TP53 and EGFR amplification are negative predictors of overall survival in patients diagnosed with non-small cell lung cancer with brain metastases.

Background: The discovery of driver genes such as EGFR, KRAS, and ALK, has dramatically shifted treatment patterns in patients harboring these oncogenes. However, dissemination into the central nervous system (CNS) is a severe complication. In addition, the particular anatomical structure of the CNS has made it difficult to obtain tissue specimens from brain metastases (BM) to generate a gene map, as such, potential predictive markers for survival in patients with non-small cell lung cancer (NSCLC) and BM (NSCLC-BM) remain unclear. Methods: Data from 28 patients diagnosed with NSCLC-BM between June 2019 and May 2021 at Guangdong Sanjiu Brain Hospital (Guangzhou, China), were reviewed. Targeted next-generation sequencing (NGS) of a 168 cancer-related gene panel was available for surgically resected brain tissues from all patients. In addition, molecular characteristics and overall survival (OS) were analyzed to determine potential predictive markers. Results: Among patients with NSCLC-BM, NGS revealed that TP53 was the most frequent mutation (61 %), with a detection rate of 39 %, closely by EGFR amplification. Additionally, CDKN2A, MYC, LRP1B, and RNF43 were frequently observed (18 %). The median OS was significantly shorter in the TP53 mutation group than in the wildtype group (14 versus undefined months, p = 0.014). Similar results were also found in the genetic alteration of EGFR amplification, suggesting that EGFR amplification was associated with worse OS (14 vs. 24 months, p = 0.039). Interestingly, NGS revealed that gene alternations such as TP53, EGFR amplification, and CDKN2A, tended to coexist and such a co-alteration panel indicated worse clinical outcomes (median OS, 5 months). In addition, the detection rate of negative survival genes, including TP53 or EGFR amplification, was much higher in tumor tissues than in plasma samples, indicating the limited predictive value of matched PLA samples. Conclusions: Gene signatures, such as TP53 or EGFR amplification, were associated with worse survival in patients diagnosed with NSCLC-BM. These valuable findings may shed light on new strategies for the prognostic assessment of specific patient groups.

Human umbilical cord mesenchymal stem cells derived extracellular vesicles ameliorate kidney ischemia-reperfusion injury by suppression of senescent tubular epithelial cells - Experimental Study.

BACKGROUND: Human umbilical cord mesenchymal stem cells derived extracellular vesicles (HUMSC-EVs) have drawn much interest in kidney transplantation, mainly because of their renoprotection by alleviating cell injury and stimulating tissue repair. Cellular senescence has been proven to play a dual regulatory role in kidney ischemia-reperfusion injury (IRI), and the regulation of HUMSC-EVs on tubular epithelial cell senescence may be a potential therapeutic target. MATERIALS AND METHODS: In vitro, the hypoxia-reoxygenation of human kidney-2 cells was used to simulate kidney IRI, and the regulation of HUMSC-EVs on human kidney-2 cells was detected. Transcriptome sequencing of human kidney-2 cells was used to explore the potential regulatory mechanism. In vivo, adult male mice were divided into five groups: control group, IRI group, HUMSC-EVs treatment group, senolytics treatment group (dasatinib + quercetin), and combined treatments group (HUMSC-EVs and senolytics). Kidney function, senescent features of tubular epithelial cells, acute kidney injury, and chronic interstitial fibrosis in mice were detected to explore the renoprotection effects of HUMSC-EVs. RESULTS: Kidney IRI significantly up-regulated expressions of LaminB1, p53, p21, p16, senescence-associated beta-galactosidase, and apoptosis of tubular epithelial cells. In the mouse kidney IRI model, kidney subcapsular injection of HUMSC-EVs significantly improved kidney function, reducing the senescent features of tubular epithelial cells and alleviating acute kidney injury and chronic interstitial fibrosis. HUMSC-EVs mainly achieved renoprotection by regulating Bax/Bcl-2-dependent apoptosis during acute kidney injury and mostly reduced tubular atrophy and kidney interstitial fibrosis by regulating Ras-pERK-Ets1-p53 pathway-dependent cell senescence. Oral administration of senolytics also alleviated kidney injury induced by IRI, while the combined treatments of HUMSC-EVs and senolytics had better renoprotection effects. CONCLUSIONS: The combination of HUMSC-EVs and senolytics alleviated acute kidney injury and chronic interstitial fibrosis by dynamic regulation of cell senescence and apoptosis, which provides a therapeutic potential strategy for organ preservation and tissue repair in kidney transplantation.

