Deficiency of histone deacetylases 3 in macrophage alleviates monosodium urate crystals-induced gouty inflammation in mice.

BACKGROUND: Gout is caused by monosodium urate (MSU) crystals deposition to trigger immune response. A recent study suggested that inhibition of Class I Histone deacetylases (HDACs) can significantly reduce MSU crystals-induced inflammation. However, which one of HDACs members in response to MSU crystals was still unknown. Here, we investigated the roles of HDAC3 in MSU crystals-induced gouty inflammation. METHODS: Macrophage specific HDAC3 knockout (KO) mice were used to investigate inflammatory profiles of gout in mouse models in vivo, including ankle arthritis, foot pad arthritis and subcutaneous air pouch model. In the in vitro experiments, bone marrow-derived macrophages (BMDMs) from mice were treated with MSU crystals to assess cytokines, potential target gene and protein. RESULTS: Deficiency of HDAC3 in macrophage not only reduced MSU-induced foot pad and ankle joint swelling but also decreased neutrophils trafficking and IL-1ß release in air pouch models. In addition, the levels of inflammatory genes related to TLR2/4/NF-κB/IL-6/STAT3 signaling pathway were significantly decreased in BMDMs from HDAC3 KO mice after MSU treatment. Moreover, RGFP966, selective inhibitor of HDAC3, inhibited IL-6 and TNF-α production in BMDMs treated with MSU crystals. Besides, HDAC3 deficiency shifted gene expression from pro-inflammatory macrophage (M1) to anti-inflammatory macrophage (M2) in BMDMs after MSU challenge. CONCLUSIONS: Deficiency of HDAC3 in macrophage alleviates MSU crystals-induced gouty inflammation through inhibition of TLR2/4 driven IL-6/STAT3 signaling pathway, suggesting that HDAC3 could contribute to a potential therapeutic target of gout.

Sde Proteins Coordinate Ubiquitin Utilization and Phosphoribosylation to Promote Establishment and Maintenance of the Legionella Replication Vacuole.

The Legionella pneumophila Sde family of translocated proteins promotes host tubular endoplasmic reticulum (ER) rearrangements that are tightly linked to phosphoribosyl-ubiquitin (pR-Ub) modification of Reticulon 4 (Rtn4). Sde proteins have two additional activities of unclear relevance to the infection process: K63 linkage-specific deubiquitination and phosphoribosyl modification of polyubiquitin (pR-Ub). We show here that the deubiquitination activity (DUB) stimulates ER rearrangements while pR-Ub protects the replication vacuole from cytosolic surveillance by autophagy. Loss of DUB activity was tightly linked to lowered pR-Ub modification of Rtn4, consistent with the DUB activity fueling the production of pR-Ub-Rtn4. In parallel, phosphoribosyl modification of polyUb, in a region of the protein known as the isoleucine patch, prevented binding by the autophagy adapter p62. An inability of Sde mutants to modify polyUb resulted in immediate p62 association, a critical precursor to autophagic attack. The ability of Sde WT to block p62 association decayed quickly after bacterial infection, as predicted by the presence of previously characterized L. pneumophila effectors that inactivate Sde and remove polyUb. In sum, these results show that the accessory Sde activities act to stimulate ER rearrangements and protect from host innate immune sensing in a temporal fashion.

Inhibition of polyphenols on Maillard reaction products and their induction of related diseases: A comprehensive review.

