SOD2 promotes the immunosuppressive function of mesenchymal stem cells at the expense of adipocyte differentiation.

The potent immunomodulatory function of mesenchymal stem/stromal cells (MSCs) elicited by proinflammatory cytokines IFN-γ and TNF-α (IT) is critical to resolve inflammation and promote tissue repair. However, little is known about how the immunomodulatory capability of MSCs is related to their differentiation competency in the inflammatory microenvironment. In this study, we demonstrate that the adipocyte differentiation and immunomodulatory function of human adipose tissue-derived MSCs (MSC(AD)s) are mutually exclusive. Mitochondrial reactive oxygen species (mtROS), which promote adipocyte differentiation, were decreased in MSC(AD)s due to IT-induced upregulation of superoxide dismutase 2 (SOD2). Furthermore, knockdown of SOD2 led to enhanced adipogenic differentiation but reduced immunosuppression capability of MSC(AD)s. Interestingly, the adipogenic differentiation was associated with increased mitochondrial biogenesis and upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A/PGC-1α) expression. IT inhibited PGC-1α expression and decreased mitochondrial mass but promoted glycolysis in an SOD2-dependent manner. MSC(AD)s lacking SOD2 were compromised in their therapeutic efficacy in DSS-induced colitis in mice. Taken together, these findings indicate that the adipogenic differentiation and immunomodulation of MSC(AD)s may compete for resources in fulfilling the respective biosynthetic needs. Blocking of adipogenic differentiation by mitochondrial antioxidant may represent a novel strategy to enhance the immunosuppressive activity of MSCs in the inflammatory microenvironment.

Chimeric antigen receptor-modified macrophages ameliorate liver fibrosis in preclinical models.

BACKGROUND & AIMS: Treatments directly targeting fibrosis remain limited. Given the unique intrinsic features of macrophages and their capacity to engraft in the liver, we genetically engineered bone marrow-derived macrophages with a chimeric antigen receptor (CAR) to direct their phagocytic activity against hepatic stellate cells (HSCs) in multiple mouse models. This study aimed to demonstrate the therapeutic efficacy of CAR macrophages (CAR-Ms) in mouse models of fibrosis and cirrhosis and to elucidate the underlying mechanisms. METHODS: uPAR expression was studied in patients with fibrosis/cirrhosis and in murine models of liver fibrosis, including mice treated with carbon tetrachloride, a 5-diethoxycarbonyl-1, 4-dihydrocollidine diet, or a high-fat/cholesterol/fructose diet. The safety and efficacy of CAR-Ms were evaluated in vitro and in vivo. RESULTS: Adoptive transfer of CAR-Ms resulted in a significant reduction in liver fibrosis and the restoration of function in murine models of liver fibrosis. CAR-Ms modulated the hepatic immune microenvironment to recruit and modify the activation of endogenous immune cells to drive fibrosis regression. These CAR-Ms were able to recruit and present antigens to T cells and mount specific antifibrotic T-cell responses to reduce fibroblasts and liver fibrosis in mice. CONCLUSION: Collectively, our findings demonstrate the potential of using macrophages as a platform for CAR technology to provide an effective treatment option for liver fibrosis. CAR-Ms might be developed for treatment of patients with liver fibrosis. IMPACT AND IMPLICATIONS: Liver fibrosis is an incurable condition that afflicts millions of people globally. Despite the clear clinical need, therapies for liver fibrosis are limited. Our findings provide the first preclinical evidence that chimeric antigen receptor (CAR)-macrophages (CAR-Ms) targeting uPAR can attenuate liver fibrosis and cirrhosis. We show that macrophages expressing this uPAR CAR exert a direct antifibrotic effect and elicit a specific T-cell response that augments the immune response against liver fibrosis. These findings demonstrate the potential of using CAR-Ms as an effective cell-based therapy for the treatment of liver fibrosis.

Genetic characterization and molecular epidemiological analysis of enterovirus C99 in China.

