Signatures of Adaptation and Purifying Selection in Highland Populations of Dasiphora fruticosa.

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.

Electrostatic tweezer for droplet manipulation.

Various physical tweezers for manipulating liquid droplets based on optical, electrical, magnetic, acoustic, or other external fields have emerged and revolutionized research and application in medical, biological, and environmental fields. Despite notable progress, the existing modalities for droplet control and manipulation are still limited by the extra responsive additives and relatively poor controllability in terms of droplet motion behaviors, such as distance, velocity, and direction. Herein, we report a versatile droplet electrostatic tweezer (DEST) for remotely and programmatically trapping or guiding the liquid droplets under diverse conditions, such as in open and closed spaces and on flat and tilted surfaces as well as in oil medium. DEST, leveraging on the coulomb attraction force resulting from its electrostatic induction to a droplet, could manipulate droplets of various compositions, volumes, and arrays on various substrates, offering a potential platform for a series of applications, such as high-throughput surface-enhanced Raman spectroscopy detection with single measuring time less than 20 s.

Pan-cancer characterization of cell-free immune-related miRNA identified as a robust biomarker for cancer diagnosis.

Minimally invasive testing is essential for early cancer detection, impacting patient survival rates significantly. Our study aimed to establish a pioneering cell-free immune-related miRNAs (cf-IRmiRNAs) signature for early cancer detection. We analyzed circulating miRNA profiles from 15,832 participants, including individuals with 13 types of cancer and control. The data was randomly divided into training, validation, and test sets (7:2:1), with an additional external test set of 684 participants. In the discovery phase, we identified 100 differentially expressed cf-IRmiRNAs between the malignant and non-malignant, retaining 39 using the least absolute shrinkage and selection operator (LASSO) method. Five machine learning algorithms were adopted to construct cf-IRmiRNAs signature, and the diagnostic classifies based on XGBoost algorithm showed the excellent performance for cancer detection in the validation set (AUC: 0.984, CI: 0.980-0.989), determined through 5-fold cross-validation and grid search. Further evaluation in the test and external test sets confirmed the reliability and efficacy of the classifier (AUC: 0.980 to 1.000). The classifier successfully detected early-stage cancers, particularly lung, prostate, and gastric cancers. It also distinguished between benign and malignant tumors. This study represents the largest and most comprehensive pan-cancer analysis on cf-IRmiRNAs, offering a promising non-invasive diagnostic biomarker for early cancer detection and potential impact on clinical practice.

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer.

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

Arc discharge method to fabricate large concave structures for open-access fiber Fabry-Pérot cavities.

We present a novel micro-fabrication technique for creating concave surfaces on the endfacets of photonic crystal fibers. A fiber fusion splicer is used to generate arc discharges to melt and reshape the fiber endfacet. This technique can produce large spherical concave surfaces with roughness as low as 0.12 nm in various types of photonic crystal fibers. The deviation of fabricated surface and a spherical profile in the region of 70 µm in diameter is less than 50 nm. The center of the concave surface and the fiber mode field are highly coincident with a deviation less than 500 nm. Finesse measurements have shown that a Fabry-Pérot cavity composed of the fiber fabricated using this method and a plane mirror maintains finesse of 20000. This method is easy to replicate, making it a practical and efficient approach to fabricate concave surface on fibers for open-access fiber Fabry-Pérot cavities.

Isolation methods, proliferation, and adipogenic differentiation of adipose-derived stem cells from different fat depots in bovines.

The adipose-derived stem cells (ASCs) are a valuable resource for regenerative medicine and essential materials for research in fat deposition. However, the isolation procedure of ASCs has not been standardized and needs to be harmonized; differences in proliferation and adipogenic differentiation of ASCs obtained from different fat depots have not been well characterized. In the present study, we compared the efficiency of ASCs isolation by enzymatic treatment and explant culture methods and the proliferation ability and adipogenic differentiation potential of ASCs isolated from subcutaneous and visceral fat depots. The explant culture method was simple and with no need for expensive enzymes while the enzymatic treatment method was complex, time consuming and costly. By the explant culture method, a larger number of ASCs were isolated from subcutaneous and visceral fat depots. By contrast, fewer ASCs were obtained by the enzymatic treatment method, especially from visceral adipose. ASCs isolated by the explant culture method performed well in cell proliferation and adipogenic differentiation, though they were slightly lower than those by the enzymatic treatment method. ASCs isolated from visceral depot demonstrated higher proliferation ability and adipogenic differentiation potential. In total, the explant culture method is simpler, more efficient, and lower cost than the enzymatic treatment method for ASCs isolation; compared with visceral adipose, subcutaneous adipose is easier to isolate ASCs; however, the visceral ASCs are superior to subcutaneous ASCs in proliferation and adipogenic differentiation.

