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Ethnopharmacological Relevance: Traditional Chinese Medicines (TCMs) have emerged as a promising complementary therapy in the management of prostate cancer (PCa), particularly in addressing resistance to Docetaxel (DTX) chemotherapy., Aim of the Review: This review aims to elucidate the mechanisms underlying the development of resistance to DTX in PCa and explore the innovative approach of integrating TCMs in PCa treatment to overcome this resistance. Key areas of investigation include alterations in microtubule proteins, androgen receptor and androgen receptor splice variant 7, ERG rearrangement, drug efflux mechanisms, cancer stem cells, centrosome clustering, upregulation of the PI3K/AKT signaling pathway, enhanced DNA damage repair capability, and the involvement of neurotrophin receptor 1/protein kinase C., Materials and Methods: With "Prostate cancer", "Docetaxel", "Docetaxel resistance", "Natural compounds", "Traditional Chinese medicine", "Traditional Chinese medicine compound", "Medicinal plants" as the main keywords, PubMed, Web of Science and other online search engines were used for literature retrieval., Results: Our findings underscore the intricate interplay of molecular alterations that collectively contribute to the resistance of PCa cells to DTX. Moreover, we highlight the potential of TCMs as a promising complementary therapy, showcasing their ability to counteract DTX resistance and enhance therapeutic efficacy., Conclusion: The integration of TCMs in PCa treatment emerges as an innovative approach with significant potential to overcome DTX resistance. This review not only provides insights into the mechanisms of resistance but also presents new prospects for improving the clinical outcomes of patients with PCa undergoing DTX therapy. The comprehensive understanding of these mechanisms lays the foundation for future research and the development of more effective therapeutic interventions., Competing Interests: Declaration of competing interest We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with submission to your esteemed journal., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The accumulation of mutant huntingtin protein aggregates in neurons is a pathological hallmark of Huntington's disease (HD). The glymphatic system, a brain-wide perivascular network, facilitates the exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF), supporting interstitial solute clearance of brain wastes. In this study, we employed dynamic glucose-enhanced (DGE) MRI to measure D-glucose clearance from CSF as a tool to predict glymphatic function in a mouse model of HD. We found significantly diminished CSF clearance efficiency in HD mice prior to phenotypic onset. The impairment of CSF clearance efficiency worsened with disease progression. These DGE MRI findings in compromised glymphatic function were further confirmed with fluorescence-based imaging of CSF tracer influx, suggesting an impaired glymphatic function in premanifest HD. Moreover, expression of the astroglial water channel aquaporin-4 (AQP4) in the perivascular compartment, a key mediator of glymphatic function, was significantly diminished in both HD mouse brain and human HD brain. Our data, acquired using a clinically translatable MRI, indicate a perturbed glymphatic network in the HD brain. Further validation of these findings in clinical studies will provide insights into the potential of glymphatic clearance as a therapeutic target as well as an early biomarker in HD.

Lithium-sulfur (Li-S) battery are considered as the next generation energy storage system owing to their ultra-high theoretical specific capacity and energy density. However, the commercialization of Li-S battery is still hindered by the intrinsically low conductivity of sulfur, sluggish catalytic conversion and notorious shuttle effect of polysulfides. The implantation of defects in sulfur electrocatalyst can effectively increase its conductivity and catalytic efficiency of lithium polysulfides, but the current mainstream defective materials are limited and lack of in-depth research. Herein, a defective niobium selenide (NbSe 2-x ) nanosheet sulfur electrocatalyst is constructed with enriched selenium defects, which demonstrates strong interaction with sulfur species, endowing NbSe 2-x with rapid and reliable sulfur reduction reaction. As a result, the Li-S cell with NbSe 2-x exhibits excellent multiplicative performance in both coin cell and pouch cell, which maintains stable cycling for over 2000 cycles under 5 C, corresponding to a low-capacity fading rate of 0.024% per cycle. Ah level pouch cell is also fabricated, showing a decent energy density of 378 Wh kg -1 . This creative strategy not only emphasizes the importance of selenium defect engineering in Li-S batterie toward practical application, but also enlightens the material engineering to realize superior performance in related energy storage and conversion area., (© 2024 Wiley‐VCH GmbH.)

ConspectusThe role of quantum mechanical coherences or coherent superposition states in excited state processes has received considerable attention in the last two decades largely due to advancements in ultrafast laser spectroscopy. These coherence effects hold promise for enhancing the efficiency and robustness of functionally relevant processes, even when confronted with energy disorder and environmental fluctuations. Understanding coherence deeply drives us to unravel mechanisms and dynamics controlled by order and synchronization at a quantum mechanical level, envisioning optical control of coherence to enhance functions or create new ones in molecular and material systems. In this frontier, the interplay between electronic and vibrational dynamics, specifically the influence of vibrations in directing electronic dynamics, has emerged as the leading principle. Here, two energetically disparate quantum degrees of freedom work in-sync to dictate the trajectory of an excited state reaction. Moreover, with the vibrational degree being directly related to the structural composition of molecular or material systems, new molecular designs could be inspired by tailoring certain structural elements.In the realm of chemical kinetics, our understanding of the dynamics of chemical transformations is underpinned by fundamental theories, such as transition state theory, activated rate theory, and Marcus theory. These theories elucidate reaction rates by considering the energy barriers that must be overcome for reactants to transform into products. Those barriers are surmounted by the stochastic nature of energy gap fluctuations within reacting systems, emphasizing that the reaction coordinate, the pathway from reactants to products, is not rigidly defined by a specific vibrational motion but encompasses a diverse array of molecular motions. While less is known about the involvement of specific intramolecular vibrational modes, their significance in certain cases cannot be overlooked.In this Account, we summarize key experimental findings that offer deeper insights into the complex electronic-vibrational trajectories encompassing excited states afforded from state-of-the-art ultrafast laser spectroscopy in three exemplary processes: photoinduced electron transfer, singlet-triplet intersystem crossing, and intramolecular vibrational energy flow in molecular systems. We delve into the rapid decoherence, or loss of phase and amplitude correlations, of vibrational coherences along promoter vibrations during subpicosecond intersystem crossing dynamics in a series of binuclear platinum complexes. This rapid decoherence illustrates the vibration-driven reactive pathways from the Franck-Condon state to the curve crossing region. We also explore the generation of new vibrational coherences induced by impulsive reaction dynamics rather than by the laser pulse in these systems, which sheds light on specific energy dissipation pathways and thereby on the progression of the reaction trajectory in the vicinity of the curve crossing on the product side. Another property of vibrational coherences, amplitude, reveals how energy can flow from one vibration to another in the electronic excited state of a terpyridine-molybdenum complex hosting a nonreactive dinitrogen substrate. A slight change in vibrational energy triggers a quasi-resonant interaction, leading to constructive wavepacket interference and ultimately intramolecular vibrational redistribution from a Franck-Condon active terpyridine vibration to a dinitrogen stretching vibration, energizing the dinitrogen bond.

Pressure-modulated self-trapped exciton (STE) emission mechanism in all-inorganic lead-free metal halide double perovskites characterized by large Stokes-shifted broadband emission, has attracted much attention across various fields such as optics, optoelectronics, and biomedical sciences. Here, by employing the all-inorganic lead-free metal halide double perovskite Cs 2 TeCl 6 as a paradigm, the authors elucidate that the performance of STE emission can be modulated by pressure, attributable to the pressure-induced evolution of the electronic state (ES). Two ES transitions happen at pressures of 1.6 and 5.8 GPa, sequentially. The electronic behaviors of Cs 2 TeCl 6 can be jointly modulated by both pressure and ES transitions. When the pressure reaches 1.6 GPa, the Huang-Rhys factor S, indicative of the strength of electron-phonon coupling, attains an optimum value of ≈12.0, correlating with the pressure-induced photoluminescence (PL) intensity of Cs 2 TeCl 6 is 4.8-fold that of its PL intensity under ambient pressure. Through analyzing the pressure-dependent STE dynamic behavioral changes, the authors have revealed the microphysical mechanism underlying the pressure-modulated enhancement and quenching of STE emission in Cs 2 TeCl 6 ., (© 2024 Wiley‐VCH GmbH.)

