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ABSTRACT: Taste interaction is a well-known phenomenon in sensory studies, but how to quantify the magnitude of the effect of one tastant on other taste attribute(s) is still largely unsolved, let alone further explorations from a salivary biochemistry perspective. Upon acquiring the individual taste threshold and evaluating the just noticeable difference (JND), this study firstly established a quantitative method to assess the magnitude of taste interaction in a binary taste mixture by evaluating the concentration difference upon psychologically-comparable stimulation. The change of salty taste intensity (CSI) was therefore defined as the subtraction of JND using sour-salty taste stimulant from JND using pure salty taste stimulant, with a dimension of concentration in mmol/L. CSI was then used to demonstrate how citric acid affected salty taste perception in a salty - sour binary taste mixture in 16 young and healthy participants. Concentrations of citric acid used in the binary taste mixture were 0.05, 0.09, 0.14, 0.24 and 0.40 mmol/L, respectively, and results showed that salty taste perception was enhanced (average CSI of 0.93 mmol/L) when the citric acid concentration was low (at 0.05 and 0.09 mmol/L), but with an increasing concentration of citric acid ranging from 0.14 to 0.40 mmol/L, this effect gradually turned from enhancement to suppression of salty taste perception (correspondingly a continuously decreasing CSI all the way down to an average of –2.94 mmol/L). It was also found that cystatin SN concentration in participants’ unstimulated saliva samples was significantly negatively correlated with salty taste threshold (with and without the presence of citric acid), and it was one of the most significant factors affecting CSI, as shown in multiple regression analysis. Carbonic anhydrase VI concentration in participants’ unstimulated saliva samples was also found to be significantly negatively correlated with salty taste recognition (with and without presence of citric acid), but it did not pose significant effect on CSI. From these results, this study had not only demonstrated a citric acid concentration-dependent salty taste perception phenomenon based on a proposed methodology to quantitively assess the taste interaction in binary taste mixtures, but also showed how salivary biochemical properties (cystatin SN and carbonic anhydrase VI) might have been associated with salty taste perception during food oral processing.

Abstract Immunotherapy is a novel treatment approach for malignant tumors, which has opened a new journey of anti-tumor therapy. Although some patients will show a positive response to immunotherapy, unfortunately, most patients and cancer types do not achieve an ideal response to immunotherapy. Therefore, it is urgent to search for the pathogenesis of sensitized immunotherapy. This review indicates that Fusobacterium nucleatum, Coprobacillus cateniformis, Akkermansia muciniphila, Bifidobacterium, among others, as well as intestinal microbial metabolites are closely associated with resistance to anti-tumor immunotherapy. While natural products of pectin, inulin, jujube, anthocyanins, ginseng polysaccharides, diosgenin, camu-camu, and Inonotus hispidus (Bull).Fr. P. Karst, Icariside I, Safflower yellow, Ganoderma lucidum, and Ginsenoside Rk3, and other Chinese native medicinal compound prescriptions to boost their efficacy of anti-tumor immunotherapy through the regulation of microbiota and microbiota metabolites. However, current research mainly focuses on intestinal, liver, and lung cancer. In the future, natural products could be a viable option for treating malignant tumors, such as pancreatic, esophageal, and gastric malignancies, via sensitizing immunotherapy. Besides, the application characteristics of different types, sources and efficacy of natural products in different immune resistance scenarios also need to be further clarified through the development of future immunotherapy-related studies.

Abstract Background Liver fibrosis is a common pathological process of chronic liver disease, characterized by excessive deposition of extracellular matrix (ECM). Mesenchymal stem cells (MSCs) have been found to have potential therapy effect on liver fibrosis, but the mechanism involved was still unclear. The objective of this study is to investigate the therapeutic efficacy of adipose-derived mesenchymal stem cells (ADMSCs) on the treatment of liver fibrosis, with particular emphasis on elucidating the underlying mechanism of action through which ADMSCs inhibit the activation of hepatic stellate cells (HSCs). Methods ADMSCs were isolated from adipose tissue and injected intravenously into hepatic fibrosis model of rats. The histopathological changes, liver function, collagen deposition, the expression of fibroin and Hippo pathway were evaluated. In vitro, ADMSCs were co-cultured with HSCs activated by transforming growth factor beta 1 (TGF-β1), and the inhibitor of Hippo pathway was used to evaluate the therapeutic mechanism of ADMSCs transplantation. Results The results showed that after the transplantation of ADMSCs, the liver function of rats was improved, the degree of liver fibrosis and collagen deposition were reduced, and the Hippo signaling pathway was activated. In vitro, ADMSCs can effectively inhibit the proliferation and activation of HSCs induced by TGF-β1 treatment. However, the inhibitory effect of ADMSCs was weakened after blocking the Hippo signaling pathway. Conclusions ADMSCs inhibit HSCs activation by regulating YAP/TAZ, thereby promoting functional recovery after liver fibrosis. These findings lay a foundation for further investigation into the precise mechanism by which ADMSCs alleviate liver fibrosis.

