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ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.

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Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Macrófagos , SARS-CoV-2 , Replicación Viral , Animales , Ratones , Células RAW 264.7 , Replicación Viral/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/virología , SARS-CoV-2/efectos de los fármacos , Antivirales/farmacología , Ratones Transgénicos , Pogostemon/química , Citocinas/metabolismo , Apoptosis/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/virología , Pulmón/patología , Glucósidos/farmacología , Glucósidos/aislamiento & purificación , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/uso terapéutico , Enzima Convertidora de Angiotensina 2/metabolismo , Antiinflamatorios/farmacología , Masculino , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Humanos

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Tropomyosin receptor kinase B (TrkB) signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory. The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre- or postsynaptic TrkB resulting in the strengthening of synapses, reflected by long-term potentiation. Postsynaptically, the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca2+/calmodulin-dependent protein kinase II and phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation. In this review, we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders. A reduction of TrkB signaling has been observed in neurodegenerative disorders, such as Alzheimer's disease and Huntington's disease, and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression. Treatment with brain-derived neurotrophic factor is problematic, due to poor pharmacokinetics, low brain penetration, and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform. Although TrkB agonists and antibodies that activate TrkB are being intensively investigated, they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions. Targeting TrkB-postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

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In 2022, mpox virus (MPXV) spread worldwide, causing 99,581 mpox cases in 121 countries. Modified vaccinia Ankara (MVA) vaccine use reduced disease in at-risk populations but failed to deliver complete protection. Lag in manufacturing and distribution of MVA resulted in additional MPXV spread, with 12,000 reported cases in 2023 and an additional outbreak in Central Africa of clade I virus. These outbreaks highlight the threat of zoonotic spillover by Orthopoxviruses. mRNA-1769, an mRNA-lipid nanoparticle (LNP) vaccine expressing MPXV surface proteins, was tested in a lethal MPXV primate model. Similar to MVA, mRNA-1769 conferred protection against challenge and further mitigated symptoms and disease duration. Antibody profiling revealed a collaborative role between neutralizing and Fc-functional extracellular virion (EV)-specific antibodies in viral restriction and ospinophagocytic and cytotoxic antibody functions in protection against lesions. mRNA-1769 enhanced viral control and disease attenuation compared with MVA, highlighting the potential for mRNA vaccines to mitigate future pandemic threats.

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We refresh the design of zero-mode waveguides (ZMWs) by introducing metamaterials that makes the zeroth order resonant mode existence. Of particular importance, the resulting electromagnetic field exhibits nearly constant distribution but not a trivial solution of Maxwell's equation, showing great advantage to equalize the excitation rate of molecules throughout the waveguides. A closed form expression for the wave impedance is derived which is verified by the finite-difference time-domain simulations. Benefitted from the cavity Purcell effect which is lacking in existing ZMWs, fluorescence amplification and lifetime reduction are simultaneously enhanced. A practical design where the excitation volume reduced down to sub-zeptoliter and the fluorescence lifetime shortened to picosecond scale is illustrated. This result makes single molecule real time (SMRT) sensing of biochemical reactions at biophysically relevant concentrations (~ µM) possible, combining off-the-shelf ultrafast lasers.

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Programmable metasurfaces have garnered significant attention for their capacity to dynamically manipulate electromagnetic (EM) waves. In particular, the programmable metasurfaces offer to generate a wide range of EM beams when the appropriate digital coding patterns are designed. Traditionally, optimizing the coding patterns involves time-consuming nonlinear optimization algorithms due to the high computational complexity. In this study, we propose a physics-assisted deep learning (DL) model that can calculate the coding pattern in milliseconds, requiring only a simple depiction of the desired beam. An extended version of the macroscopic model for digital coding metasurface is introduced as the physics-driven component, which can compute the radiation pattern rapidly based on the provided coding pattern. The integration of the macroscopic model ensures to generate the physics-compliant coding designs. We validate the proposed method experimentally by measuring several coding patterns for both single-beam and dual-beam scenarios, which demonstrate good performance of beamforming.

