A review of metal phosphides with catalytic effects in Li-S batteries: boosting the redox kinetics.

Lithium-sulfur batteries (Li-S batteries) are being widely studied as promising energy-storage solutions for the next generation owing to their excellent properties including high energy density, eco-friendliness, and low cost. Nevertheless, drawbacks, especially the severe "shuttle effect" and slow transformation of polysulfides, hinder the road to commercialization of Li-S batteries. The functional utilization of metal compounds in Li-S batteries has been verified, such as enhancing the conductivity, adsorption of lithium polysulfides (LPSs) and improving the kinetics of electrode processes. Benefiting from the outstanding catalytic capability and relatively good conductivity, metal phosphides have gradually received intense attention over the past few years. Consequently, significant progress has been achieved in the optimization of phosphides for Li-S batteries in recent years. This review introduces the application of metal phosphides in Li-S batteries from the aspects of their own characteristics, material structure design, and material interface control. The aim of this review is to enhance the understanding of the operational mechanism of metal phosphides and provide guidance for the development of Li-S batteries.

Simultaneous enrichment and speciation of lead and mercury by magnetic solid-phase extraction coupled to HPLC-ICP-MS based on magnetic hydrazine-linked covalent organic frameworks.

BACKGROUND: Trace levels of organic and inorganic lead and mercury species in the environment, including divalent lead (Pb2+), trimethyllead (TML), divalent mercury (Hg2+), monomethylmercury (MeHg), and ethylmercury (EtHg), are highly toxic to humans and ecology. It is of great importance for speciation of lead and mercury to evaluate the toxicity of lead and mercury and their biogeochemistry in the environment. However, simultaneous multi-elemental enrichment and speciation at trace level remains a challenge. There are few reports of simultaneous magnetic solid-phase extraction (MSPE) of organic and inorganic lead and mercury species at trace level in the real water. RESULTS: In this work, a novel core-shell magnetic hydrazine-linked covalent organic frameworks (Fe3O4@COF-TCH) was prepared for the first time by grafting hydrazine-linked COFs on the Fe3O4 nanoparticles. Fe3O4@COF-TCH with abundant thione and imino groups has strong adsorption for lead and mercury species. Based on it, a simple and practical magnetic solid-phase extraction high-performance liquid chromatography-inductively coupled plasma mass spectrometry (MSPE-HPLC-ICP-MS) method was developed for extraction and determination of trace lead and mercury species, including Hg2+, MeHg, EtHg, Pb2+ and TML. The limits of detection (3δ) of the developed method were 0.08, 0.81, 0.90, 0.56 and 0.88 ng L-1 with the enrichment factors (EFs) of 384, 376, 379, 389 and 360-fold for Pb2+, TML, Hg2+, MeHg and EtHg, respectively. The high accuracy and reproducibility have been proved by the spiked recoveries (94.4-103 %) in real samples. SIGNIFICANCE: The proposed method with simple operation and high sensitivity has been successfully applied to simultaneous speciation of lead and mercury at trace levels in the water samples with complicated matrices, including underground water, surface water, sea water. Meanwhile, it has the advantages of cost-saving, labor-saving and time-saving and is suitable for the investigation and risk assessment in water. The development of MSPE-HPLC-ICP-MS method provides ideas and guidance for the simultaneous multi-elemental enrichment and speciation.

Exploration of the application potential of serum multi-biomarker model in colorectal cancer screening.

Analyzing blood lipid and bile acid profile changes in colorectal cancer (CRC) patients. Evaluating the integrated model's diagnostic significance for CRC. Ninety-one individuals with colorectal cancer (CRC group) and 120 healthy volunteers (HC group) were selected for comparison. Serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoproteins (Apo) A1, ApoA2, ApoB, ApoC2, and ApoC3 were measured using immunoturbidimetric and colorimetric methods. Additionally, LC-MS/MS was employed to detect fifteen bile acids in the serum, along with six tumor markers: carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, CA19-9, CA242, CA50, and CA72-4. Group comparisons utilized independent sample t-tests and Mann-Whitney U tests. A binary logistic regression algorithm was applied to fit the indicators and establish a screening model; the diagnostic accuracy of individual Indicators and the model was analyzed using receiver operating characteristic (ROC) curves. The CRC group showed significantly lower levels in eight serum lipid indicators and eleven bile acids compared to the HC group (P < 0.05). Conversely, serum levels of TG, CA19-9, and CEA were elevated (P < 0.05). Among the measured parameters, ApoA2 stands out for its strong correlation with the presence of CRC, showcasing exceptional screening efficacy with an area under the curve (AUC) of 0.957, a sensitivity of 85.71%, and a specificity of 93.33%. The screening model, integrating ApoA1, ApoA2, lithocholic acid (LCA), and CEA, attained an impressive AUC of 0.995, surpassing the diagnostic accuracy of individual lipids, bile acids, and tumor markers. CRC patients manifest noteworthy alterations in both blood lipids and bile acid profiles. A screening model incorporating ApoA1, ApoA2, LCA, and CEA provides valuable insights for detecting CRC.

