Porcine Epidemic Diarrhea Virus nsp13 Protein Downregulates Neonatal Fc Receptor Expression by Causing Promoter Hypermethylation through the NF-κB Signaling Pathway.

Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic porcine enteric coronavirus that causes severe watery diarrhea and even death in piglets. The neonatal Fc receptor (FcRn) is the only transport receptor for IgG. FcRn expressed by intestinal epithelial cells can transport IgG from breast milk to piglets to provide immune protection. Previous studies have shown that viral infection affects FcRn expression. In this study, we showed for the first time, to our knowledge, that FcRn expression can be influenced by methyltransferases. In addition, we found that PEDV inhibited FcRn protein synthesis in porcine small intestinal epithelial cells postinfection. Then, we found that PEDV interfered with the transcription of genes through aberrant methylation modification of the FcRn promoter. DNA methyltransferase 3b (DNMT3b) has been implicated in this process. Using a series of PEDV structural and nonstructural protein (nsp) expression plasmids, we showed that nsp13 plays an important role in this aberrant methylation modification. PEDV nsp13 can affect the NF-κB canonical pathway and promote DNMT3b protein expression by facilitating p65 protein binding to chromatin. PEDV caused aberrant methylation of the FcRn promoter via DNMT3b. The same phenomenon was found in animal experiments with large white piglets. IgG transcytosis demonstrated that PEDV nsp13 can inhibit bidirectional IgG transport by FcRn. In addition, the core region of nsp13 (230-597 aa) is critical for FcRn inhibition. Taken together, to our knowledge, our findings revealed a novel immune escape mechanism of PEDV and shed new light on the design and development of vaccines and drugs.

Inhalable Textile Microplastic Fibers Impair Airway Epithelial Differentiation.

Rationale: Microplastics are a pressing global concern, and inhalation of microplastic fibers has been associated with interstitial and bronchial inflammation in flock workers. However, how microplastic fibers affect the lungs is unknown. Objectives: Our aim was to assess the effects of 12 × 31 µm nylon 6,6 (nylon) and 15 × 52 µm polyethylene terephthalate (polyester) textile microplastic fibers on lung epithelial growth and differentiation. Methods: We used human and murine alveolar and airway-type organoids as well as air-liquid interface cultures derived from primary lung epithelial progenitor cells and incubated these with either nylon or polyester fibers or nylon leachate. In addition, mice received one dose of nylon fibers or nylon leachate, and, 7 days later, organoid-forming capacity of isolated epithelial cells was investigated. Measurements and Main Results: We observed that nylon microfibers, more than polyester, inhibited developing airway organoids and not established ones. This effect was mediated by components leaching from nylon. Epithelial cells isolated from mice exposed to nylon fibers or leachate also formed fewer airway organoids, suggesting long-lasting effects of nylon components on epithelial cells. Part of these effects was recapitulated in human air-liquid interface cultures. Transcriptomic analysis revealed upregulation of Hoxa5 after exposure to nylon fibers. Inhibiting Hoxa5 during nylon exposure restored airway organoid formation, confirming Hoxa5's pivotal role in the effects of nylon. Conclusions: These results suggest that components leaching from nylon 6,6 may especially harm developing airways and/or airways undergoing repair, and we strongly encourage characterization in more detail of both the hazard of and the exposure to microplastic fibers.

Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3-MAPK Signaling to Trigger Spontaneous Aortic Dissection.

BACKGROUND: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive. METHODS: Smooth muscle cell-specific and endothelial cell-specific Best3 knockout mice (Best3SMKO and Best3ECKO, respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels. RESULTS: Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3SMKO but not Best3ECKO mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II-infused Best3SMKO and ApoE-/- mice. CONCLUSIONS: These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3-MEKK2/3 signaling represents a novel therapeutic target for AD.

Effects of computerized working memory training on neuroplasticity in healthy individuals: A combined neuroimaging and neurotransmitter study.

