Microbiological and functional traits of peri-implant mucositis and correlation with disease severity.

Osseointegrated dental implants replace missing teeth and create an artificial surface for biofilms of complex microbial communities to grow. These biofilms on implants and dental surfaces can trigger infection and inflammation in the surrounding tissue. This study investigated the microbial characteristics of peri-implant mucositis (PM) and explored the correlation between microbial ecological imbalance, community function, and disease severity by comparing the submucosal microflora from PM with those of healthy inter-subject implants and intra-subject gingivitis (G) within a group of 32 individuals. We analyzed submucosal plaques from PM, healthy implant (HI), and G sites using metagenome shotgun sequencing. The bacterial diversity of HIs was higher than that of PM, according to the Simpson index. Beta diversity revealed differences in taxonomic and functional compositions across the groups. Linear discriminant analysis of the effect size identified 15 genera and 37 species as biomarkers that distinguished PM from HIs. Pathways involving cell motility and protein processing in the endoplasmic reticulum were upregulated in PM, while pathways related to the metabolism of cofactors and vitamins were downregulated. Microbial dysbiosis correlated positively with the severity of clinical inflammation measured by the sulcus bleeding index (SBI) in PM. Prevotella and protein processing in the endoplasmic reticulum also correlated positively with the SBI. Our study revealed PM's microbiological and functional traits and suggested the importance of certain functions in disease severity.IMPORTANCEPeri-implant mucositis is an early stage in the progression of peri-implantitis. The high prevalence of it has been a threat to the widespread use of implant prosthodontics. The link between the submucosal microbiome and peri-implant mucositis was demonstrated previously. Nevertheless, the taxonomic and functional composition of the peri-implant mucositis microbiome remains controversial. In this study, we comprehensively characterize the microbial signature of peri-implant mucositis and for the first time, we investigate the correlations between microbial dysbiosis, functional potential, and disease severity. With the help of metagenomic sequencing, we find the positive correlations between microbial dysbiosis, genus Prevotella, pathway of protein processing in the endoplasmic reticulum, and more severe mucosal bleeding in the peri-implant mucositis. Our studies offer insight into the pathogenesis of peri-implant mucositis by providing information on the relationships between community function and disease severity.

Primary cervical malignant melanoma that was successfully treated with pembrolizumab: a case report and literature review.

Primary malignant melanoma (MM) arising from the cervix is an exceedingly rare occurrence, and patients diagnosed with this condition often face a dismal clinical prognosis. Here, we present a case study of a postmenopausal woman presenting with vaginal bleeding and a conspicuous 5-centimeter black mass on the cervix. Based on the staging criteria established by the International Federation of Gynecology and Obstetrics, she was diagnosed with stage IIB primary cervical MM. The patient underwent neoadjuvant therapy prior to a radical hysterectomy and a bilateral salpingo-oophorectomy. Subsequently, she completed 18 cycles of pembrolizumab therapy, achieving clinical complete remission. Notably, at the 31-month follow-up, there were no signs of recurrence. This successful treatment outcome serves as a valuable clinical reference for the management of primary cervical MM.

SYT4 binds to SNAP25 to facilitate exosomal secretion and prostate cancer enzalutamide resistance.

Prostate carcinoma represents a predominant malignancy affecting the male population, with androgen deprivation therapy (ADT) serving as a critical therapeutic modality for advanced disease states, but it often leads to the development of resistance. Enzalutamide (Enz), a second-generation antiandrogen drug, initially offers substantial therapeutic benefit, but its efficacy wanes as drug resistance ensues. In this study, we found that synaptotagmin 4 (SYT4) is an upregulated gene in enzalutamide-resistant (EnzR) cell lines. The downregulation of SYT4, in combination with enzalutamide therapy, substantially enhances the antiproliferative effect on resistant prostate cancer cells beyond the capacity of enzalutamide monotherapy. SYT4 promotes vesicle efflux by binding to the synaptosome-associated protein 25 (SNAP25), thereby contributing to cell resistance against enzalutamide. The elevated expression of SYT4 is mediated by bromodomain-containing protein 4 (BRD4), and BRD4 inhibition effectively suppressed the expression of SYT4. Treatment with a therapeutic dose of enzalutamide combined with ASO-1, an antisense oligonucleotide drug targeting SYT4, shows promising results in reversing the resistance of prostate cancer to enzalutamide.

