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Competing Interests: Conflict of Interest. The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Natural polysaccharide-based active-ingredient carriers have been a source of great concern for a long time. In order to explore potential antibiotics and probiotics carriers, a novel injectable chondroitin sulfate/salecan (CS) hydrogel was constructed by forming dynamic hydrazone bonds. Scanning electron microscope (SEM), proton nuclear magnetic resonance ( 1 H NMR), Fourier transform infrared spectroscopy (FTIR), bacteriostatic test, and rheological experiments were used to investigate the chemical structure, inherent morphology, and enzymatic corruption of the hydrogel in vitro. The resulting hydrogels exhibited ideal probiotics loading capacity, drug release behavior, excellent antimicrobial activity and variable properties. Crucially, owing to its exceptional biocompatibility and reversible crosslinking network, this hydrogel can function as a three-dimensional extracellular matrix for cells, enabling cells to maintain high vitality and proliferation, and promote wound healing. The aforementioned findings indicated that this novel hydrogel can be a promising candidate as an active-ingredient carrier and scaffold material for tissue engineering., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Explore the associations between dietary choline intake and the incidence of dementia, Alzheimer's disease (AD), mild cognitive impairment (MCI), and current cognitive performance in the UK Biobank cohort., Methods: Dietary choline intake was categorized into quartiles of consumption based on 24-hour dietary recalls, with units expressed as milligrams per day. Diagnoses of dementia, AD, and MCI were identified using ICD-9/10 codes. Current cognitive performance was assessed via the computerized touchscreen interface. After adjusting for sociodemographic factors, dietary and lifestyle behaviors, and comorbid conditions, Cox proportional hazards regression, logistic regression, and restricted cubic splines were used to analyze the association between choline intake and dementia or cognitive performance., Results: Among 125,594 participants (55.8% female), with a mean age of 56.1 years (range: 40 to 70 years) at baseline, and a median follow-up of 11.8 years, 1,103 cases of dementia (including 385 AD) and 87 cases of MCI were recorded. U-shaped associations were observed between choline intake and dementia and AD. Participants in the 2 nd quartile of total choline intake had lower risks compared to those in the lowest quartile, with HR of 0.80 (95% CI: 0.67, 0.96) for dementia and 0.76 (0.58, 1.00) for AD. Moderate intake of choline derivative, including free choline (HR, 0.77; 95%CI, 0.65, 0.92), phosphatidylcholine (0.82; 0.68, 0.98), sphingomyelin (0.82; 0.69, 0.98) and glycerophosphocholine (0.83; 0.70, 1.00), were associated with a 17% to 23% lower odds of dementia. Additionally, moderate total choline intake was associated with an 8% to 13% lower odds of poor cognitive performance in visual attention (OR, 0.92; 95%CI, 0.86, 0.99), fluid intelligence (0.87; 0.82, 0.92), and complex processing speed (0.90; 0.84, 0.95)., Conclusions: In conclusion, our findings suggest that moderate dietary choline intake, ranging from 332.89 mg/d to 353.93 mg/d, is associated with lower odds of dementia and better cognitive performance., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dan Liu reports financial support was provided by National Natural Science Foundation of China. Dan Liu reports financial support was provided by the Guangzhou Science and Technology Project. Dan Liu reports financial support was provided by Young Elite Scientists Sponsorship Program by CAST. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Producing hydrogen via seawater electrolysis is pivotal for addressing both energy and environmental crises. An industrial-current-density electrocatalyst consisting of Mo-doped FeCoP nanorods decorated with MnO x nanosheets is elaborately designed and grows in situ on nickel foam forming hierarchical Mo-FeCoP@MnO x /NF (M-FCP@MnO x /NF) for seawater electrolysis. Density functional theory calculations demonstrate that MnO x species remarkably reduce the adsorption capacity of Cl - , which enhances the corrosion resistance and selectivity of M-FCP@MnO x /NF during seawater electrolysis. Moreover, incorporating high-valence Mo species forms a superficial electrostatic layer on electrocatalysts to repel Cl - . Owing to its enhanced double protection mechanism and unique self-healing characteristics, M-FCP@MnO x /NF requires overpotentials of only 209 mV (HER) and 270 mV (OER) to reach a current density of ≈1.0 A cm -2 and maintains stable operation over 120 h during alkaline electrolysis of seawater. The colorimetric analysis indicates negligible ClO - production post stability test, indicating that the OER selectivity approaches 100%., (© 2024 Wiley‐VCH GmbH.)

The burgeoning proliferation of infections attributed to multidrug-resistant (MDR) bacterial pathogens is profoundly undermining conventional chemotherapeutic modalities, portending a grave menace to global public health. The propagation of drug resistance among bacteria is fundamentally facilitated by bacterial interactions, with extracellular vesicles (EVs) assuming a critical role in interbacterial communication. Here, we briefly delineate the methodologies for isolation, extraction, and characterization of EVs from both Gram-negative and Gram-positive bacterial origins. We further investigate assorted methodologies to augment EV production, embracing physical stimulation, chemical elicitation, and genetic engineering. Moreover, we expound on the pivotal involvement of EVs in the facilitation of bacterial drug resistance proliferation and anticipate future trajectories of research and application potential. This overview of EV-mediated novel mechanisms of horizontal gene transfer implicated in antibiotic resistance among bacteria aims to obstruct the transmission conduits of bacterial drug resistance and thus fortify public health integrity.

Background: Extranodal extension (ENE) had been included in the latest cancer staging system in hypopharyngeal squamous cell carcinoma (HypoSCC). However, the impact of ENE on HypoSCC survival and treatment outcomes are still unclear., Methods: Records from all HypoSCC patients diagnosed at the National Taiwan University Hospital from January 2007 to December 2018 were reviewed. All patients were divided into two groups, with or without ENE. Clinical features, pathological factors, and survival rates between the two groups were reviewed., Results: We analyzed data from 388 HypoSCC patients, 125 (32.22%) with and 263 (67.78%) without ENE. The 5-year overall survival of the HypoSCC patients with radiological ENE, pathological ENE, and without ENE were 22.9%, 40.3%, and 55.5%. From the multivariate analysis, primary T3/T4 classification (p = 0.001) and radiological ENE (p < 0.001) were independent risk factors for disease-free and overall survival (OS). Finally, upfront neck dissection may significantly benefit disease-free survival (DFS) and neck nodal control in ENE+ (p = 0.002 and p = 0.007, respectively) or ENE- patients (p = 0.003 and p = 0.02, respectively)., Conclusion: More than one-third of HypoSCC patients have ENE, with significantly lower OS and DFS. The upfront neck dissection could provide better DFS and neck nodal control., (© 2024 Wiley Periodicals LLC.)