Working memory (WM) is an essential cognitive function that underpins various higher-order cognitive processes. Improving WM capacity through targeted training interventions has emergered as a potential approach for enhancing cognitive abilities. The present study employed an 8-week regimen of computerized WM training (WMT) to investigate its effect on neuroplasticity in healthy individuals, utilizing neuroimaging data gathered both before and after the training. The key metrics assessed included the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and the spatial distribution correlations of neurotransmitter. The results indicated that post-training, compared to baseline, there was a reduction in ALFF in the medial superior frontal gyrus and an elevation in ALFF in the left middle occipital gyrus within the training group. In comparison to the control group, the training group also exhibited decreased ALFF in the anterior cingulate cortex, angular gyrus, and superior parietal lobule, along with increased ALFF in the postcentral gyrus post-training. VBM analysis revealed a significant increase in gray matter volume (GMV) in the right dorsal superior frontal gyrus after the training period, compared to the initial baseline measurement. Furthermore, the training group showed GMV increases in the dorsal superior frontal gyrus, Rolandic operculum, precentral gyrus, and postcentral gyrus when compared to the control group. In addition, significant associations were identifed between neuroimaging measurements (AFLL and VBM) and the spatial patterns of neurotransmitters such as serotonin (5-HT), dopamine (DA), and N-methyl-D-aspartate (NMDA), providing insights into the underlying neurochemical processes. These findings clarify the neuroplastic changes caused by WMT, offering a deeper understanding of brain plasticity and highlighting the potential advantages of cognitive training interventions.

Let­7f­5p Regulated by Hsa_circ_0000437 Ameliorates Bleomycin-Induced Skin Fibrosis.

The current treatment of skin fibrosis is limited in its effectiveness due to a lack of understanding of the underlying mechanisms. Previous research has shown a connection between microRNAs (miRNAs) and the development of skin fibrosis. Therefore, investigating miRNA for the treatment of skin fibrotic diseases is highly important and merits further exploration. In this study, we have discovered that let-7f-5p could suppress the proliferation, migration, and expression of collagen type I alpha 1 (COL1A1) in human dermal fibroblasts (HDFs). It was further determined that let-7f-5p could target thrombospondin-1 (THBS1), thereby inhibiting the TGF-ß2/Smad3 signaling pathway and exerting its biological effects. Additionally, let-7f-5p is regulated by Hsa_circ_0000437, which acts as a sponge molecule for let-7f-5p and consequently regulates the biological function of HDFs. Furthermore, our findings indicate that in vivo overexpression of let-7f-5p leads to a reduction in dermal thickness and COL1A1 expression, effectively inhibiting the progression of bleomycin (BLM)-induced skin fibrosis in mice. Hence, our research enhances the comprehension of the Hsa_circ_0000437/let-7f-5p/THBS1/TGF-ß2/Smad3 regulatory network, highlighting the potential of let-7f-5p as a therapeutic approach for the treatment of skin fibrosis.

NIR-II Light-Driven Genetically Engineered Exosome Nanocatalysts for Efficient Phototherapy against Glioblastoma.

Glioblastoma (GBM) poses a significant therapeutic challenge due to its invasive nature and limited drug penetration through the blood-brain barrier (BBB). In response, here we present an innovative biomimetic approach involving the development of genetically engineered exosome nanocatalysts (Mn@Bi2Se3@RGE-Exos) for efficient GBM therapy via improving the BBB penetration and enzyme-like catalytic activities. Interestingly, a photothermally activatable multiple enzyme-like reactivity is observed in such a nanosystem. Upon NIR-II light irradiation, Mn@Bi2Se3@RGE-Exos are capable of converting hydrogen peroxide into hydroxyl radicals, oxygen, and superoxide radicals, providing a peroxidase (POD), oxidase (OXD), and catalase (CAT)-like nanocatalytic cascade. This consequently leads to strong oxidative stresses to damage GBM cells. In vitro, in vivo, and proteomic analysis further reveal the potential of Mn@Bi2Se3@RGE-Exos for the disruption of cellular homeostasis, enhancement of immunological response, and the induction of cancer cell ferroptosis, showcasing a great promise in anticancer efficacy against GBM with a favorable biosafety profile. Overall, the success of this study provides a feasible strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM.

Differential Cantilever Enhanced Fiber-Optic Photoacoustic Sensor for Diffusion Gas Detection.

