There are concerns that regional inequality in India has increased after the economic reforms of 1991. This concern is supported by various statistical analyses. In this paper, we show that the conclusions are sensitive to what measures of attainment are used. In particular, human development indices do not show the same increase in regional inequality. Furthermore, looking at consumption and credit indicators for regions disaggregated below the state level also suggests that inequality trends may not be as bad as suggested by State Domestic Product data, although the greater strength of the economies of the western and southern states emerges in our results. Finally, we briefly discuss policy implications within the context of India's evolving federal polity.JEL Classification: D63, H73, O10, O53 Key Words: regional inequality, federalism, human development † We are grateful to the Santa Cruz Center for International Economics for financial support. We alone are responsible for the views expressed here.

Background Skin innervation is crucial for normal wound healing. However, the relationship between nerve receptors and wound healing and the intrinsic mechanism remains to be further identified. In this study, we investigated the role of a calcitonin gene-related peptide (CGRP) receptor component, receptor activity‐modifying protein 1 (RAMP1), in mouse skin fibroblast (MSF) proliferation. Methods In vivo, Western blotting and immunohistochemical (IHC) staining of mouse skin wounds tissue was used to detect changes in RAMP1 expression. In vitro, RAMP1 was overexpressed in MSF cell lines by infection with Tet-On-Flag-RAMP1 lentivirus and doxycycline (DOX) induction. An IncuCyte S3 Live-Cell Analysis System was used to assess and compare the proliferation rate differences between different treatment groups. Total protein and subcellular extraction Western blot analysis, quantitative real-time-polymerase chain reaction (qPCR) analysis, and immunofluorescence (IF) staining analysis were conducted to detect signalling molecule expression and/or distribution. The CUT & RUN assay and dual-luciferase reporter assay were applied to measure protein-DNA interactions. Results RAMP1 expression levels were altered during skin wound healing in mice. RAMP1 overexpression promoted MSF proliferation. Mechanistically, total Yes-associated protein (YAP) and nuclear YAP protein expression was increased in RAMP1-overexpressing MSFs. RAMP1 overexpression increased inhibitory guanine nucleotide-binding protein (G protein) α subunit 3 (Gαi3) expression and activated downstream protein kinase A (PKA), and both elevated the expression of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) and activated it, promoting the transcription of YAP, elevating the total YAP level and promoting MSF proliferation. Conclusions Based on these data, we report, for the first time, that changes in the total RAMP1 levels during wound healing and RAMP1 overexpression alone can promote MSF proliferation via the Gαi3-PKA-CREB-YAP axis, a finding critical for understanding RAMP1 function, suggesting that this pathway is an attractive and accurate nerve target for skin wound treatment.

The crucial role of macrophages in the healing of chronic diabetic wounds is widely known, but previous in vitro classification and marker genes of macrophages may not be fully applicable to cells in the microenvironment of chronic wounds. The heterogeneity of macrophages was studied and classified at the single-cell level in a chronic wound model. We performed single-cell sequencing of CD45 + immune cells within the wound edge and obtained 17 clusters of cells, including 4 clusters of macrophages. One of these clusters is a previously undescribed population of macrophages possessing osteoclast gene expression, for which analysis of differential genes revealed possible functions. We also analysed the differences in gene expression between groups of macrophages in the control and diabetic wound groups at different sampling times. We described the differentiation profile of mononuclear macrophages, which has provided an important reference for the study of immune-related mechanisms in diabetic chronic wounds. Graphical Abstract

Naringenin is a citrus flavonoid with various biological functions and a potential therapeutic agent for skin diseases, such as UV radiation and atopic dermatitis. The present study investigates the therapeutic effect and pharmacological mechanism of naringenin on chronic wounds. Using network pharmacology, we identified 163 potential targets and 12 key targets of naringenin. Oxidative stress was confirmed to be the main biological process modulated by naringenin. The transcription factor p65 (RELA), alpha serine/threonine-protein kinase (AKT1), mitogen-activated protein kinase 1 (MAPK1) and mitogen-activated protein kinase 3 (MAPK3) were identified as common targets of multiple pathways involved in treating chronic wounds. Molecular docking verified that these four targets stably bound naringenin. Naringenin promoted wound healing in mice in vivo by inhibiting wound inflammation. Furthermore, in vitro experiments showed that a low naringenin concentration did not significantly affect normal skin cell viability and cell apoptosis; a high naringenin concentration was cytotoxic and reduced cell survival by promoting apoptosis. Meanwhile, comprehensive network pharmacology, molecular docking and in vivo and in vitro experiments revealed that naringenin could treat chronic wounds by alleviating oxidative stress and reducing the inflammatory response. The underlying mechanism of naringenin in chronic wound therapy involved modulating the RELA, AKT1 and MAPK1/3 signalling pathways to inhibit ROS production and inflammatory cytokine expression.

