Fragility fracture of the pelvis (FFP) with a low-energy mechanism of injury is relatively common among the growing geriatric population. The incidence of postoperative complications after surgically treated FFP is not well documented. The aim of this study was to report complications after operatively treated FFP and to determine whether these complications would have a detrimental effect on outcomes. Retrospective study of 200 consecutive patients who underwent operative treatment at Oulu University Hospital, Oulu, Finland, between 1.1.2010 and 15.4.2021 for FFP with a low-energy injury mechanism. Postoperative complications were recorded, and associations with outcomes were depicted. Postoperative complications were recorded in 31 (15.5%) patients. Patients with complications had higher intraoperative bleeding (OR 2.8 (1.0-7.9), p = 0.048) and higher ASA classification 3.4 (1.3-8.4), P = 0.009). Patients with complications had longer hospital stays, but no clear association between complications and mortality or discharge location was observed. The incidence of postoperative complications was comparable with that reported in previous literature. Patients who experienced complications had longer hospital stays; however, no definitive association between complications and outcomes was identified.
The growing global energy demand and environmental impacts of fossil fuels drive the development of green, carbon-neutral energy technologies. Hydrogen (H2) is a promising clean energy carrier due to its high gravimetric energy density and zero carbon emissions. Electrocatalytic water splitting provides an efficient route to produce high-purity hydrogen using renewable power. Rare-earth (RE) elements exhibit unique 4f electronic configurations that effectively regulate the electronic structures, active sites, and reaction paths of electrocatalysts. Despite significant progress, a comprehensive review of RE-doped electrocatalysts for water splitting remains lacking. This Review Systematically Summarizes Recent Progress in RE-doped Electrocatalysts For the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). It elaborates Core Design Principles and Structure-Activity Relationships, including (i) 4f-d electronic synergies that optimize charge distribution and intermediate adsorption, (ii) RE-induced Defect Engineering and Lattice Modulation That Increase Active-Site Density and Structural Stability, and (iii) the doping strategies across metal oxides, layered double hydroxides, metal-organic frameworks, phosphides, sulfides, and heterostructures. The review also analyzes the electronic regulation mechanisms in typical catalyst platforms and clarifies corresponding doping strategies and electrochemical applications. Finally, key challenges and future perspectives are outlined to guide the design of high-efficiency, durable, and scalable RE-doped electrocatalysts for water splitting.
The amount and source of nutrition are important factors that influence an ewe's reproductive ability, but the effects of diet on the reproductive performance of its offspring are unclear. This study aimed to investigate the impact of maternal nutrition (level of nutrition and source) on the reproductive performance of ewes and their female lamb offspring. Seventy-two Dorper × Santa Inês ewes were allocated in a completely randomized block design, in five treatments: CTL (n = 14) with 100% of requirement, and the energy source was corn; RES (n = 14) with 90% of predicted requirement, and the energy source was corn; SUPP (n = 15) with 110% of requirement, and the energy source was corn; CR (n = 15) treatment SUPP plus chromium propionate; and FAT (n = 14) treatment SUPP plus calcium salts of palm oil. Non-parametric data were evaluated using the Fisher exact test, and parametric data were evaluated using the Tukey test, both at a 5% significance level. There was no difference in pregnancy rate (p = 0.1944) or prolificacy (p = 0.5729) among the treatments; however, the CR diet resulted in a faster return to estrus after lambing (p < 0.001). The RES diet decreased lamb survival (p < 0.005) and reduced offspring reproductive potential. Using chromium positively affected the reproductive parameters of female offspring, whereas FAT adversely affected them. In conclusion, the source and level of dietary energy influence fetal programming in ewes. The restriction negatively affected the reproductive performance of the offspring, and supplementation with chromium propionate improved it.
