Determination of extracellular proteinase in L. helveticus Lh191404 based on whole genome sequencing and proteomics analysis.

Lactobacillus helveticus exhibits a remarkable proteolytic system. However, the etiology of these protein hydrolysis characteristics, whether caused by extracellular proteinases (EP) or cell envelope proteinases (CEP), has been puzzling researchers. In this study, third-generation Nanopore whole genome sequencing and proteomics analysis were used to unravel the root cause of the aforementioned confusion. The genome of L. helveticus Lh191404 was 2,117,643 bp in length, with 67 secreted proteins were found. Combined with proteomic analysis, it was found that the protein composition of extraction from CEP and EP were indeed the same substance. Bioinformatics analysis indicated that the CEP belonged to the PrtH1 Variant (PrtH1_V) genotype by phylogenetic analysis. The three-dimensional structures of various domains within the PrtH1_V-191404 had been characterized, providing a comprehensive understanding of its structural features. Results of proteinase activity showed that the optimal reaction temperature was 40 °C, with a pH of 6.50. These findings suggested that the origin of EP in L. helveticus Lh191404 may be due to CEP being released into the substrate after detaching from the cell wall. This research is of guiding significance for further understanding the operational mechanism of the protein hydrolysis system in lactic acid bacteria.

Donor-Acceptor Copolymer with a Linear Backbone Induced Ordered and Robust Doping Morphology for Efficient and Stable Organic Electrochemical Devices.

Donor (D)-acceptor (A) copolymer-based organic mixed ionic-electronic conductors (OMIECs) exhibit intrinsic environmental stability for they have tailored energy levels. However, their figure-of-merit (µC*) is still falling behind the D-D polymers because of morphology deterioration during the electrochemical doping process. Herein, we developed two D-A copolymers with precisely regulated backbone curvature, namely PTBT-P and PTTBT-P. Compared to the curved PTBT-P and previously reported copolymers, PTTBT-P better keeps its backbone linear, leading to a long-range ordered doping morphology, which is revealed by the in operando X-ray technique. This optimized doping morphology enables a significantly improved operando charge mobility (µ) of 2.44 cm2 V-1 s-1 and a µC* value of 342 F cm-1 V-1 s-1, one of the highest values in D-A copolymer based on OECTs. Besides, we fabricated PTTBT-P-based electrochemical random-access memories and achieved ideal and robust conductance modulation. This study highlights the critical role of backbone curvature control in the optimization of doping morphology for efficient and robust organic electrochemical devices.

Engineered Bacterial Biomimetic Vesicles Reprogram Tumor-Associated Macrophages and Remodel Tumor Microenvironment to Promote Innate and Adaptive Antitumor Immune Responses.

Tumor-associated macrophages (TAMs) are among the most abundant infiltrating leukocytes in the tumor microenvironment (TME). Reprogramming TAMs from protumor M2 to antitumor M1 phenotype is a promising strategy for remodeling the TME and promoting antitumor immunity; however, the development of an efficient strategy remains challenging. Here, a genetically modified bacterial biomimetic vesicle (BBV) with IFN-γ exposed on the surface in a nanoassembling membrane pore structure was constructed. The engineered IFN-γ BBV featured a nanoscale structure of protein and lipid vesicle, the existence of rich pattern-associated molecular patterns (PAMPs), and the costimulation of introduced IFN-γ molecules. In vitro, IFN-γ BBV reprogrammed M2 macrophages to M1, possibly through NF-κB and JAK-STAT signaling pathways, releasing nitric oxide (NO) and inflammatory cytokines IL-1ß, IL-6, and TNF-α and increasing the expression of IL-12 and iNOS. In tumor-bearing mice, IFN-γ BBV demonstrated a targeted enrichment in tumors and successfully reprogrammed TAMs into the M1 phenotype; notably, the response of antigen-specific cytotoxic T lymphocyte (CTL) in TME was promoted while the immunosuppressive myeloid-derived suppressor cell (MDSC) was suppressed. The tumor growth was found to be significantly inhibited in both a TC-1 tumor and a CT26 tumor. It was indicated that the antitumor effects of IFN-γ BBV were macrophage-dependent. Further, the modulation of TME by IFN-γ BBV produced synergistic effects against tumor growth and metastasis with an immune checkpoint inhibitor in an orthotopic 4T1 breast cancer model which was insensitive to anti-PD-1 mAb alone. In conclusion, IFN-γ-modified BBV demonstrated a strong capability of efficiently targeting tumor and tuning a cold tumor hot through reprogramming TAMs, providing a potent approach for tumor immunotherapy.

