Toward Unified AI Drug Discovery with Multimodal Knowledge.

Background: In real-world drug discovery, human experts typically grasp molecular knowledge of drugs and proteins from multimodal sources including molecular structures, structured knowledge from knowledge bases, and unstructured knowledge from biomedical literature. Existing multimodal approaches in AI drug discovery integrate either structured or unstructured knowledge independently, which compromises the holistic understanding of biomolecules. Besides, they fail to address the missing modality problem, where multimodal information is missing for novel drugs and proteins. Methods: In this work, we present KEDD, a unified, end-to-end deep learning framework that jointly incorporates both structured and unstructured knowledge for vast AI drug discovery tasks. The framework first incorporates independent representation learning models to extract the underlying characteristics from each modality. Then, it applies a feature fusion technique to calculate the prediction results. To mitigate the missing modality problem, we leverage sparse attention and a modality masking technique to reconstruct the missing features based on top relevant molecules. Results: Benefiting from structured and unstructured knowledge, our framework achieves a deeper understanding of biomolecules. KEDD outperforms state-of-the-art models by an average of 5.2% on drug-target interaction prediction, 2.6% on drug property prediction, 1.2% on drug-drug interaction prediction, and 4.1% on protein-protein interaction prediction. Through qualitative analysis, we reveal KEDD's promising potential in assisting real-world applications. Conclusions: By incorporating biomolecular expertise from multimodal knowledge, KEDD bears promise in accelerating drug discovery.

Whitening of brown adipose tissue inhibits osteogenic differentiation via secretion of S100A8/A9.

The mechanism by which brown adipose tissue (BAT) regulates bone metabolism is unclear. Here, we reveal that BAT secretes S100A8/A9, a previously unidentified BAT adipokine (batokine), to impair bone formation. Brown adipocytes-specific knockout of Rheb (RhebBAD KO), the upstream activator of mTOR, causes BAT malfunction to inhibit osteogenesis. Rheb depletion induces NF-κB dependent S100A8/A9 secretion from brown adipocytes, but not from macrophages. In wild-type mice, age-related Rheb downregulation in BAT is associated with enhanced S100A8/A9 secretion. Either batokines from RhebBAD KO mice, or recombinant S100A8/A9, inhibits osteoblast differentiation of mesenchymal stem cells in vitro by targeting toll-like receptor 4 on their surfaces. Conversely, S100A8/A9 neutralization not only rescues the osteogenesis repressed in the RhebBAD KO mice, but also alleviates age-related osteoporosis in wild-type mice. Collectively, our data revealed an unexpected BAT-bone crosstalk driven by Rheb-S100A8/A9, uncovering S100A8/A9 as a promising target for the treatment, and potentially, prevention of osteoporosis.

The toxicity response of the electrochemical signal of the cell to the drug metabolized by the S9 system.

The electrochemical detection method of cytotoxicity using intracellular purines as biomarkers has shown great potential for in vitro drug toxicity evaluation. However, no electrochemical detection system based on an in vitro drug metabolism mechanism has been devised. In this paper, electrochemical voltammetry was used to investigate the effect of the S9 system on the electrochemical behavior of HepG2 cells, and benzo[a]pyrene, fluoranthene, and pyrene were employed to investigate the sensitivity of electrochemical signals of cells to the cytotoxicity of drugs metabolized by the S9 system. The results showed that, within 8 h of exposure to the S9 system, the electrochemical signal of HepG2 cells at 0.7 V did not alter noticeably. The levels of xanthine, guanine, hypoxanthine, and adenine in the cells were not significantly altered. Compared with the absence of S9 system metabolism, benzo[a]pyrene and fluoranthene processed by the S9 system decreased the electrochemical signal of the cells in a dose-dependent manner, while pyrene did not change it appreciably. HPLC also revealed that benzo[a]pyrene and fluoranthene metabolized by the S9 system decreased the intracellular purine levels, whereas pyrene had no effect on them before and after S9 system metabolism. The cytotoxicity results of the three drugs examined by electrochemical voltammetry and MTT assay showed a strong correlation and good agreement. The S9 system had no effect on the intracellular purine levels or the electrochemical signal of cells. When the drug was metabolized by the S9 system, variations in cytotoxicity could be precisely detected by electrochemical voltammetry.