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Metastasis contributes to the increased mortality rate of cancer, but the intricate mechanisms remain unclear. Cancer cells from a primary tumor invade nearby tissues and access the lymphatic or circulatory system. If these cells manage to survive and extravasate from the vasculature into distant tissues and ultimately adapt to survive, they will proliferate and facilitate malignant tumor formation. Traditional two-dimensional (2D) cell cultures offer a rapid and convenient method for validating the efficacy of anticancer drugs within a reasonable cost range, but their utility is limited because of tumors' high heterogeneity in vivo and spatial complexities. Three-dimensional (3D) cell cultures that mimic the physiological conditions of cancer cells in vivo have gained considerable interest. In these cultures, cells assemble into spheroids through gravity, magnetic forces, or their low-adhesion to the plates. Although these approaches address some of the limitations of 2D cultures, they often require a considerable amount of time and cost. Therefore, this study aims to enhance the effectiveness of 3D culture techniques by using microfluidic systems to provide a high-throughput and sensitive pipeline for drug screening. Using these systems, we studied the effects of lanthanide elements, which have garnered interest in cancer treatment, on spheroid formation and cell spreading. Our findings suggest that these elements alter the compactness of cell spheroids and decrease cell mobility.

Asunto(s)

Elementos de la Serie de los Lantanoides , Esferoides Celulares , Esferoides Celulares/efectos de los fármacos , Humanos , Elementos de la Serie de los Lantanoides/toxicidad , Elementos de la Serie de los Lantanoides/farmacología , Técnicas de Cultivo de Célula/métodos , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/toxicidad , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Supervivencia Celular/efectos de los fármacos , Técnicas de Cultivo Tridimensional de Células/métodos , Ensayos de Selección de Medicamentos Antitumorales/métodos

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We reported transport diagrams of self-assembled germanium (Ge) double quantum-dots (DQDs) using direct current measurement under illumination at wavelength (λ) of 850 nm and at the base temperature of 4.5 K. Ge DQDs with a coupling-barrier of Si, tunneling-barriers of Si3N4, and self-aligned p+-Si reservoirs were fabricated in a self-organized CMOS approach. Charge transport through the Ge-DQDs is facilitated by photon-assisted tunneling. Characteristic gate-controlled hexagonal-shaped cells over a wide range of hole occupancy are acquired thanks to hard-wall confinement. Large dimensions (ΔVG > 200 mV) of hexagonal-shaped cells are favored for the operation of charge states, indicating that our Ge DQDs system is less susceptible to shot noises arising from external voltage sources. Estimated intra-QD and inter-QD charging energies are EC,R/EC,L = 48.9 meV/42.7 meV and ECm = 7.8 meV, respectively.

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Various techniques have been described for reconstructing the skin of the penile shaft; however, no universally accepted standard exists for correcting buried penis in adults. We aimed to describe a new technique for correcting an adult-acquired buried penis through a diamond-shaped incision at the penopubic junction. We retrospectively analyzed data from patients treated with our technique between March 2019 and June 2023 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Forty-two adult males with buried penises, with a mean (±standard deviation [s.d.]) age of 26.6 (±6.6) years, underwent surgery. All patients were obese, with an average (±s.d.) body mass index of 35.56 (±3.23) kg m-2. In addition to phalloplasty, 32 patients concurrently underwent circumcision, and 28 underwent suprapubic liposuction. The mean (±s.d.) duration of the operation was 98.02 (±13.28) min. The mean (±s.d.) duration of follow-up was 6.71 (±3.43) months. The length in the flaccid unstretched state postoperatively was significantly greater than that preoperatively (mean ± s.d: 5.55±1.19 cm vs 1.94±0.59 cm, P < 0.01). Only minor complications, such as wound disruption (7.1%) and infection (4.8%), were observed. The mean (±s.d.) score of patient satisfaction was 4.02 (±0.84) on a scale of 5. This technique provides excellent cosmetic and functional outcomes with a minimal risk of complications. However, additional clinical studies are needed to evaluate the long-term effects of this procedure.

