognition, and finally the test strip experiment was carried out., 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.)

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation., 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.)

The matrix metalloprotease A disintegrin and metalloprotease with thrombospondin motifs 1 (ADAMTS1) was reported to be involved in tumor progression in several cancer types, but its contributions appear discrepant. At present, the role of ADAMTS1 in oral squamous cell carcinoma (SCC; OSCC) remains unclear. Herein, The Cancer Genome Atlas (TCGA) database showed that ADAMTS1 transcripts were downregulated in head and neck SCC (HNSCC) tissues compared to normal tissues, but ADAMTS1 levels were correlated with poorer prognoses of HNSCC patients. In vitro, we observed that ADAMTS1 expression levels were correlated with the invasive abilities of four OSCC cell lines, HSC-3, SCC9, HSC-3M, and SAS. Knockdown of ADAMTS1 in OSCC cells led to a decrease and its overexpression led to an increase in cell-invasive abilities in vitro as well as tumor growth and lymph node (LN) metastasis in OSCC xenografts. Mechanistic investigations showed that the cyclic increase in ADAMTS1-L1 cell adhesion molecule (L1CAM) axis-mediated epidermal growth factor receptor (EGFR) activation led to exacerbation of the invasive abilities of OSCC cells via inducing epithelial-mesenchymal transition (EMT) progression. Clinical analyses revealed that ADAMTS1, L1CAM, and EGFR levels were all correlated with worse prognoses of HNSCC patients, and patients with ADAMTS1 high /L1CAM high or EGFR high tumors had the shortest overall and disease-specific survival times. As to therapeutic aspects, we discovered that an edible plant-derived flavonoid, apigenin (API), drastically inhibited expression of the ADAMTS1-L1CAM-EGFR axis and reduced the ADAMTS1-triggered invasion and LN metastasis of OSCC cells in vitro and in vivo. Most importantly, API treatment significantly prolonged survival rates of xenograft mice with OSCC. In summary, ADAMTS1 may be a useful biomarker for predicting OSCC progression, and API potentially retarded OSCC progression by targeting the ADAMTS1-L1CAM-EGFR signaling pathway., (© 2024. The Author(s).)

In this work, we successfully designed and synthesized a methoxydisubstituted bis(salamo)-type fluorescent chemical sensor BS, which can be applied as a highly sensitive and selective fluorescence probe for HCO 3 - and CO 3 2- detection. The LODs of HCO 3 - and CO 3 2- were experimentally calculated to be 5.4068 × 10 -8 M and 4.4517 × 10 -8 M, respectively. After relevant experiments, the sensing mechanism was investigated. Moreover, the application of the sensor in practice is explored, and the sensor BS can be loaded on portable test strips for ion detection. In the field of ion detection, salamo-like chemical sensors have been less studied compared to other sensor molecules, especially for the recognition and detection of anions. Therefore, this study will to some extent contribute to expanding the application of salamo-like compounds., 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: Cardiorenal syndromes type II (CRS2) is a multi-organ ailment that manifests as a combination of cardiac and renal dysfunction, resulting in chronic kidney disease due to chronic cardiac insufficiency. It affects at least 26 million people worldwide, and its prevalence is increasing. Gualou Xiebai Decoction (GXD), a traditional Chinese medicine (TCM) with a rich history of application in the management of coronary artery disease, has been explored for its potential therapeutic benefits in CRS2. Nevertheless, the mechanism by which GXD alleviates CRS2 remains obscure, necessitating further investigation., Purpose: The aim of this study was to assess the effects of the ethanolic extract of GXD on CRS2 and to elucidate the underlying mechanism in a rat model of myocardial infarction, offering a potential target for clinical treatment for CRS2., Study Design and Methods: A rat model of CRS2 was induced by surgical myocardial infarction and treated with GXD for 10 weeks. Cardiac function was assessed using echocardiography, while serum and urine biochemistry were analyzed to evaluate potential cardiac and renal damage. Furthermore, tissue samples were obtained for histological, protein, and genetic investigations. In addition, network pharmacology analysis and molecular docking were utilized to predict the primary active compounds, potential therapeutic targets, and interventional pathways through which GXD could potentially exert its effects on CRS2. Subsequently, these predictions were confirmed in vivo and vitro through various analyses., Results: The current investigation employed echocardiography to exhibit the apparent cardiac remodeling following the induction of myocardial infarction. Damage to the heart and kidneys of CRS2 rats was effectively ameliorated by administration of GXD. The outcomes derived from the analyses of HE and Masson staining indicated that the pathological damage to the heart and kidney tissues of rats in the GXD groups was considerably alleviated. Using network pharmacology analysis, AKT1, IL-6, and TNF-α were identified as plausible therapeutic targets for the treatment of CRS with GXD. Subsequent functional and pathway enrichment analysis of the underlying targets disclosed that the PI3K/AKT/NF-κB signaling pathway may be involved in the mechanism of GXD in the treatment of CRS2. Immunohistochemical, western blot, RT-PCR and immunofluorescence staining were employed to demonstrate that GXD can regulate the PI3K/AKT/NF-κB signaling pathway in the CRS2 rat model. Ultimately, administration of the PI3K/AKT agonist 740Y-P counteracted the effect of diosmetin, which was one of the potential active components of GXD analysed by compound-target-disease network, on p-PI3K and p-AKT in vitro., Conclusions: The findings of this study suggest that GXD improves cardiac and renal function in CRS2 rats and that the underlying mechanism involves inhibition of the PI3K/AKT/NF-κB pathway., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, (Copyright © 2023. Published by Elsevier GmbH.)

