Global, regional, and national burdens of HIV/AIDS acquired through sexual transmission 1990-2019: an observational study.

Background Sexual transmission accounts for a substantial proportion of HIV infections. Although some countries are experiencing an upward trend in HIV infections, there has been a lack of studies assessing the global burden of HIV/AIDS acquired through sexual transmission. We assessed the global, regional, and national burdens of HIV/AIDS acquired through sexual transmission from 1990 to 2019. Methods Data on deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALY) of HIV/AIDS acquired through sexual transmission in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease Study (GBD) 2019. The burdens and trends were evaluated using the age-standardised rates (ASR) and estimated annual percentage change (EAPC). Results Globally, HIV/AIDS acquired through sexual transmission accounted for ~695.8 thousand (95% uncertainty interval 628.0-811.3) deaths, 33.0million (28.7-39.9) YLLs, 3.4million (2.4-4.6) YLDs, and 36.4million (32.2-43.1) DALYs in 2019. In 2019, Southern sub-Saharan Africa (11350.94), Eastern sub-Saharan Africa (3530.91), and Western sub-Saharan Africa (2037.74) had the highest ASR of DALYs of HIV/AIDS acquired through sexual transmission per 100,000. In most regions of the world, the burden of HIV/AIDS acquired through sexual transmission has been increasing from 1990 to 2019, mainly in Oceania (EAPC 17.20, 95% confidence interval 12.82-21.75), South Asia (9.00, 3.94-14.30), and Eastern Europe (7.09, 6.35-7.84). Conclusions HIV/AIDS acquired through sexual transmission results in a major burden globally, regionally, and nationally.

MTHFR as a Novel Candidate Marker for Litter Size in Rabbits.

Litter size is a significant economic trait during animal reproduction. This current study attempted to decipher whether MTHFR promotes the apoptosis of granulosa cells (GCs) and inhibits their proliferation by investigating the effects of the MTHFR gene using flow cytometry and a Cell Counting Kit-8 (CCK-8) assay. MTHFR is linked with ovarian follicle development in the reproductive performance of 104 female New Zealand rabbits. We observed that MTHFR could regulate the mRNA of follicular development-related genes (TIMP1, CITED1, FSHR, GHR, HSD17B1, and STAR) with a qRT-PCR, and we observed the protein expression of CITED1 and GHR using a western blot (WB) analysis. The dual luciferase activity assays helped identify the core promoter region of the MTHFR gene, and the polymorphism of the MTHFR promoter region was studied using Sanger sequencing. The results indicated four single nucleotide polymorphisms (SNPs) within the core promoter region, among which the g.-680C>A locus was significantly associated with both the total and alive litter sizes. Additionally, the CC genotype was associated with the largest total and alive litter sizes, compared to the CA and AA genotypes (p < 0.05). In conclusion, this study investigated the effects of MTHFR on ovarian granulosa cells and its association with selected reproductive parameters in rabbits. The results provide a theoretical foundation for the use of MTHFR as a molecular marker in rabbits.

Plasma-derived exosome miR-10a-5p promotes premature ovarian failure by target BDNF via the TrkB/Akt/mTOR signaling pathway.

Premature ovarian failure (POF) is characterized by a significant decline in the ovarian follicle pool and oocyte reserve, alongside an increase in the number of low-quality oocytes and apoptosis of granulosa cells (GCs). Exosome-derived miRNA plays a regulatory role in crucial cellular activities and contributes to the onset and progression of POF. In this study, we successfully established a rabbit model of POF and conducted in vitro and in vivo experiments that confirmed DiI-labeled Pla-Exos (exosomes derived from plasma) could enter the follicle through blood circulation, with GCs capable of uptaking these exosomes. Our RNA-seq analysis revealed elevated expression of miR-10a-5p in Pla-Exos from POF rabbits. Moreover, our findings demonstrate that exosomal miR-10a-5p suppresses GCs proliferation and induces apoptosis via the mitochondrial pathway. Additionally, exosomal miR-10a-5p inhibits the TrkB/Akt/mTOR signaling pathway by downregulating BDNF expression, thereby modulating the expression levels of proteins and genes associated with the cell cycle, follicle development, and GCs senescence. In conclusion, our study highlights the role of Pla-Exos miR-10a-5p in promoting rabbit POF through the TrkB/Akt/mTOR signaling pathway by targeting BDNF. These findings provide new insights into potential therapeutic targets for POF, offering valuable references for addressing concerns related to female reproductive function.

