Risk of secondary immune thrombocytopenia following alemtuzumab treatment for multiple sclerosis: a systematic review and meta-analysis.

Object: The purpose of this study was to evaluate the risk of secondary immune thrombocytopenia in multiple sclerosis patients treated with alemtuzumab through a meta-analysis. Methods: We searched databases including PubMed, Web of Science, OVID and EMBASE for studies reporting changes in platelet levels in MS patients treated with alemtuzumab from their inception until May 2023 and performed a meta-analysis. Information and data were screened and extracted by two researchers. The inclusion and exclusion criteria were established according to the PICOS principle. The obtained data were analyzed using the R software meta package and the quality assessment was conducted using Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger test. Results: A total of 15 studies were included, encompassing 1,729 multiple sclerosis patients. Meta-analysis of overall secondary ITP in the included studies yielded a pooled rate of 0.0243. The overall incidence of secondary autoimmune events was 0.2589. In addition, subgroup analysis was applied using study regions and study types. The results showed that the incidence rate of secondary ITP in Europe was about 0.0207, while the incidence of autoimmune events (AEs) was 0.2158. The incidence rate of secondary ITP and AEs in North America was significantly higher than in Europe, being 0.0352 and 0.2622. And the analysis showed that the incidence rates of secondary ITP and AEs in prospective studies were 0.0391 and 0.1771. Retrospective studies had an incidence rate of secondary ITP at 2.16, and an incidence rate of AEs at 0.2743. Conclusion: This study found that there was a certain incidence of Immune thrombocytopenia in multiple sclerosis patients after treatment with alemtuzumab. Alemtuzumab may have some interference with platelet levels, and the mechanism may be associated with Treg cells. But due to the absence of a control group in the included literature, we cannot determine the specific impact of Alemtuzumab on platelet levels in patients with MS. Therefore, clinical physicians should perform a comprehensive assessment of the patient's benefit-to-risk ratio before initiating alemtuzumab. Systematic Review Registration: Inplasy website, DOI number is 10.37766/inplasy2024.3.0007.

Aging under endocrine hormone regulation.

Aging is a biological process in which the environment interacts with the body to cause a progressive decline in effective physiological function. Aging in the human body can lead to a dysfunction of the vital organ systems, resulting in the onset of age-related diseases, such as neurodegenerative and cardiovascular diseases, which can seriously affect an individual's quality of life. The endocrine system acts on specific targets through hormones and related major functional factors in its pathways, which play biological roles in coordinating cellular interactions, metabolism, growth, and aging. Aging is the result of a combination of many pathological, physiological, and psychological processes, among which the endocrine system can achieve a bidirectional effect on the aging process by regulating the hormone levels in the body. In this paper, we explored the mechanisms of growth hormone, thyroid hormone, and estrogen in the aging process to provide a reference for the exploration of endocrine mechanisms related to aging.

L-Theanine and Immunity: A Review.

L-theanine (N-ethyl-γ-glutamine) is the main amino acid in tea leaves. It not only contributes to tea flavor but also possesses several health benefits. Compared with its sedative and calming activities, the immunomodulatory effects of L-theanine have received less attention. Clinical and epidemiological studies have shown that L-theanine reduces immunosuppression caused by strenuous exercise and prevents colds and influenza by improving immunity. Numerous cell and animal studies have proven that theanine plays an immunoregulatory role in inflammation, nerve damage, the intestinal tract, and tumors by regulating γδT lymphocyte function, glutathione (GSH) synthesis, and the secretion of cytokines and neurotransmitters. In addition, theanine can be used as an immunomodulator in animal production. This article reviews the research progress of L-theanine on immunoregulation and related mechanisms, as well as its application in poultry and animal husbandry. It is hoped that this work will be beneficial to future related research.

Zinc-Doping Strategy on P2-Type Mn-Based Layered Oxide Cathode for High-Performance Potassium-ion Batteries.