Highly Stretchable, Fast Self-Healing, Self-Adhesive, and Strain-Sensitive Wearable Sensor Based on Ionic Conductive Hydrogels.

Conductive hydrogels integrate the conductive performance and soft nature, which is like that of human skin. Thus, they are more suitable for the preparation of wearable human-motion sensors. Nevertheless, the integration of outstanding multiple functionalities, such as stretchability, toughness, biocompatibility, self-healing, adhesion, strain sensitivity, and durability, by a simple way is still a huge challenge. Herein, we have developed a multifunctional chitosan/oxidized hyaluronic acid/hydroxypropyl methylcellulose/poly(acrylic acid)/tannic acid/Al3+ hydrogel (CS/OHA/HPMC/PAA/TA/Al3+) by using a two-step method with hydroxypropyl methylcellulose (HPMC), acrylic acid (AA), tannic acid (TA), chitosan (CS), oxidized hyaluronic acid (OHA), and aluminum chloride hexahydrate (AlCl3·6H2O). Due to the synergistic effect of dynamic imine bonds between CS and OHA, dynamic metal coordination bonds between Al3+ and -COOH and/or TA as well as reversible hydrogen, the hydrogel showed excellent tensile property (elongation at break of 3168%) and desirable toughness (0.79 MJ/m3). The mechanical self-healing efficiency can reach 95.5% at 30 min, and the conductivity can recover in 5.2 s at room temperature without stimulation. The favorable attribute of high transparency (98.5% transmittance) facilitates the transmission of the optical signal and enables visualization of the sensor. It also shows good adhesiveness to various materials and is easy to peel off without residue. The resistance of the hydrogel-based sensors shows good electrical conductivity (2.33 S m-1), good durability, high sensing sensitivity (GF value of 4.12 under 1600% strain), low detection limit (less than 1%), and short response/recovery time (0.54/0.31 s). It adhered to human skin and monitored human movements such as the bending movements of joints, swallowing, and speaking successfully. Therefore, the obtained multifunctional conductive hydrogel has great potential applications in wearable strain sensors.

First principles studies on the adsorption of rare base-pairs on the surface of B/N atom doped γ-graphyne.

Rare base-pairs consists of guanine (G) paired with rare bases, such as 5-methylcytosine (5-meCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-caCyt), and 5-formylcytosine (5-fCyt), have become the focus of epigenetic research because they can be used as markers to detect some chronic diseases and cancers. However, the correlation detection of these rare base-pairs is limited, which in turn limits the development of diagnostic tests and devices. Herein, the interaction of rare base-pairs adsorbed on pure and B/N-doped γ-graphyne (γ-GY) nanosheets was explored using the density functional theory. The calculated adsorption energy showed that the system of rare base-pairs on B-doped γ-GY is more stable than that on pure γ-GY or N-doped γ-GY. Translocation time values indicate that rare base-pairs can be successfully distinguished as the difference in their translocation times is very large for pure and B/N-doped γ-GY nanosheets. Meanwhile, sensing response values illustrated that pure and B-doped γ-GY are the best for G-5-hmCyt adsorption, while the N-doped γ-GY is the best for G-Cyt adsorption. The findings indicate that translocation times and sensing response can be used as detection indexes for pure and B/N doped γ-GY, which will provide a new way for experimental scientists to develop the biosensor components.

Scaffolding mechanism of arrestin-2 in the cRaf/MEK1/ERK signaling cascade.

