Cobalamin C (cblC) deficiency is the most frequent disease involving intracellular cobalamin metabolism. This study evaluates the response of hydroxocobalamin (OHCbl) monotherapy in patients with stable cblC disease, aiming to simplify treatment strategies. This retrospective cohort study enrolled cblC patients with a follow-up duration exceeding six months. Clinical features and biochemical markers were assessed before and after OHCbl monotherapy. Genotype-stratified analyses were further performed. Propensity score matching (PSM,1:1) was applied to identify control patients receiving combined therapy (OHCbl plus oral agents), based on disease onset status, OHCbl dosage, and genotype. Forty-one patients received OHCbl monotherapy for a median duration of 33.0 months. At last follow-up, 39 patients remained reportedly asymptomatic, while two had a poor prognosis. All patients achieved total homocysteine (tHcy)levels≤50 μmol/L and normal free carnitine (C0) levels, accompanied by significant improvements in other metabolic biomarkers. Compared to severe genotypes, patients with mild genotypes required lower OHCbl doses (P = 0.001) but showed no significant differences in the last-visit methionine and tHcy levels and outcomes (P > 0.05). Among 125 patients who switched from combination therapy to OHCbl monotherapy, ten showed clinical improvements after a median treatment duration of 9.2 months, while 115 patients exhibited no change (58 remained reportedly asymptomatic and 57 had persistent complications). Of these, 111 achieved tHcy≤50 μmol/L and tended to have shorter durations of prior combined therapy, lower tHcy levels during treatment, and a higher frequency of milder genotypes. PSM yield 28 matched pairs. No significant differences were observed in demographics, OHCbl dosage, outcomes or most biochemical markers (P>0.05), except for lower post-treatment C0, propionyl carnitine and methionine levels in the monotherapy group (P<0.05). Evidence suggests that in cblC deficiency, OHCbl monotherapy was associated with favorable reported clinical status and sustained biochemical control particularly in milder genotypes, and may represent a practicable simplified treatment strategy. However, extrapolation to more severe genotypes should be cautioned due to the limited case numbers in this study.
The tomato leaf miner, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a major pest causing severe damage to tomato crops worldwide. The present study evaluated the insecticidal efficacy of Cymbopogon nardus (citronella) and Pelargonium graveolens (geranium) essential oils against T. absoluta larvae and their impact on selected biochemical and oxidative stress parameters under laboratory conditions. GC-MS analysis identified citral and related monoterpenes as the major components of citronella oil, while geranium oil was rich in citronellol. Toxicity assays demonstrated dose-dependent larval mortality for both oils, with citronella oil exhibiting slightly higher potency (LC50 = 3.12%; LC90 = 6.37%) than geranium oil (LC50 = 3.88%; LC90 = 7.65%). Biochemical analyses revealed significant reductions in GABA-transaminase activity, total protein, and total lipid contents in treated larvae, indicating disruption of neurotransmission, metabolism, and energy reserves. Furthermore, oxidative stress markers showed decreased total antioxidant capacity and superoxide dismutase activity, together with increased lipid peroxidation, indicating the induction of oxidative stress in treated larvae. These findings demonstrate that both essential oils possess significant insecticidal activity and induce marked biochemical and oxidative stress responses in T. absoluta larvae. Therefore, citronella and geranium essential oils may represent promising eco-friendly botanical insecticides for incorporation into integrated pest management programs for tomato crops.
