Electrolyte, acid-base, and mineral metabolism disorders are among the most common and clinically significant problems experienced in internal medicine patients. Their development reflects disturbances in regulated homeostatic mechanisms involving the kidneys, bones, endocrine systems, and cellular ion transport. Disorders such as hyponatremia, hypernatremia, hypokalemia, hyperkalemia, metabolic acidosis, metabolic alkalosis, and abnormalities of calcium and phosphorus metabolism are associated with substantial morbidity and mortality when not promptly recognized and appropriately treated. Accurate diagnosis requires a deep understanding of the underlying pathophysiology, assessment of volume status, interpretation of laboratory findings, and identification of contributing kidney, endocrine, medications, and systemic factors. This review describes the physiological mechanisms governing electrolyte and acid-base homeostasis and discusses the clinical presentation, diagnostic evaluation, and evidence-based management of common electrolyte disorders encountered by Internists. We place emphasis on distinguishing etiologies and applying practical diagnostic algorithms to guide treatment decisions. In addition, the review highlights the interconnected regulation of calcium and phosphorus by parathyroid hormone, vitamin D, and fibroblast growth factor 23 and its relevance in kidney disease and other disorders. By integrating foundational physiology with current clinical practice guidelines, this review provides internists with a practical framework to solve electrolyte issues they face with confidence.

Cancer progression and treatment failure are driven not only by genetic alterations but also by the remarkable capacity of tumor cells to adapt to metabolic stress, immune surveillance, and therapeutic pressure. Epigenetic plasticity provides a rapid and reversible mechanism that enables such adaptation. Lysine demethylase 4A (KDM4A), a JmjC-domain-containing histone demethylase targeting H3K9me3 and H3K36me3, has emerged as a central epigenetic regulator of cancer adaptability. Recent studies reveal that KDM4A functions beyond a conventional chromatin modifier and instead acts as an epigenetic hub integrating microenvironmental cues, metabolic signals, and stress responses. Through transcriptional and post-translational regulation, KDM4A coordinates chromatin remodeling programs that support metabolic adaptation, including amino acid utilization, mitochondrial quality control, lipid metabolism, and resistance to ferroptosis. In parallel, KDM4A reshapes tumor-immune interactions in a state-dependent manner. In proliferative and stress-tolerant tumor states, KDM4A-associated chromatin remodeling may support metabolic adaptation, replication-stress tolerance, and immune exclusion. By contrast, under conditions of impaired mitochondrial quality control and sustained metabolic stress, KDM4A can promote tumor-cell senescence and enhance responsiveness to immune checkpoint blockade. These divergent outcomes indicate that the consequences of KDM4A activity are determined by the interaction between substrate- and locus-specific chromatin remodeling and the cellular, metabolic, and therapeutic context in which it occurs. KDM4A-driven epigenetic reprogramming also underlies multiple mechanisms of therapy resistance, encompassing enhanced DNA damage repair capacity, metabolic buffering via mitophagy, and lineage plasticity-mediated therapy escape. These adaptive strategies allow cancer cells to survive therapeutic stress without reliance on additional genetic mutations, contributing to disease progression and poor clinical outcomes. In this review, we synthesize current mechanistic and translational evidence to present a unified framework in which KDM4A links metabolic adaptation, immune remodeling, and therapy resistance. We further discuss therapeutic opportunities, rational combination strategies, and the emerging biomarker potential of KDM4A-centered pathways, highlighting their relevance for precision oncology.

Neonatal diarrhea remains one of the most frequent causes of morbidity, mortality, and economic loss in calves worldwide. The clinical consequences in affected animals are primarily attributable to fluid losses and consecutive dehydration, but also to the occurrence of metabolic acidosis and associated imbalances in potassium homeostasis. In calves with neonatal diarrhea, metabolic acidosis mainly results from the accumulation of strong anions, in particular D-lactate, which arises from bacterial fermentation processes of undigested nutrients within the gastrointestinal tract. Increased blood D-lactate concentrations not only contribute substantially to the development of metabolic acidosis but are also responsible for most of the clinical signs such as depression, weakness, impairment of the ability to stand, and alterations of the palpebral reflex.