Abstract Background Cashmere, named as “soft gold”, derives from the secondary hair follicles (SHFs) of cashmere goat which is vital to Northwest China’s economy. The cytodifferentiation stage (E120), mirroring the complete hair follicle (HF) structure of adult goats and marking a critical phase in SHF development. Therefore, this study aims to enhance the understanding of SHF development and its impact on fiber quality, informing breeding strategies. Results From the scRNA-seq data analysis, the intricate processes and transcriptional dynamics of inner layer cell differentiation of HFs were unveiled in this study. we identified nine cell populations during cytodifferentiation and key structures such as the hair shaft and inner root sheath. And we discovered three main inner layer lineages and seven subpopulations, clarifying their roles in specialization and signaling. Pseudotime mapping analysis showed cell evolution from early stage to mature stages marked by unique gene expressions, and the intermediate stage on the differentiation of each lineage was revealed. The identification and spatial localization of specific transcription factors, such as GATA3, LEF1 and PRDM1, as well as keratin genes highlight regulatory pathways involved in HF development, which was further validated by immunofluorescence. These findings suggested the potential strategies to improve fiber quality, and the discovery of diverse cell types and their developmental molecular mechanisms, particularly in this species-specific context, offered a nuanced view of the regulatory mechanisms driving HF development in cashmere goats. Conclusion Overall, these findings provide a systematic molecular atlas of skin, defining three major branches and cell states of inner layer cells of HF, and determining how the branch-specific transcription factors, keratins, and signals coordinate HF morphogenesis during cytodifferentiation stage. This research not only advances skin tissue research in goats but also holds broader implications for the understanding of HF regeneration and development across various species.

Abstract With the widespread application of nuclear technology across various fields, ionizing radiation-induced injuries are becoming increasingly common. The bone marrow (BM) hematopoietic tissue is a primary target organ of radiation injury. Recent researches have confirmed that ionizing radiation-induced hematopoietic dysfunction mainly results from BM hematopoietic stem cells (HSCs) injury. Additionally, disrupting and reshaping BM microenvironment is a critical factor impacting both the injury and regeneration of HSCs post radiation. However, the regulatory mechanisms of ionizing radiation injury to BM HSCs and their microenvironment remain poorly understood, and prevention and treatment of radiation injury remain the focus and difficulty in radiation medicine research. In this review, we aim to summarize the effects and mechanisms of ionizing radiation-induced injury to BM HSCs and microenvironment, thereby enhancing our understanding of ionizing radiation-induced hematopoietic injury and providing insights for its prevention and treatment in the future.

Melon seeds have received considerable attention in recent years because of their high protein content, but they have not yet been fully used. The modification of melon seed protein (MSP) using ultrasound-assisted pH-shifting treatment was investigated in this study by analyzing structural characteristics and functional properties. The particle size, free sulfhydryl content, surface hydrophobicity, solubility, secondary structure, water-holding capacity, oil-holding capacity, emulsification activity index, and emulsification stability index of MSP were determined. MSP treated with ultrasound-assisted, pH-shifting had a smaller particle size, lower free sulfhydryl content, higher surface hydrophobicity, and solubility increased from 43.67 % to 89.12 %. The secondary structure of MSP was affected by ultrasonic treatment, manifesting as an α-helix increase and β-helix, β-turn, and random coil content decrease, which may be the reason why the protein structure became more compact after treatment. The water and oil holding capacities of MSP increased from 2.74 g/g and 3.14 g/g in untreated samples to 3.19 g/g and 3.97 g/g for ultrasound-treated samples, and further increased to 3.97 g/g and 5.02 g/g for ultrasound-assisted, pH-shifting treatment at pH 9.0, respectively. The emulsification activity index of MSP was 21.11 m2/g before treatment and reached a maximum of 32.34 m2/g after ultrasound-assisted, pH-shifting treatment at pH 9.0. The emulsification stability of MSP was maximized by ultrasonic treatment at pH 7.0. Ultrasound-assisted, pH-shifting treatment can effectively improve the functional properties of MSP by modifying the protein structure, which improves the potential application of melon seed protein in the food industry.

