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A Pd-catalyzed asymmetric higher-order dipolar cycloaddition between allenyl carbonates and azadienes is achieved by exploiting novel alkylidene-π-allyl-Pd dipoles. This research provides a modular platform for the synthesis of challenging chiral endocyclic allenes bearing a medium-sized heterocyclic motif and a centrally chiral stereocenter in good yields with high enantio- and diastereoselectivities (29 examples, up to 97% yield, 97:3 er and >19:1 dr). Experimental and computational studies elucidate the possible reaction mechanism and the observed stereochemical results. Based on the mechanistic understanding, a new π-propargyl-Pd dipole was designed to further extend the success of the higher order dipolar cycloaddition strategy to the synthesis of 10-membered endocyclic alkynes from propargyl carbonates and azadienes (13 examples, up to 98% yield and 94.5:5.5 er).

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The presence of refractory lignocellulose presents a significant challenge in green waste (GW) composting. This research applied both a conventional iron-based Fenton-like process (with a Fenton-like reagent composed of 1.0 % Fe3O4 nanoparticles and 1.0 % H2O2) and three modified iron-based Fenton-like processes (with a Fenton-like reagent composed of 1.0 % Fe3O4 nanoparticles and 1.0 % oxalic acid/1.0 % sodium percarbonate/0.5 % Phanerochaete chrysosporium) in GW composting to systematically assess their impacts on lignocellulose degradation during GW composting. The results revealed that iron-based Fenton-like process modified sodium percarbonate exhibited the most significant effects on lignocellulose degradation. Compared with control, degradation rates for lignin, cellulose, and hemicellulose increased by 49.8 %, 39.3 %, and 26.2 % (p < 0.05), respectively. Furthermore, this process enhanced the relative abundance of bacterial communities linked to lignocellulose degradation, particularly Firmicutes and Bacteroidota. These findings offer valuable insights into optimizing GW composting, understanding reactive oxygen species dynamics, and the application of iron-based Fenton-like process.

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Palatine tonsils are the only air-contacted lymphoid organs that constantly engage in crosstalk with commensal microorganisms and serve as the first handling sites against microbial antigens. While tonsil inflammations have been implicated in various autoimmune diseases, including rheumatoid arthritis (RA), the precise role of tonsillar microbiota in autoimmune pathogenesis remains inadequately characterized. In this study, we conducted a profiling of the tonsillar microbiota and identified a notable dysbiosis in RA patients, particularly within the Streptococcus genus. Specifically, RA patients exhibited an enrichment of pathogenic Streptococcus species, including S. pyogenes, S. dysgalactiae, and S. agalactiae. Colonization with these bacteria significantly exacerbated arthritis severity and increased autoimmune responses in collagen-induced arthritis (CIA). Furthermore, immunization with peptides derived from these pathogenic Streptococcus species directly induced experimental arthritis. Conversely, RA patients demonstrated a marked deficiency in commensal Streptococcus members, notably S. salivarius. Treatment of CIA mice with S. salivarius attenuated the progression of arthritis and downregulated autoimmune responses. These findings highlight a functional link between tonsillar microbiota and RA, shedding light on their contribution to autoimmunity.

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Isodesmic reactions, in which chemical bonds are redistributed between substrates and products, provide a general and powerful strategy for both biological and chemical synthesis. However, most isodesmic reactions involve either metathesis or functional-group transfer. Here, we serendipitously discovered a novel isodesmic reaction of indoles and anilines that proceeds intramolecularly under weakly acidic conditions. In this process, the five-membered ring of the indole motif is broken and a new indole motif is constructed on the aniline side, accompanied by the formation of a new aniline motif. Mechanistic studies revealed the pivotal role of σ→π* hyperconjugation on the nitrogen atom of the indole motif in driving this unusual isodesmic reaction. Furthermore, we successfully synthesized a diverse series of polycyclic indole derivatives; among quinolines, potential antitumor agents were identified using cellular and in vivo experiments, thereby demonstrating the synthetic utility of the developed methodology.

