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The association of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP) with inferior prognosis was demonstrated in a systematic review. However, all patients in the included studies lacked a prostate-specific membrane antigen Positron-Emissions-Tomography (PSMA-PET) before salvage radiotherapy (SRT). Since PSMA-PET has markedly improved sensitivity in detecting lymph node and distant metastases, it is unclear whether PSA persistence can be further considered a risk factor in patients or reflects an advanced tumor stage. We used a retrospective database including 1222 PSMA-PET-staged prostate cancer patients treated with SRT for biochemical recurrence (BR) at 11 centers in five countries. After patients without information on PSA persistence were excluded, 1188 patients remained. The effects of PSA persistence and recurrence on overall survival (OS), metastasis-free survival (MFS), and biochemical progression-free survival (BPFS) were evaluated. The median follow-up time was 31.0&#x202f;months (IQR range: 20.04-43.6&#x202f;months). PSMA-PET revealed a higher incidence of local recurrence (43.5% vs. 30.0%, p&#x202f;=&#x202f;0.01), and lower incidence of nodal failure in patients with PSA recurrence (40.6% vs. 30.5%, p&#x202f;<&#x202f;0.001). In univariate analysis, patients with PSA recurrence had significantly superior 3-year biochemical progression-free survival (BPFS) (71.5% vs. 63.0%, p&#x202f;=&#x202f;0.033) and MFS (83.0% vs. 78.0%, p&#x202f;=&#x202f;0.049) compared with patients with PSA persistence. In the multivariate analysis, no significant differences were observed concerning BPFS (p&#x202f;=&#x202f;0.738), MFS, (p&#x202f;=&#x202f;0.826), or OS (p&#x202f;=&#x202f;0.730). PSA persistence, traditionally considered a hallmark of a worse prognosis, may require reevaluation considering advances in imaging sensitivity. While our analysis does not definitively determine whether PSA persistence is no longer prognostic, it remains possible that its historically poorer prognosis and early focal detection via PSMA PET/CT have been therapeutically mitigated. As PSMA-PET becomes more widely available, its ability to detect hidden disease may help guide individualized treatment decisions.

Adeno-Associated Viruses (AAVs) are powerful platforms for delivering therapeutic transgenes via recombinant AAV (rAAV) vectors. However, a limited understanding of the regulation of AAV gene expression has narrowed the ability to efficiently express therapeutic transgenes from rAAV vectors. Since rAAVs retain only the wtAAV inverted terminal repeats (ITR), we hypothesized that regulatory elements outside the ITR that govern wild-type AAV (wtAAV) gene expression can be used to modify rAAV genomes to enhance vector performance. Through in silico analysis, biochemical pulldowns, and high-throughput sequencing, we have identified that the host architectural protein CCCTC-binding Factor (CTCF) associates with the wtAAV type 2 (wtAAV2) genome but is absent from rAAV vectors. Global knockdown and site-specific deletion revealed that the CTCF binding element (CBE) on the wtAAV2 genome, located upstream of the viral P5 promoter, regulates expression of the viral Rep68/78 genes. We have re-engineered new rAAV vectors expressing a GFP reporter transgene to contain the wtAAV2-CBE upstream of the vector promoter. Our results show that CTCF binding dramatically increased rAAV transduction efficiency and GFP expression by up to four-fold across multiple cell types. This enhancement was independent of the AAV capsid serotype used for packaging rAAV vectors. CUT&RUN analysis revealed that this CBE was necessary and sufficient to regulate the chromatin landscape of wtAAV2 and rAAV2. Finally, we observed that CTCF-mediated chromatin remodeling of rAAV2 led to increased production of nascent RNA transcripts from the vector genome. Based on our findings, we propose that CTCF supports wtAAV2/rAAV gene expression by shaping the local chromatin landscape. Recombinant Adeno-Associated Viruses (rAAV) gene therapy vectors have been engineered from wild-type AAV (wtAAV) by inserting the viral telomeres (that serve as replication and packaging signals) on either side of therapeutic transgenes. However, efficient expression of transgenes using current rAAV technologies require high doses, which can lead to sporadic toxic side effects. We hypothesized that uncharacterized regulatory elements in the wtAAV2 genome drive efficient viral gene expression and are absent from the current generation of rAAV vectors. Using in-silico analysis combined with biochemical pulldowns, high-throughput sequencing, and mutant viral systems, we have identified a novel cis -acting element bound by the cellular architectural protein CCCTC-binding Factor (CTCF). This CTCF binding element is necessary for wtAAV2 gene expression and is sufficient to enhance the rAAV vector's ability to express reporter transgenes. This CTCF-binding element regulates the chromatin landscape of the virus and its vectors. Our discovery that adding the 19-bp AAV2 CTCF-binding element enhances transgene expression without affecting vector production efficiency presents a promising new rAAV gene therapy platform that is likely to reduce clinical doses and minimize toxicity in therapeutic applications.

