Physiological and psychological recovery in two pure forests: interaction between perception methods and perception durations.

The forest experience is good for people's physical and mental health. However, few studies on the effects of pure forest based on the duration and way of experience on people's physical and mental recovery. In this study, we took 180 first-year college students as research objects and conducted experiments in Pinus sylvestris and Betula platyphylla and the control group of grass plot. The changes of physiological and psychological indexes of the subjects were compared by two perception methods (onsite perception, video perception) and three perception duration (10 min, 20 min, 30 min). The results indicated that: (1) Differences between the two pure forests were mainly reflected in short-term recovery of diastolic blood pressure (DBP) and long-term recovery of total mood disorder (TMD). (2) Video perception was more conducive to short-term recovery of systolic blood pressure (SBP) and diastolic blood pressure (DBP). (3) Viewing the Pinus sylvestris for 20 min in different ways was the best way to relieve stress. It is suggested that, Pinus sylvestris can be used as the rehabilitation perception material, and reasonable path length or perception time can be selected for landscape construction in future. These results can provide scientific reference for landscape design based on forest health and environmental perception.

Perspectives from Undergraduate Life Sciences Faculty: Are We Equipped to Effectively Accommodate Students With Disabilities in Our Classrooms?

Higher education has evolved in ways that may increase the challenges life science faculty face in providing accommodations for students with disabilities. Guided by Expectancy-Value Theory, we interviewed 34 life sciences faculty instructors from institutions nationwide to explore faculty motivation to create disability-inclusive educational experiences. We found that faculty in our sample perceive that providing most standard accommodations is a manageable but often challenging task. Further, faculty in our sample feel that improving accommodations necessitates additional support from their institutions. Most faculty had high attainment value for providing accommodations, in that they strongly believed that supporting students with disabilities is the fair and right thing to do. However, faculty did not perceive much utility value or intrinsic value in their task of providing accommodations, and most reported that providing accommodations can be a substantial burden on faculty. These findings imply that current approaches to providing inclusive educational experiences for students with disabilities rely primarily on the personal belief that providing accommodations is the right thing to do, which likely results in a flawed and inequitable system given that not all faculty equally share this conviction.

Beyond Gender and Race: The Representation of Concealable Identities Among College Science Instructors at Research Institutions.

Concealable stigmatized identities (CSIs) are identities that can be kept hidden and carry negative stereotypes. To understand the potential influence instructors have as role models, we must first explore the identities instructors have and whether they disclose those identities to undergraduates. We surveyed national samples of science instructors (n = 1248) and undergraduates (n = 2428) at research institutions to assess the extent to which instructors hold CSIs, whether they reveal those identities to undergraduates, how the prevalence of CSIs among instructors compares to their prevalence among undergraduates, and the reasons instructors reveal or conceal their CSIs. The most common CSIs instructors reported were having anxiety (35%) and being a first-generation college student (29%). Relatively few instructors revealed CSIs to students. The largest mismatches of CSI prevalence were for struggling academically in college (-30%) and having anxiety (-25%); all mismatches grew when accounting for instructor CSI disclosure, highlighting that students perceive fewer role models of scientists with CSIs than actually exist.

Differential Mitochondrial Genome Expression of Three Sympatric Lizards in Response to Low-Temperature Stress.