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri ( P. copri ) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo , accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri -derived LPS ( Pc -LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc -LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc -LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc -LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Although various ferroptosis inducers including magnetic nanoparticles (Fe 3 O 4 ) and iron-organic frameworks have been applied in cancer treatment, the mild immunogenicity, low targeting efficiency to the tumor, and poor tissue penetration have limited the therapeutic efficacy. Herein, a supramolecularly engineered conjugate between living bacteria (facultative anaerobic Salmonella typhimurium VNP20009, VNP) and cancer cell membranes-coated Fe 3 O 4 nanoparticles is developed for improving targeted delivery of Fe 3 O 4 nanoparticles into the tumor tissue and for synergistic ferroptosis and immunotherapy of tumor. The enhanced ferroptosis induced by both Fe 3 O 4 nanoparticles and the loaded ferroptosis inducing agent (sulfasalazine (SAS)) effectively inhibits tumor growth and generates immune response via immunogenic cell death (ICD). The colonization of VNP in tumors also induces adaptive immune responses and further promotes ferroptosis. Fundamentally, the supramolecular conjugate of VNP and cell membranes-coated Fe 3 O 4 can potentiate the therapeutic capability of each other through mutually magnifying the ferroptosis and immunotherapy, resulting in significantly enhanced antitumor effects., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

UV exposure often triggers photoaging of the skin. Pharmacological treatment suffers from severe side effects as well as poor efficacy because of insufficient skin penetration. Dissolved oxygen has been previously shown to reverse photoaged skin; however, the treatment is often limited by the availability of equipment (e.g., high-pressure oxygen). Poor oxygen diffusion into the skin has also limited its therapeutic efficacy. Herein, we developed a microneedle patch to deliver living microalgae to the deeper layers of the skin for efficient oxygenation and reversal of photoaging. The continuous release of oxygen from microalgae in the skin through photosynthesis reversed the inflammatory microenvironment and reduced reactive oxygen species levels in the photodamaged skin, leading to collagen regeneration and reduced wrinkles. This study provides not only a means for highly efficient skin oxygenation and reversal of photoaging but also an important theoretical basis for the clinical treatment of photoaging.

Camptothecin (CPT) and cisplatin (Pt) have shown synergistic effects on a variety of cancers during preclinical and clinical studies. However, the ratio of the two drugs often could not be precisely regulated in different delivery systems, which hinders the desired synergistic effect. In addition, the low delivery efficiency of the two drugs to the tumor further impedes the ideal therapeutic outcomes. Herein, we report that a platelet-mimicking supramolecular nanomedicine (SN) could precisely control of the ratio of CPT and Pt with a high tumor accumulation rate for cascade amplification of synergistic chemotherapy. The SN was fabricated via the host-guest interaction between cucurbit[7]uril conjugated hyaluronic acid (HA-CB[7]) and adamantane (ADA) respectively functionalized CPT- and Pt-based prodrugs. The ratio of CPT and Pt in the SN could be facilely regulated by simply controlling the loading ratio, based on the strong binding affinity between CB[7] and ADA, and SN60 with 60% CPT and 40% Pt showed the highest synergistic effects on 4T1 cells. To improve the tumor accumulation efficiency of SN, 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a tumor vasculature-disruptive agent) was loaded into the optimized SN and then coated with platelet membrane to yield platelet-mimicking supramolecular nanomedicine (D@SN-P). D@SN-P could first passively accumulate in tumors owing to the enhanced permeability and retention (EPR) effect after intravenous administration. The initially release of DMXAA from D@SN-P could induce tumor vascular disruption, and the resultant epithelial collagen exposure around the disrupted tumor vasculature provided a target for further recruitment of platelet-mimicking SN, leading to cascade amplification of tumor accumulation with synergistic chemotherapy. Hence, this platelet-mimicking supramolecular nanomedicine presents a universal supramolecular strategy to finely regulate the ratio of loaded pro-drugs, and improve the accumulation efficiency to amplify chemotherapy via platelet-mimics., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To observe the efficacy and safety of retrograde intrarenal surgery combined with vacuum-assisted ureteral access sheath (V-UAS) and minimally invasive percutaneous nephrolithotomy (MPCNL) in patients with 1-2 cm infectious upper ureteral stone., Patients and Methods: A total of 173 patients with 1-2 cm infectious upper ureteral stone were prospectively randomized into two groups. Eighty-six in the V-UAS group and 87 cases as control in the MPCNL group. The SFRs at different times (Postoperative 1 day, 2nd week and 4th week) was considered as the primary outcome of the study. The secondary end points were operative time, postoperative hospital stay and operative complications., Results: There was no obvious difference between two groups in patients' demographics and preoperative clinical characteristics (all P  > 0.05). Postoperative data showed that the SFR at postoperative 1 day in the V-UAS group was significantly lower than that in the MPCNL group (73.2% vs. 86.2%, P  = 0.034). However, there was no statistical significance between two groups in SFRs during postoperative 2 weeks and 4 weeks (All P  > 0.05). The levels of WBC, CRP and PCT were all significant lower in the V-UAS group than those in the MPCNL group at the postoperative 24 h and 48 h (all P  < 0.05). Postoperative complications included fever (≥38.5°C), bleeding, pain and urosepsis. In terms of the rates of fever, pain and urosepsis, MPCNL group were all significantly higher than those in the V-UAS group (10.3 vs. 2.4%, P  = 0.031; 14.9 vs. 2.4%, P  = 0.003; 4.6 vs. 0.0%, P  = 0.044; respectively). No significant difference was found between two groups in bleeding. Meanwhile, postoperative hospital stay in the V-UAS group was more shorten than that in the MPCNL group (3.7 vs. 5.9 days, P  < 0.001)., Conclusions: Our study showed that RIRS with V-UAS, a new partnership to treat 1-2 cm infectious upper ureteral stones, was satisfying as it achieved a high SFR rate and a low rate of infectious complications. This method was safe and reproducible in clinical practice., 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., (© 2023 Tang, Liang, Ding, Zhou and Tao.)

