Clinical characteristics of community-onset Clostridioides difficile infections at a tertiary hospital in mainland China: A fourteen-year (2010-2023) retrospective study.

BACKGROUND: Clostridioides difficile infection (CDI) is an increasingly common disease in healthcare facilities and community settings. However, there are limited reports of community-onset CDI (CO-CDI) in China. METHODS: We collected diarrheal stool samples from 3885 patients who went to outpatient department or emergency department in a tertiary hospital in China during 2010-2023, analyzed the correlation between patients' basic information and the detection rate of CDI. Besides, all stool samples from 3885 outpatients included were tested by culturing. Moreover, we randomly selected 89 patients' stools during the 14 years and isolated 126 C. difficile strains from them. The presence of toxin genes (tcdA, tcdB, cdtA, and cdtB) were confirmed by PCR. Toxigenic strains were typed using multilocus sequence typing (MLST). Susceptibility to 9 antimicrobials was evaluated using the E-test. RESULTS: 528 of 3885 patients (13.6 %) with diarrhea were finally diagnosed as CDI. The median age of patients included was 51 years (6 months-95 years), while the median of patients with CDI was older than patients with negative results [55.5 years (6 months-93 years) vs. 50 years (9 months -95 years), p < 0.001]. In winter, patients with diarrhea might be more likely to have CDI. The detection rate of CDI of patients in emergency department was much higher than those in other outpatients (20.7 % vs. 12.4 %, p < 0.001), and did differ from each outpatient departments (p < 0.05). There were 95 isolated strains detected as toxigenic C. difficile. Among these strains, 82 (86.3 %) had the tcdA and tcdB genes (A+B+) and 5 of these 82 strains were positive for the binary toxin genes (cdtA and cdtB) (A+B+CDT+). There were 15 different sequence types (STs) by multilocus sequence typing (MLST), while the most ST was ST-54 (23.2 %). ST types composition was relatively stable over the time span of this study. Some strains had high resistance to ciprofloxacin, clindamycin, and erythromycin. Twenty-three isolates (24.2 %) were multidrug-resistant. CONCLUSIONS: Outpatients with CDI were common among patients having diarrhea during this period in our hospital. Elderly patients and patients went to emergency department may be susceptible to CDI. Based on MLST, the result revealed that the C. difficile isolates had high genetic diversity and maintained stability in this period. All isolates were susceptible to metronidazole and vancomycin, and nearly one quarter of all isolates had multidrug resistance.

A highly sensitive fluorescence biosensor for aflatoxins B1 detection based on polydiacetylene liposomes combined with exonuclease III-assisted recycling amplification.

A fluorescence biosensor for determination of aflatoxin B1 (AFB1) based on polydiacetylene (PDA) liposomes and exonuclease III (EXO III)-assisted recycling amplification was developed. The AFB1 aptamer partially hybridizes with complementary DNA (cDNA), which is released upon recognition of AFB1 by the aptamer. Subsequently, the cDNA hybridizes with hairpin H to form double-stranded DNA that undergoes digestion by EXO III, resulting in the cyclic release of cDNA and generation of capture DNA for further reaction. The capture DNA then hybridizes with probe modified on PDA liposomes, leading to aggregation of liposomes and subsequent fluorescence production. This strategy exhibited a limit of detection of 0.18 ng/mL within the linear range 1-100 ng/mL with a determination coefficient > 0.99. The recovery ranged from 92.81 to 106.45%, with relative standard deviations (RSD) between 1.73 and 4.26%, for corn, brown rice, peanut butter, and wheat samples. The stability, accuracy, and specificity of the method demonstrated the applicability for real sample analysis.

Accurate Discrimination of Benign Biliary Diseases and Cholangiocarcinoma with Serum Multiomics Revealed by High-Throughput Nanoassisted Laser Desorption Ionization Mass Spectrometry.