Ketogenic diet (KD) therapy is a high-fat, low-carbohydrate, low-protein diet with a macronutrient ratio of 89% fat, 10% protein, and 1% carbohydrates. This causes the body's primary energy source to shift to lipids. Improved glycemic control, weight loss, and the treatment of metabolic and cardiovascular diseases are among the therapeutic advantages of this metabolic shift. Therefore, this study was designed to detect if the prolonged intake of KD has beneficial or hazardous effects on the thyroid gland and adipose tissue by using 20 adult male albino rats divided into two groups. Both groups received 30 gm of food every day for 60 days: a standard diet for the control group and KD for the ketogenic group. Blood samples were taken for measurement of lipid profile and thyroid hormones. Body weight, body mass index (BMI), and food intake with atherogenic index were also measured. Tissue samples from the thyroid gland and adipose tissue were also taken for histological analysis using Hematoxylin and Eosin (H&E), Sudan black, Masson Trichrome, PAS, and immunohistochemical staining (caspase 3 and calcitonin antibodies). The results of the present study showed that the long-term use of the KD diet produced a significantly lower body weight, BMI, and food intake, with an atherogenic serum lipid profile and increased TSH levels. Additionally, it produced histological changes in the thyroid and adipose tissues with increased caspase-3 expression and a greater number of calcitonin-positive cells. In conclusion, this study highlights the adverse effects of the KD on thyroid and adipose tissues, evidenced by reduced serum T3 and T4, elevated TSH, follicular cell disruption, and adipose tissue alterations like reduced lipid droplet size and increased vascularization. The results could be alarming for the health hazards of chronic KD consumption in humans without medical supervision.
In the search for more efficient chemical processes to valorize renewable feedstocks, oleate hydratases (Ohys) represent promising biocatalysts. These enzymes can convert cis-Δ9 fatty acids like oleic acid into their hydroxy fatty acid counterparts using only water as co-reagent and with unparallelled selectivity. A multitude of Ohys has been described, however, direct comparison is hard due to the use of different assays. For this work, we characterized and compared four Ohys across different homologous families (HFams): those from Elizabethkingia meningoseptica (EmOhy, HFam11), Stenotrophomonas nitritireducens (SnOhy, HFam11), Rhodococcus erythropolis (ReOhy, HFam3), and Rhodococcus pyridinivorans (RpOhy, HFam2). All enzymes, especially SnOhy, expressed well in Escherichia coli (28-99 mg/Lculture). FAD occupancy after purification was 51% or lower for all Ohys. ReOhy had lost the flavin altogether, making supplementation a necessity for its activity. Reduction of the cofactor to FADH2 clearly showed a favorable effect on the activity of all Ohys, with product yields increasing from modest to 12-fold. Although SnOhy showed the highest initial reaction rates, EmOhy reached the highest 10-hydroxystearic acid (10-HSA) yields at higher oleic acid loading (10 mM) and prolonged reaction times. Thermostability was analyzed by thermal shift assays, with EmOhy appearing as most thermostable (Tm app = 54 °C).
The interactive effects of microencapsulated essential oils-organic acids preparation (EOA) and non-starch polysaccharide (NSP) enzymes on intestinal health of broilers fed wheat-based diets remain poorly elucidated. This study aimed to investigate the effects of dietary supplementation with EOA alone and in combination with NSP enzymes on growth performance, slaughter characteristics, serum biochemical indexes and intestinal microenvironment of broilers fed wheat-based diets. A total of 360 one-day-old male Arbor Acres broilers were randomly allocated to five treatment groups for 42 days (n = 6 replicates/treatment, 12 birds/replicate): the basal diet supplemented with 200 mg/kg EOA (A), 400 mg/kg EOA (B), 200 mg/kg NSP enzymes (C), along with 200 mg/kg NSP enzymes plus 200 mg/kg EOA (D), and 200 mg/kg NSP enzymes plus 400 mg/kg EOA (E), respectively. Growth performance was monitored on d 1, 21, and 42; slaughter characteristics, serum biochemical indexes and jejunal digestive enzyme activities were assessed on d 42; and jejunal villus morphology on d 21 and 42 was measured using hematoxylin and eosin (HE) staining. Additionally, on d 42, jejunal