The association of calligraphy activities with peace of mind, stress self-management, and perceived health status in older adults.

Introduction: Calligraphy, as a form of mindful practice, encourages focus, creativity, and relaxation, which collectively contribute to a more peaceful mental state. Through regular engagement in calligraphy, older adults can develop better coping mechanisms for stress, leading to more effective self-management of daily stressors. This enhanced ability to manage stress can reduce the overall burden on their mental and physical health, promoting a more positive outlook on life. Methods: This study employed convenience sampling and snowball sampling to select 246 older adults aged 60-70 from Changsha, China, in March 2024 as valid samples. AMOS v.23 was used to construct a structural equation model to validate the hypotheses. Results: The study found a significant positive correlation between calligraphy activities and peace of mind/stress self-management. There is also a significant positive correlation between peace of mind/stress self-management and perceived health status. Additionally, peace of mind and stress self-management act as mediators between calligraphy activities and perceived health status. Discussion: This indicates that calligraphy activities not only contribute to the psychological well-being of older adults but also indirectly enhance their positive perception of their own health by improving their mental state. Consequently, such activities can be an integral part of holistic health interventions aimed at enhancing the quality of life and overall health of older adults.

Advances in artificial intelligence applications in the field of lung cancer.

Lung cancer remains a leading cause of cancer-related deaths globally, with its incidence steadily rising each year, representing a significant threat to human health. Early detection, diagnosis, and timely treatment play a crucial role in improving survival rates and reducing mortality. In recent years, significant and rapid advancements in artificial intelligence (AI) technology have found successful applications in various clinical areas, especially in the diagnosis and treatment of lung cancer. AI not only improves the efficiency and accuracy of physician diagnosis but also aids in patient treatment and management. This comprehensive review presents an overview of fundamental AI-related algorithms and highlights their clinical applications in lung nodule detection, lung cancer pathology classification, gene mutation prediction, treatment strategies, and prognosis. Additionally, the rapidly advancing field of AI-based three-dimensional (3D) reconstruction in lung cancer surgical resection is discussed. Lastly, the limitations of AI and future prospects are addressed.

Exploring the ability of novel choroidal biomarkers in predicting treatment outcomes of polypoidal choroidal vasculopathy.

INTRODUCTION: To explore the relationship between choroidal biomarkers and the response to anti- VEGF in PCV eyes. METHODS: A hospital-based retrospective study. We included 54 patients diagnosed with PCV who had received standard 3-monthly anti-VEGF monotherapy and had finished regular follow-ups. Choroidal thickness (CT), three-dimensional choroidal vascularity index (CVI), and the vascular density of choriocapillaris (CCVD) were measured utilizing SS-OCTA. Effective and poor responders were classified based on the changes of morphologic features. Multivariate linear regression models were performed for the outcomes to determine independent prognostic factors. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of CT and CVI as biomarkers between effective and poor responders. RESULTS: A higher CVI at baseline was the only factor that correlated with the poor response after 3-monthly injections of anti-VEGF (P=0.038). The greater change of central macular thickness (CMT) was significantly correlated with increased CMT (P=0.030), decreased CT (P=0.042) and decreased CVI (p=0.038) at baseline. Using ROC curves, we found that the CVI value demonstrated superior predictive ability compared to the CT value, with AUC of 0.842 and the best cut-off value of 0.445. CONCLUSION: A higher three-dimensional CVI using SS-OCTA is a promising biomarker to predict the poor anatomical response to anti-VEGF treatment in PCV patients.

Performance Enhancement of Self-Powered Electrochromic Device via a PEDOT:PSS Electrode Inherited with Intrinsic Roughness of Substrate.

