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Abstract. Background:. Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic–clinical–radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism. Methods:. This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram. Results:. Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276–13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086–0.405, P

Abstract Geoacoustic exploration is a rapidly evolving field investigating underground rock formations and sediment environments through acoustic waves. In this paper, we present a review of recent research progress, focusing on newly discovered physical phenomena, such as the reflection and refraction of acoustic waves at the interface between anisotropic rocks and between liquid and solid, the characteristics of electric-acoustic (and acoustic-electric) conversion of piezoelectric transducers, the physical mechanism of acoustic wave propagation in viscous media, and the generation of intrinsic noise. We developed new physical models, introduced a parallel transmission network describing piezoelectric transducers for electric-acoustic (and acoustic-electric) energy transfer, and derived new formulations and algorithms associated with the latest model. We will discuss the potential of abnormal incidence angle, acoustic attenuation, and acoustic Goos-Hänchen effect and propose a method of inversion of formation reflection coefficient using logging and seismic data acquired from anisotropic rocks with dip angle. We will also discuss the physical mechanism and potential applications of the intrinsic noise generated inside viscous solid media. Finally, we introduce a parallel/series lumped vibrational transmission network, explain the acoustic measurement process, and discuss applications of the Kaiser effect in petroleum engineering.

Myocardial ischemia is a serious threat to human health, and vascular dysfunction is its main cause. Buxu Tongyu (BXTY) Granule is an effective traditional Chinese medicine (TCM) for treating myocardial ischemia. However, the underlying mechanism of BXTY is still unclear. In this study, we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase (sGC)–3′,5′-cyclic guanosine monophosphate (cGMP)–protein kinase G (PKG) signaling pathway in vascular smooth muscle cells (VSMCs) to dilate the arteries. BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin. The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice, including electrocardiogram abnormalities and changes in plasma enzymes. In addition, BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner. These effects were eliminated by pre-incubating vascular rings with the sGC inhibitors NS 2028 or ODQ, or with the PKG inhibitor KT 5823. Moreover, BXTY increased the protein expression of sGC-β1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells (MOVAs). NS 2028 or ODQ reversed these effects of BXTY. The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY. NS 2028, ODQ, or KT 5823 also reversed this effect of BXTY. In conclusion, BXTY can improve the symptoms of acute myocardial ischemia in mice, and activating the sGC–cGMP–PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.

Abstract Study design A systematic review and Bayesian network meta-analysis (NMA). Objective To compare the effectiveness and safety of different posterior decompression techniques for LSS. Summary of background data Lumbar spinal stenosis (LSS) is one of the most common degenerative spinal diseases that result in claudication, back and leg pain, and disability. Currently, posterior decompression techniques are widely used as an effective treatment for LSS. Methods An electronic literature search was performed using the EMBASE, Web of Science, PubMed, and Cochrane Library databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was constructed to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order. Results In all, 14 eligible studies comprising 1,260 patients with LSS were included. Five interventions were identified, namely, spinal processes osteotomy (SPO), conventional laminotomy/laminectomy (CL), unilateral laminotomy/laminectomy (UL), bilateral laminotomy/ laminectomy (BL), and spinous process-splitting laminotomy/laminectomy (SPSL). Among these, SPO was the most promising surgical option for decreasing back and leg pain and for lowering the Oswestry Disability Index (ODI). SSPL had the shortest operation time, while SPSL was associated with maximum blood loss. SPO and UL were superior to other posterior decompression techniques concerning lesser blood loss and shorter length of hospital stay, respectively. Patients who underwent BL had the lowest postoperative complication rates. Conclusion Overall, SPO was found to be a good surgical choice for patients with LSS.

Abstract The Structural Genomics Consortium is an international open science research organization with a focus on accelerating early-stage drug discovery, namely hit discovery and optimization. We, as many others, believe that artificial intelligence (AI) is poised to be a main accelerator in the field. The question is then how to best benefit from recent advances in AI and how to generate, format and disseminate data to enable future breakthroughs in AI-guided drug discovery. We present here the recommendations of a working group composed of experts from both the public and private sectors. Robust data management requires precise ontologies and standardized vocabulary while a centralized database architecture across laboratories facilitates data integration into high-value datasets. Lab automation and opening electronic lab notebooks to data mining push the boundaries of data sharing and data modeling. Important considerations for building robust machine-learning models include transparent and reproducible data processing, choosing the most relevant data representation, defining the right training and test sets, and estimating prediction uncertainty. Beyond data-sharing, cloud-based computing can be harnessed to build and disseminate machine-learning models. Important vectors of acceleration for hit and chemical probe discovery will be (1) the real-time integration of experimental data generation and modeling workflows within design-make-test-analyze (DMTA) cycles openly, and at scale and (2) the adoption of a mindset where data scientists and experimentalists work as a unified team, and where data science is incorporated into the experimental design.

Abstract Background To demonstrate and analyze the 18F-FDG positron emission tomography/computed tomography (PET/CT) findings in this rare nevoid basal cell carcinoma syndrome (NBCCS). Case presentation A 71-year-old woman with the left invasive breast cancer was treated with hormone therapy for six months and underwent the 18F-FDG PET/CT examination for efficacy evaluation. 18F-FDG PET/CT revealed the improvement after treatment and other unexpected findings, including multiple nodules on the skin with 18F-FDG uptake, bone expansion of cystic lesions in the bilateral ribs, ectopic calcifications and dilated right ureter. She had no known family history. Then, the patient underwent surgical excision of the all skin nodules and the postoperative pathology were multiple basal cell carcinomas. Finally, the comprehensive diagnosis of NBCCS was made. The patient was still in follow-up. Additionally, we have summarized the reported cases (n = 3) with 18F-FDG PET/CT from the literature. Conclusions It is important to recognize this syndrome on 18F-FDG PET/CT because of different diagnoses and therapeutic consequences.

Abstract Background Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients. Methods The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator’s Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel–Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively. Discussion Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA. Trial registration This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021.

Abstract This study evaluated the impacts of sulfamethoxazole (SMX) on antioxidant, immune, histopathological dynamic changes, and gut microbiota of zebrafish. SMX was carried out five groups: 0 (C), 3 mg/L (T3), 6 mg/L (T6), 12 mg/L (T12), and 24 mg/L (T24), with 5 replicates per group for an 8-weeks chronic toxicity test. It was found that SMX is considered to have low toxicity to adult zebrafish. SMX with the concentration not higher than 24 mg/L has no obvious inhibitory effect on the growth of fish. Under different concentrations of SMX stress, oxidative damage and immune system disorder were caused to the liver and gill, with the 12 and 24 mg/L concentration being the most significant. At the same time, it also causes varying degrees of pathological changes in both intestinal and liver tissues. As the concentration of SMX increases, the composition and abundance of the gut microbiota in zebrafish significantly decrease.

AbstractCamellia tetracocca H.T. Chang 1981 is an important wild relative of cultivated tea plants. Its leaves are widely used by local people to make tea, showing great economic and breeding values. We here report the complete chloroplast genome of C. tetracocca using Illumina sequencing technology. The complete chloroplast genome of C. tetracocca is 157,026 bp in length, and structurally contains a pair of inverted repeat regions (IRa and IRb, 26,052 bp) separated by a large single-copy region (LSC, 86,669 bp) and a small single-copy region (SSC, 18,253 bp). It is composed of 131 predicted genes, including 86 protein-coding genes, 37 transfer RNA genes, and eight ribosomal RNA genes. The overall GC content is 37.31%. Phylogenetic analysis among four Camellia species and 11 other close species reveals a close relationship between C. tetracocca and C. gymnogyna.

