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A series of magnesium benzylalkoxide complexes, [L nMg(μ-OBn)]2 ( 1- 14) supported by NNO-tridentate pyrazolonate ligands with various electron withdrawing-donating subsituents have been synthesized and characterized. X-ray crystal structural studies revealed that Complexes 1- 3, 5, 7, 9, and 10 are dinuclear bridging through benzylalkoxy oxygen atoms with penta-coordinated metal centers. All of these complexes acted as efficient initiators for the ring-opening polymerization of L-lactide and rac-lactide. Based on kinetic studies, the activity of these metal complexes is significantly influenced by the electronic effect of the ancillary ligands with the electron-donating substituents at the phenyl rings enhancing the polymerization rate. In addition, the 'living' and 'immortal' character of 6 has paved a way to synthesize as much as 40-fold polymer chains of polylactides with a very narrow polydispersity index in the presence of a small amount of initiator. Among all of magnesium complexes, Complex 6 exhibits the highest stereoselectivity toward ring-opening polymerization of rac-lactide with Pr up to 88% in THF at 0 °C. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013 [ABSTRACT FROM AUTHOR]

Background: HAb18G/CD147 plays pivotal roles in invasion by hepatoma cells, but the underlying mechanism remains unclear. Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin alpha3beta1. However, it has never been investigated whether alpha3beta1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells.Methods: Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin alpha6beta1 were determined by immunofluorescent double-staining and confocal imaging analysis. Co-immunoprecipitation and Western blot analyses were performed to examine the native conformations of HAb18G/CD147 and integrin alpha6beta1. Invasion potential was evaluated with an invasion assay and gelatin zymography.Results: We found that integrin alpha6beta1 co-localizes and interacts with HAb18G/CD147 in human hepatoma cells. The enhancing effects of HAb18G/CD147 on invasion capacity and secretion of matrix metalloproteinases (MMPs) were partially blocked by integrin alpha6beta1 antibodies (P < 0.01). Wortmannin, a specific phosphatidylinositol kinase (PI3K) inhibitor that reverses the effect of HAb18G/CD147 on the regulation of intracellular Ca2+ mobilization, significantly reduced cell invasion potential and secretion of MMPs in human hepatoma cells (P < 0.05). Importantly, no additive effect between Wortmannin and alpha6beta1 antibodies was observed, indicating that alpha6beta1 and PI3K transmit the signal in an upstream-downstream relationship.Conclusion: These results suggest that alpha6beta1 interacts with HAb18G/CD147 to mediate tumor invasion and metastatic processes through the PI3K pathway. [ABSTRACT FROM AUTHOR]

Hetero-metal doping or substitution to create alloy clusters is a highly appealing strategy for improving physicochemical characteristics as well as tailoring optical and electronic properties, although high-yield synthesis of alloy clusters with precise positioning of doped metals is a daunting challenge. Herein, we manifest rational synthesis of chiral alloy cluster enantiomers R/S-Ag 6 Cu in 85 %-87 % yield by replacing one Ag(I) atom with Cu(I) in homometallic clusters R/S-Ag 7 , achieving circularly polarized luminescence (CPL) with a quantum yield beyond 90 %. As a small energy gap (ca. 0.07 eV) between S 1 and T 1 states facilitates thermally activated delay fluorescence (TADF) through reverse intersystem crossing (RISC), the photoluminescence (PL) of R/S-Ag 7 and R/S-Ag 6 Cu at ambient temperature originates mostly from TADF (85 % and 86 %) in place of phosphorescence (15 % and 14 %). Relative to those of R/S-Ag 7 , copper(I) doping not only triples PL quantum yields of R/S-Ag 6 Cu due to accelerating ISC (intersystem crossing) and RISC, but also doubles CPL asymmetry factors of R/S-Ag 6 Cu ascribed to rigidizing cluster structure through stronger Ag-Cu interaction apart from dramatically improving thermodynamic stability. Solution-processable circularly polarized organic light-emitting diodes (CP-OLEDs) demonstrate high-efficiency circularly polarized electroluminescence (CPEL) with external quantum efficiency (EQE) of 26.7 %, which is superior to most of red-emitting OLEDs through solution process., (© 2024 Wiley-VCH GmbH.)

As versatile ligands with extraordinary coordination capabilities, RPH 2 (R = alkyl or aryl) are rarely used in constructing metal nanoclusters due to their volatility, toxicity, spontaneous flammability, and susceptibility to oxidation. In this work, we designed a primary and tertiary phosphorus-bound diphosphine chelator (2-Ph 2 PC 6 H 4 PH 2 ) to create ultrastable silver nanoclusters with metallic aromaticity. By controlling the deprotonation rate of 2-Ph 2 PC 6 H 4 PH 2 and adjusting the templates, we successfully synthesized two near-infrared emissive nanoclusters, Ag30 and Ag32 , which have analogous icosidodecahedral Ag 30 shells with an I h symmetry. Deprotonated ligand (2-Ph 2 P α C 6 H 4 P β 2- ) exhibits a coordination mode of μ 5 -η 1 (P β ),η 2 (P α ,P β ), which endows a unique metallic aromaticity to Ag30 and Ag32 . The solution-processed organic light-emitting diodes based on Ag30 achieve an external quantum efficiency of 15.1%, representing the breakthrough in application of silver nanoclusters to near-infrared-emitting devices. This work represents a special ligand system for synthesizing ligand-protected coinage metal nanoclusters and opens up horizons of creating nanoclusters with distinct geometries and metal aromaticity.

Knots containing metal atoms as part of their continuous strand backbone are termed as metallaknots. While several metallaknots have been synthesized through one-pot self-assembly, the designed synthesis of metallaknots by controlling the arrangement of entanglements and strands connectivity remains unexplored. Here, we report the synthesis of metallaknots composed with Au(I)-bis(acetylide) linkages and templated by Cu(I) ions. Varying the ratio of the building blocks results in the switchable formation of two trefoil knots with different stoichiometries and symmetries ( C 2 or D 3 ) and an entangled metalla-complex. While the entangled complex formed serendipitously, the strand ends can be subsequently linked through coordinative closure to generate a 4 1 metallaknot in a highly designable fashion. The comparable structural characteristics of resulting metalla-complexes allow us to probe the correlations between their topologies and photophysical properties, showing the backbone rigidity of knots endows complexes with excellent phosphorescent properties. This strategy, in conjunction with the coordinative closure approach, provides a straightforward route for the formation of highly phosphorescent metallaknots that were previously challenging to access., Competing Interests: Competing interests statement:The authors declare no competing interest.

