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Hui Ma,1,2,* Ting Yu,3,* Zhong-Chen Li,1 Lan Zhang,1,2 Rong-Xin Chen,1 Zheng-Gang Ren1 1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Hepatic Oncology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, People’s Republic of China; 3Department of Pathology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Ma, Email mahui_676@163.comPurpose: Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored.Methods: We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis.Results: The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival.Conclusion: The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.Keywords: hepatocellular carcinoma, transarterial chemoembolization, oxidative stress, response, prognosis

Yuting He,1,2,* Chen Xue,1,2,* Yan Yu,1,2 Jianan Chen,1,2 Xiaolong Chen,1,2 Fang Ren,2 Zhigang Ren,1,2 Guangying Cui,1,2 Ranran Sun1,2 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; 2Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China *These authors contributed equally to this work Background: Gallbladder cancer (GBC) is a highly lethal disease and the most common biliary tract malignant tumor with poor prognosis. Accumulating evidence indicates that cluster of differentiation 44 (CD44) is overexpressed in several malignancies and has a crucial role in the development of cancer. However, its expression and function in GBC are unclear. The aim of this study was to explore CD44 expression and its role in GBC. Materials and methods: The expression of CD44 was measured by immunohistochemistry. Tissue microarray analysis was used to confirm the relationship between CD44 expression and clinical outcomes of GBC patients. EDU assay, colony formation assay, cell migration and invasion assay were performed to detect the functions of CD44 in GBC-SD and NOZ transfected with si-RNA. Results: CD44 was overexpressed and associated with poor outcomes in GBC patients. The univariate and multivariate analyses confirmed that elevated CD44 was an independent prognostic factor for the OS of GBC patients. Silencing CD44 could suppress the GBC cell proliferation, migration and invasion in vitro, as well as attenuated cancer stem cell functions. Conclusion: CD44 markedly correlated with aggressive tumor behaviors and contributed to the progression of GBC, which could represent a novel prognostic marker and potential therapeutic target for GBC patients. Keywords: CD44, gallbladder cancer, cancer stem cells, tumor progression

Background: Three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with or without transcatheter arterial chemoembolization (TACE) for locally advanced hepatocellular carcinoma (HCC) has shown favorable outcomes in local control and survival of locally advanced HCC. However, intra-hepatic spreading and metastasis are still the predominant treatment failure patterns. Sorafenib is a multikinase inhibitor with effects against tumor proliferation and angiogenesis. Maintenance Sorafenib would probably prevent or delay the intrahepatic and extrahepatic spread of HCC after radiotherapy, which provides the rationale for the combination of these treatment modalities.Methods and Design: Patients with solitary lesion (bigger than 5 cm in diameter) histologically or cytologically confirmed HCC receive TACE (1-3 cycles) plus 3DCRT/IMRT 4-6 weeks later. Maintenance Sorafenib will be administered only for the patients with non-progression disease 4 to 6 weeks after the completion of radiotherapy. The dose will be 400 mg, p.o., twice a day. Sorafenib will be continuously given for 12 months unless intolerable toxicities and/or tumor progression. If no more than 3 patients discontinue Sorafenib treatment who experience dose-limiting toxicity after necessary dose modification and delay and/or radiation-induced liver disease in the first 15 enrolled patients, the study will recruit second fifteen patients for further evaluating safety and efficacy of treatment. Hypothesis of the current study is that Sorafenib as a maintenance therapy after combined therapy of 3DCRT/IMRT and TACE is safe and superior to radiotherapy combined with TACE alone in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in comparison to historical data.Discussion: A recent meta-analysis showed TACE in combination with radiotherapy, improved the survival and the tumor response of patients, and was thus more therapeutically beneficial. In this study, local therapy for HCC is the combination of TACE and radiotherapy. Radiation exposure as a kind of stress might induce the compensatory activations of multiple intracellular signaling pathway mediators, such as PI3K, MAPK, JNK and NF-kB. Vascular endothelial growth factor (VEGF) was identified as one factor that was increased in a time- and dose-dependent manner after sublethal irradiation of HCC cells in vitro, translating to enhanced intratumor angiogenesis in vivo. Therefore, Sorafenib-mediated blockade of the Raf/MAPK and VEGFR pathways might enhance the efficacy of radiation, when Sorafenib is followed sequentially as a maintenance modality. (ClinicalTrials.gov number, NCT00999843.). [ABSTRACT FROM AUTHOR]

Reaction of a P/N/S hybrid ligand dpppyatc (N,N-bis((diphenylphosphaneyl)methyl)-N-(pyridin-2-yl)-amino-thiocarbamide) with Au(tht)Cl (tht=tetrahydrothiophene) and [Cu(MeCN) 4 ]BF 4 afforded cluster complex [Au 2 Cu(dpppyatc) 2 ](BF 4 ) 2 Cl (1). Upon excitation at 480 nm, 1 emitted orange phosphorescence at 646 nm, which was red-shifted to ~698 nm selectively in the presence of ammonia or amine vapor. This chromic photoluminescent response toward ammonia was sensitive and reversible. Complex1 could detect ammonia in aqueous solution down to concentrations of 2 ppm (w/w)., (© 2024 Wiley-VCH GmbH.)

Hydrogen sulfide (H 2 S), together with carbon monoxide (CO) and nitric oxide (NO), is recognized as a vital gasotransmitter. H 2 S is biosynthesized by enzymatic pathways in the skin and exerts significant physiological effects on a variety of biological processes, such as apoptosis, modulation of inflammation, cellular proliferation, and regulation of vasodilation. As a major health problem, dermatological diseases affect a large proportion of the population every day. It is urgent to design and develop effective drugs to deal with dermatological diseases. Dermatological diseases can arise from a multitude of etiologies, including neoplastic growth, infectious agents, and inflammatory processes. The abnormal metabolism of H 2 S is associated with many dermatological diseases, such as melanoma, fibrotic diseases, and psoriasis, suggesting its therapeutic potential in the treatment of these diseases. In addition, therapies based on H 2 S donors are being developed to treat some of these conditions. In the review, we discuss recent advances in the function of H 2 S in normal skin, the role of altering H 2 S metabolism in dermatological diseases, and the therapeutic potential of diverse H 2 S donors for the treatment of dermatological diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the past, hydrogen sulfide (H 2 S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H 2 S can act as an endogenous regulatory transmitter. In mammals, H 2 S-catalyzing enzymes, such as cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H 2 S. Various preclinical studies have shown that H 2 S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H 2 S in different systems and the diseases associated with disorders of H 2 S metabolism, such as ischemia-reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H 2 S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Luminescent materials with aggregation-induced emission (AIE) characteristics have been recognized as highly selective and sensitive probes for the detection of toxic metal ions in recent years. In this paper, a Au-Ag cluster-based coordination polymer [Au 3 Ag 3 ( L ) 2 (CN) 6 (H 2 O) 2 ] n [ 1 , L = 1,3-bis((diphenylphosphanyl)methyl)-4,5-dihydro-imidazolylidene] was prepared by in situ generation of the diphosphine N-heterocyclic carbene (PC NHC P)-type ligand L in the presence of the corresponding metal salts. Compound 1 exhibited 530 nm phosphorescence under 380 nm excitation with a QY of 6.30% and a lifetime (τ) of 7.14 μs in the solid state. 1 showed good AIE behavior in the mixture of MeOH/H 2 O while the best aggregation state ( f water = 90%, QY = 6.79%, τ = 6.70 μs) exhibited selective and sensitive emission quenching toward Cr(VI) ions. Ultralow detection limits of 9.7 ppb (w/w) for Cr 2 O 7 2- and 17.9 ppb (w/w) for CrO 4 2- were achieved.

