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Background: Miniature ion trap mass spectrometer enables mass-to-charge ratio analysis of ions via quadrupole field in a low vacuum environment. It plays an important role in on-site detection due to its portability and specificity. In order to gain a deeper understanding of the analysis mechanism of miniature ion trap mass spectrometers, a quadrupole MS ion trajectory numerical simulation model (QITNS) is established in this paper for ions trajectory calculation under the action of quadrupole field, exciting field and neutral gas molecule collision. Compared with the existing methods, the model in this paper is simpler and more direct, which effectively explored the effects of dipole excitation and quadrupole excitation on ion manipulation under high background pressure., Results: The simulation results demonstrate that high RF amplitude, low auxiliary AC amplitude and quadrupole excitation can effectively improve the isolation resolution. Besides, it clarified the difference between the analysis mechanism of ion trap mass spectrometers under high background pressure (above 13.332 Pa) and absolute vacuum conditions. The relevant results are consistent with the conclusions of previous experiments and other theories, proving the applicability and accuracy of the proposed calculation model and solution method., Significance: This research bears the guiding significance for further understanding the mechanism of quadrupole mass spectrometry as well as designing and developing miniature mass spectrometers., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Postoperative nausea and vomiting are common complications after surgery, and female patients are more likely to experience these adverse events. The goal of this study was to explore the relationship between the CHRM3 rs2165870 polymorphism and postoperative vomiting incidence in female patients who underwent laparoscopic surgery., Methods: Two hundred female patients who underwent elective laparoscopic surgery with subsequent patient-controlled intravenous analgesia using dexmedetomidine and sufentanil were prospectively enrolled. The CHRM3 rs2165870 and KCNB2 rs349358 polymorphisms were genotyped using MassARRAY SNP typing technology. Demographic data and preoperative laboratory results of all patients were recorded. Postoperative analgesia-related information, incidence of postoperative nausea and vomiting, and other adverse events were followed up and recorded for analysis., Results: No significant differences were observed in any of the demographic characteristics of these patients among the different genotype carriers (P>0.05). The percentages of patients with each genotype of CHRM3 were 67% (GG), 28.5% (GA) and 4.5% (AA). We found that the AA or A allele of the CHRM3 rs2165870 polymorphism elevated the risk of postoperative vomiting (AA versus GG; OR, 6.94; 95% CI, 1.49-32.46; P = 0.014; A versus G; OR, 2.52; 95% CI, 1.22-5.19; P = 0.012). The percentages of patients with each genotype of KCNB2 were 84.5% (TT), 15.5% (CT) and 0% (CC). There were no significant differences in the postoperative nausea or vomiting rate across the KCNB2 rs349358 polymorphisms (P>0.05)., Conclusion: The CHRM3 rs2165870 polymorphism is associated with the occurrence of postoperative vomiting in female patients who have undergone laparoscopic surgery. The AA genotype or A allele of the CHRM3 rs2165870 polymorphism elevates the risk of postoperative vomiting., Trial Registration: www.chictr.org.cn, registration number: ChiCTR2200062425., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Carbon(C), nitrogen(N), and phosphorus(P) are crucial elements in the element cycling in the terrestrial ecosystems. In the past decades, the spatial pattern and driving mechanism of plant and soil ecological stoichiometry have been hot topics in ecological geography. So far, many studies at different spatial and ecological scales have been conducted, but systematic review has not been reported to summarize the research status. In this paper, we tried to fill this gap by reviewing both the spatial variations and driving factors of C, N, P stoichiometric characteristics of plant and soil at regional to large scale. Additionally, we synthesized researches on the relationships between plant and soil C, N and P stoichiometric characteristics. At the global scale, plant C, N, P stoichiometric characteristics exhibited some trends along latitude and temperature gradient. Plant taxonomic classification was the main factor controlling the spatial variations of plant C, N and P stoichiometric characteristics. Climate factor and soil properties showed varying impacts on the spatial variations of plant C, N, P stoichiometric characteristics across different spatial scales. Soil C, N, P stoichiometric characteristics also vary along climate gradient at large scale. Their spatial variations result from the combined effects of climate, topography, soil properties, and vegetation characteristics at regional scale. The spatial pattern of soil C, N, P stoichiometric characteristics and the driving effects from environmental factors could be notably different among different ecosystems and vegetation types. Plant C:N:P is obviously higher than that of soil, and there exists a positive correlation between plant and soil C:N:P. Their trends along longitude and latitude are similar, but this correlation varies significantly among different vegetation types. Finally, based on the issues identified in this paper, we highlighted eight potential research themes for the future studies., (Copyright © 2024. Published by Elsevier B.V.)

We collected respiratory specimens from 128 pediatric patients diagnosed with pneumonia in Beijing in late 2023. Mycoplasma pneumoniae was detected in 77.3% (99/128) patients, with 36.4% (4/11), 82.9% (34/41), 80.3% (61/76) in children aged less than 3 years, 3-6 years, over 7 years, respectively. Mycoplasma pneumoniae ( M. pneumoniae ) was characterized using P1 gene typing, MLVA typing and sequencing of domain V of the 23S rRNA gene. P1 gene type 1 (P1-1; 76.1%, 54/71) and MLVA type 4-5-7-2 (73.7%, 73/99) were predominant. MLVA identified a new genotype: 3-4-6-2. Macrolide resistance-associated mutations were detected in 100% of samples, with A2063G accounting for 99% and A2064G for 1%. The positive rate of M. pneumoniae was higher compared to previous reports, especially in children less than 3 years, suggesting a M. pneumoniae epidemic showing a younger age trend occurred in late 2023 in Beijing, China. Higher proportions of macrolide-resistant M. pneumoniae , P1-1 and 4-5-7-2 genotype M. pneumoniae indicated increased macrolide resistance rate and genotyping shift phenomenon, which might be attributable to this epidemic. Additionally, complete clinical information from 73 M. pneumoniae pneumonia inpatients were analyzed. The incidence of severe M. pneumoniae pneumonia was 56.2% (41/73). Mycoplasma pneumoniae pneumonia patients exhibited longer duration of fever, with a median value of 10.0 days (IQR, 8.0-13.0), and higher incidence of complications (74.0%, 54/73). However, in this cohort, we found that the severity of M. pneumoniae pneumonia, co-infection, or complications were not associated with M. pneumoniae P1 gene or MLVA types. Clinicians should be aware that patients infected with macrolide-resistant M. pneumoniae exhibited more severe clinical presentations., 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 Chen, Jia, Gao, Ren, Du, Zhao, Feng, Xue, Cui, Gan, Feng, Fan, Fu, Xu, Yu, Yang, Zhao, Huang, Ke, Cao, Yan and Yuan.)

Animal personalities play a crucial role in invasion dynamics. During the invasion process, the behavioral strategies of native species vary among personalities, just as the invasive species exhibit variations in behavior strategies across personalities. However, the impact of personality interactions between native species and invasive species on behavior and growth are rarely illustrated. The red-eared slider turtle ( Trachemys scripta elegans ) is one of the worst invasive species in the world, threatening the ecology and fitness of many freshwater turtles globally. The Chinese pond turtle ( Mauremys reevesii ) is one of the freshwater turtles most threatened by T. scripta elegans in China. In this study, we used T. scripta elegans and M. reevesii to investigate how the personality combinations of native and invasive turtles would impact the foraging strategy and growth of both species during the invasion process. We found that M. reevesii exhibited bolder and more exploratory personalities than T. scripta elegans . The foraging strategy of M. reevesii was mainly affected by the personality of T. scripta elegans , while the foraging strategy of T. scripta elegans was influenced by both their own personality and personalities of M. reevesii . Additionally, we did not find that the personality combination would affect the growth of either T. scripta elegans or M. reevesii . Differences in foraging strategy may be due to the dominance of invasive species and variations in the superficial exploration and thorough exploitation foraging strategies related to personalities. The lack of difference in growth may be due to the energy allocation trade-offs between personalities or be masked by the slow growth rate of turtles. Overall, our results reveal the mechanisms of personality interaction effects on the short-term foraging strategies of both native and invasive species during the invasion process. They provide empirical evidence to understand the effects of personality on invasion dynamics, which is beneficial for enhancing comprehension understanding of the personality effects on ecological interactions and invasion biology.