Mycobacterium tuberculosis (Mtb) biofilm formation is associated with antibiotic tolerance, but its architecture remains poorly understood. Here, we reveal that these biofilms form highly-organized superstructures of cords, and through their deconstruction, provide a new molecular insight into Mtb biofilms. Using multimodal imaging, we demonstrate that the lipid Phthiocerol Dimycocerosate (PDIM) is required for organizing bacilli into foundational cords and contributes specifically to biofilm-associated antibiotic tolerance. In contrast, the ESX-1 secretion system enhances the biochemical complexity of the extracellular matrix. Notably, we identified a functional amyloid matrix that encases bacterial cords or aggregates within the biofilm, likely conferring structural integrity. Together, these findings support a three-component model that distinguishes structural integrity, physical organization, and biochemical maturation, establishing a new architectural framework for Mtb biofilms. Finally, we show that the natural compound epigallocatechin gallate (EGCG) disrupts biofilm formation, highlighting the therapeutic potential of targeting this architecture to overcome drug tolerance in tuberculosis.

Psidium guajava (guava) is an important medicinal plant used for gastrointestinal disorders, diabetes, and inflammation, primarily due to its bioactive compounds including flavonoids and tannins. To ensure safety for human use, rigorous preclinical toxicity assessments are essential. The purpose of this study was to assess the safety of ethanol extract of Psidium guajava (EEPG) by acute and subacute toxicity tests. Organization for Economic Co-operation and Development (OECD) 425 recommendations were used for the acute toxicity investigation in mice, while OECD 407 guidelines were used for the sub-acute toxicity study in mice. Mice were given oral doses of 2000 mg/kg/ body weight in the acute toxicity trial. They were then monitored individually for the first four hours, then for 24 hours, then at least once a day for 14 days. Ethanol extract of Psidium guajava (EEPG) was administered orally to male and female mice for 28 days at dosages of 250 mg/kg, 500 mg/kg, and 1000 mg/kg /body weight, respectively, in the subacute toxicity tests. Over the course of the experiment, general behavior, negative impacts, and mortality were noted. Hematological and biochemical markers, body weight, organ weight, and histopathological alterations were assessed. in acute toxicity during the observation period, the mice examined showed no evidence of acute toxicity or mortality at the limit dosages of 2000 mg/kg/body weight. The findings of sub-acute toxicity testing revealed no anomalies associated with treatment in terms of biochemical, hematological and histopathology markers at the maximum dose of 1000 mg/kg /body weight. the substance showed a favorable safety profile, with no acute and subacute toxicity or mortality at 2000 mg/kg and no treatment-related adverse effects at 1000 mg/kg/body weight/day in mice.