Currently reported circularly polarized luminescent devices are primarily based on rare earth and noble metal complexes or lead perovskite materials. Reports on electroluminescent devices employing eco-friendly luminescent materials are notably scarce. In this study, we strategically designed and synthesized manganese complexes featuring Binapo as the chiral ligand. The complex structure reveals a tetrahedral coordination configuration, with the R / S configurations exhibiting a mirror relationship. Leveraging the strong ligand field and chiral structural characteristics of Binapo, the enantiomers display red emission and exhibit significant circularly polarized luminescence with a circularly polarized luminescence asymmetric factor ( g lum ) of 5.1 × 10 -3 . The circularly polarized electroluminescent performance was investigated by using a solution processing method and host-guest doping strategy. Our efforts resulted in device performance with an external quantum efficiency (EQE) exceeding 4%, and its electroluminescent asymmetric factor ( g EL ) reached an impressive -8.5 × 10 -3 . This surpasses the performance of most devices relying on platinum (Pt) and iridium (Ir) metal complexes and perovskite related materials. Our work establishes a pathway for the development of cost-effective and environmentally friendly chiral electroluminescent materials and devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Conventional fluorescent materials frequently exhibit narrow-band emissions with a small full width at half-maximum (fwhm) due to localized-state characteristics, but electroluminescence is less efficient owing to the utilization of only singlet excitons. In this work, taking advantage of naphthalimide (NAI)-acetylide derivatives with a rigid planar structure and localized transition characteristics, we elaborately designed two mononuclear Pt(II) complexes with weak double emissions of fluorescence and phosphorescence. Taking them as synthetic precursors, we prepared three PtAu 2 heteronuclear clusters and successfully attained highly efficient narrow-band red phosphorescence with the fwhm below 30 nm. Both theoretical and experimental results suggest that the phosphorescence of PtAu 2 clusters mainly originates from the naphthalimide-localized 3 IL (intraligand) triplet state. Solution-processed organic light-emitting diodes (OLEDs) achieved highly efficient narrow-band red electroluminescence with an external quantum efficiency (EQE) of 16.7%. The CIE coordinates of the electroluminescence (0.69, 0.31) closely match the standard red emission for ultrahigh-definition display.

Chiral 3D perovskites pose challenges compared to lower-dimensional variants due to limited chiral organic cation options. Here, we present a universal and controlled method for synthesizing chiral 3D lead halide perovskites using organic amines or alcohols as chiral templates. Introducing these templates to PbCl 2 in N , N -dimethylformamide (DMF) under acidic conditions induces the crystallization of R/S [DMA]PbCl 3 (DMA = dimethylamine). The resulting structure aligns with the templates used, stemming from the helical Pb 2 Cl 9 5- chain as verified by single-crystal X-ray diffraction. Furthermore, the chiral perovskite exhibits absorption and circular dichroism (CD) signals in the high-energy band, enabling the circularly polarized light (CPL) detection in the UV spectrum. A CPL detector constructed by this chiral perovskite demonstrates excellent performance, boasting an anisotropy factor for photocurrent ( g Iph ) of 0.296. Our work not only introduces a novel and controllable method for crafting chiral perovskites but also opens new avenues for circularly polarized light detection.

Purpose: To explore the microstate characteristics and underlying brain network activity of Ménière's disease (MD) patients based on high-density electroencephalography (EEG), elucidate the association between microstate dynamics and clinical manifestation, and explore the potential of EEG microstate features as future neurobiomarkers for MD., Methods: Thirty-two patients diagnosed with MD and 29 healthy controls (HC) matched for demographic characteristics were included in the study. Dysfunction and subjective symptom severity were assessed by neuropsychological questionnaires, pure tone audiometry, and vestibular function tests. Resting-state EEG recordings were obtained using a 256-channel EEG system, and the electric field topographies were clustered into four dominant microstate classes (A, B, C, and D). The dynamic parameters of each microstate were analyzed and utilized as input for a support vector machine (SVM) classifier to identify significant microstate signatures associated with MD. The clinical significance was further explored through Spearman correlation analysis., Results: MD patients exhibited an increased presence of microstate class C and a decreased frequency of transitions between microstate class A and B, as well as between class A and D. The transitions from microstate class A to C were also elevated. Further analysis revealed a positive correlation between equilibrium scores and the transitions from microstate class A to C under somatosensory challenging conditions. Conversely, transitions between class A and B were negatively correlated with vertigo symptoms. No significant correlations were detected between these characteristics and auditory test results or emotional scores. Utilizing the microstate features identified via sequential backward selection, the linear SVM classifier achieved a sensitivity of 86.21% and a specificity of 90.61% in distinguishing MD patients from HC., Conclusions: We identified several EEG microstate characteristics in MD patients that facilitate postural control yet exacerbate subjective symptoms, and effectively discriminate MD from HC. The microstate features may offer a new approach for optimizing cognitive compensation strategies and exploring potential neurobiological markers in MD., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The objective of this study was to investigate the potential mechanisms by which (+)-catechin alleviates neuropathic pain. Thirty-two male Sprague-Dawley rats were divided into four groups: the sham group, the chronic constriction injury (CCI)group, the CCI+ ibuprofen group, and the CCI+ (+)-catechin group. CCI surgery induces thermal hyperalgesia in rats and (+)-catechin ameliorated CCI-induced thermal hyperalgesia and repaired damaged sciatic nerve in rats. CCI decreased SOD levels in male rat spinal cord dorsal horn and promoted MDA production, induced oxidative stress by increasing NOX4 levels and decreasing antioxidant enzyme HO-1 levels, and also increased protein levels of TLR4, p-NF-κB, NLRP3 inflammasome components, and IL-1β. In contrast, (+)-catechin reversed the above results. In i vitro experiments, (+)-catechin reduced the generation of reactive oxygen species (ROS) in GMI-R1 cells after LPS stimulation and attenuated the co-expression of IBA-1 and NLRP3. It also showed significant inhibition of the NF-κB and NLRP3 inflammatory pathways and activation of the Nrf2-mediated antioxidant system. Overall, these findings suggest that (+)-catechin inhibits the activation of the NLRP3 inflammasome through the triggering of the Nrf2-induced antioxidant system, the inhibition of the TLR4/NF-κB pathway, and the production of ROS to alleviate CCI-induced neuropathic pain in male rats., (© 2024 Wiley Periodicals LLC.)