Objective: The human microbiota plays a key role in cancer diagnosis, pathogenesis, and treatment. However, osteosarcoma-associated oral microbiota alterations have not yet been unraveled. The aim of this study was to explore the characteristics of oral microbiota in osteosarcoma patients compared to healthy controls, and to identify potential microbiota as a diagnostic tool for osteosarcoma., Methods: The oral microbiota was analyzed in osteosarcoma patients (n = 45) and matched healthy controls (n = 90) using 16S rRNA MiSeq sequencing technology., Results: The microbial richness and diversity of the tongue coat were increased in osteosarcoma patients as estimated by the abundance-based coverage estimator indices, the Chao, and observed operational taxonomy units (OTUs). Principal component analysis delineated that the oral microbial community was significant differences between osteosarcoma patients and healthy controls. 14 genera including Rothia, Halomonas, Rhodococcus, and Granulicatella were remarkably reduced, whereas Alloprevotella, Prevotella, Selenomonas, and Campylobacter were enriched in osteosarcoma. Eventually, the optimal four OTUs were identified to construct a microbial classifier by the random forest model via a fivefold cross-validation, which achieved an area under the curve of 99.44% in the training group (30 osteosarcoma patients versus 60 healthy controls) and 87.33% in the test group (15 osteosarcoma patients versus 30 healthy controls), respectively. Notably, oral microbial markers validated strong diagnostic potential distinguishing osteosarcoma patients from healthy controls., Conclusion: This study comprehensively characterizes the oral microbiota in osteosarcoma and reveals the potential efficacy of oral microbiota-targeted biomarkers as a noninvasive biological diagnostic tool for osteosarcoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Li, Wang, Zhang, Ren and Wang.)

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC., Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821., Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group., Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

The atom-transfer radical addition (ATRA) reaction simultaneously forges carbon-carbon and carbon-halogen bonds. However, frequently-used photosensitizers such as precious transition metal complexes, or organic dyes have limitations in terms of their potential toxicity and recyclability. Three β-ketoenamine-linked covalent organic frameworks (COFs) from 1,3,5-triformylphloroglucinol and 1,4-phenylenediamines with variable transient photocurrent and photocatalytic activity have been prepared. A COF bearing electron-deficient Cl atoms displayed the highest photocatalytic activity toward the ATRA reaction of polyhalogenated alkanes to give halogenated olefins under visible light at room temperature. This heterogeneous photocatalyst exhibited good functional group tolerance and could be recycled without significant loss of activity., (© 2024 Wiley-VCH GmbH.)

Background: Liuweiwuling Tablet (LWWL) is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus (HBV) infection. Previous studies have indicated an anti-HBV effect of LWWL, specifically in terms of antigen inhibition, but the underlying mechanism remains unclear., Aim: To investigate the potential mechanism of action of LWWL against HBV., Methods: In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines. The in vivo experiment involved a hydrodynamic injection-mediated mouse model with HBV replication. Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL., Results: In HepG2.1403F cells, LWWL (0.8 mg/mL) exhibited inhibitory effects on HBV DNA, hepatitis B surface antigen and pregenomic RNA (pgRNA) at rates of 51.36%, 24.74% and 50.74%, respectively. The inhibition rates of LWWL (0.8 mg/mL) on pgRNA/covalently closed circular DNA in HepG2.1403F, HepG2.2.15 and HepG2.A64 cells were 47.78%, 39.51% and 46.74%, respectively. Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis (PI3K-AKT, CASP8-CASP3 and P53 pathways). Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group (CG) among HBV-replicating cell lines, including HepG2.2.15 (2.92% ± 1.01% vs 6.68% ± 2.04%, P < 0.05), HepG2.A64 (4.89% ± 1.28% vs 8.52% ± 0.50%, P < 0.05) and HepG2.1403F (3.76% ± 1.40% vs 7.57% ± 1.35%, P < 0.05) (CG vs LWWL-treated group). However, there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells (5.04% ± 0.74% vs 5.51% ± 1.57%, P > 0.05), L02 cells (5.49% ± 0.80% vs 5.48% ± 1.01%, P > 0.05) and LX2 cells (6.29% ± 1.54% vs 6.29% ± 0.88%, P > 0.05). TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBV-replicating mouse model, while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model., Conclusion: Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV, potentially involving selective regulation of apoptosis. These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications., Competing Interests: Conflict-of-interest statement: The authors of this manuscript having no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

A Schiff-base porous polymer has been impregnated with ruthenium trichloride for acceptor-free dehydrogenation coupling (ADC) of secondary alcohols with γ-amino- and 2-aminobenzyl alcohols to give pyridines and quinolines. This heterogenous catalyst exhibited high catalytic efficiency over repeated cycles with wide functional group tolerance., (© 2024 Wiley‐VCH GmbH.)