Unveiling the Potential of Ambient Air Annealing for Highly Efficient Inorganic CsPbI3 Perovskite Solar Cells.

Here, we report a detailed surface analysis of dry- and ambient air-annealed CsPbI3 films and their subsequent modified interfaces in perovskite solar cells. We revealed that annealing in ambient air does not adversely affect the optoelectronic properties of the semiconducting film; instead, ambient air-annealed samples undergo a surface modification, causing an enhancement of band bending, as determined by hard X-ray photoelectron spectroscopy measurements. We observe interface charge carrier dynamics changes, improving the charge carrier extraction in CsPbI3 perovskite solar cells. Optical spectroscopic measurements show that trap state density is decreased due to ambient air annealing. As a result, air-annealed CsPbI3-based n-i-p structure devices achieved a 19.8% power conversion efficiency with a 1.23 V open circuit voltage.

Rheb1 is required for limb growth through regulating chondrogenesis in growth plate.

Ras homology enriched in the brain (Rheb) is well established as a critical regulator of cell proliferation and differentiation in response to growth factors and nutrients. However, the role of Rheb1 in limb development remains unknown. Here, we found that Rheb1 was dynamically expressed during the proliferation and differentiation of chondrocytes in the growth plate. Given that Prrx1+ limb-bud-like mesenchymal cells are the source of limb chondrocytes and are essential for endochondral ossification, we conditionally deleted Rheb1 using Prrx1-Cre and found a limb dwarfism in Prrx1-Cre; Rheb1fl/fl mice. Normalized to growth plate height, the conditional knockout (cKO) mice exhibited a significant decrease in column count of proliferative zones which was increased in hypertrophic zones resulting in decreased growth plate size, indicating abnormal endochondral ossification. Interestingly, although Rheb1 deletion profoundly inhibited the transcription factor Sox9 in limb cartilage; levels of runx2 and collagen type 2 were both increased. These novel findings highlight the essential role of Rheb1 in limb growth and indicate a complex regulation of Rheb1 in chondrocyte proliferation and differentiation.

Comparative study on the technique and efficacy of microscope-assisted MI-TLIF and naked-eye MI-TLIF in lumbar revision surgery.

BACKGROUND: Lumbar revision surgery can be performed by simple lumbar nerve decompression or lumbar interbody fusion, including percutaneous endoscopic lumbar discectomy, transforaminal lumbar interbody fusion (TLIF), etc. However, lumbar revision surgery is very difficult in surgical operation. We sought to explore the technique safety and efficacy of microscope-assisted minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) in lumbar revision surgery. METHODS: Cases of postoperative recurrence following lumbar spine surgery (n = 63) treated from December 2016 to July 2021 were retrospectively analyzed, including 24 cases of microscope-assisted MI-TLIF (microscopic group) and 39 cases of naked-eye MI-TLIF (naked-eye group). The operation time, intraoperative blood loss, incision length, postoperative drainage, length of hospital stay, initial operation, and visual analog score (VAS) of low back and leg pain before and at 7 days and 3 months after the operation and the last follow-up were compared between the two groups. The Oswestry Dysfunction Index (ODI) and the Japanese Orthopaedic Association (JOA) scores before and after the operation and the Bridwell interbody fusion grades at 1 year were compared. The independent t tests, Mann-Whitney U tests, and Chi-square tests were used for analysis. RESULTS: All 63 patients were successfully treated by operation and were followed up for an average of 31.5 ± 8.6 months (range 12-48 months). The two groups had no significant difference in sex, age, incision length, initial operation, or operative segment (P > 0.05). There was no significance in operation time, VAS score, ODI score, and JOA score of low back pain or Bridwell interbody fusion grade between the two groups (P > 0.05). Significant differences in intraoperative blood loss, postoperative drainage, and the lengths of hospital stay were observed between the two groups (P < 0.05). Cerebrospinal fluid leakage (n = 2), edema of nerve roots (n = 2), and incision infection (n = 1) were observed in the naked-eye group. There were no complications in the microscopic group, such as cerebrospinal fluid leakage, edema of nerve roots, and incision infection. CONCLUSION: Although microscope-assisted MI-TLIF and naked-eye MI-TLIF are both effective during lumbar revision surgery, microscope-assisted MI-TLIF brings less trauma, less bleeding, shorter postoperative hospital stay, and faster recovery. Unlike traditional surgery, microscope-assisted MI-TLIF provides a clear visual field, adequate hemostasis, and nerve decompression.