Observing perineuronal nets like structures via coaxial scattering quantitative interference imaging at multiple wavelengths.

Perineuronal nets (PNNs) are important functional structures on the surface of nerve cells. Observation of PNNs usually requires dyeing or fluorescent labeling. As a network structure with a micron grid and sub-wavelength thickness but no special optical properties, quantitative phase imaging (QPI) is the only purely optical method for high-resolution imaging of PNNs. We proposed a Scattering Quantitative Interference Imaging (SQII) method which measures the geometric rather than transmission or reflection phase during the scattering process to visualize PNNs. Different from QIP methods, SQII method is sensitive to scattering and not affected by wavelength changes. Via geometric phase shifting method, we simplify the phase shift operation. The SQII method not only focuses on interference phase, but also on the interference contrast. The singularity points and phase lines of the scattering geometric phase depict the edges of the network structure and can be found at the valley area of the interference contrast parameter SINDR under different wavelengths. Our SQII method has its unique imaging properties, is very simple and easy to implement and has more worth for promotion.

Mechanical and modal analysis of different implant strategies for loss of three teeth with bone atrophy in the maxillary posterior region.

PURPOSE: This study aimed to evaluate the stress distribution and secondary stability involved in five implant strategies, including implant-supported prostheses (ISP) and tooth-implant-supported prostheses (TISP), used for bone atrophy in the maxillary posterior region with teeth loss using finite element analysis, and to explore the more desirable implant methods. METHODS: Five implant strategies were made to analyze and compare: M1, implant-supported prosthesis consisting of a short implant with a regular implant; M2, implant-supported prosthesis consisting of a tilted implant with a regular implant; M3, cantilever structure; M4, tooth-implant-supported prosthesis consisting of a short implant with a regular implant; M5, tooth-implant-supported prosthesis consisting of a regular implant, and M6, with only the natural teeth as a control group. Dynamic loading of the above models was performed in finite element analysis software to assess the stress distribution of the bone tissue and implants using the von Mise criterion. Finally, the secondary stability of different models was evaluated by modal analysis. RESULTS: The maximum stress distribution in the cortical bone in M1(60 MPa) was smaller than that in M2(97 MPa) and M3(101 MPa), The first principal strain minimum was obtained in M2 (2271µÎµ). M4 (33 MPa, 10085 Hz) with the best mechanical properties and highest resonance frequency. But increased the loading on the natural teeth. CONCLUSIONS: Short implants and tilted implants are both preferred implant strategies, if cantilever construction is necessary, a tooth-implant-supported prosthesis consisting of a short implant and a regular implant is recommended.

DNA demethylase Tet2 promotes the terminal maturation of natural killer cells.

The cytotoxicity feature to eliminate malignant cells makes natural killer (NK) cells a candidate for tumor immunotherapy. However, this scenario is currently hampered by inadequate understanding of the regulatory mechanisms of NK cell development. Ten-Eleven-Translocation 2 (Tet2) is a demethylase whose mutation was recently shown to cause phenotypic defects in NK cells. However, the role of Tet2 in the development and maturation of NK cells is not entirely clear. Here we studied the modulatory role of Tet2 in NK cell development and maturation by generating hematopoietic Tet2 knockout mice and mice with Tet2 conditional deletion in NKp46+ NK cells. The results showed that both hematopoietic and NK cell conditional deletion of Tet2 had no effect on the early steps of NK cell development, but impaired the terminal maturation of NK cells defined by CD11b, CD43, and KLRG1 expression. In the liver, Tet2 deletion not only prevented the terminal maturation of NK cells, but also increased the proportion of type 1 innate lymphoid cells (ILC1s) and reduced the proportion of conventional NK cells (cNK). Moreover, hematopoietic deletion of Tet2 lowered the protein levels of perforin in NK cells. Furthermore, hematopoietic deletion of Tet2 downregulated the protein levels of Eomesodermin (Eomes), but not T-bet, in NK cells. In conclusion, our results demonstrate that Tet2 plays an important role in the terminal maturation of NK cells, and the Eomes transcription factor may be involved.

