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Abstract Objective This randomized controlled and double-blind study aimed to investigate whether the analgesic effect of the adductor canal block (ACB) combined with the genicular nerve block (GNB) after total knee arthroplasty is noninferior to that of the adductor canal block combined with local infiltration analgesia (LIA). Methods A total of 102 patients undergoing total knee arthroplasty under general anesthesia were included and randomly divided into: ACB + GNB and ACB + LIA groups; the ACB + LIA group received 80 mL of 0.2% ropivacaine with adrenaline 10 µg/mL for LIA, whereas the ACB + GNB group received 4 mL of 0.2% ropivacaine for the blockade of five peri-knee nerves. The primary outcome was the median difference in the visual analog scale scores at rest at 24 h between the two groups. Secondary outcomes involved the median differences in the pain scores at other time points. Other outcomes included the cumulative dosage of opioids calculated in morphine equivalents in the first 24 h and indicators related to knee joint functional recovery. Results In total, 36 and 38 patients were included in the ACB + GNB and ACB + LIA groups, respectively. We found that the median difference (95% confidence internal) in postoperative rest pain at 24 h (noninferiority criteria, △ = 1) was − 0.5 (− 1 to 0, p = 0.002). The median difference in cumulative opioid consumption was 1 mg (− 1 to 3, p = 0.019), meeting the noninferiority criteria, △ = 7.7 mg. Conclusions ACB combined with GNB provides noninferior analgesia compared to ACB with LIA on the first day after total knee arthroplasty while significantly reducing local anesthetic use. Trial registration Name of the Registry: Chinese Clinical Trial Registry; Trial Registration Number: ChiCTR2300074274; Date of Registration. August 2, 2023.

The effects of extrusion ratio (ER) on the microstructures, static mechanical properties, and tension-compression high cycle fatigue (HCF) behavior of the as-extruded Mg–5Zn–1Mn (ZM51) alloy was investigated systematically, and the HCF mechanism was discussed. The results show that texture weakening and grain refinement caused by increasing the ER can effectively enhance the static mechanical properties and alleviate the tensile-compressive asymmetry of the alloy. The fatigue strength at 107 cycles is 124 ± 5, 138 ± 4, and 142 ± 5 MPa for ER8, ER11.5, and ER23, respectively, and the corresponding fatigue ratio is approximately 0.45, 0.49, and 0.50, which means that the as-extruded ZM51 alloy possesses outstanding fatigue resistance. The failure analysis and microstructure evolution of post-fatigued samples demonstrated that the stress amplitudes and microstructure characteristics strongly influence the HCF mechanism of the alloy. At high-stress load, close to the tensile yield strength 160–180 MPa, abundant {101‾2} residual twin bands were observed near the fracture surface. Twinning/detwinning deformation is the dominant fatigue mechanism due to the plastic deformation incompatibility between the matrix and the residual twins. At low-stress load, close to the fatigue strength 125–145 MPa, the fatigue crack initiation mechanism transits from twinning/detwinning to dislocation slip. Grain refinement and texture weakening inhibit the activation of {101‾2} twins, alleviate the twin-dislocation interaction, and promote dislocation slip to dominate the fatigue deformation, thereby enhancing the fatigue life of the alloy. This work provides new insight into the design and development for enhancing the fatigue resistance of wrought Mg alloy to ensure the long-term service safety of structural materials.

Liquid Crystal Elastomers (LCEs) are renowned for their reversible deformation capabilities. Yet, enhancing their mechanical strength while retaining such flexibility has posed a considerable challenge. To overcome this, we utilized 4D printing to develop an innovative composite of LCE with carbon fiber fabric (LCEC). This approach has notably increased the tensile strength of LCE by eightfold, all the while maintaining its exceptional capacity for reversible deformation. By adjusting the alignment angle between carbon fiber and the LCE printing direction from 0° to 90°, the LCEC demonstrates an array of new deformation patterns, including bending, twisting, wrapping, and S-shaped transformations, which are distinct from pure LCE materials. Our study unveils that LCE composites exhibit deformation processes markedly different from their pure material counterparts, with the ability of pure LCE to sustain tensile strains exceeding 1900%. These findings, previously undocumented and unexplored, represent a substantial contribution to the field of smart materials. Employing finite element analysis, we explored the carbon fiber and LCE matrix dynamics, revealing bending mechanics in LCECs. This combined experimental and simulation approach yields crucial insights for crafting durable, high-strength LCECs with diverse deformational properties, advancing smart material technology.

Abstract Background Cow milk fat is an essential indicator for evaluating and measuring milk quality and cow performance. Growing research has identified the molecular functions of circular RNAs (circRNAs) necessary for mammary gland development and lactation in mammals. Method The present study analyzed circRNA expression profiling data in mammary epithelial cells (MECs) from cows with highly variable milk fat percentage (MFP) using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Results A total of 309 differentially expressed circRNAs (DE-circRNAs) were identified in the high and low MFP groups. WGCNA analysis revealed that the pink module was significantly associated with MFP (r = − 0.85, P = 0.007). Parental genes of circRNAs in this module were enriched mainly in lipid metabolism-related signaling pathways, such as focal adhesion, ECM-receptor interaction, adherens junction and AMPK. Finally, six DE-circRNAs were screened from the pink module: circ_0010571, circ_0007797, circ_0002746, circ_0003052, circ_0004319, and circ_0012840. Among them, circ_0002746, circ_0003052, circ_0004319, and circ_0012840 had circular structures and were highly expressed in mammary tissues. Subcellular localization revealed that these four DE-circRNAs may play a regulatory role in the mammary glands of dairy cows, mainly as competitive endogenous RNAs (ceRNAs). Seven hub target genes (GNB1, GNG2, PLCB1, PLCG1, ATP6V0C, NDUFS4, and PIGH) were obtained by constructing the regulatory network of their ceRNAs and then analyzed by CytoHubba and MCODE plugins in Cytoscape. Functional enrichment analysis revealed that these genes are crucial and most probable ceRNA regulators in milk fat metabolism. Conclusions Our study identified several vital circRNAs and ceRNAs affecting milk fat synthesis, providing new research ideas and a theoretical basis for cow lactation, milk quality, and breed improvement.