Dual- or multi-modality combination therapy has become one of the most effective strategies to overcome drug resistance in cancer therapy, and the optimized ratio of the therapeutic agents working on the tumor greatly affects the therapeutic outcomes. However, the absence of a facile method to optimize the ratio of therapeutic agents in nanomedicine has, at least in part, impaired the clinical potential of combination therapy. Herein, a new cucurbit[7]uril (CB[7])-conjugated hyaluronic acid (HA) based nanomedicine was developed, in which both chlorin e6 (Ce6) and oxaliplatin (OX) were co-loaded non-covalently at an optimized ratio via facile host-guest complexation, for optimal, combined photodynamic therapy (PDT)/chemotherapy. To maximize the therapeutic efficacy, a mitochondrial respiration inhibitor, atovaquone (Ato), was also loaded into the nanomedicine to limit consumption of oxygen by the solid tumor, sparing oxygen for more efficient PDT. Additionally, HA on the surface of nanomedicine allowed targeted delivery to cancer cells with over-expressed CD44 receptors (such as CT26 cell lines). Thus, this supramolecular nanomedicine platform with an optimal ratio of photosensitizer and chemotherapeutic agent not only provides an important new tool for enhanced PDT/chemotherapy of solid tumors, but also offers a CB[7]-based host-guest complexation strategy to facilely optimize the ratio of therapeutic agents for multi-modality nanomedicine. STATEMENT OF SIGNIFICANCE: Chemotherapy remains the most common modality for cancer treatment in clinical practice. Combination therapy by co-delivery of two or more therapeutic agents has been recognized as one of the most effective strategies to improve therapeutic outcome of cancer treatment. However, the ratio of loaded drugs could not be facilely optimized, which may greatly affect the combination efficiency and overall therapeutic outcome. Herein, we developed a hyaluronic acid based supramolecular nanomedicine with facile method to optimize the ratio of two therapeutic agents for improved therapeutic outcome. This supramolecular nanomedicine not only provides an important new tool for enhanced photodynamic therapy/chemotherapy of solid tumors, but also offers insights in using macrocyclic molecule-based host-guest complexation to facilely optimize the ratio of therapeutic agents in multi-modality nanomedicine., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Recently, water promotion effects in the selective oxidation of benzyl alcohol to benzaldehyde have been experimentally recognized and identified. However, the effects of water on the photocatalytic selective oxidation of toluene into benzaldehyde remain elusive. In this work, the Ti 3 O 9 H 6 clusters in different solvents (water and toluene solvent) are used to study the water-induced effects in photocatalytic oxidation reactions in kinetics and thermodynamics using density functional theory (DFT) calculations. In addition, the influences of the OH groups on catalysts (Ti-OH bonds) from photocatalytic water splitting are also considered. The results clearly demonstrate the water-induced double-edged sword effects in the photocatalytic selective oxidation of toluene. We expect that our work can not only shed light on the mechanisms of photocatalytic selective oxidation of toluene into benzaldehyde and other activation reactions of sp 3 C-H bonds but also design and modulate highly efficient photocatalysts.

Chemotherapy based on molecular drugs remains the most frequently used approach for the therapy of tumors, however their poor specificity, severe side effects and tumor resistance often seriously hinder their applications. It is therefore desirable to develop a new, alternative therapeutic strategy for tumor treatment without traditional chemotherapeutic drugs. Herein, we report a drug-free tumor therapy approach involving spermine (SPM)-responsive intracellular biomineralization in tumor cells. In this work, we designed calcium carbonate (CaCO 3 ) nanoparticles capped with folic acid and supramolecular peptides, which could target tumor cells and rapidly self-aggregate into micron-sized CaCO 3 aggregates in SPM-overexpressed tumor cells. Due to the extended intracellular retention, CaCO 3 aggregates could induce intracellular biomineralization and Ca 2+ overload of tumor cell, leading to mitochondrial damage and cellular apoptosis, resulting in effective inhibition of tumor growth without serious side effects otherwise seen in conventional chemotherapy., 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.)

Charge transport of conjugated polymers in functional devices closely relates to their density of states (DOS) distributions. However, systemic DOS engineering for conjugated polymers is challenging due to the lack of modulated methods and the unclear relationship between DOS and electrical properties. Here, the DOS distribution of conjugated polymers is engineered to enhance their electrical performances. The DOS distributions of polymer films are tailored using three processing solvents with different Hansen solubility parameters. The highest n-type electrical conductivity (39 ± 3 S cm -1 ), the highest power factor (63 ± 11 µW m -1 K -2 ), and the highest Hall mobility (0.14 ± 0.02 cm 2 V -1 s -1 ) of the polymer (FBDPPV-OEG) are obtained in three films with three various DOS distributions, respectively. Through theoretical and experimental exploration, it is revealed that the carrier concentration and transport property of conjugated polymers can be efficiently controlled by DOS engineering, paving the way for rationally fabricating organic semiconductors., (© 2023 Wiley-VCH GmbH.)