Global antigenic landscape and vaccine recommendation strategy for low pathogenic avian influenza A (H9N2) viruses.

The sustained circulation of H9N2 avian influenza viruses (AIVs) poses a significant threat for contributing to a new pandemic. Given the temporal and spatial uncertainty in the antigenicity of H9N2 AIVs, the immune protection efficiency of vaccines remains challenging. By developing an antigenicity prediction method for H9N2 AIVs, named PREDAC-H9, the global antigenic landscape of H9N2 AIVs was mapped. PREDAC-H9 utilizes the XGBoost model with 14 well-designed features. The XGBoost model was built and evaluated to predict the antigenic relationship between any two viruses with high values of 81.1 %, 81.4 %, 81.3 %, 81.1 %, and 89.4 % in accuracy, precision, recall, F1 value, and area under curve (AUC), respectively. Then the antigenic correlation network (ACnet) was constructed based on the predicted antigenic relationship for H9N2 AIVs from 1966 to 2022, and ten major antigenic clusters were identified. Of these, four novel clusters were generated in China in the past decade, demonstrating the unique complex situation there. To help tackle this situation, we applied PREDAC-H9 to calculate the cluster-transition determining sites and screen out virus strains with the high cross-protective spectrum, thus providing an in silico reference for vaccine recommendation. The proposed model will reduce the clinical monitoring workload and provide a useful tool for surveillance and control of H9N2 AIVs.

Clathrin mediates membrane fission and budding by constricting membrane pores.

Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles' pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles' pore closure and that clathrin around Ω-profiles' base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles' base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin's well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents' function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin's pivotal role in pore constriction/closure.

Glycerol Triacetate-Based Flame Retardant High-Temperature Electrolyte for the Lithium-Ion Battery.

Rechargeable batteries that can operate at elevated temperatures (>70 °C) with high energy density are long-awaited for industrial applications including mining, grid stabilization, naval, aerospace, and medical devices. However, the safety, cycle life, energy density, and cost of the available high-temperature battery technologies remain an obstacle primarily owing to the limited electrolyte options available. We introduce a flame-retardant electrolyte that can enable stable battery cycling at 100 °C by incorporating triacetin into the electrolyte system. Triacetin has excellent chemical stability with lithium metal, and conventional cathode materials can effectively reduce parasitic reactions and promises a good battery performance at elevated temperatures. Our findings reveal that Li-metal half-cells can be made that have high energy density, high Coulombic efficiency, and good cycle life with triacetin-based electrolytes and three different cathode chemistries. Moreover, the nail penetration test in a commercial-scale pouch battery using this new electrolyte demonstrated suppressed heat generation when the cell was damaged and excellent safety when using the triacetin-based electrolyte.

Single nucleotide polymorphisms in the KRT82 promoter region modulate irregular thickening and patchiness in the dorsal skin of New Zealand rabbits.

