Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions.

Concentrations of the secondary bile acid, deoxycholic acid (DCA), are aberrantly elevated in colorectal cancer (CRC) patients, but the consequences remain poorly understood. Here, we screened a library of gut microbiota-derived metabolites and identified DCA as a negative regulator for CD8+ T cell effector function. Mechanistically, DCA suppressed CD8+ T cell responses by targeting plasma membrane Ca2+ ATPase (PMCA) to inhibit Ca2+-nuclear factor of activated T cells (NFAT)2 signaling. In CRC patients, CD8+ T cell effector function negatively correlated with both DCA concentration and expression of a bacterial DCA biosynthetic gene. Bacteria harboring DCA biosynthetic genes suppressed CD8+ T cells effector function and promoted tumor growth in mice. This effect was abolished by disrupting bile acid metabolism via bile acid chelation, genetic ablation of bacterial DCA biosynthetic pathway, or specific bacteriophage. Our study demonstrated causation between microbial DCA metabolism and anti-tumor CD8+ T cell response in CRC, suggesting potential directions for anti-tumor therapy.

Engineering contact curved interface with high-electronic-state active sites for high-performance potassium-ion batteries.

Potassium-ion batteries (PIBs) have attracted ever-increasing interest due to the abundant potassium resources and low cost, which are considered a sustainable energy storage technology. However, the graphite anodes employed in PIBs suffer from low capacity and sluggish reaction kinetics caused by the large radius of potassium ions. Herein, we report nitrogen-doped, defect-rich hollow carbon nanospheres with contact curved interfaces (CCIs) on carbon nanotubes (CNTs), namely CCI-CNS/CNT, to boost both electron transfer and potassium-ion adsorption. Density functional theory calculations validate that engineering CCIs significantly augments the electronic state near the Fermi level, thus promoting electron transfer. In addition, the CCIs exhibit a pronounced affinity for potassium ions, promoting their adsorption and subsequently benefiting potassium storage. As a result, the rationally designed CCI-CNS/CNT anode shows remarkable cyclic stability and rate capability. This work provides a strategy for enhancing the potassium storage performance of carbonaceous materials through CCI engineering, which can be further extended to other battery systems.

Uncovering the cellular and omics characteristics of natural killer cells in the bone marrow microenvironment of patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy and the most frequently acute leukemia of stem cell precursors and the myeloid derivatives in adult. Longitudinal studies have indicated the therapeutic landscape and drug resistance for patients with AML are still intractable, which largely attribute to the deficiency of detailed information upon the pathogenesis. METHODS: In this study, we compared the cellular phenotype of resident NK cells (rAML-NKs, rHD-NKs) and expanded NK cells (eAML-NKs, eHD-NKs) from bone marrow of AML patients (AML) and healthy donors (HD). Then, we took advantage of the co-culture strategy for the evaluation of the in vitro cytotoxicity of NK cells upon diverse tumor cell lines (e.g., K562, Nalm6, U937). With the aid of RNA-sequencing (RNA-SEQ) and bioinformatics analyses (e.g., GOBP analysis, KEGG analysis, GSEA, volcano plot), we verified the similarities and differences of the omics features between eAML-NKs and eHD-NKs. RESULTS: Herein, we verified the sharp decline in the content of total resident NK cells (CD3-CD56+) in rAML-NKs compared to rHD-NKs. Differ from the expanded eHD-NKs, eAML-NKs revealed decline in diverse NK cell subsets (NKG2D+, CD25+, NKp44+, NKp46+) and alterations in cellular vitality but conservations in cytotoxicity. According to transcriptomic analysis, AML-NKs and HD-NKs showed multifaceted distinctions in gene expression profiling and genetic variations. CONCLUSIONS: Collectively, our data revealed the variations in the cytobiological and transcriptomic features between AML-NKs and HD-NKs in bone marrow environment. Our findings would benefit the further development of novel biomarkers for AML diagnosis and NK cell-based cytotherapy in future.

