Evolution of a Eukaryotic Transcription Factor's co-TF Dependence Involves Multiple Intrinsically Disordered Regions Affecting Activation and Autoinhibition.

Combinatorial control by multiple transcription factors (TFs) is a hallmark of eukaryotic gene regulation. Despite its prevalence and crucial roles in enhancing specificity and integrating information, the mechanisms behind why eukaryotic TFs depend on one another, and whether such interdependence evolves, are not well understood. We exploit natural variation in co-TF dependence in the yeast phosphate starvation (PHO) response to address this question. In the model yeast Saccharomyces cerevisiae, the main TF, Pho4, relies on the co-TF Pho2 to regulate ~28 genes. In a related yeast pathogen, Candida glabrata, its Pho4 exhibits significantly reduced Pho2 dependence and has an expanded target set of ~70 genes. Biochemical analyses showed C. glabrata Pho4 (CgPho4) binds to the same consensus motif with 3-4-fold higher affinity than ScPho4 does. A machine-learning-based prediction and yeast one-hybrid assay identified two Intrinsically Disordered Regions (IDRs) in CgPho4 that boost the activity of the main activation domain but showed little to no activity on their own. We also found evidence for autoinhibition behind the co-TF dependence in ScPho4. An IDR in ScPho4 next to its DNA binding domain was found to act as a double-edged sword: it both allows for enhanced activity with Pho2, and inhibits Pho4's activity without Pho2. This study provides a detailed molecular picture of how co-TF dependence is mediated and how its evolution, mainly driven by IDR divergence, can lead to significant rewiring of the regulatory network.

Expression Changes of miRNAs in Humans and Animal Models of Amyotrophic Lateral Sclerosis and Their Potential Application for Clinical Diagnosis.

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease. Current detection methods can only confirm the diagnosis at the onset of the disease, missing the critical window for early treatment. Recent studies using animal models have found that detecting changes in miRNA sites can predict the onset and severity of the disease in its early stages, facilitating early diagnosis and treatment. miRNAs show expression changes in motor neurons that connect the brain, spinal cord, and brain stem, as well as in the skeletal muscle in mouse models of ALS. Clinically, expression changes in some miRNAs in patients align with those in mouse models, such as the upregulation of miR-29b in the brain and the upregulation of miR-206 in the skeletal muscle. This study provides an overview of some miRNA study findings in humans as well as in animal models, including SOD1, FUS, TDP-43, and C9orf72 transgenic mice and wobbler mice, highlighting the potential of miRNAs as diagnostic markers for ALS. miR-21 and miR-206 are aberrantly expressed in both mouse model and patient samples, positioning them as key potential diagnostic markers in ALS. Additionally, miR-29a, miR-29b, miR-181a, and miR-142-3p have shown aberrant expression in both types of samples and show promise as clinical targets for ALS. Finally, miR-1197 and miR-486b-5p have been recently identified as aberrantly expressed miRNAs in mouse models for ALS, although further studies are needed to determine their viability as diagnostic targets.

Liver X receptor α contribution to neuroinflammation and glial cells activation induced by MPTP: Implications for Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder whose etiology remains unknown. The immune system has been implicated in hallmarks of PD including aggregation of α-synuclein and death of dopaminergic neurons in the substantia nigra. As a core regulator of immune response and inflammation, liver X receptors (LXRs) have been shown to have protective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. With two isoforms of LXRs (LXRα and LXRß) expressed in the brain, their roles and distributions in this tissue remain largely unexplored. Here, we used MPTP to mimic symptoms and biomedical changes seen in PD in LXRα-/- and wild-type mice to investigate the role of LXRα in the etiology and progression of PD. We found that MPTP is unable to induce motor deficits, anxiety-like behavior in LXRα-/- mice, which has been seen in WT mice. Gene ontology analysis of RNA sequencing revealed that knockout of LXRα led to enrichment of the process, including immune response and inflammation in the midbrain. In addition, MPTP did not lead to dopaminergic neuron death in the striatum and substantia nigra in LXRα-/- mice, the basal GFAP protein level, and pro-inflammatory cytokines were elevated in LXRα-/- mice. Lastly, the microglia activation and astrogliosis caused by MPTP intoxication we found in WT mice were abolished in LXRα-/- mice. To sum up, we conclude that LXRα is a critical regulator in MPTP intoxication and may play a unique role in astrogliosis seen in the neuroinflammation of PD.