Ecological factors related to climate extremes have a significant influence on the adaptability of organisms, especially for ectotherms such as reptiles that are sensitive to temperature change. Climate extremes can seriously affect the survival and internal physiology of lizards, sometimes even resulting in the loss of local populations or even complete extinction. Indeed, studies have shown that the expression levels of the nuclear genes and mitochondrial genomes of reptiles change under low-temperature stress. At present, the temperature adaptability of reptiles has rarely been studied at the mitochondrial genome level. In the present study, the mitochondrial genomes of three species of lizards, Calotes versicolor, Ateuchosaurus chinensis, and Hemidactylus bowringii, which live in regions of sympatry, were sequenced. We used RT-qPCR to explore the level of mitochondrial gene expression under low-temperature stress, as compared to a control temperature. Among the 13 protein-coding genes (PCGs), the steady-state transcript levels of ND4L, ND1, ATP6, and COII were reduced to levels of 0.61 ± 0.06, 0.50 ± 0.08, 0.44 ± 0.16, and 0.41 ± 0.09 in C. versicolor, respectively, compared with controls. The transcript levels of the ND3 and ND6 genes fell to levels of just 0.72 ± 0.05 and 0.67 ± 0.05 in H. bowringii, compared with controls. However, the transcript levels of ND3, ND5, ND6, ATP6, ATP8, Cytb, and COIII genes increased to 1.97 ± 0.15, 2.94 ± 0.43, 1.66 ± 0.07, 1.59 ± 0.17, 1.46 ± 0.04, 1.70 ± 0.16, and 1.83 ± 0.07 in A. chinensis. Therefore, the differences in mitochondrial gene expression may be internally related to the adaptative strategy of the three species under low-temperature stress, indicating that low-temperature environments have a greater impact on A. chinensis, with a small distribution area. In extreme environments, the regulatory trend of mitochondrial gene expression in reptiles is associated with their ability to adapt to extreme climates, which means differential mitochondrial genome expression can be used to explore the response of different lizards in the same region to low temperatures. Our experiment aims to provide one new research method to evaluate the potential extinction of reptile species in warm winter climates.

A role for tunneling nanotubes in virus spread.

Tunneling nanotubes (TNTs) are actin-rich intercellular conduits that mediate distant cell-to-cell communication and enable the transfer of various cargos, including proteins, organelles, and virions. They play vital roles in both physiological and pathological processes. In this review, we focus on TNTs in different types of viruses, including retroviruses such as HIV, HTLV, influenza A, herpesvirus, paramyxovirus, alphavirus and SARS-CoV-2. We summarize the viral proteins responsible for inducing TNT formation and explore how these virus-induced TNTs facilitate intercellular communication, thereby promoting viral spread. Furthermore, we highlight other virus infections that can induce TNT-like structures, facilitating the dissemination of viruses. Moreover, TNTs promote intercellular spread of certain viruses even in the presence of neutralizing antibodies and antiviral drugs, posing significant challenges in combating viral infections. Understanding the mechanisms underlying viral spread via TNTs provides valuable insights into potential drug targets and contributes to the development of effective therapies for viral infections.

Pharmacological inhibition of Kir4.1 evokes rapid-onset antidepressant responses.

Major depressive disorder, a prevalent and severe psychiatric condition, necessitates development of new and fast-acting antidepressants. Genetic suppression of astrocytic inwardly rectifying potassium channel 4.1 (Kir4.1) in the lateral habenula ameliorates depression-like phenotypes in mice. However, Kir4.1 remains an elusive drug target for depression. Here, we discovered a series of Kir4.1 inhibitors through high-throughput screening. Lys05, the most potent one thus far, effectively suppressed native Kir4.1 channels while displaying high selectivity against established targets for rapid-onset antidepressants. Cryogenic-electron microscopy structures combined with electrophysiological characterizations revealed Lys05 directly binds in the central cavity of Kir4.1. Notably, a single dose of Lys05 reversed the Kir4.1-driven depression-like phenotype and exerted rapid-onset (as early as 1 hour) antidepressant actions in multiple canonical depression rodent models with efficacy comparable to that of (S)-ketamine. Overall, we provided a proof of concept that Kir4.1 is a promising target for rapid-onset antidepressant effects.

Self-Assembly of Wheel-Shaped Nanographdiynes and Self-Template Growth of Graphdiyne.

Graphdiyne (GDY) multilayers show stacking-style-dependent physical properties; thus, controlling the stacking style of nanostructures is crucial for utilizing their electrical, optical, and transport properties in electro-optical devices. Herein, we report the assemblies of nanographdiynes decorated with substituents with different steric hindrances to adjust the stacking style. We show that the π-stacked aggregates were influenced by peripheral substituents and the substrate. Steric hexaterphenyl-substituted nanoGDY scaffolds led to dimer structures stacked in the AB-3 configuration with a twist angle of 26.01° or the AB-1 configuration with an in-plane shift along one diyne link. With the interval replacement of steric substituents with long C12 alkyl chains, nanoGDYs were stacked in the AB-2 configuration to decrease the steric congestion, eventually leading to one-dimensional (1D) nanofibrous aggregates. Self-assembly in the presence of substrates can result in ABC-stacked nanoGDYs, which endowed us with the possibility of using nanoGDY as the template for GDY growth in a homogeneous reaction. High-resolution transmission electron microscopy (HRTEM), powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and near-infrared-ultraviolet-visible (NIR-UV-vis) absorption spectroscopy indicate that the crystalline GDY prepared in this way is a 1.18 eV bandgap semiconductor.