Long-persistent luminescence (LPL) materials, celebrated for their remarkable ability to capture and gradually release light over extended durations, have catalyzed advances in domains such as optical data storage and bioimaging. However, the synthesis of efficient, multicolor ultralong LPL with precise modulation of duration remains a formidable challenge. Here, we introduce an effective strategy for inducing trichromatic ultralong LPL in Cs2NaScCl6:Sb3+ through meticulous defect engineering. By judiciously adjusting the dosage of hydrochloric acid during synthesis, we systematically regulate the formation of Na+ and Cl- vacancies as well as Sb3+-induced lattice distortions, affording unprecedented control over the material's luminescent properties. This approach culminates in the achievement of a record-breaking blue afterglow exceeding 30 h for naked eye, alongside green and red persisting for 48 and 24 h, respectively. Notably, the dual self-trapped exciton (STE) emissions exhibit disparate thermal behaviors, with the higher-energy STE demonstrating anti-thermal quenching, while the lower-energy counterpart undergoes typical thermal quenching. For the first time, we elucidate the activation of LPL via body temperature, enabling information retrieval through tactile interaction. This innovative material showcases profound potential for x-ray imaging and secure data encoding, offering a novel avenue for the development of advanced LPL materials with finely tuned emission characteristics.
Boron/nitrogen-embedded polycyclic frameworks are attractive emitters in organic light-emitting diodes (OLEDs) because they combine narrowband emission with thermally activated delayed fluorescence. Linear extension of multiresonant frameworks with zigzag boron/nitrogen alignment is predicted to enable bathochromic emission, reduced singlet-triplet energy gaps, and enhanced oscillator strengths, yet experimental access to higher-order structures remains challenging. Here we report a site-programmable, stepwise borylation strategy for constructing a triboron DABNA-extended framework with zigzag boron/nitrogen alignment, L-DABNA-TriB. Our combined theoretical and experimental studies reveal how progressive linear extension from mono- to tri-boron frameworks modulates the electronic structure, leading to bandgap narrowing, strengthened radiative transition, and near-degenerate singlet and triplet excited states. Importantly, L-DABNA-TriB in toluene exhibits yellow-orange emission at 559 nm with a narrow full width at half-maximum of 33 nm/0.13 eV, a singlet-triplet energy gap of ca. 4 meV, and a radiative decay rate of 1.5 × 108 s-1. A non-sensitized OLED based on L-DABNA-TriB achieves a maximum external quantum efficiency of 38.0% and retains 35.2% at 1000 cd m-2. This work establishes zigzag boron/nitrogen-aligned linear extension as an effective molecular design strategy for narrowband emitters with efficient exciton harvesting at long wavelengths.
All-solid-state batteries (ASSBs) represent promising next-generation energy storage systems with superior safety and energy density compared to conventional lithium-ion batteries (LIBs). This review comprehensively examines advanced electrode and cell manufacturing processes that are critical to the commercialization of ASSBs. Electrode fabrication processes are categorized into wet and dry processing approaches. The wet processing leverages existing LIB manufacturing infrastructure for cost-effectiveness but faces challenges due to chemical reactivity between sulfide solid-state electrolytes and processing solvents/binders. Conversely, dry processing offers shorter production steps and improved environmental sustainability, particularly for thick electrodes. For cell assembly, bipolar stacking architectures enhance volumetric energy density through internal series connectivity, while Z-folding methodology enables scalable manufacturing. Pressure optimization emerges as crucial for maintaining interfacial contact and electrochemical performance. The manufacturing strategies presented provide essential insights for transitioning ASSB technology from laboratory to commercial production, addressing technical and economic barriers to widespread adoption.
Conversion-type FeF3 cathodes promise ultrahigh energy density but suffer from sluggish reaction kinetics and interfacial instability in solid-state battery systems. Here, we designed a fluorine-rich NaBiF4@Bi2O3 catalyst-initiated polymer electrolyte via in situ ring-opening polymerization of 1,3-dioxolane. The NaBiF4 phase initiates polymerization and serves as a fluorine reservoir, while Bi2O3 participates in regulating the fluorine environment and contributes to the formation of a Li3Bi alloy clusters during cycling. This electrolyte enables the construction of LiF/NaF/Li2O-reinforced solid electrolyte interface with embedded Li3Bi domains, delivering the homogeneous Li+ flux and dendrite-free Li deposition, enabling the stable Li‖Li symmetric cell cycling for 9700 h. The electrolyte demonstrates broad compatibility with both intercalation and conversion cathodes, achieving excellent cycling stability (800 cycles) in LiFePO4 and high areal capacity (6 mAh cm-2) in LiNi0.8Co0.1Mn0.1O2. The Bi2O3 component further catalyzes the interfacial dissociation of LiF at FeF3 cathode and promotes the dynamic evolution of fluorine-rich cathode electrolyte interphase, enabling the remarkable reversibility in FeF3 conversion chemistry (641 mAh g-1 at 0.2 C and 300 cycles at 1 C). A 20-layer FeF3-based pouch cell is demonstrated with a discharge capacity exceeding 1 Ah for the first time, marking a critical milestone toward practical high-energy FeF3 batteries.
