Role of urea in the retention of DON in soil by clay minerals: Analysis based upon molecular weight.

As a widely used fertilizer, urea significantly promotes the leaching of dissolved organic nitrogen (DON) in soils and aggravates nitrogen contamination in groundwater. Clay minerals are considered the most important factor in retaining DON. However, the effect of urea on the retention of DON with different molecular weights by clay minerals is unknown. In this study, the retention of both low-molecular weight DON (LMWD) and high-molecular weight DON (HMWD) by clay minerals in the presence of urea was investigated. For this purpose, batch adsorption and soil column leaching experiments, characterization analysis (Fourier transform infrared spectroscopy X-ray diffraction, and X-ray photoelectron spectroscopy), and molecular dynamics simulations were carried out. Urea had a positive effect on the adsorption of LMWD, whereas a competitive effect existed for the adsorption of HMWD. The dominant interactions among DON, urea, and clay minerals included H-bonding, ligand exchange, and cation exchange. The urea was preferentially adsorbed on clay minerals and formed a complex, which provided more adsorption sites to LMWD and only a few to HMWD. The presence of urea increased the retention of LMWD and decreased the retention of HMWD in clay minerals. The retention capacity of LMWD increased by 6.9%-12.8%, while that of HMWD decreased by 6.7%-53.1%. These findings suggest that LMWD tended to be trapped in soils, while HMWD was prone to be leached into groundwater, which can be used to evaluate the leaching of DON from soil to groundwater.

Research progress and considerations on oral rehydration therapy for the prevention and treatment of severe burn shock: A narrative review.

Severe burns are a significant cause of life-threatening conditions in both peacetime and wartime. Shock is a critical complication during the early stages of burn injury, contributing substantially to mortality and long-term disability. Effective fluid resuscitation is crucial for preventing and treating shock, with prompt administration being vital. However, timely intravenous fluid resuscitation is often challenging, and errors in resuscitation significantly contribute to mortality. Therefore, exploring a more rapid and effective non-invasive method of fluid resuscitation is necessary. Oral rehydration therapy (ORT) has shown considerable potential in this regard. This paper reviews ORT's historical development and current research progress, discussing its application in early anti-shock treatment for burns. While ORT is generally safe, potential complications like diarrhoea, vomiting, and abdominal discomfort must be noted, particularly if the rehydration rate is too rapid or if gastrointestinal issues exist. Careful patient assessment and monitoring are essential during ORT administration. Based on a comprehensive review of relevant research, we present provisional guidelines for ORT in burn patients. These guidelines aim to inform clinical practice but should be applied cautiously due to limited clinical evidence. Implementation must be tailored to the patient's condition under healthcare supervision, with adjustments according to evolving circumstances: ① Initiation timing: Start as soon as possible, and the ideal start time is usually within 6 h after injury. ② Rate of application: Employing a fractional administration approach, wherein small quantities of approximately 150-250 millilitres are provided for each instance and the initial fluid rate of oral rehydration can be simplified to 100 mL/kg/24 h. ③ Composition combination: In addition to essential salts and glucose, the oral rehydration solution can incorporate various anti-inflammatory and cellular protection constituents.

Molecular glue triggers degradation of PHGDH by enhancing the interaction between DDB1 and PHGDH.

Cancer stem cells (CSCs) play a pivotal role in tumor initiation, proliferation, metastasis, drug resistance, and recurrence. Consequently, targeting CSCs has emerged as a promising avenue for cancer therapy. Recently, 3-phosphoglycerate dehydrogenase (PHGDH) has been identified as being intricately associated with the regulation of numerous cancer stem cells. Yet, reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are limited. In this study, the novel "molecular glue" LXH-3-71 was identified, and it robustly induced degradation of PHGDH, thereby modulating the stemness of colorectal cancer cells (CRCs) both in vitro and in vivo. Remarkably, LXH-3-71 was observed to form a dynamic chimera, between PHGDH and the DDB1-CRL E3 ligase. These insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH inhibitors. Additionally, compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase, facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation.