The Chinese Parenting Stress Scale for Preschoolers' Parents: Development and Initial Validation.

Parenting stress is the experience of discomfort or distress that results from the demands associated with the role of parenting. Although there are numerous parenting stress scales, relatively few scales have been developed with consideration of the Chinese cultural context. This study aimed to develop and validate the Chinese Parenting Stress Scale (CPSS) with a multidimensional and hierarchical structure for Mainland Chinese preschoolers' parents (N = 1,427, Mage = 35.63 years, SD = 4.69). In Study 1, a theoretical model and an initial 118 items were developed, drawing on prior research and existing measures of parenting stress. Exploratory factor analysis yielded 15 first-order factors with 60 items. In Study 2, confirmatory factor analyses supported a higher order solution consisting of 15 first-order factors covering four domains: Child Development (12 items), Difficult Child (16 items), Parent-Child Interaction (12 items), and Parent's Readjustment to Life (20 items). Measurement invariance indicated no gender differences between parents for the scale scores. The convergent, discriminant, and criteria validity of the CPSS scores was supported by its association with related variables in the expected directions. Moreover, the CPSS scores added significant incremental variance in predicting somatization, anxiety, and child's emotional symptoms more so than the Parenting Stress Index-Short Form-15. The CPSS total and subscale scores all had acceptable Cronbach's αs in both samples. The overall findings support the CPSS as a psychometrically sound tool.

Resting heart rate moderates the relationship between parental emotion socialization and callous-unemotional traits in children.

Although empirical findings have indicated that both familial and neurobiological risk factors contribute to the development of callous-unemotional (CU) traits in children, relatively few studies have investigated how these two factors interact to influence these traits. The current study focused on the combined effects of parental emotion socialization and child's resting heart rate on CU traits. Parents of Chinese children (N = 166) completed the Coping with Children's Negative Scale when children were 9.39 years old (SD = 0.92), while children's resting heart rate data were collected when they were 10.21 years old (SD = 0.72). When they were 11.15 years old (SD = 0.67), parents completed the Inventory of Callous-Unemotional Traits Short-Form. Results showed that parental supportive emotion socialization was negatively associated with CU traits and Callous behaviors in particular. In addition, resting heart rate moderated the relationship between parental emotion socialization and child's CU traits. Findings provide further evidence that an interdisciplinary approach that combines both psychosocial and biological factors is essential to further our understanding of CU traits in youth.

Development and validation of web calculators to predict early recurrence and long-term survival in patients with duodenal papilla carcinoma after pancreaticoduodenectomy.

BACKGROUND: Duodenal papilla carcinoma (DPC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study aimed to develop web calculators to predict early recurrence (ER) (within two years after surgery) and long-term survival in patients with DPC after PD. METHODS: Patients with DPC after radical PD were included. Univariate and multivariate logistic regression analyses were used to identify independent risk factors. Two web calculators were developed based on independent risk factors in the training cohort and then tested in the validation cohort. RESULTS: Of the 251 patients who met the inclusion criteria, 180 and 71 patients were enrolled in the training and validation cohorts, respectively. Multivariate logistic regression analysis revealed that tumor size [Odds Ratio (OR) 1.386; 95% confidence interval (CI) 1070-1.797; P = 0.014]; number of lymph node metastasis (OR 2.535; 95% CI 1.114-5.769; P = 0.027), perineural invasion (OR 3.078; 95% CI 1.147-8.257; P = 0.026), and tumor differentiation (OR 3.552; 95% CI 1.132-11.152; P = 0.030) were independent risk factors for ER. Nomogram based on the above four factors achieved good C-statistics of 0.759 and 0.729 in predicting ER in the training and the validation cohorts, respectively. Time-dependent ROC analysis (timeROC) and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic capacity and net benefit compared with single variable. CONCLUSIONS: This study developed and validated two web calculators that can predict ER and long-term survival in patients with DPC with high degree of stability and accuracy.