gene expression was analyzed by qPCR, cecal short-chain fatty acids (SCFAs) content was determined using gas chromatography (GC), and cecal microbiota composition was characterized via 16S rRNA gene sequencing. Data were analyzed using one-way analysis of variance (ANOVA) followed by Duncan's multiple range test, and statistical significance was set at P < 0.05. Results showed that compared with the single enzymes-added group (group C), dietary addition of EOA alone and combined with NSP enzymes had no significant impacts on the growth performance, slaughter characteristics and serum biochemical indexes of broilers (P > 0.05). However, group D exhibited a 23% decrease in jejunal crypt depth and a 37% increase in villus height to crypt depth ratio (VH/CD) on d 21, and a 29% decrease in crypt depth with a 36% increase in VH/CD on d 42 compared with group C (P < 0.05). Single EOA supplementation significantly decreased jejunal trypsin activity, with 53% and 50% reductions in group A and group B, respectively, relative to group C (P = 0.035). For cecal SCFAs, group B showed a 69% decrease in isovaleric acid content (P = 0.012), while group D had a 73% increase in butyric acid content and a 34% increase in total SCFAs content compared with group C (P < 0.05). In group E, the jejunal mRNA expression of IFN-γ was upregulated 2.0-fold, and the relative abundance of Bacteroides_fragilis in the cecum was reduced by 42% when compared with group C (P = 0.001 and P = 0.034, respectively). Collectively, these findings indicate that the combined application of NSP enzymes with low-dose EOA (200 mg/kg) in wheat-based diets can optimize the intestinal microenvironment of broilers by reducing crypt depth, elevating the VH/CD ratio, and increasing the content of cecal butyric acid and total SCFAs, without compromising growth performance. In contrast, the combination of NSP enzymes with high-dose EOA (400 mg/kg) triggers intestinal microbial dysbiosis and intestinal inflammatory responses in broilers. Therefore, high-dose EOA is not recommended for combined supplementation with NSP enzymes in wheat-based broiler diets under conventional conditions. With policies restricting antibiotic overuse becoming mainstream, farmers are turning to non-antibiotic feed additives to maintain poultry health. Based on this trend, this study evaluated the effects of supplementing wheat-based broiler diets with essential oils-organic acids mixture (EOA) alongside enzyme preparations. The results showed that combining a low dose of EOA with enzyme preparations effectively improved the intestinal microenvironment of poultry, outperforming the individual use of each component. However, surprisingly, high-dose supplementation exacerbated intestinal burden and worsened health conditions. These findings demonstrate that an optimal ratio of feed additives is required for maximum efficacy, whereas indiscriminate application can lead to either ineffective waste or adverse outcomes.
Secondary lymphedema, characterized by localized tissue swelling caused by lymphatic damage or dysfunction, remains a major clinical challenge that compromises quality of life. Current physical therapies provide only temporary relief, underscoring the need for effective regenerative strategies. Here, we report the fabrication of a micropatterned, small-diameter fibrous artificial lymphatic vessel incorporating hyaluronic acid (HA) via electrospinning to enhance lymphatic fluid transport. The engineered scaffold exhibits optimized mechanical properties and elicits favorable cellular responses through HA-mediated biochemical cues. Lymphatic endothelial cells (LEC) cultured on the scaffold show increased expression of lymphangiogenesis-related markers, including Prox1 and LYVE-1, accompanied by AKT activation and increased VEGF-C/VEGFR3-associated marker expression. The topographical features of the scaffold were also associated with altered YAP localization and increased lymphatic endothelial marker expression. In vivo implantation of the scaffold in a rat lymphedema model reduced ankle swelling and lymphatic retention across the surgically disrupted region toward an anatomically preserved drainage basin. Collectively, these findings suggest that HA-integrated fibrous lymphatic scaffolds represent a promising strategy for lymphedema treatment by synergistically engaging biochemical and biomechanical pathways associated with lymphatic repair and functional fluid transport.