The Impact of Intraocular Pressure Changes on Corneal Biomechanics in Primary Open-angle Glaucoma.

PURPOSE: To investigate the relationship between intraocular pressure (IOP) changes and corneal biomechanical properties, determine the quantitative relationship between IOP changes and corneal biomechanical properties in patients with glaucoma and observe the differences among different types of glaucoma when the effects of high-level IOP were excluded. DESIGN: Prospective clinical cohort study. METHODS: Setting: Institutional. PATIENTS: Treatment-naive patients with primary open-angle glaucoma or ocular hypertension (OHT) were included. OBSERVATION PROCEDURES: IOP was measured using a Goldmann applanation tonometer. Corneal biomechanics were evaluated using a corneal indentation device and corneal visualization Scheimpflug technology. Medication therapy was used for IOP reduction. Repeated measurements were taken at the baseline visit and each week thereafter within a month. Paired t tests were used to compare IOP and corneal biomechanical metrics before and after IOP-lowering therapy. One-way analysis of variance was employed to investigate potential differences across groups, with a Bonferroni post hoc correction administered for multiple intergroup comparisons. MAIN OUTCOME MEASURES: Corneal biomechanical parameters following IOP changes. RESULTS: Eighty-one participants (mean age, 41.63 ± 17.33 years) were included in this study. The cohort comprised 20 patients with normal-tension glaucoma (NTG), 47 with high-tension glaucoma (HTG), and 14 with OHT. The baseline corneal stiffness (88.58 ± 18.30 N/m) and corneal modulus (0.71 ± 0.16 MPa) were greater than the post-IOP reduction values (67.15 ± 9.24 N/m and 0.54 ± 0.08 MPa, respectively; P < .001). The relationships between changes in IOP and changes in corneal biomechanical parameters were Δ corneal stiffness = 2.06*ΔIOP+6.47 (P < .001) and Δ corneal modulus = 0.017*ΔIOP+0.051 (P < .001). After IOP reduction, the mean corneal stiffness at the 4th week in the NTG group was significantly lower (60.97 ± 6.36 N/m) than that in the HTG (67.25 ± 9.01 N/m) and OHT (75.62 ± 6.52 N/m, P < .001) groups. Additionally, the stiffness of HTG patients was lower than that of OHT patients (P = .003). CONCLUSIONS: Changes in IOP have an impact on corneal biomechanical parameters. Decreases in corneal stiffness and modulus were observed after IOP reduction. When the effect of high-level IOP was excluded, corneal biomechanics varied according to the type of glaucoma. The HTG corneas were softer than the OHT corneas, and the NTG corneas were even softer.

Lower incisor position in skeletal Class III malocclusion patients: a comparative study of orthodontic camouflage and orthognathic surgery.

OBJECTIVES: To determine the difference between orthodontic camouflage and orthodontic-orthognathic surgery using the traditional cephalometric measurement IMPA and the newly proposed IA/PAMD, the angle between the long axis of the lower incisor (IA) and the principal axis of the mandibular alveolus (PAMD). MATERIALS AND METHODS: This study included 40 cases each in the orthodontic camouflage group (OG) and orthodontic-orthognathic surgery group (SG). The differences between the IMPA and IA/PAMD before and after treatment were compared between the two groups. T0 lateral cephalometric images of the 10 cases with the highest and lowest increase in the IA/PAMD were analyzed to identify characteristics associated with a higher risk of overdecompensation of the lower incisors during presurgical orthodontic treatment. RESULTS: Both the OG and SG showed a significant improvement in hard- and soft-tissue measurements. However, in the OG, there was significant lingual inclination of the lower incisor but only a small change in the IA/PAMD. In the surgical group, the IMPA was close to 90° after treatment, but the IA/PAMD significantly increased. CONCLUSIONS: In orthodontic camouflage, the lower anterior teeth were significantly moved lingually with a better root-bone relationship. However, this relationship deteriorated in some surgical patients. Therefore, it is important to conduct cephalometric or cone-beam computed tomography examinations during preoperative orthodontics to identify and prevent possible periodontal risks.

Responsiveness to Selective Laser Trabeculoplasty in Open-Angle Glaucoma and Ocular Hypertension.

