Screening and diagnosis of cardiovascular disease using artificial intelligence-enabled cardiac magnetic resonance imaging.

Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.

Liver fat as a dietary target by Chinese Medical Nutrition Therapy (CMNT) diet for treating type 2 diabetes with non-alcoholic fatty liver disease: study protocol for a randomised controlled trial.

INTRODUCTION: Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) often coexist and increase risk for developing liver fibrosis and diabetes complications if no effective measures are taken. Dietary intervention is known to be able to achieve diabetes remission, while evidence regarding the long-term effect on liver fat is limited for comorbidity management of type 2 diabetes and NAFLD. This study aims to investigate the long-term effect of a Chinese Medical Nutrition Therapy (CMNT) diet accompanied by intermittent energy restriction on reducing liver fat and glycated haemoglobin (HbA1c) in patients with type 2 diabetes and NAFLD. METHODS AND ANALYSIS: This is a multicentre two-armed parallel randomised controlled trial study. 120 participants with type 2 diabetes and NAFLD will be recruited from the physical examination centres of multiple hospitals in China. Participants will be randomly allocated 1:1 to either the CMNT group or the usual care group. The CMNT group will be instructed to consume the provided specific meal replacement Chinese medicinal foods consisting of 6 cycles of 5 consecutive days followed by 10 days of regular food intake. The usual care group will be given standard dietary advice. Primary outcomes are changes in the controlled attenuation parameter value by transient elastography and HbA1c level. Secondary outcomes include differences in anthropometrics, clinical blood markers, questionnaires, gut microbiota and metabolomics. Further follow-up will be performed at 6 months, 1 year and 2 years. ETHICS AND DISSEMINATION: The study protocol was approved by the Biomedical Research Ethics Committee of Hunan Agricultural University (BRECHAU20200235).The results will be disseminated via relevant peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05439226.

Revisiting an old relationship: the causal associations of the ApoB/ApoA1 ratio with cardiometabolic diseases and relative risk factors-a mendelian randomization analysis.

BACKGROUND: It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. METHODS: In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European Genome-Wide Association Study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors. RESULTS: In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all PFDR<0.05). Meanwhile, the ApoB/ApoA1 ratio was significantly associated with CMD risk factors, such as hemoglobin A1c, fasting insulin levels, waist-to-hip ratio, sedentary behavior, and various others, demonstrating a notable causal relationship (all PFDR<0.05). Additionally, the ApoB/ApoA1 ratio played a mediating role in CMD and relative risk factors. CONCLUSIONS: This MR study provides evidence supporting the significant causal relationship between the ApoB/ApoA1 ratio and CMD and its risk factors. Moreover, it demonstrates the mediating effect of the ApoB/ApoA1 ratio in CMD and its risk factors. These findings suggest that the ApoB/ApoA1 ratio may serve as a potential indicator for identifying the risk of developing CMD in participants.

WGX50 mitigates doxorubicin-induced cardiotoxicity through inhibition of mitochondrial ROS and ferroptosis.

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It is indispensable to explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, its function and mechanism in DIC remain unclear. METHODS: We established DOX-induced cardiotoxicity models both in vitro and in vivo. Echocardiography and histological analyses were used to determine the severity of cardiac injury in mice. The myocardial damage markers cTnT, CK-MB, ANP, BNP, and ferroptosis associated indicators Fe2+, MDA, and GPX4 were measured using ELISA, RT-qPCR, and western blot assays. The morphology of mitochondria was investigated with a transmission electron microscope. The levels of mitochondrial membrane potential, mitochondrial ROS, and lipid ROS were detected using JC-1, MitoSOX™, and C11-BODIPY 581/591 probes. RESULTS: Our findings demonstrate that WGX50 protects DOX-induced cardiotoxicity via restraining mitochondrial ROS and ferroptosis. In vivo, WGX50 effectively relieves doxorubicin-induced cardiac dysfunction, cardiac injury, fibrosis, mitochondrial damage, and redox imbalance. In vitro, WGX50 preserves mitochondrial function by reducing the level of mitochondrial membrane potential and increasing mitochondrial ATP production. Furthermore, WGX50 reduces iron accumulation and mitochondrial ROS, increases GPX4 expression, and regulates lipid metabolism to inhibit DOX-induced ferroptosis. CONCLUSION: Taken together, WGX50 protects DOX-induced cardiotoxicity via mitochondrial ROS and the ferroptosis pathway, which provides novel insights for WGX50 as a promising drug candidate for cardioprotection.

