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Fracture healing is a complex process during which the bone restores its structural and mechanical integrity. Collagen networks and minerals are the fundamental components to rebuild the bone matrix in callus. It has been recognized that bone quality could be impaired during aging. However, how the structural and mechanical recovery of fracture healing is influenced by aging, particularly from the perspective of organization and mineralization of the collagen network in callus, remains unclear. A tibial fracture model was established for both the young (5 weeks) and aged mice (68 weeks). On the 21st day postfracture, the characteristics of the collagen network, mineralization, and the nanoscale mechanical properties of the callus were assessed. The results indicated that aging postpones the fracture healing process, leading to incomplete microstructure, less mineral content and mineralization, and weaker mechanical properties of callus. In the aged mice, the internal fixation and mechanical immobilization promoted the mineralization of callus by increasing mineral crystal length and mineral-to-matrix ratio by 48 and 42% compared to the internal fixation and free movement control group, respectively. By contrast, in the young mice, the internal fixation and mechanical immobilization induced disordered collagen fibrils and decreased the crystal length and mineral-to-matrix ratio by 32 and 36%, compared to the internal fixation and free movement control group, respectively. The present findings suggested that the aging-induced structure and mechanical differences of callus during fracture healing initiate from the organization and mineralization of collagen fibrils. Multiscale structural and mechanical analysis suggested mechanical immobilization is beneficial to the structure, composition, and mechanics of callus in the aged mice while impairing the organization and mineralization of collagen fibril in the callus of the young mice. These findings suggested that different mechanical intervention strategies should be adopted for fracture healing at different ages, which provides valuable insights for the clinical treatment of bone fracture.

Recent advances in drug design and compound synthesis have highlighted the increasing need for effective methods of toxicity evaluation. A specialized force sensor, known as the light wavelength-encoded "Chinese guzheng" is developed. This innovative sensor is equipped with optical fiber strings and utilizes a wavelength-encoded fiber Bragg grating (FBG) that is chemically etched to reduce its diameter. This design allows the sensor to detect minimal forces as low as l µN. This sensor is successfully applied to monitor human-induced pluripotent stem cell-derived human-engineered heart tissue (hEHT) models that can self-assemble and contact optical fiber-based strings. The sensor detects micro newton contraction forces in real-time by measuring the wavelength drift resulting from hEHT contractions. In addition, the sensor is precise and durable, exhibiting a fatigue resistance of up to 800 000 cycles, making it suitable for long-term monitoring. The device effectively measured the contractile force of the hEHTs under various physiological conditions, including natural contraction, electrical stimulation, and stretching. Moreover, multichannel detection enables the study and demonstration of short- and long-term effectiveness of multiple drugs. This breakthrough sensor addresses the critical need for high-precision real-time monitoring in drug evaluation and provides a solid foundation for screening drugs to treat cardiomyopathy., (© 2025 Wiley‐VCH GmbH.)

Phlomoides rotata , a traditional medicinal plant, is commonly found on the Tibetan Plateau at altitudes of 3100-5200 m. Its primary active medicinal compounds, flavonoids and phenylethanol glycosides (PhGs), exhibit various pharmacological effects, including hemostatic, anti-inflammatory, antitumor, immunomodulatory, and antioxidant activities. This study analyzed flavonoid and PhG metabolites in the roots of P. rotata collected from Henan County (HN), Guoluo County (GL), Yushu County (YS), and Chengduo County (CD) in Qinghai Province. A total of differentially abundant metabolites (DAMs) including 38 flavonoids and 21 PhGs were identified. Six genes ( UFGT1 , CHS1 , COMT2 , C4H3 , C4H8 , and C4H5 ) and four enzymes (4CL, C4H, PPO, and ALDH) were found to play key roles in regulating flavonoid and PhG biosynthesis in P. rotata roots. With increasing altitude, the relative content of 15 metabolites, the expression of seven genes, and the activity of four enzymes associated with flavonoid and PhG metabolism increased. These findings enhance our understanding of the regulatory mechanisms of flavonoid and PhG metabolism in P. rotata and provide insights into the potential pharmaceutical applications of its bioactive compounds.

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-β-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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The biodiversity of CO 2 -assimilating bacterial communities is pivotal for carbon sequestration in agricultural systems. Changes in the diversity, structure, and activity of the soil chemolithoautotrophic bacteria were examined in four agricultural areas, Dulan (DL), Gonghe (GH), Huzhu (HZ), and Datong (DT) counties in Qinghai Province, where wheat, oilseed rape, and barley were planted. This process was performed using Illumina amplicon sequencing of the ribulose-1,5-bisphosphatecarboxylase/oxygenase (RubisCO) gene ( cbbL Form I) and activity data. The diversity, community, and activity of soil autotrophic CO 2 -fixing bacteria differed significantly across soil sites, whereas cbbL -bearing bacterial diversity and activity were similar across different crop types. RubisCO activity in the HZ region was significantly greater than in the other three regions ( P < 0.001). The overall relative abundance trend of the bacterial taxa was similar among the three crop samples. Moreover, 31, 27, 10, and 8 significant linear discriminant analysis effect sizes were identified in the four regions collected from HZ, DL, DT, and GH, respectively. No significant biomarkers were detected in any of the crop groups. Some soil properties had significant relationships with the autotrophic bacterial community composition., Importance: Agricultural soil plays important roles in carbon fixation during carbon capture and storage. Autotrophic bacteria that utilize inorganic compounds as electron donors for growth fix CO 2 photosynthetically or chemo-autotrophically in diverse ecosystems and affect soil organic carbon sequestration. Soil properties, agronomic management measures, and environmental factors can influence the community composition, abundance, and activity of CO 2 -assimilating bacteria. This study aims at evaluating the effects of different regions and crop types on the abundance, composition, and activity of CO 2 -fixing bacteria in agricultural soil.

La 3-x Te 4 is a very promising high-temperature candidate applied in next-generation Radioisotope Thermoelectric Generators (RTGs). Conventional synthesis of such materials is based on the mechanochemical method, which makes the sample difficult to purify due to the high-energy ball milling. In this report, a novel synthetic method is developed, which utilizes Te-vapor transport and solid-phase diffusion to efficiently produce the RE 3-x Te 4 phases (RE = La, Ce, Pr, Nd). Notably, this method obviates the requirement for high-energy ball-milling instruments, conventionally indispensable in the mechanochemical syntheses. For as-synthesized La 2.74 Te 4 material, a high figure of merit of 1.5 is achieved at 1073 K, owning to the reduced electronic thermal conductivity with metal impurities well eliminated., (© 2024 Wiley‐VCH GmbH.)

Globally, people living with HIV (PLHIV) are at a high risk of syphilis transmission, and Hainan Province has one of the highest syphilis rates in China. However, there is no targeted syphilis screening for HIV patients in Hainan, highlighting the need for data to guide public health interventions. This study aims to assess the incidence of seropositive syphilis and its associated factors among PLHIV. A retrospective cohort study was conducted at HIV care facilities in Haikou, China, recruiting adults living with HIV. The diagnosis of syphilis was confirmed through the TRUST and TPPA tests. Univariate logistic regression was employed to compare syphilis rates across groups, while multivariate logistic regression analysis was conducted to identify factors associated with syphilis infection. Of the 650 participants, 461 (70.9%) were men who have sex with men (MSM). The median age at HIV diagnosis was 28 years, with 154 (23.7%) testing positive for syphilis. The incidence of syphilis was the highest in individuals with prior STDs before HIV (43.1%), followed by those with suboptimal HIV antiretroviral therapy (ART) adherence (38.7%) and MSM (29.5%). The study identified that PLHIV who were diagnosed with HIV through voluntary testing (aOR:1.918, 95%CI:1.113-3.306), were MSM (aOR:2.648, 95%CI:1.269-5.524), had suboptimal HIV ART adherence (aOR:2.002, 95%CI:1.060-3.780), had a history of STDs before HIV (aOR:3.025, 95%CI:1.563-5.857), and had a longer duration of HIV ART (aOR:1.431, 95%CI:1.184-1.730) were at a higher risk of syphilis. The incidence of syphilis is high among PLHIV, especially in MSM and individuals with a history of STDs prior to their HIV diagnosis and suboptimal ART adherence, highlighting the need for targeted interventions and regular screening., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Corticosteroids are the standard first-line treatment for primary immune thrombocytopenia (ITP), with a high initial response but unsatisfactory sustained response (SR). Additionally, corticosteroids usually lead to hyperglycaemia especially in patients with pre-existing type 2 diabetes mellitus (T2DM). Besides reducing the blood glucose levels, metformin was found to have immunomodulatory effects. We hereby conducted a multicentre propensity score matching analysis of corticosteroids plus metformin versus corticosteroids for newly diagnosed ITP patients with pre-existing T2DM. After matching at a ratio of 1:1, there were 57 patients in each group. Baseline characteristics, comorbidities and other medications including concurrent hypoglycaemic medications were balanced between the two groups. No statistical difference was observed in the initial response rate at day 14. It was notable that patients in the metformin group had a significantly higher SR rate and longer duration of response compared to the non-metformin group. Metformin inclusion was associated with a higher incidence of stomach upset, which were generally tolerable. Our study provided evidence that the addition of metformin to corticosteroids might be a promising front-line treatment for newly diagnosed ITP patients with pre-existing T2DM., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