Pseudorabies virus UL13 primes inflammatory response through downregulating heat shock factor 1.

Pseudorabies virus is a swine alpha-herpesvirus. We demonstrated that alpha-herpesvirus infection downregulates HSF1, a master transcription factor in the heat shock response. The serine/threonine protein kinase activity of late viral protein UL13 is indispensable for HSF1 depletion and phosphorylation, and UL13 does not degrade HSF1 posttranslationally but inhibits the HSF1 mRNA level. Importantly, UL13 increased HSF1 activity even though it reduced HSF1 mRNA. Furthermore, viral replication markedly decreased in the HSF1 knockout cell line or in the presence of an HSF1-specific inhibitor. Interestingly, HSF1 knockout accelerated the activation of NF-κB and p38MAPK. The K96 loci of UL13 are important to induce high levels of IL-6, TNF-α, and IL-ß cytokines while playing a crucial role in promoting mild interstitial pneumonia, liver necrosis, and severe inflammatory cell infiltration in the footpad. Thus, UL13 steers the heat shock response to promote viral replication and the inflammatory response. IMPORTANCE: PRV is a ubiquitous pathogen that infects a variety of mammals, such as pigs, ruminants, carnivores, and rodents as well as human beings, causing enormous economic losses in the swine industry. Here, we employed PRV as a model to determine the relationship between α-herpesvirus and the inflammatory response. Overall, our findings indicated that PRV infection inhibits the level of HSF1 mRNA via the serine/threonine protein kinase activity of UL13. Additionally, we discovered that HSF1 was involved in NF-κB activation upon PRV infection. PRV UL13 orchestrates the level of HSF1 mRNA, HSF1 protein phosphorylation, and priming of the inflammatory response. Our study reveals a novel mechanism employed by UL13 serine/threonine protein kinase activity to promote the inflammatory response, providing novel clues for therapy against alpha-herpesvirus infection.

Early tocilizumab treatment was associated with survival benefits in hospitalized kidney transplants with severe COVID-19 infection: A prospective cohort study.

BACKGROUND: The potential of Tocilizumab (TCZ) in preventing the cytokine storm caused by COVID-19 infection has been observed, while the survival benefits were inconclusive in solid-organ transplant recipients. We aimed to explore whether the timing of TCZ administration holds significance in the clinical course of COVID-19 infection and identify predicative factors of TCZ efficacy. METHODS: We conducted a prospective cohort study between December 2022, and January 2023. Early TCZ use referred to administration within 6 days after symptoms onset, while late TCZ use indicated administration after 6 days. The primary endpoint was 30-day mortality. RESULTS: Twenty-seven kidney transplant recipients with severe COVID-19 infection were enrolled, with 10 in the early use group and 17 in the late use group. In the early use group, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP) and brain natriuretic peptide(BNP) levels had shown significant inhibitions comparing to the late use group, and those inflammatory cytokines demonstrated a noticeable decreasing trend after TCZ administration, whereas only CRP levels decreased in the late use group. The Kaplan-Meier survival curve demonstrated that the early use group had a higher likelihood of survival (P = 0.0078). Receiver Operating Characteristic (ROC) analyses revealed that the time from symptoms to TCZ use (AUC: 0.645), LDH (AUC: 0.803), CRP (AUC: 0.787), and IL-6 (AUC: 0.725) were potential predictive factors of TCZ efficacy. TCZ use within 6 days from symptoms onset, with CRP < 73.5 mg/L, LDH < 435.5 IU/L, and IL-6 < 103.5 pg/mL, had higher survival rates (P = 0.008, P = 0.009, P < 0.001, P < 0.001). CONCLUSION: This study highlights the survival benefits of early TCZ use and the predicative role of cytokines levels in predicting TCZ efficacy in kidney transplant recipients with severe COVID-19 infection.

Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling.

