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Bioenvironmental and biological factors have the potential to contribute to the development of glioma, a type of brain tumor. Recent studies have suggested that a unique circular RNA called circCSNK1G3 could play a role in promoting the growth of glioma cells. It does this by stabilizing a specific microRNA called miR-181 and reducing the expression of a tumor-suppressor gene known as chromobox protein homolog 7 (CBX7). To further investigate circCSNK1G3 and its effects on glioma, we utilized a nanoplatform called adeno-associated virus (AAV)-RNAi.To explore the functional implications of circCSNK1G3, we employed siRNA to silence its expression. Along with these effects, the silencing of circCSNK1G3 led to a depletion of miR-181d and an upregulation of CBX7. When we introduced miR-181d mimics, which artificially increase the levels of miR-181d, the anti-glioma cell activity induced by circCSNK1G3 siRNA was almost completely reversed. Conversely, inhibiting miR-181d mimicked the effects of circCSNK1G3 silencing. Moreover, when we overexpressed circCSNK1G3 in glioma cells, we observed an elevation of miR-181d and a depletion of CBX7. We found that the growth of A172 xenografts (tumors) carrying circCSNK1G3 shRNA was significantly inhibited. In these xenograft tissues, we detected a depletion of circCSNK1G3 and miR-181d, as well as an upregulation of CBX7., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Protein-based subunit vaccines are weakly immunogenic, and developing self-adjuvanting vaccines with adjuvant conjugated to antigen is a promising approach for generating optimal immune responses. Here, we report a novel adjuvant-protein conjugate vaccine based on versatile oxime ligation technique. Firstly, the adjuvant properties of a series of TLR7 and TLR7/8 small molecule agonists in self-adjuvanting vaccines were systematically compared by coupling them to proteins in consistent ratio via p-carboxybenzaldehyde (p-CBA) for the first time. All conjugate vaccines induced cytokine secretion in murine and human macrophages in vitro, and promoted specific antibody production in vivo. Notably, a conjugate containing imidazoquinoline TLR7/8 agonist (TLR7/8a1) showed the greatest enhancement in Th1/2 balanced antibody response. To minimize the interference with the protein antigenic integrity, we further developed a systematic glycoconjugation strategy to conjugate this TLR7/8a1 onto the glycan chains of SARS-CoV-2 S1 glycoprotein via oxime ligation, in which S1 containing different numbers of aldehyde groups were obtained by differential periodate oxidation. The resulting TLR7/8a1-S1 conjugate triggered a potent humoral and cellular immunity in vivo. Together these data demonstrate the promise of these TLR7 and TLR7/8 agonists as effective built-in adjuvants, and the versatile oxime ligation strategy might broaden potential applications in designing different conjugate vaccines., 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.)

Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor-specific CD8+ T cells and their recruitment to tumor microenvironment. However, cDC1s are often underrepresented in the microenvironment. Systemic administration of Fms-like tyrosine kinase 3 ligand, a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to cDC1 expansion in the periphery and recruitment into the microenvironment. FLT3 pathway stimulation using GS-3583, a novel FLT3 agonistic Fc fusion protein, has the potential to promote T-cell mediated antitumor activity. This was a first-in-human, placebo-controlled study of GS-3583 in healthy participants to evaluate the safety, pharmacokinetics (PK), and pharmacodynamic (PD) of escalating single doses (75-2000 μg) of GS-3583. Each dose cohort enrolled 8-12 healthy participants who received GS-3583 or placebo as single IV infusion at 3:1 ratio. As part of the PD evaluation, the changes in the number of cDC1 cells were investigated. GS-3583 was well-tolerated in healthy participants up to the highest evaluated dose (2000 μg). There have been no serious or grade III or higher adverse events. PK analysis suggested a dose-dependent increase in GS-3583 exposure with target-mediated disposition characteristics at low doses. PD analysis shows that administration of GS-3583 resulted in transient, dose-dependent increases in cDC1 cells that returned to baseline within 3 weeks of drug administration. The pharmacokinetics and pharmacodynamics of GS-3583 following single dosing were characterized in this study which enabled subsequent phase Ib assessments in patients with advanced solid tumors., (© 2024 Gilead Sciences, Inc. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Gamma delta (γδ) T cells play a crucial role in anti-tumor immunity due to their cytotoxic properties. However, the role and extent of γδ T cells in production of pro-tumorigenic interleukin- 17 (IL-17) within the tumor microenvironment (TME) of colorectal cancer (CRC) remains controversial. In this study, we re-analyzed nine published human CRC whole-tissue single-cell RNA sequencing (scRNA-seq) datasets, identifying 18,483 γδ T cells out of 951,785 total cells, in the neoplastic or adjacent normal tissue of 165 human CRC patients. Our results confirm that tumor-infiltrating γδ T cells exhibit high cytotoxicity-related transcription in both tumor and adjacent normal tissues, but critically, none of the γδ T cell clusters showed IL-17 production potential. We also identified various γδ T cell subsets, including Teff, TRM, Tpex, and Tex, and noted an increased expression of cytotoxic molecules in tumor-infiltrating γδ T cells compared to their normal area counterparts. Our work demonstrates that γδ T cells in CRC primarily function as cytotoxic effector cells rather than IL-17 producers, mitigating the concerns about their potential pro-tumorigenic roles in CRC, highlighting the importance of accurately characterizing these cells for cancer immunotherapy research and the unneglectable cross-species discrepancy between the mouse and human immune system in the study of cancer immunology., Competing Interests: Declaration of Interests The authors declare no competing interests.

Background: Numerous studies have found that patients experiencing sudden sensorineural hearing loss (SSHL), with or without accompanying vertigo, often show impaired vestibular function. However, there is a dearth of studies analyzing vestibular-evoked myogenic potentials (VEMPs) in SSHL patients across various age groups., Aim: To investigate vestibular condition in SSHL patients across various age demographics., Methods: Clinical data of 84 SSHL patients were investigated retrospectively. Audiometry, cervical vestibular evoked myogenic potentials (c-VEMPs), and ocular vestibular evoked myogenic potentials (o-VEMPs) were conducted on these patients. Parameters assessed included the latencies of P1 and N1 waves, as well as the amplitudes of P1-N1 waves. Moreover, the study evaluated the influence of factors such as sex, affected side, configuration of hearing loss, and presence of accompanying vertigo., Results: Among the 84 SSHL patients, no significant differences were observed among the three groups in terms of gender, affected side, and the presence or absence of vertigo. Group II (aged 41-60 years) had the highest number of SSHL cases. The rates of absent o-VEMPs in the affected ears were 20.83%, 31.58%, and 22.72% for the three age groups, respectively, with no statistically significant difference among them. The rates of absent c-VEMPs in the affected ears were 8.3%, 34.21%, and 18.18% for the three age groups, respectively, with significant differences. In the unaffected ears, there were differences observed in the extraction rates of o-VEMPs in the unaffected ears among the age groups. In the three age groups, no significant differences were noted in the three age groups in the latencies of P1 and N1 waves or in the amplitude of N1-P1 waves for c-VEMPs and o-VEMPs, either on the affected side or on the unaffected side, across the three age groups., Conclusion: The extraction rate of VEMPs is more valuable than parameters. Regardless of the presence of vertigo, vestibular organs are involved in SSHL. Notably, SSHL patients aged 41-60 appear more susceptible to damage to the inferior vestibular nerve and saccule., Competing Interests: Conflict-of-interest statement: All authors declared no conflict of interest existing in this paper., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Carbon dioxide (CO 2 ) electrolysis to carbon monoxide (CO) is a very promising strategy for economically converting CO 2 , with high-temperature solid oxide electrolysis cells (SOECs) being regarded as the most suitable technology due to their high electrode reaction kinetics and nearly 100% faradaic efficiency, while their practical application is highly dependent on the performance of their fuel electrode (cathode), which significantly determines the cell activity, selectivity, and durability. In this review, we provide a timely overview of the recent progress in the understanding and development of fuel electrodes, predominantly based on perovskite oxides, for CO 2 electrochemical reduction to CO (CO 2 RR) in SOECs. Initially, the current understanding of the reaction mechanisms over the perovskite electrocatalyst for CO synthesis from CO 2 electrolysis in SOECs is provided. Subsequently, the recent experimental advances in fuel electrodes are summarized, with importance placed on perovskite oxides and their modification, including bulk doping with multiple elements to introduce high entropy effects, various methods for realizing surface nanoparticles or even single atom catalyst modification, and nanocompositing. Additionally, the recent progress in numerical modeling-assisted fast screening of perovskite electrocatalysts for high-temperature CO 2 RR is summarized, and the advanced characterization techniques for an in-depth understanding of the related fundamentals for the CO 2 RR over perovskite oxides are also reviewed. The recent pro-industrial application trials of the CO 2 RR in SOECs are also briefly discussed. Finally, the future prospects and challenges of SOEC cathodes for the CO 2 RR are suggested., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact-mediated coculture with mouse embryonic stem cells (mESCs) under the condition impermissible for human primed PSC culture. Mouse-derived mRNA contents are transmitted into adapted hPSCs only in the coculture. Transfer-specific mRNA analysis show the enrichment for divergent biological pathways involving transcription/translational machinery and stress-coping mechanisms, wherein such transfer is diminished when direct cell contacts are lost. After 5 days of mESC culture, surface marker analysis, and global gene profiling confirmed that mRNA transfer-prone hPSC efficiently gains a naïve-like state. Furthermore, transfer-specific knockdown experiments targeting mouse-specific transcription factor-coding mRNAs in hPSC show that mouse-derived Tfcp2l1 , Tfap2c, and Klf4 are indispensable for human naïve-like conversion. Thus, inter-species mRNA transfer triggers cellular reprogramming in mammalian cells. Our results support that episodic mRNA transfer can occur in cell cooperative and competitive processes(4), which provides a fresh perspective on understanding the roles of mRNA mobility for intra- and inter-species cellular communications.