Spider mites (Acari: Tetranychidae) are polyphagous pests of economic importance in agriculture, among which the two-spotted spider mite Tetranychus urticae Koch has spread widely worldwide as an invasive species, posing a serious threat to fruit tree production in China, including Beijing. The hawthorn spider mite, Amphitetranychus viennensis Zacher, is also a worldwide pest of fruit trees and woody ornamental plants. The cassava mite, Tetranychus truncatus Ehara, is mainly found in Asian countries, including China, Korea and Japan, and mainly affects fruit trees and agricultural crops. These three species of spider mites are widespread and serious fruit tree pests in Beijing. Rapid and accurate identification of spider mites is essential for effective pest and plant quarantine in Beijing orchard fields. The identification of spider mite species is difficult due to their limited morphological characteristics. Although the identification of insect and mite species based on PCR and real-time polymerase chain reaction TaqMan is becoming increasingly common, DNA extraction is difficult, expensive and time-consuming due to the minute size of spider mites. Therefore, the objective of this study was to establish a direct multiplex PCR method for the simultaneous identification of three common species of spider mites in orchards, A. viennensis, T. truncatus and T. urticae, to provide technical support for the differentiation of spider mite species and phytosanitary measures in orchards in Beijing. Based on the mitochondrial cytochrome c oxidase subunit I (COI) of the two-spotted spider mite and the cassava mite and the 18S gene sequence of the hawthorn spider mite as the amplification target, three pairs of specific primers were designed, and the primer concentrations were optimized to establish a direct multiplex PCR system for the rapid and accurate discrimination of the three spider mites without the need for DNA extraction and purification. The method showed a high sensitivity of 0.047 ng for T. truncatus and T. urticae DNA and 0.0002 ng for A. viennensis. This method eliminates the DNA extraction and sequencing procedures of spider mite samples, offers a possibility for rapid monitoring of multiple spider mites in an integrated microarray laboratory system, reducing the time and cost of leaf mite identification and quarantine monitoring in the field., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Combination therapy (lenvatinib/programmed death-1 inhibitor) is effective for treating unresectable hepatocellular carcinoma (uHCC). We reveal that responders have better overall and progression-free survival, as well as high tumor mutation burden and special somatic variants. We analyze the proteome and metabolome of 82 plasma samples from patients with hepatocellular carcinoma (HCC; n = 51) and normal controls (n = 15), revealing that individual differences outweigh treatment differences. Responders exhibit enhanced activity in the alternative/lectin complement pathway and higher levels of lysophosphatidylcholines (LysoPCs), predicting a favorable prognosis. Non-responders are enriched for immunoglobulins, predicting worse outcomes. Compared to normal controls, HCC plasma proteins show acute inflammatory response and platelet activation, while LysoPCs decrease. Combination therapy increases LysoPCs/phosphocholines in responders. Logistic regression/random forest models using metabolomic features achieve good performance in the prediction of responders. Proteomic analysis of cancer tissues unveils molecular features that are associated with side effects in responders receiving combination therapy. In conclusion, our analysis identifies plasma features associated with uHCC responders to combination therapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Thymidylate kinase (TMPK) of monkeypox virus (MPXV) has emerged as a promising target for potential therapeutics due to its significant role in pyrimidine metabolism. While smallpox drugs are advised for treating monkeypox, the European Medicine Agency has sanctioned Tecovirimat due to its potent nanomolar activity. Nonetheless, there is a need for monkeypox-specific therapeutic options. In this work, we employed docking-based virtual screening and molecular dynamics (MD) simulations to identify myxobacterial secondary metabolites as promising anti-viral natural compounds capable of inhibiting thymidylate kinase. The computational pharmacokinetics and manual curation of top-scoring compounds identified six lead compounds that were compared in terms of protein-ligand contacts and protein-essential dynamics. The study shows that among the six candidates, Aurachin A and the Soraphinol analogues such as Soraphinol A and Soraphinol C remain very stable compared to other compounds, enabling the active site integrity via a stable dynamics pattern. We also show that other compounds such as Phenoxan, Phenylnannolone C, and 8E-Aurafuron B remain unstable and have a negative impact on the active site integrity and may not be suitable binders for TMPK protein. Analyzing the Aurachin A and Soraphinol A binding, the established hydrogen bonds with Arg93 and the conserved hydrophobic interaction with Tyr101 are consistent with previous experimental interactions. Additionally, a deeper insight into the indole and the aromatic ring interaction through π-π stacking and π-cation interactions, as well as the background of Aurachin A and Soraphinol A as a bioactive compound, has significant implications not only for its potential as a promising drug but also for directing future drug discovery efforts targeting the TMPK protein., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2 (HER-2)-positive gastric cancer (GC). However, the efficacy of this treatment is hindered by substantial challenges associated with both primary and acquired drug resistance. While S-phase kinase associated protein 2 (Skp2) overexpression has been implicated in the malignant progression of GC, its role in regulating trastuzumab resistance in this context remains uncertain. Despite the numerous studies investigating Skp2 inhibitors among small molecule compounds and natural products, there has been a lack of successful commercialization of drugs specifically targeting Skp2., Aim: To discover a Skp2 blocker among currently available medications and develop a therapeutic strategy for HER2-positive GC patients who have experienced progression following trastuzumab-based treatment., Methods: Skp2 exogenous overexpression plasmids and small interfering RNA vectors were utilized to investigate the correlation between Skp2 expression and trastuzumab resistance in GC cells. Q-PCR, western blot, and immunohistochemical analyses were conducted to evaluate the regulatory effect of thioridazine on Skp2 expression. A cell counting kit-8 assay, flow cytometry, a amplex red glucose/glucose oxidase assay kit, and a lactate assay kit were utilized to measure the proliferation, apoptosis, and glycolytic activity of GC cells in vitro. A xenograft model established with human GC in nude mice was used to assess thioridazine's effectiveness in vivo ., Results: The expression of Skp2 exhibited a negative correlation with the sensitivity of HER2-positive GC cells to trastuzumab. Thioridazine demonstrated the ability to directly bind to Skp2, resulting in a reduction in Skp2 expression at both the transcriptional and translational levels. Moreover, thioridazine effectively inhibited cell proliferation, exhibited antiapoptotic properties, and decreased the glucose uptake rate and lactate production by suppressing Skp2/protein kinase B/mammalian target of rapamycin/glucose transporter type 1 signaling pathways. The combination of thioridazine with either trastuzumab or lapatinib exhibited a more pronounced anticancer effect in vivo, surpassing the efficacy of either monotherapy., Conclusion: Thioridazine demonstrates promising outcomes in preclinical GC models and offers a novel therapeutic approach for addressing trastuzumab resistance, particularly when used in conjunction with lapatinib. This compound has potential benefits for patients with Skp2-proficient tumors., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To explore the efficacy of adjuvant programmed cell death 1 (PD-1) monoclonal antibody immunotherapy in Chinese patients with resected stage Ⅱ-Ⅲ melanoma. Methods: A total of 296 patients who underwent radical surgery for stage Ⅱ-Ⅲ cutaneous orlimb melanoma at Fudan University Shanghai Cancer Center and Shanghai Electric Power Hospital between 2017 and 2021 and received adjuvant PD-1 monoclonal antibody immunotherapy, low-dose interferon (IFN), or observational follow-up were enrolled in this study. Patients were divided into the PD-1 monoclonal antibody group (164 cases) and the IFN or observation group (IFN/OBS group, 132 cases) based on postoperative adjuvant treatment methods. Patients' disease recurrence and survival were observed. Results: Among the 296 patients, 77 had cutaneous melanoma and 219 had limb melanoma; 110 were stage Ⅱ and 186 were stage Ⅲ. Among stage Ⅱ patients, the median recurrence-free survival (RFS) in the PD-1 monoclonal antibody group (46 cases) did not reach, while the median RFS in the IFN/OBS group (64 cases) was 36 months. The 1-year RFS rates were 85.3% and 92.1% and the 2-year RFS rates were 71.9% and 63.7% in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with no statistically significant difference ( P =0.394). Among stage Ⅲ patients, the median RFS rates in the PD-1 monoclonal antibody group (118 cases) and the IFN/OBS group (68 cases) were 23 and 13 months, respectively. The 1-year RFS rates were 70.0% and 51.8% and the 2-year RFS rates were 51.8% and 35.1%in the PD-1 monoclonal antibody group and the IFN/OBS group, respectively, with a statistically significant difference ( P =0.010). Stratified analysis showed that the advantage of PD-1 monoclonal antibody adjuvant therapy in improving RFS persisted in the subgroups of primary ulceration ( HR =0.558, 95% CI: 0.348-0.893), lymph node macroscopic metastasis ( HR =0.486, 95% CI: 0.285-0.828), stage ⅢC ( HR =0.389, 95% CI: 0.24-0.63), and the subgroup without BRAF/c-Kit/NRAS gene mutations ( HR =0.347, 95% CI: 0.171-0.706). In terms of recurrence patterns, in stage Ⅱ patients, the recurrence and metastasis rate was 15.2% (7/46) in the PD-1 monoclonal antibody group, significantly lower than the IFN/OBS group [43.8% (28/64), P =0.002]. In stage Ⅲ melanoma patients, the recurrence and metastasis rate was 42.4% (50/118) in the PD-1 monoclonal antibody group, also lower than the IFN/OBS group [63.2% (43/68), P =0.006]. Conclusions: In real-world settings, compared with patients receiving low-dose IFN adjuvant therapy or observational follow-up, PD-1 monoclonal antibody immunotherapy can reduce the recurrence and metastasis rate of cutaneous and limb melanoma, and prolong the postoperative RFS of stage Ⅲ cutaneous and limb melanoma patients. Patients with a heavier tumor burden benefit more from immunotherapy.

