Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia.

BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Crystal-Rigidifying Strategy in Hybrid Manganese Halide to Achieve Narrow Green Emission and High Structural Stability.

Although organic-inorganic hybrid Mn2+ halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C-H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4 [BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4 display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor ß-SiAlON:Eu2+ and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2- units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron-phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4 realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+ halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.

Relationship between neonatal respiratory distress syndrome pulmonary ultrasonography and respiratory distress score, oxygenation index, and chest radiography grading.

BACKGROUND: Accurate condition assessment is critical for improving the prognosis of neonatal respiratory distress syndrome (RDS), but current assessment methods for RDS pose a cumulative risk of harm to neonates. Thus, a less harmful method for assessing the health of neonates with RDS is needed. AIM: To analyze the relationships between pulmonary ultrasonography and respiratory distress scores, oxygenation index, and chest X-ray grade of neonatal RDS to identify predictors of neonatal RDS severity. METHODS: This retrospective study analyzed the medical information of 73 neonates with RDS admitted to the neonatal intensive care unit of Liupanshui Maternal and Child Care Service Center between April and December 2022. The pulmonary ultrasonography score, respiratory distress score, oxygenation index, and chest X-ray grade of each newborn before and after treatment were collected. Spearman correlation analysis was performed to determine the relationships among these values and neonatal RDS severity. RESULTS: The pulmonary ultrasonography score, respiratory distress score, oxygenation index, and chest X-ray RDS grade of the neonates were significantly lower after treatment than before treatment (P < 0.05). Spearman correlation analysis showed that before and after treatment, the pulmonary ultrasonography score of neonates with RDS was positively correlated with the respiratory distress score, oxygenation index, and chest X-ray grade (ρ = 0.429-0.859, P < 0.05). Receiver operating characteristic curve analysis indicated that pulmonary ultrasonography screening effectively predicted the severity of neonatal RDS (area under the curve = 0.805-1.000, P < 0.05). CONCLUSION: The pulmonary ultrasonography score was significantly associated with the neonatal RDS score, oxygenation index, and chest X-ray grade. The pulmonary ultrasonography score was an effective predictor of neonatal RDS severity.

Evaluation of pathological response to neoadjuvant chemotherapy in locally advanced cervical cancer.

Neoadjuvant chemotherapy (NACT) is a viable therapeutic option for women diagnosed locally advanced cervical cancer (LACC). However, the factors influencing pathological response are still controversial. We collected pair specimens of 185 LACC patients before and after receiving NACT and conducted histological evaluation. 8 fresh tissues pre-treatment were selected from the entire cohort to conducted immune gene expression profiling. A novel pathological grading system was established by comprehensively assessing the percentages of viable tumor, inflammatory stroma, fibrotic stroma, and necrosis in the tumor bed. Then, 185 patients were categorized into either the good pathological response (GPR) group or the poor pathological response (PPR) group post-NACT, with 134 patients (72.4%, 134/185) achieving GPR. Increasing tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating lymphocytes volume (TILV) pre-treatment were correlated with GPR, with TILV emerging as an independent predictive factor for GPR. Additionally, CIBERSORT analysis revealed noteworthy differences in the expression of immune makers between cPR and non-cPR group. Furthermore, a significantly heightened density of CD8 + T cells and a reduced density of FOXP3 + T cells were observed in GPR than PPR. Importantly, patients exhibiting GPR or inflammatory type demonstrated improved overall survival and disease-free survival. Notably, stromal type was an independent prognostic factor in multivariate analysis. Our study indicates the elevated TILV in pre-treatment specimens may predict a favorable response to NACT, while identifying stromal type in post-treatment specimens as an independent prognostic factor. Moreover, we proposed this pathological grading system in NACT patients, which may offer a more comprehensive understanding of treatment response and prognosis.

Inducing and Switching the Handedness of Polyacetylenes with Topologically Chiral [2]Catenane Pendants.