Importance: Selective laser trabeculoplasty (SLT) is becoming the recommended first choice in the treatment of open-angle glaucoma (OAG). However, whether repeat SLT can be recommended regardless of initial response remains controversial. Objective: To assess the potential of OAG and ocular hypertension (OHT) undergoing repeat laser to respond favorably to SLT, termed responsiveness to SLT. Design, Setting, and Participants: This post hoc analysis of the Laser in Glaucoma and Ocular Hypertension Trial in China (LiGHT China) was conducted from March 2015 to April 2023 in Zhongshan Ophthalmic Center. Of 1376 newly diagnosed OAG and OHT eyes of 771 adults in the original trial, 180 eyes of 105 participants were included in the present study, which underwent initial and repeat SLT as primary treatments. Exposures: Standard SLT was the primary treatment. Repeat SLT was the first choice of treatment escalation regardless of initial response. IOP reduction after SLT and the duration of effect were analyzed. The maximum reduction in IOP within 2 years after initial SLT and repeat SLT was used to identify potential nonresponsiveness. Main Outcomes and Measures: IOP reduction 2 months after SLT. Results: A total of 180 eyes from 105 Chinese participants (mean [SD] age, 45.6 [14.5] years; 58 [55.2%] male and 47 [44.8%] female) underwent repeat SLT. Initial SLT and repeat SLT were both associated with a reduction in IOP (mean, 4.5 mm Hg; 95% CI, 3.9 to 5.1; P < .001 and mean, 3.3 mm Hg; 95% CI, 2.7 to 3.8; P < .001, respectively). The mean (SD) IOP after repeat SLT was 15.8 (3.4) mm Hg, similar to 16.0 (4.0) mm Hg after initial SLT (difference, -0.4mm Hg; 95% CI, -1.0 to 0.3; P = .24). Duration of effect after repeat SLT was longer than after initial SLT (1043 days vs 419 days; hazard ratio, 0.38; 95% CI, 0.29 to 0.50; P < .001). IOP reduction after initial SLT was uncorrelated with that after repeat SLT, and 153 eyes (85.0%) responded favorably to SLT at least once. A subset of 27 eyes (15.0%) was identified as potentially nonresponsive and found distinctive with older age (mean [SD], 54.1 [12.5] years vs 44.2 [14.2] years; difference, 10.5 years; 95% CI, 2.9 to 18.1; P = .009), higher proportion of female participants (difference, 27.5%; 95% CI, 3.6 to 51.5; P = .03), and lower baseline IOP (difference, -3.2 mm Hg; 95% CI, -5.2 to -1.3; P = .001). Conclusions and Relevance: These post hoc analyses showed that most cases of OAG and OHT were highly responsive to SLT and support the consideration of repeat SLT regardless of initial response, while individuals who are nonresponsive to this treatment may have specific features.

Harnessing Large Language Models for Structured Reporting in Breast Ultrasound: A Comparative Study of Open AI (GPT-4.0) and Microsoft Bing (GPT-4).

OBJECTIVES: To assess the capabilities of large language models (LLMs), including Open AI (GPT-4.0) and Microsoft Bing (GPT-4), in generating structured reports, the Breast Imaging Reporting and Data System (BI-RADS) categories, and management recommendations from free-text breast ultrasound reports. MATERIALS AND METHODS: In this retrospective study, 100 free-text breast ultrasound reports from patients who underwent surgery between January and May 2023 were gathered. The capabilities of Open AI (GPT-4.0) and Microsoft Bing (GPT-4) to convert these unstructured reports into structured ultrasound reports were studied. The quality of structured reports, BI-RADS categories, and management recommendations generated by GPT-4.0 and Bing were evaluated by senior radiologists based on the guidelines. RESULTS: Open AI (GPT-4.0) was better than Microsoft Bing (GPT-4) in terms of performance in generating structured reports (88% vs. 55%; p < 0.001), giving correct BI-RADS categories (54% vs. 47%; p = 0.013) and providing reasonable management recommendations (81% vs. 63%; p < 0.001). As the ability to predict benign and malignant characteristics, GPT-4.0 performed significantly better than Bing (AUC, 0.9317 vs. 0.8177; p < 0.001), while both performed significantly inferior to senior radiologists (AUC, 0.9763; both p < 0.001). CONCLUSION: This study highlights the potential of LLMs, specifically Open AI (GPT-4.0), in converting unstructured breast ultrasound reports into structured ones, offering accurate diagnoses and providing reasonable recommendations.

Variations in the alveolar bone morphology in maxillary molar area: a retrospective CBCT study.