Regulation of gut microbiota and its impact on human health is the theme of intensive research. The incidence and prevalence of atrial fibrillation (AF) are continuously escalating as the global population ages and chronic disease survival rates increase; however, the mechanisms are not entirely clarified. It is gaining awareness that alterations in the assembly, structure, and dynamics of gut microbiota are intimately engaged in the AF progression. Owing to advancements in next-generation sequencing technologies and computational strategies, researchers can explore novel linkages with the genomes, transcriptomes, proteomes, and metabolomes through parallel meta-omics approaches, rendering a panoramic view of the culture-independent microbial investigation. In this review, we summarized the evidence for a bidirectional correlation between AF and the gut microbiome. Furthermore, we proposed the concept of "gut-immune-heart" axis and addressed the direct and indirect causal roots between the gut microbiome and AF. The intricate relationship was unveiled to generate innovative microbiota-based preventive and therapeutic interventions, which shed light on a definite direction for future experiments., (© 2023. The Author(s).)

The reaction of CF 3 COOAg, 3-bdppmapy ( N , N -bis(diphenylphosphanylmethyl)-3-aminopyridine) and HTZ (1,2,4-triazole-3-thiol) in CH 2 Cl 2 /MeOH resulted in a dinuclear Ag/P/S complex [Ag 2 (TZ) 2 (3-bdppmapy) 2 ]· x Sol ( 1 · x Sol). Crystals of 1 · x Sol converted to 1 ·2MeOH in air at room temperature and further to 1 under vacuum upon heating. The solid-state, room-temperature photoluminescent emission of 1 · x Sol (510 nm) shifted to 494 nm ( 1 ·2MeOH) and 486 nm ( 1 ). Grinding solids of 1 ·2MeOH in air resulted in amorphous 1G characterized by solid-state emission at 468 nm, which converted to 1GR with 513 nm emission upon MeOH treatment. Grinding 1GR in air returned 1G, and this interconversion was reproducible over five cycles. The solid-state photoluminescence of 1G changed in response to vapors containing low-molecular weight alcohols but remained unchanged after exposure to other volatile organic compounds (VOCs) or to water vapor. Test papers impregnated with 1G could detect methanol in vapors from aqueous solutions at concentrations above 50%. Complex 1G is, therefore, an example of a stimuli-responsive molecular sensor for the detection of alcohols.

Earth-abundant copper(I) coordination complexes of an imine-phosphine and a diimine have been developed as visible-light photocatalysts. Reaction of [Cu(MeCN) 4 ]BF 4 with hetero-bidentate phosphinopyrazole (phpz) ligand R 1 R 2 C 3 HN 2 PPh 3 (R 1 = R 2 = H (1a); R 1 = H, R 2 = Me (1b); R 1 = H, R 2 = Ph (1c); R 1 = R 2 = Me (1d)) and 2,9-dimethyl-1,10-phenanthroline (dmp) gave four heteroleptic bis-chelate Cu(I) complexes [Cu(dmp)(R 1 R 2 C 3 HN 2 PPh 3 )]BF 4 (R 1 = R 2 = H (2a); R 1 = H, R 2 = Me (2b); R 1 = H, R 2 = Ph (2c); R 1 = R 2 = Me (2d)) with distorted tetrahedral geometries. Complexes 2a-2d exhibited broad absorption in the visible spectrum and could facilitate photochemical intermolecular atom-transfer radical addition reactions of CBr 4 , or CCl 3 Br, CHI 3 to styrenes in yields up to 91% and with a broad substrate scope. The absorption, emission, redox potential and photocatalytic activity were dependent on the substituents on the phpz ligand. Mechanistic studies supported an atom-transfer radical addition (ATRA) mechanism.

Immune-related adverse events (irAEs) clinically resemble autoimmune diseases, indicating autoantibodies could be potential biomarkers for the prediction of irAEs. This study aimed to assess the predictive value of peripheral blood antinuclear antibody (ANA) status for irAEs, considering the time and severity of irAEs, as well as treatment outcome in liver cancer patients administered anti-PD-1 therapy. Ninety-three patients with advanced primary liver cancer administered anti-PD-1 treatment were analyzed retrospectively. They were divided into the ANA positive (ANA+, titer ≥ 1:100) and negative (ANA-, titer < 1:100) groups. Development of irAEs, progression-free survival (PFS), and overall survival (OS) were assessed. Compared with ANA- patients, ANA+ cases were more prone to develop irAEs (43.3% vs. 19.2%, P = 0.031). With the increase of ANA titers, the frequency of irAEs increased. The time interval between anti-PD-1 therapy and the onset of irAEs was significantly shorter in ANA+ patients compared with the ANA- group (median, 1.7 months vs. 5.0 months, P = 0.022). Moreover, the time between anti-PD-1 therapy and irAE occurrence decreased with increasing ANA titer. In addition, PFS and OS were decreased in ANA+ patients compared with the ANA- group (median PFS, 2.8 months vs. 4.2 months, P = 0.043; median OS, 21.1 months vs. not reached, P = 0.041). IrAEs occur at higher frequency in ANA+ liver cancer patients undergoing anti-PD-1 therapy. ANA titer could help predict irAE development and treatment outcome in these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A heterobimetallic coordination polymer [Au 4 (dppmt) 4 (AgCl) 2 ] n ( 1 ) incorporating an in situ generated P-S ligand (dppmtH) was synthesized from the solvothermal reaction of Au(tht)Cl, AgCl, and dpppyatc in CH 3 CN/CH 2 Cl 2 (dppmtH = (diphenylphosphino)methanethiol, tht = tetrahydrothiophene, dpppyatc = N , N -bis((diphenylphosphaneyl)methyl)- N -(pyridin-2-yl)-amino-thiocarbamide). The structure of 1 contains a one-dimensional helical Au-Au chain in which the unique [Au 4 Ag 2 S 2 ] cluster units are connected by [Au 2 (dppmt) 2 ] dimers. Upon excitation at 343 nm, 1 exhibited cyan (495 nm) phosphorescent emission at quantum yield (QY) = 22.3% and τ = 0.78 μs (λ ex = 375 nm). Coordination polymer 1 exhibited a rapid, selective, reversible, and visible vapor-chromic response on exposure to methanol (MeOH) vapor with its emission shifting to a more intense green (530 nm, λ ex = 388 nm) with QY = 46.8% and τ = 1.24 μs (λ ex = 375 nm). A polymethylmethacrylate film containing 1 served as a reversible chemical sensor for the sensitive detection of MeOH in air.

