Machine learning model predicts airway stenosis requiring clinical intervention in patients after lung transplantation: a retrospective case-controlled study.

BACKGROUND: Patients with airway stenosis (AS) are associated with considerable morbidity and mortality after lung transplantation (LTx). This study aims to develop and validate machine learning (ML) models to predict AS requiring clinical intervention in patients after LTx. METHODS: Patients who underwent LTx between January 2017 and December 2019 were reviewed. The conventional logistic regression (LR) model was fitted by the independent risk factors which were determined by multivariate LR. The optimal ML model was determined based on 7 feature selection methods and 8 ML algorithms. Model performance was assessed by the area under the curve (AUC) and brier score, which were internally validated by the bootstrap method. RESULTS: A total of 381 LTx patients were included, and 40 (10.5%) patients developed AS. Multivariate analysis indicated that male, pulmonary arterial hypertension, and postoperative 6-min walking test were significantly associated with AS (all P < 0.001). The conventional LR model showed performance with an AUC of 0.689 and brier score of 0.091. In total, 56 ML models were developed and the optimal ML model was the model fitted using a random forest algorithm with a determination coefficient feature selection method. The optimal model exhibited the highest AUC and brier score values of 0.760 (95% confidence interval [CI], 0.666-0.864) and 0.085 (95% CI, 0.058-0.117) among all ML models, which was superior to the conventional LR model. CONCLUSIONS: The optimal ML model, which was developed by clinical characteristics, allows for the satisfactory prediction of AS in patients after LTx.

Retinal displacement after surgery for idiopathic macular hole.

AIM: To review and summarize the mechanism hypothesis, influencing factors and possible consequences of macular retinal displacement after idiopathic macular hole (IMH) surgery. METHODS: PubMed and Web of Science database was searched for studies published before April 2023 on "Retinal displacement", "Idiopathic macular holes", and "Macular displacement". RESULTS: Recently, more academics have begun to focus on retinal displacement following idiopathic macular holes. They found that internal limiting membrane (ILM) peeling was the main cause of inducing postoperative position shift in the macular region. Moreover, several studies have revealed that the macular hole itself, as well as ILM peeling method, will have an impact on the result. In addition, this phenomenon is related to postoperative changes in macular retinal thickness, cone outer segment tips line recovery, the occurrence of dissociated optic nerve fiber layer (DONFL) and the degree of metamorphopsia. CONCLUSION: As a subclinical phenomenon, the clinical significance of postoperative macular displacement cannot be underestimated as it may affect the recovery of anatomy and function.

Retrospective analysis based on a clinical grading system for patients with hepatic hemangioma: A single center experience.

BACKGROUND: The optimal approach for managing hepatic hemangioma is controversial. AIM: To evaluate a clinical grading system for management of hepatic hemangioma based on our 17-year of single institution experience. METHODS: A clinical grading system was retrospectively applied to 1171 patients with hepatic hemangioma from January 2002 to December 2018. Patients were classified into four groups based on the clinical grading system and treatment: (1) Observation group with score < 4 (Obs score < 4); (2) Surgical group with score < 4 (Sur score < 4); (3) Observation group with score ≥ 4 (Obs score ≥ 4); and (4) Surgical group with score ≥ 4 (Sur score ≥ 4). The clinico-pathological index and outcomes were evaluated. RESULTS: There were significantly fewer symptomatic patients in surgical groups (Sur score ≥ 4 vs Obs score ≥ 4, P < 0.001; Sur score < 4 vs Obs score < 4, χ² = 8.60, P = 0.004; Sur score ≥ 4 vs Obs score < 4, P < 0.001). The patients in Sur score ≥ 4 had a lower rate of in need for intervention and total patients with adverse event than in Obs score ≥ 4 (P < 0.001; P < 0.001). Nevertheless, there was no significant difference in need for intervention and total patients with adverse event between the Sur score < 4 and Obs score < 4 (P > 0.05; χ² = 1.68, P > 0.05). CONCLUSION: This clinical grading system appeared as a practical tool for hepatic hemangioma. Surgery can be suggested for patients with a score ≥ 4. For those with < 4, follow-up should be proposed.