Application effect of behavioral cognition combined with psychological intervention on orthodontic patients: A prospective, randomized, controlled trial.

To explore the application effect of behavioral cognition combined with psychological intervention in orthodontic patients, so as to provide new ideas for clinical nursing of orthodontic patients. The 70 patients with orthodontic treatment were divided into 2 groups: the control group and the nursing group. Control group received routine clinical intervention, was treated with the normal clinical intervention, while nursing group was treated with behavior cognition and psychology intervention. The orthodontic effects of the 2 groups were evaluated, and the mental state, health behavior, gum swelling and pain were compared between the 2 groups before and after care. The cure rate of orthodontic treatment in the nursing group was significantly higher than that in the control group (P < .05). At 12 months after intervention, the nursing group scored lower than the control group on the Hamilton Anxiety Scale and the Hamilton Depression Scale (P < .05), and the score of Health Promotion Lifestyle Profile-II was higher than that in the control group (P < .05). After intervention, the degree of gum swelling and pain in 2 group were notably relieved, and the alleviation degree of nursing group was better than that of control group (P < .05). Compared with normal clinical intervention, the behavioral cognition combined with psychological intervention have obvious improvement in mental state and health behavior of orthodontic patients, and can reduce the symptoms of gum swelling and pain, promote the recovery of gum, showing high clinical application value in improving the gingival health of patients.

Exploiting immunostimulatory mechanisms of immunogenic cell death to develop membrane-encapsulated nanoparticles as a potent tumor vaccine.

Vaccine is one of the most promising strategies for cancer immunotherapy; however, there are no therapeutic cancer vaccine achieving significant clinical efficacy till now. The main limiting factors include the immune suppression and escape mechanisms developed by tumor and not enough capacity of vaccines to induce a vigorous anti-tumor immunity. This study aimed to develop a strategy of membrane-based biomimetic nanovaccine and investigate the immunological outcomes of utilizing the unique immunostimulatory mechanisms derived of immunogenic cell death (ICD) and of fulfilling a simultaneous nanoscale delivery of a highlighted tumor antigen and broad membrane-associated tumor antigens in the vaccine design. TC-1 tumor cells were treated in vitro with a mixture of mitoxantrone and curcumin for ICD induction, and then chitosan (CS)-coated polylactic co-glycolic acid (PLGA) nanoparticles loaded with HPV16 E744-62 peptides were decorated with the prepared ICD tumor cell membrane (IM); further, the IM-decorated nanoparticles along with adenosine triphosphate (ATP) were embedded with sodium alginate (ALG) hydrogel, And then, the immunological features and therapeutic potency were evaluated in vitro and in vivo. The nanovaccine significantly stimulated the migration, antigen uptake, and maturation of DCs in vitro, improved antigen lysosome escape, and promoted the retention at injection site and accumulation in LNs of the tumor antigen in vivo. In a subcutaneously grafted TC-1 tumor model, the therapeutic immunization of nanovaccine elicited a dramatical antitumor immunity. This study provides a strategy for the development of tumor vaccines.

Ultrahigh-resolution and ultra-simple fiber-optic sensor with resonant Sagnac interferometer.

The resonant fiber-optic sensor (RFOS) is well known for its high sensing resolution but usually suffers from high cost and system complexity. In this Letter, we propose an ultra-simple white-light-driven RFOS with a resonant Sagnac interferometer. By superimposing the output of multiple equivalent Sagnac interferometers, the strain signal is amplified during the resonance. A 3 × 3 coupler is employed for demodulation, by which the signal under test can be read out directly without any modulation. With 1 km delay fiber and ultra-simple configuration, a strain resolution of 28f ε/Hz at 5 kHz is demonstrated in the experiment, which is among the highest, to the best of our knowledge, resolution optical fiber strain sensors.