Cytochrome P450 Mediated Cyclization in Eunicellane Derived Diterpenoid Biosynthesis.

Terpene cyclization, one of the most complex chemical reactions in nature, is generally catalyzed by two classes of terpene cyclases (TCs). Cytochrome P450s that act as unexpected TC-like enzymes are known but are very rare. In this study, we genome-mined a cryptic bacterial terpenoid gene cluster, named ari, from the thermophilic actinomycete strain Amycolatopsis arida. By employing a heterologous production system, we isolated and characterized three highly oxidized eunicellane derived diterpenoids, aridacins A-C (1-3), that possess a 6/7/5-fused tricyclic scaffold. In vivo and in vitro experiments systematically established a noncanonical two-step biosynthetic pathway for diterpene skeleton formation. First, a class I TC (AriE) cyclizes geranylgeranyl diphosphate (GGPP) into a 6/10-fused bicyclic cis-eunicellane skeleton. Next, a cytochrome P450 (AriF) catalyzes cyclization of the eunicellane skeleton into the 6/7/5-fused tricyclic scaffold through C2-C6 bond formation. Based on the results of quantum chemical computations, hydrogen abstraction followed by electron transfer coupled to barrierless carbocation ring closure is shown to be a viable mechanism for AriF-mediated cyclization. The biosynthetic logic of skeleton construction in the aridacins is unprecedented, expanding the catalytic capacity and diversity of P450s and setting the stage to investigate the inherent principles of carbocation generation by P450s in the biosynthesis of terpenoids.

Rapid measurement and machine learning classification of colour vision deficiency.

Colour vision deficiencies (CVDs) indicate potential genetic variations and can be important biomarkers of acquired impairment in many neuro-ophthalmic diseases. However, CVDs are typically measured with tests which possess high sensitivity for detecting the presence of a CVD but do not quantify its type or severity. In this study, we introduce Foraging Interactive D-prime (FInD), a novel computer-based, generalisable, rapid, self-administered vision assessment tool and apply it to colour vision testing. This signal detection theory-based adaptive paradigm computed test stimulus intensity from d-prime analysis. Stimuli were chromatic Gaussian blobs in dynamic luminance noise, and participants clicked on cells that contained chromatic blobs (detection) or blob pairs of differing colours (discrimination). Sensitivity and repeatability of FInD colour tasks were compared against the Hardy-Rand-Rittler and the Farnsworth-Munsell 100 hue tests in 19 colour-normal and 18 inherited colour-atypical, age-matched observers. Rayleigh colour match was also completed. Detection and discrimination thresholds were higher for atypical than for typical observers, with selective threshold elevations corresponding to unique CVD types. Classifications of CVD type and severity via unsupervised machine learning confirmed functional subtypes. FInD tasks reliably detect inherited CVDs, and may serve as valuable tools in basic and clinical colour vision science.

A self-reported inhibitor of metallo-carbapenemases for reversing carbapenem resistance.

Metallo-carbapenemases-mediated carbapenem-resistant Enterobacterales (CREs) has been acknowledged as "urgent threat" by the World Health Organization. The discovery of new strategies that block metallo-carbapenemases activity to reverse carbapenem resistance is an urgent need. In this study, a coumarin copper complex containing a PEG linker and glucose ligand, GluC-Cu, was used to reverse carbapenem resistance. Interestingly, it could effectively inhibit metallo-carbapenemases (NDM-1, IMP-1 and ImiS) with an IC50 value in the range of 0.23-1.21 µM, and simultaneously release the green fluorescence signal (GluC), therefore exhibiting self-reported inhibition performance. The inhibition mechanism of oxidizing Zn(II) thiolate site of NDM-1 from Cu2+ to Cu+ was verified by fluorescence assay, HR-MS, and XPS. Moreover, GluC-Cu in combination with meropenem showed excellent synergistic antibacterial effect to effectively combat E. coli expressing metallo-carbapenemases in vitro and in a mice infection model. This bifunctional metallo-carbapenemases inhibitor provides a novel chemical tool to overcome carbapenem resistance.