The short shelf life of Litchi is due to its rapid metabolism after being harvested. Refrigeration is not a suitable method for preserving litchi, as the browning process of litchi that has been cryogenic will accelerate when it is brought to room temperature. This study introduces an alginate-based coating as a solution to control the post-harvest metabolism of litchi. The coating achieves this by simultaneously establishing crosslink and percolation networks, both of which act as barriers. The percolation network is created using rod-like cellulose nanocrystals, which possess excellent percolation properties. This network effectively reduces moisture loss. Compared to the control group, the coated litchi exhibited a 38.1 % lower browning index and a 62.5 % lower decay rate. Additionally, the soluble solid content increased by 107.1 %. The inclusion of cellulose nanocrystals and the crosslinking of calcium ions enhanced the mechanical properties of the composite membrane. Specifically, the tensile strength and elongation at break increased by 70 % and 366 % respectively. As all the components in the coating are edible, it is environmentally friendly and safe for human consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Patients with Parkinson's disease (PD) respond to deep brain stimulation (DBS) variably. However, how brain substrates restrict DBS outcomes remains unclear., Objective: In this article, we aim to identify prognostic brain signatures for explaining the response variability., Methods: We retrospectively investigated a cohort of patients with PD (n = 141) between 2017 and 2022, and defined DBS outcomes as the improvement ratio of clinical motor scores. We used a deviation index to quantify individual perturbations on a reference structural covariance network acquired with preoperative T1-weighted magnetic resonance imaging. The neurobiological perturbations of patients were represented as z scored indices based on the chronological perturbations measured on a group of normal aging adults., Results: After applying stringent statistical tests (z > 2.5) and correcting for false discoveries (P < 0.01), we found that accelerated deviations mainly affected the prefrontal cortex, motor strip, limbic system, and cerebellum in PD. Particularly, a negative network within the accelerated deviations, expressed as "more preoperative deviations, less postoperative improvements," could predict DBS outcomes (mean absolute error = 0.09, R 2  = 0.15). Moreover, a fusion of personal brain predictors and medical responses significantly improved traditional evaluations of DBS outcomes. Notably, the most important brain predictor, a pathway connecting the cognitive unit (prefrontal cortex) and motor control unit (cerebellum and motor strip), partially mediates DBS outcomes with the age at surgery., Conclusions: Our findings suggest that individual structural perturbations on the cognitive motor control circuit are critical for modulating DBS outcomes. Interventions toward the circuit have the potential for additional clinical improvements. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Copper (Cu) nanomaterials are a unique kind of electrocatalysts for high-value multi-carbon production in carbon dioxide reduction reaction (CO 2 RR), which holds enormous potential in attaining carbon neutrality. However, phase engineering of Cu nanomaterials remains challenging, especially for the construction of unconventional phase Cu-based asymmetric heteronanostructures. Here the site-selective growth of Cu on unusual phase gold (Au) nanorods, obtaining three kinds of heterophase fcc-2H-fcc Au-Cu heteronanostructures is reported. Significantly, the resultant fcc-2H-fcc Au-Cu Janus nanostructures (JNSs) break the symmetric growth mode of Cu on Au. In electrocatalytic CO 2 RR, the fcc-2H-fcc Au-Cu JNSs exhibit excellent performance in both H-type and flow cells, with Faradaic efficiencies of 55.5% and 84.3% for ethylene and multi-carbon products, respectively. In situ characterizations and theoretical calculations reveal the co-exposure of 2H-Au and 2H-Cu domains in Au-Cu JNSs diversifies the CO* adsorption configurations and promotes the CO* spillover and subsequent C-C coupling toward ethylene generation with reduced energy barriers., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

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 10 8 to 10 5 -10 6 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., Competing Interests: The authors declare no conflict of interest.

Background: Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an emerging pharmacological target in cancer immunotherapy. This study was set out to examine the expression profiles and implications for prognosis and immunotherapy of ERAP1 in CRC., Methods: Based on bioinformatics and immunohistochemical analysis, we analyzed ERAP1 for potential diagnostic and prognostic significance in CRC. Functional enrichment analysis was conducted to detect the pathways associated with ERAP1, thus determining possible mechanisms. ESTIMATE, TIMER, and CIBESORT probed the links between ERAP1 and tumor-infiltrating immune cells. Lastly, we examined how ERAP1 expression correlated with the sensitivity to immunotherapy., Results: Tumor tissues had decreased levels of ERAP1 expression relative to normal tissues. Patients whose ERAP1 expression was low suffered a worse chance of survival. Besides, it was shown that ERAP1 expression was associated with the advanced M stage and pathologic stage. Survival analysis revealed that low ERAP1 expression, age, pathologic stage, T stage, and M stage were independent indicators for unfavorable CRC patients' prognoses. The 1-, 3-, and 5-year OS calibration curves all fit well with the ideal model, suggesting that the age-ERAP1-T-stage-M-stage nomogram is a reliable predictor of OS. Additionally, we discovered that ERAP1 expression was associated with immune response and infiltration of various immune cells, such as down-regulated inhibitory immune cells and up-regulated stimulating immune cells. Sensitivity to PD-1 and CTLA4 inhibitors was associated with high ERAP1 levels., Conclusions: In summary, ERAP1 has potential as a diagnostic and prognostic biological marker, highlighting new insights into the study of CRC and the design of effective therapies., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Cognitive impairment frequently presents as a prevalent consequence following stroke, imposing significant burdens on patients, families, and society. The objective of this study was to assess the effectiveness and underlying mechanism of nerve growth factor (NGF) in treating post-stroke cognitive dysfunction in rats with cerebral ischemia-reperfusion injury (MCAO/R) through delivery into the brain using specific mode electroacupuncture stimulation (SMES). From the 28th day after modeling, the rats were treated with NGF mediated by SMES, and the cognitive function of the rats was observed after treatment. Learning and memory ability were evaluated using behavioral tests. The impact of SMES on blood-brain barrier (BBB) permeability, the underlying mechanism of cognitive enhancement in rats with MCAO/R, including transmission electron microscopy, enzyme-linked immunosorbent assay, immunohistochemistry, immunofluorescence, and TUNEL staining. We reported that SMES demonstrates a safe and efficient ability to open the BBB during the cerebral ischemia repair phase, facilitating the delivery of NGF to the brain by the p65-VEGFA-TJs pathway., (© 2024. The Author(s).)