Immunotherapy has emerged as a pivotal modality in cancer treatment, with immune checkpoint inhibitors effectively combating malignancies by impeding crucial pathways within the immune system and stimulating patients' immune responses. Soluble forms of immune checkpoints exhibit a remarkable diversity and can be readily tracked in circulation, holding immense potential as biomarkers for cancer treatment. An increasing number of studies focused on soluble immune checkpoints in cancer have emerged thanks to technological advancements. In this systematic review, we comprehensively summarized the recent studies on soluble immune checkpoints in human cancer risk prediction, outcome prediction, therapeutic applications, and potential molecular mechanisms, which demonstrated the promising future of soluble immune checkpoints in clinical applications. The clinical relevance of soluble immune checkpoints has been recognized in multiple cancers, yet the therapeutic applications and mechanisms remain obscure. Interpreting the impacts and mechanisms of soluble immune checkpoints could shed a light on the novel strategies of cancer screening, treatments, and outcome prediction., (© 2024. The Author(s).)

Melioidosis is a zoonotic disease, with its outbreaks being rare and indicative of an unusual concurrence of extreme climate and natural environmental factors. An outbreak of melioidosis cases emerged in Hainan following Typhoon "Dianmu" from October to December 2021, presenting an opportunity to identify the environmental sources of infection for these cases due to its nature as a well-defined point-source cluster. To investigate the relationship between the occurrence of these melioidosis cases and the environment, we extracted the entire genome of 25 clinical strains and conducted MLST typing, followed by whole genome sequencing and analysis of molecular genetic information for four ST46 genotypes from these strains. Phylogenetic and evolutionary relationships between Hainan sequence types (STs) and those found in other endemic regions were analyzed using IslandPath-DIMO, PHASTER, e-BURST, PHYLOViZ, and the maximum likelihood method. Notably, a total of 25 clinical strains were identified, encompassing 12 STs (ST46, ST1105, ST1991, ST30, ST1992, ST50, ST164, ST55, ST70, ST1993, ST1545, and ST58), with ST1991, ST1992, and ST1993 being newly discovered subtypes. PHYLOViZ clustering analysis divided the strains into two groups (A and B), both closely related to the Asian region. Phylogenetic tree analysis further revealed that most of the strains in this study were closely related to those found in Australia and Thailand. Analysis of patient information and visits to their residences suggested that contaminated water sources might be the primary source of infection during this outbreak. Our findings underscore that extreme weather events, such as typhoons, significantly increase the infection rate of B. pseudomallei, along with its genetic diversity, necessitating additional prevention strategies to control these B. pseudomallei infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Exogenous insulin-like growth factor-1 (IGF-1) has been reported to promote wound healing through regulation of vascular endothelial cells (VECs). Despite the existing studies of IGF-1 on VEC and its role in angiogenesis, the mechanisms regarding anti-inflammatory and angiogenetic effects of IGF-1 remain unclear. In this study, we investigated the wound-healing process and the related signaling pathway of IGF-1 using an inflammation model induced by IFN-γ. The results demonstrated that IGF-1 can increase cell proliferation, suppress inflammation in VECs, and promote angiogenesis. In vivo studies further confirmed that IGF-1 can reduce inflammation, enhance vascular regeneration, and improve re-epithelialization and collagen deposition in acute wounds. Importantly, the Ras/PI3K/IKK/NF-κB signaling pathways was identified as the mechanisms through which IGF-1 exerts its anti-inflammatory and pro-angiogenic effects. These findings contribute to the understanding of IGF-1's role in wound healing and may have implications for the development of new wound treatment approaches., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Parkinson's disease is a complex neurodegenerative disease characterized by progressive movement impairments. Predominant symptoms encompass resting tremor, bradykinesia, limb rigidity, and postural instability. In addition, it also includes a series of non-motor symptoms such as sleep disorders, hyposmia, gastrointestinal dysfunction, autonomic dysfunction and cognitive impairment. Pathologically, the disease manifests through dopaminergic neuronal loss and the presence of Lewy bodies. At present, no significant breakthrough has been achieved in clinical Parkinson's disease treatment. Exploring treatment modalities necessitate the establishment of scientifically sound animal models. In recent years, researchers have focused on replicating the symptoms of human Parkinson's disease, resulting in the establishment of various experimental animal models primarily through drugs and transgenic methods to mimic relevant pathologies and identify more effective treatments. This review examines traditional neurotoxin and transgenic animal models as well as α-synuclein pre-formed fibrils models, non-human primate models and non-mammalian specie models. Additionally, it introduces emerging models, including models based on optogenetics, induced pluripotent stem cells, and gene editing, aiming to provide a reference for the utilization of experimental animal models and clinical research for researchers in this field., Competing Interests: Declaration of Competing Interest The author declares no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lipid metabolism disorders are a major cause of several chronic metabolic diseases which seriously affect public health. Salusin‑α, a vasoactive peptide, has been shown to attenuate lipid metabolism disorders, although its mechanism of action has not been reported. To investigate the effects and potential mechanisms of Salusin‑α on lipid metabolism, Salusin‑α was overexpressed or knocked down using lentiviral vectors. Hepatocyte steatosis was induced by free fatty acid (FFA) after lentiviral transfection into HepG2 cells. The degree of lipid accumulation was assessed using Oil Red O staining and by measuring several biochemical indices. Subsequently, bioinformatics was used to analyze the signaling pathways that may have been involved in lipid metabolism disorders. Finally, semi‑quantitative PCR and western blotting were used to verify the involvement of the liver kinase B1 (LKB1)/AMPK pathway. Compound C, an inhibitor of AMPK, was used to confirm this mechanism's involvement further. The results showed that Salusin‑α significantly attenuated lipid accumulation, inflammation and oxidative stress. In addition, Salusin‑α increased the levels of LKB1 and AMPK, which inhibited the expression of sterol regulatory element binding protein‑1c, fatty acid synthase and acetyl‑CoA carboxylase. The addition of Compound C abrogated the Salusin‑α‑mediated regulation of AMPK on downstream signaling molecules. In summary, overexpression of Salusin‑α activated the LKB1/AMPK pathway, which in turn inhibited lipid accumulation in HepG2 cells. This provides insights into the potential mechanism underlying the mechanism by which Salusin‑α ameliorates lipid metabolism disorders while identifying a potential therapeutic target.