Rapid measurement and machine learning classification of color vision deficiency.

Color vision deficiencies (CVDs) indicate potential genetic variations and can be important biomarkers of acquired impairment in many neuro-ophthalmic diseases. However, CVDs are typically measured with insensitive or inefficient tools that are designed to classify dichromacy subtypes rather than track changes in sensitivity. We introduce FInD (Foraging Interactive D-prime), a novel computer-based, generalizable, rapid, self-administered vision assessment tool and applied it to color vision testing. This signal detection theory-based adaptive paradigm computes test stimulus intensity from d-prime analysis. Stimuli were chromatic gaussian blobs in dynamic luminance noise, and participants clicked on cells that contain chromatic blobs (detection) or blob pairs of differing colors (discrimination). Sensitivity and repeatability of FInD Color tasks were compared against HRR, FM100 hue tests in 19 color-normal and 18 color-atypical, age-matched observers. Rayleigh color match was completed as well. Detection and Discrimination thresholds were higher for atypical observers than for typical observers, with selective threshold elevations corresponding to unique CVD types. Classifications of CVD type and severity via unsupervised machine learning confirmed functional subtypes. FInD tasks reliably detect CVD and may serve as valuable tools in basic and clinical color vision science.

Exploration of risk factors of platelet transfusion refractoriness and its impact on the prognosis of hematopoietic stem cell transplantation: a retrospective study of patients with hematological diseases.

Platelet transfusion refractoriness (PTR) is an intractable issue in hematological patients, which increases bleeding risks and hospitalization costs to a great extent. We reviewed 108 patients with hematological diseases including acute leukemia, myelodysplastic syndrome, aplastic anemia, and others who received allogeneic hematopoietic stem cell transplantation (HSCT) from January 2019 through December 2020. After multivariable logistic regression, we found that splenomegaly (odds ratio [OR] = 26.98, p < .001) and JAK mutation (OR = 17.32, p = .024) were independent risk factors for PTR. During the period of transplantation, patients in the PTR group had a significantly higher platelet transfusion demand, which was reflected in the increased number of platelet transfusions (10.23 ± 6.696 vs. 5.06 ± 1.904, p < .001). After multivariate adjustment, PTR turned out to be independently associated with worse overall survival (hazard ratio = 2.794, 95% confidence interval = 1.083-7.207, p = .034). In conclusion, we found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases. A history of PTR prior to allo-HSCT indicates a poor prognosis.

What is the context?Platelet transfusion refractoriness is a critical issue, and it greatly increases bleeding risks and hospitalization costs.Patients with hematological diseases tend to develop PTR.PTR results from immune and nonimmune factors and the latter account for 80­90%.At present, there are few studies focused on the inducing factors of PTR, and the specific mechanism is not clear.What is new?In this study, we investigated 108 patients with hematological disorders who received allogeneic HSCT from January 2019 to December 2020.We found that splenomegaly and JAK gene mutation were independent risk factors for PTR in patients with hematological diseases.PTR had a passive effect on the prognosis of patients after HSCT, as indicated by worse OS and a trend toward lower platelets after transplantation.PTR might affect megakaryocyte reconstitution after transplantation.What is the impact?This study provides evidence that hematological patients with splenomegaly should be alert to the occurrence of PTR, which often indicates a worse prognosis of transplantation.Spleen reduction and JAK inhibitors in the treatment of PTR are worth exploring.AbbreviationsPLT: platelets; PTR: platelet transfusion refractoriness; HSCT: hematopoietic stem cell transplantation; OR: odds ratio; HR: hazard ratio; CI: confidence interval; IQR: interquartile range; SD: standard deviation; HLA: human leukocyte antigen; HPA: human platelet antigen; OS: overall survival; RFS: relapse free survival; PI: post-transfusion increment; PPR: percentage platelet recovery; CCI: corrected count increment; ICU: intensive care unit; AA: aplastic anemia; MDS: myelodysplastic syndrome; AML: acute myeloid leukemia; ALL: acute lymphocytic leukemia; CML: chronic myeloid leukemia; CMML: chronic myelomonocytic leukemia; MPN: myeloproliferative neoplasm; SI: splenic irradiation; Abs: antibodies; CR: complete remission; DAC: decitabine; GVHD: graft-versus-host disease; BM: bone marrow; PB: peripheral blood.

