Multiple factors trigger the formation and resuscitation of the VBNC state in alcohol-producing Klebsiella pneumoniae.

Klebsiella pneumoniae can enter a viable but nonculturable (VBNC) state to survive in unfavorable environments. Our research found that high-, medium-, and low-alcohol-producing K. pneumoniae strains are associated with nonalcoholic fatty liver disease. However, the presence of the three Kpn strains has not been reported in the VBNC state or during resuscitation. In this study, the effects of different strains, salt concentrations, oxygen concentrations, temperatures, and nutrients in K. pneumoniae VBNC state were evaluated. The results showed that high-alcohol-producing K. pneumoniae induced a slower VBNC state than medium-alcohol-producing K. pneumoniae, and low-alcohol-producing K. pneumoniae. A high-salt concentration and micro-oxygen environment accelerated the loss of culturability. Simultaneously, both real-time quantitative PCR and droplet digital PCR were developed to compare the quantitative comparison of three Kpn strain VBNC states by counting single-copy gene numbers. At 22°C or 37°C, the number of culturable cells decreased significantly from about 108 to 105-106 CFU/mL. In addition, imipenem, ciprofloxacin, polymyxin, and phiW14 inhibited cell resuscitation but could not kill VBNC-state cells. These results revealed that the different environments evaluated play different roles in the VBNC induction process, and new effective strategies for eliminating VBNC-state cells need to be further studied. These findings provide a better understanding of VBNC-state occurrence, maintenance, detection, and absolute quantification, as well as metabolic studies of resuscitation resistance and ethanol production.IMPORTANCEBacteria may enter VBNC state under different harsh environments. Pathogenic VBNC bacteria cells in clinical and environmental samples pose a potential threat to public health because cells cannot be found by routine culture. The alcohol-producing Kpn VBNC state was not reported, and the influencing factors were unknown. The formation and recovery of VBNC state is a complete bacterial escape process. We evaluated the influence of multiple induction conditions on the formation of VBNC state and recovery from antibiotic and bacteriophage inhibition, and established a sensitive molecular method to enumerate the VBNC cells single-copy gene. The method can improve the sensitivity of pathogen detection in clinical, food, and environmental contamination monitoring, and outbreak warning. The study of the formation and recovery of VBNC-state cells under different stress environments will also promote the microbiological research on the development, adaptation, and resuscitation in VBNC-state ecology.

Investigating the impact of schizophrenia traits on attention: the role of the theta band in a modified Posner cueing paradigm.

Joint attention is an indispensable tool for daily communication. Abnormalities in joint attention may be a key reason underlying social impairment in schizophrenia spectrum disorders. In this study, we aimed to explore the attentional orientation mechanism related to schizotypal traits in a social situation. Here, we employed a Posner cueing paradigm with social attentional cues. Subjects needed to detect the location of a target that is cued by gaze and head orientation. The power in the theta frequency band was used to examine the attentional process in the schizophrenia spectrum. There were four main findings. First, a significant association was found between schizotypal traits and attention orientation in response to invalid gaze cues. Second, individuals with schizotypal traits exhibited significant activation of neural oscillations and synchrony in the theta band, which correlated with their schizotypal tendencies. Third, neural oscillations and synchrony demonstrated a synergistic effect during social tasks, particularly when processing gaze cues. Finally, the relationship between schizotypal traits and attention orientation was mediated by neural oscillations and synchrony in the theta frequency band. These findings deepen our understanding of the impact of theta activity in schizotypal traits on joint attention and offer new insights for future intervention strategies.

High peripheral neutrophil and monocyte count distinguishes renal cell carcinoma from renal angiomyolipoma and predicts poor prognosis of renal cell carcinoma.