This study evaluates the non-invasive diagnosis of Invasive Aspergillosis Pneumonia (IPA) in mechanically ventilated patients by measuring galactomannan (GM) in exhaled breath condensate (EBC). Utilizing a rat model and a novel EBC collection device, we compared GM levels in bronchoalveolar lavage fluid (BALF) and EBC, supplemented by cytokine profiling. Analysis of 75 patients confirmed the device's efficacy, with EBC-GM and BALF-GM showing high diagnostic accuracy (AUC = 0.88). The threshold of 0.235 ng/ml for EBC-GM achieved 92.8 % sensitivity and 66.7 % specificity, with a strong correlation (r = 0.707, P < 0.001) with BALF-GM. This approach offers a safe, effective alternative to invasive diagnostics, enhancing precision with IL-6 and TNF-α measurements. The number registered on clinicaltrails.gov is NCT06333379., Competing Interests: Declaration of competing interest The authors declare that the funding received has not led to any conflicts of interest regarding the research, authorship, and/or publication of this manuscript. The research presented in the manuscript titled "[Non-Invasive Detection of Aspergillosis in Ventilated Patients: Galactomannan Analysis in Exhaled Breath]" was supported by the Sichuan Provincial People's Hospital-Clinical Research and Translational Fund (Grant No. 2020LY01). This funding was granted to support the research activities necessary for the completion of this study. The authors declare that the funding received has not led to any conflicts of interest regarding the research, authorship, and/or publication of this manuscript. The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Lin Chen conceived and designed the experiments; contributed reagents, materials, analysis tools or data; Xiaohong Tang and Lei Yang performed the experiments and wrote the paper. Rong Zhang, Hong Fang participated in data collection and analysis; Huan Tang, Qian Xie contributed to the writing and critical review of the manuscript; Hailian Wang contributed to the development of the methodology; Yang Yang assisted in the preparation and revision of the manuscript., (Copyright © 2024 University of Electronic Science and Technology of China, School of Medicine. Sichuan Provincial People's Hospital. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the accuracy of immediate anterior implantation using static computer-assisted implant surgery (s-CAIS) and robotic computer-assisted implant surgery (r-CAIS)., Materials and Methods: One hundred and six implants were immediately inserted in the anterior zone of 69 patients using a freehand technique, s-CAIS or r-CAIS. Postoperative cone-beam computed tomography scans were matched with preoperative plans to evaluate the deviations between the planned and placed implant positions., Results: The global coronal deviations in the freehand, s-CAIS, and r-CAIS groups were 1.29 ± 0.52 mm, 1.01 ± 0.41 mm, and 0.62 ± 0.28 mm, respectively. Significant differences were observed in the r-CAIS group compared to both the s-CAIS group and the freehand group (p < 0.05). However, no significant differences were found between the s-CAIS group and the freehand group (p > 0.05). The global apical deviations in the freehand, s-CAIS and r-CAIS groups were 1.78 ± 0.59 mm, 1.24 ± 0.52 mm and 0.65 ± 0.27 mm, respectively, while the angular deviations in the freehand, s-CAIS and r-CAIS groups were 6.46 ± 2.21°, 2.94 ± 1.71° and 1.46 ± 0.57°, respectively. Significant differences were observed in both the global apical deviations and angular deviations among the three groups (p < 0.05)., Conclusions: The accuracy of immediate anterior implantation with r-CAIS was better than that with s-CAIS. This difference is attributed to better control of the coronal, vertical and axial errors during r-CAIS., Clinical Significance: This study provides significant evidence to support the use of r-CAIS as a potential alternative in immediate anterior implantation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shih-Wei Wang reports financial support was provided by Ministry of Science and Technology, Taiwan. Shih-Wei Wang reports financial support was provided by National Science and Technology Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Folate is crucial for maintaining health, but humans are unable to synthesize folate and need to obtain it from food. Lactiplantibacillus plantarum can produce the necessary vitamin B for the human body, including folate. Whole genome sequencing technology can clarify the physiological characteristics of folate production in Lactiplantibacillus plantarum. In order to explore new Lactiplantibacillus plantarum that produce folate, the folate production and probiotic characteristics of Lactiplantibacillus plantarum ZFM55 isolated from infant feces were investigated, and whole genome sequencing was performed., Results: The folate synthesis ability of Lactiplantibacillus plantarum ZFM55 were measured, and its total folate production was 299.72 ± 28.81 ng mL -1 . Subsequently, its probiotic properties were explored. The antibacterial test showed that its inhibition zone diameter against Staphylococcus aureus and Salmonella typhimurium was 15.5 ± 0.82 mm and 13.88 ± 0.98 mm, respectively. The tolerance test results indicated that it maintained good activity in simulated gastrointestinal tract and bile salt environments. In vitro intestinal simulation experiments had confirmed that Lactiplantibacillus plantarum ZFM55 can increase the abundance of beneficial bacteria such as Bifidobacteria in the intestine and inhibit the growth of harmful bacteria such as Escherichia&#95;Shigella. Genomic sequencing indicated that the genetic material of Lactiplantibacillus plantarum ZFM55 contains one chromosome and three plasmids, and it has 20 genes related to folate synthesis, which explains its ability to produce folate., Conclusion: This study reports a new potential probiotic that produces folate, and provides ideas for exploring probiotics with specific probiotic characteristics. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Odorant-binding proteins (OBPs) in insects are key to detection and recognition of external chemical signals associated with survival. OBP7 in Spodoptera frugiperda's larval stage (SfruOBP7) may search for host plants by sensing plant volatiles, which are important sources of pest attractants and repellents. However, the atomic-level basis of binding modes remains elusive., Results: SfruOBP7 structure was constructed through homology modeling, and complex models of six plant volatiles ((E)-2-hexenol, α-pinene, (Z)-3-hexenyl acetate, lauric acid, O-cymene and 1-octanol) and SfruOBP7 were obtained through molecular docking. To study the detailed interactions between the six plant volatile molecules and SfruOBP7, we conducted three 300 ns molecular dynamics simulations for each study object. The correlation coefficients between binding free energy obtained by molecular mechanics/generalized Born surface area together with solvated interaction energy methods and experimental values are 0.90 and 0.88, respectively, showing a good correlation. By comparing binding free energy along with interaction patterns between SfruOBP7 and the six volatile molecules, hotspot residues of SfruOBP7 when binding with different volatile molecules were determined. Hydrophobic interactions stemming from van der Waals interactions play a significant role in SfruOBP7 and these plant volatile systems., Conclusion: The optimized three-dimensional structure of SfruOBP7 and its binding modes with six plant volatiles revealed their interactions, thus providing a means for estimating the binding energies of other plant volatiles. Our study will help to guide the rational design of effective and selective insect attractants. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The ethanol extract of the whole plant of Delphinium trichophorum Franch was subjected to a phytochemical study, leading to the isolation of ten unprecedented diterpenoid alkaloids, including nine delnudine-type C 20 -diterpenoid alkaloids named trichophodines A-I and one kusnezoline-type C 20 -diterpenoid alkaloid named trichophozine A. Additionally, seven known compounds were also identified. Their structures were elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC, 1 H- 1 H COSY, NOESY and X-ray crystallographic analysis. Most isolated compounds were screened for inhibitory activities against LPS-induced NO production in RAW 264.7 macrophage cells and acetylcholinesterase inhibitory effects. Guan-fu base V exhibited potent inhibitory activity against acetylcholinesterase, demonstrating an inhibitory rate of 53.81% at a concentration of 40 μM., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Leukocyte immunoglobulin-like receptor B4 (LILRB4) plays a significant role in regulating immune responses. LILRB4 in microglia might influence the infiltration of peripheral T cells. However, whether and how LILRB4 expression aggravates brain damage after acute ischemic stroke remains unclear. This study investigates the role of LILRB4 in modulating the immune response and its potential protective effects against ischemic brain injury in mice., Methods and Results: Microglia-specific LILRB4 conditional knockout (LILRB4-KO) and overexpression transgenic (LILRB4-TG) mice were constructed by a Cre-loxP system. Then, they were used to investigate the role of LILRB4 after ischemic stroke using a transient middle cerebral artery occlusion (tMCAO) mouse model. Spatial transcriptomics analysis revealed increased LILRB4 expression in the ischemic hemisphere. Single-cell RNA sequencing (scRNA-seq) identified microglia-cluster3, an ischemia-associated microglia subcluster with elevated LILRB4 expression in the ischemic brain. Flow cytometry and immunofluorescence staining showed increased CD8 + T cell infiltration into the brain in LILRB4-KO-tMCAO mice. Behavioral tests, cortical perfusion maps, and infarct size measurements indicated that LILRB4-KO-tMCAO mice had more severe functional deficits and larger infarct sizes compared to Control-tMCAO and LILRB4-TG-tMCAO mice. T cell migration assays demonstrated that LILRB4-KD microglia promoted CD8 + T cell recruitment and activation in vitro, which was mitigated by CCL2 inhibition and recombinant arginase-1 addition. The scRNA-seq and spatial transcriptomics identified CCL2 was predominantly secreted from activated microglia/macrophage and increased CCL2 expression in LILRB4-KD microglia, suggesting a chemokine-mediated mechanism of LILRB4., Conclusion: LILRB4 in microglia plays a crucial role in modulating the post-stroke immune response by regulating CD8 + T cell infiltration and activation. Knockout of LILRB4 exacerbates ischemic brain injury by promoting CD8 + T cell recruitment. Overexpression of LILRB4, conversely, offers neuroprotection. These findings highlight the therapeutic potential of targeting LILRB4 and its downstream pathways to mitigate immune-mediated damage in ischemic stroke., (© 2024. The Author(s).)

The aim of this study was to explore the effects of low-frequency ultrasound (US) combined with microbubbles (MBs) on breast cancer xenografts and explain its underlying mechanisms. A total of 20 xenografted nude mice were randomly divided into four groups: a group treated with US plus MBs (the US + MBs group), a group treated with US alone (the US group), a group treated with MBs alone (the MBs group), and a control group. In different groups, mice were treated with different US and injection regimens on an alternate day, three times in total. Histological changes, apoptosis of cells, microvascular changes, and the apoptosis index (AI) and microvascular density (MVD) of the breast cancer xenograft were analyzed after the mice were sacrificed. Results indicated that the tumor volume in the US + MBs group was smaller than that in the other three groups ( p < 0.001 for all). The rate of tumor growth inhibition in the US + MBs group was significantly higher than that in the US and MBs groups ( p < 0.001 for both). There were no significant differences in histological changes among the four groups. However, the AI was higher in the US + MBs group than that in the other three groups while the MVD was lower ( p < 0.001 for all). All in all, low-frequency US combined with MBs can effectively slow down the growth of breast cancer in nude mice. In summary, low-frequency US combined with MBs has a significant effect on breast cancer treatment. Cavitation, thermal effects, and mechanical effects all play a vital role in the inhibition of tumor growth., Competing Interests: The authors have no conflicts of interest to disclose., (2024, National Center for Global Health and Medicine.)

