Characterization of 2023-2024 H3N2 influenza viruses

During the 2023-2024 flu season in the Northern Hemisphere, the influenza A virus (IAV) H3N2 dominated from Feb 2024 to May 2024. Seasonal IAV can accumulate mutations on antigenic sites of the hemagglutinin (HA) protein, leading to escape from preexisting immunity and launching annual epidemics. Therefore, surveillance of emerging IAV clades is important for identifying and understanding the viral adaptations that allow for escape from vaccine induced immunity. The H3N2 subclades found during the 2023-2024 flu season are J.2, J.1, J, and G.2 with J.2 being dominant. A J.2 subclade H3N2 virus (A/Baltimore/JH23641/2024) was isolated from an infected person and its amino acid sequence was compared with the H3 vaccine strain (A/Darwin/9/2021-subclade G.2). I used RT-PCR to extract both HA sequences and align them together. There are fifteen mutations between the H3 vaccine and seasonal strains, with three located at antigenic sites. Mutations include I156K, M184I, and N202D, which could be important factors facilitating the H3N2 subclade J.2 dominance in circulation. To assess the escape from vaccine induced immunity, neutralization assays were performed on sera acquired from healthcare workers pre- and post-vaccination during the 2023- 2024 season. Post-vaccination sera have a higher neutralization titer against both vaccine and circulating H3N2 strains, indicating three mutations on HA antigenic sites do not adversely affect neutralizing antibody titers. We also investigated H3 seasonal virus replication kinetics using low multiplicity of infection (MOI) growth curves in human Nasal Epithelial Cells (hNECs) cultures under different physiological temperatures. The physiological temperatures did not affect total infectious virus production but did change the kinetics, with less virus being produced early after infection and more virus produced late after infection at 33C compared to 37C. The 2023-24 H3N2 J.2 subclade doesn’t have antigenic drift compared with the vaccine strain and no specific viral replication changes under different physiological temperatures

Characterization of 2023-2024 H3N2 influenza viruses

During the 2023-2024 flu season in the Northern Hemisphere, the influenza A virus (IAV) H3N2 dominated from Feb 2024 to May 2024. Seasonal IAV can accumulate mutations on antigenic sites of the hemagglutinin (HA) protein, leading to escape from preexisting immunity and launching annual epidemics. Therefore, surveillance of emerging IAV clades is important for identifying and understanding the viral adaptations that allow for escape from vaccine induced immunity. The H3N2 subclades found during the 2023-2024 flu season are J.2, J.1, J, and G.2 with J.2 being dominant. A J.2 subclade H3N2 virus (A/Baltimore/JH23641/2024) was isolated from an infected person and its amino acid sequence was compared with the H3 vaccine strain (A/Darwin/9/2021-subclade G.2). I used RT-PCR to extract both HA sequences and align them together. There are fifteen mutations between the H3 vaccine and seasonal strains, with three located at antigenic sites. Mutations include I156K, M184I, and N202D, which could be important factors facilitating the H3N2 subclade J.2 dominance in circulation. To assess the escape from vaccine induced immunity, neutralization assays were performed on sera acquired from healthcare workers pre- and post-vaccination during the 2023- 2024 season. Post-vaccination sera have a higher neutralization titer against both vaccine and circulating H3N2 strains, indicating three mutations on HA antigenic sites do not adversely affect neutralizing antibody titers. We also investigated H3 seasonal virus replication kinetics using low multiplicity of infection (MOI) growth curves in human Nasal Epithelial Cells (hNECs) cultures under different physiological temperatures. The physiological temperatures did not affect total infectious virus production but did change the kinetics, with less virus being produced early after infection and more virus produced late after infection at 33C compared to 37C. The 2023-24 H3N2 J.2 subclade doesn’t have antigenic drift compared with the vaccine strain and no specific viral replication changes under different physiological temperatures

A 5-Genomic Mutation Signature Can Predict the Survival for Patients With NSCLC Receiving Atezolizumab