Blockade of CCR5 and CXCR3 attenuates murine acute graft-versus-host disease through modulating donor-derived T cell distribution and function.

BACKGROUND: Lymphocyte trafficking via chemokine receptors such as CCR5 and CXCR3 plays a critical role in the pathogenesis of aGVHD. Our previous studies showed that addition of CCR5 or CXCR3 antagonist could only slightly alleviate the development of aGVHD. Given the specificity of T lymphocytes bearing CXCR3 and CCR5, we investigated whether combined CCR5 and CXCR3 blockade could further attenuate murine aGVHD. METHODS: A mouse model of aGVHD was established to assess the efficacy of CCR5 or/and CXCR3 blockade on the development of aGVHD. The distribution of lymphocytes was calculated by quantification of immunostaining cells. The immunomodulatory effect on T cells were assessed by evaluating T- cell proliferation, viability, and differentiation. RESULTS: Using murine allo-HSCT model, we demonstrated that blockade of both CCR5 and CXCR3 could efficiently alleviate the development of aGVHD. Further investigation on the immune mechanisms for this prophylactic effect showed that more T cells were detained into secondary lymphoid organs (SLOs), which may lead to reduced infiltration of T cells into GVHD target organs. Our study also showed that T cells detained into SLOs dampened the activation, suppressed the polarization toward Th1 and Tc1, and induced the production of Treg cells. CONCLUSION: These data suggest that concurrent blockade of CCR5 and CXCR3 attenuates murine aGVHD through modulating donor-derived T cell distribution and function, and this might be applicable for aGVHD prophylaxis in clinical settings.

Application of multiplatform remote sensing data over East Asia Ocean: aerosol characteristics and aerosol types.

It is important to explore the characteristics and rules of atmospheric aerosol in the East Asian Sea for monitoring and evaluating atmospheric environmental quality. Based on Aerosol Robot Network (AERONET), Visible Infrared Imaging Radiometer (VIIRS), and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) data, the temporal and spatial variation characteristics and differences of aerosol parameters and types in the East Asian Sea were studied by using figure classification method (FIGCM), aerosol optical depth (AOD)440-Angstrom exponent (AE)440-870 method (AA1M), and AOD550-AE490-670 method (AA2M). The results show that the seasonal variation trend of aerosol characteristics and types is obvious in East Asia Sea. AOD, volume concentration (Cv), and aerosol effective radius (reff) in the Bohai-Yellow Sea and the Sea of Japan in autumn are lower than those in other seasons, and the occurrence frequency of ocean-type aerosols is high. Different from the Bohai-Yellow Sea and Sea of Japan, human activities in winter, summer, and autumn seriously affect the air quality in the East China Sea and South China Sea. Especially at the Taipei CWB site, from aerosol parameters and high biomass burning/urban industrial (BB/UI) aerosol, human activity is an important factor for high pollution at the Taipei CWB site. Aerosol types of AA1M, FIGCM, AA2M, and CALIPSO were compared at Anmyon and Yonsei University sites in the Bohai-Yellow Sea in March 2020. The results show that aerosol types based on threshold classification methods generally have higher mixed aerosol results, and the marine (MA) results of AA1M, FIGCM, and AA2M are close to the clean marine aerosol results of CALIPSO. Comparing the results of AA 2 M and CALIPSO on a spatial scale, it is found that the clean marine aerosol proportion identified by CALIPSO (0.38, 0.48, 0.82) is consistent with the MA proportion identified by AA 2 M (0.43, 0.46, 0.97) in the East China Sea, South China Sea, and Western Pacific Ocean.