ß-Cyclodextrin network crosslinked by novel phosphonium-based tetrakiscarboxylic acid derived from PH3 tail gas: Synthesis and application for rapid removal of organic dyes from wastewater.

Organic dyes, such as methyl orange (MO), Congo red (CR), crystal violet (CV) and methylene blue (MB), are common organic pollutants existing in wastewater. Therefore, the exploration of bio-based adsorbents for the efficient removal of organic dyes from wastewater has gained many attentions. Here, we report a PCl3-free synthetic method for the synthesis of phosphonium-containing polymers, in which the prepared tetrakis(2-carboxyethyl) phosphonium chloride-crosslinked ß-cyclodextrin (TCPC-ß-CD) polymers were applied to the removal of dyes from water. The effects of contact time, pH (1-11), and dye concentration were investigated. The selected dye molecules could be captured by the host-gest inclusion of ß-CD cavities, and the phosphonium and carboxyl groups in the polymer structure would respectively facilitate the removal of cationic dyes (MB and CV) and anionic dyes (MO and CR) via electrostatic interactions. In a mono-component system, over 99 % of MB could be removed from water within the first 10 min. Based on the Langmuir model, the calculated maximum adsorption capacities of MO, CR, MB, and CV were 180.43, 426.34, 306.57, and 470.11 mg/g (or 0.55, 0.61, 0.96 and 1.15 mmol/g), respectively. Additionally, TCPC-ß-CD was easily regenerated using 1 % HCl in ethanol, and the regenerative adsorbent still showed high removal capacities for MO, CR, and MB even after seven treatment cycles.

Navigation-grade three-axis resonant fiber-optic gyroscope employing a multiplexed source.

A three-axis gyroscope is a vital component of an inertial measurement unit that can measure the rotation rates in three directions simultaneously. A novel three-axis resonant fiber-optic gyroscope (RFOG) configuration with a multiplexed broadband light source is proposed and demonstrated. The output light from the two vacant ports of the main gyroscope is reused as drive sources for the other two axial gyroscopes, which effectively improve the power utilization of the source. The interference between different axial gyroscopes is effectively avoided by optimizing the lengths of three fiber-optic ring resonators (FRRs) rather than by inserting other optical elements in the multiplexed link. With the optimal lengths, the influence of the input spectrum on the multiplexed RFOG is suppressed and a theoretical temperature dependence of the bias error as low as 1.08 × 10-4 °/h/°C is obtained. Finally, a navigation-grade three-axis RFOG is demonstrated with a fiber coil length of ∼100 m for each FRR.

Broadband source-driven resonant micro-optic gyroscope based on a multi-turn waveguide-type ring resonator.

The resonant micro-optic gyroscope (RMOG) is one of the most promising candidates for chip-scale optoelectronic gyroscopes. A broadband source-driven RMOG based on a multi-turn waveguide-type ring resonator (WRR) has been proposed and demonstrated. The theoretical sensitivity is enhanced with the multi-turn structure, while the parasitic backscattering can be resolved by the use of the broadband source, thus greatly improving the long-term bias stability of the RMOG. We also reduce the relative intensity noise (RIN)-induced error of the broadband source at the gyro output by optimizing the number of loop turns of the WRR, and improve the angle random walk (ARW) by 4.8 dB compared with the case of a single-turn WRR. Finally, a bias stability of 1°/h is obtained with a 5-turn WRR of 4.05 cm diameter, achieving the tactical-grade resolution. To the best of our knowledge this is the best result reported to date for an RMOG of similar size.

A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice.