BACKGROUND: While rabbits are used as models in skin irritation tests, the presence of irregular patches and thickening on the dorsal skin can affect precise evaluation. In this study, genes associated with patchiness or non-patchiness on the dorsal skin of New Zealand rabbits were investigated to identify potential regulators of the patchiness phenotype. RESULTS: The results showed that parameters associated with hair follicles (HFs), such as HF density, skin thickness, and HF depth, were augmented in rabbits with the patchiness phenotype relative to the non-patchiness phenotype. A total of 592 differentially expressed genes (DEGs) were identified between the two groups using RNA-sequencing. These included KRT72, KRT82, KRT85, FUT8, SOX9, and WNT5B. The functions of the DEGs were investigated by GO and KEGG enrichment analyses. A candidate gene, KRT82, was selected for further molecular function verification. There was a significant positive correlation between KRT82 expression and HF-related parameters, and KRT82 overexpression and knockdown experiments with rabbit dermal papilla cells (DPCs) showed that it regulated genes related to skin and HF growth and development. Investigation of single nucleotide polymorphisms (SNPs) in the exons and promoter region of KRT82 identified four SNPs in the promoter region but none in the exons. The G.-631G > T, T.-696T > C, G.-770G > T and A.-873 A > C alleles conformed to the Hardy - Weinberg equilibrium, and three identified haplotypes showed linkage disequilibrium. Luciferase reporter assays showed that the core promoter region of KRT82 was located in the - 600 to - 1200 segment, in which the four SNPs were located. CONCLUSIONS: The morphological characteristics of the patchiness phenotype were analyzed in New Zealand rabbits and DEGs associated with this phenotype were identified by RNA-sequencing. The biological functions of the gene KRT82 associated with this phenotype were analyzed, and four SNPs were identified in the promoter region of the gene. These findings suggest that KRT82 may be a potential biomarker for the breeding of experimental New Zealand rabbits.

Regulation of Hair Follicle Growth and Development by Different Alternative Spliceosomes of FGF5 in Rabbits.

This study investigated the regulatory effect of alternative spliceosomes of the fibroblast growth factor 5 (FGF5) gene on hair follicle (HF) growth and development in rabbits. The FGF5 alternative spliceosomes (called FGF5-X1, FGF5-X2, FGF5-X3) were cloned. The overexpression vector and siRNA of spliceosomes were transfected into dermal papilla cells (DPCs) to analyze the regulatory effect on DPCs. The results revealed that FGF5-X2 and FGF5-X3 overexpression significantly decreased LEF1 mRNA expression (p < 0.01). FGF5-X1 overexpression significantly reduced CCND1 expression (p < 0.01). FGF5-X1 and FGF5-X2 possibly downregulated the expression level of FGF2 mRNA (p < 0.05), and FGF5-X3 significantly downregulated the expression level of FGF2 mRNA (p < 0.01). The FGF5 alternative spliceosomes significantly downregulated the BCL2 mRNA expression level in both cases (p < 0.01). FGF5-X1 and FGF5-X2 significantly increased TGFß mRNA expression (p < 0.01). All three FGF5 alternative spliceosomes inhibited DPC proliferation. In conclusion, the expression profile of HF growth and development-related genes can be regulated by FGF5 alternative spliceosomes, inhibiting the proliferation of DPCs and has an influence on the regulation of HF growth in rabbits. This study provides insights to further investigate the mechanism of HF development in rabbits via FGF5 regulation.

N-Acetylcysteine Alleviates D-Galactose-Induced Injury of Ovarian Granulosa Cells in Female Rabbits by Regulating the PI3K/Akt/mTOR Signaling Pathway.