Biomass-related PM2.5 induced inflammatory microenvironment via IL-17F/IL-17RC axis.

Biomass exposure is a significant environmental risk factor for COPD, but the underlying mechanisms have not yet been fully elucidated. Inflammatory microenvironment has been shown to drive the development of many chronic diseases. Pollution exposure can cause increased levels of inflammatory factors in the lungs, leading to an inflammatory microenvironment which is prevalent in COPD. Our findings revealed that IL-17F was elevated in COPD, while exposure to biomass led to increased expression of IL-17F in both alveolar epithelial and macrophage cells in mice. Blocking IL-17F could alleviate the lung inflammation induced by seven days of biomass exposure in mice. We employed a transwell co-culture system to simulate the microenvironment and investigate the interactions between MLE-12 and MH-S cells. We demonstrated that anti-IL-17F antibody attenuated the inflammatory responses induced by BRPM2.5 in MLE-12 and MH-S co-cultured with BRPM2.5-MLE-12, which reduced inflammatory changes in microenvironment. We found that IL-17RC, an important receptor for IL-17F, played a key role in the interactions. Knockout of IL-17RC in MH-S resulted in inhibited IL-17F signaling and attenuated inflammatory response after MH-S co-culture with BRPM2.5-MLE-12. Our investigation suggests that BRPM2.5 induces lung epithelial-macrophage interactions via IL-17F/IL-17RC axis regulating the inflammatory response. These results may provide a novel strategy for effective prevention and treatment of biomass-related COPD.

Minimizing Interfacial Recombination in 1.8 eV Triple-Halide Perovskites for 27.5% Efficient All-Perovskite Tandems.

All-perovskite tandem solar cells show great potential to enable the highest performance at reasonable costs for a viable market entry in the near future. In particular, wide-bandgap (WBG) perovskites with higher open-circuit voltage (VOC ) are essential to further improve the tandem solar cells' performance. Here, a new 1.8 eV bandgap triple-halide perovskite composition in conjunction with a piperazinium iodide (PI) surface treatment is developed. With structural analysis, it is found that the PI modifies the surface through a reduction of excess lead iodide in the perovskite and additionally penetrates the bulk. Constant light-induced magneto-transport measurements are applied to separately resolve charge carrier properties of electrons and holes. These measurements reveal a reduced deep trap state density, and improved steady-state carrier lifetime (factor 2.6) and diffusion lengths (factor 1.6). As a result, WBG PSCs achieve 1.36 V VOC , reaching 90% of the radiative limit. Combined with a 1.26 eV narrow bandgap (NBG) perovskite with a rubidium iodide additive, this enables a tandem cell with a certified scan efficiency of 27.5%.

Smad3-mediated lncRNA HSALR1 enhances the non-classic signalling pathway of TGF-ß1 in human bronchial fibroblasts by binding to HSP90AB1.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the diseases with high mortality and morbidity with complex pathogenesis. Airway remodeling is an unavoidable pathological characteristic. However, the molecular mechanisms of airway remodeling are incompletely defined. METHODS: lncRNAs highly correlated with transforming growth factor beta 1(TGF-ß1) expression were chosen, the lncRNA ENST00000440406 (named HSP90AB1 Assoicated LncRNA 1, HSALR1) was chosen for further functional experiments. Dual luciferase and ChIP assay were used to detect the upstream of HSALR1, transcriptome sequencing, Cck-8, Edu, cell proliferation, cell cycle assay, and WB detection of pathway levels confirmed the effect of HSALR1 on fibroblast proliferation and phosphorylation levels of related pathways. Mice was infected with adeno-associated virus (AAV) to express HSALR1 by intratracheal instillation under anesthesia and was exposure to cigarette smoke, then mouse lung function was performed and the pathological sections of lung tissues were analyzed. RESULTS: Herein, lncRNA HSALR1 was identified as highly correlated with the TGF-ß1 and mainly expressed in human lung fibroblasts. HSALR1 was induced by Smad3 and promoted fibroblasts proliferation. Mechanistically, it could directly bind to HSP90AB1 protein, and acted as a scaffold to stabilize the binding between Akt and HSP90AB1 to promote Akt phosphorylation. In vivo, mice expressed HSALR1 by AAV was exposure to cigarette smoke (CS) for COPD modeling. We found that lung function was worse and airway remodeling was more pronounced in HSLAR1 mice compare to wild type (WT) mice. CONCLUSION: Our results suggest that lncRNA HSALR1 binds to HSP90AB1 and Akt complex component, and enhances activity of the TGF-ß1 smad3-independent pathway. This finding described here suggest that lncRNA can participate in COPD development, and HSLAR1 is a promising molecular target of COPD therapy.

