Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer.

Tumor-resident intracellular microbiota is an emerging tumor component that has been documented for a variety of cancer types with unclear biological functions. Here, we explored the functional significance of these intratumor bacteria, primarily using a murine spontaneous breast-tumor model MMTV-PyMT. We found that depletion of intratumor bacteria significantly reduced lung metastasis without affecting primary tumor growth. During metastatic colonization, intratumor bacteria carried by circulating tumor cells promoted host-cell survival by enhancing resistance to fluid shear stress by reorganizing actin cytoskeleton. We further showed that intratumor administration of selected bacteria strains isolated from tumor-resident microbiota promoted metastasis in two murine tumor models with significantly different levels of metastasis potential. Our findings suggest that tumor-resident microbiota, albeit at low biomass, play an important role in promoting cancer metastasis, intervention of which might therefore be worth exploring for advancing oncology care.

Reconstruction of dynamic mammary mini gland in vitro for normal physiology and oncogenesis.

Organoid culture has been extensively exploited for normal tissue reconstruction and disease modeling. However, it is still challenging to establish organoids that mimic in vivo-like architecture, size and function under homeostatic conditions. Here we describe the development of a long-term adult stem cell-derived mammary mini gland culture system that supports robust three-dimensional outgrowths recapitulating the morphology, scale, cellular context and transcriptional heterogeneity of the normal mammary gland. The self-organization ability of stem cells and the stability of the outgrowths were determined by a coordinated combination of extracellular matrix, environmental signals and dynamic physiological cycles. We show that these mini glands were hormone responsive and could recapitulate the entire postnatal mammary development including puberty, estrus cycle, lactation and involution. We also observed that these mini glands maintained the presence of mammary stem cells and could also recapitulate the fate transition from embryonic bipotency to postnatal unipotency in lineage tracing assays. In addition, upon induction of oncogene expression in the mini glands, we observed tumor initiation in vitro and in vivo in a mouse model. Together, this study provides an experimental system that can support a dynamic miniature mammary gland for the study of physiologically relevant, complex biological processes.

Hydrogen Attenuates Chronic Intermittent Hypoxia-Induced Cardiac Hypertrophy by Regulating Iron Metabolism.

The present study aimed to investigate the impact of hydrogen (H2) on chronic intermittent hypoxia (CIH)-induced cardiac hypertrophy in mice by modulating iron metabolism. C57BL/6N mice were randomly allocated into four groups: control (Con), CIH, CIH + H2, and H2. The mice were exposed to CIH (21-5% FiO2, 3 min/cycle, 8 h/d), and received inhalation of a hydrogen-oxygen mixture (2 h/d) for 5 weeks. Cardiac and mitochondrial function, levels of reactive oxygen species (ROS), and iron levels were evaluated. The H9C2 cell line was subjected to intermittent hypoxia (IH) and treated with H2. Firstly, we found H2 had a notable impact on cardiac hypertrophy, ameliorated pathological alterations and mitochondrial morphology induced by CIH (p < 0.05). Secondly, H2 exhibited a suppressive effect on oxidative injury by decreasing levels of inducible nitric oxide synthase (i-NOS) (p < 0.05) and 4-hydroxynonenal (4-HNE) (p < 0.01). Thirdly, H2 demonstrated a significant reduction in iron levels within myocardial cells through the upregulation of ferroportin 1 (FPN1) proteins (p < 0.01) and the downregulation of transferrin receptor 1 (TfR1), divalent metal transporter 1 with iron-responsive element (DMT1(+ire)), and ferritin light chain (FTL) mRNA or proteins (p < 0.05). Simultaneously, H2 exhibited the ability to decrease the levels of Fe2+ and ROS in H9C2 cells exposed to IH (p < 0.05). Moreover, H2 mediated the expression of hepcidin, hypoxia-inducible factor-1α (HIF-1α) (p < 0.01), and iron regulatory proteins (IRPs), which might be involved in the regulation of iron-related transporter proteins. These results suggested that H2 may be beneficial in preventing cardiac hypertrophy, a condition associated with reduced iron toxicity.