Hypernetwork modeling and topology of high-order interactions for complex systems.

Interactions among the underlying agents of a complex system are not only limited to dyads but can also occur in larger groups. Currently, no generic model has been developed to capture high-order interactions (HOI), which, along with pairwise interactions, portray a detailed landscape of complex systems. Here, we integrate evolutionary game theory and behavioral ecology into a unified statistical mechanics framework, allowing all agents (modeled as nodes) and their bidirectional, signed, and weighted interactions at various orders (modeled as links or hyperlinks) to be coded into hypernetworks. Such hypernetworks can distinguish between how pairwise interactions modulate a third agent (active HOI) and how the altered state of each agent in turn governs interactions between other agents (passive HOI). The simultaneous occurrence of active and passive HOI can drive complex systems to evolve at multiple time and space scales. We apply the model to reconstruct a hypernetwork of hexa-species microbial communities, and by dissecting the topological architecture of the hypernetwork using GLMY homology theory, we find distinct roles of pairwise interactions and HOI in shaping community behavior and dynamics. The statistical relevance of the hypernetwork model is validated using a series of in vitro mono-, co-, and tricultural experiments based on three bacterial species.

The DNA loop release factor WAPL suppresses Epstein-Barr virus latent membrane protein expression to maintain the highly restricted latency I program.

Epstein-Barr virus (EBV) uses latency programs to colonize the memory B-cell reservoir, and each program is associated with human malignancies. However, knowledge remains incomplete of epigenetic mechanisms that maintain the highly restricted latency I program, present in memory and Burkitt lymphoma cells, in which EBNA1 is the only EBV-encoded protein expressed. Given increasing appreciation that higher order chromatin architecture is an important determinant of viral and host gene expression, we investigated roles of Wings Apart-Like Protein Homolog (WAPL), a host factor that unloads cohesin to control DNA loop size and that was discovered as an EBNA2-associated protein. WAPL knockout (KO) in Burkitt cells de-repressed LMP1 and LMP2A expression, but not other EBV oncogenes, to yield a viral program reminiscent of EBV latency II, which is rarely observed in B-cells. WAPL KO also increased LMP1/2A levels in latency III lymphoblastoid cells. WAPL KO altered EBV genome architecture, triggering formation of DNA loops between the LMP promoter region and the EBV origins of lytic replication (oriLyt). Hi-C analysis further demonstrated that WAPL KO reprogrammed EBV genomic DNA looping. LMP1 and LMP2A de-repression correlated with decreased histone repressive marks at their promoters. We propose that EBV coopts WAPL to negatively regulate latent membrane protein expression to maintain Burkitt latency I.

Bioinspired triple-layered membranes for periodontal guided bone regeneration applications.

Barrier membranes have been used for the treatment of alveolar bone loss caused by periodontal diseases or trauma. However, an optimal barrier membrane must satisfy multiple requirements simultaneously, which are challenging to combine into a single material. We herein report the design of a bioinspired membrane consisting of three functional layers. The primary layer is composed of clay nanosheets and chitin, which form a nacre-inspired laminated structure. A calcium phosphate mineral layer is deposited on the inner surface of the nacre-inspired layer, while a poly(lactic acid) layer is coated on the outer surface. The composite membrane integrates good mechanical strength and deformability because of the nacre-inspired structure, facilitating operations during the implant surgery. The mineral layer induces the osteogenic differentiation of bone marrow mesenchymal stem cells and increases the stiffness of the membrane, which is an important factor for the regeneration process. The poly(lactic acid) layer can prevent unwanted mineralization on the outer surface of the membrane in oral environments. Cell experiments reveal that the membrane exhibits good biocompatibility and anti-infiltration capability toward connective tissue/epithelium cells. Furthermore, in vitro analyses show that the membrane does not degrade too fast, allowing enough time for bone regeneration. In vivo experiments prove that the membrane can effectively induce better bone regeneration and higher trabecular bone density in alveolar bone defects. This study demonstrates the potential of this bioinspired triple-layered membrane with hierarchical structures as a promising barrier material for periodontal guided tissue regeneration.