Background: The prognostic significance of margin-to-depth ratio (MDR) in oral cavity squamous cell carcinoma (OCSCC) remains unclear, particularly in comparison to traditional margin status. We aimed to examine the association between MDR and clinical outcomes in a large Taiwanese cohort., Methods: A total of 18,324 patients with first primary OCSCC were categorized by margin status: positive (1013), <5 mm (8371), and ≥ 5 mm (8940). Disease-specific survival (DSS) and overall survival (OS) served as the main outcome measures., Results: After excluding patients with positive margins (MDR = 0), the optimal MDR cutoff value for DSS and OS was 0.6. Patients with MDR > 0.6 showed significantly better 5-year DSS and OS rates (87 %, 81 %) compared to those with MDR ≤ 0.6 (71 %, 63 %) and MDR = 0 (53 %, 43 %). Multivariable analysis identified MDR ≤ 0.6 as independently associated with both DSS and OS in the entire cohort (hazard ratio [HR] = 1.34/1.32). This finding was consistent in the subgroups with surgical margins < 5 mm (HR = 1.39 for DSS and 1.38 for OS) and margins ≥ 5 mm (HR = 1.21 for both DSS and OS). In subgroups with surgical margins < 5 mm and ≥ 5 mm, an MDR > 0.6 was associated with better survival outcomes., Conclusions: An MDR (cutoff: 0.6) is independently associated with prognosis in OCSCC, offering improved risk stratification compared to margin status alone. While MDR may guide surgical margin modification, further research is needed to determine whether MDR could serve as a postoperative indicator for adjuvant therapy in patients with close or clear margins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Aromatic essential oils have been shown to relieve anxiety and enhance relaxation, although the neural circuits underlying these effects have remained unknown. Here, it is found that treatment with 1.0% bergamot essential oil (BEO) exerts anxiolytic-like effects through a neural circuit projecting from the anterior olfactory nucleus (AON) to the anterior cingulate cortex (ACC) in acute restraint stress model mice. Collectively, in vivo two-photon calcium imaging, viral tracing, and whole-cell patch clamp recordings show that inhalation exposure to 1.0% BEO can activate glutamatergic projections from the AON to GABAergic neurons in the ACC, which drives inhibition of local glutamatergic neurons (AON Glu →ACC GABA→Glu ). Optogenetic or chemogenetic manipulation of this pathway can recapitulate or abolish the BEO-induced anxiolytic-like behavioral effects in mice with ARS. Beyond depicting a previously unrecognized pathway involved in stress response, this study provides a circuit mechanism for the effects of BEO and suggests a potential target for anxiety treatment., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The increasing interest in hydrogel matrices and their diverse applications has fueled extensive research. However, single-component gels have a limited adjustable performance range, and multi-component gels raise concerns about biological safety, hindering their widespread use. This study focuses on harnessing high-speed shearing and ultrasound-assisted methods to incorporate active natural Haematococcus pluvialis (HP), creating novel composite hydrogels in conjunction with biological macromolecule gellan gum, and eliminating the need for structural modifications or chemical crosslinking. Rich astaxanthin, proteins, polysaccharides, and other components in HP can fill and promote the formation of a unified functional network. The study aims to explore the potential of HP as a rheology regulator and investigate its impact on the rheological properties of the gels. Various rheological models, including Power-Law, Herschel-Bulkley, and Arrhenius, were employed for comparative analysis. This pioneering report on gellan/HP hydrogels holds significant importance as they exhibit optimized elasticity, thermal stability, enhanced injectability, and self-recovery, making them suitable for a wide range of applications in specialized medical food and biomedicine., (© 2024 Institute of Food Technologists.)

The rising incidence of colistin (COL) resistance poses a significant challenge, undermining the therapeutic efficacy of COL against life-threatening bacterial infections. Therefore, the urgent identification and development of new therapeutics are imperative. It has been proven that combinations of antibiotics and promising non-antibiotic agents could be a potential strategy to combat infections caused by MDR pathogens. Due to various antimicrobial properties, medicinal plants have attracted significant attention, which could be promising adjuvant. In this study, we investigated the synergistic effects of combining COL with resveratrol (RST) and baicalin (BAI) against mcr-1-positive Escherichia coli through antibiotic susceptibility testing, checkerboard method and time-killing assays. The mechanisms of combination treatment were analyzed using SEM, fluorometric assays and transcriptome analysis. The molecular docking assay was conducted to elucidate potential interactions between RST, BAI and the MCR-1 protein. Finally, we assessed the in vivo efficacy of combination against mcr-1-positive Escherichia coli. The results demonstrated that the combination of RST, BAI and COL showed significant synergistic activity both in vitro and in vivo. Further mechanistic study revealed that the combination could increase the membrane-damaging ability of COL, disrupt the homeostasis of proton motive force (PMF), inhibit the activity of efflux pumps and impair ATP supply. The molecular docking revealed that RST and BAI could bind to MCR-1 stably, indicating the combination of RST and BAI may be an effective MCR-1 inhibitor. Our findings demonstrated that the combination of RST and BAI might be potential COL adjuvant, providing an alternative approach to address mcr-1-positive Escherichia coli infections., Competing Interests: Declaration of Competing Interest All authors disclosed no relevant relationships. The authors declared no potential conflicts of interest with respect to the research, author-ship, and publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ultrasensitive analysis of organic molecules is crucial for various fundamental research and applications. State-of-the-art techniques for this purpose can achieve detection limits of several hundred ppq (parts-per-quadrillion), while a higher sensitivity is pursued constantly. To achieve this goal, we develop femtosecond laser assisted chemical ionization for mass spectrometry. This technique combines the advantages of femtosecond laser ionization and chemical ionization, either of which enables subppt (parts-per-trillion) mass spectrometry analysis of organic molecules. The results demonstrate that the developed ionization technique, when employed in mass spectrometry, can surpass femtosecond laser ionization by more than 3 orders of magnitude in sensitivity, while still maintaining good versatility and the ability to work under ambient conditions. This work paves the way for subppq analysis of organic molecules in gas phase and even in ambient environments, which can open up new research fields for trace substance analysis in atmospheric environment, clinical diagnosis, biomedical studies, etc.

Background: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE., Methods: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted., Results: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 - 7000 cGy, n = 1155 versus 6000 - 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578)., Conclusions: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600-7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients., (© 2024. The Author(s).)

Cisplatin-induced ototoxicity occurs in approximately half of patients treated with cisplatin, and pediatric patients are more likely to be affected than adults. The oxidative stress elicited by cisplatin is a key contributor to the pathogenesis of ototoxicity. Notoginsenoside R1 (NGR1), the main bioactive compound of Panax notoginseng saponins, has antioxidant and antiapoptotic effects. This study investigated the ability of NGR1 to protect against cisplatin-induced damage in auditory HEI-OC1 cells and neonatal murine cochlear explants. The viability of HEI-OC1 cells treated with NGR1 and cisplatin was greater than that of cells treated with cisplatin alone. The results of Western blots and immunostaining for cleaved caspase-3 revealed that the level of cleaved caspase-3 in the cells treated with cisplatin was repressed by NGR1. NGR1 attenuated cisplatin-induced cytotoxicity in HEI-OC1 cells. Intracellular reactive oxygen species (ROS) were detected with a DCFDA assay and immunostaining for 4-HNE. The result revealed that its expression was induced by cisplatin and was significantly reduced by NGR1. Moreover, NGR1 can promote heme oxygenase-1 (HO-1) expression at both the mRNA and protein levels. ZNPPIX, an HO-1 inhibitor, was administered to cisplatin-treated cells to investigate the role of HO-1 in the protective effect of NGR1. The suppression of HO-1 activity by ZNPPIX markedly abolished the protective effect of NGR1 on cisplatin-treated cells. Therefore, NGR1 protects cells from cisplatin-induced damage by activating HO-1 and its antioxidative activity. In cochlear explants, NGR1 protects cochlear hair cells and attenuates cisplatin-induced ototoxicity by inhibiting ROS generation. In the group treated with cisplatin alone, prominent loss of outer hair cells and severe damage to the structure of the stereociliary bundles of inner and outer hair cells were observed. Compared with the group treated with cisplatin alone, less loss of outer hair cells ( p = 0.009) and better preservation of the stereociliary bundles of hair cells were observed in the group treated with cisplatin and NGR1. In conclusion, these findings indicate that NGR1 can protect against cisplatin-induced ototoxicity by inducing HO-1 expression and suppressing oxidative stress.

Nasopharyngeal carcinoma (NPC) risk prediction models based on Epstein-Barr virus (EBV)-antibody testing have shown potential for screening of NPC; however, the long-term stability is unclear. Here, we investigated the kinetics of two EBV-antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2-marker enzyme-linked immunosorbent assay score and 13-marker multiplex serology score using the intra-class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20-year follow-up, the 2-marker score showed high stability over time, whereas the 13-marker score was more variable (p < .05). Case-control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2-marker score than the 13-marker score (p < .05). The 2-marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13-marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high-risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high-risk regions., (© 2024 UICC.)

