Short- and long-term effects of different forage types supplemented in preweaning dairy calves on performance and milk production into first lactation.

We investigated the short- and long-term effects of different forage types supplemented in preweaning dairy calves on growth performance, blood metabolites, rumen fermentation, bacterial community, and milk production during first lactation. Sixty healthy 1-mo-old female Holstein calves were blocked by birth date and body weight and randomly assigned to one of 3 groups (n = 20): normal milk and pelleted starter feeding (CON), supplemented with chopped oat hay [75.0 g/d/calf (dry matter (DM) basis); OAH], or alfalfa hay [75.0 g/d/calf (DM basis); ALF]. The forage supplementation started when calves were 30 d old (D1 of the experimental period) and ended when they were 73 d old (D44 of the experimental period when calves were weaned. Milk and feed intakes and fecal consistency scores were recorded daily. Growth performance, rumen fluid, and blood samples were collected bi-weekly. After weaning, all the calves were integrated with the same barn and diets. After calving, the milk production was recorded daily. During the experimental period, the OAH group had greater solid feed and total DM intakes and greater rumen pH than the CON group (P ≤ 0.04), but had lower forage intake and crude protein digestibility than the ALF group (P ≤ 0.04). The ALF group had higher rumen pH and blood ß-hydroxybutyrate concentration (P ≤ 0.04), lower fecal score (P = 0.02), and greater ether extract digestibility (P = 0.02) than the CON group. The ALF and OAH groups had lower concentrations of ruminal total volatile fatty acids (P = 0.01). Still, the ALF group had a greater proportion of acetate and a relative abundance of cellulose degradation-related bacteria (Lachnoclostridium_1 and Oribacterium) and a lower relative abundance of inflammation-related bacteria (Erysipelotrichaceae_UCG-009) in the rumen compared with CON. Interestingly, the average milk production from 6 to 200 d in milk (DIM) was greater in the ALF group (P < 0.01) even though no significant effects were found on the rumen fermentation parameters and blood metabolites at 200 DIM. Generally, alfalfa hay supplementation in preweaning dairy calves had positive effects in the short- and long-term in terms of rumen development, health status, and future milk production.

Joint effect of abnormal systemic immune-inflammation index (SII) levels and diabetes on cognitive function and survival rate: A population-based study from the NHANES 2011-2014.

OBJECTIVE: The purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011-2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted. RESULTS: The RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (ß:-0.76, P<0.05) and Digit Symbol Substitution tests (ß:-5.02, P<0.05). Nevertheless, these results showed marginal significance in Total Word Recall test as well as Animal Fluency test. Among all subgroup analyses performed, participants with both abnormal SII levels and diabetes exhibited the greatest decline in cognitive function compared to those with only diabetes. Furthermore, KM curve demonstrated that the combination of abnormal SII levels and diabetes decreased survival rate among participants. CONCLUSION: The findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power.

Overexpression of PTPN21 promotes proliferation of EGF-stimulated acute lymphoblastic leukemia cells via the MAPK signaling pathways.

OBJECTIVES: This study aims to investigate the role of excessive Protein Tyrosine Phosphatase Non-Receptor Type 21 (PTPN21) in the proliferation of Acute Lymphoblastic Leukemia (ALL) cells with EGF stimulation. METHODS: PTPN21 was overexpressed in ALL cell lines by lentiviral transfection. Apoptosis was assayed by Annexin V/7-AAD staining. The proliferation and cell cycle of EGF-treated ALL cells were assessed by MTT and Ki-67/7-AAD staining respectively. The phosphorylation of Src tyrosine kinase and mediators of distinct MAPK pathways were assessed by Western blot. RESULTS: Overexpression of PTPN21 had minimal effect on the apoptosis of ALL cells, but significantly promoted the proliferation and cell cycle progression of ALL cells stimulated with EGF. The activity of Src tyrosine kinase and the MAPK pathways was elevated. Inhibition of MAPK pathways by specific inhibitors mitigated this pro-proliferative effect of excessive PTPN21 on EGF-stimulated ALL cells. CONCLUSION: PTPN21 may facilitate ALL progression by promoting cell proliferation via the Src/MAPK signaling pathways.

Characteristics of Right-Sided Accessory Pathways Associated With Right Cardiac Veins.