Population Distribution and Patients' Awareness of Food Impaction: A Cross-Sectional Study.

BACKGROUND: Food impaction can contribute to a variety of oral health problems. However, the prevalence of food impaction in the population and patient awareness of these issues are poorly reported on. METHODS: A questionnaire about food impaction was designed and uploaded to an online platform (Sojump) which was then circulated among the study participants using various social media platforms. Participants were asked to anonymously respond to the questionnaire regarding the prevalence of food impaction, its influence on their quality of life, their consultation rates and their oral cleaning methods. The survey was conducted through an online survey portal. Statistical analyses were performed using SPSS and GraphPad. The Chi-Square test, Bonferroni test and the Kruskal-Wallis H test were used to measure categorical variables from the survey. RESULTS: The results showed that the prevalence of food impaction in non-dental professional participants was 86.9%. Among these patients, 12,157 pairs/cases of proximal contacts were affected. The number of food impaction cases in posterior teeth was significantly higher than in anterior teeth. Approximately 81.9% of patients believed that food impaction could affect their lives. However, the consultation rate for these patients was only 17.7%. CONCLUSIONS: This study revealed that food impaction continued to have a high rate of incidence and a low rate of consultation, potentially due to a lack of awareness regarding its influence on oral health. To effectively prevent and address problems resulting from food impaction, both dentists and society need to enhance oral health knowledge in the population.

Comparative Analysis of Tracking and Behavioral Patterns between Wild-type and Genetically Modified Fruit Flies using Computer Vision and Statistical Methods.

Collective animal behavior occurs in groups and swarms at almost every biological scale, from single-celled organisms to the largest animals on Earth. The intriguing mysteries behind these group behaviors have attracted many scholars, and while it is known that models can reproduce qualitative features of such complex behaviors, this requires data from real animals to demonstrate, and obtaining data on the exact features of these groups is tricky.In this paper, we propose the Hidden Markov Unscented Tracker (HMUT), which combines the state prediction capability of HMM and the high-precision nonlinear processing capability of UKF. This prediction-driven tracking mechanism enables HMUT to quickly adjust tracking strategies when facing sudden changes in target motion direction or rapid changes in speed, reducing the risk of tracking loss. Videos of fruit fly swarm movement in an enclosed environment are captured using stereo cameras. For the captured fruit fly images, the thresholded AKAZE algorithm is first used to detect the positions of individual fruit flies in the images, and the motion of the fruit flies is modeled using a multidimensional hidden Markov model (HMM). Tracking is then performed using the Unscented Kalman Filter algorithm to obtain the flight trajectories of the fruit flies in two camera views. Finally, 3D reconstruction of the trajectories in both views is achieved through polar coordinate constraints, resulting in 3D motion data of the fruit flies. Additionally, the efficiency and accuracy of the proposed algorithm are evaluated by simulating fruit fly swarm movement using the Boids algorithm. Finally, based on the tracked fruit fly flight data, behavioral characteristics of the fruit flies are analyzed from two perspectives. The first is a statistical analysis of the differences between the two behaviors. The second dimension involves clustering trajectory similarity using the DTW method based on fruit fly flight trajectories, further analyzing the similarity within clusters and differences between clusters.

Spatial and temporal dynamics of microbes and genes in drinking water reservoirs: Distribution and potential for taste and odor generation.