Developing a cost-effective method for separating and concentrating tritium water (HTO) from light water (H2O) without consuming additional energy is crucial for achieving reliable and safe nuclear fission and fusion energy technologies. However, this presents a significant challenge because of the difficulties in obtaining basic information, such as the chemical and physical properties of HTO molecules. Here, we investigate the isotope exchange reaction (IER) between HTO molecules in H2O solution and H2O vapor in the atmosphere. The reduction and purification rates of HTO-containing water were measured by varying the system conditions, such as temperature (20−50 °C) and humidity (50 %–90 %), under an equilibrium state between the liquid phase (water) and vapor phase (air). Our findings indicate that the concentration of HTO in the solution can be significantly reduced by increasing H2O vapor in the atmosphere. This result can be quantitatively explained by considering the entropy of mixing between the solution and vapor phases. The results obtained here provide both basic understanding on the exchange process between liquid- and vapor-water molecules and a passive technology for treating HTO-containing water.

Abstract Highly pathogenic avian influenza virus (HPAIV) A H5, particularly clade 2.3.4.4, has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, this mechanism has not been quantified using bird movement data from different species, and the timing and location of exposure of different species is unclear. We sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences of clade 2.3.4.4 and 2.3.2.1. First, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing exposed bird orders at geographical origins and destinations of HPAIV H5 clade 2.3.4.4 lineage movements, including relatively under-discussed orders. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behavior and life history in avian influenza studies.

Hypertension has always posed a severe threat to people’s health. Food-derived angiotensin-converting enzyme (ACE)-inhibitory peptides have the potential to both prevent and treat hypertension. In the current investigation, two ACE-inhibitory peptides (SLPQ and PYVRYL) from goat milk were studied for their endothelial effects using EA.hy926 cells. PYVRYL outperformed SLPQ, yet neither impacted cell survival below 200 μg/mL. Investigation of SLPQ’s impact on EA.hy926 cell expression revealed 114 differentially expressed genes, with 65 downregulated and 49 upregulated. The genes were enriched in cytokine interactions, coagulation cascades, Hippo signaling, and ECM–receptor interaction. Decreased c-x-c motif chemokine ligand 2 (CXCL2), integrin subunit beta 2 (ITGB2), and fbj murine osteosarcoma viral oncogene homologue (FOS) expression and increased secreted phosphoprotein 1 (SPP1) expression may protect endothelial cells from inflammation. Our findings suggest that beyond ACE inhibition, SLPQ aids blood pressure control by influencing endothelial function, paving the way for its use as an antihypertensive food ingredient.

The optical properties of an off-axis integrated cavity system are influenced by both structural deformation and thermal deformation. In this paper, the finite element simulation and analysis software COMSOL multiphysics was used to numerically simulate the optical system. By coupling geometric optics, solid mechanics, and solid heat transfer and conducting parametric temperature scanning, a multiphysics simulation of the off-axis integrated cavity optical sensing system was achieved. The effects of different temperature conditions on the stress field, displacement field, and optical mirrors were analyzed, and changes in optical properties were assessed using ray trajectories and point diagrams. Additionally, optical simulation software was used to simulate and optimize the experimental optical path, obtaining the distribution of light spots on the detector surface. This provides a theoretical basis for the subsequent optimization of the off-axis integrated cavity optical system.

Background Thyroid-associated orbitopathy (TAO) is a disease associated with autoimmune thyroid disorders and it can lead to proptosis, diplopia, and vision-threatening compressive optic neuropathy. To comprehensively understand the molecular mechanisms underlying orbital adipogenesis in TAO, we characterize the intrinsic molecular properties of orbital adipose/connective tissue from patients with TAO and control individuals. Methods RNA sequencing analysis (RNA-seq) was performed to measure the gene expression of orbital adipose/connective tissues of TAO patients. Differentially expressed genes (DEGs) were detected and analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA). The protein–protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified by the Cytoscape plug-in, cytoHubba. We validated several top DEGs through quantitative real-time polymerase chain reaction (qRT–PCR). Results We identified 183 DEGs in adipose tissue between TAO patients (n = 3) and control patients (n = 3) through RNA sequencing, including 114 upregulated genes and 69 downregulated genes. The PPI network of these DEGs had 202 nodes and 743 edges. PCR-based validation results of orbital adipose tissue showed multiple top-ranked genes in TAO patients (n = 4) are immune and inflammatory response genes compared with the control individual (n = 4). They include ceruloplasmin isoform x3 (CP), alkaline tissue-nonspecific isozyme isoform x1 (ALPL), and angiotensinogen (AGT), which were overrepresented by 2.27- to 6.40-fold. Meanwhile, protein mab-21-like 1 (MAB21L1), phosphoinositide 3-kinase gamma-subunit (PIK3C2G), and clavesin-2 (CLVS2) decreased by 2.6% to 32.8%. R-spondin 1 (RSPO1), which is related to oogonia differentiation and developmental angiogenesis, was significantly downregulated in the orbital muscle tissues of patients with TAO compared with the control groups (P = 0.024). Conclusions Our results suggest that there are genetic differences in orbital adipose-connective tissues derived from TAO patients. The upregulation of the inflammatory response in orbital fat of TAO may be consistent with the clinical phenotype like eyelid edema, exophthalmos, and excess tearing. Downregulation of MAB21L1, PIK3C2G, and CLVS2 in TAO tissue demonstrates dysregulation of differentiation, oxidative stress, and developmental pathways.