Evolutionary characterization and pathogenicity of Getah virus from pigs in Guangdong Province of China.

Getah virus (GETV) is an emerging zoonotic virus that can infect humans and many mammals through mosquitoes. In this study, a novel pathogenic GETV strain, GDQY2022, was isolated from a pig farm in Guangdong Province, China. Sequence comparisons and phylogenetic analysis showed that GDQY2022 belongs to group III (GIII) and was most closely related to strain HeN202009-2, with 99.78% nucleotide sequence identity. Histopathological examination revealed significant pathological changes, such as widened alveolar septum in the lungs with mild congestion and hemorrhage. Differences in viral load between tissues were assessed by real-time RT-PCR, and significantly higher levels of GETV were found in abdominal lymph nodes and lungs of subclinically and clinically affected pigs (P < 0.01). This study provides valuable data for understanding the risk of GETV infection in the pig industry and a reliable basis for studying the pathogenic mechanisms and diagnostic surveillance of GETV.

A pseudo-Siamese framework for circRNA-RBP binding sites prediction integrating BiLSTM and soft attention mechanism.

Circular RNAs (circRNAs) are widely expressed in tissues and play a key role in diseases through interacting with RNA binding proteins (RBPs). Since the high cost of traditional technology, computational methods are developed to identify the binding sites between circRNAs and RBPs. Unfortunately, these methods suffer from the insufficient learning of features and the single classification of output. To address these limitations, we propose a novel method named circ-pSBLA which constructs a pseudo-Siamese framework integrating Bi-directional long short-term memory (BiLSTM) network and soft attention mechanism for circRNA-RBP binding sites prediction. Softmax function and CatBoost are adopted to classify, respectively, and then a pseudo-Siamese framework is constructed. circ-pSBLA combines them to get final output. To validate the effectiveness of circ-pSBLA, we compare it with other state-of-the-art methods and carry out an ablation experiment on 17 sub-datasets. Moreover, we do motif analysis on 3 sub-datasets. The results show that circ-pSBLA achieves superior performance and outperforms other methods. All supporting source codes can be downloaded from https://github.com/gyj9811/circ-pSBLA.

Danggui-Buxue decoction alleviated vascular senescence in mice exposed to chronic intermittent hypoxia through activating the Nrf2/HO-1 pathway.

CONTEXT: As a major risk factor for cardiovascular diseases (CVD), Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). Recent studies indicated that the increased cardiovascular risk in patients with OSA may be mediated by accelerated vascular senescence. Danggui-Buxue decoction (DBD) has been used for treating cardiovascular diseases, but its mechanism of vascular senescence regulation is still unclear. OBJECTIVE: To investigate the effect of DBD on vascular senescence in mice exposed to CIH and to explore the role of the Nrf2/HO-1 pathway. MATERIALS AND METHODS: C57BL/6N mice were randomly divided into Normoxia control group (CON), CIH (21%-5% O2, 20 times/h, 8 h/d) exposed group (CIH), and DBD treatment group (intragastrically treated with 2.34, 4.68, or 9.36 g/kg/day of DBD separately for 12 weeks as DBL, DBM, or DBH). Blood pressure, cardiac and vascular function, vascular senescence, inflammation response, oxidative stress, and Nrf2/HO-1 expression were determined. RESULTS: DBD (4.68 and 9.36 g/kg) significantly decreased Tail-cuff blood pressure, increased left ventricular systolic function, and alleviated arterial stiffness and vasorelaxation dysfunction in mice exposed to CIH. DBD treatment reduced SA-ß-gal activity, decreased p16 (0.68-fold, 0.62-fold), P21 (0.58-fold, 0.52-fold), and p53 expressions (0.67-fold, 0.65-fold), and increased SIRT1 expression (2.22-fold, 2.98-fold) in the aortic. DBD treatment decreased IL-6, NF-κB, and TNF-α expressions, decreased MDA but increased SOD levels, and increased Nrf2 (1.8-fold, 1.89-fold) and HO-1 (2.25-fold, 2.43-fold) expression. DISCUSSION AND CONCLUSIONS: DBD could attenuate vascular senescence accelerated by CIH exposure through inhibiting inflammatory response and oxidative stress by activating the Nrf2/HO-1 pathway.