Immunosuppression is a major hallmark of tumor progression in non-small cell lung cancer (NSCLC). Cluster of differentiation 147 (CD147), an important pro-tumorigenic factor, is closely linked to NSCLC immunosuppression. However, the role of CD147 di-methylation in the immunosuppressive tumor microenvironment (TME) remains unclear. Here, di-methylation of CD147 at Lys148 (CD147-K148me2) is identified as a common post-translational modification (PTM) in NSCLC that is significantly associated with unsatisfying survival outcomes among NSCLC sufferers, especially those in the advanced stages of the disease. The methyltransferase NSD2 catalyzes CD147 to generate CD147-K148me2. Further analysis demonstrates that CD147-K148me2 reestablishes the immunosuppressive TME and promotes NSCLC progression. Mechanistically, this modification promotes the interaction between cyclophilin A (CyPA) and CD147, and in turn, increases CCL5 gene transcription by activating p38-ZBTB32 signaling, leading to increased NSCLC cell-derived CCL5 secretion. Subsequently, CD147-K148me2-mediated CCL5 upregulation facilitates M2-like tumor-associated macrophage (TAM) infiltration in NSCLC tissues via CCL5/CCR5 axis-dependent intercellular crosstalk between tumor cells and macrophages, which is inhibited by blocking CD147-K148me2 with the targeted antibody 12C8. Overall, this study reveals the role of CD147-K148me2-driven intercellular crosstalk in the development of NSCLC immunosuppression, and provides a potential interventional strategy for PTM-targeted NSCLC therapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The aim of this study was to investigate the potential therapeutic applications of (+)-catechin in the treatment of neuropathic pain. In vivo study, 32 SD rats were randomly divided into four groups: sham group, chronic constriction injury (CCI) group, CCI + ibuprofen group and CCI+ (+)-catechin group. They were subjected to behavioural tests, ELISA, immunohistochemistry and Western blotting. The mechanisms involved were investigated using specific inhibitors in cell experiments. Results of in vivo experiments showed that (+)-catechin could reduce the cold sensitivity pain in a rat model of CCI; ELISA and immunohistochemistry results showed that (+)-catechin could decrease the levels of IL-8, IL-6, TNF-α, CCL2 and CCL5 in serum and the expression levels of nNOS, COX2, IL6, TNF-α, IBA-1 and CSF1R in DRG of CCI rats. Finally, western blot confirmed that (+)-catechin could diminish the levels of IL-34/CSF1R/JAK2/STAT3 signalling pathway in DRG of CCI rats. In vitro studies showed that (+)-catechin reduced IL-34 secretion in LPS-induced RSC96 cells. Meanwhile, (+)-catechin administration in LPS-induced Schwann cell-conditioned medium (L-CM) significantly inhibited the proliferation and migration of RAW264.7 cells; in addition, L-CM+(+)-catechin reduced the activation of the CSF1R/JAK2/STAT3 signalling pathway. (+)-Catechin attenuated the Schwann cell-macrophage cascade response in the DRG by modulating the IL34/CSFIR axis and inhibiting activation of the JAK2/STAT3 pathway, thereby attenuating CCI-induced neuropathic pain in rats., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Skeletal muscle is an important motor organ with multinucleated myofibers as its smallest cellular units. Myofibers are formed after undergoing cell differentiation, cell-cell fusion, myonuclei migration, and myofibril crosslinking among other processes and undergo morphological and functional changes or lesions after being stimulated by internal or external factors. The above processes are collectively referred to as myogenesis. After myofibers mature, the function and behavior of skeletal muscle are closely related to the voluntary movement of the body. In this review, we systematically and comprehensively discuss the physiological and pathological processes associated with skeletal muscles from five perspectives: molecule basis, myogenesis, biological function, adaptive changes, and myopathy. In the molecular structure and myogenesis sections, we gave a brief overview, focusing on skeletal muscle-specific fusogens and nuclei-related behaviors including cell-cell fusion and myonuclei localization. Subsequently, we discussed the three biological functions of skeletal muscle (muscle contraction, thermogenesis, and myokines secretion) and its response to stimulation (atrophy, hypertrophy, and regeneration), and finally settled on myopathy. In general, the integration of these contents provides a holistic perspective, which helps to further elucidate the structure, characteristics, and functions of skeletal muscle., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

The accurate construction of mono-, bi- and multi-layer networks has been an important challenge, especially for bi- and multi-layer networks. Monolayer, bilayer, sandwich bilayer, four-layer, and multi-layer two-dimensional pillararene-type metal-organic coordination networks have been constructed from functionalized pillar[5]arene and pillar[6]arene by utilizing the coordination interaction of cobalt and copper ions and combining with temperature control and guest induction. These two-dimensional coordination networks exhibit the excellent plasticity of pillararenes and structural variety, which are characterized by X-ray single crystal diffraction and PXRD, confirming that pillararenes units can function as excellent tunable scaffolds for structural regulation. Two-dimensional chiral double-layer structure products are also constructed from R - and S -pillar[6]arene, which are obtained by high-performance liquid chromatography. Atomic force microscopic imaging confirms the thicknesses of these networks. Moreover, these networks also exhibit high iodine adsorption capacity in aqueous environments at ambient temperature. The monolayer, bilayer, sandwich bilayer, four-layer and multi-layer structures of the pillararene-type networks represent a new facile supramolecular self-assembly strategy and platform for designing more mono-, bi- and multi-layer two-dimensional nanomaterials and chiral two-dimensional double-layer structures provide a new method for the construction of more two-dimensional chiral polymers., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Perovskites exhibit considerable potential as catalysts for various applications, yet their performance modulation in the carbon dioxide reduction reaction (CO 2 RR) remains underexplored. In this study, we report a strategy to enhance the electrocatalytic carbon dioxide (CO 2 ) reduction activity via Ce-doped La 2 CuO 4 (LCCO) and Sr-doped La 2 CuO 4 (LSCO) perovskite oxides. Specifically, compared to pure phase La 2 CuO 4 (LCO), the Faraday efficiency (FE) for CH 4 of LCCO at -1.4 V vs. RHE (reversible hydrogen electrode) is improved from 38.9% to 59.4%, and the FE CO 2 RR of LSCO increased from 68.8% to 85.4%. In situ attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy spectra results indicate that the doping of A-site ions promotes the formation of *CHO and *HCOO, which are key intermediates in the production of CH 4 , compared to the pristine La 2 CuO 4 . X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and double-layer capacitance ( C dl ) outcomes reveal that heteroatom-doped perovskites exhibit more oxygen vacancies and higher electrochemical active surface areas, leading to a significant improvement in the CO 2 RR performance of the catalysts. This study systematically investigates the effect of A-site ion doping on the catalytic activity center Cu and proposes a strategy to improve the catalytic performance of perovskite oxides.