Arrestins were initially identified for their role in homologous desensitization and internalization of G protein-coupled receptors. Receptor-bound arrestins also initiate signaling by interacting with other signaling proteins. Arrestins scaffold MAPK signaling cascades, MAPK kinase kinase (MAP3K), MAPK kinase (MAP2K), and MAPK. In particular, arrestins facilitate ERK1/2 activation by scaffolding ERK1/2 (MAPK), MEK1 (MAP2K), and Raf (MAPK3). However, the structural mechanism underlying this scaffolding remains unknown. Here, we investigated the mechanism of arrestin-2 scaffolding of cRaf, MEK1, and ERK2 using hydrogen/deuterium exchange-mass spectrometry, tryptophan-induced bimane fluorescence quenching, and NMR. We found that basal and active arrestin-2 interacted with cRaf, while only active arrestin-2 interacted with MEK1 and ERK2. The ATP binding status of MEK1 or ERK2 affected arrestin-2 binding; ATP-bound MEK1 interacted with arrestin-2, whereas only empty ERK2 bound arrestin-2. Analysis of the binding interfaces suggested that the relative positions of cRaf, MEK1, and ERK2 on arrestin-2 likely facilitate sequential phosphorylation in the signal transduction cascade.

Polymorphism of ADAM12, DPP6 and PRKN genes and their associations with milk production traits in Holstein.

Milk production traits as the most important economic traits of dairy cows, they directly reflect the benefits of breeding and the economic benefits of pasture. In this study, A disintegrin and metalloproteinase-12 (ADAM12), Parkinson's disease gene 2 (PRKN) and dipeptidyl peptidase-like protein subtype 6 (DPP6) polymorphism in 384 Chinese Holstein cows were detected by time-of-flight mass spectrometry and through statistical analysis using software such as Popgene 32, SAS 9.4 and Origin 2022, the relationship between single nucleotide polymorphisms (SNPs) of three genes with four milk production traits such as daily milk yield (DMY), milk fat percentage (MFP), milk protein percentage (MPP) and somatic cell score (SCS) was verified at molecular level. The results showed that four polymorphic loci (116,467,133, 116,604,487, 116,618,268 and 116,835,111) of DPP6 gene, two polymorphic loci (97,665,052 and 97,159,837) of PRKN gene and two polymorphic loci (45,542,714 and 45,553,888) of ADAM12 gene were detected. PRKN-97665052, DPP6-116467133, ADAM12-45553888, DPP6-116604487 and DPP6-116835111 were all in Hardy-Weinberg equilibrium state (p > .05). ADAM12-45542714, PRKN-97159837 and PRKN-97665052 were moderately polymorphic (0.25 ≤ PIC <0.50) in Holstein. It is evident that the selection potential and genetic variation of these five loci are relatively large, and the genetic richness is relatively high. The correlation analysis of different genotypes between these eight loci and milk production traits of Holstein showed that ADAM12-45542714 and DPP6-116835111 (p < .01) had an extremely significant effects on the DMY of Chinese Holstein in Ningxia, while PRKN-97665052 had an extremely significant effect on MFP (p < .01). The effect of PRKN-97665052 and DPP6-116467133 on MPP of Holstein were extremely significant (p < .01). DPP6-116618268 had an extremely significant effect on the SCS of Holstein in Ningxia (p < .01), and AA genotype individuals showed a higher SCS than GG genotype individuals; the other two loci (ADAM12-45553888 and DPP6-116604487) had no significant effects on milk production traits of Holstein (p > .05). In addition, through the joint analysis of DPP6, PRKN and ADAM12 gene loci, it was found that the interaction effect between the three gene loci could significantly affect the DMY, SCS (p < .01) and MPP (p < .05). In conclusion, several different loci of DPP6, PRKN and ADAM12 genes can affect the milk production traits of Holstein to different degrees. PRKN, DPP6 and ADAM12 genes can be used as potential candidate genes for milk production traits of Holstein for marker-assisted selection, providing theoretical basis for breeding of Holstein.

BNIP3 as a potential biomarker for the identification of prognosis and diagnosis in solid tumours.

BACKGROUND: Traditional radiotherapy and chemotherapy have been intensively studied for their role in the treatment of tumours. However, these therapies often cause side effects for patients, which calls for the development of novel treatment options for tumours. B-cell lymphoma-2 (Bcl-2)/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) reportedly apoptosis-inducing effects in tumour cells and is associated with the progression and treatment of multiple tumours. Nevertheless, little is known about its potential role in tumour diagnosis and targeted therapy. FINDINGS: The results of the study demonstrated that the interaction of BNIP3 with HDAC1 may affect the progression of breast invasive cancer (BRCA), sarcoma (SARC), kidney renal clear cell carcinoma (KIRC), and low-grade glioma (LGG). BNIP3 seemed to exert its effects in BRCA and SARC primarily through gene silencing and integrator complex, and in KIRC and LGG, mainly by affecting olfactory function, suggesting that targeted therapy can be developed based on the above signalling pathway and downstream molecules. INTERPRETATION: BNIP3 has emerged as a promising therapeutic and diagnostic target for BRCA, SARC, KIRC, and LGG, providing new insights into tumour molecular therapies in the clinic.