Immunotherapy has revolutionized cancer treatment, but the lack of a reliable predictive biomarker for treatment response remains a challenge. Alpha-1,6-Mannosylglycoprotein 6-β-N-Acetylglucosaminyltransferase 5 (MGAT5) is a key regulator of complex N-glycan synthesis, and its dysregulation is associated with cancer progression. The lectin Phaseolus vulgaris leukoagglutinin (PHA-L) specifically binds to mature MGAT5 products. Previous studies have indicated elevated PHA-L staining in head and neck squamous cell carcinoma (HNSCC), which implies increased activity of MGAT5. However, the specific role of MGAT5 in HNSCC remains unclear. In this study, we found significantly higher PHA-L staining and MGAT5 expression in HNSCC tumors compared to adjacent non-tumor tissues. Using a mass spectrometry (MS)-based glycoproteomic approach, we identified 163 potential protein substrates of MGAT5. Functional analysis revealed that protein substrates of MGAT5 regulated pathways related to T cell proliferation and activation. We further discovered that PD-L1 was among the protein substrates of MGAT5, and the expression of MGAT5 protected tumor cells from cytotoxic T lymphocyte (CTL) killing. Treatment of nivolumab alleviated the protective effects of MGAT5 on CTL activity. Consistently, patients with MGAT5-positive tumors showed improved responses to immunotherapy compared to those with MGAT5-negative tumors. Using purified PD-L1 from HNSCC cells and a glycoproteomic approach, we further deciphered that the N35 and N200 sites carry the majority of complex N-glycans on PD-L1. Our findings highlight the critical role of MGAT5-mediated branched N-glycans on PD-L1 in modulating the interaction with the immune checkpoint receptor PD-1. Consequently, we propose that MGAT5 could serve as a biomarker to predict patients' responses to anti-PD-1 therapy. Furthermore, targeting the branched N-glycans at N35 and N200 of PD-L1 may lead to the development of novel diagnostic and therapeutic approaches., (© 2024. The Author(s).)

A novel method was developed for the rapid detection of heavy metals in firework solutions with high sensitivity and minimal pretreatment by enriching them with ethylenediaminetetraacetic acid (EDTA) reagent and analyzing them using microwave plasma torch mass spectrometry (MPT-MS). Quantitative results showed that the limits of detection and quantification for heavy metals (Pb, Ba, Sr, and Ag) ranged from 0.05 to 0.25 and 0.38 to 0.71 μg·L -1 , respectively. The linear dynamic ranges covered at least two orders of magnitude, with correlation coefficients exceeding 0.99. Fireworks from five regions in China were also analyzed quantitatively, detecting heavy metals including Pb, Ba, Sr, and Ag, with recovery rates ranging from 87.9% to 107.5%. Good separation between the firework samples from different regions was achieved by using element ratios and principal component analysis (PCA). These results from the preliminary study showed that the EDTA-assisted MPT-MS combined with PCA is a powerful tool for characterizing firework samples and tracing them back to their sources, which is valuable to effectively regulate and manage banned fireworks., (© 2024 John Wiley & Sons Ltd.)

Different clay grains affect the structural strength of loess through the cementation of skeletal particles. This study investigates both clay-clay grains and quartz-clay grains. Clay-clay grains mixed loess (CM-L) and quartz-clay grains loess (Q-L) samples were prepared, and their unsaturated shear properties analyzed. X-ray diffractometry (XRD) analysis was conducted to determine the types and proportions of clay grains. Ball mill grinding and laser particle size analysis were employed to ensure comparable sizes of clay grains, while mercury intrusion porosimetry (MIP) tests confirmed similar pore characteristics. Scanning electron microscope (SEM) and unsaturated triaxial consolidation and drainage tests explored the impact of different clay grains on loess shear characteristics, assessing both microscopic and macroscopic performance. The results indicate that CM-L loess exhibits higher cohesion and a lower internal friction angle at the same matric suction level. The cohesion and internal friction angle of both CM-L and Q-L loess exhibit a linear relationship within the range of 50-200 kPa matrix suction. The cohesive force ranges for CM-L and Q-L loess are 60.31-80.07 kPa and 43.01-69.60 kPa, respectively, while the ranges for internal friction angles are 19.95°-19.59° and 25.91°-25.06°, respectively. Compared to Q-L loess, CM-L loess exhibits an average difference in cohesion of 23.18 kPa and in internal friction angle of -5.72°. The microscopic variation in shear strength can be attributed to the "fish scale-like" interlocking state between clay-clay grains and the "tower-like" scattering arrangement of quartz-clay grains. In conclusion, the effect of different clay-grain types on the shear strength of loess varies significantly. The present study elucidates the relationship between the influence of different clay grains on the mechanical properties of loess and their microscopic structural characteristics, thereby providing crucial data for investigating the microscopic effects on the structural strength of loess., (© 2024. The Author(s).)

Mesoscale to nanoscale three-dimensional (3D) fabrication mostly requires complicated industry processing techniques. Here, we present a protocol for 3D shaping control by solidifying a water-based TiO 2 nanofluid drop on a polygonal wettability-patterned surface. We detail the steps for preparing stable TiO 2 nanofluid and wettability-patterned surfaces. We then describe the experimental procedure to obtain various and precise 3D morphologies by adjusting the deposited TiO 2 nanofluid drop volume. This protocol provides a promising technique for future 3D manufacturing. For complete details on the use and execution of this protocol, please refer to Jiang et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Neonatal meningitis significantly contributes to neonatal morbidity and mortality, yet large-scale epidemiological data in developing countries, particularly among very preterm infants (VPIs), remain sparse. This study aimed to describe the epidemiology of meningitis among VPIs in China., Design: Cross-sectional study using the Chinese Neonatal Network database from 2019 to 2021., Setting: 79 tertiary neonatal intensive care units in China., Patients: Infants with gestational age <32 weeks or birth weight <1500 g., Main Outcome Measures: Incidence, pathogen distribution, antimicrobial use and outcomes of bacterial and fungal meningitis., Results: Of 31 915 VPIs admitted, 122 (0.38%) infants were diagnosed with culture-confirmed meningitis, with 14 (11.5%) being early-onset (≤6 days of age) and 108 (88.5%) being late-onset (>6 days of age). The overall in-hospital mortality was 18.0% (22/122). A total of 127 pathogens were identified, among which 63.8% (81/127) were Gram-negative bacteria, 24.4% (31/127) were Gram-positive bacteria and 11.8% (15/127) were fungi. In terms of empirical therapy (on the day of the first lumbar puncture), the most commonly used antibiotic was meropenem (54.9%, 67/122). For definitive therapy (on the sixth day following the first lumbar puncture, 86 cases with available antibiotic data), meropenem (60.3%, 35/58) and vancomycin (57.1%, 16/28) were the most used antibiotics for Gram-negative and Gram-positive bacterial meningitis, respectively. 44% of infants with Gram-positive bacterial meningitis and 52% with Gram-negative bacterial meningitis received antibiotics for more than 3 weeks., Conclusion: 0.38% of VPIs in Chinese neonatal intensive care units were diagnosed with meningitis, experiencing significant mortality and inappropriate antibiotic therapy. Gram-negative bacteria were the predominant pathogens, with fungi emerging as a significant cause., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Glioma is a common primary malignant brain tumor with low survival rate. Immunotherapy with immune checkpoints inhibitors (ICI) can be a choice for glioma management, and extracellular vesicles (EVs) are recognized as a potential drug delivery system for various disease management due to their enhanced barrier permeation ability and immunomodulatory effect. The aim of this study is to develop ICI-loaded EVs (ICI/EV) that have sufficient efficacy in managing glioma. Calcium phosphate particles (CaP) were used to stimulate the secretion of EVs from murine macrophage cells. CaP conditioning of cells showed an enhanced amount of EVs secretion and macrophage polarization toward a proinflammatory phenotype. The CaP-induced EVs were shown to polarize macrophages into proinflammatory phenotype in vitro , as correlated with the conditioning method. ICI/EVs were successfully prepared with high loading efficiency using the sonication method. The EVs can be distributed throughout the entire brain upon intranasal administration and facilitate ICIs distribution into glioma lesion. Combinatory treatment with ICI/EVs showed benefit in glioma-bearing mice by reducing their tumor volume and prolonging their survival. Cytotoxic T cell infiltration, polarization of tumor-associated macrophage, and lower tumor proliferation were observed in ICI/EVs-treated mice. The developed ICI/EVs showed promise in immunotherapeutic management of glioma., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yan-Jye Shyong reports financial support was provided by 10.13039/100020595National Science and Technology Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Breast cancer is a leading global health concern, necessitating advancements in recurrence prediction and management. The development of an artificial intelligence (AI)-based clinical decision support system (AI-CDSS) using ChatGPT addresses this need with the aim of enhancing both prediction accuracy and user accessibility., Objective: This study aims to develop and validate an advanced machine learning model for a web-based AI-CDSS application, leveraging the question-and-answer guidance capabilities of ChatGPT to enhance data preprocessing and model development, thereby improving the prediction of breast cancer recurrence., Methods: This study focused on developing an advanced machine learning model by leveraging data from the Tri-Service General Hospital breast cancer registry of 3577 patients (2004-2016). As a tertiary medical center, it accepts referrals from four branches-3 branches in the northern region and 1 branch on an offshore island in our country-that manage chronic diseases but refer complex surgical cases, including breast cancer, to the main center, enriching our study population's diversity. Model training used patient data from 2004 to 2012, with subsequent validation using data from 2013 to 2016, ensuring comprehensive assessment and robustness of our predictive models. ChatGPT is integral to preprocessing and model development, aiding in hormone receptor categorization, age binning, and one-hot encoding. Techniques such as the synthetic minority oversampling technique address the imbalance of data sets. Various algorithms, including light gradient-boosting machine, gradient boosting, and extreme gradient boosting, were used, and their performance was evaluated using metrics such as the area under the curve, accuracy, sensitivity, and F 1 -score., Results: The light gradient-boosting machine model demonstrated superior performance, with an area under the curve of 0.80, followed closely by the gradient boosting and extreme gradient boosting models. The web interface of the AI-CDSS tool was effectively tested in clinical decision-making scenarios, proving its use in personalized treatment planning and patient involvement., Conclusions: The AI-CDSS tool, enhanced by ChatGPT, marks a significant advancement in breast cancer recurrence prediction, offering a more individualized and accessible approach for clinicians and patients. Although promising, further validation in diverse clinical settings is recommended to confirm its efficacy and expand its use., (©Tai-Han Lin, Hsing-Yi Chung, Ming-Jr Jian, Chih-Kai Chang, Cherng-Lih Perng, Guo-Shiou Liao, Jyh-Cherng Yu, Ming-Shen Dai, Cheng-Ping Yu, Hung-Sheng Shang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.09.2024.)