Background: The presence of peripheral inflammatory cells has been linked to the prognosis of cancer. This study aims to investigate the distinct roles of absolute neutrophil count (ANC) and absolute monocyte count (AMC) in differentiating renal cell carcinoma (RCC) from renal angiomyolipoma (RAML), as well as their prognostic significance in RCC. Methods: We conducted a comprehensive analysis of peripheral immune cell data, clinicopathological data, and tumor characteristics in patients diagnosed with RCC or RAML from January 2015 to December 2021. Receiver operating characteristic (ROC) curves, as well as univariate and multivariate analyses, were employed to assess the diagnostic utility of AMC and ANC in differentiating between RCC and RAML. Kaplan-Meier curve analysis was used to study the survival of RCC patients with different AMC and ANC. The prognostic value of AMC and ANC in RCC was investigated using COX univariate and multivariate analysis. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used for bioinformatic correlation analysis. Results: A total of 1120 eligible patients were included in the study. The mean preoperative AMC and ANC in patients with RCC were found to be significantly higher compared to those in patients with RAML (P = 0.001 and P < 0.001, respectively). High preoperative AMC and ANC significantly correlated with smoking history, tumor length, gross hematuria, and high T Stage, N stage, and pathological grade. In multivariate analyses, an ANC> 3.205 *10^9/L was identified to be independently associated with the presence of RCC (HR = 1.618, P = 0.008). High AMC and ANC were significantly associated with reduced OS and PFS (P < 0.05), and ANC may be an independent prognostic factor. Public database analysis showed that signature genes of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) were highly expressed in ccRCC. Conclusions: Elevated preoperative ANC and AMC can distinguish RCC from RAML and predict poor prognosis in patients with RCC. Furthermore, the signature genes of TAMs and TANs exhibit high expression levels in clear cell RCC.

Development of a Recombinase-Aided Amplification Assay for the Rapid Detection of Candida auris.

Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.

Structural basis for the dynamic chaperoning of disordered clients by Hsp90.

Molecular chaperone heat shock protein 90 (Hsp90) is a ubiquitous regulator that fine-tunes and remodels diverse client proteins, exerting profound effects on normal biology and diseases. Unraveling the mechanistic details of Hsp90's function requires atomic-level insights into its client interactions throughout the adenosine triphosphate-coupled functional cycle. However, the structural details of the initial encounter complex in the chaperone cycle, wherein Hsp90 adopts an open conformation while engaging with the client, remain elusive. Here, using nuclear magnetic resonance spectroscopy, we determined the solution structure of Hsp90 in its open state, bound to a disordered client. Our findings reveal that Hsp90 uses two distinct binding sites, collaborating synergistically to capture discrete hydrophobic segments within client proteins. This bipartite interaction generates a versatile complex that facilitates rapid conformational sampling. Moreover, our investigations spanning various clients and Hsp90 orthologs demonstrate a pervasive mechanism used by Hsp90 orthologs to accommodate the vast array of client proteins. Collectively, our work contributes to establish a unified conceptual and mechanistic framework, elucidating the intricate interplay between Hsp90 and its clients.

TALEN-mediated homologous-recombination-based fibroin light chain in-fusion expression system in Bombyx mori.

Silkworm was the first domesticated insect and has important economic value. It has also become an ideal model organism with applications in genetic and expression studies. In recent years, the use of transgenic strategies has made the silkworm silk gland an attractive bioreactor for the production of recombinant proteins, in particular, piggyBac-mediated transgenes. However, owing to differences in regulatory elements such as promoters, the expression levels of exogenous proteins have not reached expectations. Here, we used targeted gene editing to achieve site-specific integration of exogenous genes on genomic DNA and established the fibroin light chain (FibL) in-fusion expression system by TALEN-mediated homology-directed recombination. First, the histidine-rich cuticular protein (CP) was successfully site-directed inserted into the native FibL, and the FibL-CP fusion gene was correctly transcribed and expressed in the posterior silk gland under the control of the endogenous FibL promoter, with a protein expression level comparable with that of the native FibL protein. Moreover, we showed based on molecular docking that the fusion of FibL with cuticular protein may have a negative effect on disulfide bond formation between the C-terminal domain of fibroin heavy chain (FibH) and FibL-CP, resulting in abnormal spinning and cocoon in homozygotes, indicating a significant role of FibL in silk protein formation and secretion. Our results demonstrate the feasibility of using the FibL fusion system to express exogenous proteins in silkworm. We expect that this bioreactor system will be used to produce more proteins of interest, expanding the application value of the silk gland bioreactor.

Measurement of the absorption cross-sections of sulfur compounds in the 180-270 nm region considering nonlinear effects.