Numerous reservoirs encounter challenges related to taste and odor issues, often attributed to odorous compounds such as geosmin (GSM) and 2-methylisoborneol (2-MIB). In this study, two large reservoirs located in northern and southern China were investigated. The Jinpen (JP) reservoir had 45.99 % Actinomycetes and 14.82 % Cyanobacteria, while the Xikeng (XK) reservoir contained 37.55 % Actinomycetes and 48.27 % Cyanobacteria. Most of the 2-MIB produced in surface layers of the two reservoirs in summer originated from Cyanobacteria, most of the 2-MIB produced in winter and in the bottom water originated from Actinomycetes. Mic gene abundance in the XK reservoir reached 5.42 × 104 copies/L in winter. The abundance of GSM synthase was notably high in the bottom layer and sediment of both reservoirs, while 2-MIB synthase was abundant in the surface layer of the XK reservoir, echoing the patterns observed in mic gene abundance. The abundance of odor-producing enzymes in the two reservoirs was inhibited by total nitrogen, temperature significantly influenced Actinomycetes abundance in the JP reservoir, whereas dissolved oxygen had a greater impact in the XK reservoir. Overall, this study elucidates the molecular mechanisms underlying odor compounding, providing essential guidance for water quality management strategies and the improvement of urban water reservoir quality.

Qishen Granules Modulate Metabolism Flexibility Against Myocardial Infarction via HIF-1 α-Dependent Mechanisms in Rats.

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS: QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.

Revealing the vital role of sulfur site on the surface of pyrite in 1O2 formation for promoting ciprofloxacin degradation via peracetic acid activation.

Pyrite has been widely utilized to activate oxidants for water treatment, yet the regulation of reactive oxygen species (ROS) by sulfur sites on its surface has been overlooked. In this study, the surface sulfur sites were regulated by thermal modification of natural pyrite in the N2 atmosphere (denoted as P-X, where X represented pyrolysis temperatures ranging from 400 to 700 °C), and these modified pyrites were employed to activate peracetic acid (PAA) for ciprofloxacin (CIP) degradation. The results revealed that the degradation rate of CIP increased as the reduced sulfur content increased, with the P600/PAA system achieving the highest apparent degradation rate (kobs=0.0999 min-1). Quenching experiments and electron paramagnetic resonance (EPR) analysis identified various ROS involved in the P-X/PAA system, with hydroxyl radical (·OH) and singlet oxygen (1O2) identified as dominant reactive species responsible for CIP degradation. The reduced sulfur sites served as the primary active sites facilitating the conversion of organic radicals (·CH3C(O)OO) into superoxide radicals (·O2-) and 1O2. Furthermore, the P600/PAA system demonstrated robust adaptability under both acidic and neutral pH conditions, efficiently degrading CIP even in the presence of complex matrices such as Cl-, NO3-, SO42-, NH4+, or humic acid (HA) in water bodies, although HCO3- was found to inhibit CIP degradation. This study significantly enhances our understanding of the interaction between reduced sulfur sites and ROS in PAA-based advanced oxidation processes (AOPs), offering a promising technology for efficient antibiotic treatment in water purification.

Streptococcus agalactiae isolated from clinical mastitis cases on large dairy farms in north China: phenotype, genotype of antimicrobial resistance and virulence genes.

