A TNIP1-driven systemic autoimmune disorder with elevated IgG4.

Whole-exome sequencing of two unrelated kindreds with systemic autoimmune disease featuring antinuclear antibodies with IgG4 elevation uncovered an identical ultrarare heterozygous TNIP1Q333P variant segregating with disease. Mice with the orthologous Q346P variant developed antinuclear autoantibodies, salivary gland inflammation, elevated IgG2c, spontaneous germinal centers and expansion of age-associated B cells, plasma cells and follicular and extrafollicular helper T cells. B cell phenotypes were cell-autonomous and rescued by ablation of Toll-like receptor 7 (TLR7) or MyD88. The variant increased interferon-ß without altering nuclear factor kappa-light-chain-enhancer of activated B cells signaling, and impaired MyD88 and IRAK1 recruitment to autophagosomes. Additionally, the Q333P variant impaired TNIP1 localization to damaged mitochondria and mitophagosome formation. Damaged mitochondria were abundant in the salivary epithelial cells of Tnip1Q346P mice. These findings suggest that TNIP1-mediated autoimmunity may be a consequence of increased TLR7 signaling due to impaired recruitment of downstream signaling molecules and damaged mitochondria to autophagosomes and may thus respond to TLR7-targeted therapeutics.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific proteases 25, a key member of deubiquitinating enzyme family and is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown etiology. Five heterozygous USP25 variants including two de novo and three co-segregated variants were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared to the East Asian population and all populations in the gnomAD database. The mean onset ages of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom except one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was ubiquitously expressed in mouse brain with two peaks on embryonic days (E14‒E16) and postnatal day 21, respectively. Similarly, USP25 expressed in fetus/early childhood stage with a second peak at approximately 12‒20 years old in human brain, consistent with the seizure onset age at infancy and juvenile in the patients. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knock-out mice, which showed increased seizure susceptibility compared to wild-type mice in pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we employed multiple functional detections. In HEK293T cells, the severe phenotype associated variant (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed a stable truncated dimers with increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del increased neuronal excitability in mice brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

Chronic atrophic gastritis and risk of incident upper gastrointestinal cancers: a systematic review and meta-analysis.

BACKGROUND: Previous literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer. METHODS: Rigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software. RESULTS: This meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20-5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60-2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77-2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17-2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21-3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33-77% higher risk of developing cancer compared to diagnosing CAG through serological methods. CONCLUSION: This meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.

Evaluation of the effectiveness and safety of sequential vaccination with inactivated SARS-CoV-2 vaccine and Ad5-nCoV booster in pediatric liver transplant recipients.

Amidst the COVID-19 pandemic, uncertainty persists among caregivers regarding the vaccination of pediatric liver transplant recipients (PLTRs). This study evaluates the immunogenicity and safety of COVID-19 vaccination in this vulnerable population. A cohort of 30 PLTRs underwent sequential vaccinations with an inactivated SARS-CoV-2 vaccine followed by an Ad5-nCoV booster. We collected and analyzed blood samples pre-vaccination and four weeks post-vaccination to quantify antibody and IGRA (IFN-γ Release Assay) levels. We also documented any adverse reactions occurring within seven days post-vaccination and monitored participants for infections over six months post-vaccination, culminating in a comprehensive statistical analysis. The Ad5-nCoV booster substantially elevated IgG (T1: 18.01, 20%; T2: 66.61, 55%) and nAb (T1: 119.29, 8%; T2: 3799.75, 80%) levels, as well as T-cell responses, in comparison to the initial dose. The first dose was associated with some common adverse reactions, such as injection site pain (13.3%) and fever (16.6%), but a low rate of systemic reactions (16.0%). There was no significant difference in Omicron infection rates or RTPCR conversion times between vaccinated and unvaccinated groups. Notably, following Omicron infection, vaccinated individuals exhibited significantly higher SARS-CoV-2 IgG and nAb titers (average IgG: 231.21 vs. 62.09 S/CO, p = 0.0003; nAb: 5246.11 vs. 2592.07 IU/mL, p = 0.0002). The use of inactivated vaccines followed by an Ad5-nCoV booster in PLTRs is generally safe and elicits a robust humoral response, albeit with limited T-cell responses.

