Ligand-Controlled Regiodivergent Ring Expansion of Benzosilacyclobutenes with Alkynes en Route to Axially Chiral Silacyclohexenyl Arenes.

A ligand-controlled regiodivergent and enantioselective ring expansion of benzosilacyclobutenes with internal naphthyl alkynes has been achieved by adjusting the ligand cavity size. The ligand (S)-8H-binaphthyl phosphoramidite, featuring small methyl groups on its arms, provides a spacious cavity that favors sterically demanding Si-Csp3 ring expansion, predominantly yielding axially chiral (S)-1-silacyclohexenyl arenes. In contrast, the ligand (R)-spiro phosphoramidite, with bulky t-Bu groups on its arms, offers a compact cavity that facilitates less sterically demanding Si-Csp2 ring expansion, leading primarily to axially chiral (S)-2-silacyclohexenyl arenes. Density functional theory calculations delineate distinct mechanistic pathways for each ring expansion route and elucidate their regio- and enantioselectivity.

Mutation status of the KMT2 family associated with immune checkpoint inhibitors (ICIs) therapy and implicating diverse tumor microenvironments.

Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts (n = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival (P < 0.001, hazard ratio [HR] = 0.733 [95% confidence interval (CI): 0.632-0.850]), progression-free survival (P = 0.002, HR = 0.669 [95% CI: 0.518-0.864]), durable clinical benefit (P < 0.001, 54.1% vs. 32.6%), and objective response rate (P < 0.001, 40.6% vs. 22.0%). Through a comprehensive analysis of the tumor microenvironment across different KMT2 mutation statuses, we observed that tumors harboring the KMT2 mutation exhibited enhanced immunogenicity, increased infiltration of immune cells, and higher levels of immune cell cytotoxicity, suggesting a propensity towards a "hot tumor" phenotype. Therefore, our study indicates a potential association between KMT2 mutations and a more favorable response to ICI therapy and implicates different tumor microenvironments associated with ICI therapy response.

Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: a systematic review and meta-analysis.

BACKGROUNDS: There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer. METHODS: Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest. RESULTS: Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05). CONCLUSION: ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.

Prognoses of Patients Treated With Surgical Therapy Versus Continuation of Local-Plus-Systemic Therapy Following Successful Down-Staging of Intermediate-Advanced Hepatocellular Carcinoma: A Multicenter Real-World Study.

BACKGROUND: The difference in the prognoses between treatment with surgical therapy and continuation of local-plus-systemic therapy following successful down-staging of intermediate-advanced hepatocellular carcinoma (HCC) remains unclear. METHODS: Data of 405 patients with intermediate-advanced HCC treated at 30 hospitals across China from January 2017 to July 2022 were retrospectively reviewed. All patients received local-plus-systemic therapy and were divided into the surgical (n = 100) and nonsurgical groups (n = 305) according to whether they received surgical therapy. The differences between long-term prognoses of the 2 groups were compared. Subgroup analysis was performed in 173 HCC patients who met the criteria for surgical resection following down-staging. RESULTS: Multivariable analysis of all patients showed that surgical therapy, hazard ratio (HR): 0.289, 95% confidence interval, CI, 0.136-0.613) was a protective factor for overall survival (OS), but not for event-free survival (EFS). Multivariable analysis of 173 intermediate-advanced HCC patients who met the criteria for surgical resection after conversion therapy showed that surgical therapy (HR: 0.282, 95% CI, 0.121-0.655) was a protective factor for OS, but not for EFS. Similar results were obtained after propensity score matching. For patients with Barcelona Clinic Liver Cancer stage B (HR: 0.171, 95% CI, 0.039-0.751) and C (HR: 0.269, 95% CI, 0.085-0.854), surgical therapy was also a protective factor for OS. CONCLUSIONS: Overall, for patients with intermediate-advanced HCC who underwent local-plus-systemic therapies, surgical therapy is a protective factor for long-term prognosis and can prolong OS, and for those who met the surgical resection criteria after conversion therapy, surgical therapy is recommended.