BACKGROUND: Food products undergo a pronounced Maillard reaction (MR) during the cooking process, leading to the generation of substantial quantities of Maillard reaction products (MRPs). Within this category, advanced glycation end products (AGEs), acrylamide (AA), and heterocyclic amines (HAs) have been implicated as potential risk factors associated with the development of diseases. PURPOSE: To explore the effects of polyphenols, a class of bioactive compounds found in plants, on the inhibition of MRPs and related diseases. Previous research has mainly focused on their interactions with proteins and their effects on the gastrointestinal tract and other diseases, while fewer studies have examined their inhibitory effects on MRPs. The aim is to offer a scientific reference for future research investigating the inhibitory role of polyphenols in the MR. METHODS: The databases PubMed, Embase, Web of Science and The Cochrane Library were searched for appropriate research. RESULTS: Polyphenols have the potential to inhibit the formation of harmful MRPs and prevent related diseases. The inhibition of MRPs by polyphenols primarily occurs through the following mechanisms: trapping α-dicarbonyl compounds, scavenging free radicals, chelating metal ions, and preserving protein structure. Simultaneously, polyphenols exhibit the ability to impede the onset and progression of related diseases such as diabetes, atherosclerosis, cancer, and Alzheimer's disease through diverse pathways. CONCLUSION: This review presents that inhibition of polyphenols on Maillard reaction products and their induction of related diseases. Further research is imperative to enhance our comprehension of additional pathways affected by polyphenols and to fully uncover their potential application value in inhibiting MRPs.

Anti-inflammatory effect of echinacoside in collagen-induced arthritis via Nrf2/Drp1 pathway.

BACKGROUND: Oxidative damage plays an important role in the progression of rheumatoid arthritis (RA). Emerging research evidence suggests that natural antioxidants may effectively ameliorate this disease. OBJECTIVES: To investigate the therapeutic effect of echinacoside (ECH) in a collagen-induced arthritis (CIA) mouse model and thus elucidate the underlying molecular mechanism in RA. MATERIAL AND METHODS: Collagen-induced arthritis mice were intraperitoneally administered 1% dimethyl sulfoxide (DMSO) (control) or 0.6 mg of ECH every other day for 1 month. Arthritis scores and the number of affected paws were assessed. On day 60, mice were euthanized, synovial tissue specimens were obtained, and serum interleukin (IL)-6 and IL-1â expression levels were measured. Mitochondrial morphologies, reactive oxygen species (ROS) content, expression of dynamin-related protein 1 (Drp1), IL-6, nod-like receptor protein 3 (NLRP3), kelch-like ECH-associated protein 1 (Keap1), and nuclear factor-erythroid-2-related factor 2 (Nrf2) contents in synovium were analyzed and compared between DMSOand ECH-treated CIA mice. RESULTS: Following ECH treatment, mitochondria of CIA-induced mice were found to be elongated, while their arthritis scores, inflammation and the number of affected paws, and the expression levels of Drp1, NLRP3, IL-6, ROS, and Keap1 were all found to be significantly reduced. Conversely, the level of antioxidant factor Nrf2 was found to be elevated. Further, mitochondrial fission was found to be inhibited in synovial tissues. CONCLUSIONS: Our findings validate the therapeutic efficacy of ECH in the CIA mouse model. Echinacoside may suppress oxidative stress and inhibit inflammation by regulating the Nrf2/Drp1 pathway, thus supporting its utility in the treatment of RA.

Transcription factor Hoxb5 reveals the unidirectional hierarchy of hematopoietic stem cell pool.

Hoxb5 exhibits preferential expression in hematopoietic stem cells (HSCs) and uniquely marks the long-term HSCs (LT-HSCs). Previous studies have demonstrated the remarkable capability of Hoxb5 to alter cell fates when enforced expression in blood progenitors, such as B cell progenitors and multipotent progenitors. Additionally, Hoxb5 deficiency does not hinder the generation of LT-HSCs. However, the specific impact of Hoxb5 deletion on LT-HSCs has remained unexplored. To address this, we developed a conditional Hoxb5 knockout-reporter mouse model, wherein Hoxb5 was knock out by the Vav-cre recombinase, and the endogenous Hoxb5 promoter drove the expression of the blue fluorescent protein (BFP). Our findings revealed that the primary recipients, who transplanted with HSCs indicating Hoxb5 deficiency by the presence of BFP (BFP-positive HSCs), exhibited comparable levels of donor chimerism and lineage chimerism to recipients transplanted with HSCs that spontaneously did not express Hoxb5 and thus lacked BFP expression (BFP-negative HSCs). However, during the secondary transplantation, recipients receiving total bone marrow (BM) from the primary recipients with BFP-positive HSCs showed significantly higher levels of donor chimerism and more robust multi-lineage chimerism compared to those receiving total BM from the primary recipients with BFP-negative HSCs. Our results indicate that deleting Hoxb5 in LT-HSCs transiently influences their lineage differentiation bias without compromising their long-term self-renewal capacity. These findings highlight the primary role of Hoxb5 in regulating lineage commitment decisions in LT-HSCs, while emphasizing that its presence is not indispensable for the maintenance of long-term self-renewal capacity.