For designing single-molecule devices that have both conjugation systems and structural flexibility, a hyperconjugated molecule with a σ-π bond interaction is considered an ideal candidate. In the investigation of conductance at the single-molecule level, since few hyperconjugation systems have been involved, the strategy of building hyperconjugation systems and the mechanism of electron transport within this system remain unexplored. Based on the skipped-conjugated structure, we present a rational approach to construct a hyperconjugation molecule using a hydroxyl group, which serves as a bridge to interact with the conjugated fragments. The measurement of single-molecule conductance reveals a two-fold conductance enhancement of the hyperconjugation system having the 'bridging' hydroxyl group compared to hydroxyl-free derivatives. Theoretical studies demonstrate that the hydroxyl group in the hyperconjugation system connects the LUMO of the two conjugated fragments and opens a through-space channel for electron transport to enhance the conductance.

Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on-target off-tumor toxicity limits Ab-based therapeutics. Cluster of differentiation 147 (CD147) is a tumor-associated membrane antigen overexpressed in cancer cells. Ab-based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia-activation strategies, we developed a conditional Ab-dependent cellular cytotoxicity (ADCC)-enhanced humanized anti-CD147 Ab, HcHAb18-azo-PEG 5000 (HAP18). Afucosylated ADCC-enhanced HcHAb18 Ab was produced by a fed-batch cell culture system. Azobenzene (Azo)-linked PEG 5000 conjugation endowed HAP18 Ab with features of hypoxia-responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement-dependent cytotoxicity, and Ab-dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor-inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia-activated ADCC-enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti-CD147 Ab drugs., Competing Interests: The authors declare they have no conflicts of interest., (© 2024 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Coordination cages sustained by metal-ligand interactions feature polyhedral architectures and well-defined hollow structures, which have attracted significant attention in recent years due to a variety of structure-guided promising applications. Sulfonylcalix[4]arenes-based coordination cages, termed metal-organic supercontainers (MOSCs), that possess unique multi-pore architectures containing an endo cavity and multiple exo cavities, are emerging as a new family of coordination cages. The well-defined built-in multiple binding domains of MOSCs allow the efficient encapsulation of guest molecules, especially for drug delivery. Here, we critically discuss the design strategy, and, most importantly, the recent advances in research surrounding cavity-specified host-guest chemistry and biomedical applications of MOSCs.

An asymmetric structure is an important strategy for designing highly conductive molecular wires for a gap-fixed molecular circuit. As the conductance enhancement in the current strategy is still limited to about 2 times, we inserted a methylene group as a spacer in a conjugated structure to modulate the structural symmetry. We found that the conductance drastically enhanced in the asymmetric molecular wire to 1.5 orders of magnitude as high as that in the symmetric molecular wire. First-principles quantum transport studies attributed the effective enhancement to the synchronization of improved energy alignment and nearly symmetric coupling between the frontier orbitals and the electrodes.

The absence of efficient and durable catalysts for oxygen evolution reaction (OER) is the main obstacle to hydrogen production through water splitting in an acidic electrolyte. Here, we report a controllable synthesis method of surface IrO x with changing Au/Ir compositions by constructing a range of sub-10-nm-sized core-shell nanocatalysts composed of an Au core and Au x Ir 1- x alloy shell. In particular, Au@Au 0.43 Ir 0.57 exhibits 4.5 times higher intrinsic OER activity than that of the commercial Ir/C. Synchrotron X-ray-based spectroscopies, electron microscopy and density functional theory calculations revealed a balanced binding of reaction intermediates with enhanced activity. The water-splitting cell using a load of 0.02 mg Ir /cm 2 of Au@Au 0.43 Ir 0.57 as both anode and cathode can reach 10 mA/cm 2 at 1.52 V and maintain activity for at least 194 h, which is better than the cell using the commercial couple Ir/C‖Pt/C (1.63 V, 0.2 h)., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Background: Atherosclerosis is a globally prevalent chronic inflammatory disease with high morbidity and mortality. The development of atherosclerotic lesions is determined by macrophages. This study aimed to investigate the specific role of myeloid-derived CD147 (cluster of differentiation 147) in atherosclerosis and its translational significance., Methods and Results: We generated mice with a myeloid-specific knockout of CD147 and mice with restricted CD147 overexpression, both in an apoE-deficient (ApoE -/- ) background. Here, the myeloid-specific deletion of CD147 ameliorated atherosclerosis and inflammation. Consistent with our in vivo data, macrophages isolated from myeloid-specific CD147 knockout mice exhibited a phenotype shift from proinflammatory to anti-inflammatory macrophage polarization in response to lipopolysaccharide/IFN (interferon)-γ. These macrophages demonstrated a weakened proinflammatory macrophage phenotype, characterized by reduced production of NO and reactive nitrogen species derived from iNOS (inducible NO synthase). Mechanistically, the TRAF6 (tumor necrosis factor receptor-associated factor 6)-IKK (inhibitor of κB kinase)-IRF5 (IFN regulatory factor 5) signaling pathway was essential for the effect of CD147 on proinflammatory responses. Consistent with the reduced size of the necrotic core, myeloid-specific CD147 deficiency diminished the susceptibility of iNOS-mediated late apoptosis, accompanied by enhanced efferocytotic capacity mediated by increased secretion of GAS6 (growth arrest-specific 6) in proinflammatory macrophages. These findings were consistent in a mouse model with myeloid-restricted overexpression of CD147. Furthermore, we developed a new atherosclerosis model in ApoE -/- mice with humanized CD147 transgenic expression and demonstrated that the administration of an anti-human CD147 antibody effectively suppressed atherosclerosis by targeting inflammation and efferocytosis., Conclusions: Myeloid CD147 plays a crucial role in the growth of plaques by promoting inflammation in a TRAF6-IKK-IRF5-dependent manner and inhibiting efferocytosis by suppressing GAS6 during proinflammatory conditions. Consequently, the use of anti-human CD147 antibodies presents a complementary therapeutic approach to the existing lipid-lowering strategies for treating atherosclerotic diseases., Competing Interests: Disclosures None.