High-Resolution Profiling of Head and Neck Squamous Cells Carcinoma Identifies Specific Biomarkers and Expression Subtypes of Clinically Relevant Vulnerabilities.

BACKGROUND: Head and neck squamous cell carcinoma (HNSC) is the seventh most common cancer worldwide. Although there are several options for the treatment of HNSC, there is still a lack of better biomarkers to accurately predict the response to treatment and thus be more able to correctly treat the therapeutic modality. METHODS: First, we typed cases from the TCGA-HNSC cohort into subtypes by a Bayesian non-negative matrix factorization (BayesNMF)-based consensus clustering approach. Subsequently, genomic and proteomic data from HNSC cell lines were integrated to identify biomarkers of response to targeted therapies and immunotherapies. Finally, associations between HNSC subtypes and CD8 T-cell-associated effector molecules, common immune checkpoint genes, were compared to assess the potential of HNSC subtypes as clinically predictive immune checkpoint blockade therapy. RESULTS: The 500 HNSC cases from TCGA were put through a consensus clustering approach to identify six HNSC expression subtypes. In addition, subtypes with unique proteomics and dependency profiles were defined based on HNSC cell line histology and proteomics data. Subtype 4 (S4) exhibits hyperproliferative and hyperimmune properties, and S4-associated cell lines show specific vulnerability to ADAT2, EIF5AL1, and PAK2. PD-L1 and CASP1 inhibitors have therapeutic potential in S4, and we have also demonstrated that S4 is more responsive to immune checkpoint blockade therapy. CONCLUSION: Overall, our HNSC typing approach identified robust tumor-expressing subtypes, and data from multiple screens also revealed subtype-specific biology and vulnerabilities. These HNSC expression subtypes and their biomarkers will help develop more effective therapeutic strategies.

TRPV1 inhibition suppresses non-small cell lung cancer progression by inhibiting tumour growth and enhancing the immune response.

PURPOSE: TRPV1 is a nonselective Ca2+ channel protein that is widely expressed and plays an important role during the occurrence and development of many cancers. Activation of TRPV1 channels can affect tumour progression by regulating proliferation, apoptosis and migration. Some studies have also shown that activating TRPV1 can affect tumour progression by modulating tumour immunity. However, the effects of TRPV1 on the development of non-small cell lung cancer (NSCLC) have not been explored clearly. METHOD: The Cancer Genome Atlas (TCGA) database and spatial transcriptomics datasets from 10 × Genomics were used to analyze TRPV1 expression in various tumour tissues. Cell proliferation and apoptosis were examined by cell counting kit 8 (CCK8), colony formation, and flow cytometry. Immunohistochemistry, qPCR, and western blotting were used to determine the mRNA and protein expression levels of TRPV1 and other related molecules. Tumour xenografts in BALB/C and C57BL/6J mice were used to determine the effects of TRPV1 on NSCLC development in vivo. Neurotransmitter content was examined by LC-MS/MS, ELISA and Immunohistochemistry. Immune cell infiltration was assessed by flow cytometry. RESULTS: In this study, we found that TRPV1 expression was significantly upregulated in NSCLC and that patients with high TRPV1 expression had a poor prognosis. TRPV1 knockdown can significantly inhibit NSCLC proliferation and induce cell apoptosis through Ca2+-IGF1R signaling. In addition, TRPV1 knockdown resulted in increased infiltration of CD4+ T cells, CD8+ T cells, GZMB+CD8+ T cells and DCs and decreased infiltration of immunosuppressive MDSCs in NSCLC. In addition, TRPV1 knockout effectively decreased the expression of M2 macrophage markers CD163 and increased the expression of M1-associated, costimulatory markers CD86. Knockdown or knockout of TRPV1 significantly inhibit tumour growth and promoted an antitumour immune response through supressing γ-aminobutyric acid (GABA) secretion in NSCLC. CONCLUSION: Our study suggests that TRPV1 acts as a tumour promoter in NSCLC, mediating pro-proliferative and anti-apoptotic effects on NSCLC through IGF1R signaling and regulating GABA release to affect the tumour immune response.

Exploring the role of microbial proteins in controlling environmental pollutants based on molecular simulation.