Mn-based layered oxide is extensively investigated as a promising cathode material for potassium-ion batteries due to its high theoretical capacity and natural abundance of manganese. However, the Jahn-Teller distortion caused by high-spin Mn3+ (t2g 3 eg 1 ) destabilizes the host structure and reduces the cycling stability. Here, K0.02 Na0.55 Mn0.70 Ni0.25 Zn0.05 O2 (denoted as KNMNO-Z) is reported to inhibit the Jahn-Teller effect and reduce the irreversible phase transition. Through the implementation of a Zn-doping strategy, higher Mn valence is achieved in the KNMNO-Z electrode, resulting in a reduction of Mn3+ amount and subsequently leading to an improvement in cyclic stability. Specifically, after 1000 cycles, a high retention rate of 97% is observed. Density functional theory calculations reveals that low-valence Zn2+ ions substituting the transition metal position of Mn regulated the electronic structure around the MnO bonding, thereby alleviating the anisotropic coupling between oxidized O2- and Mn4+ and improving the structural stability. K0.02 Na0.55 Mn0.70 Ni0.25 Zn0.05 O2 provided an initial discharge capacity of 57 mAh g-1 at 100 mA g-1 and a decay rate of only 0.003% per cycle, indicating that the Zn-doped strategy is effective for developing high-performance Mn-based layered oxide cathode materials in PIBs.

Altering Ligand Microenvironment of Atomically Dispersed CrN4 by Axial Ligand Sulfur for Enhanced Oxygen Reduction Reaction in Alkaline and Acidic Medium.

Because of the instability and Fenton reactivity of non-precious metal nitrogen-carbon based catalyst when processing the oxygen reduction reaction (ORR), seeking for electrocatalysts with highly efficient performance becomes very highly desired to speed up the commercialization of fuel cell. Herein, chromium (Cr)-N4  electrocatalyst containing extraterrestrial S formed axial S1 -Cr1 N4  bonds (S1 Cr1 N4 C) is achieved via an assembly polymerization and confined pyrolysis strategy. Benefiting from the adjusting  coordination configuration and electronic structure of the metal center through axial coordination, S1 Cr1 N4 C exhibits enhanced the intrinsic activity (half-wave potential (E1/2 ) is 0.90 V versus reversable hydrogen electrode, RHE) compared with that of CrN4 C and Pt/C catalysts. More notably, the catalyst is almost inert in catalyzing the Fenton reaction, and thus shows the high stability. Density functional theory (DFT) results further reveal that the existence of axial S atoms in S1 Cr1 N4 C moiety has the better ORR activity than Cr1 N4 C moieties. The axial S ligand in S1 Cr1 N4 C moiety can break the electron localization around the planar Cr1 N4  active center, which facilitated the rate-limiting reductive release of OH* and accelerated overall ORR process. The present work opens up a new avenue to modulate the axial ligand type of the single-atoms (SAs) active center to enhance intrinsic SAs performances.

Saponins from Camellia sinensis Seeds Stimulate GIP Secretion in Mice and STC-1 Cells via SGLT1 and TGR5.

Glucose-dependent insulinotropic polypeptide (GIP) is one of the important incretins and possesses lots of physiological activities such as stimulating insulin secretion and maintaining glucose homeostasis. The pentacyclic triterpenoid saponins are the major active ingredients in tea (Camellia sinensis) seeds. This study aimed to investigate the effect of tea seed saponins on the GIP secretion and related mechanisms. Our data showed that the total tea seed saponins (TSS, 65 mg/kg BW) and theasaponin E1 (TSE1, 2-4 µM) could increase the GIP mRNA and protein levels in mice and STC-1 cells. Phlorizin, the inhibitor of Sodium/glucose cotransporter 1 (SGLT1), reversed the TSE1-induced increase in Ca2+ and GIP mRNA level. In addition, TSE1 upregulated the protein expression of Takeda G protein-coupled receptor 5 (TGR5), and TGR5 siRNA significantly decreased GIP expression in TSE1-treated STC-1 cells. Network pharmacology analysis revealed that six proteins and five signaling pathways were associated with SGLT1, TGR5 and GIP regulated by TSE1. Taken together, tea seed saponins could stimulate GIP expression via SGLT1 and TGR5, and were promising natural active ingredients for improving metabolism and related diseases.