To analyze the role of disulfidptosis in ulcerative colitis (UC), large-scale datasets combined with weighted gene co-expression network analysis (WGCNA) and machine learning were utilized and analyzed. When the hub genes that are associated with UC disease phenotypes and have predictive performance were identified, immune cell infiltration and the CeRNA network were constructed, the role of hub genes in UC pathogenies and biotherapy were investigated, and molecular docking studies and mice-verified tests were carried out to further explore the potential core genes and potential target. Finally, we found 21 DRGs involved in UC pathogenesis, including SLC3A2, FLNA, CAPZB, TLN1, RPN1, etc. Moreover, SLC3A2, TLN1, and RPN1 show a notable correlation with UC inflammatory state, and the expression of DRGs is closely related to the response to UC biotherapy. Our study suggests that disulfidptosis plays a crucial role in the pathogenesis and disease progression of UC. Higher expression of DRGs is commonly observed in moderate to severe UC patients, which may also affect their response to biologic therapies. Among the identified genes, SLC3A2 stands out, providing new insights into the underlying mechanisms of UC and potentially serving as a novel therapeutic target for the treatment of UC.

Salt stress poses a serious challenge to crop production and a significant threat to global food security and ecosystem sustainability. Soil salinization commonly occurs in conjunction with alkalization, which causes combined saline-alkaline stress. Alkaline soil predominantly comprises NaHCO 3 and Na 2 CO 3 and is characterized by a high pH. The combined saline-alkaline stress is more harmful to crop production than neutral salt stress owing to the effects of both elevated salinity and high pH stress. Through genome association analysis of sorghum, a recent study has identified Alkaline tolerance 1 (AT1) as a contributor to alkaline sensitivity in crops. AT1, which is the first gene to be identified as being specifically associated with alkaline tolerance, encodes a G protein γ-subunit (Gγ). Editing of AT1 enhances the yields of sorghum, rice, maize, and millet grown in alkaline soils, indicating that AT1 has potential for generating alkaline-resistant crops. In this review, we summarize the role of AT1 in alkaline tolerance in plants and present a phylogenetic analysis along with a motif comparison of Gγ subunits of monocot and dicot plants across various species., 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 GmbH. All rights reserved.)

NHX5 and NHX6, Arabidopsis endosomal antiporters, play a vital role in facilitating ion and pH homeostasis in endosomal compartments. Studies have found that NHX5 and NHX6 are essential for protein trafficking, auxin homeostasis, and plant growth and development. Here, we report the role of NHX5 and NHX6 in brassinosteroid (BR) signaling. We found that hypocotyl growth was enhanced in nhx5 nhx6 under epibrassinolide (eBR) treatment. nhx5 nhx6 bri1 was insensitive to eBR treatment, indicating that NHX5 and NHX6 are downstream of the BRI1 receptor in BR signaling. Moreover, confocal observation with both hypocotyls and root tips showed that BRI1-YFP localization in the plasma membrane (PM) was reduced in nhx5 nhx6. Interestingly, brefeldin A (BFA) treatment showed that formation of the BFA bodies containing BRI1 and their disassembling were disrupted in nhx5 nhx6. Further genetic analysis showed that NHX5/NHX6 and SYP22 may act coordinately in BR signaling. NHX5 and NHX6 may regulate SYP22 function by modulating cellular K + and pH homeostasis. Importantly, NHX5 and NHX6 colocalize and interact with SYP22, but do not interact with BRI1. In summary, our findings indicate that NHX5/NHX6/SYP22 complex is essential for the regulation of BRI1 recycling and PM localization. The H + -leak facilitated by NHX5 and NHX6 offers a means of controlling BR signaling in plants., 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 GmbH. All rights reserved.)

Lycium chinense is acknowledged for its substantial nutritional benefits, particularly attributed to the high levels of ascorbic acid (AsA) found in its fruits. The "Mengqi No.1" variety of L. chinense , which is cultivated in Qinghai, is known for its high yield and exceptional quality. We utilized the "Mengqi No.1" variety as experimental materials and combined metabolomic, transcriptomic, and physiological analyses to investigate the metabolites, genes, and enzymes related to AsA metabolism in L. chinense fruits. The results revealed nine differential metabolites associated with AsA metabolism in L. chinense fruits across three stages, including 1D-Myo-Inositol-1,4-Bisphosphate, D-Fructose, L-(+)-Arabinose, I-Inositol, L-Arabinitol, D-Galactose-1-P, lactose, α-D-Glucose, and D-Glucose-6-P. Notably, the contents of D-Glucose-6-P, D-Galactose-1-P, and D-Fructose were increased as the fruit developed. Additionally, fresh weight, longitudinal length, and radial width were increased, while the contents of AsA and DHA were decreased. GalDH and DHAR are critical enzymes for the accumulation of AsA and DHA, exhibiting positive correlation coefficient. Furthermore, PMM1 , PMM5 , GME2 , and GME3 were identified as key regulatory genes in the L-Galactose pathway of AsA synthesis, influencing D-Galactose-1-P, D-Glucose-6-P, α-D-Glucose, and D-Fructose. DHAR1 and DHAR2 are considered key positive regulator genes of AsA and DHA in the AsA-GSH cycle. However, the majority of genes (nine) act as negative regulators of AsA and DHA. These findings provide a foundation for the understanding of the regulatory mechanism of AsA metabolism in L. chinense fruits and offer insights into the utilization of AsA from L. chinense .

Selenium (Se) has garnered increasing attention in the field of nutrition, as it is essential for both humans and animals. Certain microorganisms can enrich inorganic selenium and convert it into organic selenium. The growth and metabolomic profiles of six lactobacilli strains exposed to 50 μg/mL of sodium selenite were performed using gas chromatography tandem time-off light mass spectrometry (GC-TOF-MS) analysis. The addition of selenium significantly increased both the population and weight of the Lacticaseibacillus rhamnosus PS5, Lbs. rhamnosus RT-B, Limosilactobacillus reuteri 3630, and Lmb. reuteri 1663 strains, while those of the other two strains decreased. A total of 271 metabolites were determined, with their concentrations ranked from highest to lowest as follows: organic acids and derivatives, oxygen compounds, lipids and lipid-like molecules, and benzenoids. In certain groups, the concentrations of serine, aspartic acid, trehalose, palmitic acid, methylthreonine, and melibiose increased significantly, whereas glucuronic acid, ribose, ornithine, and methionine were downregulated. The metabolic pathways were significantly associated with ABC transporters, glycine, serine, threonine metabolism, and aminobenzoate degradation and other pathways. Based on these findings, we concluded that the transport, absorption, assimilation, and stress response to selenium by lactobacilli in metabolomic changed. Furthermore, the metabolomic alterations among different types of lactobacilli varied primarily due to their distinct properties.

