Synergistic Etching and Hydrogen Bonding-Induced Self-Assembly of MXene/MOF Hybrid Aerogel for Flexible Room-Temperature Gas Sensing.

Limited by insufficient active sites and restricted mechanical strength, designing reliable and wearable gas sensors with high activity and ductility remains a challenge for detecting hazardous gases. In this work, a thermally induced and solvent-assisted oxyanion etching strategy was implemented for selective pore opening in a rigid microporous Cu-based metal-organic framework (referred to as CuM). A conductive CuM/MXene aerogel was then self-assembled through cooperative hydrogen bonding interactions between the carbonyl oxygen atom in PVP grafted on the surface of defect-rich Cu-BTC and the surface functional hydroxyl group on MXene. A flexible NO2 sensing performance using the CuM/MXene aerogel hybridized sodium alginate hydrogel is finally achieved, demonstrating extraordinary sensitivity (S = 52.47 toward 50 ppm of NO2), good selectivity, and rapid response/recovery time (0.9/4.5 s) at room temperature. Compared with commercial sensors, the relative error is less than 7.7%, thereby exhibiting significant potential for application in monitoring toxic and harmful gases. This work not only provides insights for guiding rational synthesis of ideal structure models from MOF composites but also inspires the development of high-performance flexible gas sensors for potential multiscenario applications.

Selection criteria and method for deep inspiration breath-hold in patients with left breast cancer undergoing PMRT/IMRT.

Purpose: This study explored whether a free-breathing mean heart dose (FB-MHD) of 4 Gy is a reliable dose threshold for selecting left breast cancer patients after modified radical mastectomy suitable for deep inspiration breath-hold (DIBH) and developed anatomical indicators to predict FB-MHD for rapid selection. Materials and methods: Twenty-three patients with left breast cancer treated with DIBH were included to compare FB and DIBH plans. The patients were divided into the high-risk (FB-MHD ≥ 4 Gy) and low-risk (FB-MHD < 4 Gy) groups to compare dose difference, normal tissue complication probability (NTCP) and the DIBH benefits. Another 30 patients with FB only were included to analyze the capacity of distinguishing high-risk heart doses patients according to anatomical metrics, such as cardiac-to-chest Euclidean distance (CCED), cardiac-to-chest gap (CCG), and cardiac-to-chest combination (CCC). Results: All heart doses were significantly lower in patients with DIBH plans than in those with FB plans. Based on FB-MHD of 4 Gy cutoff, the heart dose, NTCP for cardiac death, and benefits from DIBH were significantly higher in the high-risk group than in the low-risk group. The CCED was a valid anatomical indicator with the largest area under the curve (AUC) of 0.83 and maintained 95 % sensitivity and 70 % specificity at the optimal cutoff value of 2.5 mm. Conclusions: An FB-MHD of 4 Gy could be used as an efficient dose threshold for selecting patients suitable for DIBH. The CCED may allow a reliable prediction of FB-MHD in left breast cancer patients at CT simulation.

ESRRA modulation by empagliflozin mitigates diabetic tubular injury via mitochondrial restoration.

BACKGROUND: The protection of the diabetic kidney by Empagliflozin (EMPA) is attributed to its interaction with the sodium glucose cotransporter 2 located on proximal tubular epithelial cells (PTECs). Estrogen-related receptor α (ESRRA), known for its high expression in PTECs and association with mitochondrial biogenesis, plays a crucial role in this process. This study aimed to explore the impact of ESRRA on mitochondrial mass in diabetic tubular injury and elucidate the mechanism underlying the protective effects of EMPA. METHODS: Mitochondrial changes in PTECs of 16-week-old diabetic mice were assessed using transmission electron microscopy (TEM) and RNA-sequences. In vivo, EMPA administration was carried out in db/db mice for 8 weeks, while in vitro experiments involved modifying ESRRA expression in HK2 cells using pcDNA-ESRRA or EMPA. RESULTS: Evaluation through TEM revealed reduced mitochondrial mass and swollen mitochondria in PTECs, whereas no significant changes were observed under light microscopy. Analysis of RNA-sequences identified 110 downregulated genes, including Esrra, associated with mitochondrial function. Notably, ESRRA overexpression rescued the loss of mitochondrial mass induced by high glucose (HG) in HK2 cells. EMPA treatment ameliorated the ultrastructural alterations and mitigated the downregulation of ESRRA both in db/db mice and HG-treated HK2 cells. CONCLUSION: The diminished expression of ESRRA is implicated in the decline of mitochondrial mass in PTECs during the early stages of diabetes, highlighting it as a key target of EMPA for preventing the progression of diabetic kidney injury.

