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Abstract Background To explore the associations of computed tomography (CT) image features with the serum cryptococcal antigen (CrAg) titers measured by the lateral flow assay (LFA) in localized pulmonary cryptococcosis patients. Methods A retrospective analysis of patients with pathologically confirmed pulmonary cryptococcosis admitted to the First Affiliated Hospital of Xiamen University from January 2016 to December 2022 was performed. Clinical data, CT results, serum CrAg-LFA test results, and follow-up data were collected and analyzed. Results A total of 107 patients with localized pulmonary cryptococcosis were included, of which 31 had a single lesion in chest CT and the other 76 had multiple lesions. The positivity rate was (94.74% vs 64.52%) and titers of serum CrAg-LFA (1.77 ± 0.87 vs 0.91 ± 0.98) in the multiple lesion group were higher than those in the single lesion group, respectively. Multivariate linear regression analysis showed that the serum CrAg titers were positively associated with the number of lesions (β, 0.08; 95% CI, 0.05 to 0.12) and the lesion size (β, 0.40; 95% CI, 0.31 to 0.50) after adjusting other covariates. The serum CrAg-LFA titers of 60 pulmonary cryptococcosis patients showed a decreasing trend with the reduction in pulmonary lesion size after effective therapy. Conclusion In pulmonary cryptococcosis patients, the number and size of lung lesions are positively correlated with the titers of the serum CrAg-LFA test. The CrAg-LFA test could be a useful tool for the diagnosis, severity assessment, and therapeutic monitoring of localized pulmonary cryptococcosis patients.

Abstract In addressing the challenge of ships being prone to occlusion in multi‐target situations during ship target detection, leading to missed and false detections, this paper proposes an enhanced ship detection algorithm for YOLOv7‐tiny. The proposed method incorporates several key modifications. Firstly, it introduces the Convolutional Block Attention Module in the Backbone section of the original model, emphasizing position information while attending to channel features to enhance the network's ability to extract crucial information. Secondly, it replaces standard convolution with GSConv convolution in the Neck section, preserving detailed information and reducing computational load. Subsequently, the lightweight operator Content‐Aware ReAssembly of Features is employed to replace the original nearest‐neighbour interpolation, mitigating the loss of feature information during the up‐sampling process. Finally, the localization loss function, SIOU Loss, is utilized to calculate loss, expedite training convergence, and enhance detection accuracy. The research results indicate that the precision of the improved model is 91.2%, mAP@0.5 is 94.5%, and the F1‐score is 90.7%. These values are 3.7%, 5.5%, and 4.2% higher than those of the original YOLOv7‐tiny model, respectively. The improved model effectively enhances detection accuracy. Additionally, the improved model achieves an FPS of 145.4, meeting real‐time requirements.

Background: Transanal total mesorectal excision has emerged as a potential solution to certain limitations associated with laparoscopic total mesorectal excision in rectal cancer patients. Differences in surgical approaches have raised questions regarding their impact on the risk of postoperative urinary retention, with limited data available from large scale randomized clinical study. Objective: To report incidence of postoperative urinary retention and evaluate the associated risk factors for transanal total mesorectal excision. Design: In this randomized controlled trial (ClinicalTrials. gov NCT06147492), we retrieved 524 patients who received total mesorectal excision (TME) for stage I–III rectal cancer between June 2019 and April 2022, and the patients were randomly assigned in a 1:1 ratio to undergo either taTME or laTME. Patients: We enrolled 524 patients who underwent total mesorectal excision for stage I–III rectal cancer between June 2019 and April 2022. Main outcome measures: The incidence of postoperative urinary retention. Results: Among the 524 enrolled patients, 261 were randomized to the laTME group, while 263 were were randomized the taTME group. The median age was 58 years, and 340 participants (64.8 %) were male. Notably, 37 individuals (7.0 %) experienced postoperative urinary retention during the follow-up period, with no significant disparity was observed between the taTME and laTME groups (6.8 % and 7.2 %, respectively, P = 0.98). Risk factors associated with PUR in patients following taTME encompassed early removal of the urinary catheter (P = 0.006), net infusion rate >4.09 ml kg−1.h−1 (P = 0.006), and an age surpassing 65 years (P = 0.0321). Limitations: The generalizability of the findings outside specialist rectal cancer centers may be limited. Conclusions: Transanal total mesorectal excision was not found to heighten the risk of postoperative urinary retention. Nonetheless, it is advisable removing postoperative catheter beyond the initial day and exercising caution in the administration of intravenous fluids in clinical practice for taTME procedures.

Abstract To study the braking process of the train under different adhesion conditions, this paper takes the braking system of a single rail vehicle as the research object. The author establishes a corresponding co‐simulation platform based on MATLAB/Simulink and AMESim, including the sub‐models of braking control, vehicle brake longitudinal dynamics and air brake unit. Considering the cleaning effect caused by large sliding, the author builds a suitable adhesion model for different adhesion conditions based on the improved Polach model, which is the input of the vehicle braking longitudinal dynamics sub‐model. Based on the finite state machine, the anti‐skid control algorithm of the train is constructed as the core of the brake control sub‐model, which can judge the motion state of the wheelset, and control the stage release and hold of the brake cylinder pressure. According to the International Standard EN15595 and the actual operating parameters of a certain type of train, the braking process of the train under dry and wet rail conditions is simulated on the platform. The validity of the model is verified, which provides a reliable method for future research on the braking process.

Besides all sharing an extraordinary high (i.e., up to ~450 times) sweetening power as compared to sucrose and while presenting strong similarities in their molecular structures, molecules belonging to the family of diterpene glycosides (i.e., the secondary metabolites of Stevia rebaudiana) differ in specific structural details that strongly impact on their levels of sweetness and bitter aftertaste. Given the nutritional and pharmacological benefits of steviol secondary metabolites as natural dietetic and anti-diabetic remedies, extraction and purification of steviol glycosides from plant material are nowadays widely spread among many countries. However, an unpleasant bitter aftertaste, which is linked to a genetic variation in human bitter taste receptors, hampers the full exploitation of such benefits and calls for a prompt improvement in organoleptic property control of stevia products. A deeper understanding of the molecular structure of different steviol glycosides and the consequent development of promptly measurable criteria for the organoleptic performance of their mixtures will support processing optimization and control of taste profiles within desired yields. The present research aimed at establishing Raman spectroscopic algorithms for quantitative characterizations of raw stevia-based sweetener products. First, a series of twelve high-purity diterpene glycosides were analyzed by high spectrally resolved Raman spectroscopy and their spectra analyzed in order to establish a complete Raman library of molecular structures. Then, quantitative spectroscopic parameters were built up and applied to characterize the organoleptic property of five different commercially available samples including the recently developed Rebaudioside M isoform. Raman spectroscopy was confirmed as a versatile analytical technique that could be used for quantitative quality control tasks on the production line and for prompt in situ characterizations of purchased products.