BACKGROUND: The anatomy of myocardial fibers around the right cardiac veins (RCVs) and their roles in accessory pathways (APs) are rarely reported. METHODS: Six RCV-APs were identified from 566 patients with right-sided APs. Mapping of retrograde atrial activation was performed using CARTO 3 system under orthodromic tachycardia or right ventricular pacing. Venography of RCVs was acquired at the earliest retrograde atrial activation. RESULTS: Patients enrolled had a median age of 30 (11-51) years, 5 of them were male. Venography of RCVs could be classified into 3 distinct patterns based on the identified ventricular branches, right marginal vein only (type I; n=3), both right marginal vein and anterior cardiac veins (type II; n=2), and anterior cardiac vein only (type III; n=1). Patients with type I venography had rS QRS pattern in lead V1, negative delta wave in lead III and negative or isoelectric delta wave in lead aVF. However, patients with type II and III venography had QS QRS patterns in lead V1 and variable patterns of delta wave in inferior leads. Earliest retrograde atrial activation was found at a median of 16.75 (14.60-20.00) mm away from the tricuspid annulus, all with A larger than V. At the earliest retrograde atrial activation, far-field ventricular electrogram was found 30 ms later than QRS onset in 1 patient under sinus rhythm. AP conduction was eliminated by mechanical pressure in 2 and by radiofrequency ablation in 4 at the ostium of the veins colocalizing with the earliest retrograde activation of the right atrium. No recurrence was observed during 36 (10-60) months follow-up. CONCLUSIONS: The RCV-AP is a rare form of right-sided APs characterized by atrial insertions distant from the annulus. ECG-speculated ventricular insertion sites conformed to the location of identified RCVs.

Single-sEV profiling identifies the TACSTD2 + sEV subpopulation as a factor of tumor susceptibility in the elderly.

BACKGROUND: Aging is a very complex physiological phenomenon, and sEVs are involved in the regulation of this mechanism. Serum samples from healthy individuals under 30 and over 60 years of age were collected to analyze differences in sEVs proteomics. RESULTS: Based on PBA analysis, we found that sEVs from the serum of elderly individuals highly express TACSTD2 and identified a subpopulation marked by TACSTD2. Using ELISA, we verified the upregulation of TACSTD2 in serum from elderly human and aged mouse. In addition, we discovered that TACSTD2 was significantly increased in samples from tumor patients and had better diagnostic value than CEA. Specifically, 9 of the 13 tumor groups exhibited elevated TACSTD2, particularly for cervical cancer, colon cancer, esophageal carcinoma, liver cancer and thyroid carcinoma. Moreover, we found that serum sEVs from the elderly (especially those with high TACSTD2 levels) promoted tumor cell (SW480, HuCCT1 and HeLa) proliferation and migration. CONCLUSION: TACSTD2 was upregulated in the serum of elderly individuals and patients with tumors, and could serve as a dual biomarker for aging and tumors.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Biomaterial-Based CRISPR/Cas9 Delivery Systems for Tumor Treatment.

CRISPR/Cas9 gene editing technology is characterized by high specificity and efficiency, and has been applied to the treatment of human diseases, especially tumors involving multiple genetic modifications. However, the clinical application of CRISPR/Cas9 still faces some major challenges, the most urgent of which is the development of optimized delivery vectors. Biomaterials are currently the best choice for use in CRISPR/Cas9 delivery vectors owing to their tunability, biocompatibility, and efficiency. As research on biomaterial vectors continues to progress, hope for the application of the CRISPR/Cas9 system for clinical oncology therapy builds. In this review, we first detail the CRISPR/Cas9 system and its potential applications in tumor therapy. Then, we introduce the different delivery forms and compare the physical, viral, and non-viral vectors. In addition, we analyze the characteristics of different types of biomaterial vectors. We further review recent research progress in the use of biomaterials as vectors for CRISPR/Cas9 delivery to treat specific tumors. Finally, we summarize the shortcomings and prospects of biomaterial-based CRISPR/Cas9 delivery systems.

Gate-Tunable Positive and Negative Photoconductance in Near-Infrared Organic Heterostructures for In-Sensor Computing.