Streptococcus agalactiae (Strep. agalactiae) is bovine mastitis pathogen and has thus became a matter of concern to dairy farms worldwide in terms of economic loss. The aims of this study were to (a) determine virulence genes, and (b) characterize the antimicrobial resistance (AMR) profiles and AMR genes and (c) figure out the relationship between AMR phenotypes and genotypes of Strep. agalactiae isolated from dairy cows in north China. A total of 20 virulence genes and 23 AMR genes of 140 isolates collected from 12 farms in six provinces were studied. The antimicrobial susceptibility of 10 veterinary commonly used antimicrobials were tested using the broth microdilution method. Results showed that all the isolates harbored the virulence genes lacIV, gapC, and dltA. The isolates that harbored the genes lacIII, fbsA, hylB, and cfb exhibited the high prevalence (99.29%), followed by isolates that harbored lacI (98.57%), bibA (97.86%), cylE (97.14%), lacII (92.14%), cspA (52.14%), pavA (25%), bca (2.14%), and scpB (0.71%). The fbsB, lmb, spbI, bac, and rib genes were not detected. The virulence patterns of B (fbsA_cfb_cylE_ hylB_bibA_cspA_ gapC_dltA_lacIII/IV) and C (fbsA_cfb_ bibA _ gapC_ dltA_lacIV) were dominant, accounting for 97.86% of the isolates. The following AMR genes were prevalent: pbp1A (97.14%), tet(M) (95.00%), lnu (A) (80.71%), erm (B) (75.00%), tet(O) (72.14%), blaZ (49.29%), tet(S) (29.29%), blaTEM (25.71%), erm (A) (17.14%), erm (C) (13.57%), tet (L) (10.71%), linB (2.86%), and erm (TR) (2.86%). The pbp2b, mecA1, mecC, lnu (D), erm (F/G/Q), and mef (A) genes were not detected. Eighty percent of the isolates harbored AMR genes and were highly resistant to tetracycline, followed by macrolides (10.71%), lincosamides (9.29%) and ß-lactams (4.29%). In conclusion, isolates only exhibited well correlation between tetracyclines resistance phenotype and genotype, and almost all isolates harbored intact combination of virulence genes.

Retinal ischemia-reperfusion injury and pretreatment with Lycium barbarum glycopeptide.

AIM: To investigate the antioxidant protective effect of Lycium barbarum glycopeptide (LbGP) pretreatment on retinal ischemia-reperfusion (I/R) injury (RIRI) in rats. METHODS: RIRI was induced in Sprague Dawley rats through anterior chamber perfusion, and pretreatment involved administering LbGP via gavage for 7d. After 24h of reperfusion, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (CREA) levels, retinal structure, expression of Caspase-3 and Caspase-8, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) in the retina were measured. RESULTS: The pretreatment with LbGP effectively protected the retina and retinal tissue from edema and inflammation in the ganglion cell layer (GCL) and nerve fiber layer (NFL) of rats subjected to RIRI, as shown by light microscopy and optical coherence tomography (OCT). Serum AST was higher in the model group than in the blank group (P=0.042), but no difference was found in ALT, AST, and CREA across the LbGP groups and model group. Caspase-3 expression was higher in the model group than in the blank group (P=0.006), but no difference was found among LbGP groups and the model group. Caspase-8 expression was higher in the model group than in the blank group (P=0.000), and lower in the 400 mg/kg LbGP group than in the model group (P=0.016). SOD activity was lower in the model group than in the blank group (P=0.001), and the decrease was slower in the 400 mg/kg LbGP group than in the model group (P=0.003). MDA content was higher in the model group than in the blank group (P=0.001), and lower in the 400 mg/kg LbGP group than in the model group (P=0.016). The pretreatment with LbGP did not result in any observed liver or renal toxicity in the model. CONCLUSION: LbGP pretreatment exhibits dose-dependent anti-inflammatory, and antioxidative effects by reducing Caspase-8 expression, preventing declines of SOD activity, and decreasing MDA content in the RIRI rat model.

Associations between sleep-related disorders and cardiovascular disease risk in hypertensive patients: Insights from the National Health and Nutrition Examination Survey (NHANES): A cross-sectional study.

