Regioselective 1,4-/1,3-Difunctionalization of 1,3-Enynes with Selenosulfonates in Water.

1,4-/1,3-Regioselective bifunctionalization of 1,3-enynes with selenosulfonates in water under catalyst-free conditions for the construction of sulfonyl allene and 1,3-disulfonyl-conjugated dienes respectively have been developed. The reactions feature mild reaction conditions in aqueous solution and remarkable regioselectivity controlled by substrates.

Strategic advancement of E3 ubiquitin ligase in the management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) presents a significant global health challenge due to its high incidence, poor prognosis, and limited treatment options. As a pivotal regulator of protein stability, E3 ubiquitin ligase plays a crucial role in tumorigenesis and development. This review provides an overview of the latest research on the involvement of E3 ubiquitin ligase in hepatocellular carcinoma and elucidates its significance in hepatocellular carcinoma cell proliferation, invasion, and evasion from immune surveillance. Special attention is given to the functions of RING, HECT, and RBR E3 ubiquitin ligases and their association with hepatocellular carcinoma progression. By dissecting the molecular mechanisms and regulatory networks governed by E3 ubiquitin ligase, several potential therapeutic strategies are proposed: including the development of specific inhibitors targeting E3 ligases; augmentation of their tumor suppressor activity through drug or gene therapy; utilization of E3 ubiquitin ligase to modulate immune checkpoint proteins for improved efficacy of immunotherapy; combination strategies integrating traditional therapies with E3 ubiquitin ligase inhibitors; as well as biomarker development based on E3 ubiquitin ligase activity. Furthermore, this review discusses the prospect of overcoming drug resistance in hepatocellular carcinoma treatment through these novel approaches. Overall, this review establishes a theoretical foundation and offers fresh insights into harnessing the potential of E3 ubiquitin ligase for treating hepatocellular carcinoma while highlighting future research directions that pave the way for clinical translation studies and new drug discoveries.

Effects of Indocyanine Green (ICG) Imaging-Assisted Cholecystectomy on Intraoperative and Postoperative Complications: A meta-Analysis.

BACKGROUND: Accurate recognition of Calot's triangle during cholecystectomy is important in preventing intraoperative and postoperative complications. The use of indocyanine green (ICG) fluorescence imaging has become increasingly prevalent in cholecystectomy procedures. Our study aimed to evaluate the specific effects of ICG-assisted imaging in reducing complications. MATERIALS AND METHODS: A comprehensive search of databases including PubMed, Web of Science, Europe PMC, and WANFANGH DATA was conducted to identify relevant articles up to July 5, 2023. Review Manager 5.3 software was applied to statistical analysis. RESULTS: Our meta-analysis of 14 studies involving 3576 patients compared the ICG group (1351 patients) to the control group (2225 patients). The ICG group had a lower incidence of postoperative complications (4.78% vs 7.25%; RR .71; 95%CI: .54-.95; P = .02). Bile leakage was significantly reduced in the ICG group (.43% vs 2.02%; RR = .27; 95%CI: .12-.62; I2 = 0; P = .002), and they also had a lower bile duct drainage rate (24.8% vs 31.8% RR = .64, 95% CI: .44-.91, P = .01). Intraoperative complexes showed no statistically significant difference between the 2 groups (1.16% vs 9.24%; RR .17; 95%CI .03-1.02), but the incidence of intraoperative bleeding is lower in the ICG group. CONCLUSION: ICG fluorescence imaging-assisted cholecystectomy was associated with a range of benefits, including a lower incidence of postoperative complications, decreased rates of bile leakage, reduced bile duct drainage, fewer intraoperative complications, and reduced intraoperative bleeding.

Visible Light-Catalyzed Reactions of Polysulfide (DBSPS) with Aryldiazonium.

A visible light-catalyzed radical coupling reaction of polysulfide reagents with aryldiazonium was developed, which gave thiosulfonates under mild conditions. In this reaction, the thiosulfonates were isolated in good yields with a broad tolerance to functional groups. And the synthesis of diaryl monosulfides were achieved through a step-by-step reaction of two molecular aryldiazonium with DBSPS, where the sulfur source was provided by DBSPS. It was worth noting that the reaction of this monosulfides could also be achieved by a one pot two-step process. The described polysulfide reagents were able to produce three new radicals: sulfonyl radicals, sulfur-sulfonyl radicals and sulfur-sulfur-sulfonyl radicals.