Anaplasma phagocytophilum Ats-1 enhances exosome secretion through Syntenin-1.

Anaplasma phagocytophilum is an intracellular obligate parasite that causes granulocytic anaplasmosis. Effector Ats-1 is an important virulence factor of A. phagocytophilum. Multiomics screening and validation has been used to determine that Ats-1 regulates host cell apoptosis and energy metabolism through the respiratory chain mPTP axis. In this study, a total of 19 potential binding proteins of Ats-1 in host cells were preliminarily screened using a yeast two-hybrid assay, and the interaction between syntenin-1 (SDCBP) and Ats-1 was identified through immunoprecipitation. Bioinformatics analysis showed that SDCBP interacted with SDC1, SDC2, and SDC4 and participated in the host exosome secretion pathway. Further studies confirmed that Ats-1 induced the expression of SDC1, SDC2, and SDC4 in HEK293T cells through SDCBP and increased the exosome secretion of these cells. This indicated that SDCBP played an important role in Ats-1 regulating the exosome secretion of the host cells. These findings expand our understanding of the intracellular regulatory mechanism of A. phagocytophilum, which may enhance its own infection and proliferation by regulating host exosome pathways.

Self-healing, self-adhesive, stretchable and flexible conductive hydrogels for high-performance strain sensors.

Conductive hydrogels have been widely studied for their potential application as wearable sensors due to their flexibility and biocompatibility. However, the simultaneous incorporation of excellent stretchability, toughness, conductivity, self-healing, and adhesion via a simple method remains a great challenge. Herein, a multifunctional hydrogel with self-adhesion, self-healing, conductivity, and mechanical properties was fabricated by ionic cross-linking of chitosan (CS), the acrylic acid (AA) polymer, and tea polyphenols (TPs) in the presence of graphitized carbon nanotubes (CNTs) in this work. The resultant hydrogel has unique self-healing properties (94.11% for strain self-healing and 90.60% for stress self-healing) and mechanical properties. The fracture stress was 0.075 MPa when the strain was 1184%, and the toughness reached 0.48 MJ m-3. The synergistic effect of free ions and CNTs endows the hydrogel with an excellent electrical conductivity (6.67 S m-1). Moreover, the hydrogel can adhere to various organic and inorganic materials. It exhibits repeatable self-adhesion to human skin and can be peeled off completely without any residual, irritation or allergic reactions. Additionally, the hydrogel also has good strain sensitivity and exhibits stable output signals in motion monitoring of the human body as a biosensor. Therefore, this work provides a new prospect for the design of multifunctional hydrogels for their potential applications in wearable biosensors.

Ab initio studies on graphyne (GY) for the detection of rare bases in DNA.

Graphyne (GY) and functionalized GY have become cutting-edge research materials for the scientific community. In the present work, the adsorption of rare bases -cytosine (Cyt), 5-methylcytosine (5-meCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-formoxylcytosine (5-fCyt), and 5-carboxylcytosine (5-caCyt) on pristine, B- and N-doped γ-GY was investigated by the first-principles density functional method; methods were designed to distinguish these rare bases by the translocation time and sensitivity. Initially, the stability of pristine, B- and N-doped γ-GY was ascertained by the cohesion energy, and the electronic properties were also analyzed by the energy gap and density of state (DOS). When adsorbing over pristine γ-GY, the translocation times of rare bases were 1.34 × 101, 4.71 × 101, 1.19 × 104, 3.77 × 10-1 and 1.93 × 101 s, respectively. The sensitivities were 2.19%, 0.88%, 0.22%, 2.41%, and 0.88%, respectively, which indicates that they were not clearly separated. By doping the impurity atom, the electronic properties can be fine-tuned to change their selectivity. When adsorbing on the B-doped γ-GY, these rare bases showed sensitivities of 24.69%, 27.20%, 43.32%, 29.97%, and 32.24%, respectively. The rare bases showed sensitivities of 10.15%, 9.02%, 17.29%, 0.38%, and 3.76%, respectively, when adsorbing over the N-doped γ-GY, which greatly increases selectivities for recognization. Thus, these results indicate that pristine and doped γ-GY, as the electrical sensing material, can be used to detect rare bases.