As a novel type of macrocycles with attractive planar chirality, pillar[5]arenes have gained increasing research interest over the past decades, enabling their widespread applications in diverse fields such as porous materials, molecular machines, and chiral luminescence materials. However, the catalytic methodology towards the enantioselective synthesis of planar chiral pillar[5]arenes remains elusive. Here we report a novel method for the enantioselective synthesis of planar chiral pillar[5]arenes via asymmetric Sonogashira coupling, giving access to a wide range of highly functionalized planar chiral pillar[5]arenes, including both homo- and hetero-rimmed ones, with excellent enantioselectivities. Attractively, the resultant planar chiral pillar[5]arenes show great potential for widespread use in many areas such as chiral luminescent materials. This work not only enables the successful synthesis of planar chiral pillar[5]arenes with abundant structural and functional diversity as key building blocks for practical applications but also enriches the asymmetric cross-coupling methodologies in organic synthetic chemistry.

Microalgae treatment of food processing wastewater for simultaneous biomass resource recycling and water reuse.

Food processing wastewater presents a considerable challenge for treatment owing to its elevated nitrogen and phosphorus levels. Nonetheless, it possesses inherent value attributed to its abundant nutrients and organic content. This study presents an innovative approach for treating food processing wastewater and reusing biomass. Initially, the secondary-treated wastewater undergoes flocculation and sedimentation, followed by reverse osmosis to ensure that the effluent meets reuse standards. Subsequently, reverse osmosis concentrates, generated at varying water recovery rates, are utilized for microalgae cultivation to recover nitrogen and phosphorus. Furthermore, this study highlights the potential of reverse osmosis concentrates in reducing the water demand for microalgae cultivation and in producing commercial-grade nutrients. The findings reveal that reverse osmosis achieves removal rates exceeding 90 % for both nitrogen and phosphorus and effluent meets reuse standards. Following seven days of cultivation, microalgae cultured in reverse osmosis concentrated water with an 80 % water recovery rate demonstrate denitrification and phosphorus removal rates of 73.88 % and 80.92 % respectively, with a biomass concentration of 563 mg/L and a protein yield of 128 mg/L. Moreover, a total volumetric energy yield of 10.08 kJ/L is obtained, facilitating energy valorization. In conclusion, this study offers practical solutions for wastewater treatment and resource recovery, enabling the attainment of zero discharge of pollutants while generating valuable resources through microalgae cultivation.

Spatiotemporal variation of microplastics along the long-distance raw water pipeline.

Raw water pipelines are considered a significant pathway for human exposure to microplastics (MPs, <5 mm) in surface water. However, there is currently very limited information on the longitudinal distribution characteristics of microplastics in raw water pipelines. This study assessed the abundance and distribution characteristics of microplastics in surface water from two different water sources in Jiangsu Province during different seasons. The correlation between conventional water quality indicators and microplastics was also explored. Specifically, the longitudinal variation of microplastics in raw water pipelines was investigated. Results showed that microplastics were detected in both basins during different seasons. In Basin 1, the abundance of MPs ranged from 34 ± 1 to 58 ± 2 n/L in March and from 3 ± 1 to 6.7 ± 4 n/L in June. In Basin 2, the abundance ranged from 6.5 ± 1 to 14 ± 1 n/L in March and from 2 ± 1 to 7.7 ± 1 n/L in June. The abundance of microplastics showed a decreasing trend along the pipeline. Polymethyl methacrylate (PMMA) was the main polymer type detected in both basins. Polyethylene terephthalate (PE) and polyurethane (PU) showed higher removal rates in the pipeline due to their higher density. The predominant size ranges of microplastics in the raw water were 10-50 µm and 50-100 µm. Additionally, the average particle size of MPs increased with the transportation distance, likely due to microbial colonization. This study is the first comprehensive investigation of the distribution characteristics of microplastics in raw water pipeline systems. The removal of microplastics in raw water pipelines contributes significantly to the elimination of microplastics at the source. This research helps to fill the knowledge gap regarding the fate of microplastics in raw water pipeline systems.

Identification and experimental validation of programmed cell death- and mitochondria-associated biomarkers in osteoporosis and immune microenvironment.