The ovary plays a crucial role in the reproductive system of female animals. Ovarian problems such as ovarian insufficiency, premature aging, polycystic ovary syndrome, and ovarian cysts may lead to ovulation disorders, abnormal hormone secretion, or luteal dysfunction, thereby increasing the risk of infertility and abortion. Only when the ovarian function and other organs in the reproductive system remain healthy and work normally can female animals be ensured to carry out reproductive activities regularly, improve the pregnancy rate and litter size, promote the healthy development of the fetus, and then improve their economic value. The follicle, as the functional unit of the ovary, is composed of theca cells, granulosa cells (GCs), and oocytes. GCs are the largest cell population and main functional unit in follicles and provide the necessary nutrients for the growth and development of follicles. N-acetylcysteine (NAC) is a prevalent and cell-permeable antioxidant molecule that effectively prevents apoptosis and promotes cellular survival. Over the past few years, its function in boosting reproductive performance in animals at the cellular level has been widely acknowledged. However, its specific role and mechanism in influencing GCs is yet to be fully understood. The objective of this study was to examine the effects of NAC on ovarian damage in female rabbits. For this purpose, D-galactose (D-gal) was first used to establish a model of damaged GCs, with exposure to 1.5 mg/mL of D-gal leading to substantial damage. Subsequently, varying concentrations of NAC were introduced to determine the precise mechanism through which it influences cell damage. Based on the results of the Cell Counting Kit-8 assay, flow cytometry, and Western blotting, it was found that 0.5 mg/mL of NAC could significantly suppress cell apoptosis and promote proliferation. In particular, it decreased the expression levels of Bax, p53, and Caspase-9 genes, while concurrently upregulating the expression of the BCL-2 gene. Moreover, NAC was found to alleviate intracellular oxidative stress, suppress the discharge of mitochondrial Cytochrome c, and boost the enzymatic activities of CAT (Catalase), GSH (Glutathione), and SOD (Superoxide dismutase). RNA sequencing analysis subsequently underscored the critical role of the PI3K/Akt/mTOR pathway in governing proliferation and apoptosis within GCs. These findings demonstrated that NAC could significantly influence gene expression within this pathway, thereby clarifying the exact relationship between the PI3K/Akt/mTOR signaling cascade and the underlying cellular processes controlling proliferation and apoptosis. In conclusion, NAC can reduce the expression of Bax, p53, and Caspase-9 genes, inhibit the apoptosis of GCs, improve cell viability, and resist D-gal-induced oxidative stress by increasing the activity of CAT, GSH, and SOD. The molecular mechanism of NAC in alleviating D-gal-induced ovarian GC injury in female rabbits by regulating the PI3K/Akt/mTOR signaling pathway provides experimental evidence for the effect of NAC on animal reproductive function at the cellular level.

4D label-free quantitative proteomic analysis identifies CRABP1 as a novel candidate gene for litter size in rabbits†.

In commercial rabbit breeding, litter size is a crucial reproductive trait. This trait directly determines the reproductive ability of female rabbits and is crucial for evaluating the production efficiency. We here compared differentially expressed proteins of in the ovary tissue from New Zealand female rabbits with high (H) and low (L) litter sizes by using 4D label-free quantitative proteomic technology and identified 92 differential proteins. The biological functions of these proteins were revealed through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Most distributions of GO and KEGG were related to reproduction, growth development, and metabolism. Furthermore, a novel candidate gene cellular retinoic acid binding protein-1 (CRABP1), which was highly expressed in the L group, was selected for further biological function verification. The Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis revealed that CRABP1 can promote granulosa cell (GC) apoptosis and inhibit GC proliferation. Furthermore, qRT-PCR and western blotting analysis revealed that CRABP1 regulates the genes (HSD17B1, Wnt-10b, FSHR, TAF4B, BMP15, and BMP6) and protein (Wnt-10b) associated with steroid hormone synthesis and follicle development. The PCR product direct sequencing method revealed single nucleotide polymorphisms in the core promoter region of CRABP1. Luciferase activity assays revealed that the transcriptional activity of the GG genotype was significantly higher than that of the TT or TG genotype. Different genotypes are accompanied by changes in transcription factors, which indicates that T-359G polymorphism can regulate CRABP1 expression. In general, we identified litter size-related genes and revealed the mechanism underlying the effect of CRABP1 on litter size. CRABP1 serves as a key factor in the reproductive capacity of rabbits and can act as a molecular biomarker for the breeding of New Zealand rabbits.

High-efficiency recovery of valuable metals from spent lithium-ion batteries: Optimization of SO2 pressure leaching and selective extraction of trace impurities.

The recovery of valuable metals from spent lithium-ion batteries (LIBs) is crucial for environmental protection and resource optimization. In the traditional recovery process of spent LIBs, the leaching of high-valence metals has the problems of high cost and limited reagent utilization, and some valuable metals are lost in the subsequent purification process of the leaching solution. To reduce the cost of reagents, this study proposes the use of low-cost SO2 as a reagent combined with pressure leaching to efficiently recover high-valence metals from delithiated materials of spent LIBs, while selective solvent extraction is used to remove trace impurities in the leaching solution to avoid the loss of valuable metals. Experimental results demonstrated that by optimizing the conditions to 0.25 MPa SO2 partial pressure and 60 min reaction time at 70 °C, the leaching efficiencies for Ni, Co, and Mn reached 99.6%, 99.3%, and 99.6%, respectively. The kinetic study indicated that the leaching process was diffusion-controlled. Furthermore, the delithiated materials were used to completely utilize the residual SO2 in the solution to obtain a high concentration Ni-Co-Mn rich solution. Subsequently, Fe and Al impurities were deeply removed through a synergistic extraction of Di-2-ethylhexyl phosphoric acid (D2EHPA) and tributyl phosphate (TBP) without loss of valuable metals, achieving a high-purity Ni-Co-Mn solution. The process developed based on this work has the characteristics of environmental friendliness, high valuable metal recovery, and high product purity, providing a reference technical method for the synergistic treatment of waste SO2 flue gas with spent LIBs and the deep purification of impurities in spent LIBs.