Molecular simulation has been widely used to study microbial proteins' structural composition and dynamic properties, such as volatility, flexibility, and stability at the microscopic scale. Herein, this review describes the key elements of molecular docking and molecular dynamics (MD) simulations in molecular simulation; reviews the techniques combined with molecular simulation, such as crystallography, spectroscopy, molecular biology, and machine learning, to validate simulation results and bridge information gaps in the structure, microenvironmental changes, expression mechanisms, and intensity quantification; illustrates the application of molecular simulation, in characterizing the molecular mechanisms of interaction of microbial proteins with four different types of contaminants, namely heavy metals (HMs), pesticides, dyes and emerging contaminants (ECs). Finally, the review outlines the important role of molecular simulations in the study of microbial proteins for controlling environmental contamination and provides ideas for the application of molecular simulation in screening microbial proteins and incorporating targeted mutagenesis to obtain more effective contaminant control proteins.

[Effects of post-traumatic stress disorder on the excitability of glutamatergic and GABAergic neurons in dorsal and ventral hippocampus in mice].

The purpose of this study was to investigate the effects of post-traumatic stress disorder (PTSD) on electrophysiological characteristics of glutamatergic and GABAergic neurons in dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) in mice, and to elucidate the mechanisms underlying the plasticity of hippocampal neurons and memory regulation after PTSD. Male C57Thy1-YFP/GAD67-GFP mice were randomly divided into PTSD group and control group. Unavoidable foot shock (FS) was applied to establish PTSD model. The spatial learning ability was explored by water maze test, and the changes in electrophysiological characteristics of glutamatergic and GABAergic neurons in dHPC and vHPC were examined using whole-cell recording method. The results showed that FS significantly reduced the movement speed, and enhanced the number and percentage of freezing. PTSD significantly prolonged the escape latency in localization avoidance training, shortened the swimming time in the original quadrant, extended the swimming time in the contralateral quadrant, and increased absolute refractory period, energy barrier and inter-spike interval of glutamatergic neurons in dHPC and GABAergic neurons in vHPC, while decreased absolute refractory period, energy barrier and inter-spike interval of GABAergic neurons in dHPC and glutamatergic neurons in vHPC. These results suggest that PTSD can damage spatial perception of mice, down-regulate the excitability of dHPC and up-regulate the excitability of vHPC, and the underlying mechanism may involve the regulation of spatial memory by the plasticity of neurons in dHPC and vHPC.

Research on the Efficacy of Ganpu Vine Tea in Inhibiting Uric Acid Production.

Ganpu vine tea is a new type of health care citrus fruit tea made from citrus shell, Pu-er tea, and vine tea baked as raw materials. In this study, the in vitro uric acid synthase inhibition system and hyperuric acid cell model were constructed to appraise the uric acid lowering efficacy of Ganpu vine tea, traditional Ganpu tea, and vine tea. Results showed that in the uric acid synthase inhibition system, the aqueous extract can inhibite the puric metabolically related enzymes, such as adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and xanthine oxidase (XOD). The ability of the aqueous extract to inhibit the above enzyme was as follows: vine tea > Ganpu vine tea > Ganpu tea; all teas had a strong effect on XOD inhibition. The hyperuric acid cell model test showed that the aqueous extract inhibited uric acid production through accumulating inosine and hypoxanthine and hindering xanthine synthesis. The uric acid reductive ability was as follows: Vine tea > Ganpu vine tea > Ganpu tea. The inhibition of enzymes related to uric acid synthesis and the inhibition of uric acid production were significantly enhanced through adding vine tea to Ganpu tea. It also shows that flavonoids are the main factor driving this ability because they are the main active ingredients in these botanical drinks.

Research progress on the structural characterization, biological activity and product application of polysaccharides from Crataegus pinnatifida.

Crataegus pinnatifida is a plant of the Crataegus genus in the Rosaceae family and is commonly used as a food and medicinal resource. Crataegus pinnatifida polysaccharide, as one of the main active ingredients of Crataegus pinnatifida, has a variety of beneficial biological activities, such as antioxidant, hypoglycemic activity, lipid-lowering, intestinal flora regulation, promotion immune regulation, and antitumor activities. However, the extraction methods of Crataegus pinnatifida polysaccharides lack innovation, the primary structure is relatively limited, and the biological activity mechanism needs to be further explored. Therefore, this review summarizes the research status of the extraction, purification, structural characterization, biological activity, and product application of Crataegus pinnatifida polysaccharides. The purpose of this study is to generate support for further development and application of polysaccharides from Crataegus pinnatifida.

Effects of Extraction Methods on the Physicochemical Properties and Biological Activities of Polysaccharides from Polygonatum sibiricum.

