A highly stretchable smart dressing for wound infection monitoring and treatment.

Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.

Simulated skin model for in vitro evaluation of insertion performance of microneedles: design, development, and application verification.

Microneedles, as a new efficient and safe transdermal drug delivery technology, has a wide range of applications in drug delivery, vaccination, medical cosmetology, and diagnostics. The degree of microneedles penetration into the skin determines the reliability of the delivery dose, but its evaluation is not yet well-established, which is one of the major constraints in the commercialization of microneedles. In this paper, a novel visual simulated skin model was developed with reference to the physical properties of real skin. The simulated skin model was well-designed and its prescription was optimized to make the thickness, hardness, elasticity, and other parameters close to those of real skin. It not only meets the need to assess the degree of insertion of microneedles but also provides a visual observation of the insertion state of microneedles.

Genome-wide association study for cashmere traits in Inner Mongolia cashmere goat population reveals new candidate genes and haplotypes.

BACKGROUND: The cashmere goat industry is one of the main pillars of animal husbandry in Inner Mongolia Autonomous Region, and plays an irreplaceable role in local economic development. With the change in feeding methods and environment, the cashmere produced by Inner Mongolia cashmere goats shows a tendency of coarser, and the cashmere yield can not meet the consumption demand of people. However, the genetic basis behind these changes is not fully understood. We measured cashmere traits, including cashmere yield (CY), cashmere diameter (CD), cashmere thickness (CT), and fleece length (FL) traits for four consecutive years, and utilized Genome-wide association study of four cashmere traits in Inner Mongolia cashmere goats was carried out using new genomics tools to infer genomic regions and functional loci associated with cashmere traits and to construct haplotypes that significantly affect cashmere traits. RESULTS: We estimated the genetic parameters of cashmere traits in Inner Mongolia cashmere goats. The heritability of cashmere yield, cashmere diameter, and fleece length traits of Inner Mongolia cashmere goats were 0.229, 0.359, and 0.250, which belonged to the medium heritability traits (0.2 ~ 0.4). The cashmere thickness trait has a low heritability of 0.053. We detected 151 genome-wide significantly associated SNPs with four cashmere traits on different chromosomes, which were very close to the chromosomes of 392 genes (located within the gene or within ± 500 kb). Notch3, BMPR1B, and CCNA2 have direct functional associations with fibroblasts and follicle stem cells, which play important roles in hair follicle growth and development. Based on GO functional annotation and KEGG enrichment analysis, potential candidate genes were associated with pathways of hair follicle genesis and development (Notch, P13K-Akt, TGF-beta, Cell cycle, Wnt, MAPK). We calculated the effective allele number of the Inner Mongolia cashmere goat population to be 1.109-1.998, the dominant genotypes of most SNPs were wild-type, the polymorphic information content of 57 SNPs were low polymorphism (0 < PIC < 0.25), and the polymorphic information content of 79 SNPs were moderate polymorphism (0.25 < PIC < 0.50). We analyzed the association of SNPs with phenotypes and found that the homozygous mutant type of SNP1 and SNP3 was associated with the highest cashmere yield, the heterozygous mutant type of SNP30 was associated with the lowest cashmere thickness, the wild type of SNP76, SNP77, SNP78, SNP80, and SNP81 was associated with the highest cashmere thickness, and the wild type type of SNP137 was associated with the highest fleece length. 21 haplotype blocks and 68 haplotype combinations were constructed. Haplotypes A2A2, B2B2, C2C2, and D4D4 were associated with increased cashmere yield, haplotypes E2E2, F1F1, G5G5, and G1G5 were associated with decreased cashmere fineness, haplotypes H2H2 was associated with increased cashmere thickness, haplotypes I1I1, I1I2, J1J4, L5L3, N3N2, N3N3, O2O1, P2P2, and Q3Q3 were associated with increased cashmere length. We verified the polymorphism of 8 SNPs by KASP, and found that chr7_g.102631194A > G, chr10_g.82715068 T > C, chr1_g.124483769C > T, chr24_g.12811352C > T, chr6_g.114111249A > G, and chr6_g.115606026 T > C were significantly genotyped in verified populations (P < 0.05). CONCLUSIONS: In conclusion, the genetic effect of single SNP on phenotypes is small, and SNPs are more inclined to be inherited as a whole. By constructing haplotypes from SNPs that are significantly associated with cashmere traits, it will help to reveal the complex and potential causal variations in cashmere traits of Inner Mongolia cashmere goats. This will be a valuable resource for genomics and breeding of the cashmere goat.

Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor ß-mediated mitochondrial malfunction.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

The shift in the spatiotemporal relationship between supply and demand of ecosystem services and its drivers in China.

In China, over 65% of human activities are concentrated in cities, resulting in a conflict between the supply and demand of ecosystem services (ESs). To alleviate this problem, many cities have adopted eco-friendly development modes, however, the effectiveness of these models in reducing ESs supply-demand conflicts has not been comprehensively reviewed, and the human and natural drivers behind these relationship shifts remain unclear. To bridge this gap, this study analyzed the shifts in the relationships between supply and demand of ESs across China from 2010 to 2020 at a city level, as well as identified the human and natural drivers behind them. Firstly, the InVEST models were integrated with socioeconomic data to evaluate the supply and demand distribution for three pivotal ESs: water yield (WY), habitat quality (HQ), and soil retention (SR). Then, a four-quadrant diagram approach was proposed to enhance the analysis of their spatiotemporal relationships. Furthermore, random forest models were employed to examine the drivers of the shifts in these relationships. The results showed that WY and SR services witnessed growth until 2015, and then receded, while HQ saw a modest decline from 2010 to 2020. Spatial synergies in the supply and demand of ESs were primarily observed in the southern cities, with a significant northward extension by 2020. From a temporal perspective, the percentage of cities achieving coordination in WY and SR services increased from 32.6% to 57.3%, respectively, in the 2010-2015 period to 42.4% and 63.3% between 2015 and 2020, meanwhile, HQ service conflicts diminished from 58.7% to 53.5%. The changes in socioeconomic and land use factors contributed to 64.3%, 36.1%, and 33.3% of the shifts in the supply-demand relationship for HQ, WY, and SR services, respectively. Our analysis highlights the potential of human-driven ecological management to enhance the balance of this relationship. It can support the design of city-specific policies that foster a balance between ecological processes and socio-economic development.

Enhanced immune reconstitution with albuvirtide in HIV-infected immunological non-responders.

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.

Sevoflurane and Propofol Co-affect the Development of Colorectal Cancer by Regulating TM2D1.

AIMS: Sevoflurane and propofol are the most commonly used anesthetics in surgery. In this study, we aim to explore and clarify the function of sevoflurane and propofol in colorectal cancer. METHODS: Cell counting kit-8, colony formation, western blot, and transwell assays were performed to determine cell proliferation, apoptosis, ferroptosis, invasion, and migration. We performed overexpression experiments to detect the underlying molecular mechanism of sevoflurane and propofol. The genes related to epithelial-mesenchymal transition were measured by western blot. RESULTS: We discovered that sevoflurane and propofol co-treatment exerted more anti-tumor activities than just sevoflurane or propofol treatment in colorectal cancer cells in vitro. Mechanistically, our data showed that sevoflurane and propofol-induced apoptosis and ferroptosis and inhibited cell proliferation, invasion, and migration. Additionally, TM2D1 was considered a target of sevoflurane and propofol, and TM2D1 overexpression reversed the effect of sevoflurane and propofol on colorectal cancer cell biology behaviors. CONCLUSION: Our results showed a novel anti-tumor mechanism of sevoflurane and propofol in colorectal cancer cells, and TM2D1 might be an underlying therapeutic target for treating colorectal cancer patients.

Reduced doses of emicizumab achieve good efficacy: Results from a national-wide multicentre real-world study in China.

INTRODUCTION: Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear. AIM: This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real-world setting. METHODS: We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures. RESULTS: In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0-30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0-4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0-12.0) and 4.2 (3.0-6.0) mg/kg/4 weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures. CONCLUSION: This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full-dose emicizumab is ill affordable.

Low- and moderate-intensity aerobic exercise improves the physiological acclimatization of lowlanders on the Tibetan plateau.