[Effect and mechanism of Danggui Buxue Decoction-containing serum in mitigating H9c2 cell injury caused by exposure to intermittent low oxygen].

This study aims to explore the effect and mechanism of Danggui Buxue Decoction(DBD)-containing serum in alleviating the H9c2 cell injury caused by the exposure to intermittent low oxygen. H9c2 cells were assigned into five groups: control(CON) group, intermittent low oxygen(IH) group, intermittent low oxygen plus DBD-containing serum(IH+DBD) group, intermittent low oxygen plus the autophagy enhancer rapamycin(IH+RAPA) group, and intermittent low oxygen plus DBD-containing serum and the autophagy inhibitor 3-methyladenine(IH+DBD+3-MA) group. Monodansylcadaverine(MDC) staining was employed to detect the changes of autophagosomes. Cell counting kit-8(CCK-8) assay was employed to determine the activity of myocardial cells, and lactate dehydrogenase(LDH) and creatine kinase(CK) kits were used to measure the LDH and CK levels in the cell culture, which would reflect the degree of cell damage. TdT-mediated dUTP nick-end labeling(TUNEL) staining was used to detect the apoptosis of myocardial cells, and JC-1 fluorescence probe to detect the changes in mitochondrial membrane potential. Western blot was employed to determine the expression levels of the autophagy-related proteins microtubule-associated proteins light chain 3Ⅱ(LC3Ⅱ), microtubule-associated proteins light chain 3Ⅰ(LC3Ⅰ), P62, Parkin and apoptosis related proteins pro caspase-3, caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax). The results showed that compared with the CON group, the IH group showed decreased fluorescence intensity of MDC staining, decreased LC3Ⅱ/LC3Ⅰ ratio, down-regulated Parkin expression, and up-regulated expression of P62. In addition, the IH group showed decreased cell survival rate, increased content of LDH and CK in the culture medium, increased number of TUNEL positive cells, and decreased pro caspase-3/caspase-3 and Bcl-2/Bax ratios and mitochondrial membrane potential. Compared with the IH group, the IH+DBD and IH+RAPA groups showed increased fluorescence intensity of MDC staining, increased LC3Ⅱ/LC3Ⅰ ratio, up-regulated Parkin expression, and down-regulated P62 expression. In addition, the two groups showed increased cell survival rate, reduced content of LDH and CK in the culture medium, decreased number of TUNEL positive cells, and increased pro caspase-3/caspase-3 and Bcl-2/Bax ratios and mitochondrial membrane potential. The IH+DBD+3-MA and IH groups showed no significant differences in the above indicators. Compared with the IH+DBD group, the IH+DBD+3-MA group showed decreased fluorescence intensity of MDC staining, decreased LC3Ⅱ/LC3Ⅰ ratio, down-regulated Parkin expression, and up-regulated P62 expression. In addition, the group had decreased cell survival rate, increased content of LDH and CK in the culture medium, increased number of TUNEL positive cells, decreased pro caspase-3/caspase-3 and Bcl-2/Bax ratios, and declined mitochon-drial membrane potential. To sum up, DBD could promote the mitophagy, inhibit the apoptosis, and alleviated the injury of H9c2 cells exposed to low oxygen.

Modulation of laser damage by temporal shaping of double picosecond pulses.