Significant improvements in the management of hepatocellular carcinoma (HCC) during the past three years have urged the timely update of clinical guidelines in China. In brief, aMAP score is newly recommended as an effective risk stratification tool to predict HCC occurrence especially for non-cirrhotic patients. Biomarker-based surveillance including 7 micro-RNA panel and GALAD score are advocated to assist early diagnosis. China liver cancer (CNLC) staging system proposed in the 2017 guideline continues to be the standard model for staging with modifications in the treatment allocations. Conversion therapies using multi-modal, high intensity strategies are advocated to facilitate subsequent resection for patients with technically unresectable CNLC stage Ia, Ib, IIa HCC, or technically resectable IIb, IIIa HCC. Super-selective transcatheter arterial chemoembolization (TACE) with the assistance of Cone-Beam CT if necessary is recommended to guarantee the efficacy of TACE. Hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin (FOLFOX) regimen alone or in combination with systemic therapy is recommended for TACE-refractory patients or for patients with locally advanced HCC. The systemic treatments for HCC have evolved considerably since atezolizumab plus bevacizumab, and suntilimab plus bevacizumab analogue showing superior survival benefit to sorafenib, and donafenib with comparable efficacy with sorafenib are added to the first-line treatments. In addition to regorafenib, apatinib, camrelizumab and tislelizumab are added as the second-line systemic therapies for patients who progressed on sorafenib. Updates in the 2022 Barcelona Clinic Liver Cancer (BCLC) guidelines and Japanese Society of Hepatology (JSH) consensus statement are also introduced and compared with the 2022 Chinese guidelines., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-22-469/coif). All authors reports that this work was supported by National Natural Science Foundation of China (Nos. 82130077 and 81961128025), Basic Research Project from the Science and Technology Commission of Shanghai Municipality (Nos. 21JC1410100, 21JC1401200, 20JC1418900), and Natural Science Funds of Shanghai (No. 21ZR1413800). The authors have no other conflicts of interest to declare., (2023 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Here, we report the efficacy and safety of combining toripalimab, lenvatinib, and gemcitabine plus oxaliplatin (GEMOX) as first-line therapy for advanced ICC. Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine (1 g/m 2 ) on Days 1 and 8 and oxaliplatin (85 mg/m 2 ) Q3W for six cycles along with intravenous toripalimab (240 mg) Q3W and oral lenvatinib (8 mg) once daily for one year. The expression of programmed death-ligand 1 (PD-L1) and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing (WES) analysis. The primary endpoint was the objective response rate (ORR). Secondary outcomes included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DoR). As of July 1, 2022, the median follow-up time was 23.5 months, and the ORR was 80%. Twenty-three patients achieved partial response, and one achieved complete response. Patients (21/30) with DNA damage response (DDR)-related gene mutations showed a higher ORR, while patients (14/30) with tumor area positivity ≥1 (PD-L1 staining) showed a trend of high ORR, but without significant difference. The median OS, PFS, and DoR were 22.5, 10.2, and 11.0 months, respectively. The DCR was 93.3%. Further, 56.7% of patients experienced manageable grade ≥3 adverse events (AEs), commonly neutropenia (40.0%) and leukocytopenia (23.3%). In conclusion, toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC. A phase-III, multicenter, double-blinded, randomized study to validate our findings was approved by the National Medical Products Administration (NMPA, No. 2021LP01825).Trial registration Clinical trials: NCT03951597., (© 2023. The Author(s).)

Background: Liver tumor remains an important cause of cancer-related death. Nanosecond pulsed electric fields (nsPEFs) are advantageous in the treatment of melanoma and pancreatic cancer, but their therapeutic application on liver tumors need to be further studied., Methods: Hep3B cells were treated with nsPEFs. The biological behaviors of cells were detected by Cell Counting Kit-8, 5-ethynyl-20-deoxyuridine, and transmission electron microscopy (TEM) assays. In vivo, rabbit VX2 liver tumor models were ablated by ultrasound-guided nsPEFs and radiofrequency ablation (RFA). Contrast-enhanced ultrasound (CEUS) was used to evaluate the ablation effect. HE staining and Masson staining were used to evaluate the tissue morphology after ablation. Immunohistochemistry was performed to determine the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin at different time points after ablation., Results: The cell viability of Hep3B cells was continuously lower than that of the control group within 3 days after pulse treatment. The proliferation of Hep3B cells was significantly affected by nsPEFs. TEM showed that Hep3B cells underwent significant morphological changes after pulse treatment. In vivo, CEUS imaging showed that nsPEFs could completely ablate model rabbit VX2 liver tumors. After nsPEFs ablation, the area of tumor fibrosis and the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin were decreased. However, after RFA, rabbit VX2 liver tumor tissue showed complete necrosis, but the expression of PCNA and α-smooth muscle actin did not decrease compared to the tumor group., Conclusions: nsPEFs can induce Hep3B cells apoptosis and ablate rabbit VX2 liver tumors in a non-thermal manner versus RFA. The ultrasound contrast agent can monitor immediate effect of nsPEF ablation. This study provides a basis for the clinical study of nsPEFs ablation of liver cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Monkeypox is a serious public health issue in tropical and subtropical areas. Antivirals that target monkeypox proteins might lead to more effective and efficient therapy. The F13 protein is essential for the growth and maturation of the monkeypox virus. F13 inhibition might be a viable therapeutic target for monkeypox. The in silico fragment-based drug discovery method for developing antivirals may provide novel therapeutic options. In this study, we generated 800 compounds based on tecovirimat, an FDA-approved drug that is efficacious at nanomolar quantities against monkeypox. These compounds were evaluated to identify the most promising fragments based on binding affinity and pharmacological characteristics. The top hits from the chemical screening were docked into the active site of the F13 protein. Molecular dynamics simulations were performed on the top two probable new candidates from molecular docking. The ligand-enzyme interaction analysis revealed that the C2 ligand had lower binding free energy than the standard ligand tecovirimat. Water bridges, among other interactions, were shown to stabilize the C2 molecule. Conformational transitions and secondary structure changes in F13 protein upon C2 binding show more native three-dimensional folding of the protein. Prediction of pharmacological properties revealed that compound C2 may be promising as a drug candidate for monkeypox fever. However, additional in vitro and in vivo testing is required for validation.

Monkeypox virus is a double-stranded DNA virus species that causes disease in humans and mammals. It is a zoonotic virus belongs the genus Orthopoxviral, the family of Poxviridae, associated with the smallpox virus in many aspects. The first human case of monkeypox was reported throughout the Democratic Republic of Congo in 1970. In April 2022, several cases were recorded in widespread regions of Africa, the Northern and western hemispheres. The current review spotlights taxonomic classification, clinical presentations during infection, and the pathogenicity of the monkeypox virus in humans. Furthermore, the current review also highlights different diagnostics used for virus detection.

Covalent organic frameworks (COFs) have recently emerged as prospective photoactive materials with noble Pt as a cocatalyst for photocatalytic hydrogen evolution. In this work, a series of SH-group-functionalized covalent organic frameworks, TpPa-1-SH-X, is prepared by reaction of p-phenylenediamine (Pa) and 1,3,5-triformylphloroglucinol (Tp) with p-NH 2 C 6 H 4 SH as a modulating agent. The reaction of TpPa-1-SH-X with Ni II acetylacetonate Ni(acac) 2 gave nickel thiolate-immobilized TpPa-1 (TpPa-1-SNi-X). The highest hydrogen evolution rate was 10.87 mmol h -1  g -1 , which was an enhancement of 16.47, 3.83, and 1.84 times than that of the parent TpPa-1, covalent-bond-free [(p-NH 2 C 6 H 4 S) 2 Ni] n /TpPa-1-SH-10, and 3 wt % Pt-deposited TpPa-1, respectively. This enhanced photocatalytic hydrogen evolution is ascribed to enhanced crystallinity, the use of Ni II thiolate as a cocatalyst and covalent bonding between the cocatalyst and TpPa-1., (© 2022 Wiley-VCH GmbH.)