Designing and synthesizing multifunctional hybrid copper halides with near ultraviolet (NUV) light-excited high-energy emission (<500 nm) remains challenging. Here, a pair of broadband-excited high-energy emitting isomers, namely, α-/β-(MePh 3 P) 2 CuI 3 (MePh 3 P=methyltriphenylphosphonium), were synthesized. α-(MePh 3 P) 2 CuI 3 with blue emission peaking at 475 nm is firstly discovered wherein its structure contains regular [CuI 3 ] 2- triangles and crystallizes in centrosymmetric space group P2 1 /c. While β-(MePh 3 P) 2 CuI 3 featuring distorted [CuI 3 ] 2- planar triangles shows inversion symmetry breaking and crystallizes in the noncentrosymmetric space group P2 1 , which exhibits cyan emission peaking at 495 nm with prominent near-unity photoluminescence quantum yield and the excitation band ranging from 200 to 450 nm. Intriguingly, β-(MePh 3 P) 2 CuI 3 exhibits phase-matchable second-harmonic generation response of 0.54×KDP and a suitable birefringence of 0.06@1064 nm. Furthermore, β-(MePh 3 P) 2 CuI 3 also can be excited by X-ray radioluminescence with a high scintillation light yield of 16193 photon/MeV and an ultra-low detection limit of 47.97 nGy/s, which is only 0.87 % of the standard medical diagnosis (5.5 μGy/s). This work not only promotes the development of solid-state lighting, laser frequency conversion and X-ray imaging, but also provides a reference for constructing multifunctional hybrid metal halides., (© 2024 Wiley-VCH GmbH.)

Rare earth (RE) dopants can modulate the bandgap of oxides of indium and gallium and provide extra upconversion luminescence (UCL) abilities. However, relevant UCL fine-tuning strategies and energy mechanisms have been less studied. In this research, InGaO, Ho 3+ monodoped and Yb 3+ /Ho 3+ codoped In 2 O 3 , and Ho 3+ monodoped Yb 3 Ga 5 O 12 nanoparticles (NPs) were synthesized by a solvothermal method. The effects of Yb 3+ and Ho 3+ dopants on the crystal structures, UCL properties, and optical bandgaps of the oxides were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), UCL spectroscopy, and measurements of decay times, pump power dependence, and transmittance spectra. The crystal structures of oxide products of indium and gallium were significantly modified with RE dopants. In 2 O 3 and Yb 3 Ga 5 O 12 were selected as the host materials. For Yb 3+ /Ho 3+ codoped In 2 O 3 NPs, there existed energy transfers from the defect states of In 2 O 3 to Ho 3+ and from Yb 3+ to Ho 3+ . With a fixed Ho 3+ concentration, In 2 O 3 :0%Yb 3+ ,2%Ho 3+ NPs showed the optimal UCL properties mainly due to In 2 O 3 -Ho 3+ energy transfer and Ho 3+ -Yb 3+ energy-back-transfer, while with a fixed Yb 3+ concentration, In 2 O 3 :5%Yb 3+ ,3%Ho 3+ NPs with a slight Yb 2 O 3 impurity and Yb 3 Ga 5 O 12 :2%Ho 3+ NPs did mainly due to Ho 3+ -Ho 3+ cross-relaxation. Besides, the optical bandgaps of In 2 O 3 and Yb 3 Ga 5 O 12 were noticeably broadened with RE dopants. These findings can offer feasible directions for the synthesis and UCL fine-tuning of RE-doped oxides of indium and gallium and improve their multifunction application prospects in the fields of semiconductor and UCL nanomaterials.

Chromatin-based epigenetic memory relies on the symmetric distribution of parental histones to newly synthesized daughter DNA strands, aided by histone chaperones within the DNA replication machinery. However, the mechanism of parental histone transfer remains elusive. Here, we reveal that in fission yeast, the replisome protein Mrc1 plays a crucial role in promoting the transfer of parental histone H3-H4 to the lagging strand, ensuring proper heterochromatin inheritance. In addition, Mrc1 facilitates the interaction between Mcm2 and DNA polymerase alpha, two histone-binding proteins critical for parental histone transfer. Furthermore, Mrc1's involvement in parental histone transfer and epigenetic inheritance is independent of its known functions in DNA replication checkpoint activation and replisome speed control. Instead, Mrc1 interacts with Mcm2 outside of its histone-binding region, creating a physical barrier to separate parental histone transfer pathways. These findings unveil Mrc1 as a key player within the replisome, coordinating parental histone segregation to regulate epigenetic inheritance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.5 years among 1,245 individuals aged 60 years or older who survived infection with the original SARS-CoV-2 strain in Wuhan, China, and 358 uninfected spouses. We show that the overall incidence of cognitive impairment among older COVID-19 survivors was 19.1% at 2.5 years after infection and hospitalization, evaluated using the Telephone Interview for Cognitive Status-40. Cognitive decline primarily manifested in individuals with severe COVID-19 during the initial year of infection, after which the rate of decline decelerated. Severe COVID-19, cognitive impairment at 6 months and hypertension were associated with long-term cognitive decline. These findings reveal the long-term cognitive trajectory of the disease and underscore the importance of post-infection cognitive care for COVID-19 survivors., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

It has been shown that prostaglandin (PG) E 2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE 2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE 2 in male rats. The core temperature (T core ) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE 2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE 2 . We demonstrated that EP3 receptor was a pivotal receptor for PGE 2 -induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE 2 , respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE 2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE 2 ; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (I A ) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE 2 ; however, the I A current density was significantly increased by PGE 2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE 2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE 2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of I A currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO 2 /EPM) is designed and fabricated with porous structures and 3D VO 2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO 2 /EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO 2 . Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO 2 /EPM before and after the phase transition. Moreover, the application of VO 2 /EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices., (© 2024 Wiley‐VCH GmbH.)

Objectives: Noncarious cervical lesions (NCCLs) are multifactorial and can be caused by the anatomical structure of the teeth, erosion, abrasion and abnormal occlusion. The aim of this case-control study was to explore the risk factors for NCCLs., Methods: Cone-beam computed tomography was used to determine whether a wedge-shaped defect existed at the cementoenamel junction. We compared 63 participants with NCCLs with 63 controls without NCCLs, matched for sex, age (±1 year) and toothbrushing-related factors (e.g., type of bristle and brushing patterns, frequency and strength). All participants were asked to complete a questionnaire about self-administered daily diet habits and health condition. Univariate and multivariate logistic regression analyses were conducted to determine the risk factors for NCCLs., Results: Significant variables in the univariate analysis (i.e., p < .2) included frequency of carbonated beverage consumption, sella-nasion-point B angle (SNB) and Frankfort-mandibular plane angle (FMA). Multivariate logistic regression demonstrated that the consumption frequency of carbonated beverages (odds ratio [OR] = 3.147; 95% confidence interval [CI], 1.039-9.532), FMA (OR = 1.100; 95% CI, 1.004-1.204) and SNB (OR = 0.896; 95% CI, 0.813-0.988) was independent influencing factors. The area under the receiver operating characteristic curve (AUC) value of regression Model 1 (established with the frequency of carbonated beverage consumption, FMA, SNB and sleep bruxism) was 0.700 (95% CI, 0.607-0.792; p < .001), and that of regression Model 2 (established using the frequency of carbonated beverage consumption, FMA and SNB) was 0.704 (95% CI, 0.612-0.796; p < .001)., Conclusions: The consumption frequency of carbonated beverages and FMA was risk factors for NCCLs; the higher the frequency of carbonated beverage consumption and FMA, the higher was the probability of NCCLs. SNB was a protective factor for NCCL occurrence; the larger the SNB, the lower was the probability of NCCL occurrence. These findings have further clarified the aetiology of NCCLs and provided clinicians with valuable insights into strategies for preventing the loss of dental tissue., (© 2024 John Wiley & Sons Ltd.)

