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Cutaneous T cell lymphomas (CTCLs), encompassing mycosis fungoides (MF) and Sézary syndrome (SS), present a complex landscape influenced by cytokines and cellular responses. In this work, the intricate relationship between these inflammatory proteins and disease pathogenesis is examined, focusing on what is known at the clinical and therapeutic levels regarding the most well-known inflammatory mediators. An in-depth look is given to their possible alterations caused by novel immunomodulatory drugs and how they may alter disease progression. From this narrative review of the actual scientific landscape, Interferon-gamma (IFN-γ) emerges as a central player, demonstrating a dual role in both promoting and inhibiting cancer immunity, but the work navigates through all the major interleukins known in inflammatory environments. Immunotherapeutic perspectives are elucidated, highlighting the crucial role of the cutaneous microenvironment in shaping dysfunctional cell trafficking, antitumor immunity, and angiogenesis in MF, showcasing advancements in understanding and targeting the immune phenotype in CTCL. In summary, this manuscript aims to comprehensively explore the multifaceted aspects of CTCL, from the immunopathogenesis and cytokine dynamics centred around TNF-α and IFN-γ to evolving therapeutic modalities. Including all the major known and studied cytokines in this analysis broadens our understanding of the intricate interplay influencing CTCL, paving the way for improved management of this complex lymphoma. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an abnormal inflammatory response in the skin to food, environmental IgE, or non-IgE allergens. This disease belongs to a group of inflammatory diseases that affect both children and adults. In highly developed countries, AD is diagnosed twice as often in children than in adults, which may possibly be connected to increased urbanization. The immune system's pathomechanisms of AD involve humoral mechanisms with IgE, cellular T lymphocytes, dendritic cells occurring in the dermis, Langerhans cells occurring in the epidermis, and other cells infiltrating the site of inflammation (eosinophils, macrophages, mast cells, neutrophils, and basophils). Cytokines are small proteins that affect the interaction and communication between cells. This review characterizes cytokines and potential aspects of the treatment of atopic dermatitis, as well as new strategies that are currently being developed, including targeting cytokines and their receptors. [ABSTRACT FROM AUTHOR]

Kiwifruit ripening and senescence after harvesting are closely related to its economic value. Transcriptome analysis and biochemical parameters were used to investigate the differences in gene expression levels and the potential regulation of cell wall metabolism in kiwifruit treated with ozone, thereby regulating fruit softening and prolonging postharvest life. Compared to the control group, the activities of the cell wall modification enzyme were lower under ozone treatment, the content of polysaccharide in the cell wall of primary pectin and cellulose was higher, and the content of soluble pectin was lower. Meanwhile, ozone treatment delayed the degradation of the cell wall mesosphere during storage. A total of 20 pectinesterase (PE)‐related genes were identified by sequencing analysis. The data analysis and quantitative polymerase chain reaction results confirmed that cell wall modifying enzyme genes played an important role in softening and senescence after harvesting, which may reduce or induce the expression of certain genes affecting cell wall metabolism. Ozone treatment not only regulates active genes such as xyloglucan endo glycosyltransferase/hydrolase, cellulose synthase, polygalacturonase, and PE to maintain the quality of fruit after harvest but also acts synergically with cell wall modifying enzymes to inhibit the degradation of cell wall, resulting in changes in the ultrastructure of cell wall, thereby reducing the hardness of kiwifruit. In addition, according to the results of cis‐acting elements, cell wall degradation is also related to downstream hormone signaling, especially PE‐related genes. These results provide a theoretical basis for studying the mechanism of firmness and cell wall metabolism difference of kiwifruit and also lay a good foundation for further research. [ABSTRACT FROM AUTHOR]

Data on the problems physicians face when providing care for atopic dermatitis (AD) is limited. To understand the current status of AD management in Japan and identify the difficulties physicians are having and their support requirements, a cross-sectional online survey was conducted using the AD task force of the Japanese Society for Cutaneous Immunology and Allergy. Society members were sent an online questionnaire on demographic information, daily clinical practice, and perceptions of AD management. Using responses to 17 items listed as barriers to the treatment of atopic dermatitis (Question 12) and questions about the treatment difficulty of those items, 284 respondents were divided into three groups using unstratified cluster analysis. These three groups were classified as highdifficulty, medium-difficulty, and low-difficulty groups, and the relationship between physicians' cognition and daily practice was examined for each group. There were no significant differences in affiliations or specializations among the three clusters. The low-difficulty group had a significantly higher proportion of participants believing that it was possible to achieve long-term remission, satisfaction, and motivation in AD management while carrying out precise assessments of skin lesions as part of their daily practice. Some physicians experience problems in their practice. This results indicate that AD management can be improved if satisfaction and motivation can be increased by providing appropriate support. [ABSTRACT FROM AUTHOR]

Background: Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal inflammation and the development and progression of cardiovascular disease and diabetes. However, the anti-inflammatory activity of IMP has not been investigated. This study aimed to elucidate the role of IMP in treating atopic dermatitis (AD). Methods: To understand how IMP mediates immunosuppression in AD, IMP was intraperitoneally injected into a Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions mouse model. We also characterized the anti-inflammatory mechanism of IMP by inducing an AD response in keratinocytes through TNF-α/IFN-γ or IL-4 stimulation. Results: Contrary to the prevailing view that IMP is an unhealthy microbial metabolite, we found that IMP-treated AD-like skin lesions mice showed significant improvement in their clinical symptoms, including ear thickness, epidermal and dermal thickness, and IgE levels. Furthermore, IMP antagonized the expansion of myeloid (neutrophils, macrophages, eosinophils, and mast cells) and Th cells (Th1, Th2, and Th17) in mouse skin and prevented mitochondrial reactive oxygen species production by inhibiting mitochondrial energy production. Interestingly, we found that IMP inhibited AD by reducing glucose uptake in cells to suppress proinflammatory cytokines and chemokines in an AD-like in vitro model, sequentially downregulating the PI3K and mTORC2 signaling pathways centered on Akt, and upregulating DDIT4 and AMPK. Discussion: Our results suggest that IMP exerts anti-inflammatory effects through the metabolic reprogramming of skin inflammation, making it a promising therapeutic candidate for AD and related skin diseases. [ABSTRACT FROM AUTHOR]

Background: The cochineal cactus (Opuntia cochenillifera), notable for its substantial agricultural and industrial applications, predominantly undergoes clonal reproduction, which presents significant challenges in breeding and germplasm innovation. Recent developments in mitochondrial genome engineering offer promising avenues for introducing heritable mutations, potentially facilitating selective sexual reproduction through the creation of cytoplasmic male sterile genotypes. However, the lack of comprehensive mitochondrial genome information for Opuntia species hinders these efforts. Here, we intended to sequence and characterize its mitochondrial genome to maximize the potential of its genomes for evolutionary studies, molecular breeding, and molecular marker developments. Results: We sequenced the total DNA of the O. cochenillifera using DNBSEQ and Nanopore platforms. The mitochondrial genome was then assembled using a hybrid assembly strategy using Unicycler software. We found that the mitochondrial genome of O. cochenillifera has a length of 1,156,235 bp, a GC content of 43.06%, and contains 54 unique protein-coding genes and 346 simple repeats. Comparative genomic analysis revealed 48 homologous fragments shared between mitochondrial and chloroplast genomes, with a total length of 47,935 bp. Additionally, the comparison of mitochondrial genomes from four Cactaceae species highlighted their dynamic nature and frequent mitogenomic reorganizations. Conclusion: Our study provides a new perspective on the evolution of the organelle genome and its potential application in genetic breeding. These findings offer valuable insights into the mitochondrial genetics of Cactaceae, potentially facilitating future research and breeding programs aimed at enhancing the genetic diversity and adaptability of O. cochenillifera by leveraging its unique mitochondrial genome characteristics. [ABSTRACT FROM AUTHOR]