Flavivirus infections, including dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV), present significant global public health challenges. For successful vaccine design, the assessment of neutralizing antibody activity requires reliable and robust methodologies for determining antibody titers. Although the plaque reduction neutralization test (PRNT) is commonly acknowledged as the gold standard, it has limitations in terms of time and cost, and its usage may be limited in resource-limited settings. To address these challenges, we introduced the micro-neutralization test (MNT) as a simplified alternative to the PRNT. The MNT employs a 96-well plate format, conducts microscale neutralization assays, and assesses cell viability by dissolving cells to create a uniform color solution, which is measured with a spectrometer. In this study, we evaluated the utility of the MNT by contrasting the end-point titers of the MNT and PRNT using 4 monoclonal antibodies, 15 non-human primate serum samples, and 2 therapeutic drug candidates across flaviviruses. The results demonstrated a strong correlation between the MNT and PRNT titers, affirming the robustness and reproducibility of the MNT for evaluating control measures against flaviviruses. This research contributes valuable insights toward the development of a cost-effective antibody titer testing approach that is particularly suitable for resource-limited settings.

The emerging Pb-free double perovskites (DPs) are acknowledged as the most potential nontoxic alternatives to lead halide perovskites for thin-film photovoltaics, yet their photophysical properties significantly lag behind expectations. To tackle this issue, it is imperative to conduct a systematic investigation of the structure and optoelectronic properties and to sift through vast chemical space to extract new types of Pb-free DPs with exceptional optoelectronic characteristics and thermal stability. Through high-throughput first-principal calculations, we demonstrate that apart from a select few Pb-free DPs (e.g., Cs 2 InSbCl 6 and Cs 2 TlBiBr 6 ), other categories, even with suitable direct electronic bandgaps, exhibit inferior optical absorption due to the inversion symmetry-induced parity-forbidden transitions. The mismatch between the electronic and optical bandgap, thence, casts doubt on the reliability of the electronic bandgap as a criterion for Pb-free DPs in various optoelectronics. The assessed limited thermostability under operational conditions, however, hinders any Pb-free DPs from effectively serving as photovoltaic absorbers. Alongside the compositional engineering discussed above, the prospect of manipulating local-site symmetry and disrupting the parity forbidden transitions in stabilized Pb-free DPs through materials engineering should be recognized as a pivotal and rational avenue toward achieving high performance.

Diradicaloids are generally high-energy molecules with open-shell configuration and are quite reactive. In this work, we report a feasible synthetic approach to attaining exceptionally stable copper(I) metallacyclopentadiene diradicaloids through ligand engineering. Copper(I)-hybrid cyclopentadiene diradicaloids 1c - 6c that absorb intensely in visible regions were successfully prepared in stoichiometrical yields under UV light irradiation. The diradicaloids originate from the C-C bonding coupling of two side-by-side-arranged ethynyl groups in complexes 1 - 6 upon photocyclization. By rational selection of substituents in triphosphine ligands, we systematically modulate the kinetic behavior of diradicaloids 1c - 6c in the thermal decoloration process. With precise ligand design, we are able to obtain exceptionally stable copper(I)-hybrid cyclopentadiene diradicaloids with a half-life as long as ca. 40 h in CH 2 Cl 2 solution at ambient temperature. As demonstrated by electron paramagnetic resonance (EPR) and variable-temperature magnetic studies, the diradicaloids manifest a singlet ground state, but they are readily populated to a triplet excited state through thermal activation in view of a small singlet-triplet energy gap of -0.39 kcal mol -1 . The diradicaloids show two-step quasi-reversible reduction waves at about -0.5 and -1.0 V ascribed to successive one-electron-accepting processes, coinciding perfectly with the characteristics of diradicals.

An accurate rule for predicting conductance is the cornerstone of developing molecular circuits and provides a promising solution for miniaturizing electric circuits. The successful prediction of series molecular circuits has proven the possibility of establishing a rule for molecular circuits under quantum mechanics. However, the quantitatively accurate prediction has not been validated by experiments for parallel molecular circuits. Here we used 1,3-dihydrobenzothiophene (DBT) to build the parallel molecular circuits. The theoretical simulation and single-molecule conductance measurements demonstrated that the conductance of the molecule containing one DBT is the unprecedented linear combination of the conductance of the two individual channels with respective contribution weights of 0.37 and 0.63. With these weights, the conductance of the molecule containing two DBTs is predicted as 1.81 nS, matching perfectly with the measured conductance (1.82 nS). This feature offers a potential rule for quantitatively predicting the conductance of parallel molecular circuits.

