Anatomically distinct fibroblast subsets determine skin autoimmune patterns.

The skin serves as a physical barrier and an immunological interface that protects the body from the external environment1-3. Aberrant activation of immune cells can induce common skin autoimmune diseases such as vitiligo, which are often characterized by bilateral symmetric lesions in certain anatomic regions of the body4-6. Understanding what orchestrates the activities of cutaneous immune cells at an organ level is necessary for the treatment of autoimmune diseases. Here we identify subsets of dermal fibroblasts that are responsible for driving patterned autoimmune activity, by using a robust mouse model of vitiligo that is based on the activation of endogenous auto-reactive CD8+ T cells that target epidermal melanocytes. Using a combination of single-cell analysis of skin samples from patients with vitiligo, cell-type-specific genetic knockouts and engraftment experiments, we find that among multiple interferon-γ (IFNγ)-responsive cell types in vitiligo-affected skin, dermal fibroblasts are uniquely required to recruit and activate CD8+ cytotoxic T cells through secreted chemokines. Anatomically distinct human dermal fibroblasts exhibit intrinsic differences in the expression of chemokines in response to IFNγ. In mouse models of vitiligo, regional IFNγ-resistant fibroblasts determine the autoimmune pattern of depigmentation in the skin. Our study identifies anatomically distinct fibroblasts with permissive or repressive IFNγ responses as the key determinant of body-level patterns of lesions in vitiligo, and highlights mesenchymal subpopulations as therapeutic targets for treating autoimmune diseases.

The effect of mind-body exercise in lung cancer patients: a meta-analysis of RCTs.

PURPOSE: This study aimed to evaluate the impact of mind-body exercise (yoga, tai chi, qigong, etc.) on lung cancer. METHODS: We performed a literature search of the electronic databases PubMed, Web of Science, Cochrane Library, Embase, CNKI, CBM, WanFang Data, and VIP from their inception to 16 May 2023. The primary outcome was the 6-min walk test (6MWT), while the secondary outcomes were anxiety levels and quality of life (QoL). Two independent reviewers performed the data extraction using a predefined protocol and assessed the risk of bias using the Cochrane risk of bias (ROB) tool for randomized controlled trials, with differences agreed by consensus. Meta-analysis was performed using RevMan 5.4 and Stata 15 software to analyze the extracted data. RESULTS: This meta-analysis included a total of 11 studies involving 897 patients. The results indicated that compared to the usual care group, lung cancer patients in the mind-body exercise group could increase the 6-min walk distance (5 studies, 346 participants, WMD: 18.83, 95% CI (7.55, 30.10) P = 0.001), reduce anxiety levels (4 studies, 362 participants, SMD: - 1.51, 95% CI (- 1.74, - 1.27), P < 0.05), and enhance the overall quality of life (6 studies, 594 participants, SMD: 0.71, 95% CI (0.10, 1.31), P = 0.02). The overall certainty of the evidence for all outcomes was low; seven studies were judged to be at low risk of bias, and four studies were judged to be at moderate risk of bias. CONCLUSION: Mind-body exercise could improve exercise capacity in lung cancer survivors, reduce anxiety, and positively affect overall quality of life. PROSPERO REGISTRATION NUMBER: CRD42023426800.

Timely thrombectomy can improve patency of hemodialysis arteriovenous fistulas.

OBJECTIVE: The urgency with which salvage of thrombosed vascular accesses for dialysis should be attempted remains unknown. We examined the effect of a timely thrombectomy approach on vascular access outcomes for dialysis. METHODS: A before-and-after study was conducted with patients on hemodialysis who had undergone endovascular thrombectomy. A timely thrombectomy initiative (ie, salvage within 24 hours of thrombosis diagnosis) was started in July 2015 at our institution. Data about thrombectomy procedures, performed within 1 year before and after the initiative was introduced, were abstracted from an electronic database. Immediate outcomes and patency outcomes were compared between the preinitiative (control) and postinitiative (intervention) groups. RESULTS: During the study period, 329 patients were enrolled, including 165 cases before and 164 cases after the initiative. The intervention group had more thrombectomy procedures performed within 24 hours (93% vs 55%; P < .01) and within 48 hours (97% vs 79%; P < .01) than the control group. No between-group differences in procedural success or clinical success rates were found. At 3 months, the intervention group had a higher postintervention primary patency rate than the control group, although this did not reach statistical significance (58% vs 48%; P = .06). After stratification into native or graft accesses, the patency benefit was observed in the native access group (68% vs 50%; P = .03) but not in the graft access group (50% vs 46%; P = .65). After adjusting for potential confounders, timely thrombectomy remained an independent predictor of postintervention primary patency (hazard ratio, 0.449; 95% confidence interval, 0.224-0.900; P = .02) for native dialysis accesses. CONCLUSIONS: Our results suggest that a timely thrombectomy approach, in which salvage is attempted within 24 hours of thrombosis diagnosis, improves postintervention primary patency of native but not graft accesses for dialysis.