BackgroundFerroptosis is a crucial pathogenic mechanism in Parkinson’s disease, offering significant potential for pharmacological intervention. Despite its importance, the number of bibliometric analyses examining the relationship between ferroptosis and Parkinson’s disease remains limited. This study aims to elucidate the knowledge structure and primary research focuses within this field using various bibliometric tools search.Materials and methodsWe conducted a comprehensive literature son ferroptosis in Parkinson’s disease using the Web of Science Core Collection database. Bibliometric analyses and visualizations were performed with VOSviewer, examining the geographical and institutional distribution of publications, journal interconnections, and keyword prevalence. Furthermore, CiteSpace was used to visually explore and analyze journal interactions and citation dynamics. The bibliometrix R package facilitated the delineation of collaborative networks across different countries and the construction of visual network representations illustrating relationships among authors, keywords, and journals. Data visualization was further enhanced with Microsoft Office Excel 2021.ResultsRecently, there has been a significant increase in publications on ferroptosis, with China emerging as a leading contributor in this research area. Keyword analysis highlights the critical role of ferroptosis in the pathogenesis of Parkinson’s disease, identifying GPX4 as a key enzyme mitigating lipid peroxidation. This study also elucidates the connections and distinctions between ferroptosis and other cell death processes such as apoptosis, autophagy, and pyroptosis. Current research primarily focuses on immunotherapy, prognosis, oxidative stress, lipid peroxidation, and the tumor microenvironment.ConclusionThis study provides a comprehensive initial analysis of the research landscape, identifying current focal points and potential future directions for ferroptosis research in Parkinson’s disease. The findings leverage a variety of bibliometric methodologies to offer valuable insights into this emerging field.

Abstract Targeting receptor‐interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY‐10 is reported, which may enable brain RIPK1 imaging. [11C]CNY‐10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY‐10 is characterized by PET imaging in rodents and a non‐human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY‐10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY‐10‐based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY‐10 for AD and potentially other RIPK1‐related human studies.

ObjectiveThe aim of the present study was to carry out a systematic research on bitterness quantification to provide a reference for scholars and pharmaceutical developers to carry out drug taste masking research. Significance: The bitterness of medications poses a significant concern for clinicians and patients. Scientifically measuring the intensity of drug bitterness is pivotal for enhancing drug palatability and broadening their clinical utility.MethodsThe current study was carried out by conducting a systematic literature review that identified relevant papers from indexed databases. Numerous studies and research are cited and quoted in this article to summarize the features, strengths, and applicability of quantitative bitterness assessment methods.ResultsIn our research, we systematically outlined the classification and key advancements in quantitative research methods for assessing drug bitterness, including in vivo quantification techniques such as traditional human taste panel methods, as well as in vitro quantification methods such as electronic tongue analysis. It focused on the quantitative methods and difficulties of bitterness of natural drugs with complex system characteristics and their difficulties in quantification, and proposes possible future research directions.ConclusionThe quantitative methods of bitterness were summarized, which laid an important foundation for the construction of a comprehensive bitterness quantification standard system and the formulation of accurate, efficient and rich taste masking strategies.

The aim of this study is to investigate the main active components of Gegen (Puerariae Lobatae Radix) on atherosclerosis and its mechanism of action. Bioinformatics analysis showed that β-sitosterol was the most likely active ingredient to mediate the anti-atherosclerotic effects. In vivo experiments showed that β-sitosterol inhibited plaque formation and platelet activation, and decreased serum total cholesterol (TC) and triglyceride (TG) levels. In vitro experiments showed that β-sitosterol can inhibit lipid deposition and phenotypic transformation of vascular smooth muscle cells (VSMCs). However, knocking down catalase (CAT), the direct target of β-sitosterol, not only promoted lipid deposition and phenotypic transformation of VSMCs, but also activated the PI3K/Akt/mTOR pathway, and the mTOR inhibitor (ink-128) can eliminate the effect of CAT knockdown, suggesting that β-sitosterol may inhibit lipid deposition and phenotypic transformation of VSMCs by activating CAT and silencing the PI3K/Akt/mTOR signaling pathway, thereby alleviating atherosclerosis.

In this paper, non-woven fabric and glass fiber fabric were used to prepare resin-based absorbing composite. The thermal expansion coefficient and the microwave absorbing properties of the absorbing composites with different glass fiber volume fraction were studied. The results show that the simulation results of the thermal expansion coefficient calculated by Schapery model are inconsistent with the experimental results, the metallographic results were studied to reveal that it is the added absorbent in the composite that partially replaced the resin at the interface between resin and fiber bundle causes the parameters of the material substituted in the Schapery model to be improper. A different simulation model was proposed to introduce a set of different parameters of the material to reduce the error between simulation and experiment results and the simulation results show that the error is reduced from a maximum of 53 % to a minimum of 3 %. Meanwhile the microwave absorbing properties show that the absorbing peaks of the composite materials move to low frequency with the increasing glass fiber volume fraction and the minimum reflection loss (RL) first increase and then decrease. The metallographic results show that the different distribution of absorbent in the composites within different reinforced fibers causes the movement of the absorbing peaks and the change of its minimum RL. Those research results lay a foundation for the further popularization and application of the absorbing composites.

In order to improve the mechanical properties of backfill, steel slag and straw fiber were used as materials to prepare backfill. The law of sand-cement ratio, mass concentration, steel slag content and straw fiber on strength and rheological parameters of backfill was analyzed by orthogonal test method, and the influence mechanism of steel slag content and straw fiber on physical properties of backfill was revealed. The results show that mass concentration exerts the most substantial impact on rheological parameters, emerging as a significant determinant. Moreover, the yield stress diminishes with escalating tailings-cement ratio, while it escalates with higher mass concentration, steel slag content and straw fiber content. Augmenting the tailings-cement ratio and steel slag content serves to impede the amplification effect of mass concentration on yield stress. Notably, the tailings-cement ratio emerges as the most influential factor affecting the uniaxial compressive strength (UCS) of the backfill, albeit the UCS diminishes with rising tailings-cement ratio. Elevating the mass concentration and steel slag content can counteract the debilitation caused by an increase in the tailings-cement ratio on the UCS of the backfill. Furthermore, heightened mass concentration can bolster the reinforcing impact of steel slag content on early UCS. The increase of tailings-cement ratio increases the size and range of the void inside the backfill, subsequently leading to the degradation of its macroscopic compressive strength. The adhesion between straw fiber and mortar matrix constitutes a pivotal factor in improving the integration of backfill, whereas steel slag contributes to improving the mechanical properties by enhancing the distribution of void structures within the backfill. This research not only offer data support and scientific guidance for the design of backfill ratio parameters but also facilitate the broader application of straw fiber and steel slag in mine backfilling operations.