A comprehensive evaluation of a polymeric zwitterionic hydrophilic monolith for nucleotide separation.

Rapid and effective separation of nucleotides (NTs) and their derivatives is crucial for studying their physiological functions. In this work, we comprehensively evaluated the separation ability of a zwitterionic hydrophilic monolith, i.e., poly(N,N-dimethyl-N-(3-methacrylamidopropyl)-N-(3-sulfopropyl)ammonium betaine-co-N,N'-methylenebisacrylamide) (poly(SPP-co-MBA)) for NTs analysis, including its selectivity, chemical stability under extremely basic condition and compatibility with hydrophilic interaction liquid chromatography (HILIC) coupled with mass spectrometry (HILIC-MS). The poly(SPP-co-MBA) monolith exhibited excellent chemical stability, as evidenced by the low relative standard deviation of retention time (0.16-1.05%) after 4000 consecutive injections over one month under strong alkaline elution condition (pH 10). After optimizing the separation conditions, including buffer pH and concentration, organic solvent content and column temperature, four nucleoside triphosphates, five nucleoside diphosphates and five nucleoside monophosphates were baseline separated within 7 min. Additionally, the mixtures containing one nucleoside and its corresponding mono-, di-, and triphosphates were baseline separated within only 3 min, respectively. It is good HILIC-MS compatibility was also confirmed by the satisfactory peak shape and high response of nine NTs. Overall, the proposed poly(SPP-co-MBA) monolith exhibited good mechanical stability and compatibility of HILIC-MS, making it a promising technique for NTs analysis.

The Mechanism of Ubiquitination or Deubiquitination Modifications in Regulating Solid Tumor Radiosensitivity.

Radiotherapy, a treatment method employing radiation to eradicate tumor cells and subsequently reduce or eliminate tumor masses, is widely applied in the management of numerous patients with tumors. However, its therapeutic effectiveness is somewhat constrained by various drug-resistant factors. Recent studies have highlighted the ubiquitination/deubiquitination system, a reversible molecular modification pathway, for its dual role in influencing tumor behaviors. It can either promote or inhibit tumor progression, impacting tumor proliferation, migration, invasion, and associated therapeutic resistance. Consequently, delving into the potential mechanisms through which ubiquitination and deubiquitination systems modulate the response to radiotherapy in malignant tumors holds paramount significance in augmenting its efficacy. In this paper, we comprehensively examine the strides made in research and the pertinent mechanisms of ubiquitination and deubiquitination systems in governing radiotherapy resistance in tumors. This underscores the potential for developing diverse radiosensitizers targeting distinct mechanisms, with the aim of enhancing the effectiveness of radiotherapy.

A chimeric hairpin DNA aptamer-based biosensor for monitoring the therapeutic drug bevacizumab.