One-day versus three-day low-residue diet bowel preparation regimens before colonoscopy: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Although studies have shown that the quality of bowel preparation with low-residue diet (LRD) is as effective as that of clear fluid diet (CLD), there is currently no consensus on how long an LRD should last. The aim of this study was to compare a 1-day versus 3-day LRD on bowel preparation before colonoscopy. METHODS: A systematic review search was conducted in MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane database from inception to April 2023. We identified randomized controlled trials (RCTs) that compared 1-day with 3-day LRD bowel cleansing regiments for patients undergoing colonoscopy. The rate of adequate bowel preparation, polyp detection rate, adenoma detection rate, tolerability, willingness to repeat preparation, and adverse events were estimated using odds ratios (OR) and 95% confidence interval (CI). We also performed meta-analysis to identify risk factors and predictors of inadequate preparation. RESULTS: Four studies published between 2019 and 2023 with 1927 participants were included. The present meta-analysis suggested that 1-day LRD was comparable with 3-day LRD for adequate bowel preparation (OR 0.89; 95% CI, 0.65-1.21; P = 0.45; I2 = 0%; P = 0.52). The polyp detection rate (OR 0.94; 95% CI, 0.77-1.14; P = 0.52; I2 = 23%; P = 0.27) and adenoma detection rate (OR 0.87; 95% CI, 0.71-1.08; P = 0.21; I2 = 0%; P = 0.52) were similar between the groups. There were significantly higher odds of tolerability in patients consuming 1-day LRD compared with 3-day LRD (OR 1.64; 95% CI, 1.13-2.39; P < 0.01; I2 = 47%; P = 0.15). In addition, constipation was identified as the independent predictor of inadequate preparation (OR 1.98; 95% CI, 1.27-3.11; P < 0.01; I2 = 0%; P = 0.46). CONCLUSION: The present study demonstrated that a 1-day LRD was as effective as a 3-day CLD in the quality of bowel preparation before colonoscopy and significantly improved tolerability of patients. In addition, constipation is an independent risk factor of poor bowel preparation, and the duration of LRD in patients with constipation still needs further clinical trials.

The Abca7V1613M variant reduces Aß generation, plaque load, and neuronal damage.

BACKGROUND: Variants in ABCA7, a member of the ABC transporter superfamily, have been associated with increased risk for developing late onset Alzheimer's disease (LOAD). METHODS: CRISPR-Cas9 was used to generate an Abca7V1613M variant in mice, modeling the homologous human ABCA7V1599M variant, and extensive characterization was performed. RESULTS: Abca7V1613M microglia show differential gene expression profiles upon lipopolysaccharide challenge and increased phagocytic capacity. Homozygous Abca7V1613M mice display elevated circulating cholesterol and altered brain lipid composition. When crossed with 5xFAD mice, homozygous Abca7V1613M mice display fewer Thioflavin S-positive plaques, decreased amyloid beta (Aß) peptides, and altered amyloid precursor protein processing and trafficking. They also exhibit reduced Aß-associated inflammation, gliosis, and neuronal damage. DISCUSSION: Overall, homozygosity for the Abca7V1613M variant influences phagocytosis, response to inflammation, lipid metabolism, Aß pathology, and neuronal damage in mice. This variant may confer a gain of function and offer a protective effect against Alzheimer's disease-related pathology. HIGHLIGHTS: ABCA7 recognized as a top 10 risk gene for developing Alzheimer's disease. Loss of function mutations result in increased risk for LOAD. V1613M variant reduces amyloid beta plaque burden in 5xFAD mice. V1613M variant modulates APP processing and trafficking in 5xFAD mice. V1613M variant reduces amyloid beta-associated damage in 5xFAD mice.

BIN1K358R suppresses glial response to plaques in mouse model of Alzheimer's disease.