Background: Prior research has demonstrated that programmed cell death (PCD) and mitochondria assume pivotal roles in controlling cellular metabolism and maintaining bone cell equilibrium. Nonetheless, the comprehensive elucidation of their mode of operation in osteoporosis (OP) warrants further investigation. Therefore, this study aimed at analyzing the role of genes associated with PCD (PCD-RGs) and mitochondria (mortality factor-related genes; MRGs) in OP. Methods: Differentially expressed genes (DEGs) were identified by subjecting the GSE56815 dataset obtained from the Gene Expression Omnibus database to differential expression analysis and comparing OP patients with healthy individuals. The genes of interest were ascertained through the intersection of DEGs, MRGs, and PCD-RGs; these genes were filtered using machine learning methodologies to discover potential biomarkers. The prospective biomarkers displaying uniform patterns and statistically meaningful variances were identified by evaluating their levels in the GSE56815 dataset and conducting quantitative real-time polymerase chain reaction-based assessments. Moreover, the functional mechanisms of these biomarkers were further delineated by constructing a nomogram, which conducted gene set enrichment analysis, explored immune infiltration, generated regulatory networks, predicted drug responses, and performed molecular docking analyses. Results: Eighteen candidate genes were documented contingent upon the intersection between 2,354 DEGs, 1,136 MRGs, and 1,548 PCD-RGs. The biomarkers DAP3, BIK, and ACAA2 were upregulated in OP and were linked to oxidative phosphorylation. Furthermore, the predictive ability of the nomogram designed based on the OP biomarkers exhibited a certain degree of accuracy. Correlation analysis revealed a strong positive correlation between CD56dim natural killer cells and ACAA2 and a significant negative correlation between central memory CD4+ T cells and DAP3. DAP3, BIK, and ACAA2 were regulated by multiple factors; specifically, SETDB1 and ZNF281 modulated ACAA2 and DAP3, whereas TP63 and TFAP2C governed DAP3 and BIK. Additionally, a stable binding force was observed between the drugs (estradiol, valproic acid, and CGP52608) and the biomarkers. Conclusion: This investigation evidenced that the biomarkers DAP3, BIK, and ACAA2 are associated with PCD and mitochondria in OP, potentially facilitate the diagnosis of OP in clinical settings.

Estimating the short-term effect of PM2.5 on the mortality of cardiovascular diseases based on instrumental variables.

BACKGROUND: PM2.5 can induce and aggravate the occurrence and development of cardiovascular diseases (CVDs). The objective of our study is to estimate the causal effect of PM2.5 on mortality rates associated with CVDs using the instrumental variables (IVs) method. METHODS: We extracted daily meteorological, PM2.5 and CVDs death data from 2016 to 2020 in Binzhou. Subsequently, we employed the general additive model (GAM), two-stage predictor substitution (2SPS), and control function (CFN) to analyze the association between PM2.5 and daily CVDs mortality. RESULTS: The 2SPS estimated the association between PM2.5 and daily CVDs mortality as 1.14% (95% CI: 1.04%, 1.14%) for every 10 µg/m3 increase in PM2.5. Meanwhile, the CFN estimated this association to be 1.05% (95% CI: 1.02%, 1.10%). The GAM estimated it as 0.85% (95% CI: 0.77%, 1.05%). PM2.5 also exhibited a statistically significant effect on the mortality rate of patients with ischaemic heart disease, myocardial infarction, or cerebrovascular accidents (P < 0.05). However, no significant association was observed between PM2.5 and hypertension. CONCLUSION: PM2.5 was significantly associated with daily CVDs deaths (excluding hypertension). The estimates from the IVs method were slightly higher than those from the GAM. Previous studies based on GAM may have underestimated the impact of PM2.5 on CVDs.

Predicting physical functioning status in older adults: insights from wrist accelerometer sensors and derived digital biomarkers of physical activity.