Background: Different metabolic compounds give pepper leaves and fruits their diverse colors. Anthocyanin accumulation is the main cause of the purple color of pepper leaves. The light environment is a critical factor affecting anthocyanin biosynthesis. It is essential that we understand how to use light to regulate anthocyanin biosynthesis in plants. Result: Pepper leaves were significantly blue–purple only in continuous blue light or white light (with a blue light component) irradiation treatments, and the anthocyanin content of pepper leaves increased significantly after continuous blue light irradiation. This green-to-purple phenotype change in pepper leaves was due to the expression of different genes. We found that the anthocyanin synthesis precursor-related genes PAL and 4CL, as well as the structural genes F3H, DFR, ANS, BZ1, and F3'5'H in the anthocyanin synthesis pathway, had high expression under continuous blue light irradiation. Similarly, the expression of transcription factors MYB1R1-like, MYB48, MYB4-like isoform X1, bHLH143-like, and bHLH92-like isoform X3, and circadian rhythm-related genes LHY and COP1, were significantly increased after continuous blue light irradiation. A correlation network analysis revealed that these transcription factors and circadian rhythm-related genes were positively correlated with structural genes in the anthocyanin synthesis pathway. Metabolomic analysis showed that delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside were significantly higher under continuous blue light irradiation relative to other light treatments. We selected 12 genes involved in anthocyanin synthesis in pepper leaves for qRT-PCR analysis, and the accuracy of the RNA-seq results was confirmed. Conclusions: In this study, we found that blue light and 24-hour irradiation together induced the expression of key genes and the accumulation of metabolites in the anthocyanin synthesis pathway, thus promoting anthocyanin biosynthesis in pepper leaves. These results provide a basis for future study of the mechanisms of light quality and photoperiod in anthocyanin synthesis and metabolism, and our study may serve as a valuable reference for screening light ratios that regulate anthocyanin biosynthesis in plants. [ABSTRACT FROM AUTHOR]

Aim of the study: Arthroscopy ranks among the frequently performed interventions in orthopedics. The aim of this study was to compare the palpation technique with the ultrasound technique for locating the dorsal glenohumeral joint space (JS) in shoulder joint punctures. Material and Methods: Participants inexperienced in ultrasound examinations were included. Palpatory and ultrasound finding of the joint space by the participants was performed according to current recommendations and was initially demonstrated by an instructional video. The ideal point (IP) was marked under ultrasound visualization by an experienced ultrasound examinator and shoulder–elbow surgeon. Furthermore, a corridor for a safe puncture was defined. The palpatorily determined point (pdP) was marked by the participants and evaluated by means of a coordinate system. The evaluation of the sonographically determined point (sdP) was performed similarly to that of the palpatory procedure. Results: Fifty-four participants were included in the study, and the mean length of work experience was 6.3 years. On average, participants had performed 16.5 punctures of the shoulder joint and 6.8 arthroscopies of the shoulder joint. The mean experience in performing sonographic examinations of the shoulder was 27.6 examinations. A total of 100 shoulder joints were examined (54 left, 46 right shoulders). The mean deviation from the ideal point (IP) for the palpatory approach was 17.1 mm with a maximum deviation of 59.5 mm; for the sonographic technique, the mean deviation was 10.3 mm (max. 30.2 mm). Overall, 22% of pdPs were within the defined corridor, while 42% of sdPs were within the target corridor. The average difference between palpatory and sonographic approaches was 9.0 mm in favor of the sonographic technique (max. 46.5 mm). A significantly greater deviation (p < 0.001) from the IP was observed with the palpatory approach than with the sonographic approach. Conclusion: Based on the results, the authors recommend ultrasound imaging of the shoulder joint as well as ultrasound-assisted punctures, especially for inexperienced users. Furthermore, training in ultrasound-assisted interventions should be implemented in future training curricula. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)—the most common variant of CTCL—often presents with skin lesions around the abdomen and buttocks ("bathing suit" distribution), i.e., in skin areas devoid of sun-induced vitamin D. For decades, sunlight and vitamin D have been connected to CTCL. Thus, vitamin D induces apoptosis and inhibits the expression of cytokines in malignant T cells. Furthermore, CTCL patients often display vitamin D deficiency, whereas phototherapy induces vitamin D and has beneficial effects in CTCL, suggesting that light and vitamin D have beneficial/protective effects in CTCL. Inversely, vitamin D promotes T helper 2 (Th2) cell specific cytokine production, regulatory T cells, tolerogenic dendritic cells, as well as the expression of immune checkpoint molecules, all of which may have disease-promoting effects by stimulating malignant T-cell proliferation and inhibiting anticancer immunity. Studies on vitamin D treatment in CTCL patients showed conflicting results. Some studies found positive effects, others negative effects, while the largest study showed no apparent clinical effect. Taken together, vitamin D may have both pro- and anticancer effects in CTCL. The balance between the opposing effects of vitamin D in CTCL is likely influenced by treatment and may change during the disease course. Therefore, it remains to be discovered whether and how the effect of vitamin D can be tilted toward an anticancer response in CTCL. [ABSTRACT FROM AUTHOR]

Multi-junction photovoltaics approaches are being explored to mitigate thermalization losses that occur in the absorption of high-energy photons. However, the design of tandem cells faces challenges such as light reflection and parasitic absorption. Nanostructures have emerged as promising solutions due to their anti-reflection properties, which enhances light absorption. III-V nanowires (NWs) solar cells can achieve strong power conversion efficiencies, offering the advantage of potentially integrating tunnel diodes within the same fabrication process. Metal halide perovskites (MHPs) have gained attention for their optoelectronic attributes and cost-effectiveness. Notably, both material classes allow for tunable bandgaps. This study explores the integration of MHPs with III-V NWs solar cells in both two-terminal and three-terminal configurations. Our primary focus lies in the optical analysis of a tandem design using III-V semiconductor nanowire arrays in combination with perovskites, highlighting their potential for tandem applications. The space offered by the compact footprint of NW arrays is used in an interpenetrated tandem structure. We systematically optimize the bottom cell, addressing reflectivity and parasitic absorption, and extend to a full tandem structure, considering experimentally feasible thicknesses. Simulation of a three-terminal structure highlights a potential increase in efficiency, decoupling the operating points of the subcells. The two-terminal analysis underscores the benefits of nanowires in reducing reflection and achieving a higher matched current between the top and the bottom cells. This research provides significant insights into NW tandem solar cell optics, enhancing our understanding of their potential to improve photovoltaic performance. [ABSTRACT FROM AUTHOR]