Ethnopharmacological Relevance: Pilose antler is a traditional Chinese medicine used to improve kidney function, strengthen tendons and bones, and prolong life, among other uses. It is widely employed in the treatment of osteoporosis. However, the molecular mechanisms underlying the treatment of high turnover osteoporosis are not fully understood., Aim of the Study: The present study aimed to investigate the molecular mechanism underlying pilose antler polysaccharide and polypeptide extracts in inhibiting bone resorption in high turnover osteoporosis, and compare the effects of the two components alone and in combination to explore whether they could produce synergistic enhancement effects., Materials and Methods: The quantitative and qualitative characteristics of pilose antler polysaccharide and polypeptide extracts were detected by UV-visible spectrophotometry and high-performance liquid chromatography. A rat model of retinoic acid-induced osteoporosis was used to evaluate the inhibitory effect of the extracts on bone resorption. Enzyme-linked immunosorbent assay (ELISA) was used to detect the activity of factors related to high turnover type osteoporosis in rat serum. Western blotting was used to detect the expression of proteins related to the MAKP and MMP-9 signaling pathways in rat femurs. Fluorescence quantitative PCR was used to detect the transcription levels of genes related to the MAKP and MMP-9 signaling pathways in rat femur tissues. Hematoxylin and eosin staining were used to observe the osteoprotective effects of pilose antler polysaccharides and polypeptides., Results: The yield of pilose antler polysaccharides was 8.3%, and was mainly composed of mannose, glucosamine hydrochloride, glucuronic acid, Galacturonic acid, Galactose hydrochloride, glucose, and galactose. The yield of the polypeptides was 26.2%, and eighty percent of the molecular weight of the antler polypeptides was 1.6 kDa-7kD, among which, the molecular weight of 7kD peptide accounted for 52% of the total. Both polysaccharides and peptides could reduce the activities of TRACP, OCN, ERK1, JNK, and MMP-9 in rat serum and reduce both the protein expression and gene transcription levels of ERK1, JNK, and MMP-9 in rat femur tissue with significant differences compared with the model group. Both extracts exerted significant protective effects on rat femur tissue. The effect of pilose antler polypeptides alone was better than that of polysaccharides either alone or in combination., Conclusions: Pilose antler polysaccharides, polypeptides, and their mixtures could inhibit the occurrence of bone resorption of high turnover osteoporosis by stimulating the MAKP and MMP-9 signaling pathways to reduce the expression of the ERK1, JNK, and MMP-9 genes and proteins, and could help alleviate bone loss caused by retinoic acid. Pilose antler polypeptides had a stronger effect on inhibiting bone resorption. The combination of the two components did not show synergistic enhancement effect, and the polysaccharide tended to moderate the inhibitory enhancement effect of the polypeptide., 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 © 2022 Elsevier B.V. All rights reserved.)

Fluorine atoms doping was reported in experiment to reduce the band gap, improve the oxidation potential of hole, and polarize the electron distribution of polymeric carbon nitride (PCN). However, the relationships between different types of F doping and the roles of F doping in electronic and optical properties remain elusive. In this work, we investigate several F doping types in PCN and analyze their different roles in electronic and optical properties with the first-principles calculations. The results show that two stable and cooperative F doping types are found, one is to form the C (sp 3 )-F bond (F corner type), and the other is F atom replacing amino group -NH 2 (F N3 type) forming covalent C-F bond. The F corner doping reduces the energy level of valence-band maximum (VBM), causes excited electron-hole distribution polarized, and increases the hole distribution on F atoms, which strengthens the capacity of photocatalytic oxidation and improves the electron-hole separation efficiency, while F N3 type doping plays the roles of reducing the bandgap and improving the light absorption. In addition, under the synergistic action of two types of F doping, the adsorption energy of toluene on F-codoped PCN is greatly enhanced, improving the ability of photocatalytic activation of toluene. Our work develops a new understanding of F doping and reveals the roles of different types of F doping, providing a rationale for designing and regulating more efficient photocatalysts and improving the properties of photocatalytic toluene oxidation., 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 © 2022 Elsevier Inc. All rights reserved.)

Intestinal epithelial replenishment is fueled by continuously dividing intestinal stem cells (ISCs) resident at the crypt niche. However, the cell type(s) enabling replenishment upon damage and subsequent loss of whole crypts remain largely unclear. Using Set domain-containing protein 4 (Setd4), we identify a small population with reserve stem cell characteristics in the mouse intestine. Upon irradiation-induced injury, Setd4-expressing (Setd4 + ) cells survive radiation exposure and then activate to produce Sca-1-expressing cell types to restore the epithelial wall and regenerate crypts de novo via crypt fission. Setd4 + cells are confirmed to originate from the early fetal period, subsequently contributing to the development of embryonic gut and the establishment of postnatal crypts. Setd4 + cells are therefore represented as both originators and key regenerators of the intestine., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: In 2017, China launched a new round of medical reform (NMR) to address the inaccessibility of high-priced drugs for patients with serious diseases. This study explored the impact of the NMR on the accessibility and affordability of high-priced monoclonal antibodies (mAbs), and the effective promotion policies after the NMR., Methods: We used a standard method developed by the World Health Organization to conduct two surveys on the availability of mAbs and their prices before and after the NMR in the public hospitals in Hubei province, China. By interviewing hospital pharmacy experts, we identified the potential value of the current NMR in improving the access to therapeutic mAbs., Results: The average availability of 13 mAbs increased by 8.1% in the surveyed hospitals of Hubei province after the NMR. The median unit price of 10 mAbs dropped by 34.3%. The average affordability of a treatment cycle of 10 mAbs dropped from 680 days to 298 days of the disposable daily income for a middle-income resident (56.2% reduction). The drug price negotiation of medical insurance inclusion and the promotion of consistent evaluation of generic and original drugs could effectively promote the accessibility of mAbs. However, the zero markup of drug pricing and the limit on the proportion of drug revenues in public hospitals showed certain negative effects on the availability of mAbs., Conclusion: Not all current NMR policies play a positive role in promoting the accessibility of mAbs. To further improve the accessibility of mAbs in the future in China, it is therefore critical to increase the investment in independent research and development of high-quality mAbs, establish localized guidelines for the rational use of mAbs in clinical practice, and have a cost-sharing mechanism for high-priced drugs with multiple stakeholders., (© 2022. Huazhong University of Science and Technology.)