OBJECTIVE: Conventional physical activity (PA) metrics derived from wearable sensors may not capture the cumulative, transitions from sedentary to active, and multidimensional patterns of PA, limiting the ability to predict physical function impairment (PFI) in older adults. This study aims to identify unique temporal patterns and develop novel digital biomarkers from wrist accelerometer data for predicting PFI and its subtypes using explainable artificial intelligence techniques. MATERIALS AND METHODS: Wrist accelerometer streaming data from 747 participants in the National Health and Aging Trends Study (NHATS) were used to calculate 231 PA features through time-series analysis techniques-Tsfresh. Predictive models for PFI and its subtypes (walking, balance, and extremity strength) were developed using 6 machine learning (ML) algorithms with hyperparameter optimization. The SHapley Additive exPlanations method was employed to interpret the ML models and rank the importance of input features. RESULTS: Temporal analysis revealed peak PA differences between PFI and healthy controls from 9:00 to 11:00 am. The best-performing model (Gradient boosting Tree) achieved an area under the curve score of 85.93%, accuracy of 81.52%, sensitivity of 77.03%, and specificity of 87.50% when combining wrist accelerometer streaming data (WAPAS) features with demographic data. DISCUSSION: The novel digital biomarkers, including change quantiles, Fourier transform (FFT) coefficients, and Aggregated (AGG) Linear Trend, outperformed traditional PA metrics in predicting PFI. These findings highlight the importance of capturing the multidimensional nature of PA patterns for PFI. CONCLUSION: This study investigates the potential of wrist accelerometer digital biomarkers in predicting PFI and its subtypes in older adults. Integrated PFI monitoring systems with digital biomarkers would improve the current state of remote PFI surveillance.

Lysophosphatidic acid improves development of porcine somatic cell nuclear transfer embryos.

This study was conducted to investigate whether lysophosphatidic acid (LPA) could improve the development of porcine somatic cell nuclear transfer (SCNT) embryos. Porcine SCNT-derived embryos were cultured in chemically defined polyvinyl alcohol (PVA)-based porcine zygote medium (PZM)-4 without or with LPA, and the development, cell proliferation potential, apoptosis, and expression levels of pluripotent markers were evaluated. LPA significantly increased the rates of cleavage and blastocyst formation compared to those seen in the LPA un-treatment (control) group. The expression levels of embryonic development-related genes (IGF2R, PCNA and CDH1) were higher (p < 0.05) in the LPA treatment group than in the control group. LPA significantly increased the numbers of total, inner cell mass and EdU (5-ethynyl-2'-deoxyuridine)-positive cells in porcine SCNT blastocysts compared to those seen in the control group. TUNEL assay showed that LPA significantly reduced the apoptosis rate in porcine SCNT-derived embryos; this was confirmed by decreases (p < 0.05) in the expression levels of pro-apoptotic genes, BAX and CASP3, and an increase (p < 0.05) in the expression level of the anti-apoptotic gene, BCL2L1. In addition, LPA significantly increased Oct4 expression at the gene and protein levels. Together, our data suggest that LPA improves the quality and development of porcine SCNT-derived embryos by reducing apoptosis and enhancing cell proliferation and pluripotency.

Research progress of the Otubains subfamily in hepatocellular carcinoma.

In cancer research, oncogenesis can be affected by modulating the deubiquitination pathway. Ubiquitination regulates proteins post-translationally in variety of physiological processes. The Otubain Subfamily includes OTUB1 (ovarian tumor-associated proteinase B1) and OTUB2(ovarian tumor-associated proteinase B2). They are deubiquitinating enzymes, which are research hotspots in tumor immunotherapy, with their implications extending across the spectrum of tumor development. Understanding their important role in tumorigenesis, includ-ing hepatocellular carcinoma (HCC) is crucial. HCC has alarming global incidence rates and mortality statistics, ranking among the top five prevalent cancers in Malaysia1. Numerous studies have consistently indicated significant expression of OTUB1 and OTUB2 in HCC cells. In addition, OTUB1 has important biological functions in cancer, suggesting its important role in tumorigenesis. However, the mechanism underlying the action of OTUB1 and OTUB2 in liver cancer remains inadequately explored. Therefore, Otubain Subfamily, as potential molecular target, holds promise for advancing HCC treatments. However, further clinical studies are required to verify its efficacy and application prospects.

Protocol for measuring the effects of an inhibitory signal associated with danger on honey bee dopamine levels.

The stop signal is produced in response to negative experiences at the food source and inhibits honey bee (Apis mellifera) waggle dancing. Here, we present a protocol for measuring the effects of an inhibitory signal associated with danger on honey bee dopamine levels. We describe steps for observing honey bee colonies, training them with artificial nectar, and simulating hornet attacks. We then detail procedures for recording waggle dancing and stop signals and measuring brain dopamine levels during different treatments. For complete details on the use and execution of this protocol, please refer to Dong et al.1.

Metal implant segmentation in CT images based on diffusion model.