Early diagnosis of liver disease is crucial for improving patient longevity and requires advanced tools to precisely detect biomarkers. A dual-responsive MIB probe was developed for the simultaneous detection of ONOO[-] and viscosity in green and yellow emission channels, respectively. The probe exhibited enhanced emission at 554 nm upon interaction with ONOO[-], attributed to a Lewis acid-base reaction and intramolecular charge transfer (ICT), supported by [1]H NMR, HR-MS, HPLC analyses, and DFT calculations. In viscous environments, restricting the intramolecular rotation of MIB resulted in enhanced emission owing to suppressed Twisted ICT (TICT). MIB effectively monitored mitochondrial ONOO[-] and viscosity changes in living cells and distinguished diseased/injured from normal liver tissues in mouse models. Consequently, MIB can simultaneously detect two distinct liver disease markers via different emissive pathways. It essentially serves as a reliable bioanalytical tool for the initial assessment of hepatic diseases. This simultaneous detection method overcomes the drawbacks of single-biomarker evaluations, improving diagnostic precision.

Chimeric antigen receptor (CAR) T cell therapy for acute myeloid leukemia (AML) is constrained by antigen heterogeneity and shared expression with healthy compartments, and there are often challenges in obtaining autologous T cells from heavily pretreated patients. To address these challenges, we developed universal donor-derived, base-edited, anti-CD33 CAR T cells (BE-CAR33) that used precise multiplexed cytidine deamination to simultaneously disrupt the TRAC, CD52, and CD7 loci to prevent graft-versus-host disease and evade immunotherapy effects. An open-label, nonrandomized, single-center phase 1 study (ISRCTN14430213) evaluated the safety, feasibility, and activity of BE-CAR33 cell therapy ahead of allogeneic stem cell transplantation (allo-SCT) for patients with AML. Eligible participants were aged less than 16 years with relapsed/refractory AML. Five patients were screened, and three were enrolled; one additional adult received BE-CAR33 through compassionate access. Participants received fludarabine, cyclophosphamide, and alemtuzumab followed by 1.2 to 1.8 × 10[6] BE-CAR33 cells per kilogram. Treatment-emergent adverse events included cytokine release syndrome (grade ≤2), neurotoxicity (grade 3), cytopenias (grade 4), and transient rashes. Two patients demonstrated reduced minimal residual disease and proceeded to allo-SCT. Serial flow cytometry, chimerism quantification, and vector copy number analyses tracked BE-CAR33 T cells until elimination during transplant. Differentially expressed genes included editing signatures and switched from manufacturing-related toward postexpansion effector and exhaustion profiles. Although primary end points were not met, this first-in-human study demonstrated the feasibility of an "off-the-shelf" base-edited CAR T cell approach and informs future multiantigen strategies against AML.

A novel Gram-stain-positive, rod-shaped bacterium with peritrichous flagella, designated C159[T], was isolated from tomato rhizosphere soil. Growth of strain C159[T] occurred at 4-45 °C, pH 6.0-10.0 and in the presence of 0-5% NaCl. Based on 16S rRNA gene sequence analysis, strain C159[T] belongs to the genus Pseudoneobacillus and has a sequence similarity of 98.70% with Pseudoneobacillus rhizosphaerae JJ-79[T]. The whole genome of strain C159[T] was 4.65 Mb, with a DNA G+C content of 38.65 mol%. The average nucleotide identity between strain C159[T] and P. rhizosphaerae JJ-79[T] was 75.31%, and the digital DNA-DNA hybridization value was 19.6%, supporting its designation as a novel species of the genus Pseudoneobacillus. The major respiratory quinone of strain C159[T] was menaquinone 7; the major fatty acids were iso-C14:0, iso-C15:0 and anteiso-C15:0; and the major polar lipids are diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Based on its phenotypic, chemotaxonomic, phylogenetic and genomic characteristics, strain C159[T] represents a novel species in the genus Pseudoneobacillus, for which the name Pseudoneobacillus rhizolycopersici sp. nov. is proposed. The type strain is C159[T] (=GDMCC 1.5552[T]=KCTC 43820[T]). In addition, strain C159[T] possesses the ability to produce indole-3-acetic acid (33.72 mg·l[-1]) and to mineralize insoluble organic phosphorus. In a pot experiment, this strain demonstrated a plant growth-promoting effect of 22.68-44.49% and a disease suppression efficacy of 89.29% against bacterial wilt of tomato caused by Ralstonia solanacearum. The above results confirm that strain C159[T] is a novel multifunctional rhizobacterium for the biocontrol of tomato bacterial wilt.

Osteoporosis, a metabolic bone disorder affecting nearly one-third of women and one-fifth of men globally, poses a major public health burden. Current pharmacological treatments face limitations, driving interest in safer nutritional interventions. The gut-bone axis, through which gut microbiota modulate bone homeostasis, offers a promising target. This review synthesizes recent evidence on probiotics, including both viable and heat-inactivated strains of Lactobacillus and Bifidobacterium, as modulators of osteoporosis. Probiotics exert integrated protective effects by reinforcing intestinal barrier, balancing Th17/Treg/Breg immunity, regulating RANKL/RANK/OPG signaling, producing short-chain fatty acids, and modulating serotonin metabolism. Preclinical and clinical studies show that specific strains improve bone density and microstructure, though efficacy depends on strain, dosage, duration, and host factors. Moreover, heat-inactivated forms and postbiotics offer stability advantages. Future development of synbiotics, next-generation probiotics, and functional foods tailored to specific matrices, along with personalized strategies, promises effective dietary interventions for bone health.

