Optomechanical dissipative solitons.

Nonlinear wave-matter interactions may give rise to solitons, phenomena that feature inherent stability in wave propagation and unusual spectral characteristics. Solitons have been created in a variety of physical systems and have had important roles in a broad range of applications, including communications, spectroscopy and metrology1-4. In recent years, the realization of dissipative Kerr optical solitons in microcavities has led to the generation of frequency combs in a chip-scale platform5-10. Within a cavity, photons can interact with mechanical modes. Cavity optomechanics has found applications for frequency conversion, such as microwave-to-optical or radio-frequency-to-optical11-13, of interest for communications and interfacing quantum systems operating at different frequencies. Here we report the observation of mechanical micro-solitons excited by optical fields in an optomechanical microresonator, expanding soliton generation in optical resonators to a different spectral window. The optical field circulating along the circumference of a whispering gallery mode resonator triggers a mechanical nonlinearity through optomechanical coupling, which in turn induces a time-varying periodic modulation on the propagating mechanical mode, leading to a tailored modal dispersion. Stable localized mechanical wave packets-mechanical solitons-can be realized when the mechanical loss is compensated by phonon gain and the optomechanical nonlinearity is balanced by the tailored modal dispersion. The realization of mechanical micro-solitons driven by light opens up new avenues for optomechanical technologies14 and may find applications in acoustic sensing, information processing, energy storage, communications and surface acoustic wave technology.

Tumor necrosis factor-like cytokine 1A plays a role in inflammatory bowel disease pathogenesis.

The binding of tumor necrosis factor-like cytokine 1A (TL1A) to death receptor 3 (DR3) plays an important role in the interaction between dendritic cells (DCs) and T cells and contributes to intestinal inflammation development. However, the mechanism by which DCs expressing TL1A mediate helper T (Th) cell differentiation in the intestinal lamina propria (LP) during the pathogenesis of inflammatory bowel disease remains unclear. In this study, we found that TL1A/DR3 promoted Th1 and Th17 cell differentiation in T-T and DC-T cell interaction-dependent manners. TL1A-deficient CD4+ T cells failed to polarize into Th1/Th17 cells and did not cause colonic inflammation in a T cell transfer colitis model. Notably, TL1A was located in the cytoplasm and nuclei of DCs, positively regulated the DC-specific ICAM-grabbing nonintegrin/RAF1/nuclear factor κB signaling pathway, enhanced the antigen uptake ability of DCs, and promoted TLR4-mediated DC activation, inducing naive CD4+ T cell differentiation into Th1 and Th17 cells. Our work reveals that TL1A plays a regulatory role in inflammatory bowel disease pathogenesis.

Photouranium-Catalyzed C-F Activation Hydroxylation via Water Splitting.

The C-F bond is the strongest covalent single bond (126 kcal/mol) in carbon-centered bonds, in which the highest electronegativity of fluorine (χ = 4) gives rise to the shortest bond length (1.38 Å) and the smallest van der Waals radius (rw = 1.47 Å), resulting in enormous challenges for activation and transformation. Herein, C-F conversion was realized via photouranium-catalyzed hydroxylation of unactivated aryl fluorides using water as a hydroxyl source to deliver multifunctional phenols under ambient conditions. The activation featured cascade sequences of single electron transfer (SET)/hydrogen atom transfer (HAT)/oxygen atom transfer (OAT), highly integrated from the excited uranyl cation. The *UO22+ prompted water splitting under mild photoexcitation, caging the active oxygen in a peroxo-bridged manner for the critical OAT process and releasing hydrogen via the HAT process.

Stabilizing Axin leads to optic nerve hypoplasia in a mouse model of autism.

Autism spectrum disorder (ASD) is a group of neurodevelopment disorders characterized by deficits in social interaction and communication, and repetitive or stereotyped behavior. Autistic children are more likely to have vision problems, and ASD is unusually common among blind people. However, the mechanisms behind the vision disorders in autism are unclear. Stabilizing WNT-targeted scaffold protein Axin2 by XAV939 during embryonic development causes overproduction of cortical neurons and leads to autistic-like behaviors in mice. In this study, we investigated the relationship between vision abnormality and autism using an XAV939-induced mouse model of autism. We found that the mice receiving XAV939 had decreased amplitude of bright light-adaptive ERG. The amplitudes and latency of flash visual evoked potential recorded from XAV939-treated mice were lower and longer, respectively than in the control mice, suggesting that XAV939 inhibits visual signal processing and conductance. Anatomically, the diameters of RGC axons were reduced when Axin2 was stabilized during the development, and the optic fibers had defective myelin sheaths and reduced oligodendrocytes. The results suggest that the WNT signaling pathway is crucial for optic nerve development. This study provides experimental evidence that conditions interfering with brain development may also lead to visual problems, which in turn might exaggerate the autistic features in humans.