Abstract The system outage probability of two‐way hybrid satellite‐terrestrial relaying networks with hardware impairments is investigated, using a novel method which features appropriate signal‐to‐noise‐and‐distortion ratio expression adjustment. A concise closed‐form lower bound expression is derived, which is in good agreement with the exact outage probability in all signal‐to‐noise ratio regions. Based on the tight bound, an asymptotic expression is obtained, revealing that the hardware impairments coin the system outage probability ceiling. The deducing method, characterized by generality, can be applicable to various realistic fading channels. Simulation results validate the derived expressions.

ObjectiveThe objective of this study was to explore the value of serum lactic dehydrogenase (LDH) in the early diagnosis and prognostic evaluation of pneumonia associated with the novel coronavirus infection.MethodsA total of 101 patients with coronavirus disease 2019 (COVID-19) pneumonia were included in the study. According to the severity of the initial chest computed tomography (CT), the patients were divided into the ordinary pneumonia group and the severe pneumonia group and then divided into the remission group and the nonremission group according to the changes of the chest CT after medication treatment. The differences in general characteristics, underlying diseases, clinical symptoms, laboratory findings, and imaging examination outcomes between groups were observed retrospectively. To analyze the diagnostic performance of LDH, receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was calculated.ResultsCompared with ordinary pneumonia patients, patients in the severe group presented with significantly higher LDH, neutrophil count, high-sensitivity troponin T (HS-TnT), C-reactive protein (CRP), human serum amyloid A (SAA), N-terminal pro-brain natriuretic peptide (NTproBNP), and D-dimer. Compared with remission patients, non-remission patients presented with significantly higher LDH, neutrophil count, HS-TnT, CRP, SAA, procalcitonin (PCT), creatine kinase–MB mass (CKMB_M), NTproBNP, and D-dimer. In multivariate logistic regression analysis, we found that LDH [odds ratio (OR), 1.015; 95% confidence interval (CI), 1.006–1024; p = 0.001] and neutrophil count (OR, 1.352; 95% CI, 1.008–1.811; p = 0.044) were independently associated with exacerbation in COVID-19 patients. For ROC analysis, the AUC was 0.833 (95% CI, 0.729–0.936; p < 0.001) when we use the LDH value of 256.69 U/L to discriminate the ordinary pneumonia and severe pneumonia patients. The AUC was 0.759 (95% CI, 0.603–0.914; p = 0.008) and the sensitivity is 92.3% when we combined the LDH (cutoff value 258.46 U/L) and the neutrophil count (cutoff value 6.76 × 109/L) to discriminate remission and non-remission patients.ConclusionThe level of LDH is associated with the severity of COVID-19 pneumonia and can be used as important indicators to evaluate the prognosis of patients.

The neuronal differentiation of mesenchymal stem cells offers a new strategy for the treatment of neurological disorders. Thus, there is a need to identify a noninvasive and sensitive in vivo imaging approach for real-time monitoring of transplanted stem cells. Our previous study confirmed that magnetic resonance imaging, with a focus on the ferritin heavy chain 1 reporter gene, could track the proliferation and differentiation of bone marrow mesenchymal stem cells that had been transduced with lentivirus carrying the ferritin heavy chain 1 reporter gene. However, we could not determine whether or when bone marrow mesenchymal stem cells had undergone neuronal differentiation based on changes in the magnetic resonance imaging signal. To solve this problem, we identified a neuron-specific enolase that can be differentially expressed before and after neuronal differentiation in stem cells. In this study, we successfully constructed a lentivirus carrying the neuron-specific enolase promoter and expressing the ferritin heavy chain 1 reporter gene; we used this lentivirus to transduce bone marrow mesenchymal stem cells. Cellular and animal studies showed that the neuron-specific enolase promoter effectively drove the expression of ferritin heavy chain 1 after neuronal differentiation of bone marrow mesenchymal stem cells; this led to intracellular accumulation of iron and corresponding changes in the magnetic resonance imaging signal. In summary, we established an innovative magnetic resonance imaging approach focused on the induction of reporter gene expression by a neuron-specific promoter. This imaging method can be used to noninvasively and sensitively detect neuronal differentiation in stem cells, which may be useful in stem cell-based therapies.

The thermal compression deformation behavior of homogenized Mg–5Zn–1Mn (wt.%) alloy was systematically investigated over the temperature and strain rate ranges of 285–345 °C and 0.001–1 s−1, respectively. The constitutive model and thermal processing diagrams were established. The microstructure evolution process and dynamic recrystallization (DRX) mechanisms were analyzed. The results demonstrate that the flow stress curves of the ZM51 alloy exhibit prominent DRX characteristics. The peak stress can be improved by decreasing the deformation temperature or increasing the strain rate. A finite element simulation is performed, and the Arrhenius constitutive model can accurately depict the plastic flow process of the alloy with strain correction, and the average activation energy is about 143.821 kJ/mol. Both the percentage DRX and the DRX grain size are found to be sensitive to the applied deformation conditions, including temperature, strain rate, and true strain. The formation of DRX grains promotes the weakness of the texture and the refinement of the grains. Grain boundaries nucleation (including discontinuous and continuous DRX) and particle-stimulated nucleation (PSN) are the main DRX mechanisms. Based on the processing map, ZM51 alloy is suitable for large plastic deformation by multi-pass forging. The optimum processing temperature is 345 °C, and as the degree of plastic deformation increases, the strain rate can be suitably increased. Local plastic flow and microcracking at grain boundaries are the primary instability mechanisms of the alloy.