The accurate and rapid detection of specific antibodies in blood is very important for efficient diagnosis and precise treatment. Conventional methods often suffer from time-consuming operations and/or a narrow detection range. In this work, for the rapid determination of bevacizumab in plasma, a series of chimeric hairpin DNA aptamer-based probes were designed by the modification, labeling and theoretical computation of an original aptamer. Then, the dissociation constant of the modified hairpin DNA to bevacizumab was measured and screened using microscale thermophoresis. The best chimeric hairpin DNA aptamer-based probe was then selected, and a one-step platform for the rapid determination of bevacizumab was constructed. This strategy has the advantages of being simple, fast and label-free. Because of the design and screening of the hairpin DNA, as well as the optimization of the concentration and electrochemical parameters, a low detection limit of 0.37 pM (0.054 ng mL-1) with a wide linear range (1 pM-1 µM) was obtained. Finally, the rationally constructed biosensor was successfully applied to the determination of bevacizumab in spiked samples, and it showed good accuracy and precision. This method is expected to truly realize accurate and rapid detection of bevacizumab and provides a new idea for the precise treatment of diseases.

Boosting the Electrocatalytic Activity of Pr0.5Ba0.5FeO3-δ via Ni Doping in Symmetric Solid Oxide Electrolysis Cells.

Symmetric solid oxide electrolysis cells (SSOECs) have garnered significant scientific interest due to their simplified cell architecture, robust operational reliability, and cost-effectiveness, for which a highly electrocatalytically active electrode is the decisive main factor. This work evaluates the electrochemical performance of Ni-doped Pr0.5Ba0.5FeO3-δ (PBF) perovskite materials, with a focus on Pr0.5Ba0.5Fe0.8Ni0.2O3-δ (PBFN). The experimental findings herein prove the exceptional electrocatalytic ability of PBFN in facilitating the oxygen evolution and carbon dioxide reduction reaction, surpassing the electrochemical performance of PBF. In addition, the PBFN symmetric cell has excellent performance for CO2 electrolysis, and the cell has a low polarization resistance value of 0.1 Ω·cm2. Moreover, it achieves an impressive current density value of 1.118 A·cm-2 under operating conditions of 2.0 V and 800 °C, which is superior to those of the PBF symmetric cell and the PBFN asymmetric cell. It also has a good structural and performance stability. These results imply a bright development prospect of PBFN as electrodes for SSOECs.

Polyimides as Promising Materials for Lithium-Ion Batteries: A Review.

Lithium-ion batteries (LIBs) have helped revolutionize the modern world and are now advancing the alternative energy field. Several technical challenges are associated with LIBs, such as increasing their energy density, improving their safety, and prolonging their lifespan. Pressed by these issues, researchers are striving to find effective solutions and new materials for next-generation LIBs. Polymers play a more and more important role in satisfying the ever-increasing requirements for LIBs. Polyimides (PIs), a special functional polymer, possess unparalleled advantages, such as excellent mechanical strength, extremely high thermal stability, and excellent chemical inertness; they are a promising material for LIBs. Herein, we discuss the current applications of PIs in LIBs, including coatings, separators, binders, solid-state polymer electrolytes, and active storage materials, to improve high-voltage performance, safety, cyclability, flexibility, and sustainability. Existing technical challenges are described, and strategies for solving current issues are proposed. Finally, potential directions for implementing PIs in LIBs are outlined.

Clinical performance of zirconium implants compared to titanium implants: a systematic review and meta-analysis of randomized controlled trials.