BACKGROUND: Computed tomography (CT) is widely in clinics and is affected by metal implants. Metal segmentation is crucial for metal artifact correction, and the common threshold method often fails to accurately segment metals. PURPOSE: This study aims to segment metal implants in CT images using a diffusion model and further validate it with clinical artifact images and phantom images of known size. METHODS: A retrospective study was conducted on 100 patients who received radiation therapy without metal artifacts, and simulated artifact data were generated using publicly available mask data. The study utilized 11,280 slices for training and verification, and 2,820 slices for testing. Metal mask segmentation was performed using DiffSeg, a diffusion model incorporating conditional dynamic coding and a global frequency parser (GFParser). Conditional dynamic coding fuses the current segmentation mask and prior images at multiple scales, while GFParser helps eliminate high-frequency noise in the mask. Clinical artifact images and phantom images are also used for model validation. RESULTS: Compared with the ground truth, the accuracy of DiffSeg for metal segmentation of simulated data was 97.89% and that of DSC was 95.45%. The mask shape obtained by threshold segmentation covered the ground truth and DSCs were 82.92% and 84.19% for threshold segmentation based on 2500 HU and 3000 HU. Evaluation metrics and visualization results show that DiffSeg performs better than other classical deep learning networks, especially for clinical CT, artifact data, and phantom data. CONCLUSION: DiffSeg efficiently and robustly segments metal masks in artifact data with conditional dynamic coding and GFParser. Future work will involve embedding the metal segmentation model in metal artifact reduction to improve the reduction effect.

Feasibility of simultaneous optimization of Anammox start-up and nitrogen removal performance by intermittent dosing of nanoscale zero-valent iron.

The long acclimation period and sensitivity to environmental conditions of Anammox are the bottlenecks for its promotion and application. An innovative strategy was adopted to accelerate functional microbial enhancement and improve nitrogen removal performance by inoculating cryopreserved Anammox sludge and activated sludge with intermittent dosing of nanoscale zero-valent iron (nZVI). The acclimation time was shortened by 76 days with nitrogen removal efficiency (NRE) reaching up to 91.07 %. Anammox, NDFO (nitrate/nitrite-dependent Fe(II) oxidation), Feammox (Fe(III) reduction coupled with anaerobic ammonium oxidation) and abiotic reactions were coupled in the system with nZVI, contributing to 69.79 %, 15.14 %, 9.84 % and 0.25 % of nitrogen removal, respectively. Further microbial analysis demonstrated significant enrichment of functional microorganisms, such as Candidatus Jettenia, Acidovorax and Comamonas. High-efficient nitrogen removal was attribute to the increase of functional genes involved in Anammox, electronic transfer, heme C synthesis and iron metabolism. This work provides an inspiring idea for the mainstream Anammox application.

Bamboo fiber improves piglet growth performance by regulating the microbial composition of lactating sows and their offspring piglets.

Introduction: Feeding bamboo powder is a kind of fiber raw material mainly composed of insoluble dietary fiber (IDF). In this study, IDF-based rice husk meal and feeding bamboo powder were used to compare the effects of bamboo fiber on fecal microflora and the performance of lactating sows and their offspring piglets. Methods: Thirty healthy crossbred gilts (Yorkshire × Landrace) at day 105 of gestation were randomly allocated into three groups: CON, TRE1 supplemented with 2% BBF1 (feeding bamboo powder), and TRE2 supplemented with 2% BBF2 (99% feeding bamboo powder +1% bamboo fiber polymer material). The reproductive performance, serum indexes, and fecal microbiota of sows and piglets were analyzed. The results showed that, compared with CON, the average feed intake of sows in TRE1 during the second week of lactation was significantly increased by 21.96% (p < 0.05), the average daily gain (ADG) per litter in TRE1 on 11-21 days and 3-21 days of lactation was significantly increased by 50.68 and 31.61%, respectively (p < 0.05), and the serum triglyceride content of sows in TRE1 on the 21st day of lactation was significantly increased (p < 0.05). The 16S rRNA analysis showed that dietary bamboo fiber significantly increased the fecal microbial richness index Ace, Chao, and Sobs of sows (p < 0.05) and tended to increase the Sobs index of suckling piglets on day 21 (p < 0.10). Compared with CON, BBF1 supplementation significantly decreased the abundance of Christensenellaceae_R-7_group in feces of sows on days 7 and 21 after delivery (p < 0.05), while BBF2 decreased the genera Christensenellaceae_R-7_group on days 7 (p < 0.10) and 21 (p < 0.05) after delivery. Spearman correlation analysis showed that the abundance of Phascolarctobacterium in the feces of piglets on the 21st day after delivery was significantly positively correlated with diarrhea rate and significantly negatively correlated with ADG per litter, day 21 litter weight, and 3- to 21-day survival rate. In contrast, Christensenellaceae_R-7_group was significantly negatively correlated with diarrhea rate and positively correlated with ADG per litter. Discussion: These results indicated that maternal BBF1 supplementation improved the litter weight gain of suckling piglets, which was associated with the improvement of diversity and structure of the fecal microbiota in the piglets.