Background: Microbiomics offers new methods for conducting epidemiological surveys of oral microbiota in large populations. Compared to curette sampling, swab sampling is more convenient and less technically sensitive, making it more suitable for such surveys. To verify the feasibility of using swabs for buccal mucosa sampling in large-scale studies, we collected samples from the buccal mucosa and tooth surfaces of healthy individuals using both swabs and curettes. Microbiomics was employed to analyze and compare microbial abundance and diversity between these two methods., Methods: Four sites were assessed: the buccal mucosa on both sides and the buccal surfaces of the left and right mandibular first molars. Two sampling methods, swab and curette, were used to collect bacterial communities from healthy individuals. Specifically, buccal mucosa samples (n = 10) and tooth surface samples (n = 20) were analyzed using 16 S rDNA gene sequencing. Bacterial signals were detected through fluorescence in situ hybridization (FISH), targeting the bacterial 16 S rDNA gene. Metastats analysis and Wilcoxon test were used., Results: A total of 383 OTUs were detected in the 30 samples, which belonged to 1 kingdom (bacteria), 11 phyla, 23 classes, 40 orders, 75 families, 143 genus, and 312 species. Among them, 223 OTUs were found on both the buccal mucosa and tooth surfaces. The statistics suggest that although there were no significant differences in colony composition, there were differences in the abundance and distribution of colonies on the dental and buccal mucosal surfaces. When detecting oral disease-causing pathogens such as Enterococcus faecalis and Porphyromonas gingivalis, the efficiency of detection is higher when using curette sampling. Compared to right tooth sampling with a curette, the swab sampling group had higher levels of Firmicutes, while Fusobacteria and Bacteroidetes were more prevalent in the curette tissues., Conclusions: In oral health individuals, there is no difference in the bacterial composition of the oral buccal mucosa and the dental surface, differing only in abundance. Thus, the buccal mucosa can act as a substitute for the teeth in epidemiological investigations exploring the bacterial composition of the oral cavity., (© 2024. The Author(s).)

Background: Epidemiological studies have shown an association between periodontitis and nonalcoholic fatty liver disease (NAFLD)-related diseases. However, a causal relationship between these two diseases remains unclear. To examine the causal relationship between these two diseases, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis using genetic markers as proxies., Methods: Statistical summary was obtained from a large genome-wide association study (GWAS) on NAFLD (N = 342,499), nonalcoholic steatohepatitis (NASH, N = 342,499), fibrosis (N = 339,081), cirrhosis (N = 342,499), fibrosis/cirrhosis (N = 334,553), and periodontitis (N = 34,615) in the European ancestry. The inverse variance weighted (IVW) method was used as the main method to estimate the bidirectional association. Sensitivity analysis was performed to evaluate the rigidity of the results., Results: Limited evidence indicated positive causal associations between genetically predicted NAFLD and periodontitis (IVW odds ratio [OR], 1.094; 95% confidence interval [CI], 1.006-1.189; p = 0.036) and between cirrhosis and periodontitis (IVW OR, 1.138; 95% CI, 1.001-1.294; p = 0.048). However, the opposite trend did not indicate a causative effect of periodontitis on NAFLD-related diseases. The sensitivity analysis revealed no obvious pleiotropy or heterogeneity., Conclusions: Our MR analysis provides new evidence in favor of the moderate causal impact of NAFLD on periodontitis. The causal effects of periodontitis on NAFLD-related diseases warrant further investigation., (© 2023 Wiley Periodicals LLC.)

Evidence mapping was performed to systematically search and review the clinical studies about the treatment of insomnia with Chinese patent medicines. The evidence distribution in this field was analyzed and the problems of the studies were summarized. Chinese-and English-language articles of the studies involving the Chinese patent medicines specified in three national drug catalogs for the treatment of insomnia were searched against the databases with the time interval from inception to August 2023. Figures and tables were established to present the results. Finally, 23 Chinese patent medicines were screened out, which were mentioned in 299 articles involving 236 randomized controlled trials(RCTs), 35 non-randomized controlled trials(non-RCTs), 7 retrospective studies, 17 systematic reviews/Meta-analysis, and 4 guidelines/expert recommendations or consensus. Bailemian Capsules, Wuling Capsules, and Yangxue Qingnao Granules were mentioned in a large proportion of articles. The outcome indicators included sleep rating scale, clinical response rate, safety indicators, and anxiety and depression scores. The results showed that the studies about the treatment of insomnia with Chinese patent medicines were growing. However, there was a scarcity of research evidence, and the available studies were single-center with small sample sizes and short periods. These studies spanned broad clinical scopes with inadequately emphasized advantages of TCM and insufficient outcome indicators about quality of life, follow-up, and recurrence rate. RCT exhibited a high risk of bias, and the systematic reviews/Meta-analysis demonstrated low overall quality. The retrospective studies received suboptimal scores, and the non-RCT failed to mention follow-up time, loss rate to follow-up, and sample size estimations, which compromised result reliability. It is recommended that the research protocol for Chinese patent medicines in treating insomnia should adhere to the clinical research standards of TCM. The TCM syndrome score can serves as a crucial outcome measure, and emphasis should be placed on patients' quality of life, follow-up, and recurrence prevention. Measures should be taken to enhance the accessibility and affordability of Chinese patent medicines and strengthen the connection between medical insurance policies and the policies pertaining to Chinese patent medicines. Furthermore, it is advisable to reasonably increase the inclusion of Chinese patent medicines with well-established efficacy and safety evidence in the category A list of medical insurance.

Universal coatings with versatile surface adhesion, good mechanochemical robustness, and the capacity for secondary modification are of great scientific interest. However, incorporating these advantages into a system is still a great challenge. Here, we report a series of catechol-decorated polyallylamines (CPAs), denoted as pseudo- Mytilus edulis foot protein 5 ( pseudo -Mefp-5), that mimic not only the catechol and amine groups but also the backbone of Mefp-5. CPAs can fabricate highly adhesive, robust, multifunctional polyCPA (PCPA) coatings based on synergetic catechol-polyamine chemistry as universal building blocks. Due to the interpenetrating entangled network architectures, these coatings exhibit high chemical robustness against harsh conditions (HCl, pH 1; NaOH, pH 14; H 2 O 2 , 30%), good mechanical robustness, and wear resistance. In addition, PCPA coatings provide abundant grafting sites, enabling the fabrication of various functional surfaces through secondary modification. Furthermore, the versatility, multifaceted robustness, and scalability of PCPA coatings indicate their great potential for surface engineering, especially for withstanding harsh conditions in multipurpose biomedical applications., Competing Interests: The authors declare no competing interests., (© 2024 Published by Elsevier Inc. on behalf of Youth Innovation Co., Ltd.)

Phlomoides rotata is a traditional Chinese herbal medicine that grows in the Qinghai-Tibet Plateau region at a 3100-5000 m altitude. Iridoid compounds are the main active compounds of the P. rotata used as medical ingredients and display anti-inflammatory, analgesic, and hepatoprotective properties. To better understand the biological mechanisms of iridoid compounds in this species, we performed a comprehensive analysis of the transcriptome and metabolome of P. rotata leaves from four different regions (3540-4270 m). Global metabolome profiling detected 575 metabolites, and 455 differentially accumulated metabolites (DAMs) were detected in P. rotata leaves from the four regions. Eight major DAMs related to iridoid metabolism in P. rotata leaves were investigated: shanzhiside methyl ester, 8-epideoxyloganic acid, barlerin, shanzhiside, geniposide, agnuside, feretoside, and catalpin. In addition, five soil physical and chemical indicators in P. rotata rhizosphere soils were analyzed. Four significant positive correlations were observed between alkaline nitrogen and geniposide, exchangeable calcium and geniposide, available potassium and shanzhiside, and available phosphorus and shanzhiside methyl ester. The transcriptome data showed 12 P. rotata cDNA libraries with 74.46 Gb of clean data, which formed 29,833 unigenes. Moreover, 78.91% of the unigenes were annotated using the eight public databases. Forty-one candidate genes representing 23 enzymes involved in the biosynthesis of iridoid compounds were identified in P. rotata leaves. Moreover, the DXS1 , IDI1 , 8-HGO1 , and G10H2 genes associated with iridoid biosynthesis were specifically expressed in P. rotata . The integration of transcriptome and metabolome analyses highlights the crucial role of soil physical and chemical indicators and major gene expression related to iridoid metabolism pathways in P. rotata from different areas. Our findings provide a theoretical foundation for exploring the molecular mechanisms underlying iridoid compound accumulation in P. rotata .