Psoriasis seriously harms physical and mental health of patients. Hyaluronic acid (HA)-based topical formulation can increase drug concentration in psoriatic skin via CD44-assisted targeting. Herein, we developed a supramolecular medicine composed of curcumin-loaded HA-cucurbit[7]uril (HA-CB[7]@Cur), which could efficiently sequester polyamines (PAs) via host-guest interactions of CB[7] and PAs to suppress RNA-PAs immunocomplex formation. Meanwhile, anti-psoriasis drug Cur could be released from HA-CB[7]@Cur by PAs. With phenotypical disease evaluation, psoriasis area measurements and severity index scoring, and histological characterizations, we demonstrate topical administration of Carbopol gel formulation of HA-CB[7]@Cur on psoriasis-like skin in mice exhibited an enhanced anti-psoriasis activity, in comparison with gel of free Cur or HA-CB[7]. Cytokine expression analysis in psoriatic skin also supported the observed therapeutic outcomes. We provide a novel and effective supramolecular strategy to realize cooperative anti-psoriasis via controlled release of curcumin and PAs sequestration, which can be potentially expanded to treat other PA-involved skin inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Medication therapy management (MTM) service is an effective method to reduce medication-related problems and improve patients' multiple kinds of outcomes. However, the lack of comprehensive review for MTM services has hindered its development. As a result, we are aiming to evaluate the current benefits of MTM services with multiple outcomes., Method: An electronic search will be performed for randomized controlled trials (RCTs) or non-randomized control trials (NRCTs) that reported MTM services or pharmaceutical services as interventions from PubMed, The Cochrane Library, Embase, and ClinicalTrial. gov. The odds ratios, mean differences, and standard mean differences and their 95% confidence intervals (95% confidence intervals) will be calculated with fixed or random effect models., Results: This study will evaluate the multiple benefits of MTM services in clinical endpoints, quality of life, economy, and drug-related problems., Conclusion: The results will review eligible studies released in the past twenty years and provide more comprehensive evidence of the efficacy of MTM services., Ethics and Dissemination: Ethical approval is not applicable for this study., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To study the role and mechanism of autophagy in lipopolysaccharide (LPS)-induced inflammatory response of human alveolar epithelial A549 cells., Methods: A549 cells were stimulated with LPS to establish a cell model of inflammatory response, and were then grouped ( n =3 each) by concentration (0, 1, 5, and 10 μg/mL) and time (0, 4, 8, 12, and 24 hours). The A549 cells were treated with autophagy inhibitor 3-methyladenine (3-MA) to be divided into four groups ( n =3 each): control, LPS, 3-MA, and 3-MA+LPS. The A549 cells were treated with autophagy agonist rapamycin (RAPA) to be divided into four groups ( n =3 each): control, LPS, RAPA, and RAPA+LPS. The A549 cells were transfected with the Toll-like receptor 4 (TLR4) overexpression plasmid to be divided into four groups ( n =3 each): TLR4 overexpression control, TLR4 overexpression, TLR4 overexpression control+LPS, and TLR4 overexpression+LPS. The A549 cells were transfected with TLR4 siRNA to be divided into four groups ( n =3 each): TLR4 silencing control,TLR4 silencing, TLR4 silencing control+LPS, and TLR4 silencing+LPS. CCK-8 assay was used to measure cell viability. Western blot was used to measure the protein expression levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4., Results: After stimulation with 1 μg/mL LPS for 12 hours, the levels of inflammatory indicators (NLRP3, Caspase-1, and ASC), autophagic indicators (LC3B, Beclin-1, and P62), and TLR4 increased and reached the peak ( P <0.05). Compared with the LPS group, the 3-MA+LPS group had reduced expression of autophagy-related proteins and increased expression of inflammation-related proteins and TLR4, while the RAPA+LPS group had increased expression of autophagy-related proteins and reduced inflammation-related proteins and TLR4 ( P <0.05). The TLR4 overexpression+LPS group had reduced autophagy-related proteins and increased inflammation-related proteins compared with the TLR4 overexpression control+LPS group, and the TLR4 silencing+LPS group had increased autophagy-related proteins and reduced inflammation-related proteins compared with the TLR4 silencing control+LPS group ( P <0.05)., Conclusions: In the LPS-induced inflammatory response of human alveolar epithelial A549 cells, autophagic flux has a certain protective effect on A549 cells. TLR4-mediated autophagic flux negatively regulates the LPS-induced inflammatory response of A549 cells.

Global warming is an environmental problem that cannot be ignored. High temperatures seriously affect the normal growth and development of plants, and threaten the development of agriculture and the distribution and survival of species at risk. Plants have evolved complex but efficient mechanisms for sensing and responding to high temperatures, which involve the activation of numerous functional proteins, regulatory proteins, and non-coding RNAs. These mechanisms consist of large regulatory networks that regulate protein and RNA structure and stability, induce Ca 2+ and hormone signal transduction, mediate sucrose and water transport, activate antioxidant defense, and maintain other normal metabolic pathways. This article reviews recent research results on the molecular mechanisms of plant response to high temperatures, highlighting future directions or strategies for promoting plant heat tolerance, thereby helping to identify the regulatory mechanisms of heat stress responses in plants.