Electrochemical reduction (ECR) of CO 2 to C 2 H 4 has a potential key role in realizing the carbon neutral future, which ultimately relies on the availability of an efficient electrocatalyst that can exhibit a high Faradaic efficiency (FE) for C 2 H 4 production and robust, long-term operational stability. Here, for the first time, we report that upon applying reductive potential and electrolyte to the benchmark La 2 CuO 4 catalyst, surface reconstruction occurred, i.e., the appearance of a distinctive phase evolution process over time, which was successfully monitored using ex situ powder XRD and operando Mott-Schottky (M-S) measurements of La 2 CuO 4 samples that were soaked into the electrolyte and subjected to CO 2 -ECR for different durations. At the end of such a reconstruction process, an outermost layer consisting of lanthanum carbonate, a thin outer layer made of an amorphous Cu + material formed over the core bulk La 2 CuO 4 , as confirmed by various characterization techniques, which resulted in the redistribution of interfacial electrons and subsequent formation of electron-rich and electron-deficient interfaces. This contributed to the enhancement in FE for C 2 H 4 , reaching as much as 58.7%. Such surface reconstruction-induced electronic structure tuning gives new explanations for the superior catalytic performance of La 2 CuO 4 perovskite and also provides a new pathway to advance CO 2 -ECR technology.

Mushroom poisoning contributes significantly to global foodborne diseases and related fatalities. Amanita mushrooms frequently cause such poisonings; however, identifying these toxic species is challenging due to the unavailability of fresh and intact samples. It is often necessary to analyze residues, vomitus, or stomach extracts to obtain DNA sequences for the identification of species responsible for causing food poisoning. This usually proves challenging to obtain usable DNA sequences that can be analyzed using conventional molecular biology techniques. Therefore, this study aimed to develop a DNA mini-barcoding method for the identification of Amanita species. Following the evaluation and optimization of universal primers for DNA mini-barcoding in Amanita mushrooms, we found that the internal transcribed spacer (ITS) gene sequence primer ITS-a was the most suitable DNA barcode primer for identifying Amanita species. Forty-three Amanita samples were subsequently amplified and sequenced. The sequences obtained were analyzed for intra- and inter-species genetic distances, and a phylogenetic tree was constructed. The findings indicated that the designed primers had strong universality among the Amanita samples and could accurately identify the target gene fragment with a length of 290 bp. Notably, the DNA mini-barcode accurately identified the 43 Amanita samples, demonstrating high consistency with the conventional DNA barcode. Furthermore, it effectively identified DNA from digested samples. In summary, this DNA mini-barcode is a promising tool for detecting accidental ingestion of toxic Amanita mushrooms. It may be used as an optimal barcode for species identification and traceability in events of Amanita-induced mushroom poisoning. KEY POINTS: • Development of a DNA mini-barcoding method for Amanita species identification without fresh samples. • The ITS-a primer set was optimized for robust universality in Amanita samples. • The mini-barcode is suitable for screening toxic mushroom species in mushroom poisoning cases., (© 2024. The Author(s).)

Background: Chronic postoperative surgical pain (CPSP) is a frequent complication following breast surgery and poses a challenge in terms of treatment. We hypothesized that the incidence of CPSP would be reduced at 3 months post-breast surgery with the administration of S-ketamine compared to a placebo., Patients and Methods: Participants were recruited and randomly assigned to either the S-ketamine group (S) or the control group (C). In group S, S-ketamine was administered as a 1.5 mg kg -1 bolus followed by 2 mg kg -1 h -1 infusion, while in group C, a placebo of 0.9% saline was administered in the same volume and rate as S-ketamine. The primary outcome was the incidence of CPSP, measured using a 0-10 numeric rating scale (NRS), at 3 months postsurgery., Results: A total of 72 patients scheduled for mastectomy were enrolled (group S, n = 33; group C, n = 32). The incidence of CPSP at 3 months postsurgery was significantly lower in group S compared to group C (18.2% vs. 48.3%, P < .05). There was no statistical difference between the 2 groups in terms of the incidence of moderate to severe pain. NRS scores for postoperative pain at rest and during movement were significantly lower at 4 h and 24 h post-surgery (P < .05, respectively). Patients in Group S had lower Patient Health Questionnaire-9 (PHQ-9) scores at one week and 3 months post-surgery compared to Group C (P < .05, respectively)., Conclusion: S-ketamine infusion reduces the incidence of CPSP 3 months after breast surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Perovskite solar cells (PSCs) have achieved revolutionary progress during the past decades with a rapidly boosting rate in power conversion efficiencies from 3.8% to 26.1%. However, high-efficiency PSCs with organic hole-transporting materials (HTMs) suffer from inferior long-term stability and high costs. The replacement of organic HTMs with inorganic counterparts such as metal oxides can solve the above-mentioned problems to realize highly robust and cost-effective PSCs. Nevertheless, the widely used simple metal oxide-based HTMs are limited by the low conductivity and poor light transmittance due to the fixed atomic environment. As an emerging family of inorganic HTMs, complex metal oxides with superior structural/compositional flexibility have attracted rapidly increasing interest recently, showing superior carrier conductivity/mobility and superb light transmittance. Herein, the recent advancements in the design and development of complex metal oxide-based HTMs for high-performance PSCs are summarized by emphasizing the superiority of complex metal oxides as HTMs over simple metal oxide-based counterparts. Consequently, several distinct strategies for the design of complex metal oxide-based HTMs are proposed. Last, the future directions and remaining challenges of inorganic complex metal oxide-based HTMs for PSCs are also presented. This review aims to provide valuable guidelines for the further advancements of robust, high-efficiency, and low-cost PSCs., (© 2024 Wiley‐VCH GmbH.)