VANGL2 inhibits antiviral IFN-I signaling by targeting TBK1 for autophagic degradation.

Stringent control of type I interferon (IFN-I) signaling is critical to potent innate immune responses against viral infection, yet the underlying molecular mechanisms are still elusive. Here, we found that Van Gogh-like 2 (VANGL2) acts as an IFN-inducible negative feedback regulator to suppress IFN-I signaling during vesicular stomatitis virus (VSV) infection. Mechanistically, VANGL2 interacted with TBK1 and promoted the selective autophagic degradation of TBK1 via K48-linked polyubiquitination at Lys372 by the E3 ligase TRIP, which serves as a recognition signal for the cargo receptor OPTN. Furthermore, myeloid-specific deletion of VANGL2 in mice showed enhanced IFN-I production against VSV infection and improved survival. In general, these findings revealed a negative feedback loop of IFN-I signaling through the VANGL2-TRIP-TBK1-OPTN axis and highlighted the cross-talk between IFN-I and autophagy in preventing viral infection. VANGL2 could be a potential clinical therapeutic target for viral infectious diseases, including COVID-19.

Exosome Release Delays Senescence by Disposing of Obsolete Biomolecules.

Accumulation of obsolete biomolecules can accelerate cell senescence and organism aging. The two efficient intracellular systems, namely the ubiquitin-proteasome system and the autophagy-lysosome system, play important roles in dealing with cellular wastes. However, how multicellular organisms orchestrate the processing of obsolete molecules and delay aging remains unclear. Herein, it is shown that prevention of exosome release by GW4869 or Rab27a-/- accelerated senescence in various cells and mice, while stimulating exosome release by nutrient restriction delays aging. Interestingly, exosomes isolate from serum-deprived cells or diet-restricted human plasma, enriched with garbage biomolecules, including misfolded proteins, oxidized lipids, and proteins. These cellular wastes can be englobed by macrophages, eventually, for disintegration in vivo. Inhibition of nutrient-sensing mTORC1 signaling increases exosome release and delays senescence, while constitutive activation of mTORC1 reduces exosome secretion and exacerbates senescence in vitro and in mice. Notably, inhibition of exosome release attenuates nutrient restriction- or rapamycin-delayed senescence, supporting a key role for exosome secretion in this process. This study reveals a potential mechanism by which stimulated exosome release delays aging in multicellular organisms, by orchestrating the harmful biomolecules disposal via exosomes and macrophages.

Genetic screening of MMP1 as a potential pathogenic gene in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome. Airway inflammation and remodeling are the two key processes involved in COPD pathogenesis. However, the key pathogenic genes driving COPD development have not been revealed. This study aims to identify and validate hub gene(s) underlying COPD development through bioinformatics analysis and experimental validation. METHODS: Three lung tissue sequencing datasets of the COPD (including GSE38974, GSE103174, and GSE106986) were analyzed. Further, differentially expressed genes (DEGs) were used to compare patients with COPD with non-COPD individuals, and the Robust Rank Aggregation (RRA) analysis was also performed. Results revealed a series of potential pathogenic genes of COPD. DEGs were subjected to KEGG, GO, and GSEA analyses. The scRNA dataset of human lung tissues (Human Lung Cell Atlas), and human primary airway epithelial cells (GSE134147) were used to identify the cell subtype localization. The qRT-PCR assay was performed in the human lung tissues, COPD mice model, and primary bronchial epithelial cells at the air-liquid interface (ALI) under cigarette smoke extract (CSE) stimulation to verify the expression of the hub genes. LASSO and GLM analysis with the hub genes were performed to identify the most critical gene. RNA-seq was performed after knocking down the critical gene using siRNA in HBECs at ALI. The potential role of the critical gene was confirmed through qRT-PCR, Western blot, and Immunofluorescence (IF) assays. RESULTS: A total of 98 genes were significantly and differently expressed in 3 GEO datasets. The KEGG and GO analyses showed that most of these genes are responsible for inflammation, immunity, and cell proliferation. The core gene set including 15 genes was screened out and consequently, the MMP1 was the most likely responsible for the progression of COPD. Moreover, we confirmed that MMP1 is significantly related to inflammatory effects and cilia function in human bronchial epithelial cells cultured at the air-liquid interface (ALI). CONCLUSION: In summary, we confirmed that inflammation and cell proliferation are potentially critical processes in COPD occurrence and development. A total of 15 potential hub genes were identified among which MMP1 was the most likely gene responsible for the development of COPD. Therefore, MMP1 is a potential molecular target of COPD therapy.