INTRODUCTION: The BIN1 coding variant rs138047593 (K358R) is linked to Late-Onset Alzheimer's Disease (LOAD) via targeted exome sequencing. METHODS: To elucidate the functional consequences of this rare coding variant on brain amyloidosis and neuroinflammation, we generated BIN1K358R knock-in mice using CRISPR/Cas9 technology. These mice were subsequently bred with 5xFAD transgenic mice, which serve as a model for Alzheimer's pathology. RESULTS: The presence of the BIN1K358R variant leads to increased cerebral amyloid deposition, with a dampened response of astrocytes and oligodendrocytes, but not microglia, at both the cellular and transcriptional levels. This correlates with decreased neurofilament light chain in both plasma and brain tissue. Synaptic densities are significantly increased in both wild-type and 5xFAD backgrounds homozygous for the BIN1K358R variant. DISCUSSION: The BIN1 K358R variant modulates amyloid pathology in 5xFAD mice, attenuates the astrocytic and oligodendrocytic responses to amyloid plaques, decreases damage markers, and elevates synaptic densities. HIGHLIGHTS: BIN1 rs138047593 (K358R) coding variant is associated with increased risk of LOAD. BIN1 K358R variant increases amyloid plaque load in 12-month-old 5xFAD mice. BIN1 K358R variant dampens astrocytic and oligodendrocytic response to plaques. BIN1 K358R variant decreases neuronal damage in 5xFAD mice. BIN1 K358R upregulates synaptic densities and modulates synaptic transmission.

Sleep disorder experienced by healthcare nurses after terminating Zero-COVID-19 policy.

OBJECTIVE: Medical staff, especially nurses, suffered great anxiety and stress from the COVID-19 pandemic, which negatively affected their sleep quality. In this study, we aimed to analyze the sleep quality of nursing staff after terminating the Zero-COVID-19 policy in China. METHODS: 506 participants were involved in our study. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep status of the participants. Binary regression was performed to evaluate the impact factors related to sleep difficulty. RESULTS: The majority of participants (96.44%) suffered from sleep disturbances. There were significant differences in age, education level and front-line activity between participants with good sleep quality and sleep difficulty. Younger age (16-25 years old) was independently associated with less sleep difficulty, while front-line activity was independently associated with severe sleep difficulty. CONCLUSION: Sleep disorder was very common among nurses after ending the Zero-COVID-19 policy in China. More front-line nurses suffered severe sleep difficulty in particular, which should be worthy of attention.

The gut-lung axis in critical illness: microbiome composition as a predictor of mortality at day 28 in mechanically ventilated patients.

BACKGROUND: Microbial communities are of critical importance in the human host. The lung and gut microbial communities represent the most essential microbiota within the human body, collectively referred to as the gut-lung axis. However, the differentiation between these communities and their influence on clinical outcomes in critically ill patients remains uncertain. METHODS: An observational cohort study was obtained in the intensive care unit (ICU) of an affiliated university hospital. Sequential samples were procured from two distinct anatomical sites, namely the respiratory and intestinal tracts, at two precisely defined time intervals: within 48 h and on day 7 following intubation. Subsequently, these samples underwent a comprehensive analysis to characterize microbial communities using 16S ribosomal RNA (rRNA) gene sequencing and to quantify concentrations of fecal short-chain fatty acids (SCFAs). The primary predictors in this investigation included lung and gut microbial diversity, along with indicator species. The primary outcome of interest was the survival status at 28 days following mechanical ventilation. RESULTS: Sixty-two mechanically ventilated critically ill patients were included in this study. Compared to the survivors, the diversity of microorganisms was significantly lower in the deceased, with a significant contribution from the gut-originated fraction of lung microorganisms. Lower concentrations of fecal SCFAs were detected in the deceased. Multivariate Cox regression analysis revealed that not only lung microbial diversity but also the abundance of Enterococcaceae from the gut were correlated with day 28 mortality. CONCLUSION: Critically ill patients exhibited lung and gut microbial dysbiosis after mechanical ventilation, as evidenced by a significant decrease in lung microbial diversity and the proliferation of Enterococcaceae in the gut. Levels of fecal SCFAs in the deceased served as a marker of imbalance between commensal and pathogenic flora in the gut. These findings emphasize the clinical significance of microbial profiling in predicting the prognosis of ICU patients.

Negative gallbladder stones: Diagnostic advantages of dual-energy CT and analysis of a unique case.