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The ATP-binding cassette (ABC) superfamily is involved in numerous complex biological processes. However, the understanding of ABCs in plant pathogen defense, particularly against Botryosphaeria dothidea, remains limited. In this study, we identified MdABCI17 that plays a positive role in apple resistance to B. dothidea. Overexpression of MdABCI17 significantly enhanced the resistance of apple calli and fruits to B. dothidea. Our findings revealed that the jasmonic acid (JA) content and the expression of genes associated with JA biosynthesis and signal transduction were higher in stable MdABCI17-overexpressing apple calli than that of wild-type after inoculation with B. dothidea. Similar results were obtained for apple fruits with transient overexpression of MdABCI17. Our research indicates that MdABCI17 enhances apple resistance to B. dothidea through the JA signaling pathway. We further determined that MdABCI17 plays a crucial role in the apple's response to JA signaling. Moreover, exogenous methyl jasmonate (MeJA) treatment significantly enhanced the effectiveness of MdABCI17 in boosting apple resistance to B. dothidea. We proposed a positive feedback regulatory loop between MdABCI17-mediated apple resistance to B. dothidea and JA signal. In summary, our study offers new insights into the role of ABC superfamily members in the control of plant disease resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01501-9.

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OBJECTIVE: Accumulating studies reported the crucial roles of tRFs in tumorigenesis. However, their further mechanisms and clinical values remains unclear. This study aimed at the further investigation of tRF-Leu in breast cancer chemotherapy resistance. METHODS: The high-throughput sequencing was performed and identified the downregulation of tRF-Leu in MCF7/ADR cells. The function of tRF-Leu in breast cancer cells and breast cancer chemotherapy resistance was investigated in vitro and in vivo, including colony formation assay, CCK-8 assay, transwell assay and apoptosis assay. The binding site of tRF-Leu on BIRC5 was verified by dual-luciferase assay. RESULTS: tRF-Leu was downregulated in MCF7/ADR cells. Overexpression of tRF-Leu inhibited the migration of breast cancer cells. Furthermore, tRF-Leu could reverse the resistance of MCF7/ADR cells to Adriamycin both in vitro and in vivo. BIRC5 was a target of tRF-Leu, which might be involved in the chemotherapy resistance regulation. CONCLUSION: We demonstrated that tRF-Leu could inhibit the chemotherapy resistance of breast cancer by targeting BIRC5. These findings might identify new biomarkers of breast cancer therapy and bring new strategies to reverse chemotherapy resistance.

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Cymbidium (Orchidaceae: Epidendroideae), with around 60 species, is widely-distributed across Southeast Asia, providing a nice system for studying the processes that underlie patterns of biodiversity in the region. However, phylogenetic relationships of Cymbidium have not been well resolved, hampering investigations of species diversification and the biogeographical history of this genus. In this study, we construct a plastome phylogeny of 56 Cymbidium species, with four well-resolved major clades, which provides a framework for biogeographical and diversification rate analyses. Molecular dating and biogeographical analyses show that Cymbidium likely originated in the region spanning northern Indo-Burma to the eastern Himalayas during the early Miocene (∼21.10 Ma). It then rapidly diversified into four major clades in East Asia within approximately a million years during the middle Miocene. Cymbidium spp. migration to the adjacent regions (Borneo, Philippines, and Sulawesi) primarily occurred during the Pliocene-Pleistocene period. Our analyses indicate that the net diversification rate of Cymbidium has decreased since its origin, and is positively associated with changes in temperature and monsoon intensity. Favorable hydrothermal conditions brought by monsoon intensification in the early Miocene possibly contributed to the initial rapid diversification, after which the net diversification rate was reduced with the cooling climate after the middle Miocene. The transition from epiphytic to terrestrial habits may have enabled adaptation to cooler environments and colonization of northern niches, yet without a significant effect on diversification rates. This study provides new insights into how monsoon activity and temperature changes affected the diversification dynamics of plants in Southeast Asia.

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Hydrophilic metal-organic frameworks (MOFs) are promising for solar steam generation from waste or seawater. In this study, we propose a MOF-based Janus membrane for efficient solar steam generation. We selected MOF-303 for its hydrophilic properties and 1D channels with 6.5 Å cavity diameter, making it an excellent water-absorbing layer. Characterization via Raman spectroscopy and differential scanning calorimetry indicates that the nanoconfinement within MOF-303 can reduce the water evaporation enthalpy, thereby boosting water production efficiency. When deposited on various substrates, MOF-303 aimed to optimize solar steam generation. We enhanced the membrane performance by incorporating carbon black (CB), polydopamine (PDA), and perfluoro-functionalized poly(3,4-ethylenedioxythiophene) (PEDOT-F), materials known for their solar-to-thermal energy conversion capabilities. PEDOT-F, in particular, also served as a hydrophobic layer, preventing salt recrystallization during seawater operation. Under one sun irradiation, the water evaporation flux for deionized water increased from 0.31 to 0.79 kg h-1 m-2 using a porous hydrophilic poly(vinylidene difluoride) substrate and further to 2.36 kg h-1 m-2 with the optimized MOF-303-CB/PDA-PEDOT-F membrane, achieving an energy conversion efficiency of 97%. Additionally, the desalination capability of the MOF-303 membrane effectively reduced metal ion concentrations (Na+, K+, Mg2+, and Ca2+) to meet the WHO drinking water standards. These findings demonstrate the significant potential of the MOF-303-based Janus membrane for practical applications in solar steam generation and desalination, combining high water evaporation rates with excellent energy conversion efficiency.