Comparative Transcriptome and Phytochemical Analysis Provides Insight into Triterpene Saponin Biosynthesis in Seeds and Flowers of the Tea Plant (Camellia sinensis).

Triterpene saponins exhibit various biological and pharmacological activities. However, the knowledge on saponin biosynthesis in tea plants (Camellia sinensis L.) is still limited. In this work, tea flower and seed samples at different developmental stages and leaves were collected and analyzed with UPLC-PDA-MS and RNA sequencing for saponin determination and transcriptome comparison. The saponin content reached around 19% in the freshly mature seeds and 7% in the green flower buds, and decreased with the fruit ripeness and flower blooming. Almost no saponins were detected in leaf samples. PCA and KEGG analysis suggested that the gene expression pattern and secondary metabolism in TF1 and TS2 vs. leaf samples were significantly different. Weighted gene coexpression network analysis (WGCNA) uncovered two modules related to saponin content. The mevalonate (MVA) instead of 2-C-methyl-d-erythritol-4-phospate (MEP) pathway was responsible for saponin accumulation in tea plants, and 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS), diphosphomevalonate decarboxylase (MVD) and isopentenyl diphosphate isomerase (IDI) may be the key enzymes involved in saponin biosynthesis in tea seeds and flowers. Moreover, ten transcription factors (TFs) were predicted to regulate saponin biosynthesis in the tea plant. Taken together, our study provides a global insight into the saponin biosynthesis and accumulation in the tea plant.

Transcriptome analysis provides insight into the anti-diabetic mechanism of theaflavins in high-fat diet and streptozotocin-induced mice.

Black tea exhibits potential to improve hyperglycemia and insulin resistance, where theaflavins (TFs) are its characteristic components. The aim of this study was to explore the anti-diabetic mechanism of TFs. High-fat diet and streptozotocin-induced type 2 diabetes (T2D) mice were administered with TFs by gavage daily for 5 weeks. The biochemical analysis suggested that TFs possess potential anti-diabetic activity, which is comparable to that of metformin. RNA-sequencing analysis showed that TFs had a significant influence on the hepatic transcriptional profile of the T2D mice. The nine significantly enriched KEGG pathways were mainly associated with pancreatic secretion, digestion and metabolism of fat, protein and glycerolipid, and tight junctions. Quantitative real-time PCR and immunohistochemistry analysis verified that TFs improved pancreas function and intestine tight junction, with an increase in the expression of carboxyl ester lipase (Cel), chymotrypsinogen B (Ctrb1), pancreatic triglyceride lipase (Pnlip) and chymotrypsin-like elastase 3B (Cela3b) in the pancreas and cingulin and claudin-1 in the intestine. TFs improved mitochondrial biogenesis with the downregulation of peroxisome proliferator-activated receptor coactivator (PGC) 1α and 1ß in the liver, but had less effect on the muscle. This work revealed the comprehensive mechanism of TFs against T2D, suggesting that TFs are a potential natural agent for improving type 2 diabetes.

Characterization of a new (Z)-3:(E)-2-hexenal isomerase from tea (Camellia sinensis) involved in the conversion of (Z)-3-hexenal to (E)-2-hexenal.

Two major green leaf volatiles (GLVs) in tea that contribute greatly to tea aroma, particularly the green odor, are (E)-2-hexenal and (Z)-3-hexenal. Until now, their formation and related mechanisms during tea manufacture have remained unclear. Our data showed that the contents of (E)-2-hexenal and (Z)-3-hexenal increased more than 1000-fold after live tea leaves were torn. Subsequently, a new (Z)-3:(E)-2-hexenal isomerase (CsHI) was identified in Camellia sinensis. CsHI irreversibly catalyzed the conversion of (Z)-3-hexenal to (E)-2-hexenal. Abiotic stresses including low temperature, dehydration, and mechanical wounding, did not influence the (E)-2-hexenal content in intact tea leaves during withering, but regulated the proportions of (Z)-3-hexenal and (E)-2-hexenal in torn leaves by modulating CsHI at the transcript level. For the first time, this work reveals the formation of (E)-2-hexenal during tea processing and suggests that CsHI may play a pivotal role in tea flavor development as well as in plant defense against abiotic stresses.