Introduction: Paclitaxel (PTX) cannot effectively treat glioma because it cannot cross the bloodbrain barrier (BBB). A specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, thereby improving drug delivery to the brain. This study aimed to observe SMES-mediated accumulation of PTX in the brain and its anti-glioma effect and explore the role of the Hedgehog pathway., Methods: The acupoint selectivity of SMES in opening the BBB was examined in normal rats. The penetration and anti-glioma activity were determined in a C6-Luc glioma rat model. SMES was performed using 2/100 Hz, 3 mA, 6-6 s, and 40 min The survival curve was analysed by the KaplanMeier method, brain tumour pathology and size was observed by HE staining, and in vivo imaging system respectively., Results: SMES-induced BBB opening had acupoint selectivity. SMES could improve PTX accumulation in brain and SMES-mediated PTX delivery showed enhanced anti-glioma activity due to better brain penetration. Hedgehog pathway was involved in SMES-mediated PTX delivery by regulating Occludin expression., Conclusion: SMES at the head acupoints to deliver PTX is a feasible and effective method for treating glioma. The Hedgehog pathway may play a key role in SMES-mediated PTX delivery across the BBB., Competing Interests: Declaration of Competing Interest All authors claim that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Bacterial infections caused by multidrug-resistant (MDR) gram-negative strains carrying the mobile colistin resistance gene mcr-1 are serious threats to world public health due to the lack of effective treatments. Inhibition of the ATP synthase makes bacteria such as Staphylococcus aureus and Klebsiella pneumoniae more sensitive to polymyxin. This provides new strategies for treating infections caused by polymyxins-resistant bacteria carrying mcr-1. Six mcr-1-positive strains were isolated from clinical samples, and all were identified as Escherichia coli. Here we investigated several ATP synthase inhibitors, N,N'-dicyclohexylcarbodiimide (DCCD), resveratrol, and piceatannol, for their antibacterial effects against the mcr-1-positive strains combined with polymyxin B (POL). Checkerboard assay, time-kill assay, biofilm inhibition and eradication assay indicated the significant synergistic effect of ATP synthase inhibitors/POL combination in vitro. Meanwhile, mouse infection model experiment was also performed, showing a 5 log 10 reduction of the pathogen after treatment with the resveratrol/POL combination. Moreover, adding adenosine disodium triphosphate (Na 2 ATP) could inhibit the antibacterial effect of the ATP synthase inhibitors/POL combination. In conclusion, our study confirmed that inhibition of ATP production could increase the susceptibility of bacteria carrying mcr-1 to polymyxins. This provides a new strategy against polymyxins-resistant bacteria infection., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Membrane budding, which underlies fundamental processes like endocytosis, intracellular trafficking, and viral infection, is thought to involve membrane coat-forming proteins, including the most observed clathrin, to form Ω-shape profiles and helix-forming proteins like dynamin to constrict Ω-profiles' pores and thus mediate fission. Challenging this fundamental concept, we report that polymerized clathrin is required for Ω-profiles' pore closure and that clathrin around Ω-profiles' base/pore region mediates pore constriction/closure in neuroendocrine chromaffin cells. Mathematical modeling suggests that clathrin polymerization at Ω-profiles' base/pore region generates forces from its intrinsically curved shape to constrict/close the pore. This new fission function may exert broader impacts than clathrin's well-known coat-forming function during clathrin (coat)-dependent endocytosis, because it underlies not only clathrin (coat)-dependent endocytosis, but also diverse endocytic modes, including ultrafast, fast, slow, bulk, and overshoot endocytosis previously considered clathrin (coat)-independent in chromaffin cells. It mediates kiss-and-run fusion (fusion pore closure) previously considered bona fide clathrin-independent, and limits the vesicular content release rate. Furthermore, analogous to results in chromaffin cells, we found that clathrin is essential for fast and slow endocytosis at hippocampal synapses where clathrin was previously considered dispensable, suggesting clathrin in mediating synaptic vesicle endocytosis and fission. These results suggest that clathrin and likely other intrinsically curved coat proteins are a new class of fission proteins underlying vesicle budding and fusion. The half-a-century concept and studies that attribute vesicle-coat contents' function to Ω-profile formation and classify budding as coat-protein (e.g., clathrin)-dependent or -independent may need to be re-defined and re-examined by considering clathrin's pivotal role in pore constriction/closure., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

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 10 1 CFU/mL, which was better than that of real-time PCR (10 2 -10 3 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.

Background: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens., Methods: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG)., Results: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events., Conclusions: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes., Trial Registration: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 )., (© 2024. The Author(s).)

Purpose: It is necessary to establish a mouse model of keratoconus (KC) for research and therapy. We aimed to determine corneal phenotypes in 3 Ppip5k2 mouse models., Methods: Central corneal thickness (CCT) was determined using spectral domain optical coherence tomography (SD-OCT) in Ppip5k2+/K^ (n = 41 eyes), Ppip5k2K^/K^ (n = 17 eyes) and 2 knock-in mice, Ppip5k2S419A/+ (n = 54 eyes) and Ppip5k2S419A/S419A (n = 18 eyes), and Ppip5k2D843S/+ (n = 42 eyes) and Ppip5k2D843S/D843S (n = 44 eyes) at 3 and 6 months. Pachymetry maps were generated using the Mouse Corneal Analysis Program (MCAP) to process OCT images. Slit lamp biomicroscopy was used to determine any corneal abnormalities, and, last, hematoxylin and eosin (H&E) staining using corneal sections from these animals was used to examine morphological changes., Results: CCT significantly decreased from 3 to 6 months in the Ppip5k2+/K^ and Ppip5k2K^/K^ mice compared to their littermate controls. OCT-based pachymetry maps revealed abnormally localized thinning in all three models compared to their wild-type (WT) controls. Slit lamp examinations revealed corneal abnormalities in the form of bullous keratopathy, stromal edema, stromal scarring, deep corneal neovascularization, and opacities in the heterozygous/homozygous mice of the three models in comparison with their controls. Corneal histological abnormalities, such as epithelial thickening and stromal layer damage, were observed in the heterozygous/homozygous mice of the three models in comparison with the WT controls., Conclusions: We have identified phenotypic and histological changes in the corneas of three mouse lines that could be relevant in the development of animal models of KC.