The full orchestration of synergistic geometric and electronic interaction at atomic scale is fundamental to surmounting cascade kinetic bottlenecks inherent in multistep electrochemical processes. Here, an axially-oriented, sulfur-bridged hetero-atomic motif (Ru─S─Co) is customized to achieve synergistic regulation throughout alkaline hydrogen evolution reaction (HER). The top-positioned Ru atoms are tailored for enhanced water capture, and the bottom-inserted Co atoms in lattice activate middle S atoms for balanced hydrogen adsorption-desorption. This customized multi-site synergy conspicuously lowers the energy barrier for rate-determining water scission step. The proportion of reactive free water is elevated on this modified interface to prompt alkaline HER initiation. Furthermore, the intrinsically asymmetric charge distribution along the dual-atom bridge enhances charge transfer during HER, and the prominent orbital coupling induces an upshift in the Ru d-band center together with increased density of states in S p-orbitals around the Fermi level, further augmenting Ru-S dual-site activity. With this catalyst adopted as cathode, the anion-exchange-membrane electrolysis cell maintains an industrial current density of 1000 mA cm-2 at a small voltage of 1.79 V with negligible performance decay after long-term stability test. This work provides insights into precise customization of atomic-scale synergy toward effective management of kinetically mismatched multisteps in HER-related energy conversion.
Polyethylene oxide (PEO)-based solid polymer electrolytes (SPEs) have emerged as promising candidates for advancing the all-solid-state lithium metal batteries (ASSLMBs) market. However, conventional PEO-based SPEs exhibit low room-temperature (RT) ionic conductivity and limited oxidative stability (restricted to ∼4.2 V), which impedes their compatibility with high-voltage cathodes and diminishes the achievable energy density of ASSLMBs. Here, we report the development of polymer-in-salt PEO-based networked solid polymer electrolyte (NSPE) that enables stable fast cycling at 5 C and extended electrochemical stability up to 4.5 V, demonstrated using oriented LiCoO2 (LCO) sputtered film cathodes. This system effectively overcomes the typical irreversibility of LCO cathodes above 4.3 V in conventional liquid electrolytes (LEs), which is often attributed to complex cathode-electrolyte interphase (CEI) formation, structural phase transformations, and cobalt dissolution. Furthermore, we systematically compare the electrochemical performance and interfacial evolution of cells employing conventional electrolytes with those utilizing the NSPE membrane. Our results reveal that a thin and uniform LiF-rich CEI layer forms at the interface, which facilitates rapid Li+ transport between the well-oriented LCO films and the NSPE. Here, we provide innovative mechanistic insights into interfacial interactions between layered oxide cathodes and SPEs and offer substantial potential to accelerate the development of next-generation energy storage systems.
The adsorption and photocatalytic conversion of CO2 molecules to mitigate atmospheric greenhouse gas concentrations and manufacture value-added chemicals require efficient CO2 reduction reaction catalysts. In this study, a surface bond competition approach was developed to obtain high-performance CO2 adsorbents and syngas production photocatalysts via the sulfurization-driven enhancement of surface basicity and interfacial interaction. The heat treatment of Mg-Al-layered double hydroxide nanosheets under a flow of CS2 yielded sulfur-doped MgO/MgAl2O4Sx nanosheets. The sulfur-doping-induced enhancement of surface basicity originated from the increased electron density on oxygen through competition with covalent metal-sulfur bonds, substantially enhancing the CO2 adsorptivity. The sulfur-doped MgO/MgAl2O4Sx nanosheets acted as effective hybridization matrices for ZnIn2S4 nanoplates, boosting their activity for photocatalytic syngas production (i.e., ≈3.3 mmol g-1 h-1 with the ratio of CO/H2 = 2.2). Density functional theory calculations revealed that hybridization with MgO/MgAl2O4Sx nanosheets was effective in lowering both the adsorption energy of CO2 and the energy barrier for the conversion of *COOH to *CO. Systematic in situ spectroscopic investigations highlighted that the hybridization with MgO/MgAl2O4Sx enhanced Lewis acid-base interaction between ZnIn2S4 and absorbed CO2, and the contribution of associative pathways, which were attributed to sulfur-doping-assisted reinforcement in interfacial electronic coupling between hybridized components.
