Gut-Innervating Nociceptor Neurons Regulate Peyer's Patch Microfold Cells and SFB Levels to Mediate Salmonella Host Defense.

Gut-innervating nociceptor sensory neurons respond to noxious stimuli by initiating protective responses including pain and inflammation; however, their role in enteric infections is unclear. Here, we find that nociceptor neurons critically mediate host defense against the bacterial pathogen Salmonella enterica serovar Typhimurium (STm). Dorsal root ganglia nociceptors protect against STm colonization, invasion, and dissemination from the gut. Nociceptors regulate the density of microfold (M) cells in ileum Peyer's patch (PP) follicle-associated epithelia (FAE) to limit entry points for STm invasion. Downstream of M cells, nociceptors maintain levels of segmentous filamentous bacteria (SFB), a gut microbe residing on ileum villi and PP FAE that mediates resistance to STm infection. TRPV1+ nociceptors directly respond to STm by releasing calcitonin gene-related peptide (CGRP), a neuropeptide that modulates M cells and SFB levels to protect against Salmonella infection. These findings reveal a major role for nociceptor neurons in sensing and defending against enteric pathogens.

Genetic and phenotypic profiling of single living circulating tumor cells from patients with microfluidics.

Accurate prediction of the efficacy of immunotherapy for cancer patients through the characterization of both genetic and phenotypic heterogeneity in individual patient cells holds great promise in informing targeted treatments, and ultimately in improving care pathways and clinical outcomes. Here, we describe the nanoplatform for interrogating living cell host-gene and (micro-)environment (NICHE) relationships, that integrates micro- and nanofluidics to enable highly efficient capture of circulating tumor cells (CTCs) from blood samples. The platform uses a unique nanopore-enhanced electrodelivery system that efficiently and rapidly integrates stable multichannel fluorescence probes into living CTCs for in situ quantification of target gene expression, while on-chip coculturing of CTCs with immune cells allows for the real-time correlative quantification of their phenotypic heterogeneities in response to immune checkpoint inhibitors (ICI). The NICHE microfluidic device provides a unique ability to perform both gene expression and phenotypic analysis on the same single cells in situ, allowing us to generate a predictive index for screening patients who could benefit from ICI. This index, which simultaneously integrates the heterogeneity of single cellular responses for both gene expression and phenotype, was validated by clinically tracing 80 non-small cell lung cancer patients, demonstrating significantly higher AUC (area under the curve) (0.906) than current clinical reference for immunotherapy prediction.

Systemic and Local Administration of a Dual-siRNA Complex Efficiently Inhibits Tumor Growth and Bone Invasion in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral and oropharyngeal cancer cases and is characterized by high mortality and poor prognosis. RNA-based gene therapies have been developed as an emerging option for cancer treatment, but it has not been widely explored in OSCC. In this work, we developed an efficient siRNA cationic micelle DOTAP-mPEG-PCL (DMP) by self-assembling the cationic lipid DOTAP and monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) polymer. We tested the characteristics and transformation efficiency of this micelle and combined DMP with siRNA targeting STAT3 and TGF-ß to evaluate the antitumor effect and bone invasion interfering in vitro and in vivo. The average size of the DMP was 28.27 ± 1.62 nm with an average zeta potential of 54.60 ± 0.29 mV. The DMP/siRNA complex showed high delivery efficiency, with rates of 97.47 ± 0.42% for HSC-3. In vitro, the DMP/siSTAT3 complex exhibited an obvious cell growth inhibition effect detected by MTT assay (an average cell viability of 25.1%) and clonogenic assay (an average inhibition rate of 51.9%). Besides, the supernatant from HSC-3 transfected by DMP/siTGF-ß complexes was found to interfere with osteoclast differentiation in vitro. Irrespective of local or systemic administration, DMP/siSTAT3+siTGF-ß showed antitumor effects and bone invasion inhibition in the OSCC mice mandibular invasion model according to tumor volume assays and Micro-CT scanning. The complex constructed by DMP cationic micelles and siSTAT3+siTGF-ß represents a potential RNA-based gene therapy delivery system for OSCC.

microRNA-3037 targeting CYP6CY2 confers imidacloprid resistance to Sitobion miscanthi (Takahashi).