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Rice bran, which is abundant in dietary fiber and phytochemicals, provides multiple health benefits. Nonetheless, its effects on neuroinflammation and gut microbiota in postmenopausal conditions are still not well understood. This study investigated the effects of rice bran and/or tea seed oil supplementation in d-galactose-injected ovariectomized (OVX) old mice fed a fructose drink. The combination of d-galactose injection, ovariectomy, and fructose drink administration creates a comprehensive model that simulates aging in females under multiple metabolic stressors, including oxidative stress, estrogen deficiency, and high-sugar diets, and allows the study of their combined impact on metabolic disorders and related diseases. Eight-week-old and 6-8-month-old female C57BL/6 mice were used. The mice were divided into six groups: a sham + young mice, a sham + old mice, an OVX + soybean oil, an OVX + soybean oil with rice bran, an OVX + tea seed oil (TO), and an OVX + TO with rice bran diet group. The OVX groups were subcutaneously injected with d-galactose (100 mg/kg/day) and received a 15% (v/v) fructose drink. The rice bran and tea seed oil supplementation formed 10% of the diet (w/w). The results showed that the rice bran with TO diet increased the number of short-chain fatty acid (SCFA)-producing Clostridia and reduced the number of endotoxin-producing Tannerellaceae, which mitigated imbalances in the gut-liver-brain axis. Rice bran supplementation reduced the relative weight of the liver, levels of hepatic triglycerides and total cholesterol; aspartate transaminase and alanine aminotransferase activity; brain levels of proinflammatory cytokines, including interleukin-1ß and tumor necrosis factor-α; and plasma 8-hydroxy-2-deoxyguanosine. This study concludes that rice bran inhibits hepatic fat accumulation, which mitigates peripheral metaflammation and oxidative damage and reduces neuroinflammation in the brain.

Asunto(s)

Fructosa , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Oryza , Ovariectomía , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Femenino , Ratones , Enfermedades Neuroinflamatorias , Fibras de la Dieta/farmacología , Fibras de la Dieta/administración & dosificación , Ácidos Grasos Volátiles/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Galactosa , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos

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Riptortus pedestris (Hemiptera: Alydidae), a common agricultural pest, is the major causative agent of "soybean staygreen." However, the interactions between chemosensory proteins (CSPs) in R. pedestris and host plant volatiles have yet to be comprehensively studied. In this study, we performed real-time fluorescence quantitative polymerase chain reaction (PCR) to analyze the antennal expression of RpedCSP22 and subsequently analyzed the interactions between 21 soybean volatiles, five aggregation pheromones, and RpedCSP22 protein in vitro using a protein expression system, molecular docking, site-directed mutagenesis, and fluorescence competitive binding experiments. The RpedCSP22 protein showed binding affinity to three soybean volatiles (benzaldehyde, 4-ethylbenzaldehyde, and 1-octene-3-ol), with optimal binding observed under neutral pH conditions, and lost binding ability after site-directed mutagenesis. In subsequent RNA interference (RNAi) studies, gene silencing was more than 90 %, and in silenced insects, electroantennographic responses were reduced by more than 75 % compared to non-silenced insects. Moreover, Y-tube olfactory behavioral assessments revealed that the attraction of R. pedestris to the three soybean volatiles was significantly attenuated. These findings suggest that RpedCSP22 plays an important role in the recognition of host plant volatiles by R. pedestris andprovides a theoretical basis for the development of novel inhibitors targeting pest behavior.