The inter-related effects of alcohol use severity and sleep deficiency on semantic processing in young adults.

BACKGROUND: Both alcohol misuse and sleep deficiency are associated with deficits in semantic processing. However, alcohol misuse and sleep deficiency are frequently comorbid and their inter-related effects on semantic processing as well as the underlying neural mechanisms remain to be investigated. METHODS: We curated the Human Connectome Project data of 973 young adults (508 women) to examine the neural correlates of semantic processing in link with the severity of alcohol use and sleep deficiency. The latter were each evaluated using the first principal component (PC1) of principal component analysis of all drinking metrics and the Pittsburgh Sleep Quality Index (PSQI). We employed path modeling to elucidate the interplay among clinical, behavioral, and neural variables. RESULTS: Among women, we observed a significant negative correlation between the left precentral gyrus (PCG) and PSQI scores. Mediation analysis revealed that the left PCG activity fully mediated the relationship between PSQI scores and word comprehension in language tasks. In women alone also, the right middle frontal gyrus (MFG) exhibited a significant negative correlation with PC1. The best path model illustrated the associations among PC1, PSQI scores, PCG activity, and MFG activation during semantic processing in women. CONCLUSIONS: Alcohol misuse may lead to reduced MFG activation while sleep deficiency hinder semantic processing by suppressing PCG activity in women. The pathway model underscores the influence of sleep quality and alcohol consumption severity on semantic processing in women, suggesting that sex differences in these effects need to be further investigated.

Sex differences in dorsolateral prefrontal cortical and superior colliculus activities support the impact of alcohol use severity and sleep deficiency on two-back memory.

Background: Working memory refers to a process of temporary storage and manipulation of information to support planning, decision-making, and action. Frequently comorbid alcohol misuse and sleep deficiency have both been associated with working memory deficits. However, how alcohol misuse and sleep deficiency interact to impact working memory remains unclear. In this study, we aim to investigate the neural processes inter-relating alcohol misuse, sleep deficiency and working memory. Methods: We curated the Human Connectome Project (HCP) dataset and investigated the neural correlation of working memory in link with alcohol use severity and sleep deficiency in 991 young adults (521 women). The two were indexed by the first principal component (PC1) of principal component analysis of all drinking metrics and Pittsburgh Sleep Quality Index (PSQI) score, respectively. We processed the imaging data with published routines and evaluated the results with a corrected threshold. We used path model to characterize the inter-relationship between the clinical, behavioral, and neural measures, and explored sex differences in the findings. Results: In whole-brain regression, we identified ß estimates of dorsolateral prefrontal cortex response (DLPFC ß) to 2- vs. 0-back in correlation with PC1. The DLPFC showed higher activation in positive correlation with PC1 across men and women (r=0.16, P<0.001). Path analyses showed the model PC1 → DLPFC ß â†’ differences in reaction time (2- minus 0-back; RT2-0) of correct trials → differences in critical success index (2- minus 0-back; CSI2-0) with the best fit. In women alone, in addition to the DLPFC, a cluster in the superior colliculus (SC) showed a significant negative correlation with the PSQI score (r=-0.23, P<0.001), and the path model showed the inter-relationship of PC1, PSQI score, DLPFC and SC ß's, and CSI2-0 in women. Conclusions: Alcohol misuse may involve higher DLPFC activation in functional compensation, whereas, in women only, sleep deficiency affects 2-back memory by depressing SC activity. In women only, path model suggests inter-related impact of drinking severity and sleep deficiency on 2-back memory. These findings suggest potential sex differences in the impact of drinking and sleep problems on working memory that need to be further investigated.

Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1H-benzo[d]imidazole (A25) exhibited optimal antifungal activity against Sclerotinia sclerotiorum (S. s.), affording an excellent half-maximal effective concentration (EC50) of 0.158 µg/mL, which was higher than that of the reference agent carbendazim (EC50 = 0.594 µg/mL). Pot experiments revealed that compound A25 (200 µg/mL) had acceptable protective activity (84.7%) and curative activity (78.1%), which were comparable with that of carbendazim (protective activity: 90.8%; curative activity: 69.9%). Molecular docking displayed that multiple hydrogen bonds and π-π interactions could be formed between A25 and ß-tubulin, resulting in a stronger bonding effect than carbendazim. Fluorescence imaging revealed that the structure of intracellular microtubules can be changed significantly after A25 treatment. Overall, these remarkable antifungal profiles of constructed novel benzimidazole derivatives could facilitate the application of novel microtubule-targeting agents.

Deletion of Bmal1 in aggrecan-expressing cells leads to mouse temporomandibular joint osteoarthritis.

INTRODUCTION: Articular cartilage is the major affected tissue during the development of osteoarthritis (OA) in temporomandibular joint (TMJ). The core circadian rhythm molecule Bmal1 regulates chondrocyte proliferation, differentiation and apoptosis; however, its roles in condylar cartilage function and in TMJ OA have not been fully elucidated. MATERIALS AND METHODS: TMJ OA mouse model was induced by unilateral anterior crossbite (UAC) and Bmal1 protein expression in condylar cartilage were examined by western blot analysis. To determine the role of Bmal1 in TMJ OA, we generated cartilage-specific Bmal1 conditional knockout (cKO) mice (Bmal1Agc1CreER mice) and hematoxylin and eosin staining, toluidine blue and Safranin O/fast green, immunohistochemistry, TUNEL assay, real-time PCR analysis and Western blot assay were followed. RESULTS: Bmal1 expression was reduced in condylar cartilage in a TMJ OA mouse model induced by UAC. The Bmal1 cKO mice displayed decreased cartilage matrix synthesis, reduced chondrocyte proliferation, increased chondrocyte hypertrophy and apoptosis as well as the upregulation of YAP expression in TMJ condylar cartilage. CONCLUSIONS: We demonstrated that Bmal1 was essential for TMJ tissue homeostasis and loss-of-function of Bmal1 in chondrocytes leads to the development of TMJ OA.

Cohort profile: migraine exposures and cardiovascular health in Hong Kong Chinese women (MECH-HK).

PURPOSE: Evidence about the associations of migraine features with cardiovascular risk profiles in Chinese population is lacking. The Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK) cohort was constructed to investigate longitudinal migraine features and their cardiovascular implications in Hong Kong Chinese women. PARTICIPANTS: We enrolled 4221 Hong Kong Chinese women aged 30 years or above from October 2019 to December 2020. Demographics, reproductive information, lifestyle factors, disease history, blood lipids and glucose, anthropometrics and body compositions were measured during baseline and follow-up. Migraine diagnosis followed the International Classification of Headache Disorders-3 criteria. Migraine features were longitudinally tracked using a migraine diary and summarised by a wide range of epidemiological metrics. Cardiovascular health was assessed using the Framingham risk score (FRS). FINDINGS TO DATE: From October 2021 to June 2023, 3455 women completed the first follow-up measurement. The retention rate was 81.9%. The average age at baseline was 54.40 years. The mean blood glucose, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were 6.44 mmol/L, 65.06 mg/dL and 102.40 mg/dL, respectively. The average FRS was 0.06. Participants had a 10.3% prevalence of migraine or probable migraine. After 1.27 years of follow-up, the median migraine attack frequency was 0.99 attacks/month, with an incidence rate of 2.55 attacks/person-month and a median duration of 7.70 hours/attack. Sleep problems (64.7%) and stress (54.0%) were the top triggers, while prevalent accompanying symptoms were nausea (67.4%), photophobia (39.9%), phonophobia (30.0%) and vomiting (26.2%). Migraine auras included blurred visions (59.6%), flashing lights (41.3%), blind spots (33.0%), pins and needles (6.4%) and halo (1.8%). FUTURE PLANS: The follow-up for the cohort will be implemented every 2 years. MECH-HK will provide unique longitudinal data on migraine features in Hong Kong women. The linkage between migraine features and cardiovascular disease risk progression will be identified by a long-term observation.