Targeted inhibition of m6A demethylase FTO by FB23 attenuates allergic inflammation in the airway epithelium.

Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.

Targeted dephosphorylation of SMAD3 as an approach to impede TGF-ß signaling.

TGF-ß (transforming growth factor-ß) signaling is involved in a myriad of cellular processes and its dysregulation has been implicated in many human diseases, including fibrosis and cancer. TGF-ß transcriptional responses are controlled by tail phosphorylation of transcription factors SMAD2 and SMAD3 (mothers against decapentaplegic homolog 2/3). Therefore, targeted dephosphorylation of phospho-SMAD3 could provide an innovative mechanism to block some TGF-ß-induced transcriptional responses, such as the transcription of SERPINE-1, which encodes plasminogen activator inhibitor 1 (PAI-1). Here, by developing and employing a bifunctional molecule, BDPIC (bromoTAG-dTAG proximity-inducing chimera), we redirected multiple phosphatases, tagged with bromoTAG, to dephosphorylate phospho-SMAD3, tagged with dTAG. Using CRISPR-Cas9 technology, we generated homozygous double knock-in A549 bromoTAG/bromoTAG PPM1H/ dTAG/dTAG SMAD3 cells, in which the BDPIC-induced proximity between bromoTAG-PPM1H and dTAG-SMAD3 led to a robust dephosphorylation of dTAG-SMAD3 and a significant decrease in SERPINE-1 transcription. Our work demonstrates targeted dephosphorylation of phospho-proteins as an exciting modality for rewiring cell signaling.

Phillyrin promotes autophagosome formation in A53T-αSyn-induced Parkinson's disease model via modulation of REEP1.

BACKGROUND: The preservation of autophagosome formation presents a promising strategy for tackling neurological disorders, such as Parkinson's disease (PD). Mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) serve not only as a focal point linked to various neurological disorders but also play a crucial role in supporting the biogenesis of autophagosomes. PURPOSE: This investigation aimed to elucidate the neuroprotective properties of phillyrin against PD and its underlying mechanisms in promoting autophagosome formation. METHODS: ER and mitochondria co-localization was assessed via fluorescent staining. Annexin V-fluorescein isothiocyanate (FITC) fluorescence was employed to quantify accessible cardiolipin (CL) on mitochondrial surfaces. The levels of CL within the MAM fraction of SH-SY5Y cells were evaluated using a CL probe assay kit. Monodansylcadaverine staining was utilized to detect autophagosome formation in SH-SY5Y cells. In an A53T-alpha-synuclein (αSyn)-induced PD mouse model, the anti-PD properties of phillyrin were assessed using open field, pole climbing, and rotarod tests, as well as immunohistochemistry staining of TH+ neurons in the brain sections. RESULTS: In A53T-αSyn-treated SH-SY5Y cells, phillyrin facilitated autophagosome formation by suppressing CL externalization and restoring MAM integrity. Phillyrin enhanced the localization of receptor expression-enhancing protein 1 (REEP1) within MAM and mitochondria, bolstering MAM formation. Increased REEP1 levels in mitochondria, attributed to phillyrin, enhanced the interaction between REEP1 and NDPK-D, thereby reducing CL externalization. Furthermore, phillyrin exhibited a dose-dependent enhancement of motor function in mice, accompanied by an increase in the abundance of dopaminergic neurons within the substantia nigra. CONCLUSIONS: These findings illuminate phillyrin's ability to enhance MAM formation through upregulation of REEP1 expression within MAM, while concurrently attenuating CL externalization via the REEP1-NDPK-D interaction. These mechanisms bolster autophagosome biogenesis, offering resilience against A53T-αSyn-induced PD. Thus, our study advances the understanding of phillyrin's complex mechanisms and underscores its potential as a therapeutic approach for PD, opening new avenues in natural product pharmacology.

The effector PHYL1JWB from Candidatus Phytoplasma ziziphi induces abnormal floral development by destabilising flower development proteins.