Effectiveness of Dyadic Psychoeducational Intervention on Cancer Patients and Their Caregivers: A Systematic Review and Meta-analysis.

BACKGROUND: Dyadic psychoeducational intervention targets the dyads of cancer patients and caregivers as active participants in partnership, which can potentially address the needs and challenges faced by patients with cancer and their caregivers. However, there is insufficient evidence on the effectiveness of the intervention on psychological health and illness-related outcomes among the dyads. OBJECTIVE: To systematically examine the dyadic psychoeducational intervention of cancer patients and their caregivers on psychological health and illness-related outcomes. METHODS: Cochrane Library, EMBASE, CINAHL, PsycINFO, PubMed, Web of Science, and 4 Chinese databases were searched from inception to May 29, 2022. Two investigators independently extracted data and evaluated methodological quality. RevMan 5.4 was used for meta-analysis; heterogeneity was evaluated using Higgins' I2 (%). Standardized mean difference (SMD) with a 95% confidence interval (CI) was used to assess the effects. RESULTS: Eight randomized controlled trials that involved 1234 dyads were collected. Meta-analysis showed that the intervention was effective in reducing the dyadic depression (patients' SMD, -0.41 [95% CI, -0.78 to -0.04; P = .03]; caregivers' SMD, -0.70 [95% CI, -1.31 to -0.09; P = .03]). It also improved caregivers' quality of life (SMD, -0.29 [95% CI, -0.56 to -0.03; P = .03]), whereas no significant effect was found on patients' quality of life. Dyadic results including anxiety, self-efficacy, disease communication, and appraisals of illness/caregiving were observed. CONCLUSION: Dyadic psychoeducational intervention reduced the dyadic depression. It also improved caregivers' quality of life. IMPLICATIONS FOR PRACTICE: Nurses can apply dyadic psychoeducational intervention in clinical practice. More studies are needed to draw higher-quality conclusions and investigate the effects on psychological health and illness-related outcomes in cancer patients and caregivers.

Fabrication of a Disposable Amperometric Sensor for the Determination of Nitrite in Food.

Silver nanoparticles (AgNPs) were synthesized through an environmentally friendly method with tea extract as a reduction agent. By immobilizing them on the surface of a low-cost pencil graphite electrode (PGE) with the aid of a simple and well-controlled in-situ electropolymerization method, a novel nanosensing interface for nitrite was constructed. The film-modified PGE showed good electrocatalytic effects on the oxidation of nitrite and was characterized through scanning electron microscopy, X-ray photoelectron spectroscopy, and electrochemical techniques. Characterization results clearly show that the successful modification of AgNPs improved the surface area and conductivity of PGEs, which is beneficial to the high sensitivity and short response time of the nitrite sensor. Under the optimal detection conditions, the oxidation peak current of nitrite had a good linear relationship with its concentration in the range of 0.02-1160 µmol/L with a detection limit of 4 nmol/L and a response time of 2 s. Moreover, the sensor had high sensitivity, a wide linear range, a good anti-interference capability, and stability and reproducibility. Additionally, it can be used for the determination of nitrite in food.

A mouse model of vitiligo based on endogenous auto-reactive CD8 + T cell targeting skin melanocyte.