Mapping global prevalence of menopausal symptoms among middle-aged women: a systematic review and meta-analysis.

BACKGROUND: Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. METHODS: Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. RESULTS: A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51-68.29) and lowest of formication (20.5%, 95% CI 13.44-28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems. CONCLUSION: The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.

Neutralizing Antibody Sample Testing and Report Harmonization.

Immunogenicity testing and characterization is an important part of understanding the immune response to administration of a protein therapeutic. Neutralizing antibody (NAb) assays are used to characterize a positive anti-drug antibody (ADA) response. Harmonization of reporting of NAb assay performance and results enables efficient communication and expedient review by industry and health authorities. Herein, a cross-industry group of NAb assay experts have harmonized NAb assay reporting recommendations and provided a bioanalytical report (BAR) submission editable template developed to facilitate agency filings. This document addresses key bioanalytical reporting gaps and provides a report structure for documenting clinical NAb assay performance and results. This publication focuses on the content and presentation of the NAb sample analysis report including essential elements such as the method, critical reagents and equipment, data analysis, study samples, and results. The interpretation of immunogenicity data, including the evaluation of the impact of NAb on safety, exposure, and efficacy, is out of scope of this publication.

Compressed intracellular motility via non-uniform temporal sampling in dynamic optical coherence tomography.

Significance: Optical coherence tomography has great utility for capturing dynamic processes, but such applications are particularly data-intensive. Samples such as biological tissues exhibit temporal features at varying time scales, which makes data reduction challenging. Aim: We propose a method for capturing short- and long-term correlations of a sample in a compressed way using non-uniform temporal sampling to reduce scan time and memory overhead. Approach: The proposed method separates the relative contributions of white noise, fluctuating features, and stationary features. The method is demonstrated on mammary epithelial cell spheroids in three-dimensional culture for capturing intracellular motility without loss of signal integrity. Results: Results show that the spatial patterns of motility are preserved and that hypothesis tests of spheroids treated with blebbistatin, a motor protein inhibitor, are unchanged with up to eightfold compression. Conclusions: The ability to measure short- and long-term correlations compressively will enable new applications in (3+1)D imaging and high-throughput screening.

Chemical constituent characterization and determination of Quisqualis fructus based on UPLC-Q-TOF-MS and HPLC combined with fingerprint and chemometric analysis.

Quisqualis fructus (QF) is a traditional Chinese medicine (TCM) that it has a long history in the therapeutic field of killing parasites, eliminating accumulation, and stopping diarrhea. However, the therapeutic material basis of QF is remaining ambiguous nowadays. The geographical origin differences of QF are also usually ignored in the process of medication. In this study, the alcohol-aqueous soluble constituents in QF from different origins were systematically characterized and accurately measured by ultra-high performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and high-performance liquid chromatography (HPLC) respectively. Chemometric analysis was performed for origin differentiation and screening of potential quality marker (Q-marker). Finally, A total of 106 constituents were tentatively characterized in positive and negative ion modes, including 29 fatty acids, 26 organic acids, 11 amino acids and derivatives, 10 glycosides, 9 alkaloids and derivatives, and 21 other constituents. QF from different origins were effectively distinguished and 16 constituents were selected as the potential Q-markers subsequently. Four representative components (trigonelline, adenosine, ellagic acid, and 3,3'-di-O-methylellagic acid) in QF samples were simultaneously determined. HPLC fingerprint analysis indicated that the similarity between 16 batches of QF was in the range of 0.870-0.999. The above results provide some insights for the research on the pharmacodynamic constituents, quality control, and geographical discrimination of QF.

