The inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in immunocompromised AG129 mice.

Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/ß and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.

Discovery of L15 as a novel Vif PROTAC degrader with antiviral activity against HIV-1.

Viral infectivity factor (Vif) has been recognized as a new therapeutic target for human immunodeficiency virus-1 (HIV-1) infected patients. In our previous work, we have synthesized a novel class of Vif inhibitors with 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold, which show obvious activity in HIV-1 infected cells and are also effective against drug-resistant strains. Proteolytic targeting chimera (PROTAC) utilizes the ubiquitin-proteasome system to degrade target proteins, which is well established in the field of cancer, but the antiviral PROTAC molecules are rarely reported. In order to explore the effectiveness of PROTAC in the antiviral area, we designed and synthesized a series of degrader of HIV-1 Vif based on 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold. Among them, L15 can degrade Vif protein obviously in a dose-dependent manner and shows certain antivirus activity. Meanwhile, molecular dynamics simulation indicated that the ternary complex formed by L15, Vif, and E3 ligase adopted a reasonable binding mode and maintained a stable interaction. This provided a molecular basis and prerequisite for the selective degradation of the Vif protein by L15. This study reports the HIV-1 Vif PROTAC for the first time and represents the proof-of-concept of PROTACs-based antiviral drug discovery in the field of HIV/ acquired immune deficiency syndrome (AIDS).

Retrospecting Digital Media Use, Negative Emotions, and Trust Gaps During the COVID-19 Pandemic in China: Cross-Sectional Web-Based Survey.

BACKGROUND: Retrospecting the trust gaps and their dynamics during the pandemic is crucial for understanding the root causes of postpandemic challenges and offers valuable insights into preparing for future public health emergencies. The COVID-19 pandemic eroded people's trust in strangers and acquaintances, while their trust in family members remained relatively stable. This resulted in 2 trust gaps, namely, the family members-strangers trust gap and the family members-acquaintances trust gap. Widening trust gaps impede social integration and undermine the effective management of public health crises. However, little is known about how digital media use shaped trust gaps during a pandemic. OBJECTIVE: This study aims to investigate the relationships between digital media use, negative emotions, the family members-strangers trust gap, and the family members-acquaintances trust gap during the COVID-19 pandemic in China. We test the mediating role of negative emotions between digital media use and 2 trust gaps and compare the indirect effect of digital media use on 2 trust gaps through negative emotions. METHODS: A cross-sectional web-based survey was conducted in China between January 31, 2020, and February 9, 2020. A total of 1568 adults participated in the survey. Questions related to digital media use, negative emotions, trust in family members, trust in acquaintances, and trust in strangers during the pandemic were asked. Regression analyses were performed to test the associations between the examined variables. We used a 95% bootstrap CI approach to estimate the mediation effects. RESULTS: Digital media use was positively associated with negative emotions (B=0.17, SE 0.03; P<.001), which in turn were positively associated with the family members-strangers trust gap (B=0.15, SE 0.03; P<.001). Likewise, digital media use was positively associated with negative emotions (B=0.17, SE 0.03; P<.001), while negative emotions were positively associated with the family members-acquaintances trust gap (B=0.08, SE 0.03; P=.01). Moreover, the indirect effect of digital media use on the family members-strangers trust gap (B=0.03, SE 0.01; 95% CI 0.01-0.04) was stronger than that on the family members-acquaintances trust gap (B=0.01, SE 0.01; 95% CI 0.003-0.027). CONCLUSIONS: The results demonstrate that negative emotions resulting from the frequent use of digital media are a key factor that accounts for the widening trust gaps. Considering the increasing reliance on digital media, the findings indicate that the appropriate use of digital media can prevent the overamplification of negative emotions and curb the enlargement of trust gaps. This may help restore social trust and prepare for future public health crises in the postpandemic era.

Effect of Meal-Timing on the Association of Unsaturated Fatty Acids with All-Cause and Cardiovascular Mortality among Adults: A Prospective Cohort Study with 10-Year Follow-Up.