Type 2 diabetes (T2D) accounts for over 90% of all diabetes cases and results from the interaction of genetic and environmental factors. However, the association between apolipoprotein E (APOE) gene polymorphisms and T2D risk shows considerable variation across different populations. This meta-analysis aims to clarify the association between APOE genotypes and alleles (E2E2, E2E3, E2E4, E3E4, E4E4) and the risk of T2D. Additionally, it examines the association of demographic, clinical, and biochemical parameters with T2D risk in cases and controls. Relevant articles providing genotypic and allelic frequencies of APOE polymorphisms were sourced from Google Scholar, Web of Science, Science Direct, and PubMed databases. These articles focus on peer-reviewed human case-control studies published in English until February 27, 2024. Data on APOE polymorphisms, biochemical, and clinical parameters were extracted. Statistical tests were performed using Review Manager 4.3.1 with results expressed using ORs and 95% CIs. Publication bias and heterogeneity were assessed using the Q test and Egger regression analysis. Thirty-two studies involving 19644 participants. The statistical analysis showed that BMI, SBP, DBP, TC, and LDL-C could potentially indicate a higher risk of T2D in cases compared to controls. Significant associations with T2D were found for the APOE E4E4 genotype (OR =1.94, 95% CI= [1.16, 3.23], P = 0.01, I2=75%), and the E4 allele (OR=1.26, 95% CI= [1.11, 1.43], P = 0.0005, I2=55%). No significant associations were observed for the E2E2, E2E3, E2E4, and E3E4 genotypes, or the E2 allele (P > 0.05 for all). A significant association between APOE genotype E4E4 and allele E4 with T2D was confirmed in this meta-analysis.

This study aims to evaluate the effect of low molecular weight heparin (LMWH) on pregnancy outcomes in recurrent implantation failure (RIF) women without thrombophilia undergoing freeze-thaw embryo transfer (FET) cycles. A total of 392 FET cycles conducted between January 2021 and November 2024 were included in the study. Patients were divided into two groups: the LMWH group, receiving daily subcutaneous injections of 4000 AxaIU LMWH starting on the day of embryo transfer, and the control group, following the standard luteal phase support protocol without LMWH administration. Baseline characteristics and reproductive outcomes of the patients were systematically collected. Generalized estimating equation (GEE) models incorporating logistic regression were applied to adjust for potential confounding factors. Additional subgroup analyses were performed to assess the association between maternal age and pregnancy outcomes. After adjusting for confounding variables, no statistically significant differences were observed between the two groups in the rates of ongoing pregnancy (p&#x202f;=&#x202f;0.729), biochemical pregnancy (p&#x202f;=&#x202f;0.487), clinical pregnancy (p&#x202f;=&#x202f;0.068) and miscarriage (p&#x202f;=&#x202f;0.122) between the two groups. However, subgroup analysis revealed that among women over 35 years of age, the LMWH group exhibited significantly higher rates of clinical pregnancy (p&#x202f;=&#x202f;0.016) and ongoing pregnancy (p&#x202f;=&#x202f;0.039) compared to the control group. Although LMWH does not demonstrate improve pregnancy o utcomes in the general population of women with RIF, it may offer benefits for women of advanced maternal age. Considering these potential advantages in older women, further research is warranted to clarify the role of LMWH, particularly within the subgroup of women over 35 years of age.

The growing interest in plant-based therapeutics has led to increased exploration of medicinal flora for their nutritional and pharmacological potential. The objective of this study was to determine the nutritional composition, phytochemical profile, and antioxidant activity of Cotoneaster microphyllus from Shimla, Himachal Pradesh. The proximate analysis revealed high levels of ash and fat in the leaves, while high fiber levels in the fruits. According to mineral profiling, leaves showed an abundance of Mg, Ca, Na, and Zn, while fruits indicated predominant presence of P and K. Phytochemical extractions were performed using hydromethanol, methanol, and aqueous solvents, with hydromethanol extract exhibiting the highest phytochemical content and antioxidant activity, followed by methanol and aqueous extracts. DPPH and FRAP antioxidant assays confirmed that C. microphyllus scavenges free radicals and reducing antioxidant potential effectively. Based on GC-MS and LC-MS analyses, cyclosiloxanes and phthalate ester compounds were identified via GC-MS and 50 unique compounds were identified via LC-MS, reported for the first time in Cotoneaster. UHPLC was also used to quantify chlorogenic acid, with fruit extracts showing the highest concentration. In this study, we provide a novel insight into the phytochemical composition and bioactive potential of C. microphyllus. There is a significant lack of systematic biochemical and functional evaluation of this species, so this study represents the first comprehensive integration of nutrition profiling, multi-solvent phytochemical quantification, and advanced characterization (GC-MS, LC-MS, and UHPLC) of different plant parts. These findings provide new insight into phytochemical composition of C. microphyllus and point to its potential as a source of bioactive chemicals with potential pharmacological and nutraceutical applications, which need for more biological validation.