Semi-supervised medical image segmentation presents a compelling approach to streamline large-scale image analysis, alleviating annotation burdens while maintaining comparable performance. Despite recent strides in cross-supervised training paradigms, challenges persist in addressing sub-network disagreement and training efficiency and reliability. In response, our paper introduces a novel cross-supervised learning framework, Quality-driven Deep Cross-supervised Learning Network (QDC-Net). QDC-Net incorporates both an evidential sub-network and an vanilla sub-network, leveraging their complementary strengths to effectively handle disagreement. To enable the reliability and efficiency of semi-supervised training, we introduce a real-time quality estimation of the model's segmentation performance and propose a directional cross-training approach through the design of directional weights. We further design a truncated form of sample-wise loss weighting to mitigate the impact of inaccurate predictions and collapsed samples in semi-supervised training. Extensive experiments on LA and Pancreas-CT datasets demonstrate that QDC-Net surpasses other state-of-the-art methods in semi-supervised medical image segmentation. Code release is available at https://github.com/Medsemiseg., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The interaction between tumor fatty acid metabolism and immune microenvironment is a novel topic in oncology research, and the relationship of lipid-derived factors with immune editing in tumor is unclear. The breast cancer samples from the TCGA database were used as the training set, and samples from GSE42568 were employed as the validation set for constructing a model to identify a signature associated with fatty acid metabolism through Lasso Cox regression. And the changes in immune related signatures and risk score before and after anti-PD-1 monotherapy were caught by the differential analysis in GSE225078. A 14-gene prognostic risk scoring model identifying by fatty acid metabolism relevant signature was conducted, and the high risk group had shorter overall survival and progression free survival than low risk group. Many metabolism-related pathways were enriched in the high risk group, and many immune-related pathways were enriched in low risk group. The crucial differentially expressed genes between the high/low risk groups, CYP4F8 and CD52, were found to be strongly associated with SUCLA2 and ACOT4 of 14-gene model, and strongly related to immune infiltration. Immune related signatures, fatty acid metabolism-risk score and the expression level of ALDH1A1 (in 14-gene-model) changed after anti-PD-1 monotherapy. And the mice model results also showed anti-PD-1 mAb could significantly reduce the expression level of ALDH1A1 (p < 0.01). These results brought up the crosstalk between immune components and fatty acid metabolism in breast cancer microenvironment, which provided a new possibility of targeting fatty acid metabolism for combination therapy in breast cancer immunotherapy., 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 Inc.)

Due to advances in methods for site-specific incorporation of unnatural amino acids (UAAs) into proteins, a large number of UAAs with tailored chemical and/or physical properties have been developed and used in a wide array of biological applications. In particular, UAAs with specific spectroscopic characteristics can be used as external reporters to produce additional signals, hence increasing the information content obtainable in protein spectroscopic and/or imaging measurements. In this Review, we summarize the progress in the past two decades in the development of such UAAs and their applications in biological spectroscopy and microscopy, with a focus on UAAs that can be used as site-specific vibrational, fluorescence, electron paramagnetic resonance (EPR), or nuclear magnetic resonance (NMR) probes. Wherever applicable, we also discuss future directions.

Background: The production of succinic acid (SA) from biomass has attracted worldwide interest. Saccharomyces cerevisiae is preferred for SA production due to its strong tolerance to low pH conditions, ease of genetic manipulation, and extensive application in industrial processes. However, when compared with bacterial producers, the SA titers and productivities achieved by engineered S. cerevisiae strains were relatively low. To develop efficient SA-producing strains, it's necessary to clearly understand how S. cerevisiae cells respond to SA., Results: In this study, we cultivated five S. cerevisiae strains with different genetic backgrounds under different concentrations of SA. Among them, KF7 and NBRC1958 demonstrated high tolerance to SA, whereas NBRC2018 displayed the least tolerance. Therefore, these three strains were chosen to study how S. cerevisiae responds to SA. Under a concentration of 20 g/L SA, only a few differentially expressed genes were observed in three strains. At the higher concentration of 60 g/L SA, the response mechanisms of the three strains diverged notably. For KF7, genes involved in the glyoxylate cycle were significantly downregulated, whereas genes involved in gluconeogenesis, the pentose phosphate pathway, protein folding, and meiosis were significantly upregulated. For NBRC1958, genes related to the biosynthesis of vitamin B6, thiamin, and purine were significantly downregulated, whereas genes related to protein folding, toxin efflux, and cell wall remodeling were significantly upregulated. For NBRC2018, there was a significant upregulation of genes connected to the pentose phosphate pathway, gluconeogenesis, fatty acid utilization, and protein folding, except for the small heat shock protein gene HSP26. Overexpression of HSP26 and HSP42 notably enhanced the cell growth of NBRC1958 both in the presence and absence of SA., Conclusions: The inherent activities of small heat shock proteins, the levels of acetyl-CoA and the strains' potential capacity to consume SA all seem to affect the responses and tolerances of S. cerevisiae strains to SA. These factors should be taken into consideration when choosing host strains for SA production. This study provides a theoretical basis and identifies potential host strains for the development of robust and efficient SA-producing strains., (© 2024. The Author(s).)

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objective: The study analyzed the impact of urbanization on epidemiological characteristics of respiratory infectious disease in Tongzhou District, Beijing during 2014-2022 to provide reference for prevention and control priorities of respiratory infectious diseases during the innovative urbanization process in China., Methods: The incidence data of notifiable respiratory infectious diseases (NRIDs) in Tongzhou Beijing during 2014-2022 were summarized. The trend of incidence rate was analyzed by Joinpoint regression model, and entropy method was performed to construct the comprehensive index of urbanization (CIU) and generalized linear model was used to analyze the influence of CIU on the incidence rate of respiratory infectious diseases., Results: Totally 72616 NRIDs cases were reported in Tongzhou District during 2014-2022, and the incidence rate of NRIDs was higher during 2017-2019 (153/100 000) than during 2014-2016 (930/100 000) and during 2020-2022 (371/100 000), respectively (both P < 0.001). The CIU constantly increased with slight fluctuation in 2016 and 2018, respectively. The incidence rate of NRIDs showed an increase along with the CIU during 2014-2019 ( r  = 0.95, P = 0.004), while the incidence rate's tendency was interrupted by COVID-19 during 2020 with slight decrease in 2020-2021 and rebounded in 2022. For the patients aged <15 years, the incidence rate of NRIDs revealed a very sharp rise at the urbanization period without COVID-19 pandemic compared with that under pre-urbanization period (RR = 7.93, 95 % CI 7.63-8.24), and dropped off to the similar level as of pre-urbanization period when COVID-19 pandemic spread., Conclusions: Urbanization process may increase the incidence of NRIDs but constrained by COVID-19. Certain measures should be taken to prevent and control the effects by urbanization process, such as good natural environment with less population density, ecological environment with good air quality, promoted hand hygiene, mask wearing, keeping interpersonal distance, vaccination, media publicity for NRIDs' prevention and control., 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.)

Purpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO 3 -polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy., Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80 + /CD86 + , CD3 + /CD4 + and CD3 + /CD8 + were analyzed by flow cytometry., Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80 + /CD86 + expression of DC from lymph glands, and the number of CD3 + /CD8 + T or CD3 + /CD4 + T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor., Conclusion: The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4 + T cell, and enhancing the function of tumor-reactive CD8 + T cells., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Shen et al.)

Background: To analyze the etiological distribution characteristics of drug-resistant epilepsy (DRE) in children, with the aim of providing valuable perspectives to enhance clinical practice., Methods: In this retrospective study, clinical data were collected on 167 children with DRE who were hospitalized between January 2020 and December 2022, including gender, age of onset, seizure types, video electroencephalogram(VEEG) recordings, neuroimaging, and genetic testing results. Based on the etiology of epilepsy, the enrolled children were categorized into different groups. The rank-sum test was conducted to compare the age of onset for different etiologies., Results: Of the 167 cases, 89 (53.3%) had a clear etiology. Among them, structural factors account for 23.4%, genetic factors for 19.2%, multiple factors for 7.2%, and immunological factors for 3.6%. The age of onset was significantly earlier in children with genetic causes than those with structural (P < 0.001) or immunological (P = 0.001) causes., Conclusions: More than half of children with DRE have a distinct underlying cause, predominantly attributed to structural factors, followed by genetic factors. Genetic etiology primarily manifests at an early age, especially among children aged less than one year. This underscores the need for proactive enhancements in genetic testing to unveil the underlying causes and subsequently guide treatment protocols., (© 2024. The Author(s).)

