A single-cell chromatin accessibility dataset of human primed and naïve pluripotent stem cell-derived teratoma.

Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.

VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification.

In contrast to rodents, the mechanisms underlying human trophectoderm and early placenta specification are understudied due to ethical barriers and the scarcity of embryos. Recent reports have shown that human pluripotent stem cells (PSCs) can differentiate into trophectoderm (TE)-like cells (TELCs) and trophoblast stem cells (TSCs), offering a valuable in vitro model to study early placenta specification. Here, we demonstrate that the VGLL1 (vestigial-like family member 1), which is highly expressed during human and non-human primate TE specification in vivo but is negligibly expressed in mouse, is a critical regulator of cell fate determination and self-renewal in human TELCs and TSCs derived from naïve PSCs. Mechanistically, VGLL1 partners with the transcription factor TEAD4 (TEA domain transcription factor 4) to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C. Our work is relevant to understand primate early embryogenesis and how it differs from other mammalian species.

Varicella-zoster virus infection and primary membranous nephropathy: a Mendelian randomization study.

Primary membranous nephropathy (MN) is a rare autoimmune cause of kidney failure. Observational studies have suggested some relationship between virus infection and primary MN, but the association remains unclear. The current study performed a two­sample Mendelian randomization (MR) analysis to explore the causal association between varicella-zoster virus (VZV) infection (chickenpox and shingles) and primary MN using genome­wide association studies (GWASs) summary statistics. The exposure datasets containing chickenpox and shingles were obtained from the GWASs conducted by the 23andMe cohort. And summary-level statistics for primary MN were used as the outcome dataset, comprising 2150 cases and 5829 controls from European Ancestry. The inverse variance weighted method was adopted as the main analysis. As a result, we found that both genetically determined chickenpox (odds ratio [95% confidential interval] = 3.61 [1.74-7.50], p = 5.59e-04) and shingles (p = 7.95e-03, odds ratio [95% confidential interval] = 2.49 [1.27-4.91]) were causally associated with an increased risk of developing primary MN. In conclusion, our MR findings provided novel genetic evidence supporting the causal effect of VZV infection on primary MN. Further studies are needed to elucidate the underlying mechanisms mediating the causal association.

Live birth of chimeric monkey with high contribution from embryonic stem cells.

A formal demonstration that mammalian pluripotent stem cells possess preimplantation embryonic cell-like (naive) pluripotency is the generation of chimeric animals through early embryo complementation with homologous cells. Whereas such naive pluripotency has been well demonstrated in rodents, poor chimerism has been achieved in other species including non-human primates due to the inability of the donor cells to match the developmental state of the host embryos. Here, we have systematically tested various culture conditions for establishing monkey naive embryonic stem cells and optimized the procedures for chimeric embryo culture. This approach generated an aborted fetus and a live chimeric monkey with high donor cell contribution. A stringent characterization pipeline demonstrated that donor cells efficiently (up to 90%) incorporated into various tissues (including the gonads and placenta) of the chimeric monkeys. Our results have major implications for the study of primate naive pluripotency and genetic engineering of non-human primates.

Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation.

Heterologous organ transplantation is an effective way of replacing organ function but is limited by severe organ shortage. Although generating human organs in other large mammals through embryo complementation would be a groundbreaking solution, it faces many challenges, especially the poor integration of human cells into the recipient tissues. To produce human cells with superior intra-niche competitiveness, we combined optimized pluripotent stem cell culture conditions with the inducible overexpression of two pro-survival genes (MYCN and BCL2). The resulting cells had substantially enhanced viability in the xeno-environment of interspecies chimeric blastocyst and successfully formed organized human-pig chimeric middle-stage kidney (mesonephros) structures up to embryonic day 28 inside nephric-defective pig embryos lacking SIX1 and SALL1. Our findings demonstrate proof of principle of the possibility of generating a humanized primordial organ in organogenesis-disabled pigs, opening an exciting avenue for regenerative medicine and an artificial window for studying human kidney development.

Targetoid haemosiderotic nevus: four cases and a literature review.

BACKGROUND: Targetoid haemosiderotic nevus (THN), a distinct clinical form of melanocytic nevus, is characterized by the sudden development of a purpuric halo surrounding a pre-existing nevus, easily mistaken for melanoma. OBJECTIVES: To summarise the clinical, dermoscopic and histopathological findings of THN in order to better recognize and manage this condition. MATERIALS & METHODS: We describe four cases and provide a review of the literature based on a search in PubMed. Overall, the clinical, dermoscopic and pathological findings of 15 THN cases are summarised. RESULTS: THN was characterized by a sudden onset of a purpuric halo surrounding a pre-existing nevus without any apparent trigger which occurred mainly in young females. Dermoscopically, the central nevus showed a black-brown, globular or homogeneous pattern, possibly interspersed with reddish, purple, or black structureless areas and comma-shaped vessels. The peripheric purpuric halo had two patterns: one with homogeneous reddish or purplish red areas, and another with an inner pale and outer homogeneous reddish or purplish red zone. The pathological findings showed an intradermal or compound nevus, dilated vessels, and extravasated erythrocytes, possibly accompanied by perivascular inflammatory infiltration and fibrin and hemosiderin deposits. CONCLUSION: THN is a benign lesion that usually requires no intervention other than follow-up observation. Dermoscopy is a useful non-invasive diagnostic tool, and biopsy can be avoided. The purpuric halo resolves spontaneously within two to four weeks with rare recurrence.