Objectives: Ultrasound (US)-guided procedures can be used in the evaluation and treatment of neck masses. However, these procedures need to be practiced before being executed on humans. The aim of this study is to evaluate the efficacy of a training program using a gelatin phantom to practice US-guided procedures., Methods: This program included a lecture and practice with a gelatin phantom. We recruited doctors from different hospitals to practice US-guided procedures, including fine-needle aspiration (FNA), core needle biopsy (CNB), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA). We used a questionnaire with a 5-point scale to evaluate the effectiveness of practicing US-guided procedures under a gelatin phantom., Results: Forty-four doctors participated, and 37 of them completed the questionnaires. After training, the mean (SD) scores of the doctors were 4.68 (0.47) for "Satisfaction with this course," 4.54 (0.61) for "Ease in practicing FNA&CNB using the phantom," 4.49 (0.61) for "Ease in practicing PEI using the phantom," 4.49 (0.65) for "Ease in practicing RFA using the phantom," and 4.57 (0.55) for "The course effectively familiarizing participants with US-guided procedures." Participants without experience in US examination had higher scores than those with previous US experience, but the difference was not statistically significant., Conclusion: A combination of lectures and hands-on practice of US-guided procedures using a gelatin phantom is an effective educational method for doctors interested in head and neck US. After the training program, doctors gained a better understanding of the necessary steps and skills required for these procedures. They can correctly insert the instruments into the target lesion and perform different US-guided procedures., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Single photon ionization time-of-flight mass spectrometry (SPI-TOF-MS) is a powerful analytical technique for real-time detection of trace VOCs. However, efficient ion transmission within the ionization chamber has always been a challenging issue in SPI-TOF-MS. In this study, a novel ion guide termed the Segmented Focus Quadrupole Ion Guide (SFQ-IG) was introduced for SPI-TOF-MS. The SFQ-IG device consists of 12 printed circuit boards (PCB), each containing four quarter-ring electrodes with inner diameters progressively decreasing from 26 to 4 mm. The simulation results demonstrated that SFQ-IG exhibited superior ion transmission efficiency than both ion funnel (IF) field and direct current-only (DC-only) field. By integrating into a SPI-TOF-MS, this ion guide was optimized in terms of the ionization source pressure, direct current gradient, and radio frequency amplitude. Further comparative experiments demonstrated that the SPI-TOF-MS with the SFQ-IG exhibited higher sensitivity than both the IF field (1.3-7.4 times) and DC-only field (3.5-8.8 times) for the test VOCs. The improvements in limit of detection (LOD) with the SFQ-IG ranged from 1.6 to 5.3 times compared to the DC-only field for the test VOCs. Fabricated using PCB technology, the SFQ-IG is characterized by its cost-effectiveness, compact size, and high transmission efficiency, facilitating its integration into other mass spectrometers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Head and neck surgical simulation training (SST) is an important part in otolaryngology head and neck surgical education. In this study, we provide a live porcine model for SST in recurrent laryngeal nerve (RLN) and facial nerve (FN) dissection for otolaryngology head and neck residents., Methods: A lecture with surgical manual is provided to illustrate the surgical landmarks of pig, and step-by-step procedures for thyroid and parotid surgery, as well as neck dissection. We used 4-month-old pig weighting 32 kg for the SST. The mentor demonstrated result of RLN injury with continuous nerve monitoring. Participants used monopolar stimulation probe (4 pulse/s, 100 μs, 3-8 mA; Medtronic) to identify and intermittent monitor the RLN and FN during the SST. After the dissection course, we conducted a questionnaire survey to check the effectiveness of this training model., Results: Total 30 participants were recruited, including 16 female and 14 male resident doctors. There were 1, 4 and 25 learners for 3rd year, 4th and 5th years residents, respectively. Before this training course, 53 % (16/30) and 63 % (19/30) had successful experience in finding the RLN and FN, respectively. After the SST, all of our participants had successful identify the RLN and FN (p-value <0.01); all had positive response to stimulation and familiar with the procedure., Conclusions: The live porcine model is effectiveness in SST for RLN and FN dissection. Live porcine model with real-time RLN and FN monitoring should be provided for otolaryngology head and neck resident training., Competing Interests: Declaration of competing interest The Authors declare that is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Soil pollution is predominantly attributed to the presence of heavy metal elements and organic compounds; However, current detection methodologies are restricted to the identification of only one of these two sources at a time. A novel analytical approach, known as nanoliter spray enhanced microwave plasma ionization mass spectrometry (Nano-Spray-EMPI-MS), has been developed to facilitate the simultaneous detection of both heavy metals and organic pollutants in soil samples. This technique is characterized by its requirement for minimal sample volumes, thereby allowing for efficient and rapid analysis. The research concentrated on the simultaneous analysis of five heavy metals (Pb, Zn, Cu, Cr, and Ni) and three major phthalates (PAEs), specifically DEHP, DBP, and DMP. The detection and quantification limits for the heavy metals were established to be between 0.16-0.57 and 0.53-1.88 μg L -1, respectively, while the limits for the PAEs ranged from 0.02 to 0.05 and 0.07-0.16 μg L -1 . Validation of the method's efficacy in soil detection demonstrated recovery rates of 90.9 %-105.7 % for heavy metals and 89.4 %-97.2 % for PAEs. The application of this method analyzing soil samples collected from an area adjacent to a lead-acid battery industrial park in China revealed varying levels of contamination by both heavy metals and PAEs. Notably, Lead contamination was found to be the most pronounced, with a peak concentration of 862.5 mg kg -1 and a correspondingly high pollution index. These findings are significant for evaluating local ecological risks, pinpointing sources of pollution, and formulating effective pollution management strategies in the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Proliferation is a critical characteristic of the progression of gastric cancer (GC). Receptor tyrosine kinase-like orphan receptor 2 (ROR2), the orphan receptor tyrosine kinase-like receptor, exhibits effects on tumor growth due to its abnormal expression in cancer. The goal of our study was to assess the potential regulatory role exerted by the ROR2 on GC cells. Through previous bioinformatics analysis, we discovered an association between ROR2 and the G2/M phase of the GC cell cycle. However, little is known about the link between ROR2 and the G2/M phase cell cycle in GC. Here, the findings of our study indicate that ROR2, after transcribed expression by Twist1, activates the PI3K/AKT/mTOR/S6K signal transduction pathway, thus leading to the acceleration of the G2/M phase and subsequent promotion of cell proliferation in GC. Furthermore, the functional link among ROR2, Twist1, and G2/M phase of cell cycle was also confirmed in mouse xenograft tissues and human tissues. ROR2 expression was correlated with Twist expression and lower survival in vivo. Notably, our suggestion is that focusing on ROR2 as a potential therapeutic approach could show potential for the management of GC., (© 2024 Wiley Periodicals LLC.)