BACKGROUND: Gallbladder stones are a common digestive system disease, but their diagnosis can be limited in some cases, especially in identifying "negative" stones, which may be difficult to recognize with traditional CT scans. OBJECTIVE: This study aims to explore the advantages of dual-energy CT in diagnosing negative gallbladder stones through a unique case of gallbladder stones. METHODS AND RESULTS: A case of a 31-year-old female is described, who was diagnosed with gallbladder stones during a physical examination two years ago and occasionally experienced pain in the upper right abdomen. Dual-energy CT scanning revealed a mixed-density stone, approximately 2 cm in diameter, in the neck of the gallbladder, consisting of a calcified shell (positive stone) and a homogenous density nucleus (negative stone). Verified by dual-energy CT, single-energy images and spectral curves can very intuitively identify negative stones, demonstrating significantly superior performance compared to traditional CT. CONCLUSION: Dual-energy CT, through single-energy images and spectral curves, intuitively identifies negative gallbladder stones, showcasing significant advantages compared to traditional CT, and offers a valuable approach to enhancing the diagnostic accuracy of gallbladder stones.

Enhanced depth imaging optical coherence tomography features of two types of Vogt-Koyanagi-Harada disease: fuzzy or lost pattern of the choroidal vasculature is of diagnostic value.

Objective: This study aimed to compare enhanced depth imaging optical coherence tomography (EDI-OCT) features of exudative retinal detachment (ERD) type and optic disc (OD) swelling type Vogt-Koyanagi-Harada (VKH) disease. Methods: Hospitalized VKH patients were retrospectively reviewed and classified into the ERD type and the OD swelling type. The EDI-OCT features were then analyzed. Results: The study included 32 ERD type and 15 OD swelling type VKH patients at the acute uveitis stage. The interval between the onset of ocular symptoms and the start of treatment in OD swelling type VKH disease was significantly longer compared to the ERD type (p < 0.001). A fuzzy or lost pattern of the choroidal vasculature was observed in 100% of VKH patients of both types. Moreover, high frequencies (greater than or equal to 50%) of fluctuations in the internal limiting membrane, interdigitation zone disruption, ERD, retinal pigment epithelium (RPE) folds, and ellipsoid zone disruption were observed in both types. Patients with OD swelling type VKH disease exhibited higher frequencies of OD swelling and hyperreflective substances above the RPE (p < 0.001 and p = 0.003, respectively), with lower frequencies of ERD and bacillary layer detachment (p = 0.012 and p < 0.001, respectively). At the convalescence stage, changes in the EDI-OCT images of 10 ERD type and 5 OD swelling type VKH patients were analyzed. The frequencies of the OCT features decreased with similar trends in both types of VKH disease. Conclusion: Although ERD type and OD swelling type VKH disease have their own unique characteristics, they share common EDI-OCT features. The Fuzzy or lost pattern of the choroidal vasculature that indicates choroidal inflammation may serve as a diagnostic aid for VKH disease, especially for the OD swelling type and the early-stage ERD type.

Development and validation of ELISA method for quantification of Q-1802 in serum and its application to pharmacokinetic study in ICR Mouse.

Q-1802 is a humanized bispecific antibody targeting programmed death-ligand 1 (PD-L1) and Claudin 18.2 (CLDN18.2). It can bind to CLDN18.2 and mediate antibody-dependent cell-mediated cytotoxicity against tumor cells. The Fc segment of the antibody recognizing PD-L1 blocks PD-1 signaling and activates innate immunity and adaptive immunity. In this study, we report the development, validation, and application of sensitive and high-throughput enzyme-linked immunosorbent assays (ELISA) to measure the concentrations of Q-1802 in ICR mouse serum. The assay is sensitive, with a lower limit of quantification of 50 ng/mL, has a broad dynamic range of 50-3200 ng/mL, and exhibits excellent precision and accuracy. These assays were successfully applied to in vitro serum stability and pharmacokinetic (PK) studies. In conclusion, we have developed and validated a highly sensitive and selective method for measuring Q-1802 in ICR mouse serum. The development and validation steps of assays met the required criteria for validation, which suggested that these can be applied to quantify Q-1802, as well as in PK studies.

SNAI2 enhances HPV­negative cervical cancer cell dormancy by modulating u­PAR expression and the activity of the ERK/p38 signaling pathway in vitro.