The gaseous phytohormone ethylene (ETH) plays a key role in plant growth and development, and is a major regulator of phenolic biosynthesis. Light has long been known to influence phytohormone signaling transduction. However, whether light influences the effect of ETH on the phenolic composition of grapes (Vitis vinifera L.) is an open question. Here, the accumulation and composition of anthocyanins and non-anthocyanin phenolics were analyzed in Cabernet Sauvignon grapes under four treatments: light exposure with and without ETH treatment, and box-shading with and without ETH treatment. Both light and ETH promoted ripening, decreased the color index (L*, C*, and h*), and accelerated the color change from green to red and purplish red. Sunlight-exposed grapes had the highest contents of most anthocyanins, flavonols, flavan-3-ols, and hydroxybenzoic acids. In addition, light exposure increased the ratios of 3'5'-substituted/3'-substituted anthocyanins and flavonols, but decreased the ratios of methoxylated/non-methoxylated and acylated/non-acylated anthocyanins and flavan-3-ols. Notably, the effects of ETH were influenced by light exposure. Specifically, ETH treatment promoted anthocyanin and non-anthocyanin biosynthesis in light-exposed grapes, and their increasing multiples were remarkably higher under light-exposed conditions. Furthermore, ETH treatment decreased the ratios of methoxylated/nonmethoxylated, 3'5'-substituted/3'-substituted, and acylated/non-acylated anthocyanins and flavan-3-ols in light-exposed grapes, each of which was increased by ETH treatment in shaded grapes. Fifteen differential phenolic components were identified through partial least-squares-discriminant analysis (PLS-DA). Among them, cyanidin-3-O-(cis-6-O-coumaryl)-glucoside, petunidin-3-O-(6-O-acetyl)-glucoside, petunidin-3-O-(trans-6-O-coumaryl)-glucoside, petunidin-3-O-glucoside, myricetin-3-O-galactoside, kaempferol-3-Ogalactoside, and kaempferol-3-O-glucoside were the main differential components between ETH treatments under different light conditions. This study contributes to the understanding of the impact of ethylene treatment under dark and light conditions on phenolic synthesis in grape berries. [ABSTRACT FROM AUTHOR]

Red sea bream is a commercially valuable fish that is used as ingredients in the food industry. To prevent a decrease in fishing yield, farmed red sea bream is released. However, this may cause a decrease in the genetic diversity of wild populations, so systematic resource management is required. In this study, 68 single nucleotide polymorphism (SNP) markers were developed using a genotyping-by-sequencing (GBS) analysis. The minor allele frequency (MAF) ranged from 0.1802 to 0.5000, the observed heterozygosity (Ho) ranged from 0.0864 to 0.5000, expected heterozygosity (He) ranged from 0.2955 to 0.5000, and the polymorphism information content (PIC) ranged from 0.2518 to 0.3750. Of these SNPs, 25 loci significantly deviated from the Hardy–Weinberg equilibrium after a Bonferroni correction (p < 0.00074). These SNP markers will be useful for the further genetic analysis of the red sea bream population. [ABSTRACT FROM AUTHOR]

Surface wrinkling provides an approach to fabricate micron and sub-micron-level biomaterial topographies that can mimic features of the dynamic, in vivo cell environment and guide cell adhesion, alignment, and differentiation. Most wrinkling research to date has used planar, two-dimensional (2D) substrates, and wrinkling work on three-dimensional (3D) structures has been limited. To enable wrinkle formation on architecturally complex, biomimetic 3D structures, here, we report a simple, low-cost experimental wrinkling approach that combines natural silk fibroin films with a recently developed advanced manufacturing technique for programming strain in complex 3D shape–memory polymer (SMP) scaffolds. By systematically investigating the influence of SMP programmed strain magnitude, silk film thickness, and aqueous media on wrinkle morphology and stability, we reveal how to generate and tune silk wrinkles on the micron and sub-micron scale. We find that increasing SMP programmed strain magnitude increases wavelength and decreases amplitudes of silk wrinkled topographies, while increasing silk film thickness increases wavelength and amplitude. Silk wrinkles persist after 24 h in cell culture medium. Wrinkled topographies demonstrate high cell viability and attachment. These findings suggest the potential for fabricating biomimetic cellular microenvironments that can advance understanding and control of cell–material interactions in engineering tissue constructs. [ABSTRACT FROM AUTHOR]

Aim: Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it can induce the synthesis of MMPs (matrix metalloproteinases) on the surface of tumor cells where it was originally identified. It can also function in adjacent tumor fibroblasts using CD147–CD147 interactions. The polymorphism rs8259 T/A is situated in the untranslated region (3′UTR) of the CD147 gene. HLA DRB1*1501 takes part in the process of presentation and recognition of different antigens to T cells. It can be expressed by antigen-presenting cells—macrophages, dendritic cells, and B cells. The aim of the study is to test genotype–phenotype associations of both polymorphisms including therapy in a large cohort of CTCL patients. Materials and Methods: A final total of 104 CTCL patients were enrolled in the study. For the first remission at the clinic department, they were treated by means of local skin-directed therapy, phototherapy, and systemic therapy. Genomic DNA was isolated from peripheral blood leukocytes. A standard technique using proteinase K was applied. The polymorphisms rs8259 T/A (CD147 gene) and rs3135388 (HLA DRB1*1501) were detected through standard PCR-restriction fragment length polymorphism methods. Results: The severity of the disease (patients with parapsoriasis, stages IA and IB, vs patients with stages IIB, IIIA, and IIIB) was associated with the CD147 genotype: the AA variant was 3.38 times more frequent in more severe cases, which reflects the decision on systemic therapy (p = 0.02, specificity 0.965). The AA genotype in the CD147 polymorphism was 12 times more frequent in patients who underwent systemic therapy of CTCL compared to those not treated with this therapy (p = 0.009, specificity 0.976). The same genotype was also associated with radiotherapy—it was observed 14 times more frequently in patients treated with radiotherapy (p = 0.009, specificity 0.959). In patients treated with interferon α therapy, the AA genotype was observed to be 5.85 times more frequent compared to the patients not treated with interferon therapy (p = 0.03, specificity 0.963). The HLA DRB1*1501 polymorphism was associated with local skin-directed therapy of CTCL. The CC genotype of the polymorphism was observed to be 3.57 times more frequent in patients treated with local therapy (p = 0.008, specificity 0.948). When both polymorphisms had been calculated together, even better results were obtained: the AACC double genotype was 11 times more frequent in patients with severe CTCL (p = 0.009, specificity 0.977). The TACT double genotype was associated with local skin-directed therapy (0.09 times lower frequency, p = 0.007, sensitivity 0.982). The AACC genotype was 8.9 times more frequent in patients treated by means of systemic therapy (p = 0.02, specificity 0.976) and as many as 18.8 times more frequent in patients treated with radiotherapy (p = 0.005, specificity 0.969). Thus, the AACC double genotype of CD147 and DRB1*1501 polymorphisms seems to be a clinically highly specific marker of severity, systemic therapy and radiotherapy of patients with T-cell lymphoma. Conclusion: Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well. [ABSTRACT FROM AUTHOR]

The clinical outcome of lymphocytic leukemia (CLL) is quite heterogeneous. The purpose of this observational study was to investigate the clinical merit of measuring plasma galectin-9 and CXCL-13 concentrations as predictors of CLL activity, prognosis, and early indicators of therapeutic response. These biomarkers were compared with other prognostic indicators, progression-free survival (PFS), time to first treatment (TTT), and overall survival (OS) over a follow-up period (4 years). First, plasma galectin-9 and CXCL-13 concentrations were analyzed in CLL patients at the time of diagnosis as well as healthy controls. Compared to controls, CLL patients had significantly higher serum levels of CXCL-13 and galectin-9. Second, we observed that CLL patients with high soluble CXCL-13 and galectin-9 levels had advanced clinical stages, poor prognosis, 17p del, short PFS, short TTT, and therapy resistance. The levels of CXCL-13, β2-microglobulin, LDH, CD38%, and high grade of Rai-stage were all strongly correlated with the galectin-9 levels. Soluble CXCL-13 and galectin-9 had very good specificity and sensitivity in detecting CLL disease progression and high-risk patients with the superiority of galectin-9 over CXCL-13. Although the two biomarkers were equal in prediction of TTT and treatment response, the soluble CXCL13 was superior in prediction of OS. High CXCL-13 and galectin-9 plasma levels upon CLL diagnosis are associated with disease activity, progression, advanced clinical stages, short periods of PFS, short TTT, and unfavorable treatment response. [ABSTRACT FROM AUTHOR]