Background: Domestic and international guidelines recommend endoscopic resection for stage T1 colorectal adenocarcinoma with indications. However, completion surgery remains imperative for patients exhibiting high-risk factors subsequent to endoscopic procedures., Objective: To investigate the evidence, pathological features, and surgical outcomes of completion surgery in patients with T1 colorectal adenocarcinoma following endoscopic resection., Methods: We retrospectively collect data on the clinical features and treatment outcomes of patients with stage T1 colorectal adenocarcinoma who underwent endoscopic resection followed by surgical resection and those who initially completed surgical intervention at Peking University International Hospital between January 2019 and October 2022, with the aim of assessing the necessity and feasibility of surgical intervention., Results: Seventeen patients (Group A) with high-risk factors following endoscopic procedure, especially with deep submucosal invasion and vascular or lymphatic invasion, experienced further surgical resection. The median interval between endoscopic resection and completion surgery was 23.71 days ± 15.89. Sixteen patients (Group B) underwent radical resection without any prior interventions. The surgical approach involves integration of laparoscopy and colonoscopy for precise localization and quantitative diagnosis, followed by radical surgery. The two groups demonstrated significant differences statistically with reference to tumor diameter (1.65 cm ± 0.77 vs 3.36 cm ± 1.39, P = 0.000) and the attainment of standard lymph node count (cases of detected lymph nodes larger than or equal to 12, 5 vs 12, P = 0.015). Postoperative complications and hospital stay manifested no significant disparity statistically in two groups. Patients who underwent completion surgery had no inferior outcomes compared with those who underwent direct surgery in terms of 5-year disease-free survival (Log rank test: P = 0.083, Breslow test: P = 0.089). The two groups also exhibited no significant differences statistically in the context of overall survival (Log rank test: P = 0.652, Breslow test: P = 0.758)., Conclusion: Completion surgery is a safe and feasible treatment option for T1 colorectal adenocarcinoma patients with high-risk factors, particularly those with deep submucosal invasion and vascular or lymphatic invasion following endoscopic treatment. Furthermore, subsequent treatment should be chosen based on a comprehensive analysis of the patient's history of abdominal surgery, willingness, and pathological features., (© 2024. The Author(s).)

Deep learning has been widely used in ultrasound image analysis, and it also benefits kidney ultrasound interpretation and diagnosis. However, the importance of ultrasound image resolution often goes overlooked within deep learning methodologies. In this study, we integrate the ultrasound image resolution into a convolutional neural network and explore the effect of the resolution on diagnosis of kidney tumors. In the process of integrating the image resolution information, we propose two different approaches to narrow the semantic gap between the features extracted by the neural network and the resolution features. In the first approach, the resolution is directly concatenated with the features extracted by the neural network. In the second approach, the features extracted by the neural network are first dimensionally reduced and then combined with the resolution features to form new composite features. We compare these two approaches incorporating the resolution with the method without incorporating the resolution on a kidney tumor dataset of 926 images consisting of 211 images of benign kidney tumors and 715 images of malignant kidney tumors. The area under the receiver operating characteristic curve (AUC) of the method without incorporating the resolution is 0.8665, and the AUCs of the two approaches incorporating the resolution are 0.8926 (P < 0.0001) and 0.9135 (P < 0.0001) respectively. This study has established end-to-end kidney tumor classification systems and has demonstrated the benefits of integrating image resolution, showing that incorporating image resolution into neural networks can more accurately distinguish between malignant and benign kidney tumors in ultrasound images., (© 2024. International Federation for Medical and Biological Engineering.)

The optimal discrete element model and bonding parameters that match the structural features of cornstalks during harvest were obtained. Based on the differences in mechanical properties of the stem bark and stem pith in the inter-nodal cornstalk, the biomechanical-specific parameters were measured using the compression, shear, and bending tests. The bonded particle models of stem bark and stem pith were constructed using fraction particles with radii of 1 mm and 1.47 mm, which were further bound to form a bilayer-bonded particle model of the cornstalk. The Plackett-Burman, steepest ascent, and response surface tests were conducted to identify the factors and their optimal values that significantly impacted the stem bark-stem bark, stem pith-stem pith, and stem bark-stem pith bonding parameters. The cornstalk's shear and bending mechanical properties were assessed to verify the overall characteristic parameters. The findings revealed that the cornstalk model created, and the calibrated bonding parameters, were highly accurate and capable of simulating the shearing and bending behaviors of the real cornstalk. The inter-nodal cornstalk's bonded particle model created and the identified bonding parameters for the cornstalk could contribute to a theoretical and research basis for the next stage in cornstalk modeling with nodes and other applications., (© 2024. The Author(s).)

Glioblastoma (GBM) is the most aggressive brain tumor for which current therapies have limited efficacy. Immunosuppression and difficulties in accessing tumors with therapeutic agents are major obstacles for GBM treatments. Classical monocytes (CMs) possess the strongest infiltration among myeloid cells recruited into tumors during tumorigenesis. In this study, CMs are utilized to deliver the small-molecule CUDC-907 encapsulated in nanoparticles (907-NPs@CMs) for GBM therapy. Hitchhiking on CMs enables more 907-NPs to successfully penetrate the blood-brain barrier (BBB) and reach the interior of tumors. Results demonstrate that 907-NPs@CMs significantly improve the survival rates by suppressing tumor growth and reversing the immunosuppression of tumor microenvironment (TME). Furthermore, the high delivery efficiency of CMs reduces the amount of CUDC-907 required for treatments, reducing the physiological toxicity and off-target effects caused by high doses. 907-NPs@CMs is a safe and versatile therapeutic system that provides a platform for targeted drug delivery to tumors and the ability to treat GBM through a combination of chemotherapy and immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Background: Colon cancer is a prevalent invasive neoplasm in the gastrointestinal system with a high degree of malignancy. Despite extensive research, the underlying mechanisms of its recurrence and metastasis remain elusive.Rho GTPase activating protein 4 (ARHGAP4), a member of the small GTPases protein family, may be closely related to tumor metastasis, and its expression is increased in colon cancer. However, the role of ARHGAP4 in colon cancer metastasis is uncertain. This study investigates the impact of ARHGAP4 on the metastasis of colon cancer cells. Our objective is to determine the role of ARHGAP4 in regulating the invasive behavior of colon cancer cells., Methods: We downloaded colon adenocarcinoma (COAD) data from the Cancer Genome Atlas (TCGA), and performed differential analysis and survival analysis. By using the CIBERSORT algorithm, we evaluated the proportion of infiltrating immune cells in colon cancer. We further analyzed whether ARHGAP4 is associated with T cell exhaustion. Finally, we investigated the impact of ARHGAP4 knockdown on the migration and invasion of colon cancer cells through in vitro cell experiments. Additionally, we utilized western blotting to assess the expression of protein related to the TGF-β signaling pathway and epithelial-mesenchymal transition (EMT)., Results: We found that ARHGAP4 is upregulated in colon cancer. Subsequent survival analysis revealed that the high-expression group had significantly lower survival rates compared to the low-expression group. Immune infiltration analysis showed that ARHGAP4 was not only positively correlated with CD8 + T cells, but also positively correlated with T cell exhaustion markers programmed cell death 1 (PDCD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte activating 3 (LAG-3). In vitro cell experiments, the knockdown of ARHGAP4 inhibited the migration and invasion of colon cancer cells. Among EMT-related proteins, when ARHGAP4 was knocked down, the expression of E-cadherin was increased, while the expression of N-cadherin and Vimentin was decreased. Meanwhile, the expression of TGF-β1, p-Smad2, and p-Smad3, which are associated with the TGF-β/Smad pathway, all decreased., Conclusion: ARHGAP4 promotes colon cancer metastasis through the TGF-β/Smad signaling pathway and may be associated with T cell exhaustion. It plays an important role in the progression of colon cancer and may serve as a potential target for diagnosis and treatment of colon cancer., Competing Interests: Declaration of competing interest 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 Elsevier Inc. All rights reserved.)