Hyaluronic acid-modified mesoporous silica nanoprobes for target identification of atherosclerosis.

Rupture of vulnerable plaque and secondary thrombosis caused by atherosclerosis are one of the main causes of acute cardiovascular and cerebrovascular events, and it is urgent to develop an in-situ, noninvasive, sensitive and targeted detection method at molecular level. We chose CD44, a specific receptor highly expressed on the surface of macrophages, as the target of the molecular probe, and modified the CD44 ligand HA onto the surface of Gd2O3@MSN, constructing the MRI imaging nanoprobe HA-Gd2O3@MSN for targeted recognition of atherosclerosis. The fundamental properties of HA-Gd2O3@MSN were initially investigated. The CCK-8, hemolysis, hematoxylin-eosin staining tests and blood biochemical assays confirmed that HA-Gd2O3@MSN possessed excellent biocompatibility. Laser confocal microscopy, cellular magnetic resonance imaging, flow cytometry and immunohistochemistry were used to verify that the nanoprobes had good targeting properties. The in vivo targeting performance of the nanoprobes was further validated by employing a rabbit atherosclerosis animal model. In summary, the synthesized HA-Gd2O3@MSN nanoprobes have excellent biocompatibility properties as well as good targeting properties. It could provide a new technical tool for early identification of atherosclerosis.

Toward MOF@Polymer Core-Shell Particles: Design Principles and Potential Applications.

ConspectusCompositing MOFs with polymers brings out the best properties of both worlds. The solubility and excellent mechanical properties of polymers endow the brittle, powdery MOFs with enhanced processability, thereby enriching their functions as solid sorbents, filters, membranes, catalysts, drug delivery vehicles, and so forth. While most MOF-polymer composites are random mixtures of two materials with little control over their fine structures, MOF@polymer core-shell particles have recently emerged as a new platform for precise composite design. The well-defined polymer coating can keep the rich pore characteristics of the MOF intact while furnishing the MOF with new properties such as improved dispersibility in various media, tunable surface energy, enhanced chemical stability, and regulated guest diffusion. Nevertheless, the structural and chemical complexity of MOFs poses a grand challenge to the development of a generalizable and feasible strategy for constructing MOF@polymer. Examples in the literature that showcase the presence of a well-defined polymer shell on the MOF with fully reserved porosity are rare. Moreover, methods for coating MOFs with condensation polymers (e.g., polyimide, polysulfone) are severely underexplored, despite their clear potential as membrane materials. In this Account, we present our group's effort over the past 4 years on the synthesis and applications of MOF@polymer composites. We first described a highly generalizable surface polymerization method that utilizes the rapid physisorption of a random copolymer (RCP) to carry initiating groups to the MOF surfaces. Subsequent controlled radical polymerization led to the formation of a uniform methacrylate or styrenic polymer on the MOF with tunable thickness and composition. To utilize the properties of condensation polymers, we pioneered the covalent grafting of polyimide (PI) brushes to UiO-66-NH2 surfaces. In addition, to circumvent the need for a covalent anchoring group, we further developed an MOF surface grafting method based on mechanical linkage. Instead of connecting to the ligand, polyimide (PI) oligomer was linked to a functionalized linear polymer physically entangled within an MOF, thus realizing surface grafting with PI. Alternatively, PIs, polysulfone (PSF), and polycarbonate (PC) can also be grafted to various MOF surfaces through a metal-organic nanocapsule (MONC)-mediated method using a combination of electrostatic interaction and coordination bonds. To find a rapid and low-cost surface coating method suitable for commercialization, a new approach called non-solvent-induced surface-aimed deposition (NISAP) was developed. The action of the solvent phase separation drives dianhydrides and polyamines to the MOF surface, thus realizing accelerated polymerization and the rapid formation of a polymer coating on the MOF. Finally, we provided an overview of the unique properties and potential applications of MOF@polymer composites, including improved stability, MMMs, porous liquids (PLs), and immobilizing homogeneous catalysts. We hope that this Account can inspire more researchers to further develop and optimize the synthetic strategies for MOF@polymer and uncover its full application potential.