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail., Data Sources: The data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using "minimally invasive" and "hepatocellular carcinoma" or "liver cancer" as the keywords., Results: Percutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC., Conclusions: A variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis., (Copyright © 2022 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

A new Ag/Cu bimetallic cluster [Ag 10 Cu 6 (bdppthi) 2 (C≡CPh) 12 (EtOH) 2 ](ClO 4 ) 4 ( 1 , bdppthi = N , N' -bis(diphenylphosphanylmethyl)-tetrahydroimidazole) exhibited strong phosphorescent (PL) emission at 644 nm upon excitation at 400 nm. Removal of the coordinated EtOH molecules in 1 resulted in derivative 1a , which exhibited significant red-shifted emission at 678 nm. The structure and PL of 1 was restored on exposure to EtOH vapor. Cluster 1a also exhibited a vapor-chromic PL response towards other common organic solvent vapors including acetone, MeOH and MeCN. A PMMA film of 1a was developed as a reusable visible sensor for MeCN.

The construction of molecular skeletons and modification of molecules using widely available and easily prepared alcohols as radical precursors for coupling reactions are significant and challenging subjects. We herein report a straightforward strategy for the dehydrogenative ring-opening alkenylation of cycloalkanols with alkenes by combining a proton-coupled electron transfer strategy and a dual photoredox and cobalt catalysis system. With this approach, a series of distally unsaturated ketones were obtained in 17-83% yields with high E selectivity.

Odorant-binding proteins (OBPs) play essential roles in lepidopteran insects' perception of host volatiles by binding and transporting hydrophobic ligands. The yellow peach moth (YPM), Conogethes punctiferalis (Guenée), is a serious agricultural pest, with broad host range and cryptic feeding habits. However, few studies about YPM perceiving pheromones and host plant odorants have been reported. In this study, four OBP genes (CpunOBP8, CpunOBP9, CpunABP, and CpunGOBP2) were cloned from the antennae of YPM. The recombinant proteins were expressed and purified by prokaryotic expression system, with their binding affinities to 26 ligands being tested. Four CpunOBPs all had six conserved cysteine residues, which were typical structural characteristics of classical OBPs. The fluorescence competitive binding assay indicated that CpunOBP8 and CpunABP could not only exhibit high binding affinities to female sex pheromones, but also to host plant odorants. For example, CpunOBP8 bound strongly with cis-10-hexadecenal, hexadecanal, and so forth, whereas CpunABP bound with cis-10-hexadecenal, camphene, and 3-carene. Comparatively, CpunOBP9 and CpunGOBP2 could only bind with host plant odorants, with CpunOBP9 binding strongly to 3-methyl-1-butanol, hexyl acetate, and so forth, while CpunGOBP2 displaying the widest binding spectra and correlating with 3-carene, pentyl acetate, and so forth. The results indicated that on the one hand, each of the four CpunOBPs had its specific binding spectra when binding and transporting olfactory ligands; on the other hand, the same ligand might be bound to more than one CpunOBPs, which would provide information for the potential application of semiochemicals in controlling YPM., (© 2022 Wiley Periodicals LLC.)

Hepatitis B virus (HBV) has posed a threat to public health, mainly resulting in liver damage. With long-term accumulation of extracellular matrix, patients with chronic hepatitis B are at high risk of developing into liver fibrosis and cirrhosis and even life-threatening hepatic carcinoma. The occurrence of complications such as spontaneous bacterial peritonitis and hepatic encephalopathy greatly increases disability and mortality. With deeper understanding of the bidirectional interaction between the liver and the gut (gut-liver axis), there is a growing consensus that the human health closely relates to the gut microbiota. Supported by animal and human studies, the gut microbiota alters as the HBV-related liver fibrosis initials and progresses, characterized as the decrease of the ratio between "good" and "potentially pathogenic" microbes. When the primary disease is controlled via antiviral treatment, the gut microbiota dysfunction tends to be improved. Conversely, the recovery of gut microbiota can promote the regression of liver fibrosis. Therapeutic strategies targeted on gut microbiota (rifaximin, probiotics, engineered probiotics and fecal microbiota transplantation) have been applied to animal models and patients, obtaining satisfactory results., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Matrix stiffness promotes hepatocellular carcinoma (HCC) metastasis. This study examined the contribution of lipid metabolic reprogramming to matrix stiffness-induced HCC metastasis. HCC cells were cultured on mechanically tunable polyacrylamide gels and subjected to lipidomic analysis. The key enzyme that responded to matrix stiffness and regulated lipid metabolism was identified. The comparative lipidomic screening revealed that stearoyl-CoA desaturase 1 (SCD1) is a mechanoresponsive enzyme that reprogrammed HCC cell lipid metabolism. The genetic and pharmacological inhibition of SCD1 expression/activity altered the cellular lipid composition, which in turn impaired plasma membrane fluidity and inhibited in vitro invasive motility of HCC cells in response to high matrix stiffness. Knockdown of SCD1 suppressed HCC invasion and metastasis in vivo. Conversely, the overexpression of SCD1 or exogenous administration of its product oleic acid augmented plasma membrane fluidity and rescued in vitro invasive migration in HCC cells cultured on soft substrates, mimicking the effects imposed by high matrix stiffness. In human HCC tissues, collagen content, a marker of increasing matrix stiffness, and increased expression of SCD1 together predicted poor survival of HCC patients. An SCD1-dependent mechanoresponsive pathway that responds to increasing matrix stiffness in the tumor microenvironment promotes HCC invasion and metastasis through lipid metabolic reprogramming., Competing Interests: Conflicts of interest The authors declare no competing interests., (Copyright © 2022 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background: High technical complexity limits the wide use of transradial approach (TRA) chemoembolization in the management of liver cancer. We sought to construct a thoracoabdominal aorta CTA-based nomogram model to identify ideal candidates for TRA chemoembolization in patients with liver cancer. Methods: Patients who had received thoracoabdominal aorta CTA before TRA chemoembolization from 2018 to 2020 were retrospectively enrolled and randomly divided into a training set and a validation set. The clinical characteristics and CTA features were collected to build a clinical model. Univariate and multivariate analyses were used to identify significant clinical-radiological variables. A CTA-based nomogram model was constructed by using multivariate logistic regression analysis. The predictive performance, as well as discrimination efficacy of the model, was evaluated by ROC analysis and calibration plot. Results: Vascular variation ( P =0.028), Myla classification ( P =0.030), length from left subclavian artery to the left subclavian artery ( P =0.017), and angle between common hepatic artery and abdominal aorta ( P =0.017) were identified as important factors associated with the technical complexity of TRA chemoembolization, indicated by fluoroscopy time of the total procedure. The CTA-based nomogram model was established by these abovementioned variables, which demonstrated good predictive ability in both the training cohort (AUC=0.929) and validation cohort (AUC= 0.769), with a high C-index of 0.928 and 0.827 respectively. Moreover, satisfactory calibrations were confirmed by the Hosmer-Lemeshow test with P values of 0.618 and 0.299 in the training cohort and validation cohort. Conclusion: Our study constructs a novel CTA-based nomogram, which can serve as a useful tool to identify ideal candidates for TRA chemoembolization in patients with liver cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Cancer patients, being immunocompromised, are at higher risk of coronavirus disease (COVID-19). The current study determines cancer patients’ knowledge, attitude, perception, and impact of the COVID-19 pandemic. Method: A cross-sectional online survey was conducted in Pakistan from 1 April 2020 to 1 May 2020. The study respondents were cancer patients with ages equal to or greater than 18 years. Following a request for participation, the URL for the survey was distributed on numerous channels. Other social media platforms, including WeChat, WhatsApp, Facebook, Twitter, Instagram, Messenger, and LinkedIn, were used to increase cancer patient interaction. The questionnaire comprised five different sections such as: (1) sociodemographic information, (2) knowledge, (3) attitude, (4) perception, and (5) impact of COVID-19 on cancer patients. Descriptive medical statistics such as frequency, percentage, mean, and standard deviation were used to illustrate the demographic characteristics of the study participants. To compare mean knowledge scores with selected demographic variables, independent sample t-tests and one-way analysis of variance (ANOVA) were used, which are also practical methods in epidemiological, public health and medical research. The cut-off point for statistical significance was set at a p-value of 0.05. Results: More than 300 cancer patients were invited, of which 208 agreed to take part. The response rate was 69.33% (208/300). Gender, marital status, and employment status had a significant association with knowledge scores. Of the total recruited participants, 96% (n = 200) (p < 0.01) knew about COVID-19, and 90% were aware of general symptoms of COVID-19 disease, such as route of transmission and preventive measurements. In total, 94.5% (n = 197) (p < 0.01) were willing to accept isolation if they were infected with COVID-19, and 98% (n = 204) (p < 0.01) had reduced their use of public transportation. More than 90% (n = 188) (p < 0.01) of cancer patients were found to be practicing preventative measures such as using a face mask, keeping social distance, and avoiding handshaking and hugging. Around 94.4% (n = 196) (p < 0.01) of cancer patients had been impacted by, stopped or had changed cancer treatment during this pandemic, resulting in COVID-related anxiety and depression. Conclusion: The included cancer patients exhibited a good level of COVID-19 knowledge, awareness, positive attitude, and perception. Large-scale studies and efforts are needed to raise COVID-19 awareness among less educated and high-risk populations. The present survey indicates that mass-level effective health education initiatives are required for developing countries to improve and reduce the gap between KAP and COVID-19.