Acne vulgaris is a common inflammatory skin disease with substantial physical and psychosocial burden. Trifarotene, a fourth-generation topical retinoid with selective retinoic acid receptor-gamma (RARγ) activity, is notable for having published clinical trial data in facial, truncal, and hyperpigmentation-associated acne. This narrative review summarizes available clinical trial evidence regarding its safety, tolerability, efficacy, and patient-centered outcomes. A focused literature review was conducted in August 2025 using PubMed to identify English-language clinical studies evaluating topical trifarotene for acne vulgaris, with a supplementary update search conducted in July 2026 to capture additional eligible literature. Eligible studies included interventional and prospective clinical studies reporting efficacy, safety, tolerability, or patient-reported outcomes in facial, truncal, or hyperpigmentation-associated acne, and findings were summarized narratively given differences in study design, treatment regimens, comparators, and reported outcomes. Five studies met the inclusion criteria, including four randomized controlled trials and one long-term prospective study. Across studies, trifarotene was generally well tolerated, with adverse events being predominantly mild. Any localized retinoid-associated skin reactions peaked early and improved over time. Trifarotene was also associated with improvement in lesion counts, investigator success rates, and selected patient-reported outcomes, including measurable benefit for acne-induced hyperpigmentation, although one trial did not meet its prespecified primary endpoint at Week 24. Short-term randomized trials demonstrated benefit over vehicle, while long-term data suggested sustained efficacy and acceptable tolerability over 52 weeks. Current clinical trial evidence suggests trifarotene may be a useful topical treatment option for moderate facial and truncal acne vulgaris, with a broader evidence base than most topical retinoids in these areas. The evidence base can be strengthened by additional studies, broader population diversity, and direct head-to-head comparisons with other topical retinoids.

Myocardial infarction (MI) generates a pathological microenvironment characterized by ischemia and hypoxia, and this increases mortality and morbidity worldwide. We fabricated p-hydroxyphenylpropionic acid-modified gelatin (GTN), a dual-responsive system capable of in situ gelation in the presence of hydrogen peroxide (H2O2) or iron ions. This feature enables GTN to cross-link in the infarcted myocardium, where excessive reactive oxygen species (ROS) and iron ions trigger ferroptosis. The successful modification of gelatin was verified, along with its time- and concentration-dependent responsiveness to H2O2 and iron ions in vitro. We further assessed the biocompatibility, ROS-scavenging activity, and cytoprotective effects of GTN in hostile MI microenvironments. Death receptor 5 fusion protein (DR5) was incorporated into the hydrogel to construct DR5@GTN, aiming to alleviate cardiomyocyte apoptosis. In vivo experiments demonstrated that GTN effectively targeted and accumulated in the infarcted region via transglutaminase-mediated recognition, thereby remodeling the pathological microenvironment. DR5@GTN significantly restored cardiac functions, increased the left ventricular ejection fraction, and reduced the infarct size. DR5@GTN attenuated myocardial fibrosis, promoted angiogenesis, suppressed cardiomyocyte apoptosis, decreased ROS levels, and inhibited myocardial hypertrophy. Collectively, DR5@GTN regulated the "ROS-iron-apoptosis" axis with favorable in situ gelation properties, and this represents a promising strategy for myocardial repair by ameliorating the harsh microenvironment following MI. STATEMENT OF SIGNIFICANCE: ● Adaptively responds to and eliminates ROS and iron ions at the infarcted region, matching the pathological characteristics of the MI microenvironment. ● Fosters angiogenesis in the infarcted region, mediates extracellular matrix remodeling, and synergistically attenuates cardiomyocyte death. ● Represents the first attempt to validate the feasibility of in situ gelation therapy for myocardial infarction via a minimally invasive strategy.