We propose a temporally shaped double-picosecond-pulse train at a sub-nanosecond scale to control the damage dynamics of optical glass. Both damage threshold and morphology are significantly modulated by pulse-train shaping. The ramp-up-shaped train effectively increases its damage threshold and decreases the damage density and size, which clearly shows that a pump pulse with optimized fluence has a strong positive modification of damage precursors. Furthermore, the temporal evolution of damage modulation is experimentally revealed by varying the interval of pump-probe pulses, and after pump exposure with optimized fluence, enhancement of the probe threshold reaches the maximum at a delay of about 260 ps.

[Danggui Buxue Decoction improves heart function of chronic intermittent hypoxia mice by promoting mitochondrial autophagy and inhibiting cardiomyocyte apoptosis].

The study established a chronic intermittent hypoxia(CIH) model in mice to investigate the effects of Danggui Buxue Decoction(DBD) on mitochondrial autophagy and cardiomyocyte apoptosis and explore its protective effect and mechanism on cardiac function of CIH mice. Forty C57 BL/6 N male mice were randomly divided into the control(CON) group, CIH group, CIH+DBD group, and DBD group, with 10 mice in each group. CIH was induced by filling the hypoxic chamber with N_2(90 s) to reduce the O_2 concentration to 5% and then filling the hypoxic chamber with O_2(90 s) to restore O_2 concentration to 21%, 3 min per cycle, and the CIH treatment continued for 35 d, 8 h per day. Mice in the CIH+DBD and DBD groups were treated with intragastric administration of DBD every day, while those in the CON and CIH groups with the same volume of normal saline. The cardiac function of mice was measured by echocardiography. The pathological changes in myocardium were observed after HE staining, followed by the observation of cardiomyocyte apoptosis by Tunel staining. The expression of apoptosis-related proteins pro-caspase-3, caspase-3, Bcl-2, and Bax and autophagy-related proteins LC3Ⅱ, LC3Ⅰ, P62, parkin, and cytochrome C(Cytc) was detected by Western blot. The mitochondrial membrane potential was observed using JC-1 fluorescent probe. Compared with the CON group, the CIH group exhibited remar-kably lowered left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), elevated left ventricular end-systolic volume(LVESV) and end-diastolic volume(LVEDV), disordered myocardial fiber arrangement, increased number of TUNEL-positive cells, decreased pro-caspase-3/caspase-3, Bcl-2/Bax, and LC3Ⅱ/LC3Ⅰ ratios, parkin, mitochondrial Cytc expression, and mitochondrial membrane potential, and up-regulated P62 and Cytc expression. Compared with the CIH group, DBD increased LVEF, LVFS, pro-caspase-3/caspase-3, Bcl-2/Bax, and LC3Ⅱ/LC3Ⅰ ratios, and parkin expression, as well as mitochond-rial Cytc expression, and mitochondrial membrane potential, decreased LVESV, LVEDV, and the number of Tunel-positive cells, and improved the myocardial fiber arrangement. DBD has a protective effect on the heart function of CIH mice. It improves the heart function possibly by promoting mitochondrial autophagy to ameliorate mitochondrial function and inhibiting the cardiomyocyte apoptosis.

Three-dimensional laser damage positioning by a deep-learning method.

A holographic and deep learning-based method is presented for three-dimensional laser damage location. The axial damage position is obtained by numerically focusing the diffraction ring into the conjugate position. A neural network Diffraction-Net is proposed to distinguish the diffraction ring from different surfaces and positions and obtain the lateral position. Diffraction-Net, which is completely trained by simulative data, can distinguish the diffraction rings with an overlap rate greater than 61% which is the best of results reported. In experiments, the proposed method first achieves the damage pointing on each surface of cascade slabs using diffraction rings, and the smallest inspect damage size is 8µm. A high precision result with the lateral positioning error less than 38.5µm and axial positioning error less than 2.85mm illustrates the practicability for locating the damage sites at online damage inspection.

Hydrogen gas reduces chronic intermittent hypoxia-induced hypertension by inhibiting sympathetic nerve activity and increasing vasodilator responses via the antioxidation.