Sulfur compounds (SO2, CS2, H2S and OCS) are common toxic pollutants in the atmospheric environment, and the absorption spectroscopy technique can indeed help to realize online monitoring of their concentrations. However, nonlinear effects that occur during absorption spectroscopy measurements have a serious impact on the measurement of the absorption cross-sections (ACSs) of sulfur compounds, leading to serious deviations in both the substance absorption properties and concentrations obtained based on ACS analysis. In this paper, the maximum effective ACSs of sulfur compounds in the linear region are obtained by considering the influence of nonlinear effects and eliminating interference factors such as oxygen and photolysis. In addition, the nonlinear effects are found to be greatly attenuated in spectra with broad band absorption characteristics by comparing the oscillatory absorption spectra before and after the differential treatment and by comparing the change in the oscillatory ACS with the broad band ACS. The experimental results show that the effective ACSs of SO2, CS2, H2S, and OCS with a resolution of 0.23 nm are 14.15 × 10-18 cm2 per molecule, 5.61 × 10-16 cm2 per molecule, 7.09 × 10-18 cm2 per molecule, and 3.20 × 10-19 cm2 per molecule, respectively. So far, it is the largest ACS obtained at room temperature and atmospheric pressure, which is of great significance for online measurement of sulfur compounds.

CRISPR-Cas9 mediated genome editing of Kluyveromyces marxianus for iterative, multiplexed gene disruption and pathway integration.

Kluyveromyces marxianus, a thermotolerant, fast-growing, Crabtree-negative yeast, is a promising chassis for the manufacture of various bioproducts. Although several genome editing tools are available for this yeast, these tools still require refinement to enable more convenient and efficient genetic modification. In this study, we engineered the K. marxianus NBRC 104275 strain by impairing the nonhomologous end joining and enhancing the homologous recombination machinery, which resulted in improved homology-directed repair effective on homology arms of up to 40 bp in length. Additionally, we simplified the CRISPR-Cas9 editing system by constructing a strain for integrative expression of Cas9 nuclease and plasmids bearing different selection markers for gRNA expression, thereby facilitating iterative genome editing without the need for plasmid curing. We demonstrated that tRNA was more effective than the hammerhead ribozyme for processing gRNA primary transcripts, and readily assembled tRNA-gRNA arrays were used for multiplexed editing of at least four targets. This editing tool was further employed for simultaneous scarless in vivo assembly of a 12-kb cassette from three fragments and marker-free integration for expressing a fusion variant of fatty acid synthase, as well as the integration of genes for starch hydrolysis. Together, the genome editing tool developed in this study makes K. marxianus more amenable to genetic modification and will facilitate more extensive engineering of this nonconventional yeast for chemical production.

Application of Human Acellular Dermal Matrix with Skin Graft for Lacunar Soft-Tissue Defect of Lateral Heel after Calcaneal Fracture.

OBJECTIVE: To investigate the clinical effect of human acellular dermal matrix (HADM) combined with split-thickness skin graft in repairing lacunar soft tissue defects of the lateral heel after calcaneal fracture. METHODS: From June 2018 to October 2020, providers repaired 11 cases of lacunar soft tissue defects at the lateral part of the heel using HADM combined with split-thickness skin graft. After thorough debridement, the HADM was trimmed and filled into the lacunar defect area. Once the wound was covered, a split-thickness skin graft and negative-pressure wound therapy were applied. Providers evaluated the appearance, scar, ductility of the skin graft site, appearance of the donor site, healing time, and any reoperation at follow-up. RESULTS: Of the 11 cases, 8 patients achieved successful wound healing by primary intention. Three patients showed partial necrosis in the edge of the skin graft, but the wound healed after standard wound care. Evaluation at 6 and 12 months after surgery showed that all patients had wound healing and mild local scarring; there was no obvious pigmentation or scar formation in the donor skin area. The average healing time was 37.5 days (range, 24-43 days). CONCLUSIONS: The HADM combined with split-thickness skin graft is a simple and effective reconstruction method for lacunar soft tissue defect of the lateral heel after calcaneal fracture. In this small sample, the combination demonstrated few infections, minor scar formation, few donor site complications, and relatively short hospital stays.

Autistic traits and eating behaviors in Chinese preschoolers: Role of sensory profiles and home environment.