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering agents widely used for the treatment of type 2 diabetes mellitus. A number of clinical trials in type 2 diabetic patients with different degrees of renal impairment have clearly demonstrated that SGLT2 inhibitors reduce the progression rate of diabetic kidney disease. Furthermore, recent studies have shown that SGLT2 inhibitors also exert a protective effect in the case of non-diabetic kidney disease. Consequently, it has been hypothesized that the nephroprotective activity of these drugs could exceed the canonical impact on glycemic control and that the resulting beneficial effects could be the consequence of their pleiotropic properties (proven reduction of inflammation, fibrosis, oxidative stress and sympathetic nervous activity) both at systemic and tissue levels, suggesting that the efficacy of these drugs could also be extended to non-diabetic nephropathies. This review focuses on the nephroprotective effects of SGLT2 inhibitors in different experimental models of non-diabetic kidney disease. The different glucose-independent mechanisms potentially implemented by SGLT2 inhibitors to ultimately protect the non-diabetic kidney are described in detail, and conflicting results, when present, are discussed. [ABSTRACT FROM AUTHOR]

Calcium-activated potassium (KCa) channels are ubiquitously expressed throughout the body and are able to regulate membrane potential and intracellular calcium concentrations, thereby playing key roles in cellular physiology and signal transmission. Consequently, it is unsurprising that KCa channels have been implicated in various diseases, making them potential targets for pharmaceutical interventions. Over the past two decades, numerous studies have been conducted to develop KCa channel-targeting drugs, including those for disorders of the central and peripheral nervous, cardiovascular, and urinary systems and for cancer. In this review, we synthesize recent findings regarding the structure and activating mechanisms of KCa channels. We also discuss the role of KCa channel modulators in therapeutic medicine. Finally, we identify the major reasons behind the delay in bringing these modulators to the pharmaceutical market and propose new strategies to promote their application. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome virus (PRRSV) is a typical immunosuppressive virus causing a large economic impact on the swine industry. The structural protein GP5 of PRRSV plays a pivotal role in its pathogenicity and immune evasion. Virus–host interactions play a crucial part in viral replication and immune escape. Therefore, understanding the interactions between GP5 and host proteins are significant for porcine reproductive and respiratory syndrome (PRRS) control. However, the interaction network between GP5 and host proteins in primary porcine alveolar macrophages (PAMs) has not been reported. In this study, 709 GP5-interacting host proteins were identified in primary PAMs by immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bioinformatics analysis revealed that these proteins were involved in multiple cellular processes, such as translation, protein transport, and protein stabilization. Subsequently, immunoprecipitation and immunofluorescence assay confirmed that GP5 could interact with antigen processing and presentation pathways related proteins. Finally, we found that GP5 may be a key protein that inhibits the antigen processing and presentation pathway during PRRSV infection. The novel host proteins identified in this study will be the candidates for studying the biological functions of GP5, which will provide new insights into PRRS prevention and vaccine development. [ABSTRACT FROM AUTHOR]

Context: Arthroscopic surgical repair of the shoulder is recommended when conservative treatment for shoulder instability (SI) fails. However, many patients undergoing this procedure do not return to same level of activity. Psychological factors and muscle strength have been shown to be associated with postoperative outcomes in other musculoskeletal conditions. Objective: To investigate the association between fear avoidance, muscle strength, and short-term function in patients after surgical SI repair. Methods: Twenty-five male patients who underwent shoulder surgery following at least one event of SI were included in this study. Evaluations of fear avoidance related to physical activity and disability were performed at baseline (during the first encounter with the physical therapist) and 7 to 8 weeks postsurgery. Fear avoidance beliefs were assessed using the Fear Avoidance Beliefs Questionnaire. Disability was assessed using the Disabilities of Arm, Shoulder, and Hand questionnaire and the Western Ontario SI index. The follow-up evaluation (weeks 7–8) included measurement of maximal isometric strength of the internal and external rotators. Nonparametric Kendall tau was used to determine the correlations between baseline fear avoidance, muscle strength, and disability at follow-up. Results: Disabilities of Arm, Shoulder, and Hand questionnaire at follow-up was significantly correlated with baseline Disabilities of Arm, Shoulder, and Hand questionnaire (τ =.520, P <.001), baseline fear avoidance (τ =.399, P =.008), and both internal rotator (τ = −.400, P =.005) and external rotator strength (τ = −.353, P =.014). Western Ontario SI index at follow-up was moderately correlated with baseline Western Ontario SI index (τ =.387, P =.007), internal rotator (τ = −.427, P =.003), and external rotator (τ = −.307, P =.032), but not with baseline Fear Avoidance Beliefs Questionnaire (τ =.22, P =.145). Conclusions: The results indicate a possible association between fear avoidance beliefs and short-term disability. Further studies are warranted to better explore and understand these relationships. [ABSTRACT FROM AUTHOR]

Discusses the development of an effective method for computing the double infinite integrals of an acoustic plane wave by a rectangular plate. Numerical results for far diffracted pattern; Division of subregions consisting of annular sectors with different radii; Calculation of the integral K(m.n,s,t); Scattering of acoustic plane waves.

Miyaji H, Sugaya T, Ibe K, Ishizuka R, Tokunaga K, Kawanami M. Root surface conditioning with bone morphogenetic protein-2 facilitates cementum-like tissue deposition in beagle dogs. J Periodont Res 2010; 45: 658–663. © 2010 John Wiley & Sons A/S Background and Objective: Modification of the root surface may play an important role in regenerating the periodontal attachment between the root and periodontal connective tissue. We speculated that bone morphogenetic protein (BMP) application to the root surface constructed a novel attachment by cementum-like hard tissue, although gingival connective tissue proliferated to the root surface. The aim of this study was to examine whether BMP-2 guided cementum-like tissue deposition on a BMP-conditioned root surface. Material and Methods: Root dentin on the buccal side of 24 teeth in four beagle dogs was surgically exposed. The denuded root dentin surfaces were demineralized with EDTA and washed with saline. Subsequently, 15 μL of BMP-2 solution (loading dose, 0.4 and 1.0 μg/μL) was applied to the root dentin surface. In the control roots, phosphate-buffered saline was applied to the root surface. Specimens were analyzed histologically 16 wk after surgery. Results: Formation of cementum-like tissue was frequently observed on the BMP-2-conditioned root at the coronal portion. Cellular cementum-like tissue was separated from the original cementum and encapsulated with gingival connective tissue. Cementum-like tissue formation with BMP-2 at 1.0 μg/μL was significantly greater than that in the control roots and those with BMP-2 at 0.4 μg/μL. Downgrowth of the junctional epithelium in the 1.0 μg/μL BMP-2 group was significantly less than that in the control roots. Conclusion: Root dentin surface conditioning with BMP-2 stimulated cementum-like tissue formation and inhibited epithelial downgrowth. [ABSTRACT FROM AUTHOR]

The opinions of patients with allergic skin diseases often determine their attitudes to treatment. However, little is known about the viewpoints of patients and their concerns regarding their conditions. This novel study is the first to compare relationships between the opinions of patients and their concerns regarding the severity of atopic dermatitis or chronic spontaneous urticaria and the presence or absence of biologics. We also compared and clarified the characteristics of these diseases using a questionnaire that was completed by 359 patients treated at university and city hospitals, as well as dermatology clinics. Covariance analysis was performed to compare both diseases with different backgrounds. Patients with adult atopic dermatitis were more likely than those with chronic idiopathic urticaria to believe that treatment must be continued and that the disease will not spontaneously improve. Patients with severe or poorly controlled atopic dermatitis or chronic spontaneous urticaria often had psychosomatic symptoms and also believed that the disease required continued treatment. Social factors related to wait times and medication were not associated with disease severity. Patients receiving treatment had significantly less anxiety associated with biologics than those who did not receive treatment. Patients with atopic dermatitis had higher physical and mental burden than those with chronic spontaneous urticaria. Therefore, effective treatments must be prescribed. Consideration of these disease-specific characteristics regarding the opinions and concerns of patients can improve patient satisfaction and compliance with treatment, which results in favorable outcomes. [ABSTRACT FROM AUTHOR]