A Gas Flow Measurement System Based on Lead Zirconate Titanate Piezoelectric Micromachined Ultrasonic Transducer.

Ultrasonic flowmeter is one of the most widely used devices in flow measurement. Traditional bulk piezoelectric ceramic transducers restrict their application to small pipe diameters. In this paper, we propose an ultrasonic gas flowmeter based on a PZT piezoelectric micromachined ultrasonic transducer (PMUT) array. Two PMUT arrays with a resonant frequency of 125 kHz are used as the sensitive elements of the ultrasonic gas flowmeter to realize alternate transmission and reception of ultrasonic signals. The sensor contains 5 × 5 circular elements with a size of 3.7 × 3.7 mm2. An FPGA with a resolution of ns is used to process the received signal, and a flow system with overlapping acoustic paths and flow paths is designed. Compared with traditional measurement methods, the sensitivity is greatly improved. The flow system achieves high-precision measurement of gas flow in a 20 mm pipe diameter. The flow measurement range is 0.5-7 m/s and the relative error of correction is within 4%.

Slot-Die Coated Triple-Halide Perovskites for Efficient and Scalable Perovskite/Silicon Tandem Solar Cells.

Wide bandgap halide perovskite materials show promising potential to pair with silicon bottom cells. To date, most efficient wide bandgap perovskites layers are fabricated by spin-coating, which is difficult to scale up. Here, we report on slot-die coating for an efficient, 1.68 eV wide bandgap triple-halide (3halide) perovskite absorber, (Cs0.22FA0.78)Pb(I0.85Br0.15)3 + 5 mol % MAPbCl3. A suitable solvent system is designed specifically for the slot-die coating technique. We demonstrate that our fabrication route is suitable for tandem solar cells without phase segregation. The slot-die coated wet halide perovskite is dried by a "nitrogen (N2)-knife" with high reproducibility and avoiding antisolvents. We explore varying annealing conditions and identify parameters allowing crystallization of the perovskite film into large grains reducing charge collection losses and enabling higher current density. At 150 °C, an optimized trade-off between crystallization and the PbI2 aggregates on the film's top surface is found. Thus, we improve the cell stability and performance of both single-junction cells and tandems. Combining the 3halide top cells with a 120 µm thin saw damage etched commercial Czochralski industrial wafer, a 2-terminal monolithic tandem solar cell with a PCE of 25.2% on a 1 cm2 active area is demonstrated with fully scalable processes.

LysM-positive neurons drive Tuberous Sclerosis Complex (TSC)-associated brain lesions.

Mutations of Tsc1 or Tsc2 can lead to excessive activation of mTORC1 and cause Tuberous Sclerosis Complex (TSC), which is an autosomal dominant genetic disease prominently characterized by seizures, mental retardation and multiorgan hamartoma. In TSC, pathological changes in the central nervous system are the leading cause of death and disability. In decades, series of rodent models have been established by mutating Tsc1 or Tsc2 genes in diverse neural cell lineages to investigate the underlying cellular and molecular mechanisms, however, the cellular origin triggering neural pathological changes in TSC is undetermined. In this study, we generated a novel mouse model involving conditional deletion of Tsc1 in lysozyme 2 (Lyz2)-positive cells which replicated several features of brain lesions including epileptic seizures, megalencephaly, highly enlarged pS6-positive neurons and astrogliosis. In addition, we confirmed that bone marrow-derived myeloid cells including microglia with Tsc1 deficiency are not the decisive lineage in the cerebral pathologies in TSC. These histological assays in our murine model indicate an essential contribution of Lyz2-positive neurons to TSC progression. The Lyz2-positive neural population-specific onset of Tsc1 loss in murine postnatal brain might be the key to pathological phenotypes. Our findings thus provided evidences supporting new insights into the role of Lyz2-positive neurons in TSC events.