Abstract Background As a widely distributed and aerial migratory bird, the Common Swift (Apus apus) flies over a wide geographic range in Eurasia and Africa during migration. Although some studies have revealed the migration routes and phenology of European populations, A. a. apus (from hereon the nominate apus), the route used by its East Asian counterpart A. a. pekinensis (from hereon pekinensis) remained a mystery. Methods Using light level geolocators, we studied the migration of adult pekinensis breeding in Beijing from 2014 to 2018, and analysed full annual tracks obtained from 25 individuals. In addition, we used the mean monthly precipitation to assess the seasonal variations in humidity for the distribution ranges of the nominate apus and pekinensis. This environmental variable is considered to be critically relevant to their migratory phenology and food resource abundance. Results Our results show that the swifts perform a round-trip journey of ca 30,000 km each year, representing a detour of 26% in autumn and 15% in spring compared to the shortest route between the breeding site in Beijing and wintering areas in semi-arid south-western Africa. Compared to the nominate apus, pekinensis experiences drier conditions for longer periods of time. Remarkably, individuals from our study population tracked arid habitat along the entire migration corridor leading from a breeding site in Beijing to at least central Africa. In Africa, they explored more arid habitats during non-breeding than the nominate apus. Conclusions The migration route followed by pekinensis breeding in Beijing might suggest an adaptation to semi-arid habitat and dry climatic zones during non-breeding periods, and provides a piece of correlative evidence indicating the historical range expansion of the subspecies. This study highlights that the Common Swift may prove invaluable as a model species for studies of migration route formation and population divergence.

Abstract Milk fat is the most important and energy-rich substance in milk, and its content and composition are important reference elements in the evaluation of milk quality. However, the current identification of valuable candidate genes affecting milk fat is limited. IlluminaPE150 was used to sequence bovine mammary epithelial cells (BMECs) with high and low milk fat rates (MFP), the weighted gene co-expression network (WGCNA) was used to analyze mRNA expression profile data in this study. As a result, a total of 10,310 genes were used to construct WGCNA, and the genes were classified into 18 modules. Among them, violet (r = 0.74), yellow (r = 0.75) and darkolivegreen (r = − 0.79) modules were significantly associated with MFP, and 39, 181, 75 hub genes were identified, respectively. Combining enrichment analysis and differential genes (DEs), we screened five key candidate DEs related to lipid metabolism, namely PI4K2A, SLC16A1, ATP8A2, VEGFD and ID1, respectively. Relative to the small intestine, liver, kidney, heart, ovary and uterus, the gene expression of PI4K2A is the highest in mammary gland, and is significantly enriched in GO terms and pathways related to milk fat metabolism, such as monocarboxylic acid transport, phospholipid transport, phosphatidylinositol signaling system, inositol phosphate metabolism and MAPK signaling pathway. This study uses WGCNA to form an overall view of MFP, providing a theoretical basis for identifying potential pathways and hub genes that may be involved in milk fat synthesis.

Abstract Maternally inherited diabetes and deafness is a rare genetic disease mainly caused by a point mutation in mitochondrial deoxyribonucleic acid. Lipoprotein lipase gene mutations are associated with familial dyslipidemias, which are difficult to manage. We reported for the first time a case that had both maternally inherited diabetes and severe hyperlipidemia caused by lipoprotein lipase gene mutation (C.347(exon3)G>C) that was resistant to fenofibrate and atorvastatin. We were able to manage the patient’s hyperlipidemia with bezafibrate, and her diabetes was well controlled with insulin. In conclusion, genetic testing is helpful in identifying rare and interesting cases when clinicians suspect inheritable diseases. Additionally, when one fibrate drug is ineffective in treating hyperlipidemia, it might be worthwhile trying another fibrate.

BackgroundMobile health (mHealth) is a promising intervention mode for HIV prevention, but little is known about its feasibility and effects in promoting pre-exposure prophylaxis (PrEP) uptake among Chinese gay, bisexual and other men who have sex with men (GBMSM).MethodsWe evaluated an instant messaging application using a WeChat-based mini-app to promote PrEP uptake among GBMSM via a mixed-methods design that includes a 12-week, two-arm randomized controlled pilot trial and in-depth progress interviews in Guangzhou, China. Primary outcomes include the number of PrEP initiations, individual-level psychosocial variables related to PrEP initiation, and usability of the PrEP mini-app.ResultsBetween November 2020 and April 2021, 70 GBMSM were successfully enrolled and randomized into two arms at 2:1 ratio (46 to the intervention arm, 24 to the control arm). By the end of 12-week follow-up, 22 (31.4%) participants completed the initial consultation and lab tests for PrEP, and 13 (18.6%) filled their initial PrEP prescription. We observed modest but non-significant improvements in participants' intention to use PrEP, actual PrEP initiation, PrEP-related self-efficacy, stigma, and attitudes over 12 weeks when comparing the mini-app and the control arms. Qualitative interviews revealed the key barriers to PrEP uptake include anticipated stigma and discrimination in clinical settings, burden of PrEP care, and limited operating hours of the PrEP clinic. In-person clinic navigation support was highly valued.ConclusionsThis pilot trial of a mobile phone-based PrEP mini-app demonstrated feasibility and identified limitations in facilitating PrEP uptake among Chinese GBMSM. Future improvements may include diversifying the content presentation in engaging media formats, adding user engagement features, and providing off-line in-clinic navigation support during initial PrEP visit. More efforts are needed to understand optimal strategies to identify and implement alternative PrEP provision models especially in highly stigmatized settings with diverse needs.Trial registrationTrial registration: The study was prospectively registered on clinicaltrials.gov (NCT04426656) on 11 June, 2020.