The co-culture of two adult human colorectal cancer cell lines, Caco-2 and HT29, on Transwell is commonly used as an in vitro gut mimic, yet the translatability of insights from such a system to adult human physiological contexts is not fully characterized. Here, we used single-cell RNA sequencing on the co-culture to obtain a detailed survey of cell type heterogeneity in the system and conducted a holistic comparison with human physiology. We identified the intestinal stem cell-, transit amplifying-, enterocyte-, goblet cell-, and enteroendocrine-like cells in the system. In general, the co-culture was fetal intestine-like, with less variety of gene expression compared to the adult human gut. Transporters for major types of nutrients were found in the majority of the enterocytes-like cells in the system. TLR 4 was not expressed in the sample, indicating that the co-culture model is incapable of mimicking the innate immune aspect of the human epithelium., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

A variety of compounds in Artemisia annua were simultaneously determined to evaluate the quality of A. annua from multiple perspectives. A method based on ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QQQ-MS/MS) was established for the simultaneous determination of seven compounds: amorpha-4,11-diene, artemisinic aldehyde, dihydroartemisinic acid, artemisinic acid, artemisinin B, artemisitene, and artemisinin, in A. annua. The content of the seven compounds in different tissues(roots, stems, leaves, and lateral branches) of A. annua were compared. The roots, stems, leaves, and lateral branches of four-month-old A. annua were collected and the content of seven artemisinin-related compounds in different tissues was determined. A multi-reaction monitoring(MRM) acquisition mode of UPLC-QQQ-MS/MS was used, with a positive ion mode of atmospheric pressure chemical ion source(APCI). Chromatographic separation was achieved on an Eclipse Plus RRHD C&#95;(18) column(2.1 mm×50 mm, 1.8 μm). The gradient elution was performed with the mobile phase consisted of formic acid(0.1%)-ammonium formate(5 mmol·L~(-1))(A) and the methanol(B) gradient program of 0-8 min, 55%-100% B, 8-11 min, 100% B, and equilibrium for 3 min, the flow rate of 0.6 mL·min~(-1), the column temperature of 40 ℃, the injection volume of 5 μL, and the detection time of 8 min. Through methodological investigation, a method based on UPLC-QQQ-MS/MS was established for the simultaneous quantitative determination of seven representative compounds involved in the biosynthesis of artemisinin. The content of artemisinin in A. annua was higher than that of artemisinin B, and the content of artemisinin and dihydroartemisinic acid were high in all the tissues of A. annua. The content of the seven compounds varied considerably in different tissues, with the highest levels in the leaves and neither artemisinene nor artemisinic aldehyde was detected in the roots. In this study, a quantitative method based on UPLC-QQQ-MS/MS for the simultaneous determination of seven representative compounds involved in the biosynthesis of artemisinin was established, which was accurate, sensitive, and highly efficient, and can be used for determining the content of artemisinin-related compounds in A. annua, breeding new varieties, and controlling the quality of Chinese medicinal materials.

Wenchang chicken, a prized local breed in Hainan Province of China renowned for its exceptional adaptability to tropical environments and good meat quality, is deeply favored by the public. However, an insufficient understanding of its population architecture and the unclear genetic basis that governs its typical attributes have posed challenges in the protection and breeding of this precious breed. To address these gaps, we conducted whole-genome resequencing on 200 Wenchang chicken samples derived from 10 distinct strains, and we gathered data on an array of 21 phenotype traits. Population genomics analysis unveiled distinctive population structures in Wenchang chickens, primarily attributed to strong artificial selection for different feather colors. Selection sweep analysis identified a group of candidate genes, including PCDH9, DPF3, CDIN1, and SUGCT, closely linked to adaptations that enhance resilience in tropical island habitats. Genome-wide association studies (GWAS) highlighted potential candidate genes associated with diverse feather color traits, encompassing TYR, RAB38, TRPM1, GABARAPL2, CDH1, ZMIZ1, LYST, MC1R, and SASH1. Through the comprehensive analysis of high-quality genomic and phenotypic data across diverse Wenchang chicken resource groups, this study unveils the intricate genetic backgrounds and population structures of Wenchang chickens. Additionally, it identifies multiple candidate genes linked to environmental adaptation, feather color variations, and production traits. These insights not only provide genetic reference for the purification and breeding of Wenchang chickens but also broaden our understanding of the genetic basis of phenotypic diversity in chickens., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The intestinal bacteria of longhorn beetles would be ideal targets for pest control and lignocellulosic resources by destroying or exploiting their cellulose-degrading function. This article aims to investigate the diversity and community structure of intestinal bacteria the oligophagous longhorn beetle Glenea cantor . Additionally, it seeks to identify the presence of lignocellulose-degrading bacteria in the gut, and explore their role in consuming host kapok trees Bombax malabaricum . In this study, the bacterial community from G. cantor was examined by Illumina sequencing of 16S ribosomal RNA (rRNA) targeting the V3 and V4 regions. A total of 563,201 valid sequences and 814 OTUs were obtained. The dominant phyla were Proteobacteria, and the dominant genera were Acinetobacter and Lactococcus. The analysis of microbial diversity revealed a high bacterial diversity in the samples, with the gut bacteria playing a crucial role in the physiological activities of the host, particularly, 9 genera of intestinal bacteria with cellulose degradation function were found, highlighting their vital role in cellulose degradation. Five strains of cellulose-degrading bacteria, belonging to the genus Pseudomonas, were obtained from the intestinal tract of G. cantor larvae using traditional isolation and culture techniques as well as 16S rDNA sequencing. Among these strains, A4 exhibited a cellulase activity of 94.42 ± 0.42 U/mL, while A5 displayed the highest filter paper enzyme activity of 127.46 ± 3.54 U/mL. These results offered valuable insights into potential targets for pest control through internal attack digestion and cellulose-degrading bacteria in longhorn beetles., 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 Su, Pan, Luo, Zheng, Lu and Wang.)

Semi-supervised learning methods have been explored to mitigate the scarcity of pixel-level annotation in medical image segmentation tasks. Consistency learning, serving as a mainstream method in semi-supervised training, suffers from low efficiency and poor stability due to inaccurate supervision and insufficient feature representation. Prototypical learning is one potential and plausible way to handle this problem due to the nature of feature aggregation in prototype calculation. However, the previous works have not fully studied how to enhance the supervision quality and feature representation using prototypical learning under the semi-supervised condition. To address this issue, we propose an implicit-explicit alignment (IEPAlign) framework to foster semi-supervised consistency training. In specific, we develop an implicit prototype alignment method based on dynamic multiple prototypes on-the-fly. And then, we design a multiple prediction voting strategy for reliable unlabeled mask generation and prototype calculation to improve the supervision quality. Afterward, to boost the intra-class consistency and inter-class separability of pixel-wise features in semi-supervised segmentation, we construct a region-aware hierarchical prototype alignment, which transmits information from labeled to unlabeled and from certain regions to uncertain regions. We evaluate IEPAlign on three medical image segmentation tasks. The extensive experimental results demonstrate that the proposed method outperforms other popular semi-supervised segmentation methods and achieves comparable performance with fully-supervised training methods.

Reversible proton ceramic electrochemical cells are promising solid-state ion devices for efficient power generation and energy storage, but necessitate effective air electrodes to accelerate the commercial application. Here, we construct a triple-conducting hybrid electrode through a stoichiometry tuning strategy, composed of a cubic phase Ba 0.5 Sr 0.5 Co 0.8 Fe 0.2 O 3-δ and a hexagonal phase Ba 4 Sr 4 (Co 0.8 Fe 0.2 ) 4 O 16-δ . Unlike the common method of creating self-assembled hybrids by breaking through material tolerance limits, the strategy of adjusting the stoichiometric ratio of the A-site/B-site not only achieves strong interactions between hybrid phases, but also can efficiently modifies the phase contents. When operate as an air electrode for reversible proton ceramic electrochemical cell, the hybrid electrode with unique dual-phase synergy shows excellent electrochemical performance with a current density of 3.73 A cm -2 @ 1.3 V in electrolysis mode and a peak power density of 1.99 W cm -2 in fuel cell mode at 650 °C., (© 2024. The Author(s).)

Triple bonds, such as that formed between two carbon atoms (i.e., C≡C) or that formed between one carbon atom and one nitrogen atom (i.e., C≡N), afford unique chemical bonding and hence vibrational characteristics. As such, they are not only frequently used to construct molecules with tailored chemical and/or physical properties but also employed as vibrational probes to provide site-specific chemical and/or physical information at the molecular level. Herein, we offer our perspective on the emerging applications of various triple-bond vibrations in energy and biological sciences with a focus on C≡C and C≡N triple bonds.