Mounting an immune response and locomotor activity are energetically costly processes that can generate trade-offs affecting energy allocation, muscle performance, and activity patterns. The balance between these demands can be modulated by factors such as food availability and ecological conditions, influencing the ability to mount an immune response and maintenance of locomotor activity. In a previous study, we demonstrated that Xenopus laevis subjected to an immune challenge maintained voluntary movement, indicating that behavioral depression did not occur in these animals, contrary to what is observed in most species. We hypothesized that food availability influenced this response, since the animals were captive and fed ad libitum. Here, we investigated the effects of food restriction on the locomotor activity of X. laevis after an immune challenge induced by lipopolysaccharide (LPS). We evaluated locomotor endurance, jump force, and spontaneous voluntary movement in individuals subjected to a progressive, 30-day, food restriction protocol. These results suggest that food restriction alters the energetic prioritization following immune activation, leading to reduced locomotor output and behavioral activity. Furthermore, the reduction in jump force and locomotor endurance was more pronounced in individuals on restricted diet, indicating a direct impact of energy availability on locomotor capacity. These findings reinforce the idea that resource availability influences the immune and locomotor response in anurans, highlighting how nutritional stress may constrain immune-locomotor trade-offs in amphibians, with potential consequences for survival and fitness in resource-limited habitats.
In-beam positron emission tomography (PET) integrates dedicated detectors into proton therapy systems, enabling real-time acquisition of proton-induced positron-emitting activity. By pre-delivering a subset of single-energy proton spots as probes, in-beam PET has the potential to support online proton range verification and may inform subsequent spot delivery. However, the limited acquisition time and low yields of positron emitters result in noisy reconstructed images, and the open geometry of dual-panel PET further introduces stretching artifacts. To address these issues, this study proposed a 3D U-Net-based post-processing method to enhance in-beam PET image quality and evaluated its feasibility through Monte Carlo simulations and preliminary experimental validation. Thirteen head computed tomography (CT) phantoms were irradiated with horizontally and vertically incident single-energy probes, representing two scenarios in which beams passed through relatively homogeneous and heterogeneous tissues. A phantom-level split was used, with seven CT phantoms for training, two for validation, and four held-out CT phantoms for testing. Proton probes in 3×3, 5×5, 7×7, and 9×9 spot patterns were simulated, with each spot delivering 2×107 protons. In-beam PET acquisition was performed for 30 s. Unfiltered reconstructed PET images were used as network inputs, and ground-truth activity distributions served as labels. Gaussian-filtered PET images served as the baseline for performance evaluation. Image quality was quantified by peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM), and proton range verification accuracy was evaluated by absolute range error (ARE). Additional simulations with CT density perturbations were conducted to evaluate sensitivity to proton range shifts. Preliminary experimental validation was performed using an all-digital PET prototype and polymethyl methacrylate (PMMA) phantoms. For horizontal beams, median PSNR values increased from 21.4-23.9 to 35.2-37.4, median SSIM values increased from 0.450-0.621 to 0.906-0.961, and median ARE values decreased from 1.05-1.18 mm to 0.52-0.73 mm. For vertical beams, median PSNR values improved from 21.9-23.2 to 29.2-34.1, median SSIM values improved from 0.480-0.560 to 0.745-0.895, and median ARE values decreased from 1.80-2.40 mm to 1.50-1.73 mm. The proposed method also demonstrated improved sensitivity to simulated range shifts and consistent improvements on experimental PET data. These findings demonstrate the preliminary feasibility of using 3D U-Net-based post-processing to enhance dual-panel in-beam PET image quality and improve PET-based proton range verification.