The electrode optimization and rational design are of great significance for the performance enhancement of self-powered electrochromic devices (ECDs). It can be effectively enhanced by developing interfacial properties of electrodes, which can promote the internal ion transport within functional components consisting of an electrode, electrochromic layer, and electrolyte layer and thus obtain performance improvement of fabricated devices. This work aims to construct the electrode of poly(3,4-ethylenedioxythiophene): polystyrenesulfonate (PEDOT:PSS) on different substrates and promote interface performance of the prepared electrodes via inheriting the surface topography of substrates. Besides, the prepared PEDOT:PSS electrodes as a dual-function layer including the electrochromic and electrode layer are employed to assemble the ECDs. It is found that the intrinsic roughness of the paper substrate can facilitate the electrochemical performance of the prepared PEDOT:PSS electrode on it effectively, thereby showing a superior electrochemical surface area and diffusion coefficient as well as a lower charge-transfer resistance of 13.56 Ω. Similarly, for the prepared self-powered ECD on the paper substrate, it also indicates a high light absorption property (0.413), well-defined electrochromic contrast (33.09), fast switching (τc = 4.0 s, τb = 6.8 s), high coloration efficiency (92.275 cm2 C-1), high areal capacity (10.93 mAh m-2) at 0.01 mA cm-2, and lower equivalent series resistance (176.2 Ω) in comparison to parallel ECDs on the PET and glass substrate. Leveraging the intrinsic roughness of the substrate is able to enhance the electrochemical performance of electrodes, which can also provide a new strategy for the construction of high-performance self-powered ECDs.

Ultralow dose coronary calcium scoring CT at reduced tube voltage and current by using deep learning image reconstruction.

OBJECTIVE: To explore the potential of the deep learning reconstruction (DLR) for ultralow dose calcium scoring CT (CSCT) with simultaneously reduced tube voltage and current. METHODS: In this prospective study, seventy-five patients (group A) undergoing routine dose CSCT (120kVp/30mAs) were followed by a low dose (120kVp/20mAs) scan and another 81 (group B) were followed by an ultralow dose (80kVp/20mAs) scan. The hybrid iterative reconstruction was used for the routine dose data while the DLR for data of reduced dose. The calcium score and risk categorization were compared, where the correlation was evaluated using the intraclass correlation coefficient (ICC). The noise suppression performance of DLR was characterized by the contrast-to-noise ratio (CNR) between coronary arteries and pericoronary fat. RESULTS: The effective dose was 0.32 ± 0.03 vs. 0.48 ± 0.05 mSv for the two scans in group A and 0.09 ± 0.01 vs. 0.49 ± 0.05 mSv in group B. No significant difference was found on CACSs within either group (A: p = 0.10, ICC=0.99; B: p = 0.14, ICC=0.99), nor was it different on risk categorization (A: p = 0.32, ICC=0.99; B: p = 0.16, ICC=0.99). The DLR images exhibited higher CNR in both groups (A: p < 0.001; B: p = 0.001). CONCLUSIONS: The DLR allowed reliable calcium scoring in not only low dose CSCT with reduced tube current but ultralow dose CSCT with simultaneously reduced tube voltage and current, showing feasibility to be adopted in routine applications.

Effect of chronic alcohol consumption on oral microbiota in rats with periodontitis.

Background: The imbalance of oral microbiota can contribute to various oral disorders and potentially impact general health. Chronic alcohol consumption beyond a certain threshold has been implicated in influencing both the onset and progression of periodontitis. However, the mechanism by which chronic alcohol consumption affects periodontitis and its association with changes in the oral microbial community remains unclear. Objective: This study used 16S rRNA gene amplicon sequencing to examine the dynamic changes in the oral microbial community of rats with periodontitis influenced by chronic alcohol consumption. Methods: Twenty-four male Wistar rats were randomly allocated to either a periodontitis (P) or periodontitis + alcohol (PA) group. The PA group had unrestricted access to alcohol for 10 weeks, while the P group had access to water only. Four weeks later, both groups developed periodontitis. After 10 weeks, serum levels of alanine aminotransferase and aspartate aminotransferase in the rats' serum were measured. The oral swabs were obtained from rats, and 16S rRNA gene sequencing was conducted. Alveolar bone status was assessed using hematoxylin and eosin staining and micro-computed tomography. Results: Rats in the PA group exhibited more severe periodontal tissue damage compared to those in the periodontitis group. Although oral microbial diversity remained stable, the relative abundance of certain microbial communities differed significantly between the two groups. Actinobacteriota and Desulfobacterota were more prevalent at the phylum level in the PA group. At the genus level, Cutibacterium, Tissierella, Romboutsia, Actinomyces, Lawsonella, Anaerococcus, and Clostridium_sensu_stricto_1 were significantly more abundant in the PA group, while Haemophilus was significantly less abundant. Additionally, functional prediction using Tax4Fun revealed a significant enrichment of carbohydrate metabolism in the PA group. Conclusion: Chronic alcohol consumption exacerbated periodontitis in rats and influenced the composition and functional characteristics of their oral microbiota, as indicated by 16S rRNA gene sequencing results. These microbial alterations may contribute to the exacerbation of periodontitis in rats due to chronic alcohol consumption.