Molecular hydrogen is reported to be used medically to ameliorate various systemic pathological conditions. This study aimed to investigate the effect of hydrogen (H2 ) gas on hypertension induced by intermittent hypoxia in rats. The adult rats were exposed to chronic intermittent hypoxia (CIH) 8 hours/day for 5 weeks and/or H 2 gas 2 hours/day. We found that the systolic and diastolic blood pressure (BP) increased significantly in rats exposed to intermittent hypoxia, both of which were markedly attenuated after H treatment. Furthermore, intermittent hypoxia exposure elevated renal sympathetic nerve activity, consistent with plasma norepinephrine. Additionally, H 2 gas significantly improved CIH-induced abnormal vascular relaxation. Nevertheless, inhalation of H 2 gas alone did not cause such changes. Moreover, H 2 gas-treated rats exposed to CIH showed a significant reduction in 8-hydroxy-2 deoxyguanosine content and increases in superoxide dismutase activity, indicating improved oxidative stress. Taken together, these results indicate that H 2 gas has significant effects on the reduction of BP without any side effects. Mechanistically, inhibition of sympathetic activity and reduction of systemic vascular resistance may participate in this process via the antioxidant activity of H 2 .

Copper-Catalyzed Cope-Type Hydroamination of Nonactivated Olefins toward Cyclic Nitrones: Scope, Mechanism, and Enantioselective Process Development.

The catalytic synthesis of cyclic nitrones, an important type of functional molecules for both synthetic chemistry and related fields, remains underdeveloped. Herein we report the copper-catalyzed Cope-type hydroamination of oximes with pendant nonactivated olefins, which enables facile access to a series of five- and six-membered cyclic nitrones under mild conditions. In this study, heterocycle-tethered oximes were employed in the Cope-type hydroamination reaction for the first time. High enantioselectivity was achieved for carbon-tethered γ,δ-vinyl oximes to afford enantioenriched five-membered cyclic nitrones. The results of preliminary mechanistic studies indicate a mononuclear catalytic species and a unified catalytic pathway over a large temperature range.

Asymmetrical damage growth of multilayer dielectric gratings induced by picosecond laser pulses.

We experimentally investigated the laser damage growth behavior of multilayer dielectric gratings (MLDGs) by the picosecond pulses at 1053nm. The damage growth threshold of 2.43J/cm2 is significantly lower than the 20/1 damage threshold of 3.06 J/cm2. Once the damage site is initiated, the damage area grows linearly with shot number and saturates after sufficient shots due to the Gaussian spot. The barycenter of the growing damage site deviates from the laser spot center and their distance increases with the shot number, which indicates the asymmetry of the damage growth along the laser propagation axis. The growth rate of the damage site along the laser propagation direction is larger than that in the reverse direction by a factor of ~1.8 for various fluences. The comparison of the experimental and numerical results reveals that the asymmetrical intensity modulation induced by the damage sites causes the asymmetry in growth. The revealed characteristics and mechanisms of the damage growth can be of great significance to predict the lifetime of the MLDGs in high-power laser systems.

Determination of the damage growth threshold of multilayer dielectric gratings by picosecond laser pulses based on saturation damage size analysis.

We propose two efficient methods of determining damage growth threshold (DGT) based on the saturation damage size analysis (SDSA) for multilayer dielectric gratings by picosecond pulsed lasers. The damage size at laser fluences above DGT increases with the shot number and finally saturates due to the Gaussian focal spot. The DGT is extracted by mapping the boundary of a saturation damage site obtained at single fluence to the beam profile, which is called the monofluence SDSA method. Meanwhile, the saturation damage size decreases when reducing laser fluence. The fitting and extrapolation of the saturation damage sizes at different fluences are also useful to accurately determine the DGT, which is called the multifluence SDSA method. Although the saturation damage site is asymmetric, the DGTs measured with two SDSA methods are almost identical for the same axis, and both are in very good agreement with those obtained with the growth probability method. The underlying mechanisms and advantages of two SDSA methods are extensively discussed. The consistence of two SDSA methods in determining DGT is attributed to the same morphology of the initial damage and the saturation damage boundary, as well as the local damage dynamics. The relation of the lifetime damage threshold and DGT obtained with the SDSA method is also revealed.