Background: Human papillomavirus (HPV) is a crucial prognostic factor in oropharyngeal cancer (OPC). p16 is a surrogate marker for diagnosing HPV+ OPC, however it is not direct evidence of HPV existence., Objective: The purpose of our study was to evaluate an HPV DNA test-Cobas HPV assay-in diagnosing HPV+ OPC through neck lymph node aspiration., Methods: Patients with suspected neck mass who received fine needle aspiration (FNA) or core needle biopsy (CNB) at the National Taiwan University Hospital between January 2018 and December 2022 were reviewed. Besides routine cytology and pathology study, needle rinse fluid was collected for the Cobas HPV assay to detect high-risk HPV., Results: We analyzed 137 patients with suspected lymph nodes, 32 (23.4%) of whom were HPV+ OPC patients and 105 (76.6%) of whom had non-HPV-related disease. FNA was performed in 31 patients and CNB was performed in 106 patients, according to the size and necrosis status of the lymph nodes. For diagnosing HPV+ OPC, CNB combined with p16 immunohistochemistry staining showed sensitivity of 93.3%, specificity of 97.8%, positive predictive value (PPV) of 87.5%, negative predictive value (NPV) of 98.9%, and accuracy of 97.2%. On the other hand, for the needle rinse Roche Cobas HPV assay, the test showed sensitivity of 96.9%, specificity of 100%, PPV of 100%, NPV of 99.1%, and accuracy of 99.3%. Compared with p16 IHC staining, the Cobas HPV test showed better PPV with statistical significance (p = 0.04)., Conclusion: The Cobas HPV assay is a US FDA-approved, highly automated, and readily used technique to directly detect the presence of high-risk HPV. We recommend utilizing the Cobas HPV assay in combination with routine cytology or histopathology examination in the work-up of neck lymphadenopathy., (© 2024. Society of Surgical Oncology.)

Elevated levels of Epstein-Barr virus (EBV) gp350 and gH/gL antibodies have been associated with a lower risk of developing nasopharyngeal carcinoma (NPC), although the evidence remains inconclusive and unexplained. We conducted a longitudinal study within a high-risk Taiwanese cohort, analyzing total immunoglobulin against EBV-gp350 and -gH/gL in blood and EBV DNA shedding in saliva. Contrary to our hypothesis-that elevated levels of antibodies previously shown to be associated with a lower NPC risk should result in a decrease in EBV shedding in saliva-higher anti-gp350 antibodies at baseline were significantly associated with detectable EBV DNA in saliva at follow-up (odds ratio [OR], 1.99 [95% confidence interval {CI}, 1.03-3.97]; P = .04). Higher anti-EBV-gH/gL antibodies at baseline were not significantly associated with risk of detectable EBV DNA at follow-up (OR, 0.69 [95% CI, .35-1.32]; P = .26). These findings underscore the complexity of virus-host interactions and emphasize the need for further investigations into their role in EBV-associated diseases., Competing Interests: Potential conflicts of interest. Z. L. is currently an employee at Merck & Co, Inc, Rahway, New Jersey. The views and opinions expressed in this article do not represent the views and opinions of any public or private entity (e.g. agency, government, organization, institution, or company). All other authors report no conflicts of interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

This study examines biomass energy policies in the EU, US, and Japan, noting high implementation rates in Poland (86.5 %) and Finland (90.6 %). Germany's biogas utilization is particularly noteworthy, accounting for 29.6 %. The paper summarizes China's national and provincial waste biomass management and energization policies, encompassing agriculture, biomass energy, and environmental governance aspects. Analyzing China's biomass energy industry reveals challenges requiring a comprehensive development plan based on waste biomass resources and environmental zoning. Proposed solutions include establishing ecological energy agriculture demonstration zones, optimizing policies for environmental benefits, encouraging technological innovation, establishing a trade association, improving standards, setting up a waste biomass fund, introducing green certificates and quotas, and integrating waste biomass into the national carbon trading system., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors.)

Although Mo 2 C and earth-abundant 3d transition metals are regarded as potential catalysts to replace noble metal catalysts for effective hydrogen evolution reaction, their large-scale application is still inhibited by their own defects. Here, a facile thermal treatment method for nonprecious metal catalysts is developed to prepare a porous Ni/Mo 2 C composite catalyst. The loading density of Ni nanoparticles on the Mo 2 C surface has an important effect on the activity of the catalyst. By optimizing the Ni doping ratio, the Ni-40/Mo 2 C-17 sample exhibits the lowest onset overpotential and lowest overpotential at 10 mA cm -2 in both acidic and alkaline electrolytes, compared to other reported Ni- and Mo 2 C-based catalysts. In addition, theoretical calculations have also confirmed the synergistic effect between Ni nanoparticles and Mo 2 C, which can balance the thermodynamics between H adsorption and desorption of H 2 . This work provides an avenue for designing high-performance water-splitting catalytic materials using low-cost species, which exhibit excellent HER activity in a wide pH range.

The major limitation of cancer treatment is multidrug resistance (MDR), which leads to the inactivation of chemotherapeutic drugs and greater than 90% mortality. To solve this ordeal, we applied ligand-based drug design and bioiosteric replacement strategy from an indazole to a pyrazole ring to discover compounds 27 and 43 with good potential for reversing drug resistance in combination with paclitaxel, and their reversal fold values were 53.2 and 51.0 at 5 μM, respectively, against an MDR cancer cell line (KBvin). Based on the PK profile results, we selected compound 43 with a longer half-life for mechanistic and animal experiments. Combination treatment with compound 43 and paclitaxel-induced apoptosis and enhanced subG1 by decreasing mitochondrial membrane potential in KBvin cells. In addition, 43 also inhibited P-gp function by interfering with ATPase activity. Meanwhile, cotreatment with compound 43 and paclitaxel significantly suppressed tumor growth (TGI = 55.5%) at a dose of 200 mg/kg (PO) in a xenograft model and showed no obvious liver or kidney toxicity by H&E staining. Overall, compound 43 may serve as a safe and effective oral resistance reversal chemotherapeutic agent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Objective quantitative texture characteristics may be helpful in salivary glandular tumor differential diagnosis. This study uses machine learning (ML) to explore and validate the performance of ultrasound (US) texture features in diagnosing salivary glandular tumors., Material and Methods: 122 patients with salivary glandular tumors, including 71 benign and 51 malignant tumors, are enrolled. Representative brightness mode US pictures are selected for further Gray Level Co-occurrence Matrix (GLCM) texture analysis. We use a t -test to test the significance and use the receiver operating characteristic curve method to find the optimal cut-point for these significant features. After splitting 80% of the data into a training set and 20% data into a testing set, we use five machine learning models, k-nearest Neighbors (kNN), Naïve Bayes, Logistic regression, Artificial Neural Networks (ANNs) and supportive vector machine (SVM), to explore and validate the performance of US GLCM texture features in diagnosing salivary glandular tumors., Results: This study includes 49 female and 73 male patients, with a mean age of 53 years old, ranging from 21 to 93. We find that six GLCM texture features (contrast, inverse difference movement, entropy, dissimilarity, inverse difference and difference entropy) are significantly different between benign and malignant tumors ( p < 0.05). In ML, the overall accuracy rates are 74.3% (95%CI: 59.8-88.8%), 94.3% (86.6-100%), 72% (54-89%), 84% (69.5-97.3%) and 73.5% (58.7-88.4%) for kNN, Naïve Bayes, Logistic regression, a one-node ANN and SVM, respectively., Conclusions: US texture analysis with ML has potential as an objective and valuable tool to make a differential diagnosis between benign and malignant salivary gland tumors.