Overexpression and potential roles of midkine via regulation of vascular endothelial growth factor A in psoriasis.

Midkine plays a critical role in angiogenesis by regulating the vascular endothelial growth factor (VEGF) signalling pathway, which is known to be associated with psoriasis pathogenesis. However, research on midkine-psoriasis relationship remains limited. The objective of this study was to detect midkine expression in psoriasis and investigate its potential role in the disease. Midkine expression was measured using immunohistochemistry and ELISA. Effects of midkine on HaCaT cell proliferation, VEGF-A production and signalling pathways were assessed using CCK8, RT-PCR and WB. Scratch and in vitro tube formation tests were used to evaluate the effects of HaCaT-cell-activated midkine on the migration and tube formation of human dermal microvascular endothelial cells. Murine psoriasiform models were injected with midkine recombinant protein and midkine monoclonal antibody to investigate skin lesions, tissue sections and dermal microvessel density. Levels of midkine significantly increased in both lesions and serum of patients with psoriasis. Serum expression of midkine decreased after treatment and a positive correlation was found between midkine and disease severity. Midkine promoted HaCaT cell proliferation and VEGF-A production. The Notch2/HES1/JAK2-STAT5A pathway expression increased after midkine treatment of HaCaT cells. The supernatant of HaCaT cells treated with midkine promoted HMEC-1 migration and angiogenesis in vitro. Recombinant midkine protein exacerbated psoriasiform lesions with increased expressions of VEGF-A and microvessel density, while midkine monoclonal antibody alleviated psoriasis lesions. Midkine may have a significant impact on psoriasis angiogenesis by regulating VEGF-A expression through the Notch2/HES1/JAK2-STAT5A pathway, highlighting a potential therapeutic target for psoriasis treatment.

Reactivation rates of hepatitis B or C or HIV in patients with psoriasis using biological therapies: a systematic review and meta-analysis.

Some biological therapies for psoriasis can cause the reactivation of viral infections. Although recent studies suggest no increased rate of reactivation with biological therapies, some life-threatening cases have been reported. Therefore, this meta-analysis examined the rate of virus reactivation in patients with psoriasis with biological therapies and concurrent hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. PubMed, Embase, and the Cochrane Library were searched for available papers from inception to December 2021. The outcome was the number of patients with virus reactivation after using biological therapies. The random-effect model was used in all analyses. Fourteen reports (1033 patients) were included. The pooled overall rate of virus reactivation was 0.04 (95%CI 0.01-0.09; I2 = 67.7%, P < 0.001). The pooled rates of HBV, HCV, and HIV reactivation were 0.04 (95%CI 0.00-0.10; I2 = 79.9%, P < 0.001), 0.07 (95%CI 0.02-0.14; I2 = 23.7%, P = 0.24), and 0.12 (95%CI 0.00-0.40), respectively. The pooled rates of HBV and HCV reactivation were 0.10 (95%CI 0.03-0.19) and 0.08 (95%CI 0.03-0.15) in Asia, but 0.00 (95%CI 0.00-0.01) and 0.04 (95%CI 0.00-0.21) in Europe. The publication type also influenced the results. The use of biological therapy in patients with psoriasis and HBV, HCV, or HIV infection might be associated with the rate of viral reactivation, but this meta-analysis had limitations, and the evidence might be weak. Nevertheless, it might suggest that at least a consultation with an infection specialist might be warranted in patients with psoriasis in whom biological therapies are considered.

Effect of Electroacupuncture Added to Pelvic Floor Muscle Training in Women with Stress Urinary Incontinence: A Randomized Clinical Trial.