The wheat aphid Sitobion miscanthi is a dominant and destructive pest in agricultural production. Insecticides are the main substances used for effective control of wheat aphids. However, their extensive application has caused severe resistance of wheat aphids to some insecticides; therefore, exploring resistance mechanisms is essential for wheat aphid management. In the present study, CYP6CY2, a new P450 gene, was isolated and overexpressed in the imidacloprid-resistant strain (SM-R) compared to the imidacloprid-susceptible strain (SM-S). The increased sensitivity of S. miscanthi to imidacloprid after knockdown of CYP6CY2 indicates that it could be associated with imidacloprid resistance. Subsequently, the posttranscriptional regulation of CYP6CY2 in the 3' UTR by miR-3037 was confirmed, and CYP6CY2 participated in imidacloprid resistance. This finding is critical for determining the role of P450 in relation to the resistance of S. miscanthi to imidacloprid. It is of great significance to understand this regulatory mechanism of P450 expression in the resistance of S. miscanthi to neonicotinoids.

Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: a propensity score matching and multicentre study.

PURPOSE: With increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear. METHODS: Clinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis. RESULTS: Of the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, Child‒Pugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, Child‒Pugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS. CONCLUSION: Age itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.

Incidence of Unintentional Intraoperative Hypothermia and Its Risk Factors in Oral and Maxillofacial Surgery: A Prospective Study.

PURPOSE: Unintentional intraoperative hypothermia is a common complication in patients who undergo open surgery, increasing the risk of adverse outcomes. However, few studies have focused on intraoperative hypothermia during oral and maxillofacial surgery. Our study aimed to analyze the prevalence and risk factors of hypothermia in patients who underwent oral and maxillofacial surgery. DESIGN: A prospective cohort study was conducted on 128 patients who underwent oral and maxillofacial surgery. METHODS: This prospective study was conducted at West China Hospital of Stomatology between December 2020 and May 2021, and each patient was followed for at least 1-month postoperatively. Patients who underwent oral and maxillofacial surgery under general anesthesia, with at least 1-month follow-up were analyzed. The primary variable was intraoperative hypothermia, defined as core body temperature less than 36°C, measured using a tympanic thermometer during the surgery. We performed univariate and multivariate logistic regression analyses to identify the risk factors of unintentional intraoperative hypothermia. FINDINGS: The mean age of the 128 patients was 31.0 ± 20.9 years, and there was a male predominance (53.1%), with male to female ratio of 1.13:1. Thirty-one patients (24.2%) developed hypothermia intraoperatively. Older age (OR = 1.068, 95% CI: 1.028-1.110, P = .001), lower weight (OR = 0.878, 95% CI: 0.807-0.955, P = .002), greater blood loss (OR = 1.003, 95% CI: 1.000-1.006, P = .034), and undergoing cancer surgery (OR = 0.210, 95% CI: 0.067-0.656, P = .007) were associated with intraoperative hypothermia. CONCLUSIONS: Unintentional intraoperative hypothermia is common in patients who undergo surgery for oral cancer. Warming interventions to prevent intraoperative hypothermia for high-risk patients (older, lower weight, or more intraoperative bleeding) should be considered. Meanwhile, with careful nursing and rehabilitation instructions, intraoperative hypothermia does not lead to serious perioperative complications.

Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve injury, chemotherapy, and diabetes in mice.