BACKGROUND Tonic-clonic seizures can precipitate severe rhabdomyolysis due to sustained muscle activity, leading to release of intracellular contents, including proteins, that can pose an elevated risk for acute kidney injury (AKI). Rhabdomyolysis management centers on aggressive intravenous (IV) fluid resuscitation while the risk of volume overload is vigilantly minimized. Nephrologists regularly assess the need for dialysis while addressing the nuances in each case. This case illustrates the clinical decision-making involved in managing extreme biochemical derangements in seizure-induced rhabdomyolysis with conservative medical management. CASE REPORT A 32-year-old man with a history of seizure disorder presented following a generalized tonic-clonic seizure. Laboratory studies reflected marked abnormalities, including a creatine kinase level of 83 261 u/L, peaking at 133 300 u/L shortly after admission, creatinine of 9.3 mg/dL from baseline of 1.0 mg/dL, aspartate aminotransferase of 819 u/L, and alanine aminotransferase of 192 u/L. Despite significantly elevated creatine kinase and creatinine levels, the patient remained hemodynamically stable, with preserved urine output and no life-threatening electrolyte or acid-base disturbances. He received aggressive IV fluids to enhance kidney perfusion and prevent further myoglobulin induced injury, with intermittent diuretics use to maintain euvolemia. Ultimately, kidney function and laboratory markers improved. CONCLUSIONS Rhabdomyolysis can cause AKI by various mechanisms. This report highlights the importance of timely and appropriate nephrology-guided management. Although aggressive hydration remains the standard of care, careful monitoring is required to prevent fluid overload. Close monitoring and conservative management alone may be sufficient in select patients without life-threatening biochemical derangements, thereby preventing the need for kidney replacement therapy.

Gestational diabetes mellitus (GDM) is a highly prevalent metabolic disorder of pregnancy that carries immediate and long-term health risks for both mothers and their offspring. Emerging evidence implicates maternal gut microbiota dysbiosis as a critical contributor to the onset and progression of GDM, primarily through the induction of chronic low-grade systemic inflammation. This review synthesizes recent advances in understanding the compositional shifts in the maternal gut microbiota-including depletion of short-chain fatty acid-producing taxa such as Bifidobacterium and Faecalibacterium, and enrichment of pro-inflammatory genera-and examines how these changes compromise intestinal barrier integrity, promote microbial metabolite translocation, and subsequently activate innate immune pathways. The resultant elevation of pro-inflammatory cytokines directly impairs insulin signaling, exacerbating insulin resistance and fueling a vicious cycle between dysbiosis and metabolic deterioration. Beyond the peripartum period, this review highlights the emerging concept of transgenerational programming, whereby maternal GDM-associated dysbiosis and inflammation may shape the offspring's microbiome, immune set-point, and metabolic trajectory, predisposing them to later-life metabolic and neurodevelopmental disorders. Finally, we critically evaluate current microbiota-targeted interventions, including probiotics, synbiotics, and dietary modifications, and discuss the sources of heterogeneity in clinical trial outcomes. By integrating these mechanistic and translational insights, this review proposes a conceptual framework for early risk stratification and personalized management of GDM, emphasizing that effective clinical translation requires moving beyond one-size-fits-all probiotic trials toward stratified, microbiome-guided strategies.

Pharmacological inhibition of the chloride-bicarbonate exchanger pendrin with PDSinh-C01 potentiates the diuretic action of furosemide in healthy mice. Because pendrin contributes to acid-base regulation and blood pressure control, it may represent an attractive therapeutic target in chronic kidney disease (CKD). We investigated whether this pendrin inhibitor improves metabolic acidosis and salt-sensitive hypertension in the 5/6 nephrectomy (5/6Nx) model of CKD. Seven-week-old female Sprague Dawley rats underwent 5/6Nx and implantation of telemetry devices for blood pressure monitoring. All animals received a high-salt (2% NaCl) diet and were randomized (n = 7-9/group) to daily subcutaneous injections for three days of vehicle, PDSinh-C01 (10 mg/kg), furosemide (6 mg/kg), or their combination. The 5/6Nx model recapitulated key features of CKD, including reduced eGFR, hypertension, proteinuria, and hyperchloremic metabolic acidosis. Combination therapy produced the greatest reduction in mean arterial pressure (-11 ± 2 mmHg) compared with vehicle (-3 ± 2 mmHg), furosemide (-6 ± 1 mmHg), or pendrin inhibitor alone (-6 ± 2 mmHg). Furosemide and combination therapy increased urine volume at 6h, whereas only combination therapy increased urine volume at 24h. After three days, the pendrin inhibitor alone and combination therapy increased venous bicarbonate concentrations compared with vehicle (24.5 ± 2.1 and 24.3 ± 1.4 vs. 21.4 ± 1.4 mmol/l). In conclusion, PDSinh-C01 combined with furosemide improves salt-sensitive hypertension in CKD, while PDSinh-C01 alone and in combination with furosemide ameliorates metabolic acidosis. These findings support pendrin as a regulator of electrolyte and acid-base balance and as a potential therapeutic target in CKD.