Analysis and comparison of retinal vascular parameters under different glucose metabolic status based on deep learning.

AIM: To develop a deep learning-based model for automatic retinal vascular segmentation, analyzing and comparing parameters under diverse glucose metabolic status (normal, prediabetes, diabetes) and to assess the potential of artificial intelligence (AI) in image segmentation and retinal vascular parameters for predicting prediabetes and diabetes. METHODS: Retinal fundus photos from 200 normal individuals, 200 prediabetic patients, and 200 diabetic patients (600 eyes in total) were used. The U-Net network served as the foundational architecture for retinal artery-vein segmentation. An automatic segmentation and evaluation system for retinal vascular parameters was trained, encompassing 26 parameters. RESULTS: Significant differences were found in retinal vascular parameters across normal, prediabetes, and diabetes groups, including artery diameter (P=0.008), fractal dimension (P=0.000), vein curvature (P=0.003), C-zone artery branching vessel count (P=0.049), C-zone vein branching vessel count (P=0.041), artery branching angle (P=0.005), vein branching angle (P=0.001), artery angle asymmetry degree (P=0.003), vessel length density (P=0.000), and vessel area density (P=0.000), totaling 10 parameters. CONCLUSION: The deep learning-based model facilitates retinal vascular parameter identification and quantification, revealing significant differences. These parameters exhibit potential as biomarkers for prediabetes and diabetes.

Healthcare utilization and economics evaluation of paliperidone palmitate once-monthly in schizophrenia: a one-year, real-world, and retrospective mirror image study in China.

Background: Investigation and analysis of the changes in healthcare resources and burden of schizophrenia in the real world before and after switching from oral antipsychotics (OAPs) to paliperidone palmitate once-monthly (PP1M) could provide evidence to clinicians and patients for choosing treatment modality and data support for health policy optimization. Methods: The first dosage of PP1M was set as mirror point, and patients with mirror point between January 2020 and June 2022 were recruited in the study. The differences in treatment patterns, healthcare resource utilization, and costs within one year before and after the mirror point were compared. Results: A total of 72 patients transitioning from OAPs to PP1M (mean age, 35.33 years; 43.06% female) were included in the study. Of the 72 patients, the application of PP1M resulted in a significant reduction in the hospitalization times, emergency room visits, and direct medical costs (P < 0.001), while the pharmacy cost and total cost increased by 222.57% (P < 0.001) and 16.35% (P < 0.001), respectively; PP1M accounted for 88.48% of the pharmacy cost. For patients with ≥1 hospitalization during the OAPs phase (n = 25), the number of hospitalizations, hospitalization days and hospitalization expenses decreased by more than 90% (P < 0.001). Total one-year expenses decreased by 37.67% (P < 0.001), and pharmacy expenses increased by 185.21% (P < 0.001). For patients with no hospitalizations during the OAPs phase (n = 47), emergency and outpatient visits decreased by 70% (P < 0.001) and 30.27% (P < 0.05), respectively, while the total cost increased by 117.56% (P < 0.001), and the pharmacy cost increased by 260.15% (P < 0.001) after initiation of PP1M treatment. Conclusion: After the transition to PP1M, the number of hospitalizations and outpatient and emergency department visits reduced, and healthcare resources were conserved. Switching to PP1M may be more economically beneficial for patients with prior hospitalizations while on OAP regimens. The high price of PP1M might be an obstacle to its widespread use.

From fractional quantum anomalous Hall smectics to polar smectic metals: nontrivial interplay between electronic liquid crystal order and topological order in correlated topological flat bands.

Symmetry-breaking orders can not only compete with each other, but also be intertwined, and the intertwined topological and symmetry-breaking orders make the situation more intriguing. This work examines the archetypal correlated flat band model on a checkerboard lattice at fillingν=2/3and we find that the unique interplay between smectic charge order and topological order gives rise to two novel quantum states. As the interaction strength increases, the system first transitions from a Fermi liquid (FL) into FQAH smectic (FQAHS) state, where the topological order coexists cooperatively with smectic charge order with enlarged ground-state degeneracy and interestingly, the Hall conductivity isσxy=ν=2/3, different from the band-folding or doping scenarios. Further increasing the interaction strength, the system undergoes another quantum phase transition and evolves into a polar smectic metal (PSM) state. This emergent PSM is an anisotropic non-Fermi liquid, whose interstripe tunneling is irrelevant while it is metallic inside each stripe. Different from the FQAHS and conventional smectic orders, this PSM spontaneously breaks the two-fold rotational symmetry, resulting in a nonzero electric dipole moment and ferroelectric order. In addition to the exotic ground states, large-scale numerical simulations are also used to study low-energy excitations and thermodynamic characteristics. We find that the onset temperature of the incompressible FQAHS state, which also coincides with the onset of non-polar smectic order, is dictated by the magneto-roton modes. Above this onset temperature, the PSM state exists at an intermediate-temperature regime. Although theT = 0 quantum phase transition between PSM and FQAHS is first order, the thermal FQAHS-PSM transition could be continuous. We expect the features of the exotic states and thermal phase transitions could be accessed in future experiments.

