Laser-Scribed Graphene for Human Health Monitoring: From Biophysical Sensing to Biochemical Sensing.

Laser-scribed graphene (LSG), a classic three-dimensional porous carbon nanomaterial, is directly fabricated by laser irradiation of substrate materials. Benefiting from its excellent electrical and mechanical properties, along with flexible and simple preparation process, LSG has played a significant role in the field of flexible sensors. This review provides an overview of the critical factors in fabrication, and methods for enhancing the functionality of LSG. It also highlights progress and trends in LSG-based sensors for monitoring physiological indicators, with an emphasis on device fabrication, signal transduction, and sensing characteristics. Finally, we offer insights into the current challenges and future prospects of LSG-based sensors for health monitoring and disease diagnosis.

Evidence supported by Mendelian randomization: impact on inflammatory factors in knee osteoarthritis.

Background: Prior investigations have indicated associations between Knee Osteoarthritis (KOA) and certain inflammatory cytokines, such as the interleukin series and tumor necrosis factor-alpha (TNFα). To further elaborate on these findings, our investigation utilizes Mendelian randomization to explore the causal relationships between KOA and 91 inflammatory cytokines. Methods: This two-sample Mendelian randomization utilized genetic variations associated with KOA from a large, publicly accessible Genome-Wide Association Study (GWAS), comprising 2,227 cases and 454,121 controls of European descent. The genetic data for inflammatory cytokines were obtained from a GWAS summary involving 14,824 individuals of European ancestry. Causal relationships between exposures and outcomes were primarily investigated using the inverse variance weighted method. To enhance the robustness of the research results, other methods were combined to assist, such as weighted median, weighted model and so on. Multiple sensitivity analysis, including MR-Egger, MR-PRESSO and leave one out, was also carried out. These different analytical methods are used to enhance the validity and reliability of the final results. Results: The results of Mendelian randomization indicated that Adenosine Deaminase (ADA), Fibroblast Growth Factor 5(FGF5), and Hepatocyte growth factor (HFG) proteins are protective factors for KOA (IVWADA: OR = 0.862, 95% CI: 0.771-0.963, p = 0.008; IVWFGF5: OR = 0.850, 95% CI: 0.764-0.946, p = 0.003; IVWHFG: OR = 0.798, 95% CI: 0.642-0.991, p = 0.042), while Tumor necrosis factor (TNFα), Colony-stimulating factor 1(CSF1), and Tumor necrosis factor ligand superfamily member 12(TWEAK) proteins are risk factors for KOA. (IVWTNFα: OR = 1.319, 95% CI: 1.067-1.631, p = 0.011; IVWCSF1: OR = 1.389, 95% CI: 1.125-1.714, p = 0.002; IVWTWEAK: OR = 1.206, 95% CI: 1.016-1.431, p = 0.032). Conclusion: The six proteins identified in this study demonstrate a close association with the onset of KOA, offering valuable insights for future therapeutic interventions. These findings contribute to the growing understanding of KOA at the microscopic protein level, paving the way for potential targeted therapeutic approaches.

Two new oleanane triterpenes from Maytenus hookeri.

Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36-3.44 µM.

Investigating the distribution of microplastics in soils from e-waste dismantling sites and their adsorption of heavy metals.

Microplastics are characterized by strong hydrophobicity, large specific surface area. In addition to the pollutant they contain, the heavy metals adsorbed on the surface of microplastics can migrate or be transformed with them into the environmental medium, which is potentially harmful to humans. The distribution characteristics of microplastics in contaminated soil at the e-waste dismantling site were studied. The study investigated the adsorption characteristics of polyvinyl chloride (PVC), polypropylene (PP) and acrylonitrile-butadiene-styrene (ABS) on copper (Cu), zinc (Zn) and lead (Pb). It analysed the influence of various factors on the adsorption process of heavy metals, the adsorption law of microplastics on some of the heavy metals in the environment, and the risk of heavy metal release from microplastics to soil. The results showed that ABS and PP were the main microplastics in the contaminated soil. Among them, black, white and transparent microplastics accounted for 89.91%. The shape of microplastics is mainly granular, and microplastics with a particle size of 1-2 mm accounted for the largest proportion. Further studies showed that plastic particles made of ABS, PP and PVC also have the adsorption capacity for different types of heavy metals in soil, and the trends of adsorption capacity are: PP>PVC>ABS. When PP does not reach adsorption equilibrium in the adsorption process, the smaller the particle size and the more added amount, the greater the adsorption capacity. This is because the smaller the particle size of the microplastic is, the more adsorption points it can provide, increasing its ability to adsorb heavy metal ions.