BACKGROUND: Conflicting results have been reported on the association of dietary unsaturated fatty acids (UFAs) with longevity and cardiovascular health. Most previous studies have focused only on the amount of UFAs consumed, not the timing of intake. METHODS: This prospective cohort study used data from 30,136 adults aged 18 years and older. Intakes of UFAs by meal time and types were assessed by a 24-h dietary recall for two days. The covariate-adjusted survey-weighted Cox proportional hazards models were performed to evaluate the associations of dietary total unsaturated fatty acid (TUFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) intakes throughout the day and three meals with mortality. RESULTS: During a median of 10.0 years of follow-up, 4510 total deaths occurred. All-cause mortality decreased with increasing intakes at dinner of TUFA (HR: 0.87 [0.77-0.98]), PUFA (HR: 0.81 [0.73-0.91]), and MUFA (HR: 0.88 [0.77-0.99]). With an increased intake of PUFA at dinner, CVD mortality showed a decreasing trend. However, the inverted L-shaped non-linear trend in all-cause mortality was found with increasing intake at breakfast of TUFA (HR: 1.35 [1.17-1.57], Q3 vs. Q1), PUFA (HR: 1.30 [1.13-1.50]), and MUFA (HR: 1.28 [1.13-1.45]). Meanwhile, increased breakfast intake of UFAs was associated with increased CVD and heart disease mortality. CONCLUSIONS: Meal timing influences the association of UFAs with all-cause and CVD-related mortality.

The zinc absorption of the novel peptide-Zn complex in Caco-2 cells: effects of soybean peptides charge and hydrophobicity.

BACKGROUND: The supplemental effect of zinc depends not only on adequate intake, but also on how efficiently it is absorbed in the small intestine. In the present study, weak hydrophobic peptides (WHP), strong hydrophobic peptides (SHP), positively charged peptides (PCP) and negatively charged peptides (NCP) were isolated from soybean peptides (SP). The peptide-Zn complexes (PCP-Zn, NCP-Zn, WHP-Zn, SHP-Zn and SP-Zn) were prepared to compare their promotion zinc absorption capacity in the Caco-2 cells monolayers model. RESULTS: We found that the carboxyl, carbonyl and amino groups in peptide were the primary binding sites of Zn. Compared with zinc sulfate, the peptide-Zn complexes with different charge and hydrophobic peptides could improve zinc solubility at different pH. NCP-Zn had a lower Zn-binding capacity but a higher zinc absorption capacity compared to that of PCP-Zn in Caco-2 cells. In addition, the capacity of PCP-Zn to promote zinc absorption was lower than the control group (SP-Zn). There were no significant differences in transport rates, retention rates and uptake rates of WHP-Zn, SHP-Zn and SP-Zn. NCP-Zn could improve the activity of Zn-related enzymes, and the expression levels of PepT1 and ZnT1 were higher than other peptide-Zn complexes. CONCLUSION: The promotion zinc absorption capacity of peptide-Zn complexes was not completely dependent on the Zn-binding capacity, but also depended on the charge and hydrophobicity of peptides. © 2024 Society of Chemical Industry.

A bibliometric and knowledge-map study on the treatment of hematological malignancies with CAR-T cells from 2012 to 2023.

Recently, CAR-T cell therapy in hematological malignancies has received extensive attention. The objective of this study is to gain a comprehensive understanding of the current research status, development trends, research hotspots, and emerging topics pertaining to CAR-T cells in the treatment of hematological malignancies. Articles pertaining to CAR-T cell therapy for hematological malignancies from the years 2012 to 2023 were obtained and assessed from the Web of Science Core Collection (WoSCC). A bibliometric approach was employed to conduct a scientific, comprehensive, and objective quantitative analysis, as well as a visual analysis, of this particular research domain. A comprehensive analysis was conducted on a corpus of 3643 articles, which were collaboratively authored by 72 countries and various research institutions. CAR-T cell research in treating hematological malignancies shows an increasing trend each year. Notably, the study identified the countries and institutions displaying the highest level of activity, the journals with the most citations and output, as well as the authors who garnered the highest frequency of citations and co-citations. Furthermore, the analysis successfully identified the research hotspots and highlighted six emerging topics within this domain. This study conducted a comprehensive exploration and analysis of the research status, development trends, research hotspots, and emerging topics about CAR-T cells in the treatment of hematological malignancies from 2012 to 2023. The findings of this study will serve as a valuable reference and guide for researchers seeking to delve deeper into this field and determine the future direction of their research.

Biochar Blended with Alkaline Mineral Can Better Inhibit Lead and Cadmium Uptake and Promote the Growth of Vegetables.