The prognosis of patients with human papillomavirus (HPV)­negative cervical cancer is significantly worse than that of patients with HPV­positive cervical cancer. Understanding the mechanisms of this is crucial for preventing disease evolution. In the present study, the GV367­snail family transcriptional repressor 2 (SNAI2) lentiviral vector was constructed and transduced into C­33A cells. Subsequently, the proliferation of tumor cells was detected using the Cell Counting Kit (CCK)­8 method. Flow cytometry was used to analyze the cell cycle progression of tumor cells. The glucose consumption of tumor cells was detected using an oxidase assay, and the senescence of tumor cells was detected using beta­galactosidase staining. The gene expression and the activity of p38 and ERK1/2 were detected using reverse transcription­quantitative PCR and western blotting, respectively. The C­33A­SNAI2 cell line was successfully established. Compared with HeLa and C­33A­Wild cells, the proliferation and percentage of G0/G1­phase cells in the C­33A­SNAI2 group were decreased, as detected by the CCK­8 assay (100±0 vs. 239.1±58.3 vs. 39.7±20.1, P<0.01) and flow cytometry (34.0±7.1% vs. 46.2±10.6% vs. 61.3±5.3%, P<0.05). Compared with the HeLa group, the glucose consumption of the C­33A­Wild and C­33A­SNAI2 groups was significantly decreased (P<0.01). The results of beta­galactosidase staining showed that the proportion of beta­galactosidase­positive cells in the C­33A­SNAI2 group was significantly decreased compared with the C­33A­Wild group (P<0.01). Upregulation of SNAI2 enhanced the increase in p21 expression, and the decrease in CDK1, urokinase plasminogen activator receptor (u­PAR) and cyclin D1 expression in C­33A cells compared with C­33A­Wild cells (P<0.05). In addition, the activities of p38, ERK1/2 and the phosphorylated (p)­ERK1/2/p­p38 ratio were decreased in the C­33A­SNAI2 group compared with the C­33A­Wild and HeLa groups (P<0.05). In conclusion, SNAI2 enhanced HPV­negative cervical cancer C­33A cell dormancy, which was characterized by G0/G1 arrest, by the downregulation of u­PAR expression, and a decrease in the activity of the p­ERK1/2 and p­p38MAPK signaling pathways in vitro. Cancer recurrence and metastases are responsible for most cancer­related deaths. Given that SNAI2 is required for enhancing HPV­negative cervical cancer cell dormancy, regulating this process may promote cervical tumor cells to enter a continuous dormant state, which could be a potential approach for tumor therapy.

Serum HER2 Level Predicts Therapeutic Efficacy and Prognosis in Advanced Breast Cancer Patients.

Background: The purpose of this study was to investigate the therapeutic efficacy and prognosis of serum HER2 (sHER2) in patients with advanced breast cancer. Methods: We analyzed the sHER2 levels of 200 patients with advanced breast cancer receiving first or second line treatment, the tissue HER2 (tHER2) level was also analyzed. Indicators of therapeutic efficacy and prognosis were objective response rate (ORR), disease control rate (DCR), and time to progression (TTP). Results: The baseline sHER2 level was high in 132 patients and low in 68 patients. The high level of sHER2 is correlated with molecular subtype (p=0.016), visceral metastasis (p<0.001), liver metastasis (p<0.001), tissue HER-2 (tHER2) (p=0.001), and, among tHER2-low tumors (59 patients), the baseline sHER2 high level was associated with a higher proportion of brain metastasis. The ORR of patients with baseline sHER2 high level is higher than those with baseline sHER2 low level (p=0.026). The TTP of patients with baseline sHER2 low level is longer than the patients with baseline sHER2 high level (p=0.024). For patients with baseline sHER2 high level, a significant decrease in sHER2 after two cycles of treatment indicates higher ORR, DCR, and an extension of TTP. After multiple cycles of treatment, for patients with tHER-2 positive and baseline sHER2 high level, the DCR in the sHER2 decrease in the negative group was higher than that in the continuous positive group (p=0.037). Patients with a rapid decline type of sHER2 dynamic change curve had higher ORR and prolonged TTP compared with patients with other types of sHER2 dynamic change curve. There is no correlation between OS and sHER2 levels. Conclusion: Our study showed that patients with advanced breast cancer had a high level of sHER2 at recurrence, regardless of whether they are tHER2 positive or negative. Dynamic detection of sHER2 can help predict therapeutic efficacy and prognosis, regardless of whether tHER-2 is positive or negative.

FEN1 upregulation mediated by SUMO2 via antagonizing proteasomal degradation promotes hepatocellular carcinoma stemness.