FUSCA 3 (FUS3), a seed master regulator, plays critical roles in seed dormancy and oil accumulation. However, its downstream regulation mechanisms remain poorly understood. Here, we explored the roles of AINTEGUMENTA-like 6 (AIL6), a seed transcription factor, in these processes. The activation of AIL6 by FUS3 was demonstrated by dual-LUC assay. Seeds of ail6 mutants showed alterations of fatty acid compositions, and both AtAIL6 (AIL6 from Arabidopsis thaliana) and BnaAIL6 (AIL6 from Brassica napus) rescued the phenotype. Over-expression (OE) of AIL6s reversed changes in seed fatty acid composition. Notably, OE lines showed low seed germination rates down to 12% compared to 100% of wild-type Col-0. Transcriptome analysis of the mutant and an OE line indicated widespread expression changes of genes involved in lipid metabolism and phytohormone pathways. In OE mature seeds, GA4 content decreased more than 15-fold, while ABA and IAA contents clearly increased. Exogenous GA3 treatments did not effectively rescue the low germination rate. Nicking seed coats increased germination rates from 25% to nearly 80% while the wild-type rdr6-11 is 100% and 98% respectively, and elongation of storage time also improved seed germination. Furthermore, dormancy imposed by AIL6 was fully released in the della quintuple mutant. Together, our results indicate AIL6 acts as a manager downstream of FUS3 in seed dormancy and lipid metabolism.

BackgroundSkin innervation plays an important role in wound healing by either direct contact with or indirect secretions that impact skin cells. Many studies in this field have been published; however, there is a lack of bibliometric analyses focusing on the effect of skin innervation on skin wound healing. In this study, we aimed to analyse the research trends, status, and hotspots in this field.MethodsReviews and articles published in English were extracted from the Web of Science Core Collection (WoSCC) database based on subject term searches. Microsoft Office Excel, VOSviewer, and CiteSpace were used to analyse publication date, country or region, institution, author, and author keywords.ResultsA total of 368 papers published between 1959 and 2022 were included in the analysis. Although there was a pulsation during this period, there was an overall upward trend in studies related to the effect of skin innervation on wound healing. The United States, particularly the University of Washington, and Gibran, Nicole S. from the University of Washington, was the most active in this field. Wound Repair and Regeneration published the most relevant literature, and “Calcitonin gene-related peptide: physiology and pathophysiology” had the highest total number of citations. “Diabetic foot ulcer,” “epidermal stem cells,” “mesenchymal stem cells,” and “mast cells” are current and potential future research hotspots.ConclusionThis bibliometric analysis will inform the overall trends in research related to the effect of skin innervation on wound healing, summarise relevant research hotspots, and guide future work.

Reactive oxygen species (ROS) production is critical for the initiation of wound repair; however, persistently high levels of ROS can lead to lipid peroxidation in cells and thus affect wound healing. Iron is a transition metal that is an essential component of almost all living cells and organisms. When present in excess in cells and tissues, iron disrupts redox homeostasis and catalyzes the generation of ROS, leading to increased lipid peroxidation. In this study, we found that after treating interfollicular epidermal (IFE) cells with different concentrations of holotransferrin (0 µg/ml, 1 µg/ml, 10 µg/ml, 100 µg/ml, and 1 mg/ml), the intracellular iron content increased, and cell viability and function did not differ significantly among the treatment groups of cells. In addition, the level of lipid peroxidation in IFE cells did not increase following holotransferrin treatment. We speculated that there is a protective mechanism within IFE cells that reduces the occurrence of intracellular lipid peroxidation. We also found that the elevated intracellular iron content of IFE cells was accompanied by elevated ALDH3B1 expression. We investigated the effect of ALDH3B1 on the level of lipid peroxidation in IFE cells and found that elevated ALDH3B1 expression decreased the damage to IFE cells induced by lipid peroxidation. In addition, the NRF2 pathway was found to affect the expression of ALDH3B1, which in turn affected lipid peroxidation in IFE cells. These findings suggest that in IFE cells, activation of the NRF2 pathway can increase the expression of ALDH3B1 and thus reduce the production of intracellular ROS and the occurrence of intracellular lipid peroxidation. Therefore, ALDH3B1 may be a potential target for the treatment of chronic wounds.

Background: The crucial role of macrophages in the healing of chronic diabetic wounds is widely known, but previous in vitro classification and marker genes of macrophages may not be fully applicable to cells in the microenvironment of chronic wounds. The heterogeneity of macrophages was studied and classified at the single-cell level in a chronic wound model. Results: We performed single-cell sequencing of CD45+ immune cells within the wound edge and obtained 17 clusters of cells, including 4 clusters of macrophages. One of these clusters is a previously undescribed population of macrophages possessing osteoclast gene expression, for which analysis of differential genes revealed possible functions. We also analysed the differences in gene expression between groups of macrophages in the control and diabetic wound groups at different sampling times. Conclusions: we described the differentiation profile of mononuclear macrophages, which has provided an important reference for the study of immune-related mechanisms in diabetic chronic wounds.