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BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

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BACKGROUND: Aplastic anemia (AA) presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells, with the current therapeutic options being notably limited. AIM: To assess the therapeutic potential of ginsenoside Rg1 on AA, specifically its protective effects, while elucidating the mechanism at play. METHODS: We employed a model of myelosuppression induced by cyclophosphamide (CTX) in C57 mice, followed by administration of ginsenoside Rg1 over 13 d. The investigation included examining the bone marrow, thymus and spleen for pathological changes via hematoxylin-eosin staining. Moreover, orbital blood of mice was collected for blood routine examinations. Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice. Additionally, the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot. RESULTS: Administration of CTX led to significant damage to the bone marrow's structural integrity and a reduction in hematopoietic cells, establishing a model of AA. Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice. In comparison to the AA group, ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX. Furthermore, it helped alleviate the blockade in the cell cycle. Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway. CONCLUSION: This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression, primarily through modulating the MAPK signaling pathway, which paves the way for a novel therapeutic strategy in treating AA, highlighting the potential of ginsenoside Rg1 as a beneficial intervention.

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BACKGROUND: The global burden of invasive fungal infections (IFIs) has shown an upsurge in recent years due to the higher load of immunocompromised patients suffering from various diseases. The role of early and accurate diagnosis in the aggressive containment of the fungal infection at the initial stages becomes crucial thus, preventing the development of a life-threatening situation. With the changing demands of clinical mycology, the field of fungal diagnostics has evolved and come a long way from traditional methods of microscopy and culturing to more advanced non-culture-based tools. With the advent of more powerful approaches such as novel PCR assays, T2 Candida, microfluidic chip technology, next generation sequencing, new generation biosensors, nanotechnology-based tools, artificial intelligence-based models, the face of fungal diagnostics is constantly changing for the better. All these advances have been reviewed here giving the latest update to our readers in the most orderly flow. MAIN TEXT: A detailed literature survey was conducted by the team followed by data collection, pertinent data extraction, in-depth analysis, and composing the various sub-sections and the final review. The review is unique in its kind as it discusses the advances in molecular methods; advances in serology-based methods; advances in biosensor technology; and advances in machine learning-based models, all under one roof. To the best of our knowledge, there has been no review covering all of these fields (especially biosensor technology and machine learning using artificial intelligence) with relevance to invasive fungal infections. CONCLUSION: The review will undoubtedly assist in updating the scientific community's understanding of the most recent advancements that are on the horizon and that may be implemented as adjuncts to the traditional diagnostic algorithms.

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Invasive Aspergillus fumigatus infection poses a serious threat to global human health, especially to immunocompromised individuals. Currently, triazole drugs are the most commonly used antifungals for aspergillosis. However, owing to the emergence of drug-resistant strains, the effect of triazole drugs is greatly restricted, resulting in a mortality rate as high as 80%. Succinylation, a novel post-translational modification, is attracting increasing interest, although its biological function in triazole resistance remains unclear. In this study, we initiated the screening of lysine succinylation in A. fumigatus. We discovered that some of the succinylation sites differed significantly among strains with unequal itraconazole (ITR) resistance. Bioinformatics analysis showed that the succinylated proteins are involved in a broad range of cellular functions with diverse subcellular localizations, the most notable of which is cell metabolism. Further antifungal sensitivity tests confirmed the synergistic fungicidal effects of dessuccinylase inhibitor nicotinamide (NAM) on ITR-resistant A. fumigatus. In vivo experiments revealed that treatment with NAM alone or in combination with ITR significantly increased the survival of neutropenic mice infected with A. fumigatus. In vitro experiments showed that NAM enhanced the killing effect of THP-1 macrophages on A. fumigatus conidia. Our results suggest that lysine succinylation plays an indispensable role in ITR resistance of A. fumigatus. Dessuccinylase inhibitor NAM alone or in combination with ITR exerted good effects against A. fumigatus infection in terms of synergistic fungicidal effect and enhancing macrophage killing effect. These results provide mechanistic insights that will aid in the treatment of ITR-resistant fungal infections.