OBJECTIVE: This study aims to 1) explore the association between autistic traits and eating behaviors in Chinese preschoolers; 2) explore the mediating role of sensory processing patterns on the relation of autistic traits and eating-related behaviors; and 3) examine home nurturing environment as a moderator between autistic traits and eating-related behaviors. We hypothesize that there is a significant association between autistic traits and eating behaviors, which is mediated by sensory processing patterns and moderated by the home nurturing environment. METHOD: 509 children aged 3-4 years participated in this cross-sectional research. They were assessed using the Social Responsiveness Scale-Second Edition (SRS-2) for autistic traits, the Chinese Preschoolers' Eating Behavior Questionnaire (CPEBQ) for eating-related behaviors, the Short Sensory Profile-Second Edition (SSP-2) for sensory processing patterns, and the Children Home Nurture Environment Questionnaire (CHNEQ) for home nurturing environment. Mediation regression analyses were used to examine the role of sensory processing patterns, while moderation analyses to examine the role of home nurturing environment. RESULTS: We observed a positive association between autistic traits and eating behavior problems among typically developed children. Sensory processing patterns significantly mediated the impact of autistic traits on children's eating-related behaviors and home nurturing environment also moderated this relationship. DISCUSSION: Our research suggests that Chinese preschoolers with higher autistic traits may face more eating challenges when they possess more heightened sensory processing patterns, while living in supportive home environments helps to improve their eating behaviors. These findings contribute to the understanding of how and to what extent eating problems are influenced by autistic traits, and they offer insight into the alleviation of eating problems from the perspectives of sensory patterns and family nurturing environments.

Crystalline MnCO3@Amorphous MnOx Composite as Cathode Material for High-Performance Aqueous Zinc-Ion Batteries.

Rechargeable aqueous zinc-ion batteries (RAZIBs) have received extensive attention because of their advantages of low cost, high safety, and nontoxicity. However, problems such as dissolution of the active cathode material, dendrites/passivation of the zinc anode, and slow reaction kinetics hindered their further applications. In this work, a crystalline/amorphous composite-type material composed of crystalline MnCO3 and amorphous MnOx was prepared and used as the cathode material for RAZIBs. The MnCO3@amorphous MnOx (MnCO3@A-MnOx) composite possesses the merits of both the pure crystalline phase of MnCO3 and the amorphous phase of MnOx, which can deliver better electrochemical performance than the corresponding single component in repeated cycles. In addition, crystalline MnCO3 undergoes a complex phase transition to the active MnO2 during the first charge process, providing the composite with a stable structure and additional electrochemical capacity. The electrochemical measurement results indicate that the MnCO3@A-MnOx electrode can display high reversible discharge capacity at 0.1 A g-1, excellent rate performance at 5.0 A g-1, and long cycling stability over 2000 cycles, showing great potential as a cathode material for high-performance RAZIBs.

A Hexanuclear Gadolinium(III)-Based Nanoprobe for Magnetic Resonance Imaging of Tumor Apoptosis.

Magnetic resonance imaging (MRI) is instrumental in the noninvasive evaluation of tumor tissues in patients subjected to chemotherapy, thereby yielding essential diagnostic data crucial for the prognosis of tumors and the formulation of therapeutic strategies. Currently, commercially available MRI contrast agents (CAs) predominantly consist of mononuclear gadolinium(III) complexes. Because there is only one Gd(III) atom per molecule, these CAs often require administration in high doses to achieve the desired contrast quality, which inevitably leads to some adverse events. Herein, we develop a six-nuclei, apoptosis-targeting T1 CA, Gd6-ZnDPA nanoprobe, which consists of a hexanuclear gadolinium nanocluster (Gd6) with an apoptosis-targeting group (ZnDPA). The amplification of Gd(III) by the hexanuclear structure generates its high longitudinal relaxivity (44.67 mM-1 s-1, 1T) and low r1/r2 ratio (0.68, 1T). Based on the Solomon-Bloembergen-Morgan (SBM) theory, this notable improvement is primarily ascribed to a long correlation tumbling time (τR). More importantly, the Gd6-ZnDPA nanoprobe shows excellent tumor apoptosis properties with an enhanced MR signal ratio (∼74%) and a long MRI imaging acquisition time window (∼48 h) in 4T1 tumor-bearing mice. This study introduces an experimental gadolinium-based CA for the potential imaging of tumor apoptosis in the context of MRI.

Deep learning-based platform performs high detection sensitivity of intracranial aneurysms in 3D brain TOF-MRA: An external clinical validation study.