Neutrophil-secreted S100A8/A9 participates in fatty liver injury and fibrosis by promoting myofibroblast migration.

Fatty liver, which is induced by abnormal lipid metabolism, is one of the most common causes of chronic liver disease globally and causes liver fibrosis. During this process, bone marrow-derived mesenchymal stromal cells (BMSCs) and hepatic stellate cells (HSCs) migrate toward the injured liver and participate in fibrogenesis by transdifferentiating into myofibroblasts. S100A8/A9 is a powerful inducer of cell migration and is involved in liver injury. But there are few reports about the effects of S100A8/A9 on BMSC/HSC migration. In the current study, we found that S100A8/A9 expression was increased during fatty liver injury/fibrogenesis. Moreover, S100A8/A9 expression had a positive correlation with fibrosis marker gene expressions in the injured liver. S100A8/A9 was mainly produced by neutrophils in the fibrotic liver. In vitro, neutrophil-secreted S100A8/A9 promoted BMSC/HSC migration via remodeling of microfilaments. Using specific siRNA and inhibitor, we proved that S100A8/A9-induced BMSC/HSC migration is dependent on TLR4/Rho GTPases signaling. Moreover, S100A8/A9 knock-down alleviated liver injury and fibrogenesis in vivo, while injection of S100A9 neutralizing antibody performed similar roles. We proved that S100A8/A9 was involved in liver injury and fibrogenesis via inducing BMSC/HSC migration. Our research reveals a new mechanism underlying BMSC/HSC migration in liver fibrosis and suggests S100A8/A9 as a potential therapeutic target of liver fibrosis. KEY MESSAGES: S100A8/A9 is secreted by neutrophils and increased in fatty liver injury. Neutrophil-secreted S100A8/A9 is a mediator of BMSC/HSC migration in vitro. S100A8/A9-induced BMSC/HSC migration is dependent on TLR4/Rho GTPases signaling. S100A8/A9 blockade alleviates liver injury and fibrogenesis in vivo.

Bovine colostrum prevents formula-induced gut microbiota dysbiosis in preterm pigs.

BACKGROUND: Preterm birth and formula feeding increase the risk of necrotizing enterocolitis (NEC), a gut inflammatory disease known to be associated with gut microbiota (GM) changes in infants. Supplemental bovine colostrum may protect against formula-induced NEC via GM changes. We hypothesised that feeding colostrum before, after, or during formula feeding affects NEC sensitivity via changes to GM. METHODS: Colonic GM (profiled by 16S ribosomal RNA gene amplicon sequencing) was compared in preterm pigs fed colostrum for 4 days, either before, after, or together with formula feeding for 4 days. Correlations between GM and gut parameters were assessed on day 5 or 9. RESULTS: Both exclusive and partial colostrum feeding induced higher GM diversity, lower Enterococcus abundance, and improved intestinal maturation parameters (villus structure, digestive enzyme activities, permeability), relative to exclusive formula feeding (all p < 0.05). Across feeding regimens, Enterococcus abundance was inversely correlated with intestinal maturation parameters. Conversely, there was no correlation between GM changes and early NEC lesions. CONCLUSION: Bovine colostrum inhibits formula-induced Enterococcus overgrowth and gut dysfunctions just after preterm birth but these effects are not causally linked. Optimising diet-related host responses, not GM, may be critical to prevent NEC in preterm newborn pigs and infants. IMPACT: Supplement of bovine colostrum to formula feeding modified the gut microbiota by increasing species diversity and reducing Enterococcus abundance, while concurrently improving intestinal functions in preterm pigs. Diet-related changes to the gut microbiota were not clearly associated with development of necrotizing enterocolitis (NEC) in preterm pigs, suggesting that diet-related gut microbiota effects are not critical for diet-related NEC protection. The study highlights the potential to use bovine colostrum as a supplement to formula feeding for preterm infants lacking human milk.