Abstract The search for topological superconductivity (TSC) is currently an exciting pursuit, since non-trivial topological superconducting phases could host exotic Majorana modes. However, the difficulty in fabricating proximity-induced TSC heterostructures, the sensitivity to disorder and stringent topological restrictions of intrinsic TSC place serious limitations and formidable challenges on the materials and related applications. Here, we report a new type of intrinsic TSC, namely intrinsic surface topological superconductivity (IS-TSC) and demonstrate it in layered AuSn4 with T c of 2.4 K. Different in-plane and out-of-plane upper critical fields reflect a two-dimensional (2D) character of superconductivity. The two-fold symmetric angular dependences of both magneto-transport and the zero-bias conductance peak (ZBCP) in point-contact spectroscopy (PCS) in the superconducting regime indicate an unconventional pairing symmetry of AuSn4. The superconducting gap and surface multi-bands with Rashba splitting at the Fermi level (E F ), in conjunction with first-principle calculations, strongly suggest that 2D unconventional SC in AuSn4 originates from the mixture of p-wave surface and s-wave bulk contributions, which leads to a two-fold symmetric superconductivity. Our results provide an exciting paradigm to realize TSC via Rashba effect on surface superconducting bands in layered materials.

Abstract Mutations in Atp2b2, an outer hair cell gene, cause dominant hearing loss in humans. Using a mouse model Atp2b2 Obl/+, with a dominant hearing loss mutation (Oblivion), we show that liposome-mediated in vivo delivery of CRISPR-Cas9 ribonucleoprotein complexes leads to specific editing of the Obl allele. Large deletions encompassing the Obl locus and indels were identified as the result of editing. In vivo genome editing promotes outer hair cell survival and restores their function, leading to hearing recovery. We further show that in a double-dominant mutant mouse model, in which the Tmc1 Beethoven mutation and the Atp2b2 Oblivion mutation cause digenic genetic hearing loss, Cas9/sgRNA delivery targeting both mutations leads to partial hearing recovery. These findings suggest that liposome-RNP delivery can be used as a strategy to recover hearing with dominant mutations in OHC genes and with digenic mutations in the auditory hair cells, potentially expanding therapeutics of gene editing to treat hearing loss.

Purpose: Malignant biliary obstruction (MBO) is common in patients with advanced malignant tumors, leading to poor prognosis and hindering antitumor therapy. The purpose of our study was to assess the survival outcomes for patients under therapy after percutaneous transhepatic biliary drainage (PTBD) and identify prognostic factors associated with survival in patients with MBO. Methods: From July 2010 to February 2021, 269 patients with MBO secondary to malignant tumor were divided into two groups (functional success and non-functional success). Survival time and prognostic factors were analyzed by Kaplan–Meier curves and the Cox model. Results: The overall median survival time after PTBD was 4.6 months (95 % IC:3.9–5.3). The 3- and 6-month survival rates were 68.0 % and 38.7 %, respectively. The median survival improved from 3.2 months to 8.4 months when the procedure achieved functional success. Multivariate analysis demonstrated that functionally successful drainage and antitumor treatment after PTBD were independent positive prognostic factors, but the total bilirubin after drainage and tumor size were independent negative predictive values. Conclusions: Functionally successful drainage could prolong survival time in patients with malignant biliary obstruction. Palliative care after drainage can prolong patient survival and improve their quality of life.

Direct conversion of syngas to aromatics (STA) over oxide-zeolite composite catalysts is promising as an alternative method for aromatics production. However, the structural effect of the oxide component in composite catalysts is still ambiguous. Herein, we investigate the size effect by selecting ZnCr2O4 spinel, as a probe oxide, mixing with H-ZSM-5 zeolite as a composite catalyst for STA reaction. The CO conversion, aromatics selectivity and space-time yield (STY) of aromatics are all significantly improved with the crystal size of ZnCr2O4 oxide decreases, which can mainly attribute to the higher oxygen vacancy concentration and thus the rapid generation of more C1 oxygenated intermediate species. Based on the understanding of the size–performance relationship, ZnCr2O4-400 with a smaller size mixing with H-ZSM-5 can achieve 32.6% CO conversion with 76% aromatics selectivity. The STY of aromatics reaches as high as 4.79 mmol gcat−1 h−1, which outperforms the previously reported some typical catalysts. This study elucidates the importance of regulating the size of oxide to design more efficient oxide-zeolite composite catalysts for conversion of syngas to value-added chemicals.

Solar water evaporation offers a promising solution to address global water scarcity, utilizing renewable energy for purification and desalination. Transition-metal selenite hydrates (specifically nickel and cobalt) have shown potential as solar absorbers with high evaporation rates of 1.83 and 2.34 kg∙m−2∙h−1, but the reported discrepancy in evaporation rate deserves further investigation. This investigation aims to clarify their thermal stability for applications and determine the underlying mechanisms responsible for the differences. Nickel and cobalt selenite hydrate compositions were synthesized and investigated via thermogravimetric analysis, X-ray diffraction, and Raman spectroscopy to assess their temperature-induced structural and compositional variations. The results reveal distinct phase transitions and structural alterations under various temperature conditions for these two photothermal materials, providing valuable insights into the factors influencing water transportation and evaporation rates.

In this study, electrospun scaffolds were fabricated using polycaprolactone (PCL) loaded with varying concentrations of β-carotene (1.2%, 2.4%, and 3.6%) via the electrospinning technique. The electrospinning process involved the melting of PCL in acetic acid, followed by the incorporation of β-carotene powder under constant stirring. Raman spectroscopy revealed a homogeneous distribution of β-carotene within the PCL matrix. However, the β-carotene appeared in particulate form, rather than being dissolved and blended with the PCL matrix, a result also confirmed by thermogravimetric analysis. Additionally, X-ray diffraction analysis indicated a decrease in crystallinity with increasing β-carotene concentration. Mechanical testing of the scaffolds demonstrated an increase in ultimate strain, accompanied by a reduction in ultimate stress, indicating a potential plasticizing effect. Moreover, antimicrobial assays revealed a marginal antibacterial effect against Escherichia coli for scaffolds with higher β-carotene concentrations. Conversely, preliminary biological assessment using KUSA-A1 mesenchymal cells indicated enhanced cellular proliferation in response to the scaffolds, suggesting the potential biocompatibility and cell-stimulating properties of β-carotene-loaded PCL scaffolds. Overall, this study provides insights into the fabrication and characterization of electrospun PCL scaffolds containing β-carotene, laying the groundwork for further exploration in tissue engineering and regenerative medicine applications.

Key points 125I brachytherapy is a treatment for locally recurrent HCC after ablation. 125I brachytherapy combined with ablation may improve tumor control. Vascular invasion, multiple lesions, and AFP are prognostic risk factors. 125I brachytherapy is a safe method with a curative effect.