Regularization Meets Enhanced Multi-Stage Fusion Features: Making CNN More Robust against White-Box Adversarial Attacks.

Regularization has become an important method in adversarial defense. However, the existing regularization-based defense methods do not discuss which features in convolutional neural networks (CNN) are more suitable for regularization. Thus, in this paper, we propose a multi-stage feature fusion network with a feature regularization operation, which is called Enhanced Multi-Stage Feature Fusion Network (EMSF2Net). EMSF2Net mainly combines three parts: multi-stage feature enhancement (MSFE), multi-stage feature fusion (MSF2), and regularization. Specifically, MSFE aims to obtain enhanced and expressive features in each stage by multiplying the features of each channel; MSF2 aims to fuse the enhanced features of different stages to further enrich the information of the feature, and the regularization part can regularize the fused and original features during the training process. EMSF2Net has proved that if the regularization term of the enhanced multi-stage feature is added, the adversarial robustness of CNN will be significantly improved. The experimental results on extensive white-box attacks on the CIFAR-10 dataset illustrate the robustness and effectiveness of the proposed method.

Biomass-related PM2.5 induces mitochondrial fragmentation and dysfunction in human airway epithelial cells.

The use of biomass for cooking and heating is considered an important factor associated with chronic obstructive pulmonary disease (COPD), but few studies have previously addressed its underlying mechanisms. Therefore, this research aimed to evaluate the effects of biomass-related PM2.5 (BRPM2.5) exposure on 16HBE human airway epithelial cells and in mice with regard to mitochondrial dysfunction. Our study indicated that BRPM2.5 exposure of 16HBE cells resulted in mitochondrial dysfunction, including decreased mitochondrial membrane potential, increased expression of fission proteins-phospho-DRP1, increased mitochondrial ROS (mtROS), and decreased levels of ATP. BRPM2.5 altered the mitochondrial metabolism of 16HBE cells by decreasing mitochondrial oxygen consumption and glycolysis. However, Mitochondria targeted peptide SS-31 eliminated mitochondrial ROS and alleviated the ATP deficiency and proinflammatory cytokines release. BRPM2.5 exposure resulted in abnormal mitochondrial morphological alterations both in 16HBE and in lung tissue. Taken together, these results suggest that BRPM2.5 has detrimental effects on human airway epithelial cells, leading to mitochondrial dysfunction, abnormal mitochondrial metabolism and altered mitochondrial dynamics. The present study provides the first evidence that disruption of mitochondrial structure and mitochondrial metabolism may be one of the mechanisms of BRPM2.5-induced respiratory dysfunction.

Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease.

BACKGROUND: Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood. METHODS: We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes. RESULTS: We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed. CONCLUSION: These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.

Analysis and Construction of a Competitive Endogenous RNA Regulatory Network of Baicalin-Induced Apoptosis in Human Osteosarcoma Cells.

BACKGROUND: Baicalin is an extract from the traditional Chinese herb Scutellaria baicalensis and has the potential to treat osteosarcoma (OS). However, the transcriptome-level mechanism of baicalin-mediated antitumor effects in OS has not yet been investigated. The aim of this study was to analyze the competitive endogenous RNA (ceRNA) regulatory network involved in baicalin-induced apoptosis of OS cells. METHODS: In this study, CCK-8 and flow cytometry assays were used to detect the antitumor effects of baicalin on human OS MG63 cells. Furthermore, transcriptome sequencing was employed to establish the long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA profiles. RESULTS: Baicalin inhibited MG63 cell proliferation and induced apoptosis. Totals of 58 lncRNAs, 31 miRNAs, and 2136 mRNAs in the baicalin-treated MG63 cells were identified as differentially expressed RNAs compared to those in control cells. Of these, 2 lncRNAs, 3 miRNAs, and 18 mRNAs were included in the ceRNA regulatory network. The differentially expressed RNAs were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSIONS: By identifying the ceRNA network, our results provide new information about the possible molecular basis of baicalin, which has potential applications in OS treatment.