Study on the habitat evolution after dam removal in a habitat-alternative tributary of large hydropower station.

The establishment of large hydropower stations in the main stream poses a threat to fish habitats. Selecting suitable tributaries as alternative habitats is a practical measure for ecological environment protection during large hydropower station's construction. The small dams constructed on certain tributaries need to be removed in order to restore river connectivity. The removal of dams will activate hydro-sedimentary dynamics and change the original habitat in terms of topography and hydrodynamics. To explore the evolution of fish habitats following the removal of small dams, a dam-removed reach of a habitat-alternative tributary was selected as the research object, and the model of water-sediment transport and riverbed evolution in strongly disturbed dam-removed reaches and the model of fish habitat suitability evaluation were established. The key parameters calibration and model verification were completed by field monitoring results. The simulation results showed dramatic evolution in the reservoir riverbed in the initial stage after dam removal and during the high discharge period. One year after dam removal, there was a noticeable 4.0 m incision in front of the dam, along with a decrease in channel slope at the dam site from about 4.8% to approximately 1.5%. Downstream of the dam, alterations to the riverbed were mainly concentrated near the dam, and sedimentary bodies with a height of around 2.0 m have formed on the left bank following the high discharge period. The fish habitat in most areas of the dam-removed reach was suitable, except for the downstream high-velocity area. To compare the evolution process of fish habitat under two dam removal periods in wet and dry seasons, two dam removal schemes were implemented in March and June. The results showed that the riverbed evolved more gradually in the March scheme, creating a larger and continuous suitable habitat for fish. Therefore, the March scheme was recommended. By revealing the evolutionary pattern of fish habitat after dam removal, this research provides a reliable model for assessing and restoring habitats in dam-removed reaches, and enjoys significant implications for protecting river ecology in hydropower development reaches.

Palladium-Catalyzed Asymmetric Decarboxylation of 5-Vinyloxazolidine-2,4-Diones Triggering the Dearomatization of Electron-Deficient Indoles for the Synthesis of Chiral Highly Functionalized Pyrroloindolines.

A catalyst system consisting of a chiral phosphoramidite ligand and Pd2(dba)3·CHCl3 causes the decarboxylation of 5-vinyloxazolidine-2,4-diones to generate amide-containing aza-π-allylpalladium 1,3-dipole intermediates, which are capable of triggering the dearomatization of 3-nitroindoles for diastereo- and enantioselective [3+2] cycloaddition, leading to the formation of a series of highly functionalized pyrroloindolines containing three contiguous stereogenic centers with excellent results (up to 99% yield, 88:12 dr, and 96% ee).

A comparative study of the use of digital technology in the anterior smile experience.

OBJECTIVES: this study aims to compare the clinical outcomes of traditional and digital crown extension guides in the aesthetic restoration of anterior teeth. Additionally, the study will analyze the differences in the results of various digital crown extension guides in anterior aesthetic restorations. METHODS: Sixty-two patients who required aesthetic restoration of their anterior teeth were selected for this study. The patients had a total of 230 anterior teeth and were randomly divided into three groups: a control group of 22 cases who received diagnostic wax-up with pressure film, an experimental group 1 of 20 cases who received 3D printed digital models with pressure film, and an experimental group 2 of 20 patients who received digital dual-positioning guides. The control group had a total of 84 anterior teeth, experimental group 1 had 72 anterior teeth, and experimental group 2 had 74 anterior teeth. The study compared three methods for fabricating crown extension guides: the control group used the diagnostic wax-up plus compression film method, while experimental group 1 used compression film on 3D printed models and experimental group 2 used 3D printed digital dual-positioning crown extension guides. After the crown lengthening surgery, the control group patients wore DMG resin temporary crown material for gingival contouring, while the experimental group patients wore 3D printed resin temporary crowns for the same purpose. The patients were followed up in the outpatient clinic after wearing temporary crowns for 1 month, 3 months, and 6 months, respectively. The clinical results were evaluated in terms of marginal fit, red aesthetic index, and white aesthetic index. RESULTS: Based on the statistical analysis, the experimental group required significantly fewer follow-up visits and less time for guide design and fabrication compared to the control group. Additionally, the surgical time for the experimental group was significantly shorter than that of the control group. During the postoperative period between the 1st and 3rd month, the PES index scores for the marginal gingival level, proximal, and distal mesiodistal gingival papillae of the experimental group showed a trend of superiority over those of the control group. By the 6th month, the marginal gingival level exhibited a significant difference between the experimental and control groups. The experimental group demonstrated superior results to the control group in terms of shape, contour, and volume of the teeth, color, surface texture, and transparency of the restorations, and features during the 1st and 3rd postoperative months. In the 6th month, the comparative results indicated that the experimental group continued to exhibit superior outcomes to the control group in terms of the shape, color, surface texture, and transparency of the restorations, as well as the characteristics of the teeth. Additionally, the experimental group demonstrated significantly fewer gingival alterations than the control group at 1 month, 3 months, and 6 months post-procedure, with this difference being statistically significant. Furthermore, the combination of 3D printing technology and restorative techniques was utilized, resulting in consistent patient satisfaction. CONCLUSION: Digitalisation plays an important role in anterior aesthetic restorations. The use of digital technology to manage the entire process of anterior cosmetic restorations can improve restorative results, reduce the number of follow-up appointments, shorten consultation time, and achieve better patient satisfaction.