Copper-Catalyzed Chemoselective Coupling of N-Dithiophthalimides and Alkyl Halides: Synthesis of Unsymmetrical Disulfides and Sulfides.

In this paper, we report an unprecedented copper-catalyzed disulfides or sulfides coupling reaction involving unactivated alkyl halides and N-dithiophthalimides. This reaction can be conducted under mild conditions using low-cost metal catalysts and exhibits high chemical selectivity and functional group compatibility, enabling the efficient assembly of various sulfides and disulfides.

microRNA-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation.

BACKGROUND: Epigenetic alterations contribute greatly to the development and progression of colorectal cancer, and effect of aberrant miR-622 expression is still controversial. This study aimed to discover miR-622 regulation in CRC proliferation. METHODS: miR-622 expression and prognosis were analyzed in clinical CRC samples from Nanfang Hospital. miR-622 regulation on cell cycle and tumor proliferation was discovered, and FOLR2 was screened as functional target of miR-622 using bioinformatics analysis, which was validated via dual luciferase assay and gain-of-function and loss-of-function experiments both in vitro and in vivo. RESULTS: miR-622 overexpression in CRC indicated unfavorable prognosis and it regulated cell cycle to promote tumor growth both in vitro and in vivo. FOLR2 is a specific, functional target of miR-622, which negatively correlates with signature genes in cell cycle process to promote CRC proliferation. CONCLUSIONS: miR-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation, proposing a novel mechanism and treatment target in CRC epigenetic regulation of miR-622.

Regioselective Thiol-yne Reaction of Thiol with ((Methyl-d3)sulfonyl)ethyne: Synthesis of (2-((Methyl-d3)sulfonyl)vinyl)sulfides.

Herein, we have developed a new method for the synthesis of ((methyl-d3)sulfonyl)ethyne, which is cost-effective and environmentally friendly and can be synthesized at the gram level. As an ideal thiol-yne reagent, it can be reacted with various types of thiols to afford (Z)- and (E)-type vinyl sulfides under different conditions with high selectivity. In addition, it can complete the conformational transition from Z- to E-type products under suitable conditions, and can also carry out further derivatization smoothly. The deuterium content of all products was greater than 99%. The preliminary mechanistic studies support the visible light-mediated radical course, and herein provide a novel and efficient synthetic strategy for the direct introduction of deuterated methyl groups, enriching the methods for the construction of C-S bond-containing compounds.

Overcoming Radical Stability Order via DABCO-Triggered Desulfurization: Visible-Light-Promoted 1,2,4-Trifunctionalization of Butenyl Benzothiazole Sulfone with Thiosulfonate.

A radical 1,2,4-trifunctional reaction of thiosulfonate to unactivated olefin is achieved by a migration strategy under mild conditions. In this reaction, the more unstable primary free radicals are in situ generated after the migration of heteroaryl groups in the presence of DABCO. This trifunctionalization of unactivated olefins involves two C-S bond formations and one C-C bond formation.

Simultaneous Preparation of Sulfides/Selenides and Sulfones via Synergistic Nickel-Catalyzed Reductive Coupling and SN2 Reaction.

Sulfone compounds and thioether compounds are two highly valuable classes of compounds, but it is challenging to prepare sulfone and thioether compounds simultaneously and efficiently. Here we report that sulfides/selenides and sulfones can be obtained simultaneously using allyl bromide/benzyl bromide-activated alkyl bromides and thiosulfonates/selenosulfonates using a nickel-catalyzed reductive coupling and SN2 synergistic strategy, which is characterized by excellent atom and step economy, mild reaction conditions, broad functional group compatibility, and excellent yields.

Nickel-Catalyzed Acid Chlorides with Tetrasulfides for the Synthesis of Thioesters and Acyl Disulfides.

Herein, we report a novel method for the synthesis of thioesters and acyl disulfides via nickel-catalyzed reductive cross-electrophile coupling of acid chlorides with tetrasulfides. This approach for the synthesis of thioesters and acyl disulfides is convenient and practical under mild reaction conditions, relying on easy availability. In addition, a wide range of thioesters and acyl disulfides were obtained in medium to good yields with good functional group tolerance. Moreover, thioesters and acyl disulfides can also be prepared at the gram scale, indicating that they have certain potential for industrial application.

RNF173 suppresses RAF/MEK/ERK signaling to regulate invasion and metastasis via GRB2 ubiquitination in Hepatocellular Carcinoma.