The rapid growth of sensor data in the artificial intelligence often causes significant reductions in processing speed and power efficiency. Addressing this challenge, in-sensor computing is introduced as an advanced sensor architecture that simultaneously senses, memorizes, and processes images at the sensor level. However, this is rarely reported for organic semiconductors that possess inherent flexibility and tunable bandgap. Herein, an organic heterostructure that exhibits a robust photoresponse to near-infrared (NIR) light is introduced, making it ideal for in-sensor computing applications. This heterostructure, consisting of partially overlapping p-type and n-type organic thin films, is compatible with conventional photolithography techniques, allowing for high integration density of up to 520 devices cm-2 with a 5 µm channel length. Importantly, by modulating gate voltage, both positive and negative photoresponses to NIR light (1050 nm) are attained, which establishes a linear correlation between responsivity and gate voltage and consequently enables real-time matrix multiplication within the sensor. As a result, this organic heterostructure facilitates efficient and precise NIR in-sensor computing, including image processing and nondestructive reading and classification, achieving a recognition accuracy of 97.06%. This work serves as a foundation for the development of reconfigurable and multifunctional NIR neuromorphic vision systems.

Cardiac resident macrophages: The core of cardiac immune homeostasis.

Cardiac resident macrophages (CRMs) are essential in maintaining the balance of the immune homeostasis in the heart. One of the main factors in the progression of cardiovascular diseases, such as myocarditis, myocardial infarction(MI), and heart failure(HF), is the imbalance in the regulatory mechanisms of CRMs. Recent studies have reported novel heterogeneity and spatiotemporal complexity of CRMs, and their role in maintaining cardiac immune homeostasis and treating cardiovascular diseases. In this review, we focus on the functions of CRMs, including immune surveillance, immune phagocytosis, and immune metabolism, and explore the impact of CRM's homeostasis imbalance on cardiac injury and cardiac repair. We also discuss the therapeutic approaches linked to CRMs. The immunomodulatory strategies targeting CRMs may be a therapeutic approach for the treatment of cardiovascular disease.

Cyaonoside A-loaded composite hydrogel microspheres to treat osteoarthritis by relieving chondrocyte inflammation.

Cyaonoside A (CyA), derived from the natural Chinese medicine, Cyathula officinalis Kuan, which was for a long time used to treat knee injuries and relieve joint pain in traditional Chinese medicine, showed an unclear mechanism for protecting cartilage. In addition, CyA was poorly hydrosoluble and incapable of being injected directly into the joint cavity, which limited its clinical application. This study reveals that CyA resisted IL-1ß-mediated chondrogenic inflammation and apoptosis. Next, transcriptome sequencing is used to explore the potential mechanisms underlying CyA regulation of MSC chondrogenic differentiation. Based on these findings, CyA-loaded composite hydrogel microspheres (HLC) were developed and they possessed satisfactory loading efficiency, a suitable degradation rate and good biocompatibility. HLC increased chondrogenic anabolic gene (Acan, COL2A, and SOX9) expression, while downregulating the expression of the catabolic marker MMP13 in vitro. In the osteoarthritis mouse model, HLC demonstrated promising therapeutic capabilities by protecting the integrity of articular cartilage. In conclusion, this study provides insights into the regulatory mechanisms of CyA for chondrocytes and proposes a composite hydrogel microsphere-based advanced therapeutic strategy for osteoarthritis.

Single-Molecule Electrical Profiling of Peptides and Proteins.

In recent decades, there has been a significant increase in the application of single-molecule electrical analysis platforms in studying proteins and peptides. These advanced analysis methods have the potential for deep investigation of enzymatic working mechanisms and accurate monitoring of dynamic changes in protein configurations, which are often challenging to achieve in ensemble measurements. In this work, the prominent research progress in peptide and protein-related studies are surveyed using electronic devices with single-molecule/single-event sensitivity, including single-molecule junctions, single-molecule field-effect transistors, and nanopores. In particular, the successful commercial application of nanopores in DNA sequencing has made it one of the most promising techniques in protein sequencing at the single-molecule level. From single peptides to protein complexes, the correlation between their electrical characteristics, structures, and biological functions is gradually being established. This enables to distinguish different molecular configurations of these biomacromolecules through real-time electrical monitoring of their life activities, significantly improving the understanding of the mechanisms underlying various life processes.