Automated detection of otosclerosis with interpretable deep learning using temporal bone computed tomography images.

Objective: This study aimed to develop an automated detection schema for otosclerosis with interpretable deep learning using temporal bone computed tomography images. Methods: With approval from the institutional review board, we retrospectively analyzed high-resolution computed tomography scans of the temporal bone of 182 participants with otosclerosis (67 male subjects and 115 female subjects; average age, 36.42 years) and 157 participants without otosclerosis (52 male subjects and 102 female subjects; average age, 30.61 years) using deep learning. Transfer learning with the pretrained VGG19, Mask RCNN, and EfficientNet models was used. In addition, 3 clinical experts compared the system's performance by reading the same computed tomography images for a subset of 35 unseen subjects. An area under the receiver operating characteristic curve and a saliency map were used to further evaluate the diagnostic performance. Results: In prospective unseen test data, the diagnostic performance of the automatically interpretable otosclerosis detection system at the optimal threshold was 0.97 and 0.98 for sensitivity and specificity, respectively. In comparison with the clinical acumen of otolaryngologists at P < 0.05, the proposed system was not significantly different. Moreover, the area under the receiver operating characteristic curve for the proposed system was 0.99, indicating satisfactory diagnostic accuracy. Conclusion: Our research develops and evaluates a deep learning system that detects otosclerosis at a level comparable with clinical otolaryngologists. Our system is an effective schema for the differential diagnosis of otosclerosis in computed tomography examinations.

Construction and validation of a folate metabolism-related gene signature for predicting prognosis in HNSCC.

PURPOSE: Metabolic reprogramming is currently considered a hallmark of tumor and immune development. It is obviously of interest to identify metabolic enzymes that are associated with clinical prognosis in head and neck squamous cell carcinomas (HNSCC). METHODS: Candidate genes were screened to construct folate metabolism scores by Cox regression analysis. Functional enrichment between high- and low-folate metabolism groups was explored by GO, KEGG, GSVA, and ssGSEA. EPIC, MCPcounter, and xCell were utilized to explore immune cell infiltration between high- and low-folate metabolism groups. Relevant metabolic scores were calculated and visually analyzed by the "IOBR" software package. RESULTS: To investigate the mechanism behind metabolic reprogramming of HNSCC, 2886 human genes associated with 86 metabolic pathways were selected. Folate metabolism is significantly enriched in HNSCC, and that the six-gene (MTHFD1L, MTHFD2, SHMT2, ATIC, MTFMT, and MTHFS) folate score accurately predicts and differentiates folate metabolism levels. Reprogramming of folate metabolism affects CD8T cell infiltration and induces immune escape through the MIF signaling pathway. Further research found that SHMT2, an enzyme involved in folate metabolism, inhibits CD8T cell infiltration and induces immune escape by regulating the MIF/CD44 signaling axis, which in turn promotes HNSCC progression. CONCLUSIONS: Our study identified a novel and robust folate metabolic signature. A folate metabolic signature comprising six genes was effective in assessing the prognosis and reflecting the immune status of HNSCC patients. The target molecule of folate metabolic reprogramming, SHMT2, probably plays a very important role in HNSCC development and immune escape.

Asiaticasics A-O, structurally intriguing coumarins from Toddalia asiatica with potential inflammatory inhibitory activity.