This study investigates whether exercise as a strategy for improving physical fitness at sea level also offers comparable benefits in the unique context of high altitudes (HA), considering the physiological challenges of hypoxic conditions. Overall, 121 lowlanders who had lived on the Tibetan Plateau for >2 years and were still living at HA during the measurements were randomly classified into four groups. Each individual of the low-intensity (LI), moderate-intensity (MI), and high-intensity (HI) groups performed 20 sessions of aerobic exercise at HA (3680 m) over 4 weeks, while the control group (CG) did not undergo any intervention. Physiological responses before and after the intervention were observed. The LI and MI groups experienced significant improvement in cardiopulmonary fitness (0.27 and 0.35 L/min increases in peak oxygen uptake [ V ˙ $\dot{\mathrm{V}}$ O2peak], both p < 0.05) after exercise intervention, while the hematocrit (HCT) remained unchanged (p > 0.05). However, HI exercise was less efficient for cardiopulmonary fitness of lowlanders (0.02 L/min decrease in V ˙ $\dot{\mathrm{V}}$ O2peak, p > 0.05), whereas both the HCT (1.74 %, p < 0.001) and glomerular filtration rate (18.41 mL/min, p < 0.001) increased with HI intervention. Therefore, LI and MI aerobic exercise, rather than HI, can help lowlanders in Tibet become more acclimated to the HA by increasing cardiopulmonary function and counteracting erythrocytosis.

Benefits and costs: Understanding the influence of heavy metal pollution on environmental adaptability in Strauchbufo raddei tadpoles through an energy budget perspective.

Understanding the impact of environmental pollution on organismal energy budgets is crucial for predicting adaptive responses and potential maladaptation to stressors. However, the regulatory mechanism governing the trade-off between energy intake and consumption remains largely unknown, particularly considering the diverse adaptations influenced by exposure history in realistic field conditions. In the present study, we conducted a simulated field reciprocal transplant experiment to compare the energy budget strategies of Strauchbufo raddei tadpoles exposed to heavy metal. The simulated heavy metal concentrations (0.29 mg/L Cu, 1.17 mg/L Zn, 0.47 mg/L Pb, 0.16 mg/L Cd) mirrored the actual environmental exposure concentrations observed in the field habitat. This allowed for a comparison between tadpoles with parental chronic exposure to heavy metal pollutants in their habitat and those without such exposure. Results revealed that under heavy metal exposure, tadpoles originating from unpolluted areas exhibited heightened vulnerability, characterized by reduced food intake, diminished nutrient absorption, increased metabolism cost, reduced energy reserves, and increased mortality rates. In contrast, tadpoles originating from areas with long-term heavy metal pollution demonstrated adaptive strategies, manifested through adjustments in liver and small intestine phenotypes, optimizing energy allocation, and reducing energy consumption to preserve energy, thus sustaining survival. However, tadpoles from polluted areas exhibited certain maladaptive such as growth inhibition, metabolic suppression, and immune compromise due to heavy metal exposure. In conclusion, while conserving energy consumption has proven to be an effective way to deal with long-term heavy metal stress, it poses a threat to individual survival and population development in the long run.

Genome-wide association analysis of fleece traits in Northwest Xizang white cashmere goat.

Northwest Xizang White Cashmere Goat (NXWCG) is the first new breed of cashmere goat in the Xizang Autonomous Region. It has significant characteristics of extremely high fineness, gloss, and softness. Genome-wide association analysis is an effective biological method used to measure the consistency and correlation of genotype changes between two molecular markers in the genome. In addition, it can screen out the key genes affecting the complex traits of biological individuals. The aim of this study was to analyze the genetic mechanism of cashmere trait variation in NXWCG and to discover SNP locus and key genes closely related to traits such as superfine cashmere. Additionally, the key genes near the obtained significant SNPs were analyzed by gene function annotation and biological function mining. In this study, the phenotype data of the four traits (cashmere length, fiber length, cashmere diameter, and cashmere production) were collected. GGP_Goat_70K SNP chip was used for genotyping the ear tissue DNA of the experimental group. Subsequently, the association of phenotype data and genotype data was performed using Gemma-0.98.1 software. A linear mixed model was used for the association study. The results showed that four fleece traits were associated with 18 significant SNPs at the genome level and 232 SNPs at the chromosome level, through gene annotated from Capra hircus genome using assembly ARS1. A total of 107 candidate genes related to fleece traits were obtained. Combined with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we can find that CLNS1A, CCSER1, RPS6KC1, PRLR, KCNRG, KCNK9, and CLYBL can be used as important candidate genes for fleece traits of NXWCG. We used Sanger sequencing and suitability chi-square test to further verify the significant loci and candidate genes screened by GWAS, and the results show that the base mutations loci on the five candidate genes, CCSER1 (snp12579, 34,449,796, A → G), RPS6KC1 (snp41503, 69,173,527, A → G), KCNRG (snp41082, 67,134,820, G → A), KCNK9 (14:78472665, 78,472,665, G → A), and CLYBL (12: 9705753, 9,705,753, C → T), significantly affect the fleece traits of NXWCG. The results provide a valuable basis for future research and contribute to a better understanding of the genetic structure variation of the goat.