BACKGROUND: This study quantitatively analyzed the anatomic structure of the alveolar bone in the maxillary molar region at three potential locations for Temporary Anchorage Device (TAD) placement. Additionally, the study compared the variability in this region across different age groups, sagittal skeletal patterns, vertical facial types, and sexes. METHODS: In this retrospective cone-beam computed tomography study, the buccal alveolar bone was analyzed in the posterior molar area of 200 patients, the measurement items include buccal alveolar bone height, alveolar bone thickness, interradicular distance, and maxillary retromolar space. RESULTS: Buccal alveolar height was greatest in the U56 region. The interradicular space was largest in the U56 region and increased from the alveolar crest to the sinus floor. Buccal alveolar bone thickness was highest in the U67 region and generally increased from the alveolar crest to the sinus floor. The maxillary retromolar space gradually increased from the alveolar crest to the root apex. CONCLUSIONS: TADs are safest when placed in the buccal area between the maxillary second premolar and the first molar, particularly at the 9 mm plane. The U67 region is the optimal safe zone for TAD placement for maxillary dentition distalization. TADs placement in adolescents can be challenging. Maxillary third molar extraction can be considered for maxillary dentition distalization.

Breaking the in-coupling efficiency limit in waveguide-based AR displays with polarization volume gratings.

Augmented reality (AR) displays, heralded as the next-generation platform for spatial computing, metaverse, and digital twins, empower users to perceive digital images overlaid with real-world environment, fostering a deeper level of human-digital interactions. With the rapid evolution of couplers, waveguide-based AR displays have streamlined the entire system, boasting a slim form factor and high optical performance. However, challenges persist in the waveguide combiner, including low optical efficiency and poor image uniformity, significantly hindering the long-term usage and user experience. In this paper, we first analyze the root causes of the low optical efficiency and poor uniformity in waveguide-based AR displays. We then discover and elucidate an anomalous polarization conversion phenomenon inherent to polarization volume gratings (PVGs) when the incident light direction does not satisfy the Bragg condition. This new property is effectively leveraged to circumvent the tradeoff between in-coupling efficiency and eyebox uniformity. Through feasibility demonstration experiments, we measure the light leakage in multiple PVGs with varying thicknesses using a laser source and a liquid-crystal-on-silicon light engine. The experiment corroborates the polarization conversion phenomenon, and the results align with simulation well. To explore the potential of such a polarization conversion phenomenon further, we design and simulate a waveguide display with a 50° field of view. Through achieving first-order polarization conversion in a PVG, the in-coupling efficiency and uniformity are improved by 2 times and 2.3 times, respectively, compared to conventional couplers. This groundbreaking discovery holds immense potential for revolutionizing next-generation waveguide-based AR displays, promising a higher efficiency and superior image uniformity.

Evidence for Regulation of Cordycepin Biosynthesis by Transcription Factors Krüppel-Like Factor 4 and Retinoid X Receptor Alpha in Caterpillar Medicinal Mushroom Cordyceps militaris (Ascomycetes).

Cordyceps militaris, Chinese traditional medicinal fungus, has many bioactive properties. Cordycepin (3'-deoxyadenosine) is a major bioactive component of C. militaris. Various methods can significantly elevate cordycepin production, which suggests a diverse set of metabolic regulatory mechanisms. Thus, we aimed to identify transcription factors that regulate cordycepin biosynthesis pathways. Transcriptome analysis of wild-type C. militaris, C. militaris GYS60, a cordycepin high-producing strain, and C. militaris GYS80, a low-producing strain, were used to measure expression and function of genes related to cordycepin biosynthesis. The transcriptome expression data were confirmed by quantitative real-time polymerase chain reaction. We identified 155 relevant transcription factors in 19 families that included Fork head/winged helix factors, other C4 zinc finger-type factors, C2H2 zinc finger factors, tryptophan cluster factors, nuclear receptors with C4 zinc fingers, homeodomain factors, and Rel homology region factors. Energy generation and amino acid conversion pathways were activated in GYS60 so that abundance of cordycepin precursors was increased. Genes and transcription factors for rate-limiting enzymes in these pathways were identified. Overexpression of two key transcription factors, Kruppel-like factor 4 (Klf4) and Retinoid X receptor alpha (Rxra), promoted high cordycepin production in GYS60. In GYS60, Klf4 and Rxra were responsible for upregulation of genes in cordycepin biosynthesis, namely an oxidoreductase, 3',5'-cyclic AMP phosphodiesterase, a transferase, and adenylate cyclase. Upregulation of these genes increased 3'-AMP content, thereby elevating cordycepin synthesis.