Ethyl acetate fraction of Toddalia asiatica was fractionated to yield fifteen previously undescribed prenylated coumarins, asiaticasics A-O (1-15) along with nine (16-24) known derivatives. The structures of these undescribed coumarins were established by spectroscopic analysis and reference data. Biological activity evaluation showed that compound 3 with the IC50 value of 2.830 µM and compound 12 with the IC50 value of 0.682 µM owned anti-inflammatory activity by detecting the rate of lactate dehydrogenase release in pyroptosis J774A.1 cells. The results showed that the expression of Caspase-1 and IL-1ß was decreased in a dose-dependent manner in the compound 12 treatment group, suggesting that compound 12 may reduce pyroptosis by inhibiting NLRP3 inflammasome. To further determine that compound 12 treatment can inhibit macrophage pyroptosis, morphological observation was performed and the results were consistent with the bioactivity evaluation.

Identification of a family with van der Hoeve's syndrome harboring a novel COL1A1 mutation and generation of patient-derived iPSC lines and CRISPR/Cas9-corrected isogenic iPSCs.

Van der Hoeve's syndrome, also known as osteogenesis imperfecta (OI), is a genetic connective tissue disorder characterized by fragile, fracture-prone bone and hearing loss. The disease is caused by a gene mutation in one of the two type I collagen genes COL1A1 or COL1A2. In this study, we identified a novel frameshift mutation of the COL1A1 gene (c.1607delG) in a family with OI using whole-exome sequencing, bioinformatics analysis and Sanger sequencing. This mutation may lead to the deletion of a portion of exon 23 and the generation of a premature stop codon in the COL1A1 gene. To further investigate the impact of this mutation, we established two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells of OI patients carrying a novel mutation in the COL1A1 gene. Osteoblasts (OB) derived from OI-iPSCs exhibited reduced production of type I collagen and diminished ability to differentiate into osteoblasts. Using a CRISPR-based homology-directed repair strategy, we corrected the OI disease-causing COL1A1 novel mutations in iPSCs generated from an affected individual. Our results demonstrated that the diminished expression of type I collagen and osteogenic potential were enhanced in OB induced from corrected OI-iPSCs compared to those from OI-iPSCs. Overall, our results provide new insights into the genetic basis of Van der Hoeve's syndrome and highlight the potential of iPSC technology for disease modeling and therapeutic development.

Protoilludane-Type and Related Nor-Sesquiterpenes from Phellinus hartigii and Their Anti-Hypertrophic Activities in Rat Cardiomyocytes.

Three nor-sesquiterpenes, phellinharts A-C (1-3), isolated from Phellinus hartigii, exhibited unprecedented protoilludane and cerapicane-type structures. The structures of compounds 1-3 were elucidated via spectroscopic analysis, quantum chemical calculations, and X-ray diffraction. Potential biogenic pathways involving demethylation, ring cleavage, and rearrangement were proposed. Compounds 1-3 displayed potent anti-hypertrophic activities with low cytotoxicity (CC50 > 50 µM) in rat cardiomyocytes, underscoring their therapeutic potential.

[Application and efficacy analysis of tympanic cartilage shaping device in endoscopic type â tympanoplasty].

Objective:To study the feasibility and efficacy of using a tympanic cartilage shaping device in endoscopic type Ⅰ tympanoplasty. Methods:A tympanic cartilage shaper was designed and manufactured by measuring tympanic membrane dimensions with HRCT imaging for cutting and shaping cartilage to repair the tympanic membrane. From August 2019 to October 2021, 66 patients（72 ears） with chronic suppurative otitis media in Xiangya Hospital underwent endoscopic type Ⅰ tympanoplasty with this tympanic cartilage shaping device, and were observed the tympanic membrane healing and hearing recovery effect after surgery. Postoperative follow-up ranged from 3-24 months, with an average of 9 months. The data were analyzed by the SPSS 26.0 software. Results:According to the imaging measurements, tympanic pars tensa width（8.60±0.20） mm, height（8.64±0.19） mm, design and manufacture a cylindrical cartilage shaping device with inner diameter 8.60 mm. After tympanoplasty, the healing rate of tympanic membrane was 100%; The average air-bone gap before surgery was（23.10±7.33） dB, then（14.30±6.40） dB 1 month after surgery, which were significant reduced compared with those before surgery. The average air-bone gap was（14.30±6.40） dB 3 month after surgery compared with 1 month after surgery, the difference was also statistically significant（t=6.630, P<0.05）. Conclusion:The tympanic membrane cartilage shaper shaping cartilage in endoscopic tympanoplasty is simple, stable and reliable, which can reduce the time of graft cartilage processing, improve the efficiency of surgery, and restore the tympanic membrane morphology and function in the postoperative period.