Aiming at the problem of the fiber-optic photoacoustic (PA) sensor being easily disturbed by external vibration and noise, a differential cantilever enhanced fiber-optic PA sensor is proposed for diffusion gas detection. The sensor comprises two PA tubes with the same structure and a pair of differential interferometric cantilevers. The two PA tubes are symmetrically distributed. The laser is incident on the PA tube as the signal channel to excite the PA pressure wave. Another tube without incident laser is used as the reference channel to suppress external disturbance. The external interference signals and PA signals superimposed with disturbance are detected by the differential cantilevers from the two channels. The signals are simultaneously restored by a single white-light interferometry demodulator, which multiplexed the spectral frequency domain of the superimposed interference spectrum. The experimental results show that the suppression effect of the differential cantilever enhanced PA sensor on ambient noise is improved by 80%, compared to the traditional single-cantilever sensor. The external cofrequency disturbance is suppressed by 20.9 dB. The minimum detection limit to acetylene (C2H2) downs to about 60 ppb with an integration time of 100 s. The sensor has excellent antivibration and electromagnetic interference ability.

Fiber-Optic Photoacoustic Gas Microsensor Dual Enhanced by Helmholtz Resonator and Interferometric Cantilever.

A high-sensitivity fiber-optic photoacoustic (PA) gas microsensor is demonstrated with dual enhancement based on acoustics and detection. Due to the characteristic of small size, a Helmholtz resonator is integrated into a miniature PA sensor. The acoustically amplified PA signal is detected by a high-sensitivity fiber Fabry-Perot (F-P) interferometric cantilever. The first-order resonant frequencies of the interferometric cantilever and Helmholtz resonator are matched by subtle adjustments. The weak PA signal is significantly enhanced in a volume of only 0.35 mL, which breaks the volume limitation of the resonance modes in traditional PA sensing systems. To improve the resolution of the microsensor, a white light interferometry (WLI)-based spectral demodulation algorithm is utilized. The experimental results indicate that the minimum detection limit of acetylene (C2H2) drops to about 15 ppb with an averaging time of 100 s, corresponding to the normalized noise equivalent absorption (NNEA) coefficient of 2.7 × 10-9 W·cm-1·Hz-1/2. The dual resonance enhanced fiber-optic PA gas microsensor has the merits of high sensitivity, intrinsic safety, and compact structure.

Fiber-Optic Photoacoustic CO Sensor for Gas Insulation Equipment Monitoring Based on Cantilever Differential Lock-In Amplification and Optical Excitation Enhancement.

A fiber-optic photoacoustic CO sensor for gas insulation equipment is proposed, which relies on F-P interferometric cantilever-based differential lock-in amplification and optical multipass excitation enhancement. The sensor has excellent characteristics of high sensitivity, antielectromagnetic interference, fast response, and long-distance detection. The photoacoustic pressure waves in the two resonators of the differential photoacoustic cell (DPAC) are simultaneously detected by two fiber-optic interferometric cantilevers and processed differentially; thereby, the gas flow noise is effectively suppressed. Based on the comprehensive analysis of the superposition of photoacoustic excitation and multipass absorption, the diameter of the resonator is determined to be 6 mm. The optical power emitted by the 1566.6 nm distributed feedback laser is increased to 500 mW by an erbium-doped fiber amplifier. The near-infrared light is reflected 30 times in the multipass cell, which improves the order of magnitude of optical effective excitation. Due to the low sound velocity of SF6 gas, the resonant frequency of the DPAC with a resonator length of 80 mm is 760 Hz. The response time to CO/SF6 gas is 93 s with a flow rate of 500 sccm. The detection limit of the CO sensor is 53 ppb, which realizes the accurate and timely perception of the SF6 decomposition derivative CO and provides technical support for trouble-free operation of gas insulation equipment.

High-Precision Multipass Fiber-Optic Photoacoustic Gas Analyzer Based on 2f/1f Wavelength Modulation Spectroscopy.

A self-calibration fiber-optic photoacoustic (PA) gas analyzer based on 2f/1f wavelength modulation spectroscopy (WMS) is proposed, which utilizes gas and solid multipass absorption enhancement. The laser light is incident obliquely on the cell wall, and one end of the cell is equipped with a highly reflective mirror. The gas analyzer takes full advantage of the miniature multipass PA cell, which enhances the absorption of gas and solid simultaneously. As a result, the double absorption enhancement of 1f and 2f PA signals are realized. A dual-channel lock-in white-light interferometer based on fiber-optic PA demodulation is designed to simultaneously extract the 1f and 2f PA signals detected by the silicon cantilever. The experimental results of methane gas detection show that the minimum detection limit (MDL) of the PA gas analyzer is 20 ppb when the integration time is 60 s. Moreover, the detection error of gas concentration is within 3% when the laser power is reduced by half. The fiber-optic PA gas analyzer eliminates the influence of changes in the laser power and optical path loss, which can be used for the high-precision detection of trace gases.