Three successive vegetable pot experiments were conducted to assess the effects on the long-term immobilization of heavy metals in soil and crop yield improvement after the addition of peanut shell biochar and an alkaline mineral to an acidic soil contaminated with lead and cadmium. Compared with the CK treatment, the change rates of biomass in the edible parts of the three types of vegetables treated with B0.3, B1, B3, B9, R0.2 and B1R0.2 were -15.43%~123.30%, 35.10%~269.09%, 40.77%~929.31%, -26.08%~711.99%, 44.14%~1067.12% and 53.09%~1139.06%, respectively. The cadmium contents in the edible parts of the three vegetables treated with these six additives reduced by 2.08%~13.21%, 9.56%~24.78%, 9.96%~35.61%, 41.96%~78.42%, -4.19%~57.07% and 12.43%~65.92%, respectively, while the lead contents in the edible parts reduced by -15.70%~59.47%, 6.55%~70.75%, 3.40%~80.10%, 55.26%~89.79%, 11.05%~70.15% and 50.35%~79.25%, respectively. Due to the increases in soil pH, soil cation-exchange capacity and soil organic carbon content, the accumulation of Cd and Pb in the vegetables was most notably reduced with a high dosage of 9% peanut shell biochar alone, followed by the addition of a low dosage of 1% peanut shell biochar blended with 0.2% alkaline mineral. Therefore, the addition of a low dosage of 1% peanut shell biochar blended with 0.2% alkaline mineral was the best additive in increasing the vegetable biomass, whereas the addition of 9% peanut shell biochar alone was the worst. Evidently, the addition of 0.2% alkaline mineral can significantly reduce the amount of peanut shell needed for passivating heavy metals in soil, while it also achieves the effect of increasing the vegetable yield.

Analysis of changes in social isolation, loneliness, or both, and subsequent cognitive function among older adults: Findings from a nationwide cohort study.

INTRODUCTION: The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function. METHODS: Data were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine-category variable to represent the joint changes. Tobit regression models and Cox models were performed. RESULTS: Incident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p < 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p < 0.001). Notably, short-term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p < 0.05). DISCUSSION: Short-term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment. HIGHLIGHTS: Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short-term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk.

Commensal microbiome dysbiosis elicits interleukin-8 signaling to drive fibrotic skin disease.

Wound healing is an intensely studied topic involved in many relevant pathophysiological processes, including fibrosis. Despite the large interest in fibrosis, the network that is related to commensal microbiota and skin fibrosis remains mysterious. Here, we pay attention to keloid, a classical yet intractable skin fibrotic disease to establish the association between commensal microbiota to scaring tissue. Our histological data reveal the presence of microbiota in the keloids. 16S rRNA sequencing characterizes microbial composition and divergence between the pathological and normal skin tissues. Moreover, the data show elevation of interleukin-8 (IL-8) in both the circulation and keloid tissue, which elicited the collagen accumulation and migratory program of dermal fibroblasts via CXCR1/2 receptor. Our research provides insights into the pathology of human fibrotic diseases, advocating commensal bacteria and IL-8 signaling as useful targets in future interventions of recurrent keloid disease.

Constructing Functional Radiation-Resistant Thorium Clusters for Catalytic Redox Reactions.

When catalytic reactions are interfered with by radiation sources, thorium clusters are promising as potential catalysts due to their superior radiation resistance. However, there is currently very little research on the design synthesis and catalytic application of radiation-stable thorium clusters. In this work, we have elaborately engineered and fabricated three high-nuclear thorium cluster catalysts denoted as Th12L3-MA12, Th12L3-MA6-BF6, and Th12L3-Fcc12, which did not undergo any significant alterations in their molecular structures and compositions after irradiation with 690 kGy γ-rays. We systematically investigated the photocatalytic/thermocatalytic properties of these radiation-resistant thorium clusters for the first time and found that γ-rays could not alter their catalytic activities. In addition, it was found that ligand engineering could modulate the catalytic activity of thorium clusters, thus expanding the range of catalytic applications of thorium clusters, including reduction reactions (nitroarene reduction) and some oxidation reactions (N-heterocyclic oxidative dehydrogenation and diphenylmethane oxidation). Meanwhile, all of these organic transformation reactions achieved a >80% conversion and nearly 100% product selectivity. Radiation experiments combined with DFT calculations showed that the synergistic catalysis of thorium-oxo core and ligands led to the generation of specific active species (H+, O2•-, or tBuO/tBuOO•) and activation of substrate molecules, thus achieving superior catalytic performance. This work is not only the first to develop radiation-resistant thorium cluster catalysts to perform efficient redox reactions but also provides design ideas for the construction of high-nuclearity thorium clusters under mild conditions.