Morphine is a frequently used analgesic that activates the mu-opioid receptor (MOR), which has prominent side effects of tolerance. Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance, currently, there is no effective therapy to treat morphine tolerance. In the current study, we aimed to develop a monoclonal antibody (mAb) precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms. We successfully prepared a mAb targeting MOR, named 3A5C7, by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization, and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation. Treatment of two cell lines, HEK293T and SH-SY5Y, with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2 (GRK2)/β-arrestin2-dependent mechanism, as demonstrated by immunofluorescence staining, flow cytometry, Western blotting, coimmunoprecipitation, and small interfering ribonucleic acid (siRNA)-based knockdown. This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR. We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid. Western blot, enzyme-linked immunosorbent assays, and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase, the in vitro biomarker of morphine tolerance, via the GRK2/β-arrestin2 pathway. Furthermore, in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alleviated morphine tolerance in mice, and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence. Finally, intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway. Collectively, our study provided a therapeutic mAb, 3A5C7, targeting MOR to treat morphine tolerance, mediated by enhancing morphine-induced MOR endocytosis. The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Optimizing cell substrates by surface modification of neural stem cells (NSCs), for efficient and oriented neurogenesis, represents a promising strategy for treating neurological diseases. However, developing substrates with the advanced surface functionality, conductivity, and biocompatibility required for practical application is still challenging. Here, Ti 3 C 2 T x MXene is introduced as a coating nanomaterial for aligned poly(l-lactide) (PLLA) nanofibers (M-ANF) to enhance NSC neurogenesis and simultaneously tailor the cell growth direction. Ti 3 C 2 T x MXene treatment provides a superior conductivity substrate with a surface rich in functional groups, hydrophilicity, and roughness, which can provide biochemical and physical cues to support NSC adhesion and proliferation. Moreover, Ti 3 C 2 T x MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti 3 C 2 T x MXene acts synergistically with the alignment of nanofibers to promote the growth of neurites, indicating enhanced maturation of these neurons. RNA sequencing analysis further reveals the molecular mechanism by which Ti 3 C 2 T x MXene modulates the fate of NSCs. Notably, surface modification by Ti 3 C 2 T x MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti 3 C 2 T x MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration., (© 2023 Wiley-VCH GmbH.)

Background: The mechanism of hepatitis B virus (HBV)-induced carcinogenesis remains an area of interest. The accumulation of hepatitis B surface antigen in the endoplasmic reticulum (ER) of hepatocytes stimulates persistent ER stress. Activity of the unfolded protein response (UPR) pathway of ER stress may play an important role in inflammatory cancer transformation. How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV-related hepatocellular carcinoma (HCC) is still unclear. Here, we aimed to define the key molecule hyaluronan-mediated motility receptor (HMMR) in this process and explore its role under ER stress in HCC development., Methods: An HBV-transgenic mouse model was used to characterize the pathological changes during the tumor progression. Proteomics and transcriptomics analyses were performed to identify the potential key molecule, screen the E3 ligase, and define the activation pathway. Quantitative real-time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines. Luciferase reporter assay, chromatin immunoprecipitation, coimmunoprecipitation, immunoprecipitation, and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress. Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues., Results: We found sustained activation of ER stress in the HBV-transgenic mouse model of hepatitis-fibrosis-HCC. HMMR was transcribed by c/EBP homologous protein (CHOP) and degraded by tripartite motif containing 29 (TRIM29) after ubiquitination under ER stress, which caused the inconsistent expression of mRNA and protein. Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR. HMMR could alleviate ER stress by increasing autophagic lysosome activity. The negative correlation between HMMR and ER stress, positive correlation between HMMR and autophagy, and negative correlation between ER stress and autophagy were verified in human tissues., Conclusions: This study identified the complicated role of HMMR in autophagy and ER stress, that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression, which could be a novel explanation for HBV-related carcinogenesis., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

As an emerging treatment strategy for malignant tumors, chimeric antigen receptor T (CAR-T) cell therapy has been widely used in clinical practice, and its efficacy has been markedly improved in the past decade. However, the clinical effect of CAR-T therapy is not so satisfying, especially in solid tumors. Even in hematologic malignancies, a proportion of patients eventually relapse after receiving CAR-T cell infusions, owing to the poor expansion and persistence of CAR-T cells. Recently, CRISPR/Cas9 technology has provided an effective approach to promoting the proliferation and persistence of CAR-T cells in the body. This technology has been utilized in CAR-T cells to generate a memory phenotype, reduce exhaustion, and screen new targets to improve the anti-tumor potential. In this review, we aim to describe the major causes limiting the persistence of CAR-T cells in patients and discuss the application of CRISPR/Cas9 in promoting CAR-T cell persistence and its anti-tumor function. Finally, we investigate clinical trials for CRISPR/Cas9-engineered CAR-T cells for the treatment of cancer.

The efficient production of γ-valerolactone (GVL) from renewable lignocellulose that is synthesized in plants by photosynthesis to replace the declining fossil resources conforms to the principles of circular economy. Compared to direct hydrogenation by H 2 molecules, catalytic transfer hydrogenation (CTH) of levulinic acid (LA) and/or its esters to GVL with organic alcohols as a hydrogen source is a much milder route. The synergistic catalysis between Lewis and Brønsted acids is indispensable in the CTH process. Considering that unsaturated coordinated Zr species could act as Lewis acid sites and phosphotungstic acid (PTA) could dissociate protons as Brønsted acid sites, UiO-66 (Zr) was thus "acidified" by encapsulating PTA in its channels to tune the ratio of Brønsted to Lewis acid sites as a bifunctional catalyst so as to better understand the catalytic structure-performance relationship in the CTH process. To address the dilemma of encapsulated PTA that is prone to leach, a rapid surface sealing strategy was adopted to establish a polyimide (PI) coating over the surface of UiO-66 introducing a space confinement effect via an anhydride-amine coupling reaction. The as-synthesized PTA/UiO-66@PI catalyst exhibited 100% of LA conversion, a 93.2% of GVL yield and high recyclability for at least five consecutive cycles. Moreover, a reaction pathway followed by esterification, hydrogenation and dealcoholization as well as a catalytic hydrogenation mechanism based on intermolecular hydride β-H transfer were proposed. Current work not only provides a high-performance and high-stability catalytic system to selectively produce GVL from LA or its esters, but also sheds light on the catalytic mechanism of the CTH process at the molecular level.

Background: Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention affects the structure and function of the GM in patients with OP., Method: In a 3-month clinical study, 43 patients were randomly divided into two groups receiving conventional treatment and combined TCM (Yigu decoction, YGD) treatment. The correlation between the intestinal flora and its metabolites was analyzed using 16S rDNA and untargeted metabolomics and the combination of the two., Results: After three months of treatment, patients in the treatment group had better bone mineral density (BMD) than those in the control group ( P < 0.05). Patients in the treatment group had obvious abundance changes in GM microbes, such as Bacteroides, Escherichia-Shigella, Faecalibacterium, Megamonas, Blautia, Klebsiella, Romboutsia, Akkermansia, and Prevotella&#95;9. The functional changes observed in the GM mainly involved changes in metabolic function, genetic information processing and cellular processes. The metabolites for which major changes were observed were capsazepine, Phe-Tyr, dichlorprop, D-pyroglutamic acid and tamsulosin. These metabolites may act through metabolic pathways, the citrate cycle (TCA cycle) and beta alanine metabolism. Combined analysis showed that the main acting metabolites were dichlorprop, capsazepine, D-pyroglutamic acid and tamsulosin., Conclusion: This study showed that TCM influenced the structure and function of the GM in patients with OP, which may be one mechanism by which TCM promotes the rehabilitation of patients with OP through the GM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Yan, Chen, Zhang, Li, Chen, Ge, Cheng, Chen and Yao.)