Clinical and metagenomic characteristics of lymphadenopathy related to fever of unknown origin in children.

BACKGROUND: Diagnosis of fever of unknown origin remains challenge for pediatricians. Lymphadenopathy is a separate entity that mainly originates from infection or malignancy. METHODS: 168 patients with FUO accompanied by lymphadenectasis were reviewed. 33 lymph node tissue samples were examined by mNGS. Differences in clinical characteristics were compared among different disease groups. The value of mNGS in diagnosing and improving the clinical situation was assessed. RESULTS: Multivariate analysis revealed that hepatosplenomegaly and LDH levels were associated with infectious diseases. Arthralgia was correlated with non-infectious inflammatory diseases. Weight loss and a node located in supraclavicular region may indicate neoplastic diseases. mNGS-positive rate was 60.60%, higher than that obtained with traditional methods. Treatment for 3/4 patients was adjusted according to the pathogen detected by mNGS, and antibiotics uses was discontinued or degraded in over 1/2 of the patients according to mNGS results. CONCLUSIONS: Clinical characteristics of children with lymphadenopathy related to FUO have limited diagnostic value for distinguishing different kinds of diseases, while mNGS of lymph node tissue serves as a useful tool for identifying infectious diseases, especially those caused by rare pathogens. mNGS results can lead to not only adjustments in targeted treatment but also further confirmation of underlying diseases. IMPACT STATEMENT: 1. The clinical features of children with FUO and lymphadenopathy differ according to disease group,although multivariate analysis indicated little diagnostic value for these features. 2. mNGS on lymph node tissue from children with FUO may serve as a efficient tool for distinguishing infectious diseases from other diseases. This is especially useful when a diagnosis cannot be determined with traditional methods. 3. mNGS targeted treatment can be administered in a timely manner and some underlying diseases can be indicated.

Can "Risk-Sharing" Mechanisms Help Clonal Aquatic Plants Mitigate the Stress of Nanoplastics?

Most aquatic plants applied to ecological restoration have demonstrated a clonal growth pattern. The risk-spreading strategy plays a crucial role in facilitating clonal plant growth under external environmental stresses via clonal integration. However, the effects of different concentrations of nanoplastics (NPs) on the growth traits of clonal aquatic plants are not well understood. Therefore, this study aimed to investigate the impact of NPs exposure on seedlings of parent plants and connected offspring ramets. A dose response experiment (0.1, 1, and 10 mg L-1) showed that the growth of Eichhornia crassipes (water hyacinth) was affected by 100 nm polystyrene nanoplastics after 28 days of exposure. Tracer analysis revealed that NPs are accumulated by parent plants and transferred to offspring ramets through stolon. Quantification analysis showed that when the parent plant was exposed to 10 mg L-1 NPs alone for 28 days, the offspring ramets contained approximately 13 ± 2 µg/g NPs. In the case of connected offspring ramets, leaf and root biomass decreased by 24%-51% and 32%-51%, respectively, when exposed to NP concentrations ranging from 0.1 to 10 mg L-1. Excessive enrichment of NPs had a detrimental effect on the photosynthetic system, decreasing the chlorophyll content and nonphotochemical quenching. An imbalance in the antioxidant defense systems, which were unable to cope with the oxidative stress caused by NP concentrations, further damaged various organs. The root system can take up NPs and then transfer them to the offspring through the stolon. Interference effects of NPs were observed in terms of root activity, metabolism, biofilm composition, and the plant's ability to purify water. However, the risk-spreading strategy employed by parent plants (interconnected offspring ramets) offered some relief from NP-induced stress, as it increased their relative growth rate by 1 to 1.38 times compared to individual plants. These findings provide substantial evidence of the high NP enrichment capacity of E. crassipes for ecological remediation. Nevertheless, we must also remain aware of the environmental risk associated with the spread of NPs within the clonal system of E. crassipes, and contaminated cloned individuals need to be precisely removed in a timely manner to maintain normal functions.

SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus.

Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes ("eGenes", whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.

[A case of Neonatal generalized atrophic benign epidermolysis bullosa due to variants of COL17A1 gene].

OBJECTIVE: To diagnose and explore the genetic etiology of a neonate with Hereditary epidermolysis bullosa. METHODS: A neonate who was admitted to Suqian Hospital Affiliated to Xuzhou Medical University on July 10, 2021 was selected as the study subject. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. And target gene capture and next-generation sequencing were carried out. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. RESULTS: The child was found to harbor compound heterozygous variants of the COL17A1 gene, namely c.997C>T (p.Q333X) and c.3481dupT (p.Y1161fs*2), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic. CONCLUSION: The child was diagnosed with Generalized atrophic benign epidermolysis bullosa due to the compound heterozygous variants of the COL17A1 gene.

Non-coding DNA variants for risk in lupus.

Systemic Lupus Erythematosus (SLE) is a multifactorial autoimmune disease that arises from a dynamic interplay between genetics and environmental triggers. The advent of sophisticated genomics technology has catalyzed a shift in our understanding of disease etiology, spotlighting the pivotal role of non-coding DNA variants in SLE pathogenesis. In this review, we present a comprehensive examination of the non-coding variants associated with SLE, shedding light on their role in influencing disease risk and progression. We discuss the latest methodological advancements that have been instrumental in the identification and functional characterization of these genomic elements, with a special focus on the transformative power of CRISPR-based gene-editing technologies. Additionally, the review probes into the therapeutic opportunities that arise from modulating non-coding regions associated with SLE. Through an exploration of the complex network of non-coding DNA, this review aspires to decode the genetic puzzle of SLE and set the stage for groundbreaking gene-based therapeutic interventions and the advancement of precision medicine strategies tailored to SLE management.

A reciprocal association between interpersonal relationship quality and student's positive affect: A three-wave random intercept cross-lagged study in a Chinese primary mathematics learning context.

AIM: This study adopted a three-wave random intercept cross-lagged panel model to explore the longitudinal reciprocal relationships between (a) the teacher-student relationship (TSR) quality and (b) the parent-child relationship (PCR) quality and positive affect among Chinese primary school students. SAMPLES: Two primary school student samples, including 3505 and 2505 students, were tracked with their perceived relationship quality with math teachers and parents and their positive affect levels in mathematics learning over three academic years. RESULTS: The results demonstrated that more closeness with parents could significantly predict students' subsequent higher level of positive affect in mathematics learning. However, more closeness with their math teachers did not show significant prediction. Meanwhile, more conflict with math teachers and parents could significantly predict their subsequent lower degree of perceived positive affect in mathematics learning. That is, a reciprocal association lines in the PCR quality and positive affect, whereas only a unidirectional association exists between the TSR and positive affect. The predictions of the experienced positive affect on their perceived interpersonal relationships with math teachers and parents were stronger than those in the reverse association. CONCLUSIONS: This study identifies that while the effects of closeness with math teachers and parents on positive affect in students' math learning differ, conflict with math teachers and parents indeed harms students' experienced positive affect in math learning. More attention should also be paid to fostering positive affect in math learning.

A bridge dynamic response analysis and load recognition method using traffic imaging.

As the primary variable load of bridges, vehicle load is an important parameter for bridge health monitoring. However, traditional Weigh-in-Motion (WIM) systems and the commonly used method of placing sensors on the bridge are challenging to apply in load monitoring for many small and medium-sized bridges. Therefore, this paper proposes a bridge vehicle load identification method based on traffic surveillance video data. Leveraging the surveillance video data on the bridge, without introducing additional hardware devices, the displacement of target points is detected through sub-pixel level image detection algorithms, enabling non-contact measurement of bridge structural response through imaging. A spatiotemporal relationship model of structural displacement, vehicle load, and load distribution is established to solve for vehicle load. Finally, model bridge tests under various loading conditions and engineering practice experiments are conducted to validate the feasibility of the method. The results of the model bridge tests show that the structural displacement measured using traffic video measurement has a deviation of less than 10% compared to the measurements obtained using contact displacement sensors (LVDT), and it can accurately reflect the displacement characteristics of the structure. The results of the field tests demonstrate that the average estimation deviation for heavy vehicle loads ranging from 12 to 18 tons is approximately 18%, meeting the engineering requirements. The proposed method can provide load statistical information for the extensive health monitoring of small and medium-sized bridges and offer a new technical pathway for obtaining bridge load information.