Heme is a coordination complex formed by the binding of iron ions and porphyrin rings. Its metabolic processes are associated with various cancers, including gastric cancer (GC). In recent years, long non-coding RNAs (LncRNAs) have been identified as key regulatory factors in GC. However, the role of LncRNAs associated with heme metabolism in GC and their relationship with prognosis have not been reported. In this study, we constructed a novel LncRNAs signature related to heme metabolism (HMlncSig) and validated its prognostic value for predicting the survival of GC patients through training, test, and entire cohorts. Kaplan-Meier analysis demonstrated that patients in the high-risk group had shorter survival times. Univariate and multivariate Cox regression analysis showed that HMlncSig was an independent prognostic indicator for GC patients, regardless of other clinical pathological features. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis and gene set variation analysis pathways showed that the activation of these markers may be involved in tumor progression, influencing the survival of GC patients. The nomogram, based on HMlncSig score and clinical features, demonstrated the strong predictive ability of this signature. Additionally, significant differences were observed between the high-risk and low-risk groups in terms of immune cell subtypes, expression of immune checkpoint genes, and response to chemotherapy and immunotherapy. Through clinical validation, we found that the risk score and heme levels of GC patients were both significantly elevated and correlated with the degree of malignancy. Furthermore, we found that AP000692.1, a key gene in this signature, promoted the proliferation, migration, and invasion of GC cells. In conclusion, our HMlncSig model has significant predictive value for the prognosis of GC patients and can provide clinical guidance for personalized immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The effect of grainyhead-like transcription factor 3 (GRHL3) on cancer development depends on the cancer subtypes as shown in tumor entities such as colorectal or oral squamous cell carcinomas. Here, we analyzed the subtype-specific role of GRHL3 in bladder carcinogenesis, comparing common urothelial carcinoma (UC) with squamous bladder cancer (sq-BLCA). We examined GRHL3 mRNA and protein expression in cohorts of patient samples, its prognostic role and its functional impact on tumorigeneses in different molecular and histopathological subtypes of bladder cancer. We showed for GRHL3 a reverse expression in squamous and urothelial bladder cancer subtypes. Stably GRHL3-overexpressing EJ28, J82, and SCaBER in vitro models revealed a tumor-suppressive function in squamous and an oncogenic role in the urothelial cancer cells affecting cell and colony growth, and migratory and invasive capacities. Transcriptomic profiling demonstrated highly subtype-specific GRHL3-regulated expression networks coined by the enrichment of genes involved in integrin-mediated pathways. In SCaBER, loss of ras homolog family member A (RHOA) GTPase activity was demonstrated to be associated with co-regulation of eukaryotic translation initiation factor 4E family member 3 (EIF4E3), a potential tumor suppressor gene. Thus, our data provide for the first time a detailed insight into the role of the transcription factor GRHL3 in different histopathological subtypes of bladder cancer., (© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The mattic layer is a main ecological function bearer of alpine meadow soils in the Qinghai-Tibet Plateau. It has high soil organic carbon (SOC) content with a variety of SOC fractions, which are thought to have different sensitivities to climate change. The effects of soil properties and climate on the SOC fractions in the mattic layer are not well understood. To address this, we analyzed the effects of environmental factors on two SOC fractions: particulate organic carbon (POC) and mineral-associated organic carbon (MAOC). A random forest model (RFM), partial correlation analysis, and structural equation model (SEM) were used to quantify the relative effects of soil and climatic factors on SOC fractions. We found that SOC and its fractions are primarily regulated by soil properties rather than climate. Partial correlation analysis and SEM revealed that climate indirectly affects SOC by influencing soil properties. Silt+Clay and exchangeable calcium (Ca ex ) were found to be the strongest contributing factors of MAOC and POC, respectively. A distinct shift occurs in the mechanism underlying SOC stabilization with varying soil pH. In acidic and neutral environments, amorphous Al/Fe-(hydr) oxides contribute to the stability of MAOC, whereas free Al/Fe-(hydr) oxides promote SOC mineralization. Conversely, Ca ex positively influences the stabilization of both POC and MAOC throughout the pH range. These results can be extrapolated to predict SOC dynamics in future soil conditions affected by environmental change, especially for use in Earth system models., 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 B.V.)

A novel terahertz polarization isolator using a two-dimensional square lattice tellurium rod array is numerically investigated at the interesting band of 0.22 THz in this short paper. The isolator is designed by inserting six hexagonal tellurium rods into a fully polarized photonic crystals waveguide with high efficiency of -0.34 dB. The TE and TM photonic band gaps of the 7 × 16 tellurium photonic crystals are computed based on the plane wave expansion method, which happen to coincide at the normalized frequency domain from 0.3859( a / λ ) to 0.4033( a / λ ), corresponding to the frequency domain from 0.2152 to 0.2249 THz. The operating bandwidth of the tellurium photonic crystals waveguide covers 0.2146 to 0.2247 THz, calculated by the finite element method. The six hexagonal tellurium rods with smaller circumradii of 0.16 a serve to isolate transverse electric waves and turn a blind eye to transverse magnetic waves. The polarization isolation function and external characteristic curves of the envisaged structure are numerically simulated, which achieves the highest isolation of -33.49 dB at the central frequency of 0.2104 THz and the maximum reflection efficiency of 98.95 percent at the frequency of 0.2141 THz. The designed isolator with a unique function and high performance provides a promising approach for implementing fully polarized THz devices for future 6G communication systems.

Background: Aldosterone plays important parts in development of cardio-metabolic diseases as end product of renin-angiotensin-aldosterone system. However, factors elevating circulating aldosterone are not clear, and lifestyle-related factors are suggested to be involved, whereas less studied. Therefore, we aimed to explore the association of lifestyle factors with plasma aldosterone concentration (PAC) in community population., Methods: In this cross-sectional study, we recruited participants using multistage random sampling from Emin China in 2019, and collected data and fasting blood samples. The considered lifestyle factors included obesity parameters (neck circumference, abdominal circumference), alcohol consumption, blood pressure (BP), physical activity, sleep duration, sleep quality, mental state (depression and anxiety), fasting blood glucose (FBG), and lipid profiles (total cholesterol and triglyceride). PAC was measured using radioimmunoassay. We performed sex-stratified linear and logistic regressions to explore associated factors of PAC. Component analysis was further performed to identify the main factors affecting PAC., Results: Twenty-seven thousand four hundred thirty-six participants with 47.1% men were included. Obesity parameters (neck circumference, abdominal circumference), glucose metabolism (FBG), psychological status (anxiety status in men and women, depression status in men), BP, liver function (in men), lipid metabolism (TC and TG in men), sleep parameters (sleep quality in women), and renal function (in women) are the main factors associated with elevated PAC., Conclusion: lower physical activity, alcohol consumption, higher BP, fat accumulation, dyslipidemia, higher fasting blood glucose, and presence of depression and anxiety were the main factors associated with eleveated PAC., (© 2024. The Author(s).)

This editorial provides an overview of recent advancements in the understanding and treatment of neurological disorders, focusing on aging, immunity, and blood flow, as featured in this special issue. The first section explores the importance of identifying biomarkers of aging and aging-related diseases, such as Alzheimer's Disease, highlighting the emerging role of saliva-based biomarkers and the gut-brain axis in disease diagnosis and management. In the subsequent section, the dysregulated immune systems associated with aging are discussed, emphasizing the intricate landscape of the immune system during aging and its bidirectional relationship with neuroinflammation. Additionally, insights into the involvement of Myeloid-Derived Suppressor Cells (MDSCs) in Multiple Sclerosis (MS) pathogenesis are presented. The third section examines the role of microglia in neuroinflammation and various neurological diseases, including age-related macular degeneration (AMD) and Tuberculous Meningitis (TBM). Furthermore, the therapeutic potential of stem cell and extracellular vesicle-based therapies for stroke is explored, along with molecular mechanism of how inflammation regulates cerebral and myocardial ischemia. Finally, the importance of blood flow in maintaining vascular health and its impact on neurological disorders are discussed, highlighting the potential of novel assessment methods for optimizing patient care. Overall, this special issue offers valuable insights into the complex mechanisms underlying neurological disorders and identifies potential avenues for therapeutic intervention.

Controlling and understanding the heat flow at a nanometer scale are challenging, but important for fundamental science and applications. Two-dimensional (2D) layered materials provide perhaps the ultimate solution for meeting these challenges. While there have been reports of low thermal conductivities (several mW m -1 K -1 ) across the 2D heterostructures, phonon-dominant thermal transport remains strong due to the nearly-ideal contact between the layers. Here, this work experimentally explores the heat transport mechanisms by increasing the interlayer distance from perfect contact to a few nanometers and demonstrates that the phonon-dominated thermal conductivity across the WS 2 /graphene interface decreases further with the increasing interlayer distance until the air-dominated thermal conductivity increases again. This work finds that the resulting tradeoff of the two heat conduction mechanisms leads to the existence of a minimum thermal conductivity at 2.11 nm of 1.41 × 10 -5  W m -1 K -1 , which is two thousandths of the smallest value reported previously. This work provides an effective methodology for engineering thermal insulation structures and understanding heat transport at the ultimate small scales., (© 2024 Wiley‐VCH GmbH.)