BackgroundAt present, there is a lack of studies focusing on the survival prediction of patients with non-small cell lung cancer (NSCLC) receiving atezolizumab in light of gene mutation characteristic.MethodsPatients with NSCLC receiving atezolizumab from the OAK study were defined as the training group. LASSO Cox regressions were applied to establish the gene mutation signature model to predict the overall survival (OS) rate of the training group. NSCLC patients receiving atezolizumab from the POPLAR study were defined as the testing group to validate the gene mutation signature model. In addition, we compared the OS rate between patients receiving atezolizumab and docetaxel classified according to their risk score based on our gene mutation signature model.ResultsWe successfully established a 5-genomic mutation signature that included CREBBP, KEAP1, RAF1, STK11 and TP53 mutations. We found it was superior to the blood tumor mutation burden (bTMB) score and programmed death ligand 1 (PDL1) expression in the prediction of the OS rate for patients receiving atezolizumab. High-risk patients receiving atezolizumab had a worse OS rate compared with low-risk patients in the training (P = 0.0004) and testing (P = 0.0001) groups. In addition, low-risk patients using atezolizumab had a better OS rate compared with those in use of docetaxel for the training (P <0.0001) and testing groups (P = 0.0095). High-risk patients of the training group (P = 0.0265) using atezolizumab had a better OS rate compared with those using docetaxel. However, the OS difference between atezolizumab and docetaxel was not found in high-risk patients from the testing group (P = 0.6403). Multivariate Cox regression analysis showed that the risk model in light of 5-genomic mutation signature was an independent prognostic factor on OS for patients receiving atezolizumab (P <0.0001). In addition, significant OS benefit could only be found in low-risk patients receiving atezolizumab compared with docetaxel (P <0.0001).ConclusionsThe 5-genomic mutation signature could predict OS benefit for patients with NSCLC receiving atezolizumab. Therefore, the establishment of the 5-genomic mutation panel will guide clinicians to identify optimal patients who could benefit from atezolizumab treatment

Scalable metasurface-enhanced supercool cement

Structural materials with the capability for passive daytime radiative cooling (PDRC) show promise for the sustainable cooling of buildings. However, developing durable PDRC structural materials with optical robustness, ease of deployment, and scalability remain a challenge for civil engineering applications. We synthesized a metasurface-enhanced cooling cement using a universal, scalable pressure-driven fabrication strategy during a low-carbon production process. The self-assembly of multiple-sized reflective ettringites as main hydration products toward the metasurface, coupled with hierarchical pores, guaranteed high solar reflectance (96.2%), whereas raw materials containing alumina- and sulfur-rich function groups leveraged inherent mid-infrared emissivity (96.0%). This photonic-architectured cement achieved a temperature drop of 5.4°C during midday conditions with a solar intensity of 850 watts per square meter. This supercool cement featured intrinsic high strength, armored abrasive resistance, and optical stability, even when exposed to harsh conditions, such as corrosive liquids, ultraviolet radiation, and freeze-thaw cycles. A machine learning–guided life-cycle assessment indicated its potential to achieve a net-negative carbon emission profile

Effects of partial silage replacement with corn stover pellets on the rumen microbiota and serum metabolome of breeding cows

IntroductionStraw pellet ration replacing part of silage is of great significance for farmers to save farming costs and solve the lack of feed resources. A comprehensive analysis of rumen microbial and serum metabolite compositions is conducted to promote the development of the modern breeding cows-feeding industry.MethodsIn this study, 18 healthy 2-year-old Simmental breeding cows weighing 550 ± 20 kg were selected and randomly divided into two groups. They were fed under the same feeding conditions for 70 days, of which 8 in the control (CON) group were fed 65% roughage (100% silage) + 35% concentrate, and 10 in the treatment (TRT) group were fed 65% roughage (50% corn stover pellets +50% silage) + 35% concentrate, and milk quality, serum immunity indexes, serum metabolomes, rumen fermentation parameters, rumen Microorganisms.ResultsThe results showed that there was no significant difference in production performance between the two groups of breeding cows fed hay and Corn stover pellet feed (p < 0.05); Immunoglobulin A (IgA) was significantly higher in TRT compared to CON (p < 0.05), and there was no significant difference in Immunoglobulin G (IgG) and Immunoglobulin M (IgM) between the two groups (p > 0.05); a total of 92 differential metabolites were screened out in the serum metabolomics analysis, among them, L-valine, L-leucine, L-arginine, L-cysteine, L-tyrosine, and L-tryptophan were up-regulated; In rumen fermentation parameters there was no significant difference between CON and TRT in rumen pH, rumen ammonia nitrogen (NH3-N) content, rumen Acetic/Propionic concentration (p > 0.05), and the concentration of Acetic, Propionic, butyric and Total volatile fatty acids (TVFA) in CON was significantly lower than that in TRT (p < 0.05). Among the rumen microorganisms, the dominant groups were Thick-walled Firmicutes, Bacteroidota, Prevotella and Ruminalococcus. In the correlation analysis between rumen fermentation parameters and rumen microorganisms, Propionic and TVFA showed a significant positive correlation with Prevotella (p < 0.05), butyric showed a highly significant positive correlation with Prevotella (p < 0.01), and propionic butyric, and TVFA showed a positive correlation with Bacteroides (p < 0.05); L-cysteine was significantly positively correlated with Prevotella and Anaeroplasma (p < 0.05) and Eubaterium in rumen microbial-serum metabolite correlation analysis (p < 0.01).ConclusionThe microbial and metabolomic analyses provide us with essential data support to further provide a scientific basis for breeding cows feeding through the feeding pattern of straw pellets instead of silage, which will help breeding cows farming in future research