Effects of oropharyngeal exercises on CPAP compliance: A prospective intervention study.

PURPOSE: To investigate the effects of oropharyngeal exercise on continuous positive airway pressure (CPAP) compliance in patients with moderate to severe obstructive sleep apnea over a period of 6 months. MATERIALS AND METHODS: This study was conducted as a prospective, observational, and interventional investigation. A total of 70 patients with moderate to severe obstructive sleep apnea were randomly assigned to either the oropharyngeal exercise group (n = 44) or the sham-therapy group (n = 26). The compliance of the enrolled patients with CPAP therapy was assessed at baseline, 3-month follow-up and 6-month follow-up. Objective sleep data, questionnaire and CPAP use time were collected over a half-year period (i.e., baseline, 6 months, and 12 months). RESULTS: The study found that the average use time of CPAP within one month was significantly longer in the oropharyngeal exercises group compared to the sham-therapy group at the 3-month assessment (5.5 ± 1.2 vs 4.8 ± 1.3 h per night; p=0.030), and much significantly longer at 6-months assessment (6.0 ± 1.4 vs 4.9 ± 1.3 h per night; p=0.001). Furthermore, the average use time of CPAP increased over time, with the oropharyngeal exercises group exhibiting a more pronounced growth from baseline to the six-month follow-up (4.8 ± 1.0 h per night to 6.0 ± 1.3 h per night, p < 0.001) compared to the sham-therapy group (4.8 ± 1.3 h per night to 4.9 ± 1.3 h per night, p=0.952). Additionally, the oropharyngeal exercise group demonstrated an improvement in the Epworth sleepiness scale compared to the sham-therapy group at the 3-month follow-up (6.0 ± 2.0 vs 8.8 ± 3.2; p < 0.001), as well as decreased significantly at 6-month follow-up (p = 0.032). CONCLUSIONS: CPAP adherence can be improved with oropharyngeal exercises therapy among moderate to severe OSA patients. Notably, the average duration of CPAP usage and reduction in daytime sleepiness were maintained even after six months of oropharyngeal exercise therapy.

A new triterpenoid saponin and a new natural saponin from the roots of Bupleurum scorzonerifolium willd.

Sixteen triterpenoid saponins were isolated from the roots of Bupleurum scorzonerifolium Willd., including a new triterpenoid saponin and new natural saponin that was characterised by NMR for the first time, along with 14 known triterpenoid saponins. The structures of the compounds were established by 1D and 2D NMR spectroscopy, HR-ESI-MS, and comparison with the literature. The cytotoxic activity of the compounds against 4T1 cells was determined using the CCK8 method. Compounds 9 and 6 showed the strongest cytotoxic activity with IC50 values of 2.75 ± 0.86 and 3.78 ± 0.50 µM, respectively. Compounds 2-5 and 8 showed potent cytotoxic activity. Compounds 14 and 16 showed moderate cytotoxicity.

Unlocking the power of postbiotics: A revolutionary approach to nutrition for humans and animals.

Postbiotics, which comprise inanimate microorganisms or their constituents, have recently gained significant attention for their potential health benefits. Extensive research on postbiotics has uncovered many beneficial effects on hosts, including antioxidant activity, immunomodulatory effects, gut microbiota modulation, and enhancement of epithelial barrier function. Although these features resemble those of probiotics, the stability and safety of postbiotics make them an appealing alternative. In this review, we provide a comprehensive summary of the latest research on postbiotics, emphasizing their positive impacts on both human and animal health. As our understanding of the influence of postbiotics on living organisms continues to grow, their application in clinical and nutritional settings, as well as animal husbandry, is expected to expand. Moreover, by substituting postbiotics for antibiotics, we can promote health and productivity while minimizing adverse effects. This alternative approach holds immense potential for improving health outcomes and revolutionizing the food and animal products industries.

Cytotoxicity phenylpropanoid amides from the seed of Cannabis sativa L.

Two novel phenylpropanoid amides, namely huomarenamide A (1) and huomarenamide B (2), along with twelve known compounds (3-14), were isolated from the seeds of Cannabis sativa L. The structures with absolute configurations of new compounds were unequivocally determined by spectroscopic analyses and the ECD method. The identification of the known compounds was based on a comparison of their 1D NMR data with literature references. All compounds were assessed for cytotoxic activity against LN229 cells, revealing that compounds 2, 13, and 14 exhibited significant cytotoxicity with IC50 values ranging from 9.02 to 21.26 µM.