Enterovirus C99 (EV-C99) is a newly identified EV serotype within the species Enterovirus C. Few studies on EV-C99 have been conducted globally. More information and research on EV-C99 are needed to assess its genetic characteristics, phylogenetic relationships, and associations with enteroviral diseases. Here, the phylogenetic characteristics of 11 Chinese EV-C99 strains have been reported. The full-length genomic sequences of these 11 strains show 79.4-80.5% nucleotide identity and 91.7-94.3% amino acid (aa) identity with the prototype EV-C99. A maximum likelihood phylogenetic tree constructed based on the entire VP1 coding region identified 13 genotypes (A-M), revealing a high degree of variation among the EV-C99 strains. Phylogeographic analysis showed that the Xinjiang Uygur Autonomous Region is an important source of EV-C99 epidemics in various regions of China. Recombination analysis revealed inter-serotype recombination events of 16 Chinese EV-C99 strains in 5' untranslated regions and 3D regions, resulting in the formation of a single recombination form. Additionally, the Chinese strain of genotype J showed rich aa diversity in the P1 region, indicating that the genotype J of EV-C99 is still going through variable dynamic changes. This study contributes to the global understanding of the EV-C99 genome sequence and holds substantial implications for the surveillance of EV-C99.

Recent Developments of Nontraditional Single-Molecule Toroics.

Single-molecule toroics (SMTs), defined as a type of molecules with toroidal arrangement of magnetic moment associated with bi-stable non-magnetic ground states, are promising candidates for high-density information storage and the development of molecule based multiferroic materials with linear magneto-electric coupling and multiferroic behavior. The design and synthesis of SMTs by arranging the magnetic anisotropy axis in a circular pattern at the molecular level have been of great interest to scientists for last two decades since the first detection of the SMT behavior in the seminal Dy3 molecules. DyIII ion has long been the ideal candidate for constructing SMTs due to its Kramer ion nature as well as high anisotropy. Nevertheless, other LnIII ions such as TbIII and HoIII ions, as well as some paramagnetic transition metal ions, have also been used to construct many nontraditional SMTs. Therefore, we review the progress in the studies of SMTs based on the nontraditional perspective, ranging from the 3D topological to 1D&2D&3D polymeric SMTs, and 3d-4f to non Dy-based SMTs. We hope the understanding we provide about nontraditional SMTs will be helpful in designing novel SMTs.

Internal Vanadium Doping and External Modification Design of P2-Type Layered Mn-Based Oxides as Competitive Cathodes toward Sodium-Ion Batteries.

P2-type layered manganese-based oxides have attracted considerable interest as economical, cathode materials with high energy density for sodium-ion batteries (SIBs). Despite their potential, these materials still face challenges related to sluggish kinetics and structural instability. In this study, a composite cathode material, Na0.67Ni0.23Mn0.67V0.1O2@Na3V2O2(PO4)2F was developed by surface-coating P2-type Na0.67Ni0.23Mn0.67V0.1O2 with a thin layer of Na3V2O2(PO4)2F to enhance both the electrochemical sodium storage and material air stability. The optimized Na0.67Ni0.23Mn0.67V0.1O2@5wt %Na3V2O2(PO4)2F exhibited a high discharge capacity of 176 mA h g-1 within the 1.5-4.1 V range at a low current density of 17 mA g-1. At an increased current density of 850 mA g-1 within the same voltage window, it still delivered a substantial initial discharge capacity of 112 mAh g-1. These findings validate the significant enhancement of ion diffusion capabilities and rate performance in the P2-type Na0.67Ni0.33Mn0.67O2 material conferred by the composite cathode.

Structural and Property Characterizations of Dual-Responsive Core-Shell Tecto Dendrimers for Tumor Penetration and Gene Delivery Applications.

Core-shell tecto dendrimers (CSTDs) with excellent physicochemical properties and good tumor penetration and gene transfection efficiency have been demonstrated to have the potential to replace high-generation dendrimers in biomedical applications. However, their characterization and related biological properties of CSTDs for enhanced tumor penetration and gene delivery still lack in-depth investigation. Herein, three types of dual-responsive CSTDs are designed for thorough physicochemical characterization and investigation of their tumor penetration and gene delivery efficiency. Three types of CSTDs are prepared through phenylborate ester bonds of phenylboronic acid (PBA)-decorated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers as cores and monose (galactose, glucose, or mannose)-conjugated G3 PAMAM dendrimers as shells and thoroughly characterized via NMR and other techniques. It is shown that the produced CSTDs display strong correlation signals between the PBA and monose protons, similar hydrodynamic diameters, and dual reactive oxygen species- and pH-responsivenesses. The dual-responsive CSTDs are proven to have structure-dependent tumor penetration property and gene delivery efficiency in terms of small interference RNA for gene silencing and plasmid DNA for gene editing, thus revealing a great potential for different biomedical applications.