Cholangiocarcinoma (CCA) is an aggressive malignant tumor with a poor prognosis. Carbohydrate antigen 19-9 is an essential biomarker for CCA diagnosis, but its low sensitivity (72%) makes the diagnosis unreliable. To explore potential biomarkers for the diagnosis of CCA, a high-throughput nanoassisted laser desorption ionization mass spectrometry technique was constructed. We performed serum lipidomics and peptidomics analyses from 112 patients with CCA and 123 patients with benign biliary diseases. Lipidomics analysis showed that various lipids, such as glycerophospholipids, glycerides, and sphingolipids, were perturbed. Peptidomics analysis revealed perturbations of multiple proteins involved in the coagulation cascade, lipid transport, and so on. After data mining, 25 characteristic molecules including 20 lipids and 5 peptides were identified as potential diagnostic biomarkers. After screening various machine learning algorithms, artificial neural network was selected to construct a multiomics model for CCA diagnosis with 96.5% sensitivity and 96.4% specificity. The sensitivity and specificity of the model in the independent test cohort were 93.8 and 87.5%, respectively. Furthermore, integrated analysis with transcriptomic data in the cancer genome atlas confirmed that genes altered in CCA significantly affected multiple lipid- and protein-related pathways. Data are available via MetaboLights with the identifier MTBLS6712.

Biological Evaluation of 8-Methoxy-2,5-dimethyl-5H-indolo[2,3-b] Quinoline as a Potential Antitumor Agent via PI3K/AKT/mTOR Signaling.

Chemotherapy is commonly used clinically to treat colorectal cancer, but it is usually prone to drug resistance, so novel drugs need to be developed continuously to treat colorectal cancer. Neocryptolepine derivatives have attracted a lot of attention because of their good cytotoxic activity; however, cytotoxicity studies on colorectal cancer cells are scarce. In this study, the cytotoxicity of 8-methoxy-2,5-dimethyl-5H-indolo[2,3-b] quinoline (MMNC) in colorectal cells was evaluated. The results showed that MMNC inhibits the proliferation of HCT116 and Caco-2 cells, blocks the cell cycle in the G2/M phase, decreases the cell mitochondrial membrane potential and induces apoptosis. In addition, the results of western blot experiments suggest that MMNC exerts cytotoxicity by inhibiting the expression of PI3K/AKT/mTOR signaling pathway-related proteins. Based on these results, MMNC is a promising lead compound for anticancer activity in the treatment of human colorectal cancer.

Dual-Mechanism-Driven Strategy for High-Coverage Detection of Serum Lipids on a Novel SALDI-MS Target.

Serum lipid metabolites have been emerging as ideal biomarkers for disease diagnosis and prediction. In the current stage, nontargeted or targeted lipidomic research mainly relies on a liquid chromatography-mass spectrometry (LC-MS) platform, but future clinical applications need more robust and high-speed platforms. Surface-assisted laser desorption ionization mass spectrometry (SALDI-MS) has shown excellent advantages in the high-speed analysis of lipid metabolites. However, the platform in the positive ion mode is more inclined to target a certain class of lipids, leading to the low coverage of lipid detection and limiting its practical translation to clinical applications. Herein, we proposed a dual-mechanism-driven strategy for high-coverage detection of serum lipids on a novel SALDI-MS target, which is a composite nanostructure comprising vertical silicon nanowires (VSiNWs) decorated with AuNPs and polydopamine (VSiNW-Au-PDA). The performance of laser desorption and ionization on the target can be enhanced by charge-driven desorption coupled with thermal-driven desorption. Simultaneous detection of 236 serum lipids (S/N ≥ 5) including neutral and polar lipids can be achieved in the positive ion mode. Among these, 107 lipid peaks were successfully identified. When combined with VSiNW-Au-PDA and VSiNW chips, 479 lipid peaks can be detected in serum samples in positive and negative ion modes, respectively. Based on the platform, serum samples from 57 hepatocellular carcinoma (HCC) patients and 76 healthy controls were analyzed. After data mining, 14 lipids containing different lipid types (TAG, CE, PC) were selected as potential lipidomic biomarkers. With the assistance of an artificial neural network, a diagnostic model with a sensitivity of 92.7% and a specificity of 96% was constructed for HCC diagnosis.

Synthesis of 8-Fluoroneocryptolepine and Evaluation for Cytotoxic Activity against AGS Cancer Cells.