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Pharmaceutical peptide Octreotide is a somatostatin analog with targeting and therapeutic abilities. Over the last decades, Octreotide has been developed and approved to treat acromegaly and neuroendocrine tumours, and Octreotide-based radioactive conjugates have been leveraged clinically to detect small neuroendocrine tumour sites. Meanwhile, variety of Octreotide-derived delivery strategies have been proposed and explored for tumour targeted therapeutics or diagnostics in preclinical or clinical settings. In this review, we especially focus on the preclinical development and applications of Octreotide-derived drug delivery systems, diagnostic nanosystems, therapeutic nanosystems and multifunctional nanosystems, we also briefly discuss challenges and prospects of these Octreotide-derived delivery systems.

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Thidiazuron (TDZ) is a widely used chemical defoliant in cotton and can stimulate the production of ethylene in leaves, which is believed to be the key factor in inducing leaf abscission. Ethephon (Eth) can also stimulate ethylene production in leaves, but it is less effective in promoting leaf shedding. In this study, the enzyme-linked immunosorbent assays (ELISA) and RNA-seq were used to determine specific changes at hormonal levels as well as transcriptomic mechanisms induced by TDZ compared with Eth. The TDZ significantly reduced the levels of auxin and cytokinin in cotton leaves, but no considerable changes were observed for Eth. In addition, TDZ specifically increased the levels of brassinosteroids and jasmonic acid in the leaves. A total of 13 764 differentially expressed genes that specifically responded to TDZ were identified by RNA-seq. The analysis of KEGG functional categories suggested that the synthesis, metabolism, and signal transduction of auxin, cytokinin, and brassinosteroid were all involved in the TDZ-induced abscission of cotton leaves. Eight auxin transport genes (GhPIN1-c_D, GhPIN3_D, GhPIN8_A, GhABCB19-b_A, GhABCB19-b_D, GhABCB2-b_D, GhLAX6_A, and GhLAX7_D) specifically responded to TDZ. The pro35S::GhPIN3a::YFP transgenic plants showed lower defoliation than the wild type treated with TDZ, and YFP fluorescence in leaves was almost extinguished after treatment with TDZ rather than Eth. This provides direct evidence that GhPIN3a is involved in the leaf abscission induced by TDZ. We found that 959 transcription factors (TFs) specifically responded to TDZ, and a co-expression network analysis (WGCNA) showed five hub TFs (GhNAC72, GhWRKY51, GhWRKY70, GhWRKY50, and GhHSF24) during chemical defoliation with TDZ. Our work sheds light on the molecular basis of TDZ-induced leaf abscission in cotton.

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Neutropenia is a common complication in the treatment of hematological diseases and the most common predisposing factor for invasion by fungi, such as Candida krusei. Recent studies have shown that C. krusei, a life-threatening pathogen, has developed resistance to amphotericin B (AMB). However, the mechanisms that led to the rapid emergence of this AMB-resistant phenotype are unclear. In this study, we found the sensitivity for AMB could be promoted by inhibiting histone acyltransferase activity and western blot analysis revealed differences in the succinylation levels of C. krusei isolated from immunocompromised patients and of the corresponding AMB-resistant mutant. By comparative succinyl-proteome analysis, we identified a total of 383 differentially expressed succinylated sites in with 344 sites in 134 proteins being upregulated in the AMB-resistant mutant, compared to 39 sites in 23 proteins in the wild-type strain. These differentially succinylated proteins were concentrated in the ribosome and cell wall. The critical pathways associated with these proteins included those involved in glycolysis, gluconeogenesis, the ribosome, and fructose and mannose metabolism. In particular, AMB resistance was found to be associated with enhanced ergosterol synthesis and aberrant amino acid and glucose metabolism. Analysis of whole-cell proteomes, confirmed by parallel reaction monitoring, showed that the key enzyme facilitating lysine acylation was significantly upregulated in the AMB-resistant strain. Our results suggest that lysine succinylation may play an indispensable role in the development of AMB resistance in C. krusei. Our study provides mechanistic insights into the development of drug resistance in fungi and can aid in efforts to stifle the emergence of AMB-resistant pathogenic fungi.

