Mendelian randomization analysis reveals no causal relationship between thyroid function and sarcopenia-related traits.

Background: Recent research has indicated a potential association between thyroid function and sarcopenia, but the specific mechanisms and a definitive causal relationship have yet to be established. Therefore, the objective of this study is to examine the potential causal connection between thyroid function and sarcopenia-related traits, including hand-grip strength, appendicular lean mass (ALM), and walking pace. Methods: The study used a bi-directional two-sample MR design, with thyroid function examined as the exposure and sarcopenia-related traits as the outcome in the first stage, and then reversed in the second stage. The genetic instruments for thyroid function were obtained from a comprehensive meta-analysis involving 271,040 participants. Data on sarcopenia-related traits based on GWASs were collected from the UK Biobank, which includes up to 461,026 European participants. The estimates for MR were calculated using the inverse-variance weighted (IVW) method, and several sensitivity analyses were performed. Results: After applying the Bonferroni correction for multiple testing, our MR analyses revealed no significant impact of thyroid function liability on sarcopenia-related traits. Similarly, our reverse MR analysis did not provide evidence supporting the influence of liability to sarcopenia-related traits on thyroid function. The results of the primary IVW MR analyses were largely in line with those obtained from our sensitivity MR analyses. Conclusion: Our research findings do not suggest a link between thyroid function and sarcopenia-related traits. The associations identified in epidemiological studies may be influenced, at least in part, by shared biological mechanisms or environmental confounders.

Benefits of intensive lipid-lowering therapies in patients with acute coronary syndrome: a systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses have investigated the efficacy of lipid-lowering therapies for atherosclerotic cardiovascular disease; however, few have focused on patients with acute coronary syndrome (ACS). This meta-analysis aimed to compare the benefits of intensive lipid-lowering therapy with those of background statin therapy in patients with ACS. METHODS: Searches were performed on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for articles published until April 13, 2023. Randomized controlled trials that compared intensive lipid-lowering therapies and background statin therapies in patients with prior ACS and recorded the outcome of three-point major cardiovascular events (MACE) were included. The risk ratio (RR) with 95% confidence interval (CI) was used as a measure of primary and secondary outcomes. RESULTS: Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83-0.94; p < 0.001), recurrent ACS (RR, 0.82; 95% CI, 0.71-0.96; p = 0.013), nonfatal myocardial infarction (MI) (RR, 0.87; 95% CI, 0.81-0.93; p < 0.001), stroke (RR, 0.83; 95% CI, 0.73-0.94; p = 0.003), and unstable angina-related hospitalization (RR, 0.57; 95% CI, 0.33-0.99; p = 0.046), but not all-cause mortality (RR, 0.94; 95% CI, 0.82-1.07; p = 0.329), cardiovascular disease-related mortality (RR, 0.96; 95% CI, 0.88-1.06; p = 0.457) or coronary revascularization (RR, 0.89; 95% CI, 0.79-1.00; p = 0.057). CONCLUSIONS: Intensive lipid-lowering therapies may reduce the risk of three-point MACE, recurrent ACS, nonfatal MI, stroke, and hospitalization for unstable angina in patients with ACS undergoing background statin therapy. These results may assist in clinical decision-making for the secondary prevention of cardiovascular events to initiate intensive lipid-lowering therapies immediately after ACS.

Nicotinamide riboside restores nicotinamide adenine dinucleotide levels and alleviates brain injury by inhibiting oxidative stress and neuroinflammation in a mouse model of intracerebral hemorrhage.

Hemorrhagic stroke is a global health problem owing to its high morbidity and mortality rates. Nicotinamide riboside is an important precursor of nicotinamide adenine dinucleotide characterized by a high bioavailability, safety profile, and robust effects on many cellular signaling processes. This study aimed to investigate the protective effects of nicotinamide riboside against collagenase-induced hemorrhagic stroke and its underlying mechanisms of action. An intracerebral hemorrhage model was constructed by stereotactically injecting collagenase into the right striatum of adult male Institute for Cancer Research mice. After 30 minutes, nicotinamide riboside was administered via the tail vein. The mice were sacrificed at different time points for assessments. Nicotinamide riboside reduced collagenase-induced hemorrhagic area, significantly reduced cerebral water content and histopathological damage, promoted neurological function recovery, and suppressed reactive oxygen species production and neuroinflammation. Nicotinamide riboside exerts neuroprotective effects against collagenase-induced intracerebral hemorrhage by inhibiting neuroinflammation and oxidative stress.

Screening, identification and evaluation of an acidophilic strain of Bacillus velezensis B4-7 for the biocontrol of tobacco bacterial wilt.