Regulation of Molecular Microheterogeneity in Electrolytes Enables Ampere-Hour-Level Aqueous LiMn2O4||Li4Ti5O12 Pouch Cells.

Aqueous batteries are attractive due to their high safety and fast reaction kinetics, but the narrow electrochemical stability window of H2O limits their applications. It is a big challenge to broaden the electrochemical operation window of aqueous electrolytes while retaining fast reaction kinetics. Here, a new organic aqueous mixture electrolyte of manipulatable (3D) molecular microheterogeneity with H2O-rich and H2O-poor domains is demonstrated. H2O-poor domains molecularly surround the reformed microclusters of H2O molecules through interfacial H-bonds, which thus not only inhibit the long-range transfer of H2O but also allow fast and consecutive Li+ transport. This new design enables low-voltage anodes reversibly cycling with aqueous-based electrolytes and high ionic conductivity of 4.5 mS cm-1. LiMn2O4||Li4Ti5O12 full cells demonstrate excellent cycling stability over 1000 cycles under various C rates and a low temperature of -20 °C. 1 Ah pouch cell delivers a high energy density of 79.3 Wh kg-1 and high Coulombic efficiency of 99.4% at 1 C over 200 cycles. This work provides new insights into the design of electrolytes based on the molecular microheterogeneity for rechargeable batteries.

A real-world, cross-sectional, and longitudinal study on high-risk human papillomavirus genotype distribution in 31,942 women in Dongguan, China.

Background: Persistent human papillomavirus (HPV) infection remains a key risk factor for cervical cancer. HPV-based primary screening is widely recommended in clinical guidelines, and further longitudinal studies are needed to optimize strategies for detecting high-grade cervical lesions compared to cytology. Methods: From November 2015 to December 2023, 31,942 participants were included in the real-world observational study. Among those, 4,219 participants underwent at least two rounds of HPV tests, and 397 completed three rounds of HPV tests. All participants were tested for high-risk types of HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68 (hrHPV) and low-risk types of HPV6/11 genotyping. Some participants also received cytology or colposcopy with pathology. Results: In the cross-sectional cohort, the prevalence of hrHPV and all HPV subtypes was 6.6% (2,108/31,942) and 6.8% (2,177/31,942), respectively. The three top hrHPV genotypes were HPV52 (1.9%), HPV58 (0.9%), and HPV16 (0.9%). Age distributions showed two peaks at 45-49 and 60-65 years. For the primary screening cohort, the hrHPV prevalence rate increased from 4.8% in 2015-2017 to 7.0% in 2020-2020 and finally reached 7.2% in 2023. For the longitudinal cohort study, the hrHPV prevalence rates in the repeated population (3.9, 5.3, and 6.0%) were lower than the primary hrHPV screening rates (6.6%), which indicated that repeated screening might decrease the prevalence rate. Methodologically, the hrHPV (89.5%) and the screening group of 16 subtypes (92.3%) demonstrated superior sensitivity than the cytology group (54.4%). Moreover, the longitudinal study indicated that the persistent hrHPV subgroup had a significantly higher (p = 0.04) incidence of high-grade squamous intraepithelial lesions and more histology progression events (7/17 vs. 0/5) than the reinfection group. Conclusion: The study indicates a rising high-risk HPV prevalence in Dongguan, with repeated screening reducing this trend. The findings support HPV-based primary screening and might guide HPV vaccination and cervical cancer prevention in South China.

A General Approach for the Synthesis of Cyanoisopropyl Bicyclo[1.1.1]pentane (BCP) Motifs by Energy Transfer Process.