Due to their immobility and possession of underground parts, plants have evolved various mechanisms to endure and adapt to abiotic stresses such as extreme temperatures, drought, and salinity. However, the contribution of long noncoding RNAs (lncRNAs) to different abiotic stresses and distinct rice seedling parts remains largely uncharacterized beyond the protein-coding gene (PCG) layer. Using transcriptomics and bioinformatics methods, we systematically identified lncRNAs and characterized their expression patterns in the roots and shoots of wild type (WT) and ososca1.1 (reduced hyperosmolality-induced [Ca 2+ ] i increase in rice) seedlings under hyperosmolarity and salt stresses. Here, 2937 candidate lncRNAs were identified in rice seedlings, with intergenic lncRNAs representing the largest category. Although the detectable sequence conservation of lncRNAs was low, we observed that lncRNAs had more orthologs within the Oryza . By comparing WT and ososca1.1 , the transcription level of OsOSCA1.1-related lncRNAs in roots was greatly enhanced in the face of hyperosmolality stress. Regarding regulation mode, the co-expression network revealed connections between trans -regulated lncRNAs and their target PCGs related to OsOSCA1.1 and its mediation of hyperosmolality stress sensing. Interestingly, compared to PCGs, the expression of lncRNAs in roots was more sensitive to hyperosmolarity stress than to salt stress. Furthermore, OsOSCA1.1-related hyperosmolarity stress-responsive lncRNAs were enriched in roots, and their potential cis -regulated genes were associated with transcriptional regulation and signaling transduction. Not to be ignored, we identified a motif-conserved and hyperosmolarity stress-activated lncRNA gene ( OSlncRNA ), speculating on its origin and evolutionary history in Oryza . In summary, we provide a global perspective and a lncRNA resource to understand hyperosmolality stress sensing in rice roots, which helps to decode the complex molecular networks involved in plant sensing and adaptation to stressful environments.

Objective: To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis, by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis., Methods: Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected, and the samples of necrotic osteonecrosis from chronic osteomyelitis (necrotic group), and normal bone tissue (control group) were collected. Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform, and the gene expression in bone tissue was calculated by FPKM. The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group. Genes were enriched by GO and KEGG. MAP3K7 and NFATC1 were selected as differential targets in the verification experiments, by using rat osteomyelitis animal model and immunohistochemical analysis., Results: A total of 5548 differentially expressed genes were obtained by high throughput sequencing by comparing the necrotic group and control group, including 2701 up-regulated and 2847 down-regulated genes. The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened, the common genes expressed in both MAPK and osteoclast differentiation pathway were (inhibitor of nuclear factor κ subunit Beta, IκBKβ), (mitogen-activated protein kinase 7, MAP3K7), (nuclear factor of activated t cells 1, NFATC1) and (nuclear factor Kappa B subunit 2, NFκB2). In rat osteomyelitis model, MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue., Conclusion: Based on the transcriptome analysis, the MAPK signaling and osteoclast differentiation pathways were closely related to chronic osteomyelitis, and the key genes IκBKβ, MAP3K7, NFATC1, NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Osteoarthritis (OA) is a degenerative disease with a high prevalence in the elderly population, but our understanding of its mechanisms remains incomplete. Analysis of serum exosomal small RNA sequencing data from clinical patients and gene expression data from OA patient serum and cartilage obtained from the GEO database revealed a common dysregulated miRNA, miR-199b-5p. In vitro cell experiments demonstrated that miR-199b-5p inhibits chondrocyte vitality and promotes extracellular matrix degradation. Conversely, inhibition of miR-199b-5p under inflammatory conditions exhibited protective effects against damage. Local viral injection of miR-199b-5p into mice induced a decrease in pain threshold and OA-like changes. In an OA model, inhibition of miR-199b-5p alleviated the pathological progression of OA. Furthermore, bioinformatics analysis and experimental validation identified Gcnt2 and Fzd6 as potential target genes of MiR-199b-5p . Thus, these results indicated that MiR-199b-5p / Gcnt2 and Fzd6 axis might be a novel therapeutic target for the treatment of OA., Competing Interests: TF, QZ, SL, YP, MT, SZ, XW, JW, FL, SY, QW No competing interests declared, (© 2023, Feng, Zhang et al.)

The improvement of sandy soils with poor seismic properties to modify their dynamic characteristics is of great importance in seismic design for engineering sites. In this study, a series of dynamic tests on sandy soils sandy soils with poor seismic conditions were conducted using the GCTS resonant column system to investigate the improvements effects of different cement contents on dynamic characteristic parameters. The research findings are as follows: The cement content has certain influences on the dynamic shear modulus, dynamic shear modulus ratio, the maximum dynamic shear modulus, and the damping ratio of sandy soils with poor seismic properties. Among them, the influence on dynamic shear modulus is limited, while the damping ratio is significantly affected. The addition of cement to seismic-poor sandy soils significantly enhances their dynamic characteristics. The most noticeable improvement is observed when the cement content is 8%. Through curve fitting analysis, a relationship equation is established between the maximum dynamic shear modulus and the cement content, and the relevant parameters are provided. A comparative test between the improved soils and the remolded soils reveals that the addition of cement significantly improves the seismic performance of the poor soils. The recommended values for the range of variation of the dynamic shear modulus ratio and damping ratio are provided, considering the effect of improvement. These research findings provide reference guidelines for seismic design and engineering sites., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhao 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.)

Long noncoding RNAs (lncRNAs) are RNA molecules longer than 200 nt, which lack the ability to encode proteins and are involved in multifarious growth, development, and regulatory processes in plants and mammals. However, the environmental-regulated expression profiles of lncRNAs in Orinus that may associated with their adaptation on the Qinghai-Xizang (Tibet) Plateau (QTP) have never been characterized. Here, we utilized transcriptomic sequencing data of two Orinus species ( O. thoroldii and O. kokonoricus ) to identify 1624 lncRNAs, including 1119 intergenic lncRNAs, 200 antisense lncRNAs, five intronic lncRNAs, and 300 sense lncRNAs. In addition, the evolutionary relationships of Orinus lncRNAs showed limited sequence conservation among 39 species, which implied that Orinus -specific lncRNAs contribute to speciation adaptation evolution. Furthermore, considering the cis -regulation mechanism, from 286 differentially expressed lncRNAs (DElncRNAs) and their nearby protein coding genes (PCGs) between O. thoroldii and O. kokonoricus , 128 lncRNA-PCG pairs were obtained in O. thoroldii , whereas 92 lncRNA-PCG pairs were obtained in O. kokonoricus . In addition, a total of 19 lncRNA-PCG pairs in O. thoroldii and 14 lncRNA-PCG pairs in O. kokonoricus were found to participate in different biological processes, indicating that the different expression profiles of DElncRNAs between O. thoroldii and O. kokonoricus were associated with their adaptation at different elevations on the QTP. We also found several pairs of DElncRNA nearby transcription factors (TFs), indicating that these DElncRNAs regulate the expression of TFs to aid O. thoroldii in adapting to the environment. Therefore, this work systematically identified a series of lncRNAs in Orinus , laying the groundwork for further exploration into the biological function of Orinus in environmental adaptation.