Tobacco (Nicotiana tabacum L.) bacterial wilt, caused by Ralstonia solanacearum, is indeed a highly destructive plant disease, leading to substantial damage in tobacco production. While biological control is considered an effective measure for managing bacterial wilt, related research in this area has been relatively limited compared to other control methods. In order to discover new potential antagonistic bacteria with high biocontrol efficacy against tobacco bacterial wilt, we conducted an analysis of the microbial composition differences between disease-suppressive and disease-conducive soils using Illumina sequencing. As a result, we successfully isolated six strains from the disease-suppressive soil that exhibited antibacterial activity against Ralstonia solanacearum. Among these strains, B4-7 showed the strongest antibacterial activity, even at acidic conditions with a pH of 4.0. Based on genome analysis using Average Nucleotide Identity (ANI), B4-7 was identified as Bacillus velezensis. In greenhouse and field trials, strain B4-7 significantly reduced the disease index of tobacco bacterial wilt, with control efficiencies reaching 74.03% and 46.88% respectively. Additionally, B4-7 exhibited plant-promoting abilities that led to a 35.27% increase in tobacco production in field conditions. Quantitative real-time (qPCR) analysis demonstrated that strain B4-7 effectively reduced the abundance of R. solanacearum in the rhizosphere. Genome sequencing and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis revealed that strain B4-7 potentially produces various lipopeptide metabolites, such as microlactin, bacillaene, difficidin, bacilysin, and surfactin. Furthermore, B4-7 influenced the structure of the rhizosphere soil microbial community, increasing bacterial abundance and fungal diversity, while also promoting the growth of different beneficial microorganisms. In addition, B4-7 enhanced tobacco's resistance to R. solanacearum by increasing the activities of defense enzymes, including superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), peroxidase (POD), catalase (CAT), and polyphenol oxidase (PPO). Collectively, these findings suggest that B. velezensis B4-7 holds significant biocontrol potential and can be considered a promising candidate strain for eco-friendly management of tobacco bacterial wilt.

Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study.

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P＜0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

Visible-Light-Driven NO Release from Postmodified MOFs via Photoinduced Electron Transfer for Antibacterial Application.

Photoresponsive nitric oxide (NO)-releasing materials (NORMs) enable the spatiotemporal delivery of NO to facilitate their potential applications in physiological conditions. Here two novel metal-organic frameworks (MOFs)-based photoactive NORMs achieved by the incorporation of prefunctionalized NO donors into the photosensitive Fe-MOFs via a postmodification strategy is reported. The modified Fe-MOFs display superior photoactivity of NO release when exposed to visible light (up to 720 nm). Significantly, the visible-light-driven NO release properties are further corroborated by their efficient antibacterial performance.

The Multiple Roles of Autophagy in Neural Function and Diseases.

Autophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes, where proteins, lipids, and organelles are degraded and recycled. According to the way the cytoplasmic components are engulfed, autophagy can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy. Recently, many studies have found that autophagy plays an important role in neurological diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, neuronal excitotoxicity, and cerebral ischemia. Autophagy maintains cell homeostasis in the nervous system via degradation of misfolded proteins, elimination of damaged organelles, and regulation of apoptosis and inflammation. AMPK-mTOR, Beclin 1, TP53, endoplasmic reticulum stress, and other signal pathways are involved in the regulation of autophagy and can be used as potential therapeutic targets for neurological diseases. Here, we discuss the role, functions, and signal pathways of autophagy in neurological diseases, which will shed light on the pathogenic mechanisms of neurological diseases and suggest novel targets for therapies.

Preemptive inotuzumab ozogamicin eradicated measurable residual disease in Ph-negative acute lymphoblastic leukemia relapsed post CD19 CART therapy.

There are no reports of application of inotuzumab ozogamicin (InO) for the treatment of MRD in r/r B-ALL. We firstly report the efficacy of InO for a patient experienced morphological relapse after HSCT and molecular relapse after CART therapy.

Analysis of influencing factors and interaction of body weight and disease outcome in patients with prediabetes.