Polygonatum sibiricum polysaccharides (PSPs) have important biological functions, such as antioxidation, immunomodulatory, and hypolipidemic functions. Different extraction methods have effects on their structures and activities. In this study, six extraction methods, including hot water extraction (HWE), alkali extraction (AAE), ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), microwave-assisted extraction (MAE), and freeze-thaw-assisted extraction (FAE) were used to extract PSPs, and their structure-activity relationships were analyzed. The results showed that all six PSPs had similar functional group compositions, thermal stability, and glycosidic bond compositions. PSP-As (PSPs extracted by AAE) exhibited better rheological properties due to their higher molecular weight (Mw). PSP-Es (PSPs extracted by EAE) and PSP-Fs (PSPs extracted by FAE) had better lipid-lowering activity due to their lower Mw. PSP-Es and PSP-Ms (PSPs extracted by MAE), which do not contain uronic acid and have a moderate Mw, had better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical-scavenging activity. On the contrary, PSP-Hs (PSPs extracted by HWE) and PSP-Fs, with the Mw of uronic acid, had the best OH-radical-scavenging activity. The high-Mw PSP-As had the best Fe2+-chelating ability. In addition, mannose (Man) may play an important role in the immunomodulatory activity. These results indicate that different extraction methods affect the structure and biological activity of polysaccharides to varying degrees, and these results are helpful for understanding the structure-activity relationship of PSPs.

Ginsenoside Rg3 Sensitizes Nasopharyngeal Carcinoma Cells to Radiation by Suppressing Epithelial Mesenchymal Transition.

Radioresistance restrains the therapeutic effect of nasopharyngeal carcinoma (NPC). Ginsenoside Rg3 (Rg3), an active pharmaceutical component extracted from ginseng, shows antitumor effects in various cancers. In this study, we aimed to determine whether Rg3 sensitized NPC cells to radiation and to explore the possible mechanisms. Our results revealed that Rg3 increased radiosensitivity in both HNE1 and CNE2 cell lines. Radiation induced epithelial mesenchymal transition (EMT) in NPC cells and Rg3 blocked this effect. In addition, Rg3 attenuated radiation-induced epidermal growth factor receptor (EGFR) nuclear transport and DNA-dependent protein kinase expression. What's more, Rg3 significantly accelerated the apoptosis rates in irradiated NPC cells. In summary, our data suggested that Rg3 sensitized NPC cells to radiation and suppressed radiation-induced EMT. This effect is mediated through restrained EGFR nuclear translocation and increased cell apoptosis. Thus, Rg3 may be a potential radiation sensitizing agent for NPC.

Monitoring of Sleep Breathing States Based on Audio Sensor Utilizing Mel-Scale Features in Home Healthcare.

Sleep-related breathing disorders (SBDs) will lead to poor sleep quality and increase the risk of cardiovascular and cerebrovascular diseases which may cause death in serious cases. This paper aims to detect breathing states related to SBDs by breathing sound signals. A moment waveform analysis is applied to locate and segment the breathing cycles. As the core of our study, a set of useful features of breathing signal is proposed based on Mel frequency cepstrum analysis. Finally, the normal and abnormal sleep breathing states can be distinguished by the extracted Mel-scale indexes. Young healthy testers and patients who suffered from obstructive sleep apnea are tested utilizing the proposed method. The average accuracy for detecting abnormal breathing states can reach 93.1%. It will be helpful to prevent SBDs and improve the sleep quality of home healthcare.

Effect of an Intermittent Calorie-restricted Diet on Type 2 Diabetes Remission: A Randomized Controlled Trial.