Neocryptolepine derivatives have attracted great interest because of their unique cytotoxic activity. 8-Fluoroneocryptolepine (8FNC) was synthesized, and its cytotoxicity was evaluated by MTT assay in AGS gastric cancer cells and gastric mucosa GES-1 cells. 8-Fluoroneocryptolepine showed greater selectivity and cytotoxicity to AGS cells than the cisplatin (CIS) and fluorouracil (5-Fu) commonly used in clinical treatment of gastric cancer. Most importantly, we significantly improved the cytotoxic effect of 8FNC against AGS cells by structural modification and reduced the cytotoxicity against GES-1 cells compared with neocryptolepine. We further evaluated the activity of 8FNC against AGS cells in vitro. Our results indicate that 8FNC arrests the AGS cell cycle in the G2/M phase, reduces the mitochondrial membrane potential of AGS cells, and drives the initiation of apoptotic body formation in 8FNC-induced apoptosis. Moreover, 8FNC exhibits strong inhibitory effects on AGS cell migration. Studies on the molecular mechanisms of the cytotoxic activities of 8FNC revealed that it may play a significant role in the inhibitory effect on AGS human gastric cancer cells through the PI3K/AKT signaling pathway. In conclusion, 8FNC may become a promising lead compound in the development of potential clinical drug candidates for the treatment of gastric cancer.

Natural Environmental Variation Determines Microbial Diversity Patterns in Serofluid Dish, a Traditional Chinese Fermented Vegetable Food.

Serofluid dish is a traditional fermented food that contains rich microbial populations. To gain insight into the environmental variables shaping the microbial diversity patterns, serofluid dish samples were collected from different areas, and 16S rRNA sequencing was performed. Analyses revealed both species and community diversity, including phylotype richness, Shannon index and phylogenetic diversity, were mostly influenced by pH. Additionally, such effects were corroborated by the Mantel test of pairwise UniFrac distances and variable selection of multiple linear regression models. Eventually, correlations between dominant lineages and the pH of serofluid dish other than geographical distance explained a large portion of the changes in microbial composition and diversity. Lactobacillus and related genera, Pediococcus and Acetobacter were largely driven by the variability of pH, and higher richness was observed under moderate pH ranges. Collectively, the results demonstrated that a microbial diversity pattern in serofluid dish is predictable by natural environmental variation and can be better understood through pH conditions.

Design, synthesis, and cytotoxic activities of isaindigotone derivatives as potential anti-gastric cancer agents.

A series of novel derivatives of isaindigotone, which comes from the root of isaits indinatca Fort, were synthesised (Compound 1-26). Four human gastrointestinal cancer cells (HCT116, PANC-1, SMMC-7721, and AGS) were employed to evaluate the anti-proliferative activity. Among them, Compound 6 displayed the most effective inhibitory activity on AGS cells with an IC50 (50% inhibitory concentration) value of 2.2 µM. The potential mechanism study suggested that Compound 6 induced apoptosis in AGS cells. The collapse of mitochondrial membrane potential (MMP) in AGS cells was proved. In docking analysis, good affinity interaction between Compound 6 and AKT1 was discovered. Treatment of AGS cells with Compound 6 also resulted in significant suppression of PI3K/AKT/mTOR signal pathway. The collapse of MMP and suppression of PI3K/AKT/mTOR signal pathway may be responsible for induction of apoptosis. This derivative Compound 6 could be useful as an underlying anti-tumour agent for treatment of gastric cancer.

Design, Synthesis and Biological Evaluation of Neocryptolepine Derivatives as Potential Anti-Gastric Cancer Agents.

Natural products play an important role in drug development and lead compound synthesis. Neocryptolepine is a polycyclic quinoline compound isolated from Cryptolepis sanguinolent. The cytotoxicity of neocryptolepine to gastric cancer cells AGS, MKN45, HGC27, and SGC7901 was not very strong, and it also had certain toxicity to gastric mucosa cells GES-1. Therefore, a series of neocryptolepine derivatives were synthesized by the modification of the structure of neocryptolepine, and their cytotoxicity was evaluated. The results showed that compounds C5 and C8 exhibited strong cytotoxicity to AGS cells. The cell colony formation and cell migration experiments suggested that compounds C5 and C8 could inhibit the proliferation and cell migration of AGS and HGC27 cells. Cell cycle and apoptosis experiments showed that compounds C5 and C8 did not cause the apoptosis of AGS and HGC27 cells but, mainly, caused cell necrosis. Compound C5 had no significant effect on AGS and HGC27 cell cycles at low concentration. After treatment with AGS cells for 24 h at high concentration, compound C5 could significantly arrest the AGS cell cycle in the G2/M phase. Compound C8 had no significant effect on the AGS and HGC27 cell cycles. The results of molecular docking and Western blot showed that compounds C5 and C8 might induce cytotoxicity through the PI3K/AKT signaling pathway. Therefore, compounds C5 and C8 may be promising lead compounds for the treatment of gastric cancer.