Novel KCNMA1 variants, encoding the BK K+ channel, are associated with a debilitating dyskinesia and epilepsy syndrome. Neurodevelopmental delay, cognitive disability, and brain and structural malformations are also diagnosed at lower incidence. More than half of affected individuals present with a rare negative episodic motor disorder, paroxysmal nonkinesigenic dyskinesia (PNKD3). The mechanistic relationship of PNKD3 to epilepsy and the broader spectrum of KCNMA1-associated symptomology is unknown. This review summarizes patient-associated KCNMA1 variants within the BK channel structure, functional classifications, genotype-phenotype associations, disease models, and treatment. Patient and transgenic animal data suggest delineation of gain-of-function (GOF) and loss-of-function KCNMA1 neurogenetic disease, validating two heterozygous alleles encoding GOF BK channels (D434G and N999S) as causing seizure and PNKD3. This discovery led to a variant-defined therapeutic approach for PNKD3, providing initial insight into the neurological basis. A comprehensive clinical definition of monogenic KCNMA1-linked disease and the neuronal mechanisms currently remain priorities for continued investigation. [ABSTRACT FROM AUTHOR]

Heparan sulfate (HS) is a linear polysaccharide that plays a key role in cellular signaling networks. HS functions are regulated by its 6-O-sulfation, which is catalyzed by three HS 6-O-sulfotransferases (HS6STs). Notably, HS6ST2 is mainly expressed in the brain and HS6ST2 mutations are linked to brain disorders, but the underlying mechanisms remain poorly understood. To determine the role of Hs6st2 in the brain, we carried out a series of molecular and behavioral assessments on Hs6st2 knockout mice. We first carried out strong anion exchange-high performance liquid chromatography and found that knockout of Hs6st2 moderately decreases HS 6-O-sulfation levels in the brain. We then assessed body weights and found that Hs6st2 knockout mice exhibit increased body weight, which is associated with abnormal metabolic pathways. We also performed behavioral tests and found that Hs6st2 knockout mice showed memory deficits, which recapitulate patient clinical symptoms. To determine the molecular mechanisms underlying the memory deficits, we used RNA sequencing to examine transcriptomes in two memory-related brain regions, the hippocampus and cerebral cortex. We found that knockout of Hs6st2 impairs transcriptome in the hippocampus, but only mildly in the cerebral cortex. Furthermore, the transcriptome changes in the hippocampus are enriched in dendrite and synapse pathways. We also found that knockout of Hs6st2 decreases HS levels and impairs dendritic spines in hippocampal CA1 pyramidal neurons. Taken together, our study provides novel molecular and behavioral insights into the role of Hs6st2 in the brain, which facilitates a better understanding of HS6ST2 and HS-linked brain disorders. [ABSTRACT FROM AUTHOR]

Fresh Codonopsis pilosula is highly susceptible to fungus contamination during post-harvest storage, which not only compromises the quality of C. pilosula but also contributes mycotoxin contamination, posing a significant threat to human health. Studies have indicated that ozone treatment can inhibit post-harvest diseases in fruits and vegetables. The impact of ozone treatment on the disease incidence, disease severity index, and weight loss rate of the fresh C. pilosula infected with Actinomucor elegans was investigated through the spray inoculation of A. elegans on C. pilosula tissues. Changes in the main active ingredients of C. pilosula after ozone treatment were analyzed, and the effects of ozone treatment on the integrity of cell membranes in C. pilosula tissue and reactive oxygen species (ROS) metabolism were studied. The results showed that ozone treatment had a significant inhibitory effect on the A. elegans-induced mucor rot in C. pilosula, significantly reducing the incidence of the disease. Compared with the control group, the ozone-treated group maintained the effective components of C. pilosula well. Furthermore, ozone treatment reduced the cell membrane permeability and Malondialdehyde (MDA) content in C. pilosula, significantly increased the activity of antioxidant enzymes in the ROS metabolism pathway, prevented oxidative stress caused by the accumulation of ROS in C. pilosula tissues, and maintained the integrity of cell membranes. [ABSTRACT FROM AUTHOR]

Ciguatoxins (CTXs) stand as the primary toxins causing ciguatera fish poisoning (CFP) and are essential compounds distinguished by their characteristic polycyclic ether structure. In a previous report, we identified the structures of product ions generated via homolytic fragmentation by assuming three charge sites in the mass spectrometry (MS)/MS spectrum of ciguatoxin-3C (CTX3C) using LC-MS. This study aims to elucidate the homolytic fragmentation of a ciguatoxin-3C congener. We assigned detailed structures of the product ions in the MS/MS spectrum of a naturally occurring ciguatoxin-3C congener, 51-hydroxyciguatoxin-3C (51-hydoxyCTX3C), employing liquid chromatography/quadrupole time-of-flight mass spectrometry with an atmospheric pressure chemical ionization (APCI) source. The introduction of a hydroxy substituent on C51 induced different fragmentation pathways, including a novel cleavage mechanism of the M ring involving the elimination of 51-OH and the formation of enol ether. Consequently, new cleavage patterns generated product ions at m/z 979 (C55H79O15), 439 (C24H39O7), 149 (C10H13O), 135 (C9H11O), and 115 (C6H11O2). Additionally, characteristic product ions were observed at m/z 509 (C28H45O8), 491 (C28H43O7), 481 (C26H41O8), 463 (C26H39O7), 439 (C24H39O7), 421 (C24H37O6), 171 (C9H15O3), 153 (C9H13O2), 141 (C8H13O2), and 123 (C8H11O). [ABSTRACT FROM AUTHOR]

Aim: To investigate the relationship between interleukin‐17 (IL‐17), ferroptosis and osteogenic differentiation. Materials and Methods: We first analysed the changes in ferroptosis‐related molecules in experimental periodontitis models. The effects of erastin, a small‐molecule ferroptosis inducer, and IL‐17 on alveolar bone loss and repair in animal models were then investigated. Primary mouse mandibular osteoblasts were exposed to erastin and IL‐17 in vitro. Ferroptosis‐ and osteogenesis‐related genes and proteins were detected. Further, siRNA, immunofluorescence co‐localization and immunoprecipitation were used to confirm the roles of the nuclear factor erythroid‐2‐related factor 2 (NRF2) and phosphorylated signal transducer and activator of transcription 3 (p‐STAT3), as well as their interaction. Results: The levels of NRF2, glutathione peroxidase 4 and solute carrier family 7 member 11 were lower in the ligated tissues than in normal periodontal tissues. Alveolar bone loss in an in vivo experimental periodontitis model was aggravated by erastin and alleviated by IL‐17. In vitro, IL‐17 ameliorated erastin‐inhibited osteogenic differentiation by reversing ferroptosis. Altered NRF2 expression correlated with changes in ferroptosis‐related molecules and osteogenesis. Furthermore, the physical interaction between NRF2 and p‐STAT3 was confirmed in the nucleus. In IL‐17 + erastin‐stimulated osteoblasts, the p‐STAT3–NRF2 complex might actively participate in the downstream transcription of ferroptosis‐ and osteogenesis‐related genes. Conclusions: IL‐17 administration conferred resistance to erastin‐induced osteoblast ferroptosis and osteogenesis. The possible mechanism may involve p‐STAT3 directly interacting with NRF2. [ABSTRACT FROM AUTHOR]

The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL. [ABSTRACT FROM AUTHOR]