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity. Here, we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-programmed death-1 (anti-PD-1) and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy, and the patient remained disease-free for 69 months. The patient received DC vaccines loaded with multiple forms of tumor antigens, including mRNA-tumor associated antigens (TAA), mRNA-neoantigens, and hypochlorous acid (HOCl)-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex (MHC) class I and II antigen presentation. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy-related adverse events were observed during the treatment. Robust antitumor CD4 + and CD8 + T-cell responses were detected. The patient remains free of disease progression. This is the first case report on the combination of the above three agents to treat glioblastoma patients. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient. A large-scale trial to validate these findings is warranted., Competing Interests: You-Wen He and Shi-You Li are co-founders of Tricision Biotherapeutics Inc., and the contribution of You-Wen He in this project was through his scientific advisor to tricision Biotherapeutic Inc. Sheng-Nan Sun, Jun Jiang, Qian-Ting Wang, and Shi-You Li are full-time employees of Tricision Biotherapeutics Inc. You-Wen He and Jun O. Liu are co-inventors of the TriVac technology patented by Duke University and Johns Hopkins University and co-founders of TriVac Inc. TriVac technology used by Tricision Biotherapeutics Inc. was licensed by Duke/JHU through TriVac Inc. Other authors declare that there are no conflicts of interest., (© 2023 The Author(s).)

Herein, we describe an efficient method involving the synthesis of diverse quinoxalines using the DMSO/ t BuONa/O 2 system as a single-electron oxidant to form α-imino radicals and nitrogen radicals for the direct construction of C-N bonds. This methodology provides a novel approach to form α-imino radicals with good reactivity.

Perovskites are promising environmentally sustainable materials for circularly polarized electroluminescence (CPEL). While another chiral nonemissive layer is required for the developed perovskite-based CPEL, we report herein a highly efficient circularly polarized electroluminescence based on a single layer of quasi-2D perovskite with achiral phenethylammonium iodide (PEAI) and chiral S / R -1-(1-naphthyl)ethylammonium iodide (S/R-NEAI) as dual spacer cations. The quasi-2D perovskite was further passivated by carbazole-functionalized phosphonium. The as-fabricated film exhibits not only a circular dichroism (CD) signal but also prominent circularly polarized luminescence (CPL) activity with a maximum photoluminescence dissymmetry factor ( g lum ) of ∼2.1 × 10 -3 . More importantly, a highly efficient, spin-polarized light-emitting diode (LED) was fabricated based on the in situ passivated quasi-2D perovskite with a peak external quantum efficiency of 3.7% and a maximum electroluminescence dissymmetry factor ( g EL ) of ∼4.0 × 10 -3 .

Neurofilament light chain (NF-L) plays critical roles in synapses that are relevant to neuropsychiatric diseases. Despite postmortem evidence that NF-L is decreased in opiate abusers, its role and underlying mechanisms remain largely unknown. We found that the microinjection of the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) into the ventrolateral orbital cortex (VLO) attenuated chronic morphine-induced behavioral sensitization. The microinjection of TSA blocked the chronic morphine-induced decrease of NF-L. However, our chromatin immunoprecipitation (ChIP)-qPCR results indicated that this effect was not due to the acetylation of histone H3-Lysine 9 and 14 binding to the NF-L promotor. In line with the behavioral phenotype, the microinjection of TSA also blocked the chronic morphine-induced increase of p-ERK/p-CREB/p-NF-L. Finally, we compared chronic and acute morphine-induced behavioral sensitization. We found that although both chronic and acute morphine-induced behavioral sensitization were accompanied by an increase of p-CREB/p-NF-L, TSA exhibited opposing effects on behavioral phenotype and molecular changes at different addiction contexts. Thus, our findings revealed a novel role of NF-L in morphine-induced behavioral sensitization, and therefore provided some correlational evidence of the involvement of NF-L in opiate addiction.

Reaction of [Au(tht) 2 ](ClO 4 ) (tht = tetrahydrothiophene), [Cu(CH 3 CN) 4 ](ClO 4 ), 3,6-di- tert -butyl-1,8-diethynyl-9 H -carbazole (H 3 decz), and bis(2-diphenylphosphinophenyl)ether (POP) in the presence of triethylamine (NEt 3 ) gave the cluster complex Au 4 Cu 2 (decz) 2 (POP) 2 as yellow crystals. As revealed by X-ray crystallography, the Au 4 Cu 2 cluster exhibits scissor-like structure sustained by two decz and two POP ligands and stabilized by Au-Cu and Au-Au interactions. The Au 4 Cu 2 cluster shows bright yellow to orange photoluminescence upon irradiation at >300 nm, arising from 3 [π (decz)→5d (Au)] 3 LMCT (ligand-to-metal charge transfer) and 3 [π→π* (decz)] 3 IL (intraligand) triplet states as revealed by theoretical and computational studies. When it is mechanically ground, reversible phosphorescence conversion from yellow to red is observed owing to more compact molecular packing and thus stronger intermetallic interaction. Variable-temperature luminescence studies reveal that it displays distinct red-shifts of the emission whether the temperature is elevated or lowered from ambient temperature, suggestive of exceptional thermochromic phosphorescence characteristics.

Introduction: Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment., Methods: Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation., Results: RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes., Conclusion: Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, we identified a panel of cysteine residues differentially modified by carboxyethylation that required 3-hydroxypropionic acid to generate neoantigens in patients with AS. The lysosomal degradation of integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated carboxyethylated peptides that were presented by HLA-DRB1*04 to stimulate CD4 + T cell responses and induce autoantibody production. Immunization of HLA-DR4 transgenic mice with the ITGA2B-ceC96 peptide promoted colitis and vertebral bone erosion. Thus, metabolite-induced cysteine carboxyethylation can give rise to pathogenic neoantigens that lead to autoreactive CD4 + T cell responses and autoantibody production in autoimmune diseases.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile., (© 2023. The Author(s).)