Building microbial consortia to enhance straw degradation, phosphorus solubilization, and soil fertility for rice growth.

Straw pollution and the increasing scarcity of phosphorus resources in many regions of China have had severe impacts on the growing conditions for crop plants. Using microbial methods to enhance straw decomposition rate and phosphorus utilization offers effective solutions to address these problems. In this study, a microbial consortium 6 + 1 (consisting of a straw-degrading bacterium and a phosphate-solubilizing bacterium) was formulated based on their performance in straw degradation and phosphorus solubilization. The degradation rate of straw by 6 + 1 microbial consortium reached 48.3% within 7 days (The degradation ability was 7% higher than that of single bacteria), and the phosphorus dissolution rate of insoluble phosphorus reached 117.54 mg·L- 1 (The phosphorus solubilization ability was 29.81% higher than that of single bacteria). In addition, the activity of lignocellulosic degrading enzyme system was significantly increased, the activities of endoglucanase, ß-glucosidase and xylanase in the microbial consortium were significantly higher than those in the single strain (23.16%, 28.02% and 28.86%, respectively). Then the microbial consortium was processed into microbial agents and tested in rice pots. The results showed that the microbial agent significantly increased the content of organic matter, available phosphorus and available nitrogen in the soil. Ongoing research focuses on the determination of the effects and mechanisms of a functional hybrid system of straw degradation and phosphorus removal. The characteristics of the two strains are as follows: Straw-degrading bacteria can efficiently degrade straw to produce glucose-based carbon sources when only straw is used as a carbon source. Phosphate-solubilizing bacteria can efficiently use glucose as a carbon source, produce organic acids to dissolve insoluble phosphorus and consume glucose at an extremely fast rate. The analysis suggests that the microbial consortium 6 + 1 outperformed individual strains in terms of both performance and application effects. The two strains within the microbial consortium promote each other during their growth processes, resulting in a significantly higher rate of carbon source consumption compared to the individual strains in isolation. This increased demand for carbon sources within the growth system facilitates the degradation of straw by the strains. At the same time, the substantial carbon consumption during the metabolic process generated a large number of organic acids, leading to the solubilization of insoluble phosphorus. It also provides a basis for the construction of this type of microbial consortium.

U.S. trends in methamphetamine-involved psychiatric hospitalizations in the United States, 2015-2019.

BACKGROUND: In the U.S., overdose deaths and substance treatment admissions related to methamphetamine are rising. This study aims to measure and compare U.S. temporal trends in methamphetamine-involved psychiatric hospitalizations. METHODS: We conducted a population-based, trend analysis of U.S. psychiatric hospitalizations and calculated quarterly (Q) rates per 100,000 population of substance-involved psychiatric hospitalizations. We assessed U.S. regional quarterly percentage hospitalization rate changes using Joinpoint regression. RESULTS: From Q4 2015-Q4 2019, there were 963,202 psychiatric hospitalizations, 50,223 (5.2 %) involved methamphetamine and 102,877 (10.7 %) involved opioids and/or cocaine without methamphetamine. Methamphetamine-involved psychiatric hospitalization rates increased by 68.0 %, psychiatric hospitalizations rates involving opioid and/or cocaine without methamphetamine decreased by 22 %, while nonsubstance-involved psychiatric hospitalizations rates remained unchanged. The largest significant increases in methamphetamine-involved psychiatric hospitalization rates were among people >61 years old, males, and Midwesterners. Methamphetamine-involved psychiatric hospitalization rates doubled among Black patients. The largest average percent increase among methamphetamine-involved psychiatric hospitalizations was 10.2 % from Q4 2015-Q2 2017 in the Midwest. CONCLUSION AND RELEVANCE: Most psychiatric hospitalizations did not involve substances. Methamphetamine-involved psychiatric hospitalizations greatly increased while opioid-involved psychiatric hospitalizations decreased, but involved more total encounters. Greater access to harm reduction services, contingency management programs, and mental health services is urgently needed.