Benchmarking PathCLIP for Pathology Image Analysis.

Accurate image classification and retrieval are of importance for clinical diagnosis and treatment decision-making. The recent contrastive language-image pre-training (CLIP) model has shown remarkable proficiency in understanding natural images. Drawing inspiration from CLIP, pathology-dedicated CLIP (PathCLIP) has been developed, utilizing over 200,000 image and text pairs in training. While the performance the PathCLIP is impressive, its robustness under a wide range of image corruptions remains unknown. Therefore, we conduct an extensive evaluation to analyze the performance of PathCLIP on various corrupted images from the datasets of osteosarcoma and WSSS4LUAD. In our experiments, we introduce eleven corruption types including brightness, contrast, defocus, resolution, saturation, hue, markup, deformation, incompleteness, rotation, and flipping at various settings. Through experiments, we find that PathCLIP surpasses OpenAI-CLIP and the pathology language-image pre-training (PLIP) model in zero-shot classification. It is relatively robust to image corruptions including contrast, saturation, incompleteness, and orientation factors. Among the eleven corruptions, hue, markup, deformation, defocus, and resolution can cause relatively severe performance fluctuation of the PathCLIP. This indicates that ensuring the quality of images is crucial before conducting a clinical test. Additionally, we assess the robustness of PathCLIP in the task of image-to-image retrieval, revealing that PathCLIP performs less effectively than PLIP on osteosarcoma but performs better on WSSS4LUAD under diverse corruptions. Overall, PathCLIP presents impressive zero-shot classification and retrieval performance for pathology images, but appropriate care needs to be taken when using it.

[Effects of Straw and Fertilizer Managements on Nitrogen Loss in Rice Cultivation in Taihu Lake Basin].

Nitrogen loss from rice systems is an important source of agricultural non-point source pollution. Many studies revolve around reducing the rate of nitrogen fertilizer application. However, studies examining the characteristics of nitrogen loss in multiple loss paths （runoff, leaching, and lateral seepage） under different straw and fertilizer managements are lacking. Therefore, a study was carried out based on a rice field planted for more than 20 years with straw continuously returned to the field for more than 5 years in Taihu lake basin. The effects of straw and fertilizer managements on nitrogen loss in different paths during the whole growth period of rice were studied. Moreover, straw and fertilizer managements were evaluated by their production suitability and environmental friendliness based on crop yield, nitrogen use efficiency, and nitrogen loss. The results showed that straw removal from the field increased the response sensitivity of nitrogen accumulation in plant tissue to nitrogen application. The nitrogen loss in the rice season was 9-17 kg·hm-2, accounting for 5%-7% of the nitrogen application rate. Straw removal increased the risk of nitrogen loss when soaking water discharged. Straw returning could decrease the nitrogen loss by more than 15%, though the effect of straw on nitrogen loss via lateral seepage was not clear. Furthermore, the suitable substitution of organic fertilizer （30% in this study） could respectively reduce the amount of nitrogen loss via runoff, leaching, and lateral seepage by 16%, 26%, and 37% compared with the fertilizer application under the same nitrogen gradient. In conclusion, the implementation of straw returning and fertilizer type optimization measures effectively reduced the nitrogen loss for unit weight of rice production and realized the balance between agricultural production and environmental protection.

Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection.

Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.

Medcheck: a novel software for automated de-formulation of traditional Chinese medicine (TCM) prescriptions by liquid chromatography-mass spectrometry.

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