Innate immune cells are critical in antitumor immune surveillance and the development of antitumor adaptive cellular immunity. Trained innate immune cells demonstrate immune memory-like characteristics, producing more vigorous immune responses to secondary homologous or heterologous stimuli. This study aimed to investigate whether inducing trained immunity is beneficial when using a tumor vaccine to promote antitumor adaptive immune responses. A biphasic delivery system was developed with the trained immunity inducer Muramyl Dipeptide (MDP) and specific tumor antigen human papillomavirus (HPV) E7 peptide encapsulated by poly(lactide-co-glycolide)-acid(PLGA) nanoparticles (NPs), and the NPs along with another trained immunity agonist, ß-glucan, were further embedded in a sodium alginate hydrogel. The nanovaccine formulation demonstrated a depot effect for E7 at the injection site and targeted delivery to the lymph nodes and dendritic cells (DCs). The antigen uptake and maturation of DCs were significantly promoted. A trained immunity phenotype, characterized by increased production of IL-1ß, IL-6, and TNF-α, was induced in vitro and in vivo in response to secondary homologous or heterologous stimulation. Furthermore, prior innate immune training enhanced the antigen-specific INF-γ-expressing immune cell response elicited by subsequent stimulation with the nanovaccine. Immunization with the nanovaccine completely inhibited the growth of TC-1 tumors and even abolished established tumors in mice. Mechanistically, the inclusion of ß-glucan and MDP significantly enhanced the responses of tumor-specific effector adaptive immune cells. The results strongly suggest that the controlled release and targeted delivery of an antigen and trained immunity inducers with an NP/hydrogel biphasic system can elicit robust adaptive immunity, which provides a promising tumor vaccination strategy.

Engineered Norovirus-Derived Nanoparticles as a Plug-and-Play Cancer Vaccine Platform.

In recent years, virus-derived self-assembled protein nanoparticles (NPs) have emerged as attractive antigen delivery platforms for developing both preventive and therapeutic vaccines. In this study, we exploited the genetically engineered Norovirus S domain (Nov-S) with SpyCatcher003 fused to the C-terminus to develop a robust, modular, and versatile NP-based carrier platform (Nov-S-Catcher003). The NPs can be conveniently armed in a plug-and-play pattern with SpyTag003-linked antigens. Nov-S-Catcher003 was efficiently expressed in Escherichia coli and self-assembled into highly uniform NPs with a purified protein yield of 97.8 mg/L. The NPs presented high stability at different maintained temperatures and after undergoing differing numbers of freeze-thaw cycles. Tumor vaccine candidates were easily obtained by modifying Nov-S-Catcher003 NPs with SpyTag003-linked tumor antigens. Nov-S-Catcher003-antigen NPs significantly promoted the maturation of bone marrow-derived dendritic cells in vitro and were capable of efficiently migrating to lymph nodes in vivo. In TC-1 and B16F10 tumor-bearing mice, the subcutaneous immunization of NPs elicited robust tumor-specific T-cell immunity, reshaped the tumor microenvironment, and inhibited tumor growth. In the TC-1 model, the NPs even completely abolished established tumors. In conclusion, the Nov-S-Catcher003 system is a promising delivery platform for facilitating the development of NP-based cancer vaccines.

Brain-Derived Neurotrophic Factor Regulates Differentiation of Stem Cells From Human Exfoliated Deciduous Teeth Through Growth Factor Receptor-Bound Protein 2-Extracellular Signal-Regulated Kinase Signaling Pathway.