PURPOSEThis study explored the clinical efficacy of transcatheter retrograde shunt occlusion with coils to prevent pulmonary oil or particle embolization prior to transarterial chemoembolization (TACE) in patients with artero-hepatic venous shunts (AHVS) secondary to hepatocellular carcinoma (HCC).METHODSFrom July 2017 to January 2021, 6 patients with advanced, unresectable HCC were found to have an AHVS by hepatic arteriography at the time of attempted TACE. The AHVS was embolized retrogradely with metal coils through a transfemoral or transjugular venous approach. After venous embolization and confirmation of the absence of the AHVS, TACE was performed using an emulsion of iodized oil and doxorubicin or drug-eluting beads. Follow-up computed tomography (CT) was performed within 1 month after the first TACE to evaluate the results and complications.RESULTSHepatic angiography after venous embolization showed that AHVS had utterly disappeared in all patients during the operation. The immediate technical success of the retrograde venous embolization was 100%. The AHVS had disappeared entirely during the follow-up period through triple-phase enhancement CT scanning. According to the modified response evaluation criteria in solid tumors, TACE in all 6 patients had a disease control response rate of 100% (6/6) with complete response in 2 patients and partial response in 4 patients. One patient died during the 6-month follow-up, and the other 5 were still alive. No complications related to pulmonary embolism occurred.CONCLUSIONRetrograde venous coil embolization of AHVS via the draining hepatic vein appears to be a safe, feasible, and effective treatment to allow TACE treatment without pulmonary embolic events. This approach appears to provide better tumor control and effectively decreases the occurrence of pulmonary embolism.

Thanks to their thermal stability, resistance to oxidation and mechanical strength, cobalt-chrome molybdenum alloys are considered an ideal alloy for high temperature applications. The surface oxide layer evolves as a function of time and temperature, changing its chemical structure and increasing its thickness from a few nanometers to various microns. Making use of various diffractographic and spectroscopic techniques, namely X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy and glow-discharge optical emission spectroscopy, coupled with complementary analysis, this work gives new insights on the chemical bonding, crystallographic structure, thickness and elemental composition of the oxide layers as a function of both time and temperature of oxidation. Results show that the initial nanometric passive layer of Co3O4 evolves into a metastable, sub-micrometric CoCrO4 structure and finally stabilizes into a micrometric Cr2O3 at the highest temperatures. This paper fills a fundamental gap in the understanding of the chemistry and stability of Cobalt-based alloys used for high temperature applications, such as in poppet or exhaust valves, aerospace components or hot gas turbines. Once calibrated, this innovative, complete surface characterization approach can be ideally extended to other metallic alloys.

Electro-optical detection systems face numerous challenges due to the complexity and difficulty of targeting controls for “low, slow and tiny” moving targets. In this paper, we present an optimal model of an advanced n-step adaptive Kalman filter and gyroscope short-term integration weighting fusion (nKF-Gyro) method with targeting control. A method is put forward to improve the model by adding a spherical coordinate system to design an adaptive Kalman filter to estimate target movements. The targeting error formation is analyzed in detail to reveal the relationship between tracking controller feedback and line-of-sight position correction. Based on the establishment of a targeting control coordinate system for tracking moving targets, a dual closed-loop composite optimization control model is proposed. The outer loop is used for estimating the motion parameters and predicting the future encounter point, while the inner loop is used for compensating the targeting error of various elements in the firing trajectory. Finally, the modeling method is substituted into the disturbance simulation verification, which can monitor and compensate for the targeting error of moving targets in real time. The results show that in the optimal model incorporating the nKF-Gyro method with targeting control, the error suppression was increased by up to 36.8% compared to that of traditional KF method and was 25% better than that of the traditional nKF method.

Oxide-dispersion- and hard-particle-strengthened (ODS) laser-cladded single-layer multi-tracks with a Ni-based alloy composition with 20 wt.% μm-WC particles and 1.2 wt.% nano-Y2O3 addition were produced on ultra-high-strength steel in this study. The investigation of the composite coating designed in this study focused on the reciprocating friction and wear workpiece surface under heavy load conditions. The coating specimens were divided into four groups: (i) Ni-based alloy, nano-Y2O3, and 2 μm-WC (2 μm WC-Y/Ni); (ii) Ni-based alloy with added 2 μm-WC (2 μmWC/Ni); (iii) Ni-based alloy with added 80 μm-WC (80 μmWC/Ni); and (iv) base metal ultra-high-strength alloy steel 30CrMnSiNi2A. Four conclusions were reached: (1) Nano-Y2O3 could effectively inhibit the dissolution of 2 μm-WC. (2) It can be seen from the semi-space dimensionless simulation results that the von Mises stress distribution of the metal laser composite coating prepared with a 2 μm-WC particle additive was very uniform and it had better resistance to normal impact and tangential loads than the laser coating prepared with the 80 μm-WC particle additive. (3) The inherent WC initial crack and dense stress concentration in the 80 μm-WC laser coating could easily cause dislocations to accumulate, as shown both quantitatively and qualitatively, resulting in the formation of micro-crack nucleation. After the end of the running-in phase, the COF of the 2 μm-WC-Y2O3/Ni component samples stabilized at the minimum of the COF of the four samples. The numerical order of the four COF curves was stable from small to large as follows: 2 μm-WC-Y2O3/Ni, 2 μm-WC/Ni, 80 μm-WC/Ni, and 30CrMnSiNi2A. (4) The frictional volume loss rate of 2 μm-WC-Y2O3/Ni was 1.3, which was significantly lower than the corresponding values of the other three components: 2.4, 3.5, and 13.

Abstract Alcoholic hepatitis (AH), a kind of alcoholic liver disease, shows poor prognosis. Long noncoding RNAs (lncRNAs) exert critical role in liver diseases. Here, we intended to investigate the possible molecular mechanism that 1700020I14Rik-based regulation of microRNA (miR)-137/Aldo-keto reductase family 1 member B10 (AKR1B10) affecting the inflammatory response and hepatocyte damage in AH. AH-related genes and the down-stream regulatory pathway were screnned by bioinformatics. Mouse normal hepatocyte cell line AML12 was selected to construct an ethanol-induced hepatocyte injury model for in vitro mechanistic validation, while we also established an AH mouse model using the ethanol with gradually increased concentration of 2–4% (v/v) for in vivo study. Specific role of 1700020I14Rik/miR-137/AKR1B10 in AML12 cell viability, proliferation and apoptotic capacity as well as inflammation and liver damage in mice were analyzed following ectopic and depletion approaches. We found elevated AKR1B10 and 1700020I14Rik but reduced miR-137 in AH. 1700020I14Rik was able to elevated miR-137-mediated AKR1B10. In vitro cell experiments and in vivo animal experiments validated that 1700020I14Rik reduced ethanol-induced hepatocyte damage and inflammation in AH mice through regulation of miR-137–mediated AKR1B10/Erk axis. The current study underlied that 1700020I14Rik could activate AKR1B10/Erk signaling through inhibition of miR-137, thereby promoting the hepatocyte damage in AH mice.