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Background: The skin cutaneous melanoma (SKCM) is a devastating form of skin cancer triggered by genetic and environmental factors, and the incidence of SKCM has rapidly increased in recent years. Immune infiltration of the tumor microenvironment is positively associated with overall survival in many tumors. Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor of the immunoglobulin superfamily and a crucial signaling hub for multiple pathological pathways that mediate immunity. Although numerous evidences suggest a crucial role for TREM2 in tumorigenesis of some tumors, no systematic SKCM analysis of TREM2 is available. Mehods. The relationship between TREM2 expression and diagnostic and prognostic value of SKCM patients via using The Cancer Genome Atlas (TCGA) data. The expression level of TREM2 and clinical characteristic correlation in SKCM patients were assessed by the Wilcoxon rank sum test. The cox regression methods, Kaplan-Meier (KM), and log-rank test were used to assess the impact of TREM2 expression on the overall survival (OS). Furthermore, the Gene Set Enrichment Analysis (GSEA) and TIMER were performed to evaluate the enrichment pathways and potential functions and quantify the immune cell infiltration level for TREM2 expression. Results: The TREM2 in SKCM sample expression levels was significantly higher than in normal tissues. Moreover, this expression level of TREM2 was also associated with the BMI of SKCM patients. KM overall survival analysis and OS curve displayed that a high-level TREM2 expression was significantly correlated with a better SKCM prognosis of patients as compared with a low level of TREM2 expression. The GSEA analysis also revealed that TREM2 was associated with immune functions, such as neutrophil activation. Conclusion: TREM2 played a crucial role in SKCM, which might be a prognostic biomarker and correlated with immune infifiltrates in SKCM patients.

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Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections with Candida of the skin, nails, and mucous membranes (e.g., mouth, esophagus, and vagina). Compared with that of other infectious diseases, the immune pathogenic mechanism of CMC is still poorly understood. We identified a signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutation in a CMC patient. Single-cell transcriptional profiling on peripheral blood mononuclear cells from this patient revealed decreases in immature B cells and monocytes. Further analysis revealed several differentially expressed genes related to immune regulation, including RGS1, TNFAIP3, S100A8/A9, and CTSS. In our review of the literature on signal transducer and activator of transcription 1 gain-of-function (c.Y289C) mutations, we identified seven cases in total. The median age of onset for CMC (n=4, data lacking for three cases) was 10.5 years (range: birth to 11 years), with an average onset age of 8 years. There were no reports linking tumors to the c.Y289C mutation, and the incidence of pre-existing clinical disease in patients with the c.Y289C mutation was similar to previous data.

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Thidiazuron (TDZ) is widely used as a defoliant to induce leaf abscission in cotton. However, the underlying molecular mechanism is still unclear. In this study, RNA-seq and enzyme-linked immunosorbent assays (ELISA) were performed to reveal the dynamic transcriptome profiling and the change of endogenous phytohormones upon TDZ treatment in leaf, petiole, and abscission zone (AZ). We found that TDZ induced the gene expression of ethylene biosynthesis and signal, and promoted ethylene accumulation earlier in leaf than that in AZ. While TDZ down-regulated indole-3-acetic acid (IAA) biosynthesis genes mainly in leaf and IAA signal and transport genes. Furthermore, the IAA content reduced more sharply in the leaf than that in AZ to change the auxin gradient for abscission. TDZ suppressed CTK biosynthesis genes and induced CTK metabolic genes to reduce the IPA accumulation for the reduction of ethylene sensitivity. Furthermore, TDZ regulated the gene expression of abscisic acid (ABA) biosynthesis and signal and induced ABA accumulation between 12-48 h, which could up-regulate ABA response factor genes and inhibit IAA transporter genes. Our data suggest that TDZ orchestrates metabolism and signal of ethylene, auxin, and cytokinin, and also the transport of auxin in leaf, petiole, and AZ, to control leaf abscission.

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BACKGROUND: Mepiquat chloride (MC), a plant growth regulator, enhances root growth by promoting lateral root formation in cotton. However, the underlying molecular mechanisms of this phenomenon is still unknown. METHODS: In this study, we used 10 cotton (Gossypium hirsutum Linn.) cultivars to perform a seed treatment with MC to investigate lateral root formation, and selected a MC sensitive cotton cultivar for dynamic monitor of root growth and transcriptome analysis during lateral root development upon MC seed treatment. RESULTS: The results showed that MC treated seeds promotes the lateral root formation in a dosage-depended manner and the effective promotion region is within 5 cm from the base of primary root. MC treated seeds induce endogenous auxin level by altering gene expression of both gibberellin (GA) biosynthesis and signaling and abscisic acid (ABA) signaling. Meanwhile, MC treated seeds differentially express genes involved in indole acetic acid (IAA) synthesis and transport. Furthermore, MC-induced IAA regulates the expression of genes related to cell cycle and division for lateral root development. CONCLUSIONS: Our data suggest that MC orchestrates GA and ABA metabolism and signaling, which further regulates auxin biosynthesis, transport, and signaling to promote the cell division responsible for lateral root formation.