Preclinical Characterization of ARX517, a Site-specific Stable PSMA-Targeted Antibody Drug Conjugate for Treatment of Metastatic Castration-Resistant Prostate Cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an advanced disease in which patients ultimately fail standard of care androgen-deprivation therapies and exhibit poor survival rates. The prostate-specific membrane antigen (PSMA) has been validated as a mCRPC tumor antigen with over-expression in tumors and low expression in healthy tissues. Using our proprietary technology for incorporating synthetic amino acids (SAAs) into proteins at selected sites, we have developed ARX517, an antibody drug conjugate (ADC) which is composed of a humanized anti-PSMA antibody site-specifically conjugated to a tubulin inhibitor at a drug-to-antibody ratio of 2. After binding PSMA, ARX517 is internalized and catabolized, leading to cytotoxic payload delivery and apoptosis. To minimize premature payload release and maximize delivery to tumor cells, ARX517 employs a non-cleavable PEG linker and stable oxime conjugation enabled via SAA protein incorporation to ensure its overall stability. In vitro studies demonstrate that ARX517 selectively induces cytotoxicity of PSMA-expressing tumor cell lines. ARX517 exhibited a long terminal half-life and high serum exposure in mice, and dose-dependent anti-tumor activity in both enzalutamide-sensitive and -resistant CDX and PDX prostate cancer models. Repeat dose toxicokinetic studies in non-human primates demonstrated ARX517 was tolerated at exposures well above therapeutic exposures in mouse pharmacology studies, indicating a wide therapeutic index. In summary, ARX517 inhibited tumor growth in diverse mCRPC models, demonstrated a tolerable safety profile in monkeys, and had a wide therapeutic index based on preclinical exposure data. Based on the encouraging preclinical data, ARX517 is currently being evaluated in a Phase 1 clinical trial ([NCT04662580]).

High-resolution 3D spatial distribution of complex microbial colonies revealed by mass spectrometry imaging.

INTRODUCTION: Bacterial living states and the distribution of microbial colony signaling molecules are widely studied using mass spectrometry imaging (MSI). However, current approaches often treat 3D colonies as flat 2D disks, inadvertently omitting valuable details. The challenge of achieving 3D MSI in biofilms persists due to the unique properties of microbial samples. OBJECTIVES: The study aimed to develop a new biofilm sample preparation method that can realize high-resolution 3D MSI of bacterial colonies to reveal the spatial organization of bacterial colonies. METHODS: This article introduces the moisture-assisted cryo-section (MACS) method, enabling embedding-free sectioning parallel to the growth plane. The MACS method secures intact sections by controlling ambient humidity and slice thickness, preventing molecular delocalization. RESULTS: Combined with matrix-assisted laser desorption ionization mass spectrometry (MALDI)-MSI, the MACS method provides high-resolution insights into endogenic and exogenous molecule distributions in Pseudomonas aeruginosa (P. aeruginosa) biofilms, including isomeric pairs. Moreover, analyzed colonies are revived into 3D models, vividly depicting molecular distribution from inner to outer layers. Additionally, we investigated metabolite spatiotemporal dynamics in multiple colonies, observing changes over time and distinct patterns in single versus merged colonies. These findings shed light on the repel-merge process for multi-colony formation. Furthermore, our study monitored chemical responses inside biofilms after antibiotic treatment, showing increased antibiotic levels in the outer biofilm layer over time while maintaining low levels in the inner region. Moreover, the MACS method demonstrated its universality and applicability to other bacterial strains. CONCLUSION: These results unveil complex cell activities within biofilm colonies, offering insights into microbe communities. The MACS method is universally applicable to loosely packed microorganism colonies, overcoming the limitations of previously reported MSI methods. It has great potential for studying bacterial-infected cancer tissues and artificial organs, making it a valuable tool in microbiological research.