DNA sequence and chromatin differentiate sequence-specific transcription factor binding in the human malaria parasite Plasmodium falciparum.

Development of the malaria parasite, Plasmodium falciparum, is regulated by a limited number of sequence-specific transcription factors (TFs). However, the mechanisms by which these TFs recognize genome-wide binding sites is largely unknown. To address TF specificity, we investigated the binding of two TF subsets that either bind CACACA or GTGCAC DNA sequence motifs and further characterized two additional ApiAP2 TFs, PfAP2-G and PfAP2-EXP, which bind unique DNA motifs (GTAC and TGCATGCA). We also interrogated the impact of DNA sequence and chromatin context on P. falciparum TF binding by integrating high-throughput in vitro and in vivo binding assays, DNA shape predictions, epigenetic post-translational modifications, and chromatin accessibility. We found that DNA sequence context minimally impacts binding site selection for paralogous CACACA-binding TFs, while chromatin accessibility, epigenetic patterns, co-factor recruitment, and dimerization correlate with differential binding. In contrast, GTGCAC-binding TFs prefer different DNA sequence context in addition to chromatin dynamics. Finally, we determined that TFs that preferentially bind divergent DNA motifs may bind overlapping genomic regions due to low-affinity binding to other sequence motifs. Our results demonstrate that TF binding site selection relies on a combination of DNA sequence and chromatin features, thereby contributing to the complexity of P. falciparum gene regulatory mechanisms.

Advancing mRNA Therapeutics: The Role and Future of Nanoparticle Delivery Systems.

The coronavirus (COVID-19) pandemic has underscored the critical role of mRNA-based vaccines as powerful, adaptable, readily manufacturable, and safe methodologies for prophylaxis. mRNA-based treatments are emerging as a hopeful avenue for a plethora of conditions, encompassing infectious diseases, cancer, autoimmune diseases, genetic diseases, and rare disorders. Nonetheless, the in vivo delivery of mRNA faces challenges due to its instability, suboptimal delivery, and potential for triggering undesired immune reactions. In this context, the development of effective drug delivery systems, particularly nanoparticles (NPs), is paramount. Tailored with biophysical and chemical properties and susceptible to surface customization, these NPs have demonstrated enhanced mRNA delivery in vivo and led to the approval of several NPs-based formulations for clinical use. Despite these advancements, the necessity for developing a refined, targeted NP delivery system remains imperative. This review comprehensively surveys the biological, translational, and clinical progress in NPs-mediated mRNA therapeutics for both the prevention and treatment of diverse diseases. By addressing critical factors for enhancing existing methodologies, it aims to inform the future development of precise and efficacious mRNA-based therapeutic interventions.

High-fat-diet-induced obesity promotes simultaneous progression of lung cancer and atherosclerosis in apolipoprotein E-knockout mice.

Background: Clinical studies have shown that atherosclerotic cardiovascular disease and cancer often co-exist in the same individual. The present study aimed to investigate the role of high-fat-diet (HFD)-induced obesity in the coexistence of the two diseases and the underlying mechanism in apolipoprotein E-knockout (ApoE-/-) mice. Methods: Male ApoE-/- mice were fed with a HFD or a normal diet (ND) for 15 weeks. On the first day of Week 13, the mice were inoculated subcutaneously in the right axilla with Lewis lung cancer cells. At Weeks 12 and 15, serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and vascular endothelial growth factor levels were measured by enzyme-linked immunosorbent assay, and blood monocytes and macrophages were measured by fluorescence-activated cell sorting. At Week 15, the volume and weight of the local subcutaneous lung cancer and metastatic lung cancer and the amount of aortic atherosclerosis were measured. Results: At Week 15, compared with mice in the ND group, those in the HFD group had a larger volume of local subcutaneous cancer (p = 0.0004), heavier tumors (p = 0.0235), more metastatic cancer in the lungs (p < 0.0001), a larger area of lung involved in metastatic cancer (p = 0.0031), and larger areas of atherosclerosis in the aorta (p < 0.0001). At Week 12, serum LOX-1, serum vascular endothelial growth factor, and proportions of blood monocytes and macrophages were significantly higher in the HFD group than those in the ND group (p = 0.0002, p = 0.0029, p = 0.0480, and p = 0.0106, respectively); this trend persisted until Week 15 (p = 0.0014, p = 0.0012, p = 0.0001, and p = 0.0204). Conclusions: In this study, HFD-induced obesity could simultaneously promote progression of lung cancer and atherosclerosis in the same mouse. HFD-induced upregulation of LOX-1 may play an important role in the simultaneous progression of these two conditions via the inflammatory response and VEGF.

