Elevated triglycerides and low triiodothyronine: Key risk factors for coronary artery calcification in patients with schizophrenia.

OBJECTIVE: Coronary artery calcification (CAC) is a well-established independent predictor of coronary heart disease, and patients with schizophrenia have significantly higher rates compared to the general population. We performed this study to examine the population-specific risk factors associated with CAC in patients with schizophrenia. METHODS: In this cross-sectional study, patients with schizophrenia who underwent low-dose chest CT scans between January 2020 and December 2021 were analyzed. Ordinary CAC scores and results of routine blood tests were obtained. Logistic regression was used to calculate the odds ratio (OR) for potential risk factors in patients with and without CAC, while the negative binomial additive model was used to explore the dose-response relationship between risk factors and CAC score. RESULTS: Of the 916 patients, 233 (25.4 %) had CAC, while 683 (74.6 %) did not. After adjusting for confounding factors, higher triglyceride levels (OR = 1.20, 95 % confidence interval (CI): 1.04 to 1.38, p = 0.013) and low triiodothyronine levels (OR = 0.50, 95 % CI: 0.29 to 0.84; p = 0.010) were identified as risk factors for CAC. Both triglycerides (p = 0.021) and triiodothyronine (p = 0.010) were also found to have significant dose-response relationships with CAC scores according to the negative binomial additive model in the exploratory analysis. CONCLUSIONS: This study highlights elevated serum triglycerides and decreased triiodothyronine levels as population-specific risk factors for CAC in patients with schizophrenia, suggest the need for close monitoring of CAC in patients with schizophrenia and further prospective trials to provide additional evidence on this topic.

Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A∗02:01 patients with advanced soft tissue sarcoma.

New York esophageal squamous cell carcinoma-1 (NY-ESO-1)-specific T cell receptor (TCR) T cell therapy is effective in tumors with NY-ESO-1 expression, but a safe and effective TCR-T cell therapeutic protocol remains to be improved. Here, we report a phase 1 investigational new drug clinical trial with TCR affinity-enhanced specific T cell therapy (TAEST16001) for targeting NY-ESO-1. Enrolled patients receive TAEST16001 cell infusion after dose-reduced lymphodepletion with cyclophosphamide (15 mg/kg/day × 3 days) combined with fludarabine (20 mg/m2/day × 3 days), and the TCR-T cells are maintained with low doses of interleukin-2 injection post-adoptive transfer. Analysis of 12 patients treated with the regimen demonstrates no treatment-related serious adverse events. The overall response rate is 41.7%. The median progression-free survival is 7.2 months, and the median duration of response is 13.1 months. The protocol of TAEST16001 cells delivers a safe and highly effective treatment for patients with advanced soft tissue sarcoma (ClinicalTrials.gov: NCT04318964).

Machine Learning-Aided Design of Gold Core-Shell Nanocatalysts toward Enhanced and Selective Photooxygenation.

We demonstrate the use of the machine learning (ML) tools to rapidly and accurately predict the electric field as a guide for designing core-shell Au-silica nanoparticles to enhance 1O2 sensitization and selectivity of organic synthesis. Based on the feature importance analysis, obtained from a deep neural network algorithm, we found a general and linear dependent descriptor (θ ∝ aD0.25t-1, where a, D, and t are the shape constant, size of metal nanoparticles, and distance from the metal surface) for the electric field around the core-shell plasmonic nanoparticle. Directed by the new descriptor, we synthesized gold-silica nanoparticles and validated their plasmonic intensity using scanning transmission electron microscopy-electron energy loss spectroscopy (STEM-EELS) mapping. The nanoparticles with θ = 0.40 demonstrate an ∼3-fold increase in the reaction rate of photooxygenation of anthracene and 4% increase in the selectivity of photooxygenation of dihydroartemisinic acid (DHAA), a long-standing goal in organic synthesis. In addition, the combination of ML and experimental investigations shows the synergetic effect of plasmonic enhancement and fluorescence quenching, leading to enhancement for 1O2 generation. Our results from time-dependent density functional theory (TD-DFT) calculations suggest that the presence of an electric field can favor intersystem crossing (ISC) of methylene blue to enhance 1O2 generation. The strategy reported here provides a data-driven catalyst preparation method that can significantly reduce experimental cost while paving the way for designing photocatalysts for organic drug synthesis.

Improved Safety of Hybrid Electroconvulsive Therapy Compared With Standard Electroconvulsive Therapy in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Parallel-Group Pilot Trial.