Homologous recombination (HR) repair for DNA double‐strand breaks (DSBs) is critical for maintaining genome stability and conferring the resistance of tumor cells to chemotherapy. Nuclear PTEN which contains both phosphatidylinositol 3,4,5‐trisphosphate 3‐phosphatase and protein phosphatase plays a key role in HR repair, but the underlying mechanism remains largely elusive. We find that SUMOylated PTEN promotes HR repair but represses nonhomologous end joining (NHEJ) repair by directly dephosphorylating TP53‐binding protein 1 (53BP1). During DNA damage responses (DDR), tumor suppressor ARF (p14ARF) was phosphorylated and then interacted efficiently with PTEN, thus promoting PTEN SUMOylation as an atypical SUMO E3 ligase. Interestingly, SUMOylated PTEN was subsequently recruited to the chromatin at DSB sites. This was because SUMO1 that was conjugated to PTEN was recognized and bound by the SUMO‐interacting motif (SIM) of breast cancer type 1 susceptibility protein (BRCA1), which has been located to the core of 53BP1 foci on chromatin during S/G2 stage. Furthermore, these chromatin‐loaded PTEN directly and specifically dephosphorylated phosphothreonine‐543 (pT543) of 53BP1, resulting in the dissociation of the 53BP1 complex, which facilitated DNA end resection and ongoing HR repair. SUMOylation‐site‐mutated PTENK254R mice also showed decreased DNA damage repair in vivo. Blocking the PTEN SUMOylation pathway with either a SUMOylation inhibitor or a p14ARF(2‐13) peptide sensitized tumor cells to chemotherapy. Our study therefore provides a new mechanistic understanding of PTEN in HR repair and clinical intervention of chemoresistant tumors.

This study evaluated the nutrients, flavour and antioxidant capacity in the embryo, colloid and fruiting body of Dictyophora rubrovalvata. The embryo had the highest protein [2.91 ± 0.39 g.(100 g)-1] and polysaccharides (17.44 ± 1.49 mg.g-1), the fruiting body had the highest total phenol content (0.87 ± 0.17 mg.g-1), the colloid was rich in minerals [1.57 ± 0.16 g.(100 g)-1]. The antioxidant capacity of the embryo was higher than that of the other parts, in terms of different solvents, the antioxidant capacity of D. rubrovalvata extracted with ethanol was higher than that of water. 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing capacity were positively correlated with polysaccharides, proteins and polyphenols. The free amino acid content ranged from 7.44 to 11.52 mg.g-1, the distribution was fruiting body > embryo > colloid, of which glutamic acid content was the highest, and the flavour characteristics were mainly umami and sweetness. The nucleotide content of fruiting body and embryo was higher than in the colloid. In addition, the compositions of volatile flavour compounds were identified by headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), mainly alcohols, aldehydes and ketones, their distributions varied greatly among the three samples. These results indicated that different parts of D. rubrovalvata have different nutritional characteristics, the fruiting body has a high content of volatile and non-volatile components, the embryo and the colloid have good functional activity, laying a foundation for the functional development and comprehensive utilisation of D. rubrovalvata.

Abstract AcrIIA15 is an anti-CRISPR (Acr) protein that inhibits Staphylococcus aureus Cas9 (SaCas9). Although previous studies suggested it has dual functions, the structural and biochemical basis for its two activities remains unclear. Here, we determined the cryo-EM structure of AcrIIA15 in complex with SaCas9-sgRNA to reveal the inhibitory mechanism of the Acr’s C-terminal domain (CTD) in mimicking dsDNA to block protospacer adjacent motif (PAM) recognition. For the N-terminal domain (NTD), our crystal structures of the AcrIIA15-promoter DNA show that AcrIIA15 dimerizes through its NTD to recognize double-stranded (ds) DNA. Further, AcrIIA15 can simultaneously bind to both SaCas9-sgRNA and promoter DNA, creating a supercomplex of two Cas9s bound to two CTDs converging on a dimer of the NTD bound to a dsDNA. These findings shed light on AcrIIA15’s inhibitory mechanisms and its autoregulation of transcription, enhancing our understanding of phage-host interactions and CRISPR defense.

Abstract Background Mechanical power (MP) is the total energy released into the entire respiratory system per minute which mainly comprises three components: elastic static power, Elastic dynamic power and resistive power. However, the energy to overcome resistance to the gas flow is not the key factor in causing lung injury, but the elastic power (EP) which generates the baseline stretch of the lung fibers and overcomes respiratory system elastance may be closely related to the ARDS severity. Thus, this study aimed to investigate whether EP is superior to other ventilator variables for predicting the severity of lung injury in ARDS patients. Methods We retrieved patient data from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The retrieved data involved adults (≥ 18 years) diagnosed with ARDS and subjected to invasive mechanical ventilation for ≥ 48 h. We employed univariate and multivariate logistic regression analyses to investigate the correlation between EP and development of moderate-severe ARDS. Furthermore, we utilized restricted cubic spline models to assess whether there is a linear association between EP and incidence of moderate-severe ARDS. In addition, we employed a stratified linear regression model and likelihood ratio test in subgroups to identify potential modifications and interactions. Results Moderate-severe ARDS occurred in 73.4% (296/403) of the patients analyzed. EP and MP were significantly associated with moderate-severe ARDS (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.15–1.28, p

Endoribonuclease DICER is an RNase III enzyme that mainly processes microRNAs in the cytoplasm but also participates in nuclear functions such as chromatin remodelling, epigenetic modification and DNA damage repair. The expression of nuclear DICER is low in most human cancers, suggesting a tight regulation mechanism that is not well understood. Here, we found that ubiquitin carboxyl‐terminal hydrolase 7 (USP7), a deubiquitinase, bounded to DICER and reduced its nuclear protein level by promoting its ubiquitination and degradation through MDM2, a newly identified E3 ubiquitin‐protein ligase for DICER. This USP7‐MDM2‐DICER axis impaired histone γ‐H2AX signalling and the recruitment of DNA damage response (DDR) factors, possibly by influencing the processing of small DDR noncoding RNAs. We also showed that this negative regulation of DICER by USP7 via MDM2 was relevant to human tumours using cellular and clinical data. Our findings revealed a new way to understand the role of DICER in malignant tumour development and may offer new insights into the diagnosis, treatment and prognosis of cancers.

Background Keloid is a chronic proliferative fibrotic disease caused by abnormal fibroblasts proliferation and excessive extracellular matrix (ECM) production. Numerous fibrotic disorders are significantly influenced by ferroptosis, and targeting ferroptosis can effectively mitigate fibrosis development. This study aimed to investigate the role and mechanism of ferroptosis in keloid development. Methods Keloid tissues from keloid patients and normal skin tissues from healthy controls were collected. Iron content, lipid peroxidation (LPO) level, and the mRNA and protein expression of ferroptosis-related genes including solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), transferrin receptor (TFRC), and nuclear factor erythroid 2-related factor 2 (Nrf2) were determined. Mitochondrial morphology was observed using transmission electron microscopy (TEM). Keloid fibroblasts (KFs) were isolated from keloid tissues, and treated with ferroptosis inhibitor ferrostatin-1 (fer-1) or ferroptosis activator erastin. Iron content, ferroptosis-related marker levels, LPO level, mitochondrial membrane potential, ATP content, and mitochondrial morphology in KFs were detected. Furthermore, the protein levels of α-smooth muscle actin (α-SMA), collagen I, and collagen III were measured to investigate whether ferroptosis affect fibrosis in KFs. Results We found that iron content and LPO level were substantially elevated in keloid tissues and KFs. SLC7A11, GPX4, and Nrf2 were downregulated and TFRC was upregulated in keloid tissues and KFs. Mitochondria in keloid tissues and KFs exhibited ferroptosis-related pathology. Fer-1 treatment reduced iron content, restrained ferroptosis and mitochondrial dysfunction in KFs, Moreover, ferrostatin-1 restrained the protein expression of α-SMA, collagen I, and collagen III in KFs. Whereas erastin treatment showed the opposite results. Conclusion Ferroptosis exists in keloid. Ferrostatin-1 restrained ECM deposition and fibrosis in keloid through inhibiting ferroptosis, and erastin induced ECM deposition and fibrosis through intensifying ferroptosis.