The non-covalent and covalent interactions of whey proteins and saccharides: influencing factor and utilization in food.

During the application of Whey proteins (WPs), they often have complex interactions with saccharides (Ss), another important biopolymer in food substrate. The texture and sensory qualities of foods containing WPs and Ss are largely influenced by the interactions of WPs-Ss. Moreover, the combination of WPs and Ss is possible to produce many excellent functional properties including emulsifying properties and thermal stability. However, the interactions between WPs-Ss are complex and susceptible to some processing conditions. In addition, with different interaction ways, they can be applied in different fields. Therefore, the non-covalent interaction mechanisms between WPs-Ss are firstly summarized in detail, including electrostatic interaction, hydrogen bond, hydrophobic interaction, van der Waals force. Furthermore, the existence modes of WPs-Ss are introduced, including complex coacervates, soluble complexes, segregation, and co-solubility. The covalent interactions of WPs-Ss in food applications are often formed by Maillard reaction (dry or wet heat reaction) and occasionally through enzyme induction. Then, two common influencing factors, pH and temperature, on non-covalent/covalent bonds are introduced. Finally, the applications of WPs-Ss complexes and conjugations in improving WP stability, delivery system, and emulsification are described. This review can improve our understanding of the interactions between WPs-Ss and further promote their wider application.

An Ultra-Wideband Frequency Selective Rasorber with Low Infrared Emissivity.

The paper proposes an ultra-wideband frequency selective rasorber (FSR) with low infrared emissivity for the composite detection threat of both radars and infrared sensors. Firstly, the equivalent circuit (EC) method based on transmission line (TL) theory is utilized to analyze the absorption/transmission conditions. Then, based on the analysis above, sinusoidal microstrip lines with non-frequency-varying characteristics are adopted in the design, which significantly enhances the transmission bandwidth of FSR. The FSR demonstrates an absorption band ranging from 2.65 GHz to 8.80 GHz and a transmission band ranging from 9.15 GHz to 17.71 GHz. Furthermore, an infrared shielding layer (IRSL) exhibiting low emissivity in the infrared band and high transmittance in the microwave band is applied to the FSR. The simulation and experiment results verify that the IRSL-FSR demonstrates an ultra-wide transmission band ranging from 9.16 GHz to 17.94 GHz and an ultra-wide absorption band ranging from 2.66 GHz to 8.01 GHz. Additionally, it exhibits a low emissivity value (0.23) in 8-14 µm, providing a viable solution to the formidable challenge of radar-infrared bistealth for satellites and other communication-enabled flying platforms.

Age-related alveolar bone maladaptation in adult orthodontics: finding new ways out.

Compared with teenage patients, adult patients generally show a slower rate of tooth movement and more pronounced alveolar bone loss during orthodontic treatment, indicating the maladaptation of alveolar bone homeostasis under orthodontic force. However, this phenomenon is not well-elucidated to date, leading to increased treatment difficulties and unsatisfactory treatment outcomes in adult orthodontics. Aiming to provide a comprehensive knowledge and further inspire insightful understanding towards this issue, this review summarizes the current evidence and underlying mechanisms. The age-related abatements in mechanosensing and mechanotransduction in adult cells and periodontal tissue may contribute to retarded and unbalanced bone metabolism, thus hindering alveolar bone reconstruction during orthodontic treatment. To this end, periodontal surgery, physical and chemical cues are being developed to reactivate or rejuvenate the aging periodontium and restore the dynamic equilibrium of orthodontic-mediated alveolar bone metabolism. We anticipate that this review will present a general overview of the role that aging plays in orthodontic alveolar bone metabolism and shed new light on the prospective ways out of the impasse.

[The expression and prognosis prediction of CFL-1 in head and neck squamous cell carcinoma].