ChIP-Seq analysis reveals PRKACB as a target gene of HOXC13 involved in rabbit hair follicle development.

Dermal papilla cells (DPCs) are key regulators of hair follicle (HF) development and growth, which not only regulate HF growth and cycling but play a role in the pathogenesis of hair loss. The transcription factor Homeobox C13 (HOXC13) can modulate the growth and development of HFs. Nevertheless, the specific genes and pathways regulated by HOXC13 in DPCs have yet to be determined. Thus, to gain a better understanding of genomic binding sites involved in HOXC13-regulated HF development, chromatin immunoprecipitation followed by high throughput sequencing (ChIP-Seq) was performed on rabbit DPCs with pcDNA3.1-3 × Flag-HOXC13 overexpression. A complete set of 9670 enrichment peaks was acquired by applying HOXC13-Flag ChIP. Subsequently, the peak sequence was annotated to the rabbit genome, revealing that 6.1 % of the peaks were identified within in the promoter region. Thereafter, five annotated genes were verified using RT-qPCR. The peak-associated genes were mainly enriched in signaling pathways related to HF development, such as MAPK and PI3K-Akt. Furthermore, by using a dual-luciferase reporter assay, we found that HOXC13 can target the protein kinase cAMP­dependent catalytic ß (PRKACB) promoter region (-1596 âˆ¼ -1107 bp) and inhibit its transcription, which was consistent with data obtained from ChIP-seq analysis. Overexpression of PRKACB gene significantly modulated the expression of BCL2, WNT2, LEF1, and SFRP2 genes related to HF development as determined by RT-qPCR (P < 0.01, P < 0.05). The CCK-8 and flow cytometry assays showed that PRKACB significantly inhibited the proliferation of DPCs and promoted apoptosis (P < 0.01). In conclusion, our research revealed that PRKACB has the potential to serve as a novel target gene of HOXC13, contributing to the regulation of the proliferation and apoptosis of DPCs. The process of identifying global target genes can contribute to the understanding of the intricate pathways that HOXC13 regulates in the growth of HFs.

Characterization and establishment of an immortalized rabbit ovary granulosa cell line for reproductive biology experiments.

Granulosa cells (GCs) are the key components of ovarian follicles and regulate the maturation, communication, growth, and development of oocytes. GCs have great potential as human therapeutic models and in livestock breeding. In this study, we established an immortalized cell line (Im-RGCs) by transforming primary rabbit granulosa cells (Pri-RGCs) with lentivirus-mediated simian virus 40 Large T (SV40LT). Morphologically, Im-RGCs were indistinguishable from Pri-RGCs and maintained intact cell structure as observed by H&E staining. Also, Im-RGCs exhibited no significant change in cell proliferation, viability, and growth. Furthermore, GC-specific markers, such as FSHR, StAR, CYP11A1, and CYP19A1, were examined by PCR, immunofluorescence, and Western blotting. ELISA and karyotype analysis showed that Im-RGCs can synthesize steroid hormones and maintain the normal number of chromosomes during the infinite passage. Furthermore, soft-agar cloning and nude mice tumorigenic experiments indicated the absence of any malignancy transformation in Im-RGCs. In conclusion, we successfully established the immortalized granulosa cell line of rabbit follicles that can be used for biological, animal husbandry, and female reproductive research.

Global, regional, and national burden of HIV and other sexually transmitted infections in older adults aged 60-89 years from 1990 to 2019: results from the Global Burden of Disease Study 2019.