Injectable and NIR-responsive CDN-POM hydrogels for combined non-inflammatory photo-immunotherapy.

Similar to clinically applied thermal ablation techniques, the cellular necrosis that occurs during photothermal tumor therapy (PTT) can induce inflammatory response, severely compromising the therapeutic efficacy and clinical translation of the PTT. Inspired by the remarkable ROS-scavenging activity and high photothermal efficiency of molybdenum-based polyoxometalate (POM) and the immunostimulatory effect of cyclic dinucleotides (CDNs), a NIR-responsive and injectable DNA-mediated hybrid hydrogel (CDN-POM) has been developed. The hydrogels have superior photothermal efficiency (43.41%) to POM, impressive anti-inflammatory capability and prolonged intratumoral CDN-releasing behavior, thus enabling synergistic anti-tumor therapeutic outcomes. Meanwhile, local treatment induced by CDN-POM hydrogels displays minimal side effects on normal tissue. Taking advantage of the high phototherapeutic effect, ROS-scavenging activity and sustained CDN release of CDN-POM hydrogels, a novel combined approach that integrates photothermal therapy and immunotherapy of breast tumor is successfully pioneered.

A sophisticated mechanism governs Pol ζ activity in response to replication stress.

DNA polymerase ζ (Pol ζ) plays an essential role in replicating damaged DNA templates but contributes to mutagenesis due to its low fidelity. Therefore, ensuring tight control of Pol ζ's activity is critical for continuous and accurate DNA replication, yet the specific mechanisms remain unclear. This study reveals a regulation mechanism of Pol ζ activity in human cells. Under normal conditions, an autoinhibition mechanism keeps the catalytic subunit, REV3L, inactive. Upon encountering replication stress, however, ATR-mediated phosphorylation of REV3L's S279 cluster activates REV3L and triggers its degradation via a caspase-mediated pathway. This regulation confines the activity of Pol ζ, balancing its essential role against its mutations causing potential during replication stress. Overall, our findings elucidate a control scheme that fine tunes the low-fidelity polymerase activity of Pol ζ under challenging replication scenarios.

Off-Axis Integral Cavity Carbon Dioxide Gas Sensor Based on Machine-Learning-Based Optimization.

Accurately detecting atmospheric carbon dioxide is a vital part of responding to the global greenhouse effect. Conventional off-axis integral cavity detection systems are computationally intensive and susceptible to environmental factors. This study deploys an Extreme Learning Machine model incorporating a cascaded integrator comb (CIC) filter into the off-axis integrating cavity. It is shown that appropriate parameters can effectively improve the performance of the instrument in terms of lower detection limit, accuracy, and root mean square deviation. The proposed method is incorporated successfully into a monitoring station situated near an industrial area for detecting atmospheric carbon dioxide (CO2) concentration daily.

Air Pollution, Genetic Susceptibility, and Risk of Incident Systemic Lupus Erythematosus: A Prospective Cohort Study.