China's coastal wetlands provide breeding, migration stopover, and wintering habitats for about 230 waterbird species, which is more than a quarter of all waterbirds in the world. Large-scale and high intensity human activities have resulted in serious loss and degradation of coastal wetlands over the past half century, causing population declines in many waterbirds. Through a literature review and expert surveys, this article reviews conservation measures taken in recent decades to protect waterbirds in China's coastal wetlands and provides recommendations for future conservation action from three aspects: policy and administration, habitat conservation and management, and multiparty participation. Over the past decades, many conservation legislation, regulations and action plans at the national level and more site-specific measures and interventions have been implemented, with notable improvement in the effectiveness in policy making and multi-stakeholder participation. Accordingly, some threats to waterbirds have been mitigated and many key sites for waterbirds have been designated as strictly protected nature reserves. However, some critical issues still remain, mostly related to habitat conservation and management, such as coastal wetland restoration, control of invasive Spartina alterniflora, control of environmental pollution, and improvement of artificial habitat quality. We highlight that protecting natural tidal wetlands and improving habitat quality are critical for the conservation of coastal waterbirds, especially those highly dependent on the intertidal wetlands. China has demonstrated strong commitment to ecological conservation and restoration for the future, in terms of both funding and policies for biodiversity and wetland ecosystems. It is important that this commitment to conserve coastal waterbirds is supported continuously by science- and evidence-based decisions and actions.

BackgroundMilk fat is one of the main reference elements for evaluating milk quality and is a primary objective trait in dairy cattle breeding. In recent years, circular RNAs (circRNAs) have been found to play crucial roles in many biological processes. However, the function and expression profiles of circRNAs in milk fat synthesis in cows are not completely understood. We performed RNA sequencing to analyze the genome-wide expression of circRNA transcripts in bovine mammary epithelial cells (BMECs) from cows with extreme differences in milk fat percentage. We identified candidate differential circRNAs associated with milk fat metabolism using functional enrichment analysis and constructed a lipid metabolism-related competing endogenous RNA (ceRNA) interactive regulatory network.ResultsA total of 290 circRNAs were significantly differentially expressed (DE-circRNAs) in high milk fat percentage (HMF) cows compared to that in low milk fat percentage (LMF) cows. Of the 290 circRNAs, 142 were significantly upregulated and 148 were significantly downregulated. Enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) identified four DE-circRNAs (circ_0001122, circ_0007367, circ_0018269, and circ_0015179) that potentially regulate milk fat metabolism. Among them, circ_0001122, circ_0007367, and circ_0015179 had relatively high expression levels in cow mammary gland tissue compared to other tissues (heart, liver, kidney, uterus, ovaries, and small intestine) of cows. The regulatory networks circ_0001122:miR-12043:LIPG, circ_0007367:miR-331-3p:CIDEA/PML, and circ_0018269:miR-11989:RORC/HPX are potential networks to explore the mechanism of milk fat regulation.ConclusionsThese results reveal the possible role of circRNAs in milk fat metabolism in dairy cows. Several important circRNAs and ceRNAs affecting milk fat synthesis were identified, providing insights into the complex biology of milk fat synthesis as well as a novel theoretical perspective for future research on lactation, milk quality, and breed improvement in dairy cows.

The liver plays a key role in keeping the homeostasis of glucose and lipid metabolism. Insulin resistance of the liver induced by extra glucose and lipid ingestion contributes greatly to chronic metabolic disease, which is greatly threatening to human health. The small peptide, VLPVPQK, originating from casein hydrolysates of milk, shows various health-promoting functions. However, the effects of VLPVPQK on metabolic disorders of the liver are still not fully understood. Therefore, in the present study, the effects and regulatory mechanism of VLPVPQK on insulin-resistant HepG2 cells was further investigated. The results showed that VLPVPQK exerted strong scavenging capacities against various free radicals, including oxygen radicals, hydroxyl radicals, and cellular reactive oxygen species. In addition, supplementation of VLPVPQK (62.5, 125, and 250 μM) significantly reversed the high glucose and fat (30 mM glucose and 0.2 mM palmitic acid) induced decrement of glucose uptake in HepG2 cells without affecting cell viability. Furthermore, VLPVPQK intervention affected the transcriptomic profiling of the cells. The differentially expressed (DE) genes (FDR < 0.05, and absolute fold change (FC) > 1.5) between VLPVPQK and the model group were mostly enriched in the carbohydrate metabolism-related KEGG pathways. Interestingly, the expression of two core genes (HKDC1 and G6PC1) involved in the above pathways was dramatically elevated after VLPVPQK intervention, which played a key role in regulating glucose metabolism. Furthermore, supplementation of VLPVPQK reversed the high glucose and fat-induced depression of AKR1B10. Overall, VLPVPQK could alleviate the metabolic disorder of hepatocytes by elevating the glucose uptake and eliminating the ROS, while the HKDC1 and AKR1B10 genes might be the potential target genes and play important roles in the process.

Functional cells in embryonic myogenesis and postnatal muscle development undergo multiple stages of proliferation and differentiation, which are strict procedural regulation processes. N6-methyladenosine (m6A) is the most abundant RNA modification that regulates gene expression in specific cell types in eukaryotes and regulates various biological activities, such as RNA processing and metabolism. Recent studies have shown that m6A modification-mediated transcriptional and post-transcriptional regulation plays an essential role in myogenesis. This review outlines embryonic and postnatal myogenic differentiation and summarizes the important roles played by functional cells in each developmental period. Furthermore, the key roles of m6A modifications and their regulators in myogenesis were highlighted, and the synergistic regulation of m6A modifications with myogenic transcription factors was emphasized to characterize the cascade of transcriptional and post-transcriptional regulation during myogenesis. This review also discusses the crosstalk between m6A modifications and non-coding RNAs, proposing a novel mechanism for post-transcriptional regulation during skeletal muscle development. In summary, the transcriptional and post-transcriptional regulatory mechanisms mediated by m6A and their regulators may help develop new strategies to maintain muscle homeostasis, which are expected to become targets for animal muscle-specific trait breeding and treatment of muscle metabolic diseases.