BACKGROUND: The trend of prediabetes progressing to type 2 diabetes mellitus (T2DM) is prominent, and effective intervention can lead to a return to prediabetes. Exploring the factors influencing the outcome of prediabetes is helpful to guide clinical intervention. The weight change in patients with prediabetes has not attracted much attention. AIM: To explore the interaction between body weight and the factors affecting the progression of prediabetes to T2DM. METHODS: We performed a retrospective analysis of 236 patients with prediabetes and 50 with normal glucose tolerance (NGT), and collected clinical data and follow-up results of all patients. Based on natural blood glucose outcomes, we classified 66 patients with progression to T2DM into the disease progression (DP) group, and 170 patients without progression to T2DM into the disease outcome (DO) group. We analyzed the factors that influenced prediabetes outcome and the influence of body weight on prediabetes blood glucose outcome by unconditional logistic regression. A general linear model (univariate) was used to analyze the inter-action between body weight and independent influencing factors. RESULTS: There were 98 cases of impaired fasting glucose (IFG), 90 cases of impaired glucose tolerance (IGT), and 48 cases of coexistent IFG and IGT. The body weight, waist circumference, body mass index, fasting blood glucose, and 2 h plasma glucose of patients with IFG, IGT, and coexistent IFG and IGT were higher than those in patients with NGT (P < 0.05). Logistic regression analysis showed that body weight, glycosylated hemoglobin, uric acid, fasting insulin, and homeostatic model assessment for insulin resistance were independent factors affecting progression of prediabetes to T2DM (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve predicted by the above indicators combined was 0.905 [95% confidence interval (CI): 0.863-0.948], which was greater than that predicted by each indicator alone. Logistic regression analysis with baseline body weight as an independent variable showed that compared with body weight 1, the odds ratio (95%CI) of body weight 3 was 1.399 (1.142-2.126) (P = 0.033). There was a multiplicative interaction between body weight and uric acid (ß = 1.953, P = 0.005). CONCLUSION: High body weight in patients with prediabetes is an independent risk factor for progression to T2DM, and the risk of progression is increased when coexisting with high uric acid level.

Efficacy and mechanism of Wuzi Yanzong pill on the prevention and treatment of EAE.

Objective: Studies have shown that Wuzi Yanzong Pill (WYP) can be used to treat neurological diseases, but its mechanisms for multiple sclerosis (MS) remain unclear. This study aims to determine the effect of WYP on MS in an animal model of experimental autoimmune encephalomyelitis (EAE), and explore its mechanism. To provide theoretical basis for the clinical treatment of MS with WYP. Methods: C57BL/6 female mice were randomly divided into Blank control, EAE control, low dose WYP, medium dose WYP, and high dose WYP groups. One week before model generation, the mice were gavaged with saline (50 mL/kg/d) in Blank control and EAE control groups. The treatment groups was gavaged with different doses of WYP solution (4, 8, or 16 g/kg/d respectively) Clinical scores were recorded daily. Sample collection was conducted on the 14th and 28th days, respectively The expressions of IL-10, IL-17, IL-12, TNF-α and IFN-γ in spleen were detected by ELISA. The expressions of ROCKII, P-MYPT1, TLR4, NF-κB/p65, MCP-1, CCR2 in spleen, brain and spinal cord were detected by Western Blot. The types of macrophages and the contents of intracellular IL-10 and IL-12 were detected by Flow Cytometry. The contents of TNF-α and TLR4 mRNA in the spleen were detected by RT-PCR. Results: WYP treatment improved the clinical score of EAE mice in a significant dose-dependent manner, with the WYP high-dose group showed the most significant improvement in clinical score. Compared with the EAE control group, WYP high dose group had significantly lower levels of IL-17, IFN-γ, ROCKII, P-MYPT1, TLR4, NF-κB/p65, MCP-1, and CCR2 as well as TNF-α and TLR4 mRNA, but increased the number of M2 macrophages and IL-10. Conclusion: WYP treatment relieves clinical symptoms in EAE mice, which may be related to regulate inflammatory pathway and inhibiting expressions of inflammatory cytokines.

Rituximab induces a transient fluctuation of peripheral and follicular helper T cells in neuromyelitis optica spectrum disorder.

Autoreactive CD4+ helper T cells are implicated in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). Both PD-1+CXCR5+CD4+ T follicular helper (Tfh) cells and PD-1+CXCR5-CD4+ T peripheral helper (Tph) cells can contribute to B-cell immune responses and the production of antibodies. Here we show the effect of B-cell depletion with rituximab on the homeostasis of Tfh cells, Tph cells and their subsets in patients with NMOSD. After rituximab treatment, total Tph cells, total Tfh cells, Tph17 cells, Tph17.1 cells, Tph1 cells, and Tfh1 cells tended to decrease at month 1, but gradually increased at month 6 and restored at month 12. Besides, Tph17.1 cells and Tfh17.1 cells were correlated with the proportion of CD19- antibody-secreting cells. Our data suggest that rituximab induced a fluctuation of proinflammatory Tph and Tfh subsets within one year after initiation of the treatment.