Novel evanescently coupled waveguide modified uni-traveling carrier photodiodes (MUTC-PDs) employing a thick multi-layer coupling waveguide are reported. To improve the optical-to-electrical (O/E) conversion efficiency, a thick multi-layer coupling waveguide with a gradually increased refractive index from the bottom layer to the absorption layer is utilized. The refractive index profile facilitates the upward transmission of incident light into the absorption region, thereby enhancing the evanescent coupling efficiency. Meanwhile, the coupling waveguide, with a total thickness of 1.75 µm, expands the mode field diameter, thereby reducing the input coupling loss. Additionally, the top layer of the coupling waveguide also serves as the drift layer. This configuration facilitates efficient light absorption within a short PD length, thus ensuring ultrawide bandwidth and high O/E conversion efficiency simultaneously. Without an additional spot size coupler or anti-reflection coating, the measured responsivity is as high as 0.38 A/W for the PD with an active area of 5 × 6 µm 2 . Meanwhile, an ultrawide 3-dB bandwidth of 153 GHz has been demonstrated.

Background: It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related., Methods: We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium ( n  = 18,340) and the Dutch Microbiota Project ( n  = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found., Results: LachnospiraceaeUCG001 (OR = 1.12, 95% CI: 1.05-1.20) was a risk factor for migraine. Blautia (OR = 0.93, 95% CI: 0.88-0.99), Eubacterium ( nodatum group; OR = 0.94, 95% CI: 0.90-0.98), and Bacteroides fragilis (OR = 0.97, 95% CI: 0.94-1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83-0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73-1.00), which are downstream metabolites of Blautia and Bacteroides fragilis , respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified., Conclusion: This Mendelian randomization analysis showed that LachnospiraceaeUCG001 was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut-brain axis in migraine as well as possible targets for treatment interventions., 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 Qu, Li, Gan, Cui, Li, Yang and Dong.)

Global estimates of the size, distribution, and vulnerability of soil inorganic carbon (SIC) remain largely unquantified. By compiling 223,593 field-based measurements and developing machine-learning models, we report that global soils store 2305 ± 636 (±1 SD) billion tonnes of carbon as SIC over the top 2-meter depth. Under future scenarios, soil acidification associated with nitrogen additions to terrestrial ecosystems will reduce global SIC (0.3 meters) up to 23 billion tonnes of carbon over the next 30 years, with India and China being the most affected. Our synthesis of present-day land-water carbon inventories and inland-water carbonate chemistry reveals that at least 1.13 ± 0.33 billion tonnes of inorganic carbon is lost to inland-waters through soils annually, resulting in large but overlooked impacts on atmospheric and hydrospheric carbon dynamics.

The "pace-of-life" syndrome (POLS) framework can encompass multiple personality axes that drive important functional behaviors (e.g., foraging behavior) and that co-vary with multiple life history traits. Food hoarding is an adaptive behavior important for an animal's ability to adapt to seasonal fluctuations in food availability. However, the empirical evidence for the relationships between animal personality and hoarding behavior remains unclear, including its fitness consequences in the POLS framework. In this study, the Mongolian gerbil ( Meriones unguiculatus ), a social rodent, was used as a model system to investigate how boldness or shyness is associated with food hoarding strategies during the food hoarding season and their impact on over-winter survival and reproduction at both individual and group levels. The results of this study showed that, compared with shy gerbils, bold gerbils had a lower effort foraging strategy during the food hoarding season and exhibited lower over-winter survival rates. However, bold-shy personality differences had no effect on over-winter reproduction. These findings suggest that the personality is a crucial factor influencing the foraging strategy during the food hoarding season in Mongolian gerbils. Personality may be related to energy states or the reaction to environmental changes (e.g., predation risk and food availability) in bold or shy social animals. These results reflect animal life history trade-offs between current versus future reproduction and reproduction versus self-maintenance, thereby helping Mongolian gerbils in adapting to seasonal fluctuations in their habitat., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: This study aimed to evaluate the therapeutic effect and tolerance of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) use for 24 weeks in anti-retroviral therapy (ART)-naïve patients in China., Methods: This single-center retrospective cohort study included ART-naïve patients who received BIC/FTC/TAF from July 2021 to April 2022. The proportion of patients with HIV RNA < 50 copies/mL at the end point of 24 weeks (virological suppression rate) was the primary outcome, and the changes in CD4 cell count, CD4/CD8 ratio, weight, blood lipid, and safety were secondary outcomes., Results: A total of 80 ART-naïve patients were enrolled. The virological suppression rate was 86.3% at 24 weeks. The median CD4 cell count increased from 212 cells/μL (interquartile range [IQR]: 90.3-398.3) at baseline to 348 cells/μL (IQR: 219.8-541.0) at 24 weeks. The median CD4/CD8 ratio increased from 0.25 (IQR: 0.13-0.37) at baseline to 0.40 (IQR: 0.26-0.66) at 24 weeks. During the follow-up of 80 ART-naïve patients using BIC/FTC/TAF, 16 participants had adverse events; however, these events did not lead to drug withdrawal., Conclusion: This real-world cohort study showed that BIC/FTC/TAF could achieve good immunological and virological responses in ART-naïve patients. In addition, this study also shows good safety.

Introduction: The efficacy and safety of ainuovirine+lamivudine+tenofovir (ANV+3TC+TDF) and efavirenz+lamivudine+tenofovir (EFV+3TC+TDF) have been confirmed in previous clinical trials; however, there are no related studies on patient-reported outcomes. This study aimed to evaluate the effectiveness and safety of these 2 antiretroviral therapy regimens and to understand the patient's symptom experience and subjective experience of sleep quality through patient-reported outcomes., Methods: This is a single-center prospective cohort study with 243 patients evaluated from October 1, 2021 to June 30, 2022. Virological effectiveness and patient-reported outcomes results were analyzed. The primary endpoint was the proportion of HIV viral load <50 copies/mL (virological suppression rate) at 48 weeks and the changes in the HIV symptom index and Pittsburgh sleep quality index., Results: The virological suppression rates in the ANV+3TC+TDF and EFV+3TC+TDF groups were 83.6% (102/122) and 87.6% (106/121), respectively, at 48 weeks. In the ANV+3TC+TDF group, the scores of HIV symptom index and pittsburgh sleep quality index in the 48th week were lower than the baseline level (p < 0.05). Logistic regression results showed that the baseline regimen EFV+3TC+TDF was a risk factor for dizziness/lightheadedness (odds ratio = 3.153, 95% confidence interval: 1.473-6.748, p = 0.003), sadness/depression odds ratio = 2.404, 95% confidence interval:1.188-4.871, p = 0.015), and difficulty sleeping (odds ratio = 2.802, 95% confidence interval: 1.437-5.463, p = 0.002) at 48 weeks., Conclusions: Both regimens showed good virological effectiveness; however, compared with ANV+3TC+TDF, the EFV+3TC+TDF regimen reduced the prevalence of HIV-related symptoms., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients., (© 2024 Wiley Periodicals LLC.)

Background: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant., Method/design: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12., Trial Registration: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023., (© 2024. The Author(s).)