PURPOSE: The purpose of this study was to explore the expression, prognostic value and immune correlation of Cofilin 1 protein(CFL-1) in head and neck squamous cell carcinoma(HNSCC). METHODS: The expression and prognostic value of CFL-1 in head and neck squamous cell carcinoma(HNSCC) was explored in the cancer genome map database (TCGA) and gene expression total databases (GEO), and the potential immune pathway of CFL-1 in HNSCC was revealed by GESA and cibersoft analysis. The data were statistically analyzed using SPSS 26.0 software package. RESULTS: CFL-1 was significantly up-regulated in HNSCC tissue. The expression level of CFL-1 was significantly correlated with the overall survival status of HNSCC. High expression of CFL-1 was significantly associated with a lower overall survival rate. In addition, multivariate Cox survival analysis showed that CFL-1 expression was independent predictors of poor prognosis of HNSCC. GESA and cibersoft analysis showed that the imbalance of CFL-1 expression affected multiple signal pathways and infiltration of immune cells. CONCLUSIONS: CFL-1 is highly expressed in HNSCC and is significantly associated with poor prognosis of NHSCC. It is a potential prognostic marker of HNSCC.

Loss-Assisted Anomalous Hong-Ou-Mandel Interference Based on Nonunitary Multilayer Graphene.

Hong-Ou-Mandel interference is an intrinsic quantum phenomenon that goes beyond the possibilities of classical physics, and enables numerous applications in quantum information science. While the photon-photon interaction is fundamentally limited to the bosonic nature of photons and the restricted phase responses from commonly used unitary optical elements, we present that a nonunitary material provides an alternative degree of freedom to control the two-photon quantum interference, even revealing anomalous quantum interference paths that do not exist in a unitary configuration. An elaborate lossy multilayer graphene that can work as a nonunitary beam splitter is used to explore its tunability over the effective photon-photon interaction in spatial modes, and to verify the particle exchange statistics by its experimental implementation in quantum state filter. This scheme is further extended to observe four-dimensional quantum interference patterns on the lossless and lossy beam splitters, and thus show its applicability even in higher-dimensional Hilbert space.

Formation of a planar biomimetic membrane with a novel zwitterionic polymer for nanopore sequencing.

Biological membranes containing transmembrane channels play a crucial role in numerous cellular processes, and mimicking of cell membranes has garnered significant interest in various biomedical applications, particularly nanopore sequencing technology, where remarkable progress has been made with nanopore membranes. Considering the fragility of biomimetic membranes formed by artificial lipids and the limited mimicry of those formed by common block copolymers, this study developed a novel amphiphilic polymer by covalently linking hydrophilic heads of phospholipids to the ends of hydrophobic poly(dimethyl siloxane) (PDMS) chains. The absence of hydrophilic blocks allowed for good control over the polydispersity of this polymer within a narrow range. The high flexibility of PDMS chains, combined with relatively uniform molecular weights, would confer enhanced stability and robustness to polymeric membranes. Dynamic light scattering measurements and microdroplet formation tests demonstrated good amphipathic properties of these novel polymers when maintaining an appropriate hydrophilic-hydrophobic ratio. Moreover, the high similarity between the hydrophilic heads and natural phospholipids makes this polymer more compatible with biomolecules. A successful protein insertion experiment confirmed both the stability of this polymeric membrane and its compatibility with membrane proteins. As a result, this novel amphiphilic polymer exhibits great potential for biomembrane mimicking and paves a new path for material design in biomedical applications.

Simulation of gradient period polarization volume gratings for augmented reality displays.

Augmented reality (AR) displays are gaining attention as next-generation intelligent display technologies. Diffractive waveguide technologies are progressively becoming the AR display industry's preferred option. Gradient period polarization volume holographic gratings (PVGs), which are considered to have the potential to expand the field of view (FOV) of waveguide display systems due to their wide bandwidth diffraction characteristics, have been proposed as coupling elements for diffraction waveguide systems in recent years. Here, what we believe to be a novel modeling method for gradient period PVGs is proposed by incorporating grating stacking and scattering analysis utilizing rigorous coupled-wave analysis (RCWA) theory. The diffraction efficiency and polarization response were extensively explored using this simulation model. In addition, a dual-layer full-color diffractive waveguide imaging simulation using proposed gradient period PVGs is accomplished in Zemax software using a self-compiled dynamic link library (DLL), achieving a 53° diagonal FOV at a 16:9 aspect ratio. This work furthers the development of PVGs by providing unique ideas for the field of view design of AR display.