The term "mega gland" commonly refers to prostates > 200 mL on preoperative imaging. These glands are traditionally perceived as technically challenging for holmium laser enucleation of the prostate (HoLEP) due to increased vascularity, difficult dissection planes, and instrument length limitations. We evaluated perioperative outcomes and procedural efficiency of HoLEP for mega glands compared with large glands (120-200 mL). We performed a single-center retrospective analysis of patients undergoing HoLEP for glands ≥ 120 mL between January 2021 and June 2025. Patients were categorized into large (120-200 mL) and mega (> 200 mL) gland groups. Baseline characteristics, intraoperative parameters, efficiency metrics, and postoperative outcomes were compared using Wilcoxon rank-sum, Pearson's Chi square, and Fisher's exact tests. Among 602 HoLEPs performed, 243 patients met inclusion criteria, including 208 with large glands and 35 with mega glands. Baseline characteristics were similar, although mega glands had higher PSA values (9.9 vs 5.6 ng/mL, p = 0.001). Operative time was longer in mega glands (114 vs 96 min, p = 0.003). However, enucleation speed (2.8 vs 1.6 g/min, p < 0.001) and energy efficiency (0.8 vs 0.5 g/kJ, p < 0.001) were significantly higher despite similar enucleation times. Postoperative outcomes, including catheter duration, failed void trial, emergency department visits, readmissions, and 3-month PROMs, were similar between groups. HoLEP for prostates > 200 mL showed higher enucleation speed and energy efficiency without worse short-term outcomes. These findings suggest HoLEP may be a size-enhanced procedure, not merely size-independent. Further work is needed to define this efficiency threshold more precisely and explore its clinical implications.
Sodium-ion batteries (SIBs) have shown significant potential for application in large-scale energy storage systems due to their abundance of sodium resources, cost-effectiveness, and environmental compatibility. Polyanionic cathode materials, with their unique crystal structure and high theoretical specific capacity, have become a focus of research in SIBs. In this study, we develop a novel pyrophosphate- and sulfate-containing Na2+2xFe2-xP2O7SO4 (NFPS) polyanionic chemical material featuring a three-dimensional open-framework structure for the first time via the sol-gel method. The diffraction peaks are successfully indexed to the Pna21 orthorhombic system for NFPS. In situ carbon-coated NFPS cathode materials are prepared successfully with a lower-cost biomass carbon source. The cathode material delivers an initial specific capacity of up to 101.46 mAh g-1 at 0.05 C and retains 83.56% of its capacity after 500 cycles at 5 C, demonstrating its feasibility for application in SIBs. This study provides an innovative NFPS polyanionic material and methods for developing high-performance cathode materials for SIBs, which are expected to promote the application of SIBs in large-scale energy storage.
The development of efficient electrocatalysts for biomass-derived furfural hydrogenation is crucial for sustainable chemical production. Herein, we report a systematic study of transition metal catalysts for electrocatalytic furfural reduction to furfuryl alcohol (FA) synthesized by precisely controlled magnetron sputtering. Monometallic thin films (Cu, Ni, Co, Ag, Cr, Mo and W) on Ti substrates reveal a volcano-shaped correlation between the d-band center position and catalytic activity, establishing fundamental binding energy-activity relationships. Building on these insights, we designed bimetallic CuNi alloys with tunable compositions, where the Cu40Ni60 variant demonstrated exceptional performance, achieving twice the FA formation rate of pure Ni while maintaining 100% selectivity. Mechanistic studies reveal that the Cu40Ni60 catalyst exhibits intermediate behavior between Cu (preferring the Langmuir-Hinshelwood pathway) and Ni (favoring the proton-coupled electron transfer pathway), with enhanced contributions from both pathways synergistically boosting the overall reaction rate. Alloying induces synergistic electronic effects that optimize furfural and H adsorption energy to regulate surface coverage and balance the reaction pathways. This work establishes a standardized platform for evaluating composition-activity relationships in furfural hydrogenation and provides fundamental design principles for non-precious metal alloy catalysts, highlighting electronic structure engineering as a key strategy for optimizing hydrogenation performance.