Solid non-aqueous phases (NAPs), such as silicone rubber, have been used extensively to improve the removal of volatile organic compounds (VOCs). However, the removal of VOCs is difficult to be further improved because the poor understanding of the mass transfer and reaction processes. Further, the conventional reactors were either complicated or uneconomical. In view of this, herein, an airlift bioreactor with silicone rubber was designed and investigated for dichloromethane (DCM) treatment. The removal efficiency of Reactor 1 (with silicone rubber) was significantly higher than that of Reactor 2 (without silicone rubber), with corresponding higher chloride ion and CO 2 production. It was found that Reactor 1 achieved a much better DCM shock tolerance capability and biomass stability than Reactor 2. Silicone rubber not only enhanced the mass transfer in terms of both gas/liquid and gas/microbial phases, but also decreased the toxicity of DCM to microorganisms. Noteworthily, despite the identical inoculum used, the relative abundance of potential DCM-degrading bacteria in Reactor 1 (91.2%) was much higher than that in Reactor 2 (24.3%) at 216 h. Additionally, the silicone rubber could be automatically circulated in the airlift bioreactor due to the driven effect of the airflow, resulting in a significant reduction of energy consumption., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Induction chemotherapy followed by concurrent chemoradiotherapy (IC-CCRT) may be beneficial for nasopharyngeal carcinoma. However, the evidence on medium- and long-term effects of IC-CCRT is limited, and new randomized controlled trials (RCTs) have been published after 2018. Therefore, this systematic review and meta-analysis compared survival rates between patients with nasopharyngeal carcinoma receiving IC-CCRT or concurrent chemoradiotherapy (CCRT)., Methods: Four databases were searched for RCTs on this topic. Two authors independently selected studies, assessed evidence, and extracted data on progression-free survival, overall survival, metastasis-free survival, and local recurrence-free survival. Available data were pooled in a random-effects model and mainly presented in hazard ratio (HR). Heterogeneity and small study effects were also evaluated., Results: Eleven RCTs (n = 3345) were deemed eligible. Pooled results revealed that patients receiving IC-CCRT had significantly improved progression-free survival (HR = 0.66, P < 0.05), overall survival (HR = 0.64, P < 0.05), metastasis-free survival (HR = 0.58, P < 0.05), and local recurrence-free survival (HR = 0.69, P < 0.05) at 3 years, but no significant difference in 5-year overall survival was noted between IC-CCRT and CCRT (HR = 0.84, P > 0.05). Most findings had low heterogeneity., Conclusion: IC-CCRT may benefit patients with nasopharyngeal carcinoma in the medium term, although no significant difference was observed in 5-year survival compared with CCRT. All outcomes had decreased survival rate from the 3-years to 5-year follow-up. Differences in patient ethnicities and regimens of IC-CCRT may be sources of heterogeneity., 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 © 2022 Huang, Chen, Ding and Kang.)

Cellular quiescence facilitates maintenance of neural stem cells (NSCs) and their subsequent regenerative functions in response to brain injury and aging. However, the specification and maintenance of NSCs in quiescence from embryo to adulthood remain largely unclear. Here, using Set domain-containing protein 4 (SETD4), an epigenetic determinant of cellular quiescence, we mark a small but long-lived NSC population in deep quiescence in the subventricular zone of adult murine brain. Genetic lineage tracing shows that SETD4 + cells appear before neuroectoderm formation and contribute to brain development. In the adult, conditional knockout of Setd4 resulted in quiescence exit of NSCs, generating newborn neurons in the olfactory bulb and contributing to damage repair. However, long period deletion of SETD4 lead to exhaustion of NSC reservoir or SETD4 overexpression caused quiescence entry of NSCs, leading to suppressed neurogenesis. This study reveals the existence of long-lived deep quiescent NSCs and their neurogenetic capacities beyond activation., Competing Interests: Conflicts of interest The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Excessive bleeding has always been of great medical challenge, particularly in trauma and surgery. Due to the fast clearance of medicine and complex hemodynamics during hemorrhage, it is often difficult to achieve rapid and effective hemostasis on irregularly shaped, noncompressible visceral bleeding wounds. Herein, we report a hemostatic derived from supramolecularly functionalized platelets (SPLTs), showing rapid hemorrhage controlling effects via efficiently targeting injured vessels and in-situ aggregation. Von Willebrand factor-binding peptide (VBP) modified hyaluronic acid (HA-VBP) decorated platelets (PLTs) were fabricated via supramolecular host-guest interactions between cucurbit[7]uril (CB[7], a host molecule) modified on HA-VBP (HA-CB[7]-VBP) and adamantane (ADA, a guest molecule) anchored on the surface of PLTs (ADA-PLTs). The SPLTs demonstrated approximately 10-fold improvements than the native PLTs in the targeting efficiency into the injured vessels in mice upon intravenous injection. More significantly, the total bleeding time and bleeding volume were dramatically reduced down to less than 1/4 and 1/10 of the control group, respectively, in both external and internal major bleeding mice models. This SPLTs provide a facile yet effective approach for rapid control of major hemorrhage and offers important new insights to the design and development PLTs-based hemostatics. STATEMENT OF SIGNIFICANCE: Hemorrhage is one of the greatest threats to humans in trauma and surgery. To reduce bleeding volume and time, transfusion of hematological products such as platelets (PLTs)-rich plasma is one of the most commonly used therapeutics, but with low targeting and hemostatic efficiency. Thus, engineered PLTs with expanded structural repertoire and functionalities are in urgent clinical needs. Herein, we developed supramolecularly functionalized PLTs (SPLTs), prepared with a mild and facile approach, for rapid control of hemorrhage with significantly enhanced targeting efficiency. The SPLTs not only provide a facile approach for rapid control of major hemorrhage, but also offer important new insights into the development PLTs-based hemostatics., 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 © 2022. Published by Elsevier Ltd.)