PURPOSE: Metastasis of hepatocellular carcinoma (HCC) critically impacts the survival prognosis of patients, with the pivotal role of hepatocellular carcinoma stem cells in initiating invasive metastatic behaviors. The Flap Endonuclease 1 (FEN1) is delineated as a metallonuclease, quintessential for myriad cellular processes including DNA replication, DNA synthesis, DNA damage rectification, Okazaki fragment maturation, baseexcision repair, and the preservation of genomic stability. Furthermore, it has been recognized as an oncogene in a diverse range of malignancies. Our antecedent research has highlighted a pronounced overexpression of protein FEN1 in hepatocellular carcinoma, where it amplifies the invasiveness and metastatic potential of liver cancer cells. However, its precise role in liver cancer stem cells (LCSCs) remains an enigma and requires further investigation. METHODS: To rigorously evaluate the stemness attributes of LCSCs, we employed sphere formation assays and flow cytometric evaluations. Both CD133+ and CD133- cell populations were discerningly isolated utilizing immunomagnetic bead separation techniques. The expression levels of pertinent genes were assayed via real-time quantitative PCR (RT-qPCR) and western blot analyses, while the expression profiles in hepatocellular carcinoma tissues were gauged using immunohistochemistry. Subsequent immunoprecipitation, in conjunction with mass spectrometry, ascertained the concurrent binding of proteins FEN1 and Small ubiquitin-related modifier 2 (SUMO2) in HCC cells. Lastly, the impact of SUMO2 on proteasomal degradation pathway of FEN1 was validated by supplementing MG132. RESULTS: Our empirical findings substantiate that protein FEN1 is profusely expressed in spheroids and CD133+ cells. In vitro investigations demonstrate that the upregulation of protein FEN1 unequivocally augments the stemness of LCSCs. In a congruent in vivo context, elevation of FEN1 noticeably enhances the tumorigenic potential of LCSCs. Conversely, inhibiting protein FEN1 resulted in a marked reduction in LCSC stemness. From a mechanistic perspective, there exists a salient positive correlation between the protein expression of FEN1 and SUMO2 in liver cancer tissues. Furthermore, the level of SUMO2-mediated modification of FEN1 is pronouncedly elevated in LCSCs. Interestingly, SUMO2 has the ability to bind to FEN1, leading to a inhibition in the proteasomal degradation pathway of FEN1 and an enhancement in its protein expression. However, it is noteworthy that this interaction does not affect the mRNA level of FEN1. CONCLUSION: In summation, our research elucidates that protein FEN1 is an effector in augmenting the stemness of LCSCs. Consequently, strategic attenuation of protein FEN1 might proffer a pioneering approach for the efficacious elimination of LCSCs.

Quest for the Nitrogen-Metabolic Versatility of Microorganisms in Soil and Marine Ecosystems.

Whether nitrogen (N)-metabolic versatility is a common trait of N-transforming microbes or if it only occurs in a few species is still unknown. We collected 83 soil samples from six soil types across China, retrieved 19 publicly available metagenomic marine sample data, and analyzed the functional traits of N-transforming microorganisms using metagenomic sequencing. More than 38% and 35% of N-transforming species in soil and marine ecosystems, respectively, encoded two or more N-pathways, although N-transforming species differed greatly between them. Furthermore, in both soil and marine ecosystems, more than 80% of nitrifying and N-fixing microorganisms at the species level were N-metabolic versatile. This study reveals that N-metabolic versatility is a common trait of N-transforming microbes, which could expand our understanding of the functional traits of drivers of nitrogen biogeochemistry.

Development of modern Chinese medicine guided by molecular compatibility theory.