CONTEXT: The 2021 consensus report on the definition and interpretation of remission of type 2 diabetes (T2D) has been released. Although intermittent fasting diets (IF) are becoming very popular, no studies have investigated their benefit in diabetes remission. OBJECTIVE: The present study examined the effectiveness of IF in diabetes remission and potential remission durability. METHODS: Participants between ages 38 and 72 years with a duration of T2D of 1 to 11 years, a body mass index (BMI) of 19.1 to 30.4, 66.7% male, and antidiabetic agent use and/or insulin injection were randomly allocated at a ratio of 1:1 to the Chinese Medical Nutrition Therapy (CMNT) or control group. The primary outcome was diabetes remission, defined as a stable glycated hemoglobin A1c (HbA1c) level of less than 48 mmol/mol (< 6.5%) for at least 3 months after discontinuing all antidiabetic medications. The secondary outcomes included HbA1c level, fasting blood glucose level, blood pressure, weight, quality of life, and medication costs. We conducted a 12-month follow-up to assess the continuation of remission. RESULTS: On completing the 3-month intervention plus 3-month follow-up, 47.2% (17/36) of participants achieved diabetes remission in the CMNT group, whereas only 2.8% (1/36) of individuals achieved remission in the control group (odds ratio 31.32; 95% CI, 2.39-121.07; P < 0.0001). The mean body weight of participants in the CMNT group was reduced by 5.93 kg (SD 2.47) compared to 0.27 kg (1.43) in the control group. After the 12-month follow-up, 44.4% (16/36) of the participants achieved sustained remission, with an HbA1c level of 6.33% (SD 0.87). The medication costs of the CMNT group were 77.22% lower than those of the control group (60.4/month vs 265.1/month). CONCLUSION: This study demonstrated the clinical efficacy of CMNT in achieving diabetes remission for at least 1 year.

The glucotoxicity protecting effect of honokiol in human hepatocytes via directly activating AMPK.

Introduction: Sustained hyperglycemia causes glucotoxicity, which has been regarded as a contributor to hepatocyte damage in type 2 diabetes (T2D) and its metabolic comorbidities. Honokiol is a natural biphenolic component derived from the dietary supplement Magnolia officinalis extract. This study aimed to investigate the effects of honokiol on glucose metabolism disorders and oxidative stress in hepatocytes and the underlying mechanisms. Methods: HepG2 cells were treated with glucosamines (18 mM) to induce glucotoxicity as a diabetic complication model in vitro. Results and discussion: Honokiol significantly increased glucose consumption, elevated 2-NBDG uptake, and promoted GLUT2 translocation to the plasma membrane in glucosamine-treated HepG2 cells, indicating that honokiol ameliorates glucose metabolism disorders. Furthermore, glucosamine-induced ROS accumulation and loss of mitochondrial membrane potential were markedly reduced by honokiol, suggesting that honokiol alleviated glucotoxicity-induced oxidative stress. These effects were largely abolished by compound C, an AMPK inhibitor, suggesting an AMPK activation-dependent manner of honokiol function in promoting glucose metabolism and mitigating oxidative stress. Molecular docking results revealed that honokiol could interact with the amino acid residues (His151, Arg152, Lys243, Arg70, Lys170, and His298) in the active site of AMPK. These findings provide new insights into the antidiabetic effect of honokiol, which may be a promising agent for the prevention and treatment of T2D and associated metabolic comorbidities.

[Effects of acute fear stress on spatial memory and neuronal plasticity in the medial prefrontal cortex in mice].

The purpose of this study was to investigate the effects of acute fear stress on the spatial memory and neuronal plasticity of medial prefrontal cortex (mPFC) neurons in mice, and to elucidate the mechanisms underlying mPFC plasticity and post-stress memory regulation. Male C57BL/6 mice (6 weeks old) were randomly divided into control group and stress group. Foot shock stress was applied to establish an acute fear stress model. Changes in spatial memory were examined by the Morris water maze test, and the dynamic changes in the spike encoding of pyramidal neurons and GABAergic neurons in the prelimbic cortex (PrL) and infralimbic cortex (IL) of mPFC were detected by whole-cell recording. The results showed that acute fear stress significantly enhanced the percentage of freezing and the number of freezing, reduced the average speed, decreased the escape latency during acquisition phase, extended the probing time in the first quadrant and shortened the probing time in the third quadrant during probe trial, increased inter-spike interval, energy barrier and absolute refractory period of GABAergic neurons in the PrL and pyramidal neurons in the IL, while decreased inter-spike interval, energy barrier and absolute refractory period of pyramidal neurons in the PrL and GABAergic neurons in the IL. These results suggest that acute fear stress can enhance the spatial memory of mice, elevate the excitability and function of the PrL, while deteriorate the excitability and function of the IL, and the underlying mechanism may involve the role of mPFC microcircuitry plasticity in spatial memory after stress.

A Chinese medical nutrition therapy diet accompanied by intermittent energy restriction alleviates type 2 diabetes by enhancing pancreatic islet function and regulating gut microbiota composition.