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Morpholines are widespread in many biologically and catalytically active agents, thus being an important aim of pharmaceutical and synthetic chemists. However, efficient strategies for the catalytic asymmetric synthesis of chiral morpholines bearing crowded stereogenic centers still remain elusive. Herein, we disclose a Cu-catalyzed asymmetric propargylic amination/desymmetrization strategy to help resolve this challenge. As a result, two kinds of structurally various chiral morpholines bearing rich functional groups and N-α-quaternary stereocenters were produced with high efficiency and selectivity (42 examples, up to 91 % yield, 97:3 er and > 19:1 dr). In addition, a series of transformations were performed to demonstrate the synthetic utility of this methodology. In particular, a hit compound for new antitumor drugs was identified through cellular evaluation. Furthermore, mechanistic investigations reveal that, hydrogen bonding in the key copper-allenylidene intermediate together with π-π stacking aids remote enantioinduction.

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Radical-involved arylative cross-coupling reactions have recently emerged as an attractive strategy to access valuable aryl-substituted motifs. However, there still exist several challenges such as limited scope of radical precursors/acceptors, and lack of general asymmetric catalytic systems, especially regarding the multicomponent variants. Herein, we reported a general copper-Box system for asymmetric three-component arylative radical cross-coupling of vinylarenes and 1,3-enynes, with oxime carbonates and aryl boronic acids. The reactions proceed under practical conditions in the absence or presence of visible-light irradiation, affording chiral 1,1-diarylalkanes, benzylic alkynes and allenes with good enantioselectivities. Mechanistic studies imply that the copper/Box complexes play a dual role in both radical generation and ensuing asymmetric cross-coupling. In the cases of 1,3-enynes, visible-light irradiation could improve the activity of copper/Box complex toward the initial radical generation, enabling better efficiency match between radical formation and cross-coupling.

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This study demonstrated the effects of adding specific proportions of vermiculite (VMT: 0%, 10%, and 20%) and earthworm casts (EWCs: 0%, 10%, and 20%) on the physico-chemical properties of composted green waste (CGW), and the impacts of amended CGW as growth media on the growth of three common ornamental plants (Dahlia pinnata Cav. [dahlia], Centaurea cyanus L. [cornflower], and Consolida ajacis [L.] Schur [delphinium]). Compared with Treatment T1 (CK), the addition of 10% VMT and 20% EWCs greatly (p < 0.05) increased the total porosity, aeration porosity, water-holding porosity, total nitrogen, available phosphorus, available potassium, and organic matter of CGW by 9%, 35%, 4%, 18%, 27%, 13%, and 33%, respectively. In addition, this pattern increased (p < 0.05) the total fresh biomass, total chlorophyll content, and root length of dahlias by 9%, 19%, and 27%, respectively; those of cornflowers by 17%, 30%, and 29%, respectively (p < 0.05); and those of delphiniums by 23%, 14%, and 63%, respectively. Therefore, the amended CGW supplemented with 10% VMT and 20% EWCs was an ideal growth medium for the three plants.

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Herein, we designed a reaction for the desymmetrization-addition of cyclopropenes to imines by leveraging the synergy between photoredox and asymmetric cobalt catalysis. This protocol facilitated the synthesis of a series of chiral functionalized cyclopropanes with high yield, enantioselectivity, and diastereoselectivity (44 examples, up to 93% yield and >99% ee). A possible reaction mechanism involving cyclopropene desymmetrization by Co-H species and imine addition by Co-alkyl species was proposed. This study provides a novel route to important chiral cyclopropanes and extends the frontier of asymmetric metallaphotoredox catalysis.