Phytoplasmas can induce complex and substantial phenotypic changes in their hosts in ways that favour their colonisation, but the mechanisms underlying these changes remain largely unknown. Jujube witches' broom (JWB) disease is a typical phytoplasma disease causing great economic loss in Chinese jujube (Ziziphus jujuba Mill.). Here, we reported an effector, PHYL1JWB from Candidatus Phytoplasma ziziphi, which implicated in inducing abnormal floral organogenesis. Utilising a combination of in vivo and in vitro methods, we investigated the influence of PHYL1JWB on the proteins associated with floral development. Our findings reveal that PHYL1JWB facilitates the proteasome-mediated degradation of essential flower morphogenetic regulators, including AP1, SEP1, SEP2, SEP3, SEP4, CAL, and AGL6, through a distinctive pathway that is dependent on the activity of the 26S proteasome, thus obviating the requirement for lysine ubiquitination of the substrates. Further, the Y2H analysis showed that the leucine at position 75th in second α helix of PHYL1JWB is fundamental for the interactions of PHYL1JWB with AP1 and SEP1-4 in jujube and Arabidopsis. Our research carry profound implications for elucidating the contribution of PHYL1JWB to the aberrant floral development in diseased jujube, and help to establish a robust theoretical underpinning for the prophylaxis and therapy of JWB disease.

Exploring the crosstalk molecular mechanisms between IgA nephropathy and Sjögren's syndrome based on comprehensive bioinformatics and immunohistochemical analyses.

IgA nephropathy (IgAN) and Sjogren's syndrome (SS) are two autoimmune diseases with undetermined etiology and related to abnormal activation of lymphocytes. This study aims to explore the crucial genes, pathways and immune cells between IgAN and SS. Gene expression profiles of IgAN and SS were obtained from the Gene Expression Omnibus and Nephroseq data. Differentially expressed gene (DEG) and weighted gene co-expression network analyses (WGCNA) were done to identify common genes. Enrichment analysis and protein-protein interaction network were used to explore potential molecular pathways and crosstalk genes between IgAN and SS. The results were further verified by external validation and immunohistochemistry (IHC) analysis. Additionally, immune cell analysis and transcription factor prediction were also conducted. The DEG analysis revealed 28 commonly up-regulated genes, while WGCNA identified 98 interactively positive-correlated module genes between IgAN and SS. The enrichment analysis suggested that these genes were mainly involved in the biological processes of response to virus and antigen processing and presentation. The external validation and IHC analysis identified 5 hub genes (PSMB8, PSMB9, IFI44, ISG15, and CD53). In the immune cell analysis, the effector memory CD8 T and T follicular helper cells were significantly activated, and the corresponding proportions showed positively correlations with the expressions of the 5 hub genes in the two autoimmune diseases. Together, our data identified the crosstalk genes, molecular pathways, and immune cells underlying the IgAN and SS, which provides valuable insights into the intricate mechanisms of these diseases and offers potential intervention targets.

Factors influencing the generation of teachers' emotions.

Background and aim: The teaching profession plays an important role in shaping individuals' lives, with teachers performing complex emotional labour. The management of emotions is an integral part of teachers' professional work, and it is essential to clarify their emotional experiences and the generating of their emotions within a specific cultural context. Methods: Based on a phenomenological approach and the use of anecdotal texts, this study examined six common emotional states among teachers, including happiness, guilt, worry, fear, annoyance, and anger, along with the emotional experiences of two specialised categories of teachers, class supervisors, and pre-service teachers. The factors influencing teachers' emotions and their generative mechanisms were analysed. Results and discussion: This investigation found that key influences on teachers' emotions stem from factors within the teachers' themselves, the contextual nature of their work, and sociocultural dynamics. Drawing on the analytical frameworks of emotional geography theory, ecological theory of human development, and the ecosystem model of teachers' emotional interactions, the study constructs a model highlighting the generative mechanisms of teachers' emotions, and in which three systems are reflected. Conclusion: Teachers' personal attributes are in the direct area of the model and directly govern the formation of their emotions, while their work context consists of a transitional area in emotion formation and the sociocultural system acts as the latent band influencing emotion development. The mechanism model helps us to understand and recognise teachers' emotions and to explore their pedagogical implications.

Enhancing prognostic guidance in renal light-chain amyloidosis: a new staging system incorporating pathological characters.