Characterization of lipids and volatile compounds in boiled donkey meat by lipidomics and volatilomics.

Lipids are crucial substances for the formation and retention of volatile compounds (VOCs). The lipid and VOC profiles of boiled donkey meat were investigated by lipidomics and volatilomics. In total, 4277 lipids belonging to 39 subclasses were identified, comprising 26.93% triglycerides (TGs), 15.74% phosphatidylcholins (PCs), and 9.40% phosphatidylethanolamines. The relative percentage of TG in the meat significantly decreases (p < 0.001) from 0 to 40 min, after which there is no significant change, whereas PCs, sphingomyelins, and methyl phosphatidylcholines (MePCs) show the opposite trend. TG(16:1_18:1_18:2) and TG(16:0_16:1_18:2) appear to be key lipids for retaining VOCs in boiled donkey meat. Furthermore, PC(18:3e_16:0) and MePC(31:0e) were found to be potential markers for discriminating donkey meat. A total of 83 VOCs were detected, including 25.30% aldehydes, 18.07% hydrocarbons, 14.46% ketones, and 13.25% alcohols. Eleven characteristic VOCs with relative odor activity values >1 were identified as the predominant flavor compounds in boiled donkey meat, mainly hexanal and 1-octen-3-ol. Of the 258 differential lipids, 72 of them, especially polyunsaturated-fatty acid-rich lipids, are the main contributors to the formation of VOCs. Together, the key lipids for retention and formation of VOCs in donkey meat were revealed, providing a theoretical basis for VOC regulation.

Molecular dynamics simulation of the initial stage induction of alkali-activated aluminosilicate minerals.

With the increasing global concern over carbon emissions, geopolymers have garnered significant attention due to their energy-saving, waste utilization, and eco-friendly advantages. Metakaolin and slag, as aluminum-containing mineral materials in geopolymer production, have been widely studied and applied. Previous research has mainly focused on performance design and theoretical development, while the underlying mechanisms at the microscopic level remain unclear. In this study, we employed molecular dynamics simulations to investigate the microscale reaction behavior of geopolymers, exploring the induction process and structural evolution during the initial stages, and revealing the similarities and differences under alkali activation for different materials. Our findings indicate that the alkali activation process can be divided into two stages: mineral crystal deconstruction and oligomer polymerization. The role of NaOH differs between low-calcium and high-calcium systems, where in the low-calcium system, Na+ substitutes Ca2+ due to Ca2+ deficiency, participating in the formation of the network framework. Moreover, the high-calcium system exhibits a faster formation of the gel phase during alkali activation compared to the low-calcium system. This study provides valuable insights into the research and application of geopolymers.

Sulfasalazine-induced drug reaction with eosinophilia and systemic symptoms (DRESS) coinfected with COVID-19 complicated by hemophagocytic lymphohistiocytosis: a case report.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is characterized by a widespread maculopapular rash, lymphadenopathy, fever, and multisystem involvement. Conversely, hemophagocytic lymphohistiocytosis (HLH) is an infrequent yet critical condition presenting with fever, hepatosplenomegaly, cytopenias, coagulation abnormalities, and elevated inflammatory markers. The overlapping clinical and laboratory features between DRESS and HLH poses a significant diagnostic challenge. Secondary HLH (sHLH) typically occurs in adults triggered by viral infections, malignancies, rheumatologic diseases, or immune deficiencies. Recently, COVID-19 has also been identified as one of the triggers for sHLH. Herein, we present a case of Sulfasalazine-induced DRESS coinfected with COVID-19 that subsequently progressed into HLH. Our patient exhibited common hepatorenal and splenic involvement along with rare cholecystitis and appendicitis. However, a significant improvement was observed upon the addition of etoposide and azathioprine. We hypothesize that excessive activation of the immune system and cytokine storm due to DRESS combined with COVID-19 infection led to more extensive systemic damage resulting in HLH development. This highlights the potential for severe consequences when DRESS coincides with HLH during a COVID-19 infection.