Pheochromocytoma is a rare neuroendocrine tumor that may present with atypical and potentially life-threatening cardiovascular manifestations due to catecholamine excess. Reverse Takotsubo cardiomyopathy, a distinct form of stress-induced cardiomyopathy, has been strongly associated with catecholamine crisis but remains underrecognized. The purpose of this report is to describe a rare case of pheochromocytoma-induced reverse Takotsubo cardiomyopathy complicated by acute severe mitral regurgitation and to emphasize the importance of early endocrine recognition. A 40-year-old woman presented with hypertensive emergency, acute chest pain, electrocardiographic changes suggestive of acute coronary syndrome, and markedly elevated cardiac biomarkers. Transthoracic echocardiography revealed reduced left ventricular ejection fraction with basal and mid-ventricular akinesis, apical hyperkinesis, and acute severe mitral regurgitation consistent with reverse Takotsubo cardiomyopathy. Emergency coronary angiography demonstrated normal coronary arteries. Recurrent stress-induced cardiomyopathy in a young patient without conventional cardiovascular risk factors, accompanied by autonomic symptoms, hyperglycemia, and lactic acidosis, raised suspicion of pheochromocytoma-related catecholamine crisis. Cross-sectional imaging identified a left adrenal mass and biochemical testing confirmed markedly elevated plasma metanephrines. After appropriate preoperative α-adrenergic blockade, laparoscopic adrenalectomy resulted in complete clinical and biochemical remission with full recovery of cardiac function. Pheochromocytoma should be considered in younger patients presenting with recurrent or atypical Takotsubo cardiomyopathy, particularly in the case of reverse pattern and when associated with acute mitral regurgitation or hypertensive emergency. Early endocrine diagnosis is critical as definitive surgical treatment leads to complete resolution and prevents recurrence of severe cardiovascular complications.
Due to production of some important biochemicals including secondary metabolites (SM), medicinal plants are of economic and health significance. However, medicinal plants are subjected to different types of stress including drought affecting their growth and biochemical properties including SM production. There is an increasing demand for cultivation of medicinal plants and subsequent production of SM as suitable alternatives for conventional pharmaceuticals. Additionally, although research has indicated drought stress may alter SM production in medicinal plants, affecting their health and economic values, the related mechanisms must be investigated in greater details. This review is about drought stress affecting the production of different types of SM (alkaloids, terpenoids and flavonoids), and so, plant response in drought stress as indicated by omics analyses. Moreover, role of elicitors including plant growth regulators such as plant hormones on SM production in drought stress conditions has also been reviewed. Plant stress tolerance (sensitive or tolerant) is an important factor determining the accumulation of SM and plant response in drought stress conditions. Accumulation of flavonoids including anthocyanins and flavonols may alleviate unfavorable effects of drought stress on plant, though the related mechanisms have yet to be indicated. Finding methods, which enhance tolerance of medicinal plants in stress conditions, and so, improve their quality and quantity, is of significance for innovation in the synthesis of therapeutic drugs. This indicates the applicability of this review including the present research gap. Proper level of drought stress may enhance SM production in medicinal plants, and so, their economic and health significance.
Sharing the most recent common ancestor, receptor-like kinases EXCESS MICROSPOROCYTES1 (EMS1) and BRASSINOSTEROID INSENSITIVE1 (BRI1) family members respectively perceive the peptide ligand TAPETUM DETERMINANT1 (TPD1) and the phytohormone brassinosteroids (BRs) to activate the same downstream BRI1 EMS SUPPRESSOR1 (BES1)/BRASSINAZOLE RESISTANT1 (BZR1) transcription factor family. Yet only their distinct canonical functions have been revealed. TPD1 specifically sustains tapetum development but is dispensable for global plant growth, whereas BRs regulate overall plant growth without impacting tapetum development. This generates a fundamental evolutionary conflict: gradual biochemical divergence with saltational biological diversification. Here, we identify an unrecognized redundant role of TPD1 and BR signaling in controlling early anther lobe formation. Simultaneous disruption of both pathways causes a lobeless anther defect, phenocopying the loss of the entire BES1/BZR1 family. Single-pathway disruption produces no such defect. Interestingly, we found that pathway specificity during tapetum development is caused by spatiotemporal ligand dynamics. The expression of DWF4 (encoding a rate-limiting BR biosynthetic enzyme) decreases sharply at the onset of tapetum development, while TPD1 expression remains stable. Consistently, exogenous BR application or the introduction of an active, ligand-independent BRI1 rescues tapetum defects in either the ems1 mutant or the dual-pathway-deficient mutant background. Our findings reconcile biochemical divergence and biological diversification with gradual evolution, likely stimulating study of the functional divergence of numerous other receptor-like kinases at multiple levels.