Research Progress on the Mechanism for the Effect of Ubiquitination on Meat Quality

Meat quality is closely related to consumer experience and the benefits of deep processing enterprises, and it is influenced by diverse and complex factors. Recently, the impact of ubiquitination on meat quality has attracted increasing attention, and multiple studies have confirmed its crucial role in meat quality. This paper reviews the literature on the effect of ubiquitination on postmortem muscle energy metabolism, and discusses the potential mechanisms through which ubiquitination affects meat tenderness, color, water-holding capacity, and fat content. Furthermore, it highlights the regulatory mechanisms of protein ubiquitination on meat tenderness in terms of the ubiquitin-proteasome system and the apoptotic pathway. This review is anticipated to enhance the understanding the mechanism through which ubiquitination affects meat quality, thereby laying a theoretical foundation for regulating meat quality through ubiquitination

Aqueous Extract of Mori Folium Exerts Bone Protective Effect Through Regulation of Calcium and Redox Homeostasis via PTH/VDR/CaBP and AGEs/RAGE/Nox4/NF-κB Signaling in Diabetic Rats

Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process.Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2′-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays. Histopathological alterations in the femurs were evaluated by the stainings of hematoxylin-eosin (H&E) and alizarin red S. In addition, femoral strength was detected by a three-point bending assay, bone microstructure was detected with micro-computer tomography. Bone material properties were examined by Fourier-transform infrared spectroscopy. Furthermore, the expressions of IGF-1, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin K, AGEs, receptor of advanced glycation end products (RAGE), NADPH oxidase 4 (Nox4), and nuclear factor kappa-B (NF-κB) in the femurs and tibias, and the alterations in the levels of calcium-binding protein-28k (CaBP-28k), transient receptor potential V6 (TRPV6), and vitamin D receptor (VDR) in the kidneys and duodenums were determined by western blot and immunohistochemical analysis.Results: Treatment of diabetic rats with MF aqueous extract induces an increase in the levels of OC and IGF-1 as well as a decrease in TRAP level in serum. MF treatment also upregulates the expression of OPG, downregulates the expressions of AGEs, RAGE, Nox4, NF-κB, and RANKL, which leads to improve bone microstructure and strength exhibited by an increase in cortical area ratio, cortical thickness, and trabecular area ratio as well as ultimate load, elastic modulus, and bending stress in the femurs and tibias of diabetic rats. In addition, MF aqueous extract preserves bone material properties by decreasing the ratio of fatty acid/collagen and increasing the ratio of mineral/matrix in the femurs of diabetic rats. Moreover, MF treatment increases the levels of P, Ca, and 1,25(OH)2D3, and decreases the level of PTH in the serum, as well as upregulates the expressions of TRPV6 and VDR in the duodenums and CaBP-28k in the kidneys of diabetic rats. Additionally, MF has ability of rebuilding redox homeostasis and eliminating inflammatory stress by increasing the levels of SOD and TAC as well as decreasing the levels of IL-6, AGEs, MDA, and 8-OH-dG.Conclusions: MF treatment may improve bone quality through maintenance of calcium homeostasis via regulating the PTH/VDR/CaBP signaling, and elimination of oxidative stress via regulating the AGEs/RAGE/Nox4/NF-κB signaling. These results may suggest the potential of MF in preventing the development of diabetic osteoporosis

Studies on fatty acids and microbiota characterization of the gastrointestinal tract of Tianzhu white yaks