Purpose: To quantitatively assess and compare the clinical outcomes, including survival rate, success rate, and peri-implant indices of titanium and zirconium implants in randomized controlled trials. Methods: The electronic databases searched included the Cochrane Central Register of Controlled Trials (CENTRAL), Medline via Ovid, EMBASE, and Web of Science. Randomized controlled trials (RCTs) that reported the effects of zirconium implants on primary outcomes, such as survival rate, success rate, marginal bone loss (MBL), and probing pocket depth (PPD), compared to titanium implants were included in this review. Two reviewers independently screened and selected the records, assessed their quality, and extracted the data from the included studies. Results: A total of four studies from six publications reviewed were included. Two of the comparative studies were assessed at minimal risk of bias. Zirconium implants may have a lower survival rate (risk ratio (RR) = 0.91, CI [0.82-1.02], P = 0.100, I 2 = 0%) and a significantly lower success rate than titanium implants (RR = 0.87, CI [0.78-0.98], P = 0.030, I 2 = 0%). In addition, there was no difference between the titanium and zirconium implants in terms of MBL, PPD, bleeding on probing (BOP), plaque index (PI), and pink esthetic score (PES) (for MBL, MD = 0.25, CI [0.02-0.49], P = 0.033, I 2 = 0%; for PPD, MD = -0.07, CI [-0.19-0.05], P = 0.250, I 2 = 31%). Conclusion: Zirconium implants may have higher failure rates due to their mechanical weakness. Zirconium implants should be strictly assessed before they enter the market. Further studies are required to confirm these findings.

Inside-Out Oriented Choline Phosphate-Based Biomimetic Magnetic Nanomaterials for Precise Recognition and Analysis of C-Reactive Protein.

Phospholipid-based materials exhibit great application potential in the fields of chemistry, biology, and pharmaceutical sciences. In this study, an inside-out oriented choline phosphate molecule, 2-{2-(methacryloyloxy)ethyldimethylammonium}ethyl n-butyl phosphate (MBP), was proposed and verified as a novel ligand of C-reactive protein (CRP) to enrich the functionality of these materials. Compared with phosphorylcholine (PC)-CRP interactions, the binding between MBP and CRP was not affected by the reverse position of phosphate and choline groups and even found more abundant binding sites. Thus, high-density MBP-grafted biomimetic magnetic nanomaterials (MBP-MNPs) were fabricated by reversible addition-fragmentation chain transfer polymerization based on thiol-ene click chemistry. The novel materials exhibited multifunctional applications for CRP including purification and ultrasensitive detection. On the one hand, higher specificity, recovery (90%), purity (95%), and static binding capacity (198.14 mg/g) for CRP were achieved on the novel materials in comparison with traditional PC-based materials, and the enriched CRP from patient serum can maintain its structural integrity and bioactivity. On the other hand, the CRP detection method combining G-quadruplex and thioflavin T developed with MBP-MNPs showed a lower detection limit (10 pM) and wider linear range (0.1-50 nM) than most PC-functionalized analytical platforms. Therefore, the inside-out oriented choline phosphate can not only precisely recognize CRP but also be combined with biomimetic nanomaterials to provide high application potential.

Identification of the BcLEA Gene Family and Functional Analysis of the BcLEA73 Gene in Wucai (Brassica campestris L.).

Late embryogenesis abundant (LEA) proteins are important developmental proteins in the response of plants to abiotic stress. In our previous study, BcLEA73 was differentially expressed under low-temperature stress. Herein, we combined bioinformatics analysis, subcellular localization, expression assays, and stress experiments (including salt, drought, and osmotic stress) to identify and analyze the BcLEA gene family. Gene cloning and functional analysis of BcLEA73 were performed in tobacco and Arabidopsis. Based on the sequence homology and the available conservative motif, 82 BrLEA gene family members were identified and were divided into eight subfamilies in the genome-wide database of Chinese cabbage. The analysis showed that the BrLEA73 gene was located on chromosome A09 and belonged to the LEA_6 subfamily. Quantitative real-time PCR analysis indicated that the BcLEA genes were differentially expressed to varying degrees in the roots, stems, leaves, and petioles of Wucai. The overexpressed BcLEA73 transgenic plants exhibited no significant differences in root length and seed germination rates compared to the wild-type (WT) plants under control conditions. Under salt and osmotic stress treatment, the root length and seed germination rates of the BcLEA73-OE strain were significantly greater than those of WT plants. Under salt stress, the total antioxidant capacity (T-AOC) of the BcLEA73-OE lines increased significantly, and the relative conductivity, (REL), hydrogen peroxide (H2O2) content, and superoxide anion (O2-) production rate decreased significantly. Under drought treatment, the survival rate of the BcLEA73-OE lines was significantly higher than that of WT plants. These results showed that the BcLEA73 gene of Wucai functions in enhancing the tolerance of plants to salt, drought, and osmotic stress. This study provides a theoretical basis to explore the relevant functions of the BcLEA gene family members of Wucai.