Background: Shenzhen, a city with a substantial mobile population, was identified as the first discovered region of HIV-1 CRF55&#95;01B and epicenter of its severe epidemic. During the implementation of venue-based behavioral interventions and the "treat-all" policy, discerning the spread patterns and transmission hotspots of CRF55&#95;01B is imperative., Methods: In this study, 1,450 partial pol sequences, with demographic information, were collected from all newly diagnosed CRF55&#95;01B infections in Shenzhen from 2008 to 2020. Molecular networks were constructed using the maximum likelihood and time-resolve phylogenies. Transmission rates, effective reproduction numbers (Re) of clusters and viral dispersal were evaluated using Bayesian inference., Results: In total, 526 sequences formed 114 clusters, including seven large clusters. The status and size of clusters were strongly correlated with age, ethnicity, occupation and CD4+ T cell counts. The transmission rates of clusters were significantly higher than the national epidemic estimate. Four large clusters had Re exceeding 1 at the end of sampling period. Immigrants from Guangdong and Hunan, along with local residents, were identified as the transmission hubs, with heterosexual men being the main source and MSM being the main destination. The virus exhibited a high movement frequency from individuals aged 30-49 years toward diverse age groups., Conclusions: This study demonstrated the hidden CRF55&#95;01B transmissions continued despite current combined interventions in Shenzhen, and special at-risk individuals susceptible to infection or transmission were identified, potentially serving as targets for more effective prevention and control of the local epidemic, thereby mitigating cross-regional spread nationwide due to population migration., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Study Design: A retrospective, cross-sectional cohort study., Objective: This study aims to investigate the association between paraspinal muscle parameters and single-segment degenerative lumbar spondylolisthesis (DLS)., Summary of Background Data: The relationship between lumbar paraspinal muscles morphology and single-segment DLS remains unclear., Methods: A retrospective review was conducted on 115 patients with L4/5 single-segment DLS and 105 subjects without DLS. Two independent investigators assessed the relative cross-sectional area and fat infiltration rate of the multifidus, erector spinae, and psoas major at L3/4, L4/5, and L5/S1 levels, comparing these measurements between the two groups. Additionally, binary logistic regression analysis was performed with DLS as the dependent variable to analyze the relative cross-sectional area and fat infiltration rate of different paraspinal muscles. Within the DLS group, the correlation between paraspinal muscle characteristics and the anteroposterior diameter of the spinal canal was examined., Results: The fat infiltration rate of multifidus, erector spinae, and psoas major were higher in the DLS group than in the control group, while the relative cross-sectional area of multifidus and psoas major were lower in the DLS group. Binary logistic regression analysis revealed a significant correlation between fat infiltration rate of multifidus and psoas major and DLS. The relative cross-sectional area of multifidus and erector spinae was significantly smaller below the affected segment in the DLS group compared to the control group. A significant positive correlation was observed between the relative cross-sectional area of multifidus and erector spinae and the anteroposterior diameter of the spinal canal., Conclusion: There is a close association between paraspinal muscle degeneration and single-segment DLS, with increased relative cross-sectional area of the multifidus and psoas major possibly being risk factors for single-segment DLS. The restoration or enhancement of paraspinal muscle function could potentially serve as a pivotal target for the prevention and treatment of single-segment DLS., Level of Evidence: III., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

A rapid method was developed for determining the total flavonoid and protein content in Tartary buckwheat by employing near-infrared spectroscopy (NIRS) and various machine learning algorithms, including partial least squares regression (PLSR), support vector regression (SVR), and backpropagation neural network (BPNN). The RAW-SPA-CV-SVR model exhibited superior predictive accuracy for both Tartary and common buckwheat, with a high coefficient of determination (R 2 p = 0.9811) and a root mean squared error of prediction (RMSEP = 0.1071) for flavonoids, outperforming both PLSR and BPNN models. Additionally, the MMN-SPA-PSO-SVR model demonstrated exceptional performance in predicting protein content (R 2 p = 0.9247, RMSEP = 0.3906), enhancing the effectiveness of the MMN preprocessing technique for preserving the original data distribution. These findings indicate that the proposed methodology could efficiently assess buckwheat adulteration analysis. It can also provide new insights for the development of a promising method for quantifying food adulteration and controlling food quality., 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. The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aims to identify potential targets and regulatory mechanisms of Astragaloside Ⅳ (AS-Ⅳ) in treating intervertebral disc degeneration (IDD) through network pharmacology analysis with experimental validation. Lumbar spine instability (LSI) mouse models were first established and treated with AS-Ⅳ. Micro-CT, safranin O-fast green staining, IDD score, RT-PCR and immunohistochemistry staining were employed to demonstrate the effect of AS-Ⅳ. Network pharmacology was used to predict the signaling pathways and potential targets of AS-Ⅳ in treating IDD. RT-PCR and immunohistochemistry staining were used to elucidate and validate the mechanism of AS-Ⅳ in vivo. Animal experiments showed that AS-Ⅳ maintained disc height and volume, improved matrix metabolism in LSI mice, and restored Col2α1, ADAMTS-5, Aggrecan, and MMP-13 expression in degenerated discs. Network pharmacology analysis identified 32 cross-targets between AS-Ⅳ and IDD, and PPI network analysis filtered out 11 core genes, including ALB, MAPK1, MAPK14 (p38 MAPK), EGFR, TGFBR1, MAPK8, MMP3, ANXA5, ESR1, CASP3, and IGF1. Enrichment analysis revealed that 7 of the 11 core target genes enriched in the MAPK signaling pathway, and AS-Ⅳ exhibited stable binding to them according to molecular docking results. Experimental validation indicated that AS-Ⅳ reversed mRNA levels of 7 core targets in degenerated disc tissues in LSI mice. Immunohistochemistry staining further revealed that AS-Ⅳ treatment mainly depressed IDD-elevated protein levels of EGFR, p38 MAPK and CASP3 in the annulus fibrosus. This study elucidates that AS-Ⅳ alleviates lumbar spine instability-induced IDD in mice, suggesting the mechanism may involve inhibition of the EGFR/MAPK signaling pathway., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Liquid biopsy provides a convenient and safer procedure for the diagnosis and genomic profiling of tumors that are inaccessible to biopsy by analyzing exfoliated tumor cells (ETCs) or tumor-derived cell-free DNA (cfDNA). However, its primary challenge lies in its limited accuracy in comparison to tissue-based approaches. We report a parallel single-ETC genomic sequencing (Past-Seq) method for the accurate diagnosis and genomic profiling of hard-to-biopsy tumors such as cholangiocarcinoma (CCA) and upper tract urothelial carcinoma (UTUC). For CCA, a prospective cohort of patients with suspicious biliary strictures ( n = 36) was studied. Parallel single-cell whole genome sequencing and whole exome sequencing were performed on bile ETCs for CCA diagnosis and resolving mutational profiles, respectively, along with bile cfDNA sequenced for comparison. Concordant single-cell copy number alteration (CNA) profiles in multiple ETCs provided compelling evidence for generating a malignant diagnosis. Past-Seq yielded bile-based accurate CCA diagnosis (96% sensitivity, 100% specificity, and positive predictive value), surpassing pathological evaluation (56% sensitivity) and bile cfDNA CNA analysis (13% sensitivity), and generated the best performance in the retrieval tissue mutations. To further explore the applicability of Past-Seq, 10 suspicious UTUC patients were investigated with urine specimens, and Past-Seq exhibited 90% sensitivity in diagnosing UTUC, demonstrating its broad applicability across various liquid biopsies and cancer types.