BACKGROUND: Gut microbiota has been found involved in neuronal functions and neurological disorders. Whether and how gut microbiota impacts chronic somatic pain disorders remain elusive. METHODS: Neuropathic pain was produced by different forms of injury or diseases, the chronic constriction injury (CCI) of the sciatic nerves, oxaliplatin (OXA) chemotherapy, and streptozocin (STZ)-induced diabetes in mice. Continuous feeding of antibiotics (ABX) cocktail was used to cause major depletion of the gut microbiota. Fecal microbiota, biochemical changes in the spinal cord and dorsal root ganglion (DRG), and the behaviorally expressed painful syndromes were assessed. RESULTS: Under condition of gut microbiota depletion, CCI, OXA, or STZ treatment-induced thermal hyperalgesia or mechanical allodynia were prevented or completely suppressed. Gut microbiota depletion also prevented CCI or STZ treatment-induced glial cell activation in the spinal cord and inhibited cytokine production in DRG in OXA model. Interestingly, STZ treatment failed to induce the diabetic high blood glucose and painful hypersensitivity in animals with the gut microbiota depletion. ABX feeding starting simultaneously with CCI, OXA, or STZ treatment resulted in instant analgesia in all the animals. ABX feeding starting after establishment of the neuropathic pain in CCI- and STZ-, but not OXA-treated animals produced significant alleviation of the thermal hyeralgesia or mechanical allodynia. Transplantation of fecal bacteria from SPF mice to ABX-treated mice partially restored the gut microbiota and fully rescued the behaviorally expressed neuropathic pain, of which, Akkermansia, Bacteroides, and Desulfovibrionaceae phylus may play a key role. CONCLUSION: This study demonstrates distinct roles of gut microbiota in the pathogenesis of chronic painful conditions with nerve injury, chemotherapy and diabetic neuropathy and supports the clinical significance of fecal bacteria transplantation.

Overcoming Outcoupling Limit in Perovskite Light-Emitting Diodes with Enhanced Photon Recycling.

Photon recycling (PR), reabsorption and reemission of photons, can randomize the propagation direction of photons trapped in the waveguide mode and potentially increase the outcoupling efficiency of perovskite light-emitting diodes (PeLEDs). However, the contribution of PR in PeLEDs has not been experimentally quantified in real device structures. Here, we show that, with the PR effect, the external quantum efficiency (EQE) of PeLEDs remains above 15% with extraordinary thick perovskite layers up to 2200 nm, which is much higher than the outcoupling efficiency (4.3%) of the thick emissive layer device with an emission zone near the TPBi layer without PR. We designed monolithic device structures to experimentally quantify the PR contribution under device working conditions and reveal that the PR can contribute 2.4%-40.4% of the total emission in PeLEDs depending on film thickness. This work provides an important way of manipulation and quantification of PR contribution in perovskite optoelectronic devices.

Application of Platelet-Rich Fibrin Derivatives for Mandibular Third Molar Extraction Related Post-Operative Sequelae: A Systematic Review and Network Meta-Analysis.

PURPOSE: Leukocyte- and platelet-rich fibrin (L-PRF) and advanced-platelet-rich fibrin (A-PRF) that are derivatives of PRF (platelet-rich fibrin) accelerate wound healing and reduce postoperative sequelae after tooth extraction. This network meta-analysis aimed to investigate the effectiveness of L-PRF and A-PRF in mandibular third molar extraction and provide suggestions for alleviating postoperative symptoms and signs. METHODS: A comprehensive search of the literature was conducted in PubMed, Embase, Web of Science, and SinoMed databases up to Oct 9, 2020. Three types of randomized controlled trials were included to investigate the effects of PRF derivatives after extracting mandibular third molars: A-PRF and L-PRF groups; A-PRF and control groups; L-PRF and control groups. Their relative effectiveness and ranking were assessed using network meta-analysis and the surface under the cumulative ranking curve (SUCRA) with STATA 16.0 and Revman 5.3, respectively. RESULTS: Ten randomized controlled trials were included, with 307 mandibular third molar extraction patients involved. The results showed that A-PRF had the best effect among the 3 groups in improving postoperative pain on the third (SUCRA = 98.2%) and seventh (SUCRA = 88.4%) days; L-PRF promoted soft tissue healing (MD = -0.90, 95% CI [-1.40, -0.40], P = .0004) on the seventh day compared with the control. However, other comparisons showed no significant differences (P > .05). CONCLUSION: The limited results confirmed that PRF derivatives only reduced some postoperative symptoms and did not prevent them all. Application of A-PRF after third molar extraction reduced postoperative pain, and L-PRF improved the degree of soft tissue healing.