Bicyclo[1.1.1]pentane (BCP) heteroaryls make up an important class of BCP derivatives in drug discovery. Herein, we report the visible-light-mediated synthesis of cyanoisopropyl BCP-heteroaryls motifs from N-containing heterocycles, [1.1.1]propellane, and AIBN (2,2'-azobis(isobutyronitrile)) through three-component cascade reaction. Importantly, this protocol is compatible with pyrazinones, quinoxaline-2(1H)-one, azauracils, quinoline derivatives, and imidazo[1,2-b]pyridazine, as well as various phenyl disulfide derivatives; thus, this operationally simple and general methodology could enable rapid library generation of sought-after BCP derivatives for drug development.

Crystal structure of lipase from Pseudomonas aeruginosa reveals an unusual catalytic triad conformation.

The Pseudomonas aeruginosa lipase PaL catalyzes the stereoselective hydrolysis of menthyl propionate to produce L-menthol. The lack of a three-dimensional structure of PaL has so far prevented a detailed understanding of its stereoselective reaction mechanism. Here, the crystal structure of PaL was determined at a resolution of 1.80 Å by single-wavelength anomalous diffraction. In the apo-PaL structure, the catalytic His302 is located in a long loop on the surface that is solvent exposed. His302 is distant from the other two catalytic residues, Asp274 and Ser164. This configuration of catalytic residues is unusual for lipases. Using metadynamics simulations, we observed that the enzyme undergoes a significant conformational change upon ligand binding. We also explored the catalytic and stereoselectivity mechanisms of PaL by all-atom molecular dynamics simulations. These findings could guide the engineering of PaL with an improved diastereoselectivity for L-menthol production.

Ultrahigh Energy Storage Performance of BiFeO3-BaTiO3 Flexible Film Capacitor with High-Temperature Stability via Defect Design.

Nanoengineering polar oxide films have attracted great attention in energy storage due to their high energy density. However, most of them are deposited on thick and rigid substrates, which is not conducive to the integration of capacitors and applications in flexible electronics. Here, an alternative strategy using van der Waals epitaxial oxide dielectrics on ultra-thin flexible mica substrates is developed and increased the disorder within the system through high laser flux. The introduction of defects can efficiently weaken or destroy the long-range ferroelectric ordering, ultimately leading to the emergence of a large numbers of weak-coupling regions. Such polarization configuration ensures fast polarization response and significantly improves energy storage characteristics. A flexible BiFeO3-BaTiO3 (BF-BT) capacitor exhibits a total energy density of 43.5 J cm-3 and an efficiency of 66.7% and maintains good energy storage performance over a wide temperature range (20-200 °C) and under large bending deformation (bending radii ≈ 2 mm). This study provides a feasible approach to improve the energy storage characteristics of dielectric oxide films and paves the way for their practical application in high-energy density capacitors.

Phases of (2+1)D SO(5) Nonlinear Sigma Model with a Topological Term on a Sphere: Multicritical Point and Disorder Phase.

Novel critical phenomena beyond the Landau-Ginzburg-Wilson paradigm have been long sought after. Among many candidate scenarios, the deconfined quantum critical point (DQCP) constitutes the most fascinating one, and its lattice model realization has been debated over the past two decades. Here we apply the spherical Landau level regularization upon the exact (2+1)D SO(5) nonlinear sigma model with a topological term to study the potential DQCP therein. We perform a density matrix renormalization group (DMRG) simulation with SU(2)_{spin}×U(1)_{charge}×U(1)_{angular-momentum} symmetries explicitly implemented. Using crossing point analysis for the critical properties of the DMRG data, accompanied by quantum Monte Carlo simulations, we accurately obtain the comprehensive phase diagram of the model and find various novel quantum phases, including Néel, ferromagnet (FM), valence bond solid (VBS), valley polarized (VP) states and a gapless quantum disordered phase occupying an extended area of the phase diagram. The VBS-disorder and Néel-disorder transitions are continuous with non-Wilson-Fisher exponents. Our results show the VBS and Néel states are separated by either a weakly first-order transition or the disordered region with a multicritical point in between, thus opening up more interesting questions on the two-decade long debate on the nature of the DQCP.

Au nanoparticles decorated ß-Bi2O3 as highly-sensitive SERS substrate for detection of methylene blue and methyl orange.