Introduction: The elderly population experiences more postoperative complications. A comprehensive geriatric assessment, which is multidimensional and coordinated, could help reduce these unfavorable outcomes. However, its effectiveness is still uncertain., Methods: We searched multiple online databases, including Medline, PubMed, Web of Science, Cochrane Library, Embase, CINAL, ProQuest, and Wiley, for relevant literature from their inception to October 2023. We included randomized trials of individuals aged 65 and older undergoing surgery. These trials compared comprehensive geriatric assessment with usual surgical care and reported on postoperative outcomes. Two researchers independently screened the literature, extracted data, and assessed the certainty of evidence from the identified articles. We conducted a meta-analysis using RevMan 5.3 to calculate the Odds Ratio (OR) and Mean Difference (MD) of the pooled data., Results: The study included 1325 individuals from seven randomized trials. Comprehensive geriatric assessment reduced the rate of postoperative delirium (28.5% vs. 37.0%; OR: 0.63; CI: 0.47-0.85; I2: 54%; P = 0.003) based on pooled data. However, it did not significantly improve other parameters such as length of stay (MD: -0.36; 95% CI: -0.376, 3.05; I2: 96%; P = 0.84), readmission rate (18.6% vs. 15.4%; OR: 1.26; CI: 0.86-1.84; I2: 0%; P = 0.24), and ADL function (MD: -0.24; 95% CI: -1.27, 0.19; I2: 0%; P = 0.64)., Conclusions: Apart from reducing delirium, it is still unclear whether comprehensive geriatric assessment improves other postoperative outcomes. More evidence from higher-quality randomized trials is needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This work uses first-principles calculations to investigate the phase stability, thermophysical and mechanical properties of refractory high-entropy alloys (RHEAs) at finite temperatures. Based on plane wave quasi-potential and density functional theory, construct the structure model of a solid solution. The TiMoNbX (X = Cr, Ta, Cr and Ta) RHEAs have been determined to preserve a single BCC solid solution structure by calculations, and the equilibrium lattice parameters and elastic modulus are consistent with experimental data obtained by laser cladding, which is combined with TC4 (Ti-6Al-4V) substrate. Using the quasi-harmonic Debye-Grüneisen model, the thermophysical characteristics of three RHEAs are investigated. The Voigt-Reuss-Hill (VRH) scheme is used for calculating Young's modulus (E), bulk modulus (B), shear modulus (G), and Poisson's ratio (ν), which indicates that all three RHEAs are ductile materials. Additionally, the calculation results indicate the modulus and hardness of TiMoNbX RHEAs decrease as temperature rises. Comparing with experimental results, the nanoindentation hardness values at 300 K are higher than the calculated values. It can be attributed that the coating was strengthened by Laves phases and dislocation interaction.&#xD., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Bees (Apis mellifera), as important pollinators of agricultural crops, are at risk when pesticides are used. Sulfoxaflor is a new insecticide which acts on the nicotinic acetylcholine receptor (nAChR) in a similar way to neonicotinoids. The goal of this study is to evaluate the toxicity of sulfoxaflor and its effect on the A. mellifera exposure., Results: Initially, developmental indicators such as larval survival, pupation, and eclosion were inhibited by 5.0 mg/L (field concentration) sulfoxaflor. In the pupal stage, fat content was significantly increased, while the glycogen content decreased. In addition, A. mellifera heads were treated with 2.0 mg/L (sublethal concentration) of sulfoxaflor and analyzed by RNA sequencing. The transcriptome results indicated that 2.0 mg/L amounts of sulfoxaflor have adverse effects on the immune, digestive, and nervous systems. Sulfoxaflor down-regulated the expression of many genes involved in immunity, detoxification, the myosin cytoskeleton, sensory neurons, and odor-binding proteins., Conclusion: Field concentration and sublethal concentration were used for the combined analysis of honeybees. The effect of sublethal concentration of sulfoxaflor on honeybees was studied for the first time from the perspective of transcriptome sequencing of honeybee head. A preliminary study was carried out on the stress of sulfoxaflor at sublethal concentration on honeybee workers, which has certain research significance and can provide theoretical basis for the use of sulfoxaflor in the field environment. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background:  Caruncular sebaceous gland hyperplasia (SGH) is an uncommon, benign lesion. Its cause is still unclear. It has not been reported in the pediatric population, with few cases diagnosed in the fourth to eighth decades of life. Case Report:  A 6-year-old boy presented with a slowly growing caruncular mass in the right eye. A diagnosis of caruncular SGH was made by histopathology. The clinical, histopathology, treatment, and prognosis are reviewed. Conclusion:  This is the first described pediatric case of caruncular SGH that occurs since birth. There are many similarities between adult and pediatric caruncular SGH. Surgical excision is the recommended treatment.

Background: The effectiveness and safety of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in elderly patients with locoregionally advanced nasopharyngeal carcinomas (LANPCs) remain subjects of debate. This study evaluated the efficacy of IC+CCRT compared to CCRT alone in elderly LANPC patients., Materials and Methods: This retrospective, single-center study analyzed 335 elderly patients diagnosed with stage III or IVa NPC who received CCRT with or without IC between 2010 and 2016. Kaplan-Meier analysis and log-rank tests were used to estimate and compare survival rates. Multivariate analysis using Cox proportional hazards regression model was conducted to assess prognostic risk factors. Toxicities were compared using the χ 2 test., Results: The median follow-up duration was 69.3 months (interquartile range: 42.7-72.6). Baseline clinical characteristics were well-balanced between groups. No significant differences were observed between IC+CCRT and CCRT for any survival-related endpoints, including overall survival (hazard ratio [HR] = 1.26, 95 % confidence interval [CI]: 0.89-1.77, p = 0.188), locoregional relapse-free survival (HR=1.03, 95 % CI: 0.56-1.91, p = 0.913), distant metastasis-free survival (HR=1.39, 95 % CI: 0.90-2.16, p = 0.139), and failure-free survival (HR = 1.25, 95 % CI: 0.85-1.83, p = 0.255). However, the incidence and severity of acute and late toxicities were significantly higher in the IC+CCRT group compared to the CCRT group., Conclusion: In elderly LANPC patients, the addition of IC to CCRT did not improve survival outcomes, but was associated with significant toxicities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The mitogen-activated protein kinase (MAPK) cascade is crucial cell signal transduction mechanism that plays an important role in plant growth and development, metabolism, and stress responses. The MAPK cascade includes three protein kinases, MAPK, MAPKK, and MAPKKK. The three protein kinases mediate signaling to downstream response molecules by sequential phosphorylation. The MAPK gene family has been identified and analyzed in many plants, however it has not been investigated in alfalfa., Results: In this study, Medicago sativa MAPK genes (referred to as MsMAPKs) were identified in the tetraploid alfalfa genome. Eighty MsMAPKs were divided into four groups, with eight in group A, 21 in group B, 21 in group C and 30 in group D. Analysis of the basic structures of the MsMAPKs revealed presence of a conserved TXY motif. Groups A, B and C contained a TEY motif, while group D contained a TDY motif. RNA-seq analysis revealed tissue-specificity of two MsMAPKs and tissue-wide expression of 35 MsMAPKs. Further analysis identified MsMAPK members responsive to drought, salt, and cold stress conditions. Two MsMAPKs (MsMAPK70 and MsMAPK75) responds to salt and cold stresses; two MsMAPKs (MsMAPK60 and MsMAPK73) responds to cold and drought stresses; four MsMAPKs (MsMAPK1, MsMAPK33, MsMAPK64 and MsMAPK71) responds to salt and drought stresses; and two MsMAPKs (MsMAPK5 and MsMAPK7) responded to all three stresses., Conclusion: This study comprehensively identified and analysed the alfalfa MAPK gene family. Candidate genes related to abiotic stresses were screened by analysing the RNA-seq data. The results provide key information for further analysis of alfalfa MAPK gene functions and improvement of stress tolerance., (© 2024. The Author(s).)

Although vibronic coupling phenomena have been recognized in the excite state dynamics of transition metal complexes, its impact on photoinduced electron transfer (PET) remains largely unexplored. This study investigates coherent wavepacket (CWP) dynamics during PET processes in a covalently linked electron donor-acceptor complex featuring a cyclometalated Pt(ii) dimer as the donor and naphthalene diimide (NDI) as the acceptors. Upon photoexciting the Pt(ii) dimer electron donor, ultrafast broadband transient absorption spectroscopy revealed direct modulation of NDI radical anion formation through certain CWP motions and correlated temporal evolutions of the amplitudes for these CWPs with the NDI radical anion formation. These results provide clear evidence that the CWP motions are the vibronic coherences coupled to the PET reaction coordinates. Normal mode analysis identified that the CWP motions originate from vibrational modes associated with the dihedral angles and bond lengths between the planes of the cyclometalating ligand and the NDI, the key modes altering their π-interaction, consequently influencing PET dynamics. The findings highlight the pivotal role of vibrations in shaping the favorable trajectories for the efficient PET processes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Entoloma is a relatively large genus in Agaricales, with a rich diversity of species and a wide distribution. In this study, seven new species of Entoloma belonging to the subgenus Cubospora have been identified based on morphological and phylogenetic evidence from subtropical regions of China. Morphologically, E. excavatum is characterized by the yellow, depressed, estriate pileus and medium-sized basidiospores; E. lacticolor is recognized by the white and papillate pileus, adnexed lamellae, and presence of clamp connections; E. phlebophyllum is identified by the pink-to-maroon and estriate pileus, and lamellae with lateral veins; E. rufomarginatum differs from other cuboid-spored species by the lamellae edge which is red-brown-underlined; E. subcycneum is characterized by the white pileus and carneogriseum-type cheilocystidia; E. submurrayi is recognized by the pileus margin exceeding the lamellae, 2-layered pileipellis with hyphae of different widths, and the presence of clamp connections; E. tomentosum is identified by the tomentose pileus, heterogeneous lamella edge, and versiform cheilocystidia with brown-yellow contents. Their distinct taxonomic status is confirmed by the positions of the seven new species in both the ITS + LSU and 3-locus (LSU, tef-1α , rpb2 ) phylogenetic trees. Detailed descriptions, color photos, and a key to related species are presented.