Low molecular weight chitosan based GSH-responsive self-assembled cationic micelle with enhanced anti-tumor effect by combining oxidative damage and chemotherapy.

A novel cationic lipoic acid grafted low molecular weight chitosan (LCNE-LA) conjugate was constructed and further self-assembled into GSH-responsive cationic nanocarrier to achieve better antitumor effect by combining encapsulated chemotherapy and oxidative damage induced by ROS. The resultant LCNE-LA cationic micelle exhibited favorable physicochemical properties (low CMC, small size, positively zeta potential and good stability), excellent biosafety and desired redox sensitivity. Next, doxorubicin (Dox) was embedded into hydrophobic core to form stable Dox/LCNE-LA micelle that had superior loading capacity. The GSH-induced release behavior, cellular uptake ability, ROS generation and GSH consumption capacity and in vitro antitumor activity of Dox/LCNE-LA micelle were systematically evaluated. Consequently, Dox/LCNE-LA cationic micelle with positively charged could efficiently enter into cancer cell and redox-sensitive release Dox via disulfide-thiol exchange reaction, which usually expend abundant GSH and disrupt redox homeostasis. Studies further confirmed that Dox/LCNE-LA micelle could increase ROS and reduced GSH content which might cause oxidative damage to tumor cell. Antitumor activity indicated that Dox/LCNE-LA micelle achieved an excellent cancer-killing effect, which might be attributed to combination treatment of Dox and ROS induce oxidative damage. Overall, this research was expected to provide a platform for antitumor treatment by triggering Dox release and promoting ROS generation.

Molecularly Imprinted Heterostructure-Assisted Laser Desorption Ionization Mass Spectrometry Analysis and Imaging of Quinolones.

Quinolone residues resulting from body metabolism and waste discharge pose a significant threat to the ecological environment and to human health. Therefore, it is essential to monitor quinolone residues in the environment. Herein, an efficient and sensitive matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS) method was devised by using a novel molecularly imprinted heterojunction (MIP-TNs@GCNs) as the matrix. Molecularly imprinted titanium dioxide nanosheets (MIP-TNs) and graphene-like carbon nitrides (GCNs) were associated at the heterojunction interface, allowing for the specific, rapid, and high-throughput ionization of quinolones. The mechanism of MIP-TNs@GCNs was clarified using their adsorption properties and laser desorption/ionization capability. The prepared oxygen-vacancy-rich MIP-TNs@GCNs heterojunction exhibited higher light absorption and ionization efficiencies than TNs and GCNs. The good linearity (in the quinolone concentration range of 0.5-50 pg/µL, R2 > 0.99), low limit of detection (0.1 pg/µL), good reproducibility (n = 8, relative standard deviation [RSD] < 15%), and high salt and protein resistance for quinolones in groundwater samples were achieved using the established MIP-TNs@GCNs-MALDI/MS method. Moreover, the spatial distributions of endogenous compounds (e.g., amino acids, organic acids, and flavonoids) and xenobiotic quinolones from Rhizoma Phragmitis and Rhizoma Nelumbinis were visualized using the MIP-TNs@GCNs film as the MALDI/MS imaging matrix. Because of its superior advantages, the MIP-TNs@GCNs-MALDI/MS method is promising for the analysis and imaging of quinolones and small molecules.