Vitiligo is the most common human skin depigmenting disorder. It is mediated by endogenous autoreactive CD8 + T cells that destruct skin melanocytes. This disease has an estimated prevalence of 1% of the global population and currently has no cure. Animal models are indispensable tools for understanding vitiligo pathogenesis and for developing new therapies. Here, we describe a vitiligo mouse model which recapitulates key clinical features of vitiligo, including epidermis depigmentation, CD8 + T cell infiltration in skin, and melanocyte loss. To activate endogenous autoreactive cytotoxic CD8 + T cells targeting melanocytes, this model relies on transient inoculation of B16F10 melanoma cells and depletion of CD4 + regulatory T cells. At cellular level, epidermal CD8 + T cell infiltration and melanocyte loss start as early as Day 19 after treatment. Visually apparent epidermis depigmentation occurs 2 months later. This protocol can efficiently induce vitiligo in any C57BL/6 background mouse strain, using only commercially available reagents. This enables researchers to carry out in-depth in vivo vitiligo studies utilizing mouse genetics tools, and provides a powerful platform for drug discovery.

Hair shaft miniaturization causes stem cell depletion through mechanosensory signals mediated by a Piezo1-calcium-TNF-α axis.

In aging, androgenic alopecia, and genetic hypotrichosis disorders, hair shaft miniaturization is often associated with hair follicle stem cell (HFSC) loss. However, the mechanism causing this stem cell depletion in vivo remains elusive. Here we show that hair shaft loss or a reduction in diameter shrinks the physical niche size, which results in mechanical compression of HFSCs and their apoptotic loss. Mechanistically, cell compression activates the mechanosensitive channel Piezo1, which triggers calcium influx. This confers tumor necrosis factor alpha (TNF-α) sensitivity in a hair-cycle-dependent manner in otherwise resistant HFSCs and induces ectopic apoptosis. Persistent hair shaft miniaturization during aging and genetic hypotrichosis disorders causes long-term HFSC loss by inducing continuous ectopic apoptosis through Piezo1. Our results identify an unconventional role of the inert hair shaft structure as a functional niche component governing HFSC survival and reveal a mechanosensory axis that regulates physical-niche-atrophy-induced stem cell depletion in vivo.

Hoxc-Dependent Mesenchymal Niche Heterogeneity Drives Regional Hair Follicle Regeneration.

Mesenchymal niche cells instruct activity of tissue-resident stem and progenitor cell populations. Epithelial stem cells in hair follicles (HFs) have region-specific activity, which may arise from intrinsic cellular heterogeneity within mesenchymal dermal papilla (DP) cells. Here we show that expression of Hoxc genes is sufficient to reprogram mesenchymal DP cells and alter the regenerative potential of epithelial stem cells. Hoxc gene expression in adult skin dermis closely correlates with regional HF regeneration patterns. Disrupting the region-specific expression patterns of Hoxc genes, by either decreasing their epigenetic repression via Bmi1 loss or inducing ectopic interactions of the Hoxc locus with an active epigenetic region, leads to precocious HF regeneration. We further show that a single Hoxc gene is sufficient to activate dormant DP niches and promote regional HF regeneration through canonical Wnt signaling. Altogether, these results reveal that Hoxc genes bestow mesenchymal niches with tissue-level heterogeneity and plasticity.

[Molecular markers and its clone for salt tolerance gene in wheat].

Genetic and RAPD analysis were studied among [4] individuals in F2 segregated population originating from a cross between wheat cultivator Nongda 85021 (female parent, salt sensitive) and Chadian Red (male parent, salt tolerant). For genetic analysis and chi-square test gave a good fit of 1:2:1 ratio showing that one major gene was controlling the salt tolerant character in Chadian Red. DNA of F2 population was extracted to develop tolerant and sensitive gene pools, respectively, based the BSA (Bulked Segregate Analysis). By RAPD (Randomly Amplified Polymorphic DNAs), 520 random primers were used to amplify the two types of gene pools. Only primer OPZ09 was found to be polymorphic with a fragment of 590 bp in the two parents, F1 and F2 populations. So, the specific fragment OPZ09-590 was, a RAPD marker linked to salt tolerance gene in Chadian Red. By the software JOINMAP (Version 1.4), the recombination was 5.674% and the linking distance was 6.557 cM. OPZ09-590 was extracted from the agarose and mixed with pUCm-T vector, then the vector was transferred into JM109. The clone was determined 591 bp after being sequenced. It indicated that the RAPD marker of salt tolerance gene in Chadian Red was OPZ09-591.