Background: The COVID-19 pandemic underscored the critical importance of biosafety in microbiology laboratories worldwide. In response, China has ramped up its efforts to enhance biosafety measures within its Centers for Disease Control and Prevention (CDC) laboratories. This study provides the first comprehensive assessment of biosafety practices across provincial, city, and county levels of CDC microbiology laboratories in China., Methods: We conducted a nationwide cross-sectional survey from 2021 to 2023, targeting staff from microbiology laboratories within CDCs at all administrative levels in China. Stratified sampling was employed to select respondents, ensuring a representative mix across different CDC hierarchies, job titles, and academic qualifications. The survey encompassed questions on biosafety training, the presence of BSL-2 and BSL-3 laboratories, adherence to general biosafety guidelines, and management practices regarding specimens, reagents, and consumables. Statistical analysis was performed to identify significant differences in biosafety practices among different CDC levels., Results: A total of 990 valid responses were received, highlighting a nearly universal presence (98.69%) of BSL-2 laboratories and a significant yet varied presence of BSL-3 laboratories across the CDC network. The survey revealed high levels of biosafety training (98.69%) and adherence to biosafety protocols. However, challenges remain in the consistent application of certain safety practices, especially at lower administrative levels. Notable differences in the management of specimens, reagents, and consumables point to areas for improvement in ensuring biosecurity., Conclusion: Our findings indicate a robust foundation of biosafety practices within CDC microbiology laboratories in China, reflecting significant advancements in the wake of the Biosecurity Law's implementation. Nevertheless, the variability in adherence to specific protocols underscores the need for ongoing training, resources allocation, and policy refinement to enhance biosafety standards uniformly across all levels. This study's insights are crucial for guiding future improvements in laboratory biosafety, not just in China but potentially in other countries enhancing their public health infrastructures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Niu, Sun, Zhang, Zhao, Tian, Cheng, Zheng, Guo, Zhang, Ma and Wang.)

Background: While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery., Methods: We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)-matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1-T4b tumors, clinical N0-3 disease, and clinical stage I-IV., Results: In the PS-matched cohort, the 5-year disease-specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5-year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5-year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5-year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2-3, cN1, and c-Stage II disease in the IC + OP group were significantly more likely to achieve pT0-1 status (p < 0.05)., Conclusions: Following PS matching, the IC + OP group generally exhibited similar prognosis to the OP group. However, for pT4a tumors, the OP group showed superior 5-year outcomes. While IC may not universally improve survival, it could be advantageous for patients who respond positively to the treatment., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori -associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA -dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/- , Angptl4 -/- , and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4 + T cells (T regs ) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced T reg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori -associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Rui Xie et al.)

Background: Despite the growing use of cervical (cVEMP) and ocular (oVEMP) VEMP tests, their effectiveness in predicting chronic dizziness in vestibular neuritis (VN) patients remains unclear. Our research examines the link between long-lasting dizziness and inner ear assessments, encompassing VEMPs induced by air-conducted sound (ACS), bone-conducted vibration (BCV), and galvanic vestibular stimulation (GVS)., Objectives: This study explores prognostic markers by examining the relationship between the persistence of dizziness symptoms and various inner ear test findings in VN patients., Material and Methods: A retrospective cohort of 60 unilateral VN patients underwent comprehensive audiovestibular tests, including pure tone audiometry, cVEMP and oVEMP induced by ACS, BCV, GVS, and caloric tests. Patient subgroups were established based on dizziness duration: short-term (<3 months) and long-term (≥3 months)., Results: No substantial correlation existed between the dizziness duration and the outcomes of any particular single inner ear test. However, patients exhibiting concurrent abnormal GVS-cVEMP and GVS-oVEMP were more likely to experience prolonged dizziness, indicating more extensive vestibular system involvement., Conclusions: Concurrent abnormalities in GVS-cVEMP and GVS-oVEMP may indicate a higher chance of long-term dizziness in VN., Significance: This study identifies concurrent abnormalities in GVS-cVEMP and GVS-VEMP as a potential prognostic marker for prolonged dizziness in VN.