Structural characterization of a distinct fucan sulfate from Pattalus mollis through an oligosaccharide mapping approach.

The elucidation of the precise structure of fucan sulfate is essential for understanding the structure-activity relationship and promoting potential biomedical applications. In this work, the structure of a distinct fucan sulfate fraction V (PmFS in Ref 15 and FSV in Ref 16 → PFV) from Pattalus mollis was investigated using an oligosaccharide mapping approach. Six size-homogeneous fractions were purified from the mild acid hydrolyzed PFV and identified as fucitols, disaccharides and trisaccharides by 1D/2D NMR and MS analysis. Significantly, the sulfation pattern, glycosidic linkages, and sequences of all the oligosaccharides were unambiguously identified. The common 2-desulfation of the reducing end residue of the oligosaccharides was observed. Overall, the backbone of PFV was composed of L-Fuc2S (major) and L-Fuc3S (minor) linked by α1,4 glycosidic bonds. Importantly, the branches contain both monosaccharide and disaccharide linked to the backbone by α1,3 glycosidic linkages. Thus, the tentative structure of natural PFV was shown to be {-(R-α1,3)-L-Fuc2S-α1,4-(L-Fuc2S/3S-α1,4)x-}n, where R is L-Fuc(2S)4S-α1,3/4-L-Fuc4S(0S)- or L-Fuc(2S)4S-. Our results provide insight into the heterogeneous structure of the fucan sulfate found in sea cucumbers. Additionally, PFV and its fractions showed strong anticoagulant and anti-iXase activities, which may be related to the distinct structure of PFV.

Effect of phosphoric acid additive on the electrolyte of all-vanadium flow batteries.

A phosphoric acid additive with an optimal concentration of 0.1 M can vastly promote the diffusion kinetics of the redox reaction between V(IV) and V(V) without a significant decline in energy efficiency for 300 cycles, and maintain the high-temperature stability (55 °C) of an electrolyte at a high state of charge (SOC) of 70% over the course of 30 days.

PAX3 mutation suppress otic progenitors proliferation and induce apoptosis by inhibiting WNT1/ß-catenin signaling pathway in WS1 patient iPSC-derived inner ear organoids.

Waardenburg syndrome type 1 (WS1) is a hereditary disease mainly characterized by sensorineural hearing loss, dystopia canthorum, and pigmentary defects. To elucidate molecular mechanisms underlying PAX3-associated hearing loss, we developed inner ear organoids model using induced pluripotent stem cells (iPSCs) derived from WS1 patient and healthy individual. Our results revealed a significant reduction in the size of inner ear organoids, accompanied by an increased level of apoptosis in organoids derived from WS1 patient-iPSCs carrying PAX3 c.214A > G. Transcriptome profiling analysis by RNA-seq indicated that inner ear organoids from WS1 patients were associated with suppression of inner ear development and WNT signaling pathway. Furthermore, the upregulation of the WNT1/ß-catenin pathway which was achieved through the correction of PAX3 isogenic mutant iPSCs using CRISPR/Cas9, contributed to an increased size of inner ear organoids and a reduction in apoptosis. Together, our results provide insight into the underlying mechanisms of hearing loss in WS.

Susceptibility of immature spiral ganglion neurons to aminoglycoside-induced ototoxicity is mediated by the TRPV1 channel in mice.