Abstract The incidence rate of cancer is increasing year by year due to the aging of the population, unhealthy living, and eating habits. At present, surgery and medication are still the main treatments for cancer, without paying attention to the impact of individual differences in health management on cancer. However, increasing evidence suggests that individual psychological status, dietary habits, and exercise frequency are closely related to the risk and prognosis of cancer. The reminder to humanity is that the medical concept of the unified treatment plan is insufficient in cancer treatment, and a personalized treatment plan may become a breakthrough point. On this basis, the concept of “Humanistic Health Management” (HHM) is proposed. This concept is a healthcare plan that focuses on self‐health management, providing an accurate and comprehensive evaluation of individual lifestyle habits, psychology, and health status, and developing personalized and targeted comprehensive cancer prevention and treatment plans. This review will provide a detailed explanation of the relationship between psychological status, dietary, and exercise habits, and the regulatory mechanisms of cancer. Intended to emphasize the importance of HHM concept in cancer prevention and better prognostic efficacy, providing new ideas for the new generation of cancer treatment.

IntroductionThis study was undertaken to explore the potential therapeutic effects of Tongyang Huoxue Granules (TYHX) on sinoatrial node (SAN) dysfunction, a cardiac disorder characterized by impaired impulse generation or conduction. The research question addressed whether TYHX could positively influence SAN ion channel function, specifically targeting the sodium-calcium exchanger (INCX) and L-type calcium channel (ICaL) of the SAN.MethodsSinoatrial node cells (SANCs) were isolated and cultured from neonatal Japanese big-eared white rabbits within 24 h of birth. The study encompassed five groups: Control, H/R (hypoxia/reoxygenation), H/R+100 μg/mL TYHX, H/R+200 μg/mL TYHX, and H/R+400 μg/mL TYHX. The H/R model, simulating hypoxia/reoxygenation stress, was induced within 5 days of culture. Whole-cell patch clamp technique was employed to record currents following a 3-min perfusion and stabilization period with TYHX.ResultsTYHX administration demonstrated improvements in the ignition phase of impaired SANCs. The half-maximal effective dose of TYHX, as determined by SANC beating frequency, was found to be 323.63 μg/mL. Inward current density of INCX increased in response to TYHX (200 and 400 μg/mL), while TYHX enhanced ICaL current density in H/R SANCs, with 400 μg/mL exhibiting greater efficacy. Additionally, TYHX regulated the gating mechanisms of ICaL by right-shifting the steady-state inactivation curve and accelerating recovery from inactivation. Notably, TYHX increased the activation time constant under 200 and 400 μg/mL, prolonged the fast inactivation time constant τ1 with 400 μg/mL, and extended the slow inactivation time constant τ2 with 100 and 400 μg/mL.Discussion and conclusionThe findings suggest that TYHX may hold promise as a therapeutic intervention for sinus node dysfunction, offering potential avenues for drug development aimed at safeguarding SAN function.

Traumatic splenic rupture is rare in pregnant women; and multiple venous thromboses of the portal vein system, inferior vena cava and ovarian vein after caesarean section and splenectomy for splenic rupture has not been previously reported. This case report describes a case of multiple venous thromboses after caesarean section and splenectomy for traumatic splenic rupture in late pregnancy. A 34-year-old G3P1 female presented with abdominal trauma at 33 +1 weeks of gestation. After diagnosis of splenic rupture, she underwent an emergency caesarean section and splenectomy. Multiple venous thromboses developed during the recovery period. The patient eventually recovered after anticoagulation therapy with low-molecular-weight heparin and warfarin. These findings suggest that in patients that have had a caesarean section and a splenectomy, which together might further increase the risk of venous thrombosis, any abdominal pain should be thoroughly investigated and thrombosis should be ruled out, including the possibility of multiple venous thromboses. Anticoagulant therapy could be extended after the surgery.

Abstract Flexible wearable sensors have the characteristics of flexibility, comfort, and wearability, and have shown great potential in future electronic products. Despite significant efforts in developing stretchable electronic materials and structures, the development of flexible strain sensors with a wide temperature range, high sensitivity, broad detection range, and good interface stability remains challenging. Here, strain sensors with buckled structures are fabricated using high and low‐temperature resistant material Ti3C2Tx MXene/graphene, PDMS 184. The conductive material Ti3C2Tx MXene/graphene exhibits excellent interface interaction with PDMS 184, addressing not only the poor compatibility issue between the conductive material and the flexible substrate, but also demonstrating good stability and cycling performance. Buckled structure improves the stretchability and linearity of strain sensors. The fabricated strain sensor is suitable for a wide temperature range (−40 to 120 °C) and exhibits high stretchability (120% strain). The strain sensor demonstrates rapid response times at different temperatures: −40 (72.6 ms), 0 (62.7 ms), and 120 °C (52.7 ms). The strain sensor exhibits high sensitivity at different temperatures: −40 (GF = 0.38), 0 (GF = 0.24), 40 (GF = 0.66), and 120 °C (GF = 1.47). The strain sensor has a wide detection range (0.1% to 120%) and excellent cycling stability. In addition, Ti3C2Tx MXene/graphene strain sensors can accurately capture various human activities, such as blinking, speaking, finger bending, and wrist bending.

BackgroundTraditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity, leading to delayed treatment. We aimed to evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) for microbial diagnosis of suspected pulmonary infections in PLHIV.MethodsWe retrospectively analyzed PLHIV who were hospitalized due to suspected pulmonary infections at the sixth people hospital of Zhengzhou from November 1, 2021 to June 30, 2022. Bronchoalveolar lavage fluid (BALF) samples of PLHIV were collected and subjected to routine microbiological examination and mNGS detection. The diagnostic performance of the two methods was compared to evaluate the diagnostic value of mNGS for unknown pathogens.ResultsThis study included a total of 36 PLHIV with suspected pulmonary infections, of which 31 were male. The reporting period of mNGS is significantly shorter than that of CMTs. The mNGS positive rate of BALF samples in PLHIV was 83.33%, which was significantly higher than that of smear and culture (44.4%, P

Abstract Non‐small‐cell lung cancer (NSCLC) is a highly lethal tumor that often develops resistance to targeted therapy. It is shown that Tank‐binding kinase 1 (TBK1) phosphorylates AGO2 at S417 (pS417‐AGO2), which promotes NSCLC progression by increasing the formation of microRNA‐induced silencing complex (miRISC). High levels of pS417‐AGO2 in clinical NSCLC specimens are positively associated with poor prognosis. Interestingly, the treatment with EGFR inhibitor Gefitinib can significantly induce pS417‐AGO2, thereby increasing the formation and activity of oncogenic miRISC, which may contribute to NSCLC resistance to Gefitinib. Based on these, two therapeutic strategies is developed. One is jointly to antagonize multiple oncogenic miRNAs highly expressed in NSCLC and use TBK1 inhibitor Amlexanox reducing the formation of oncogenic miRISC. Another approach is to combine Gefitinib with Amlexanox to inhibit the progression of Gefitinib‐resistant NSCLC. This findings reveal a novel mechanism of oncogenic miRISC regulation by TBK1‐mediated pS417‐AGO2 and suggest potential therapeutic approaches for NSCLC.