This study intends to investigate the effects of miR-142-5p encapsulated by serum-derived extracellular vesicles (EVs) on septic acute lung injury (ALI) following remote ischemic preconditioning (RIPC) through a PTEN-involved mechanism. ALI was induced in rats by lipopolysaccharide (LPS) injection, 24 h before which RIPC was performed via the left lower limb. Next, the binding affinity between miR-142-5p and PTEN was identified. EVs were isolated from serum and injected into rats. The morphology of lung tissues, pulmonary edema, and inflammatory cell infiltration into lung tissues were then assessed, and TNF-α and IL-6 levels in serum and lung tissues were measured. The results indicated that RIPC could attenuate ALI in sepsis. miR-142-5p expression was increased in serum, lung tissues, and serum-derived EVs of ALI rats following RIPC. miR-142-5p could target PTEN to activate the PI3K/Akt signaling pathway. miR-142-5p shuttled by serum-derived EVs reduced pulmonary edema, neutrophil infiltration, and TNF-α and IL-6 levels, thus alleviating ALI in LPS-induced septic rats upon RIPC. Collectively, serum-derived EVs-loaded miR-142-5p downregulated PTEN and activated PI3K/Akt to inhibit ALI in sepsis following RIPC, thus highlighting potential therapeutic molecular targets against ALI in sepsis.

Raman spectroscopy was applied to study the structural differences between herpes simplex virus Type I (HSV-1) and Epstein–Barr virus (EBV). Raman spectra were first collected with statistical validity on clusters of the respective virions and analyzed according to principal component analysis (PCA). Then, average spectra were computed and a machine-learning approach applied to deconvolute them into sub-band components in order to perform comparative analyses. The Raman results revealed marked structural differences between the two viral strains, which could mainly be traced back to the massive presence of carbohydrates in the glycoproteins of EBV virions. Clear differences could also be recorded for selected tyrosine and tryptophan Raman bands sensitive to pH at the virion/environment interface. According to the observed spectral differences, Raman signatures of known biomolecules were interpreted to link structural differences with the viral functions of the two strains. The present study confirms the unique ability of Raman spectroscopy for answering structural questions at the molecular level in virology and, despite the structural complexity of viral structures, its capacity to readily and reliably differentiate between different virus types and strains.

This study exploits quantitative algorithms of Raman spectroscopy to assess, at the molecular scale, the nutritional quality of individual kernels of the Japanese short-grain rice cultivar Koshihikari in terms of amylose-to-amylopectin ratio, fractions of phenylalanine and tryptophan aromatic amino acid residues, protein-to-carbohydrate ratio, and fractions of protein secondary structures. Statistical assessments on a large number of rice kernels reveal wide distributions of the above nutritional parameters over nominally homogeneous kernel batches. This demonstrates that genetic classifications cannot catch omic fluctuations, which are strongly influenced by a number of extrinsic factors, including the location of individual grass plants within the same rice field and the level of kernel maturation. The possibility of collecting nearly real-time Raman “multi-omic snapshots” of individual rice kernels allows for the automatic (low-cost) differentiation of groups of kernels with restricted nutritional characteristics that could be used in the formulation of functional foods for specific diseases and in positively modulating the intestinal microbiota for protection against bacterial infection and cancer prevention.

This study is aimed at establishing optimal soybean lecithin (SL) enrichment protocols in Artemia nauplii and at comparing the growth performance, body composition, and liver tissue metabolism in rock bream (Oplegnathus fasciatus) larvae reared on SL-enriched Artemia nauplii or SL-enriched microdiet (MD). The enrichment protocol experiment results indicated 12 h enrichment, and 10 g SL/m3 seawater could obtain desirable results. Rock bream larvae (25 days posthatching (dph)) were fed Artemia nauplii or MD for 30 days with three replicates. At stage 1 (larval 25–40 dph), significantly higher growth performance was observed in larvae fed the live prey (P

The aim of this study was to elucidate the chemistry of cellular degeneration in human neuroblastoma cells upon exposure to outer-membrane vesicles (OMVs) produced by Porphyromonas gingivalis (Pg) oral bacteria by monitoring their metabolomic evolution using in situ Raman spectroscopy. Pg-OMVs are a key factor in Alzheimer’s disease (AD) pathogenesis, as they act as efficient vectors for the delivery of toxins promoting neuronal damage. However, the chemical mechanisms underlying the direct impact of Pg-OMVs on cell metabolites at the molecular scale still remain conspicuously unclear. A widely used in vitro model employing neuroblastoma SH-SY5Y cells (a sub-line of the SK-N-SH cell line) was spectroscopically analyzed in situ before and 6 h after Pg-OMV contamination. Concurrently, Raman characterizations were also performed on isolated Pg-OMVs, which included phosphorylated dihydroceramide (PDHC) lipids and lipopolysaccharide (LPS), the latter in turn being contaminated with a highly pathogenic class of cysteine proteases, a key factor in neuronal cell degradation. Raman characterizations located lipopolysaccharide fingerprints in the vesicle structure and unveiled so far unproved aspects of the chemistry behind protein degradation induced by Pg-OMV contamination of SH-SY5Y cells. The observed alterations of cells’ Raman profiles were then discussed in view of key factors including the formation of amyloid β (Aβ) plaques and hyperphosphorylated Tau neurofibrillary tangles, and the formation of cholesterol agglomerates that exacerbate AD pathologies.

Hydrolytic reactions taking place at the surface of a silicon nitride (Si3N4) bioceramic were found to induce instantaneous inactivation of Human herpesvirus 1 (HHV-1, also known as Herpes simplex virus 1 or HSV-1). Si3N4 is a non-oxide ceramic compound with strong antibacterial and antiviral properties that has been proven safe for human cells. HSV-1 is a double-stranded DNA virus that infects a variety of host tissues through a lytic and latent cycle. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) tests of HSV-1 DNA after instantaneous contact with Si3N4 showed that ammonia and its nitrogen radical byproducts, produced upon Si3N4 hydrolysis, directly reacted with viral proteins and fragmented the virus DNA, irreversibly damaging its structure. A comparison carried out upon testing HSV-1 against ZrO2 particles under identical experimental conditions showed a significantly weaker (but not null) antiviral effect, which was attributed to oxygen radical influence. The results of this study extend the effectiveness of Si3N4’s antiviral properties beyond their previously proven efficacy against a large variety of single-stranded enveloped and non-enveloped RNA viruses. Possible applications include the development of antiviral creams or gels and oral rinses to exploit an extremely efficient, localized, and instantaneous viral reduction by means of a safe and more effective alternative to conventional antiviral creams. Upon incorporating a minor fraction of micrometric Si3N4 particles into polymeric matrices, antiherpetic devices could be fabricated, which would effectively impede viral reactivation and enable high local effectiveness for extended periods of time.

To make unmanned surface vehicles that are better applied to the field of environmental monitoring in inland rivers, reservoirs, or coasts, we propose a global path-planning algorithm based on the improved A-star algorithm. The path search is carried out using the raster method for environment modeling and the 8-neighborhood search method: a bidirectional search strategy and an evaluation function improvement method are used to reduce the total number of traversing nodes; the planned path is smoothed to remove the inflection points and solve the path folding problem. The simulation results reveal that the improved A-star algorithm is more efficient in path planning, with fewer inflection points and traversing nodes, and the smoothed paths are more to meet the actual navigation demands of unmanned surface vehicles than the conventional A-star algorithm.