The therapeutic effect of continuous blood purification on sepsis in children: a systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses have systematically assessed the therapeutic effect of continuous blood purification (CBP) in adult patients with sepsis. Considering infection etiology and host response of sepsis is different in children, this systematic review and meta-analysis aims to evaluate the clinical efficacy of CBP in children with sepsis. METHODS: Studies were searched from the Pubmed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and VIP databases. Outcomes included vital signs, coagulation markers, organ function markers, immune markers, inflammatory markers, and prognostic markers. Heterogeneity was evaluated by the I-square statistic (I2), and sensitivity analysis was performed. RESULTS: 24 studies were included in this meta-analysis. Pooled results showed that CBP decreased levels of alanine transaminase (ALT) (weighted mean difference [WMD] = -44.867, 95%CI: -64.809 to -24.926), aspartate aminotransferase (AST) (WMD = -55.373, 95%CI: -73.286 to -37.460), blood urea nitrogen (BUN) (WMD = -2.581, 95%CI: -4.539 to -0.622), and serum creatinine (Scr) (WMD = -11.567, 95%CI: -19.509 to -3.625). The percentage of CD3+ cells (WMD = 8.242, 95%CI: 3.339 to 13.144) and CD4+ cells (WMD = 4.278, 95%CI: 3.252 to 5.303, I2 = 3.1%) were increased in the CBP group. C-reaction protein (CRP) (WMD = -20.699, 95%CI: -34.740 to -6.657) and tumor necrosis factor-α (TNF-α) (WMD = -19.185, 95%CI: -34.133 to -4.237) were reduced after CBP treatment. Pediatric critical illness score (PCIS) was increased (WMD = 7.916, 95%CI: 4.317 to 11.516) and the risk of 28-day mortality (risk ratio [RR] = 0.781, 95%CI: 0.632 to 0.965) was lower in the CBP group. CONCLUSIONS: CBP reduced the level of inflammatory markers, increased the level of immune markers, and improved organ function and prognosis, which may provide evidence for the use of CBP in sepsis children patients.

Ferrocene-modified covalent organic framework for efficient oxygen evolution reaction and CO2 electroreduction.

A ferrocene-modified COF, namely Ni-Tph-COF-Fc, was synthesized and applied in OER. Compared with Ni-Tph-COF-OH, Ni-Tph-COF-Fc shows improved performance with a current density of 99.6 mA cm-2, an overpotential of 450 mV, and a Tafel slope of 73.1 mV dec-1, which may be attributed to a synergy between introduced ferrocene and metalloporphyrin in the COFs. Moreover, the enhanced OER performance leads to an improved CO2RR performance with an FECO of 93.1%. This work represents an effective strategy to enhance the anodic OER performance and realize efficient CO2RR.

Association of insomnia symptoms and trajectories with the risk of functional disability: a prospective cohort study.

BACKGROUND: There is limited understanding regarding prospective associations of insomnia symptoms and trajectories with functional disability. We aimed to investigate the associations of insomnia symptoms and trajectories with functional disability. METHOD: A total of 13 197 participants were eligible from the Health and Retirement Study. Insomnia symptoms included non-restorative sleep, difficulty initiating sleep, early morning awakening, and difficulty maintaining sleep. We also identified four distinct trajectories of insomnia symptoms: low, decreasing, increasing, and high insomnia symptoms. Functional status was assessed through activities of daily living (ADL) and instrumental activities of daily living (IADL). RESULTS: Participants experiencing one (HR, 1.21; 95% CI, 1.13-1.29), two (HR, 1.43; 95% CI, 1.29-1.57), or three to four (HR, 1.41; 95% CI, 1.25-1.60) insomnia symptoms had a higher risk of ADL disability than asymptomatic respondents. Similarly, participants with one or more insomnia symptoms had a higher risk of IADL disability. Furthermore, using the trajectory with low insomnia symptoms as the reference, decreasing insomnia symptoms (HR, 1.22; 95% CI, 1.12-1.34), increasing insomnia symptoms (HR, 1.21; 95% CI, 1.05-1.41), and high insomnia symptoms (HR, 1.36; 95% CI, 1.18-1.56) were all associated with an increased risk of ADL disability. CONCLUSION: Both a single measurement and dynamic trajectory of insomnia symptoms are associated with the onset of ADL disability. Increased awareness and management of insomnia symptoms may contribute to the prevention of functional disability occurrence.

Plasma exosomes from patients with active thyroid-associated orbitopathy induce inflammation and fibrosis in orbital fibroblasts.