Precise control of strength is of significant importance in upper limb functional rehabilitation. Understanding the neuro-muscular response in strength regulation can help optimize the rehabilitation prescriptions and facilitate the relative training process for recovery control. This study aimed to investigate the inherent characteristics of neural-muscular activity during dynamic hand strength adjustment. Four dynamic grip force tracking modes were set by manipulating different magnitude and speed of force variations, and thirteen healthy young individuals took participation in the experiment. Electroencephalography were recorded in the contralateral sensorimotor cortex area, as well as the electromyography from the first dorsal interosseous muscle were collected synchronously. The metrics of the Event-related desynchronization, the electromyography stability index, and the force variation, were used to represent the corresponding cortical neural responses, muscle contraction activities, and the level of strength regulation, respectively; and further neuro-muscular coupling between the sensorimotor cortex and the first dorsal interosseous muscle was investigated by transfer entropy analysis. The results indicated a strong relationship that the increase of force regulation demand would result in a force variation increase as well as a stability reduction in muscle motor unit output. Meanwhile, the intensity of neural response increased in both the α and β frequency bands. As the force regulation demand increased, the strength of bidirectional transfer entropy showed a clear shift from β to the γ frequency band, which facilitate rapid integration of dynamic strength compensation to adapt to motor task changes.

The cultivation of microalgae is significantly influenced by light intensity and utilization efficiency. This study developed a modified Cornet (M-Cornet) model to assess the distribution of light intensity and flux in microalgae cultivation systems. Algal biofilm cultivation represents a more concentrated approach of algal suspension cultivation. Both follow the M-Cornet model and exhibit the same growth rates when cultured under identical conditions. Algal pigments and morphologies greatly impact the light absorption and scattering, resulting in light attenuation in intensity, penetration distance and light flux distribution. Algae varieties exhibit diverse light flux characteristics. 37% - 90% of the incident light is absorbed, of which, 80% to 90% is dissipated as heat. 10% to 63% of the incident light is scattered off the photobioreactor. The overall light utilization efficiency ranges 6% to 13%. The light footprint using the M-Cornet model offers valuable insights for photobioreactors designing and cultivation operating., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lin Chen, Associate professor, Dr. reports financial support was provided by National Key Research and Development Program of China. Tianzhong Liu, Professor,Dr. reports financial support was provided by Shandong Energy Institute of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The existence of heterogeneity has plunged cancer treatment into a challenging dilemma. We profiled malignant epithelial cells from 5 gastric adenocarcinoma patients through single-cell sequencing (scRNA-seq) analysis, demonstrating the heterogeneity of gastric adenocarcinoma (GA), and identified the CCKBR+ stem cell-like cancer cells associated poorly differentiated and worse prognosis. We further conducted targeted analysis using single-cell transcriptome libraries, including 40 samples, to confirm these screening results. In addition, we revealed that FOXOs are involved in the progression and development of CCKBR+ gastric adenocarcinoma. Inhibited the expression of FOXOs and disrupting cancer cell stemness reduce the CCKBR+ GA organoid formation and impede tumor progression. Mechanically, CUT&Tag sequencing and Lectin pulldown revealed that FOXOs can activate ST3GAL3/4/5 as well as ST6GALNAC6, promoting elevated sialyation levels in CCKBR+ tumor cells. This FOXO-sialyltransferase axis contributes to the maintenance of homeostasis and the growth of CCKBR+ tumor cells. This insight provides novel perspectives for developing targeted therapeutic strategies aimed at the treating CCKBR associated gastric cancer., (© 2024. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

The accumulation of soil carbon (C) is crucial for the productivity and ecological function of farmland ecosystems. The balance between microbial carbon dioxide (CO 2 ) emission and fixation determines the sustained accumulation potential of C in soil. Microorganisms involved in this process are highly obscure, thus hindering identification and further application of microorganisms with fertile soil function. In this study, a series of typical upland farmland soils were collected from 29 regions and their microbial community structure and soil C fractions were analyzed. Additionally, the rates of CO 2 emission and fixation in each soil were measured. The results showed that the correlation between soil CO 2 emissions and the SOC concentration was logarithmic, while that between CO 2 fixation and SOC was linear. Bacterial and fungal diversity showed an upward trend with increasing soil C, and their α diversity was significantly correlated with CO 2 fixation, but not correlated with CO 2 emission. Fungi were more associated with soil C than bacteria, and the strength of linkage with soil C varied among the different phyla of microorganisms. Furthermore, the core microbial taxa in soils with low, medium and high SOC levels were identified by discarding redundant amplicon sequence variants, and their community differentiation was significantly driven by soil CO 2 emission and fixation based on Mantel analysis. The high abundance of Chloroflexi, Nitrospirota, Actinobacteria, and Mortierellomycota in core taxa might indicate a high level of SOC level. This study highlights that SOC fluctuations are mainly driven by the core microbial taxa, rather than all microbial taxa in the agricultural system. Our research sheds light on the targeted regulation of the soil microbial community structure in upland farmland for soil fertility enhancement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: Subjective Cognitive Decline (SCD) refers to self-reported cognitive decline with normal global cognition. This study aimed to capture SCD among low educated patients with Parkinson's disease (PD) using a newly established indicator., Methods: We recruited 64 PD patients with low education levels (education ≤12 years) for the study. The presence of SCD was determined based on a Unified Parkinson's Disease Rating Scale Part I (1.1) score ≥ 1. Spearman analysis and multivariate binary logistic regression analyses were conducted to investigate factors associated with the PD-SCD group. The receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the new combined index., Results: The prevalence of SCD in PD patients was 43.75%. Low educated PD-SCD patients had higher scores on the Non-Motor Symptoms Scale (NMSS), Parkinson's Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), as well as higher scores on the UPDRS-I and UPDRS-II, compared to PD patients without SCD. They also demonstrated poorer performance on the Montreal Cognitive Assessment (MoCA), particularly in the domains of executive abilities/attention/language. Multivariate binary regression confirmed the significant association between PD-SCD and MoCA-executive abilities/attention/language. Based on these findings, a combined index was established by summing the scores of MoCA-executive abilities, MoCA-attention, and MoCA-language. ROC analysis showed that the combined index could differentiate PD-SCD patients with an area under the curve (AUC) of 0.876. A score of 12 or less on the combined index had a sensitivity of 73.9% and a specificity of 76.2% for diagnosing PD-SCD., Conclusion: These low education patients with PD-SCD may exhibit potential PD-related pathological changes. It is important for clinicians to identify PD-SCD patients as early as possible. The newly combined index can help capture these low educated PD-SCD patients, with an AUC of 0.867, and is expected to assist clinicians in earlier identification and better management of PD patients., 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 Huang, Wang, Chen, Hu, Qin, Yang, Cui, Chen and Huang.)

(1) Background: Mianning ham is a dry-cured ham from Southwest China, known for its distinct regional characteristics and delicious taste. It is particularly favored by consumers due to its safety, as no artificial nitrites are added during processing. The microbial changes during its different processing stages significantly influence the final product's flavor. This study aims to investigate the changes in microbial communities and flavor compounds across the nine stages of Mianning ham production, from raw material preparation to salting, drying, fermentation, and maturation, using 16S and ITS sequencing, as well as solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS). The goal is to explore the correlation between these changes and provide a basis for process improvement from the initial raw material preparation. (2) Results: The microbiota of Mianning ham across different processing stages mainly consisted of Proteobacteria, Firmicutes, and Ascomycota . A total of 324 volatile compounds were identified, of which 27 were key contributors to the ham's flavor. Aldehydes contributed the most to flavor, with octanal, trans-2-nonenal, and trans, trans-2,4-decadienal being the most significant contributors at various stages. Mature Mianning ham, fermented for 1-3 years, exhibited fresh grass and earthy aromas, buttery and fatty flavors, and a distinctive roasted potato note. Correlation analysis revealed that Cobetia was the primary bacterial contributor to the main flavor compounds, especially prominent in the second year of fermentation. Among fungi, Yamadazyma and Aspergillus positively influenced several key aldehyde flavor compounds throughout the processing stages, significantly contributing to the flavor profile of Mianning ham. (3) Conclusions: Correlation analysis showed that the Mianning ham that matured for two years had the richest and most characteristic flavor. The positive and consistent impact of fungi on the ham's flavor suggests that they may warrant further research and application in Mianning ham production. This provides a theoretical basis for improving the flavor quality and enhancing the market competitiveness of Mianning ham. One of the key features of Mianning ham is its substantial accumulation of hydrocarbons, which surpasses that of hams from other regions in China. A notable characteristic of Mianning ham processing is the absence of artificially added nitrites as antioxidants and color fixatives. Whether this absence is a contributing factor to the significant accumulation of hydrocarbons warrants further investigation.