Medicine food homologous (MFH) plants and wholegrains have gained increasing attention for prevention and treatment of type 2 diabetes (T2D). Substantial evidence supports the effectiveness of intermittent energy restriction (IER) in T2D management. However, there are few studies that report intermittent use of a low-calorie pre-prepared food including MFH plants and wholegrains in T2D. The aim of this study was to investigate the effects of Chinese Medical Nutrition Therapy (CMNT), a MFH plants and wholegrains diet accompanied by IER, on glycemic control and potential mechanism. Ten-week-old diabetic db/db mice were randomly divided into CMNT group (feeding low-calorie mouse CMNT diet in day 1-4 and ad libitum regular chow for up to 7 days per cycle) and control group (ad libitum access to regular chow). The results showed that CMNT reduced fasting blood glucose, improved glucose tolerance with higher insulin secretion, attenuated macrophage infiltration, promoted ß-cell proliferation of pancreatic islets, and increased diabetes-improving microbiota (Bacteroides, Rikenellaceae_RC9_gut_group and Coprococcus_1) in db/db mice. Additionally, we performed a pilot study evaluating CMNT in thirty-nine T2D patients without obesity. Participants with T2D randomly assigned to two groups: CMNT group (receiving a consecutive 5-day low-calorie human CMNT diet with 10 days of habitual eating per cycle for 90 days) and control group (continuing on a normal diet). We observed an improvement in glycemic control in CMNT group with significant reduction in HbA1c, fasting glucose, 2 h postprandial blood glucose but control group were not affected. After CMNT intervention, the abundance of the phylum Bacteroidetes, and genus Bacteroides, Parabacteroides and Roseburia were significantly higher than baseline in T2D patient, which were closely associated with glycemic control. These findings suggested that CMNT is a promising nutritional intervention approach in diabetes management.

PARPi treatment enhances radiotherapy-induced ferroptosis and antitumor immune responses via the cGAS signaling pathway in colorectal cancer.

In cancer cells, poly (ADP-ribose) polymerase (PARP)-1 and PARP2 initiate and regulate DNA repair pathways to protect against DNA damage and cell death caused by radiotherapy or chemotherapy. Radiotherapy and PARP inhibitors (PARPis) have been combined in clinical trials, but their action mechanisms remain unclear. Here, we show that activated by ionizing radiation (IR) generated dsDNA, cyclic GMP-AMP synthase (cGAS) signaling promoted regulated cell death, specifically ferroptosis, via the activating transcription factor 3 (ATF3)-solute carrier family 7 member 11 axis and the antitumor immune response via the interferon-ß-CD8+ T cell pathway. Niraparib, a widely used PARPi, augmented cGAS-mediated ferroptosis and immune activation. In colorectal cancer models, cGAS knockdown (KD) compromised IR-induced ferroptosis via downregulation of ATF3 (key ferroptosis regulator) expression. cGAS depletion reversed IR-induced infiltration of CD8+ T or CD8+GZMB+ T cells in the cGAS KD group. Survival analysis of paired tumor samples before and after standard radiotherapy revealed that high expression levels of cGAS, ATF3, and PTGS2 and high density of CD8+ T cells resulted in a significantly high disease-free survival rate in patients with rectal cancer. Therefore, PARPi treatment increases the cytoplasmic accumulation of dsDNA caused by IR, triggering the cGAS signaling-mediated tumor control in cancer cell lines and mouse xenograft models.

Microbial Succession and Interactions During the Manufacture of Fu Brick Tea.

Fu Brick tea is a very popular post-fermented tea that is known for its "golden flower fungus," Aspergillus cristatus, which becomes the dominant microbe during the maturation process. This study used both culture-dependent methods and high-throughput sequencing to track microbial succession and interactions during the development of the golden flower fungus, a crucial component of the manufacturing process of Fu Brick tea. Among the bacterial communities, Klebsiella and Lactobacillus were consistently cultured from both fresh tea leaves and in post-fermentation Fu Brick tea. Methylobacterium, Pelomonas, and Sphingomonas were dominant genera in fresh tea leaves but declined once fermentation started, while Bacillus, Kluyvera, and Paenibacillus became dominant after piling fermentation. The abundance of A. cristatus increased during the manufacturing process, accounting for over 98% of all fungi present after the golden flower bloom in the Fu Brick tea product. Despite their consistent presence during culture work, network analysis showed Lactobacillus and Klebsiella to be negatively correlated with A. cristatus. Bacillus spp., as expected from culture work, positively correlated with the presence of golden flower fungus. This study provides complete insights about the succession of microbial communities and highlights the importance of co-occurrence microbes with A. cristatus during the manufacturing process of Fu Brick tea.