A Novel Isaindigotone Derivative Displays Better Anti-Proliferation Activities and Induces Apoptosis in Gastric Cancer Cells.

Isaindigotone is an alkaloid containing a pyrrolo-[2,1-b]quinazoline moiety conjugated with a benzylidene group and isolated from the root of Isatis indigotca Fort. However, further anticancer activities of this alkaloid and its derivatives have not been fully explored. In this work, a novel isaindigotone derivative was synthesized and three different gastric cell lines and one human epithelial gastric cell line were used to study the anti-proliferation effects of the novel isaindigotone derivative BLG26. HGC27 cells and AGS cells were used to further explore the potential mechanisms. BLG26 exhibited better anti-proliferation activities in AGS cells with a half-maximal inhibitory concentration (IC50) of 1.45 µM. BLG26 caused mitochondrial membrane potential loss and induced apoptosis in both HGC27 cells and AGS cells by suppressing mitochondrial apoptotic pathway and PI3K/AKT/mTOR axis. Acute toxicity experiment showed that LD50 (median lethal dose) of BLG26 was above 1000.0 mg/kg. This research suggested that BLG26 can be a potential candidate for the treatment of gastric cancer.

High-Throughput Salivary Metabolite Profiling on an Ultralow Noise Tip-Enhanced Laser Desorption Ionization Mass Spectrometry Platform for Noninvasive Diagnosis of Early Lung Cancer.

Lung cancer (LC) is a widespread cancer that is the cause of the highest mortality rate accounting for 25% of all cancer deaths. To date, most LC patients are diagnosed at the advanced stage owing to the lack of obvious symptoms in the early stage and the limitations of current clinical diagnostic techniques. Therefore, developing a high throughput technique for early screening is of great importance. In this work, we established an effective and rapid salivary metabolic analysis platform for early LC diagnosis and combined metabolomics and transcriptomics to reveal the metabolic fluctuations correlated to LC. Saliva samples were collected from a total of 150 volunteers including 89 patients with early LC, 11 patients with advanced LC, and 50 healthy controls. The metabolic profiling of noninvasive samples was investigated on an ultralow noise TELDI-MS platform. In addition, data normalization methods were screened and assessed to overcome the MS signal variation caused by individual difference for biomarker mining. For untargeted metabolic profiling of saliva samples, around 264 peaks could be reliably detected in each sample. After multivariate analysis, 23 metabolites were sorted out and verified to be related to the dysfunction of the amino acid and nucleotide metabolism in early LC. Notably, transcriptomic data from online TCGA repository were utilized to support findings from the salivary metabolomics experiment, including the disorder of amino acid biosynthesis and amino acid metabolism. Based on the verified differential metabolites, early LC patients could be clearly distinguished from healthy controls with a sensitivity of 97.2% and a specificity of 92%. The ultralow noise TELDI-MS platform displayed satisfactory ability to explore salivary metabolite information and discover potential biomarkers that may help develop a noninvasive screening tool for early LC.

Ultrasensitive and High Reproducible Detection of Urinary Metabolites Using the Tip-Contact Extraction Method Coupled with Negative LDI-MS.