Neuro-immune interactions in inflammation and host defense: Implications for transplantation.

Sensory and autonomic neurons of the peripheral nervous system (PNS) play a critical role in regulating the immune system during tissue inflammation and host defense. Recent studies have identified the molecular mechanisms underlying the bidirectional communication between the nervous system and the immune system. Here, we highlight the studies that demonstrate the importance of the neuro-immune interactions in health and disease. Nociceptor sensory neurons detect immune mediators to produce pain, and release neuropeptides that act on the immune system to regulate inflammation. In parallel, neural reflex circuits including the vagus nerve-based inflammatory reflex are physiological regulators of inflammatory responses and cytokine production. In transplantation, neuro-immune communication could significantly impact the processes of host-pathogen defense, organ rejection, and wound healing. Emerging approaches to target the PNS such as bioelectronics could be useful in improving the outcome of transplantation. Therefore, understanding how the nervous system shapes the immune response could have important therapeutic ramifications for transplantation medicine.

Inhibition of YAP/TAZ Activity in Spinal Cord Suppresses Neuropathic Pain.

UNLABELLED: Neuropathic pain, often caused by nerve injury, is a major clinical challenge. Mechanisms that underlie neuropathic pain remain elusive and effective medications are limited. Numerous investigations of pain mechanisms have focused on alterations and phenotypic switches of the nociceptive transmitters and modulators, as well as on their receptors and downstream signaling pathways that have already exerted roles in the pain processes of mature nervous systems. We have demonstrated recently that nerve injury may elicit neuronal alterations that recapitulate events occurring during development. Signaling of the representative activated molecule Wnt thus becomes a trigger for the development of neuropathic pain and is a potential therapeutic target. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the ß-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status in rats. Peripheral nerve injury causes rapid-onset and long-lasting nuclear accumulation of YAP/TAZ/ß-catenin in the spinal dorsal horn. Spinal inhibition or knock-down of either YAP or TAZ suppresses mechanical allodynia induced by nerve injury or the pain initiators lysophosphatidic acid and Wnt3a. Promoting the nuclear accumulation of YAP/TAZ leads to mechanical hypersensitivity in naive animals. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/ß-catenin and can greatly suppress neuropathic pain and the associated neurochemical alterations. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening for potent analgesics for the treatment of neuropathic pain. SIGNIFICANCE STATEMENT: Mechanisms that underlie neuropathic pain remain elusive. We have demonstrated recently that nerve injury can activate Wnt signaling, which becomes a trigger for the development of neuropathic pain. We report that the transcriptional regulators YAP and TAZ, which orchestrate Wnt response via incorporation in the ß-catenin destruction complex, are key in the pathogenesis of neuropathic pain and may serve as an "ON-OFF" switch for neuropathic pain status. Further, we discovered a new small molecule, dCTB, which targets YAP/TAZ/ß-catenin and can greatly suppress neuropathic pain. Our study reveals that YAP and TAZ are core mechanisms underlying the pathogenesis of neuropathic pain and are targets in the screening of potent analgesics for the treatment of neuropathic pain.

The photoluminescence, thermal properties and tunable color of Na1-xAl1+2xSi1-2xO4:xCe3+/Tb3+/Dy3+via energy transfer: a single-component multicolor-emitting phosphor.