Rare Earth Nanoprobes for Targeted Delineation of Triple Negative Breast Cancer and Enhancement of Radioimmunotherapy.

Radiotherapy demonstrates a synergistic effect with immunotherapy by inducing a transformation of "immune cold" tumors into "immune hot" tumors in triple negative breast cancer (TNBC). Nevertheless, the effectiveness of immunotherapy is constrained by low expression of tumor-exposed antigens, inadequate inflammation, and insufficient tumor infiltrating lymphocyte (TILs). To address this predicament, novel lutecium-based rare earth nanoparticles (RENPs) are synthesized with the aim of amplifying radiation effect and tumor immune response. The nanoprobe is characterized by neodymium-based down-conversion fluorescence, demonstrating robust photostability, biocompatibility, and targetability. The conjugation of RENPs with a CXCR4 targeted drug enables precise delineation of breast tumors using a near-infrared imaging system and improves radiation efficacy via lutetium-based radio-sensitizer in vivo. Furthermore, the study shows a notable enhancement of immune response through the induction of immunogenic cell death and recruitment of TILs, resulting in the inhibition of tumor progression both in vitro and in vivo models following the administration of nanoparticles. Hence, the novel multifunctional nanoprobes incorporating various lanthanide elements offer the potential for imaging-guided tumor delineation, radio-sensitization, and immune activation post-radiation, thus presenting an efficient radio-immunotherapeutic approach for TNBC.

Hierarchical porous amorphous metal-organic frameworks constructed from ZnO/MOF glass composites.

For the first time, hierarchical porous amorphous metal-organic frameworks (HP-aMOFs) containing ultramicropores, micropores, and mesopores were synthesized by etching a composite of MOF glass (agZIF-76) and ZnO using ammonia. These materials show potential applications in the adsorption of C2 hydrocarbons.

Enhancing vitamin D3 bioaccessibility: Unveiling hydrophobic interactions in soybean protein isolate and vitamin D3 binding via an infant in vitro digestion model.

In the domain of infant nutrition, optimizing the absorption of crucial nutrients such as vitamin D3 (VD3) is paramount. This study harnessed dynamic-high-pressure microfluidization (DHPM) on soybean protein isolate (SPI) to engineer SPI-VD3 nanoparticles for fortifying yogurt. Characterized by notable binding affinity (Ka = 0.166 × 105 L·mol-1) at 80 MPa and significant surface hydrophobicity (H0 = 3494), these nanoparticles demonstrated promising attributes through molecular simulations. During simulated infant digestion, the 80 MPa DHPM-treated nanoparticles showcased an impressive 74.4% VD3 bioaccessibility, delineating the pivotal roles of hydrophobicity, bioaccessibility, and micellization dynamics. Noteworthy was their traversal through the gastrointestinal tract, illuminating bile salts' crucial function in facilitating VD3 re-encapsulation, thereby mitigating crystallization and augmenting absorption. Moreover, DHPM treatment imparted enhancements in nanoparticle integrity and hydrophobic properties, consequently amplifying VD3 bioavailability. This investigation underscores the potential of SPI-VD3 nanoparticles in bolstering VD3 absorption, thereby furnishing invaluable insights for tailored infant nutrition formulations.

NUPR1 induces autophagy and promotes the progression of Esophageal squamous cell carcinoma via the MAPK-mTOR pathway.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a dominant pathological type in China. NUPR1 is a complex molecule implicated in various physiological and biological functions whose expression is upregulated in response to stress. Furthermore, autophagy is a vital physiological mechanism in the onset and metastasis of malignancies. This study aims to uncover the influence of NUPR1 on ESCC occurrence and development by regulating autophagy while also exploring its association with the MAPK signaling pathway. METHODS: First, the differences in NUPR1 between ESCC and normal tissues were analyzed through online databases. Subsequently, the pathological tissues of clinical samples were stained and scored using immunohistochemistry. And NUPR1 expression in ESCC cells was investigated, as was the function of NUPR1 in the modulation of ESCC's malignant behavior. Furthermore, a nude mouse ESCC xenograft model was developed. Finally, RNA sequencing was performed on NUPR1-downregulated ESCC cells, which was verified using WB. RESULTS: Our findings initially uncovered differences in the expression of NUPR1 in ESCC and normal tissues. In vitro experiments demonstrated that NUPR1 downregulation significantly inhibited ESCC cell proliferation, invasion, and migration, as well as promoted their apoptosis. Our xenograft model exhibited significant inhibition of ESCC tumors upon NUPR1 downregulation. Subsequently, RNA sequencing uncovered that NUPR1 regulates its malignant biological behavior through MAPK-mTOR signaling pathway. Finally, we found that NUPR1 downregulation can inhibit autophagic flux in ESCC. CONCLUSION: Collectively, our findings show that NUPR1 enhances the progression of ESCC by triggering autophagy and is associated with the MAPK-mTOR signaling pathway.

