Metal-Organic Frameworks-Based Frustrated Lewis Pairs for Selective Reduction of Nitroolefins to Nitroalkanes.

Nitroalkanes serve as essential intermediates in the synthesis of pharmaceuticals, agrochemicals, and functional materials. To date, nitroalkanes are mainly prepared from homogeneous catalysts such as noble transition metal catalysts with poor recyclability. Herein, we propose a metal-organic framework-frustrated Lewis pair (MOF-FLP) heterogeneous catalyst for selectively reducing nitroolefins to nitroalkanes under moderate reaction conditions. MOF enrichment effect can significantly improve the catalytic efficiency compared to homogeneous FLP catalysts. Benefiting from the strong interaction between FLP and MOF, the MOF-FLP catalyst exhibits outstanding recyclability. This work not only provides a convenient route for nitroalkane synthesis but also showcases the potential of porous heterogeneous FLP catalysts, offering inspiration for future catalytic design strategies.

Accuracy of new intraocular lens calculation formulas in Chinese eyes with short axial lengths.

Purpose: To compare the measurement accuracy of new/updated intraocular lens (IOL) power calculation methods, namely, Kane, Emmetropia Verifying Optical (EVO), with existing methods (Barrett Universal II, Olsen, Haigis, Hoffer Q, Holladay 1, SRK/T) in Chinese eyes with axial lengths ≤ 22.5 mm. Methods: The study included data from patients who underwent uneventful cataract surgery with the insertion of ZCB00 IOL. Refractive prediction errors were determined by calculating the difference between postoperative refraction and the predicted refraction using each formula. Various parameters were evaluated, including mean prediction error (ME), mean absolute error (MAE), median absolute error (MedAE), and the percentage of eyes with prediction errors (PE) within different ranges. Results: The study enrolled 38 eyes of 38 patients, and the Barrett Universal II formula demonstrated the lowest MAE and MedAE among the tested formulas. Post hoc analysis using Wilcoxon signed-rank pairwise comparisons for non-parametric samples with Bonferroni correction revealed no significant difference in postoperative refractive prediction among all the formulas (P > 0.05). The percentage of eyes with PE within ± 0.5 D was as follows: Barrett Universal II, 81.58%; Haigis, 78.95%; EVO, 76.32%; Olsen, 76.32%; Holladay I, 73.68%; SRK/T, 71.05%; Kane, 68.42%; and Hoffer Q, 65.79%. Conclusion: The Barrett Universal II formula was more accurate than the other formulas for Chinese eyes with AL ≤ 22.5 mm.

STING signaling in inflammaging: a new target against musculoskeletal diseases.

Stimulator of Interferon Gene (STING) is a critical signaling linker protein that plays a crucial role in the intrinsic immune response, particularly in the cytoplasmic DNA-mediated immune response in both pathogens and hosts. It is also involved in various signaling processes in vivo. The musculoskeletal system provides humans with morphology, support, stability, and movement. However, its aging can result in various diseases and negatively impact people's lives. While many studies have reported that cellular aging is a leading cause of musculoskeletal disorders, it also offers insight into potential treatments. Under pathological conditions, senescent osteoblasts, chondrocytes, myeloid cells, and muscle fibers exhibit persistent senescence-associated secretory phenotype (SASP), metabolic disturbances, and cell cycle arrest, which are closely linked to abnormal STING activation. The accumulation of cytoplasmic DNA due to chromatin escape from the nucleus following DNA damage or telomere shortening activates the cGAS-STING signaling pathway. Moreover, STING activation is also linked to mitochondrial dysfunction, epigenetic modifications, and impaired cytoplasmic DNA degradation. STING activation upregulates SASP and autophagy directly and indirectly promotes cell cycle arrest. Thus, STING may be involved in the onset and development of various age-related musculoskeletal disorders and represents a potential therapeutic target. In recent years, many STING modulators have been developed and used in the study of musculoskeletal disorders. Therefore, this paper summarizes the effects of STING signaling on the musculoskeletal system at the molecular level and current understanding of the mechanisms of endogenous active ligand production and accumulation. We also discuss the relationship between some age-related musculoskeletal disorders and STING, as well as the current status of STING modulator development.

Introducing Frustrated Lewis Pairs to Metal-Organic Framework for Selective Hydrogenation of N-Heterocycles.

Hydrogenated nitrogen heterocyclic compounds play a critical role in the pharmaceutical, polymer, and agrochemical industries. Recent studies on partial hydrogenation of nitrogen heterocyclic compounds have focused on costly and toxic precious metal catalysts. As an important class of main-group catalysts, frustrated Lewis pairs (FLPs) have been widely applied in catalytic hydrogenation reactions. In principle, the combination of FLPs and metal-organic framework (MOF) is anticipated to efficiently enhance the recyclability performance of FLPs; however, the previously studied MOF-FLPs showed low reactivity in the hydrogenation of N-heterocycles compounds. Herein, we offer a novel P/B type MOF-FLP catalyst that was achieved via a solvent-assisted linker incorporation approach to boost catalytic hydrogenation reactions. Using hydrogen gas under moderate pressure, the proposed P/B type MOF-FLP can serve as a highly efficient heterogeneous catalyst for selective hydrogenation of quinoline and indole to tetrahydroquinoline and indoline-type drug compounds in high yield and excellent recyclability.