BACKGROUND: Traditional Chinese Medicine (TCM) has gained global attention, particularly after Professor Youyou Tu was awarded the Nobel Prize for her discovery of artemisinin as a treatment for malaria. However, the theory behind TCM is often perceived as a "black-box" with complex components and an unclear structure and mechanism of action. This had hindered the development of TCM within the framework of modern medicine. AIM OF REVIEW: The molecular compatibility theory proposed by Professor Tian Xie's team integrates TCM with Western medicine in clinical practice, and provide a feasible direction for TCM modernization. It is necessary to summarize and popularize this theory. This review aims to systematically introduce this theory to provide some new insight for development of TCM. KEY SCIENTIFIC CONCEPTS OF REVIEW: According to the molecular compatibility theory, the desired effects can be achieved by organically combining multiple active molecules from TCM. These TCM molecular compounds have specific ingredients, precise mechanisms, and controllable quality that meet the standards of modern medicine. The molecular compatibility theory has guided the development of antitumor new drug elemene emulsions, and has also revealed extensive compatibility between TCM-derived active molecules and other TCM, Western medicine, or biomaterials. This discovery opens up potential TCM-based treatment options. In conclusion, the molecular compatibility theory holds promise as a strategy for modernizing TCM.

Comparison of the value of adipose tissues in abdomen and lumbar vertebra for predicting disease activity in Crohn's disease: A preliminary study based on CSE-MRI.

BACKGROUND: To compare the value of adipose tissues in abdomen and lumbar vertebra for predicting Crohn's disease (CD) activity based on chemical shift encoded magnetic resonance imaging (CSE-MRI). METHODS: 84 CD patients were divided into remission, mild, and moderate-severely groups based on CD activity index (CDAI). Differences in different adipose parameters [subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), mesenteric fat index (MFI), and bone marrow fat fraction (BMFF)] and blood inflammatory indicators among three groups, as well as the correlation of above parameters and CDAI were analyzed. The areas under the receiver-operating characteristic curves (AUCs) for the parameters selected by multivariate logistic regression analysis for predicting active CD were calculated. RESULTS: There were no significant differences in VAT and MFI among three groups (both P > 0.05). The cross-sectional areas of SAT in moderate-severe group were significantly lower than those in remission group (P = 0.014). BMFF values of remission group were significantly higher than those in the mild and moderate-severe groups (both P < 0.001). BMFF was negatively correlated with CDAI (r = -0.595, P < 0.001). SAT exhibited no significant correlation with CDAI. Erythrocyte sedimentation rate (ESR) and BMFF were the independent predictors of CDAI. Both combined had a higher diagnostic efficacy for active CD with an AUC of 0.895. CONCLUSIONS: BMFF is the best marker for predicting CD activity in fat parameters of abdomen and lumbar vertebra based on CSE-MRI. The model based on BMFF and ESR has a high efficiency in predicting active CD. TRIAL REGISTRATION: No. 22 K164 (Registered 18-07-2022).

Reprogramming the Metabolism of Yeast for High-Level Production of Miltiradiene.

Miltiradiene serves as a crucial precursor in the synthesis of various high-value abietane-type diterpenes, exhibiting diverse pharmacological activities. Previous efforts to enhance miltiradiene production have primarily focused on the mevalonate acetate (MVA) pathway. However, limited emphasis has been placed on optimizing the supply of acetyl-CoA and NADPH. In this study, we constructed a platform yeast strain for miltiradiene production by reinforcing the biosynthetic pathway of geranylgeranyl diphosphate (GGPP) and acetyl-CoA, and addressing the imbalance between the supply and demand of the redox cofactor NADPH within the cytoplasm, resulting in an increase in miltiradiene yield to 1.31 g/L. Furthermore, we conducted modifications to the miltiradiene synthase fusion protein tSmKSL1-CfTPS1. Finally, the comprehensive engineering strategies and protein modification strategies culminated in 1.43 g/L miltiradiene in the engineered yeast under shake flask culture conditions. Overall, our work established efficient yeast cell factories for miltiradiene production, providing a foothold for heterologous biosynthesis of abietane-type diterpenes.

Neutrophil extracellular traps in central nervous system (CNS) diseases.

Excessive induction of inflammatory and immune responses is widely considered as one of vital factors contributing to the pathogenesis and progression of central nervous system (CNS) diseases. Neutrophils are well-studied members of inflammatory and immune cell family, contributing to the innate and adaptive immunity. Neutrophil-released neutrophil extracellular traps (NETs) play an important role in the regulation of various kinds of diseases, including CNS diseases. In this review, current knowledge on the biological features of NETs will be introduced. In addition, the role of NETs in several popular and well-studied CNS diseases including cerebral stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurological cancers will be described and discussed through the reviewing of previous related studies.