RNA interference (RNAi) is a specific post-transcriptional gene-silencing phenomenon, which plays an important role in the regulation of gene expression and the protection from transposable elements in eukaryotic organisms. In Drosophila melanogaster, RNAi can be induced by microRNA (miRNA), endogenous small interfering RNA (siRNA), or exogenous siRNA. However, the biogenesis of miRNA and siRNA in these RNAi pathways is aided by the double-stranded RNA binding proteins (dsRBPs) Loquacious (Loqs)-PB, Loqs-PD or R2D2. In this study, we identified three alternative splicing variants of Loqs, namely Loqs-PA, -PB, and -PC in the orthopteran Locusta migratoria. We performed in vitro and in vivo experiments to study the roles of the three Loqs variants in the miRNA- and siRNA-mediated RNAi pathways. Our results show that Loqs-PB assists the binding of pre-miRNA to Dicer−1 to lead to the cleavage of pre-miRNA to yield matured miRNA in the miRNA-mediated RNAi pathway. In contrast, different Loqs proteins participate in different siRNA-mediated RNAi pathways. In exogenous siRNA-mediated RNAi pathway, binding of Loqs-PA or LmLoqs-PB to exogenous dsRNA facilitates the cleavage of dsRNA by Dicer−2, whereas in endogenous siRNA-mediated RNAi pathway, binding of Loqs-PB or Loqs-PC to endogenous dsRNA facilitates the cleavage of dsRNA by Dicer−2. Our findings provide new insights into the functional importance of different Loqs proteins derived from alternative splicing variants of Loqs in achieving high RNAi efficiency in different RNAi pathways in insects.

Transradial access (TRA) is a safe and comfortable approach and the preferred access for percutaneous coronary intervention. However, TRA is not widely used for peripheral interventions. Currently, there is a lack of data on patient selection, appropriate medical devices, complication prevention, and TRA adoption. Therefore, the Chinese Society of Interventional Oncology of the China Anti-Cancer Association organized nationwide experts to establish a Working Group of China Expert Consensus on TRA in percutaneous peripheral interventions in 2022, and jointly formulated this consensus to better promote the application of TRA in peripheral interventions to guide clinicians on patient selection, technical recommendations, and physician training. This consensus mainly focuses on the current situation, advantages and limitations of TRA in peripheral interventions, anatomical characteristics of the radial artery, patient selection, technical aspects, prevention and management of complications, radiation dose, and learning curve. A consensus was reached through a literature evaluation and by referring to the opinions of the expert group.

Improving both the magnetic properties and strength of non-oriented electrical steel used in driving motors of new energy vehicles is a great challenge. In this study, a 4.5 wt% Si non-oriented electrical steel that had a strong {114} texture and exhibited excellent magnetic and high strength, was produced via hot rolling, cold rolling and annealing. The texture evolution of hot-rolled plate with strong Goss and medium strength λ-fiber ({100}) was investigated in detail during rolling and annealing. The VPSC model was used to simulate the texture evolution during the rolling process, of which the neff model could satisfactorily explain the classical rotation route of Goss and Cube. At the initial stage of recrystallization, the orientation of the recrystallized grains, characterized by electron backscatter diffraction (EBSD), was closely related to the orientation of the hot-rolled plate and rotation path during the rolling process. This clear evidence indicated that the initial recrystallized grains were oriented nucleation. During the recrystallization process, the characterization of specific orientations by quasi-in-situ EBSD revealed that the unusual {114} was formed by an oriented growth mechanism. Texture evolution during the recrystallization indicated oriented nucleation as an inherent property responsible for the initial recrystallization texture, while oriented growth was influenced by deformed grain size and grain boundary characteristics.

Abstract The prediction of low visibility is essential for proactive traffic safety management on freeways under fog conditions. However, few studies have developed prediction models for visibility on freeways at a short‐term time interval. This study proposes an ensemble learning approach to develop a short‐term prediction model of low visibility on freeways using meteorological data. Spearman's rank correlation coefficient is used to select meteorological variables related to low visibility. Random forests (RF) and extreme gradient boosting (XGB) are employed to develop visibility prediction models, and back propagation neural network (BPNN) and logistic regression (LR) are used for comparison. The models are evaluated over five prediction time intervals (5, 10, 15, 30, and 60 min). The results indicate that the RF models outperform the other models with precision of 73.9%, recall of 59.8% and F1 score of 0.65. Moreover, the prediction model with a 15‐min time interval shows better performance. With the proposed short‐term prediction of low visibility, it is expected that more crashes could be prevented with more appropriate proactive traffic safety management strategies.

N6-methyladenosine (m6A) represents the most prevalent and significant internal modification in mRNA, with its critical role in gene expression regulation and cell fate determination increasingly recognized in recent research. The immune system, essential for defense against infections and maintaining internal stability through interactions with other bodily systems, is significantly influenced by m6A modification. This modification acts as a key post-transcriptional regulator of immune responses, though its effects on different immune cells vary across diseases. This review delineates the impact of m6A modification across major system-related cancers—including those of the respiratory, digestive, endocrine, nervous, urinary reproductive, musculoskeletal system malignancies, as well as acute myeloid leukemia and autoimmune diseases. We explore the pathogenic roles of m6A RNA modifications within the tumor immune microenvironment and the broader immune system, highlighting how RNA modification regulators interact with immune pathways during disease progression. Furthermore, we discuss how the expression patterns of these regulators can influence disease susceptibility to immunotherapy, facilitating the development of diagnostic and prognostic models and pioneering new therapeutic approaches. Overall, this review emphasizes the challenges and prospective directions of m6A-related immune regulation in various systemic diseases throughout the body.

Genetic and environmental factors influence the growth and quality of medicinal plants. In recent years, rhizosphere microorganisms have also emerged as significant factors affecting the quality of medicinal plants. This study aimed to identify Schisandra resources with high lignan content and analyze the microbial diversity of the rhizosphere soil. High-performance liquid chromatography was used to measure the lignan content in nine Schisandra fruits. High-throughput sequencing was used to analyze the 16S rDNA sequences of rhizosphere bacteria to identify bacterial species diversity. The total lignan content of the nine Schisandra resources ranged from 9.726 mg/g to 14.031 mg/g, with ZJ27 having the highest content and ZJ25 the lowest. Among the six lignan components, Schisandrol A had the highest content, ranging from 5.133 mg/g to 6.345 mg/g, with a significant difference between ZJ25, ZJ27, and other resources (p < 0.05). Schizandrin C had the lowest content, ranging from 0.062 mg/g to 0.419 mg/g, with more significant differences among the resources. A total of 903,933 sequences were obtained from the rhizosphere soil of the nine Schisandra resources, clustered into 10,437 OTUs at a 97% similarity level. The dominant bacterial phyla were Actinobacteriota, Acidobacteriota, Proteobacteria, Chloroflexi, Gemmatimonadota, and Verrucomicrobiota. The dominant bacterial genera were Candidatus_Udaeobacter, Candidatus_Solibacter, RB41, Bradyrhizobium, Gaiella, and Arthrobacter. ZJ27 is the Schisandra resource with the highest lignan content, and the rhizosphere bacteria of Schisandra are rich in diversity. Schisandra B is negatively correlated with Bryobacter, Candidatus_Solibacter, and unnamed genera of Gaiellales.