Prolonged generation of multi-lineage blood cells in wild-type animals from pluripotent stem cells.

Regenerating prolonged multi-lineage hematopoiesis from pluripotent stem cells (PSCs), an unlimited cell source, is a crucial aim of regenerative hematology. In this study, we used a gene-edited PSC line and revealed that simultaneous expression of three transcription factors, Runx1, Hoxa9, and Hoxa10, drove the robust emergence of induced hematopoietic progenitor cells (iHPCs). The iHPCs engrafted successfully in wild-type animals and repopulated abundant and complete myeloid-, B-, and T-lineage mature cells. The generative multi-lineage hematopoiesis distributed normally in multiple organs, persisted over 6 months, and eventually declined over time with no leukemogenesis. Transcriptome characterization of generative myeloid, B, and T cells at the single-cell resolution further projected their identities to natural cell counterparts. Thus, we provide evidence that co-expression of exogenous Runx1, Hoxa9, and Hoxa10 simultaneously leads to long-term reconstitution of myeloid, B, and T lineages using PSC-derived iHPCs as the cell source.

Artificial intelligence-assisted determination of available sites for palatal orthodontic mini implants based on palatal thickness through CBCT.

OBJECTIVES: To develop an artificial intelligence (AI) system for automatic palate segmentation through CBCT, and to determine the personalized available sites for palatal mini implants by measuring palatal bone and soft tissue thickness according to the AI-predicted results. MATERIALS AND METHODS: Eight thousand four hundred target slices (from 70 CBCT scans) from orthodontic patients were collected, labelled by well-trained orthodontists and randomly divided into two groups: a training set and a test set. After the deep learning process, we evaluated the performance of our deep learning model with the mean Dice similarity coefficient (DSC), average symmetric surface distance (ASSD), sensitivity (SEN), positive predictive value (PPV) and mean thickness percentage error (MTPE). The pixel traversal method was proposed to measure the thickness of palatal bone and soft tissue, and to predict available sites for palatal orthodontic mini implants. Then, an example of available sites for palatal mini implants from the test set was mapped. RESULTS: The average DSC, ASSD, SEN, PPV and MTPE for the segmented palatal bone tissue were 0.831%, 1.122%, 0.876%, 0.815% and 6.70%, while that for the palatal soft tissue were 0.741%, 1.091%, 0.861%, 0.695% and 12.2%, respectively. Besides, an example of available sites for palatal mini implants was mapped according to predefined criteria. CONCLUSIONS: Our AI system showed high accuracy for palatal segmentation and thickness measurement, which is helpful for the determination of available sites and the design of a surgical guide for palatal orthodontic mini implants.

Identification and characterization of innate lymphoid cells generated from pluripotent stem cells.

Innate lymphoid cells (ILCs) play important roles in regulating tissue homeostasis and innate immune responses. Generation of ILCs after engraftment of pluripotent stem cell (PSC)-derived hematopoietic progenitors (iHPCs) has not yet been reported. Here, we document that ILCs exist in Rag2-/-Il2rg-/- recipients engrafted with PSC-derived iHPCs guided by Runx1 and Hoxa9 expression. Upon transplantation, iHPCs immediately give rise to ILC-related progenitors containing common helper ILC progenitors in the bone marrow, followed by a more restricted population named ILC progenitors, which are able to further differentiate into mature ILCs in the primary and secondary immunodeficient recipients. The PSC-derived ILCs exhibit multiple tissue distributions and normal immunological functions. Single-cell transcriptomics illustrates the developmental trajectory of PSC-derived ILCs in vivo, which is consistent with that of natural ILCs. Our study provides insights into the generation of ILCs in animals transplanted with PSC-derived iHPCs as a cell source.