BACKGROUND: Advancements in treatment regimens have led to improved outcomes in renal Immunoglobulin light-chain amyloidosis. Nevertheless, a subset of patients may still experience renal adverse events despite achieving hematologic very good partial response or better. This discrepancy may be attributed to the deposition pattern of amyloid in renal tissue. To enhance prognostic assessment, a staging system that incorporates both pathological characteristics and clinical indicators should be developed. METHODS: Patients newly diagnosed through renal biopsy between January 1, 2017, and December 31, 2022, were included. The renal pathology of patients was evaluated according to amyloid score (AS). Risk factors for end-stage renal disease or renal progression were identified by the competing risk model, then to develop a renal staging system. The Concordance index (C-index), internal cross-validation and Decision Curve Analysis (DCA) were used to evaluate the performance of the new staging system. RESULTS: 74 patients were included, and 16 (21.6%) patients had end-stage renal disease or renal progression within 24.7 (11.9, 50.7) months. AS and estimated glomerular filtration rate (eGFR) were identified as independent risk factors and the staging system based on them, which the C-index was 0.81 (95%CI, 0.73-0.89), had greater improvement than previous staging systems. The internal cross-validation and DCA also confirmed its great clinical benefits. CONCLUSION: The AS demonstrated its prognostic significance in Chinese patients, and the novel renal staging system based on AS and eGFR may provide great prognostic guidance for these patients.

[Vertical Distribution Characteristics and Driving Factors of Bacterioplankton and Nitrogen Phosphorus Cycle Genes in Danjiangkou Reservoir].

Danjiangkou Reservoir is a critical water source for the South-to-North Water Diversion Project, which harbors a diverse bacterioplankton community with varying depths, and the understanding of its nitrogen and phosphorus cycle and associated driving factors remains limited. In this study, we selected five ecological sites within Danjiangkou Reservoir and conducted metagenomics analysis to investigate the vertical distribution of bacterioplankton communities in the surface, middle, and bottom layers. Furthermore, we analyzed and predicted the function of nitrogen and phosphorus cycles, along with their driving factors. Our findings revealed the dominance of Proteobacteria, Actinobacteria, and Planctomycetes in the Danjiangkou Reservoir. Significant differences were observed in the structure of bacterioplankton communities across different depths, with temperature （T）, oxidation-reduction potential （ORP）, dissolved oxygen （DO）, and Chla identified as primary factors influencing the bacterioplankton composition. Analysis of nitrogen cycle functional genes identified 39 genes, including gltB, glnA, gltD, gdhA, NRT, etc., which were involved in seven main pathways, encompassing nitrogen fixation, nitrification, denitrification, and dissimilatory nitrate reduction. Phosphorus cycle function gene analysis identified 54 genes, including pstS, ppx-gppA, glpQ, ppk1, etc., primarily participating in six main pathways, including organic P mineralization, inorganic P solubilization, and regulatory. Cluster analysis indicated that different depths were significant factors influencing the composition and abundance of nitrogen and phosphorus cycle functional genes. The composition and abundance of nitrogen and phosphorus cycle functional genes in the surface and bottom layers differed and were generally higher than those in the middle layer. Deinococcus, Hydrogenophaga, Limnohabitans, Clavibacter, and others were identified as key species involved in the nitrogen and phosphorus cycle. Additionally, we found significant correlations between nitrogen and phosphorus cycle functional genes and environmental factors such as DO, pH, T, total dissolved solids （TDS）, electrical conductivity （EC）, and Chla. Furthermore, the content of these environmental factors exhibited depth-related changes in the Danjiangkou Reservoir, resulting in a distinct vertical distribution pattern of bacterioplankton nitrogen and phosphorus cycle functional genes. Overall, this study sheds light on the composition, function, and influencing factors of bacterioplankton communities across different layers of Danjiangkou Reservoir, offering valuable insights for the ecological function and diversity protection of bacterioplankton in this crucial reservoir ecosystem.

Effective intervention of brucellosis prevention in developing countries: A dynamic modelling study.