Background: Due to the outbreak and rapid spread of coronavirus disease 2019 (COVID-19), more than 160 million patients have become convalescents worldwide to date. Significant alterations have occurred in the gut and oral microbiome and metabonomics of patients with COVID-19. However, it is unknown whether their characteristics return to normal after the 1-year recovery., Methods: We recruited 35 confirmed patients to provide specimens at discharge and one year later, as well as 160 healthy controls. A total of 497 samples were prospectively collected, including 219 tongue-coating, 129 stool and 149 plasma samples. Tongue-coating and stool samples were subjected to 16S rRNA sequencing, and plasma samples were subjected to untargeted metabolomics testing., Results: The oral and gut microbiome and metabolomics characteristics of the 1-year convalescents were restored to a large extent but did not completely return to normal. In the recovery process, the microbial diversity gradually increased. Butyric acid-producing microbes and Bifidobacterium gradually increased, whereas lipopolysaccharide-producing microbes gradually decreased. In addition, sphingosine-1-phosphate, which is closely related to the inflammatory factor storm of COVID-19, increased significantly during the recovery process. Moreover, the predictive models established based on the microbiome and metabolites of patients at the time of discharge reached high efficacy in predicting their neutralizing antibody levels one year later., Conclusions: This study is the first to characterize the oral and gut microbiome and metabonomics in 1-year convalescents of COVID-19. The key microbiome and metabolites in the process of recovery were identified, and provided new treatment ideas for accelerating recovery. And the predictive models based on the microbiome and metabolomics afford new insights for predicting the recovery situation which benefited affected individuals and healthcare., (© 2022. The Author(s).)

The transformations that allow the direct removal of hydrogen from their corresponding saturated counterparts by the dehydrogenative strategy are a dream reaction that has remained largely underexplored. In this report, a straightforward and robust cobaloxime-catalyzed photochemical dehydrogenation strategy via intramolecular HAT is described for the first time. The reaction proceeds through an intramolecular radical translocation followed by the cobalt assisted dehydrogenation without needing any other external photosensitizers, noble-metals or oxidants. With this approach, a series of valuable unsaturated compounds such as α,β-unsaturated amides, enamides and allylic and homoallylic sulfonamides were obtained in moderate to excellent yields with good chemo- and regioselectivities, and the synthetic versatility was demonstrated by a range of transformations. And mechanistic studies of the method are discussed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The NDVI (normalized difference vegetation index) was used as the vegetation coverage index. Based on the NDVI and weather data from 2000 to 2020, the characteristics of the spatiotemporal evolution and the driving mechanism of vegetation were investigated by using correlation analysis, the Theil-Sen estimator, the Mann-Kendall method, and multivariate residual trend analysis. The results showed that the growing season average NDVI in the Yellow River basin was a fluctuating upward trend of 0.005 a -1 from 2000 to 2020. Areas with significantly improved vegetation in the basin were mainly distributed in the Qinling Mountains, the Northern Shaanxi Plateau, and the Lvliang Mountains in the midstream. The average value of the partial correlation coefficient between the growing season average NDVI and rainfall in the Yellow River basin was 0.57, and the average value of the partial correlation coefficient between the growing season average NDVI and temperature was 0.49. The impact of rainfall on vegetation was higher than that of temperature. The areas where human activities significantly improved vegetation growth were mainly distributed in the northern Shaanxi Plateau, the Lvliang Mountains, and southern Ningxia. The areas where human activities inhibited vegetation growth were mainly distributed in cities with strong human activities such as Yinchuan, Baotou, Xi'an, Luoyang, Zhengzhou, and Taiyuan. Human activities and climate change contributed to 72% and 28% of the vegetation change in the Yellow River basin. Driven by human activities and climate change, the area where vegetation growth has improved in the Yellow River basin accounted for 96.4% of the basin area, of which the contribution rate of human activities greater than 80% of the area accounted for 34.3%, which was mainly distributed in the middle and southeast of the basin. The area with a contribution rate of climate change greater than 80% accounted for 4.2%, which was mainly distributed in the Sichuan-Tibet Plateau and Longzhong Loess Plateau in the basin. The results of this research can provide scientific support for the ecological protection and high-quality development of the Yellow River basin.

Reaction of [(3-bdppmapy)(AuCl) 2 ] with NaHmba (3-bdppmapy = N , N '-bis-(diphenylphosphanylmethyl-3-aminopytidine, H 2 mba = 2-mercaptobenzoic acid) resulted in a new tetranuclear Au/P/S complex [(3-bdppmapy) 2 (AuHmba) 3 (AuCl)] (1). Upon excitation at 370 nm, 1 exhibited solid state, room temperature, green fluorescent emission (QY = 4.7%, τ = 2.58 ns) which was significantly enanced at lower temperatures due to strengthening of the Au-Au interaction. Different ratios of 1 with phosphor N630 in PMMA were used to make thermochromic photoluminescent films and fibres that could be fabricated into an optical thermometer sensitive over temperature ranges 80-300 K and 300-370 K.