Effect of low frequency alternating magnetic field for erythritol production in Yarrowia lipolytica.

Numerous works have reported that magnetic fields serve as signals capable of influencing microbial metabolism. However, little is known about the effect of magnetic field on erythritol production by the model microorganism Yarrowia lipolytica (Y. lipolytica). Therefore, we investigated the effect of low-frequency alternating magnetic fields (LF-AMF) with different magnetic field intensities (0-1.5 mT) and different magnetic field treatment times (1-10 days) on the production of erythritol by Y. lipolytica -JZ204. The optimal treatment condition was 0.5 mT for 8 days. As a result, a maximal erythritol yield was achieved 63.74 g/L, the biomass was reached 37 g/L, and the specific erythritol yield per unit of biomass was 1.7227 g/g, which were 60.72%, 32.09%, and 24.85% higher than the control, respectively. We investigated the internal mechanism of magnetic fields impact by using transcriptomics and RT-qPCR technology. This study demonstrated the effectiveness of LF-AMF in enhancing erythritol production by Y. lipolytica JZ-204, providing insights for the application of magnetic field in assisting microbial fermentation and improving the synthesis of beneficial products.

Low frequency magnetic field assisted production of acidic protease by Aspergillus niger.

Acid protease is widely used in industries such as food processing and feed additives. In the study, low frequency magnetic field (LF-MF) as an aid enhances acid protease production by Aspergillus niger (A. niger). The study assessed mycelial biomass, the enzymic activity of the acidic protease and underlying mechanism. At low intensities, alternating magnetic field (AMF) is more effective than static magnetic fields (SMF). Under optimal magnetic field conditions, acid protease activity and biomass increased by 91.44% and 16.31%, as compared with the control, respectively. Maximum 19.87% increase in enzyme activity after magnetic field treatment of crude enzyme solution in control group. Transcriptomics analyses showed that low frequency alternating magnetic field (LF-AMF) treatment significantly upregulated genes related to hydrolases and cell growth. Our results showed that low-frequency magnetic fields can enhance the acid protease production ability of A. niger, and the effect of AMF is better at low intensities. The results revealed that the effect of magnetic field on the metabolic mechanism of A. niger and provided a reference for magnetic field-assisted fermentation of A. niger.

Lactobacillus rhamnosus GG ameliorates triptolide-induced liver injury through modulation of the bile acid-FXR axis.

Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic.

The value of SDC2 and Septin9 combined with serum tumor markers in early diagnosis of colorectal cancer.

OBJECTIVE: The aim of this study is to evaluate the significance of combined detection of Septin9 and syndecan-2 (SDC2) methylation markers and serum tumor markers for the early diagnosis of colorectal cancer. METHODS: A total of 116 patients diagnosed with colorectal cancer between December 2022 and February 2024 were designated as the colorectal cancer group. Additionally, 31 patients with colorectal adenoma were assigned to the adenoma group, while 44 individuals undergoing routine physical examinations were included in the control group. Concentrations of Septin9, SDC2, fecal occult blood (FOB), and four tumor markers-carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 724 (CA724)-were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves for Septin9, SDC2, the four tumor markers, FOB, the combination of Septin9 and SDC2, and the combined use of all seven indicators (CEA, CA19-9, CA125, CA72-4, FOB, Septin9, and SDC2). RESULTS: The colorectal cancer group exhibited the highest positive rates for Septin9, SDC2, the four tumor markers, the combined detection of Septin9 and SDC2, and the combined detection of all seven indicators, compared to both the adenoma and control groups (P < 0.05). The adenoma group also showed higher positive rates than the control group (P < 0.05). For patients with stage I-III colorectal cancer, the positive rates for the combined detection of Septin9 and SDC2 were 81.3%, 78.9%, and 90.2%, respectively, surpassing those for the combined detection of the four tumor markers (43.8%, 55.3%, and 61.0%). Additionally, the positive rates for the two-gene combination in stage III colorectal cancer were higher than those for FOB (P < 0.05). The sensitivity and area under the curve (AUC) for SDC2 were 73.3% and 0.855, respectively, exceeding the sensitivity and AUC for the combined four tumor markers, which were 60.3% and 0.734 (P < 0.05). The combined detection of the two methylated genes demonstrated a sensitivity of 86.2% and an AUC of 0.908, outperforming both FOB and the combined detection of the four tumor markers (P < 0.05). CONCLUSION: The detection of SDC2 exhibits high sensitivity for colorectal cancer, and when combined with Septin9, it significantly enhances the diagnostic accuracy for early-stage colorectal cancer, offering substantial clinical value.