Zwitterion-Modified MXene Quantum Dot as a Nanocarrier for Traditional Chinese Medicine Sanguinarine Delivery and Its Application for Photothermal-Chemotherapy Synergistic Antibacterial and Wound Healing.

The nanomaterialization of traditional Chinese medicine (TCM) has aroused widespread interest among researchers. Sanguinarine (SAN) is a kind of TCM with good antibacterial properties, which has important applications in anti-infection of wounds. Additionally, the combination of photothermal therapy and chemotherapy can overcome bacterial resistance, further improving bactericidal and wound healing efficiency. In this paper, we prepared an antibacterial agent by loading SAN on the zwitterion-modified MXene quantum dot nanocarrier (SAN@AHEP@Ta4C3), realizing pH/NIR controlled drug release and photothermal/chemotherapy synergistic antibacterial and wound healing. The particle size of SAN@AHEP@Ta4C3 is about 120 nm, and it has a good water solubility and stability. In addition, it also has excellent photothermal conversion performance (η = 39.2%), which can effectively convert light energy into heat energy under near-infrared (NIR) laser irradiation, further promoting drug release and achieving bactericidal effects by synergistic chemotherapy and photothermal therapy. The in vitro and in vivo experiments show that SAN@AHEP@Ta4C3 exhibits an excellent antibacterial effect against Staphylococcus aureus and Escherichia coli, and it can effectively promote the wound healing of mice. Moreover, the SAN@AHEP@Ta4C3 also has good biocompatibility and has no side effects on normal tissue and organs. This work introduces a multifunctional antibacterial agent based on TCM and hot-spot material MXene, which will have considerable application prospects in biomedical fields.

Induced transparency by interference or polarization.

Polarization of optical fields is a crucial degree of freedom in the all-optical analogue of electromagnetically induced transparency (EIT). However, the physical origins of EIT and polarization-induced phenomena have not been well distinguished, which can lead to confusion in associated applications such as slow light and optical/quantum storage. Here we study the polarization effects in various optical EIT systems. We find that a polarization mismatch between whispering gallery modes in two indirectly coupled resonators can induce a narrow transparency window in the transmission spectrum resembling the EIT lineshape. However, such polarization-induced transparency (PIT) is distinct from EIT: It originates from strong polarization rotation effects and shows a unidirectional feature. The coexistence of PIT and EIT provides additional routes for the manipulation of light flow in optical resonator systems.

Bilateral Unsymmetrical Disulfurating Reagent Design for Polysulfide Construction.

Polysulfides are significant compounds in life science, pharmaceutical science, and material science. Therefore, polysulfide construction is in great demand. The controllable sequential installation on both ends of S-S motif faces an enormous challenge, due to the reversible covalent S-S bond. A library was established with two divergent mask groups for bilateral unsymmetrical disulfurating reagents (R1O-SS-SO2R2). Sequential coupling was successfully achieved with preferential activation of S-SO2 bond (37.6 kcal/mol) and controllable activation of S-O bond (54.8 kcal/mol) superior to S-S bond (62.0 kcal/mol), enabled untrammeled installation on the bilateral sides of S-S motif to afford unsymmetrical disulfides and trisulfides, even for natural products, pharmaceuticals, peptides, and protein (bovine serum albumin) cross-linkage successively.

Linkage Chemistry of S(VI) Fluorides.