All-Optical Photoacoustic Spectroscopy-Based Dual-Component Greenhouse Gas Analyzer.

To achieve high sensitivity detection of dual-component greenhouse gases carbon dioxide and methane simultaneously, a multimechanism synergistic enhanced all-optical photoacoustic spectroscopy gas analyzer is presented. The acoustic resonance of the photoacoustic cell and the mechanical resonance of a fiber-optic cantilever acoustic sensor are used to enhance the photoacoustic signals of the dual-component gas. The optimized multipass beam reflection structure enhances the effective excitation power of the dual-component gas. The highly sensitive detection of carbon dioxide and methane at dual-frequency operating points is realized by dual-channel laser modulation combined with dual-input digital lock-in amplification technology. The Allan-Werle deviation analysis results show that with a 100 s average time, the minimum detection limits of carbon dioxide and methane are 76.5 and 1.9 ppb, respectively. The corresponding normalized noise equivalent absorption (NNEA) coefficients are 3.1 × 10-10 and 2.9 × 10-10 cm-1 W/Hz1/2, respectively.

Ultrahigh Sensitive Trace Gas Sensing System with Dual Fiber-Optic Cantilever Multiplexing-Based Differential Photoacoustic Detection.

An ultrahigh sensitive trace gas sensing system was presented with dual cantilever-based differential photoacoustic detection. By combining the double enhancement of multipass absorption and optical differential detection, the gas detection sensitivity was significantly improved. The dual-channel synchronous photoacoustic detection was realized by fiber-optic Fabry-Perot interference spectrum multiplexing. The photoacoustic signals detected by two fiber-optic cantilever microphones installed in a differential photoacoustic cell (DPAC) were out of phase, while the detected gas flow noises were in phase. The optical differential detection method achieved both highly sensitive optical interference measurement and differential noise suppression. In the multipass configuration, the interaction path between excitation light and target gas achieved 4.1 m, which improved the photoacoustic signal by an order of magnitude compared with a single reflection. The maximum gas flow allowed by the system based on the DPAC was 250 sccm, which realized the dynamic monitoring of H2S in the SF6 background. The detection limit for H2S in SF6 background was 5.1 ppb, which corresponds to the normalized noise equivalent absorption coefficient of 9 × 10-10 cm-1 W Hz-1/2.

Low-frequency rTMS induces modifications in cortical structural connectivity - functional connectivity coupling in schizophrenia patients with auditory verbal hallucinations.

Auditory verbal hallucinations (AVH) are distinctive clinical manifestations of schizophrenia. While low-frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in mitigating AVH, the precise mechanisms by which it operates remain obscure. This study aimed to investigate alternations in structural connectivity and functional connectivity (SC-FC) coupling among schizophrenia patients with AVH prior to and following treatment with 1 Hz rTMS that specifically targets the left temporoparietal junction. Initially, patients exhibited significantly reduced macroscopic whole brain level SC-FC coupling compared to healthy controls. Notably, SC-FC coupling increased significantly across multiple networks, including the somatomotor, dorsal attention, ventral attention, frontoparietal control, and default mode networks, following rTMS treatment. Significant alternations in SC-FC coupling were noted in critical nodes comprising the somatomotor network and the default mode network, such as the precentral gyrus and the ventromedial prefrontal cortex, respectively. The alternations in SC-FC coupling exhibited a correlation with the amelioration of clinical symptom. The results of our study illuminate the intricate relationship between white matter structures and neuronal activity in patients who are receiving low-frequency rTMS. This advances our understanding of the foundational mechanisms underlying rTMS treatment for AVH.

Epigenetic silencing of LDHB promotes hepatocellular carcinoma by remodeling the tumor microenvironment.

Lactate dehydrogenase B (LDHB) reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate and expressed in various malignancies. However, the role of LDHB in modulating immune responses against hepatocellular carcinoma (HCC) remains largely unknown. Here, we found that down-regulation of lactate dehydrogenase B (LDHB) was coupled with the promoter hypermethylation and knocking down the DNA methyltransferase 3A (DNMT 3A) restored LDHB expression levels in HCC cell lines. Bioinformatics analysis of the HCC cohort from The Cancer Genome Atlas revealed a significant positive correlation between LDHB expression and immune regulatory signaling pathways and immune cell infiltrations. Moreover, immune checkpoint inhibitors (ICIs) have shown considerable promise for HCC treatment and patients with higher LDHB expression responded better to ICIs. Finally, we found that overexpression of LDHB suppressed HCC growth in immunocompetent but not in immunodeficient mice, suggesting that the host immune system was involved in the LDHB-medicated tumor suppression. Our findings indicate that DNMT3A-mediated epigenetic silencing of LDHB may contribute to HCC progression through remodeling the tumor immune microenvironment, and LDHB may become a potential prognostic biomarker and therapeutic target for HCC immunotherapy.