Introduction: Considering the role of bacteria in the onset of acute exacerbation of COPD (AECOPD), we hypothesized that the use of influenza- Streptococcus pneumoniae vaccination, oral probiotics or inhaled amikacin could prevent AECOPD., Methods: In this pilot prospective, muti-central, randomized trial, moderate-to-very severe COPD subjects with a history of moderate-to-severe exacerbations in the previous year were enrolled and assigned in a ratio of 1:1:1:1 into 4 groups. All participants were managed based on the conventional treatment recommended by GOLD 2019 report for 3 months, with three groups receiving additional treatment of inhaled amikacin (0.4 g twice daily, 5-7 days monthly for 3 months), oral probiotic Lactobacillus rhamnosus GG (1 tablet daily for 3 months), or influenza- S. pneumoniae vaccination. The primary endpoint was time to the next onset of moderate-to-severe AECOPD from enrollment. Secondary endpoints included CAT score, mMRC score, adverse events, and survival in 12 months., Results: Among all 112 analyzed subjects (101 males, 96 smokers or ex-smokers, mean ± SD age 67.19 ± 7.39 years, FEV 1 41.06 ± 16.09% predicted), those who were given dual vaccination (239.7 vs. 198.2 days, p  = 0.044, 95%CI [0.85, 82.13]) and oral probiotics (248.8 vs. 198.2 days, p  = 0.017, 95%CI [7.49, 93.59]) had significantly delayed onset of next moderate-to-severe AECOPD than those received conventional treatment only. For subjects with high symptom burden, the exacerbations were significantly delayed in inhaled amikacin group as compared to the conventional treatment group (237.3 vs. 179.1 days, p  = 0.009, 95%CI [12.40,104.04]). The three interventions seemed to be safe and well tolerated for patient with stable COPD., Conclusion: The influenza- S. pneumoniae vaccine and long-term oral probiotic LGG can significantly delay the next moderate-to-severe AECOPD. Periodically amikacin inhalation seems to work in symptomatic patients. The findings in the current study warrants validation in future studies with microbiome investigation. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT03449459., 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 Hua, Yang, Cheng, Han, Li, Dai, He, Wu and Zhang.)

Objective: Post-traumatic seizure (PTS) is a well-known complication of traumatic brain injury (TBI). The objective of this study was to identify risk factors associated with breakthrough early PTS in TBI patients receiving phenytoin prophylaxis., Methods: This was a single-centered retrospective study including adult patients admitted to the intensive care unit (ICU), had a TBI, and started on phenytoin for seizure prophylaxis within 24 h of admission. The primary outcome was the incidence and factors associated with early PTS, defined as a confirmed seizure on a continuous electroencephalogram within 7 days of TBI. Secondary outcomes included the association between early post-traumatic seizures and ICU length of stay, hospital length of stay, and in-hospital mortality., Results: A total of 105 patients were included in the final analysis. Patients with early PTS were older (65 vs. 48 years old, p  = 0.01), had a higher Marshall score (5 vs. 2, p  = 0.01), were more likely to have a Marshall score > 2 (73 vs. 37%, p  = 0.01), and had more neurosurgeries for hematoma evacuation (57 vs. 19%, p  = 0.01). In patients with early PTS, 57% had a level at the time of seizure, and of those, 87.5% had a therapeutic level (>10 mcg/mL). Patients with early PTS had a longer ICU length of stay (14.7 vs. 5.9 days, p  = 0.04) and a greater proportion of hospital mortality (21 vs. 2%, p  = 0.02)., Conclusion: Patients with higher age, Marshall score, and neurosurgical procedures for hematoma evacuation had higher incidences of breakthrough early PTS despite the use of phenytoin prophylaxis. The majority of patients with early PTS had therapeutic phenytoin levels at the time of seizure when a level was available; however, approximately half (43%) did not have a level., 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 Generoso, Diep, Hua, Rader, Ran, Lee and Rivera-Lara.)

Long noncoding RNAs (lncRNAs) play critical roles in the carcinogenesis and progression of cancers. However, the role and mechanism of the pseudogene lncRNA PIN1P1 in gastric carcinoma remain unclear. The expression and effects of lncRNA PIN1P1 in gastric cancer were investigated. The transcriptional regulation of CREB1 on PIN1P1 was determined by ChIP and luciferase assays. The mechanistic model of PIN1P1 in gastric cancer was further explored by RNA pull-down, RIP and western blot analysis. PIN1P1 was overexpressed in gastric cancer tissues, and upregulated PIN1P1 predicted poor prognosis in patients. CREB1 was directly combined with the promoter region of PIN1P1 to promote the transcription of PIN1P1. CREB1-mediated enhanced proliferation, migration and invasion could be partially reversed by downregulation of PIN1P1. Overexpressed PIN1P1 promoted the proliferation, migration and invasion of gastric cancer cells, whereas decreased PIN1P1 showed the opposite effects. PIN1P1 directly interacted with YBX1 and promoted YBX1 protein expression, leading to upregulation of PIN1, in which E2F1 may be involved. Silencing of YBX1 during PIN1P1 overexpression could partially rescue PIN1 upregulation. PIN1, the parental gene of PIN1P1, was elevated in gastric cancer tissues, and its upregulation was correlated with poor patient outcomes. PIN1 facilitated gastric cancer cell proliferation, migration and invasion. To sum up, CREB1-activated PIN1P1 could promote gastric cancer progression through YBX1 and upregulating PIN1, suggesting that it is a potential target for gastric cancer., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

To improve the hydration properties of high-temperature pressed peanut protein isolate (HPPI), we investigated the effect of cold plasma (CP) oxidation on functional and structural properties. Compared to HPPI, the hydrated molecules number and the surface contact angle were significantly decreased at 70 W, from 77.2 × 10 9 to 17.7 × 10 9 and from 85.74° to 57.81°, respectively. The reduction of the sulfhydryl content and the increase of the disulfide bond and di-tyrosine content indicated that the structural transformation was affected by the oxidation effect. In terms of structural changes, a stretched tertiary structure, ordered secondary structure, and rough apparent structure were observed after CP treatment. Additionally, the enhancement of surface free energy and group content such as -COOH, -CO and -OH on the surface of HPPI contributed to the formation of hydrated crystal structures. In general, the oxidation effect of CP effectively improved the hydration properties of HPPI and broaden its application field., 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 B.V.)

Purpose: The opioid crisis resulting from its use disorder and overdose poses additional challenges for cancer pain management. The American Society of Clinical Oncology Practice Guideline recommends acupuncture therapy for the management of adult cancer-related pain (CRP), but the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on CRP remains uncertain., Methods: This 5-week prospective randomized clinical trial was conducted at 2 hospitals in China, and participants with CRP receiving chronic opioid therapy were randomized 1:1 into two groups between December 2014 and June 2018. The true TEAS group underwent 15 sessions of TEAS treatments over 3 consecutive weeks, while the control group received sham stimulation. The primary outcome was the numerical rating scale (NRS) score in the past 24h at week 3. The secondary outcomes included morphine equivalent daily dose, quality of life and adverse events., Results: A total of 159 participants were included in the modified intention-to-treat population. The baseline characteristics were similar in both groups. The mean NRS scores were 0.98 points at week 3 in the true TEAS group and 1.41 points in the sham group, with the mean difference between groups of -0.43 points (P < 0.001; OR = 0.68, P < 0.05). The proportion of patients with NRS reduction more than thirty percentage at week 3 was 50.00% in the true TEAS group and 35.44% in the sham group (RD = 0.15, P > 0.05; RR = 1.41, P > 0.05). No significant difference in pain intensity between the two groups was observed during the follow-up period without TEAS intervention (week 4, OR = 0.83, P > 0.05; week 5, OR = 0.83, P > 0.05). The Karnofsky Performance Status value suggested that patients in the true TEAS group experienced an improved quality of life (Between-group differences: week 3, 3.5%, P < 0.05; week 4, 4.6%, P < 0.001; week 5, 5.6%, P < 0.001)., Conclusions: The 3-week application of TEAS in patients with CRP receiving chronic opioid therapy resulted in a statistically significant reduction in pain scores, but the observed reduction was of uncertain clinical significance. The prolonged analgesic effect of TEAS was not confirmed in this trial., Clinicaltrial: GOV: ChiCTR-TRC-13003803., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This head-to-head study compared a 3-week versus 4-week schedule of nab-paclitaxel in patients with metastatic breast cancer (mBC)., Methods: Patients with HER2-negative mBC were enrolled and randomly assigned (1:1) to receive nab-paclitaxel for a 3-week schedule (125 mg/m2 on days 1 and 8) or a 4-week schedule (same dose on days 1, 8, and 15) until disease progression or treatment intolerance. Patients with intolerable toxicities were allowed to receive a maintenance regimen after benefiting from nab-paclitaxel. The primary endpoint was progression-free survival (PFS)., Results: Ninety-four patients were included in the analysis (n = 47 in each arm). A longer median PFS (mPFS) was observed in the 3-week versus the 4-week schedule in the overall population (not reached vs. 6.8 months; hazard ratio [HR] = 0.44; P = .029). Patients in the 2 arms had a similar overall survival (28.0 vs. 25.8 months), objective response rate (51.1% vs. 48.9%), and disease control rate (93.6% vs. 80.9%). The 3-week schedule was associated with a lower rate of toxicity-related treatment discontinuation (8.5% vs. 29.8%) and dose delays (6.4% vs. 23.4%)., Conclusion: This study demonstrated the better antitumor activity and safety profile of a 3-week over 4-week nab-paclitaxel schedule in HER2-negative mBC, suggesting that a 3-week schedule may be a better treatment regimen in clinical practice (ClinicalTrials.gov Identifier: NCT04192331)., (© The Author(s) 2023. Published by Oxford University Press.)