To explore the chirality induction and switching of topological chirality, poly[2]catenanes composed of helical poly(phenylacetylenes) (PPAs) main chain and topologically chiral [2]catenane pendants are described for the first time. These poly[2]catenanes with optically active [2]catenanes on side chains were synthesized by polymerization of enantiomerically pure topologically chiral [2]catenanes with ethynyl polymerization site and/or point chiral moiety. The chirality information of [2]catenane pendants was successfully transferred to the main chain of polyene backbones, leading to preferred-handed helical conformations, while the introduction of point chiral units has negligible effect on the overall helices. More interestingly, attributed to unique dynamic feature of the [2]catenane pendants, these polymers revealed dynamic response behaviors to solvents, temperature, and sodium ions, resulting in the fully reversible switching on/off of the chirality induction. This work provides not only new design strategy for novel chiroptical switches with topologically chiral molecules but also novel platforms for the development of smart chiral materials.

Chiral Brønsted Acid-Catalyzed Asymmetric Reaction via Vinylidene ortho-Quinone Methides.

Vinylidene ortho-quinone methides (VQMs) have been proven to be versatile and crucial intermediates in the catalytic asymmetric reaction in last decade, and thus have drawn considerable concentrations on account of the practical application in the construction of enantiomerically pure functional organic molecules. However, in comparison to the well established chiral Brønsted base-catalyzed asymmetric reaction via VQMs, chiral Brønsted acid-catalyzed reaction is rarely studied and there is no systematic summary to date. In this review, we summarize the recent advances in the chiral Brønsted acid-catalyzed asymmetric reaction via VQMs according to three types of reactions: a) intermolecular asymmetric nucleophilic addition to VQMs; b) intermolecular asymmetric cycloaddition of VQMs; c) intramolecular asymmetric cyclization of VQMs. Finally, we put forward the remained challenges and opportunities for potential breakthroughs in this area.

Long-term outcomes and predictive factors of achieving low disease activity status in childhood systemic lupus erythematosus: a Chinese bicentric retrospective registered study.

Background: This study aims to explore the clinical value of low disease activity state (LDAS) in the treat-to-target strategy of pediatric systemic lupus erythematosus (pSLE) and find the risk factors for never reaching LDAS. Methods: A total of 272 children with SLE who were diagnosed and followed up in two tertiary hospitals in China during the period from January 2012 to December 2019 were involved in this study, and the clinical presentation, pathology, and treatment were retrospectively studied. Results: The male-to-female ratio was 1:5.2, the age at diagnosis was 11.1 years (IQR, 9.8-13.1 years), the disease duration was 1.0 month (IQR, 0.5-2.0 months), and follow-up was 36.5 months (IQR, 25.7-50.9 months). During follow-up, 230 children achieved LDAS, and 42 were never been in. Male (P = 0.018), mucosal ulcer (P = 0.048), liver function damage (P = 0.026), cardiac effusion (P = 0.034), anemia (P = 0.048), urine red blood cells (P = 0.017), urinary leukocytes (P = 0.032), and endothelial cell proliferation in renal biopsy (P = 0.004)-these indexes have statistical differences between the two groups in the baseline. At baseline, endothelial cell proliferation (P = 0.02) is an independent risk factor for never achieving LDAS by multivariate logistic analysis. During follow-up, non-compliance was a risk factor for never achieving LDAS by comparing between groups. Children with biologics achieved LDAS at a higher rate than children without biologics (P = 0.038). The proportion of organ damage in patients never been in LDAS was significantly higher than that in patients who achieved LDAS (P < 0.001). Conclusion: Endothelial cell proliferation in renal biopsy and non-compliance during follow-up were independent risk factors for never achieving LDAS. At the end of the follow-up, the organ damage in the remission group was similar to that in the LDAS group, indicating that LDAS can be used as a target for pSLE treatment.

Supramolecular DNA nanogels through host-guest interaction for targeted drug delivery.