Objective: Brucellosis has a considerable impact on human health and the economy in developing countries. In China, the biggest developing country, brucellosis shifted spread of the epidemic from northern to southern regions. Understanding the transmission characteristic of brucellosis on Hunan province, located in central China, is of great significance for successful control. Methods: We developed a multi-population and multi-route dynamic model (MPMRDM), which is an animal-human-environment coupled model. The model is an extension of the SEIR model, taking into account direct transmission and indirect transmission. We used the model to explore the spread of brucellosis and evaluate the effectiveness of various intervention strategies. Results: The animal-to-animal transmission rate was the highest at 5.14 × 10-8, while the environment-to-person transmission rate was the lowest at 9.49 × 10-12. The mean R0 was 1.51. The most effective intervention was taking personal protection, followed by shortening the infection period. Shortening the infection period combined with personal protection is the most effective two-combined intervention strategy. After any comprehensive intervention strategy was implemented, TAR dropped by 90% or more. Conclusion: The results demonstrate that animal transmission route is essential for controlling human brucellosis. Strengthening personal protection, early detection, and early treatment can effectively control the trend of brucellosis. These results can provide an important reference for optimizing brucellosis intervention plans.

Experimental study on the effect of PVP, NaCl and EG on the methane hydrates formation and dissociation kinetics.

The problem of hydrate plug, low efficiency of hydrate dissociation and short production time in hydrate exploitation processes have significantly hindered the commercial viability of gas hydrate extraction. This study investigated the inhibitory effects of ethylene glycol (EG), EG + polyvinyl pyrrolidone (PVP), and EG + PVP + sodium chloride (NaCl) on methane hydrate formation through experiment. The hydrate inhibitory performance is evaluated by using differential of pressure curve, the amount of hydrate, and pressure drop values, and the effects of different temperatures, pressures, inhibitors, and injection time on hydrate dissociation are further studied. The experiment results indicate that the rank of inhibitors combination in terms of effectiveness is 5%EG + 0.5 wt%PVP + 3 wt%Nacl > 10%EG + 1 wt%PVP > 30% EG. At low-temperature conditions, 30% EG exhibits good inhibition of hydrate synthesis but poor dissociation efficiency. As temperature increases, the hydrates dissociation rate with 30% EG also increases. For the combination inhibitor system of EG, PVP, and NaCl, PVP will reduce the dissociation efficiency of hydrates, while EG and Nacl will improve the hydrate dissociation performance. For low production pressure, it is found that 10% EG + 10% NaCl have a good promotion effect on hydrate dissociation, whereas under high production pressure, 20% EG + 10% NaCl is more effective. Furthermore, injecting the inhibitors earlier enhances the dissociation of hydrates more effectively.

Analyzing risk factors for second malignancies in early gastric carcinoma from the SEER database.

This retrospective study analyzed a large population of gastric cancer (GC) patients treated between 2010 and 2015 to investigate the clinical features and predictive risk factors for developing secondary primary malignancies (SPMs). The cumulative incidence of SPM was assessed using Kaplan-Meier analysis. Competing risk analyses adjusted for mortality were conducted using stratified Cox proportional hazard regression models and multivariate analyses to identify independent predictors of SPM. A total of 3289 out of 167,747 GC patients were included in the analytic cohort, with 155 patients diagnosed with SPM. Patients whose histologic type other than adenocarcinomas (AC) and signet ring cell carcinoma (SRCC) emerged as an independent risk factor for developing SPM (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.146-4.465, P = 0.019) in multivariate Cox regression analysis. The surgical method, including biopsy/local excision (HR 2.3, [CI] 1.291-4.095, P = 0.005) and subtotal/total resection ([HR] 1.947, [CI] 1.028-3.687, P = 0.041), chemotherapy ([HR] 1.527, [CI] 1.006-2.316, P = 0.047), and histologic type ([HR] 2.318, [CI] 1.193-4.504, P = 0.013)), were identified as independent risk factors in the competitive risk model. Subgroup analyses, stratified by chemotherapy, revealed an increased risk of SPM among older patients. Furthermore, a nomogram was developed and internally validated to predict the cumulative incidence of SPM in GC patients (C-index = 0.73 for 72 months). These findings suggested that in specific histologic types of GC, the lymph node infiltration region missed after local surgical resection, and concomitant chemotherapy would have an increased risk of SPM for cancer survivors.

Incorporation of Zinc-Strontium Phosphate into Gallic Acid-Gelatin Composite Hydrogel with Multiple Biological Functions for Bone Tissue Regeneration.