BACKGROUND: Sexually active older adults are often more susceptible to HIV and other sexually transmitted infections (STIs) due to various health conditions (especially a weakened immune system) and low use of condoms. We aimed to assess the global, regional, and national burdens and trends of HIV and other STIs in older adults from 1990 to 2019. METHODS: We retrieved data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 on the incidence and disability-adjusted life-years (DALYs) of HIV and other STIs (syphilis, chlamydia, gonorrhoea, trichomoniasis, and genital herpes) for older adults aged 60-89 years in 204 countries and territories from 1990 to 2019. Estimated annual percentage changes in the age-standardised incidence and DALY rates of HIV and other STIs, by age, sex, and Socio-demographic Index (SDI), were calculated to quantify the temporal trends. Spearman correlation analysis was used to examine the relationship between age-standardised rates and SDI. FINDINGS: In 2019, among older adults globally, there were an estimated 77 327 (95% uncertainty interval 59 443 to 97 648) new cases of HIV (age-standardised incidence rate 7·6 [5·9 to 9·6] per 100 000 population) and 26 414 267 (19 777 666 to 34 860 678) new cases of other STIs (2607·1 [1952·1 to 3440·8] per 100 000). The age-standardised incidence rate decreased by an average of 2·02% per year (95% CI -2·38 to -1·66) for HIV and remained stable for other STIs (-0·02% [-0·06 to 0·01]) from 1990 to 2019. The number of DALYs globally in 2019 was 1 905 099 (95% UI 1 670 056 to 2 242 807) for HIV and 132 033 (95% UI 83 512 to 225 630) for the other STIs. The age-standardised DALY rate remained stable from 1990 to 2019, with an average change of 0·97% (95% CI -0·54 to 2·50) per year globally for HIV but decreased by an annual average of 1·55% (95% CI -1·66 to -1·43) for other STIs. Despite the global decrease in the age-standardised incidence rate of HIV in older people from 1990 to 2019, many regions showed increases, with the largest increases seen in eastern Europe (average annual change 17·84% [14·16 to 21·63], central Asia (14·26% [11·35 to 17·25]), and high-income Asia Pacific (7·52% [6·54 to 8·51]). Regionally, the age-standardised incidence and DALY rates of HIV and other STIs decreased with increases in the SDI. INTERPRETATION: Although the incidence and DALY rates of HIV and STIs either declined or remained stable from 1990 to 2019, there were regional and demographic disparities. Health-care providers should be aware of the effects of ageing societies and other societal factors on the risk of HIV and other STIs in older adults, and develop age-appropriate interventions. The disparities in the allocation of health-care resources for older adults among regions of different SDIs should be addressed. FUNDING: Natural Science Foundation of China, Fujian Province's Third Batch of Flexible Introduction of High-Level Medical Talent Teams, Science and Technology Innovation Team (Tianshan Innovation Team) Project of Xinjiang Uighur Autonomous Region, Cure Alzheimer's Fund, Helse Sør-Øst, the Research Council of Norway, Molecule/VitaDAO, NordForsk Foundation, Akershus University Hospital, the Civitan Norges Forskningsfond for Alzheimers Sykdom, the Czech Republic-Norway KAPPA programme, and the Rosa Sløyfe/Norwegian Cancer Society & Norwegian Breast Cancer Society.

Study on changing disciplinarian of beak colors in ducks and the regulation network based on transcriptome sequencing.