OBJECTIVE: There are few existing studies that investigate the risk of systemic lupus erythematosus (SLE) associated with long-term exposure to air pollutants. This study aimed to explore associations between long-term exposure to air pollutants and incident SLE and further evaluate interactions and joint effects of genetic risk and air pollutants. METHODS: A total of 459,815 participants were included from UK Biobank. The concentrations of air pollutants (fine particulate matter with diameter ≤2.5 µm [PM2.5], particulate matter diameter ≤10 µm [PM10], nitrogen dioxide [NO2], and nitrogen oxides [NOx]) were estimated by land-use regression model. We applied Cox proportional hazards model to explore linkages of air pollutants and incident SLE. The polygenic risk score (PRS) was used for further assessing the interactions and joint effects of genetic risk and air pollutants. RESULTS: A total of 399 patients with SLE were identified during a median follow-up of 11.77 years. There were positive associations between air pollutant exposure and incident SLE, as the adjusted hazard ratios were 1.18 (95% confidence interval [95% CI] 1.06-1.32), 1.23 (1.10-1.39), 1.27 (1.14-1.41), and 1.13 (1.03-1.23) for each interquartile range increase in PM2.5, PM10, NO2, and NOx, respectively. Moreover, participants with high genetic risk and high air pollution exposure had the highest risk of incident SLE compared with those with low genetic risk and low air pollution exposure (adjusted hazard ratio: PM2.5, 4.16 [95% CI 2.67-6.49]; PM10, 5.31 [95% CI 3.30,-8.55]; NO2, 5.61 [95% CI 3.45-9.13]; and NOx, 4.80 [95% CI 3.00-7.66]). There was a significant multiplicative interaction between NO2 and PRS. CONCLUSION: Long-term exposure to air pollutants (PM2.5, PM10, NO2, and NOx) may increase the risk of developing SLE.

Decellularized Amnion Membrane Triggers Macrophage Polarization for Desired Host Immune Response.

Appropriate regulation of immunomodulatory responses, particularly acute inflammation involving macrophages, is crucial for the desired functionality of implants. Decellularized amnion membrane (DAM) is produced by removing cellular components and antigenicity, expected to reduce immunogenicity and the risk of inflammation. Despite the potential of DAM as biomaterial implants, few studies have investigated its specific effects on immunomodulation. Here, it is demonstrated that DAM can regulate macrophage-driven inflammatory response and potential mechanisms are investigated. In vitro results show that DAM significantly inhibits M1 polarization in LPS-induced macrophages by inhibiting Toll-like receptors (TLR) signaling pathway and TNF signaling pathway and promotes macrophage M2 polarization. Physical signals from the 3D micro-structure and the active protein, DCN, binding to key targets may play roles in the process. In the subcutaneous implant model in rats, DAM inhibits the persistence of inflammation and fibrous capsule formation, while promoting M2 macrophage polarization, thereby facilitating tissue regeneration. This study provides insights into DAM's effect and potential mechanisms on the balance of M1/M2 macrophage polarization in vitro and vivo, emphasizing the immunomodulation of ECM-based materials as promising implants.

Prediction of glypican-3 expression in hepatocellular carcinoma using multisequence magnetic resonance imaging-based histology nomograms.

Background: Hepatocellular carcinoma (HCC) is often associated with the overexpression of multiple proteins and genes. For instance, patients with HCC and a high expression of the glypican-3 (GPC3) gene have a poor prognosis, and noninvasive assessment of GPC3 expression before surgery is helpful for clinical decision-making. Therefore, our primary aim in this study was to develop and validate multisequence magnetic resonance imaging (MRI) radiomics nomograms for predicting the expression of GPC3 in individuals diagnosed with HCC. Methods: We conducted a retrospective analysis of 143 patients with HCC, including 123 cases from our hospital and 20 cases from The Cancer Genome Atlas (TCGA) or The Cancer Imaging Archive (TCIA) public databases. We used preoperative multisequence MRI images of the patients for the radiomics analysis. We extracted and screened the imaging histologic features using fivefold cross-validation, Pearson correlation coefficient, and the least absolute shrinkage and selection operator (LASSO) analysis method. We used logistic regression (LR) to construct a radiomics model, developed nomograms based on the radiomics scores and clinical parameters, and evaluated the predictive performance of the nomograms using receiver operating characteristic (ROC) curves, calibration curves, and decision curves. Results: Our multivariate analysis results revealed that tumor morphology (P=0.015) and microvascular (P=0.007) infiltration could serve as independent predictors of GPC3 expression in patients with HCC. The nomograms integrating multisequence radiomics radiomics score, tumor morphology, and microvascular invasion had an area under the curve (AUC) value of 0.989. This approach was superior to both the radiomics model (AUC 0.979) and the clinical model (AUC 0.793). The sensitivity, specificity, and accuracy of 0.944, 0.800, and 0.913 for the test set, respectively, and the model's calibration curve demonstrated good consistency (Brier score =0.029). The decision curve analysis (DCA) indicated that the nomogram had a higher net clinical benefit for predicting the expression of GPC3. External validation of the model's prediction yielded an AUC value of 0.826. Conclusions: Our study findings highlight the close association of multisequence MRI imaging and radiomic features with GPC3 expression. Incorporating clinical parameters into nomograms can offer valuable preoperative insights into tailoring personalized treatment plans for patients diagnosed with HCC.