Phaeodactylum tricornutum is identified by its capacity for rapid growth, reproduction, and in vitro cultivation, as well as the presence of a range of high-value active compounds, including proteins, with potential food applications. The objective of this study was to investigate the effects of pH shift treatments (pH of 3, 5, 7, 9, and 11) on the structural and functional properties of the Phaeodactylum tricornutum protein (PTP). The molecular weight of the PTP was predominantly distributed within the following ranges: below 5 kDa, 5–100 kDa, and above 100 kDa. Compared to the acidic environment, the PTP demonstrated higher solubility and greater free sulfhydryl group content in the alkaline environment. Additionally, PTP had a smaller particle size and higher thermal stability in alkaline environments. The PTP exhibited superior foaming ability (135%), emulsification activity index (3.72 m2/g), and emulsion stability index (137.71 min) in alkaline environments. The results of this investigation provide a foundation for the future development and application of the PTP in the food industry.

PurposeTo investigate the contrast sensitivity function (CSF) changes in simple high myopia (SHM) and evaluate the correlations between these changes with the early changes in the retinal microstructure.MethodsThis prospective study comprised 81 subjects, 20 with emmetropia (EM), 26 with low myopia and moderate myopia (LM/MM), and 35 with SHM. The area under the log CSF curve (AULCSF) and the cut-off spatial frequency (Cut-off SF) were employed as measures of CSF. Adaptive optics (AO) was employed to quantify the cone density, spacing, and regularity. The thickness and blood flow of the retinal sublayers were determined from vertical and horizontal optical coherence tomography angiography (OCTA) A-scans. Swept-source optical coherence tomography (SS-OCT) was employed to analyze the choroidal thickness (CT) and choroidal vascularity using a custom algorithm. Differences in the retinal and choroidal parameters, cone distribution, AULCSF, and Cut-off SF were compared among the three groups. Multivariate linear mixed models were used to elucidate the associations between photoreceptor morphological alterations, retinal and choroidal parameters, and AULCSF.ResultsThe AULCSF and Cut-off SF were significantly lower in the SHM group compared to the EM and LM groups (p

Summary: Loss of Protocadherin 9 (PCDH9) is associated with the metastasis and the prognosis of gastric cancer patients, while the molecular mechanism of PCDH9-impaired gastric cancer metastasis remains unclear. Here we show that PCDH9 is cleaved in gastric cancer cells. Intracellular domain of PCDH9 translocates into nucleus, where it interacts with DNA methyltransferase 1 (DNMT1) and increases DNMT1 activity. Activated DNMT1 downregulates cadherin 2 (CDH2) expression by increasing DNA methylation at its promoter, thereby dampening the migration and in vivo metastasis of gastric cancer cells. In addition, the levels of nuclear PCDH9 correlate with CDH2 expression, lymph node metastasis, and the prognosis of gastric cancer patients. Our finding demonstrates a unique mechanism of nuclear PCDH9-impaired gastric cancer metastasis by promoting DNA methylation of CDH2 promoter.

Abstract Histone deacetylase 6 (HDAC6) is one of the key histone deacetylases (HDACs) that regulates various cellular functions including clearance of misfolded protein and immunological responses. Considerable evidence suggests that HDAC6 is closely related to amyloid and tau pathology, the two primary hallmarks of Alzheimer's disease (AD). It is still unclear whether HDAC6 expression changes with amyloid deposition in AD during disease progression or HDAC6 may be regulating amyloid phagocytosis or neuroinflammation or other neuropathological changes in AD. In this work, the pathological accumulation of HDAC6 in AD brains over age as well as the relationship of its regulatory activity ‐ with amyloid pathogenesis and pathophysiological alterations is aimed to be enlightened using the newly developed HDAC6 inhibitor (HDAC6i) PB118 in microglia BV2 cell and 3D‐AD human neural culture model. Results suggest that the structure‐based rational design led to biologically compelling HDAC6i PB118 with multiple mechanisms that clear Aβ deposits by upregulating phagocytosis, improve tubulin/microtubule network by enhancing acetyl α‐tubulin levels, regulate different cytokines and chemokines responsible for inflammation, and significantly reduce phospho‐tau (p‐tau) levels associated with AD. These findings indicate that HDAC6 plays key roles in the pathophysiology of AD and potentially serves as a suitable pharmacological target through chemical biology‐based drug discovery in AD.

Abstract Background Environmental changes are expected to intensify in the future. The invasion of toxic plants under environmental changes may change herbivore feeding environments. Herbivores living long-term in toxic plant-feeding environments will inevitably ingest plant secondary metabolites (PSMs), and under different feeding environments are likely to have unique protection mechanisms that support improved adaptation to PSMs in their habitat. We aimed to compare different subterranean herbivore population responses and adaptations to toxic plants to unveil their feeding challenges. Results Here, we investigated the adaptive capacity of the liver in two geographically separated populations of plateau zokors (Eospalax baileyi) before and after exposure to the toxic plant Stellera chamaejasme (SC), at the organ, biochemical, and transcriptomic levels. The results showed no significant liver granules or inflammatory reactions in the Tianzhu (TZ) population after the SC treatment. The transaminase level in the TZ population was significantly lower than that in the Luqu population. Transcriptome analysis revealed that the TZ population exhibited interactions with other detoxification metabolic pathways by oxytocin pathway-associated genes, including diacylglycerol lipase alpha (Dagla), calcium/calmodulin dependent protein kinase II Alpha (Camk2a), and CD38 molecule (Cd38). The phase II process of liver drug metabolism increased to promote the rate of metabolism. We found that alternative splicing (AS) and the expression of the cyclin D (Ccnd1) gene interact—a TZ population hallmark—reduced liver inflammatory responses. Conclusion Our study supports the detoxification limitation hypothesis that differences in liver detoxification metabolism gene expression and AS are potential factors in herbivore adaptation to PSMs and may be a strategy of different herbivore populations to improve toxic plant adaptability.

Abstract Ulcerative colitis (UC) faces some barriers in oral therapy, such as how to safely deliver drugs to the colon and accumulate in the colon lesions. Hence, we report an advanced yeast particles system loaded with supramolecular nanoparticles with ROS scavenger (curcumin) to treat UC by reducing oxidative stress state and inflammatory response and accelerating the reprogramming of macrophages. In this study, the dual-sensitive materials are bonded on β-cyclodextrin (β-CD), the D-mannose (Man) is modified to adamantane (ADA), and then loaded with curcumin (CUR), to form a functional supramolecular nano-delivery system (Man-CUR NPs) through the host-guest interaction. To improve gastrointestinal stability and colonic accumulation of Man-CUR NPs, yeast cell wall microparticles (YPs) encapsulated Man-CUR NPs to form Man-CUR NYPs via electrostatic adsorption and vacuum extrusion technologies. As expected, the YPs showed the strong stability in complex gastrointestinal environment. In addition, the Man modified supramolecular nanoparticles demonstrated excellent targeting ability to macrophages in the in vitro cellular uptake study and the pH/ROS sensitive effect of Man-CUR NPs was confirmed by the pH/ROS-dual stimulation evaluation. They also enhanced lipopolysaccharide (LPS)-induced inflammatory model in macrophages through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and scavenging the excess ROS. Notably, in DSS-induced mice colitis model, Man-CUR NYPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways, alleviate oxidative stress by Nrf2/HO-1 signaling pathway, promote macrophages reprogramming and improve the favorable recovery of the damaged colonic tissue. Taken together, this study not only provides strategy for “supramolecular curcumin nanoparticles with pH/ROS sensitive and multistage therapeutic effects” in “advanced yeast particles”, but also provided strong theoretical support multi-effect therapy for UC.

