Urolithin A (UA, Mitopure), a postbiotic that promotes mitophagy and mitochondrial function following oral administration, was evaluated for its effects on skin health in human skin models and when applied topically to healthy subjects in randomized clinical studies. UA tested in 2D and 3D reconstructed human skin and ex vivo human skin explants showed enhanced mitochondrial respiration, activated mitophagy markers, reduced inflammatory mediators and senescence-associated markers, and increased proteins involved in extracellular matrix structure and epidermal differentiation. Safety was confirmed in a human repeat-insult patch test. In randomized, placebo-controlled clinical studies, UA reduced periorbital wrinkle depth after 8 weeks and attenuated UVB-induced erythema. Skin transcriptomics supported increased extracellular matrix and epidermal development programs together with decreased inflammatory and senescence-associated signaling. These findings indicate that topical UA engages cellular pathways associated with skin resilience to promote skin health and longevity.

Acute kidney injury (AKI) recovery is a major determinant of long-term renal and patient outcomes. While transient AKI is associated with a more favorable prognosis, persistent or incomplete recovery increases the risk of chronic kidney disease, dialysis dependence, cardiovascular complications, and mortality. Renal recovery after AKI reflects the balance between adaptive repair processes and maladaptive pathways leading to fibrosis and nephron loss. Experimental and clinical evidence highlights the roles of tubular epithelial regeneration, macrophage phenotypes, inflammatory mediators, complement activation, and aging-related decline in regenerative capacity in determining recovery trajectories. Recurrent injury and persistent hemodynamic stress may further impair renal repair and promote progression to chronic kidney disease. Renal replacement therapy (RRT) may itself contribute to delayed renal recovery through "dialytrauma", a concept that encompasses all harmful adverse events related to RRT. Major mechanisms of dialytrauma include hemodynamic instability and organ ischemia, blood-membrane inflammatory activation, metabolic and osmotic perturbations, and access-related complications. Intermittent hemodialysis is particularly associated with circulatory and osmotic stress, whereas continuous RRT may expose patients to prolonged extracorporeal circulation, anticoagulation-related complications, and cumulative metabolic derangements. Peritoneal dialysis avoids extracorporeal blood contact but has other potential risks. This review summarizes the current understanding of dialytrauma as a potentially modifiable determinant of nonrecovery of renal function in patients with AKI receiving RRT. No single modality is universally superior, and minimizing unnecessary exposure, excessive intensity, and hemodynamic instability is essential. In this article, we discuss strategies to minimize the risk of dialytrauma to guide individualized RRT strategies with the aim to promote renal recovery and preserve long-term kidney health.

Recent advances in regenerative medicine advanced therapies (RMAT) are revolutionizing health care by providing curative treatments for previously untreatable diseases. Flow cytometry assays have been used to measure critical quality attributes, including viability, identity, purity, strength, and potency of the RMAT. However, the lack of reproducibility, comparability, and measurement confidence of results across various flow cytometry platforms, sites, and over time remain a major challenge.

Tinnitus is thought to be suppressed through partial reversal of auditory deafferentation via cochlear implantation (CI). By stimulating the deafferented auditory pathway, multiple studies have revealed that tinnitus is significantly suppressed in 66-92% of patients undergoing CI. This study aimed to evaluate the efficacy of CI as a treatment for tinnitus and to investigate post-CI audiologic outcomes in patients with single-sided deafness (SSD). From November 2018 to July 2020, 10 patients who were diagnosed with SSD and suffering from tinnitus were prospectively recruited at three tertiary referral hospitals. Participants in this study agreed to undergo CI as a treatment for tinnitus. Postoperative aided pure tone audiometry (PTA) and word recognition score (WRS) were measured. Questionnaires related to tinnitus, such as the tinnitus handicap inventory (THI) and visual analogue scale (VAS) scores including loudness, distress, and perception, were administered. Additionally, a tinnitogram was obtained for loudness and pitch matching. Audiological outcomes of CI were analyzed in conjunction with the results of pitch-matching from the tinnitogram. All 10 patients completed device-on evaluations, and 9 patients completed device-off evaluations. THI scores showed statistically significant improvement 3 months after CI in both the device-on and device-off conditions (preoperative: 78; device on: 38, p = 0.027; device off: 50, p = 0.049). VAS scores also demonstrated significant improvement after CI (preoperative: 8.2; device on: 3.3, p = 0.011; device off: 6.5, p = 0.012). Four patients demonstrated changes in psychoacoustic tinnitus features after CI: 2 changed to lower frequency, 1 changed to higher frequency, and 1 patient's tinnitus changed from white noise to a specific identifiable frequency. There was no significant tendency for threshold (T-level and C-level) changes in pitch-matching frequency. In line with previous literature, this exploratory multicenter study demonstrated improvement in tinnitus loudness and distress after CI in patients with single-sided deafness and tinnitus, with a tendency for greater reduction in tinnitus intensity observed when the device was activated. Additionally, approximately half of the patients showed changes in the psychoacoustic characteristics of tinnitus after CI. Given the small sample size and the absence of a non-implanted control group, these findings should be regarded as exploratory and hypothesis-generating, and warrant confirmation in adequately powered controlled trials.