Emerging Two-Dimensional Covalent and Coordination Polymers for Stable Lithium Metal Batteries: From Liquid to Solid.

Lithium metal anodes (LMAs) have attracted much attention in recent years because of their high theoretical capacity (3860 mAh g-1) and low electrochemical potential (-3.040 V vs standard hydrogen electrode). Lithium metal can be coupled with various cathodes to construct high-energy-density lithium metal batteries (LMBs) which hold great promise for next-generation batteries. However, the unstable solid electrolyte interphases (SEIs) and the uncontrollable lithium dendrite growth severely hinder the commercial development of LMAs. The emerging 2D polymers (2DPs), which possess high mechanical flexibility, high specific surface area, abundant surface chemistry, and rich chemical modification characteristics, have shown great advantages in addressing the inherent issues of LMAs. Herein, the current progress of 2DPs for stable and dendrite-free LMAs in liquid- and solid-based batteries is comprehensively reviewed. Some perspectives for the application of 2DPs in LMBs are also discussed. It is believed that the emerging 2DPs will provide insights into developing high-energy-density LMBs and beyond.

High-Performance Ammonium Cobalt Phosphate Nanosheet Electrocatalyst for Alkaline Saline Water Oxidation.

The development of highly efficient electrocatalysts toward the oxygen evolution reaction is imperative for advancing water splitting technology to generate clean hydrogen energy. Herein, a two dimensional (2D) nanosheet ammonium cobalt phosphate hydrate (NH4CoPO4·H2O) catalyst based on the earth-abundant non-noble metal is reported. When used for the challenging alkaline saline water electrolysis, the NH4CoPO4·H2O catalyst with the optimal thickness of 30 nm achieves current densities of 10 and 100 mA cm-2 at the record low overpotentials of 252 and 268 mV, respectively, while maintaining remarkable stability during the alkaline saline water oxidation at room temperature. X-ray absorption fine spectra reveal that the activation of Co (II) ions (in NH4CoPO4·H2O) to Co (III) species constructs the electrocatalytic active sites. The 2D nanosheet morphology of NH4CoPO4·H2O provides a larger active surface area and more surface-exposed active sites, which enable the nanosheet catalyst to facilitate the alkaline freshwater and simulated seawater oxidation with excellent activity. The facile and environmentally-benign H2O-mediated synthesis route under mild condition makes NH4CoPO4·H2O catalyst highly feasible for practical manufacturing. In comparison with noble metals, this novel electrocatalyst offers a cost-effective alternative for economic saline water oxidation to advance water electrolysis technology.

Recent progress in metal-organic framework/graphene-derived materials for energy storage and conversion: design, preparation, and application.

Graphene or chemically modified graphene, because of its high specific surface area and abundant functional groups, provides an ideal template for the controllable growth of metal-organic framework (MOF) particles. The nanocomposite assembled from graphene and MOFs can effectively overcome the limitations of low stability and poor conductivity of MOFs, greatly widening their application in the field of electrochemistry. Furthermore, it can also be utilized as a versatile precursor due to the tunable structure and composition for various derivatives with sophisticated structures, showing their unique advantages and great potential in many applications, especially energy storage and conversion. Therefore, the related studies have been becoming a hot research topic and have achieved great progress. This review summarizes comprehensively the latest methods of synthesizing MOFs/graphene and their derivatives, and their application in energy storage and conversion with a detailed analysis of the structure-property relationship. Additionally, the current challenges and opportunities in this field will be discussed with an outlook also provided.

Dual-lasing channel quantum cascade laser based on scattering-assisted injection design: erratum.