BACKGROUND: The role of the membrane-associated RING-CH (MARCH) family in carcinogenesis has been widely studied, but the member of this family, RNF173, has not yet been thoroughly explored in the context of hepatocellular carcinoma (HCC). METHODS: With the use of an HCC tissue microarray and IHC staining, we aim to determine the differential expression of RNF173 in HCC patients and its clinical significance. The biological role of RNF173 is investigated through in vitro and in vivo experiments. RNA sequencing, mass spectrometry, and immunoprecipitation are performed to uncover the underlying mechanism of RNF173's impact on the development of HCC. RESULTS: The mRNA and protein levels of RNF173 were significantly lower in HCC tissues than in normal tissues. HCC patients with low RNF173 expression had shorter overall survival and recurrence-free survival, and RNF173 was significantly correlated with tumor number, tumor capsule, tumor differentiation, and BCLC stage. In addition, in vitro and in vivo experiments showed that RNF173 downregulation exacerbated tumor progression, including migration, invasion, and proliferation. GRB2 is a key molecule in the RAF/MEK/ERK pathway. RNF173 inhibits the RAF/MEK/ERK signaling by ubiquitinating and degrading GRB2, thereby suppressing HCC cell proliferation, invasion and migration. Combining clinical samples, we found that HCC patients with high RNF173 and low GRB2 expression had the best prognosis. CONCLUSION: RNF173 inhibits the invasion and metastasis of HCC by ubiquitinating and degrading GRB2, thereby suppressing the RAF/MEK/ERK signaling pathway. RNF173 is an independent risk factor for the survival and recurrence of HCC patients. RNF173 may serve as a novel prognostic molecule and potential therapeutic target for HCC. Video Abstract Graphical abstract Model of RNF173 on RAF/MEK/ERK signaling. RNF173 knockdown resulted in impaired ubiquitination and degradation of GRB2, leading to the activation of the RAF/MEK/ERK signaling pathway and promotion of invasion and metastasis in HCC cells.

The protection of CoronaVac against the infection of wild-type SARS-CoV-2 (WH-09) or Omicron variant in nude-hACE2 mice.

BACKGROUND: Immunocompromised individuals have an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe outcomes, but we pay less attention to these people. Athymic nude mice are a murine strain with a spontaneous deficiency of the Foxn1 gene, which can result in thymic degeneration or its absence, leading to immunosuppression and a decrease in the number of T cells, and are widely used in preclinical evaluations of disease in immunocompromised populations. METHODS: We investigated the protection of the coronavirus disease 2019 (COVID-19) inactivated vaccine (CoronaVac) against the infection of wild-type SARS-CoV-2 (WH-09) or Omicron variant utilizing a hybrid-type nude-hACE2 mouse model. RESULTS: Compared with nude-hACE2/W mice, the viral load in the brain and lung tissue of nude-hACE2 mice (nude-hACE2/WV) infected with WH-09 after vaccination significantly decreased, and the histopathological changes were also reduced. The viral load in the brain and lung tissue of nude-hACE2 mice (nude-hACE2/OV) infected with the Omicron variant after vaccination was lower than that in nude-hACE2/O, but histopathological symptoms did not improve significantly. CONCLUSION: CoronaVac provides some protection against infection of both WH-09 and the Omicron variant in the nude-hACE2 mice. Our findings aimed to provide a reference for vaccination against SARS-CoV-2 in immunocompromised populations.

Copper-Catalyzed Synthesis of S-S Bond-Containing Silanols from SCBs and Trisulfide-1,1-dioxides.

In this work, an efficient method for the copper-catalyzed ring-opening hydrolysis of silacyclobutanes to silanols was developed. This strategy has the advantages of friendly reaction conditions, simple operation, and good functional group compatibility. No additional additives are required in the reaction, and the S-S bond can also be introduced into the organosilanol compounds in one step. Furthermore, the success at the gram scale demonstrates the great potential of the developed protocol for practical industrial applications.

Clinical Efficacy and Imaging Observation of Three Surgical Approaches in Treatment of Thoracolumbar Fractures.