Phlomoides rotata is a traditional medical plant at 3100-5200 m altitude in the Tibet Plateau. In this study, flavonoid metabolites were investigated in P. rotata from Henan County (HN), Guoluo County (GL), Yushu County (YS), and Chengduo County (CD) habitats in Qinghai. The level of kaempferol 3-neohesperidoside, sakuranetin, and biochanin A was high in HN. The content of limocitrin and isoquercetin was high in YS. The levels of ikarisoside A and chrysosplenol D in GL were high. Schaftoside, miquelianin, malvidin chloride, and glabrene in CD exhibited high levels. The results showed a significant correlation between 59 flavonoids and 29 DEGs. Eleven flavonoids increased with altitude. PAL2, UFGT6, COMT1, HCT2, 4CL4, and HCT3 genes were crucial in regulating flavonoid biosynthesis. Three enzymes CHS, 4CL, and UFGT, were crucial in regulating flavonoid biosynthesis. This study provided biological and chemical evidence for the different uses of various regional plants of P. rotata., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: This study aimed to investigate the relationship between ulcerative colitis (UC) and anxiety and explore its central mechanisms using colitis mice., Methods: Anxiety-like behavior was assessed in mice induced by 3% dextran sodium sulfate (DSS) using the elevated plus maze and open-field test. The spatial transcriptome of the hippocampus was analyzed to assess the distribution of excitatory and inhibitory synapses, and Toll-like receptor 4 (TLR4) inhibitor TAK-242 (10 mg/kg) and AAV virus interference were used to examine the role of peripheral inflammation and central molecules such as Glutamate Receptor Metabotropic 1 (GRM1) in mediating anxiety behavior in colitis mice., Results: DSS-induced colitis increased anxiety-like behaviors, which was reduced by TAK-242. Spatial transcriptome analysis of the hippocampus showed an excitatory-inhibitory imbalance mediated by glutamatergic synapses, and GRM1 in hippocampus was identified as a critical mediator of anxiety behavior in colitis mice via differential gene screening and AAV virus interference., Conclusion: Our work suggests that the hippocampus plays an important role in brain anxiety caused by peripheral inflammation, and over-excitation of hippocampal glutamate synapses by GRM1 activation induces anxiety-like behavior in colitis mice. These findings provide new insights into the central mechanisms underlying anxiety in UC and may contribute to the development of novel therapeutic strategies for UC-associated anxiety., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Chromatin-based epigenetic memory relies on the accurate distribution of parental histone H3-H4 tetramers to newly replicated DNA strands. Mcm2, a subunit of the replicative helicase, and Dpb3/4, subunits of DNA polymerase ε, govern parental histone H3-H4 deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here, using fission yeast heterochromatin inheritance systems that eliminate interference from initiation pathways, we show that a Mcm2 histone binding mutation severely disrupts heterochromatin inheritance, while mutations in Dpb3/4 cause only moderate defects. Surprisingly, simultaneous mutations of Mcm2 and Dpb3/4 stabilize heterochromatin inheritance. eSPAN (enrichment and sequencing of protein-associated nascent DNA) analyses confirmed the conservation of Mcm2 and Dpb3/4 functions in parental histone H3-H4 segregation, with their combined absence showing a more symmetric distribution of parental histone H3-H4 than either single mutation alone. Furthermore, the FACT histone chaperone regulates parental histone transfer to both strands and collaborates with Mcm2 and Dpb3/4 to maintain parental histone H3-H4 density and faithful heterochromatin inheritance. These results underscore the importance of both symmetric distribution of parental histones and their density at daughter strands for epigenetic inheritance and unveil distinctive properties of parental histone chaperones during DNA replication., (© 2024 Fang et al.; Published by Cold Spring Harbor Laboratory Press.)

The invasion-metastasis cascade in head and neck squamous cell carcinoma (HNSCC) is predominantly caused by the interaction between tumor cells and tumor microenvironment, including hypoxia as well as stromal cells. However, the mechanism of hypoxia-activated tumor-stroma crosstalk in HNSCC metastasis remains to be deciphered. Here, we demonstrated that HIF1α was upregulated in HNSCC specimens compared with adjacent normal tissues, whose overexpression was associated with lymph node metastasis and predicted unfavorable prognosis. HIF1α expression correlated positively with the levels of miR-5100 as well as α-SMA, the marker of CAFs. Hypoxia/HIF1α regulated transcriptionally miR-5100 to promote the degradation of its target gene QKI, which acts as a tumor suppressor in HNSCC. Hypoxic HNSCC-derived exosomal miR-5100 promoted the activation of CAFs by orchestrating QKI/AKT/STAT3 axis, which further facilitated HNSCC metastasis. Additionally, miR-5100 derived from plasma exosomes indicated HNSCC malignant progression. In conclusion, our findings illuminate a novel HIF1α/miR-5100/QKI pathway in HNSCC metastasis, and suggest that miR-5100 might be a potential biomarker and therapeutic target for HNSCC., (© 2024. The Author(s).)

Background: To analyze the clinical characteristics and outcomes of children with severe neurological symptoms associated with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the Omicron pandemic in China., Methods: This study used a questionnaire to obtain data from pediatric intensive care unit (PICU) centers in seven tertiary hospitals in Northeast China from December 1, 2022, to January 31, 2023., Results: A total of 255 patients were confirmed to have SARS-CoV-2 infection, and 45 patients (17.65 %) were included in this study. Of these, seven (15.6%) patients died, and the median time from admission to death was 35 h (IQR, 14-120 h). Twenty (52.6%) survivors experienced neurological sequelae. Patients with platelet counts lower than 100 × 10 9 /L had a higher incidence of complications such as multiple organ dysfunction, mechanical ventilation rate, and mortality. Cranial magnetic resonance imaging (MRI) always reveals cerebral tissue edema, with some severe lesions forming a softening site., Conclusion: Children infected with SARS-CoV-2 often exhibit severe neurological symptoms, and in some cases, they may rapidly develop malignant cerebral edema or herniation, leading to a fatal outcome. An early decrease in platelet count may associated with an unfavorable prognosis., Impact: Since early December 2022, China has gradually adjusted its prevention and control policy of SARS-CoV-2; Omicron outbreaks have occurred in some areas for a relatively short period. Due to the differences in ethnicity, endemic strains and vaccination status, there was a little difference from what has been reported about children with SARS-CoV-2 infection with severe neurological symptoms in abroad. This is the first multicenter clinical study in children with nervous system involvement after acute SARS-CoV-2 infection in China, and helpful for pediatricians to have a more comprehensive understanding of the clinical symptoms and prognosis of such disease., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

The remarkable properties of carbon nanotubes (CNTs) have led to promising applications in the field of electromagnetic interference (EMI) shielding. However, for macroscopic CNT assemblies, such as CNT film, achieving high electrical and mechanical properties remains challenging, which heavily depends on the tube-tube interactions of CNTs. Herein, we develop a novel strategy based on metal-organic decomposition (MOD) to fabricate a flexible silver-carbon nanotube (Ag-CNT) film. The Ag particles are introduced in situ into the CNT film through annealing of MOD, leading to enhanced tube-tube interactions. As a result, the electrical conductivity of Ag-CNT film is up to 6.82 × 10 5  S m -1 , and the EMI shielding effectiveness of Ag-CNT film with a thickness of ~ 7.8 μm exceeds 66 dB in the ultra-broad frequency range (3-40 GHz). The tensile strength and Young's modulus of Ag-CNT film increase from 30.09 ± 3.14 to 76.06 ± 6.20 MPa (~ 253%) and from 1.12 ± 0.33 to 8.90 ± 0.97 GPa (~ 795%), respectively. Moreover, the Ag-CNT film exhibits excellent near-field shielding performance, which can effectively block wireless transmission. This innovative approach provides an effective route to further apply macroscopic CNT assemblies to future portable and wearable electronic devices., (© 2024. The Author(s).)

Objectives: To observe the effects of moxibustion at "Zusanli" (ST36) on the expression levels of tumor necrosis factor (TNF)-α, TNF receptor 1 (TNF-R1), p38 mitogen-activated protein kinase (P38 MAPK), and transient receptor potential vanilloid 1 (TRPV1) in the colon tissue of mice with chronic ulcerative colitis (UC), so as to explore the underlying mechanisms of moxibustion in improving visceral hypersensitivity in chronic UC., Methods: Male C57BL/6J mice were randomly divided into normal group, normal with moxibustion (NM) group, model group, and model with moxibustion (MM) group, with 10 mice in each group. The chronic UC model was established by drinking 2.5% dextran sodium sulfate for 3 cycles. Mice in the NM and MM groups received moxibustion at ST36 for 20 min, 5 days per week with a 2-day break, for a total of 4 weeks. The disease activity index (DAI) score of each group was evaluated before and after treatment. The minimum volume threshold of abdominal wall retraction reflex (AWR) was measured to observe the intestinal sensitivity of mice. The colon length was measured. The pathological changes of colon tissue were observed by HE staining. The expression of mucin in colon goblet cells was detected by periodate Scheff staining. The intestinal fibrosis was observed by Masson staining. The number of trypsin-positive cells (i.e., mast cell) and the expression level of TNF-α in colon tissue were detected by immunofluorescence staining. The expression levels of TNF-R1, P38 MAPK and TRPV1 in colon tissue were detected by immunohistochemistry., Results: Compared with the normal group after treatment, the model group showed increased DAI score ( P <0.001), decreased AWR minimum volume threshold ( P <0.01), shortened colon length ( P <0.001), significant inflammatory infiltration in the colon tissue, reduced mucin secretion ( P <0.01), increased collagen fiber deposition ( P <0.001), and elevated expression levels of TNF-α, TNF-R1, P38 MAPK, and TRPV1 ( P <0.001, P <0.01, P <0.05). Compared with the model group, the MM group showed decreased DAI score ( P <0.01), increased AWR minimum volume threshold ( P <0.001), elongated colon length ( P <0.001), reduced inflammatory cell infiltration, improved integrity of mucosal glandular structure, enhanced mucin secretion ( P <0.01), decreased collagen fiber deposition (P<0.001), decreased number of mast cells in the colon tissue ( P <0.001), and decreased expression levels of TNF-α, TNF-R1, P38 MAPK, and TRPV1 ( P <0.001, P <0.01, P <0.05). There were no significant differences in the above index between the NM group and the normal group., Conclusions: Moxibustion can reduce visceral hypersensitivity, alleviate inflammatory infiltration and fibrotic damage in the colon tissue of mice with chronic UC. These effects may be associated with the down-regulation of TNF-α, TNF-R1, P38 MAPK, and TRPV1 expression in colon.