Thiol-Triggered Tandem Dearomative Michael Addition/Intramolecular Henry Reaction of 2-Nitrobenzofurans: Access to Sulfur-Containing Polyheterocyclic Compounds.

An efficient dearomative cyclization of 2-nitrobenzofurans via a thiol-triggered tandem Michael addition/intramolecular Henry reaction has been developed. A range of thiochromeno[3,2-b]benzofuran-11-ols and tetrahydrothieno[3,2-b]benzofuran-3-ols could be obtained in up to 99% yield and up to >20:1 dr. The valuable thiochromone fused benzofurans could be prepared with the reaction of 2-nitrobenzofurans and 2-mercaptobenzaldehyde via the tandem dearomative Michael addition/intramolecular Henry reaction/rearomatization/oxidative dehydrogenation process in a one-pot two-step operation. A mechanism for the reaction was tentatively proposed.

Trophic transfer of heavy metals across four trophic levels based on muscle tissue residuals: a case study of Dachen Fishing Grounds, the East China Sea.

In this study, we collected 56 species of fishery organisms (including fish, crustaceans, cephalopods, gastropods, and bivalves) from four seasonal survey cruises at the Dachen fishery grounds. We measured the concentrations of seven heavy metals (Cd, Zn, Cu, Pb, Cr, As, and Hg) in these fisheries organisms. We determined their trophic levels using carbon and nitrogen stable isotope techniques. We analyzed the characteristics of heavy metal transfer in the food chain. The results showed significant differences in heavy metal concentrations among different species. Among all biological groups, bivalves and gastropods exhibited higher levels of heavy metal enrichment than other biological groups, while fish had the lowest levels of heavy metal enrichment. Heavy metals exhibited different patterns of nutritional transfer in the food chain. While Hg showed a biomagnification phenomenon in the food chain, it was not significant. Cd, Zn, Cu, Pb, Cr, and As exhibited a trend of biodilution with increasing nutritional levels, except for As, which showed no significant correlation with δ15N.

Evaluation of probiotic properties of a Brevibacillus laterosporus strain.

Brevibacillus laterosporus is a strain of probiotic bacteria that has been widely used in pest control, cash crop, and other production areas. However, few studies have been conducted on its use as a feed additive in animals. Therefore, the probiotic potential of B. laterosporus PBC01 was evaluated by characterizing hydrophobicity, auto-aggregation activity, bile salt and simulated gastrointestinal fluid tolerance, bienzymatic, and antibacterial activity. Antibiotic susceptibility, hemolysis assays, and supplemental feeding of mice were also performed to evaluate safety features. Our results showed that B. laterosporus PBC01 had moderate hydrophobicity, high auto-agglutination ability. Meanwhile, B. laterosporus PBC01 had good tolerance to bile salt and simulated gastrointestinal fluid. It had the ability to secrete protease, cellulase, and to inhibit various pathogens. In addition, B. laterosporus PBC01 was sensitive to many antibiotics, and did not produce hemolysin. In the safety assessment of mice, it did not cause any deaths, nor did it affect the cell components of blood, antioxidant capacity, and reproductive health. The study indicated the great probiotic characteristics and safety of B. laterosporus PBC01. This may provide a theoretical basis for the clinical application and development of probiotic-based feed additives.

Synthesis of Benzofuro[3,2-b]indol-3-one Derivatives via Dearomative (3 + 2) Cycloaddition of 2-Nitrobenzofurans and para-Quinamines.

An efficient dearomative (3 + 2) cycloaddition of para-quinamines and 2-nitrobenzofurans has been developed. This reaction proceeds smoothly under mild conditions and affords a series of benzofuro[3,2-b]indol-3-one derivatives in good to excellent yields (up to 98%) with perfect diastereoselectivities (all cases > 20:1 dr). The scale-up synthesis and versatile derivatizations demonstrate the potential synthetic application of the protocol. A plausible reaction mechanism is also proposed to account for the observed reaction process. This work represents the first instance of the N-triggered dearomative (3 + 2) cycloaddition of 2-nitrobenzofurans.