PURPOSE: To evaluate the diagnostic efficacy of a developed artificial intelligence (AI) platform incorporating deep learning algorithms for the automated detection of intracranial aneurysms in time-of-flight (TOF) magnetic resonance angiography (MRA). METHOD: This retrospective study encompassed 3D TOF MRA images acquired between January 2023 and June 2023, aiming to validate the presence of intracranial aneurysms via our developed AI platform. The manual segmentation results by experienced neuroradiologists served as the "gold standard". Following annotation of MRA images by neuroradiologists using InferScholar software, the AI platform conducted automatic segmentation of intracranial aneurysms. Various metrics including accuracy (ACC), balanced ACC, area under the curve (AUC), sensitivity (SE), specificity (SP), F1 score, Brier Score, and Net Benefit were utilized to evaluate the generalization of AI platform. Comparison of intracranial aneurysm identification performance was conducted between the AI platform and six radiologists with experience ranging from 3 to 12 years in interpreting MR images. Additionally, a comparative analysis was carried out between radiologists' detection performance based on independent visual diagnosis and AI-assisted diagnosis. Subgroup analyses were also performed based on the size and location of the aneurysms to explore factors impacting aneurysm detectability. RESULTS: 510 patients were enrolled including 215 patients (42.16 %) with intracranial aneurysms and 295 patients (57.84 %) without aneurysms. Compared with six radiologists, the AI platform showed competitive discrimination power (AUC, 0.96), acceptable calibration (Brier Score loss, 0.08), and clinical utility (Net Benefit, 86.96 %). The AI platform demonstrated superior performance in detecting aneurysms with an overall SE, SP, ACC, balanced ACC, and F1 score of 91.63 %, 92.20 %, 91.96 %, 91.92 %, and 90.57 % respectively, outperforming the detectability of the two resident radiologists. For subgroup analysis based on aneurysm size and location, we observed that the SE of the AI platform for identifying tiny (diameter＜3mm), small (3 mm ≤ diameter＜5mm), medium (5 mm ≤ diameter＜7mm) and large aneurysms (diameter ≥ 7 mm) was 87.80 %, 93.14 %, 95.45 %, and 100 %, respectively. Furthermore, the SE for detecting aneurysms in the anterior circulation was higher than that in the posterior circulation. Utilizing the AI assistance, six radiologists (i.e., two residents, two attendings and two professors) achieved statistically significant improvements in mean SE (residents: 71.40 % vs. 88.37 %; attendings: 82.79 % vs. 93.26 %; professors: 90.07 % vs. 97.44 %; P < 0.05) and ACC (residents: 85.29 % vs. 94.12 %; attendings: 91.76 % vs. 97.06 %; professors: 95.29 % vs. 98.82 %; P < 0.05) while no statistically significant change was observed in SP. Overall, radiologists' mean SE increased by 11.40 %, mean SP increased by 1.86 %, and mean ACC increased by 5.88 %, mean balanced ACC promoted by 6.63 %, mean F1 score grew by 7.89 %, and Net Benefit rose by 12.52 %, with a concurrent decrease in mean Brier score declined by 0.06. CONCLUSIONS: The deep learning algorithms implemented in the AI platform effectively detected intracranial aneurysms on TOF-MRA and notably enhanced the diagnostic capabilities of radiologists. This indicates that the AI-based auxiliary diagnosis model can provide dependable and precise prediction to improve the diagnostic capacity of radiologists.

Is P3 amplitude associated with greater gaze distraction effect in schizotypy?

A recently proposed "Hyperfocusing hypothesis" suggests that schizotypy is associated with a more narrow but more intense way of allocating attention. The current study aims to test a vital prediction of this hypothesis in a social context, that schizotypy may be related to greater difficulty overcoming the distracting effects of gaze. This could cause a longer time to respond to targets that are invalidly cued by gaze. The current study tested this prediction in a modified Posner cueing paradigm by using P3 as an indicator for attentional resources. Seventy-four young healthy individuals with different levels of schizotypy were included, they were asked to detect the location of a target that was cued validly or invalidly by the gaze and head orientation. The results revealed that (a) schizotypy is associated with hyperfocusing on gaze direction, leading to greater difficulty overcoming the distracting effect of gaze. The higher the trait-schizotypy score, the more time needed to respond to targets that were invalidly cued by gaze (b) schizotypy is associated with reduced P3 which is directed by social communicative stimuli. The higher the trait-schizotypy score, the smaller the amplitude of P3 (c) the relationship between schizotypal traits and response times of the gaze-invalid condition is fully intermediated by P3. The findings of the current study suggest the P3 component may be a crucial neural mechanism underlying joint attention deficits in schizophrenia.