Background and PurposeIntraspinal tuberculoma is a rare disease in children, and its imaging findings have been described in only a few case reports. This study aimed to investigate the magnetic resonance imaging (MRI) features of pediatric intraspinal tuberculoma and to explore the possible pathogenesis of the disease.Materials and MethodsThe clinical and MRI data of 24 child patients with intraspinal tuberculoma (such as 6 cases of intramedullary tuberculoma, 8 cases of intradural extramedullary tuberculoma, and 10 cases of epidural tuberculoma) were retrospectively analyzed. All patients underwent plain and contrast-enhanced MR scans. The diagnosis was confirmed by surgical pathology or by antituberculous treatment and follow-up data.ResultsIntramedullary tuberculoma had a round shape, while intradural extramedullary tuberculoma and epidural tuberculoma presented long-fusiform or en plaque shapes. Regarding MRI signals, intramedullary tuberculoma and extramedullary tuberculoma were mainly isointense on T1-weighted imaging (T1WI) and hypointense or isointense on T2WI. Rim enhancement was observed in intramedullary tuberculoma, and marked homogeneous enhancement was dominant in extramedullary tuberculoma. Ten (10/24) tuberculomas occurred during antituberculous therapy, with intradural extramedullary tuberculoma accounting for 7 cases (7/8), which was significantly more frequent than intramedullary tuberculoma (1/6) or epidural tuberculoma (2/10).ConclusionMRI is important in the diagnosis of intraspinal tuberculoma, which is characterized by isointensity on T1WI, isointensity, or hypointensity on T2WI, and rim or obvious homogeneous enhancement. Some intraspinal tuberculomas, especially intradural extramedullary tuberculomas, might be associated with the “paradoxical response” mechanism during the tuberculosis treatment.

Introduction The large number of key populations in China who would benefit from HIV pre-exposure prophylaxis (PrEP) in the context of limited health system capacity and public awareness will pose challenges for timely PrEP scale-up, suggesting an urgent need for innovative and accessible interventions. This study aims to develop and pilot test a theory-informed, tailored mobile phone intervention that was codeveloped by young gay men, HIV clinicians and public health researchers to increase engagement in PrEP education and initiation among Chinese gay, bisexual and other men who have sex with men (GBMSM), who bear a disproportionate burden of HIV infections and remain underserved in the healthcare system.Methods and analysis This two-phase study includes a formative assessment using in-depth interviews (N=30) and a 12-week experimental pilot study using a two-arm randomised controlled trial design (N=70). The primary intervention is delivered through a WeChat-based mini-app (a program built into a Chinese multipurpose social media application) developed by young GBMSM from a 2019 crowdsourcing hackathon. Using mixed methods, we will further investigate the specific needs and concerns among GBMSM in terms of using PrEP as an HIV prevention strategy, how their concerns and PrEP use behaviours may change with exposure to the mini-app intervention during the study period and how we can further refine this intervention tool to better meet GBMSM’s needs for broader implementation.Ethics and dissemination This study and its protocols have been reviewed and approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill, USA (19-3481), the Guangdong Provincial Dermatology Hospital, China (2020031) and the Guangzhou Eighth People’s Hospital, China (202022155). Study staff will work with local GBMSM community-based organisations to disseminate the study results to participants and the community via social media, workshops and journal publications.Trial registration number The study was prospectively registered on clinicaltrials.gov (NCT04426656) on 11 June 2020.

Pentacyclic triterpenoids (PTs) functionalized at the D/E rings possess a wide spectrum of biological activities but are poorly accessible. Here, the authors report a site-selective C-H hydroxylation at the D/E rings of PTs by exploiting transient pyridine-imino directing groups and disclose the synthesis of related natural products.

Long noncoding RNAs (lncRNAs) play an important regulatory role in various biological processes as a key regulatory factor. However, the complete expression profile of lncRNAs in dairy cows and its function in milk fat synthesis are unknown. In this study, RNA sequencing (RNA-seq) was used to research the whole genome expression of lncRNAs and mRNA transcripts in high and low milk fat percentage (MFP) bovine mammary epithelial cells (BMECs), and joint analysis was carried out. We identified a total of 47 differentially expressed genes (DEGs) and 38 differentially expressed lncRNAs (DELs, Padj

As one of the most sensitive regions to global climate change, Tibet is subject to remarkable changes in biota over the past decades, including endemic fish species. However, no study has attempted to predict the changes in the distribution of Tibetan fishes, leaving a great blank for aquatic conservation in Tibet. Based on the Maximum Entropy model (MaxEnt), this study predicted the changes in the suitable habitats of three endemic fish species, including two species mainly inhabiting the rivers (Glyptosternon maculatum, Oxygymnocypris stewartii) and one species mainly inhabiting lakes (Gymnocypris selincuoensis) in Tibet under two representative concentration pathways (RCP2.6 and RCP8.5) under two future scenarios (2050 and 2090), and explored the impact of the barrier effects of hydropower projects on the suitable habitats of fish. The results showed that under the four scenarios, the net change in the suitable habitats of the G. maculatum was negative (−2.0–−18.8%), while the suitable habitats of the O. stewartii and G. selincuoensis would be expanded, with the net change of 60.0–238.3% and 46.4–56.9%, respectively. Under different scenarios, the suitable habitats of the three species had a tendency to migrate to a higher elevation, and the largest expansion in the range of migration was projected to occur under the 2090-RCP8.5 scenario. In addition, due to the impact of the hydropower projects, the ability of G. maculatum to obtain new suitable habitats from climate change would be reduced by 2.0–8.1%, which was less than the loss induced by climate change (5.5–25.1%), while the suitable habitats of O. stewartii would be reduced by 3.0–9.7%, which was more than the impact of climate change (about 1%). The results of this study have guiding significance for the conservation and management of fish resources diversity in the Yarlung Tsangpo River basin and Siling Co basin of Tibet, and also provide a reference for the coordination and scientific planning of hydropower projects in Tibet.