Groundwater resources is not only important essential water resources but also imperative connectors within the intricate framework of the ecological environment. High nitrate concentrations in groundwater can exerting adverse impacts on human health. It is imperative to accurately delineate the distribution characteristics of groundwater nitrate concentrations. Four different machine learning models (Gradient Boosting Regression (GB), Random Forest Regression (RF), Extreme Gradient Boosting Regression (XG) and Adaptive Boosting Regression (AD)) which combine spatial environmental data and different radius contributing area was developed to predict the distribution of nitrate concentration in groundwater. The models use 595 groundwater samples and included topography, remote sensing, hydrogeological and hydrological, climate, nitrate input, and socio-economic predictor. Gradient Boosting Regression model outperforms the other models (R2 = 0.627, MAE = 0.529, RMSE = 0.705, PICP = 0.924 for test dataset) under 500 m radius contributing area. A high-resolution (1 km) groundwater nitrate concentration distribution map reveal in the majority of the study area, groundwater nitrate concentrations are below 1 mg/L and high nitrate concentration (>10 mg/L) proportion in southeast, northeast and central main urban area karst valley regions is 1.89%, 0.91%, and 0.38% respectively. In study area, hydrogeological conditions, soil parameters, nitrogen input factors, and percentage of arable land are among the most influential explanatory factors. This work, serving as the inaugural application of utilizing effective spatial methods for predicting groundwater nitrate concentrations in Chongqing city, furnish decision-making support for the prevention and control of groundwater pollution, particularly in areas primarily dependent on groundwater for water supply and holds profound significance as a milestone achievement., Competing Interests: 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., (© 2024 The Authors.)

The two-test in vitro battery for genotoxicity testing (Ames and micronucleus) has in the majority of cases replaced the three-test battery (as two-test plus mammalian cell gene mutation assay) for the routine testing of chemicals, pharmaceuticals, cosmetics, and agrochemical metabolites originating from food and feed as well as from water treatment. The guidance for testing agrochemical groundwater metabolites, however, still relies on the three-test battery. Data collated in this study from 18 plant protection and related materials highlights the disparity between the often negative Ames and in vitro chromosome aberration data and frequently positive in vitro mammalian cell gene mutation assays. Sixteen of the 18 collated materials with complete datasets were Ames negative, and overall had negative outcomes in in vitro chromosome damage tests (weight of evidence from multiple tests). Mammalian cell gene mutation assays (HPRT and/or mouse lymphoma assay (MLA)) were positive in at least one test for every material with this data. Where both MLA and HPRT tests were performed on the same material, the HPRT seemed to give fewer positive responses. In vivo follow-up tests included combinations of comet assays, unscheduled DNA synthesis, and transgenic rodent gene mutation assays, all gave negative outcomes. The inclusion of mammalian cell gene mutation assays in a three-test battery for groundwater metabolites is therefore not justified and leads to unnecessary in vivo follow-up testing., (© The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society.)

Globally, nitrate (NO 3 - ) leaching from agroecosystems has been of major concern. There is evidence that NO 3 - leaching exhibits intense seasonal variation in subtropical regions. However, influencing factors to the seasonal dynamics remain unclear. In this study, a two-year field lysimeters experiment was conducted with three red soils derived from different parent materials (Quaternary red clay (QR), red sandstone (RS), and basalt (BA)). An N fertilizer ( 15 N-enriched urea, 10 atom% excess) of 200 kg N ha -1  yr -1 was applied for maize. The effect of parent material on NO 3 - leaching characteristics was examined in surface (0-20 cm) and subsoil (20-100 cm) layers. The results showed due to the weakening of abundant drainage, there was no significant effect of parent materials on NO 3 - leaching characteristics in surface layers. Environmental factors (precipitation and temperature) and fertilization together led to obvious seasonal characteristics, i.e. abundant NO 3 - leaching during both crop growth and fallow periods. In subsoil layers, NO 3 - leaching characteristics were completely different among three soils. The concentrations and δ 15 N of NO 3 - in QR and RS soils showed a continuous increase after first year's fertilization, while those in BA soil remained relatively stable after reaching peak levels around harvest in first year. Meanwhile, the NO 3 - leaching amount in BA soil was significantly lower than in the other two soils. These might be explained by different NO 3 - adsorption capacities caused by the differences in mineral composition and free iron and aluminium contents. These elucidated in subsoil layers, NO 3 - leaching characteristics highly depended on parent materials. Meanwhile, adsorption capacity was limited and cannot slow NO 3 - leaching in the long run. Our results suggest that seasonal variation of NO 3 - leaching in surface layers and temporary retardant effect from NO 3 - adsorption capacity in subsoil layers should receive much attention when calculating and predicting NO 3 - leaching in subtropical regions., 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.)

The crosstalk between reactive astrocytes and infiltrated immune cells plays a critical role in maintaining blood-brain barrier (BBB) integrity. However, how astrocytes interact with immune cells and the effect of their interaction on BBB integrity after hemorrhagic stroke are still unclear. By performing RNA sequencing in astrocytes that were activated by interleukin-1α (IL-1α), tumor necrosis factor α (TNFα), and complement component 1q (C1q) treatment, we found CCL5 was among the top upregulated genes. Immunostaining and western blot results demonstrated that CCL5 was increased in mice brain after hemorrhagic stroke. Flow cytometry showed that knockout of astrocytic CCL5 reduced the infiltration of CD8 + but not CD4 + T and myeloid cells into the brain ( p  < 0.05). In addition, knockout CCL5 in astrocytes increased tight junction-related proteins ZO-1 and Occludin expression; reduced Evans blue leakage, perforin and granzyme B expression; improved neurobehavioral outcomes in hemorrhagic stroke mice ( p  < 0.05), while transplantation of CD8 + T cells reversed these protective effects. Moreover, co-culture of CD8 + T cells with bEnd.3 cells induced the apoptosis of bEnd.3 cells, which was rescued by inhibiting perforin. In conclusion, our study suggests that CCL5 mediated crosstalk between astrocytes and CD8 + T cells represents an important therapeutic target for protecting BBB in stroke., 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.

Deletions on the long arm of chromosome 9 (del(9q)) are recurrent abnormalities in about 2 % of acute myeloid leukemia cases, which usually involve HNRNPK and are frequently associated with other known aberrations. Based on an Hnrnpk haploinsufficient mouse model, a recent study demonstrated a function of hnRNP K in pathogenesis of myeloid malignancies via the regulation of cellular proliferation and myeloid differentiation programs. Here, we provide evidence that reduced hnRNP K expression results in the dysregulated expression of C/EBPα and additional transcription factors. CyTOF analysis revealed monocytic skewing with increased levels of mature myeloid cells. To explore the role of hnRNP K during normal and pathological myeloid differentiation in humans, we characterized hnRNP K-interacting RNAs in human AML cell lines. Notably, RNA-sequencing revealed several mRNAs encoding key transcription factors involved in the regulation of myeloid differentiation as targets of hnRNP K. We showed that specific sequence motifs confer the interaction of SPI1 and CEBPA 5' and 3'UTRs with hnRNP K. The siRNA mediated reduction of hnRNP K in human AML cells resulted in an increase of PU.1 and C/EBPα that is most pronounced for the p30 isoform. The combinatorial treatment with the inducer of myeloid differentiation valproic acid resulted in increased C/EBPα expression and myeloid differentiation. Together, our results indicate that hnRNP K post-transcriptionally regulates the expression of myeloid master transcription factors. These novel findings can inaugurate novel options for targeted treatment of AML del(9q) by modulation of hnRNP K function., 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 © 2023 Elsevier B.V. All rights reserved.)