Quantifying functional redundancy in polysaccharide-degrading prokaryotic communities.

BACKGROUND: Functional redundancy (FR) is widely present, but there is no consensus on its formation process and influencing factors. Taxonomically distinct microorganisms possessing genes for the same function in a community lead to within-community FR, and distinct assemblies of microorganisms in different communities playing the same functional roles are termed between-community FR. We proposed two formulas to respectively quantify the degree of functional redundancy within and between communities and analyzed the FR degrees of carbohydrate degradation functions in global environment samples using the genetic information of glycoside hydrolases (GHs) encoded by prokaryotes. RESULTS: Our results revealed that GHs are each encoded by multiple taxonomically distinct prokaryotes within a community, and the enzyme-encoding prokaryotes are further distinct between almost any community pairs. The within- and between-FR degrees are primarily affected by the alpha and beta community diversities, respectively, and are also affected by environmental factors (e.g., pH, temperature, and salinity). The FR degree of the prokaryotic community is determined by deterministic factors. CONCLUSIONS: We conclude that the functional redundancy of GHs is a stabilized community characteristic. This study helps to determine the FR formation process and influencing factors and provides new insights into the relationships between prokaryotic community biodiversity and ecosystem functions. Video Abstract.

Chemoenzymatic synthesis of sialyl-α2,3-lactoside-functionalized BSA conjugate inhibits influenza infection.

Influenza remains a global public health threat, and the development of new antivirals is crucial to combat emerging drug-resistant influenza strains. In this study, we report the synthesis and evaluation of a sialyl lactosyl (TS)-bovine serum albumin (BSA) conjugate as a potential multivalent inhibitor of the influenza virus. The key trisaccharide component, TS, was efficiently prepared via a chemoenzymatic approach, followed by conjugation to dibenzocyclooctyne-modified BSA via a strain-promoted azide-alkyne cycloaddition reaction. Biophysical and biochemical assays, including surface plasmon resonance, isothermal titration calorimetry, hemagglutination inhibition, and neuraminidase inhibition, demonstrated the strong binding affinity of TS-BSA to the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus as well as intact virion particles. Notably, TS-BSA exhibited potent inhibitory activity against viral entry and release, preventing cytopathic effects in cell culture. This multivalent presentation strategy highlights the potential of glycocluster-based antivirals for combating influenza and other drug-resistant viral strains.

A Zanamivir-protein conjugate mimicking mucin for trapping influenza virion particles and inhibiting neuraminidase activity.

Influenza viruses contribute significantly to the global health burden, necessitating the development of strategies against transmission as well as effective antiviral treatments. The present study reports a biomimetic strategy inspired by the natural antiviral properties of mucins. A bovine serum albumin (BSA) conjugate decorated with the multivalent neuraminidase inhibitor Zanamivir (ZA-BSA) was synthesized using copper-free click chemistry. This synthetic pseudo-mucin exhibited potent neuraminidase inhibitory activity against several influenza strains. Virus capture and growth inhibition assays demonstrated its effective absorption of virion particles and ability to prevent viral infection in nanomolar concentrations. Investigation of the underlying antiviral mechanism of ZA-BSA revealed a dual mode of action, involving disruption of the initial stages of host-cell binding and fusion by inducing viral aggregation, followed by blocking the release of newly assembled virions by targeting neuraminidase activity. Notably, the conjugate also exhibited potent inhibitory activity against Oseltamivir-resistant neuraminidase variant comparable to the monomeric Zanamivir. These findings highlight the application of multivalent drug presentation on protein scaffold to mimic mucin adsorption of viruses, together with counteracting drug resistance. This innovative approach has potential for the creation of antiviral agents against influenza and other viral infections.