[Bosentan ameliorates hypertension in rats exposed to chronic intermittent hypoxia through inhibiting renal sympathetic nerve activity].

The purpose of this study is to investigate the effect of the oral endothelin antagonist Bosentan on blood pressure and renal sympathetic nerve activity (RSNA) in rats exposed to chronic intermittent hypoxia (CIH), and to explore the sympathoexcitation mechanism of endothelin-1 (ET-1) in CIH-induced hypertension. Twenty-four male SD rats were randomly divided into normoxia, CIH and Bosentan groups. Rats in the normoxia group were exposed to normoxic environment, and rats in CIH or Bosentan group were exposed to intermittent hypoxia for 3 weeks. Bosentan was given at 50 mg/kg by intragastric administration before intermittent hypoxia exposure in Bosentan group. Systolic blood pressure (SBP) was measured by BP-2000, and the change of RSNA to sodium nitroprusside (SNP) or phenylephrine (PE) was recorded by PowerLab signal acquisition system. Serums of all rats were collected and the contents of ET-1 and norepinephrine (NE) were measured by ELISA. Results showed that blood pressure was gradually increased following CIH exposure compared with the normoxia group during the 3 weeks (P < 0.01, P < 0.01, P < 0.001). The basal RSNA was increased and baroreflex sensitivity was decreased in rats exposed to CIH. Furthermore, the blood pressure was positively correlated with the level of ET-1 in serum in rats exposed to CIH (r = 0.833, P = 0.01). Bosentan administration significantly decreased SBP and basal RSNA, increased the baroreflex sensitivity, and decreased serum NE level in rats exposed to CIH. These results suggest that ET-1 is related with blood pressure elevation in rats exposed to CIH, and Bosentan reverses CIH-induced hypertension by decreasing RSNA.

Homogeneous Electrochemical Biosensor for Melamine Based on DNA Triplex Structure and Exonuclease III-Assisted Recycling Amplification.

Abasic site (AP site) in the triplex structure can recognize specific target with high selectivity. In this study, this character was first applied to develop a simple, sensitive, and selective homogeneous electrochemical biosensor for melamine determination. The assay combines the advantage of the high selectivity of the DNA triplex structure containing an AP site to melamine and high efficiency of exonuclease (Exo) III-assisted recycling amplification. DNA-1 (T1), DNA-2 (T2), poly[dA] probe containing an AP site (8A) and methylene blue-labeled DNA probe (dMB probe) were carefully designed. Melamine can specifically locate in the AP site through hydrogen bonding interaction between thymine and melamine to make T1, T2, and 8A close to each other, therefore, forming a stable T-melamine-T DNA triplex structure. Under the optimal conditions, the differential pulse voltammetric (DPV) response had a linear relationship with the logarithm of melamine concentration in the range of 1 nM∼0.5 µM. The developed biosensor has been successfully applied to detect the migration of melamine from melamine bowl. Result showed that the migration in 4% acetic acid solvent was the largest, which is similar to that detected by high performance liquid chromatography. This homogeneous electrochemical sensor may have a potential prospect in detecting melamine in dairy products and migration of melamine from multicategory food packaging or application materials.

A new open-loop fiber optic gyro error compensation method based on angular velocity error modeling.