Aminoglycoside antibiotics are among the most common agents that can cause sensorineural hearing loss. From clinical experience, premature babies, whose inner ear is still developing, are more susceptible to aminoglycoside-induced ototoxicity, which is echoed by our previous study carried out in organotypic cultures. This study aimed to investigate whether a nonselective cation channel, TRPV1, contributes to the susceptibility of immature spiral ganglion neurons (SGNs) to the damage caused by aminoglycosides. Through western blotting and immunofluorescence, we found that the TRPV1 expression levels were much higher in immature SGNs than in their mature counterparts. In postnatal day 7 cochlear organotypic cultures, AMG-517 reduced reactive oxygen species generation and inhibited SGN apoptosis under aminoglycoside challenge. However, in adult mice, AMG-517 did not ameliorate the ABR threshold increase at high frequencies (16 kHz and 32 kHz) after aminoglycoside administration, and the SGNs within the cochleae had no morphological changes. By further regulating the function of TRPV1 in primary cultured SGNs with its inhibitor AMG-517 and agonist capsaicin, we demonstrated that TRPV1 is a major channel for aminoglycoside uptake: AMG-517 can significantly reduce, while capsaicin can significantly increase, the uptake of GTTR. In addition, TRPV1 knockdown in SGNs can also significantly reduce the uptake of GTTR. Taken together, our results demonstrated that aminoglycosides can directly enter immature SGNs through the TRPV1 channel. High expression of TRPV1 contributes to the susceptibility of immature SGNs to aminoglycoside-induced damage. The TRPV1 inhibitor AMG-517 has the potential to be a therapeutic agent for preventing aminoglycoside-induced ototoxicity in immature SGNs.

Diverse diterpenoids from Callicarpa rubella Lindl. as natural inhibitors of macrophage foam cell formation.

Ten undescribed diterpenoids namely rubellawus E-N of structural types pimarane (1, 3-4), nor-abietane (2), nor-pimarane (5-6), isopimarane (7-9), and nor-isopimarane (10), along with eleven known compounds, were isolated and identified from the aerial parts of Callicarpa rubella Lindl. The structures of the isolated compounds were confirmed by comprehensive spectroscopic analyses and quantum chemical computations. Pharmacologically, almost all the compounds exhibited a potential inhibitory effect on oxidized low-density lipoprotein-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment of atherosclerosis.

An optical and visual multi-mode sensing platform base on nitrogen, sulfur, boron co-doped carbon dots for rapid and simple determination of ferric ions in water.

Abnormal iron ions levels may lead to some diseases and serious environmental pollution. Herein, optical and visual detection strategies of Fe3+ in water based on co-doped carbon dots (CDs) were established in the present study. Firstly, a one-pot synthetic strategy for the preparation of the N, S, B co-doped CDs with a home microwave oven was developed. Secondly, the optical properties, chemical structures, and morphology of CDs were further characterized by fluorescence spectroscopy, Uv-vis absorption spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and transmission electron microscope. Finally, the results indicated that the fluorescence of the co-doped CDs was quenched by ferric ions via the static mechanism and the aggregation of CDs, accompanied by the increased red color. The multi-mode sensing strategies of Fe3+ with fluorescence photometer, UV-visible spectrophotometer, portable colorimeter and smartphone had the advantages of good selectivity, excellent stability and high sensitivity. Fluorophotometry based on co-doped CDs was a powerful probe platform for measuring lower concentrations of Fe3+ due to its higher sensitivity, better linear relationship, lower limit of detection (0.27 µM) and limit of quantitation (0.91 µM). In addition, the visual detection methods with a portable colorimeter and smartphone had been proven to be very suitable for rapid and simple sensing of higher concentrations of Fe3+. Moreover, the co-doped CDs utilized for Fe3+ probes in tap water and boiler water obtained satisfactory results. Consequently, the efficient, versatile optical and visual multi-mode sensing platform could be extended to apply such a visual analysis of ferric ions in the biological, chemical and other fields.

Structure-constrained deep feature fusion for chronic otitis media and cholesteatoma identification.