Corrigendum: Field pest monitoring and forecasting system for pest control.

[This corrects the article DOI: 10.3389/fpls.2022.990965.].

Field pest monitoring and forecasting system for pest control.

Insect pest is an essential factor affecting crop yield, and the effect of pest control depends on the timeliness and accuracy of pest forecasting. The traditional method forecasts pest outbreaks by manually observing (capturing), identifying, and counting insects, which is very time-consuming and laborious. Therefore, developing a method that can more timely and accurately identify insects and obtain insect information. This study designed an image acquisition device that can quickly collect real-time photos of phototactic insects. A pest identification model was established based on a deep learning algorithm. In addition, a model update strategy and a pest outbreak warning method based on the identification results were proposed. Insect images were processed to establish the identification model by removing the background; a laboratory image collection test verified the feasibility. The results showed that the proportion of images with the background completely removed was 90.2%. Dataset 1 was obtained using reared target insects, and the identification accuracy of the ResNet V2 model on the test set was 96%. Furthermore, Dataset 2 was obtained in the cotton field using a designed field device. In exploring the model update strategy, firstly, the T_ResNet V2 model was trained with Dataset 2 using transfer learning based on the ResNet V2 model; its identification accuracy on the test set was 84.6%. Secondly, after reasonably mixing the indoor and field datasets, the SM_ResNet V2 model had an identification accuracy of 85.7%. The cotton pest image acquisition, transmission, and automatic identification system provide a good tool for accurately forecasting pest outbreaks in cotton fields.

Efficacy and safety of ruxolitinib for steroid-refractory graft-versus-host disease: Systematic review and meta-analysis of randomised and non-randomised studies.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD. OBJECTIVES: To assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects. STUDY DESIGN: Meta-analysis. SEARCH METHODS: Randomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger's test, and the trim and fill method were used to assess publication bias. RESULTS: In total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9-67.4) and 80.3% (95% CI 69.7-87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6-81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5-81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4-90.2%; skin, 52.5-80.6%; and liver, 41.8-71.8%. In cGVHD, the response rates were gastrointestinal, 30.1-70.4%; skin, 30.1-84.4%; lung, 27.0-83.0%; and mouth 3.5-98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications. CONCLUSIONS: Our systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.

Regulation of Dendrite-Free Li Plating via Lithiophilic Sites on Lithium-Alloy Surface.

Lithium (Li) deposition behavior plays an important role in dendrite formation and the subsequent performance of lithium metal batteries. This work reveals the impact of the lithiophilic sites of lithium-alloy on the Li plating process via the first-principles calculations. We find that the Li deposition mechanisms on the Li metal and Li22Sn5 surface are different due to the lithiophilic sites. We first propose that Li plating on the Li metal surface goes through the "adsorption-reduction-desorption-heterogeneous nucleation-cluster drop" process, while it undergoes the "adsorption-reduction-growth" process on the Li22Sn5 surface. The lower adsorption energy contributes to the easy adsorption of Li on the lithiophilic sites of the Li22Sn5 surface. The lower Li reduction energy on the Li metal surface indicates that it is easy for Li to be reduced on the Li metal surface, attributed to its higher Fermi energy level. Furthermore, the faster Li diffusion on the Li22Sn5 surface results in smooth Li deposition, which is based on a "two-Li synergy diffusion" mechanism. However, Li diffuses more slowly on the Li metal surface than on the Li22Sn5 surface due to the "single Li diffusion" mechanism. This work provides a fundamental understanding on the impact of lithiophilic sites of Li alloy on the Li plating process and points out that the future design of 3D Li-alloy substrates decorated with multilithiophilic sites can prevent dendrite formation on the lithium-alloy substrate by guiding uniform Li deposition.