DNA hydrogels have been demonstrated with the advantages of good stability, easy modification, and extraordinary biocompatibility, which enables their great application prospects in biosensing, tissue engineering, and biomedicine. Based on the host-guest recognition properties of cucurbit[8]uril (CB[8]), we proposed a general method for constructing functional supramolecular DNA nanogels. Guest molecules have been conjugated into the DNA building units, which could be further crosslinked with CB[8] to construct supramolecular DNA nanogels. At the same time, the aptamer has also been modified into the hydrogel network to achieve cell targeting. These supramolecular DNA nanogels have been demonstrated with a controllable size and multiple stimuli responses, in addition to the excellent biocompatibility, stability and good targeting drug transport ability. Such a host-guest based strategy will provide a molecular library as a "toolbox" for the functionalization of DNA nanogels.

Topological phases, local magnetic moments, and spin polarization triggered by C558-line defects in armchair graphene nanoribbons.

The topological and magnetic properties induced by topological defects in graphene have attracted attention. Here, we study a novel topological defect structure for graphene nanoribbons interspersed with C558-line defects along the armchair boundary, which possesses topological properties and is tritopic. Using strain engineering to regulate the magnitude of hopping at defects, the position of the energy level can be easily changed to achieve a topological phase transition. We also discuss the local magnetic moment and the ferromagnetic ground state in the context of line defects. This leads to spin polarization of the whole system. Finally, when C558 graphene nanoribbons are controlled by a nonlocal exchange magnetic field, spin-polarized quantum conductivity occurs near the Fermi level. Consequently, spin filtering can be achieved by varying the incident energy of the electrons. Our results provide new insights into realizing topological and spin electronics in low-dimensional quantum devices.

Chemodynamic therapy combined with endogenous ferroptosis based on "sea urchin-like" copper sulfide hydrogel for enhancing anti-tumor efficacy.

Chemodynamic therapy (CDT) is a promising strategy for cancer treatment, however, its application is restricted by low hydrogen peroxide (H2O2) concentration, insufficient reactive oxygen species (ROS) generation, and high glutathione (GSH) levels. Here, we developed an injectable thermosensitive hydrogel (DSUC-Gel) based on "sea urchin-like" copper sulfide nanoparticles (UCuS) loaded with dihydroartemisinin (DHA) and sulfasalazine (SAS) to overcome these limitations of CDT. DSUC was cleaved to release DHA, SAS and Cu2+ under acidic tumor microenvironment to enhance CDT. DHA with peroxide bridge responded to intracellular Fe2+ to alleviate H2O2 deficiency. SAS prevented GSH synthesis by targeting SLC7A11 and inhibited glutathione peroxidase (GPX4) activity to induce endogenous ferroptosis. ROS produced by Fenton-like reaction of Cu2+ promoted lipid peroxidation (LPO) accumulation to promote ferroptosis. Enhanced CDT and ferroptosis induced immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation and cytotoxic T lymphocytes (CTLs) infiltration. As a result, DSUC-Gel significantly inhibited tumor growth both in vitro and in vivo. Our study provides a novel approach for enhancing anti-tumor efficacy by combining CDT, endogenous ferroptosis and ICD.

Unraveling the Origin of Multichannel Circularly Polarized Luminescence in a Pyrene-Functionalized Topologically Chiral [2]Catenane.

Mechanically interlocked molecules (MIMs) are promising platforms for developing functionalized artificial molecular machines. The construction of chiral MIMs with appealing circularly polarized luminescence (CPL) properties has boosted their potential application in biomedicine and the optical industry. However, there is currently little knowledge about the CPL emission mechanism or the emission dynamics of these related MIMs. Herein, we demonstrate that time-resolved circularly polarized luminescence (TRCPL) spectroscopy combined with transient absorption (TA) spectroscopy offers a feasible approach to elucidate the origins of CPL emission in pyrene-functionalized topologically chiral [2]catenane as well as in a series of pyrene-functionalized chiral molecules. For the first time, direct evidence differentiating the chiroptical signals originating from either topological (local state emission) or Euclidean chirality (excimer state emission) in these pyrene-functionalized chiral molecules has been discovered. Our work not only establishes a novel and ideal approach to study CPL mechanism, but also provides a theoretical foundation for the rational design of novel chiral materials in the future.

A Redox-active Phenothiazine-based Pd2L4-type Coordination Cage and Its Isolable Crystalline Polyradical Cations.