Role of hepatitis B core-related antigen in predicting the occurrence and recurrence of hepatocellular carcinoma in patients with chronic hepatitis B: A systemic review and meta-analysis.

BACKGROUND AND AIM: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. RESULTS: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I2 = 7.89%, P = 0.031). CONCLUSIONS: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions.

Application of artificial intelligence-assisted image diagnosis software based on volume data reconstruction technique in medical imaging practice teaching.

BACKGROUND: In medical imaging courses, due to the complexity of anatomical relationships, limited number of practical course hours and instructors, how to improve the teaching quality of practical skills and self-directed learning ability has always been a challenge for higher medical education. Artificial intelligence-assisted diagnostic (AISD) software based on volume data reconstruction (VDR) technique is gradually entering radiology. It converts two-dimensional images into three-dimensional images, and AI can assist in image diagnosis. However, the application of artificial intelligence in medical education is still in its early stages. The purpose of this study is to explore the application value of AISD software based on VDR technique in medical imaging practical teaching, and to provide a basis for improving medical imaging practical teaching. METHODS: Totally 41 students majoring in clinical medicine in 2017 were enrolled as the experiment group. AISD software based on VDR was used in practical teaching of medical imaging to display 3D images and mark lesions with AISD. Then annotations were provided and diagnostic suggestions were given. Also 43 students majoring in clinical medicine from 2016 were chosen as the control group, who were taught with the conventional film and multimedia teaching methods. The exam results and evaluation scales were compared statistically between groups. RESULTS: The total skill scores of the test group were significantly higher compared with the control group (84.51 ± 3.81 vs. 80.67 ± 5.43). The scores of computed tomography (CT) diagnosis (49.93 ± 3.59 vs. 46.60 ± 4.89) and magnetic resonance (MR) diagnosis (17.41 ± 1.00 vs. 16.93 ± 1.14) of the experiment group were both significantly higher. The scores of academic self-efficacy (82.17 ± 4.67) and self-directed learning ability (235.56 ± 13.50) of the group were significantly higher compared with the control group (78.93 ± 6.29, 226.35 ± 13.90). CONCLUSIONS: Applying AISD software based on VDR to medical imaging practice teaching can enable students to timely obtain AI annotated lesion information and 3D images, which may help improve their image reading skills and enhance their academic self-efficacy and self-directed learning abilities.

Ammonia oxidizing bacteria (AOB) denitrification and bacterial denitrification as the main culprit of high N2O emission in SBR with low C/N ratio wastewater.

A large amount of greenhouse gas nitrous oxide (N2O) will be produced during the biological nitrogen removal process for organic wastewater of low C/N ratio. One of the effective methods to solve this problem is to incorporate inexpensive carbon source. In this study, raw wastewater (RW) from pig farm, that was not anaerobically digested, was utilized as exogenous carbon in both A/O and SBR aerobic reactor to treat liquid digestate with high ammonia nitrogen and low C/N ratio. The results showed that N2O emission in SBR was higher than that of A/O process under the same nitrogen load. The N2O conversion in the biological nitrogen removal process was investigated by the strategy of integrating stable isotope method and metagenomics. The δO18-N2O, δN15-N2O, and SP values of the SBR were closer to the denitrification values of Ammonia-Oxidizing Bacteria (AOB) than those of A/O. The abundance of AOB in the SBR reactor was higher than that in the A/O reactor, while the abundance of denitrifying bacteria was lower. The amoA/B/C gene abundance in the SBR was greater than that in the A/O, and the NOS gene abundance was the opposite. The results indicated that both AOB denitrification and bacterial denitrification led to the increase of N2O emissions of the SBR.