More and more evidence has proved that urinary metabolites can instantly reflect disease state. Therefore, ultra-sensitive and reproducible detection of urinary metabolites in a high-throughput way is urgently desirable for clinical diagnosis. Matrix-free laser desorption/ionization mass spectrometry (LDI-MS) is a high-throughput platform for metabolites detection, but it is encountered by severe interference from numerous salts in urine samples, because the crystallized urine salt on dried samples could result in poor reproducibility in LDI-MS detection. The present work proposed a tip-contact extraction (TCE) technique to eliminate interference from the urine salt. Vertical silicon nanowire arrays decorated with the fluorinated ethylene propylene film (FEP@VSiNWs) could effectively extract metabolites from the urine sample dropping on its surface. High salt tolerance was observed in the subsequent LDI-MS detection of the metabolites extracted on the tip of FEP@VSiNWs even in the presence of 1 M urea. Stable and reproducible mass spectra for non-target metabolic analysis were obtained in real urine samples with different dilution folds. Urinary metabolites collected from bladder cancer (BC) patients were reliably profiled by the TCE method coupled with negative LDI-MS. Based on this platform, potential metabolic biomarkers that can distinguish BC patients and normal controls were uncovered.

Hepatocarcinoma Discrimination by Ratiometric Lipid Profiles Using Tip-Contact Sampling/Ionization Mass Spectrometry.

Precise diagnosis at the molecular level is essential for the improvement of surgery and treatment. High-throughput and spatial-resolved mass spectrometric (MS) methods for in situ detection of metabolites on tissue samples can reveal the dysregulation of metabolism in abnormal tissue and help identification of tumor. We here report a nondestructive MS method named as tip-contact sampling/ionization (TCSI)-MS technology which can quickly acquire lipidomic information from liver tissue and thereby realize tumor identification. Using this technology, fatty acids and lipids at the liver tissue surface can be rapidly imprinted onto a silicon nanowire tip attached with reduced graphene oxide (rGO) and sensitively detected by on-chip MS. With proper data pretreatment and statistical analysis, the clinical primary hepatocellular carcinoma (HCC) tissues can be discriminated from the nontumor parts. In addition, we found that a panel of adjacent dual peaks' ratio can be used to build a prediction model in artificial neural networks (ANN), resulting in high accuracy (91.7-98.3%) for tumor discrimination. Ratiometric TCSI-MS imaging using a selected dual peaks' ratio can greatly enhance the spatial resolution of tumor margin. The feature ratiometric data of lipid molecules may guide the study of metabolism pathways involved in hepatocarcinoma and ultimately become new metabolic biomarkers in clinical diagnosis. The present work demonstrated that the TCSI-MS technology may pave a novel way for surgery guidance and precision diagnosis in tissue biopsy.

Isoporous Membrane Mediated Imprinting Mass Spectrometry Imaging for Spatially-Resolved Metabolomics and Rapid Histopathological Diagnosis.

Surface-assisted laser desorption/ionization (SALDI) mass spectrometry imaging (MSI) holds great value in spatial metabolomics and tumor diagnosis. Tissue imprinting on the SALDI target can avoid laser-induced tissue ablation and simplifies the sample preparation. However, the tissue imprinting process always causes lateral diffusion of biomolecules, thereby losing the fidelity of metabolite distribution on tissue. Herein, a membrane-mediated imprinting mass spectrometry imaging (MMI-MSI) strategy is proposed using isoporous nuclepore track-etched membrane as a mediating imprinting layer to selectively transport metabolites through uniform and vertical pores onto silicon nanowires (SiNWs) array. Compared with conventional direct imprinting technique, MMI-MSI can not only exclude the adsorption of large biomolecules but also avoid the lateral diffusion of metabolites. The whole time for MMI-based sample preparation can be reduced to 2 min, and the lipid peak number can increase from 46 to 113 in kidney tissue detection. Meanwhile, higher resolution of MSI can be achieved due to the confinement effect of the pore channel in the diffusion of metabolites. Based on MMI-MSI, the tumor margins of liver cancer can be clearly discriminated and their different subtypes can be precisely classified. This work demonstrates MMI-MSI is a rapid, highly sensitive, robust and high-resolution technique for spatially-resolved metabolomics and pathological diagnosis.

Study on the mechanism of naringin in promoting bone differentiation: In vitro and in vivo study.