Evaluation of the Immunity Responses in Mice to Recombinant Bacillus subtilis Displaying Newcastle Disease Virus HN Protein Truncations.

Bacillus subtilis, a probiotic bacterium with engineering potential, is widely used for the expression of exogenous proteins. In this study, we utilized the integrative plasmid pDG364 to integrate the hemagglutinin-neuraminidase (HN) gene from Newcastle disease virus (NDV) into the genome of the B. subtilis 168 model strain. We successfully constructed a recombinant B. subtilis strain (designated B. subtilis RH) that displays a truncated HN antigen fragment on the surface of its spores and further evaluated its immunogenic effects in mice. Using ELISA, we quantified the levels of IgG in serum and secretory IgA (sIgA) in intestinal contents. The results revealed that the recombinant B. subtilis RH elicited robust specific mucosal and humoral immune responses in mice. Furthermore, B. subtilis RH demonstrated potential mucosal immune adjuvant properties by fostering the development of immune organs and augmenting the number of lymphocytes in the small intestinal villi. Additionally, the strain significantly upregulated the relative expression of inflammatory cytokines such as IL-1ß, IL-6, IL-10, TNF-α, and IFN-γ in the small intestinal mucosa. In conclusion, the B. subtilis RH strain developed in this study exhibits promising mucosal immunogenic effects. It holds potential as a candidate for an anti-NDV mucosal subunit vaccine and offers a novel preventive strategy for the poultry industry against this disease.

Phyllosphere bacterial community dynamics in response to bacterial wildfire disease: succession and interaction patterns.

Plants interact with complex microbial communities in which microorganisms play different roles in plant development and health. While certain microorganisms may cause disease, others promote nutrient uptake and resistance to stresses through a variety of mechanisms. Developing plant protection measures requires a deeper comprehension of the factors that influence multitrophic interactions and the organization of phyllospheric communities. High-throughput sequencing was used in this work to investigate the effects of climate variables and bacterial wildfire disease on the bacterial community's composition and assembly in the phyllosphere of tobacco (Nicotiana tabacum L.). The samples from June (M1), July (M2), August (M3), and September (M4) formed statistically separate clusters. The assembly of the whole bacterial population was mostly influenced by stochastic processes. PICRUSt2 predictions revealed genes enriched in the M3, a period when the plant wildfire disease index reached climax, were associated with the development of the wildfire disease (secretion of virulence factor), the enhanced metabolic capacity and environmental adaption. The M3 and M4 microbial communities have more intricate molecular ecological networks (MENs), bursting with interconnections within a densely networked bacterial population. The relative abundances of plant-beneficial and antagonistic microbes Clostridiales, Bacillales, Lactobacillales, and Sphingobacteriales, showed significant decrease in severally diseased sample (M3) compared to the pre-diseased samples (M1/M2). Following the results of MENs, we further test if the correlating bacterial pairs within the MEN have the possibility to share functional genes and we have unraveled 139 entries of such horizontal gene transfer (HGT) events, highlighting the significance of HGT in shaping the adaptive traits of plant-associated bacteria across the MENs, particularly in relation to host colonization and pathogenicity.

Targeting SHMTs and MTHFDs in cancer: attractive opportunity for anti-tumor strategy.

One-carbon metabolism is a universal metabolic process that mediates the transfer of one-carbon units for purine and thymidine synthesis. One-carbon metabolism has been found to be dysregulated in various cancer types due to its role in production of purine and pyrimidine nucleotides, epigenetic program, and redox homeostasis. One-carbon metabolism is composed a network of one-carbon metabolic enzymes. Disturbing the expression and enzymatic activity of these one-carbon metabolic enzymes could lead to fluctuations of metabolites in the tumor microenvironment. Serine hydroxymethyltransferases (SHMTs) and methylenetetrahydrofolate dehydrogenases (MTHFDs) are gradually recognized as important one-carbon metabolic enzymes for regulating tumor initiation and development, representing potential therapeutic targets for anti-tumor strategies. In the review, we primarily focused on the role of SHMTs and MTHFDs in cancer. Several inhibitors targeting MTHFDs and SHMTs have exert its potential to decrease tumor burden and inhibit tumor proliferation, highlighting the potential of targeting one-carbon metabolic enzymes for anti-cancer strategies.