Background: Few studies have reported clinical outcomes and tendon healing rates after arthroscopic isolated subscapularis (SSC) repair (AISR). Purpose/Hypothesis: The primary purpose of this study was to evaluate clinical outcomes and tendon healing after AISR. It was hypothesized that AISR would result in satisfactory clinical outcomes along with a high rate of tendon healing at the midterm follow-up. The secondary purpose was to assess the influence of tear size and muscle atrophy on SSC tendon healing and patient-reported outcomes. It was hypothesized that both would be negatively correlated with healing but would have no effect on clinical outcomes. Study Design: Case series; Level of evidence, 4. Methods: A retrospective analysis was conducted on prospectively collected data for 77 patients who underwent primary AISR between 2011 and 2021 at a single institution, with a minimum 2-year postoperative follow-up for all patients. Functional outcomes were assessed using the American Shoulder and Elbow Surgeons (ASES) score, the Subjective Shoulder Value (SSV), and the visual analog scale for pain. Repair techniques and concomitant procedures were also collected. SSC tendon healing was evaluated via ultrasound at the final follow-up. Linear regression analysis was performed to determine factors affecting SSC healing. Results: The mean follow-up was 58.1 ± 3.3 months. ASES scores significantly improved from 41.5 to 81.6, and the SSV improved from 38.2 to 80.5 (P <.01 for both). Among the 40 patients (51.9%) who underwent postoperative ultrasound, 87.5% showed complete tendon healing. There were no significant differences in outcome scores between healed and unhealed tendons. Increased muscle atrophy and larger tears were correlated with failure of SSC healing (β = −0.285 [ P =.015] and β = −0.157 [ P =.045], respectively). Conclusion: Improved clinical outcomes and an overall high rate of tendon healing were seen at the midterm follow-up after AISR. Smaller tear sizes with less muscle atrophy were correlated with improved tendon healing. However, even when the tendon incompletely healed, the procedure improved functional outcomes. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic skin condition with intense pruritus, eczema, and dry skin. The recurrent intense pruritus and numerous complications in patients with AD can profoundly affect their quality of life. Obesity is one of its comorbidities that has been confirmed to be the hazard factor of AD and also worsen its severity. Nevertheless, the specific mechanisms that explain the connection between obesity and AD remain incompletely recognized. Recent studies have built hopes on various adipokines to explain this connection. Adipokines, which are disturbed by an obese state, may lead to immune system imbalances in people with AD and promote the development of the disease. This review focuses on the abnormal expression patterns of adipokines in patients with AD and their potential regulatory molecular mechanisms associated with AD. The connection between AD and obesity is elucidated through the involvement of adipokines. This conduces to the in-depth exploration of AD pathogenesis and provides a new perspective to develop therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer ranks as the second most common cause of cancer-related deaths. In this research, we analyzed the prognostic and predictive roles of three potential serum biomarkers (Cyclophilin A (CypA), copeptin and Tie2) in 56 patients with metastatic colorectal cancer treated with bevacizumab and chemotherapy. We assessed the serum levels of biomarkers before and after one and six months of therapy. Based on Kaplan–Meier curves and multivariate Cox analysis, low levels of CypA at baseline and after one month of treatment were associated with better overall survival, being independent prognostic factors after adjustment for baseline and post-treatment factors. For copeptin and Tie2, the results show no correlation between these biomarkers and overall survival or progression-free survival. Colorectal cancer (CRC) ranks as second most common cause of cancer-related deaths. The CRC management considerably improved in recent years, especially due to biological therapies such as bevacizumab. The lack of predictive or prognostic biomarkers remains one of the major disadvantages of using bevacizumab in the CRC management. We performed a prospective study to analyze the prognostic and predictive roles of three potential serum biomarkers (Cyclophilin A (CypA), copeptin and Tie2) investigated by ELISA in 56 patients with metastatic CRC undergoing bevacizumab and chemotherapy between May 2019 and September 2021 at baseline and after one and six months of therapy. We showed that low levels of CypA at baseline and after one month of treatment were associated with better overall survival (OS) (42 versus 24 months, p = 0.029 at baseline; 42 versus 25 months, p = 0.039 after one month). For copeptin and Tie2, Kaplan–Meier curves showed no correlation between these biomarkers and OS or progression-free survival. When adjusting for baseline and post-treatment factors, a multivariate Cox analysis showed that low values of CypA at baseline and after one month of treatment were independent prognostic factors for OS and correlated with a better prognosis in metastatic CRC patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate and characterize the mutations induced by two TALE-based approaches, double-strand break (DSB) induction by the FokI nuclease (mitoTALEN) and targeted base editing by the DddA cytidine deaminase (mitoTALECD), to edit, for the first time, the mitochondrial genome of potato, a vegetatively propagated crop. The two methods were used to knock out the same mitochondrial target sequence (orf125). Results: Targeted chondriome deletions of different sizes (236–1066 bp) were induced by mitoTALEN due to DSB repair through ectopic homologous recombination of short direct repeats (11–12 bp) present in the target region. Furthermore, in one case, the induced DSB and subsequent repair resulted in the amplification of an already present substoichiometric molecule showing a 4288 bp deletion spanning the target sequence. With the mitoTALECD approach, both nonsense and missense mutations could be induced by base substitution. The deletions and single nucleotide mutations were either homoplasmic or heteroplasmic. The former were stably inherited in vegetative offspring. Conclusions: Both editing approaches allowed us to obtain plants with precisely modified mitochondrial genomes at high frequency. The use of the same plant genotype and mtDNA region allowed us to compare the two methods for efficiency, accuracy, type of modifications induced and stability after vegetative propagation. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic immune-mediated disease, linked to local and systemic inflammation and predisposing patients to a higher risk of associated comorbidities. Cytokine levels are not widely available for disease progression monitoring due to high costs. Validated low-cost and reliable markers are needed for assessing disease progression and outcome. This study aims to assess the reliability of blood-count-derived inflammatory markers as disease predictors and to identify prognostic factors for disease severity. Patients fulfilling the inclusion criteria were enrolled in this study. Patients were divided into three study groups according to disease severity measured by the Body Surface Area (BSA) score: mild, moderate, and severe psoriasis. White blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (d-NLR), systemic immune index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) positively were correlated with disease severity (p < 0.005). d-NLR, NLR, and SII are independent prognostic factors for mild and moderate psoriasis (p < 0.05). d-NLR is the only independent prognostic factor for all three study groups. Moderate psoriasis is defined by d-NLR values between 1.49 and 2.19. NLR, PLR, d-NLR, MLR, SII, SIRI, and AISI are useful indicators of systemic inflammation and disease severity in psoriasis. [ABSTRACT FROM AUTHOR]

Background: The risk of developing cutaneous T cell lymphoma (CTCL) in patients using psoriasis biologics has not been well characterized. The goals of this review were to investigate the incidence of CTCL in patients with psoriasis receiving biologic therapy in clinical trials and psoriasis registries, and to review cases of CTCL and biologic use reported in scientific publications. Methods: The US National Library of Medicine clinical trials database (clinicaltrials.gov) was queried to identify phase 3 and 4 clinical trials of the 12 biologic agents currently FDA approved for psoriatic disease. The incidence of CTCL in these trials was examined and summarized. To examine the incidence of CTCL in psoriasis registries, a Medline search was conducted. Finally, we performed a systematic review of CTCL cases reported in the literature. Results: Only two cases of CTCL were reported in 35,801 subjects with psoriasis receiving a biologic agent in the active arm of 108 psoriasis phase 3 clinical trials. One of these CTCL cases was determined by the investigator to be CTCL misdiagnosed as psoriasis prior to randomization. No cases of CTCL were reported in 5440 subjects with psoriasis in 34 phase 4 clinical trials. Only one case of CTCL was identified in 34,111 registry subjects. In the literature, tumor necrosis factor (TNF) inhibitors had the highest number of reported cases of CTCL (34 cases), followed by interleukin (IL)-17 inhibitors (7 cases), and IL-12/23 inhibitors (6 cases). No cases of CTCL were found to be reported with IL-23 inhibitors. Conclusion: Our findings indicate that the development of CTCL is rare in the setting of psoriasis biologic use. Of the limited number of cases of CTCL found, most were in the setting of TNF inhibitor use and no cases of CTCL were reported in the setting of IL-23 inhibitor use. [ABSTRACT FROM AUTHOR]