Risks of bleeding and thromboembolic events in patients undergoing colonoscopy on uninterrupted and interrupted anticoagulant therapy in real-world setting.

BACKGROUND: Although anticoagulants may potentially increase the risk of post-colonoscopy bleeding events, temporary discontinuation of medications could elevate the risk of thromboembolism (TE). There is a paucity of data regarding the incidence of bleeding and TE events in patients undergoing colonoscopy while on uninterrupted or interrupted anticoagulant therapy. Therefore, we aimed to ascertain the risks of post-colonoscopy TE and bleeding in patients with continuous or interrupted use of anticoagulant agents. METHODS: The electronic databases of PubMed, Embase, and the Cochrane library were comprehensively searched from inception to March 15, 2024. We identified studies reporting the incidence of bleeding and TE events in patients undergoing colonoscopy with uninterrupted or interrupted anticoagulant therapy. The pooled incidence rate of bleeding and TE events was estimated using a random-effects model. RESULTS: This study included a total of 15 studies involving 63, 017 patients. Overall, the incidence of post-procedural bleeding for uninterrupted and interrupted direct oral anticoagulants (DOACs) was found to be 3.60 % (95 % CI: 1.60 %-5.60 %), and 0.90 % (95 % CI: 0.10 %-10.30 %), respectively. Subgroup analysis revealed that older age patients (≥65 years) had a significantly higher rate of bleeding with uninterrupted DOACs therapy compared to younger age patients (< 65 years) (7.20 % vs. 2.00 %). The highest rate of bleeding was observed in Asia (7.20 %, 95 % CI: 2.20 %-12.10 %). Similarly, the risk of bleeding was significantly increased among patients interrupting DOACs therapy in Asia compared to North America (1.40 % vs. 0.26 %). For patients on uninterrupted and interrupted warfarin, a higher rate of bleeding events was observed in older age patients than younger age patients (4.90 % vs. 0.80 %, and 2.20 % vs. 1.70 %, respectively). Uninterrupted warfarin showed a more significant risk of bleeding in Asia (4.20 %, 95%CI: 1.90 %-6.60 %) compared to North America (1.00 %, 95%CI: 0.50 %-1.50 %). Among those who did not interrupt DOACs therapy, the incidence of TE was the lowest (0.08 %, 95%CI: 0.04 %-0.11 %). CONCLUSION: This study provides a comprehensive assessment of bleeding and TE risks in patients undergoing colonoscopy while receiving uninterrupted or interrupted anticoagulant therapy in the real-world setting. The overall incidence of post-colonoscopy bleeding and TE events is relatively low. However, the uninterrupted DOACs and warfarin are associated with an elevated risk of bleeding, particularly among elderly patients and the Asian population.

Dual-functional mediators of high-entropy Prussian blue analogues for lithiophilicity and sulfiphilicity in Li-S batteries.

Lithium-sulfur (Li-S) batteries are considered promising next-generation energy storage systems due to their high energy density (2600 W h kg-1) and cost-effectiveness. However, the shuttle effect of lithium polysulfides in sulfur cathodes and uncontrollable Li dendrite growth in Li metal anodes significantly impede the practical application of Li-S batteries. In this study, we address these challenges by employing a high-entropy Prussian blue analogue Mn0.4Co0.4Ni0.4Cu0.4Zn0.4[Fe(CN)6]2 (HE-PBA) composite containing multiple metal ions as a dual-functional mediator for Li-S batteries. Specifically, the HE-PBA composite provides abundant metal active sites that efficiently chemisorb lithium polysulfides (LiPSs) to facilitate fast redox conversion kinetics of LiPSs. In Li metal anodes, the exceptional lithiophilicity of the HE-PBA ensures a homogeneous Li ion flux, resulting in uniform Li deposition while mitigating the growth of Li dendrites. As a result, our work demonstrates outstanding long-term cycling performance with a decay rate of only 0.05% per cycle over 1000 cycles at 2.0 C. The HE-PBA@Cu/Li anode maintains a stable overpotential even after 600 h at 0.5 mA cm-2 under the total areal capacity of 1.0 mA h cm-2. This study showcases the application potential of the HE-PBA in Li-S batteries and encourages further exploration of prospective high-entropy materials used to engineer next-generation batteries.