β-thalassemia major is a chronic, transfusion-dependent disorder marked by severe iron overload and systemic inflammation. However, the interplay among inflammatory cytokines, iron chelation therapy, and hepcidin regulation remains incompletely understood. In this case-control study, 140 participants (100 patients, 40 healthy controls) were examined for associations between inflammatory and biochemical parameters and serum hepcidin. Hematological and biochemical parameters, inflammatory cytokines (IL-10 and TNF-α), and serum hepcidin levels were evaluated using nonparametric tests, Spearman's correlation, and bootstrapped multiple linear regression, with adjustment for serum ferritin, hemoglobin, TNF-α, and age to account for potential confounding. Patients had significantly higher levels of ferritin, liver enzymes, blood glucose, inflammatory cytokines, and hepcidin than controls (p < 0.05). IL-10 and hepcidin showed a strong positive correlation (r = 0.838, p < 0.001). Bootstrapped Multiple regression showed that IL-10 was significantly associated with serum hepcidin in the adjusted model (B = 1.078, 95% CI: 0.876-1.288, p < 0.001), whereas ferritin was not independently associated with hepcidin. The model explained 74.2% of the variance (Adjusted R2 = 0.742). Moreover, significant variations in these parameters were observed across iron chelation therapy groups. These findings suggest a potential association between inflammatory activity and hepcidin-related iron regulation in β-thalassemia major, but longitudinal studies are needed to clarify the clinical relevance of this relationship.
Ischemic stroke accounts for 87% of all stroke cases, and remains a leading cause of mortality and disability worldwide. Current reperfusion therapies are limited by narrow therapeutic windows, and cerebral ischemia-reperfusion injury (CIRI) remains a major clinical challenge. Ferroptosis, an iron-dependent form of regulated cell death characterized by lethal lipid peroxidation, has been identified as a key pathological driver of CIRI. Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has shown neuroprotective effects in ischemic stroke, but its underlying mechanism, especially the regulatory effect on ferroptosis via the TAK1-CREB1 signaling axis, remains unclear. To investigate the neuroprotective effect of DHA in ischemic stroke and its molecular mechanism related to the TAK1-CREB1 signaling pathway and ferroptosis regulation. Wild-type (WT) C57BL/6 J mice and astrocyte-specific CREB1 conditional knockout (CREB1 CKO) mice were used to establish a photothrombotic stroke (PTs) model. Neurological function was evaluated by modified neurological severity score (mNSS), Bederson score, Garcia scale and hanging test. Cerebral infarct volume was measured by TTC staining. Cerebral blood flow (CBF) was detected by laser speckle contrast imaging. Histopathological changes were observed by HE and Nissl staining. Mitochondrial ultrastructure was examined by transmission electron microscopy (TEM). The levels of malondialdehyde (MDA), glutathione (GSH), NADPH/NADP+ ratio, ferrous iron (Fe2+) and total iron in brain tissue were detected by biochemical kits. The expression of ferroptosis-related proteins and CREB1 was detected by Western blot and immunofluorescence staining. DHA treatment dose-dependently improved neurological function, reduced infarct volume, restored CBF, and ameliorated histopathological damage in PTs mice. TEM revealed that DHA reversed ferroptosis-typical mitochondrial changes in ischemic brain tissue. Biochemically, DHA decreased MDA, Fe²⁺, and total iron, while increasing GSH and NADPH/NADP⁺ ratio. Mechanistically, DHA dose-dependently upregulated GPX4, xCT, and FTH1, and downregulated ACSL4. Notably, astrocyte-specific CREB1 knockout nearly completely abolished DHA's neuroprotective and anti-ferroptosis effects. DHA promotes neurological rehabilitation after ischemic stroke by targeting the astrocytic TAK1-CREB1 signaling pathway to inhibit ferroptosis. This study provides a novel theoretical basis and promising candidate drug for the clinical treatment of ischemic stroke.