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E&#95;{QG,1}>10 times the Planck energy E&#95;{Pl} for the linear LIV effect, and E&#95;{QG,2}>6×10^{-8}E&#95;{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

Functionally diverse devices with artificial neuron and synapse properties are critical for neuromorphic systems. We present a two-terminal artificial leaky-integrate-fire (LIF) neuron based on 6 nm Hf 0.1 Zr 0.9 O 2 (HZO) antiferroelectric (AFE) thin films and develop a synaptic device through work function (WF) engineering. LIF neuron characteristics, including integration, firing, and leakage, are achieved in W/HZO/W devices due to the accumulated polarization and spontaneous depolarization of AFE HZO films. By engineering the top electrode with asymmetric WFs, we found that Au/Ti/HZO/W devices exhibit synaptic weight plasticity, such as paired-pulse facilitation and long-term potentiation/depression, achieving >90% accuracy in digit recognition within constructed artificial neural network systems. These findings suggest that AFE HZO capacitor-based neurons and WF-engineered artificial synapses hold promise for constructing efficient spiking neuron networks and artificial neural networks, thereby advancing neuromorphic computing applications based on emerging AFE HZO devices.

Most teas, including white tea, are produced from tender shoots containing both leaf and stem. However, the effect of the stem on white tea quality remains unclear, especially during withering, an essential process. Therefore, this study investigated the withering-induced changes in the leaves and stems of Camellia sinensis cv. 'Fudingdabai' by multi-group analysis. During withering, the levels of catechin and theobromine (i.e., major flavor-related compounds) decreased slightly, mainly in the leaves. The abundance of some proteinaceous amino acids related to fresh taste increased in stems due to increased protein hydrolysis. In addition, changes in biosynthetic pathways caused a decrease in theanine (a major non-proteinaceous amino acid) and an increase in gamma-aminobutyric acid in stems. Terpenes, mainly in the stems, were partially affected by withering. Phenylacetaldehyde, a major contributor to white tea aroma, increased mainly in the stems. These findings reflect the positive contribution of the stem to white tea quality., 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 Ltd. All rights reserved.)

The treatment of internal hemorrhage remains challenging due to the current limited antibacterial capability, hemostatic efficacy, and biocompatibility of hemostatic materials. The TEMPO-oxidized cellulose nanofibers/collagen/chitosan (TCNF/COL/CS) hemostatic aerogel was developed in this work by physically encasing COL in a sandwich structure and electrostatically self-assembling polyanionic TCNF with polycationic CS. In vitro coagulation experiments revealed the favorable procoagulant properties of TCNF/COL/CS along with high adhesion to erythrocytes and platelets. TCNF/COL/CS significantly increased the hemostatic efficacy by 59.8 % and decreased blood loss by 62.2 % in the liver injury model when compared to Surgicel®, the most frequently used hemostatic material. Furthermore, it demonstrated outstanding biodegradability both in vitro and in vivo , and a substantial increase in resistance (96.8 % against E. coli and 95.4 % against S. aureus ) compared to TCNF. The significant hemostatic and biodegradable characteristics of TCNF/COL/CS can be ascribed to its interconnected porous structure, increased porosity, and efficient water absorption, along with the synergistic effect of the three constituents. The TCNF/COL/CS aerogel shows significant potential to control internal bleeding. A novel plant-derived nanocellulose composite aerogel has been described here for the first time; it has outstanding antibacterial characteristics, higher biocompatibility, and outstanding hemostatic characteristics in vivo ., 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.)

Background: There is an urgent need to develop an efficient therapeutic strategy for heart failure with preserved ejection fraction (HFpEF), which is mediated by phenotypic changes in cardiac macrophages. We previously reported that vitamin B-6 inhibits macrophage-mediated inflammasome activation., Objectives: We sought to examine whether the prophylactic use of vitamin B-6 prevents HFpEF., Methods: HFpEF model was elicited by a combination of high-fat diet and N ω -nitro-l-arginine methyl ester supplement in mice. Cardiac function was assessed using conventional echocardiography and Doppler imaging. Immunohistochemistry and immunoblotting were used to detect changes in the macrophage phenotype and myocardial remodeling-related molecules., Results: Co-administration of vitamin B-6 with HFpEF mice mitigated HFpEF phenotypes, including diastolic dysfunction, cardiac macrophage phenotypic shifts, fibrosis, and hypertrophy. Echocardiographic improvements were observed, with the E/E' ratio decreasing from 42.0 to 21.6 and the E/A ratio improving from 2.13 to 1.17. The exercise capacity also increased from 295.3 to 657.7 min. However, these beneficial effects were negated in downstream of kinase (DOK) 3-deficient mice. Mechanistically, vitamin B-6 increased DOK3 protein concentrations and inhibited macrophage phenotypic changes, which were abrogated by an AMP-activated protein kinase inhibitor., Conclusions: Vitamin B-6 increases DOK3 signaling to lower risk of HFpEF by inhibiting phenotypic changes in cardiac macrophages., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Tyramine signaling amplification (TSA) technology is generally applied in immunofluorescence, enzyme-linked immunoassays, in situ hybridization techniques, etc. Successful amplification of fluoresence signals cannot be achieved without excellent fluorescent dyes. BODIPY fluorophore is an ideal probe for cell fluorescence imaging, but pristine BODIPY cannot be direct used in the TSA system. In the paper, the new red-shifted tyramide-conjugated BODIPY (BDP-B/C/D) was synthesized via the Knoevenagel condensation reaction, which based on the tyramide-conjugated BODIPY (BDP-A). The synthesized dyes were combined with tyramine to obtain which could be used as a fluorescent substrate for enzymatic reaction of TSA. By using the selected substrate (BDP-C) in TSA, we found it to be more sensitive than the commercial dye 594 styramide for the detection of low-abundance antigen proteins., 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.)

Root nodule symbiosis within nitrogen-fixing clade (NFC) plants is thought to have arisen from a single gain followed by massive losses in the genomes of ancestral non-nodulating plants. However, molecular evidence supporting this model is limited. Here, we confirm through bioinformatic analysis that NODULES WITH ACTIVATED DEFENSE1 (NAD1) is present only in NFC plants and is thus an NFC-specific gene. Moreover, NAD1 was specifically expressed in nodules. We identified three conserved nodulation-associated cis-regulatory elements (NACE1-3) in the promoter of LjNAD1 from Lotus japonicus that are required for its nodule specific expression. A survey of NFC plants revealed that NACE1 and NACE2 are specific to the Fabales and Papilionoideae, respectively, while NACE3 is present in all NFC plants. Moreover, we found that Nodule inception (NIN) directly binds to all three NACEs to activate NAD1 expression. Mutation of L. japonicus LjNAD1 resulted in the formation of abnormal symbiosomes with enlarged symbiosome space and frequent breakdown of bacteroids in nodules, resembling phenotypes reported for Medicago truncatula Mtnad1 and Mtnin mutants. These data point to NIN-NAD1 as an important module regulating rhizobial accommodation in nodules. The regulation of NAD1 by NIN in the NFC ancestor represent an important evolutionary adaptation for nodulation., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Atomically ordered intermetallic compounds (IMCs) have been extensively studied for exploring catalysts with high activity, selectivity, and longevity. Compared to random alloys, IMCs present a more pronounced geometric and electronic effect with desirable catalytic performance. Their well-defined structure makes IMCs ideal model catalysts for studying the catalytic mechanism. This review focuses especially on elemental composition, electron transfer, and structure/phase evolution under high temperature treatment conditions, providing direct evidence for the migration and rearrangement of metal atoms through electron microscopy. We then present the outstanding applications of IMCs in growing single-walled nanotubes, hydrogenation/dehydrogenation reactions, and electrocatalysis from the perspective of electronic, geometric, strain, and bifunctional effects of ordered IMCs. Finally, the current obstacles associated with the use of in situ techniques are proposed, as well as future research possibilities.