A nomogram to predict ventricular thrombus in dilated cardiomyopathy patients.

BACKGROUND: VT (Ventricular Thrombus) is a serious complication of dilated cardiomyopathy (DCM). Our goal is to develop a nomogram for personalized prediction of incident VT in DCM patients. METHODS: 1267 patients (52.87 ± 11.75 years old, 73.8% male) were analyzed retrospectively from January 01, 2015, to December 31, 2020. A nomogram model for VT risk assessment was established using minimum absolute contraction and selection operator (LASSO) and multivariate logistic regression analysis, and its effectiveness was validated by internal guidance. The model was evaluated by the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). We compared the performance in predicting VT between nomogram and CHA2DS2, CHA2DS2- VASc or ATRIA by AUC, akaike information criterion (AIC), bayesian information criterion (BIC), net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: 89 patients (7.02%) experienced VT. Multivariate logistic regression analysis revealed that age, left ventricular ejection fraction (LVEF), uric acid (UA), N-terminal precursor B-type diuretic peptide (NT-proBNP), and D-dimer (DD) were important independent predictors of VT. The nomogram model correctly separates patients with and without VT, with an optimistic C score of 0.92 (95%CI: 0.90-0.94) and good calibration (Hosmer-Lemeshow χ2 = 11.51, P = 0.12). Our model showed improved prediction of VT compared to CHA2DS2, CHA2DS2-VASc or ATRIA (all P < 0.05). CONCLUSIONS: The novel nomogram demonstrated better than presenting scores and showed an improvement in predicting VT in DCM patients.

Quantitative evaluation of disc degeneration using dual-energy CT: advantages of R-VH, D-VH values and the IVNCa + CT model.

OBJECTIVE: To evaluate the correlation between dual-energy CT (DECT) virtual calcium free (VNCA), CT attenuation, the ratio and difference of VNCA to CT attenuation, and Pfirrmann grading of lumbar disc degeneration. METHODS: A retrospective analysis on 135 intervertebral discs from 30 patients who underwent DECT and MR. Discs was graded using the Pfirrmann system. ROIs on the sagittal plane assessed HU value, VNCA value, Rho value, Z value, R-VH value, and D-VH value. Correlation, grade differences, and multivariate regression models were assessed. Diagnostic performance and cut-off values were determined using AUC. RESULTS: VNCA (r = 0.589, P < 0.001), R-VH (r = 0.622, P < 0.001), and D-VH (r = 0.613, P < 0.001) moderately correlated with Pfirrmann grading. HU (r = 0.388, P < 0.001), Rho (r = 0.142, P = 0.102), and Z (r = -0.125, P = 0.153) showed a weak correlation. R-VH, D-VH, and VNCA had significantly higher correlation than HU. Statistically significant differences were observed in P values of VNCA, HU, R-VH, and D-VH in relative groups (P < 0.05), but not in Rho and Z values (P > 0.05). R-VH and D-VH had significant differences between Pfirrmann grades 1 and 2, and grades 2 and 3 (early stage) (P < 0.05). AUC readings of R-VH and D-VH (≥2, ≥3, ≥4) were higher. The multivariate model IVNCa + CT had the highest AUC. CONCLUSION: The new quantitative indices R-VH value and D-VH value of DECT have advantages over VNCA value and HU value in evaluating early-stage disc degeneration (≥2 grades, ≥3 grades). The multivariate model IVNCa + CT has the best AUC values for evaluating disc degeneration at all stages.

Combined treatment with cetuximab and STA9090 has synergistic anticancer effects on human non-small cell lung cancer.