ADP-ribosylation (ADPr), long recognized as a canonical protein post-translational modification, has recently expanded to include targeting nucleic acids, uncovering a diverse landscape of noncanonical biological functions. Emerging evidence suggests that ADPr at the 5'-phosphate terminus of DNA is implicated in the DNA damage response, yet understanding its precise molecular function has been hampered by the lack of structurally defined chemical probes. Here, we report the stereoselective synthesis of deoxynucleotide-phospho-ADPr (dN-P-ADPr) probes, representing native fragments of terminal DNA-ADPr. Our strategy leverages a mild, stereocontrolled glycosylation to construct the challenging ribosyl-phosphate linkage, followed by P(III)-P(V) coupling to establish the pyrophosphate bridge. This robust toolkit enabled the systematic biochemical profiling of DNA-ADPr hydrolases across diverse kingdoms of life. Remarkably, using these newly developed probes, we uncover hydrolases across the diversity of life capable of reversing ADPr modifications at phosphorylated DNA ends. We further show that these enzymes exhibit an absolute preference for the native-like α-anomer, independent of the identity of the adjacent DNA nucleobase, suggesting that substrate recognition is governed primarily by the ADPr-phosphate linkages rather than the local nucleobase context. Together, these synthetic probes and biochemical insights provide an essential foundation for deciphering the biological landscape of noncanonical ADPr.
To evaluate 68Ga-pentixafor PET/CT in the surgical management of primary aldosteronism (PA), with emphasis on its relationship with adrenal venous sampling (AVS), KCNJ5 mutation status, tracer uptake, and postoperative outcomes. This retrospective single-center cohort screened 929 consecutive patients with suspected PA from November 2021 to February 2025. The final cohort included 162 patients who underwent unilateral adrenalectomy and 6-month follow-up; 83 also underwent AVS. Patients treated before September 2024 followed an AVS-guided pathway, and those treated thereafter followed a PET/CT-guided pathway. Outcomes were assessed by PASO criteria. Firth logistic regression, overlap weighting, paired PET/CT-versus-AVS analysis, and genotype-stratified analyses were performed. Clinical and biochemical complete success did not differ significantly between the PET-guided and AVS-guided groups. Among patients with both tests, unilateral PET/CT showed high positive predictive value versus AVS (56/57, 98.2%), but 26 of 82 AVS-confirmed unilateral PA cases had negative or bilateral PET findings. All KCNJ5-mutated patients in the PET-status cohort were PET-positive, whereas 22 of 52 KCNJ5-nonmutated patients were PET-negative. KCNJ5 mutation and CT lesion size were independently associated with PET positivity. SUVmax LI was associated with biochemical complete success, including within KCNJ5-nonmutated patients. 68Ga-pentixafor PET/CT provides strong rule-in information when uptake is clearly unilateral. Negative or bilateral PET/CT, especially in small or KCNJ5-nonmutated lesions, should be interpreted cautiously and should not preclude AVS-based evaluation.
Celiac disease (CeD) is an autoimmune enteropathy; nearly 60-80% of first-degree relatives (FDRs) of CeD patients carry HLA-DQ2/DQ8 haplotypes; however, only 7.5% of them develop enteropathy. This suggests the modulation of biochemical and molecular mechanisms that might help in maintaining intestinal integrity. Thus, the present study investigated the metabolome of FDRs to gain insight into biochemical mechanisms that might help in maintaining intestinal integrity. The metabolome of small intestinal mucosal biopsies, blood plasma and urine of serologically negative first-degree relatives (FDRs, n = 50) was investigated using proton NMR spectroscopy and compared with CeD patients (n = 64) and controls (disease controls, n = 35 or healthy controls, n = 32) using both univariate and multivariate statistical analyses. The metabolic profiles of FDRs of CeD patients differed significantly from both CeD patients and controls. Higher myo-inositol and fumarate in the mucosa of FDRs suggest the role of these metabolites in modulating the immune response and inflammation, which may protect intestinal integrity in FDRs. Elevated formate and tyrosine levels in the intestinal mucosa of FDRs, compared to both CeD patients and controls, suggested alterations in gut microbiota that may support intestinal homeostasis. Furthermore, significant changes in levels of branched-chain amino acids in FDRs compared to CeD patients indicated their increased utilization for enterocytes renewal, upregulation of tight junction proteins and modulating immune response to maintain villous architecture. Our data showed that FDRs exhibit a specific metabolic signature that may represent an adaptive response aimed at maintaining intestinal homeostasis and mucosal integrity despite genetic predisposition.