Objectives: ECT is a rapid and effective treatment for depression. While efficacy is often remarkable over the initial 3-4 sessions, the efficacy of later sessions is less rapid, and the side-effects, especially cognitive impairment limit its use. To preliminarily compare the efficacy and acceptability of a novel hybrid-ECT (HECT) protocol for patients with major depressive disorder (MDD) with standard ECT, we conducted this pilot trial. Methods: Thirty patients were randomly assigned to ECT or HECT. Both arms received three ECT sessions (phase 1) but, in phase 2, the HECT arm received low-charge electrotherapy instead of ECT. The primary outcome was the change in 24-item Hamilton depression rating scale (HAMD-24) scores between baseline and the end of treatment. Cognitive function was assessed by repeatable battery for the assessment of neuropsychological status (RBANS), Stroop color word, and orientation recovery tests (ORT). Safety was measured by the drop-out rate and adverse events (AEs). Four visits were conducted at baseline, post-phase 1, post-phase 2, and at 1-month follow-up. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/), identifier: ChiCTR1900027701. Results: Patients in both arms showed significant within-group improvements in HAMD-24, but the between-group differences were non-significant. Participants in the HECT arm outperformed ECT patients for most cognitive tests at the end of treatment or at follow-up. There was a significantly lower AE rate and shorter ORT in phase 2 of the HECT ar. Conclusion: In this pilot trial, HECT was associated with fewer AEs and better cognitive function including executive and memory function, but its possible similar antidepressive efficacy needs to be further investigated in future.

Conductive Hydrogel Conduits with Growth Factor Gradients for Peripheral Nerve Repair in Diabetics with Non-Suture Tape.

Diabetic patients suffer from peripheral nerve injury with slow and incomplete regeneration owing to hyperglycemia and microvascular complications. This study develops a graphene-based nerve guidance conduit by incorporating natural double network hydrogel and a neurotrophic concentration gradient with non-invasive treatment for diabetics. GelMA/silk fibroin double network hydrogel plays quadruple roles for rapid setting/curing, suitable mechanical supporting, good biocompatibility, and sustainable growth factor delivery. Meanwhile, graphene mesh can improve the toughness of conduit and enhance conductivity of conduit for regeneration. Here, novel silk tapes show quick and tough adhesion of wet tissue by dual mechanism to replace suture step. The in vivo results demonstrate that gradient concentration of netrin-1 in conduit have better performance than uniform concentration caused by chemotaxis phenomenon for axon extension, remyelination, and angiogenesis. Altogether, GelMA/silk graphene conduit with gradient netrin-1 and dry double-sided adhesive tape can significantly promote repairing of peripheral nerve injury and inhibit the atrophy of muscles for diabetics.

Aqueous Protein-Polymer Bioconjugation via Photoinduced RAFT Polymerization Using High Loading Heterogeneous Catalyst.

Light-driven polymerization, such as photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization, enables biological benign conditions and versatile functional polymer structure design, which is readily used in protein-polymer bioconjugates. However, conventional metalloporphyrinic homogeneous catalysts for PET-RAFT polymerization suffer from limited aqueous solubility and tedious purification. Here we demonstrate the design of PET-RAFT photocatalyst from the reticular assembled Zr-porphyrinic metal-organic frameworks (MOFs), along with a biomacromolecule-based chain transfer agent, as efficient bioconjugation tools in water. Our methodology offers manufacturing advantages on bioconjugates under mild conditions such that MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and cytotoxicity assays have shown the preservation of the protein integrity, bioactivity, and high cell viability after PET-RAFT polymerization. We find that the fast kinetics are benefiting from the ultrahigh loading of metalloporphyrins in MOF-525-Zn. This heterogeneous catalyst also allows us to maintain living characteristics to incorporate myriads of monomers into block copolymers. Other advantages like easy postreaction purification, reusability, and high oxygen tolerance even in an open system are demonstrated. This study provides a tool of highly efficient heterogeneous photocatalysts for polymer-protein bioconjugation in aqueous media and paves the road for biological applications.

Simultaneous silencing of TGF-ß1 and COX-2 reduces human skin hypertrophic scar through activation of fibroblast apoptosis.

Excessive skin scars due to elective operations or trauma represent a challenging clinical problem. Pathophysiology of hypertrophic scars entails a prolonged inflammatory and proliferative phase of wound healing. Over expression of TGF-ß1 and COX-2 play key regulatory roles of the aberrant fibrogenic responses and proinflammatory mediators. When we silenced TGF-ß1 and COX-2 expression simultaneously in primary human fibroblasts, a marked increase in the apoptotic cell population occurred in contrast to those only treated with either TGF-ß1 or COX-2 siRNA alone. Furthermore, using human hypertrophic scar and skin graft implant models in mice, we observed significant size reductions of the implanted tissues following intra-scar administration of TGF-ß1/COX-2 specific siRNA combination packaged with Histidine Lysine Polymer (HKP). Gene expression analyses of those treated tissues revealed silencing of the target gene along with down regulations of pro-fibrotic factors such as α-SMA, hydroxyproline acid, Collagen 1 and Collagen 3. Using TUNEL assay detection, we found that the human fibroblasts in the implanted tissues treated with the TGF-ß1/COX-2siRNAs combination exhibited significant apoptotic activity. Therefore we conclude that a synergistic effect of the TGF-ß1/COX-2siRNAs combination contributed to the size reductions of the hypertrophic scar implants, through activation of fibroblast apoptosis and re-balancing between scar tissue deposition and degradation.