Oenological characteristics of two indigenous Starmerella bacillaris strains isolated from Chinese wine regions.

To broaden knowledge about the oenological characteristics of Starmerella bacillaris, the influence of two Chinese indigenous S. bacillaris strains on the conventional enological parameters and volatile compounds of Cabernet Sauvignon wines were investigated under different inoculation protocols (single inoculation and simultaneous/sequential inoculation with the commercial Saccharomyces cerevisiae EC1118). The results showed that the two S. bacillaris strains could complete alcohol fermentation alone under high sugar concentrations while increasing the content of glycerol and decreasing the content of acetic acid. Compared with wines fermented by EC1118 single inoculation, S. bacillaris single inoculation and S. bacillaris/EC1118 sequential inoculation increased the contents of isobutanol, ethyl isobutanoate, terpenes, and ketones and decreased the contents of isopentanol, phenylethyl alcohol, fatty acids, acetate esters, and total ethyl esters. Furthermore, for S. bacillaris/EC1118 simultaneous inoculation, the concentrations of ethyl esters were increased, contributing to a higher score of "floral" and "fruity" notes in agreement with sensory analysis. KEY POINTS: • S. bacillaris single and simultaneous/sequential inoculation. • Conventional enological parameters and volatile compounds were investigated. • S. bacillaris/EC1118 simultaneous fermentation increased ethyl esters.

A long non-coding RNA lnc210 promotes adipogenic differentiation of buffalo intramuscular adipocytes.

Intramuscular fat (IMF) content is one of the most significant factors influencing beef quality in terms of tenderness, flavor, and juiciness. Thus, internal factors affecting IMF deposition have received considerable attention for decades. In this study, we demonstrated a long non-coding RNA, lnc210, promoted adipogenic differentiation of buffalo intramuscular adipocytes. lnc210 was rich in adipose tissue and showed increased expression with the adipogenic differentiation of buffalo intramuscular adipocytes. lnc210 was mainly expressed in the nucleus of adipocytes. Full-length lnc210 was obtained by rapid amplification of cDNA ends technology. lnc210 overexpression promoted lipid accumulation by upregulating the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) and CCAAT enhancer binding protein alpha (C/EBPα) in buffalo intramuscular adipocytes. These results provide a basis for an in-depth analysis of the role of lnc210 in accelerating IMF deposition in buffaloes.

Enantioselective C3-Allylation of Pyridines via Tandem Borane and Palladium Catalysis.

Herein, we report a one-pot method for enantioselective C-H allylation of pyridines at C3 via tandem borane and palladium catalysis. This method involves borane-catalyzed pyridine hydroboration to generate dihydropyridines, then palladium-catalyzed enantioselective allylation of the dihydropyridines with allylic esters, and finally air oxidation of the allylated dihydropyridines to afford the products. This method enables the introduction of an allylic group at C3 with excellent regio- and enantioselectivities.

TRPV1 participates in the protective effect of propolis on colonic tissue of ulcerative colitis. / TRPV1å‚ä¸Žèœ‚èƒ¶å¯¹æºƒç–¡æ€§ç»“è‚ ç‚Žç»“è‚ ç»„ç»‡çš„ä¿æŠ¤ä½œç”¨.