Cetuximab (CET), a human murine chimeric IgG monoclonal antibody and an inhibitor of epidermal growth factor receptor (EGFR), has been shown to be effective in treating various types of cancer. However, its use is hindered by limitations such as resistance development, variability in patient response, side effects, and challenges in biomarker identification. Therefore, CET is often combined with other targeted therapies or chemotherapies to enhance its effectiveness. In this study, we investigate the anticancer effects and underlying mechanisms of the combination of CET, an EGFR inhibitor, and STA9090, an inhibitor of heat shock protein 90 (Hsp90), in both in vitro and in vivo models of non-small cell lung cancer (NSCLC). The results demonstrate significantly stronger effects on NSCLC cells in response to combination therapy than to treatment with either agent alone, indicating that the combination of CET and STA9090 has potential synergistic effects. Additionally, the combination therapy inhibits tumor growth in a xenograft nude mouse model more effectively than treatment with either agent alone, suggesting improved efficacy when used together. Furthermore, the synergistic effects of the combination therapy are likely due to inactivation of the receptor tyrosine kinase (RTK) pathway, which is overly activated in cancer and contributes to tumor growth, angiogenesis, and metastasis. Consequently, our findings suggest that STA9090 has potent direct antitumor activity and synergizes with CET against NSCLC tumors. It is highly likely that these synergistic effects are mediated through RTK pathway inactivation caused by the combination. Therefore, our findings strongly and consistently support the potential synergistic effect of STA9090, an RTK inhibitor, in combination with EGFR-targeting agents.

Comparison of two minimally invasive surgical approaches for hypertensive intracerebral hemorrhage: a study based on postoperative intracranial pressure parameters.

BACKGROUND: Increased intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage (HICH) has been associated with poor prognosis. The transsylvian insular approach (TIA) and the transcortical (TCA) approach are applied for patients with HICH. We aimed to compare the postoperative ICP parameters of TIA and TCA to identify which procedure yields better short-term outcomes in patients with basal ganglia hematoma volumes ranging from 30 to 50 mL. METHODS: Eighty patients with basal ganglia hematomas 30-50 mL were enrolled in this study. Patients were implanted with ICP probes and divided into TIA and TCA groups according to the procedure. The ICP values were continuously recorded for five days at four-hour intervals. Short-term outcomes were evaluated using the length of hospitalization and postoperative consciousness recovery time. RESULTS: No statistically significant differences were found in age, sex, GCS score at admission, hematoma volume, and hematoma clearance rate (p > 0.05). The results showed that postoperative initial ICP, ICP on the first postoperative day, mean ICP, DICP20 mmHg × 4 h, postoperative consciousness recovery time, the length of hospitalization, mannitol utilization rate and the mannitol dosage were lower in the TIA group than in the TCA group (p < 0.05). Postoperative consciousness recovery time was positively correlated with ICP on the first postoperative day, and the length of hospitalization was positively correlated with mean ICP. CONCLUSIONS: TIA is more effective than TCA in improving the short-term outcomes of patients with basal ganglia hematoma volumes ranging from 30 to 50 mL according to comparisons of postoperative ICP parameters.

Two new sesquiterpenoid glycoside compounds from the calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino.

Two new sesquiterpenoid glycosides, 8α (H)-eudesmane-1,3,11 (13)-triene-2-one -12-O-ß-D-glucopyranoside (1) and dmetelisproside B (2), together with ten known compounds (3-12) were isolated from calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF). Their structures were unambiguously elucidated through HR-ESI-MS, UV, IR, and NMR spectral data. Compounds 1, 10, and 12 exhibited DPPH scavenging ability with IC50 values of 33.69 ± 6.65, 6.29 ± 0.06, and 25.66 ± 3.06 µM, respectively. Additionally, 10 and 12 demonstrated weak α-glucosidase inhibition activity with IC50 values of 250.9 ± 6.60 and 347.6 ± 2.48 µM, respectively.

[Clinical characteristics of children on prolonged mechanical ventilation due to different primary diseases]. / ä¸åŒåŽŸå‘ç— å¯¼è‡´é•¿æœŸæœºæ¢°é€šæ°”æ‚£å„¿çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation (PMV) due to different primary diseases. METHODS: A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022. According to the primary disease, they were divided into respiratory disease (RD) group, central nervous system (CNS) group, neuromuscular disease (NMD) group, and other disease group. The four groups were compared in terms of general information, treatment, and outcome. RESULTS: There were significant differences among the four groups in age, body weight, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, Pediatric Risk of Mortality III (PRISM Ⅲ) score, analgesic and sedative treatment, nutrition supply, rehabilitation treatment, tracheotomy, successful ventilator weaning, and outcomes (P<0.05). Compared with the RD group, the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment, and the CNS group had a significantly higher proportion of children receiving tracheotomy (P<0.008). Compared with the other disease group, the CNS group and the NMD group had significantly lower PELOD-2 and PRISM III scores, and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged (P<0.008). CONCLUSIONS: There are differences in clinical characteristics among children receiving PMV due to different etiologies. Most children in the RD group have a younger age, and children in the CNS group have a relatively good prognosis.