BACKGROUND: The pathogenesis of thyroid-associated orbitopathy (TAO) remains incompletely understand. The interaction between immunocytes and orbital fibroblasts (OFs) play a critical role in orbital inflammatory and fibrosis. Accumulating reports indicate that a significant portion of plasma exosomes (Pla-Exos) are derived from immune cells; however, their impact upon OFs function is unclear. METHODS: OFs were primary cultured from inactive TAO patients. Exosomes isolated from plasma samples of patients with active TAO and healthy controls (HCs) were utilized for functional and RNA cargo analysis. Functional analysis in thymocyte differentiation antigen-1+ (Thy-1+) OFs measured expression of inflammatory and fibrotic markers (mRNAs and proteins) and cell activity in response to Pla-Exos. RNA cargo analysis was performed by RNA sequencing and RT-qPCR. Thy-1+ OFs were transfected with miR-144-3p mimics/inhibitors to evaluate its regulation of inflammation, fibrosis, and proliferation. RESULTS: Pla-Exos derived from active TAO patients (Pla-ExosTAO-A) induced stronger production of inflammatory cytokines and hyaluronic acid (HA) in Thy-1+ OFs while inhibiting their proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single sample gene set enrichment analysis (ssGSEA) suggested that the difference in mRNA expression levels between Pla-ExosTAO-A and Pla-ExosHC was closely related to immune cells. Differential expression analysis revealed that 62 upregulated and 45 downregulated miRNAs in Pla-ExosTAO-A, with the elevation of miR-144-3p in both Pla-Exos and PBMCs in active TAO group. KEGG analysis revealed that the target genes of differentially expressed miRNA and miR-144-3p enriched in immune-related signaling pathways. Overexpression of the miR-144-3p mimic significantly upregulated the secretion of inflammatory cytokines and HA in Thy-1+ OFs while inhibiting their proliferation. CONCLUSION: Pla-Exos derived from patients with active TAO were immune-active, which may be a long-term stimulus casual for inflammatory and fibrotic progression of TAO. Our finding suggests that Pla-Exos could be used as biomarkers or treatment targets in TAO patients.

A patent review of P2X7 receptor antagonists to treat inflammatory diseases (2018-present).

INTRODUCTION: The purinergic P2X7 receptor (P2X7R) is expressed on the surface of many different types of cells, including immune cells. Targeting P2X7R with antagonists has been studied for its potential therapeutic effects in a variety of inflammatory illnesses. AREA COVERED: Many chemical substances, including carboxamides, benzamides and nitrogen containing heterocyclic derivatives have demonstrated promising inhibitory potential for P2X7 receptor. The chemistry and clinical applications of P2X7R antagonists patented from 2018- present are discussed in this review. EXPERT OPINION: Purinergic receptor inhibitor discovery and application has demonstrated the potential for therapeutic intervention, as demonstrated by pharmacological research. Few chemical modalities have been authorized for use in clinical settings, despite the fact that breakthroughs in crystallography and chemical biology have increased the knowledge of purinergic signaling and its consequences in disease. The many research projects and pharmaceutical movements that sustain dynamic P2X receptor programs over decades are evidence of the therapeutic values and academic persistence in purinergic study. P2X7R is an intriguing therapeutic target and possible biomarker for inflammation. Although several companies like Merck and AstraZeneca have published patents on P2X3 antagonists, the search for P2X7R antagonists has not stopped. Numerous pharmaceutical companies have disclosed different scaffolds, and some molecules are presently being studied in clinical studies.

Regioselective Electrooxidative [3+2] Annulation between Indole and Aniline Derivatives to Construct Functionalized Indolo[2,3-b]indoles.

A protocol for the electrooxidative [3+2] annulation to generate indolo[2,3-b]indoles in an undivided cell is reported. It exhibits good yields with excellent regioselectivities and tolerates various functional groups without external chemical oxidants. Cyclic voltammetry and density functional theory calculations indicate that the [3+2] annulation is initiated by the simultaneous anodic oxidation of indole and aniline derivatives, and the step to determine the rate relies on the combination of radical cations.

Characterization of ribostamycin and its impurities using a nano-quantity analyte detector: Systematic comparison of performance among three different aerosol detectors.