Polyradical cages are of great interest because they show very fascinating physical and chemical properties, but many challenges remain, especially for their synthesis and characterization. Herein, we present the synthesis of a polyradical cation cage 14•+ through post-synthetic oxidation of a redox-active phenothiazine-based Pd2L4-type coordination cage 1. It's worth noting that 1 exhibits excellent reversible electrochemical and chemical redox activity due to the introduction of a bulky 3,5-di-tert-butyl-4-methoxyphenyl substituent. The generation of 14•+ through reversible electrochemical oxidation is investigated by in situ UV-vis-NIR and EPR spectroelectrochemistry. Meanwhile, chemical oxidation of 1 can also produce 14•+ which can be reversibly reduced back to the original cage 1, and the process is monitored by EPR and NMR spectroscopies. Eventually, we succeed in the isolation and single crystal X-ray diffraction analysis of 14•+, whose electronic structure and conformation are distinct to original 1. The magnetic susceptibility measurements indicate the predominantly antiferromagnetic interactions between the four phenothiazine radical cations in 14•+. We believe that our study including the facile synthesis methodology and in situ spectroelectrochemistry will shed some light on the synthesis and characterization of novel polyradical systems, opening more perspectives for developing functional supramolecular cages.

The association between triglyceride glucose-body mass index and all-cause and cardiovascular mortality in diabetes patients: a retrospective study from NHANES database.

The triglyceride glucose body mass index (TyG-BMI) is a potential indicator for insulin resistance, but its association with mortality in diabetic patients is unclear. This study investigates the relationship between TyG-BMI and all-cause and cardiovascular mortality in diabetics. The study included 3109 diabetic patients from the National Health and Nutrition Examination Survey (2001-2018). Mortality data were obtained from National Death Index records until 31 December 2019. Multivariate Cox models analyzed the association between TyG-BMI and mortality. Non-linear correlations were assessed using restricted cubic splines, and a two-piecewise Cox model evaluated the relationship on both sides of the inflection point. Over a median 7.25-year follow-up, 795 total and 238 cardiovascular deaths occurred. A U-shaped link was found between initial TyG-BMI and mortality in diabetic patients. Low TyG-BMI (< 279.67 for all-cause, < 270.19 for CVD) reduced death risks (all-cause: HR 0.77, 95% CI 0.69-0.86; CVD: HR 0.64, 95% CI 0.48-0.86). High TyG-BMI (> 279.67 for all-cause, > 270.19 for CVD) increased these risks (all-cause: HR 1.26, 95% CI 1.10-1.44; CVD: HR 1.33, 95% CI 1.06-1.68). In the NHANES study population, a U-shaped association was observed between the baseline TyG-BMI index and all-cause mortality or CVD in diabetic patients.

Metabolomics unveil key pathways underlying the synergistic activities of aztreonam and avibactam against multidrug-resistant Escherichia coli.

PURPOSE: Aztreonam/avibactam is effective against serious infections caused by Gram-negative bacteria including Enterobacterales harboring metallo-ß-lactamases. While the utility of this combination has been established in vitro and in clinical trials, the purpose of this study is to enhance our understanding of the underlying mechanism responsible for their activities through metabolomic profiling of a multidrug-resistant Escherichia coli clinical isolate. METHODS: Metabolomic analyses of time-dependent changes in endogenous bacterial metabolites in a clinical isolate of a multidrug-resistant E. coli treated with aztreonam and avibactam were performed. E. coli metabolomes were compared at 15 min, 1 h and 24 h following treatments with either avibactam (4 mg/L), aztreonam (4 mg/L), or aztreonam (4 mg/L) + avibactam (4 mg/L). RESULTS: Drug treatment affected 326 metabolites with magnitude changes of at least 2-fold, most of which are involved primarily in peptidoglycan biosynthesis, nucleotide metabolism, and lipid metabolism. The feedstocks for peptidoglycan synthesis were depleted by aztreonam/avibactam combination; a significant downstream increase in nucleotide metabolites and a release of lipids were observed at the three timepoints. CONCLUSION: The findings indicate that the aztreonam/avibactam combination accelerates structural damage to the bacterial membrane structure and their actions were immediate and sustained compared to aztreonam or avibactam alone. By inhibiting the production of crucial cell wall precursors, the combination may have inflicted damages on bacterial DNA.