Delicate Regulation of Central Substituents Boosts Organic Photovoltaic Performance of Dimeric Acceptors.

Dimeric acceptors are expected to satisfy both excellent power conversion efficiency (PCE) and operational stability of organic solar cells (OSCs). However, comparing to highly planar and symmetrical monomer-like acceptors, the quite different steric/spatial configurations of dimeric acceptors affect device outcomes greatly. Herein, on basis of the same dimeric molecular platform that constructed by bridging central units of two monomer-like acceptor, diverse substituents (─OCH3 for D1, ─CH3 for D2, and ─CF3 for D3) are grafted on central units to regulate the three dimensions (3D) geometries of dimeric acceptors delicately. A systematic investigation reveals the substituent-dependent variation of energy level, absorption, and molecular packing behavior. Consequently, D2 acceptor, characteristic of more favorable configuration, affords a superior film morphology and charge transfer/transport dynamics in resulting OSCs, thus yielding an excellent PCE of 17.50% along with a good long-term stability. This work manifests the crucially important role of central substituents in constructing high-performance dimeric acceptors.

What is the Limit Size of 2D Conjugated Extension on Central Units of Small Molecular Acceptors in Organic Solar Cells?

2D conjugated extension on central units of small molecular acceptors (SMAs) has gained great successes in reaching the state-of-the-art organic photovoltaics. Whereas the limit size of 2D central planes and their dominant role in constructing 3D intermolecular packing networks are still elusive. Thus, by exploring a series of SMAs with gradually enlarged central planes, it is demonstrated that, at both single molecular and aggerated levels, there is an unexpected blue-shift for their film absorption but preferable reorganization energies, exciton lifetimes and binding energies with central planes enlarging, especially when comparing to their Y6 counterpart. More importantly, the significance of well-balanced molecular packing modes involving both central and end units is first disclosed through a systematic single crystal analysis, indicating that when the ratio of central planes area/end terminals area is no more than 3 likely provides a preferred 3D intermolecular packing network of SMAs. By exploring the limit size of 2D central planes, This work indicates that the structural profiles of ideal SMAs may require suitable central unit size together with proper heteroatom replacement instead of directly overextending 2D central planes to the maximum. These results will likely provide some guidelines for future better molecular design.

Balancing Flexible Side Chains on 2D Conjugated Acceptors Enables High-Performance Organic Solar Cell.

Balancing the rigid backbones and flexible side chains of light-harvesting materials is crucially important to reach optimized intermolecular packing, micromorphology, and thus photovoltaic performance of organic solar cells (OSCs). Herein, based on a distinctive CH-series acceptor platform with 2D conjugation extended backbones, a series of nonfullerene acceptors (CH-6F-Cn) are synthesized by delicately tuning the lengths of flexible side chains from n-octyl to n-amyl. A systemic investigation has revealed that the variation of the side chain's length can not only modulate intermolecular packing modes and crystallinity but also dramatically improve the micromorphology of the active layer and eventual photovoltaic parameters of OSCs. Consequently, the highest PCE of 18.73% can be achieved by OSCs employing D18:PM6:CH-6F-C8 as light-harvesting materials.

Palmitoylation at Residue C221 of Japanese Encephalitis Virus NS2A Protein Contributes to Viral Replication Efficiency and Virulence.