LAFL Factors in Seed Development and Phase Transitions.

Development is a chain reaction in which one event leads to another until the completion of a life cycle. Phase transitions are milestone events in the cycle of life. LEAFY COTYLEDON1 (LEC1), ABA INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2 proteins, collectively known as LAFL, are master transcription factors (TFs) regulating seed and other developmental processes. Since the initial characterization of the LAFL genes (44, 71, 98-100), more than three decades of active research has generated tremendous amounts of knowledge about these TFs, whose roles in seed development and germination have been comprehensively reviewed (63, 43, 65, 81). Recent advances in cell biology and genetic and genomic tools have allowed the characterization of the LAFL regulatory networks in previously challenging tissues at a higher throughput and resolution in reference species and crops. In this review, we provide a holistic perspective by integrating advances at the epigenetic, transcriptional, posttranscriptional, and protein levels to exemplify the spatiotemporal regulation of the LAFL networks in Arabidopsis seed development and phase transitions, and we briefly discuss the evolution of these TF networks.

Effects of lianas on forest biogeochemistry during their lives and afterlives.

Climate change and other anthropogenic disturbances are increasing liana abundance and biomass in many tropical and subtropical forests. While the effects of living lianas on species diversity, ecosystem carbon, and nutrient dynamics are receiving increasing attention, the role of dead lianas in forest ecosystems has been little studied and is poorly understood. Trees and lianas coexist as the major woody components of forests worldwide, but they have very different ecological strategies, with lianas relying on trees for mechanical support. Consequently, trees and lianas have evolved highly divergent stem, leaf, and root traits. Here we show that this trait divergence is likely to persist after death, into the afterlives of these organs, leading to divergent effects on forest biogeochemistry. We introduce a conceptual framework combining horizontal, vertical, and time dimensions for the effects of liana proliferation and liana tissue decomposition on ecosystem carbon and nutrient cycling. We propose a series of empirical studies comparing traits between lianas and trees to answer questions concerning the influence of trait afterlives on the decomposability of liana and tree organs. Such studies will increase our understanding of the contribution of lianas to terrestrial biogeochemical cycling, and help predict the effects of their increasing abundance.

Effect of angled abutments in the posterior maxillary region on tilted implants: a 3D finite element analysis.

The aim of this study was to evaluate the bone tissue effects under dynamic loading using finite element analysis (FEA) for four angled abutments with different deviated palatal lateral tilt angles. A three-dimensional model of the posterior maxillary region and an implant crown model were reconstructed and assembled with a three-dimensional model of the implant, angled abutment, and central screw to create a total of 10 three-dimensional finite element models tilted at 15 ∘ , 20 ∘ , 25 ∘ , and 30 ∘ in three groups, and the dynamic loads simulating oral mastication were loaded on the implant crown to analyze the equivalent stresses and strains in the peri-implant bone tissues. Under the dynamic loading, the cortical bone on the buccal side of the implant neck showed different degrees of stress concentration, and the cortical bone stress was much higher than the cancellous bone, and the strain concentration area of each model was located in the bone tissue around the implant neck and base. For the use of angular abutment, under the premise that the cortical bone stresses and strains of the 10 models meet the requirements for use, the peak stresses of 2.907 MPa, 3.018 MPa, and 2.164 MPa were achieved by using the 20 ∘ angular abutment to achieve the tilt angles of 20 ∘ , 25 ∘ , and 30 ∘ implantation, which is more advantageous compared with other models.

mTOR signaling promotes rapid m6A mRNA methylation to regulate NK-cell activation and effector functions.