OBJECTIVES: Stem cells from human exfoliated deciduous teeth are a population of multipotent mesenchymal stem cells that can self-renew and actively secrete a broad spectrum of trophic and immunomodulatory factors.Brain-derivedneurotrophic factor is able to induce stem cells to neural differentiation to repair the nervous system. However,the mechanism ofbrain-derivedneurotrophic factor-induced neural differentiation in stem cells from human exfoliated deciduous teeth remains unclear. MATERIALS AND METHODS: In this study, we focused on brain-derived neurotrophic factor and investigated its effects on neural differentiation in stem cells from human exfoliated deciduous teeth. We cultured stem cells from human exfoliated deciduous teeth under various different brain-derived neurotrophic factor concentrations. We then analyzed the effects of brain-derived neurotrophic factor to the neural differen-tiation and associated signaling pathways in stem cells from human exfoliated deciduous teeth. RESULTS: We demonstrated that a high concentration of brain-derived neurotrophic factor could induce neural differentiation in stem cells from human exfoliated deciduous teeth, and brain-derived neurotrophic factor also increased the expression levels of neural differentiation-related proteins in stem cells from human exfoliated deciduous teeth, which was associated with the suppression of growth factor receptor-bound protein 2/extracellular signal-regulated kinase 1 and 2 signaling pathways. CONCLUSIONS: Knockdown of growth factor receptor- bound protein 2 inhibited the neural differentiation of stem cells from human exfoliated deciduous teeth via changes in growth factor receptor-bound protein 2/extracellular signal-regulated kinase signaling pathways, but this phenotype could be rescued by overexpression of extracellular signal-regulated kinase. Our findings suggested that brain-derived neurotrophic factor can regulate the differentiation of stem cells from human exfoliated deciduous teeth through the growth factor receptor-bound protein 2/extracellular signal-regulated kinase signaling pathway.

A new personalized vaccine strategy based on inducing the pyroptosis of tumor cells in vivo by transgenic expression of a truncated GSDMD N-terminus.

The variability and heterogeneity of tumor antigens and the tumor-driven development of immunosuppressive mechanisms leading to tumor escape from established immunological surveillance. Here, the tumor cells were genetically modified to achieve an inducible overexpression of the N-terminal domain of gasdermin D (GSDMD-NT) and effectively cause pyroptosis under a strict control. Pyroptotic tumor cells release damage-associated molecular patterns (DAMPs) and inflammatory cytokines to promote the maturation and migration of bone marrow-derived dendritic cells (BMDCs). Furthermore, local tumor delivery, and preventive or therapeutic subcutaneous immunization of the modified cells, followed by the induction of GSDMD-NT expression, significantly stimulated both the systemic and local responses of antitumor immunity, and reprogrammed the tumor microenvironment, leading to the dramatic suppression of tumor growth in mice. This study has explored the application potency of inducing the pyroptosis of tumor cells in the field of tumor immunotherapy, especially for developing a new and promising personalized tumor vaccine.

Performance of a resonant fiber-optic gyroscope based on a broadband source.

A resonant fiber-optic gyroscope (RFOG) based on a broadband source can avoid the fundamental drawback of coherence detection processing while possessing the greater sensitivity afforded by the finesse of the fiber-optic ring resonator. In this paper, the basic operation principle is presented and demonstrated in detail, and various noise sources, as well as the temperature effect encountered in this broadband source-driven RFOG, are studied and analyzed. Then a combined modulation technique is proposed to suppress the residual backscattering noise. To further reduce the effect of temperature transience, an asymmetric fiber ring resonator is designed. In the experiment, a bias stability of 0.01°/h is successfully demonstrated with a 100 m-long fiber ring resonator of 8 cm diameter in a laboratory environment without temperature control.

Quasi-distributed fiber-optic acoustic sensor based on a low coherence light source: publisher's note.

This publisher's note contains a correction to Opt. Lett.47, 3780 (2022)10.1364/OL.464020.

Reduction of relative intensity noise in a broadband source-driven RFOG using a high-frequency modulation technique.

A broadband source-driven resonant fiber-optic gyroscope (RFOG) can reduce coherence-related noise, thus achieving a better sensitivity with a much simpler configuration than the traditional system with a coherent source. Its detection sensitivity, however, is still limited by the excess relative intensity noise (RIN) of the broadband source. In this paper, the RIN error mechanism in this broadband source-driven RFOG is revealed and countermeasures are presented. We demonstrate that the use of a high-finesse fiber-optic ring resonator and a high-frequency modulation-demodulation technique can reduce the RIN-induced error. It is indicated that the optimal modulation parameters can provide a RIN-induced error reduction of 6.1 dB, allowing the broadband source-driven RFOG to operate near the shot-noise-limited theoretical sensitivity. With the optimal high-frequency modulation-demodulation technique, an angle random walk of 0.0013°/√h is achieved with a 200-m-long fiber-optic ring resonator of 7.6 cm diameter. This is the best result reported to date, to the best of our knowledge, for fiber-optic gyroscopes of this size.