BACKGROUND: Pelvic floor muscle training (PFMT) is a first-line conservative therapy for stress urinary incontinence (SUI). Electroacupuncture (EA) has been used to treat SUI recently. OBJECTIVE: To compare the effectiveness of PFMT + EA versus PFMT + sham EA for SUI in women. DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, randomized, controlled clinical trial was conducted at four hospitals in China involving 304 women with SUI from May 20, 2014 to November 21, 2017. Data were analyzed from April 20 to December 21, 2018. INTERVENTION: Participants were randomized to receive 8 wk of PFMT+ EA (n = 154) or PFMT + sham EA (n = 150). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the change in the amount of urine leakage measured on a 1-hr pad test. Student's t test, the χ2 test, and the Wilcoxon rank-sum test were used for data analysis. RESULTS AND LIMITATIONS: Among the 304 participants randomized, 286 completed the study. The mean age was 57.6 yr (standard deviation [SD] 8.9) for the PFMT + sham EA group and 57.2 yr (SD 9.1) for the PFMT + EA group. The mean urine leakage at baseline was 13.6 g for the PFMT + sham EA group and 13.9 g for the PFMT + EA group. After the 8-wk intervention, the PFMT + EA group had a greater decrease in mean urine leakage (-9.8 g) than the PFMT + sham EA group (-5.8 g) with a mean difference of 4.0 g (95% confidence interval [CI] 0.8-7.2). Significantly more patients experienced a ≥50% reduction in urine leakage and the mean number of incontinence episodes in 24 h in the PFMT + EA group than in the PFMT + sham EA group (26.3%, 95%CI 15.8-36.8%). The PFMT + EA group experienced better improvement in participant-reported SUI severity at 6 wk (p < 0.001) and 8 wk (p < 0.001) and self-evaluated therapeutic effects at 2-32 wk (p < 0.001) after the intervention. Lack of measurement of the amount of urine leakage during follow-up is a limitation. CONCLUSIONS: In this randomized clinical trial, 8-wk combined treatment with PFMT + EA led to a greater improvement in SUI symptoms and better outcomes than with PFMT + sham EA. PATIENT SUMMARY: We evaluated the effectiveness and safety of pelvic floor muscle training combined with electroacupuncture for stress urinary incontinence in women, Our results show that this is a promising therapeutic approach for the treatment of stress urinary incontinence.

Mendelian randomization study of the genetic interaction between psoriasis and celiac disease.

Epidemiological studies have observed some relationship between psoriasis and celiac disease (CD), while the causal link between these 2 autoimmune diseases was unclear. In the current study, we aimed to explore the causal link between psoriasis and celiac disease with bidirectional 2-sample Mendelian Randomization (MR) study. Eligible instrument variables (IVs) with genome-wide significance (p < 5E-08) were extracted from the summary-level datasets from the published genome-wide association studies (GWAS), which were conducted in the European population. The inverse variance weighted (IVW) method was performed as the main analysis, sensitivity analyses and post-MR analyses were also performed. Our MR analyses found that genetically doubling the odds of CD would increase the risk for psoriasis (p = 1.58e-03, OR [95% CI] 1.232 [1.061-1.432]). And the results were supported by sensitivity analyses. While we found that genetically determined psoriasis was not associated with the risk for CD (IVW: p = 0.985, OR [95% CI] 1.000 [0.965-1.037]). Our study provided novel genetic evidence that patients with CD were at an increased risk of developing psoriasis, while psoriasis was not associated with the risk for CD. Clinicians should be aware of the associations and pay attention to skin manifestations in patients with CD.

The Transmission Properties of One-Dimensional Photonic Crystals with Gradient Materials.

In this paper, we studied the transmission properties, including photonic band gap (PBG) and defect mode properties, of one-dimensional photonic crystals (1D PCs) consisting of gradient materials. When keeping the average refractive index of the gradient materials in the 1D gradient-material PCs (1D GPCs) the same as the index of the corresponding normal materials in the 1D normal-material PCs (1D NPCs), by transfer matrix method, we found that the complete 1D GPCs with high-index gradient materials benefit to achieve larger omni-PBG than that in 1D NPCs. In our high-index gradient material case, for TE(TM) wave, the optimal omni-PBGs in 1D GPCs with first- and second-order gradient materials are 38.6% (50.2%) and 15.9% (22.3%) larger than that in 1D NPCs; while for the optimal relative bandwidths of omni-PBG, the corresponding promotions are 41.1% (52.3%) and 16.1% (22.6%), respectively. In addition, when defective 1D GPCs have gradient-material defect, the position of defect modes can be adjusted by selecting proper parameters of the gradient materials. These types of research are useful for designing wide PBG devices and tunable narrow-band filters which have potential application in optical communication.

[FU Li-xin's experience in treatment of vertigo with "regulating the middle jiao, opening gate and relaxing tendon" method of acupuncture].

The paper introduces professor FU Li-xin's theoretic ideas and experience in treatment of vertigo. Professor FU believes that this disease is closely related to the blockage of qi movement in the middle jiao, opening-closing disarrangement in the pivot, "gate" obstruction, malnutrition of brain orifice and decreased blood flow in the nape. Based on the holistic idea of qi movement in traditional Chinese medicine and the circulatory theory of western medicine, the characteristics of the specific acupuncture therapy for "regulating the middle jiao, opening gate and relaxing tendon" are summarized. Using the layered needling technique at Zhongwan (CV 12) and "gate points" in the neck region, the tendon-bone needling technique with modified "dark tortoise seeking hole" at local tendon blockage points, vertigo is cured through regulating qi in the middle jiao, opening gate and nourishing marrow, relaxing tendon and harmonizing the mind.