A cuproptosis-related gene expression signature predicting clinical prognosis and immune responses in intrahepatic cholangiocarcinoma detected by single-cell RNA sequence analysis.

BACKGROUND: Cholangiocarcinoma represents a malignant neoplasm originating from the hepatobiliary tree, with a subset of tumors developing inside the liver. Intrahepatic cholangiocarcinomas (ICC) commonly exhibit an asymptomatic presentation, rendering both diagnosis and treatment challenging. Cuproptosis, an emerging regulated cell death pathway induced by copper ions, has garnered attention recently. As cancer cells show altered copper metabolism and comparatively higher copper needs, cuproptosis may play a role in the development of ICC. However, studies investigating this possibility are currently lacking. METHODS: Single-cell and bulk RNA sequence data were analyzed, and correlations were established between the expression of cuproptosis-related molecules and ICC patient survival. Genes with predicting survival were used to create a CUPT score using Cox and LASSO regression and tumor mutation burden (TMB) analysis. The CIBERSORT software was employed to characterize immune cell infiltration within the tumors. Furthermore, immune infiltration prediction, biological function enrichment, and drug sensitivity analyses were conducted to explore the potential implications of the cuproptosis-related signature. The effects of silencing solute carrier family 39 member 4 gene (SLC39A4) expression using siRNA were investigated using assays measuring cell proliferation, colony formation, and cell migration. Key genes of cuproptosis were detected by western blotting. RESULTS: The developed CUPT score divided patients into high and low CUPT score groups. Those with a low score had significantly better prognosis and longer survival. In contrast, high CUPT scores were associated with worse clinical outcomes and significantly higher TMB. Comparisons of the two groups also indicated differences in the immune infiltrate present in the tumors. Finally, we were able to identify 95 drugs potentially affecting the cuproptosis pathway. Some of these might be effective in the treatment of ICC. The in vitro experiments revealed that suppressing the expression of SLC39A4 in ICC cell lines resulted in reduced cell proliferation, colony formation, and cell migration. It also led to an increase in cell death and the upregulation of key genes associated with cuproptosis, namely ferredoxin 1 (FDX1) and dihydrolipoyl transacetylase (DLAT). These findings strongly suggest that this cuproptosis-associated molecule may play a pivotal role in the development and metastasis of ICC. CONCLUSIONS: Changes in the expression of a cuproptosis-related gene signature can predict the clinical prognosis of ICC with considerable accuracy. This supports the notion that cuproptosis influences the diversity and complexity of the immune microenvironment, mutational landscape, and biological behavior of ICC. Understanding this pathway better may hold promise for the development of innovative strategies in the management of this disease.

Cu-Catalyzed Direct Asymmetric Mannich Reaction of 2-Alkylazaarenes and Isatin-Derived Ketimines.

The first direct catalytic asymmetric Mannich reaction of 2-alkylazaarenes and ketimines was realized with a chiral Cu-bis(oxazoline) complex as the catalyst. The asymmetric addition of 2-alkylpyridines to isatin-derived ketimines proceeded smoothly to afford α,ß-functionalized 2-substituted pyridines bearing 3-amino-3,3-disubstituted oxindole motifs with excellent results (≤99% yield, 99:1 dr, and 98% ee). The catalytic system was also extended to 2-alkylbenzothiazoles as nucleophiles for the asymmetric Mannich reaction of ketimines.

Palladium-Catalyzed Ligand-Directed Divergent Decarboxylative Cycloadditions of Vinyloxazolidine-2,4-diones with 1,3,5-Triazinanes.

This study demonstrates a highly efficient regiodivergent ligand-controlled palladium-catalyzed cycloaddition reaction of vinyloxazolidine-2,4-diones with 1,3,5-triazinanes. In the presence of a diphosphine ligand, the reaction proceeds via a (5+2) cycloaddition pathway to afford 1,3-diazepin-4-ones in excellent yields, while using a monophosphine ligand, the reaction proceeds smoothly via a (3+2) cycloaddition pathway to give imidazolidin-4-ones in good yields.