Soil salinity influences various aspects of crop growth and development. Identification of novel germplasm and genetic regulators of salt tolerance will help to alleviate the threat of land salinization. Here, we identified salt-tolerant SHEN5003 and -sensitive YZ26 maize germplasm from different heterotic groups. Salt-grown SHEN5003 (PA group) lines exhibited decreased reduction in fresh weight and dry weight, high SPAD value, total sugar and K+ contents, as well as low Na+ content relative to salt-treated YZ26 (BSSS group) plants. Salt-tolerant SHEN5003 and -sensitive YZ26 lines were followingly used for the discovery of genetic regulators of salt tolerance. Transcriptome outcome showed the expression of genes relevant to Na+/K+ homeostasis, such as H+-ATPase, HKT1, and HAKs together with CAT2 for ROS detoxification was altered in salt-treated SHEN5003 line. Moreover, GO enrichment analysis indicated differentially expressed genes of SHEN5003 upon salt treatment was significantly enriched in the stress response pathway (GO:0006950). By integrated transcriptome analyses of SHEN5003 and YZ26 lines grown in normal and salinity conditions, positive regulator of salt tolerance ZmSWEET1b was revealed, which exhibited the opposite expression pattern between salt-treated SHEN5003 and YZ26 lines. ZmSWEET1b interacted with multiple partners, such as Sucrose synthase 2 to shape a functional association network in the modulation of sugar metabolism upon salinity stress. [ABSTRACT FROM AUTHOR]

Mutations of large conductance Ca2+- and voltage-activated K+ channels (BK) are associated with cognitive impairment. Here we report that CA1 pyramidal neuron-specific conditional BK knock-out (cKO) mice display normal locomotor and anxiety behavior. They do, however, exhibit impaired memory acquisition and retrieval in the Morris Water Maze (MWM) when compared to littermate controls (CTRL). In line with cognitive impairment in vivo, electrical and chemical long-term potentiation (LTP) in cKO brain slices were impaired in vitro. We further used a genetically encoded fluorescent K+ biosensor and a Ca2+-sensitive probe to observe cultured hippocampal neurons during chemical LTP (cLTP) induction. cLTP massively reduced intracellular K+ concentration ([K+]i) while elevating L-Type Ca2+ channel- and NMDA receptor-dependent Ca2+ oscillation frequencies. Both, [K+]i decrease and Ca2+ oscillation frequency increase were absent after pharmacological BK inhibition or in cells lacking BK. Our data suggest that L-Type- and NMDAR-dependent BK-mediated K+ outflow significantly contributes to hippocampal LTP, as well as learning and memory. [ABSTRACT FROM AUTHOR]

Background: Internet addiction (IA) has been drawing attention to mental health. However, few reports have been found on the related factors of at‐risk IA among regular workers by a nationwide survey. The study aimed to evaluate the characteristics of at‐risk IA and identify related factors among senior high school teachers in Japan. Methods: This survey was a cross‐sectional survey of high schools across Japan in 2017. There were 3189 teachers (2088 males and 1098 female) who participated in this survey. The questionnaire asked about their devices, both the time and the activities of using their internet, and sociodemographic factors. IA was measured by the internet addiction test (IAT) by which 40–79 points were classified as at‐risk IA, and more as IA. We compared the related factors of at‐risk IA and non‐IA using descriptive analysis and multivariable regression analysis. Results: The rates of IA and at‐risk IA were 0.09% (n = 3) and 6.91% (n = 220), respectively. At‐risk IA was positively associated with activities on the internet for gaming, entertainment, net‐surfing, and younger ages. In addition, the at‐risk IA group had a longer time spent on the internet than the non‐IA group. Conclusions: Around 7% of high school teachers are at‐risk IA in this survey, though they have regular work. Our results suggest that at‐risk IA may be reinforced not only by the active internet use such as gaming, but also by purposeless behaviors, such as net‐surfing. Managing time on the internet may support preventing at‐risk IA among senior high school teachers. [ABSTRACT FROM AUTHOR]

The worldwide occurrence of diabetic kidney disease (DKD) is swiftly rising, primarily attributed to the growing population of individuals affected by type 2 diabetes. This surge has been transformed into a substantial global concern, placing additional strain on healthcare systems already grappling with significant demands. The pathogenesis of DKD is intricate, originating with hyperglycemia, which triggers various mechanisms and pathways: metabolic, hemodynamic, inflammatory, and fibrotic which ultimately lead to renal damage. Within each pathway, several mediators contribute to the development of renal structural and functional changes. Some of these mediators, such as inflammatory cytokines, reactive oxygen species, and transforming growth factor β are shared among the different pathways, leading to significant overlap and interaction between them. While current treatment options for DKD have shown advancement over previous strategies, their effectiveness remains somewhat constrained as patients still experience residual risk of disease progression. Therefore, a comprehensive grasp of the molecular mechanisms underlying the onset and progression of DKD is imperative for the continued creation of novel and groundbreaking therapies for this condition. In this review, we discuss the current achievements in fundamental research, with a particular emphasis on individual factors and recent developments in DKD treatment. [ABSTRACT FROM AUTHOR]

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There is a high retail demand for 'Crimson Seedless' grape. Cluster shape, berry size, colour, and sugar contents influence the overall fruit quality and marketability. In many commercial vineyards of flood-irrigated clay soils under warm and humid semi-arid climates, adequate irrigation may lead to an enhanced fruit set that could potentially be associated with restricted berry growth, compact clusters, and poor berry colour and taste. To assess the role of some agronomic practices that may influence the canopy microclimate, and affect primary and secondary metabolites, seven treatments arranged in a randomised complete block design (RCBD) system with three replicates each (three vines per replicate) were applied as follow; the control (T1), 5-leaf basal defoliation at pre-bloom (BDPB) (T2), BDPB + foliar spray (FS) of 200 mg · L–1 salicylic acid (SA) (T3), BDPB + FS of 20 mg · L–1 cyanocobalamin (CCA) (T4), 5-leaf basal defoliation at full bloom (BDFB) (T5), BDFP + SA (T6) and BDFB + CCA (T7). Foliar applications were applied at 1) 2 weeks after the beginning of vegetative growth, 2) full bloom and 3) veraison stages. The analysis of variance (ANOVA), the principle component analysis (PCA) and the two-way hierarchical cluster analysis (HCA) indicated that BDPB (T2) generally has a better effect than that of BDFB (T5). The most pronounced effect on vegetative growth (shoot length and leaf area), photosynthesis activity (leaf chlorophyll and carbohydrate contents), fruit weight and dimensions, and total yield was observed in the case of T3, followed by T6, whereas concerning berry firmness, colour (anthocyanins) and sensory characteristics (soluble solids: acids ratio, total sugars and phenols), the most pronounced effect was observed in the case of T4, followed by T7. [ABSTRACT FROM AUTHOR]