M. M. Luchetti, G. Moroncini, M. Jose Escamez, S. Svegliati Baroni, T. Spadoni, A. Grieco, C. Paolini, A. Funaro, E. V. Avvedimento, F. Larcher, M. Del Rio, and A. Gabrielli, "Induction of Scleroderma Fibrosis in Skin-humanized Mice by Administration of Anti-platelet-derived Growth Factor Receptor Agonistic Autoantibodies," Arthritis & Rheumatology 68, no. 9 (2016): 2263-2273, https://doi.org/10.1002/art.39728. This Expression of Concern is for the above article, published online on 25 April 2016 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, S. Louis Bridges, Jr.; the American College of Rheumatology; and Wiley Periodicals LLC. Concerns were raised by a third party on PubPeer [1] regarding a high level of similarity between the beta-actin bands in Figures 1C and 2B. Additional investigation by the publisher also found that there was evidence of splicing in the PDGFR-alpha band in Figure 3B. The authors responded to an inquiry by the publisher and shared original data. However, original data were not available for the bands originally published in Figure 3B, and the authors supplied data from replicate experiments performed during the same period of the original experiments. A review of these data found that not all of the data could be verified. Therefore, this Expression of Concern has been agreed to in order to inform and alert readers as to the results of this investigation. The authors have been informed of the Expression of Concern.

Driven by large language models, AI agents are transforming drug discovery, enabling AI to break free from task-specific tools and advance toward the vision of autonomous virtual scientists. This perspective reviews applications across the R&D lifecycle. To evaluate system maturity, we introduce a 6-level "Spectrum of Agentic Autonomy." We advocate for novel evaluation paradigms centered on full-chain traceability and outline adoption barriers, positioning AI agents as pragmatic scientist-in-the-loop co-pilots.

Autosomal dominant (AD) distal renal tubular acidosis (dRTA) generally has a later onset and milder clinical course than autosomal recessive forms. However, delayed diagnosis may result in prolonged metabolic acidosis and severe growth impairment. Here we report the case of a Japanese boy with a de novo SLC4A1 (NM_000342.4):c.1765C > T (p.Arg589Cys) variant who presented with marked growth failure from 6 months of age and was diagnosed with AD-dRTA at 27 months. Because severe short stature was the predominant clinical feature, venous blood gas analysis was performed and revealed metabolic acidosis (pH 7.197, HCO3- 11.5 mmol/L). Additional investigations demonstrated hyperchloremia, hypokalemia, hypercalciuria, bilateral nephrocalcinosis, rickets, an inappropriately high urine pH, and a positive urinary anion gap. Targeted gene panel analysis using next-generation sequencing, followed by Sanger confirmation, established the genetic diagnosis. After initiation of alkali therapy, metabolic acidosis progressively improved; serum bicarbonate first reached the normal range at 9 months and remained within or close to the normal range thereafter. Radiographic improvement of rickets was observed within 3 months, before cholecalciferol supplementation was initiated, and substantial catch-up growth occurred during 5 years of follow-up, with the height standard deviation score improving from - 4.1 to - 2.3, while renal function remained preserved. Prolonged auxological and biochemical follow-up of early-onset SLC4A1-associated AD-dRTA has rarely been reported. This case illustrates that AD-dRTA may present during infancy and that assessment of acid-base status may facilitate timely diagnosis in children with otherwise unexplained growth failure.