A small deviation in the time-delay of the image tracker is essential for improving the tracking precision of an electro-optical system, and for future advances in actuator technology. The core goal of this manuscript is to address issues such as tracking the controller time-delay compensation and the precision of an electro-optical detection system using an advanced filter design, a fire control modeling, and an anti-occlusion target detection system. To address this problem, a small deviation in the time-delay prediction and control method of the image tracker is proposed based on the principle of linear motion transformation. The time-delay error formation is analyzed in detail to reveal the scientific mechanism between the tracking controller feedback and the line-of-sight position correction. An advanced N-step Kalman filtering controller model is established by combining a line-of-sight firing control judgment and a single-sample training anti-occlusion DSST target tracking strategy. Finally, an actuator platform with three degrees of freedom is used to test the optical mechatronics system. The results show that the distribution probability of the line-of-sight measuring error in a circle with a radius of 0.15 mrad is 72%. Compared with the traditional control method, the tracking precision of the optimal method is improved by 58.3%.

Investigations have demonstrated a strong and positive association between dietary intact phospholipid (PL) inclusion and aquatic larval growth, nevertheless, the precise molecular mechanism underlying PL inclusion on growth performance has not been well elucidated. This study aimed to investigate the effects of dietary soybean lecithin (SL) inclusion on growth performance, liver metabolism, resistance to hypoxia stress, and potential molecular mechanisms in rock bream (Oplegnathus fasciatus) larvae. Four types of equal-protein and equal-lipid content microdiets (MDs) were formulated with graded levels of SL to achieve phospholipid levels of (PLs, dry matter) 3.84% (SL0), 6.71% (SL4), 9.38% (SL8), and 12.21% (SL12). Rock bream larvae (25 days post-hatching) were fed the respective MDs for 30 days with three replicates. We found that dietary SL inclusion promoted growth performance, survival rate, and stress resistance to hypoxia stress. The increased dietary SL inclusion improved intestinal structure, as shown by the increased perimeter ratio, muscular thickness, and mucosal fold height of the mid-intestinal tissue. Moreover, a high SL inclusion diet (SL12) increased the activity of the key lipolysis-related enzyme (lipase [LP]) in liver tissue but decreased the activity of amino acid catabolism-related enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). RNA sequencing results in liver tissue revealed that the SL12 diet increased the transcriptional level of fatty acid activation-related genes (acsl6 and acsbg2), phospholipid catabolism-related genes (acat2, lpin2, and crls), and amino acid synthesis-related genes (gs, csb, aldh18a1, and oct), but decreased the expression of amino acid catabolism-related gene gprt2. Notably, the SL12 diet significantly increased the expression of ribosome biogenesis-related genes (pes1, nop56, nop58, and rpf2) in liver tissue. The ribosome protein-related pathways were the most enriched pathways mapped in the GO database. Collectively, this study demonstrated the necessity of dietary SL for survival, growth performance, promotion of mid-intestinal morphology, and hypoxia stress during the rock bream larval stage. The SL-induced growth performance promotion was likely attributed to increasing nutrient acquisition by intestinal morphology improvement and to increasing SL catabolism and thereby sparing amino acids for protein synthesis.

Abstract The recent increase of the number of unidentified cadavers has become a serious problem throughout the world. As a simple and objective method for age estimation, we attempted to utilize Raman spectrometry for forensic identification. Raman spectroscopy is an optical-based vibrational spectroscopic technique that provides detailed information regarding a sample’s molecular composition and structures. Building upon our previous proof-of-concept study, we measured the Raman spectra of abdominal skin samples from 132 autopsy cases and the protein-folding intensity ratio, RPF, defined as the ratio between the Raman signals from a random coil an α-helix. There was a strong negative correlation between age and RPF with a Pearson correlation coefficient of r = 0.878. Four models, based on linear (RPF), squared (RPF 2), sex, and RPF by sex interaction terms, were examined. The results of cross validation suggested that the second model including linear and squared terms was the best model with the lowest root mean squared error (11.3 years of age) and the highest coefficient of determination (0.743). Our results indicate that the there was a high correlation between the age and RPF and the Raman biological clock of protein folding can be used as a simple and objective forensic age estimation method for unidentified cadavers.

This study probed in vitro the mechanisms of competition/coexistence between Streptococcus sanguinis (known for being correlated with health in the oral cavity) and Streptococcus mutans (responsible for aciduric oral environment and formation of caries) by means of quantitative Raman spectroscopy and imaging. In situ Raman assessments of live bacterial culture/coculture focusing on biofilm exopolysaccharides supported the hypothesis that both species engaged in antagonistic interactions. Experiments of simultaneous colonization always resulted in coexistence, but they also revealed fundamental alterations of the biofilm with respect to their water-insoluble glucan structure. Raman spectra (collected at fixed time but different bacterial ratios) showed clear changes in chemical bonds in glucans, which pointed to an action by Streptococcus sanguinis to discontinue the impermeability of the biofilm constructed by Streptococcus mutans. The concurrent effects of glycosidic bond cleavage in water-insoluble α − 1,3–glucan and oxidation at various sites in glucans’ molecular chains supported the hypothesis that secretion of oxygen radicals was the main “chemical weapon” used by Streptococcus sanguinis in coculture.

Abstract Surface inactivation of human microbial pathogens has a long history. The Smith Papyrus (2600 ~ 2200 B.C.) described the use of copper surfaces to sterilize chest wounds and drinking water. Brass and bronze on doorknobs can discourage microbial spread in hospitals, and metal-base surface coatings are used in hygiene-sensitive environments, both as inactivators and modulators of cellular immunity. A limitation of these approaches is that the reactive oxygen radicals (ROS) generated at metal surfaces also damage human cells by oxidizing their proteins and lipids. Silicon nitride (Si3N4) is a non-oxide ceramic compound with known surface bacterial resistance. We show here that off-stoichiometric reactions at Si3N4 surfaces are also capable of inactivating different types of single-stranded RNA (ssRNA) viruses independent of whether their structure presents an envelop or not. The antiviral property of Si3N4 derives from a hydrolysis reaction at its surface and the subsequent formation of reactive nitrogen species (RNS) in doses that could be metabolized by mammalian cells but are lethal to pathogens. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) tests of viral RNA and in situ Raman spectroscopy suggested that the products of Si3N4 hydrolysis directly react with viral proteins and RNA. Si3N4 may have a role in controlling human epidemics related to ssRNA mutant viruses.