Abstract Background Platelet Concentrate (PC) injection therapy has shown potential as a local therapy for oral lichen planus (OLP). However, its safety and efficacy have not yet been fully established. Our research compared the efficacy of PC with topical steroid treatment in alleviating pain and symptoms related to OLP. We aims to present evidence-based alternatives that dentists can use to improve patient outcomes while reducing potential side effects. Methods We conducted a systematic search of five electronic databases up to April 2023, including Embase, Cochrane Central Register of Controlled Trials, PubMed, OVID Medline, and WanFang, to evaluate PCs' efficacy compared to topical corticosteroid therapy for OLP. The literature quality was assessed using the Cochrane ROB tool. A fixed-effects model was used to determine the Weighted Mean Difference (WMD) and Mean Difference (MD) at a 95% confidence interval (CI) for pain severity and other relevant clinical indicators. Results The comparison between topical corticosteroid therapy and PCs showed no significant difference for pain relief (WMD = -0.07, CI = 95% -0.34 to 0.19), symptom improvement (MD = -0.21, CI = 95% -0.55 to 0.13), or the severity of included lesions measured by REU scores (MD = -0.25, CI = 95% -0.32 to 0.82). Conclusions Locally injected PC have been found efficient in managing oral lichen planus, indicating that they are a promising alternative option to steroid therapy for OLP patients, particularly those who have not responded favorably to steroid therapy. However, further research is needed to establish determining the recurrence rate and long-term adverse effects. Trial registration The systematic review protocol has been registered in advance with the PROSPERO database (CRD42023415372).

Abstract Resveratrol, curcumin, and quercetin are the secondary metabolites from medicinal food homology plants, that have been proven their potency in cancer treatment. However, the antitumor effect of a single component is weak. So, herein, we designed an antitumor compound named RCQ composed of resveratrol, curcumin, and quercetin. This study examined the effect on tumorigenesis and development of 4T1 breast cancer-bearing mice following administering RCQ by intragastric administration. RCQ increased the recruitment of T cells and reduced the accumulation of neutrophils and macrophages in the tumor microenvironment. Meanwhile, RCQ suppressed the development of tumor-infiltrating lymphocytes into immunosuppressive cell subpopulations, including CD4+ T cells to T helper Type 2 type (Th2), tumor-associated neutrophils (TANs) to the N2 TANs, and tumor-associated macrophages (TAMs) cells to M2 TAMs. RCQ reversed the predominance of immunosuppressive infiltrating cells in the tumor microenvironment and tipped the immune balance toward an immune activation state. In vitro the study showed that RCQ significantly increased reactive oxygen species (ROS), reduce mitochondrial membrane potentials in cancer cells, and modulate pro-apoptotic Bcl-2 family members. In conclusion, RCQ can promote the ROS apoptosis mechanism of tumor cells and alleviate immunosuppression of the tumor microenvironment to enhance the anti-tumor effect.

Abstract Background To comprehensively evaluate the influence of dienogest (DNG) versus non-DNG pretreatment on in vitro fertilization and embryo transfer (IVF-ET) outcomes for patients with endometriosis. Methods PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, and VIP were comprehensively searched for relevant publications until September 14, 2022. Primary outcomes included clinical pregnancy rate and live birth rate. Secondary outcomes included retrieved oocytes, mature oocytes, blastocysts, growing follicles, transferrable embryos, fertilization rate, implantation rate, and miscarriage rate. Subgroup analysis was performed according to different grouping methods and embryo types. Results Five studies of 568 females with endometriosis were involved in this systematic review and meta-analysis. DNG treatment exhibited similar effects to non-DNG treatment on either the primary or the secondary outcomes (all P > 0.05). The DNG group had a significantly greater clinical pregnancy rate than the non-hormonal treatment group (pooled relative risk [RR]: 2.055, 95% confidence interval [CI]: 1.275, 3.312, P = 0.003), and exhibited a significantly lower clinical pregnancy rate than the long gonadotropin-releasing hormone agonist (GnRH-a) group (RR: 0.542, 95%CI: 0.321, 0.916, P = 0.022). For patients undergoing fresh embryo transfer, the DNG group displayed a significantly greater clinical pregnancy rate versus the non-DNG group (pooled RR: 1.848, 95%CI: 1.234, 2.767, P = 0.003). Patients receiving DNG had a significantly greater live birth rate than those with non-hormonal treatment (pooled RR: 2.136, 95%CI: 1.223, 3.734, P = 0.008), while having a significantly lower live birth rate than the long GnRH-a group (RR: 0.441, 95%CI: 0.214, 0.907, P = 0.026). While using fresh embryos, patients with DNG treatment had an increased live birth rate, compared with those without DNG treatment (pooled RR: 2.132, 95%CI: 1.090, 4.169, P = 0.027). Conclusion DNG treatment may have similar effects to non-DNG treatment on IVF-ET outcomes. The clinical pregnancy rate and live birth rate after DNG treatment may be significantly higher than those after non-hormonal treatment. More evidence is warranted to corroborate these findings.

Abstract Background To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the treatment of refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods Eighty-two RMPP patients admitted to Pediatrics at The First People’s Hospital of Zhengzhou were retrospectively evaluated between August 2016 and August 2019. All patients were administered BAL in addition to intravenous Azithromycin, expectoration, and nebulizer inhalation. The medications added to the BLA separated the patients into the Budesonide group, Ambroxol + budesonide group, and acetylcysteine + budesonide group. Analyzed were the variations in laboratory examination indices, improvement in lung imaging, overall effective rate, and adverse responses in the three groups. Results The laboratory test indices of patients in all three groups improved significantly relative to pre-treatment levels, and the results were statistically significant. After therapy, there were no significant differences between the three groups in terms of white blood cell (WBC), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR). Serum lactate dehydrogenase (LDH) and serum ferritin (SF) varied significantly across the three groups (P 0.05). Conclusions BLA-coupled acetylcysteine + budesonide was superior to the other two groups in enhancing the effectiveness of RMPP in children, which might increase lung opacity absorption and minimize lung inflammation.