ObjectiveSuperselective adrenal arterial embolization with ethanol has demonstrated promising efficacy in patients with primary aldosteronism and lateralized aldosterone secretion. However, approximately 40% of patients have nonlateralized disease, defined as bilateral primary aldosteronism based on adrenal venous sampling.MethodsIn this prospective observational cohort study, 30 patients with primary aldosteronism underwent superselective adrenal arterial embolization, including 16 patients with unilateral primary aldosteronism and 14 patients with bilateral primary aldosteronism confirmed by adrenal venous sampling. Patients were stratified into the unilateral primary aldosteronism and bilateral primary aldosteronism groups. Blood pressure and biochemical parameters were assessed at 15-40 h and at 1, 3, and 6 months after the procedure.ResultsPlasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio improved significantly in both groups within 15-40 h after superselective adrenal arterial embolization compared with baseline. At 6 months, the rates of complete or partial clinical and biochemical success were 85.7% and 92.9%, respectively, in the bilateral primary aldosteronism group compared with 81.3% and 87.5%, respectively, in the unilateral primary aldosteronism group. Significant reductions in serum sodium levels and microalbuminuria were observed in patients undergoing bilateral superselective adrenal arterial embolization. Body mass index also decreased significantly at 1, 3, and 6 months in both groups. No procedure-related complications were observed during a median follow-up of 6 months.ConclusionsBilateral superselective adrenal arterial embolization may represent a valuable adjunctive treatment strategy for patients with bilateral primary aldosteronism.
Parenteral iron is widely prescribed by medical practitioners, with more than 600 000 outpatient prescriptions dispensed in 2025 through the Australian Pharmaceutical Benefits Scheme. While intravenous iron has transformed the management of iron deficiency, hypophosphataemia is now recognised as a common complication, with incidences reported as high as 92% depending on formulation. Although most cases are mild and transient, vulnerable patient groups may develop profound and symptomatic hypophosphataemia, sometimes requiring hospitalisation and intravenous phosphate replacement. The clinical spectrum ranges from subtle biochemical abnormalities to lethargy, weakness and myalgias and, rarely, severe manifestations including muscle weakness, osteomalacia, myopathy, arrhythmias and cardiomyopathy. This narrative review presents five illustrative cases, highlighting the varied presentations of iron-induced hypophosphataemia and potential patient groups at high risk. To address this growing challenge, we present an institutionally endorsed management pathway based on our review of the literature and current practice after multidisciplinary consultation. The algorithm emphasises early recognition of high-risk patients, primary prevention by using formulations of iron associated with the lowest risk of hypophosphataemia, timely identification of symptomatic hypophosphataemia and coordinated correction of concurrent electrolyte disturbances, with the aim of improving patient safety and outcomes.
To investigate nosocomial non-vector-borne transmission of Dabie bandavirus (DBV) using clinical, epidemiological, virological, and genomic evidence. We conducted a comprehensive multidisciplinary study of six patients within a hospital setting, integrating detailed epidemiological contact tracing, dynamic monitoring and tracing of viremia, the neutralizing antibodies, hematologic and biochemical markers, viral isolation, and whole-genome sequencing of clinical specimens. Genomic analysis was used for phylogenetic placement and verification of high-confidence sequence differences between the index and secondary patients. This study demonstrated that DBV is capable of vector-independent human- to-human transmission in healthcare settings. Whole-genome sequencing showed that viruses isolated from the secondary cases were highly genetically related to the virus from the index case and clustered within an established Chinese lineage, strongly supporting a common origin and confirming that the secondary infections were acquired from the index patient through nosocomial transmission. Viral isolation and microneutralization assays further characterized the virological and humoral immune features of the secondary cases. This study reports a nosocomial cluster of DBV infections, which occurred through human-to-human transmission. It highlights the value of integrating epidemiological investigation, virus isolation, microneutralization assays, and whole-genome sequencing to establish transmission chain, reconstruct the outbreak, and assess infection-control risks in this epidemiological event.