A series of emission-tunable Na1-xAl1+2xSi1-2xO4:xCe3+/Tb3+/Dy3+ phosphors were synthesized via a high temperature solid-state reaction method. Luminescence properties, energy transfer from Ce3+ to Tb3+ or Dy3+ ions, color tuning and thermal stability were systematically investigated. Particularly, the charge compensating defect generated by doping of rare earth ions was remedied through Al3+ substituted Si4+. Meanwhile, the emission intensity was significantly improved. The presence and content of various elements were demonstrated through data combined with the crystallographic data from Rietveld refinements and the analysis of SEM and mapping for each element. The results indicated that this charge balance strategy was an effective method. The energy transfer from Ce3+ to Tb3+ and Dy3+ in the co-doped NaAlSiO4 (NAS) samples was deduced from the spectral overlap between the Ce3+ emission and Tb3+/Dy3+ excitation spectra, the photoluminescence spectra and the fluorescence decay curves. The energy transfer mechanisms of Ce3+ to Tb3+ and Dy3+ in the host were studied. And the emission hue can be tuned from blue to green and yellow by properly varying the ratio of Ce3+ and Tb3+/Dy3+. Additionally, the temperature-dependent photoluminescence of the as-prepared phosphors was investigated in detail. All these properties indicate that the developed phosphor may potentially be used as a single-component multicolor-emitting phosphor for UV light-emitting diodes.

Association between COVID 19 exposure and expression of malignant pathological features in oral squamous cell carcinoma: A retrospective cohort study.

OBJECTIVES: To analyze the relationship between the clinical and pathological characters of OSCC and COVID 19 exposure. MATERIALS AND METHODS: A retrospective cohort study in patients with OSCC with or without COVID 19 was performed. A total of 200 OSCC patients treated with surgery from 2019 to 2023 were included. Clinical and pathological features were analysed between two groups. Characters with statistical difference were further analysed by performing univariate analysis and logistic regression analysis. RESULTS: The expression of Ki67 (n = 57, 71.3 %, P < 0.001) and CyclinD1 (n = 64, 80 %, P < 0.001) in OSCC with the exposure history of COVID 19 is higher than that in patients never exposed to COVID 19. COVID 19 exposure history is an independent influencing factor for higher expression of Ki67 (OR = 4.04, 95 % CI: 1.87-8.72, P < 0.001) and CyclinD1 (OR = 5.45, 95 % CI: 2.56-11.60, P < 0.001). CONCLUSION: COVID 19 may suggest more invasive malignant biological behavior of cancer cells in OSCC.

Interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma after hepatectomy: a multicenter population-based study.

An interactive model for predicting the oncological outcome of patients with early-stage huge hepatocellular carcinoma (ES-HHCC) after hepatectomy is still lacking. This study was aimed at exploring the independent risk parameters and developing an interactive model for predicting the cancer-specific survival (CSS) of ES-HHCC. Data from patients with ES-HHCC who underwent hepatectomy were collected. The dimensionality of the clinical features was reduced by least absolute shrinkage and selection operator regression and further screened as predictors of CSS by Cox regression. Then, an interactive prediction model was developed and validated. Among the 514 screened patients, 311 and 203 of them were assigned into the training and validation cohort, respectively. Six independent variables, including alpha-fetoprotein, cirrhosis, microvascular invasion, satellite, tumor morphology, and tumor diameter, were identified and incorporated into the prediction model for CSS. The model achieved C-indices of 0.724 and 0.711 in the training and validation cohorts, respectively. Calibration curves showed general consistency in both cohorts. Compared with single predictor, the model had a better performance and greater benefit according to the time-independent receiver operating characteristic curve and decision curve analysis (P < 0.05). The calculator owned satisfactory accuracy and flexible operability for predicting the CSS of ES-HHCC, which could serve as a practical tool to stratify patients with different risks, and guide decision-making.

Fast and slow: Recording neuromodulator dynamics across both transient and chronic time scales.