Background: while most gut microbiota research has focused on term infants, the health outcomes of preterm infants are equally important. Very-low-birth-weight (VLBW) or extremely-low-birth-weight (ELBW) preterm infants have a unique gut microbiota structure, and probiotics have been reported to somewhat accelerate the maturation of the gut microbiota and reduce intestinal inflammation in very-low preterm infants, thereby improving their long-term outcomes. The aim of this study was to investigate the structure of gut microbiota in ELBW neonates to facilitate the early identification of different types of low-birth-weight (LBW) preterm infants. Methods: a total of 98 fecal samples from 39 low-birth-weight preterm infants were included in this study. Three groups were categorized according to different birth weights: ELBW (n = 39), VLBW (n = 39), and LBW (n = 20). The gut microbiota structure of neonates was obtained by 16S rRNA gene sequencing, and microbiome analysis was conducted. The community state type (CST) of the microbiota was predicted, and correlation analysis was conducted with clinical indicators. Differences in the gut microbiota composition among ELBW, VLBW, and LBW were compared. The value of gut microbiota composition in the diagnosis of extremely low birth weight was assessed via a random forest-machine learning approach. Results: we briefly analyzed the structure of the gut microbiota of preterm infants with low birth weight and found that the ELBW, VLBW, and LBW groups exhibited gut microbiota with heterogeneous compositions. Low-birth-weight preterm infants showed five CSTs dominated by Enterococcus, Staphylococcus, Klebsiella, Streptococcus, Pseudescherichia, and Acinetobacter. The birth weight and clinical indicators related to prematurity were associated with the CST. We found the composition of the gut microbiota was specific to the different types of low-birth-weight premature infants, namely, ELBW, VLBW, and LBW. The ELBW group exhibited significantly more of the potentially harmful intestinal bacteria Acinetobacter relative to the VLBW and LBW groups, as well as a significantly lower abundance of the intestinal probiotic Bifidobacterium. Based on the gut microbiota’s composition and its correlation with low weight, we constructed random forest model classifiers to distinguish ELBW and VLBW/LBW infants. The area under the curve of the classifiers constructed with Enterococcus, Klebsiella, and Acinetobacter was found to reach 0.836 by machine learning evaluation, suggesting that gut microbiota composition may be a potential biomarker for ELBW preterm infants. Conclusions: the gut bacteria of preterm infants showed a CST with Enterococcus, Klebsiella, and Acinetobacter as the dominant genera. ELBW preterm infants exhibit an increase in the abundance of potentially harmful bacteria in the gut and a decrease in beneficial bacteria. These potentially harmful bacteria may be potential biomarkers for ELBW preterm infants.

The epidermal cells of insects are polarized epithelial cells that play a pivotal role in the insect’s molting process. Sinuous, a pivotal structural protein involved in the formation of septate junctions among epithelial cells, is essential for its physiological function. In this study, to determine whether sinuous participates in the regulation of insect molting, we identified the sinuous gene, Lmsinu, in Locusta migratoria, which encodes a protein belonging to the claudin family and shares 62.6% identity with Drosophila’s sinuous protein. Lmsinu is expressed in multiple tissues, and its expression level in the integument significantly increases prior to molting. Knockdown of Lmsinu in L. migratoria results in larval mortality during molting. Furthermore, hematoxylin and eosin and chitin staining demonstrate that the downregulation of Lmsinu led to a prolonged degradation process of the old cuticle during the molting process. Electron microscopy analysis further revealed that knockdown of Lmsinu disrupts the formation of septate junctions among epidermal cells, which are a monolayer of polarized epithelial cells, which may hinder the functionality of epidermal cells during the process of molting. In summary, these findings suggest that Lmsinu plays a role in nymph molting by regulating the formation of septate junctions among epidermal cells.

Due to the growing demand for human-edible protein sources, microalgae are recognized as an economically viable alternative source of proteins. The investigation into the structural characteristics and functional properties of microalgin is highly significant for its potential application in the food industry as an alternative source of protein. In this research, we extracted protein from Euglena gracilis by using alkaline extraction and acid precipitation and investigated its structural characteristics and functional properties in different acidic and alkaline environments. The molecular weight distribution of Euglena gracilis protein (EGP), as revealed by the size exclusion chromatography results, ranges from 152 to 5.7 kDa. EGP was found to be rich in hydrophobic amino acids and essential amino acids. Fourier infrared analysis revealed that EGP exhibited higher α-helix structure content and lower β-sheet structure content in alkaline environments compared with acidic ones. EGP exhibited higher foaming properties, emulsifying activity index, solubility, free sulfhydryl, and total sulfhydryl in pH environments far from its isoelectric point, and lower fluorescence intensity (2325 A.U.), lower surface hydrophobicity, larger average particle size (25.13 µm), higher emulsifying stability index, and water-holding capacity in pH environments near its isoelectric point. In addition, X-ray diffraction (XRD) patterns indicated that different acidic and alkaline environments lead to reductions in the crystal size and crystallinity of EGP. EGP exhibited high denaturation temperature (Td; 99.32 °C) and high enthalpy (ΔH; 146.33 J/g) at pH 11.0, as shown by the differential scanning calorimetry (DSC) results. The findings from our studies on EGP in different acidic and alkaline environments provide a data basis for its potential commercial utilization as a food ingredient in products such as emulsions, gels, and foams.

Liver disease is a significant global health issue that affects the liver and contributes to approximately 2 million deaths worldwide each year. Although treatment options including surgery and medication are available, effective treatment remains a challenge because of limitations of the traditional drug-delivery methods, such as uneven and nonspecific drug distribution, which lead to negative effects on healthy tissues and a reduction in drug bioavailability. Nanotechnology provides a promising solution for targeted drug delivery to the liver, which has unique anatomical and physiological structures that render it an ideal target for nanomedicine. Several categories of nanomaterials, including inorganic nanomaterials, polymer nanomaterials, and multifunctional nanoparticles (NPs), have been studied as potential agents for targeting this organ in the context of liver diseases. Using surface modification and functionalization, nanomaterials can be selectively targeted to liver tissue or hepatocytes, thus delivering drugs, and enhancing their efficacy while minimizing their side effects. Nanomaterials exhibit numerous benefits; however, their stability and toxicity pose potential risks to living organisms result in adverse effects, such as protein adsorption, and inflammation. Despite the challenges inherent to the development of nanomaterials, ongoing research and development have a great potential for the liver-targeted treatment of liver diseases through the use of nanotechnology. In this review, we first describe the nanomaterials used to target liver diseases, i.e., metallic NPs, ceramic nanomaterials, micelles, polysaccharides, liposomes, dendrimers, carbon nanotubes, and multifunctional NPs. Moreover, the mechanisms for nanomaterials target liver disease are discussed. Finally, this review discusses the current challenges and prospects for future research directions in this field.

Public transportation (PT) often fails to provide door-to-door service. Passengers often have to walk a distance to reach their destination after getting off the public transportation station. Therefore, the walking accessibility of the station area directly affects the attractiveness of the PT. For walking, accurate calculation or prediction of accessibility should consider not only the objective distance, but also the environment and psychological perception factors of pedestrians. This paper aims to map the pedestrian perceived cost to the transportation environment to evaluate the walking accessibility of the public transportation station area accurately. From the perspective of psychological perception of walking environment, four key impedance factors are selected and a pedestrian perceived impedance model is established. Then an evaluation model of station area accessibility is set employing POIs (Point of Interests) based on the accumulative opportunity method. Finally, the case is given to show the application of the model. The results show that the number of crosswalks with signal lights, mixed use of sidewalk and non-motorized lane, the obstacle quantity and the vehicle entrance quantity on sidewalks can increase perceived impedance significantly. For example, pedestrians are willing to spend 4.21 extra minutes to adopt routes with one fewer obstacle per 100 meters. Within 10 minutes of walking time, walking perception has a greater impact on station area accessibility. The perceived walking time thresholds for evaluating bus and rail transit station area accessibility are recommended to be 15 minutes and 20 minutes, respectively. The evaluation results can provide a reliable basis for improving the walking network around public transportation station.