Plants have evolved multilayered mechanisms against microbial pathogens. We highlight work from Wang and colleagues, demonstrating the biochemical and genetic basis of plant chemical defenses against cross-kingdom viral, bacterial, and fungal pathogens, while conceptualizing a new classification system for these multifaceted resistances based on core genetic defenses.

Soil enzyme activity is a key determinant of crop productivity, as it regulates nutrient cycling, organic matter decomposition, and nitrogen transformation. The existing Machine Learning (ML) and Deep Learning (DL) approaches for soil fertility assessment often underutilize biochemical indicators owing to noise, missing data, and complex feature interactions. These models treat Feature Selection (FS) and Hyperparameter Tuning (HPT) as separate process. This limits the overall model performance. Conventional Sand Cat Swarm Optimization (SCO) method suffers from rigid exploration-exploitation transitions and premature convergence. To overcome these limitations, an Improved Sand Cat Swarm Optimization (Improved SCSO) based framework is implemented in this work. The proposed work sequentially performs FS and HPT within a unified optimization process and includes a stochastic escape-from-worst update mechanism. Cosine-modulated search behavior is incorporated in the model to enhance exploration. Exploitation and convergence stability are improved by Time-adaptive best-solution inheritance strategy. Enzyme-related soil attributes were explicitly incorporated into the optimization process, enabling the selection of biologically meaningful features. A correlation-based filtering step was applied to remove redundant features and improve the prediction consistency. The optimized feature subset was evaluated using multiple ML, DL and Hybrid models have also been assessed to understand the predictive performance of proposed framework. The model was evaluated using stratified k-fold cross-validation with Accuracy, Precision, Recall, and F1-score. The experimental results show that the proposed framework consistently outperforms traditional SCO-based methods. Gradient Boost (GB) achieved the highest accuracy of 98.48%, followed by hybrid models such as Decision Tree (DT)&#x2009;+&#x2009;Random Forest (RF) (98.38%) and GB&#x2009;+&#x2009;RF (98.28%) respectively. In addition, a dynamic crop mapping strategy was developed to estimate crop suitability based on predicted fertility levels and enzyme activity, thereby improving its practical application. Overall, the proposed framework improves prediction accuracy and interpretability, providing an effective solution for soil fertility assessment and data-driven crop recommendation.

A major outstanding question in neuroscience is whether the neocortex uses the same powerful learning algorithm as current AI models: error backpropagation. One way this could be accomplished is as a function of the temporal derivative (i.e., differences in neural activity states over time), which can closely approximate the backpropagated error gradient. We tested the hypothesis that the direction of synaptic plasticity is a function of the temporal derivative in synaptic activity over the course of a 200 ms (5 Hz) theta cycle. Using mouse hippocampal slices, we drove presynaptic activity across the two 100 ms halves of a 200 ms window at either 25 Hz or 50 Hz, combined with corresponding low and high magnitudes of postsynaptic depolarization, testing all four 2&#xd7;2 combinations of these low and high activity levels, while measuring the resulting effects on synaptic efficacy (as measured by EPSP amplitude to standard test probes). Consistent with the computational hypothesis, a positive temporal derivative (low to high) resulted in LTP (increased synaptic strength), while a negative temporal derivative (high to low) resulted in LTD. Critically, both no-change conditions (stable low or high across 200 ms) resulted in no net synaptic change, even though the high no-change condition had the highest overall synaptic activity levels. Possible biochemical mechanisms that could support these results are discussed.