Intense Pulsed Light Attenuates Oxidative Stress in Perennial Allergic Conjunctivitis.

Objective: To assess the effects of intense pulsed light (IPL) on oxidative stress (OS) in perennial allergic conjunctivitis (PAC). Background: IPL treatment has been proven effective for dry eye disease (DED). However, we have observed that, after IPL treatment, some patients with DED combined with allergic conjunctivitis (AC), an immune response condition in which excessive OS causes and exacerbates inflammatory damage, not only show an improvement in eye dryness, but also their AC-related eye itching is relieved. The mechanism by which IPL inhibits allergic reactions is not clear. Methods: Five patients with moderate-to-severe PAC were given two IPL treatments on the periorbital skin with a 2-week interval. Visual analog scale (VAS) scores and signs of AC, including eye redness and conjunctival follicles, were assessed before the first treatment (day 1) and 2 weeks after the second treatment (day 30). Tears were also collected at the same time, and lipid oxidation (LPO) metabolite analysis was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to investigate the effects of IPL on OS response. Results: The average VAS score significantly decreased with treatment (30.2 for day 1, 10.6 for day 30; p < 0.001). The general signs of PAC showed no difference (p > 0.05). LPO metabolite analysis revealed that 17,18-diHETE, which is an oxidation product of eicosapentaenoic acid, and 13-OXoODE, which is an oxidation product of linoleic acid, are significantly downregulated after IPL treatment. Conclusions: The photothermal effect of IPL attenuates OS in PAC, and this seems to be one of the mechanisms by which IPL treatment improves PAC. Clinical Trial Registration number: ChiCTR1900022202.

Intense Pulsed Light Therapy to Inhibit Meibomian Gland Inflammation: Untargeted Metabolomics Analysis of Meibomian Gland Secretions.

Objective: To assess the inhibitory effects of intense pulsed light (IPL) on meibomian gland (MG) inflammation. Background: IPL treatment is effective for dry eye disease (DED) caused by meibomian gland dysfunction (MGD). However, the anti-inflammatory and regeneration stimulating effects of IPL on MGD remain unclear. Moreover, studies on inflammatory metabolites in MG secretions are lacking. Methods: Six patients with DED were administered two IPL treatments. Ocular surface disease index (OSDI) questionnaires were used to assess DED, MGD signs, including degree of obstruction, secretion, and atrophy of the MG, tear film break-up time (TBUT) was assessed before and after treatments. To determine IPL treatment-induced changes in metabolites, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze MG secretions. Results: Data were gathered before the first treatment (time A) and 2 weeks after the second treatment (time B). Average OSDI score showed a significant decrease (time A and B measurements were 44.07 and 16.65, respectively). Besides, statistically significant differences were observed in MG signs before and after treatments: degree of obstruction improved and secretions became thinner. TBUT was significantly increased to the normal range. LC-MS/MS led to the identification of 53 differential metabolites: 23 were upregulated (e.g., estradiol, coenzyme Q, and azelaic acid) and 30 were downregulated (e.g., prostaglandins, 20-hydroxyeicosatetraenoic acid, and arachidonic acid). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that most differential metabolites were involved in steroid hormone biosynthesis. Conclusions: Periorbital IPL treatment can improve chronic inflammation of the MG and promote its normal secretion. The steroid hormone biosynthetic pathways may be activated to participate in this anti-inflammatory effect.

Stringing Bimetallic Metal-Organic Framework-Derived Cobalt Phosphide Composite for High-Efficiency Overall Water Splitting.

Water electrolysis is an emerging energy conversion technology, which is significant for efficient hydrogen (H2) production. Based on the high-activity transition metal ions and metal alloys of ultrastable bifunctional catalyst, the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are the key to achieving the energy conversion method by overall water splitting (OWS). This study reports that the Co-based coordination polymer (ZIF-67) anchoring on an indium-organic framework (InOF-1) composite (InOF-1@ZIF-67) is treated followed by carbonization and phosphorization to successfully obtain CoP nanoparticles-embedded carbon nanotubes and nitrogen-doped carbon materials (CoP-InNC@CNT). As HER and OER electrocatalysts, it is demonstrated that CoP-InNC@CNT simultaneously exhibit high HER performance (overpotential of 153 mV in 0.5 m H2SO4 and 159 mV in 1.0 m KOH) and OER performance (overpotential of 270 mV in 1.0 m KOH) activities to reach the current density of 10 mA cm-2. In addition, these CoP-InNC@CNT rods, as a cathode and an anode, can display an excellent OWS performance with η10 = 1.58 V and better stability, which shows the satisfying electrocatalyst for the OWS compared to control materials. This method ensures the tight and uniform growth of the fast nucleating and stable materials on substrate and can be further applied for practical electrochemical reactions.

The hinge region fragment of immunoglobulin G improves immunogenicity of recombinant gonadotrophin-releasing hormone conjugated to the T-helper epitope in designing peptide vaccines.