Palmitoylation of viral proteins is crucial for host-virus interactions. In this study, we examined the palmitoylation of Japanese encephalitis virus (JEV) nonstructural protein 2A (NS2A) and observed that NS2A was palmitoylated at the C221 residue of NS2A. Blocking NS2A palmitoylation by introducing a cysteine-to-serine mutation at C221 (NS2A/C221S) impaired JEV replication in vitro and attenuated the virulence of JEV in mice. NS2A/C221S mutation had no effect on NS2A oligomerization and membrane-associated activities, but reduced protein stability and accelerated its degradation through the ubiquitin-proteasome pathway. These observations suggest that NS2A palmitoylation at C221 played a role in its protein stability, thereby contributing to JEV replication efficiency and virulence. Interestingly, the C221 residue undergoing palmitoylation was located at the C-terminal tail (amino acids 195 to 227) and is removed from the full-length NS2A following an internal cleavage processed by viral and/or host proteases during JEV infection. IMPORTANCE An internal cleavage site is present at the C terminus of JEV NS2A. Following occurrence of the internal cleavage, the C-terminal tail (amino acids 195 to 227) is removed from the full-length NS2A. Therefore, it was interesting to discover whether the C-terminal tail contributed to JEV infection. During analysis of viral palmitoylated protein, we observed that NS2A was palmitoylated at the C221 residue located at the C-terminal tail. Blocking NS2A palmitoylation by introducing a cysteine-to-serine mutation at C221 (NS2A/C221S) impaired JEV replication in vitro and attenuated JEV virulence in mice, suggesting that NS2A palmitoylation at C221 contributed to JEV replication and virulence. Based on these findings, we could infer that the C-terminal tail might play a role in the maintenance of JEV replication efficiency and virulence despite its removal from the full-length NS2A at a certain stage of JEV infection.

Ultrahigh-speed phase demodulation of a Fabry-Perot sensor based on fiber array parallel spectral detection.

An ultrahigh-speed phase demodulation system was designed for the Fabry-Perot (F-P) interferometric sensor based on fiber array parallel spectral detection. A high-power amplified spontaneous emission (ASE) source served as the broadband detection light. The spectrum generated by the dispersion of the F-P interference light through an arrayed waveguide grating (AWG) was incident into the fiber array and was detected in parallel by 48 photodiodes. The 48-channel signals were acquired synchronously and processed in real time to achieve a phase demodulation for the F-P cavity at 200 kHz. As a result, a low-resolution spectral detection and demodulation system was constructed with high speed. The length demodulation range of the F-P cavity was 60-700 µm, and the demodulation resolution was as high as 0.22 nm. The designed high-sensitivity demodulator is expected to be used for ultrasonic and high-frequency vibration detection.

Association of DOK3 and infiltrated tumor-associated macrophages with risk for the prognosis of Porphyromonas gingivalis-infected oral cancer: a 12-year data analysis of 200 patients from a tertiary teaching hospital, Urumqi, China.

BACKGROUND: While there is an understanding of the association between the expression of Porphyromonas gingivalis (P. gingivalis) and prognosis of oral squamous cell carcinoma (OSCC), significance specially to address the relevance between different immunohistochemical intensities of P. gingivalis and tumor-associated macrophages (TAMs) in OSCC tissue and related clinicopathologic characteristics has not been well investigated. The present study aimed to investigate the pathological features related to M2-TAM in P. gingivalis-infected OSCC and ascertain its clinical relevance with patients' prognosis. METHODS: A prospective cohort study was designed to comparatively analyze 200 patients from June 2008 to June 2020. Bioinformatics analyses were implemented to identify DOK3 as a key molecule and to appraise immunocyte infiltration using Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunohistochemical evaluation was performed to analyze the association between the expression levels of P. gingivalis, DOK3, and M2-TAM and clinicopathological variables using Fisher's exact test or Pearson's chi-square test. Cox analysis was used to calculate hazard ratios (HR) with corresponding 95% confidence interval (CI) for various clinicopathological features. The Kaplan-Meier approach and log-rank test were used to plot the survival curves. RESULTS: The expression level of P. gingivalis was positively associated with DOK3 and M2-TAMs expression level (P < 0.001). Parameters, including body mass index, clinical stage, recurrence, tumor differentiation, and P. gingivalis, DOK3, and M2-TAM immunoexpression levels, affected the prognosis of patients with OSCC (all P < 0.05). In addition, P. gingivalis (HR = 1.674, 95%CI 1.216-4.142, P = 0.012), DOK3 (HR = 1.881, 95%CI 1.433-3.457, P = 0.042), and M2-TAM (HR = 1.649, 95%CI 0.824-3.082, P = 0.034) were significantly associated with the 10-year cumulative survival rate. CONCLUSIONS: Elevated expression of P. gingivalis and DOK3 indicates M2-TAM infiltration and unfavorable prognosis of OSCC, and could be considered as three novel independent risk factors for predicting the prognosis of OSCC.