Objective: To observe the efficacy and imaging of surgical treatment of thoracolumbar fractures via the paravertebral muscle space approach. Methods: A retrospective analysis was conducted on patients with thoracolumbar fractures receiving surgery in Baoding First Central Hospital from January 2019 to December 2020. According to different surgical approaches, they were divided into paravertebral approach group, posterior median approach group and minimally invasive percutaneous approach group. They received surgery via the paravertebral muscle space approach, posterior median approach and minimally invasive percutaneous approach, respectively. Results: Statistically significant differences were found in surgical duration, intraoperative bleeding volume, intraoperative fluoroscopy frequency, postoperative drainage volume and hospital stay among the three groups. One year after surgery, the VAS, ADL and JOA scores of the paravertebral approach group and the minimally invasive percutaneous approach group had statistically significant differences from the posterior median approach group (P < 0.05). Conclusion: For the surgical treatment of thoracolumbar fractures, the clinical efficacy of the paravertebral muscle space approach is superior to that of the traditional posterior median approach, and the clinical efficacy of the minimally invasive percutaneous approach is similar to that of the posterior median approach. All the three approaches can effectively improve the postoperative function and pain symptoms of patients without increasing the incidence of complications. Compared with the posterior median approach, the surgery via the paravertebral muscle space and minimally invasive percutaneous approaches presents shorter surgical duration, less bleeding and shorter hospital stay, which is more conducive to postoperative recovery of patients.

Synthesis of 1,3-Dibenzenesulfonylpolysulfane (DBSPS) and Its Application in the Preparation of Aryl Thiosulfonates from Boronic Acids.

Herein, we provide a novel method for the synthesis of 1,3-dibenzenesulfonylpolysulfane (DBSPS), which further reacts with boronic acids to afford thiosulfonates. Commercially available boron compounds greatly expanded the range of thiosulfonates. Experimental and theoretical mechanistic investigations suggested that DBSPS could provide both thiosulfone fragments and dithiosulfone fragments, but the generated aryl dithiosulfonates were unstable and decomposed into thiosulfonates.

Identification of the mitophagy-related diagnostic biomarkers in hepatocellular carcinoma based on machine learning algorithm and construction of prognostic model.

Background and aims: As a result of increasing numbers of studies most recently, mitophagy plays a vital function in the genesis of cancer. However, research on the predictive potential and clinical importance of mitophagy-related genes (MRGs) in hepatocellular carcinoma (HCC) is currently lacking. This study aimed to uncover and analyze the mitophagy-related diagnostic biomarkers in HCC using machine learning (ML), as well as to investigate its biological role, immune infiltration, and clinical significance. Methods: In our research, by using Least absolute shrinkage and selection operator (LASSO) regression and support vector machine- (SVM-) recursive feature elimination (RFE) algorithm, six mitophagy genes (ATG12, CSNK2B, MTERF3, TOMM20, TOMM22, and TOMM40) were identified from twenty-nine mitophagy genes, next, the algorithm of non-negative matrix factorization (NMF) was used to separate the HCC patients into cluster A and B based on the six mitophagy genes. And there was evidence from multi-analysis that cluster A and B were associated with tumor immune microenvironment (TIME), clinicopathological features, and prognosis. After then, based on the DEGs (differentially expressed genes) between cluster A and cluster B, the prognostic model (riskScore) of mitophagy was constructed, including ten mitophagy-related genes (G6PD, KIF20A, SLC1A5, TPX2, ANXA10, TRNP1, ADH4, CYP2C9, CFHR3, and SPP1). Results: This study uncovered and analyzed the mitophagy-related diagnostic biomarkers in HCC using machine learning (ML), as well as to investigate its biological role, immune infiltration, and clinical significance. Based on the mitophagy-related diagnostic biomarkers, we constructed a prognostic model(riskScore). Furthermore, we discovered that the riskScore was associated with somatic mutation, TIME, chemotherapy efficacy, TACE and immunotherapy effectiveness in HCC patients. Conclusion: Mitophagy may play an important role in the development of HCC, and further research on this issue is necessary. Furthermore, the riskScore performed well as a standalone prognostic marker in terms of accuracy and stability. It can provide some guidance for the diagnosis and treatment of HCC patients.

NF-κB Activator 1 downregulation in macrophages activates STAT3 to promote adenoma-adenocarcinoma transition and immunosuppression in colorectal cancer.