In this work, Au/Bi2O3 was synthesized by loading Au nanoparticles (NPs) onto ß-Bi2O3 by a simple solution reduction method. ß-Bi2O3 was synthesized by a precipitation-thermal decomposition procedure, which results in significantly improved SERS detection limits down to 10-9 M for methylene blue (MB) and 10-7 M for methyl orange (MO) as probe molecules, comparable to those reported for the best semiconductor SERS substrates. In particular, further deposition of Au NPs (5.20% wt%) onto ß-Bi2O3 results in a two-order-of-magnitude enhancement in detection sensitivity, achieving a detection limit of 10-11 M for MB and 10-9 M for MO. Under ultraviolet/visible irradiation, the Au/Bi2O3 hybrids substrate exhibits superior self-cleaning ability due to its photocatalytic degradation ability which can be applied repeatedly to the detection of pollutants. The advanced composite substrate simultaneously achieved ultra-low mass loading of Au NPs, outstanding detection performance, good reproducibility, high stability and self-cleaning ability. The development strategy of low load noble metal coupled high performance semiconductor ß-Bi2O3 to obtain nano-hybrid materials provides a method to balance SERS sensitivity, cost effectiveness and operational stability, and can be synthesized in large quantities, which is a key step towards commercialization and has good reliability prospects.

Dissecting the shared genetic architecture between anti-Müllerian hormone and age at menopause based on genome-wide association study.

BACKGROUND: While the phenotypic association between anti-Müllerian hormoneand age at menopause has been widely studied, the role of anti-Müllerian hormone in predicting the age at menopause is currently controversial, and the genetic architecture or causal relationships underlying these 2 traits is not well understood. AIM: We aimed to explore the shared genetic architecture between anti-Müllerian hormone and age at menopause, to identify shared pleiotropic loci and genes, and to investigate causal association and potential causal mediators. STUDY DESIGN: Using summary statistics from publicly available genome-wide association studies on anti-Müllerian hormone (N=7049) and age at menopause (N=201,323) in Europeans, we investigated the global genetic architecture between anti-Müllerian hormone and age at menopause through linkage disequilibrium score regression. We employed pleiotropic analysis under composite null hypothesis, Functional Mapping and Annotation of Genetic Associations, multimarker analysis of GenoMic annotation, and colocalization analysis to identify loci and genes with pleiotropic effects. Tissue enrichment analysis based on Genotype-Tissue Expression data was conducted using the Linkage Disequilibrium Score for the specific expression of genes analysis. Functional genes that were shared were additionally identified through summary data-based Mendelian randomization. The relationship between anti-Müllerian hormone and age at menopause was examined through 2-sample Mendelian randomization, and potential mediators were further explored using colocalization and metabolite-mediated analysis. RESULTS: A positive genetic association (correlation coefficient=0.88, P=1.33×10-5) was observed between anti-Müllerian hormone and age at menopause. By using pleiotropic analysis under composite null hypothesis and Functional Mapping and Annotation of Genetic Associations, 42 significant pleiotropic loci were identified that were associated with anti-Müllerian hormone and age at menopause, and 10 of these (rs10734411, rs61913600, rs2277339, rs75770066, rs28416520, rs9796, rs11668344, rs403727, rs6011452, and rs62237617) had colocalized loci. Additionally, 245 significant pleiotropic genes were identified by multimarker analysis of GenoMic annotation. Genetic associations between anti-Müllerian hormone and age at menopause were markedly concentrated in various tissues including whole blood, brain, heart, liver, muscle, pancreas, and kidneys. Further, summary data-based Mendelian randomization analysis revealed 9 genes that may have a causative effect on both anti-Müllerian hormone and age at menopause. A potential causal effect of age at menopause on anti-Müllerian hormone was suggested by 2-sample Mendelian randomization analysis, with very-low-density lipoprotein identified as a potential mediator. CONCLUSION: Our study revealed a shared genetic architecture between anti-Müllerian hormone and age at menopause, providing a basis for experimental investigations and individual therapies to enhance reproductive outcomes. Furthermore, our findings emphasized that relying solely on anti-Müllerian hormone is not sufficient for accurately predicting the age at menopause, and a combination of other factors needs to be considered. Exploring new therapeutics aimed at delaying at the onset of menopause holds promise, particularly when targeting shared genes based on their shared genetic architecture.

Thermodynamic Response and Neutral Excitations in Integer and Fractional Quantum Anomalous Hall States Emerging from Correlated Flat Bands.