Background: To explore the association between the number of missing teeth and the prevalence of hyperlipidemia in a Chinese adult population., Methods: 13,932 adults were investigated in the TCLSIH cohort study. The number of missing teeth was determined at baseline through a self-reported questionnaire, and then classified into three categories: 0, 1-2, and ≥3. We defined hyperlipidemia as total cholesterol (TC) ≥ 5.17 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density lipoprotein (LDL) cholesterol ≥ 3.37 mmol/L or a self-report of physician-diagnosed hyperlipidemia during follow-up visits. Cox proportional-hazards regression models were employed to assess the relationship between the number of missing teeth and incident hyperlipidemia., Results: A total of 6756 first-incident cases of hyperlipidemia occurred during 42,048 person-years of follow-up (median follow-up, 4.2 years). After adjusted confounders, multivariable HRs and 95% CI for incident of hyperlipidemia across the categories of missing teeth were as follows: in male participants, 1.00 (reference), 1.10 (0.98, 1.22), and 1.03 (0.91, 1.16) ( P for trend = 0.30); in female participants, 1.00 (reference), 1.09 (0.99, 1.19), and 1.18 (1.04, 1.33) ( P for trend < 0.01)., Conclusion: The number of missing teeth is associated with an increased risk of hyperlipidemia in female participants but not in male participants. Systemic chronic inflammation may potentially mediate this association., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Qiao et al.)

Accumulating evidence shows that the abnormal increase in the mortality of intestinal epithelial cells (IECs) caused by apoptosis, pyroptosis, and necroptosis is closely related to the function of mucous membrane immunity and barrier function in patients with ulcerative colitis (UC). As a procedural death path that integrates the above-mentioned many deaths, the role of PANoptosis in UC has not been clarified. This study aims to explore the characterization of PANoptosis patterns and determine the potential biomarkers and therapeutic targets. We constructed a PANoptosis gene set and revealed significant activation of PANoptosis in UC patients based on multiple transcriptome profiles of intestinal mucosal biopsies from the GEO database. Comprehensive bioinformatics analysis revealed five key genes (ZBP1, AIM2, CASP1/8, IRF1) of PANoptosome with good diagnostic value and were highly correlated with an increase in pro-inflammatory immune cells and factors. In addition, we established a reliable ceRNA regulatory network of PANoptosis and predicted three potential small-molecule drugs sharing calcium channel blockers that were identified, among which flunarizine exhibited the highest correlation with a high binding affinity to the targets. Finally, we used the DSS-induced colitis model to validate our findings. This study identifies key genes of PANoptosis associated with UC development and hypothesizes that IRF1 as a TF promotes PANoptosome multicomponent expression, activates PANoptosis, and then induces IECs excessive death.

Objectives: To observe the effect of moxibustion on the polarization of microglia towards M2 direction in Alzheimer's disease (AD) mice through the interleukin-33 (IL-33)/growth stimulating gene 2 protein (ST2) signaling pathway., Methods: Five-month-old APP/PS1 male mice were randomly divided into model and moxibustion (Moxi) groups, and C57BL/6J mice of the same age were as the control group, with 9 mice in each group. In the Moxi group, moxibustion was applied at "Baihui" (GV20) and "Yongquan" (KI1) for 30 min, once a day, 5 days a week for 4 weeks. The spatial learning memory ability was observed by the Morris water maze test. The relative expressions of IL-33 and ST2 in hippocampus were detected by Western blot. The positive expression of amyloid-β (Aβ), phosphorylated Tau (p-Tau), IL-33/ionized calcium binding adapter molecule 1(Iba-1), ST2/Iba-1, arginase 1 (Arg1)/Iba-1 and indu-cible nitric oxide synthase (iNOS)/Iba-1 in hippocampal CA1 region were detected by immunofluorescence., Results: Compared with the control group, the escape latency of the mice in the model group was prolonged ( P <0.001, P <0.01), the number of times to enter the effective area and the percentage of target quadrant swimming time were reduced ( P <0.001), the positive expression of both Aβ and p-Tau, the positive expression of iNOS/Iba-1 in the hippocampal CA1 region was increased ( P <0.001), while the expression of IL-33 and ST2 protein in hippocampal tissue, the positive expression levels of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all decreased ( P <0.05, P <0.001). After treatment, compared with the model group, the escape latency of the mice in the moxibustion group was shortened ( P <0.001, P <0.01), the number of entries into the effective area and the percentage of target quadrant swimming time were increased ( P <0.001), the positive expression of Aβ and p-Tau in the hippocampal CA1 region, and the positive expression of iNOS/Iba-1 were decreased ( P <0.001), while the expression of IL-33 and ST2 protein in the hippocampal tissue, the positive expression of IL-33/Iba-1, ST2/Iba-1 and Arg1/Iba-1 in hippocampal CA1 region were all increased ( P <0.05, P <0.01, P <0.001)., Conclusions: Moxibustion can improve the spatial learning and memory abilities, reduce the pathological deposition of Aβ and p-Tau in APP/PS1 mice, which may be related to its function in up-regulating the IL-33/ST2 signaling pathway to regulate the polarization of microglia towards M2 direction.

Background: Giant keratoacanthoma, a rare variant solitary of keratoacanthoma is characterized by a diameter exceeding 20 mm, rapid growth, and destruction of underlying tissue. Traditionally, it has been considered to be a self-resolving or low-grade squamous proliferation. Due to their atypical appearance, Giant keratoacanthomas may present a diagnostic challenge. Histopathological examination remains the reference standard for distinguishing squamous cell carcinoma (SCC) from keratoacanthoma. Surgical management is still the standard treatment for solitary keratoacanthoma., Case Description: We present the case of a 75-year-old man with a giant keratoacanthoma of the cheek, with a transverse length of 25 mm and a longitudinal length of 30 mm located 30 mm below the earlobe that was surgically excised with no obvious recurrence during follow-up. We used the Intraoperative frozen-section examination, which played a crucial role in ensuring clear margins and complete tumor removal., Conclusions: This case demonstrates that keratoacanthoma can be considered surgically curable and should be distinguished from SCC and other crateriform tumors. After surgical resection of giant isolated keratoacanthoma on the face, the high risk of cosmetic problems should be considered. We suggest free-flap transplantation be performed for functional repair, when the invasion range of the tumor is large and a perforation defect is formed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-23-100/coif). The authors have no conflicts of interest to declare., (2024 AME Case Reports. All rights reserved.)

JTE-607 is an anticancer and anti-inflammatory compound and its active form, compound 2, directly binds to and inhibits CPSF73, the endonuclease for the cleavage step in pre-messenger RNA (pre-mRNA) 3' processing. Surprisingly, compound 2-mediated inhibition of pre-mRNA cleavage is sequence specific and the drug sensitivity is predominantly determined by sequences flanking the cleavage site (CS). Using massively parallel in vitro assays, we identified key sequence features that determine drug sensitivity. We trained a machine learning model that can predict poly(A) site (PAS) relative sensitivity to compound 2 and provide the molecular basis for understanding the impact of JTE-607 on PAS selection and transcription termination genome wide. We propose that CPSF73 and associated factors bind to the CS region in a sequence-dependent manner and the interaction affinity determines compound 2 sensitivity. These results have not only elucidated the mechanism of action of JTE-607, but also unveiled an evolutionarily conserved sequence specificity of the mRNA 3' processing machinery., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear., Materials and Methods: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals., Results: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000∼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells., Conclusion: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.