Prognostic Significance of Small Pulmonary Vessel Alteration Measured by Chest Computed Tomography in Connective Tissue Diseases With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by structural alterations of pulmonary vessels. Few studies have explored the clinical significance of quantitative assessment of pulmonary small vessels by chest computed tomography (CT). Our aim was to assess whether the prognosis of connective tissue diseases (CTD)-PAH patients could be assessed through pulmonary small vessels measured by chest CT. METHODS: In all, 42 CTD-PAH patients diagnosed based on right heart catheterization were retrospectively investigated. All patients underwent a chest CT within 1 month before and after right heart catheterization examination. Main pulmonary artery (MPA) and the cross-sectional area of small pulmonary vessels <5 mm2 as a percentage of total lung area (%CSA <5) were measured. The primary endpoint was a composite clinical worsening endpoint. RESULTS: After a median follow-up time of 30.5 (interquartile range, 8.5 to 45.25) months, endpoint events occurred in 16 (38.1%) patients after 19.5 (interquartile range, 10.0 to 45.5) months. Cox univariate proportional hazard analysis showed that pulmonary vascular resistance, MPA diameter, and %CSA <5 were associated with the end point. A combination of MPA diameter and %CSA < 5 was the independent risk factor for the prognosis (hazard ratio, 2.180 [95% confidence interval, 1.405-3.383], P=0.001). Kaplan-Meier analysis showed that CTD-PAH patients satisfying %CSA < 5 of <0.382 and MPA >36.75 mm had the highest risk of experiencing the endpoint. CONCLUSION: Among the pulmonary vascular indicators measured by chest CT, in addition to MPA, %CSA < 5 may be a potential independent risk factor for poor long-term prognosis in Chinese CTD-PAH patients.

Femto-strain resolution fiber-optic sensing with an ultra-simple white-light round trip filtering method.

In the past decade, laser-driven resonant fiber-optic sensors (RFOSs) have been reported touching their ultimate resolution limit. The practicability of these high-performance sensors is, however, discounted because of high system complexity and dependence on narrow-linewidth lasers. In this paper, a novel, to the best of our knowledge, white-light-driven RFOS is established based on a round trip filtering (RTF) method. Via measuring the RTF loss of an add-drop fiber ring resonator (FRR) sensor, strain signal can be read out with an ultra-simple open-loop configuration. In the sensing experiment, even a resolution of several femto-strain around 1 kHz is demonstrated, representing the highest resolution level of RFOS to date. Thanks to the obvious superiority in both resolution, simplicity, and cost over traditional laser-driven RFOSs, the proposed white-light-driven RFOS is believed to be a milestone in the development of fiber-optic strain sensors.

Quasi-distributed fiber-optic acoustic sensor based on a low coherence light source.

A quasi-distributed acoustic sensor using in-line weak reflectors and a low coherence light source is presented. The dynamic strain is retrieved from the phase change of the two interfering light beams reflected by the same weak reflector. In the experiments, two vibrations at different channels along a weak reflector array are successfully detected simultaneously. A strain resolution of 50 pɛ/H z with 20-m interval is achieved in experiments, and no cross talk is observed. With simple system configuration and low cost, this approach provides a new, to the best of our knowledge, solution for quasi-distributed acoustic sensing.

Pico-strain resolution fiber-optic sensor with white-light interferometry.

The fiber Bragg grating (FBG) sensor is well known for simple fabrication, absolute measurement, inherent multiplexing capability, etc. To date, most FBG sensors that use a broadband light source for demodulation can only achieve resolution at the µÉ› level. In this Letter, we propose a white-light-driven self-reference sensing system with FBGs, using a Mach-Zehnder interferometer (MZI) and a white light source, to realize multiplexed high-resolution vibration sensing with a very simple system configuration. A strain resolution of 35p ε/Hz at 1 kHz is demonstrated, which is several orders of magnitude better than the current FBG sensor systems with white light sources. The performance of the sensing system is analyzed, and multiplexing capability is also experimentally evaluated; there is no observable cross talk.