UBXN3B is crucial for B lymphopoiesis.

BACKGROUND: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. METHODS: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. FINDINGS: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. INTERPRETATION: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. FUNDING: United States National Institutes of Health grants, R01AI132526 and R21AI155820.

Copper-Catalyzed Dual Remote Asymmetric Vinylogous Alkynylallylic Substitution of Yne-Allylic Esters with Coumarins.

Chiral coumarins and their derivatives are ubiquitous structural motifs found in an array of biologically and therapeutically active natural products and drugs. Herein, a highly enantioselective dual remote copper-catalyzed vinylogous alkynylallylic substitution of yne-allylic esters with coumarins has been developed. The practicality of this method is exemplified by the use of readily available starting materials; mild reaction conditions; excellent regio-, enantio-, and stereoselectivities; and the very broad substrate scope (67 examples), while the scalability and further applications of this method are illustrated by the gram-scale reaction and the series of derivations of the products.

DNA Origami Enhanced Cytokine Immunotherapy for Alleviating Renal Ischemia-Reperfusion Injury.

Renal ischemia-reperfusion injury (IRI) is a major contributing factor to the development of acute kidney injury (AKI) and has resulted in considerable morbidity and mortality. Persistent inflammatory responses and excessive reactive oxygen species (ROS) in the kidney following IRI can severely delay tissue repair, making it challenging to effectively promote IRI regeneration. Herein, we report an approach to enhance immunotherapy using interleukin-10 (IL-10) to promote IRI regeneration by loading IL-10 onto rectangular DNA origami nanostructures (rDON). rDON can significantly enhance the renal accumulation and retention time of IL-10, enabling it to effectively polarize type 1 macrophages into type 2 macrophages, thereby significantly reducing proinflammatory factors and increasing anti-inflammatory factors. In addition, DNA origami helps mitigate the harmful effects of ROS during renal IRI. The administration of IL-10-loaded DNA origami effectively improves kidney function, resulting in a notable reduction in blood urea nitrogen, serum uric acid, and serum creatinine levels. Our study demonstrates that the integration of anti-inflammatory cytokines within DNA origami holds promise as a strategic approach for cytokine immunotherapy in patients with AKI and other renal disorders.

Joint Exfoliation of MXene by Dimensional Mismatched SiC/ZIF-67 Toward Multifunctional Flame Retardant Thermoplastic Polyurethane.

The single-layer MXene fully demonstrates the advantages of 2D materials, especially catalytic, conductive, and mechanical properties. However, the high energy consumption and low efficiency faced by MXene in the divestiture process are still challenges that need to be solved urgently. In this article, dimension mismatch and collaborative stripping strategies are skillfully combined to easily realize the transformation from multi-layer MXene to single layer. In addition, the functionalized MXene@SiC@polyaniline (MXene@SiC@PANI) nano-hybrid materials are used as fillers to improve the thermal conductivity, flame retardant, and antibacterial properties of thermoplastic polyurethane (TPU). The surface temperature of TPU/MXene@SiC@PANI composites increased from 33.4 °C to 59.8 °C within 10 s. In addition, the antibacterial efficiency of TPU composites against Escherichia coli and Staphylococcus aureus is 69.6% and 88.9%, respectively. Compared with pure TPU, the peak heat release rate and total heat release are reduced by 71.4% and 34.6%, respectively. The flame-retardant mechanism of MXene hybrid materials is systematically discussed. It is worth noting that the introduction of PANI enhances the compatibility between the filler and the polymer, effectively maintaining the mechanical properties of the TPU itself. This work provides a convenient method for the multi-functional practical application of TPU.