Both sleep-related disorders (SRD) and hypertension (HTN) are closely related to the occurrence of cardiovascular disease (CVD); however, few studies have explored their combined effect. Based on the National Health and Nutrition Examination Survey (NHANES) database, we comprehensively analyzed the combined effect of SRD and HTN on the occurrence of CVD. The weighted multivariate logistic regression analysis was adopted to explore how SRD and HTN can affect the occurrence of CVD. Specifically, the additive interaction was evaluated by the relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (SI), and the multiplicative interaction was evaluated by the odds ratio (OR) along with 95% confidence interval (CI) from the product term. All the 33,383 participants from the NHANES database were divided into 2 groups, i.e., the CVD (n = 3712) and non-CVD (n = 29,671) groups. The results indicated that SRD (Model 3: OR = 1.90, 95% CI: 1.60-2.25) and HTN (Model 3: OR = 2.28, 95% CI: 1.87-2.79) were both significantly associated with an increased risk of CVD. Additionally, we observed a significant additive interaction (RERI = 0.88, 95% CI: 0.03-0.65; AP = 0.22, 95% CI: 0.01-0.21; SI = 1.15, 95% CI: 1.07-1.33) and a significant multiplicative interaction (OR = 1.07, 95% CI: 1.03-1.10) between SRD and HTN on the occurrence of CVD. While both SRD and HTN are associated with CVD occurrence, their interaction can also contribute to the development of CVD.

Two-dimensional silk.

Despite the promise of silk-based devices, the inherent disorder of native silk limits performance. Here, we report highly ordered two-dimensional silk fibroin (SF) films grown epitaxially on van der Waals (vdW) substrates. Using atomic force microscopy, nano-Fourier transform infrared spectroscopy, and molecular dynamics, we show that the films consist of lamellae of SF molecules that exhibit the same secondary structure as the nanocrystallites of native silk. Increasing the SF concentration results in multilayers that grow either by direct assembly of SF molecules into the lamellae or, at high concentrations, along a two-step pathway beginning with a disordered monolayer that then crystallizes. Scanning Kelvin probe measurements show that these films substantially alter the surface potential; thus, they provide a platform for silk-based electronics on vdW solids.

Observation of Spin Splitting in Room-Temperature Metallic Antiferromagnet CrSb.

Recently, unconventional antiferromagnets that enable the spin splitting (SS) of electronic states have been theoretically proposed and experimentally realized, where the magnetic sublattices containing moments pointing at different directions are connected by a novel set of symmetries. Such SS is substantial, k-dependent, and independent of the spin-orbit coupling (SOC) strength, making these magnets promising materials for antiferromagnetic spintronics. Here, combined with angle-resolved photoemission spectroscopy (ARPES) and density functional theory (DFT) calculations, a systematic study on CrSb, a metallic spin-split antiferromagnet candidate with Néel temperature TN = 703 K, is conducted. The data reveal the electronic structure of CrSb along both out-of-plane and in-plane momentum directions, rendering an anisotropic k-dependent SS that agrees well with the calculational results. The magnitude of such SS reaches up to at least 0.8 eV at non-high-symmetry momentum points, which is significantly higher than the largest known SOC-induced SS. This compound expands the choice of materials in the field of antiferromagnetic spintronics and is likely to stimulate subsequent investigations of high-efficiency spintronic devices that are functional at room temperature.

Machine learning in predicting postoperative complications in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease of unknown origin that can cause significant disability and morbidity with its progression. Due to the unique nature of CD, surgery is often necessary for many patients during their lifetime, and the incidence of postoperative complications is high, which can affect the prognosis of patients. Therefore, it is essential to identify and manage postoperative complications. Machine learning (ML) has become increasingly important in the medical field, and ML-based models can be used to predict postoperative complications of intestinal resection for CD. Recently, a valuable article titled "Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study" was published by Wang et al. We appreciate the authors' creative work, and we are willing to share our views and discuss them with the authors.

Human leukocyte antigen evolutionary divergence as a novel risk factor for donor selection in acute lymphoblastic leukemia patients undergoing haploidentical hematopoietic stem cell transplantation.