A review of the leaf-beetle genus Sinoluperus Gressitt & Kimoto, 1963 (Coleoptera, Chrysomelidae, Galerucinae) from China, with the description of a new species.

In this study, all species of the leaf-beetle genus Sinoluperus Gressitt & Kimoto, 1963 from China are redescribed based on the reexamination of type specimens, and a new species, S.variegatussp. nov. from Nanling Mountains, is described. A key to the three Chinese species of Sinoluperus is provided, as well as photographs of the habiti and aedeagi of these species.

Tuning vibration-induced emission through macrocyclization and catenation.

In order to investigate the effect of macrocyclization and catenation on the regulation of vibration-induced emission (VIE), the typical VIE luminogen 9,14-diphenyl-9,14-dihydrodibenzo[a, c]phenazine (DPAC) was introduced into the skeleton of a macrocycle and corresponding [2]catenane to evaluate their dynamic relaxation processes. As investigated in detail by femtosecond transient absorption (TA) spectra, the resultant VIE systems revealed precisely tunable emissions upon changing the solvent viscosity, highlighting the key effect of the formation of [2]catenane. Notably, the introduction of an additional pillar[5]arene macrocycle featuring unique planar chirality endows the resultant chiral VIE-active [2]catenane with attractive circularly polarized luminescence in different states. This work not only develops a new strategy for the design of new luminescent systems with tunable vibration induced emission, but also provides a promising platform for the construction of smart chiral luminescent materials for practical applications.

Coordination cages integrated into swelling poly(ionic liquid)s for guest encapsulation and separation.

Coordination cages have been widely reported to bind a variety of guests, which are useful for chemical separation. Although the use of cages in the solid state benefits the recycling, the flexibility, dynamicity, and metal-ligand bond reversibility of solid-state cages are poor, preventing efficient guest encapsulation. Here we report a type of coordination cage-integrated solid materials that can be swelled into gel in water. The material is prepared through incorporation of an anionic FeII4L6 cage as the counterion of a cationic poly(ionic liquid) (MOC@PIL). The immobilized cages within MOC@PILs have been found to greatly affect the swelling ability of MOC@PILs and thus the mechanical properties. Importantly, upon swelling, the uptake of water provides an ideal microenvironment within the gels for the immobilized cages to dynamically move and flex that leads to excellent solution-level guest binding performances. This concept has enabled the use of MOC@PILs as efficient adsorbents for the removal of pollutants from water and for the purification of toluene and cyclohexane. Importantly, MOC@PILs can be regenerated through a deswelling strategy along with the recycling of the extracted guests.

Copper-Catalyzed [3 + 2] Annulation of O-Acyl Oximes with 4-Sulfonamidophenols for the Synthesis of 5-Sulfonamidoindoles and 2-Amido-5-sulfonamidobenzofuran-3(2H)-ones.

A copper-catalyzed [3 + 2] annulation of O-acyl oximes with 4-sulfonamidophenols is developed. The advantage of this method lies in the concurrent double activation of two substrates to form nucleophilic enamines and electrophilic quinone monoimines. The substituent on the α-carbon of O-acyl oxime determines two different reaction pathways, thereby leading to the selective generation of 5-sulfonamidoindoles and 2-amido-5-sulfonamidobenzofuran-3(2H)-ones.

Supramolecular cage-mediated cargo transport.

A steady stream of material transport based on carriers and channels in living systems plays an extremely important role in normal life activities. Inspired by nature, researchers have extensively applied supramolecular cages in cargo transport because of their unique three-dimensional structures and excellent physicochemical properties. In this review, we will focus on the development of supramolecular cages as carriers and channels for cargo transport in abiotic and biological systems over the past fifteen years. In addition, we will discuss future challenges and potential applications of supramolecular cages in substance transport.

Antiviral C-geranylated flavonoids from Artocarpus communis.

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.