Natural killer (NK) cells can be rapidly activated in response to cytokines during host defense against malignant cells or viral infection. However, it remains unclear what mechanisms precisely and rapidly regulate the expression of the numerous genes involved in activating NK cells. In this study, we discovered that NK-cell N6-methyladenosine (m6A) methylation levels were rapidly upregulated upon short-term NK-cell activation and were repressed in the tumor microenvironment. Deficiency of methyltransferase-like 3 (METTL3) or METTL14 moderately influenced NK-cell homeostasis, while double knockout of METTL3/14 significantly impacted NK-cell homeostasis, maturation, and antitumor immunity. This suggests a cooperative role of METTL3 and METTL14 in regulating NK-cell development and effector functions. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq), we demonstrated that genes involved in NK-cell effector functions, such as Prf1 and Gzmb, were directly modified by m6A methylation. Furthermore, inhibiting mTOR complex 1 (mTORC1) activation prevented m6A methylation levels from increasing when NK cells were activated, and this could be restored by S-adenosylmethionine (SAM) supplementation. Collectively, we have unraveled crucial roles for rapid m6A mRNA methylation downstream of the mTORC1-SAM signal axis in regulating NK-cell activation and effector functions.

Association between urinary phthalates and phthalate metabolites and cancer risk: A systematic review and meta-analysis.

Phthalates, widely utilized in industrial products, are classified as endocrine-disrupting chemicals (EDCs). Although certain phthalate and their metabolites have been implicated in cancer development, the reported findings have exhibited inconsistencies. Therefore, we conducted the comprehensive literature search to assess the association between phthalate and their metabolites and cancer risk by identifying original studies measuring phthalates or their metabolites and reporting their correlation with cancer until July 4, 2023. The Odds Ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted and analyzed to estimate the risk. Pooled data from eleven studies, including 3101 cancer patients and 6858 controls, were analyzed using a fixed- or random-effects model based on heterogeneity tests. When comparing extreme categories of different phthalates and their metabolites, we observed a significant association between urinary phthalates and phthalate metabolites (MEHHP, MECPP, DBP and MBzP) and cancer risk. The findings of our meta-analysis reinforce the existing evidence that urinary phthalates and phthalate metabolites is strongly associated with cancer development. Further investigations are warranted to elucidate the underlying mechanisms of this association. These results may offer novel insights into cancer development.

Porous covalent organic framework nanofibrous membrane for excellent enrichment and ultra-high sensitivity detection of trace organochlorine pesticides in water.

Developing adsorbents with high performance and long service life for effective extracting the trace organochlorine pesticides (OCPs) from real water is attracting numerous attentions. Herein, a self-standing covalent organic framework (COF-TpPa) membrane with fiber morphology was successfully synthesized by using electrospun nanofiber membranes as template and employed as solid-phase microextraction (SPME) coating for ultra-high sensitivity extraction and analysis of trace OCPs in water. The as-synthesized COF-TpPa membrane exhibited a high specific surface area (800.83 m2 g-1), stable nanofibrous structure, and excellent chemical and thermal stability. Based on the COF-TpPa membrane, a new SPME analytical method in conjunction with gas chromatography-mass spectrometry (GC-MS) was established. This proposed method possessed favorable linearity in concentration of 0.05-2000 ng L-1, high sensitivity with enrichment factors ranging from 2175 to 5846, low limits of detection (0.001-0.150 ng L-1), satisfactory precision (RSD < 10 %), and excellent repeatability (>150 cycles), which was better than most of the reported works. Additionally, the density functional theory (DFT) calculations and XPS results demonstrated that the outstanding enrichment performance of the COF-TpPa membrane was owing to synergistic effect of π-π stacking effects, high specific surface area and hydrogen bonding. This work will expect to extend the applications of COF membrane to captures trace organic pollutants in complex environmental water, as well as offer a multiscale interpretation for the design of effective adsorbents.

Influence mechanism of the temporal duration of laser irradiation on photoacoustic technique: a review.