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Glycine max , Proteínas de Insectos , Compuestos Orgánicos Volátiles , Animales , Glycine max/metabolismo , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/química , Compuestos Orgánicos Volátiles/metabolismo , Mutagénesis Sitio-Dirigida , Simulación del Acoplamiento Molecular , Hemípteros/metabolismo , Hemípteros/genética , Antenas de Artrópodos/metabolismo , Feromonas/metabolismo , Heterópteros/metabolismo , Heterópteros/genética

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INTRODUCTION: In percutaneous endoscopic lumbar discectomy (PELD), pain occurs when the posterior longitudinal ligament (PLL) is exposed, removed, and decompressed. However, pain characteristics of the PLL stimulated in PELD have not been reported. METHODS: A total of 932 patients underwent PELD under local anesthesia. Pain distribution and intensity were recorded on a posterior body diagram during the operation. Pain intensity was assessed by the visual analog scale scores for the back (VAS-B). The PLL specimens were collected and observed using hematoxylin-eosin (HE) staining and immunohistochemistry. RESULTS: Patients with lumbar disc herniation (LDH) at L4/5 and L5/S1 had pain foci in different regions. The mean VAS-B scores between the ventral and dorsal sides of the PLL were 6.14 ± 0.97 and 4.80 ± 1.15, respectively (P < 0.05). The distribution of nociceptive nerve fibers in the dorsal side was uniform and scattered, while those in the ventral side were mainly distributed near the outer surface of the annulus fibrosus. The positive expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was higher in the ventral side of the PLL than in the dorsal side (P < 0.0001). CONCLUSIONS: Differences in pain distribution and intensity were observed when the PLL was incited at different spinal levels during PELD surgery.

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The c. 270 endemic species of Pedicularis in the Himalaya-Hengduan Mountains (HHM) region exhibit high diversity in geographic distribution, elevational range and floral morphology. Many of these, including the species with the longest corolla tubes and beaked galeas, are monophyletic and represent a putative in situ radiation. In this study, we focus on the representative Clade 3 within the HHM region. We integrate the plastid phylogeny of this clade with environmental data and species distributions to infer environmental correlates of species diversity. We estimate macroevolutionary rates and reconstructed ancestral states for geographic ranges and corolla traits, and analyse patterns of range overlap and niche evolution to assess drivers of diversification in the HHM region. Our results show that the region from northwest Yunnan to southwest Sichuan is the centre of diversity for this clade of Pedicularis. Rates of diversification are associated with precipitation and multiple environmental factors. Multiple range expansions from the Sanjiang (Three Parallel Rivers) region, followed by allopatric speciation across the HHM region, contributed to early rapid diversification. Corolla traits are not significantly associated with species diversification. This study highlights the importance of integrated evidence for understanding species diversification dynamics and contributes to our understanding of the origins of the remarkable richness of plant species in the HHM region.

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BACKGROUND: Although tumor cells undergoing epithelial-mesenchymal transition (EMT) typically exhibit spindle morphology in experimental models, such histomorphological evidence of EMT has predominantly been observed in rare primary spindle carcinomas. The characteristics and transcriptional regulators of spontaneous EMT in genetically unperturbed non-spindled carcinomas remain underexplored. METHODS: We used primary culture combined with RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq), and in situ RNA-seq to explore the characteristics and transcription factors (TFs) associated with potential spontaneous EMT in non-spindled breast carcinoma. RESULTS: Our primary culture revealed carcinoma cells expressing diverse epithelial-mesenchymal traits, consistent with epithelial-mesenchymal plasticity. Importantly, carcinoma cells undergoing spontaneous EMT did not necessarily exhibit spindle morphology, even when undergoing complete EMT. EMT was a favored process, whereas mesenchymal-epithelial transition appeared to be crucial for secondary tumor growth. Through scRNA-seq, we identified TFs that were sequentially and significantly upregulated as carcinoma cells progressed through the EMT process, which correlated with increasing VIM expression. Once upregulated, the TFs remained active throughout the EMT process. ZEB1 was a key initiator and sustainer of EMT, as indicated by its earliest significant upregulation in the EMT process, its exact correlation with VIM expression, and the reversal of EMT and downregulation of EMT-upregulated TFs upon ZEB1 knockdown. The correlation between ZEB1 and vimentin expression in triple-negative breast cancer and metaplastic breast carcinoma tumor cohorts further highlighted its role. The immediate upregulation of ZEB2 following that of ZEB1, along with the observation that the knockdown of ZEB1 or ZEB2 downregulates both ZEB1 and ZEB2 concomitant with the reversal of EMT, suggests their functional cooperation in EMT. This finding, together with that of a lack of correlation of SNAI1, SNAI2, and TWIST1 expression with the mesenchymal phenotype, indicated EMT-TFs have a context-dependent role in EMT. Upregulation of EMT-related gene signatures during EMT correlated with poor patient outcomes, highlighting the biological importance of the model. Elevated EMT gene signatures and increased ZEB1 and ZEB2 expression in vimentin-positive compared to vimentin-negative carcinoma cells within the corresponding primary tumor tissue confirmed ZEB1 and ZEB2 as intrinsic, instead of microenvironmentally-induced, EMT regulators, and vimentin as an in vivo indicator of EMT. CONCLUSIONS: Our findings provide insights into the characteristics and transcriptional regulators of spontaneous EMT in primary non-spindled carcinoma.