Carbon Dots Anchoring Single-Atom Pt on C3N4 Boosting Photocatalytic Hydrogen Evolution.

Carbon nitride (C3N4) has gained considerable attention and has been regarded as an ideal candidate for photocatalytic hydrogen evolution. However, its photocatalytic efficiency is still unsatisfactory due to the rapid recombination rate of photo-generated carriers and restricted surface area with few active sites. Herein, we successfully synthesized a single-atom Pt cocatalyst-loaded photocatalyst by utilizing the anchoring effect of carbon dots (CDs) on C3N4. The introduction of CDs onto the porous C3N4 matrix can greatly enhance the specific surface area of C3N4 to provide more surface-active sites, increase light absorption capabilities, as well as improve the charge separation efficiency. Notably, the functional groups of CDs can efficiently anchor the single-atom Pt, thus improving the atomic utilization efficiency of Pt cocatalysts. A strong interaction is formed via the connection of Pt-N bonds, which enhances the efficiency of photogenerated electron separation. This unique structure remarkably improves its H2 evolution performance under visible light irradiation with a rate of 15.09 mmol h-1 g-1. This work provides a new approach to constructing efficient photocatalysts by using CDs for sustainable hydrogen generation, offering a practical approach to utilizing solar energy for clean fuel production.

Improvement on wheat bread quality by in situ produced dextran-A comprehensive review from the viewpoint of starch and gluten.

Deterioration of bread quality, characterized by the staling of bread crumb, the softening of bread crust and the loss of aroma, has caused a huge food waste and economic loss, which is a bottleneck restriction to the development of the breadmaking industry. Various bread improvers have been widely used to alleviate the issue. However, it is noteworthy that the sourdough technology has emerged as a pivotal factor in this regard. In sourdough, the metabolic breakdown of carbohydrates, proteins, and lipids leads to the production of exopolysaccharides, organic acids, aroma compounds, or prebiotics, which contributes to the preeminent ability of sourdough to enhance bread attributes. Moreover, sourdough exhibits a "green-label" feature, which satisfies the consumers' increasing demand for additive-free food products. In the past two decades, there has been a significant focus on sourdough with in situ produced dextran due to its exceptional performance. In this review, the behaviors of bread crucial compositions (i.e., starch and gluten) during dough mixing, proofing, baking and bread storing, as well as alterations induced by the acidic environment and the presence of dextran are systemically summarized. From the viewpoint of starch and gluten, results obtained confirm the synergistic amelioration on bread quality by the coadministration of acidity and dextran, and also highlight the central role of acidification. This review contributes to establishing a theoretical foundation for more effectively enhancing the quality of wheat breads through the application of in situ produced dextran.

Preserving Mesoporosity in Type III Porous Liquids through Dual-layer Surface Weaving.

The fundamental limitation for pore preservation in a Type III porous liquid (T3PL) is the need for a small aperture from the porous filler to realize size exclusion of a bulky solvent. We present a dual-layer surface weaving strategy that can disregard this limitation and achieve micro- and mesoporous metal-organic framework (MOF)-based T3PLs even with apertures much larger than the solvent molecules. By first weaving a tight network of poly(tert-butyl methacrylate) on the MOF surface, the poly(dimethylsiloxane) (PDMS) solvent can be effectively excluded from the pores while smaller guest molecules such as CO2, C2H4, and H2O can freely access the interior, as confirmed by low-pressure adsorption isotherms. Further application of a PDMS-containing polymer coating helps lower the viscosity of the PL due to increased particle dispersibility. This strategy has resulted in the successful construction of T3PLs with aperture sizes up to 3.1 nm.

Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients.

BACKGROUND AND AIMS: The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. METHODS: Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. RESULTS: Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). CONCLUSION: The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention.

Transcriptional landscape of cholangiocarcinoma revealed by weighted gene coexpression network analysis.