Sulfur(VI)-fluoride exchange linkage as a next generation of click chemistry was introduced by Sharpless and coworkers in 2014. Distinguished from CuAAC, the SuFEx reaction proceeds under metal-free conditions, and the reactive linkers are variable, enabling access to a diverse class of linkage compounds. Therein, a series of SuFEx linkers emerged has been widely prevalent in diverse fields. The SVI -F bond in comparison to SVI -Cl bond features excellent stability and chemoselectivity. The linkage chemistry primarily involves the formation of S-O and S-N bonds via commercially available phenols and amines, yet less study on C-SuFEx linkage. This review will focus on three types of linkage for SuFEx linkers comprising S-O, S-N, and S-C bonds, and we hope to provide a practical guidance for SuFEx linkage chemistry.

α-Fe2O3@Au-PEG-Ce6-Gd Nanoparticles as Acidic H2O2-Driven Oxygenators for Multimodal Imaging and Synergistic Tumor Therapy.

Nanoparticles with visual imaging capabilities and synergistic therapeutics have a bright future in antitumor applications. However, most of the current nanomaterials lack multiple imaging-guided therapeutic capabilities. In this study, a novel enhanced photothermal photodynamic antitumor nanoplatform with photothermal imaging, fluorescence (FL) imaging, and MRI-guided therapeutic capabilities was constructed by grafting gold, dihydroporphyrin Ce6, and Gd onto α-iron trioxide. This antitumor nanoplatform can convert NIR light into local hyperthermia at a temperature of up to 53 °C under NIR light irradiation, while Ce6 can generate singlet oxygen, which further synergizes the tumor-killing effect. At the same time, α-Fe2O3@Au-PEG-Ce6-Gd can also have significant photothermal imaging effect under light irradiation, which can guide to see the temperature change near the tumor tissue. It is worth noting that α-Fe2O3@Au-PEG-Ce6-Gd can have obvious MRI and FL imaging effects after tail vein injection in mice with blood circulation, realizing imaging-guided synergistic antitumor therapy. α-Fe2O3@Au-PEG-Ce6-Gd NPs provide a new solution for tumor imaging and treatment.

Identification of Crotonylation Metabolism Signature Predicting Overall Survival for Clear Cell Renal Cell Carcinoma.

Background: Immunotherapy shows promise in treating cancer by leveraging the immune system to combat cancer cells. However, the influence of crotonylation metabolism on the prognosis and tumor environment in ccRCC patients is not fully understood. Methods: We conducted various systematic analyses, including prognosis and cluster analyses, to investigate the role of KAT2A in immunotherapy. We used qRT-PCR to compare KAT2A expression in cancer and adjacent tissues and among different cell lines. Additionally, we employed Cell Counting Kit-8, wound healing, and Transwell chamber assays to assess changes in the proliferative and metastatic ability of A498 and 786-O cells. Results: We identified three clusters related to crotonylation metabolism, each with distinct prognosis and immune characteristics in ccRCC. We categorized CT1 as immune-inflamed, CT2 as immune-excluded, and CR3 as immune-desert. A new system, CRS, emerged as an effective predictor of patient outcomes with differing immune characteristics. Moreover, qRT-PCR revealed elevated KAT2A levels in ccRCC tissues and cell lines. KAT2A was found to promote ccRCC and correlate significantly with immunosuppressive elements and checkpoints. Reducing KAT2A expression hindered ccRCC cell growth and metastasis. Conclusion: Our study highlights the critical role of crotonylation metabolism in cancer development and progression, particularly its link to poor prognosis. CRS proves to be an accurate predictor of patient outcomes and immune features in ccRCC. KAT2A shows strong associations with clinical factors and the immunosuppressive environment, suggesting potential for innovative immunotherapies in ccRCC treatment.

Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in recurrent vulvovaginal candidiasis.

AIM: Recurrent vulvovaginal candidiasis (RVVC) is a chronic, difficult to treat vaginal infection, caused by Candida species, which affects women of all ages and ethnic and social background. Most RVVC studies use animal models, and there is still a lack of observation on human tissue samples and effective therapy to reduce recurrence. MATERIALS AND METHODS: We observed CD163+ macrophages and NLRP3 expression by immunohistochemistry, also investigated bacteria and fungi co-invasion by fluorescence in situ hybridization from 144 human vaginal biopsy tissues (48 RVVC, 48 VVC, 48 healthy volunteers), and we also explored the effect of combining metronidazole in the treatment of RVVC. RESULTS: A large number of neutrophils, lymphocytes and plasma cells infiltrated the mucosa, basement membrane and submucosa, accompanied by significantly overexpressed NLRP3 inflammasome. While CD163+ macrophages often infiltrated under the basement membrane in patients with RVVC, 29.2% of cases were found Gardnerella and fungi jointly invaded the vaginal mucosas. RVVC vaginal mucosal histopathology revealed mucosal inflammatory responses dominated by neutrophils, which may involve activation of NLRP3 and immune tolerance of M2 macrophages (CD163+ ). Fluconazole combined with metronidazole can achieve higher efficiency (95.8% vs. 70.8%) and reduce the recurrence rate more (8.3% vs. 37.5%) at 6-month follow-up. CONCLUSION: Inflammatory invasion on human vaginal mucosa correlated with combined drug treatment and recurrence in RVVC. The combined medication will need to further evaluate in future.