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Neoplasias de la Mama , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción , Transición Epitelial-Mesenquimal/genética , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Vimentina/metabolismo , Vimentina/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/genética , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/metabolismo , Línea Celular Tumoral , Animales , Ratones , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo

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OBJECTIVES: Unique lifestyle and cultural factors in China may lead to distinct patterns of risk factors for oral frailty among older adults, especially in regions inhabited by northeastern border minority groups. METHODS: From July to November 2023, a convenience sampling method was employed to select older adults from three communities in Yanji City as the subjects. Data were collected by a set of questionnaires. RESULTS: A total of 478 older adults were included, revealing a prevalence rate of 71.6 % for oral frailty. Factors influencing were found to include age, ethnicity, gender, income, number of chronic diseases, body mass index, drinking, physical frailty, sleep disorders, and attitudes towards aging (p < 0.05). CONCLUSIONS: There is a higher prevalence of oral frailty. It is crucial to prioritize the oral health issues of older adults with high-risk factors and implement targeted intervention measures to reduce and control the occurrence and progression of oral frailty.

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Interleukin (IL)-37, a unique member of the IL-1 family, is known for its anti-inflammatory properties. However, its effects on immune-mediated liver diseases, such as primary biliary cholangitis (PBC) and acute immune-mediated hepatitis, remain unclear. Using mouse models of autoimmune cholangitis and hepatitis induced by 2-OA-OVA and concanavalin A (Con A) respectively, we introduced the human IL-37 gene via a liver-preferred adeno-associated virus vector (AAV-IL-37) to mice, as mice lack endogenous IL-37. Our findings reveal that IL-37 did not affect autoimmune cholangitis. Surprisingly, IL-37 exacerbated inflammation in Con A-induced hepatitis rather than mitigating it. Mechanistic insights suggest that this exacerbation involves the interferon (IFN)-γ pathway, supported by elevated serum IFN-γ levels in AAV-IL-37-treated Con A mice. Specifically, IL-37 heightened the number of hepatic NK and NKT cells, increased the production of the NK cell chemoattractant CCL5, and elevated the frequency of hepatic NK and NKT cells expressing IFN-γ. Moreover, IL-37 enhanced IFN-γ secretion from NK cells when combined with other proinflammatory cytokines, highlighting its synergistic effect in promoting IFN-γ production. These unexpected outcomes underscore a novel role for IL-37 in exacerbating liver inflammation during immune-mediated liver diseases, implicating its influence on NK cells and the production of IFN-γ by these cells.

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Control of the electrochemical environment in living cells is typically attributed to ion channels. Here, we show that the formation of biomolecular condensates can modulate the electrochemical environment in bacterial cells, which affects cellular processes globally. Condensate formation generates an electric potential gradient, which directly affects the electrochemical properties of a cell, including cytoplasmic pH and membrane potential. Condensate formation also amplifies cell-cell variability of their electrochemical properties due to passive environmental effect. The modulation of the electrochemical equilibria further controls cell-environment interactions, thus directly influencing bacterial survival under antibiotic stress. The condensate-mediated shift in intracellular electrochemical equilibria drives a change of the global gene expression profile. Our work reveals the biochemical functions of condensates, which extend beyond the functions of biomolecules driving and participating in condensate formation, and uncovers a role of condensates in regulating global cellular physiology.