Effect of maleylation and denaturation of human serum albumin on its interaction with scavenger receptors.

The specific recognition of serum proteins by scavenger receptors is critical and fundamental in many biological processes. However, the underlying mechanism of scavenger receptor-serum protein interaction remains elusive. In this work, taking scavenger receptors class A1 (SR-A1) as an example, we systematically investigate its interaction with human serum albumin (HSA) at different states through a combination of molecular docking and all-atom molecular dynamics simulations. It is found that native HSA can moderately bind to collagen-like (CL) region or scavenger receptor cysteine-rich (SRCR) region, with both electrostatic (ELE) and van der Waals (VDW) interactions, playing important roles. After maleylation, the binding energy, particularly the ELE energy, between HSA and CL region is significantly enhanced, while the binding energy between HSA and SRCR region remains nearly unchanged. Additionally, we also observe that unfolding of the secondary structures in HSA leads to a larger contact surface area between denatured HSA and CL region, but has little impact on the HSA-SRCR region interaction. Therefore, similar to maleylated HSA, denatured HSA is also more likely to bind to the CL region of SR-A1.

Solid-State Synthesis of Aluminophosphate Zeotypes by Calcination of Amorphous Precursors.

Because of the growing interest in the applications of zeolitic materials and the various challenges associated with traditional synthesis methods, the development of novel synthesis approaches remains of fundamental importance. Herein, we report a general route for the synthesis of aluminophosphate (AlPO) zeotypes by simple calcination of amorphous precursors at moderate temperatures (250-450 °C) for short reaction times (3-60 min). Accordingly, highly crystalline AlPO zeotypes with various topologies of AST, SOD, LTA, AEL, AFI, and -CLO, ranging from ultra-small to extra-large pores, have been successfully synthesized. Multinuclear multidimensional solid-state NMR techniques combined with complementary operando mass spectrometry (MS), powder X-ray diffraction, high-resolution transmission electron microscopy, and Raman characterizations reveal that covalently bonded fluoride in the intermediates catalyze the bond breaking and remaking processes. The confined organic structure-directing agents with high thermal stability direct the ordered rearrangement. This novel synthesis strategy not only shows excellent synthesis efficiency in terms of a simple synthesis procedure, a fast crystallization rate, and a high product yield, but also sheds new light on the crystallization mechanism of zeolitic materials.

Colchicine inhibits the proliferation and promotes the apoptosis of papillary thyroid carcinoma cells likely due to the inhibitory effect on HDAC1.

Although the prognosis for papillary thyroid carcinoma (PTC) is generally good, a certain proportion of patients show recurrent or advanced disease, indicating the need for further development of targeted medications. The purpose of this study was to explore the interventional effects of colchicine on PTC and the potential mechanisms or targets. We obtained PTC-related targets from the database and colchicine targets by predicting them. We screened the common targets of colchicine and the PTC-related target histone deacetylase 1 (HDAC1) and verified through molecular docking that colchicine has a good affinity for HDAC1, i.e., colchicine may act on PTC by affecting HDAC1. We then used CCK-8, colony formation, mitochondrial membrane potential and apoptosis assays to confirm that colchicine could inhibit the proliferation and promote the apoptosis of PTC cells and verified by RT‒qPCR, Western blot, and cellular immunofluorescence assays that colchicine could inhibit the expression of HDAC1 in PTC cells. The cytotoxicity and inhibitory effect of colchicine on HDAC1 in PTC cells was stronger than that in normal thyroid cells. We then applied an HDAC1 inhibitor, pyroxamide, to verify that inhibition of HDAC1 inhibits proliferation and promotes apoptosis in PTC cells. Therefore, we conclude that colchicine can inhibit the proliferation and promote the apoptosis of PTC cells likely due to its inhibitory effect on HDAC1. This finding implies that colchicine may be helpful for therapeutic intervention in PTC and that HDAC1 may be a promising clinical therapeutic target.

A scheme for rapid evaluation of the intermolecular three-body polarization effect in water clusters.