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The C(sp3)-N bond is ubiquitous in natural products, pharmaceuticals, biologically active molecules and functional materials. Consequently, the development of practical and efficient methods for C(sp3)-N bond formation has attracted more and more attention. Compared to the conventional ionic pathway-based thermal methods, photochemical processes that proceed through radical mechanisms by merging photoredox and transition-metal catalyses have emerged as powerful and alternative tools for C(sp3)-N bond formation. In this review, recent advances in the burgeoning field of C(sp3)-N bond formation via metallaphotoredox catalysis have been highlighted. The contents of this review are categorized according to the transition metals used (copper, nickel, cobalt, palladium, and iron) together with photocatalysis. Emphasis is placed on methodology achievements and mechanistic insight, aiming to inspire chemists to invent more efficient radical-involved C(sp3)-N bond-forming reactions.

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Radical-involved multicomponent difunctionalization of 1,3-dienes has recently emerged as a promising strategy for rapid synthesis of valuable allylic compounds in one-pot operation. However, the expansion of radical scope and enantiocontrol remain two major challenges. Herein, we describe an unprecedented photoinduced copper-catalyzed highly enantioselective three-component radical 1,2-azidooxygenation of 1,3-dienes with readily available azidobenziodazolone reagent and carboxylic acids. This mild protocol exhibits a broad substrate scope, high functional group tolerance, and exceptional control over chemo-, regio- and enantioselectivity, providing practical access to diverse valuable azidated chiral allylic esters. Mechanistic studies imply that the chiral copper complex is implicated as a bifunctional catalyst in both the photoredox catalyzed azidyl radical generation and enantioselective radical C-O cross-coupling.

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Loss-of-function mutations in the Breast Cancer Susceptibility Gene (BRCA1 and BRCA2) are often detected in patients with breast cancer. Poly(ADP-ribose) polymerase-1 (PARP1) plays a key role in the repair of DNA strand breaks, and PARP inhibitors have been shown to induce highly selective killing of BRCA1/2-deficient tumor cells, a mechanism termed synthetic lethality. In our previous study, a novel PARP1 inhibitor─(E)-2-(2,3-dibromo-4,5-dimethoxybenzylidene)-N-(4-fluorophenyl) hydrazine-1-carbothioamide (4F-DDC)─was synthesized, which significantly inhibited PARP1 activity with an IC50 value of 82 ± 9 nM. The current study aimed to explore the mechanism(s) underlying the antitumor activity of 4F-DDC under in vivo and in vitro conditions. 4F-DDC was found to selectively inhibit the proliferation of BRCA mutant cells, with highly potent effects on HCC-1937 (BRCA1-/-) cells. Furthermore, 4F-DDC was found to induce apoptosis and G2/M cell cycle arrest in HCC-1937 cells. Interestingly, immunofluorescence and Western blot results showed that 4F-DDC induced DNA double strand breaks and further activated the cGAS-STING pathway in HCC-1937 cells. In vivo analysis results revealed that 4F-DDC inhibited the growth of HCC-1937-derived tumor xenografts, possibly via the induction of DNA damage and activation of the cGAS-STING pathway. In summary, the current study provides a new perspective on the antitumor mechanism of PARP inhibitors and showcases the therapeutic potential of 4F-DDC in the treatment of breast cancer.

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Camptothecin (CPT) is a potent anti-cancer agent targeting topoisomerase I (TOP1). However, CPT has poor pharmacokinetic properties, causes toxicities, and leads to drug resistance, which limit its clinical use. In this paper, to review the current state of CPT research. We first briefly explain CPT's TOP1 inhibition mechanism and the key hurdles in CPT drug development. Then we examine strategies to overcome CPT's limitations through structural modifications and advanced delivery systems. Though modifications alone seem insufficient to fully enhance CPT's therapeutic potential, structure-activity relationship analysis provides insights to guide optimization of CPT analogs. In comparison, advanced delivery systems integrating controlled release, imaging capabilities, and combination therapies via stimulus-responsive linkers and targeting moieties show great promise for improving CPT's pharmacological profile. Looking forward, multifaceted approaches combining selective CPT derivatives with advanced delivery systems, informed by emerging biological insights, hold promise for fully unleashing CPT's anti-cancer potential.