Introduction: The human leukocyte antigen (HLA) evolutionary divergence (HED) reflects immunopeptidome diversity and has been shown to predict the response of tumors to immunotherapy. Its impact on allogeneic hematopoietic stem cell transplantation (HSCT) is controversial in different studies. Methods: In this study, we retrospectively analyzed the clinical impact of class I and II HED in 225 acute lymphoblastic leukemia patients undergoing HSCT from related haploidentical donors. The HED for recipient, donor, and donor-recipient pair was calculated based on Grantham distance, which accounts for variations in the composition, polarity, and volume of each amino acid within the peptide-binding groove of two HLA alleles. The median value of HED scores was used as a cut-off to stratify patients with high or low HED. Results: The class I HED for recipient (R_HEDclass I) showed the strongest association with cumulative incidence of relapse (12.2 vs. 25.0%, P = 0.00814) but not with acute graft-versus-host disease. The patients with high class II HED for donor-recipient (D/R_HEDclass II) showed a significantly higher cumulative incidence of severe aGVHD than those with low D/R_HEDclass II (24.0% vs. 6.1%, P = 0.0027). Multivariate analysis indicated that a high D/R_HEDclass II was an independent risk factor for the development of severe aGVHD (P = 0.007), and a high R_HEDclass I had a more than two-fold reduced risk of relapse (P = 0.028). However, there was no discernible difference in overall survival (OS) or disease-free survival (DFS) for patients with high or low HED, which was inconsistent with the previous investigation. Discussion: While the observation are limited by the presented single center retrospective cohort, the results show that HED has poor prognostic value in OS or DFS, as well as the associations with relapse and aGVHD. In haploidentical setting, class II HED for donor-recipient pair (D/R_HEDclass II) is an independent and novel risk factor for finding the best haploidentical donor, which could potentially influence clinical practice if verified in larger cohorts.

Understanding the role of bats as fungal vectors in the environment.

Bats (Chiroptera), the second largest group of mammals, are known for their unique immune system and their ability to act as vectors for various zoonoses. Bats also act as important carriers of fungi, which include plant, animal, and human pathogens. Their roosting areas, foraging behaviors, and even migration routes make bats ideal vectors for fungi. We isolated 75 culturable fungal species from bats in Yunnan Province, China, with 36 species representing known pathogens of plants, animals, and humans, while 39 species are non-pathogenic fungi. Among these species, 77% (58 species) belonged to Ascomycota, 9% (seven species) belonged to Basidiomycota, and 13% (10 species) belonged to Mucoromycota. Even though several taxonomic studies on fungi associated with bats have been published, studies exploring the role of bats as fungal vectors are lacking. This study discusses the fungi host-specific traits and pathogenicity and the impact and ecological significance of bats as fungal vectors.

Structural basis for the concerted antiphage activity in the SIR2-HerA system.

Recently, a novel two-gene bacterial defense system against phages, encoding a SIR2 NADase and a HerA ATPase/helicase, has been identified. However, the molecular mechanism of the bacterial SIR2-HerA immune system remains unclear. Here, we determine the cryo-EM structures of SIR2, HerA and their complex from Paenibacillus sp. 453MF in different functional states. The SIR2 proteins oligomerize into a dodecameric ring-shaped structure consisting of two layers of interlocked hexamers, in which each subunit exhibits an auto-inhibited conformation. Distinct from the canonical AAA+ proteins, HerA hexamer alone in this antiphage system adopts a split spiral arrangement, which is stabilized by a unique C-terminal extension. SIR2 and HerA proteins assemble into a ∼1.1 MDa torch-shaped complex to fight against phage infection. Importantly, disruption of the interactions between SIR2 and HerA largely abolishes the antiphage activity. Interestingly, binding alters the oligomer state of SIR2, switching from a dodecamer to a tetradecamer state. The formation of the SIR2-HerA binary complex activates NADase and nuclease activities in SIR2 and ATPase and helicase activities in HerA. Together, our study not only provides a structural basis for the functional communications between SIR2 and HerA proteins, but also unravels a novel concerted antiviral mechanism through NAD+ degradation, ATP hydrolysis, and DNA cleavage.