Neuromodulators transform animal behaviors. Recent research has demonstrated the importance of both sustained and transient change in neuromodulators, likely due to tonic and phasic neuromodulator release. However, no method could simultaneously record both types of dynamics. Fluorescence lifetime of optical reporters could offer a solution because it allows high temporal resolution and is impervious to sensor expression differences across chronic periods. Nevertheless, no fluorescence lifetime change across the entire classes of neuromodulator sensors was previously known. Unexpectedly, we find that several intensity-based neuromodulator sensors also exhibit fluorescence lifetime responses. Furthermore, we show that lifetime measures in vivo neuromodulator dynamics both with high temporal resolution and with consistency across animals and time. Thus, we report a method that can simultaneously measure neuromodulator change over transient and chronic time scales, promising to reveal the roles of multi-time scale neuromodulator dynamics in diseases, in response to therapies, and across development and aging.

Beyond conventional wisdom: unveiling quantitative insights in fluorescence lifetime imaging via realistic simulation of biological systems.

Fluorescence lifetime imaging microscopy (FLIM) and photometry (FLiP) are illuminating the dynamics of biological signals. Because fluorescence lifetime is an intensive property of a fluorophore that is insensitive to sensor expression levels, it excels over fluorescence intensity measurements by allowing comparison across animals, over chronic time periods, and quantitation of the absolute levels of biological signals. However, the insensitivity of lifetime to sensor expression level does not always hold true in biological experiments where autofluorescence, ambient light, dark currents and afterpulses of the detectors are present. To quantitatively evaluate the potential and limitations of fluorescence lifetime measurements, we introduce FLiSimBA, a flexible platform enabling realistic F luorescence Li fetime Sim ulation for B iological A pplications. FLiSimBA accurately recapitulates experimental data and provides quantitative analyses. Using FLiSimBA, we determine the photons required for minimum detectable differences in lifetime and quantify the impact of hardware innovation. Furthermore, we challenge the conventional view that fluorescence lifetime is insensitive to sensor expression levels and define the conditions in which sensor express levels do not result in statistically significant difference in biological experiments. Thus, we introduce an adaptable simulation tool that allows systematic exploration of parameters to define experimental advantages and limitations in biological applications. Moreover, we provide a statistical framework and quantitative insights into the impact of key experimental parameters on signal-to-noise ratio and fluorescence lifetime responses. Our tool and results will enable the growing community of FLIM users and developers to optimize FLIM experiments, expose limitations, and identify opportunities for future innovation of fluorescence lifetime technologies.

Near-field terahertz nonlinear optics with blue light.

The coupling of terahertz optical techniques to scattering-type scanning near-field microscopy (s-SNOM) has recently emerged as a valuable new paradigm for probing the properties of semiconductors and other materials on the nanoscale. Researchers have demonstrated a family of related techniques, including terahertz nanoscopy (elastic scattering, based on linear optics), time-resolved methods, and nanoscale terahertz emission spectroscopy. However, as with nearly all examples of s-SNOM since the technique's inception in the mid-1990s, the wavelength of the optical source coupled to the near-field tip is long, usually at energies of 2.5 eV or less. Challenges in coupling of shorter wavelengths (i.e., blue light) to the nanotip has greatly inhibited the study of nanoscale phenomena in wide bandgap materials such as Si and GaN. Here, we describe the first experimental demonstration of s-SNOM using blue light. With femtosecond pulses at 410 nm, we generate terahertz pulses directly from bulk silicon, spatially resolved with nanoscale resolution, and show that these signals provide spectroscopic information that cannot be obtained using near-infrared excitation. We develop a new theoretical framework to account for this nonlinear interaction, which enables accurate extraction of material parameters. This work establishes a new realm of possibilities for the study of technologically relevant wide-bandgap materials using s-SNOM methods.

End-to-End Video-to-Speech Synthesis Using Generative Adversarial Networks.