This study aimed to use bioinformatics approaches for predicting the anticancer mechanisms of curcumin on triple-negative breast cancer (TNBC) and to verify these predictions through in vitro experiments. Initially, the Cell Counting Kit-8 (CCK8) assay was employed to rigorously investigate the influence of curcumin on the proliferative capacity of TNBC cells. Subsequently, flow cytometry was employed to meticulously assess the impact of curcumin on cellular apoptosis and the cell cycle regulation. Transwell assays were employed to meticulously evaluate the effect of curcumin on the motility of TNBC cells. RNA sequencing was conducted, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of differentially expressed genes, aiming to elucidate the potential anticancer mechanisms underlying curcumin's effects. To thoroughly elucidate the interactions among multiple proteins, we constructed a protein-protein interaction (PPI) network. Finally, the expression levels of several key proteins, including fibronectin, mTOR, β-Catenin, p-Akt, Akt, N-Cadherin, p-S6, and S6, were assessed using the western blot. The CCK8 assay results showed that curcumin significantly inhibited the proliferation of Hs578T and MDA-MB-231 cells. Flow cytometry results showed that curcumin induced apoptosis in these cells and arrested the cell cycle at the G2/M phase. Additionally, Transwell assay results showed that curcumin effectively reduced the motility of Hs578T and MDA-MB-231 cells. Enrichment analysis of RNA sequencing data showed that the mechanism of action of curcumin was significantly associated with signaling pathways such as pathways in cancer, focal adhesion, and PI3K-Akt signaling pathways. Subsequently, we constructed a protein-protein interaction network to elucidate the interactions among multiple proteins. Finally, Western blotting analysis showed that curcumin significantly decreased the expression levels of key proteins including Fibronectin, mTOR, β-Catenin, p-Akt, Akt, N-Cadherin, p-S6, and S6. Curcumin exhibits its therapeutic potential in TNBC by modulating multiple signaling pathways. It may inhibit the epithelial-mesenchymal transition process by downregulating the expression of proteins involved in the mTOR and PI3K-Akt signaling pathways, thereby suppressing the motility of TNBC cells. These findings provide experimental evidence for considering curcumin as a potential therapeutic strategy in the treatment of TNBC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The inner ear sensory neurons play a pivotal role in auditory processing and balance control. Though significant progresses have been made, the underlying mechanisms controlling the differentiation and survival of the inner ear sensory neurons remain largely unknown. During development, ISL1 and POU4F transcription factors are co-expressed and are required for terminal differentiation, pathfinding, axon outgrowth and the survival of neurons in the central and peripheral nervous systems. However, little is understood about their functional relationship and regulatory mechanism in neural development. Here, we have knocked out Isl1 or Pou4f1 or both in mice of both sexes. In the absence of Isl1 , the differentiation of cochleovestibular ganglion (CVG) neurons is disturbed and with that Isl1 -deficient CVG neurons display defects in migration and axon pathfinding. Compound deletion of Isl1 and Pou4f1 causes a delay in CVG differentiation and results in a more severe CVG defect with a loss of nearly all of spiral ganglion neurons (SGNs). Moreover, ISL1 and POU4F1 interact directly in developing CVG neurons and act cooperatively as well as independently in regulating the expression of unique sets of CVG-specific genes crucial for CVG development and survival by binding to the cis -regulatory elements including the promoters of Fgf10 , Pou4f2 , and Epha5 and enhancers of Eya1 and Ntng2 These findings demonstrate that Isl1 and Pou4f1 are indispensable for CVG development and maintenance by acting epistatically to regulate genes essential for CVG development., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Background: Immunotherapy brings new hope to patients with advanced gastric cancer. However, liver metastases can reduce the efficacy of immunotherapy in patients. Tumor-associated macrophages (TAMs) may be the cause of this reduction in efficacy. SPP1 + TAMs are considered to have immunosuppressive properties. We aimed to investigate the involvement of SPP1 + TAMs in the metastasis of gastric cancer., Methods: The single-cell transcriptome was combined with batched BULK datasets for analysis. Animal models were used to verify the analysis results., Results: We reveal the interaction of SPP1 + TAMs with CD8 + exhausted T cells in metastatic cancer. Among these interactions, GDF15-TGFBR2 may play a key immunosuppressive role. We constructed an LR score to quantify interactions based on ligands and receptors. The LR score is highly correlated with various immune features and clinical molecular subtypes. The LR score may also guide the prediction of the efficacy of immunotherapy and prognosis., Conclusions: The crosstalk between SPP1 + TAMs and CD8 + exhausted T cells plays a key immunosuppressive role in the gastric metastatic cancer microenvironment., (© 2024. The Author(s).)

The quantum supremacy experiment, such as Google Sycamore [F. Arute et al., Nature (London) 574, 505 (2019).NATUAS0028-083610.1038/s41586-019-1666-5], poses a great challenge for classical verification due to the exponentially increasing compute cost. Using a new-generation Sunway supercomputer within 8.5 d, we provide a direct verification by computing 3×10^{6} exact amplitudes for the experimentally generated bitstrings, obtaining a cross-entropy benchmarking fidelity of 0.191% (the estimated value is 0.224%). The leap of simulation capability is built on a multiple-amplitude tensor network contraction algorithm which systematically exploits the "classical advantage" (the inherent "store-and-compute" operation mode of von Neumann machines) of current supercomputers, and a fused tensor network contraction algorithm which drastically increases the compute efficiency on heterogeneous architectures. Our method has a far-reaching impact in solving quantum many-body problems, statistical problems, as well as combinatorial optimization problems.

Molecular understanding of the solid-liquid interface is challenging but essential to elucidate the role of the environment on the kinetics of electrochemical reactions. Alkali metal cations (M + ), as a vital component at the interface, are found to be necessary for the initiation of carbon dioxide reduction reaction (CO 2 RR) on coinage metals, and the activity and selectivity of CO 2 RR could be further enhanced with the cation changing from Li + to Cs + , while the underlying mechanisms are not well understood. Herein, using ab initio molecular dynamics simulations with explicit solvation and enhanced sampling methods, we systematically investigate the role of M + in CO 2 RR on Cu surface. A monotonically decreasing CO 2 activation barrier is obtained from Li + to Cs + , which is attributed to the different coordination abilities of M + with *CO 2 . Furthermore, we show that the competing hydrogen evolution reaction must be considered simultaneously to understand the crucial role of alkali metal cations in CO 2 RR on Cu surfaces, where H + is repelled from the interface and constrained by M + . Our results provide significant insights into the design of electrochemical environments and highlight the importance of explicitly including the solvation and competing reactions in theoretical simulations of CO 2 RR., (© 2024. The Author(s).)

Crystalline cellulose exhibits photoluminescent properties, making it ideal for solid-state emission through properly assembling crystal arrays. However, assembling in water or other polar solvents poses structural integrity issues. To address this, a micro-assembly method is proposed. Cellulose nanocrystals (CNCs) are organized within a sub-micrometer-sized ZIF-8 metal-organic framework and coated with TiO 2 . Notably, the assembly within ZIF-8 improves the CNCs' emission quantum yield to 37.8 %. The bonding between ZIF-8 and CNCs relies on electrostatic interactions and hydrogen bonds, which are sensitive to polar solvents. Yet, the sturdy coordination bonds between TiO 2 and ZIF-8 enhance resistance. Solvent-resistance tests confirm that TiO 2 prevents CNC assembly breakdown, resulting in only an 8.0 % drop in photoluminescent intensity in an alkaline solution after 24 h, compared to 33 % without the coating. For anti-counterfeiting purposes, TiO 2 @ZIF-8@CNC is combined with a polymer matrix, allowing information to be revealed under specific wavelengths using screen-printed labels., 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 © 2023. Published by Elsevier Ltd.)