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Organic molecules bearing chiral sulfur stereocenters exert a great impact on asymmetric catalysis and synthesis, chiral drugs, and chiral materials. Compared with acyclic ones, the catalytic asymmetric synthesis of thio-heterocycles has largely lagged behind due to the lack of efficient synthetic strategies. Here we establish the first modular platform to access chiral thio-oxazolidinones via Pd-catalyzed asymmetric [3+2] annulations of vinylethylene carbonates with sulfinylanilines. This protocol is featured by readily available starting materials, and high enantio- and diastereoselectivity. In particular, an unusual effect of a non-chiral supporting ligand on the diastereoselectivity was observed. Possible reaction mechanisms and stereocontrol models were proposed.

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Alkene radical ions constitute an integral and unique class of reactive intermediates for the synthesis of valuable compounds because they have both unpaired spins and charge. However, relatively few synthetic applications of alkene radical anions have emerged due to a dearth of generally applicable and mild radical anion generation approaches. Precise control over the chemo- and stereoselectivity in alkene radical anion-mediated processes represents another long-standing challenge due to their high reactivity. To overcome these issues, here, we develop a new redox-neutral strategy that seamlessly merges photoredox and copper catalysis to enable the controlled generation of alkene radical anions and their orthogonal enantioselective cyanofunctionalization via distonic-like species. This new strategy enables highly regio-, chemo-, and enantioselective hydrocyanation, deuterocyanation, and cyanocarboxylation of alkenes without stoichiometric reductants or oxidants under visible light irradiation. This protocol provides a new blueprint for the exploration of the transformation potential of alkene radical anions.

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Radiotherapy (RT) has been a classical therapeutic method of cancer for several decades. It attracts tremendous attention for the precise and efficient treatment of local tumors with stimuli-responsive nanomaterials, which enhance RT. However, there are few systematic reviews summarizing the newly emerging stimuli-responsive mechanisms and strategies used for tumor radio-sensitization. Hence, this review provides a comprehensive overview of recently reported studies on stimuli-responsive nanomaterials for radio-sensitization. It includes four different approaches for sensitized RT, namely endogenous response, exogenous response, dual stimuli-response, and multi stimuli-response. Endogenous response involves various stimuli such as pH, hypoxia, GSH, and reactive oxygen species (ROS), and enzymes. On the other hand, exogenous response encompasses X-ray, light, and ultrasound. Dual stimuli-response combines pH/enzyme, pH/ultrasound, and ROS/light. Lastly, multi stimuli-response involves the combination of pH/ROS/GSH and X-ray/ROS/GSH. By elaborating on these responsive mechanisms and applying them to clinical RT diagnosis and treatment, these methods can enhance radiosensitive efficiency and minimize damage to surrounding normal tissues. Finally, this review discusses the additional challenges and perspectives related to stimuli-responsive nanomaterials for tumor radio-sensitization.

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The construction of an all-in-one catalyst, in which the photosensitizer and the transition metal site are close to each other, is important for improving the efficiency of metallaphotoredox catalysis. However, the development of convenient synthetic strategies for the precise construction of an all-in-one catalyst remains a challenging task due to the requirement of precise installation of the catalytic sites. Herein, we have successfully established a facile bottom-up strategy for the direct synthesis of Ni(II)-incorporated covalent organic framework (COF), named LZU-713@Ni, as a versatile all-in-one metallaphotoredox catalyst. LZU-713@Ni showed excellent activity and recyclability in the photoredox/nickel-catalyzed C-O, C-S, and C-P cross-coupling reactions. Notably, this catalyst displayed a better catalytic activity than its homogeneous analogues, physically mixed dual catalyst system, and, especially, LZU-713/Ni which was prepared through post-synthetic modification. The improved catalytic efficiency of LZU-713@Ni should be attributed to the implementation of bottom-up strategy, which incorporated the fixed, ordered, and abundant catalytic sites into its framework. This work sheds new light on the exploration of concise and effective strategies for the construction of multifunctional COF-based photocatalysts.