Chronic suppurative otitis media (CSOM) and middle ear cholesteatoma (MEC) were two most common chronic middle ear disease(MED) clinically. Accurate differential diagnosis between these two diseases is of high clinical importance given the difference in etiologies, lesion manifestations and treatments. The high-resolution computed tomography (CT) scanning of the temporal bone presents a better view of auditory structures, which is currently regarded as the first-line diagnostic imaging modality in the case of MED. In this paper, we first used a region-of-interest (ROI) network to find the area of the middle ear in the entire temporal bone CT image and segment it to a size of 100*100 pixels. Then, we used a structure-constrained deep feature fusion algorithm to convert different characteristic features of the middle ear in three groups as suppurative otitis media (CSOM), middle ear cholesteatoma (MEC) and normal patches. To fuse structure information, we introduced a graph isomorphism network that implements a feature vector from neighbourhoods and the coordinate distance between vertices. Finally, we construct a classifier named the "otitis media, cholesteatoma and normal identification classifier" (OMCNIC). The experimental results achieved by the graph isomorphism network revealed a 96.36% accuracy in all CSOM and MEC classifications. The experimental results indicate that our structure-constrained deep feature fusion algorithm can quickly and effectively classify CSOM and MEC. It will help otologist in the selection of the most appropriate treatment, and the complications can also be reduced.

Clinical characteristics and surgical strategy of glomus tympanicum tumors. / 鼓室体瘤的临床特征及手术策略.

OBJECTIVES: To summarize the clinical characteristics of glomus tympanicum tumors, and to explore the surgical methods and the strategy for auditory protection. METHODS: Ten cases (ears) of glomus tympanicum tumors were collected from the Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University from August 2014 to February 2022. All patients underwent endoscopic or microscopic surgery to achieve total removal of the tumor, followed up for 3 months to 8 years. We summarized and analyzed its clinical characteristics, compared the preoperative and postoperative hearing levels of patients, and made a retrospective summary of the surgical methods and the strategy for auditory protection. RESULTS: Ten patients were all female at (49.50±8.00) years old. Their medical history ranged from 15 days to 6 years. Seven patients complained of pulsatile tinnitus, and 80% (8/10) of the affected ears suffered different degrees of hearing loss. According to the modified Fisch & Mattox classification of glomus tympanicum tumors, 3 ears (30%) of 10 ears were A1, 2 ears (20%) were A2 and 5 ears (50%) were B1. In all 10 cases (ears), hearing was improved in 3 cases, bone gas conductance was maintained in 6 cases, and hearing was slightly decreased in 1 case. The difference of bone gas conductance was 0-10 dB in 7 cases (ears) after operation, and 10-20 dB in 3 cases (ears). There was no significant difference in the average air conduction hearing threshold, bone conduction hearing threshold and air-bone conduction difference between before and after operation (all P>0.05). All cases had no postoperative complications, and the external auditory canal and the incision behind the ear healed well. There was no recurrence after follow-up. CONCLUSIONS: Glomus tympanicum tumor is easy to bleed, so it is a challenge for total tumor resection and hearing function protection during operation. For type A and type B1 tumors, they can be completely removed under the condition of keeping the tympanic membrane and the ossicular chain. At the same time, the postoperative hearing function can be preserved, and even the hearing can be improved.

Research and application progress in deep learning in otology. / æ·±åº¦å­¦ä¹ åœ¨è€³ç§‘å­¦ä¸­çš„ç ”ç©¶ä¸Žåº”ç”¨è¿›å±•.

With the optimization of deep learning algorithms and the accumulation of medical big data, deep learning technology has been widely applied in research in various fields of otology in recent years. At present, research on deep learning in otology is combined with a variety of data such as endoscopy, temporal bone images, audiograms, and intraoperative images, which involves diagnosis of otologic diseases (including auricular malformations, external auditory canal diseases, middle ear diseases, and inner ear diseases), treatment (guiding medication and surgical planning), and prognosis prediction (involving hearing regression and speech learning). According to the type of data and the purpose of the study (disease diagnosis, treatment and prognosis), the different neural network models can be used to take advantage of their algorithms, and the deep learning can be a good aid in treating otologic diseases. The deep learning has a good applicable prospect in the clinical diagnosis and treatment of otologic diseases, which can play a certain role in promoting the development of deep learning combined with intelligent medicine.