Highly transparent Ho:Y 2 O 3 ceramics for laser diode lighting were prepared using the vacuum sintering method with 0.3 at.% Nb 2 O 5 as a sintering additive. The microstructures, transmittance, and luminescence properties of the Ho:Y 2 O 3 ceramic samples were investigated in detail. The transmittance levels of all samples with various Ho 3+ concentrations reached ~81.5% (2 mm thick) at 1100 nm. Under the excitation of 363 nm (ultraviolet) or 448 nm (blue) light, Ho:Y 2 O 3 transparent ceramic samples showed that green emission peaked at 550 nm. The emission intensity was strongly affected by the concentration of Ho 3+ ions, reaching its highest level in the sample doped with 1 at.% Ho 3+ . The CIE coordinates of the luminescence were in the green region (i.e., the CIE coordinates of the sample doped with 1 at.% Ho 3+ were [0.27, 0.53] and [0.30, 0.69], under the excitation of 363 nm and 448 nm light, respectively). The possibility of its application as laser diode lighting was reported. Under the excitation of 450 nm blue laser, the sample doped with 0.5 at.% Ho 3+ had the best performance: the saturated luminous flux, lumen efficiency, and the luminescence saturation power densities were 800 lm, 57.7 lm/W, and 17.6 W/mm 2 , respectively. Furthermore, the materials have high thermal conductivity and mechanical strength due to their host of rare-earth sesquioxide. Thus, Ho:Y 2 O 3 transparent ceramics are expected to be a promising candidate for green-light-emitting devices for solid-state lighting, such as laser diode lighting.

Visual processing depends on sensitive and balanced synaptic neurotransmission. Extracellular matrix proteins in the environment of cells are key modulators in synaptogenesis and synaptic plasticity. In the present study, we provide evidence that the combined loss of the four extracellular matrix components, brevican, neurocan, tenascin-C, and tenascin-R, in quadruple knockout mice leads to severe retinal dysfunction and diminished visual motion processing in vivo . Remarkably, impaired visual motion processing was accompanied by a developmental loss of cholinergic direction-selective starburst amacrine cells. Additionally, we noted imbalance of inhibitory and excitatory synaptic signaling in the quadruple knockout retina. Collectively, the study offers insights into the functional importance of four key extracellular matrix proteins for retinal function, visual motion processing, and synaptic signaling., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Aims: Structural cells play an important role in regulating immune cells during infection. Our aim was to determine whether structural porcine tracheal epithelial cells (PTECs) can regulate alveolar macrophages (AMs) to prevent bacterial pneumonia, explore the underlying mechanism(s) and therapeutic target., Materials and Methods: Actinobacillus pleuropneumoniae (APP) was used as the model strain for infection studies. Small RNA sequencing was used to identify differentially abundant exosome-derived miRNAs. The role of PTECs exosome-derived miR-21-5p in regulating AMs autophagy, pyroptosis, reactive oxygen species (ROS) was determined using RT-qPCR, western-blotting, flow cytometry, immunohistochemistry. Luciferase reporter assays were conducted to identify potential binding targets of miR-21-5p. The universality of miR-21-5p action on resistance to bacterial pulmonary infection was demonstrated using Klebsiella pneumoniae or Staphylococcus aureus in vitro and in vivo infection models., Key Findings: MiR-21-5p was enriched in PETCs-derived exosomes, which protected AMs against pulmonary bacterial infection. Mechanistically, miR-21-5p targeted PIK3CD, to promote autophagy of AMs, which reduced the pyroptosis induced by APP infection via inhibiting the over-production of ROS, which in turn suppressed the over-expression of pro-inflammatory cytokines, and increased bacterial clearance. Importantly, the protective effect and mechanism of miR-21-5p were universal as they also occurred upon challenge with Klebsiella pneumoniae and Staphylococcus aureus., Significance: Our data reveals miR-21-5p can promote pulmonary resistance to bacterial infection by inhibiting pyroptosis of alveolar macrophages through the PIK3CD-autophagy-ROS pathway, suggesting PIK3CD may be a potential therapeutic target for bacterial pneumonia., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Recent research has linked lethal (3) malignant brain tumor-like 3 (L3MBTL3) to cancer aggressiveness and a dismal prognosis, but its function in gastric cancer (GC) is unclear. This research investigated the association between L3MBTL3 expression and clinicopathological characteristics of GC cases, as well as its prognostic value and biological function based on large-scale databases and clinical samples. The results showed that L3MBTL3 expression was upregulated in malignant GC tissues, which was associated with a shortened survival time and poor clinicopathological characteristics, including TNM staging. A functional enrichment analysis including GO/KEGG and GSEA illustrated the enrichment of different L3MBTL3-associated pathways involved in carcinogenesis and immune response. In addition, the correlations between L3MBTL3 and tumor-infiltrating immune cells were determined based on the TIMER database; the results showed that L3MBTL3 was associated with the immune infiltration of macrophages and their polarization from M1 to M2. Furthermore, our findings suggested a possible function for L3MBTL3 in the regulation of the tumor immune microenvironment of GC. In summary, L3MBTL3 has diagnostic potential, and it also offers new insights into the development of aggressiveness and prognosis in GC.

Acute intermittent porphyria (AIP) is characterized by acute neurovisceral attacks that are precipitated by the induction of hepatic 5-aminolevulinic acid synthase 1 (ALAS1). In erythropoietic protoporphyria (EPP), sun exposure leads to skin photosensitivity due to the overproduction of photoreactive porphyrins in bone marrow erythroid cells, where heme synthesis is primarily driven by the ALAS2 isozyme. Cimetidine has been suggested to be effective for the treatment of both AIP and EPP based on limited case reports. It has been proposed that cimetidine acts by inhibiting ALAS activity in liver and bone marrow for AIP and EPP, respectively, while it may also inhibit the hepatic activity of the heme catabolism enzyme, heme oxygenase (HO). Here, we show that cimetidine did not significantly modulate the activity or expression of endogenous ALAS or HO in wildtype mouse livers or bone marrow. Further, cimetidine did not effectively decrease hepatic ALAS activity or expression or plasma concentrations of the putative neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which were all markedly elevated during an induced acute attack in an AIP mouse model. These results show that cimetidine is not an efficacious treatment for acute attacks and suggest that its potential clinical benefit for EPP is not via ALAS inhibition.

To explore a new method that patients with brain diseases such as stroke sequelae are hindered by blood-brain barrier (BBB) in clinical treatment. Research preliminarily found that acupuncture with specific mode electro-stimulation (EA) to open BBB-assisted drug delivery may be is an effective means to improve the clinical efficacy of brain disease patients. So here we further explore the features and mechanism. Middle cerebral artery occlusion/R recovery rats were employed as the animal model. Laser Doppler monitoring cerebral blood flow decreased to 45 ± 10% of the baseline value as modeling criteria and TTC staining observed infarcted areas of brain tissue. The permeability of FITC-Dextran and EB in the frontal lobe of rats was observed by microscope. After that, Western blot and Immunofluorescence staining for the detection of the shh and Gli1 signal molecule, Claudin-5 Occludin ZO-1 tight junction (TJ) proteins. EA can open the BBB stably and effectively, and has the characteristics of starting to close soon after the end of EA; EA inhibits the Shh-Gli1 signaling pathway, and downregulates Occludin ZO-1 TJ proteins. These results suggest that EA is safe and reversible in opening the BBB, and its mechanism is related to the inhibition of Shh signaling pathway to down-regulate the expression of TJ proteins., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)