The journal retracts the article titled, "Retinoic Acid Induced 1 and Smith-Magenis Syndrome: From Genetics to Biology and Possible Therapeutic Strategies" [...].

The journal retracts the article titled "Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice" [...].

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The economic output of sea urchin aquaculture depends almost entirely on a single organ. Gonads, marketed as uni, determine value through their size, color, texture and flavor, and feed formulations have been optimized empirically for decades with limited reference to the molecular machinery governing gametogenesis, sex differentiation and gonadal maturation in echinoids. This review integrates four lines of mechanistic evidence around the adult gonad, namely developmental gene regulatory networks, sex-biased gonadal transcriptomics, germ-cell and nutritive-phagocyte biology, and endocrine, neuroendocrine and retinoid signaling, and reads them in terms of the control points connecting molecular state to production outcome. Rather than advancing a unified mechanistic model, which the current evidence does not support, each component is classified by the strength of the evidence attached to it: demonstrated in an echinoid, inferred from another taxon, plausible but untested, or hypothetical. The resulting picture is one in which descriptive resources have outpaced functional tests. Candidate sex-determination transcription factors have been identified but none have yet been directly perturbed in an echinoid, the retinoid pathway is architecturally present yet biochemically incomplete, and responses to exogenous steroids remain heterogeneous across species and protocols. Priority experimental directions are ranked by commercial return and by experimental falsifiability.

In the context of the global diabetes epidemic, diabetic nephropathy (DN)-a condition directly associated with diabetes-has become the primary cause of end-stage renal disease, significantly impacting patients' quality of life and placing substantial demands on public healthcare resources. The pathogenesis of DN is characterized by metabolic disturbances induced by high glucose levels, hemodynamic abnormalities, and the synergistic amplification of various stress signals. These factors collectively contribute to the progressive loss of nephrons and irreversible renal dysfunction. Although current standard treatments can partially slow disease progression, they significantly fail to meet clinical needs. Therefore, there is an urgent necessity to identify multi-target intervention strategies that utilize novel mechanisms of action. Alkaloids, a class of natural nitrogen-containing compounds known for their significant structural diversity, have recently demonstrated multiple renoprotective effects in experimental models of DN. This review is based on a search of the PubMed, Web of Science and CNKI databases. The keywords alkaloids, diabetic nephropathy, diabetic nephropathies, diabetic kidney disease, inflammation, oxidative stress, fibrosis, autophagy and apoptosis were used to search for original research articles in both Chinese and English, published between 2010 and 2026, which investigated the mechanisms by which alkaloid compounds exert their anti-DN effects. Focusing on anti-inflammatory effects, anti-oxidative stress, anti-renal fibrosis, autophagy modulation, apoptosis regulation and ferroptosis inhibition, the review then summarized the relevant literature by systematizing the experimental models, intervention protocols, dosages and key results. This provided a new theoretical perspective and experimental basis for the clinical translation and new drug development of alkaloid compounds for the treatment of DN. The review provides a new theoretical perspective and an experimental basis for the clinical translation of, and new drug development based on, alkaloid compounds for the treatment of DN.

Temporomandibular joint osteoarthritis (TMJ OA) is characterized by progressive degeneration of the fibrocartilaginous articular surface. We previously demonstrated that combined bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) inhibition promotes endogenous hyaline cartilage regeneration in appendicular joints. Whether this regenerative strategy can be extended to the specialized fibrocartilage of the TMJ remains unknown. In this study, we evaluated the regenerative potential of BMP-2 combined with cabozantinib, an FDA-approved multikinase inhibitor with activity against VEGF receptors, using complementary murine and porcine TMJ cartilage injury models. In mice, needle-induced abrasion of the mandibular condyle resulted in loss of the fibrocartilaginous articular surface and extracellular matrix; treatment with BMP-2 and cabozantinib was associated with improved cartilage architecture and increased fibrocartilage thickness. To examine translational feasibility, we developed a surgically accessible porcine TMJ cartilage defect model and demonstrated the technical feasibility of local BMP-2 and cabozantinib delivery with formation of repair tissue within the defect. Collectively, these findings provide preliminary evidence supporting further investigation of combined BMP-2 and cabozantinib for TMJ cartilage repair.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease involving progressive loss of pancreatic β-cells. Although B cells have been implicated in T1DM progression, the molecular characteristics associated with disease-related B-cell states remain unclear. Here, we investigated B-cell-associated molecular alterations in T1DM and explored the potential immunomodulatory effects of a natural compound. Public T1DM transcriptomic datasets were analyzed using differential expression analysis, WGCNA, and machine-learning approaches. Single-cell RNA sequencing was used to characterize Cd180 expression across B-cell states. Molecular docking and molecular dynamics simulations were used to explore potential interactions between CD180 and candidate compounds, and an exploratory DARTS assay was performed to assess CGA-associated changes in CD180 proteolytic susceptibility. CD180 expression was examined in pancreatic tissues from vehicle- and MSA-2-treated NOD mice. The effects of chlorogenic acid (CGA) were evaluated in vitro by exposing B cells to CGA during inflammatory stimulation, followed by washing and co-culture with MIN6 cells in CGA-free medium. Integrated transcriptomic analysis identified four T1DM-associated genes (CD180, KCNJ2, STEAP4, and ZXDA), among which CD180 showed the strongest association with B-cell-related immune alterations. Single-cell analysis showed increased Cd180 expression in inflammatory B-cell states together with enrichment of antigen-presentation-related programs. An exploratory DARTS experiment with matched loading-control data suggested altered CD180 proteolytic susceptibility following CGA exposure, although independent reproducibility remains to be established. In vitro, CGA exposure during inflammatory stimulation was associated with reduced CD180 expression in B cells and improved MIN6 cell viability and insulin-secretory responses during subsequent co-culture in CGA-free medium. CD180 is associated with inflammatory B-cell alterations in T1DM and may represent a candidate molecular feature of B-cell dysregulation. CGA treatment was associated with changes in CD180 expression in activated B cells and improved β-cell functional outcomes in vitro. These findings support further investigation of the relationship between CGA and CD180; however, whether the effects of CGA are specifically mediated through CD180 requires further experimental validation.