Characterization of aminoglycoside antibiotics like ribostamycin is important due to the complex composition and common toxic impurities. Aerosol detectors are often employed for determination of these non-absorbent analytes. In this work, a robust and cost-effective method was developed for simultaneous detection of ribostamycin and its related substances using high-performance liquid chromatography (HPLC) with a relative new aerosol detector named nano-quantity analyte detector (NQAD). With the introduction of less toxic but more compatible ion-pairs pentafluoropropionic acid (PFPA) and trifluoroacetic acid (TFA) in the eluent, an optimized separation effect was achieved. Compared with the other two aerosol detectors namely ELSD (evaporative light scattering detector) and CAD (charged aerosol detector), method verification and quantitative detection results revealed that NQAD had higher sensitivity than ELSD with a 0.8 µg/mL limit of detection, as well as wider linear range (from 2 µg/mL to 1000 µg/mL) than both CAD (from 2 µg/mL to 200 µg/mL) and ELSD (from 8 µg/mL to 200 µg/mL) detector. The performance of NQAD helped to realize detection of ribostamycin and its impurities with significant concentration differences in a single run. With a cation suppressor to eliminate the ion-suppression caused by the ion-pairs in the eluent, the structure of nine impurities in ribostamycin sample was characterized by liquid chromatography-mass spectrum (LC-MS). Both external standard and area normalization calculation were investigated, and NQAD obtained more accurate results due to its full-range linear response-to-concentration relationship, providing an alternative for routine quality control of multi analyte systems.

Comparison of SOX and CAPOX in patients with advanced gastric cancer after laparoscopic D2 gastrectomy: A randomized controlled trial.

BACKGROUND: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S-1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. METHODS: A non-inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. RESULTS: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent-to-treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3-year overall survival (OS) and disease-free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153-1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064-0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076-0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110-1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. CONCLUSION: Adjuvant SOX was non-inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.

Study on the anti-skin aging effect and mechanism of Sijunzi Tang based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Si Jun Zi Tang (SJZT) is a famous traditional Chinese medicine formula composing of 4 herbal medicines (Ginseng Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Poria, and Glycyrrhizae Radix et Rhizoma) with tonifying spleen and anti-aging effects. It is also known that SJZT can be used to tone, nourish the skin and accelerate wound healing. However, due to the complexity of the formulation, the anti-aging especially anti-skin aging mechanisms as well as the key components of SJZT have not been fully investigated. Therefore, further in vitro and in vivo experimental studies are particularly needed to investigate the anti-skin ageing efficacy of SJZT. AIM OF THE STUDY: The purpose of this article was to explore the therapeutic effect and possible pharmacological mechanism of SJZT in the treatment of skin aging by topical application using network pharmacology and to validate the findings using in vitro and in vivo tests. MATERIALS AND METHODS: Network pharmacology method was applied to predict the underlying biological function and mechanism involved in the anti-skin aging effect of SJZT. Molecular docking was used to preliminarily predict the active components of SJZT-Skin Aging. UPLC QTOF MS/MS was carried out to analyze the chemical compounds. Finally, to confirm the anti-skin aging effort of SJZT, a mouse skin-aging model and UVB-induced EpiSCs (epidermal stem cells) senescence model were established. RESULTS: PPI network analysis and KEGG studies indicated that TP53, CDKN2A, TNF, IL6, and IL1B might be parts of the core targets associated with EpiSCs senescence. Furthermore, molecular docking suggested the top active components, glycyrrhizin, ginsenoside Rg5, ginsenoside Rh2, liquiritin, polyporenic acid C and atractylenolide II showed strong affinity to the key proteins involved in cellular senescence signaling. UPLC QTOF MS/MS analysis of SJZT confirmed the presence of these key components. In-vivo experiments revealed that SJZT could improve UVB-induced skin thickening, increase the number of collagen fibers, strengthen the structure of elastin fibers, and decrease the expression of MDA, as well as increase the expression of CAT and T-SOD in the skin tissue of mouse. And, in-vitro experiments indicated that SJZT could reduce ROS generation and oxidative stress, increase mitochondrial membrane potential, and upregulate the expression of stem cell markers. Moreover, SJZT could suppress the expression of p53, p-p53 and p21, downregulated p38 phosphorylation. Furthermore, the anti-cellular senescence effect of SJZT on EpiSCs disappeared after treatment with the p38 inhibitor adesmapimod. Taken all together, the regulation of senescence signaling in EpiSCs is an important mechanism of SJZT in combating skin aging. CONCLUSION: The research results indicate that SJZT has anti-skin aging effects on UVB-induced skin-aging model, possibly by mediating p38/p53 signaling pathway. These findings strongly demonstrate the great potential of SJZT as an active composite for anti-skin aging and cosmeceutical applications.