The multidrug-resistant Candida auris often defies treatments and presently represents a worldwide public health threat. Currently, the ergosterol-targeting Amphotericin B (AmB) and the DNA/RNA-synthesis inhibitor 5-flucytosine (5-FC) are the two main drugs available for first-line defense against life-threatening Candida auris infections. However, important aspects of their mechanisms of action require further clarification, especially regarding metabolic reactions of yeast cells. Here, we applied Raman spectroscopy empowered with specifically tailored machine-learning algorithms to monitor and to image in situ the susceptibility of two Candida auris clades to different antifungal drugs (LSEM 0643 or JCM15448T, belonging to the East Asian Clade II; and, LSEM 3673 belonging to the South African Clade III). Raman characterizations provided new details on the mechanisms of action against Candida auris Clades II and III, while also unfolding differences in their metabolic reactions to different drugs. AmB treatment induced biofilm formation in both clades, but the formed biofilms showed different structures: a dense and continuous biofilm structure in Clade II, and an extra-cellular matrix with a “fluffy” and discontinuous structure in Clade III. Treatment with 5-FC caused no biofilm formation but yeast-to-hyphal or pseudo-hyphal morphogenesis in both clades. Clade III showed a superior capacity in reducing membrane permeability to the drug through chemically tailoring chitin structure with a high degree of acetylation and fatty acids networks with significantly elongated chains. This study shows the suitability of the in situ Raman method in characterizing susceptibility and stress response of different C. auris clades to antifungal drugs, thus opening a path to identifying novel clinical solutions counteracting the spread of these alarming pathogens.

Abstract Introduction Long QT syndrome (LQTS) is a life‐threatening inherited channelopathy, and prolonged QT intervals easily trigger malignant arrhythmias, especially torsades de pointes and ventricular fibrillation. Materials and methods The proband with overlapped phenotypes of LQTS and sinoatrial node dysfunction underwent some necessary examinations, including echocardiography, electrocardiogram (ECG), and Holter monitoring. Next, whole‐exome sequencing was performed, and candidate genes were validated by Sanger sequencing. RNA secondary structure and protein physical‐chemical parameter analyses were used to predict the possible structural change of the proteins induced by the mutations. Results We identified the digenic heterozygous mutations of KCNH2 p.307_308del (NM_001204798, c.921_923del) and SCN5A p.R1865H (NM_001160160, c.G5594A) in the female and young proband (II: 1) of LQTS and ventricular fibrillation with repeat syncope at rest. Subsequently, she occurred with obvious sinus arrest with persistent ventricular pacing of implantable cardioverter‐defibrillator. The heterozygous SCN5Ap.R1865H was carried by her father and sister but not carried by I:2. II:1 carried with KCNH2 p.307_308del as a de novo mutation, but not existed in other family members. RNA secondary structure of KCNH2 p.307_308del showed a false regional double helix, and its amino acids' hydrophobicity was significantly weakened. For the Nav1.5 protein property, SCN5A p.R1865H slightly increased the molecular weight and aliphatic index but reduced the instability index. Conclusions The digenic heterozygous KCNH2 and SCN5A mutations were associated with young early‐onset long QT syndrome and sinoatrial node dysfunction.

Abstract The multiple mutations of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus have created variants with structural differences in both their spike and nucleocapsid proteins. While the functional relevance of these mutations is under continuous scrutiny, current findings have documented their detrimental impact in terms of affinity with host receptors, antibody resistance, and diagnostic sensitivity. Raman spectra collected on two British variant sub‐types found in Japan (QK002 and QHN001) are compared with that of the original Japanese isolate (JPN/TY/WK‐521), and found bold vibrational differences. These included: i) fractions of sulfur‐containing amino acid rotamers, ii) hydrophobic interactions of tyrosine phenol ring, iii) apparent fractions of RNA purines and pyrimidines, and iv) protein secondary structures. Building upon molecular scale results and their statistical validations, the authors propose to represent virus variants with a barcode specially tailored on Raman spectrum. Raman spectroscopy enables fast identification of virus variants, while the Raman barcode facilitates electronic recordkeeping and translates molecular characteristics into information rapidly accessible by users.

While joint arthroplasty remains nowadays the most popular option available to repair chronically degenerated osteoarthritic joints, possibilities are recently emerging for regeneration of damaged cartilage rather than its replacement with artificial biomaterials. This latter strategy could allow avoiding the quite intrusive surgical procedures associated with total joint replacement. Building upon this notion, we first apply Raman spectroscopy to characterize diseased cartilage in a mice model of instability-induced knee osteoarthritis (OA) upon medial collateral ligament (MCL) and medial meniscus (MM) transections. Then, we examine the same OA model after cartilage regeneration by means of messenger RNA (mRNA) delivery of a cartilage-anabolic runt-related transcription factor 1 (RUNX1). Raman spectroscopy is shown to substantiate at the molecular scale the therapeutic effect of the Runx1 mRNA cartilage regeneration approach. This study demonstrates how the Raman spectroscopic method could support and accelerate the development of new therapies for cartilage diseases.

Invasive fungal infections caused by yeasts of the genus Candida carry high morbidity and cause systemic infections with high mortality rate in both immunocompetent and immunosuppressed patients. Resistance rates against antifungal drugs vary among Candida species, the most concerning specie being Candida auris, which exhibits resistance to all major classes of available antifungal drugs. The presently available identification methods for Candida species face a severe trade-off between testing speed and accuracy. Here, we propose and validate a machine-learning approach adapted to Raman spectroscopy as a rapid, precise, and labor-efficient method of clinical microbiology for C. auris identification and drug efficacy assessments. This paper demonstrates that the combination of Raman spectroscopy and machine learning analyses can provide an insightful and flexible mycology diagnostic tool, easily applicable on-site in the clinical environment.

Human dermal fibroblasts (HDFs) were converted into osteoblasts using a ALK inhibitor II (inhibitor of transforming growth factor-β signal) on freeze-dried nanogel-cross-linked porous (FD-NanoClip) polysaccharide sheets or fibers. Then, the ability of these directly converted osteoblasts (dOBs) to produce calcified substrates and the expression of osteoblast genes were analyzed in comparison with osteoblasts converted by exactly the same procedure but seeded onto a conventional atelocollagen scaffold. dOBs exposed to FD-NanoClip in both sheet and fiber morphologies produced a significantly higher concentration of calcium deposits as compared to a control cell sample (i.e., unconverted fibroblasts), while there was no statistically significant difference in calcification level between dOBs exposed to atelocollagen sheets and the control group. The observed differences in osteogenic behaviors were interpreted according to Raman spectroscopic analyses comparing different polysaccharide scaffolds and Fourier transform infrared spectroscopy analyses of dOB cultures. This study substantiates a possible new path to repair large bone defects through a simplified transplantation procedure using FD-NanoClip sheets with better osteogenic outputs as compared to the existing atelocollagen scaffolding material.

The microstructural and molecular-scale variations induced by laser irradiation treatment on human teeth enamel in comparison with synthetic hydroxyapatite (HAp) were examined through Raman microprobe spectroscopy as a function of irradiation power. The results demonstrated that laser irradiation could modify stoichiometry, microstructure, and the population of crystallographic defects, as well as the hardness of the materials. These modifications showed strong dependences on both laser power and initial nonstoichiometric structure (defective content of HPO4), because of the occurrence of distinct reactions and structural reconstruction. The reported observations can redirect future trends in tooth whitening by laser treatment and the production of HAp coatings because of the important role of stoichiometric defects.