Ni-catalyzed C-S bond construction and cleavage.

Sulfur-containing compounds have attracted considerable interest due to their wide-ranging applications in pharmaceuticals, agriculture, natural products, and organic materials. The development of efficient and rapid methods for the construction and transformation of sulfur-containing compounds is of great importance. Since nickel is inexpensive and has a variety of valence states, strong nucleophilicity and low energy barriers for oxidative addition, the construction and transformation of sulfur-containing compounds by nickel-catalyzed cross-coupling have become important strategies. In addition, sulfur-containing compounds have also been playing increasingly important roles in the field of cross-coupling due to their thermodynamically stable but dynamic activity. This review will focus on nickel-catalyzed construction and transformation of various sulfide-containing compounds, such as sulfides, disulfides, and hypervalent sulfur-containing compounds.

Advances in emission control of diesel vehicles in China.

Diesel vehicles have caused serious environmental problems in China. Hence, the Chinese government has launched serious actions against air pollution and imposed more stringent regulations on diesel vehicle emissions in the latest China VI standard. To fulfill this stringent legislation, two major technical routes, including the exhaust gas recirculation (EGR) and high-efficiency selective catalytic reduction (SCR) routes, have been developed for diesel engines. Moreover, complicated aftertreatment technologies have also been developed, including use of a diesel oxidation catalyst (DOC) for controlling carbon monoxide (CO) and hydrocarbon (HC) emissions, diesel particulate filter (DPF) for particle mass (PM) emission control, SCR for the control of NOx emission, and an ammonia slip catalyst (ASC) for the control of unreacted NH3. Due to the stringent requirements of the China VI standard, the aftertreatment system needs to be more deeply integrated with the engine system. In the future, aftertreatment technologies will need further upgrades to fulfill the requirements of the near-zero emission target for diesel vehicles.

Disulfide Click Reaction for Stapling of S-terminal Peptides.

A disulfide click strategy is disclosed for stapling to enhance the metabolic stability and cellular permeability of therapeutic peptides. A 17-membered library of stapling reagents with adjustable lengths and angles was established for rapid double/triple click reactions, bridging S-terminal peptides from 3 to 18 amino acid residues to provide 18- to 48-membered macrocyclic peptides under biocompatible conditions. The constrained peptides exhibited enhanced anti-HCT-116 activity with a locked α-helical conformation (IC50 =6.81 µM vs. biological incompetence for acyclic linear peptides), which could be unstapled for rehabilitation of the native peptides under the assistance of tris(2-carboxyethyl)phosphine (TCEP). This protocol assembles linear peptides into cyclic peptides controllably to retain the diverse three-dimensional conformations, enabling their cellular uptake followed by release of the disulfides for peptide delivery.

Construction of Thioamide Peptides from Chiral Amino Acids.

Thioamide peptides were synthesized in a straightforward one-pot process via the linkage of diverse natural amino acids in the presence of thiolphosphonate and trichlorosilane, wherein carbonyl groups were replaced with thiono compounds with minimal racemization. Experimental and computational mechanistic studies demonstrated that the trichlorosilane enables the activation of carboxylic acids via intense interactions with the Si-O bond, followed by coupling of the carboxylic acids with thiolphosphonate to obtain the key intermediate S-acyl dithiophosphate. Silyl-activated quadrangular metathesis transition states afforded the thioamide peptides. The potential applications of these thioamide peptides were further highlighted via late-stage linkages of diverse natural products and pharmaceutical drugs and the thioamide moiety.