Enhancing Efficiency of Large-Area Wide-Bandgap Perovskite Solar Modules with Spontaneously Formed Self-Assembled Monolayer Interfaces.

Wide-bandgap (WBG) perovskites play a crucial role in perovskite-based tandem cells. Despite recent advances using self-assembled monolayers (SAMs) to facilitate efficiency breakthroughs, achieving precise control over the deposition of such ultrathin layers remains a significant challenge for large-scale fabrication of WBG perovskite and, consequently, for the tandem modules. To address these challenges, we propose a facile method that integrates MeO-2PACz and Me-4PACz in optimal proportions (Mixed SAMs) into the perovskite precursor solution, enabling the simultaneous codeposition of WBG perovskite and SAMs. This technique promotes the spontaneous formation of charge-selective contacts while reducing defect densities by coordinating phosphonic acid groups with the unbonded Pb2+ ions at the bottom interface. The resulting WBG perovskite solar cells (PSCs) demonstrated a power conversion efficiency of 19.31% for small-area devices (0.0585 cm2) and 17.63% for large-area modules (19.34 cm2), highlighting the potential of this codeposition strategy for fabricating high-performance, large-area WBG PSCs with enhanced reproducibility. These findings offer valuable insights for advancing WBG PSCs and the scalable fabrication of modules.

Metabolomics analysis reveals the metabolite profiles of Rheum tanguticum grown under different altitudinal gradients.

BACKGROUND: Plant growth and quality are often affected by environmental factors, including geographical location, climate, and soil. In this study, we describe the effect of altitudinal differences on the growth and active ingredients in Rheum tanguticum Maxim. ex Balf. (R. tanguticum), a traditional Chinese medicinal herb known for its laxative properties. RESULTS: The results showed that plants grown at lower altitudes had better growth performances than those in higher altitude areas. The yield varied by 2.45-23.68 times with altitude, reaching a maximum of 102.01 t/ha. In addition, total anthraquinone and total sennoside contents decreased with increasing altitude, whereas total tannins increased with increasing altitude. The total anthraquinone content of the indicator compound reached 5.15% at five experimental sites, which exceeded the Chinese Pharmacopoeia standard by 70.87%. The content of the other two categories of active ingredients reached a maximum value of 0.94% (total sennosides) and 2.65% (total tannins). Redundancy analysis revealed that annual rainfall, annual average temperature, annual sunshine hours, and pH significantly affected growth and active ingredients. Moreover, key metabolites, such as flavonoids, amino acids and their derivatives, phenolic acids, lipids, and terpenes, were differentially expressed between samples from low- and high-altitude cultivation areas. These metabolites were enriched in the flavonoid and flavonol biosynthetic pathway and the monoterpene biosynthetic pathway. CONCLUSIONS: These results suggest that high anthraquinone content was observed in the lowest-latitude cultivation area due to low rainfall and alkaline soil pH. Key metabolites were significantly upregulated in high-latitude cultivation areas. These results provide a scientific basis for quality control and the systematic cultivation of R. tanguticum.

Establishment of a pharmacokinetics and pharmacodynamics model of Schisandra lignans against hippocampal neurotransmitters in AD rats based on microdi-alysis liquid chromatography-mass spectrometry.

Objective: Our previous studies substantiated that the biological activity of Schisandra chinensis lignans during the treatment of Alzheimer's disease (AD) was mediated by neurotransmitter levels, and 15 of its active components were identified. However, the pharmacokinetic and pharmacodynamic relationship of Schisandra chinensis lignans has been less studied. The objective of this study was to investigate the relationship between the pharmacokinetics and pharmacodynamics of Schisandra chinensis lignans in the treatment of AD, and to establish a pharmacokinetic-pharmacodynamic (PK-PD) model. Methods and Results: Herein, we established a microdialysis-ultra performance liquid chromatography-triple quadruple mass spectrometry (MD-LC-TQ-MS) technique that could simultaneously and continuously collect and quantitatively analyze the active compounds and neurotransmitters related to the therapeutic effects of Schisandra chinensis in awake AD rats. Eight lignans were detected in the hippocampus, and a PK-PD model was established. The fitted curves highlighted a temporal lag between the maximum drug concentration and the peak drug effect. Following treatment, the levels of four neurotransmitters tended to converge with those observed in the sham operation group. Conclusion: By establishing a comprehensive concentration-time-effect relationship for Schisandra chinensis lignans in AD treatment, our study provides novel insights into the in vivo effects of these lignans in AD rats.