The emerging lead halide perovskites show great potential for their use as emitters in electrically driven light-emitting diodes (LEDs) with external quantum efficiency (EQE) over 25%. While the toxicity of lead and inferior device stability are the main obstacles for their commercialization, replacing Pb 2+ with low- or non-toxic metal ions to form low- or zero-dimensional structures provides an alternative approach to effectively tackle these issues. Recently, luminescent lead-free metal halides have been increasingly developed toward eco-friendly and highly efficient electroluminescence. In this feature article, we give a brief overview of recent advances in luminescent lead-free metal halides and their applications in electrically driven LEDs. The challenges and prospects in this field are outlined at the end.

The Omicron variants of SARS-CoV-2, primarily authenticated in November 2021 in South Africa, has initiated the 5th wave of global pandemics. Here, we systemically examined immunological and metabolic characteristics of Omicron variants infection. We found Omicron resisted to neutralizing antibody targeting receptor binding domain (RBD) of wildtype SARS-CoV-2. Omicron could hardly be neutralized by sera of Corona Virus Disease 2019 (COVID-19) convalescents infected with the Delta variant. Through mass spectrometry on MHC-bound peptidomes, we found that the spike protein of the Omicron variants could generate additional CD8 + T cell epitopes, compared with Delta. These epitopes could induce robust CD8 + T cell responses. Moreover, we found booster vaccination increased the cross-memory CD8 + T cell responses against Omicron. Metabolic regulome analysis of Omicron-specific T cell showed a metabolic profile that promoted the response of memory T cells. Consistently, a greater fraction of memory CD8 + T cells existed in Omicron stimulated peripheral blood mononuclear cells (PBMCs). In addition, CD147 was also a receptor for the Omicron variants, and CD147 antibody inhibited infection of Omicron. CD147-mediated Omicron infection in a human CD147 transgenic mouse model induced exudative alveolar pneumonia. Taken together, our data suggested that vaccination booster and receptor blocking antibody are two effective strategies against Omicron., (© 2023. The Author(s).)

Background and Aims: Pancreatic adenocarcinoma (PAAD) is highly aggressive and characterized by a poor prognosis. Oxidative stress has great impacts on the occurrence and development of tumors. However, the predictive role of oxidative stress related genes on PAAD patients' prognosis remains unclear. In this study, we aimed to construct a prognostic model for PAAD based on oxidative stress genes and to evaluate its predictive value., Methods: The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets were used to identify differentially expressed oxidative stress genes. Univariate Cox regression, Kaplan-Meier and multivariate Cox regression analysis were used to select genes and to construct a prognosis model. According to the median value of the model's risk score, patients were divided into high and low risk groups, and gene set enrichment analysis (GSEA), immune infiltration and immunotherapy effect, drug resistance and the expression of immune checkpoint related genes and synthetic driver genes of T cell proliferation were analyzed. Finally, the mRNA and protein levels of four genes in PAAD were verified by the clinical proteomic tumor analysis consortium (CPTAC) database and the immunostaining of patients' tissue., Results: 55 differentially expressed oxidative stress genes were identified, and four genes including MET, FYN, CTTN and CDK1 were selected to construct a prognosis model. GESA indicated that immune related pathways, metabolic pathways and DNA repair pathways were significantly enriched in the high risk group as compared to the low risk group. The frequency of genetic mutations was also significantly higher in high risk groups than that in low risk groups. Moreover, the infiltration level of 23 immune cells as well as the expression of immune checkpoint related and synthetic driver genes of T cell proliferation were significantly altered, with the better immunotherapy effect occurring in low risk group. In patient PAAD tissues, the mRNA and protein levels of these four genes were up-regulated., Conclusion: We have successfully constructed a four oxidative stress gene prognostic model that has important predictive value for PAAD patients, and this model might be a promising guidance for prognostic prediction and efficacy monitoring in clinical individualized therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Tian, Liang, Fan, Duan, Fan, Zhang, Yao, Chen and Li.)

Immuno-checkpoint inhibitors (ICIs) bring a promising prospect for patients with cancers, which restrains the growth of tumor cells by enhancing anti-tumor activity. Nevertheless, not all patients benefit from the administration of ICIs monotherapy. The partial response or resistance to ICIs is mainly due to the complex and heterogenous tumor microenvironment (TME). The combined therapy is necessary for improving the efficacy of tumor treatment. Chemotherapy is reported not only to kill tumor cells directly, but also to stimulate effective anti-tumor immune responses. Several combined therapies of ICIs and chemotherapeutic agents have been approved for the first-line treatment of cancers, including PD-1/PD-L1 inhibitors. This review summarizes the potential mechanisms of the combined therapy of ICIs and chemotherapeutic agents in inducing immunogenic cell death (ICD) and reprogramming TME, and elucidates the possible anti-tumor effects of combined therapy from the perspective of metabolic reprogramming and microbiome reprogramming., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi, Liu, Chen, Tian, Chen and Wang.)

The overwhelmingly competitive hydrogen evolution reaction (HER) is a bottleneck challenge in the electrocatalytic nitrogen reduction reaction (eNRR) process. Herein, we develop a general and effective strategy to suppress the HER via covalent surface functionalization to modulate the local microenvironment of the electrocatalyst. A hydrophobic molecular layer with tunable coverage density was coated on the surface of Ti 3 C 2 T x MXene, and the one with appropriate coverage density significantly improved the eNRR efficiency with an excellent faradaic efficiency (FE) of 38.01% at -0.35 V and a high NH 3 yield rate of 17.81 μg h -1 mg cat -1 at -0.55 V (vs RHE) in a Na 2 SO 4 solution, which were 3.5-fold in FE and 6.5-fold in NH 3 yield rate higher than those of the pristine Ti 3 C 2 T x . Experimental results combined with molecular dynamics (MD) simulations reveal that the hydrophobic molecular layer on the surface greatly limits the proton transfer and benefits higher exposure of active sites with enhanced N 2 chemisorption ability, which cumulatively contribute to the boosted eNRR efficiency.