Candida orthopsilosis endocarditis is rare and underdiagnosed due to the inability of conventional biochemical platforms to achieve species-level identification within the Candida parapsilosis complex. We report a 60-year-old hemodialysis-dependent woman with diabetes mellitus and chronic kidney disease who developed catheter-related fungemia progressing to infective endocarditis. C. orthopsilosis was identified by MALDI-TOF mass spectrometry. Broth microdilution per BrCAST/EUCAST demonstrated susceptibility to amphotericin B, fluconazole, and anidulafungin. Transesophageal echocardiography (TEE) revealed a mobile tricuspid valve vegetation fulfilling modified Duke Criteria for definite infective endocarditis. Despite antifungal therapy, blood cultures remained positive and septic pulmonary embolism developed. Surgical valve replacement achieved microbiological clearance within 24 hours; C. orthopsilosis was confirmed in excised tissue. Fluconazole step-down completed a six-week course. MALDI-TOF-guided species identification, susceptibility-directed echinocandin therapy, and timely surgical source control constitute an effective management framework for Candida endocarditis, achieving complete microbiological clearance despite severe systemic complications.

Polystyrene nanoplastics (PS-NPs) are an emerging class of environmental contaminants with increasing concern regarding their potential effects on reproductive development. This study examined whether maternal lactational exposure to PS-NPs is associated with alterations in ovarian growth, structure, and function in female rat offspring. The dams were administered PS-NPs at doses of 0, 0.1, 1, or 10&#xa0;mg/kg/day exclusively during the 21-day lactation period. Female offspring were evaluated on postnatal days 30 (PD30) and 60 (PD60). Macroscopic assessments indicated dose-related reductions in body weight, ovarian weight, and ovarian length at both postnatal stages in females. Qualitative fluorescence microscopy using rhodamine-labeled PS-NPs revealed dose-related fluorescent signals within the follicular and stromal compartments of the ovary at PD30 and PD60, supporting particle localization in ovarian tissue. Histological and morphometric analyses revealed a reduction in pre-antral follicle numbers at PD30, progressive thinning of the granulosa layer, and a decreased parenchyma-to-stroma ratio, particularly in high-dose offspring. Biochemical analyses indicated oxidative imbalance, characterized by an elevated total oxidant status (TOS) and oxidative stress index (OSI) at PD30, along with a reduced total antioxidant capacity (TAC) and higher oxidative indices at PD60. Endocrine evaluation at PD60 showed dose-related decreases in circulating estradiol and progesterone levels. Immunohistochemical analysis demonstrated increased P53 immunoreactivity and reduced BCL-2 expression, consistent with apoptosis-related signaling in ovarian tissue. Collectively, these findings suggest that lactational exposure to PS-NPs is associated with dose-related ovarian alterations accompanied by oxidative imbalance, endocrine disruption, particle localization, and apoptosis-associated responses, highlighting lactation as a potentially sensitive postnatal exposure window.