Large bone defects resulting from fractures and diseases have become a significant medical concern, usually impeding spontaneous healing through the body's self-repair mechanism. Calcium phosphate (CaP) bioceramics are widely utilized for bone regeneration, owing to their exceptional biocompatibility and osteoconductivity. However, their bioactivities in repairing healing-impaired bone defects characterized by conditions such as ischemia and infection remain limited. Recently, an emerging bioceramics zinc-strontium phosphate (ZSP, Zn2Sr(PO4)2) has received increasing attention due to its remarkable antibacterial and angiogenic abilities, while its plausible biomedical utility on tissue regeneration is nonetheless few. In this study, gallic acid-grafted gelatin (GGA) with antioxidant properties was injected into hydrogels to scavenge reactive oxygen species and regulate bone microenvironment while simultaneously incorporating ZSP to form GGA-ZSP hydrogels. The GGA-ZSP hydrogel exhibits low swelling, and in vitro cell experiments have demonstrated its favorable biocompatibility, osteogenic induction potential, and ability to promote vascular regeneration. In an in vivo bone defect model, the GGA-ZSP hydrogel significantly enhanced the bone regeneration rates. This study demonstrated that the GGA-ZSP hydrogel has pretty environmentally friendly therapeutic effects in osteogenic differentiation and massive bone defect repair.

Epidermal growth factor-loaded, dehydrated physical microgel-formed adhesive hydrogel enables integrated care of wet wounds.

Integrated wound care, a sequential process of promoting wound hemostasis, sealing, and healing, is of great clinical significance. However, the wet environment of wounds poses formidable challenges for integrated care. Herein, we developed an epidermal growth factor (EGF)-loaded, dehydrated physical microgel (DPM)-formed adhesive hydrogel for the integrated care of wet wounds. The DPMs were designed using the rational combination of hygroscopicity and reversible crosslinking of physical hydrogels. Unlike regular bioadhesives, which consider interfacial water as a barrier to adhesion, DPMs utilize water to form desirable adhesive structures. The hygroscopicity allowed the DPMs to absorb interfacial water and subsequently, the interfacial adhesion was realized by the interactions between tissue and DPMs. The reversible crosslinks further enabled DPMs to integrate into hydrogels (DPM-Gels), thus achieving wet adhesion. Importantly, the water-absorbing gelation mode of DPMs enabled facile loading of biologically active EGF to promote wound healing. We demonstrated that the DPM-Gels possessed wet tissue adhesive performance, with about 40 times the wet adhesive strength of fibrin glue and about 4 times the burst pressure of human blood pressure. Upon application at the injury site, the EGF-loaded DPM-Gels sequentially promoted efficient wound hemostasis, stable sealing, and quick healing, achieving integrated care of wet wounds.

Through virtual saturation mutagenesis and rational design for superior substrate conversion in engineered d-amino acid oxidase.

The d-amino acid oxidase (DAAO) is pivotal in obtaining optically pure l-glufosinate (l-PPT) by converting d-glufosinate (d-PPT) to its deamination product. We screened and designed a Rasamsonia emersonii DAAO (ReDAAO), making it more suitable for oxidizing d-PPT. Using Caver 3.0, we delineated three substrate binding pockets and, via alanine scanning, identified nearby key residues. Pinpointing key residues influencing activity, we applied virtual saturation mutagenesis (VSM), and experimentally validated mutants which reduced substrate binding energy. Analysis of positive mutants revealed elongated side-chain prevalence in substrate binding pocket periphery. Although computer-aided approaches can rapidly identify advantageous mutants and guide further design, the mutations obtained in the first round may not be suitable for combination with other advantageous mutations. Therefore, each round of combination requires reasonable iteration. Employing VSM-assisted screening multiple times and after four rounds of combining mutations, we ultimately obtained a mutant, N53V/F57Q/V94R/V242R, resulting in a mutant with a 5097% increase in enzyme activity compared to the wild type. It provides valuable insights into the structural determinants of enzyme activity and introduces a novel rational design procedure.

Recombinant FOXN1 fusion protein increases T cell generation in old mice.