We correct three typographical errors in our published paper [Opt. Express26, 9194 (2018)10.1364/OE.26.009194]. First, we correct the error in the Table 1. The injection coupling strength for the summarized device in the first raw is corrected to 1.5 meV. Second, we correct the listed reference 10 to "S. Kumar, C. W. I. Chan, Q. Hu, and J. L. Reno, "A 1.8-THz quantum cascade laser operating significantly above the temperature of ℏω/kB," Nat. Phys. 7(2), 166-171 (2011)." Third, we correct the typographical error in the quantum structure layer thickness description. The text description on quantum structure layer thickness is correct to 40.3/74.4/24.1/103.6/29.7/79.7/40.3/156.7, which is the correct number extracted from high-resolution X-ray diffraction (HRXRD) measurement and used in simulation through the manuscript. The corrections do not alter the figures and conclusions in manuscript.

NEURO-LEARN: a Solution for Collaborative Pattern Analysis of Neuroimaging Data.

The development of neuroimaging instrumentation has boosted neuroscience researches. Consequently, both the fineness and the cost of data acquisition have profoundly increased, leading to the main bottleneck of this field: limited sample size and high dimensionality of neuroimaging data. Therefore, the emphasis of ideas of data pooling and research collaboration has increased over the past decade. Collaborative analysis techniques emerge as the idea developed. In this paper, we present NEURO-LEARN, a solution for collaborative pattern analysis of neuroimaging data. Its collaboration scheme consists of four parts: projects, data, analysis, and reports. While data preparation workflows defined in projects reduce the high dimensionality of neuroimaging data by collaborative computation, pooling of derived data and sharing of pattern analysis workflows along with generated reports on the Web enlarge the sample size and ensure the reliability and reproducibility of pattern analysis. Incorporating this scheme, NEURO-LEARN provides an easy-to-use Web application that allows users from different sites to share projects and processed data, perform pattern analysis, and obtain result reports. We anticipate that this solution will help neuroscientists to enlarge sample size, conquer the curse of dimensionality and conduct reproducible studies on neuroimaging data with efficiency and validity.

Characterization of iron nanoparticles/reduced graphene oxide composites synthesized by one step eucalyptus leaf extract.

Biosynthesis of nanoparticles using plant extract is one kind of the effective approach in developing rapid, clean, nontoxic, and eco-friendly technology. In this work, iron nanoparticles/reduced graphene oxide composites (Fe NPs/rGO) were facilely fabricated through one-step method with eucalyptus leaf extract. The synthesized Fe NPs/rGO was investigated by various characterization methods. SEM results disclosed that Fe NPs with regular spherical shape of 70 ±â€¯10 nm was uniformly dispersed on rGO. A basal plane of rGO with high surface area, providing more load sites for Fe NPs, which was confirmed by TEM. XRD and FTIR results indicated that biomolecules from eucalyptus extract were capped on Fe NPs/rGO. The EDS mapping showed that Fe NPs dispersed evenly on rGO, and XPS further confirmed that Fe NPs/rGO composite was mainly comprised with Fe NPs and rGO. Furthermore, the biomolecules of eucalyptus leaf extract were identified by GC-MS to confirm that alcohol phenols acted as reducing agent, while alcohol acids and ketones acted as capping agents. In addition, the removal efficiency of Methylene blue (MB) up to 93% with Fe NPs/rGO. This work provides a simple, green cost-effective and environmentally friendly method to fabricate metal/rGO composite.

[Analysis of genomic DNA methylation level in foxtail millet by Methylation Sensitive Amplified Polymorphism].

DNA methylation is an important type of epigenetic modification in eukaryotes. In order to research genome-wide methylation levels and patterns in foxtail millet (Setaria italica), the Methylation Sensitive Amplified Polymorphism (MSAP) analysis (employing double digestion with EcoR I and Hpa II/Msp I) was established and applied in two foxtail millet cultivars (Chaogu 58 and Yugu 1). The results showed that 32 pairs of MSAP primers were selected from 100 MSAP primers, and 1 615 and 1 482 clearly distinguishable and reproducible bands were amplified from Chaogu 58 and Yugu 1 respectively, including 3 types of methylation patterns. Cytosine methylation levels of CCGG context in Chaogu 58 and Yugu 1 were characterized as 6.93% and 8.77% respectively. Such different genomic DNA methylation levels between two foxtail millet varieties may provide a preliminary reference for the cultivation of this crop from a novel epigenetic viewpoint.