Milk fat is the most important and energy-rich substance in milk and plays an important role in the metabolism of nutrients during human growth and development. It is mainly used in the production of butter and yogurt. Milk fat not only affects the flavor and nutritional value of milk, but also is the main target trait of ruminant breeding. There are many key genes involve in ruminant milk fat synthesis, including ACSS2, FASN, ACACA, CD36, ACSL, SLC27A, FABP3, SCD, GPAM, AGPAT, LPIN, DGAT1, PLIN2, XDH, and BTN1A1. Taking the de novo synthesis of fatty acids (FA) and intaking of long-chain fatty acids (LCFA) in blood to the end of lipid droplet secretion as the mainline, this manuscript elucidates the complex regulation model of key genes in mammary epithelial cells (MECs) in ruminant milk fat synthesis, and constructs the whole regulatory network of milk fat synthesis, to provide valuable theoretical basis and research ideas for the study of milk fat regulation mechanism of ruminants.

Cow mastitis, with high incidence rate and complex cause of disease, is one of the main diseases that affect the development of dairy industry in the world. Clinical mastitis and subclinical mastitis caused by Staphylococcus aureus, Escherichia coli, Streptococcus, and other pathogens have a huge potential safety hazard to food safety and the rapid development of animal husbandry. The economic loss caused by cow mastitis is billions of dollars every year in the world. In recent years, the omics technology has been widely used in animal husbandry with the continuous breakthrough of sequencing technology and the continuous reduction of sequencing cost. For dairy cow mastitis, the traditional diagnostic technique, such as histopathological screening, somatic cell count, milk pH test, milk conductivity test, enzyme activity test, and infrared thermography, are difficult to fully and comprehensively clarify its pathogenesis due to their own limitations. Metabolomics technology is an important part of system biology, which can simultaneously analyze all low molecular weight metabolites such as amino acids, lipids, carbohydrates under the action of complex factors including internal and external environment and in a specific physiological period accurately and efficiently, and then clarify the related metabolic pathways. Metabolomics, as the most downstream of gene expression, can amplify the small changes of gene and protein expression at the level of metabolites, which can more fully reflect the cell function. The application of metabolomics technology in cow mastitis can analyze the hetero metabolites, identify the related biomarkers, and reveal the physiological and pathological changes of cow mammary gland, so as to provide valuable reference for the prediction, diagnosis, and treatment of mastitis. The research progress of metabolomics technology in cow mastitis in recent years was reviewed, in order to provide guidance for the development of cow health and dairy industry safety in this manuscript.

A screw pile is a special-shaped pile with several advantages, including good bearing capacity, economy, and rapid construction. The calculation of the screw piles’ ultimate bearing capacity in the individual bearing failure state remains controversial. To address the problems of an unclear failure mechanism and the pile–soil contact relationship in screw piles, we conducted large-scale direct shear tests using a partial amplification method. The variation law for soil stress and the failure pattern of soil around the screw teeth were analyzed. The bearing capacity of the screw shear plate with screw teeth was found to be significantly higher than that of the plane shear plate, while that of the screw pile first increased and then decreased with an increase in the screw pitch. The optimal screw pitch allowed the determination of the maximum bearing capacity. Furthermore, the optimal screw pitch was generally equal to the critical screw pitch, which distinguished the individual bearing failure from the cylindrical shearing failure. A new calculation method for the critical screw pitch and ultimate bearing capacity in the individual bearing failure state was presented, and its rationality was proved using the direct shear test results. The calculation of the critical screw pitch considers the shear strength of soil and the geometric parameters of the screw teeth, making it more widely applicable. These results can provide a theoretical basis for the subsequent design of screw piles.

Energy storage systems have aroused public interest because of the blooming development of intermittent renewable energy sources. Vanadium redox flow batteries (VRFBs) are the typical candidates owing to their flexible operation and good cycle durability. However, due to the usage of perfluorinated separator membranes, VRFBs suffer from both high cost and serious vanadium ions cross penetration. Herein, we fabricate a series of low-budget and high-performance blend membranes from polyvinylpyrrolidone (PVP) and cardo-poly(etherketone) (PEKC) for VFRB. A PEKC network gives the membrane excellent mechanical rigidity, while PVP endows the blend membranes with superior sulfonic acid uptake owing to the present N-heterocycle and carbonyl group in PVP, resulting in low area resistance. Meanwhile, blend membranes also display low vanadium ion permeability resulting from the electrostatic repulsion effect of protonated PVP polymer chains towards vanadium ions. Consequently, the 50%PVP-PEKC membrane has a high ionic selectivity of 1.03 × 106 S min cm−3, while that of Nafion 115 is nearly 17 times lower (6.03 × 104 S min cm−3). The VRFB equipped with 50%PVP-PEKC membrane has high coulombic efficiencies (99.3–99.7%), voltage efficiencies (84.6–67.0%) and energy efficiencies (83.9–66.8%) at current densities of 80–180 mA cm−2, and possesses excellent cycle constancy, indicating that low-cost x%PVP-PEKC blend membranes have a great application potentiality for VRFBs.

Dairy cow longevity is an essential economic trait that can supplement the breeding value of production traits, which is related to the herd time and lifetime milk yield of dairy cows. However, longevity is a relatively difficult trait to select for dairy cow breeding due to low heritability and numerous influence factors of the longevity in dairy cows. Longevity trait has been used as an important breeding target of a comprehensive selection index in many dairy developed countries; however, it has not been included in performance index in many developing countries. At present, cows in these countries are still in the primary stage of “large quantity, low quality, high cost, and low yield.” The average parity of dairy cows is less than 2.7, which is difficult to maintain the production efficiency to meet the demands of the dairy industry. Therefore, there is an urgent need to select and breed for the longevity of dairy cows. The various definitions and models (including linear, threshold, random regression, sire, and survival analysis) of longevity were reviewed and standardized. Survival analysis is the optimal model to evaluate longevity, and the longevity heritability is 0.01–0.30 by using different definitions and models. Additionally, the relationship between longevity and other traits was summarized, and found that longevity was regulated by multiple factors, and there were low or medium genetic correlations between them. Conformation traits, milk production traits, reproductive traits, and health traits may be used as indicators to select and breed the longevity of dairy cows. The genetic assessment methods, heritability, influencing factors, importance, breeding, and genetics of longevity were reviewed in the manuscript, which could provide a valuable reference for the selective breeding to extend the productive life of Holstein cattle.