Objective: Osteoporosis is a common clinical bone disease that occurs most frequently in middle-aged and elderly people. Various traditional herbal medicine formulations have shown significant benefits in models of osteoporosis. In this study, we aim to investigate the osteogenic efficacy of naringin (NRG) in the osteoporotic state. Design: We treated Bone marrow stromal cells (BMSCs) with various concentrations of NRG for 3 and 7 days. BMSC proliferation was measured by the MTT assay. The effect of NRG on the osteogenic differentiation of BMSCs was detected by ALP and alizarin red staining. The effect of NRG on the BMP2/Runx2/Osterix signaling pathway was analyzed by using real-time PCR. The effect of NRG on the oestrogen receptor was measured by Enzyme-linked immunosorbent assay. In vivo animal experiments were performed by micro-computed tomography and ALP immunohistochemistry to determine the ectopic osteogenic effect of NRG sustained-release nanoparticles in a mouse model of osteoporosis. Results: NRG promoted the proliferation and osteogenic differentiation of BMSCs. Moreover, it also activated the BMP2/Runx2/Osterix signaling pathway. When NRG sustained-release nanoparticles were added in vivo in animal experiments, we found that NRG sustained-release nanoparticles had better ectopic osteogenic effects in a mouse model of osteoporosis. Conclusions: NRG induced osteoblastic differentiation of BMSCs by activating the BMP2/Runx2/Osterix signaling pathway and promoted the regulation of oestrogen receptor pathway protein expression, and NRG sustained-release nanoparticles exerted a more significant in vivo ectopic osteogenic effect in an osteoporosis mouse model. Therefore, naringin is expected to be developed as a novel treatment for inducing osteogenesis, because of its ubiquitous, cost-efficient, and biologically active characteristics. However, further research is needed on how to improve the pharmacokinetic properties of naringin and its specific mechanism.

Effect of CNT Oxidation on the Processing and Properties of Superacid-Spun CNT Fibers.

Spinning fibers from carbon nanotube (CNT)/superacid dispersions has emerged as a promising strategy for industrial-scale production of high-performance CNT fibers (CNTFs). The oxygen content and types of functional groups on CNT surfaces significantly influence dispersion, assembly processes, and fiber properties. In this study, Tuball-SWCNTs were purified and oxidized at varying levels. The dispersion behavior of CNTs with different oxidation levels in chlorosulfonic acid was systematically observed, and the mechanical properties of fibers spun from these dispersions were compared. By adjusting the dispersion concentration, highly oriented CNTFs were produced with a specific strength of 1.03 N/tex, a tensile strength of 1.59 GPa, and an electrical conductivity of 3.58 MS/m. Further investigations indicated that oxygen-containing functional groups decrease the coagulation rate, increasing the maximum draw ratio during spinning and improving CNT alignment in the fibers. Molecular dynamics simulations demonstrated that these functional groups (-OH, -COOH) enhance load transfer between CNTs through hydrogen bonding. This specific strength is the highest achieved using Tuball-SWCNTs for superacid-spun fibers, surpassing previous works due to the oxidation-controlled coagulation rate, enhanced fiber orientation, and improved load transfer via hydrogen bonding. This study provides insights for designing and optimizing high-performance CNTFs.

Whole-genome sequencing analyses and antibiotic resistance situation of 48 Helicobacter pylori strains isolated in Zhejiang, China.

PURPOSE: In the Zhejiang region, research on Helicobacter pylori is lacking. The purpose of this study was to assess the extent of antibiotic resistance in H. pylori in this region, explore alternative methods for predicting the resistance patterns of H. pylori, and investigate the colonization of native gastric mucosa by other clades of H. pylori in the structure population of this bacterium. METHODS: Strains were cultured under microaerobic conditions, and antimicrobial susceptibility testing (AST) was performed via agar dilution. Whole-genome sequencing (WGS) was performed via next-generation sequencing (NGS) technology. Epidemiological data including data from this study and reported articles from Zhejiang, China, were included. Further analyses based on AST, WGS, and epidemiological date include virulence genes, antibiotic resistance-related mutations, and phylogenetic trees based on 7 housekeeping genes and core-genome single nucleotide polymorphisms (SNPs). RESULTS: The bacterial isolates in this study presented higher antibiotic resistance rates than previously reported, especially against levofloxacin and clarithromycin. The point mutation A2147G in 23 S rRNA is specific to clarithromycin resistance. Mutations at position/s 87 and/or 91 of the gyrA gene amino acid sequence are highly consistent with levofloxacin resistance highly. The point mutations C1707T in 23 S rRNA and E463K in the gyrB gene have not been previously documented in China. All the bacterial isolates belong to Asian branches in the structure population. The resistance rate to clarithromycin of isolates from hosts born after January 1, 1977 is statistically higher than that of hosts born before 1977. CONCLUSION: Eradication therapy based on AST results is urgently needed in Zhejiang. The point mutation A2147G in 23 S rRNA and point mutations in the gyrA gene at amino acid/s 87 and/or 91 are sufficient for predicting resistance to clarithromycin and levofloxacin, respectively. The isolate with the mutation E463K in the gyrB gene represents a significant contribution to the field. Mutations in 23 S rRNA may offer valuable insights into the dynamics of H. pylori transmission among hosts.