Objective: To develop and validate a nomogram for predicting 6-week mortality in patients with liver cirrhosis and acute upper gastrointestinal bleeding (UGIB) and to compare it with other commonly used scoring systems., Methods: This retrospective study included cirrhotic patients with acute UGIB hospitalized between January 2013 and December 2020. Random sampling was used to divide patients into the training (n = 676) and validation cohorts (n = 291) at a 7:3 ratio. Multivariate logistic stepwise regression was used to establish a model for predicting 6-week mortality. Multiple indicators were used to validate the nomogram, including the area under the receiver operating characteristic curve (AUROC), calibration curve, and decision curve analysis (DCA)., Results: In the training cohort, total bilirubin (TBIL) (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.22-2.50), hemoglobin (Hb) (OR 0.97, 95% CI 0.95-0.99), C-reactive protein (OR 2.79, 95% CI 1.30-6.07), prothrombin time (OR 1.17, 95% CI 1.05-1.30), and hepatic encephalopathy (stage I-II: OR 4.15, 95% CI 1.73-9.61; stage III-IV: OR 19.6, 95% CI 5.33-76.8) were identified as independent factors of 6-week mortality. The AUROC of the UGIB-LC score was 0.873 (95% CI 0.820-0.927), which was higher than that of the Child-Pugh score (0.781), model for end-stage liver disease score (0.766), and neutrophil-to-lymphocyte ratio (0.716)., Conclusion: The UGIB-LC score is useful for predicting 6-week mortality in patients with liver cirrhosis and acute UGIB, which is superior to the other three scoring systems., (© 2022 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Marine sponges are productive sources of bioactive secondary metabolites with over 200 new compounds isolated each year, contributing 23% of approved marine drugs so far. This review describes statistical research, structural diversity, and pharmacological activity of sponge derived new natural products from 2009 to 2018. Approximately 2762 new metabolites have been reported from 180 genera of sponges this decade, of which the main structural types are alkaloids and terpenoids, accounting for 50% of the total. More than half of new molecules showed biological activities including cytotoxic, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, enzyme inhibition, and antimalarial activities. As summarized in this review, macrolides and peptides had higher proportions of new bioactive compounds in new compounds than other chemical classes. Every chemical class displayed cytotoxicity as the dominant activity. Alkaloids were the major contributors to antibacterial, antifungal, and antioxidant activities while steroids were primarily responsible for pest resistance activity. Alkaloids, terpenoids, and steroids displayed the most diverse biological activities. The statistic research of new compounds by published year, chemical class, sponge taxonomy, and biological activity are presented. Structural novelty and significant bioactivities of some representative compounds are highlighted. Marine sponges are rich sources of novel bioactive compounds and serve as animal hosts for microorganisms, highlighting the undisputed potential of sponges in the marine drugs research and development., Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-022-00132-3., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interests., (© The Author(s) 2022.)

Nail disease in psoriasis has been found to be associated with psoriatic arthritis (PsA); however, which subtype of nail disease holds greater relevance to PsA remains unclear. This study was performed to explore the associations between three subtypes of fingernail disease (pitting, onycholysis, and hyperkeratosis) and PsA among patients with psoriasis. Patients with psoriasis attending five dermatology clinics in Shanghai between January 2020 and May 2021 were examined for skin, joint, and fingernail changes. Multivariate logistic regression analyses were utilized to test the strength of associations between subtypes of fingernail disease and PsA. The receiver operator characteristic (ROC) curve with area under curve (AUC) was used to evaluate their accuracies in diagnosing PsA. Sensitivity and specificity were also calculated. Of 1985 patients with psoriasis included, 228 (11.5%) patients were diagnosed with PsA, and the remaining patients were cutaneous-only psoriasis (PsC). One-hundred and fifty-seven (68.9%) patients with PsA and 748 (42.6%) patients with PsC had fingernail disease. Adjusted models showed that onycholysis and hyperkeratosis were the only type of fingernail disease independently associated with PsA. This association was further confirmed by the forward conditional stepwise regression model (OR, 95% CI for onycholysis: 2.34, 1.79 to 4.27, p < 0.01; for hyperkeratosis: 1.62, 1.12 to 2.66, p = 0.037). ROC analysis showed that, compared to pitting and hyperkeratosis, onycholysis had higher AUC (0.630) and sensitivity (52.6%). The psoriatic fingernail onycholysis and hyperkeratosis hold greater relevance to PsA than pitting. Clinically, psoriatic patients with fingernail onycholysis and hyperkeratosis should be assessed for arthritis. Key Points • Psoriatic fingernail onycholysis and hyperkeratosis, rather than pitting, are significantly associated with PsA • Clinically, psoriatic patients with fingernail onycholysis and hyperkeratosis should be assessed for arthritis., (© 2022. International League of Associations for Rheumatology (ILAR).)

Improving the precise accumulation and retention of nanomedicines in tumor cells is one of the keys to effective therapy of tumors. Herein, supramolecular peptides capped Au nanocages (AuNCs) that may self-aggregate into micron-sized clusters intracellularly in response to spermine (SPM), leading to specific accumulation and retention of AuNCs in SPM-overexpressed tumor cells, are developed. In this design, polydopamine (PDA) is in situ coated on the surface of AuNCs with doxorubicin (DOX) encapsulated. A small peptide, Phe-Phe-Val-Leu-Lys (FFVLK), is conjugated with PDA via esterification, and cucurbit[7]uril (CB[7]) is threaded onto the N-terminal Phe via host-guest interactions. Once the supramolecular peptide (CB[7]-FFVLK) capped AuNCs are internalized in SPM-overexpressed breast cancer cells, CB[7] can be competitively removed from FFVLK by SPM, due to the much higher binding affinity between CB[7] and SPM than that between CB[7] and Phe, leading to exposure of free FFVLK, which can subsequently self-assemble and induce the aggregation of AuNCs to micron-sized clusters, resulting in the significantly enhanced accumulation and retention of DOX-loaded AuNCs in tumor cells. Under NIR laser irradiation, the enhanced photothermal conversion of AuNCs aggregates, together with photothermia-induced release of DOX leads to synergistic photothermal therapy and chemotherapy against breast cancer., (© 2022 Wiley-VCH GmbH.)