In our previous study, the hinge fragment (225-232/225'-232') of human immunoglobulin G1 (IgG1) was used as a space peptide linker for synthesizing the GnRH3-hinge-MVP chimeric peptide, whereby three repeated gonadotrophin-releasing hormone (GnRH) units and a T-cell epitope from measles virus fusion protein (MVP) were amide-bond-linked at the N and C terminus, respectively, to the hinge peptide for producing anti-GnRH antibody responses. To investigate whether or not the hinge region fragment can improve the immunogenicity of GnRH, we further synthesized and purified GnRH3-hinge-MVP, GnRH3-hinge and GnRH3-MVP using recombinant DNA technology. Under high pH conditions, GnRH3-hinge-MVP was capable of forming double-chain structures. Immunization of male mice with the immunogens of GnRH3-hinge-MVP resulted in the generation of high-titre antibodies specific for GnRH. The synthetic GnRH3-hinge and GnRH3-MVP induced a lower titre of anti-GnRH antibody than GnRH3-hinge-MVP. This was followed by a decrease in serum testosterone levels, which resulted in a low level of expression of the relaxin-like factor gene in the testis. Our data suggest that peptide and T-cell epitopes oriented at the N-terminus or C-terminus of hinge peptides simplify the antigenic peptide conjugates and may be considered as potential synthetic immunogens.

Immunization with a recombinant GnRH vaccine conjugated to heat shock protein 65 inhibits tumor growth in orthotopic prostate cancer mouse model.

We have previously shown that anti-GnRH antibodies responses can be induced by synthetic GnRH3-hinge-MVP peptide. In this study, GnRH3-hinge-MVP of conjugation to heat shock protein 65 was used as an adjuvant-free vaccine to assess the therapeutic effects of GnRH immunoneutralisation on tumor development in the mice model. Compared with mice treated with Hsp65 and PBS, mice of the o.t. model receiving in situ treatment GnRH3-hinge-MVP-Hsp65 had significant prolongation of survival and suppression of local tumor growth. Serum levels of both testosterone and luteinizing hormone were reduced by treatment with GnRH3-hinge-MVP-Hsp65 (p<0.05). Further analyses of cell mediated immune responses showed that GnRH3-hinge-MVP-Hsp65 induced stronger lymphocyte proliferative responses and higher levels of IFN-gamma (p<0.001). The conjugation of the recombinant GnRH peptide to Hsp65 could be considered a promising approach for the development of an efficacious vaccine against the prostate cancer.

Cloning, expression, and purification of a highly immunogenic recombinant gonadotropin-releasing hormone (GnRH) chimeric peptide.

To design an anti-gonadotropin-releasing hormone (GnRH) vaccine capable of eliciting strong immunogenicity, a gene fragment encoding a chimeric peptide was constructed using polymerase chain reaction and ligated into a novel expression vector for recombinant expression in a T7 RNA polymerase-based expression system. The chimeric peptide called GnRH3-hinge-MVP contained three linear repeats of GnRH (GnRH3), a fragment of the human IgG1 hinge region, and a T-cell epitope of measles virus protein (MVP). The expression plasmid contained the GnRH3-hinge-MVP construct ligated to its fusion partner (AnsB-C) via an unique acid labile Asp-Pro linker. The recombinant fusion protein was expressed in an inclusion body in Escherichia coli under IPTG or lactose induction and the target peptide was easily purified using washing of urea and ethanol precipitation. The target chimeric peptide was isolated from the fusion partner following acid hydrolysis and purified using DEAE-Sephacel chromatography. The purified GnRH3-hinge-MVP was determined to be highly homogeneous by IEF analysis and the N-terminal sequencing. Further, immunization of female mice with the recombinant chimeric peptide resulted in generation of high-titer antibodies specific for GnRH. The results showed that GnRH3-hinge-MVP could be considered as a candidate anti-GnRH vaccine.

Stability of plasmid and expression of a recombinant gonadotropin-releasing hormone (GnRH) vaccine in Escherichia coli.

In our previous studies, the recombinant gonadotropin-releasing hormone (GnRH) peptide was constructed into a T7 RNA polymerase-based expression system. The recombinant gene encoding GnRH3-hinge-MVP, which contained three repeated GnRH units, a fragment of hinge region (225-232/225'-232'), and a T cell epitope of measles virus protein, was cloned into Escherichia coli BL21 harboring pED-GnRH3. The high activity of T7 RNA polymerase could make the expression system very powerful for high-level expression of the recombinant protein. However, during the large-scale production of recombinant protein, the productivity of the fermentation process was directly affected by many factors, such as plasmid stability, protein production, and culture conditions. In this study, we studied the effects of various culture conditions on the plasmid stability and the target protein yield including selective pressure, the time of induction by lactose, and the number of successive cultures. The results indicate that the plasmid instability may be caused by a loss of plasmid rather than structural change. However, to go down to future generations, engineered bacteria have the stability of plasmid and protein yield to a large extent. The amount of the fusion protein was also up to 40% of the total cell protein after the 50th generation. These data would be useful for the industrial production of the recombinant GnRH vaccine.