Functional Characterization of Pheromone Receptors in the Beet Webworm, Loxostege sticticalis (Lepidoptera: Pyralidae).

Lepidopteran insects mainly rely on sex pheromones to complete sexual communications. Pheromone receptors (PRs) are expressed on the olfactory receptor neurons (ORNs) of the sensilla trichodea and play an essential role in sexual communication. Despite extensive investigations into the mechanisms of peripheral recognition of sex pheromones in Lepidoptera, knowledge about these mechanisms in L. sticticalis remains limited. In this study, five candidate LstiPRs were analyzed in a phylogenetic tree with those of other Lepidopteran insects. Electroantennography (EAG) assays showed that the major sex pheromone component E11-14:OAc elicited a stronger antennal response than other compounds in male moths. Moreover, two types of neurons in sensilla trichodea were classified by single sensillum recordings, of which the "a" neuron specifically responded to E11-14:OAc. Five candidate PRs were functionally assayed by the heterologous expression system of Xenopus oocytes, and LstiPR2 responded to the major sex pheromone E11-14:OAc. Our findings suggest that LstiPR2 is a PR sensitive to L. sticticalis's major sex pheromone compound, E11-14:OAc. Furthermore, this study offers valuable insights into the sexual communication behavior of L. sticticalis, forming a foundation for further analysis of the species' central nervous system.

Effects of naturally occurring S47F/A mutations on the structure and function of human cytochrome c.

The sequence and structure of human cytochrome c (hCyt c) exhibit evolutionary conservations, with only a limited number of naturally occurring mutations in humans. Herein, we investigated the effects of the naturally occurring S47F/A mutations on the structure and function of hCyt c in the oxidized form. Although the naturally occurring S47F/A mutations did not largely alter the protein structure, the S47F and S47A variants exhibited a small fraction of high-spin species. Kinetic studies showed that the peroxidase activity of the variants was enhanced by ∼2.5-fold under neutral pH conditions, as well as for the rate in reaction with H2O2, when compared to those of wild-type hCyt c. In addition, we evaluated the interaction between hCyt c and human neuroglobin (hNgb) by isothermal titration calorimetry (ITC) studies, which revealed that the binding constant was reduced by ∼8-fold as result of the mutation of the hydrophilic Ser to the hydrophobic Phe/Ala. These findings provide valuable insights into the role of Ser47 in Ω-loop C in sustaining the structure and function of hCyt c.

Ultrafast Photocatalytic Detoxification of Mustard Gas Simulants by a Mesoporous Metal-Organic Framework with Dangling Porphyrin Molecules.

Developing effective catalysts to degrade chemical warfare agents is of great significance. Herein, a mesoporous MIL-101(Cr) composite material dangled with porphyrin molecules (denote as TCPP@MIL-101(Cr), TCPP = tetra(4-carboxyphenyl)porphyrin) is reported, which can be used as a heterogeneous photocatalyst for detoxification of mustard gas simulants 2-chloroethyl ethyl sulfide (CEES) to 2-chloroethyl ethyl sulfoxide (CEESO) with a half-life of 1 min. The catalytic performance of TCPP@MIL-101(Cr) is comparable to that of homogeneous molecular porphyrin. Mechanistic studies reveal that both 1 O2 and O2 •- are efficiently generated and play vital roles in the oxidation reaction. Gold nanoparticles (AuNPs) are attached to the TCPP@MIL-101(Cr) to further enhance the catalytic activity with a benchmark half-life of 45 s, which is the fastest record so far. A medical mask loaded TCPP@MIL-101(Cr) is fabricated for practical applications, which can selectively photoxidize CEES to CEESO under sunlight and air atmosphere, exhibiting the best degradation performance among the reported fabric-like composite materials.

Rapid molecular response to dasatinib in Ph-like acute lymphoblastic leukemia patients with ABL1 rearrangements: case series and literature review.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk subtype with a poor prognosis under conventional chemotherapy. Ph-like ALL has a similar gene expression profile to Philadelphia chromosome-positive (Ph+) ALL, but is highly heterogeneous in terms of genomic alterations. Approximately 10-20% of patients with Ph-like ALL harbor ABL class (e.g. ABL1, ABL2, PDGFRB, and CSF1R) rearrangements. Additional genes that form fusion genes with ABL class genes are still being researched. These aberrations result from rearrangements including chromosome translocations or deletions and may be targets of tyrosine kinase inhibitors (TKIs). However, due to the heterogeneity and rarity of each fusion gene in clinical practice, there is limited data on the efficacy of tyrosine kinase inhibitors. Here, we report three cases of Ph-like B-ALL with ABL1 rearrangements treated with the dasatinib backbone for the CNTRL::ABL1, LSM14A::ABL1, and FOXP1::ABL1 fusion genes. All three patients achieved rapid and profound remission with no significant adverse events. Our findings suggest that dasatinib is a potent TKI for the treatment of ABL1-rearranged Ph-like ALL and can be used as a first-line treatment option for such patients.