This study targets on-site/real-time taxonomic identification and metabolic profiling of seven different Candida auris clades/subclades by means of Raman spectroscopy and imaging. Representative Raman spectra from different Candida auris samples were systematically deconvoluted by means of a customized machine-learning algorithm linked to a Raman database in order to decode structural differences at the molecular scale. Raman analyses of metabolites revealed clear differences in cell walls and membrane structure among clades/subclades. Such differences are key in maintaining the integrity and physical strength of the cell walls in the dynamic response to external stress and drugs. It was found that Candida cells use the glucan structure of the extracellular matrix, the degree of α-chitin crystallinity, and the concentration of hydrogen bonds between its antiparallel chains to tailor cell walls’ flexibility. Besides being an effective ploy in survivorship by providing stiff shields in the α–1,3–glucan polymorph, the α–1,3–glycosidic linkages are also water-insoluble, thus forming a rigid and hydrophobic scaffold surrounded by a matrix of pliable and hydrated β–glucans. Raman analysis revealed a variety of strategies by different clades to balance stiffness, hydrophobicity, and impermeability in their cell walls. The selected strategies lead to differences in resistance toward specific environmental stresses of cationic/osmotic, oxidative, and nitrosative origins. A statistical validation based on principal component analysis was found only partially capable of distinguishing among Raman spectra of clades and subclades. Raman barcoding based on an algorithm converting spectrally deconvoluted Raman sub-bands into barcodes allowed for circumventing any speciation deficiency. Empowered by barcoding bioinformatics, Raman analyses, which are fast and require no sample preparation, allow on-site speciation and real-time selection of appropriate treatments.

Following the rising interested on 3D-printing technologies, this research explores the possibility to apply nitride-polymethylmethacrylate composite coatings on 3D printed parts in order to increase their resistance to bacteria colonization. Four different nitrides were tested: silicon, zirconium, hafnium and aluminum. Trans-micrometric particles of hafnium nitride (average size 1 µm) could be dispersed better than the other three nitrides (average size between 8 and 10 µm), but the chemical analysis confirmed that the former, due to the higher surface area, are more prone to spontaneous oxidation in air. After deposition, the surface of the various coatings contained between 40% (silicon nitride) and 90% (hafnium nitride) of exposed ceramic particles. All composite materials showed antibacterial effects when compared to standard polymethylmethacrylate, with hafnium nitride being the most effective against E. coli and aluminum nitride against S. epidermidis. It has been postulated that while Si3N4 long-term antibacterial effects are granted by the constant dissolution of the SiO2 surface layer, zirconium and hafnium composites are effective because they possess antibacterial properties both in their nitride and oxide forms.

The effect of crystal size of HMOR from micro size to 50 nm, with the apparent similar acid site density, on catalytic performance for the dimethyl ether (DME) carbonylation was investigated. The crystal size of HMOR is sensitive to the deactivation rate of DME carbonylation reaction, and the higher stability around 200 nm can be achieved. The characterization studies reveal that the diffusions of MA product play a key role during the induction and deactivation period in DME carbonylation. These will be helpful for guiding the large-scale synthesis of mordenite zeolites catalysts with high efficiencies for DME carbonylation.

The nutritional quality of rice is contingent on a wide spectrum of biochemical characteristics, which essentially depend on rice genome, but are also greatly affected by growing/environmental conditions and aging during storage. The genetic basis and related identification of genes have widely been studied and rationally linked to accumulation of micronutrients in grains. However, genetic classifications cannot catch quality fluctuations arising from interannual, environmental, and storage conditions. Here, we propose a quantitative spectroscopic approach to analyze rice nutritional quality based on Raman spectroscopy, and disclose analytical algorithms for the determination of: (i) amylopectin and amylose concentrations, (ii) aromatic amino acids, (iii) protein content and structure, and (iv) chemical residues. The proposed Raman algorithms directly link to the molecular composition of grains and allow fast/non-destructive determination of key nutritional parameters with minimal sample preparation. Building upon spectroscopic information at the molecular level, we newly propose to represent the nutritional quality of labeled rice products with a barcode specially tailored on the Raman spectrum. The Raman barcode, which can be stored in databases promptly consultable with barcode scanners, could be linked to diet applications (apps) to enable a rapid, factual, and unequivocal product identification based on direct molecular screening.

Alumina (Al2O3) ceramic implants do not stimulate osteoblasts in vivo. Surface alterations targeted at changing the chemistry or topography have been proposed to enhance the bioactivity of alumina. This surface modification is intended to improve oxide bioceramic’s ability to integrate with the biological environment and, in particular, to rapidly osteointegrate. In this study, the surface of zirconia-toughened alumina (ZTA) was functionalized using two methods: (i) Surface laser-patterning and successive filling of patterned wells with powder mixtures of bioglass and Si3N4; and, (ii) Si3N4 coating by pulse-laser sintering. Functionalized ZTA surfaces were characterized with vibrational spectroscopy, biological testing, and laser microscopy. Both enhancements resulted in osteoblast activation, a property that is relevant to osteosynthesis.

Altered dosage of developmental regulators such as transcription factors can result in disorders, such as FOXG1 syndrome. Here, the authors demonstrate the utility of SMASh technology for modulating protein dosage by modeling FOXG1 syndrome using human pluripotent stem cell-derived neurons and neural organoids.

Non-invasive continuous blood pressure monitoring is of great significance for the preventing, diagnosing, and treating of cardiovascular diseases (CVDs). Studies have demonstrated that photoplethysmogram (PPG) and electrocardiogram (ECG) signals can effectively and continuously predict blood pressure (BP). However, most of the BP estimation models focus on the waveform features of the PPG signal, while the peak value of R-wave in ECG is only used as a time reference, and few references investigated the ECG waveforms. This paper aims to evaluate the influence of three characteristic waveforms in ECG on the improvement of BP estimation. PPG is the primary signal, and five input combinations are formed by adding ECG, P wave, QRS complex, T wave, and none. We employ five common convolutional neural networks (CNN) to validate the consistency of the contribution. Meanwhile, with the visualization of Gradient-weighted class activation mapping (Grad-CAM), we generate the heat maps and further visualize the distribution of CNN’s attention to each waveform of PPG and ECG. The heat maps show that networks pay more attention to the QRS complex and T wave. In the comparison results, the QRS complex and T wave have more contribution to minimizing errors than P wave. By separately adding P wave, QRS complex, and T wave, the average MAE of these networks reaches 7.87 mmHg, 6.57 mmHg, and 6.21 mmHg for systolic blood pressure (SBP), and 4.27 mmHg, 3.65 mmHg, and 3.73 mmHg, respectively, for diastolic blood pressure (DBP). The results of the experiment show that QRS complex and T wave deserves more attention and feature extraction like PPG waveform features in the continuous BP estimation.