This study aimed to clarify the pharmacodynamic effects of YaJieShaBa (YJSB) against alcoholic hepatic fibrosis (HF) and elucidate its mechanism in regulating the transforming growth factor-&#x3b2;1 (TGF-&#x3b2;1)/Smad pathway. Induce the alcoholic HF model in rats using 56% ethanol (10&#x2009;mL/kg). The pharmacological efficacy of YJSB in combating liver fibrosis was evaluated through comprehensive assessments of key indicators: body weight, liver mass and index, biochemical liver function parameters (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), liver fibrosis biomarkers (type &#x2162; procollagen amino-terminal propeptide [P&#x2162;NP], type-&#x2163; collagen (COL-&#x2163;), laminin (LN), and hyaluronic acid [HA]), serum hydroxyproline (Hyp) and TGF-&#x3b2;1 levels, hepatocyte homogenate levels of COL-I, COL-&#x2162;, and &#x3b1;-smooth muscle actin (&#x3b1;-SMA), along with histopathological changes observed in liver tissue via hematoxylin and eosin (H&E) staining, Ag staining, and Masson staining. Pathway-focused qPCR array analysis was used to detect the expression of 72 genes related to signaling pathways such as TGF-&#x3b2;1, Keap1-Nrf2, and TLR4/MyD88 in liver tissue from the control group, model group, and YJSB group, identifying differentially expressed genes (DEGs) and key signaling pathways between the model group and the YJSB treatment group. Finally, based on the results of the pathway-focused qPCR array, the mechanism of action of YJSB against HF was validated using ELISA, WB, and immunofluorescence methods. Concurrently, TGF-&#x3b2;1 receptor inhibitors were employed in vitro experiments to determine whether YJSB could still provide additional protective effects when the TGF-&#x3b2;1/Smad pathway was maximally blocked. Furthermore, after confirming that YJSB could inhibit TGF-&#x3b2;1-induced activation, a rescue experiment was conducted by adding exogenous TGF-&#x3b2;1 to observe whether it could reverse the inhibitory effects of YJSB. YJSB administration significantly increased body mass and decreased liver index in alcoholic HF rats. Serum levels of AST, ALT, P&#x2162;NP, COL-&#x2163;, LN, HA, Hyp, and TGF-&#x3b2;1 were significantly reduced, as were the levels of COL-I, &#x2162;, and &#x3b1;-SMA in liver homogenates. Histological analyses, including H&E, Ag, and Masson staining, revealed a significant reduction in liver damage. Pathway-focused qPCR array results showed that, compared with the blank group, 65 genes were upregulated and seven genes were downregulated in the model group, among which the relative expression levels of 40 genes were statistically significant (expression change factor&#x2009;&#x2265;&#x2009;1 and p&#x2009; < 0.05). Compared with the model group, 68 genes were downregulated, and four genes were upregulated in the YJSB group, with 34 genes showing statistically significant relative expression levels (fold change [FC]&#x2009;&#x2265;&#x2009;2 and p&#x2009; < 0.05). The DEGs were primarily enriched in the TGF-&#x3b2;1 signaling pathway. Additionally, YJSB reduced the levels of inflammatory factors IL-1&#x3b2;, TNF-&#x3b1;, IL-6, and IL-8 in liver tissue homogenates while increasing SOD, GSH-Px, and catalase (CAT) levels and decreasing MDA and ROS levels. Western blotting results showed that YJSB downregulated the expression levels of TGF-&#x3b2;1, Smad2, Smad3, P-Smad2, and P-Smad3 in the liver. Immunofluorescence results indicated that YJSB downregulated the expression levels of Smad4 in hepatocyte nuclei. In vitro experiments demonstrated that the mechanism of YJSB involves primarily inhibiting TGF-&#x3b2;R1 receptor activation, effectively downregulating P-Smad2/3 protein levels, as validated by the TGF-&#x3b2;R1 inhibitor LY2157299. Concurrently, in rescue experiments, the inhibitory effect of YJSB on P-Smad2/3 protein was partially reversed by exogenous TGF-&#x3b2;1, indicating that YJSB's antifibrotic action is highly correlated with the TGF-&#x3b2;1/Smad pathway. YJSB effectively inhibits the inflammatory and oxidative stress-related cascade by regulating the TGF-&#x3b2;1/Smad signaling pathway (TSSP), thus suppressing the progression of alcoholic HF. This demonstrates that YJSB possesses potential for combating alcoholic HF in animal models, providing experimental evidence for its subsequent research and clinical application.

Advanced prostate cancer, particularly metastatic castration-resistant disease (mCRPC), represents a major clinical challenge due to its evasion of classical apoptotic pathways. Exploiting alternative regulated cell death modalities, specifically ferroptosis and cuproptosis, has emerged as a critical therapeutic goal. This review evaluates the complex biochemical structure of these metal-dependent vulnerabilities, emphasizing their intersection with mitochondrial bioenergetics, lipid remodeling, and the inflammatory tumor microenvironment. We review the role of the NRF2/GPX4 antioxidant axis and the modulatory influence of pro-inflammatory signaling on metal ion homeostasis. By synthesizing current multi-omics data and pharmacological strategies, including nanotherapies and theranostic radiopharmaceuticals, this manuscript emphasizes the necessity for predictive biomarkers and combinatorial rationales. Bridging these mechanistic discoveries with precision oncology is essential for overcoming therapeutic resistance and improving clinical outcomes in advanced prostate cancer.