Video-to-speech is the process of reconstructing the audio speech from a video of a spoken utterance. Previous approaches to this task have relied on a two-step process where an intermediate representation is inferred from the video and is then decoded into waveform audio using a vocoder or a waveform reconstruction algorithm. In this work, we propose a new end-to-end video-to-speech model based on generative adversarial networks (GANs) which translates spoken video to waveform end-to-end without using any intermediate representation or separate waveform synthesis algorithm. Our model consists of an encoder-decoder architecture that receives raw video as input and generates speech, which is then fed to a waveform critic and a power critic. The use of an adversarial loss based on these two critics enables the direct synthesis of the raw audio waveform and ensures its realism. In addition, the use of our three comparative losses helps establish direct correspondence between the generated audio and the input video. We show that this model is able to reconstruct speech with remarkable realism for constrained datasets such as GRID, and that it is the first end-to-end model to produce intelligible speech for Lip Reading in the Wild (LRW), featuring hundreds of speakers recorded entirely "in the wild." We evaluate the generated samples in two different scenarios-seen and unseen speakers-using four objective metrics which measure the quality and intelligibility of artificial speech. We demonstrate that the proposed approach outperforms all previous works in most metrics on GRID and LRW.

Self-Supervised Video-Centralised Transformer for Video Face Clustering.

This article presents a novel method for face clustering in videos using a video-centralised transformer. Previous works often employed contrastive learning to learn frame-level representation and used average pooling to aggregate the features along the temporal dimension. This approach may not fully capture the complicated video dynamics. In addition, despite the recent progress in video-based contrastive learning, few have attempted to learn a self-supervised clustering-friendly face representation that benefits the video face clustering task. To overcome these limitations, our method employs a transformer to directly learn video-level representations that can better reflect the temporally-varying property of faces in videos, while we also propose a video-centralised self-supervised framework to train the transformer model. We also investigate face clustering in egocentric videos, a fast-emerging field that has not been studied yet in works related to face clustering. To this end, we present and release the first large-scale egocentric video face clustering dataset named EasyCom-Clustering. We evaluate our proposed method on both the widely used Big Bang Theory (BBT) dataset and the new EasyCom-Clustering dataset. Results show the performance of our video-centralised transformer has surpassed all previous state-of-the-art methods on both benchmarks, exhibiting a self-attentive understanding of face videos.

Efficient Colon Cancer Immunogene Therapy Through Co-Delivery of IL-22BP mRNA and Tumor Cell Lysate by CLSV Nanoparticles.

Background: Messenger ribonucleic acid (mRNA)-based gene therapy has great potential in cancer treatment. However, the application of mRNA-based cancer treatment could be further developed. Elevated delivery ability and enhanced immune response are advantages for expanding the application of mRNA-based cancer therapy. It is crucial that the prepared carrier can cause an immune reaction based on the efficient delivery of mRNA. Methods: We reported DMP nanoparticle previously, which was obtained by the self-assembly of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL). Research demonstrated that DMP can deliver mRNA, siRNA, and plasmid. And it is applied to various tumor types. In our work, the tumor cell lysate was introduced to the internal DMP chain, fusing cell-penetrating peptides (CPPs) modification on the surface forming the CLSV system. And then mixed encoded IL-22BP (interleukin-22 binding protein) mRNA and CLSV to form CLSV/IL-22BP complex. Results: The size of the CLSV system was 213.2 nm, and the potential was 45.7 mV. The transfection efficiency of the CLSV system is up to 76.45% in C26 cells via the micropinocytosis pathway. The CLSV system also could induce an immune response and significantly elevate the expression of CD80, CD86, and MHC-II in vivo. Then, by binding with IL-22BP (Interleukin-22 binding protein) mRNA, the CLSV/IL-22BP complex inhibited tumor cell growth, with an inhibition rate of up to 82.3% in vitro. The CLSV/IL-22BP complex also inhibited tumor growth in vivo, the tumor cell growth inhibition up to 75.0% in the subcutaneous tumor model, and 84.9% in the abdominal cavity metastasis tumor model. Conclusion: Our work demonstrates that the CLSV system represents a potent potential for mRNA delivery.