Synthesis and Biological Activity of 2-Chloro-8-methoxy-5-methyl-5H-indolo [2,3-b] Quinoline for the Treatment of Colorectal Cancer by Modulating PI3K/AKT/mTOR Pathways.

Developing novel drugs from natural products has proven to be a very effective strategy. Neocryptolepine was isolated from Cryptolepis sanguinolenta, a traditional endemic African herb, which exerts a wide range of biological activities such as antimalaria, antibacterial, and antitumor. 2-Chloro-8-methoxy-5-methyl-5H-indolo [2,3-b] quinoline (compound 49) was synthesized, and its cytotoxicity was assessed on pancreatic cancer PANC-1 cells, colorectal cancer HCT116 cells, liver cancer SMMC-7721 cells, and gastric cancer AGS cells in vitro. The results of the in vitro assay showed that compound 49 exerted remarkable cytotoxicity on colorectal cancer HCT116 and Caco-2 cells. The cytotoxicity of compound 49 to colorectal cancer HCT116 cells was 17 times higher than that of neocryptolepine and to human normal intestinal epithelial HIEC cells was significantly reduced. Compound 49 exhibited significant cytotoxicity against the colorectal cancer HCT116 and Caco-2 cells, with IC50 of 0.35 and 0.54 µM, respectively. The mechanism of cytotoxicity of compound 49 to colorectal cancer HCT116 and Caco-2 cells was further investigated. The results showed that compound 49 could inhibit colony formation and cell migration. Moreover, compound 49 could arrest the cell cycle at the G2/M phase, promote the production of reactive oxygen species, reduce mitochondrial membrane potential, and induce apoptosis. The results of Western blot indicated that compound 49 showed cytotoxicity on HCT116 and Caco-2 cells by modulating the PI3K/AKT/mTOR signaling pathway. In conclusion, these results suggested that compound 49 may be a potentially promising lead compound for the treatment of colorectal cancer.

The mechanism of efferocytosis in the pathogenesis of periodontitis and its possible therapeutic strategies.

Periodontitis is an inflammatory disease characterized by the destruction of periodontal tissues, and its etiology is related to several systemic factors. At present, the destruction of periodontal tissues is considered to be the result of inflammation resolution disorders. Efferocytosis plays an important role in the resolution of inflammation, and defective efferocytosis is an essential factor in the persistence of many chronic inflammatory diseases. Therefore, this review will describe the mechanisms involved in the efferocytosis of macrophages in the pathogenesis of periodontitis and highlight emerging therapeutic strategies to provide new ideas for future periodontal treatment.

Relevant mechanisms of MAIT cells involved in the pathogenesis of periodontitis.

Mucosal-associated invariant T (MAIT) cells are a group of unconventional T cells that are abundant in the human body, recognize microbial-derived vitamin B metabolites presented by MHC class I-related protein 1 (MR1), and rapidly produce proinflammatory cytokines, which are widely involved in the immune response to various infectious diseases. In the oral mucosa, MAIT cells tend to accumulate near the mucosal basal lamina and are more inclined to secrete IL-17 when activated. Periodontitis is a group of diseases that manifests mainly as inflammation of the gums and resorption of the alveolar bone due to periodontal tissue invasion by plaque bacteria on the dental surface. The course of periodontitis is often accompanied by a T-cell-mediated immune response. This paper discussed the pathogenesis of periodontitis and the potential contribution of MAIT cells to periodontitis.