Androgen receptor (AR) gene mutations are a common cause of 46, XY disorders of sex development (DSD), resulting in varying degrees of androgen insensitivity. This study aims to comprehensively evaluate the clinical features, hormone profiles, and AR gene variants of patients diagnosed with Androgen Insensitivity Syndrome (AIS), and to analyze the distribution of these variants across different functional domains. This retrospective, single-center study analyzed 16 cases of 46, XY DSD, all of whom were found to have AR variants from a single tertiary center in Turkey. Patients were evaluated based on their complaints, hormonal measurements, clinical features, and genetic diagnoses. Patients were classified as having Complete, Partial, or Mild AIS. The variants were categorized based on their location within the functional domains: The Ligand Binding Domain (LBD) and the N-terminal Domain (NTD). Patients were classified as having CAIS (8/16), PAIS (6/16), MAIS (1/16), and suspected diagnosis (1/16). The most common clinical finding was cryptorchidism (11/16). Ten different AR variants were detected: eight missense (p.Pro392Ser, p.Ala749Val, p.Val890Met, p.Asp733Asn, p.Arg856His, p.Arg856Cys, p.Glu494Ala, and p.Glu710Lys), one nonsense (p.Lys659Ter), and with p.Lys659Ter, p.Glu494Ala and being novel. A CAIS associated with p.Pro392Ser has been reported, and intrafamily variability has been documented in variants such as p.Arg856His and p.Pro392Ser. Most variants (10/16 patients) localized to the LBD. Individuals harboring LBD variants demonstrated lower external genital scores and shorter phallus lengths compared to those with NTD variants. T/DHT ratio was available in 11 patients and did not yield false-positive AIS diagnoses. Marked intrafamilial phenotypic variability was observed. This study expands the AR variant spectrum in AIS and represents one of the more comprehensively characterized cohorts from our country. While LBD variants were more often associated with severe phenotypes and NTD variants with milder presentations, marked phenotypic variability was observed. Nevertheless, considerable phenotypic variability, including marked intrafamilial heterogeneity, was evident. The T/DHT ratio provided supportive biochemical information but did not replace the need for molecular confirmation. Molecular confirmation remains essential, and multidisciplinary, patient-centered management is warranted.

To evaluate the regenerative effects of platelet-rich plasma (PRP) combined with 3% low-molecular-weight hyaluronic acid (HA) gel in treating ligature-induced periodontitis in rats. &#x2022;40 male albino rats divided into 5 groups: Control (no treatment), Periodontitis only, Periodontitis&#xa0;+&#xa0;HA, Periodontitis&#xa0;+&#xa0;PRP, Periodontitis&#xa0;+&#xa0;HA&#xa0;+&#xa0;PRP.&#x2022;After 2 weeks, histological (light microscopy and SEM) and biochemical (TNF-&#x3b1;, IL-1&#x3b2;) evaluations were performed. Histological and SEM examinations showed structural damage in the periodontitis group, including pocket formation and disorganized bone. Inflammatory markers (TNF-&#x3b1; and IL-1&#x3b2;) were significantly higher in this group than in the control group. Treatment with HA, PRP, and especially their combination significantly reduced these markers. The combined therapy (Group V) showed the most effective recovery, while HA (Group III) and PRP (Group IV) alone led to partial improvement. Treatment modalities that include HA or PRP administration could improve periodontal healing. However, the combined administration of HA and PRP yielded superior histological and statistical outcomes. This might be due to the intensifying collection of the adjunctives' anti-inflammatory and regenerative properties. However, additional studies are needed to evaluate this combination.

Micro(nano)plastics (MNPs) often coexist with antibiotics in soil ecosystems via organic fertilizer applications. They can be taken up and accumulated by plants, especially food crops, thereby threatening food safety. Despite increasing global concern, the distinct phytotoxic mechanisms of MNPs and their interactive dynamics with antibiotics remain dispersed. First, the uptake, translocation, and distribution of MNPs in plants are systematically synthesized. Based on the clarification of plant phenotypic and physiological responses to MNP stress, the review assesses their biochemical and molecular mechanisms, ranging from oxidative stress and antioxidant defense to signal transduction and transcriptional regulation to metabolic trade-offs. After clarifying the physicochemical interactions and cotransport mechanisms between MNPs and antibiotics, the review elucidates their combined phytotoxicity and their crucial role in antibiotic resistance gene (ARG) transmission in soil-plant systems. Finally, we identify research gaps and propose future research directions, which will facilitate the evaluation of ecological risks and the formulation of environmental regulations for copollutants.