Cotton is a major crop that provides the most important renewable textile fibers in the world. Studies of the taxonomy and evolution of cotton species have received wide attentions, not only due to cotton’s economic value but also due to the fact that Gossypium is an ideal model system to study the origin, evolution, and cultivation of polyploid species. Previous studies suggested the involvement of mitochondrial genome editing sites and copy number as well as mitochondrial functions in cotton fiber elongation. Whereas, with only a few mitogenomes assembled in the cotton genus Gossypium, our knowledge about their roles in cotton evolution and speciation is still scarce. To close this gap, here we assembled 20 mitogenomes from 15 cotton species spanning all the cotton clades (A-G, K, and AD genomes) and 5 cotton relatives using short and long sequencing reads. Systematic analyses uncovered a high level of mitochondrial gene sequence conservation, abundant sequence repeats and many insertions of foreign sequences, as well as extensive structural variations in cotton mitogenomes. The sequence repeats and foreign sequences caused significant mitogenome size inflation in Gossypium and its close relative Kokia in general, while there is no significant difference between the lint and fuzz cotton mitogenomes in terms of gene content, RNA editing, and gene expression level. Interestingly, we further revealed the specific presence and expression of two novel mitochondrial open reading frames (ORFs) in lint-fiber cotton species. Finally, these structural features and novel ORFs help us gain valuable insights into the history of cotton evolution and polyploidization and the origin of species producing long lint fibers from a mitogenomic perspective. [ABSTRACT FROM AUTHOR]

NKp30 is an activating natural killer cell receptor (NKR) with a single-exon variable (VJ)–type immunoglobulin superfamily (IgSF) domain. Such VJ-IgSF domains predate the emergence of the antigen receptors (immunoglobulin and T cell receptor), which possess the same domain but undergo gene rearrangement. NCR3, the gene encoding NKp30, is present in jawed vertebrates from sharks to mammals; thus, unlike most NKR that are highly divergent among vertebrate taxa, NKp30 is uniquely conserved. We previously hypothesized that an ancestral NCR3 gene was encoded in the proto-major histocompatibility complex (MHC), the region where many immune-related genes have accumulated. Herein, we searched in silico databases to identify NCR3 paralogues and examined their genomic locations. We found a paralogue, NCR3H, in many vertebrates but was lost in mammals. Additionally, we identified a set of voltage-gated sodium channel beta (SCNB) genes as NCR3-distantly-related genes. Like NCR3, both NCR3H and SCNB proteins contain a single VJ-IgSF domain followed by a transmembrane region. These genes map to MHC paralogous regions, originally described in an invertebrate, along with genes encoding cell adhesion molecules involved in NK cell recognition networks. Other genes having no obvious relationship to immunity also map to these paralogous regions. These gene complexes were traced to several invertebrates, suggesting that the foundation of these cellular networks emerged before the genome-wide duplications in early gnathostome history. Here, we propose that this ancestral region was involved in cell-mediated immunity prior to the emergence of adaptive immunity and that NCR3 piggybacked onto this primordial complex, heralding the emergence of vertebrate NK cell/T cells. [ABSTRACT FROM AUTHOR]

Cartilaginous fish (sharks, rays, and chimeras) comprise the oldest living jawed vertebrates with a mammalian-like adaptive immune system based on immunoglobulins (Ig), T-cell receptors (TCRs), and the major histocompatibility complex (MHC). Here, we show that the cartilaginous fish "adaptive MHC" is highly regimented and compact, containing (i) a classical MHC class Ia (MHC-Ia) region containing antigen processing (antigen peptide transporters and immunoproteasome) and presenting (MHC-Ia) genes, (ii) an MHC class II (MHC-II) region (with alpha and beta genes) with linkage to beta-2-microglobulin (β2m) and bromodomain-containing 2 , (iii) nonclassical MHC class Ib (MHC-Ib) regions with 450 million-year-old lineages, and (iv) a complement C4 associated with the MHC-Ia region. No MHC-Ib genes were found outside of the elasmobranch MHC. Our data suggest that both MHC-I and MHC-II genes arose after the second round of whole-genome duplication (2R) on a human chromosome (huchr) 6 precursor. Further analysis of MHC paralogous regions across early branching taxa from all jawed vertebrate lineages revealed that Ig/TCR genes likely arose on a precursor of the huchr9/12/14 MHC paralog. The β2m gene is linked to the Ig/TCR genes in some vertebrates suggesting that it was present at 1R, perhaps as the donor of C1 domain to the primordial MHC gene. In sum, extant cartilaginous fish exhibit a conserved and prototypical MHC genomic organization with features found in various vertebrates, reflecting the ancestral arrangement for the jawed vertebrates. [ABSTRACT FROM AUTHOR]

Main Conclusion: This paper highlights the need for innovative approaches to enhance cold tolerance. It underscores how genome-editing tools can deepen our understanding of genes involved in cold stress. Cold stress is a significant abiotic factor in high-altitude regions, adversely affecting plant growth and limiting crop productivity. Plants have evolved various mechanisms in response to low temperatures that enable resistance at both physiological and molecular levels during chilling and freezing stress. Several cold-inducible genes have been isolated and characterized, with most playing key roles in providing tolerance against low-temperature stress. However, many plants fail to survive at low temperatures due to the absence of cold acclimatization mechanisms. Conventional breeding techniques, such as inter-specific or inter-genic hybridization, have had limited effectiveness in enhancing the cold resistance of essential crops. Thus, it is crucial to develop crops with improved adaptability, high yields and resistance to cold stress using advanced genomic approaches. The current availability of gene editing tools offers the opportunity to introduce targeted modifications in plant genomes efficiently, thereby developing cold-tolerant varieties. This review discusses advancements in gene editing tools, including zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)/Cas12a(Cpf1), prime editing (PE) and retron library recombineering (RLR). We focus specifically on the CRISPR/Cas system, which has garnered significant attention in recent years as a groundbreaking tool for genome editing across various species. These techniques will enhance our understanding of molecular interactions under low-temperature stress response and highlight the progress of genome editing in designing future climate-resilient crops., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this systematic review and survival analysis was to quantify the benefits of orthobiologic augmentation therapies for the treatment of avascular necrosis (AVN) of the femoral head and identify the most effective approach to delay the need for total hip arthroplasty (THA)., Methods: A systematic review of the literature was performed on PubMed, Scopus, and Cochrane on clinical studies on orthobiologic therapies used alone or as an augmentation to core decompression or other procedures to address hip AVN. A qualitative analysis of the different biological therapies applied was performed. Afterward, the results of these procedures were quantitatively analysed to document their survivorship from THA compared to treatment groups without orthobiologics. Kaplan-Meier analysis was performed for all studies and then by categorising orthobiologics into treatment subgroups., Results: A total of 106 studies were included (4505 patients). Different orthobiologic approaches have been evaluated: cell-based therapies including bone marrow aspirate concentrate (BMAC) and bone marrow mesenchymal stromal cells (BM-MSCs), platelet-rich plasma (PRP), or other bioactive molecules applied in the osteonecrotic area or as intra-arterial injections. The survival analysis at 120 months documented a higher (p < 0.0005) cumulative survivorship with orthobiologics (69.4%) compared to controls (48.5%). The superiority was shown specifically for BMAC (p < 0.0005), BM-MSCs (p < 0.0005), intra-arterial (p < 0.0005) and PRP (p = 0.011) approaches, but the direct comparison of these approaches with their controls confirmed benefits only for BMAC (p < 0.0005)., Conclusion: This systematic review and survival analysis demonstrated that orthobiologics have the potential to improve survivorship in patients affected by hip AVN. In particular, the specific analysis of different orthobiologic products supported relevant benefits for BMAC augmentation in terms of survival from the need for THA, while no clear benefits were confirmed for other orthobiologics., Level of Evidence: Level III., (© 2024 The Author(s). Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)