The distortion process of kaolinite annealed from 25 °C to 550 °C for different holding times can be characterized using a thermogravimetric/differential scanning calorimeter (TG/DSC) for thermal analysis, X-ray diffraction (XRD) for establishing the crystal structure, the Fourier transform infrared spectrum (FTIR) for identifying the functional groups, and a scanning electron microscope (SEM) for establishing the microstructure. Dehydroxylation is the main reaction during annealing from 25 °C to 550 °C and leads to kaolinite crystal distortion. A stable crystal structure during distortion was obtained by optimizing the bulk phase with quantum chemistry. Then, the crystal structure was studied by using ab initio multiple scattering calculations for X-ray absorption of the fine structure (XAFS). The results of X-ray absorption near the edge structures (XANES) determined that peak shifts and intensity phases slightly increased. The crystal structure distortion of kaolinite during annealing can be explained by the experimental and simulation results. This work provides theoretical support for identifying kaolinite with different degrees of distortion and has the potential for further developments in coal gangue separation.

This study presents a set of vibrational characterizations on a nanogel-cross-linked porous freeze-dried gel (NanoCliP-FD gel) scaffold for tissue engineering and regenerative therapy. This scaffold is designed for the in vitro culture of high-quality cartilage tissue to be then transplanted in vivo to enable recovery from congenital malformations in the maxillofacial area or crippling jaw disease. The three-dimensional scaffold for in-plate culture is designed with interface chemistry capable of stimulating cartilage formation and maintaining its structure through counteracting the dedifferentiation of mesenchymal stem cells (MSCs) during the formation of cartilage tissue. The developed interface chemistry enabled high efficiency in both growth rate and tissue quality, thus satisfying the requirements of large volumes, high matrix quality, and superior mechanical properties needed in cartilage transplants. We characterized the cartilage tissue in vitro grown on a NanoCliP-FD gel scaffold by human periodontal ligament-derived stem cells (a type of MSC) with cartilage grown by the same cells and under the same conditions on a conventional (porous) atelocollagen scaffold. The cartilage tissues produced by the MSCs on different scaffolds were comparatively evaluated by immunohistochemical and spectroscopic analyses. Cartilage differentiation occurred at a higher rate when MSCs were cultured on the NanoCliP-FD gel scaffold compared to the atelocollagen scaffold, and produced a tissue richer in cartilage matrix. In situ spectroscopic analyses revealed the cell/scaffold interactive mechanisms by which the NanoCliP-FD gel scaffold stimulated such increased efficiency in cartilage matrix formation. In addition to demonstrating the high potential of human periodontal ligament-derived stem cell cultures on NanoCliP-FD gel scaffolds in regenerative cartilage therapy, the present study also highlights the novelty of Raman spectroscopy as a non-destructive method for the concurrent evaluation of matrix quality and cell metabolic response. In situ Raman analyses on living cells unveiled for the first time the underlying physiological mechanisms behind such improved chondrocyte performance.

In vitro and in vivo studies have recently shown that silicon nitride (Si3N4) is an osseoconductive and potential osseoinductive biomaterial. Even though the amount of bone mineral produced by Si3N4 was inferior when compared to commercial Bioglass®, it strongly stimulated the production of extracellular matrix and collagen tissues. Consequently, this study was designed to determine if appropriate mixtures of Bioglass® and Si3N4 might improve the ratio of mineral apatite to its biological matrix. Commercial 45S5 Bioglass® powder was mixed with 5 and 10 mol% Si3N4 powder, followed by melting, cooling, crushing, and comminution. The composite powders had modified morphologies and chemical structures including a reduced average particle size, a reduction of oxygen in the SiO backbone structure, and trapped CO2 gas which was converted into calcium carbonate. When exposed to human osteosarcoma cells within an osteogenic medium, the 5 mol% Si3N4 composite powder resulted in higher amounts of hydroxyapatite while the 10 mol% Si3N4 powder provided in a more balanced combination of collagen and mineral fractions closer to the natural composition of native human bone. Keywords: Bioglass, Si3N4, Osteosarcoma, Nitrogen, Spectroscopy, Osseointegration

Downy mildew of grapevine, caused by Plasmopara viticola (Berk. and Curt.) Berl. and de Toni, is one of the most devastating diseases of grapevine, severely affecting grape and wine production and quality worldwide. Infections are usually controlled by the intensive application of synthetic fungicides or by copper-based products in organic farming, rising problems for soil contamination and adverse impacts on environment and human health. While strict regulations attempt to minimize their harmful consequences, the situation calls for the development of alternative fungicidal strategies. This study presents the unprecedented case of a bioceramic, silicon nitride, with antimicrobial properties against P. viticola, but without adverse effects on human cells and environment, opening the way to the possible extension of silicon nitride applications in agriculture. Raman spectroscopic assessments of treated sporangia in conjunction with microscopic observations mechanistically showed that the nitrogen-chemistry of the bioceramic surface affects pathogen’s biochemical components and cell viability, thus presenting a high potential for host protection from P. viticola infections.

Background: Currently, hepatocellular carcinoma (HCC) patients with refractory ascites (RA) have a very poor prognosis, and there are no effective treatments recommended by the guidelines. A treatment strategy that utilizes a transjugular intrahepatic portosystemic shunt (TIPS) combined with subsequent antitumor treatment is explored in this study for its feasibility and clinical value. Methods: One month after TIPS, the ascites grade and Child-Pugh scores and stages were reassessed to compare changes in the preoperative indicators. Results: A total of 68 patients from 3 centers were enrolled. After TIPS, the following results were obtained: a complete response (CR), partial response (PR), or absent RA response (AR) of 38 [55.9%], 21 [30.9%], and 9 [13.2%], respectively. The control of RA was 86.8%. The median Child–Pugh scores prior to TIPS and one month after TIPS were 8 (IQR 7–9) and 7 (IQR 6–8), respectively. The down, unchanged, and elevated Child–Pugh stages were 26 [38.2%], 36 [53.0%], and 6 [8.8%], respectively. The postoperative Child–Pugh scores were significantly lower than the preoperative (p

Oral candidiasis, a common opportunistic infection of the oral cavity, is mainly caused by the following four Candida species (in decreasing incidence rate): Candida albicans, Candida glabrata, Candida tropicalis, and Candida krusei. This study offers in-depth Raman spectroscopy analyses of these species and proposes procedures for an accurate and rapid identification of oral yeast species. We first obtained average spectra for different Candida species and systematically analyzed them in order to decode structural differences among species at the molecular scale. Then, we searched for a statistical validation through a chemometric method based on principal component analysis (PCA). This method was found only partially capable to mechanistically distinguish among Candida species. We thus proposed a new Raman barcoding approach based on an algorithm that converts spectrally deconvoluted Raman sub-bands into barcodes. Barcode-assisted Raman analyses could enable on-site identification in nearly real-time, thus implementing preventive oral control, enabling prompt selection of the most effective drug, and increasing the probability to interrupt disease transmission.