Beak color in ducks is a primary characteristic of local breeds and genetic resources. Among them, black beaks, a rare packaging trait of high-quality duck products, have attracted much attention. In this study, Runzhou White Created ducks (black beak) and white-feathered Putian black ducks (yellow beak) were used to construct the F2 generation resource population to study the changing discipline of beak color combined with the beak color statistics of gray-beaked ducklings of Runzhou White Created ducks. Subsequently, transcriptome sequencing was performed to identify genetic markers related to beak color. To explore the rules of beak color change and its regulatory network, trends, and trend analysis and weighted gene co-expression network analysis（WGCNA）were performed. The screening results were verified by real-time quantitative polymerase chain reaction. A large difference was observed between the beak colors of birds from the F1 generation at 0 and 42 d of age. The F2 generation results show that nearly half of the black-beaked ducklings become green-beaked; the proportion of black spots for gray- and patterned-beaked ducklings increases with age, with most becoming green-beaked. Moreover, the beak color darkened from the first day, and the gray color value decreased significantly from the second day. Transcriptome sequencing indicated that TYR was differentially expressed between black and yellow beaks at 4 to 6 wk of age, and trend and WGCNA analyses showed that EDNRB signaling pathway genes and MITF were highly expressed in the first week, and TYR, TYRP1, and DCT were highly expressed at 4 to 6 wk of age. Therefore, there is melanin synthesis and deposition after hatching for gray- and patterned-beaked ducklings, while the yellow pigment might be deposited in the epidermis of beaks for black-beaked ducklings. The EDNRB signaling pathway is probably involved in early melanosome maturation and melanin formation in duck beaks, and genes such as TYR can maintain the black-beak phenotype.

Establishment of SLC7A11-knockout mouse and its preliminary investigation in melanoma.

Solute carrier family 7 member 11 (SLC7A11)/xCT is an amino acid transporter that mediates the cystine uptake and glutamate export, participates in several malignant tumors' progression. However, the role of SLC7A11 on the occurrence and development of melanoma still remains unclear. Here, the transcribed mRNA encoding for Cas9 and sgRNA targeting SLC7A11 in vitro were microinjected into zygotes, to establish the SLC7A11 knockout (KO) mice (SLC7A11-/-). Further, we conducted melanoma-bearing mice using the metastatic melanoma cell line (B16-F10) to observe the melanoma development. There was no off-target in KO mice detected by T7E1 cleavage assay. The results showed that the tumor volume of KO mice was significantly lower than that of SLC7A11+/+ (WT) mice at 8d, 10d, 12d, 14d, and 16d (P < 0.05). The tumors of WT appeared to more disorganized morphology, more unbalanced nuclear-cytoplasmic ratio, less defined boundary, and increased tumor necrosis. And after SLC7A11 deletion, the expression of CXCL9 and TLR6 were significantly up-regulated, and that of NOS2 and CCL8 were significantly down-regulated (P < 0.01). Additionally, Ki67 immunostaining revealed lower proliferating cells in the tumors of SLC7A11 KO mice compared to WT mice. In summary, the deletion of SLC7A11 significantly inhibited the development of melanoma. Our results provide direct evidence to identify SLC7A11 as a novel target for molecular therapy and prognosis judgment of melanoma.

Behavioral and Physiological Differences in Female Rabbits at Different Stages of the Estrous Cycle.

Estrus involves a series of complex physiological signs and changes in behavior before ovulation, which play a crucial role in animal reproduction. However, there have been few studies that evaluate behaviors during the different stages of estrus cycle in female rabbits. Therefore, more detailed information is needed on distinguishing the various stages of the estrous cycle. This study explored the behavioral and physiological differences at various estrous cycle stages in female New Zealand White rabbits. The continuous recording method was employed to record the daily behaviors of twenty postpartum female rabbits during the estrous cycle. Compared with the diestrus stage, the duration of foraging and drinking behavior in estrus decreased significantly, and the frequency of grooming and biting behaviors increased (p < 0.05). Differences in reproductive hormone levels (FSH, LH, P4, and E2) and follicle development were measured at each stage via ELISA and HE staining. The FSH and LH levels showed an increasing trend and then decreased, with the lowest being in late estrus (p < 0.05). The P4 level was the lowest in estrus (p < 0.05), and E2 showed a gradually increasing trend. There was no significant difference in the number of primordial follicles at each stage, but the number of primary follicles in estrus was significantly higher than at the other stages (p < 0.05). To further understand the molecular regulation mechanism of the estrous cycle in female rabbits, we analyzed the ovarian transcription patterns of female rabbits in diestrus (D group) and estrus (E group) employing RNA-seq. A total of 967 differentially expressed genes (DEGs) were screened from the ovaries of female rabbits between the diestrus and estrus groups. A KEGG analysis of DEGs enriched in the estrogen signaling pathway, aldosterone synthesis, and secretion pathway, such as CYP19A1 and IGF1R, was performed. The rabbits' behavior, related physiological hormones, and molecular regulation also differed at different estrous cycle stages. The results provide recommendations for the adequate management practices of postpartum re-estrus and breeding female rabbits.