Objective: This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with modified FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as an alternative treatment option in advanced hepatocellular carcinoma (HCC) patients with failed or unsuitability for transarterial chemoembolization (TACE). MATERIALS AND METHODS: From September 2018 to January 2020, 87 advanced HCC patients who progressed on TACE or were not eligible for TACE received HAIC treatment with modified FOLFOX. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1, and adverse events graded according to CTCAE 5.0. Based on prognostic factors determined by multivariate analysis, a nomogram was developed to predict patient survival., Results: The median OS and PFS were 9.0 months (95%CI 7.6-10.4) and 3.7 months (95%CI 3.1-4.3), respectively. The objective response rate was 13.8%, with a disease control rate of 48.3%. Grade 3 adverse events were observed, such as infection (9.2%), thrombocytopenia (5.7%), hyperbilirubinemia (3.4%), abdominal pain (2.3%) and alanine aminotransferase increase (2.3%). Albumin, AST, and extrahepatic metastasis were incorporated to construct a new nomogram that could stratify patients into three prognostic subgroups, including low-, intermediate-, and high-risk groups, with significant differences in 9-month OS rates (71%, 42% and 6%, respectively; p< 0.001). The nomogram was better than the Okuda, AJCC, and CLIP staging systems for OS prediction., Conclusion: These findings support the feasibility of HAIC with modified FOLFOX as an alternative treatment strategy for advanced HCC when TACE is ineffective or unsuitable., Competing Interests: DECLARATION OF COMPETING INTERESTS The authors declare no conflict of interests., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

A photoluminescent bimetallic cluster [Ag 10 Cu 6 (bdppthi) 2 (C≡CPh) 12 (MeOH) 2 (H 2 O)](ClO 4 ) 4 (1, bdppthi=N,N'-bis(diphenylphosphanylmethyl)-tetrahydroimidazole} was synthesized from the PNNP type ligand bdppthi generated in-situ. Upon excitation at 365 nm, 1 exhibited strong phosphorescent emission at 630 nm, which was selectively quenched by NH 3 in air or water. The sensing of NH 3 was rapid and recoverable, with detection limits of 53 ppm (v/v) in N 2 and 21 μmol/L (0.36 ppm, w/w) for NH 3  ⋅ H 2 O in water. Cluster 1 could potentially serve as a bifunctional chemical sensor for the efficient detection of ammonia in waste-gas and waste-water., (© 2021 Wiley-VCH GmbH.)

Background: Patients with hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (mPVTT) have poor prognosis. Promising systemic therapies, such as target therapies, have limited benefits. The purpose of this study is to retrospectively evaluate the benefits of conventional TACE (c-TACE) and to establish a prognostic stratification of HCC patients with mPVTT., Methods: This is a single center retrospective study conducted over 5 years (duration of performing c-TACE), on consecutive HCC patients with mPVTT receiving c-TACE. Univariable and multivariable analysis were used to explore factors independently associated with overall survival (OS). Based on Cox-regression analysis, prognostic models were developed and internally validated by bootstrap methods. Discrimination and performance were measured by Akaike information criterion, concordance index, and likelihood ratio test., Results: A total of 173 patients were included. Median OS was 6.0 months (95%CI: 3.92~8.08). The independent variables correlated with survival were largest tumor diameter, tumor number, mPVTT extension, and AFP. In the final model, patients were assigned 2 points if largest tumor diameter ≥8 cm, or tumor number ≥2, 1point if main trunk was complete obstructed, or AFP ≥400 ng/ml. By summing up these points, patients were divided into three risk groups according to the score at the 15rd and 85th percentiles, in which median OS were 18, 7, and 3.5months, respectively (p<0.001). The model shown optimal discrimination, performance, and calibration., Conclusions: c-TACE could provide survival benefits in HCC patients with mPVTT and the proposed prognostic stratification may help to identify good candidates for the treatment, and those for whom c-TACE may be futile., 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 © 2021 Li, Yin, Fan, Zhang, Chen, Chen, Li, Ge, Gan, Wang and Ren.)

Researches have shown that lung injury due to excessive spontaneous breathing effort, that is, patient self-inflicted lung injury (P-SILI), may be the important manifestation and possible mechanism of ventilation-associated lung injury and ventilation-induced diaphragmatic dysfunction in acute respiratory distress syndrome (ARDS) patients who were mechanically ventilated with intense spontaneous breathing. This paper reviews the concept of P-SILI, possible occurrence mechanism, clinical significance, and prevention and treatment, in order to provide more ideas for clinical ARDS management.

The application of immune checkpoint inhibitors has significantly improved the immunotherapy effect of a variety of solid tumors. With the US Food and Drug Administration's approval of nivolumab and pembrolizumab as second-line treatments for hepatocellular carcinoma, the application of immune checkpoint inhibitors, especially in combination with other treatment methods, has become more and more widely used in hepatocellular carcinoma. Notably, these drugs play a therapeutic role in tumor immunosuppression; however, they can also stimulate related side effects caused by autoimmunity, so their side effects are very different from traditional chemotherapy and targeted drugs. Therefore, effective monitoring, detection and intervention of immune-related side effects are obligatory assurances for patients to attain clinical benefits.

Trinuclear complex [Au2Ag(dppmaphen)2(CN)2]PF6 photoluminesces on exposure to low molecular weight alcohols. This emission is likely due to C-Hπ interactions between the analyte and -PPh2 group, that inhibits non-radiative relaxation of the photoexcited state. Photoluminescene was quenched by removing the analyte under a stream of N2 or replacing it with H2O. This on/off switching was clearly visible, relatively rapid and recyclable.

Background: HMex-3A, an RNA-binding protein, was found to be associated with tumorigenesis. However, the roles of hMex-3A in hepatocellular carcinoma (HCC) progression remained unclear., Methods: The different expression of hMex-3A between HCC tissues and non-tumor tissues was evaluated using The Cancer Genome Atlas database. Thereafter, the hMex-3A expression was evaluated in HCC tissues using Western blotting and qRT-PCR. Immunohistochemistry was performed to investigate the association between hMex-3A level and clinicopathological features including prognosis in HCC patients. In addition, we used si-hMex-3A to knockdown hMex-3A in HCC cells to test Cell Counting Kit-8, colony formation, cell migration and invasion., Results: The hMex-3A expression was significantly elevated in HCC tissues. Analysis of the clinicopathological parameters suggested that hMex-3A expression was significantly associated with pathological grade (P = 0.019) and TNM stage (P = 0.001) in HCC. Moreover, univariate and multivariate Cox-regression analyses revealed that high hMex-3A expression (HR = 1.491, 95% CI: 1.107-2.007; P = 0.009) was an independent risk factor for overall survival in HCC patients. Finally, we confirmed that si-hMex-3A could significantly inhibit HCC cell proliferation, migration, and invasion in vitro., Conclusions: HMex-3A may contribute to the progression of HCC and might be used as a novel therapeutic target and prognostic marker in HCC., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Albumin-to-alkaline phosphatase ratio (AAPR), a newly developed blood biomarker, has been reported to have prognostic value in several types of cancer. This study aimed to investigate the predictive value of AAPR in patients with early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) as initial therapy., Methods: This retrospective study analyzed 445 patients with newly diagnosed HCC undergoing RFA as initial therapy. A series of survival analyses were performed to evaluate the prognostic value of AAPR. Univariate and multivariate analyses were performed to identify independent prognostic factors. An AAPR-based nomogram was constructed, and its predictive performance was validated., Results: Patients with a low AAPR had a significantly reduced recurrence-free survival (RFS) and overall survival (OS) compared with those with a high AAPR. AAPR was found to be an independent prognostic indicator and showed superior discrimination efficacy than other liver function indices. The AAPR-based nomogram had a concordance index value of 0.72 (95% confidence interval [CI]: 0.65-0.79) in the training cohort and 0.72 (95% CI: 0.63-0.81) in the validation cohort, which significantly outperformed other existing staging systems., Conclusions: AAPR serves as a promising indicator of prognosis in patients with early-stage HCC undergoing RFA. The AAPR-based nomogram might contribute to individualized prognosis prediction and clinical decision making.