Undescribed amino acid-sesquiterpene lactone adducts and sesquiterpene glycosides from the roots of Saussurea lappa and their anti-HBV activity.

Saussurea lappa (Asteraceae family), a traditional Chinese medicine, has been found to possess anti-inflammatory, immune-promoting, antibacterial, antitumor, anti-HBV, cholestatic, and hepatoprotective activities. Herein, two undescribed amino acid-sesquiterpene lactone adducts, saussureamines G and H (1 and 2), and two new sesquiterpene glycosides, saussunosids F and G (3 and 4), along with 26 known sesquiterpenoids (5-30) have been isolated from the roots of S. lappa. Their structures and absolute configurations of these compounds were established by physical data analyses such as HRESIMS, IR, 1D and 2D NMR and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (5, 6, 12, 13, 17, 19, 23, 26, 29, and 30) exhibited activities against the secretions of HBsAg and HBeAg. In particular, compound 6 showed inhibition of HBsAg and HBeAg secretion with IC50 values of 11.24 and 15.12 µM, with SI values of 1.25 and 0.93, respectively. Molecular docking studies were also conducted on the anti-HBV compounds. Overall, this study provides insights into the potential therapeutic uses of the compounds found in the roots of S. lappa, particularly in the treatment of hepatitis B virus infections.

Efficacy and safety of caplacizumab in the treatment of thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy. Several studies have demonstrated the efficacy of caplacizumab in iTTP. However, the effect on different populations remains controversial. Therefore, we performed a systematic review and meta-analysis to assess the effectiveness and safety of caplacizumab for treating iTTP. MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Library for studies until 24 March 2023. Participants were hospitalized patients with iTTP. Interventions included caplacizumab versus placebo or standard of care (SOC). Outcomes assessed included all-cause mortality, exacerbation, relapse, refractory, time-to-platelet-count-recovery, length of TPE and hospital stay, bleeding, and thrombosis. RESULTS: A total of 1119 patients from eight studies were subjected to meta-analysis. The results of the meta-analysis showed that iTTP patients treated with caplacizumab achieved a reduction in mortality (RR 0.38, 95% CI: 0.19-0.75), exacerbation (RR 0.29, 95% CI: 0.14-0.61) and refractory (RR 0.50, 95% CI: 0.31-0.81). Besides, adding caplacizumab to SOC was associated with a shorten time-to-platelet-count-recovery (MD - 2.31, 95% CI: -3.86 to -0.77) and length of TPE (MD - 4.61, 95% CI: -6.20 to -3.02). In terms of safety, the bleeding rate was higher in the caplacizumab group (RR 1.57, 95% CI: 1.21-2.02), while there was no significant difference in hospital stay and thrombosis between the two groups. CONCLUSIONS: Caplacizumab is an effective treatment for patients with iTTP, especially in reducing all-cause mortality, exacerbations, refractoriness, and the time-to-platelet-count-recovery. Although the risk of bleeding may be increased, it is generally modest and manageable.

B Lymphocyte Development in the Bursa of Fabricius of Young Broilers is Influenced by the Gut Microbiota.