New Insights into the Role of Mild Hypoxia in Regulating Neural Stem Cell Characteristics.

The proliferation of neural stem cells (NSCs) is precisely regulated by extracellular environmental factors. In situ hypoxia, one of the key factors involved in the regulation of NSC characteristics, has attracted increasing amounts of attention. Numerous studies have demonstrated that hypoxia can significantly promote the formation of neurospheres and the proliferation of NSCs in vitro and that intermittent hypoxia can promote the proliferation of endogenous NSCs in vivo. In this article, the effects of different concentrations of oxygen on NSC proliferation and differentiation both in vivo and in vitro are reviewed, and the potential applications of hypoxia-preconditioned NSCs, as well as research progress and challenges in the treatment of central nervous system diseases, are further summarized. Here, the critical role of oxygen in the neurogenesis of NSCs is emphasized, and insights into the use of hypoxia to regulate NSC characteristics are provided.

Multi-grained visual pivot-guided multi-modal neural machine translation with text-aware cross-modal contrastive disentangling.

The goal of multi-modal neural machine translation (MNMT) is to incorporate language-agnostic visual information into text to enhance the performance of machine translation. However, due to the inherent differences between image and text, these two modalities inevitably suffer from semantic mismatch problems. To tackle this issue, this paper adopts a multi-grained visual pivot-guided multi-modal fusion strategy with cross-modal contrastive disentangling to eliminate the linguistic gaps between different languages. By using the disentangled multi-grained visual information as a cross-lingual pivot, we can enhance the alignment between different languages and improve the performance of MNMT. We first introduce text-guided stacked cross-modal disentangling modules to progressively disentangle image into two types of visual information: MT-related visual and background information. Then we effectively integrate these two kinds of multi-grained visual elements to assist target sentence generation. Extensive experiments on four benchmark MNMT datasets are conducted, and the results demonstrate that our proposed approach achieves significant improvement over the other state-of-the-art (SOTA) approaches on all test sets. The in-depth analysis highlights the benefits of text-guided cross-modal disentangling and visual pivot-based multi-modal fusion strategies in MNMT. We release the code at https://github.com/nlp-mnmt/ConVisPiv-MNMT.

Effect of Chinese Medicine in Patients with COVID-19: A Multi-center Retrospective Cohort Study.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).

Predicting effect of anti-PD-1/PD-L1 inhibitors therapy for hepatocellular carcinoma by detecting plasma metabolite based on UHPLC-MS.

Introduction: Anti-PD-1/PD-L1 inhibitors therapy has become a promising treatment for hepatocellular carcinoma (HCC), while the therapeutic efficacy varies significantly among effects for individual patients are significant difference. Unfortunately, specific predictive biomarkers indicating the degree of benefit for patients and thus guiding the selection of suitable candidates for immune therapy remain elusive.no specific predictive biomarkers are available indicating the degree of benefit for patients and thus screening the preferred population suitable for the immune therapy. Methods: Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) considered is an important method for analyzing biological samples, since it has the advantages of high rapid, high sensitivity, and high specificity. Ultra-high-pressure liquid chromatography-mass spectrometry (UHPLC-MS) has emerged as a pivotal method for analyzing biological samples due to its inherent advantages of rapidity, sensitivity, and specificity. In this study, potential metabolite biomarkers that can predict the therapeutic effect of HCC patients receiving immune therapy were identified by UHPLC-MS. Results: A partial least-squares discriminant analysis (PLS-DA) model was established using 14 glycerophospholipid metabolites mentioned above, and good prediction parameters (R2 = 0.823, Q2 = 0.615, prediction accuracy = 0.880 and p < 0.001) were obtained. The relative abundance of glycerophospholipid metabolite ions is closely related to the survival benefit of HCC patients who received immune therapy. Discussion: This study reveals that glycerophospholipid metabolites play a crucial role in predicting the efficacy of immune therapy for HCC.

Comparison of genomic prediction methods for early growth traits of Inner Mongolia cashmere goats based on multi trait models.

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.

In vitro studies on the effects of cryopreserved platelet-rich plasma on cells related to wound healing.

Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1ß levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

What is the context? Platelet-rich plasma (PRP) is a potential bioactive material for wound healing, but using it immediately faces issues like volume, concentration, and consistency.Low-temperature freezing is a method employed to preserve PRP. However, the current understanding of the effects of the freezing-thawing process on the components of PRP and its impact on cells relevant to wound healing remains unclear.What is new? This study explores the feasibility and effectiveness of using cryopreserved PRP at −80°C for promoting wound healing. This research stands out for its focus on cellular responses and practical implications in therapeutic contexts.To understand their distinct impact on different cell types relevant to wound healing, the study meticulously examined various final concentrations of cPRP (1%, 5%, 10%).The study identified the superior effects of 5% cPRP on crucial cellular activities, notably in cell polarization, proliferation, angiogenesis, and migration.What is the impact? Low-temperature freezing can be considered an effective method for PRP preservation.Some bioactive components in cPRP exhibit subtle changes; however, these changes result in better effects on certain cell types related to healing.The study illustrates that all concentrations of cPRP effectively enhance cell proliferation, migration, and differentiation, emphasizing the comparable efficacy of cryopreserved PRP to non-cryopreserved PRP.

PCBP1 interacts with the HTLV-1 Tax oncoprotein to potentiate NF-κB activation.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma. The HTLV-1 Tax constitutively activates nuclear factor-κB (NF-κB) to promote the survival and transformation of HTLV-1-infected T cells. Despite extensive study of Tax, how Tax interacts with host factors to regulate NF-κB activation and HTLV-1-driven cell proliferation is not entirely clear. Here, we showed that overexpression of Poly (rC)-binding protein 1 (PCBP1) promoted Tax-mediated IκB kinase (IKK)-NF-κB signaling activation, whereas knockdown of PCBP1 attenuated Tax-dependent IKK-NF-κB activation. However, Tax activation of HTLV-1 long terminal repeat was unaffected by PCBP1. Furthermore, depletion of PCBP1 led to apoptosis and reduced proliferation of HTLV-1-transformed cells. Mechanistically, PCBP1 interacted and co-localized with Tax in the cytoplasm, and PCBP1 KH3 domain was indispensable for the interaction between PCBP1 and Tax. Moreover, PCBP1 facilitated the assembly of Tax/IKK complex. Collectively, our results demonstrated that PCBP1 may exert an essential effect in Tax/IKK complex combination and subsequent NF-κB activation, which provides a novel insight into the pathogenetic mechanisms of HTLV-1.

Discovery of novel melatonin-mydroxyquinoline hybrids as multitarget strategies for Alzheimer's disease therapy.

Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects human health, and current treatment strategies are far from meeting clinical needs. Inspired by multi-target drug design strategies, a series of novel natural products-based melatonin-hydroxyquinoline hybrids were designed and synthesized, targeting anti-oxidation and metal-chelating at the same time. Most of the compounds showed significant oxygen radical absorbance capacity and Aß1-42 aggregation inhibition. Moreover, the compounds possess good blood-brain barrier permeability. 6b and 6c have a good ability to alleviate oxidative stress induced by hydrogen peroxide. 6b and 6c possess metal-chelating properties with the chelation ratio being 2:1. Furthermore, 6b can significantly mitigate metal-induced Aß aggregation. This work may provide a new multi-target treatment strategy for Alzheimer's disease.

GDSL Lipase Gene HTA1 Negatively Regulates Heat Tolerance in Rice Seedlings by Regulating Reactive Oxygen Species Accumulation.

High temperature is a significant environmental stress that limits plant growth and agricultural productivity. GDSL lipase is a hydrolytic enzyme with a conserved GDSL sequence at the N-terminus, which has various biological functions, such as participating in plant growth, development, lipid metabolism, and stress resistance. However, little is known about the function of the GDSL lipase gene in the heat tolerance of rice. Here, we characterized a lipase family protein coding gene HTA1, which was significantly induced by high temperature in rice. Rice seedlings in which the mutant hta1 was knocked out showed enhanced heat tolerance, whereas the overexpressing HTA1 showed more sensitivity to heat stress. Under heat stress, hta1 could reduce plant membrane damage and reactive oxygen species (ROS) levels and elevate the activity of antioxidant enzymes. Moreover, real-time quantitative PCR (RT-qPCR) analysis showed that mutant hta1 significantly activated gene expression in antioxidant enzymes, heat response, and defense. In conclusion, our results suggest that HTA1 negatively regulates heat stress tolerance by modulating the ROS accumulation and the expression of heat-responsive and defense-related genes in rice seedlings. This research will provide a valuable resource for utilizing HTA1 to improve crop heat tolerance.