Objective: The feasibility of using deep learning in ultrasound imaging to predict the ambulatory status of patients with Duchenne muscular dystrophy (DMD) was previously explored for the first time. The present study further used clustering algorithms for the texture reconstruction of ultrasound images of DMD data sets and analyzed the difference in echo intensity between disease stages., Methods: k-means (Kms) and fuzzy c-means (FCM) clustering algorithms were used to reconstruct the DMD data-set textures. Each image was reconstructed using seven texture-feature categories, six of which were used as the primary analysis items. The task of automatically identifying the ambulatory function and DMD severity was performed by establishing a machine-learning model., Results: The experimental results indicated that the Gaussian Naïve Bayes and k-nearest neighbors classification models achieved an accuracy of 86.78% in ambulatory function classification. The decision-tree model achieved an identification accuracy of 83.80% in severity classification. A deep convolutional neural network model was established as the main structure of the deep-learning model while automatic auxiliary interpretation tasks of ambulatory function and severity were performed, and data augmentation was used to improve the recognition performance of the trained model. Both the visual geometry group (VGG)-16 and VGG-19 models achieved 98.53% accuracy in ambulatory-function classification. The VGG-19 model achieved 92.64% accuracy in severity classification., Conclusion: Regarding the overall results, the Kms and FCM clustering algorithms were used in this study to reconstruct the characteristic texture of the gastrocnemius muscle group in DMD, which was indeed helpful in quantitatively analyzing the deterioration of the gastrocnemius muscle group in patients with DMD at different stages. Subsequent combination of machine-learning and deep-learning technologies can automatically and accurately assist in identifying DMD symptoms and tracking DMD deterioration for long-term observation., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Cerebral microcirculation disturbance manifested by decrease of cerebral blood flow (CBF) is one of early features of Alzheimer's disease (AD). Shenqi Yizhi prescription (SQYZ) is widely used in the treatment of AD. However, the effect of SQYZ on the early feature of AD is not clarified., Purpose: To explore the effect and mechanism of SQYZ on AD-like behavior from the perspective of early pathological features of AD., Methods: The fingerprint of SQYZ was established by ultra-high-performance liquid chromatograph. The improvement effect of SQYZ on Aβ 1-42 Oligomer (AβO)-induced AD-like behavior of mice was evaluated by behavioral test. The changes of CBF were detected by laser doppler meter and laser speckle imaging. The pathological changes of the hippocampus were observed by HE staining and transmission electron microscope. The expressions of intercellular communication molecules were detected by western blotting or immunofluorescence staining. The content of platelet-derived growth factor-BB (PDGF-BB) was detected by ELISA. Finally, the core components of SQYZ were docked with platelet-derived growth factor receptor beta (PDGFRβ) using AutoDock Vina software., Results: The similarity of the components in SQYZ extracted from different batches of medicinal materials was higher than 0.9. SQYZ administration could improve AβO-induced memory impairment and CBF reduction. Compared with the sham group, the number of neurons in the hippocampi of AβO group was significantly reduced, and the microvessels were shrunken and deformed. By contrary, SQYZ administration mitigated those pathological changes. Compared with the sham mice, the expressions of CD31, N-cadherin, PDGFRβ, glial fibrillary acidic protein, phosphorylation of focal adhesion kinase, integrin β1, and integrin α5 in the hippocampi of AβO mice were significantly increased. However, SQYZ administration significantly reduced AβO-induced expression of those proteins. Interestingly, the effect of PDGFRβ inhibitor, sunitinib demonstrated a consistent modulating effect as SQYZ. Finally, the brain-entering components of SQYZ, including ginsenoside Rg5, coptisine, cryptotanshinone, dihydrotanshinone IIA, stigmasterol, and tanshinone IIA had high binding force with PDGFRβ, implicating PDGFRβ as a potential target for SQYZ., Conclusions: Our data indicate that SQYZ improves CBF in AβO-triggered AD-like mice through inhibiting brain pericyte contractility, indicating the treatment potential of SQYZ for AD at the early stage., Competing Interests: Declaration of competing interest The authors declare that the work was conducted without any competing financial interests or personal relationships., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background and Objective: This review aims to investigate the ferroptosis mechanism of fumarate hydratase (FH)-related tumors for the purpose of possible treatment of tumors. Ferroptosis is an iron (Fe)-dependent form of regulated cell death caused by lipid peroxidation on the cell membrane. Studies have implicated FH in tumorigenesis. As mutations in the FH gene alter cellular metabolism and increase tumorigenesis risk, particularly in the kidneys. As most tumor cells require higher amounts of ferrous ions (Fe 2+ ) than normal cells, they are more susceptible to ferroptosis. Recent studies have indicated that ferroptosis is inhibited the pathogenesis and progression of FH-deficient tumors by regulating lipid and iron metabolism, glutathione-glutathione peroxidase 4 (GSH-GPX4), nuclear factor-erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathways. While the Fe 2+ content is significantly lower in FH-deficient tumor cells, than that in normal cells. It is promising to promote ferroptosis by increasing the concentration of Fe 2+ in cells to achieve the purpose of tumor treatment., Methods: In this study, we searched for relevant articles on ferroptosis and FH-deficient tumors using PubMed database., Key Content and Findings: FH is a tumor suppressor. A number of basic studies have shown that the loss of FH plays an important role in hereditary leiomyomas and tumors such as renal cell carcinoma, ovarian cancer, and other tumors. This type of tumor cells can through induce ferroptosis, inhibit proliferation, migration and invasion of tumor cells, increase the sensitivity of tumor cells to chemotherapy, and reverse the drug resistance through various molecular mechanisms. At present, the research on ferroptosis in FH-related tumors is still in the basic experimental stage., Conclusions: This article reviews the anti-tumor effects and mechanisms of FH and ferroptosis, in order to further explore the medical value of ferroptosis in FH-related tumor therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-21/coif). R.X. reports the National Natural Science Foundation of China (No. 81974115). X.W. reports the Central Government guiding local funds for scientific and Technological Development (No. XZ202201YD0024C), Key R & D Program of Hubei Province (No. 2021BGD010), Hubei Province Scientific and Technological Research Project (No. D20201306), Hubei Province Health Research Project (No. WJ2019-01), Hubei Medical Youth Tip-Top Talent, Leading Talent Program of Yangtze Talent Project and the College Students Innovative Entrepreneurial Training Program in Yangtze University (Nos. YZ2021296 and YZ2022307). The other author has no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) protein plays an essential role in the cisplatin (CDDP)-induced generation of reactive oxygen species (ROS). In this study, we evaluated the suitability of ultrasound-mediated lysozyme microbubble (USMB) cavitation to enhance NOX4 siRNA transfection in vitro and ex vivo. Lysozyme-shelled microbubbles (LyzMBs) were constructed and designed for siNOX4 loading as siNOX4/LyzMBs. We investigated different siNOX4-based cell transfection approaches, including naked siNOX4, LyzMB-mixed siNOX4, and siNOX4-loaded LyzMBs, and compared their silencing effects in CDDP-treated HEI-OC1 cells and mouse organ of Corti explants. Transfection efficiencies were evaluated by quantifying the cellular uptake of cyanine 3 (Cy3) fluorescein-labeled siRNA. In vitro experiments showed that the high transfection efficacy (48.18%) of siNOX4 to HEI-OC1 cells mediated by US and siNOX4-loaded LyzMBs significantly inhibited CDDP-induced ROS generation to almost the basal level. The ex vivo CDDP-treated organ of Corti explants of mice showed an even more robust silencing effect of the NOX4 gene in the siNOX4/LyzMB groups treated with US sonication than without US sonication, with a marked abolition of CDDP-induced ROS generation and cytotoxicity. Loading of siNOX4 on LyzMBs can stabilize siNOX4 and prevent its degradation, thereby enhancing the transfection and silencing effects when combined with US sonication. This USMB-derived therapy modality for alleviating CDDP-induced ototoxicity may be suitable for future clinical applications.

The complex air environment makes it urgent to build good and safe indoor environments, and the study and application of new materials have become the focus of current research. In this study, we tested and analyzed the structural parameters and filtration performances of the four most commonly used new filter materials in the current market. The results showed that all four new filter materials showed a trend of first increasing and then decreasing their filtration efficiency with an increase in filtration velocity. The filtration efficiency of the materials was as follows: PTFE > glass fiber > nanomaterial > electret. The filtration efficiency of all materials reached its maximum when the filtration velocity was 0.2 m/s. The filtration efficiency of the PTFE for PM 10 , PM 2.5 , and PM 1.0 was higher than that of the other three materials, with values of 0.87% to 24.93%, 1.21% to 18.69%, and 0.56% to 16.03%, respectively. PTFE was more effective in capturing particles smaller than 1.0 μm. Within the testing velocity range, the resistance of the filter materials was as follows: glass fiber > PTFE > electret > nanomaterial, and the resistance of the four materials showed a good fitting effect. It is also necessary to match the resistance with the filtration efficiency during use, as well as to study the effectiveness of filter materials in blocking microorganisms and absorbing toxic gases. Overall, PTFE showed the best comprehensive performance, as well as providing data support for the selection of related materials or the synthesis and research of filter materials in the future.