The southwest alpine canyon area is a typical ecologically fragile area. Understanding the characteristics of vegetation change here and its influencing factors can provide a theoretical basis for formulating countermeasures for ecological environment construction in the southwest alpine canyon area and has practical significance for realizing the harmonious and unified development of the regional economy, environment, and ecology. Based on the data set of NDVI, socio-economic factors, and natural factors from 2000 to 2019, the spatial and temporal variation and stability characteristics of NDVI in the southwest alpine canyon area were analyzed by using the methods of unary linear regression, Hurst index, geographic detector model, and coefficient of variation, and the influencing factors of the spatial differentiation of NDVI were also discussed. The results showed that:① in terms of spatial distribution, the vegetation was high in the southeast and low in the northwest. The area covered by medium and high vegetation accounted for 71.71%, and the vegetation cover was at a relatively high level. From the perspective of time, the area of vegetation showing an improvement trend accounted for 85.90%, and the recovery effect was obvious, and the future vegetation change trend will continue to be improved. ② Elevation, vegetation type, and soil type were the main factors affecting the spatial differentiation of NDVI, and the q value was no less than 0.40. Temperature and rainfall were secondary factors, with q values of 0.274 and 0.225, respectively. The dual-factor interaction enhanced the single factor influence, which was manifested as the dual-factor enhancement and nonlinear enhancement relationship. The highest q value was 0.714 for the combination of altitude ∩ vegetation, followed by 0.688 for the combination of altitude ∩ soil. ③ The overall stability of NDVI during the study period was good, and the proportion of the regional area with low fluctuating changes and slightly low fluctuating changes was 89.95%. The area with moderate fluctuation accounted for 10.05%, concentrated in the relatively fragile ecological environment with factors such as high altitude, low temperature, little rainfall, barren soil, and sparse vegetation. Vegetation change is the result of a combination of multiple factors, so it is necessary to adapt to local conditions and adopt different strategies to restore the ecological environment of the southwest alpine canyon area.

Objective: To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL)., Methods: A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed., Results: The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group ( P <0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group ( P <0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group ( P >0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group ( P <0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with β2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement( P <0.05), but not related to age and sex ( P >0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion( r s =-0.32， r s =-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring ( r s =0.79， r s =0.54， r s =0.58； r s =0.72， r s =0.63， r s =0.45), but not with WBC, CD4 + T cells and CD8 + T cells ( P >0.05). The proportion of Th9 was positively correlated with IL-9 ( r s =0.53)., Conclusion: Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.

Background: Music therapy is often used to relieve anxiety and depression in breast cancer patients, but the clinical effect of music therapy on breast cancer patients is still controversial. This study was a systematic review to investigate the effects of music intervention on anxiety, depression, pain, and quality of life in breast cancer patients., Method: A computer search of PubMed, Embase, Web of Science, and The Cochrane Library repositories was conducted. We searched for randomized controlled trials (RCTs), published in English until October 2023, on the effects of music interventions on anxiety, depressive symptoms, pain levels, and quality of life in breast cancer patients. The Cochrane Manual of Systematic Review 5.3 was used to evaluate the quality of the included references, and Stata15.0 software was selected for meta-analysis of the study indicators., Results: A total of 10 articles were included in this study, including 593 patients. Meta-analysis showed that music intervention could effectively alleviate anxiety symptoms [standardized mean difference (SMD) = -2.12, 95% confidence interval (CI): -3.17~-1.07], depression symptoms (SMD: -0.77, 95% CI: -1.47~-0.07), and pain degree (SMD: -3.47, 95% CI: -6.45~-0.48). There was no significant difference in the improvement of patients' quality of life (SMD: -0.07, 95% CI: -0.48~0.34)., Conclusion: Music intervention can effectively relieve anxiety and depression symptoms in patients with breast cancer, and reduce the degree of pain, but demonstration of its ability to improve the quality of life of patients requires additional research.

Remdesivir (RDV) and tenofovir alafenamide (TAF) are prodrugs designed to be converted to their respective active metabolites. Plasma protein binding (PPB) determination of these prodrugs is important for patients with possible alteration of free fraction of the drugs due to plasma protein changes in renal impairment, hepatic impairment, or pregnancy. However, the prodrugs' instability in human plasma presents a challenge for accurate PPB determination. In this research work, two approaches were used in the method development and qualification for PPB assessment of RDV and TAF. For RDV, dichlorvos was used to inhibit esterase activity to stabilize the prodrug in plasma during equilibrium dialysis (ED). The impact of dichlorvos on protein binding was evaluated and determined to be insignificant by comparing the unbound fraction (f u ) determined by the ED method with dichlorvos present and the f u determined by an ultrafiltration method without dichlorvos. In contrast to RDV, TAF degradation in plasma is ∼3-fold slower, and TAF stability cannot be improved by dichlorvos. Fit-for-purpose acceptance criteria for the TAF PPB method were chosen, and an ED method was developed based on these criteria. These two methods were then qualified and applied for PPB determinations in clinical studies., 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 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