Human herpesvirus 6A promotes glycolysis in infected T cells by activation of mTOR signaling.

Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus worldwide. However, whether and how HHV-6 infection influences the metabolic machinery of the host cell to provide the energy and biosynthetic resources for virus propagation remains unknown. In this study, we identified that HHV-6A infection promotes glucose metabolism in infected T cells, resulting in elevated glycolytic activity with an increase of glucose uptake, glucose consumption and lactate secretion. Furthermore, we explored the mechanisms involved in HHV-6A-mediated glycolytic activation in the infected T cells. We found increased expressions of the key glucose transporters and glycolytic enzymes in HHV-6A-infected T cells. In addition, HHV-6A infection dramatically activated AKT-mTORC1 signaling in the infected T cells and pharmacological inhibition of mTORC1 blocked HHV-6A-mediated glycolytic activation. We also found that direct inhibition of glycolysis by 2-Deoxy-D-glucose (2-DG) or inhibition of mTORC1 activity in HHV-6A-infected T cells effectively reduced HHV-6 DNA replication, protein synthesis and virion production. These results not only reveal the mechanism of how HHV-6 infection affects host cell metabolism, but also suggest that targeting the metabolic pathway could be a new avenue for HHV-6 therapy.

Environmentally Friendly Zr-Based MOF for Pesticide Delivery: Ultrahigh Loading Capacity, pH-Responsive Release, Improved Leaf Affinity, and Enhanced Antipest Activity.

The stimuli responsive pesticide delivery system (PDS) has drawn increasing attention in recent years, a system which can effectively improve the utilization of pesticides. In the current research, we report a pH responsive PDS by using carboxymethyl cellulose (CMC) modified Zr-based metal organic frameworks (UiO-66-NH2) as the nanocarrier for acetamiprid (ATP). UiO-66-NH2-CMC possesses a large surface area and abundant pores, which can effectively load ATP, and the loading rate is as high as 90.79%. Compared with free ATP, the ATP@UiO-66-NH2-CMC nanopesticide exhibits pH responsive controlled release behavior, and the pesticide can sustained release to the medium. In addition, it also shows improved leaf affinity, which makes it easier to wet the leaf surface and improve the utilization of pesticide. Therefore, ATP@UiO-66-NH2-CMC displays better antipest activity against aphids than free ATP does. Meanwhile, ATP@UiO-66-NH2-CMC shows no negative effects on the germination and growth of maize, showing good biosafety. Moreover, the ATP@UiO-66-NH2-CMC nanopesticide does not contain any toxic organic solvents or additives. Therefore, we hope that it can be a suitable candidate for plant protection and sustainable agriculture.

The Linkage of Sulfonimidoyl Fluorides and Unactivated Alkenes via Hydrosulfonimidoylation.

Sulfur(VI) fluoride cleavage and exchanging linkage, a new generation of linkage chemistry, exhibits enormous potential for combining a range of functional molecules in an increasing number of fields. Herein, we established a metal-free linkage of unactivated alkenes and sulfonimidoyl fluorides via hydrosulfonimidoylation to construct sulfoximines within minutes. An intermolecular hydride transfer process is the key step, and it occurs via overlap of the LUMO in the sulfonimidoyl cation and HOMO in the unactivated alkene, which was confirmed via control experiments with deuterated compounds. DFT calculations further demonstrated the concerted process involving formation of the S-C(sp3 ) bond and hydride transfer. Remarkably, abundant natural products and pharmaceuticals with multiple heteroatoms and sensitive functional groups have been subjected to the current linkage reaction to achieve various sulfoximine linkages, furnishing the basis for drug discovery and drug conjugation.

Rh(I)-Catalyzed Carbene Migration/Carbonylation/Cyclization: Straightforward Construction of Fully Substituted Aryne Precursors.

The Rh(I)-catalyzed cascade formation of carbenoid followed by a carbonylative cyclization of silyl diynes has been established to achieve diverse ortho silyl-substituted phenolics, enabling access to fully substituted aryne precursors via a one-step fluorosulfurylation. The silyl mask on the termini of alkynes is demonstrated not only to suppress the undesired oxidation but also to control the selectivity of CO insertion. Straightforward access to fully substituted arynes was comprehensively established and applied for the efficient construction of polycyclic aromatic molecules.