Background: The acute stage of COVID-19 often presents with neurological manifestations., Objective: This study aims to investigate the long-term neurological effects on survivors., Methods: This study recruited 1,546 COVID-19 survivors from Wuhan, including 1,119 nonsevere cases and 427 severe survivors. Participants were interviewed two years after discharge to report their neurological symptoms. The neurological symptoms of COVID-19 were compared between survivors of severe and nonsevere COVID-19., Results: Among the 1,546 COVID-19 survivors, 44.24% discovered at least one neurological symptom. The most prevalent self-reported symptom was fatigue (28.33%), memory deficit (13.26%), attention deficit (9.96%), myalgia (8.34%), dizziness (3.82%), and headache (2.52%). Severe cases had higher incidences of fatigue, myalgia, memory deficit, attention deficit than nonsevere cases. Older age, severe COVID-19, and comorbidity burden were associated with long-term neurological symptoms., Conclusion: Neurological symptoms are common among COVID-19 survivors, especially in severe cases., Competing Interests: The authors have no conflict of interest to report., (© 2023 – The authors. Published by IOS Press.)

Background: Digital technologies have recently been introduced into the fabrication of removable partial dentures (RPDs). However, it is still unclear whether the digitally fabricated RPDs fit better than conventionally cast ones in the rest region. The aim of this study was to evaluate the fit accuracy in the rest region of RPDs fabricated by digital technologies and compare it to those made by conventional lost-wax (CLW) technique., Methods: A comprehensive search was conducted in Cochrane Library, PubMed, EMbase, Web of Science and SpringerLink. Studies published up to August 2022 were collected. Two authors analyzed the studies independently and assessed the risk of bias on the modified methodological index for non-randomized studies (MINORS) scale. The mean values of gap distance between rests and corresponding rest seats of each study were extracted as outcome. A random-effects model at a significance level of P < 0.05 was used in the global comparison and subgroup analysis was carried out., Results: Overall, 11 articles out of 1214 complied with the inclusion criteria and were selected, including 2 randomized controlled trials (RCTs), 1 non-randomized clinical trial and 8 in vitro studies. Quantitative data from Meta-analysis revealed that fit accuracy in the rest region of RPDs fabricated with CLW showed no statistically significant difference with digital techniques (SMD = 0.33, 95%CI (-0.18, 0.83), P = 0.21). Subgroup analysis revealed a significantly better fit accuracy of CLW-fabricated RPDs in the rest region than either additive manufacturing (AM) groups or indirect groups (P = 0.03, P = 0.00), in which wax or resin patterns are milled or printed before conventional casting. While milled RPDs fit significantly better than cast ones in the rest region (P = 0.00). With digital relief and heat treatment, hybrid manufactured (HM) clasps obtained better fit accuracy in the rest region (P < 0.05). In addition, finishing and polishing procedure had no significant influence in the fit accuracy in all groups (P = 0.83)., Conclusions: RPDs fabricated by digital technologies exhibit comparable fit accuracy in rest region with those made by CLW. Digital technologies may be a promising alternative to CLW for the fabrication of RPDs and additional studies are recommended to provide stronger evidence., Trial Registration: CRD42020201313., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Influenza A viruses can be transmitted indirectly by surviving on the surface of an object. Photodynamic inactivation (PDI) is a promising approach for disinfection of pathogens., Methods: PDI was generated using Hypocrellin A (HA) and red light emitting diode (625-635 nm, 280 W/m 2 ). Effects of the HA-mediated PDI on influenza viruses H1N1 and H3N2 were evaluated by the reduction of viral titers compared to virus control. After selection of the HA concentrations and illumination times, the applicability of PDI was assessed on surgical masks. Reactive oxygen species (ROS) were determined using a 2'-7'-dichlorodihydrofluorescein diacetate fluorescence probe., Results: In solution, 10 μM HA inactivated up to 5.11 ± 0.19 log 10 TCID 50 of H1N1 and 4.89 ± 0.38 log 10 TCID 50 of H3N2 by illumination for 5 and 30 min, respectively. When surgical masks were contaminated by virus before HA addition, PDI inactivated 99.99% (4.33 ± 0.34 log reduction) of H1N1 and 99.40% (2.22 ± 0.39 log reduction) of H3N2 under the selected condition. When the masks were pretreated with HA before virus addition, PDI decontaminated 99.92% (3.11 ± 0.19 log reduction) of H1N1 and 98.71% (1.89 ± 0.20 log reduction) of H3N2 virus. The fluorescence intensity of 2',7'-dichlorofluorescein in photoactivated HA was significantly higher than the cell control (P > 0.05), indicating that HA efficiently generated ROS., Conclusions: HA-mediated PDI is effective for the disinfection of influenza viruses H1N1 and H3N2. The approach could be an alternative to decontaminating influenza A viruses on the surfaces of objects., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: We aimed to use transcriptomics, bioinformatics analysis, and core gene validation to identify the core gene and potential mechanisms for electroacupuncture (EA) treatment of ulcerative colitis (UC)., Materials and Methods: EA was performed in mice after induction of UC via dextran sodium sulfate. Body weight, disease activity index (DAI), colon length, and hematoxylin-eosin of the colon tissue were used to evaluate the effects of EA. Mice transcriptome samples were analyzed to identify the core genes, and further verified with human transcriptome database; the ImmuCellAI database was used to analyze the relationship between the core gene and immune infiltrating cells (IICs); and immunofluorescence was used to verify the results., Results: EA could reduce DAI and histological colitis scores, increase bodyweight and colon length, and improve the expression of local and systemic proinflammatory factors in the serum and colon of UC mice. Eighteen co-differentially expressed genes were identified by joint bioinformatics analyses of mouse and human transcriptional data; Cxcl1 was the core gene. EA affected IICs by inhibiting Cxcl1 expression and regulated the polarization of macrophages by affecting the Th1 cytokine IFN-γ, inhibiting the expression of CXCL1., Conclusions: CXCL1 is the target of EA, which is associated with the underlying immune mechanism related to Th1 cytokine IFN-γ., 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 © 2023 Zhang, Dong, Shen, Li, Huang, Yu and Wu.)

Lamiophlomis rotata is a medicinal plant in Qinghai-Tibet Plateau, in which flavonoid compounds are the major medicinal components. However, it remains unclear how flavonoid metabolism of L. rotata is influenced by soil properties and microbial community. In this study, we collected L. rotata seedlings and rhizosphere soils from five habitats ranging from 3750 to 4270 m of altitude and analyzed the effects of habitat conditions on flavonoid metabolism. The activities of peroxidase, cellulase, and urease were increased with altitude, while those of alkaline phosphatase, alkaline protease, and sucrase were decreased with altitude. Analysis of OTUs showed that the total number of bacterial genera was higher than that of fungal genera. The highest number of fungal genera was 132, and that of bacterial genera was 33 in Batang (BT) town in Yushu County at an altitude of 3880 m, suggesting that the fungal communities may play a critical role in L. rotata rhizosphere soils. Flavonoids in leaves and roots of L. rotata shared a similar pattern, with a trend of increasing levels with altitude. The highest flavonoid content measured, 12.94 mg/g in leaves and 11.43 mg/g in roots, was from Zaduo (ZD) County at an altitude of 4208 m. Soil peroxidases affected quercetin content in leaves of L. rotata, while the fungus Sebacina affected flavonoid content in leaves and roots of L. rotata. The expression of PAL, F3'H, FLS, and FNS genes showed a declining trend in leaves with altitude, while F3H showed an increasing trend in both leaves and roots. Overall, soil physicochemical properties and microbial community affect flavonoid metabolism in L. rotata in Qinghai-Tibet Plateau. The variations in flavonoid content and gene expression as well as their associations with soil factors revealed the complexity of the growth conditions and genetic makeup in L. rotata habitats of Qinghai-Tibet Plateau., Competing Interests: Declaration of competing interest The authors declare they have no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)