Phosphorus release and realignment in anaerobic digestion of thermal hydrolysis pretreatment sludge - Masking effects from high ammonium.

Waste activated sludge (WAS) is a significant phosphorus (P) repository, and there is a growing interest in P recovery from WAS. Typically, the commercial technology for treating WAS involves thermal hydrolysis pretreatment (THP) coupled with anaerobic digestion (AD). However, there is ongoing debate regarding the transformation and distribution of P throughout this process. To address this, a long-term THP-AD process was operated in this study to comprehensively investigate P transformation and distribution. The results revealed that a substantial biodegradation of dissolved organic nitrogen (DON) raised the pH of the digestate to 8.3 during the AD process. This increased pH facilitated the dissolution of Al, leading to a reduction of 6.92 mg/L of NaOH-P. Simultaneously, sulfate reduction contributed to a decrease of 11.04 mg/L of Bipy-P in the solid. However, the reduction of Bipy-P and NaOH-P in the solid did not result in an improved P release to the supernatant. Conversely, a decrease of 23.60 mg/L P in the aqueous phase was observed after anaerobic digestion. The disappeared P was primarily precipitated with Mg and Ca, driven by the increased pH, and it contributed to the increase of HCl-P in the solid from 107.80 to 144.52 mg/L. These findings were further confirmed by results obtained from scanning electron microscopy (SEM), X-ray powder diffraction (XRD), and solid-state 31P nuclear magnetic resonance (NMR) spectroscopy. This study provides valuable insights into the mechanisms of P transformation during THP-AD process that is nearly opposite from conventional AD system.

Beneficial changes in gut microbiota after phototherapy for neonatal hyperbilirubinemia.

Phototherapy is the most commonly used treatment for neonatal hyperbilirubinemia (NH). Gut microbiota is involved in bilirubin metabolism; however, it is uncertain whether this is affected by phototherapy. The present study included 43 newborns with hyperbilirubinemia and collected fecal samples for high-throughput sequencing before and after phototherapy. Selection α diversity analysis was used to determine the differences in diversity and abundance between the two groups, whereas similarity was determined using ß diversity analysis. Linear discriminant analysis effect size analysis was used to screen for markedly different bacteria. The structure of the gut microbiota in newborns with hyperbilirubinemia changed after phototherapy, with a significant decrease in abundance and diversity. The changes in the key bacterial species were characterized by an increase in the abundance of Streptococcus salivarius and a decrease in the abundance of Escherichia, Klebsiella pneumoniae, Rothia mucilaginosa and Streptococcus oralis. These changes mainly manifested as an increase in beneficial bacteria and a decrease in opportunistic bacteria, which may not be related to the side effects of phototherapy. These results can provide theoretical assistance for microbiological research on the later stages of NH.

Bifunctional Role of High-Entropy Selenides in Accelerating Redox Conversion and Modulating Lithium Plating towards Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries, recognized as one of the most promising next-generation energy storage systems, are still limited by the "shuttle effect" of soluble polysulfides (LiPSs) on the cathode and the uncontrolled growth of lithium dendrites on the anode. These issues are critical obstacles to their practical application. Currently, many researchers have addressed these challenges from a unilateral perspective. Herein, we propose bifunctional hosts based on high-entropy selenides (HE-Se) to simultaneously tackle the persistent problems on both the positive and negative electrodes of Li-S batteries. On the one hand, HE-Se interacts with polysulfides to promote their conversion, effectively mitigating the shuttle effect. On the other hand, HE-Se provides multiple lithophilic sites during the initial nucleation of Li+, which reduces overpotential and exhibits excellent lithophilicity and cyclic stability. As a result, Li-S batteries incorporating the HE-Se host demonstrate outstanding performance in terms of rate capability and cycling stability. Additionally, the porous lithophilic HE-Se structure offers sufficient nucleation sites, inhibits the growth of dendritic lithium, and accommodates volume changes during charging and discharging cycles. This study highlights the potential of sulphophilic/lithophilic high-entropy materials in designing advanced Li-S batteries and encourages further exploration in this area.

Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta­analysis of randomized controlled trials.

Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors on megakaryocyte membranes in the bone marrow. This promotes megakaryocyte maturation and increases platelet production. Despite a 2-6% incidence of thrombotic events during TPO-RA treatment, it remains uncertain whether TPO-RAs elevate thrombosis rates. A comprehensive search of electronic databases was conducted using the relevant search criteria. To assess the risk of bias, the included studies were assessed using the revised Cochrane Risk of Bias Assessment Tool 2.0, and a meta-analysis was performed using RevMan 5.4.1. A total of 1,698 patients with ITP were included from randomized controlled trials (RCTs). There were 26 thromboembolic events in the TPO-RAs group and 4 in the control group. However, there was no significant difference in the incidence of thrombotic events between the two groups [odds ratio (OR)=1.76, 95% confidence interval (CI): 0.78-4.00, P=0.18], even if the duration of treatment was >12 weeks (OR=2.46, 95% CI: 0.81-7.43, P=0.11). Subgroup analysis showed that none of the four drugs significantly increased the incidence of thrombotic events (romiplostim: OR=0.92, 95% CI: 0.14-6.13, P=0.93; eltrombopag: OR=2.32, 95% CI: 0.64-8.47, P=0.20; avatrombopag: OR=4.15, 95% CI: 0.20-85.23, P=0.36; and hetrombopag: OR=0.76, 95% CI: 0.03-18.76, P=0.87). There was also no significant difference in the results of the double-blinded placebo-controlled RCTs (OR=1.21, 95% CI: 0.41-3.58, P=0.73). Compared to patients with ITP who did not receive TPO-RA treatment, those receiving TPO-RA treatment did not exhibit a significantly increased risk of thrombotic events.

Research in the application of artificial intelligence to lung cancer diagnosis.

The morbidity and mortality rates in lung cancer are high worldwide. Early diagnosis and personalized treatment are important to manage this public health issue. In recent years, artificial intelligence (AI) has played increasingly important roles in early screening, auxiliary diagnosis, and prognostic assessment. AI uses algorithms to extract quantitative feature information from high-volume and high-latitude data and learn existing data to predict disease outcomes. In this review, we describe the current uses of AI in lung cancer-focused pathomics, imageomics, and genomics applications.

Near-gapless genome and transcriptome analyses provide insights into fruiting body development in Lentinula edodes.

Fruiting body development in macrofungi is an intensive research subject. In this study, high-quality genomes were assembled for two sexually compatible monokaryons from a heterokaryotic Lentinula edodes strain WX1, and variations in L. edodes genomes were analyzed. Specifically, differential gene expression and allele-specific expression (ASE) were analyzed using the two monokaryotic genomes and transcriptome data from four different stages of fruiting body development in WX1. Results revealed that after aeration, mycelia sensed cell wall stress, pheromones, and a decrease in CO2 concentration, leading to up-regulated expression in genes related to cell adhesion, cell wall remodeling, proteolysis, and lipid metabolism, which may promote primordium differentiation. Aquaporin genes and those related to proteolysis, mitosis, lipid, and carbohydrate metabolism may play important roles in primordium development, while genes related to tissue differentiation and sexual reproduction were active in fruiting body. Several essential genes for fruiting body development were allele-specifically expressed and the two nuclear types could synergistically regulate fruiting body development by dominantly expressing genes with different functions. ASE was probably induced by long terminal repeat-retrotransposons. Findings here contribute to the further understanding of the mechanism of fruiting body development in macrofungi.