Chickens have been used as a valuable and traditional model for studies on basic immunology. B lymphocytes were first identified in the bursa of Fabricius (BF) of broilers. The microbiota is important for immune system development and function. However, the effect of the microbiota on mediating B cell development and its regulatory mechanism is poorly elucidated. Here, we show that the gut microbiota is associated with the development of bursal B cells in young chickens. Changing patterns of both the alpha diversity and the expression of the B cell marker Bu-1α in the gut microbiota were related to the ages of chickens at different growth phases. Further correlation analysis revealed the marked correlation between the relative abundances of Intestinimonas, Bilophila, Parasutterella, Bacteroides, Helicobacter, Campylobacter, and Mucispirillum and the expression of Bu-1α. In antibiotic-treated chickens, BF and B cell development had aberrations as the relative abundance of the microbiota in early life decreased. These findings were consistent with Spearman's correlation results. Single-cell transcriptome analysis indicated that the heterogeneity in the cellular composition and developmental trajectory of bursal B cells from antibiotic-treated chickens was large. We found a novel subpopulation of unnamed B cells and identified Taf1 as a new pivotal regulator of B cell lineage differentiation. Therefore, we provide novel insights into the regulatory role of the gut microbiota in B cell development in early life and the maturation of host humoral immunity. IMPORTANCE In this study, we used young broilers to investigate the relationship between their gut microbiota and bursal B cell development. We characterized the important variables, microbes, B cells, and immunoglobulins during the posthatch development of birds. We also identified several candidate taxa in the cecal contents associated with B cells. Our study provides a rich resource and cell-cell cross talk model supporting B cell differentiation from the bursa in vitro at single-cell resolution. Furthermore, we determined a new pivotal regulator (Taf1) of B cell differentiation. We believe that our study makes a significant contribution to the literature because our findings may elucidate the role of the gut microbiota in B cell differentiation. This study also serves as a basis for developing new strategies that modulate B cell differentiation to prevent diseases.

AIM (Angular Indication Measurement)- Visual Acuity: An adaptive, self-administered, and generalizable vision assessment method used to measure visual acuity.

This proof-of-concept study introduces Angular Indication Measurement and applies it to VA (AIM-VA). First, we compared the ability of AIM-VA and ETDRS to detect defocus and astigmatic blur in 22 normally-sighted adults. Spherical and cylindrical lenses (±0.00D, +0.25D, +0.50D, +0.75D, +1.00D, +2.00D and +0.50D, +1.00D, +2.00D each at 0°, 90°, 135°, respectively) in the dominant eye induced blur. Second, we compared repeatability over two tests of AIM-VA and ETDRS. A 2-way-ANOVA showed a main effect for defocus-blur and test with no interaction. A 3-way-ANOVA for the astigmatism experiment revealed main effects for test type, blur, and direction and with no interactions. Planned multiple comparisons showed AIM had greater astigmatic-induced VA loss than ETDRS. Bland-Altman plots showed small bias and no systematic learning effect for either test type and improved repeatability with >2 adaptive steps for AIM-VA. AIM-VA's ability to detect defocus was comparable with that of an ETDRS letter chart and showed greater sensitivity to astigmatic blur, and AIM-VA's repeatability is comparable with ETDRS when using 2 or more adaptive steps. AIM's self-administered orientation judgment approach is generalizable to interrogate other visual functions, e.g., contrast, color, motion, stereo-vision.

Resting natural killer cell homeostasis relies on tryptophan/NAD+ metabolism and HIF-1α.

Natural killer (NK) cells are forced to cope with different oxygen environments even under resting conditions. The adaptation to low oxygen is regulated by oxygen-sensitive transcription factors, the hypoxia-inducible factors (HIFs). The function of HIFs for NK cell activation and metabolic rewiring remains controversial. Activated NK cells are predominantly glycolytic, but the metabolic programs that ensure the maintenance of resting NK cells are enigmatic. By combining in situ metabolomic and transcriptomic analyses in resting murine NK cells, our study defines HIF-1α as a regulator of tryptophan metabolism and cellular nicotinamide adenine dinucleotide (NAD+ ) levels. The HIF-1α/NAD+ axis prevents ROS production during oxidative phosphorylation (OxPhos) and thereby blocks DNA damage and NK cell apoptosis under steady-state conditions. In contrast, in activated NK cells under hypoxia, HIF-1α is required for glycolysis, and forced HIF-1α expression boosts glycolysis and NK cell performance in vitro and in vivo. Our data highlight two distinct pathways by which HIF-1α interferes with NK cell metabolism. While HIF-1α-driven glycolysis is essential for NK cell activation, resting NK cell homeostasis relies on HIF-1α-dependent tryptophan/NAD+ metabolism.