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BACKGROUND: In order to efficiently determine genotypic differences in rooting patterns of crops, novel hardware and software are needed simultaneously to characterize dynamics of root development. RESULTS: We describe a prototype robotic monitoring platform-the RhizoChamber-Monitor for analyzing growth patterns of plant roots automatically. The RhizoChamber-Monitor comprises an automatic imaging system for acquiring sequential images of roots which grow on a cloth substrate in custom rhizoboxes, an automatic irrigation system and a flexible shading arrangement. A customized image processing software was developed to analyze the spatio-temporal dynamics of root growth from time-course images of multiple plants. This software can quantify overall growth of roots and extract detailed growth traits (e.g. dynamics of length and diameter) of primary roots and of individual lateral roots automatically. It can also identify local growth traits of lateral roots (pseudo-mean-length and pseudo-maximum-length) semi-automatically. Two cotton genotypes were used to test both the physical platform and the analysis software. CONCLUSIONS: The combination of hardware and software is expected to facilitate quantification of root geometry and its spatio-temporal growth patterns, and therefore to provide opportunities for high-throughput root phenotyping in support of crop breeding to optimize root architecture.

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The growth regulator mepiquat chloride (MC) is globally used in cotton (Gossypium hirsutum L.) canopy manipulation to avoid excess growth and yield loss. However, little information is available as to whether the modification of plant architecture by MC is related to alterations in gibberellic acid (GA) metabolism and signaling. Here, the role of GA metabolism and signaling was investigated in cotton seedlings treated with MC. The MC significantly decreased endogenous GA3 and GA4 levels in the elongating internode, which inhibited cell elongation by downregulating GhEXP and GhXTH2, and then reducing plant height. Biosynthetic and metabolic genes of GA were markedly suppressed within 2-10d of MC treatment, which also downregulated the expression of DELLA-like genes. A remarkable feedback regulation was observed at the early stage of MC treatment when GA biosynthetic and metabolic genes expression was evidently upregulated. Mepiquat chloride action was controlled by temporal translocation and spatial accumulation which regulated GA biosynthesis and signal expression for maintaining GA homeostasis. The results suggested that MC application could reduce endogenous GA levels in cotton through controlled GA biosynthetic and metabolic genes expression, which might inhibit cell elongation, thereby shortening the internode and reducing plant height.

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Defoliants can increase machine harvest efficiency of cotton (Gossypium hirusutum L.), prevent lodging and reduce the time from defoliation to harvest. Coronatine (COR) is a chlorosis-inducing non-host-specific phytotoxin that induces leaf and/or fruit abscission in some crops. The present study investigates how COR might induce cotton leaf abscission by modulating genes involved in cell wall hydrolases and ACC (ethylene precursor) in various cotton tissues. The effects of COR on cotton boll ripening, seedcotton yield, and seed development were also studied. After 14 d of treatment with COR, cells within the leaf abscission zone (AZ) showed marked differentiation. Elevated transcripts of GhCEL1, GhPG and GhACS were observed in the AZs treated with COR and Thidiazuron (TDZ). The relative expression of GhCEL1 and GhACS in TDZ treated plants was approximately twice that in plants treated with COR for 12 h. However, only GhACS expression increased in leaf blade and petiole. There was a continuous increase in the activity of hydrolytic enzymes such as cellulase (CEL) and polygalacturonase (PG), and ACC accumulation in AZs following COR and TDZ treatments, but there was greater increase in ACC activity of COR treated boll crust, indicating that COR had greater ripening effect than TDZ. Coronatine significantly enhanced boll opening without affecting boll weight, lint percentage and seed quality. Therefore, COR can be a potential cotton defoliant with different physiological mechanism of action from the currently used TDZ.