Identification and validation of m6A-associated ferroptosis genes in renal clear cell carcinoma.

Urinary cancer is synonymous with clear cell renal cell carcinoma (ccRCC). Unfortunately, existing treatments for this illness are ineffective and unpromising. Finding novel ccRCC biomarkers is crucial to creating successful treatments. The Cancer Genome Atlas provided clear cell renal cell carcinoma transcriptome data. Functional enrichment analysis was performed on ccRCC and control samples' differentially expressed N6-methyladenosine RNA methylation and ferroptosis-related genes (DEMFRGs). Machine learning was used to find and model ccRCC patients' predicted genes. A nomogram was created for clear cell renal cell carcinoma patients. Prognostic genes were enriched. We examined patients' immune profiles by risk score. Our prognostic genes predicted ccRCC treatment drugs. We found 37 DEMFRGs by comparing 1913 differentially expressed ccRCC genes to 202 m6A RNA methylation FRGs. Functional enrichment analysis showed that hypoxia-induced cell death and metabolism pathways were the most differentially expressed methylation functional regulating genes. Five prognostic genes were found by machine learning: TRIB3, CHAC1, NNMT, EGFR, and SLC1A4. An advanced renal cell carcinoma nomogram with age and risk score accurately predicted the outcome. These five prognostic genes were linked to various cancers. Immunological cell number and checkpoint expression differed between high- and low-risk groups. The risk model successfully predicted immunotherapy outcome, showing high-risk individuals had poor results. NIACIN, TAE-684, ROCILETINIB, and others treat ccRCC. We found ccRCC prognostic genes that work. This discovery may lead to new ccRCC treatments.

Effects of sintering additives and sintering methods on the mechanical, antimicrobial and optical properties of Si3N4 bioceramics.

Si3N4 bioceramics were fabricated using GPS and SPS method with MgO-RE2O3 (RE = La, Nd, Gd, Ho and Lu) sintering additives. The effect of sintering methods and sintering additives on the grain growth, mechanical, antimicrobial properties and color of Si3N4 bioceramics were studied. Samples sintered with GPS are composed of ß-Si3N4 and samples sintered with SPS are composed of α-Si3N4 and ß-Si3N4. The growth of ß-Si3N4 grains in samples sintered with GPS are more adequate. Samples sintered with GPS exhibit a S. aureus inactivation rate up to 98% and a bright color appearance with a hardness of about 13 GPa and a fracture toughness up to 7.5 MPa m1/2, suitable for dental implants. And samples sintered with SPS exhibit a hardness of about 17 GPa and a fracture toughness about 6 MPa m1/2.

Autistic traits and ARFID-associated eating behaviors in preschoolers: Mediating effects of sensory processing patterns.

OBJECTIVE: This study aimed to examine the association between autistic traits and Avoidant Restrictive Food Intake Disorder (ARFID)-associated eating behaviors in preschool-age children and investigated whether this association was mediated by sensory processing patterns. METHOD: A cross-sectional, parent-reported study was conducted between July 2022 and March 2023 among 503 preschoolers aged 4-6 years in China. Parents provided assessments of their children's autistic traits using the Social Responsiveness Scale, sensory processing patterns using the Short Sensory Profile 2, and ARFID-associated eating behaviors using the Nine Items ARFID Screen. The mediation model based on ordinary least squares regression was employed to test the mediating effects of sensory processing patterns between autistic traits and ARFID-associated eating behaviors. RESULTS: The results indicated significant associations among autistic traits, ARFID-associated eating behaviors, and sensory processing patterns. Moreover, mediation analyses revealed that sensory processing patterns played a partial mediating role in the relationship between autistic traits and ARFID-associated eating behaviors. Specifically, autistic traits were observed to weaken ARFID-associated eating behaviors, particularly picky eating and poor appetite, through Registration, while simultaneously fostering them through Sensitivity and Avoiding. DISCUSSION: Our study is limited to some extent by the inability to draw longitudinal conclusions from cross-sectional data. Nevertheless, it underscores the significance of early identification and intervention for food avoidance/restriction behaviors due to sensory processing abnormalities in children with heightened autistic traits. This proactive approach may contribute to mitigating ARFID-associated eating behaviors that might drive clinical symptoms of ARFID.