Background: Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in-hospital stay and long-term survival outcomes in patients with OCSCC., Methods: A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5-year disease-specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)-matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS-matched analysis., Results: Prior to PS matching, patients with tracheotomy had significantly lower 5-year DSS and OS rates compared to those without (71% vs. 82%, p < 0.0001; 62% vs. 75%, p < 0.0001, respectively). Multivariable analysis identified tracheotomy as an independent adverse prognostic factor for 5-year DSS (hazard ratio = 1.10 [1.03-1.18], p = 0.0063) and OS (hazard ratio = 1.10 [1.04-1.17], p = 0.0015). In the PS-matched cohort, the 5-year DSS was 75% for patients with tracheotomy and 76% for those without (p = 0.1488). Five-year OS rates were 66% and 67%, respectively (p = 0.0808). Prior to PS matching, patients with tracheotomy had a significantly longer mean hospital stay compared to those without (23.37 ± 10.56 days vs. 14.19 ± 8.34 days; p < 0.0001). Following PS matching, the difference in hospital stay duration between the two groups remained significant (22.34 ± 10.25 days vs. 17.59 ± 9.54 days; p < 0.0001)., Conclusions: While elective tracheotomy in resected OCSCC patients may not significantly affect survival, it could be associated with prolonged hospital stays., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Glove reuse poses risks, as chemicals can persist even after cleaning. Decontamination methods like thermal aeration, recommended by US OSHA, vary in effectiveness. Some studies show promising results, while others emphasize the importance of considering both permeation and tensile strength changes. This research advocates for informed glove reuse, emphasizing optimal thermal aeration temperatures and providing evidence to guide users in maintaining protection efficiency., Methods: The investigation evaluated Neoprene and Nitrile gloves (22 mils). Permeation tests with toluene and acetone adhered to American Society for Testing Materials (ASTM) F739 standards. Decontamination optimization involved aeration at various temperatures. The experiment proceeded with a maximum of 22 re-exposure cycles. Tensile strength and elongation were assessed following ASTM D 412 protocols. Breakthrough time differences were statistically analyzed using t -test and ANOVA., Results: At room temperature, glove residuals decreased, and standardized breakthrough time (SBT) 2 was significantly lower than SBT 1 , indicating reduced protection. Higher temperature decontamination accelerated residual removal, with ΔSBT (SBT 2 /SBT 1 ) exceeding 100%, signifying restored protection. Tensile tests showed stable neoprene properties postdecontamination. Results underscore thermal aeration's efficacy for gloves reuse, emphasizing temperature's pivotal role. Findings recommend meticulous management strategies, especially post-breakthrough, to uphold glove-protective performance., Conclusions: Thermal aeration at 100°C for 1 hour proves effective, restoring protection without compromising glove strength. The study, covering twenty cycles, suggests safe glove reuse with proper decontamination, reducing costs significantly. However, limitations in chemical-glove combinations and exclusive focus on specific gloves caution against broad generalization. The absence of regulatory directives on glove reuse highlight the importance of informed selection and rigorous decontamination validation for workplace safety practices., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 Occupational Safety and Health Research Institute. Published by Elsevier B.V. on behalf of Institute, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency.)

The CRISPR system is an adaptive immune system found in prokaryotes that defends host cells against the invasion of foreign DNA 1 . As part of the ongoing struggle between phages and the bacterial immune system, the CRISPR system has evolved into various types, each with distinct functionalities 2 . Type II Cas9 is the most extensively studied of these systems and has diverse subtypes. It remains uncertain whether members of this family can evolve additional mechanisms to counter viral invasions 3,4 . Here we identify 2,062 complete Cas9 loci, predict the structures of their associated proteins and reveal three structural growth trajectories for type II-C Cas9. We found that novel associated genes (NAGs) tended to be present within the loci of larger II-C Cas9s. Further investigation revealed that CbCas9 from Chryseobacterium species contains a novel β-REC2 domain, and forms a heterotetrameric complex with an NAG-encoded CRISPR-Cas-system-promoting (pro-CRISPR) protein of II-C Cas9 (PcrIIC1). The CbCas9-PcrIIC1 complex exhibits enhanced DNA binding and cleavage activity, broader compatibility for protospacer adjacent motif sequences, increased tolerance for mismatches and improved anti-phage immunity, compared with stand-alone CbCas9. Overall, our work sheds light on the diversity and 'growth evolutionary' trajectories of II-C Cas9 proteins at the structural level, and identifies many NAGs-such as PcrIIC1, which serves as a pro-CRISPR factor to enhance CRISPR-mediated immunity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

This paper presents a newly developed high-performance mobile single-photon ionization time-of-flight mass spectrometry (M-SPI-TOFMS) system for on-line analysis and stereoscopic monitoring of complex gas mixtures. The system is designed for stereoscopic imaging to map the distribution of volatile organic compounds (VOCs) and trace their emission sources in urban areas and industrial parks. It mainly consists of a SPI-TOFMS instrument, a customized commercial vehicle, a meteorological five-parameter monitor with GPS, a high-power generator, and an uninterruptible power supply. The SPI technique, using a 118 nm VUV lamp, can ionize compounds with an ionization potential below 10.78 eV. Mass spectra obtained using this technique show the profiles of various VOCs and some inorganic compounds. The VOCs composition information and mobile location data are simultaneously sent to the GIS software. In GIS software, this data is used for real-time stereoscopic imaging of VOC distribution and precise tracking of VOC movement. The system can achieve a spatial data resolution of 0.69 mm at 25 km/h due to the microsecond detection speed of the M-SPI-TOFMS instrument. The laboratory test provides a rapid overview characterization of benzene, toluene, and xylene. The M-SPI-TOFMS has limits of detection and mass resolution of 33.7 pptv and 1060, respectively. Several field applications were carried out using M-SPI-TOFMS at various locations to identify VOC sources near different factories. The M-SPI-TOFMS system has a navigation monitoring speed of 25 km/h with a time resolution of 1 s. The widespread use of this system will provide accurate data to support environmental management departments in formulating VOCs pollution control policies and improving control efficiency., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The burgeoning interest in the versatile hydrogel matrix, with its multifarious applications, has spurred extensive research in recent years. However, the implementation of chemically crosslinked gels on a large-scale has been hindered by their poor biosafety and excessive energy consumption. To address these challenges, this study focuses on harnessing physical methods to engineer novel composite hydrogels utilizing natural polysaccharides Salecan and whey protein isolate, obviating the need for structural modification or chemical crosslinking. The aim was to explore the rheological properties to understand their multiple behaviors. Various models, including Power-Law, Herschel-Bulkley, and Arrhenius, were also employed to compare and analyze rheological parameters. This study holds significance as it is the pioneering report on the hydrogels fabricated from Salecan/Whey protein isolate. These gels possess favorable attributes encompassing optimized elasticity, thermal-stability, enhanced injectability, and self-recovery, rendering them suitable for a multitude of applications in the realms of food and biomedicine., Competing Interests: Declaration of competing interest This project has no known conflicts of interest which could inappropriately affect our work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Currently, there is a lack of ideal risk prediction tools in the field of emergency general surgery (EGS). The American Association for the Surgery of Trauma recommends developing risk assessment tools specifically for EGS-related diseases. In this study, we sought to utilize machine learning (ML) algorithms to explore and develop a web-based calculator for predicting five perioperative risk events of eight common operations in EGS., Method: This study focused on patients with EGS and utilized electronic medical record systems to obtain data retrospectively from five centers in China. Five ML algorithms, including Random Forest (RF), Support Vector Machine, Naive Bayes, XGBoost, and Logistic Regression, were employed to construct predictive models for postoperative mortality, pneumonia, surgical site infection, thrombosis, and mechanical ventilation >48 h. The optimal models for each outcome event were determined based on metrics, including the value of the Area Under the Curve, F1 score, and sensitivity. A comparative analysis was conducted between the optimal models and Emergency Surgery Score (ESS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and American Society of Anesthesiologists (ASA) classification. A web-based calculator was developed to determine corresponding risk probabilities., Result: Based on 10 993 patients with EGS, we determined the optimal RF model. The RF model also exhibited strong predictive performance compared with the ESS, APACHE II score, and ASA classification. Using this optimal model, the authors developed an online calculator with a questionnaire-guided interactive interface, catering to both the preoperative and postoperative application scenarios., Conclusions: The authors successfully developed an ML-based calculator for predicting the risk of postoperative adverse events in patients with EGS. This calculator accurately predicted the occurrence risk of five outcome events, providing quantified risk probabilities for clinical diagnosis and treatment., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

QED atoms are composed of unstructured and point-like lepton pairs bound together by the electromagnetic force. The smallest and heaviest QED atom is formed by a τ + τ - pair. Currently, the only known atoms of this type are the e + e - and μ + e - atoms, which were discovered 64 years ago and remain the sole examples found thus far. We demonstrate that the J τ (τ + τ - atom with J PC =1 -- ) atom signal can be observed with a significance larger than 5σ including both statistical and systematic uncertainties, via. the process e + e - →X + Y - Ɇ (X,Y=e,μ,π,K, or ρ, and Ɇ is the missing energy due to unobserved neutrinos) with 1.5ab -1 data taken around the τ pair production threshold. The τ lepton mass can be measured with a precision of 1 keV with the same data sample. This is within one year's running time of the proposed super tau-charm facility in China or super charm-tau factory in Russia., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)