IntroductionThe gut microbiota significantly influences the host’s production performance and health status, with different gastrointestinal tissues exhibiting functional diversity reflected in their microbial diversity.MethodsIn this study, five adult male Tianzhu white yaks (4.5 years old) were selected and fed under the same nutritional conditions. After the feeding experiment, the yaks were slaughtered, and chyme samples were collected from the rumen, abomasum, jejunum, and colon for 16S rRNA full-length sequencing and volatile fatty acid analysis.ResultsThe results showed that the microbial composition and diversity of the rumen and abomasum were similar, with close genetic distances and functional projections. In contrast, the jejunum and colon had distinct microbial compositions and diversity compared to the rumen and abomasum. At the phylum level, the dominant phyla in the rumen, abomasum, and colon were Firmicutes and Bacteroidetes, while in the jejunum, the dominant phyla were Firmicutes and Proteobacteria. The abundance of Firmicutes differed significantly between the jejunum (87.24%) and the rumen (54.67%), abomasum (67.70%), and colon (65.77%). Similarly, Bacteroidetes showed significant differences between the jejunum (2.21%) and the rumen (36.54%), abomasum (23.81%), and colon (28.12%). At the genus level, Rikenellaceae_RC9_gut_group and Christensenellaceae_R-7_group were dominant in both the rumen and abomasum. In the jejunum, Romboutsia and Paeniclostridium were dominant, while Rikenellaceae_RC9_gut_group and UCG-005 were the dominant genera in the colon. At the species level, rumen_bacterium_g_Rikenellaceae_RC9_gut_group and rumen_bacterium_g_Christensenellaceae_R-7_group were dominant in both the rumen and abomasum, while Clostridium_sp._g_Romboutsia and bacterium_g_Paeniclostridium were unique to the jejunum. Ruminococcaceae_bacterium_g_UCG-005 and bacterium_g_Rikenellaceae_RC9_gut_group were unique to the colon. KEGG functional prediction of the microbiota indicated that the dominant functions in the rumen, abomasum, colon, and jejunum were amino acid metabolism, glycan biosynthesis and metabolism, carbohydrate metabolism, and membrane transport, respectively, reflecting the digestive functions of these organs. Volatile fatty acid analysis showed that the concentrations of acetic acid, propionic acid, and butyric acid in the rumen were significantly higher than those in the abomasum, jejunum, and colon (p < 0.05). Among these, the propionic acid concentration in the jejunum was significantly lower than in the abomasum and colon. Additionally, correlation analysis results indicated that acetic acid and butyric acid were significantly positively correlated with the ruminal bacterial community (p < 0.05). The total volatile fatty acid concentration was highest in the rumen, decreased to less than one-fifth of the rumen’s total volatile fatty acid concentration in the abomasum and jejunum, and then reached a second peak in the colon.ConclusionThis study explored the microbial composition and differential bacterial genera in the rumen and intestines of Tianzhu white yak, comparing the differences in volatile fatty acid levels and microbial composition and function across different regions. This is important for understanding their gastrointestinal microbiota’s spatial heterogeneity

Health impacts of parental migration on left-behind children and adolescents: a systematic review and meta-analysis.

BACKGROUND: Globally, a growing number of children and adolescents are left behind when parents migrate. We investigated the effect of parental migration on the health of left behind-children and adolescents in low-income and middle-income countries (LMICs). METHODS: For this systematic review and meta-analysis we searched MEDLINE, Embase, CINAHL, the Cochrane Library, Web of Science, PsychINFO, Global Index Medicus, Scopus, and Popline from inception to April 27, 2017, without language restrictions, for observational studies investigating the effects of parental migration on nutrition, mental health, unintentional injuries, infectious disease, substance use, unprotected sex, early pregnancy, and abuse in left-behind children (aged 0-19 years) in LMICs. We excluded studies in which less than 50% of participants were aged 0-19 years, the mean or median age of participants was more than 19 years, fewer than 50% of parents had migrated for more than 6 months, or the mean or median duration of migration was less than 6 months. We screened studies using systematic review software and extracted summary estimates from published reports independently. The main outcomes were risk and prevalence of health outcomes, including nutrition (stunting, wasting, underweight, overweight and obesity, low birthweight, and anaemia), mental health (depressive disorder, anxiety disorder, conduct disorders, self-harm, and suicide), unintentional injuries, substance use, abuse, and infectious disease. We calculated pooled risk ratios (RRs) and standardised mean differences (SMDs) using random-effects models. This study is registered with PROSPERO, number CRD42017064871. FINDINGS: Our search identified 10 284 records, of which 111 studies were included for analysis, including a total of 264 967 children (n=106 167 left-behind children and adolescents; n=158 800 children and adolescents of non-migrant parents). 91 studies were done in China and focused on effects of internal labour migration. Compared with children of non-migrants, left-behind children had increased risk of depression and higher depression scores (RR 1·52 [95% CI 1·27-1·82]; SMD 0·16 [0·10-0·21]), anxiety (RR 1·85 [1·36-2·53]; SMD 0·18 [0·11-0·26]), suicidal ideation (RR 1·70 [1·28-2·26]), conduct disorder (SMD 0·16 [0·04-0·28]), substance use (RR 1·24 [1·00-1·52]), wasting (RR 1·13 [1·02-1·24]) and stunting (RR 1·12 [1·00-1·26]). No differences were identified between left-behind children and children of non-migrants for other nutrition outcomes, unintentional injury, abuse, or diarrhoea. No studies reported outcomes for other infectious diseases, self-harm, unprotected sex, or early pregnancy. Study quality varied across the included studies, with 43% of studies at high or unclear risk of bias across five or more domains. INTERPRETATION: Parental migration is detrimental to the health of left-behind children and adolescents, with no evidence of any benefit. Policy makers and health-care professionals need to take action to improve the health of these young people. FUNDING: Wellcome Trust