Integer and fractional Chern insulators have been extensively explored in correlated flat band models. Recently, the prediction and experimental observation of fractional quantum anomalous Hall (FQAH) states with spontaneous time-reversal symmetry breaking have garnered attention. While the thermodynamics of integer quantum anomalous Hall (IQAH) states have been systematically studied, our theoretical knowledge on thermodynamic properties of FQAH states has been severely limited. Here, we delve into the general thermodynamic response and collective excitations of both IQAH and FQAH states within the paradigmatic flat Chern-band model with remote band considered. Our key findings include (i) in both ν=1 IQAH and ν=1/3 FQAH states, even without spin fluctuations, the charge-neutral collective excitations would lower the onset temperature of these topological states, to a value significantly smaller than the charge gap, due to band mixing and multiparticle scattering; (ii) by employing large-scale thermodynamic simulations in FQAH states in the presence of strong interband mixing between C=±1 bands, we find that the lowest collective excitations manifest as the zero-momentum excitons in the IQAH state, whereas in the FQAH state, they take the form of magnetorotons with finite momentum; (iii) the unique charge oscillations in FQAH states are exhibited with distinct experimental signatures, which we propose to detect in future experiments.

Long non-coding RNA MIAT serves as a biomarker of fragility fracture and promotes fracture healing.

BACKGROUND: Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated. METHODS: 90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis. RESULTS: Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation. CONCLUSIONS: LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p.

2D Janus Polarization Functioned by Mechanical Force.

2D polarization materials have emerged as promising candidates for meeting the demands of device miniaturization, attributed to their unique electronic configurations and transport characteristics. Although the existing inherent and sliding mechanisms are increasingly investigated in recent years, strategies for inducing 2D polarization with innovative mechanisms remain rare. This study introduces a novel 2D Janus state by modulating the puckered structure. Combining scanning probe microscopy, transmission electron microscopy, and density functional theory calculations, this work realizes force-triggered out-of-plane and in-plane dipoles with distorted smaller warping in GeSe. The Janus state is preserved after removing the external mechanical perturbation, which could be switched by modulating the sliding direction. This work offers a versatile method to break the space inversion symmetry in a 2D system to trigger polarization in the atomic scale, which may open an innovative insight into configuring novel 2D polarization materials.

Electrolyte Design Chart Reframed by Intermolecular Interactions for High-Performance Li-Ion Batteries.

Developing advanced electrolytes has been regarded as a pivotal strategy for enhancing the electrochemical performance of batteries; however, the criteria for electrolyte design remain elusive. In this study, we present an electrolyte design chart reframed through intermolecular interactions. By combining systematic nuclear magnetic resonance, Fourier transform infrared measurements, molecular dynamics (MD) simulations, and machine-learning-assisted classifications, we establish semiquantitative correlations between electrolyte components and the electrochemical reversibility of electrolytes. We propose the equivalent increment of Li salt resulting from functional cosolvent and solvent-solvent interactions for effective electrolyte design and prediction. The controllable regulation of the electrolyte design chart by the properties of solvent-solvent interactions presents varying equivalent effects of increasing Li salt concentrations in different electrolyte systems. Based on this mechanism, we demonstrate highly reversible and nonflammable phosphate-based electrolytes for graphite||NCM811 full cells. The proposed electrolyte design chart, semiquantitatively determined by intermolecular interactions, provides the necessary experimental foundation and basis for the future rapid screening and prediction of electrolytes using machine-learning methods.

Spatial evolution of the proton-coupled Mott transition in correlated oxides for neuromorphic computing.

The proton-electron coupling effect induces rich spectrums of electronic states in correlated oxides, opening tempting opportunities for exploring novel devices with multifunctions. Here, via modest Pt-aided hydrogen spillover at room temperature, amounts of protons are introduced into SmNiO3-based devices. In situ structural characterizations together with first-principles calculation reveal that the local Mott transition is reversibly driven by migration and redistribution of the predoped protons. The accompanying giant resistance change results in excellent memristive behaviors under ultralow electric fields. Hierarchical tree-like memory states, an instinct displayed in bio-synapses, are further realized in the devices by spatially varying the proton concentration with electric pulses, showing great promise in artificial neural networks for solving intricate problems. Our research demonstrates the direct and effective control of proton evolution using extremely low electric field, offering an alternative pathway for modifying the functionalities of correlated oxides and constructing low-power consumption intelligent devices and neural network circuits.