With the open-loop fiber optic gyro (OFOG) model, output voltage and angular velocity can effectively compensate OFOG errors. However, the model cannot reflect the characteristics of OFOG errors well when it comes to pretty large dynamic angular velocities. This paper puts forward a modeling scheme with OFOG output voltage u and temperature T as the input variables and angular velocity error Δω as the output variable. Firstly, the angular velocity error Δω is extracted from OFOG output signals, and then the output voltage u, temperature T and angular velocity error Δω are used as the learning samples to train a Radial-Basis-Function (RBF) neural network model. Then the nonlinear mapping model over T, u and Δω is established and thus Δω can be calculated automatically to compensate OFOG errors according to T and u. The results of the experiments show that the established model can be used to compensate the nonlinear OFOG errors. The maximum, the minimum and the mean square error of OFOG angular velocity are decreased by 97.0%, 97.1% and 96.5% relative to their initial values, respectively. Compared with the direct modeling of gyro angular velocity, which we researched before, the experimental results of the compensating method proposed in this paper are further reduced by 1.6%, 1.4% and 1.42%, respectively, so the performance of this method is better than that of the direct modeling for gyro angular velocity.

Protocol to prepare MUC1 glycopeptide vaccines and evaluate immunization effects in mice.

The tumor-associated mucin MUC1 is overexpressed in almost all types of epithelial tumor tissues, making it an attractive target antigen for cancer immunotherapy. Here we present a protocol to prepare MUC1 glycopeptide vaccines and to evaluate immunization effects in mice. We describe steps for synthesizing glycopeptide antigen and conjugating it with carrier protein to make vaccine candidates. We then detail procedures for mice immunization, antibody response evaluation, and cellular immune response. For complete details on the use and execution of this protocol, please refer to Cai et al.1,2.

Deciphering the spatiotemporal transcriptional landscape of intestinal diseases (Review).

The intestines are the largest barrier organ in the human body. The intestinal barrier plays a crucial role in maintaining the balance of the intestinal environment and protecting the intestines from harmful bacterial invasion. Single­cell RNA sequencing technology allows the detection of the different cell types in the intestine in two dimensions and the exploration of cell types that have not been fully characterized. The intestinal mucosa is highly complex in structure, and its proper functioning is linked to multiple structures in the proximal­distal intestinal and luminal­mucosal axes. Spatial localization is at the core of the efforts to explore the interactions between the complex structures. Spatial transcriptomics (ST) is a method that allows for comprehensive tissue analysis and the acquisition of spatially separated genetic information from individual cells, while preserving their spatial location and interactions. This approach also prevents the loss of fragile cells during tissue disaggregation. The emergence of ST technology allows us to spatially dissect enzymatic processes and interactions between multiple cells, genes, proteins and signals in the intestine. This includes the exchange of oxygen and nutrients in the intestine, different gradients of microbial populations and the role of extracellular matrix proteins. This regionally precise approach to tissue studies is gaining more acceptance and is increasingly applied in the investigation of disease mechanisms related to the gastrointestinal tract. Therefore, this review summarized the application of ST in gastrointestinal diseases.

Potential of natural products in inflammation: biological activities, structure-activity relationships, and mechanistic targets.

A balance between the development and suppression of inflammation can always be found in the body. When this balance is disturbed, a strong inflammatory response can damage the body. It sometimes is necessary to use drugs with a significant anti-inflammatory effect, such as nonsteroidal anti-inflammatory drugs and steroid hormones, to control inflammation in the body. However, the existing anti-inflammatory drugs have many adverse effects, which can be deadly in severe cases, making research into new safer and more effective anti-inflammatory drugs necessary. Currently, numerous types of natural products with anti-inflammatory activity and distinct structural features are available, and these natural products have great potential for the development of novel anti-inflammatory drugs. This review summarizes 260 natural products and their derivatives with anti-inflammatory activities in the last two decades, classified by their active ingredients, and focuses on their structure-activity relationships in anti-inflammation to lay the foundation for subsequent new drug development. We also elucidate the mechanisms and pathways of natural products that exert anti-inflammatory effects via network pharmacology predictions, providing direction for identifying subsequent targets of anti-inflammatory natural products.