Highly Boosting Circularly Polarized Luminescence of Chiral Metal-Imidazolate Frameworks.

To develop a simple and general method for improving the circularly polarized luminescence (CPL) performances of materials is of great significance. In this work, two pairs of CPL-active homochiral metal-organic frameworks (MOFs) P/M-Et and P/M-Et(Cd) with eta topology are reported. In comparison to the reported isomorphic Zn-imidazolate MOFs P-Me and M-Me, both luminescence dissymmetry factor (glum ) and photoluminescence quantum yields (ΦPL ) of P-Et and M-Et are largely improved by simply changing the methyl group to an ethyl group of ligands in P-Et and M-Et. Furthermore, the |glum | values are significantly amplified up to 0.015 from 0.0057 by introducing the non-luminescent halogenated aromatics, while an enhanced fluorescence efficiency is observed simultaneously (from 27.2% to 47.3%). The figure of merit value is about 40 times larger than that of P-Me and M-Me. Similarly, the CPL performances of P/M-Et(Cd) are improved by about five times after encapsulating fluorobenzene molecules. This work represents a new and simple method for developing CPL-active MOF materials.

Synergy of Cd Doping and S Vacancies in CdxZn1-xIn2S4 Hierarchical Nanotubes for Highly Improved Visible-Light-Driven H2 Evolution.

Photocatalytic water splitting over semiconductors is believed as a promising avenue to obtain H2 fuel from renewable solar energy. However, developing highly active and non-noble-metal photocatalysts for H2 evolution is still quite challenging to date. In this work, by constructing nanosheet-based nanotubes with Cd-doping and S vacancies, a highly improved visible-light-driven H2 production for ZnIn2S4 is achieved. Unlike nanoflowers aggregated with nanosheets, the nanosheet-assembled hierarchical nanotubes allow multiple scattering and reflection of incident light within the interior space, leading to an enhanced light-harvesting efficiency. Together with the benefits from Cd doping and S-vacancy engineering, including narrowed band gaps, efficient transmission and separation of charge carriers, abundant catalytically active sites, heightened photo-stability and photo-electron reduction capacity, as well as a strong electrostatic attraction to protons, the synthesized S-deficient CdxZn1-xIn2S4 hierarchical nanotubes exhibit an extraordinary photocatalytic H2 evolution capability under visible-light irradiation, delivering an outstanding H2-generation activity of 28.99 mmol·g-1·h-1 (corresponding to an apparent quantum yield of 37.1% at 400 nm), which is much superior to that of CdxZn1-xIn2S4 nanoflowers, Pt-loaded ZnIn2S4 nanotubes, and most ever reported ZnIn2S4-based photocatalysts. Our study could inspire the development of low-cost and high-performance photocatalysts via rational structural design and optimization.

The association between systemic immune-inflammation index and rheumatoid arthritis: evidence from NHANES 1999-2018.

PURPOSE: We aimed to explore the relationship between the systemic immune-inflammation index (SII) and rheumatoid arthritis (RA) using NHANES from 1999 to 2018. METHODS: We collected data from the NHANES database from 1999 to 2018. The SII is calculated from the counts of lymphocytes (LC), neutrophils (NC), and platelets (PC). The RA patients were derived from questionnaire data. We used weighted multivariate regression analysis and subgroup analysis to explore the relationship between SII and RA. Furthermore, the restricted cubic splines were used to explore the non-linear relationships. RESULT: Our study included a total of 37,604 patients, of which 2642 (7.03%) had rheumatoid arthritis. After adjusting for all covariates, the multivariate logistic regression analysis showed that high SII (In-transform) levels were associated with an increased likelihood of rheumatoid arthritis (OR=1.167, 95% CI=1.025-1.328, P=0.020). The interaction test revealed no significant effect on this connection. In the restricted cubic spline regression model, the relationship between ln-SII and RA was non-linear. The cutoff value of SII for RA was 578.25. The risk of rheumatoid arthritis increases rapidly when SII exceeds the cutoff value. CONCLUSION: In general, there is a positive correlation between SII and rheumatoid arthritis. Our study shows that SII is a novel, valuable, and convenient inflammatory marker that can be used to predict the risk of rheumatoid arthritis in US adults.