Nanomedicine has revolutionized brain-targeted therapeutics; however, most design paradigms remain centered on overcoming the blood-brain barrier while overlooking the dynamic physiological milieu that governs nanoparticle fate after entry. Emerging evidence reveals that barrier penetration alone is insufficient to ensure efficacy, particularly in the aging brain, where vascular stiffness, impaired interstitial flow, reduced glymphatic clearance, and chronic immune activation reshape nanoparticle distribution, retention, and metabolism. Aging introduces structural and functional heterogeneity that can invert design principles validated in young systems, leading to reduced therapeutic performance and unpredictable outcomes. This review integrates current insights into how age-related vascular remodeling, altered cerebrospinal fluid dynamics, and disrupted circadian-metabolic coupling influence nanoformulation performance. We highlight the need for adaptive design strategies, including stimuli-responsive carriers, redox- or enzyme-triggered release systems, and chronopharmacological dosing, that exploit residual rhythmicity and local biochemical cues to optimize delivery. Beyond design, we discuss translational and regulatory implications, emphasizing age-specific protein corona profiling, biomarker-guided patient stratification, and physiologically relevant safety evaluation. Integrating these insights establishes aging not as a confounder but as a biological framework enables the creation of adaptive, context-aware nanomedicines aligned with the evolving physiology of the aging brain which advancing the field toward durable efficacy, enhanced safety, and genuine precision neurotherapeutics.
Crude oil contamination alters soil health and induces phytotoxicity, with effects varying by soil properties and plant species. Understanding these impacts is crucial for developing effective bioremediation techniques for ecosystem restoration and plant conservation. This study evaluated effects of crude oil contamination (0-2.5% per kg soil) on soil health using biochemical, physicochemical, and biological parameters over a 12-week experimental period, with maize (Zea mays L.) as the test plant. Effects of crude oil contamination on enzyme distribution, physical and chemical properties of soil were monitored while oxidative stress in maize plants was determined at the end of the experimental period. Results showed that the activity of enzymes in control and test soils decrease with plant growth. Significant increase in activity was recorded in oil contaminated soils for dehydrogenase, α-amylase, β-glucosidase, cellulase, polyphenol oxidase, lipase, acid phosphatase and arylsulfatase when compared with control. Amidase and protease activities were significantly lower in contaminated soil compared to pure soil. Crude oil contamination increased bulk density and reduced pore size with minimal significant impact at 0.5% crude oil per Kg of soil. Bacterial population significantly increased in contaminated soils compared to pure soils. Oxidative stress in maize plant grown on 0.5% crude oil contaminated soil was not significant compared with control. Crude oil contamination induced oxidative stress at higher concentrations as revealed by increase in superoxide dismutase, catalase and guaiacol oxidase. Findings provide information that would guide the design of bioremediation techniques for restoration of crude oil contaminated soils.
Our understanding of transcript elongation by metazoan RNA polymerase II (Pol II) has grown notably in recent years. Advances in structural biology have defined the interactions that underlie promoter-proximal pausing of Pol II and the transition from pausing to productive elongation. Improved targeted protein degradation together with sensitive, time-resolved assays of RNA synthesis has transformed our view of transcript elongation control in living cells. In this Review, we discuss the highly orchestrated interactions between elongating Pol II and co-transcriptional RNA-processing factors, revealing that the splicing factor U1 small nuclear ribonucleoprotein (U1 snRNP) directly stimulates productive elongation. Biochemical and cell-based techniques have shed new light on how Pol II overcomes obstacles to elongation such as nucleosomes. Emerging studies have demonstrated the importance of quality control during early transcript elongation by factors such as Integrator and Restrictor. These surveillance machineries ensure the integrity of mRNA synthesis and suppress spurious RNAs arising from transposable elements or regulatory regions such as enhancers. Finally, we discuss how defects in Pol II elongation contribute to diseases ranging from developmental disorders to cancer and inflammation, emphasizing the importance of a fuller understanding of Pol II elongation to human health.