The advent of generative artificial intelligence and large language models has ushered in transformative applications within medicine. Specifically in ophthalmology, large language models offer unique opportunities to revolutionise digital eye care, address clinical workflow inefficiencies, and enhance patient experiences across diverse global eye care landscapes. Yet alongside these prospects lie tangible and ethical challenges, encompassing data privacy, security, and the intricacies of embedding large language models into clinical routines. This Viewpoint highlights the promising applications of large language models in ophthalmology, while weighing up the practical and ethical barriers towards their real-world implementation. This Viewpoint seeks to stimulate broader discourse on the potential of large language models in ophthalmology and to galvanise both clinicians and researchers into tackling the prevailing challenges and optimising the benefits of large language models while curtailing the associated risks., Competing Interests: Declaration of interests PvW declares financial interests as a cofounder of Enlighten Imaging, an early-stage medical technology start-up company devoted to hyperspectral retinal imaging and image analysis, including the development of artificial intelligence systems; research grant support from Roche and Bayer; and honoraria from Roche, Bayer, Novartis, and Mylan. RT declares consulting fees from Novartis, AbbVie, Allergan, Bayer, Alcon, Roche Genentech, Thea, Apellis, Iveric Bio, and Oculis; honoraria from Optic 2000; support for attending meetings from Novartis, AbbVie, Allergan, and Bayer; participation on advisory boards for Novartis, AbbVie, Allergan, Bayer, Apellis, Iveric Bio, Oculis, and Roche Genentech; a leadership role as the President Elect of Euretina; stock in Oculis; and equipment and materials from Zeiss. SS declares grants from Bayer and Boehringer Ingleheim; consulting fees from Roche, AbbVie, Apellis, Bayer, Biogen, Boehringer Ingelheim, Novartis, Janssen Pharmaceuticals, Optos, Ocular Therapeutix, and OcuTerra; support for attending meetings and travel from Bayer and Roche; participation on data safety monitoring boards or advisory boards for Novo Nordisk and Bayer; leadership in RCOphth, Macular Society, and Editor of EYE; stock in Eyebiotech; and equipment and materials from Boehringer Ingleheim. AYL reports grants to their affiliated institutions from Santen, Novartis, Carl Zeiss Meditec, Microsoft, NVIDIA, the National Institutes of Health (NIH; grant numbers NIH/NEI K23EY029246 and NIH OT2OD032644), Research to Prevent Blindness, and the Latham Vision Innovation Award. AYL reports consulting fees from USDA, Genentech, Verana Health, Johnson & Johnson, Gyroscope, Janssen Research and Development, and Regeneron; payment for lectures from Topcon; and payment from Alcon Research for various educational events and activities. ARR declares a grant from the Health and Medical Research Fund (grant number 19201991). CSL reports grants to their institution from the NIH (grant numbers NIH/NIA R01AG060942, NIH/NIA U19AG066567, and NIH OT2OD032644), Research to Prevent Blindness, and the Latham Vision Innovation Award; and consulting fees from Boehringer Ingelheim. TYW declares consulting fees from Aldropika Therapeutics, Bayer, Boehringer Ingelheim, Genentech, Iveric Bio, Novartis, Plano, Oxurion, Roche, Sanofi, and Shanghai Henlius; funding from the National Key R&D Program, China (grant number 2022YFC2502800); and being an inventor, patent holder, and cofounder of the start-up companies EyRiS and Visre. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Two new eriophyid mite species (Acari: Prostigmata: Eriophyoidea) were described from the host plants of the genus Callerya Endl. during a field survey in China: Tetra nitidae sp. nov. vagrant on leaves ofCallerya nitida (Bentham) R. Geesink (Leguminosae),and Calepitrimerus calleryus sp. nov. vagrant on leaves ofCallerya tsui (F. P. Metcalf) Z. Wei & Pedley. Both species caused no apparent symptoms in their host plants. Additionally, this paper provides a supplementary morphological description and illustrations of Fujianacarus wisterianis Song, Xue & Hong, 2008 (Eriophyoidea).

Motivation: T cell heterogeneity presents a challenge for accurate cell identification, understanding their inherent plasticity, and characterizing their critical role in adaptive immunity. Immunologists have traditionally employed techniques such as flow cytometry to identify T cell subtypes based on a well-established set of surface protein markers. With the advent of single-cell RNA sequencing (scRNA-seq), researchers can now investigate the gene expression profiles of these surface proteins at the single-cell level. The insights gleaned from these profiles offer valuable clues and a deeper understanding of cell identity. However, CD45RA, the isoform of CD45 which distinguishes between naive/central memory T cells and effector memory/effector memory cells re-expressing CD45RA T cells, cannot be well profiled by scRNA-seq due to the difficulty in mapping short reads to genes., Results: In order to facilitate cell-type annotation in T cell scRNA-seq analysis, we employed machine learning and trained a CD 45 RA + / - classifier on single-cell mRNA count data annotated with known CD45RA antibody levels provided by cellular indexing of transcriptomes and epitopes sequencing data. Among all the algorithms we tested, the trained support vector machine with a radial basis function kernel with optimized hyperparameters achieved a 99.96% accuracy on an unseen dataset. The multilayer perceptron classifier, the second most predictive method overall, also achieved a decent accuracy of 99.74%. Our simple yet robust machine learning approach provides a valid inference on the CD45RA level, assisting the cell identity annotation and further exploring the heterogeneity within human T cells. Based on the overall performance, we chose the support vector machine with a radial basis function kernel as the model implemented in our Python package scCD45RA., Availability and Implementation: The resultant package scCD45RA can be found at https://github.com/BrubakerLab/ScCD45RA and can be installed from the Python Package Index (PyPI) using the command "pip install sccd45ra.", Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press.)

Aflatoxins are toxic secondary metabolites that often contaminate food and animal feed, causing huge economic losses and serious health hazards. Aflatoxin contamination has become a major concern worldwide. Biological methods have been used to reduce aflatoxins in food and feed by inhibiting toxin production and detoxification. Among biological methods, lactic acid bacteria are of significant interest because of their safety, efficiency, and environmental friendliness. This study aimed to review the mechanisms by which lactic acid bacteria degrade aflatoxins and the factors that influence their degradation efficiency, including the action of the lactic acid bacteria themselves (cell wall adsorption) and the antifungal metabolites produced by the lactic acid bacteria. The current applications of lactic acid bacteria to food and feed were also reviewed. This comprehensive analysis provided insight into the binding mechanisms between lactic acid bacteria and aflatoxins, facilitating the practical applications of lactic acid bacteria to food and agriculture., Competing Interests: Competing interests: The authors declare that they have no competing interests.

To quantify colloidal filtration, a quartz crystal microbalance (QCM) with a silicon dioxide surface is embedded on the inner surface of a microfluidic channel to monitor the real-time particle deposition. Potassium chloride solution with micrometer-size polystyrene particles simulating bacterial strains flows down the channel. In the presence of intrinsic Derjaguin-Landau-Verwey-Overbeek (DLVO) intersurface forces, particles are trapped by the quartz surfaces, and the increased mass shifts the QCM resonance frequency. The method provides an alternative way to measure filtration efficiency in an optically opaque channel and its dependence on the ionic concentration.