Longitudinal trajectories of weight changes among people living with HIV on antiretroviral therapy: A group-based study.

Weight changes vary among people living with HIV (PLHIV) on different antiretroviral therapy (ART) regimens. Here, we performed multi-trajectory modeling fitting growth mixture models (GMM) to identify longitudinal weight change trajectories of PLHIV. Multiple logistic regression was used to assess correlates of rapid weight gains; 12,683 PLHIV (median age: 34 years [interquartile range 29-42], 91.1% male) who initiated ART at the Third People's Hospital of Shenzhen, China, between January 2003 and September 2022 were included. We identified two trajectories: slow (70.5%) and rapid weight gains (29.5%). PLHIV who initiated ART with dolutegravir- (adjusted odds ratio [aOR] 2.46, 1.92-3.15), raltegravir- (2.74, 1.96-3.82), and lopinavir (1.62, 1.36-1.94)-based regimens were more likely to have rapid weight gains compared with efavirenz-based regimen. The monitoring of nutritional status should be strengthened for PLHIV who initiated these regimens during regular ART follow-ups.

Identification of SNPs in MITF associated with beak color of duck.

Introduction: Beak color-a pigment-related trait-is an important feature of duck breeds. Recently, little research has addressed genetic mechanism of the beak colors in poultry, whereas the process and the regulation factors of melanin deposition have been well described. Methods: To investigate the genetic mechanism of beak colors, we conducted an integrated analysis of genomic selection signatures to identify a candidate site associated with beak color. For this, we used black-billed (Yiyang I meat duck synthetic line H1, H2, H3&HF) and yellow-billed ducks (Cherry Valley ducks and white feather Putian black duck). Quantitative real-time PCR and genotyping approaches were used to verify the function of the candidate site. Results: We identified 3,895 windows containing 509 genes. After GO and KEGG enrichment analysis, nine genes were selected. Ultimately, MITF was selected by comparing the genomic differentiation (FST). After loci information selection, 41 extreme significantly different loci were selected, which are all located in intron regions of MITF and are in almost complete linkage disequilibrium. Subsequently, the site ASM874695v1:10:g.17814522T > A in MITF was selected as the marker site. Furthermore, we found that MITF expression is significantly higher in black-beaked ducks than in yellow-beaked ducks of the F2 generation (p < 0.01). After genotyping, most yellow-billed individuals are found with homozygous variant; at the same time, there are no birds with homozygous variant in black-billed populations, while the birds with homozygous and heterozygous variant share the same proportion. Conclusion: MITF plays a very critical role in the melanogenesis and melanin deposition of duck beaks, which can effectively affect the beak color. The MITF site, ASM874695v1:10:g.17814522T > A could be selected as a marker site for the duck beak color phenotype.

Associations of modern initial antiretroviral therapy regimens with all-cause mortality in people living with HIV in resource-limited settings: a retrospective multicenter cohort study in China.

Despite the proven virological advantages, there remains some controversy regarding whether first-line integrase strand transfer inhibitors (INSTIs)-based antiretroviral therapy (ART) contributes to reducing mortality of people living with HIV (PLHIV) in clinical practice. Here we report a retrospective study comparing all-cause mortality among PLHIV in China who were on different initial ART regimens (nevirapine, efavirenz, dolutegravir, lopinavir, and others [including darunavir, raltegravie, elvitegravir and rilpivirine]) between 2017 and 2019. A total of 41,018 individuals were included across China, representing 21.3% of newly reported HIV/AIDS cases collectively in the country during this period. Only the differences in all-cause mortality of PLHIV between the efavirenz group and the nevirapine group, the dolutegravir group and the nevirapine group, and the lopinavir group and the nevirapine group, were observed in China. After stratifying the cause of mortality, we found that the differences in mortality between initial ART regimens were mainly observed in AIDS-related mortality.