Gene signatures of endoplasmic reticulum stress and mitophagy for prognostic risk prediction in lung adenocarcinoma.

Genes associated with endoplasmic reticulum stress (ERS) and mitophagy can be conducive to predicting solid tumour prognosis. The authors aimed to develop a prognosis prediction model for these genes in lung adenocarcinoma (LUAD). Relevant gene expression and clinical information were collected from public databases including Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A total of 265 differentially expressed genes was finally selected (71 up-regulated and 194 downregulated) in the LUAD dataset. Among these, 15 candidate ERS and mitophagy genes (ATG12, CSNK2A1, MAP1LC3A, MAP1LC3B, MFN2, PGAM5, PINK1, RPS27A, SQSTM1, SRC, UBA52, UBB, UBC, ULK1, and VDAC1) might be critical to LUAD based on the expression analysis after crossing with the ERS and mitochondrial autophagy genes. The prediction model demonstrated the ability to effectively predict the 5-, 3-, and 1-year prognoses of LUAD patients in both GEO and TCGA databases. Moreover, high VDAC1 expression was associated with poor overall survival in LUAD (p < 0.001), suggesting it might be a critical gene for LUAD prognosis prediction. Overall, the prognosis model based on ERS and mitophagy genes in LUAD can be useful for evaluating the prognosis of patients with LUAD, and VDAC1 may serve as a promising biomarker for LUAD prognosis.

Genomic landscape and tumor mutational features of resected preinvasive to invasive lung adenocarcinoma.

Introduction: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are considered pre-invasive forms of lung adenocarcinoma (LUAD) with a 5-year recurrence-free survival of 100%. We investigated genomic profiles in early tumorigenesis and distinguished mutational features of preinvasive to invasive adenocarcinoma (IAC) for early diagnosis. Methods: Molecular information was obtained from a 689-gene panel in the 90 early-stage LUAD Chinese patients using next-generation sequencing. Gene signatures were identified between pathology subtypes, including AIS/MIA (n=31) and IAC (n=59) in this cohort. Mutational and clinicopathological information was also obtained from the Cancer Genome Atlas (TCGA) as a comparison cohort. Results: A higher mutation frequency of TP53, RBM10, MUC1, CSMD, MED1, LRP1B, GLI1, MAP3K, and RYR2 was observed in the IAC than in the AIS/MIA group. The AIS/MIA group showed higher mutation frequencies of ERBB2, BRAF, GRIN2A, and RB1. Comparable mutation rates for mutually exclusive genes (EGFR and KRAS) across cohorts highlight the critical transition to invasive LUAD. Compared with the TCGA cohort, EGFR, KRAS, TP53, and RBM10 were frequently mutated in both cohorts. Despite limited gene mutation overlap between cohorts, we observed variant mutation types in invasive LUAD. Additionally, the tumor mutation burden (TMB) values were significantly lower in the AIS/MIA group than in the IAC group in both the Chinese cohort (P=0.0053) and TCGA cohort (P<0.01). Conclusion: These findings highlight the importance of distinguishing preinvasive from invasive LUAD in the early stages of LUAD and both pathology and molecular features in clinical practice, revealing genomic tumor heterogeneity and population differences.

X chromosome rearrangement associated with premature ovarian insufficiency as diagnosed by molecular cytogenetic methods: a case report and review of the literature.

BACKGROUND: Premature ovarian insufficiency (POI) is a clinical condition characterized by ovarian dysfunction in women under 40. The etiology of most POI cases remains unidentified and is believed to be multifactorial, including factors such as autoimmunity, metabolism, infection, and genetics. POI exhibits significant genetic heterogeneity, and it can result from chromosomal abnormalities and monogenic defects. CASE PRESENTATION: The study participant, a 33-year-old woman, presented with a history of irregular menstruation that commenced two years ago, progressing to prolonged menstrual episodes and eventual cessation. The participant exhibits a rearrangement of the X chromosome, characterized by heterozygosity duplication on the long arm and heterozygosity deletion on the short arm by whole exome sequencing(WES) combined with cell chromosome detection. CONCLUSIONS: This study expands the spectrum of mutations associated with POI resulting from X chromosomal abnormalities. WES-Copy number variation analysis, in conjunction with chromosome karyotype analysis and other detection techniques, can provide a more comprehensive understanding of the genetic landscape underlying complex single or multi-system diseases.