OBJECTIVES: Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) mainly characterized by inflammation, ulceration and erosion of colonic mucosa and submucosa. Transient receptor potential vanilloid 1 (TRPV1) is an important mediator of visceral pain and inflammatory bowel disease. This study aims to investigate the protective effect of water soluble propolis (WSP) on UC colon inflammatory tissue and the role of TRPV1. METHODS: Male SD rats were randomly divided into 6 groups (n=8): a normal control (NC) group, an ulcerative colitis model (UC) group, a low-WSP (L-WSP) group, a medium-WSP (M-WSP) group, a high-WSP (H-WSP) group, and a salazosulfapyridine (SASP) group. The rats in the NC group drank water freely, and the other groups drank 4% dextran sulfate sodium (DSS) solution freely for 7 d to replicate the ulcerative colitis model. Based on the successful replication of the UC, the L-WSP, M-WSP, and H-WSP groups were given 50, 100, and 200 mg/kg of water-soluble propolis by gavage for 7 d, and the SASP group was given 100 mg/kg of sulfasalazine by gavage for 7 d. The body weight of rats in each group was measured at the same time every day, the fecal traits and occult blood were observed to record the disease activity index (DAI). After intragastric administration, the animals were sacrificed after fasted 24 h. Serum and colonic tissue were collected, and the changes of MDA, IL-6 and TNF-α were detected. The pathological changes of colon tissues were observed by HE staining, and the expression of TRPV1 in colon tissues was observed by Western blotting, immunohistochemistry, and immunofluorescence. RESULTS: The animals in each group that drank DSS freely showed symptoms such as weight loss, decreased appetite, depressed state, and hematochezia, indicating that the model was successfully established. Compared with the NC group, DAI scores of other groups were increased (all P<0.05). MDA, IL-6, TNF-α in serum and colon tissues of the UC group were increased compared with the NC group (all P<0.01), and they were decreased after WSP and SASP treatment (all P<0.01). The results of showed that the colon tissue structure was obviously broken and inflammatory infiltration in the UC group, while the H-WSP group and the SASP group significantly improved the colon tissue and alleviated inflammatory infiltration. The expression of TRPV1 in colon tissues in the UC group was increased compared with the NC group (all P<0.01), and it was decreased after WSP and SASP treatment. CONCLUSIONS: WSP can alleviate the inflammatory state of ulcerative colitis induced by DSS, which might be related to the inhibition of inflammatory factors release, and down-regulation or desensitization of TRPV1.

Multiomics analyses reveals Anaplasma phagocytophilum Ats-1 induces anti-apoptosis and energy metabolism by upregulating the respiratory chain-mPTP axis in eukaryotic mitochondria.

BACKGROUND: Anaplasma translocated substrate 1 (Ats-1) is an effector of type 4 secretory systems (T4SS) and the main virulence factor of Anaplasma phagocytophilum. Ats-1 is involved in the regulation of host cell biological processes, but the specific molecular mechanism of its action is unclear. RESULTS: In this study, we identified Ats-1 as involved in mitochondrial respiratory regulation of HEK293T cells by multi-omics analysis. After intracellular expression of Ats-1, adenosine triphosphate levels and the proliferation of HEK293T cells were both up-regulated, while HEK293T cells apoptosis was inhibited. Ats-1 targeted translocation to the mitochondria where it up-regulated the expression of NDUFB5, NDUFB3, NDUFS7, COX6C, and SLC25A5, thereby enhancing energy production and inhibiting HEK293T cells apoptosis while enhancing HEK293T cells proliferation, and ultimately facilitating Anaplasma phagocytophilum replication in HEK293T cells. CONCLUSIONS: This study demonstrated that Anaplasma phagocytophilum Ats-1 induces anti-apoptosis and energy metabolism by upregulating the respiratory chain-mPTP axis in eukaryotic mitochondria. These results provide a better understanding of the pathogenic mechanism of Anaplasma phagocytophilum within host cells.

A versatile multi-tone laser system for manipulating atomic qubits based on a fiber Mach-Zehnder modulator and second harmonic generation.

Stimulated Raman transition is a fundamental method to coherently manipulate quantum states in different physical systems. Phase-coherent dichromatic radiation fields matching the energy level splitting are the key to realizing stimulated Raman transition. Here we demonstrate a flexible-tuning, spectrum-clean and fiber-compatible method to generate a highly phase-coherent and high-power multi-tone laser. This method features the utilization of a broadband fiber Mach-Zehnder modulator working at carrier suppression condition and second harmonic generation. We generate a multi-tone continuous-wave 532 nm laser with a power of 1.5 Watts and utilize it to manipulate the spin and motional states of a trapped 171Yb+ ion via stimulated Raman transition. For spin state manipulation, we acquire an effective Rabi frequency of 2π × 662.3 kHz. Due to the broad bandwidth of the fiber modulator and nonlinear crystal, the frequency gap between tones can be flexibly tuned. Benefiting from the features above, this method can manipulate 171Yb+ and 137Ba+ simultaneously in the multi-species ion trap and has potential to be widely applied in atomic, molecular and optical physics.