Cholangiocarcinoma (CCA) is a type of cancer with limited treatment options and a poor prognosis. Although some important genes and pathways associated with CCA have been identified, the relationship between coexpression and phenotype in CCA at the systems level remains unclear. In this study, the relationships underlying the molecular and clinical characteristics of CCA were investigated by employing weighted gene coexpression network analysis (WGCNA). The gene expression profiles and clinical features of 36 patients with CCA were analyzed to identify differentially expressed genes (DEGs). Subsequently, the coexpression of DEGs was determined by using the WGCNA method to investigate the correlations between pairs of genes. Network modules that were significantly correlated with clinical traits were identified. In total, 1478 mRNAs were found to be aberrantly expressed in CCA. Seven coexpression modules that significantly correlated with clinical characteristics were identified and assigned representative colors. Among the 7 modules, the green and blue modules were significantly related to tumor differentiation. Seventy-eight hub genes that were correlated with tumor differentiation were found in the green and blue modules. Survival analysis showed that 17 hub genes were prognostic biomarkers for CCA patients. In addition, we found five new targets (ISM1, SULT1B1, KIFC1, AURKB and CCNB1) that have not been studied in the context of CCA and verified their differential expression in CCA through experiments. Our results not only promote our understanding of the relationship between the transcriptome and clinical data in CCA but will also guide the development of targeted molecular therapy for CCA.

Dual-band terahertz absorber based on square ring metamaterial structure.

In this paper, a dual-band terahertz absorber based on metamaterial structure is designed, fabricated, and measured. The metal periodic array is located on the upper surface of a silicon wafer with a metal ground plane, while the metamaterial structure is created utilizing a square metal ring with four T-shaped metal strips loaded inside of the ring. Two absorption peaks are realized at 0.715 and 1.013 THz with high Q-factors of 152.1 and 98.3, respectively, under normal TE and TM polarized incidence. A prototype of the proposed metamaterial absorber is fabricated by electron beam lithography (EBL) and electron beam evaporation (EBE) technology. Furthermore, a terahertz time-domain spectroscopy (TDS) measurement system is employed to test the absorber sample, with good measurement results obtained. This work provides a new option for the design of multi-band terahertz metamaterial absorbers.

Afzelin protects against doxorubicin-induced cardiotoxicity by promoting the AMPKα/SIRT1 signaling pathway.

BACKGROUND: Doxorubicin (DOX), a chemotherapeutic drug, could relieve the progressions of various diseases. However, its clinical application is limited due to its cardiotoxicity. This study aimed to investigate the effects of afzelin (a flavonol glycoside found in Houttuynia cordata) on the cardiotoxicity induced by DOX. METHODS: In ex-vivo, H9C2 cells were incubated with 20, 40, or 80 µM afzelin for 12 h, followed by the treatment with 1 µM DOX for 12 h. In vivo, C57BL/6 J mice were intraperitoneally injected with 4 mg/kg/day DOX on days 1, 7, and 14. Meanwhile, starting from day 1, mice were intragastrically administrated with 5 mg/kg/day or 10 mg/kg/day afzelin for 20 days. The cardiac function of mice was evaluated by detecting hemodynamic parameters using the M-mode echocardiography. RESULTS: DOX decreased the cell survival rate, and elevated apoptotic rate, as well as induced the oxidative stress and mitochondrial dysfunction in H9C2 cells. All these changes were alleviated by afzelin treatment in a concentration-dependent manner. The results were further proven by the mitigation of cardiac injury in vivo, as evidenced by the elevation of fractional shortening, heart weight/tibia length, and the rate of the increase/decrease of left ventricular pressure in mice subjected to DOX-induced cardiotoxicity. Furthermore, afzelin upregulated the expression of p-AMP-activated protein kinase alpha (AMPKα) and sirtuin1 (SIRT1). Dorsomorphin (an AMPKα inhibitor) abrogated the anti-cardiotoxicity effects of afzelin in H9C2 cells induced by DOX. CONCLUSION: Afzelin protected against DOX-induced cardiotoxicity by promoting the AMPKα/SIRT1 signaling pathway.