T cell development in the thymus is dependent on the thymic microenvironment, in which thymic epithelial cells (TECs) are the major component. However, TECs undergo both a qualitative and quantitative loss during aging, which is believed to be the major factor responsible for age-dependent thymic atrophy. FOXN1 plays a critical role in TEC development and adult TECs maintenance. We have previously reported that intrathymic injection of a recombinant (r) protein containing murine FOXN1 and a protein transduction domain increases the number of TECs in mice, leading to enhanced thymopoiesis. However, intrathymic injection may not be an ideal choice for clinical applications. In this study, we produced a rFOXN1 fusion protein containing the N-terminal of CCR9, human FOXN1 and a protein transduction domain. When injected intravenously into 14-month-old mice, the rFOXN1 fusion protein enters the thymus and TECs, and enhances thymopoiesis, resulting in increased T cell generation in the thymus and increased number of T cells in peripheral lymphoid organ. Our results suggest that the rFOXN1 fusion protein has the potential to be used in preventing and treating T cell immunodeficiency in older adults.

CFD of the diffusion movement and concentration distribution of culinary particles in the respiratory zone of restaurant diners.

Released aerosol particles during restaurant culinary activity affect diners' health. The air conditioning system is crucial for regulating indoor air quality. However, its improper air distribution increases the individuals' exposure to particle pollution. This study investigates restaurants employing side-up airflow during summer with numerous heat sources and examines the culinary particle diffusion in the diners' respiratory zone under the combined influence of air conditioning cold jet air supply and culinary heat source heat plume. It elucidates the change rule of the concentration distribution of culinary particles under the combined action of these two heterogeneous airflows. This study investigated the movement and concentration distribution of indoor particle by numerical simulation under various air supply velocities, culinary heat source strengths and positions and tuyere opening modes. In restaurants with culinary sources, the thermal buoyancy by the heat plume causes particles to rise. However, the drag force exerted by the cold air supply jet impedes the particles' upward motion. The particle concentration distribution is significantly influenced by both the air supply velocity and the relative positioning of the heat source and the tuyere. Particle concentration increases by 27.13 % in the respiratory zone when the air supply jet trajectory is above the pollution emission source than below. Therefore, lowered air supply velocity is ideal with increased horizontal distance between the emission source and the tuyere under the condition of comfort satisfaction. This scenario mitigates the downward movement exerted by the jet on the particles. The drag force is increased with the air supply velocity increasing from 2.5 m/s to 4.0 m/s. Particle concentration is raised to 41.38 % in the respiratory zone. The drag force by the cold jet on the particles is also heightened with the bilateral tuyere than its single-side counterpart which increases particle concentration maximum by 40.30 % in the respiratory zone.

The changes in zoological publication rates and focal subdisciplines between 1960 and 2022.

Since ancient times, zoology, as the branch of biology dealing with animals, has been a cornerstone of natural science and has developed substantially over the last century. We conducted a bibliometric analysis using structural topic modeling (STM) to determine changes in the representation of principal zoological subdisciplines in the literature between 1960 and 2022. We collated a corpus of 217 414 articles from 88 top-ranked zoology journals and identified three main fields: (i) ecology, (ii) evolution, and (iii) applied research. Within these, we identified 10 major subdisciplines. The number of studies published per year grew from 118 in 1960 to 6635 in 2022. Macroscale-related subdisciplines increased while classical and traditional subdisciplines decreased. Mammals (34.4%) and insects (18.1%) were the dominant taxa covered, followed by birds (15.2%) and fish (8.0%). Research on mammals, insects, and fish involved a broad range of subdisciplines, whereas studies of birds focused on ecological subdisciplines. Most publications were from the United States, followed by the United Kingdom, Germany, Canada, Australia, China, and Japan, with two developing countries, China and South Africa among the top 15 countries. There were different subdiscipline biases between countries, and the gross domestic product of each country correlated positively with its publication output (R2 = 0.681). We discuss our findings in the context of advances in technological innovations and computing power, as well as the emergence of ecology as a formal sister discipline, driven by changing environmental pressures and societal values. We caution that valuable publications from traditional zoological fields must not be completely supplanted by more contemporary topics and increasingly sophisticated analyses.