Significance: In the photoacoustic (PA) technique, the laser irradiation in the time domain (i.e., laser pulse duration) governs the characteristics of PA imaging-it plays a crucial role in the optical-acoustic interaction, the generation of PA signals, and the PA imaging performance. Aim: We aim to provide a comprehensive analysis of the impact of laser pulse duration on various aspects of PA imaging, encompassing the signal-to-noise ratio, the spatial resolution of PA imaging, the acoustic frequency spectrum of the acoustic wave, the initiation of specific physical phenomena, and the photothermal-PA (PT-PA) interaction/conversion. Approach: By surveying and reviewing the state-of-the-art investigations, we discuss the effects of laser pulse duration on the generation of PA signals in the context of biomedical PA imaging with respect to the aforementioned aspects. Results: First, we discuss the impact of laser pulse duration on the PA signal amplitude and its correlation with the lateral resolution of PA imaging. Subsequently, the relationship between the axial resolution of PA imaging and the laser pulse duration is analyzed with consideration of the acoustic frequency spectrum. Furthermore, we examine the manipulation of the pulse duration to trigger physical phenomena and its relevant applications. In addition, we elaborate on the tuning of the pulse duration to manipulate the conversion process and ratio from the PT to PA effect. Conclusions: We contribute to the understanding of the physical mechanisms governing pulse-width-dependent PA techniques. By gaining insight into the mechanism behind the influence of the laser pulse, we can trigger the pulse-with-dependent physical phenomena for specific PA applications, enhance PA imaging performance in biomedical imaging scenarios, and modulate PT-PA conversion by tuning the pulse duration precisely.

Validation of a new non-hyperemic physiological index: the constant-resistance ratio (cRR).

OBJECTIVES: The instantaneous wave-free ratio (iwFR) has limited availability. A new resting index called the constant-resistance ratio (cRR), which dynamically identifies cardiac intervals with constant and minimum resistance, has been developed; however, its diagnostic performance is unknown. The aim of this study was to validate the cRR by retrospectively calculating the cRR values from raw pressure waveforms of 2 publicly available datasets and compare them with those of the iwFR. METHODS: Waveform data from the CONTRAST and VERIFY 2 studies were used. The primary endpoint was Bland-Altman bias between cRR and iwFR. Secondary endpoints included diagnostic agreement, correlation, receiver operating characteristic (ROC) analysis, and success rates of cRR and iwFR. RESULTS: Among the 1036 waveforms, 871 were successful in determining paired cRR and iwFR values, while cRR was 6% more successful than iwFR (P less than .0001). The mean bias between cRR and iwFR was 0.003, with 95% limits of agreement [-0.021,0.028]. These 2 indices were highly correlated (r = 0.991; P less than .0001). Using an iwFR of 0.89 or less as the reference standard, the optimal cRR cutoff was 0.89, with an area under the ROC curve of 0.991 (P less than .001) and a diagnostic accuracy of 96.9% (95% CI [96%, 98%]). CONCLUSIONS: The cRR, a new resting index for identifying dynamic cardiac intervals with constant and minimum resistance, demonstrated high numerical agreement, diagnostic consistency, and a higher success rate than the iwFR based on the 2 publicly available datasets.

Characteristics of germline DNA damage response gene mutations in ovarian cancer in Southwest China.

DNA damage response (DDR) pathways are responsible for repairing endogenous or exogenous DNA damage to maintain the stability of the cellular genome, including homologous recombination repair (HRR) pathway, mismatch repair (MMR) pathway, etc. In ovarian cancer, current studies are focused on HRR genes, especially BRCA1/2, and the results show regional and population differences. To characterize germline mutations in DDR genes in ovarian cancer in Southwest China, 432 unselected ovarian cancer patients underwent multi-gene panel testing from October 2016 to October 2020. Overall, deleterious germline mutations in DDR genes were detected in 346 patients (80.1%), and in BRCA1/2 were detected in 126 patients (29.2%). The prevalence of deleterious germline mutations in BRCA2 is higher than in other studies (patients are mainly from Eastern China), and so is the mismatch repair genes. We identified three novel BRCA1/2 mutations, two of which probably deleterious (BRCA1 p.K1622* and BRCA2 p.L2987P). Furthermore, we pointed out that deleterious mutations of FNACD2 and RECQL4 are potential ovarian cancer susceptibility genes and may predispose carriers to ovarian cancer. In conclusion, our study highlights the necessity of comprehensive germline mutation detection of DNA damage response genes in ovarian cancer patients, which is conducive to patient management and genetic counseling.