The gut microbiome is increasingly recognized as an important determinant of host immune regulation, intestinal homeostasis, and recovery after colorectal cancer (CRC) surgery. Although our previous randomized, double-blind, placebo-controlled clinical trial demonstrated that fungal nutraceutical supplementation with Micodigest[®] was associated with favorable taxonomic and systemic inflammatory changes in patients undergoing CRC surgery with curative intent, the functional consequences of this intervention remain poorly understood. Here, we performed a functional metagenomic analysis of fecal samples collected from patients enrolled in the original clinical trial to investigate whether Micodigest[®] supplementation was associated with changes in the functional potential of the gut microbiome. A total of 37 patients were analyzed, including 24 receiving Micodigest[®] and 13 receiving placebo, with paired samples collected before supplementation and after 4-6 weeks of intervention. Shallow shotgun metagenomic sequencing was performed, and microbial functional potential was characterized using KEGG Orthologues (KOs). Differential abundance analysis identified 14 significantly different KOs between groups at baseline and 23 after intervention, with no overlap between the two sets of orthologues. Following supplementation, Micodigest[®]-treated patients exhibited increased representation of functions related to CRISPR-associated systems, bacteriophage biology, and chitin-derived carbohydrate utilization, together with reduced representation of nutrient acquisition systems, conjugative transfer, sulfur metabolism, and components of the Wood-Ljungdahl pathway. These functional signatures suggest coordinated changes in microbial ecological adaptation, nutrient utilization, genetic exchange, and metabolic activity following fungal nutraceutical supplementation. Integration with previously reported taxonomic and inflammatory findings supports the hypothesis that Micodigest[®] may promote coordinated remodeling of the gut microbiome and host-microbiota interactions during the perioperative period. Although the present study cannot establish causality or directly infer microbial activity from metagenomic potential, these findings provide novel functional insights into the microbiome response to fungal nutraceutical supplementation in patients with CRC and highlight functional metagenomics as a valuable complement to taxonomic profiling.

Intraosseous lidocaine trigger point injection (LTPI) has been utilized for an extended period in the management of chronic vertebrogenic pain; yet, its molecular mechanisms and clinical efficacy require critical appraisal. This narrative review highlights the milestones of osteoreception and elucidates the molecular mechanisms driving intraosseous receptor irritation and its pivotal role in chronic pain development. Pathological vertebral bone remodeling triggers a receptor activator of nuclear factor-kappa B ligand/osteoprotegerin (RANKL/OPG) imbalance, accelerating hyperactive osteoclastogenesis. Enhanced osteoclastic vacuolar-type H+-ATPase (V-ATPase) expression drives microenvironment acidity and intraosseous hypertension, persistently stimulating acid-sensing ion channel 3 (ASIC3) and purinergic P2X2/3 receptors on intraosseous afferents. Concurrently, upregulated nerve growth factor (NGF) binds to tropomyosin receptor kinase A (TrkA), driving peripheral sensitization via transient receptor potential vanilloid 1 (TRPV1) phosphorylation. The available clinical studies investigating intraosseous LTPI for vertebrogenic pain are scarce and heterogeneous, focusing primarily on low back pain, cervicalgia, and residual chronic pain after degenerative lumbar spinal stenosis decompression surgery. The reviewed data provide preliminary signals of potential benefit, observing a statistically significant analgesic effect of intraosseous LTPI within the studied cohorts. In two trials comparing it to intramuscular LTPI, one of which utilized a randomized controlled design, the intraosseous approach was reported to provide more pronounced short-term pain relief. However, these trials are limited by small sample sizes, heterogeneous designs, and a lack of active long-term safety monitoring. Nevertheless, although current data provide promising but still limited insights, future double-blinded, multicenter randomized controlled trials are required to comprehensively establish the clinical efficacy, safety profile, and prolonged effect of intraosseous LTPI in the treatment of vertebrogenic pain.