Although large oil spills cause intense ecological damage and receive heavy media and research attention, small spills occur much more frequently and have ecological consequences. Currently, assessment of damage to wildlife after oil spills of any magnitude primarily involves carcass counts and observation of individuals with visible oiling. Such methods do not account for sublethal or non-visible oil exposures that accompany the consumption of contaminated prey or soils. Recent research demonstrates that mild oil exposure can affect time-energy budgeting in birds, as they alter foraging and preening time, and metabolic rates. There is a need to understand how both frequency and length of exposure (duration) to oil spills interact with mechanisms of lethality and sublethality to affect population declines and recoveries. We developed a dynamic energy budget individual-based model to represent a generalized altricial bird and simulate the outcomes of various oiling scenarios. The models revealed that sublethal effects of oil exposure are important to population decline and recovery because they altered trajectories of population recovery through reduced fecundity and embryo survival. Our models also indicate that small oil spills can have significant effects on populations, particularly when spills occur frequently or persist in the environment. Our findings agree with empirical studies showing that sublethal effects of oil exposure in birds are important to population dynamics and indicate that frequent or long-lasting small spills can have significant effects on populations. Minimizing frequency and prioritizing expeditious clean-up of all, including small, spills could result in better conservation outcomes.
DNA is widely employed in biological science and materials science, driving a growing demand for its effective preservation. The conventional cryopreservation method is highly resource-intensive, requiring substantial storage space and continuous energy input. These limitations highlight the urgent need to develop cost-effective and efficient alternative strategies. In this study, we creatively extended the application of chitosan derivatives to the preservation of extracellular DNA, based on our previous work on chitosan-mediated nucleic acid enrichment and detection. Among different types of chitosan derivatives, chitosan oligosaccharide lactate (COL) was identified for its outstanding DNA-binding and re-release capabilities. Upon complexation with COL, DNA is effectively protected against major environmental stressors including enzymatic hydrolysis, oxidative damage, and ultraviolet irradiation, which were the major environmental stressors. This protective interaction significantly enhances the stability of DNA under non-cryogenic conditions, which in turn minimizes the losses in DNA concentration and integrity while preserving critical sequence information. Furthermore, the binding and release of COL with DNA could be achieved handily by pH adjustment. Moreover, COL could be readily available and amenable to large-scale production. Collectively, our findings provide a great potential method for realizing convenient and cost-effective DNA preservation at room temperature.
Emotional states fluctuate continuously, yet it remains unclear how momentary emotional states and their temporal variability relate to cognition in daily life. We examined how fluctuations along the two principal dimensions of emotion, valence and arousal, are associated with objective cognitive performance and subjective mental effort using ecological momentary assessment. To address this question, we conducted two complementary studies. In Experiment 1 (online sample, n = 289), four brief state items (happiness, calmness, energy, fatigue) were validated as measures of state valence and arousal using a semantic association task and factor analysis. In Experiment 2, participants (July 2024-February 2025; n = 59) completed a 5-day ecological momentary assessment protocol with three assessments per day (682 completed sessions), combining repeated emotional state ratings with a working memory task and subjective mental effort reports. Associations were tested using linear mixed models. In Experiment 1, happiness and calmness loaded on a valence factor, whereas energy and fatigue loaded on an arousal factor. In Experiment 2, greater between-day variability in valence was associated with reduced working memory performance, driven by increased intrusion errors, together with lower perceived mental effort. In contrast, higher momentary arousal was associated with lower perceived mental effort without changes in working memory performance. Together, our results support a dissociation between emotional influences on cognitive control and on the subjective experience of effort. This dissociation suggests that emotion-cognition interactions in everyday life cannot be captured by a single affective dimension and that different emotional dimensions exert distinct effects on cognitive performance and its subjective experience. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Puberty is a critical window for bone mass acquisition, determining lifelong fracture risk. Gonadotropin-releasing hormone agonist (GnRHa)-based pubertal suppression followed by gender-affirming hormone therapy (GAHT) is increasingly used in transgender and gender-diverse (TGD) adolescents, raising concerns about peak bone mass. To quantify changes in bone mineral density (BMD), bone mineral apparent density (BMAD), and z scores in TGD adolescents undergoing GnRHa with or without GAHT, and to identify predictors of skeletal outcomes. PubMed, Scopus, Web of Science, and Cochrane Library, from inception through September 2025. Longitudinal cohorts assessing BMD, BMAD, or z scores at the lumbar spine, total hip, or femoral neck in TGD adolescents treated with GnRHa with or without GAHT. Ten studies met the inclusion criteria. Data were extracted in duplicate; study quality was assessed using the Newcastle-Ottawa Scale. Random-effects models pooled mean changes across baseline (time 0 [T0]), after GnRHa (T1), and after GAHT (T2), stratified by skeletal site and sex assigned at birth. Metaregressions examined body mass index, age, Tanner stage, and treatment duration. Dual-energy x-ray absorptiometry-derived BMD, BMAD, and z scores. Ten cohorts comprising 751 adolescents (427 assigned female at birth [AFAB]; 324 assigned male at birth [AMAB]) were included. Lumbar spine z scores declined during GnRHa (AFAB: z-score change, -0.97 [95% CI, -1.09 to -0.85]; AMAB: z-score change, -0.73 [95% CI, -0.93 to -0.53]) despite stable BMD. z Scores used sex-assigned-at-birth normative references. After GAHT, BMD increased (AFAB: BMD mean difference, 0.09 g/cm2 [95% CI, 0.07-0.10 g/cm2]; AMAB: BMD mean difference, 0.13 g/cm2 [95% CI, 0.10-0.16 g/cm2]), with partial z-score recovery; values remained below baseline at T2 (AFAB: z-score change, -0.51 [95% CI, -0.69 to -0.34]; AMAB: z-score change, -0.52 [95% CI, -0.82 to -0.21]) but were not consistently statistically different across skeletal sites. Recovery at the total hip and femoral neck was smaller and more heterogeneous. Higher body mass index, shorter GnRHa duration, and longer GAHT exposure were associated with more favorable outcomes. This systematic review and meta-analysis found that pubertal suppression followed by GAHT was associated with transient z-score reductions and subsequent BMD increases. At T2, z scores remained numerically below baseline but were not consistently statistically different, suggesting an uncertain rather than demonstrated persistent deficit. Timely GAHT initiation is recommended.
Human topoisomerase 1B (hTopo1B) is a validated anticancer target due to its key role in relieving torsional stress during DNA replication and transcription, as well as its overexpression in rapidly proliferating tumor cells. Camptothecin (CPT) and its derivatives are principal hTopo1B-targeting agents but face challenges including lactone ring instability, dose-limiting toxicities, and acquired drug resistance. This research investigated seven protoberberine alkaloids from Coptis teeta alkaloids-berberine, coptisine, epiberberine, berberastine, jatrorrhizine, palmatine, and fetidine as potential CPT-like hTopo1B inhibitors using comprehensive computational methods. Density functional theory (DFT) calculations showed that six of the seven alkaloids had HOMO-LUMO gaps (2.608-3.015 eV) and electrophilicity indices similar to CPT, suggesting a capacity for charge transfer and DNA intercalation. Molecular docking of the hTopo1B-DNA binary complex (PDB:1A36) revealed that all compounds stabilized the covalent cleavage complex through π-π stacking and hydrogen bonds at the scissile site, with coptisine and epiberberine showing the strongest binding affinities (----10.32 and -10.53 kcal/mol, respectively). Molecular dynamics simulations over 250 ns confirmed the structural stability of the complexes, with low RMSD and RMSF values and minimal fluctuations in the radius of gyration. MM/GBSA and MM/PBSA binding free energy analyses consistently ranked epiberberine as the strongest binder (DG = -18.86 and -14.12 kcal/mol), followed by berberine and coptisine. Per-residue decomposition identified key contacts with the DNA bases DT118, DA17, and DA14, as well as with the protein residues GLU179 and GLY201. All protoberberine analogs showed drug-likeness in ADME profiling, good oral availability, and no PAINS alerts. These findings suggest that protoberberine alkaloids from C.teeta, especially epiberberine, coptisine, and berberine, are promising candidates for next-generation hTopo1B-targeted anticancer therapeutics. Experimental validation is required to confirm the proposed mechanism.