The ability to accurately and rapidly evaluate the intermolecular many-body polarization effect of the water system is very important for computer simulations of biomolecule in aqueous. In this paper, a scheme is proposed based on the polarizable dipole-dipole interaction model and used to rapidly estimate the intermolecular many-body polarization effect in water clusters. We use a bond-dipole-based polarization function to evaluate the polarization energy. We regard two OH bonds of a water molecule as two bond-dipoles and set the permanent OH bond-dipole moment of a water molecule to be 1.51 Debye. We estimate the induced OH bond-dipole moment via a simple formula in which only one correction factor is needed. This scheme is then applied to tens of water clusters to calculate the three- and four-body interaction energies. The three-body interaction energies of 93 water clusters produced by our scheme are compared with those produced by the counterpoise-corrected CCSD(T)/aug-cc-pVDZ, MP2/aug-cc-pVDZ, M06-2X/jul-cc-pVTZ methods, by the AMOEBApro13, iAMOEBA, AMOEBA+, AMOEBA+(CF) methods, and by the MB-pol method. The four-body interaction energies of 47 water clusters yielded by our scheme are compared with those yielded by the counterpoise-corrected MP2/aug-cc-pVDZ and M06-2X/ jul-cc-pVTZ methods, by the AMOEBApro13, AMOEBA+, AMOEBA+(CF) methods, and by the MB-pol method. The comparison results show that the scheme proposed in this paper can reproduce the counterpoise-corrected CCSD(T)/aug-cc-pVDZ three-body interaction energies and reproduce the counterpoise-corrected MP2/aug-cc-pVDZ four-body interaction energies both accurately and efficiently. We anticipate the scheme proposed here can be useful for computer simulations of liquid water and aqueous solutions.

Molecular evolution and antigenic drift of type 3 iVDPVs excreted from a patient with immunodeficiency in Ningxia, China.

A 2.5-year-old pediatric patient with acute flaccid paralysis was diagnosed with primary immunodeficiency (PID) in Ningxia Province, China, in 2011. Twelve consecutive stool specimens were collected from the patient over a period of 10 months (18 February 2011 to 20 November 2011), and 12 immunodeficiency vaccine-derived poliovirus (iVDPV) strains (CHN15017-1 to CHN15017-12) were subsequently isolated. Nucleotide sequencing analysis of the plaque-purified iVDPVs revealed 2%-3.5% VP1-region differences from their parental Sabin 3 strain. Full-length genome sequencing showed they were all Sabin 3/Sabin 1 recombinants, sharing a common 2C-region crossover site, and the two key determinants of attenuation (U472C in the 5' untranslated region and T2493C in the VP1 region) had reverted. Temperature-sensitive experiments demonstrated that the first two iVDPV strains partially retained the temperature-sensitive phenotype's nature, while the subsequent ten iVDPV strains distinctly lost it, possibly associated with increased neurovirulence. Nineteen amino-acid substitutions were detected between 12 iVDPVs and the parental Sabin strain, of which only one (K1419R) was found on the subsequent 10 iVDPV isolates, suggesting this site's potential as a temperature-sensitive determination site. A Bayesian Monte Carlo Markov Chain phylogenetic analysis based on the P1 coding region yielded a mean iVDPV evolutionary rate of 1.02 × 10-2 total substitutions/site/year, and the initial oral-polio-vaccine dose was presumably administered around June 2009. Our findings provide valuable information regarding the genetic structure, high-temperature growth sensitivity, and antigenic properties of iVDPVs following long-term evolution in a single PID patient, thus augmenting the currently limited knowledge regarding the dynamic changes and evolutionary pathway of iVDPV populations with PID during long-term global replication.

Chiral All-Nitrogen-Coordinated Dysprosium Single-Molecule Magnets.

Two pairs of chiral end-on azido-bridged dinuclear hexaazamacrocycles, [Dy2 (LN6 R/S )2 (N3 )2 Cl2 ](BPh4 )2 (1R/1S) and [Dy2 (LN6 R/S )2 (N3 )4 ]Cl2 (2R/2S) (LN6 R/S is hexaazamacrocyclic neutral Schiff base ligand derived from 2,6-diformylpyridine and (1R, 2R)/(1S, 2S)-diaminocyclohexane), were constructed by adjusting the molar ratio of sodium azide to Dy(III) macrocycle precursor. Structural analyses reveal that all Dy(III) centers in complexes 1R/1S and 2R/2S are nine-coordinate with hula-loop coordination geometry, and the differences between 1R/1S and 2R/2S are the terminal coordination anion and counter anion. Magnetic studies indicate that complex 2S displays typical SMM behaviors under a zero dc field, whereas 1S just shows slow relaxation of magnetization resulting from a relatively weak axial crystal field. Significantly, complex 2R/2S represents the first homochiral all-nitrogen-coordinated lanthanide single-molecule magnet.