Background. The prognostic nutritional index (PNI) has been reported to significantly correlate with poor survival and postoperative complications in patients with various diseases, but its relationship with mortality in COVID-19 patients has not been addressed. Method. A multicenter retrospective study involving patients with severe COVID-19 was conducted to investigate whether malnutrition and other clinical characteristics could be used to stratify the patients based on risk. Results. A total of 395 patients were included in our study, with 236 patients in the training cohort, 59 patients in the internal validation cohort, and 100 patients in the external validation cohort. During hospitalization, 63/236 (26.69%) and 14/59 (23.73%) patients died in the training and validation cohorts, respectively. PNI had the strongest relationships with the neutrophil-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level but was less strongly correlated with the CURB65, APACHE II, and SOFA scores. The baseline PNI score, platelet (PLT) count, LDH level, and PaO2/FiO2 (P/F) ratio were independent predictors of mortality in COVID-19 patients. A nomogram incorporating these four predictors showed good calibration and discrimination in the derivation and validation cohorts. A PNI score less than 33.405 was associated with a higher risk of mortality in severe COVID-19 patients in the Cox regression analysis. Conclusion. These findings have implications for predicting the risk of mortality in COVID-19 patients at the time of admission and provide the first direct evidence that a lower PNI is related to a worse prognosis in severe COVID-19 patients.

Fulminant type 1 diabetes mellitus (FT1DM) has received clinical attention for its low incidence and poor prognosis. Currently, few cases of FT1DM are associated with pregnancy in clinical practice, but it poses a great threat to the life of mothers and infants. Here, we present two cases of FT1DM in pregnancy. In Case 1, the patient was a 26-year-old woman who was admitted to the hospital with reduced fetal movement. She was diagnosed with FT1DM and delivered a dead female fetus. Lispro and lantus were administered to control blood glucose, and lipoic acid for antioxidant therapy. In Case 2, the patient was a 28-year-old woman who developed nausea, vomiting, diarrhea, and polydipsia, which later proved to be FT1DM. An abortion was induced and blood glucose levels were controlled using an insulin pump. All physicians should be aware of this disease in order to provide prompt diagnosis and emergency treatment, thus improving maternal prognosis. We suggest that plasma glucose/hemoglobin A1C ratio be adopted as a new clinical parameter in predicting FT1DM.

In this paper, we propose a new technique to generate a range-angle dependent transmit beampattern by introducing a nonlinear frequency modulation scheme based on arctangent function in the frequency diverse array (FDA) system. The propagation process of the transmitted signals is usually neglected in most of the existing range-angle dependent transmit beampattern synthesis schemes. More specifically, the time variable is considered to be a constant value or defined from 0 to T, where Tis the pulse duration for pulsed FDA. As a result, such schemes cease to focus the signal power at a desired position for a period of time when this practical constraint is taken into account. The proposed methodology incorporates the propagation process of the transmitted signal and simultaneously focuses the signal power at a desired position and lasting for a period of time. We investigate the consequences of this constraint briefly and also explain the corrected model. Numerical simulations are implemented to validate the theoretical analysis of the proposed methodology.

Saikosaponin A (SSa) and D (SSd) are typical oleanane-type saponins featuring a unique 13,28-epoxy-ether moiety at D ring of the aglycones, which exhibit a wide range of biological and pharmacological activities. Herein, we report the first synthesis of saikosaponin A/D (1–2) and their natural congeners, including prosaikosaponin F (3), G (4), saikosaponin Y (5), prosaikogenin (6), and clinoposaponin I (7). The present synthesis features ready preparation of the aglycones of high oxidation state from oleanolic acid, regioselective glycosylation to construct the β-(1→3)-linked disaccharide fragment, and efficient gold(I)-catalyzed glycosylation to install the glycans on to the aglycones.

In this study, we examined correlations between the deposition of inosine monophosphate (IMP) and mRNA expression of the adenylate kinase 1 (AK1) gene in Jingyuan chicken. The IMP content was determined by high-performance liquid chromatography. Transcriptome sequencing was used to screen the differentially expressed gene AK1 and real-time quantitative polymerase chain reaction (PCR) to determine the expression level of AK1 mRNA associated with IMP synthesis. IMP and inosine content in the breast muscles of both Jingyuan cocks and hens was found to be significantly higher than that in the leg muscles. Similarly, the expression of AK1 mRNA in the breast muscles of cocks and hens was significantly higher than that in the leg muscles. Moreover, AK1 mRNA expression in cock breast muscles was negatively correlated with IMP content, whereas its expression in cock leg muscles was positively correlated with IMP content. In contrast, the expression of AK1 mRNA in hen breast and leg muscles was significantly positively correlated with IMP content. These findings provide a scientific basis for enhancing the meat flavor of Jingyuan chicken and promoting the development and utilization of local variety resources, as well as constituting a basis for screening IMP-regulated genes. Our study will advance our current understanding of AK1 function.

The migration routes of red‐necked phalaropes breeding around the Bering Sea are poorly known, despite the fact that the Bering Sea could mark the boundary between the East Palearctic populations that winter in the Pacific Ocean around the East Indies and the West Nearctic populations that winter in the Pacific Ocean off the coast of South America. Geolocator data retrieved from two male phalaropes tagged in southern Chukotka, Far Eastern Russia, confirm that birds breeding in this region belong to the East Palearctic population and winter in the East Indies, suggesting that the division line with the West Nearctic population is farther to the east. The routes taken by the two phalaropes were almost entirely pelagic, totaling around 18 000–20 000 km round‐trip, with the birds continuously on the move during migration, rather than resident in any particular stopover site, contrary to most other migratory shorebirds.