Sudden sensorineural hearing loss (SSNHL) accompanied by benign paroxysmal positional vertigo (BPPV) is relatively common in the clinic. There are unified standards for the treatment of primary BPPV with good reduction effect, while there are few studies on the treatment of BPPV secondary to SSNHL within 1 week of onset. The study was to investigate the treatment of BPPV secondary to SSNHL and compare its manual reduction with that of primary BPPV. We selected 90 patients with BPPV accompanied by SSNHL within a week of onset and 210 primary BPPV patients at Hebei Provincial Eye Hospital from June 2020 to December 2022. The former group was divided into the medicine group and manual reduction plus medicine group. The medicines used were extract of Ginkgo biloba leaves injection, betahistine hydrochloride injection and oral prednisone. We contrasted the efficacy respectively for posterior semicircular canal BPPV (psc-BPPV), horizontal semicircular canal BPPV (hsc-BPPV) and multiple semicircular canal BPPV (msc-BPPV). In addition, we compared the manual reduction effect for primary BPPV and manual reduction group, and the evaluation of efficacy are the intensity of nystagmus and the clinical symptoms. In the secondary BPPV group, there was no difference in efficacy between the medicine group and manual reduction group at the 7th-day after reduction for psc-BPPV, hsc-BPPV, and msc-BPPV (P > .05). The immediate effect of reduction was significantly different between the primary BPPV group and the group with SSNHL and BPPV for both psc-BPPV and hsc-BPPV (P < .05), and the effect of the primary BPPV group was better, but it was no difference for msc-BPPV (P > .05). For the treatment of BPPV accompanied by SSNHL within 1 week of onset, the additional reduction therapy showed no benefit, so we need to apply medication for SSNHL., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To observe the effect of ketorolac tromethamine combined with remifentanil in sedation and analgesia during general anesthesia emergence and reducing general anesthesia complications., Design: This is an experimental design., Methods: A total of 90 patients who underwent partial or total thyroidectomy in our hospital were selected and randomly divided into three groups with 30 cases in each group. Routine general anesthesia combined with endotracheal intubation was given for general anesthesia, and different treatments were administered when the skin was sutured. Group K: intravenous injection of ketorolac tromethamine 0.9 mg/kg, intravenous injection of normal saline 10 mL/h by micropump until awakening and extubation; R group: intravenous injection of normal saline 2 mL, micropump intravenous injection of remifentanil 0.1 mcg/kg/min until awakening and extubation; KR group: intravenous injection of ketorolac tromethamine 0.5 mg/kg, micropump intravenous injection remifentanil 0.05 mcg/kg/min until awakening and extubation. After the operation, all patients entered the postanesthesia care unit (PACU) for recovery, extubation, scoring. The incidence and condition of various complications were counted., Findings: There was no significant difference in the general information or operation duration of the patients (P > .05). The types of general anesthesia induction drugs in each group were the same, and there was no significant difference in drug measurement (P > .05). The visual analogue scales of KR group were: 2.2 ± 0.6(T0) and 2.4 ± 0.9(T1), the Self-Rating Anxiety Scale scores of the KR groups were: 4.1 ± 0.6(T0), 3.7 ± 0.4(T1). Compared with the KR group, the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were increased (P < .05); the visual analogue scale and Self-Rating Anxiety Scale scores of the K and R groups at T0 and T1 were not significantly different (P > .05); at T2, there was no significant difference in visual analogue scale and Self-Rating Anxiety Scale scores among the three groups (P > .05). There was no significant difference in extubation time or PACU transfer time among the three groups (P > .05). The incidence of adverse reactions in KR group were: 3.3% (nausea), 3.3% (vomit), 0 (coughing and drowsiness). Compared with the KR group, the incidence of adverse reactions was higher in the K and R groups., Conclusions: Ketorolac tromethamine combined with remifentanil can effectively relieve pain and sedation during general anesthesia recovery and reduce the incidence of complications related to general anesthesia recovery. At the same time, the application of ketorolac tromethamine can reduce the dosage of remifentanil and inhibit the occurrence of adverse reactions when used alone., (Copyright © 2023 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Artemisia argyi is an important medicinal and economic plant in China, with the effects of warming channels, dispersing cold, and relieving pain, inflammation, and allergy. The essential oil of this plant is rich in volatile terpenoids and widely used in moxi-bustion and healthcare products, with huge market potential. The bZIP transcription factors compose a large family in plants and are involved in the regulation of plant growth and development, stress response, and biosynthesis of secondary metabolites such as terpenoids. However, little is known about the bZIPs and their roles in A. argyi. In this study, the bZIP transcription factors in the genome of A. argyi were systematically identified, and their physicochemical properties, phylogenetic relationship, conserved motifs, and promoter-binding elements were analyzed. Candidate AarbZIP genes involved in terpenoid biosynthesis were screened out. The results showed that a total of 156 AarbZIP transcription factors were identified at the genomic level, with the lengths of 99-618 aa, the molecular weights of 11.7-67.8 kDa, and the theoretical isoelectric points of 4.56-10.16. According to the classification of bZIPs in Arabidopsis thaliana, the 156 AarbZIPs were classified into 12 subfamilies, and the members in the same subfamily had similar conserved motifs. The cis-acting elements of promoters showed that AarbZIP genes were possibly involved in light and hormonal pathways. Five AarbZIP genes that may be involved in the regulation of terpenoid biosynthesis were screened out by homologous alignment and phylogenetic analysis. The qRT-PCR results showed that the expression levels of the five AarbZIP genes varied significantly in different tissues of A. argyi. Specifically, AarbZIP29 and AarbZIP55 were highly expressed in the leaves and AarbZIP81, AarbZIP130, and AarbZIP150 in the flower buds. This study lays a foundation for the functional study of bZIP genes and their regulatory roles in the terpenoid biosynthesis in A. argyi.

Purpose: Most studies have supported the view that individuals prefer to reward the in-group and discriminate against the out-group in response to unfair offers in the Ultimatum Game. However, the current study advanced a different view, that is, the "black sheep effect", in which in-group members were punished more severely compared with out-group members. This study aimed to incorporate proposer identity and allocation motive as possible explanations for offer rejection., Methods: In the current study, the in-group and out-group identities were distinguished by their health condition, and the allocation motive was defined according to its benefit maximization. With a total of 89 healthy college student participants, a mixed design of 2 (proposer identity: out-group vs in-group) × 2 (allocation motive: selfish vs random) × 2 (offer type: unfair vs fair) was used in the Ultimatum Game. Event-related potential (ERP) technology was used, and ERPs were recorded while participants processed the task., Results: The behavioral result showed that the "black sheep effect" was found on the fair offer when a random allocation motive was used. Our ERP result suggested that feedback-related negativity (FRN) and P300 were modulated by proposer identity but not by allocation motive. However, the allocation motive interacted with proposer identity affecting FRN and P300 when the fair offer was proposed., Conclusion: These findings demonstrated that the "black sheep effect" was related to the experience of the out-group member, such as disadvantage or distress, but it was also modulated by allocation motive. Meanwhile, the out-group (depressed college students) captured more attention because they violated individual expectations, according to the P300. This finding plays an integral role in understanding the mechanism of response to the "black sheep effect"., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Zhang et al.)

Previously, several studies have shown that, for a set of structurally related nitrile compounds, there could be a linear relationship between the total charge on the nitrile group ( q CN ) and its stretching frequency (ν CN ). However, it is unclear whether the corresponding frequency and charge properties of structurally different nitrile compounds can be described by a single linear ν CN - q CN relationship. Herein, we compute the q CN magnitudes of a large number of nitrile-containing molecules whose ν CN values cover a spectral range of ca. 200 cm -1 and are measured under different experimental conditions. Our results reveal that ν CN indeed exhibits a linear dependence on q CN , with a slope of 637 ± 30 cm -1 /charge. Because the nitrile moiety is a commonly used building block in electronic donor-acceptor (D-A) molecular systems, we believe that this linear relationship will find utility in a wide range of applications where such D-A constructs are used, such as in organic photovoltaic assemblies. In addition, we apply this linear relationship to characterize the degree of charge transfer upon photoexcitation of two indole derivatives, 5-cyanoindole and 6-cyanoindole, and are able to show that in both cases, the fluorescence emission arises from a charge-transfer or L a state.

Paracoccus marginatus is a highly polyphagous invasive pest that poses a significant quarantine threat to tropical and subtropical countries. Infested commodities in international trade should undergo phytosanitary treatment, and irradiation is recommended as a viable alternative to replace methyl bromide fumigation. Dose-response tests were conducted on the 2-, 4-, and 6-day-old eggs and gravid females of P . marginatus using the X-ray radiation doses of 15-105 Gy with an interval of 15 Gy. Radiotolerance was compared using ANOVA, fiducial overlapping and lethal dose ratio (LDR) test, resulting in no significant difference among treatments, except for the overall mortality and LDR at LD 90 (a dose causing 90% mortality at 95% confidence level). The estimated dose for LD 99.9968 was 176.5-185.2 Gy, which was validated in the confirmatory tests. No nymphs emerged from a total of 60,386 gravid females exposed to a gamma radiation dose range of 146.8-185.0 Gy in the confirmatory tests. The largest dose in confirmatory tests should be the minimum threshold for phytosanitary treatment, consequently, a minimum dose of 185 Gy is recommended for the phytosanitary irradiation treatment of papaya mealybug-infested commodities, ensuring a treatment efficacy of ≥99.9950% at 95% confidence level.

Abstract: Mitochondrial damage is an important cause of heart dysfunction after severe burn injury. However, the pathophysiological process remains unclear. This study aims to examine the mitochondrial dynamics in the heart and the role of μ-calpain, a cysteine protease, in this scenario. Rats were subjected to severe burn injury treatment, and the calpain inhibitor MDL28170 was administered intravenously 1 h before or after burn injury. Rats in the burn group displayed weakened heart performance and decreased mean arterial pressure, which was accompanied by a diminishment of mitochondrial function. The animals also exhibited higher levels of calpain in mitochondria, as reflected by immunofluorescence staining and activity tests. In contrast, treatment with MDL28170 before any severe burn diminished these responses to a severe burn. Burn injury decreased the abundance of mitochondria and resulted in a lower percentage of small mitochondria and a higher percentage of large mitochondria. Furthermore, burn injury caused an increase in the fission protein DRP1 in the mitochondria and a decrease in the inner membrane fusion protein OPA1. Similarly, these alterations were also blocked by MDL28170. Of note, inhibition of calpain yielded the emergence of more elongated mitochondria along with membrane invagination in the middle of the longitude, which is an indicator of the fission process. Finally, MDL28170, administered 1 h after burn injury, preserved mitochondrial function and heart performance, and increased the survival rate. Overall, these results provided the first evidence that mitochondrial recruitment of calpain confers heart dysfunction after severe burn injury, which involves aberrant mitochondrial dynamics., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)