Oral administration of Lactobacillus plantarum JC7 alleviates OVA-induced murine food allergy through immunoregulation and restoring disordered intestinal microbiota.

PURPOSE: The incidence and prevalence of food allergy have sharply risen over the past several decades. Oral administration of probiotic stains has been proven as a safe and effective method to control food allergy. In this study, it aims to comprehensively investigate the anti-allergic effect of Lactobacillus plantarum JC7. METHODS: Balb/c mice were randomly divided into three groups and received OVA (20 µg/mouse, intraperitoneal injection), L. plantarum JC7 (2 × 108 CFU/mouse, intragastric administration) + OVA (20 µg/mouse, intraperitoneal injection) or 0.9% saline (intragastric administration) for 3 weeks. Body weight was monitored weekly, and allergic reactions were evaluated after challenge of OVA. Serum levels of OVA-specific immunoglobulins and various cytokines were tested using ELISA, and the cecum microbiota was analysed by 16S rRNA sequencing to explore the relationships between these indicators and OVA-induced food allergy. Western blotting was used to identify the expression levels of phosphorylated IκBα and nuclear factor kappa B p65. RESULTS: OVA-sensitised mice showed mitigation of respiratory manifestations, alleviation of lung inflammation and congestion, and the presence of an intact intestinal villus structure. Furthermore, OVA-specific immunoglobulin E (IgE), OVA-specific-IgG1, and plasma histamine levels were declined in mice treated with L. plantarum JC7 than in OVA-sensitised mice. In addition, interferon-γ (IFN-γ) and interleukin 10 (IL-10) levels were significantly increased, while IL-4 and IL-17A levels were clearly decreased in mice that had undergone oral administration of L. plantarum JC7, compared with OVA-sensitised mice. These findings indicated imbalances of T helper cell type 1 (Th1)/Th2 and regulatory T cells (Treg)/Th17, which were confirmed by quantitative polymerase chain reaction (PCR). Western blotting demonstrated that the expression levels of phosphorylated IκBα and nuclear factor kappa B p65 were significantly increased in OVA-sensitised mice, but these changes were partly reversed after treatment with L. plantarum JC7. Oral administration of L. plantarum JC7 increased the richness, diversity, and evenness of cecum microbiota, characterised by higher Bacteroidetes abundance and lower Firmicutes abundance. Additionally, the intestinal microbial community composition was significantly altered in the OVA-sensitised group, indicating a disordered intestinal microbiota that was restored by the oral administration of L. plantarum JC7. CONCLUSION: Overall, L. plantarum JC7 can prevent food allergy by rectifying Th1/Th2 and Treg/Th17 imbalances, combined with modifications of disordered intestinal microbiota.

A novel mutation in the TTN gene resulted in left ventricular noncompaction: a case report and literature review.

BACKGROUND: Left ventricular noncompaction (LVNC) is a specific type of cardiomyopathy characterized by coarse trabeculae and interspersed trabecular crypts within the ventricles. Clinical presentation varies widely and may be nonsignificant or may present with progressive heart failure, malignant arrhythmias, and multiorgan embolism. The mode of inheritance is highly heterogeneous but is most commonly autosomal dominant. The TTN gene encodes titin, which is not only an elastic component of muscle contraction but also mediates multiple signalling pathways in striated muscle cells. In recent years, mutations in the TTN gene have been found to be associated with LVNC, but the exact pathogenesis is still not fully clarified. CASE PRESENTATION: In this article, we report a case of an adult LVNC patient with a TTN gene variant, c.87857G > A (p. Trp29286*), that has not been reported previously. This 43-year-old adult male was hospitalized repeatedly for heart failure. Echocardiography showed reduced myocardial contractility, dilated left ventricle with many prominent trabeculae, and a loose texture of the left ventricular layer of myocardium with crypt-like changes. During the out-of-hospital follow-up, the patient had no significant signs or symptoms of discomfort. CONCLUSION: This case report enriches the mutational spectrum of the TTN gene in LVNC and provides a basis for genetic counselling and treatment of this patient. Clinicians should improve their understanding of LVNC, focusing on exploring its pathogenesis and genetic characteristics to provide new directions for future diagnosis and treatment.