BACKGROUND: Adenoma-adenocarcinoma transition is a key feature of colorectal cancer (CRC) occurrence and is closely regulated by tumor-associated macrophages (TAMs) and CD8+ T cells. Here, we investigated the effect of the NF-κB activator 1 (Act1) downregulation of macrophages in the adenoma-adenocarcinoma transition. METHODS: This study used spontaneous adenoma-developing ApcMin/+, macrophage-specific Act1-knockdown (anti-Act1), and ApcMin/+; anti-Act1 (AA) mice. Histological analysis was performed on CRC tissues of patients and mice. CRC patients' data retrieved from the TCGA dataset were analyzed. Primary cell isolation, co-culture system, RNA-seq, and fluorescence-activated cell sorting (FACS) were used. RESULTS: By TCGA and TISIDB analysis, the downregulation of Act1 expression in tumor tissues of CRC patients negatively correlated with accumulated CD68+ macrophages in the tumor. Relative expression of EMT markers in the tumor enriched ACT1lowCD68+ macrophages of CRC patients. AA mice showed adenoma-adenocarcinoma transition, TAMs recruitment, and CD8+ T cell infiltration in the tumor. Macrophages depletion in AA mice reversed adenocarcinoma, reduced tumor amounts, and suppressed CD8+ T cell infiltration. Besides, macrophage depletion or anti-CD8a effectively inhibited metastatic nodules in the lung metastasis mouse model of anti-Act1 mice. CRC cells induced activation of IL-6/STAT3 and IFN-γ/NF-κB signaling and the expressions of CXCL9/10, IL-6, and PD-L1 in anti-Act1 macrophages. Anti-Act1 macrophages facilitated epithelial-mesenchymal-transition and CRC cells' migration via CXCL9/10-CXCR3-axis. Furthermore, anti-Act1 macrophages promoted exhaustive PD1+ Tim3+ CD8+ T cell formation. Anti-PD-L1 treatment repressed adenoma-adenocarcinoma transition in AA mice. Silencing STAT3 in anti-Act1 macrophages reduced CXCL9/10 and PD-L1 expression and correspondingly inhibited epithelial-mesenchymal-transition and CRC cells' migration. CONCLUSIONS: Act1 downregulation in macrophages activates STAT3 that promotes adenoma-adenocarcinoma transition via CXCL9/10-CXCR3-axis in CRC cells and PD-1/PD-L1-axis in CD8+ T cells.

Patellar development after patella instability and early reduction in growing rabbits.

BACKGROUND: Patella-shaped disorder has been considered as a predisposing factor for patella instability. But the influence of early patella reduction for patellar development remains unclear. This study aimed to evaluate whether early operation in patella instability could improve patella morphology in growing rabbits. METHODS: Fifty rabbits (1-month-old) were included in the study. The control group underwent no surgical procedures. The two experimental groups (reduction group and non-reduced group), underwent medial soft tissue restraint release surgery. The reduction group, rabbits underwent the medial soft tissue sutura surgery in order to stabilize the patella 2 months after release surgery. The non-reduced group, rabbits did not undergo suture surgery. Computed Tomography (CT) scans analysis in two experimental endpoints (2, 5 months after release surgery) were selected to evaluate the transverse diameter, thickness, Wiberg index and Wiberg angle. Gross observation was conducted to assess morphological changes of the patella. RESULTS: CT scans showed significant difference in the mean transverse diameter, Wiberg angle between the two experimental groups and the control group 2 months after release surgery. 5 months after release surgery, the indices of patella were found no statistically difference in the reduction group versus the control group. However, the transverse diameter, Wiberg angle in the non-reduced group were significantly differences than that in the reduction group (P < 0.05). Gross observation showed a flattened articular surface of the patella in the non-reduced group. CONCLUSIONS: The results indicated that patella instability may lead to patella-shaped disorder, showing a flattened morphology. Early patella reduction can improve the patella morphology in growing rabbits.

Photoinduced Construction of Thieno[3,4-c]quinolin-4(5H)-ones/Selenopheno[3,4-c]quinolin-4(5H)-ones Using Diphenyl Disulfide or Diphenyl Diselenide as Sulfur or Selenium Sources.

A photocatalytic synthesis of thieno[3,4-c]quinolin-4(5H)-ones/selenopheno[3,4-c]quinolin-4(5H)-ones using diphenyl disulfide or diphenyl diselenide as sulfur or selenium sources was developed. Two C-S/Se bonds and one C-C bond were constructed simultaneously without transition metals and other additives.

Cu-catalyzed efficient construction of S (Se)-containing functional organosilicon compounds.

A Cu-catalyzed cascade reaction of four-membered silacyclobutanes (SCBs) and thiosulfonates to construct S (Se)-containing organosilicon compounds was developed. The protocol shows a wide range of substrate scope, high functional group compatibility and mild reaction conditions. New C-S (Se) and Si-O bonds were constructed in one step.