Three new polyacetylenes, pellynols P (1), Q (2), and R (3) were isolated from the marine sponge Petrosia sp., along with the known compound pellynol H (4). Their structures were determined by analyses of extensive NMR, HR-MS, and ESI-MS/MS data. All compounds displayed potent cytotoxicities against human hepatocellular carcinoma HepG2, human melanoma A375, and human colorectal carcinoma HT29 cell lines with IC 50 values at the range of 1.4-4.4 μM., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Several screening tools have been developed to facilitate early diagnosis of psoriatic arthritis (PsA); however, their performance varied greatly across different studies. In this study, we validated and compared the performance of four screening tools in detecting undiagnosed PsA Chinese patients with psoriasis, and determined the key questions and their weights. The four screening tools were the Early Arthritis for Psoriatic Patients (EARP) questionnaire, Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire, Psoriasis and Arthritis Screening Questionnaire (PASQ), and Psoriasis Epidemiology Screening Tool (PEST). The receiver-operator curve (ROC) with area under curve (AUC) was used to determine sensitivity, specificity, and accuracy. Least absolute shrinkage and selection operator and logistic regression were utilized to retrieve key questions, and a nomogram was utilized to visualize their weights. Of 482 psoriasis patients from dermatology clinics, 77 were newly diagnosed with PsA. Another 68 patients with newly diagnosed PsA from rheumatology clinics were incorporated in the analysis. ROC analysis indicated that the optimal cut-off values for EARP, PASE, PASQ, and PEST were 3, 40, 7, and 3, with corresponding sensitivities of 91.4%, 88.6%, 86.2%, and 88.5%, and specificities of 88.6%, 75.2%, 80.2%, and 83.6%, respectively. The AUC of EARP (0.925) was higher than those of PASE (0.885), PASQ (0.905), and PEST (0.827). However, none of them were sufficiently sensitive to identify pure axial PsA (sensitivities of EARP, PASQ, and PASE were 25.0%, 36.8%, and 42.1%, respectively). Twelve key questions were retrieved from these four tools to establish a nomogram with a high discrimination (C-index = 0.993) and a good calibration (mean absolute error = 0.014). In conclusion, to screen undiagnosed PsA, EARP has slightly better balanced sensitivity and specificity, and higher accuracy. The retrieval of key questions and nomogram signify the necessity of attributing different scores to differently weighted questions when developing a new screening tool to make it function more efficiently., (© 2022 Japanese Dermatological Association.)

Oral squamous cell carcinoma (OSCC) is the most frequently encountered type of oral cancer. Histamine receptor H1 ( HRH1 ) was reported to play a crucial role in OSCC carcinogenesis, but impacts of genetic variants of HRH1 on OSCC remain unclear. Herein, we investigated the association between functional single-nucleotide polymorphisms (SNPs) of HRH1 and OSCC susceptibility or clinicopathologic variables by logistic regression models. HRH1 genotypes at four loci (rs346074, rs346076, rs901865, and rs2606731) were analyzed by a TaqMan allelic discrimination assay, and we found that patients harboring HRH1 rs901865 T and rs346074 T alleles had a significantly lower risk of developing larger tumor sizes (>T2) under a dominant model. Based on the environmental carcinogen exposure status, we observed that HRH1 rs901865 polymorphic variants were also associated with a lower risk of developing more-advanced clinical stages (III or IV) in patients with a betel-quid-chewing habit. Moreover, genotype screening of rs901865 and rs346074 in OSCC cell lines showed that cells respectively carrying the CT and TT genotypes expressed lower HRH1 levels compared to cells carrying the CC genotype of rs901865 and rs346074. Furthermore, analyses of TCGA and GEO databases revealed that HRH1 expression levels were upregulated in head and neck squamous cell carcinoma (HNSCC) and OSCC tissues compared to normal tissues and were correlated with larger tumor sizes and poorer prognoses. These results indicated the involvement of HRH1 SNPs rs901865 and rs346074 in OSCC development and support the interaction between HRH1 gene polymorphisms and an environmental carcinogen as a predisposing factor for OSCC progression.

Background: GO-Y078, a new synthetic analogue of curcumin (CUR), has higher oral bioavailability and anticancer activity than CUR, but the oncostatic effect of GO-Y078 on oral squamous cell carcinoma (OSCC) is largely unknown., Research Design and Methods: In the present study, we examined the oncostatic properties and possible mechanisms of GO-Y078 on human SCC-9 and HSC-3 OSCC cells., Results: Our results indicated that GO-Y078 showed a cytostatic effect against OSCC cells, and this antiproliferative phenomenon stemmed from a mechanism involving multiple levels of cooperation, including cell-cycle G 2 /M arrest and apoptosis induction. Mechanistically, GO-Y078 treatment induced caspase-mediated apoptosis via upregulating two apoptosis-modulating proteins, SMAC/DIABLO and heme oxygenase (HO)-1. GO-Y078 transcriptionally induced upregulation of the HO-1 gene by increasing the AP-1 DNA-binding activity, which was initiated by activation of the p38 /JNK1/2 pathways. In the clinic, patients with head and neck cancers expressed lower HO-1 and SMAC/DIABLO levels in primary cancer tissues compared to normal tissues. Clinical datasets also revealed that patients with head and neck cancers expressing high HO-1 had afavorable prognosis., Conclusions: Our results provide new insights into the role of GO-Y078-induced molecular regulation in suppressing OSCC growth and suggest that GO-Y078 has potential therapeutic applications for OSCC.

Strong interchain interactions of conjugated polymers usually result in poor miscibility with molecular dopants, limiting the doping efficiency because of uncontrolled phase separation. We have developed a strategy to achieve efficient charge-transport and high doping miscibility in n-doped conjugated polymers. We solve the miscibility issue through disorder side-chains containing dopants better. Systemic structural characterization reveals a farther side-chain branching point will lead to higher disorders, which provides appropriate sites to accommodate extrinsic molecular dopants without harming original chain packings and charge-transport channels. Therefore, better sustainability of solid-state microstructure is obtained, yielding a stable conductivity even when overloading massive dopants. This work highlights the importance of realizing high host-dopant miscibility in molecular doping of conjugated polymers., (© 2022 Wiley-VCH GmbH.)