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To elucidate the phytohormonal basis of the feedback regulation of leaf senescence induced by potassium (K) deficiency in cotton (Gossypium hirsutum L.), two cultivars contrasting in sensitivity to K deficiency were self- and reciprocally grafted hypocotyl-to-hypocotyl, using standard grafting (one scion grafted onto one rootstock), Y grafting (two scions grafted onto one rootstock), and inverted Y grafting (one scion grafted onto two rootstocks) at the seedling stage. K deficiency (0.03mM for standard and Y grafting, and 0.01mM for inverted Y grafting) increased the root abscisic acid (ABA) concentration by 1.6- to 3.1-fold and xylem ABA delivery rates by 1.8- to 4.6-fold. The K deficiency also decreased the delivery rates of xylem cytokinins [CKs; including the zeatin riboside (ZR) and isopentenyl adenosine (iPA) type] by 29-65% and leaf CK concentration by 16-57%. The leaf ABA concentration and xylem ABA deliveries were consistently greater in CCRI41 (more sensitive to K deficiency) than in SCRC22 (less sensitive to K deficiency) scions under K deficiency, and ZR- and iPA-type levels were consistently lower in the former than in the latter, irrespective of rootstock cultivar or grafting type, indicating that cotton shoot influences the levels of ABA and CKs in leaves and xylem sap. Because the scions had little influence on phytohormone levels in the roots (rootstocks) of all three types of grafts and rootstock xylem sap (collected below the graft union) of Y and inverted Y grafts, it appears that the site for basipetal feedback signal(s) involved in the regulation of xylem phytohormones is the hypocotyl of cotton seedlings. Also, the target of this feedback signal(s) is more likely to be the changes in xylem phytohormones within tissues of the hypocotyl rather than the export of phytohormones from the roots.

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Taking the super-high yielding cotton fields (lint yield > or = 4000 kg x hm(-2)) in Xinjiang as the objects, this paper studied the canopy light distribution, photosynthetic rate, and dry matter accumulation at different growth stages, as well as the relationships between the characteristics of canopy light environment and the photosynthetic production. From full flowering stage to late full bolling stage, the light absorption proportion in the upper, middle and lower canopy layers in the super-high yielding cotton fields was 2:2:1, and the canopy transmission coefficients for radiation penetration and diffuse penetration were 0.20-0.55 and 0.22-0.56, respectively, being at reasonable level. The leaves in the middle and lower canopy layers could well accept light, and the leaf photosynthetic rate had little difference among different canopy layers. Compared with high yielding (3500 kg x hm(-2)) and generally high yielding (3000 kg x hm(-2)) cotton fields, super-high yielding cotton field had higher leaf area index and the highest canopy photosynthesis rate at early full boiling stage, and slowly decreased leaf area index, higher canopy photosynthesis rate, increased contribution of non-foliar organs to photosynthetic production, and larger dry matter accumulation from early boll-opening stage to full boll-opening stage. In cotton cultivation, to adjust the canopy structure for the equidistribution of light and canopy photosynthesis capacity in vertical direction could be the important strategy for the efficient utilization of absorbed light energy and the realization of super-high yielding.

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A soil column culture experiment was conducted under the ecological and climatic conditions of Xinjiang to study the effects of water storage in deeper (> 60 cm) soil layers on the root physiological characteristics and leaf photosynthetic traits of cotton variety Xinluzao 13. Two treatments were installed, i.e., well-watered and no watering. The moisture content in plough layer was controlled at 70% +/- 5% and 55% +/- 5% of field capacity by drip irrigation under mulch during growth season. It was shown that the water storage in deeper soil layers enhanced the SOD activity and the vigor of cotton root, and increased the water use efficiency of plant as well as the leaf water potential, chlorophyll content, and net photosynthesis rate, which finally led to a higher yield of seed cotton and higher water use efficiency. Under well-watered condition and when the moisture content in plough layer was maintained at 55% of field capacity, the senescence of roots in middle and lower soil layers was slower, and the higher root vigor compensated the negative effects of impaired photosynthesis caused by water deficit to some extent. The yield of seed cotton was lower when the moisture content in plough layer was maintained at 55% of field capacity than at 70% of field capacity, but no significant difference was observed in the water use efficiency. Our results emphasized the importance of pre-sowing irrigation in winter or in spring to increase the water storage of deeper soil layers. In addition, proper cultivation practices and less frequent drip irrigation (longer intervals between successive rounds of irrigation) were also essential for conserving irrigation water and achieving higher yield.

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