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Vinyldiazo compounds are one of the most important synthons in the construction of a cyclic ring. Most photochemical transformations of vinyldiazo compounds are mainly focusing on utilization of their C═C bond site, while reactions taking place at terminal nitrogen atom are largely unexplored. Herein, a photocatalytic cascade radical cyclization of LBRs with vinyldiazo reagents through sequential B─N/C─N bond formation is described. The reaction starts with the addition of LBRs (Lewis base-boryl radicals) at diazo site, followed by intramolecular radical cyclization to access a wide range of important boron-handled pyrazoles in good to excellent yields. Control experiments, together with detailed mechanism studies well explain the observed reactivity. Further studies demonstrate the utility of this approach for applications in pharmaceutical and agrochemical research.

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BACKGROUND: Donor-recipient size mismatch (DRSM) is considered a crucial factor for poor outcomes in liver transplantation (LT) because of complications, such as massive intraoperative blood loss (IBL) and early allograft dysfunction (EAD). Liver volumetry is performed routinely in living donor LT, but rarely in deceased donor LT (DDLT), which amplifies the adverse effects of DRSM in DDLT. Due to the various shortcomings of traditional manual liver volumetry and formula methods, a feasible model based on intelligent/interactive qualitative and quantitative analysis-three-dimensional (IQQA-3D) for estimating the degree of DRSM is needed. AIM: To identify benefits of IQQA-3D liver volumetry in DDLT and establish an estimation model to guide perioperative management. METHODS: We retrospectively determined the accuracy of IQQA-3D liver volumetry for standard total liver volume (TLV) (sTLV) and established an estimation TLV (eTLV) index (eTLVi) model. Receiver operating characteristic (ROC) curves were drawn to detect the optimal cut-off values for predicting massive IBL and EAD in DDLT using donor sTLV to recipient sTLV (called sTLVi). The factors influencing the occurrence of massive IBL and EAD were explored through logistic regression analysis. Finally, the eTLVi model was compared with the sTLVi model through the ROC curve for verification. RESULTS: A total of 133 patients were included in the analysis. The Changzheng formula was accurate for calculating donor sTLV (P = 0.083) but not for recipient sTLV (P = 0.036). Recipient eTLV calculated using IQQA-3D highly matched with recipient sTLV (P = 0.221). Alcoholic liver disease, gastrointestinal bleeding, and sTLVi > 1.24 were independent risk factors for massive IBL, and drug-induced liver failure was an independent protective factor for massive IBL. Male donor-female recipient combination, model for end-stage liver disease score, sTLVi ≤ 0.85, and sTLVi ≥ 1.32 were independent risk factors for EAD, and viral hepatitis was an independent protective factor for EAD. The overall survival of patients in the 0.85 < sTLVi < 1.32 group was better compared to the sTLVi ≤ 0.85 group and sTLVi ≥ 1.32 group (P < 0.001). There was no statistically significant difference in the area under the curve of the sTLVi model and IQQA-3D eTLVi model in the detection of massive IBL and EAD (all P > 0.05). CONCLUSION: IQQA-3D eTLVi model has high accuracy in predicting massive IBL and EAD in DDLT. We should follow the guidance of the IQQA-3D eTLVi model in perioperative management.

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The exploration of value-added conversions of naturally abundant amino acids has received considerable attention from the synthetic community. Compared with the well-established asymmetric decarboxylative transformation, the asymmetric deaminative transformation of amino acids still remains a formidable challenge, mainly due to the lack of effective strategies for the C-N bond activation and the potential incompatibility with chiral catalysts. Here, we disclose a photoinduced Cu-catalyzed asymmetric deaminative coupling reaction of amino acids with arylboronic acids. This new protocol provides a series of significant chiral phenylacetamides in generally good yields and excellent stereoselectivity under mild and green conditions (42-85 % yields, up to 97 % ee). Experimental investigations and theoretical calculations were performed to reveal the crucial role of additional phenols in improving catalytic efficiency and enantiocontrol.