Dual-lasing channel quantum cascade laser based on scattering-assisted injection design.

A dual lasing channel Terahertz Quantum Cascade laser (THz QCL) based on GaAs/Al0.17Ga0.83As material system is demonstrated. The device shows the lowest reported threshold current density (550A/cm2 at 50K) of GaAs/AlxGa1-xAs material system based scattering-assisted (SA) structures and operates up to a maximum lasing temperature of 144K. Dual lasing channel operation is investigated theoretically and experimentally. The combination of low frequency emission, dual lasing channel operation, low lasing threshold current density and high temperature performance make such devices ideal candidates for low frequency applications, and initiates the design strategy for achieving high-temperature performance terahertz quantum cascade laser with wide frequency coverage at low frequency.

An In Vitro Organ Culture Model of the Murine Intervertebral Disc.

Intervertebral disc (IVD) degeneration is a significant contributor to low back pain. The IVD is a fibrocartilaginous joint that serves to transmit and dampen loads in the spine. The IVD consists of a proteoglycan-rich nucleus pulposus (NP) and a collagen-rich annulus fibrosis (AF) sandwiched by cartilaginous end-plates. Together with the adjacent vertebrae, the vertebrae-IVD structure forms a functional spine unit (FSU). These microstructures contain unique cell types as well as unique extracellular matrices. Whole organ culture of the FSU preserves the native extracellular matrix, cell differentiation phenotypes, and cellular-matrix interactions. Thus, organ culture techniques are particularly useful for investigating the complex biological mechanisms of the IVD. Here, we describe a high-throughput approach for culturing whole lumbar mouse FSUs that provides an ideal platform for studying disease mechanisms and therapies for the IVD. Furthermore, we describe several applications that utilize this organ culture method to conduct further studies including contrast-enhanced microCT imaging and three-dimensional high-resolution finite element modeling of the IVD.

[Automatic classification of first-episode, drug-naive schizophrenia with multi-modal magnetic resonance imaging].

A great number of studies have demonstrated the structural and functional abnormalities in chronic schizophrenia (SZ) patients. However, few studies analyzed the differences between first-episode, drug-naive SZ (FESZ) patients and normal controls (NCs). In this study, we recruited 44 FESZ patients and 56 NCs, and acquired their multi-modal magnetic resonance imaging (MRI) data, including structural and resting-state functional MRI data. We calculated gray matter volume (GMV), regional homogeneity (ReHo), amplitude of low frequency fluctuation (ALFF), and degree centrality (DC) of 90 brain regions, basing on an automated anatomical labeling (AAL) atlas. We then applied these features into support vector machine (SVM) combined with recursive feature elimination (RFE) to discriminate FESZ patients from NCs. Our results showed that the classifier using the combination of ReHo and ALFF as input features achieved the best performance (an accuracy of 96.97%). Moreover, the most discriminative features for classification were predominantly located in the frontal lobe. Our findings may provide potential information for understanding the neuropathological mechanism of SZ and facilitate the development of biomarkers for computer-aided diagnosis of SZ patients.

[Comparison of MITE transposons mPing in different rice subspecies].

The mPing family is the first active MITE TE family identified in rice genome. In order to compare the compositions and distributions of mPing family in the genomes of two rice subspecies japonica (cv. Nipponbare) and indica (cv. 93-11), we initially estimated the copy numbers of mPing family in those two subspecies using Southern blot and then confirmed the results by searching homologous copies in each reference genome using Blastn program, which turned out to have 52 and 14 mPing copies in corresponding reference genome, respectively. All mPing members in Nipponbare genome belong to mPing-1, while there are 3 mPing-1 and 11 mPing-2 copies in 93-11 genome. By further investigating the 5-kb flanking sequences of those mPing copies, it was found that 23 and 3 protein-coding genes in Nipponbare and 93-11 genome are residing adjacent to those mPing copies respectively. These results establish the preliminary theoretical foundation for further dissecting the genetic differences of japonica and indica rice in terms of the diversities and distributions of their component mPing.