ABSTRACT Oxidative stress is encountered by fungi in almost all niches, resulting in fungal degeneration or even death. Fungal tolerance to oxidative stress has been extensively studied, but the current understanding of the mechanisms regulating oxidative stress tolerance in fungi remains limited. The entomopathogenic and endophytic fungus Metarhizium robertsii encounters oxidative stress when it infects insects and develops a symbiotic relationship with plants, and we found that host reactive oxygen species (ROSs) greatly limited fungal growth in both insects and plants. We identified a histone H3 deacetylase (HDAC3) that catalyzed the deacetylation of lysine 56 of histone H3. Deleting Hdac3 significantly reduced the tolerance of M. robertsii to oxidative stress from insects and plants, thereby decreasing fungal ability to colonize the insect hemocoel and plant roots. HDAC3 achieved this by regulating the expression of three genes in the ergosterol biosynthesis pathway, which includes the lanosterol synthase gene Las1. The deletion of Hdac3 or Las1 reduced the ergosterol content and impaired cell membrane integrity. This resulted in an increase in ROS accumulation in fungal cells that were thus more sensitive to oxidative stress. We further showed that HDAC3 regulated the expression of the three ergosterol biosynthesis genes in an indirect manner. Our work significantly advances insights into the epigenetic regulation of oxidative stress tolerance and the interactions between M. robertsii and its plant and insect hosts.IMPORTANCEOxidative stress is a common challenge encountered by fungi that have evolved sophisticated mechanisms underlying tolerance to this stress. Although fungal tolerance to oxidative stress has been extensively investigated, the current understanding of the mechanisms for fungi to regulate oxidative stress tolerance remains limited. In the model entomopathogenic and plant symbiotic fungus Metarhizium robertsii, we found that the histone H3 deacetylase HDAC3 regulates the production of ergosterol, an essential cell membrane component. This maintains the cell membrane integrity to resist the oxidative stress derived from the insect and plant hosts for successful infection of insects and development of symbiotic associates with plants. Our work provides significant insights into the regulation of oxidative stress tolerance in M. robertsii and its interactions with insects and plants.

IntroductionThe most common factor leading to renal failure or death is renal IR (ischemia-reperfusion). Studies have shown that mesenchymal stem cells (MSCs) and their exosomes have potential therapeutic effects for IR injury by inhibiting M1 macrophage polarization and inflammation. In this study, the protective effect and anti-inflammatory mechanism of adipose-derived mesenchymal stem cell-derived exosomes (ADMSC-Exos) after renal IR were investigated.MethodInitially, ADMSC-Exos were intravenously injected into IR experimental beagles, and the subsequent assessment focused on inflammatory damage and macrophage phenotype. Furthermore, an in vitro inflammatory model was established by inducing DH82 cells with LPS. The impact on inflammation and macrophage phenotype was then evaluated using ADMSC and regulatory miR-146a.ResultsFollowing the administration of ADMSC-Exos in IR canines, a shift from M1 to M2 macrophage polarization was observed. Similarly, in vitro experiments demonstrated that ADMSC-Exos enhanced the transformation of LPS-induced macrophages from M1 to M2 type. Notably, the promotion of macrophage polarization by ADMSC-Exos was found to be attenuated upon the inhibition of miR-146a in ADMSC-Exos.ConclusionThese findings suggest that miR-146a plays a significant role in facilitating the transition of LPS-induced macrophages from M1 to M2 phenotype. As a result, the modulation of macrophage polarization by ADMSC-Exos is achieved via the encapsulation and conveyance of miR-146a, leading to diminished infiltration of inflammatory cells in renal tissue and mitigation of the inflammatory reaction following canine renal IR.

IntroductionPostoperative recurrence and metastasis of gastric cancer (GC) are primary factors that contribute to poor prognosis. GC recurs at a rate of approximately 70%–80% within 2 years after local treatment and approximately 90% within 5 years. “Yang-deficient toxic node” is the core pathogenesis of GC recurrence and metastasis. The Yiqi Wenyang Jiedu prescription (YWJP), a form of complementary and alternative medicine in China, is an empirical remedy to prevent postoperative recurrence and metastasis of GC. Taking the main therapeutic principles of “nourishing Qi and warming Yang, strengthening Zhengqi, and detoxifying” can aid in preventing the recurrence and metastasis of GC in patients during the watchful waiting period after surgery and adjuvant chemotherapy. This approach aims to enhance the quality of life of patients. However, high-quality evidence to support this hypothesis is lacking. This study will aim to investigate the efficacy and safety of YWJP to prevent and treat postoperative metastasis and GC recurrence.MethodsThe study will be a multicenter, randomized, double-blind, placebo-parallel-controlled clinical trial. A total of 212 patients who completed adjuvant chemotherapy within 8 months of radical gastrectomy will be enrolled. Patients in the intervention group will receive the YWJP, whereas those in the control group will receive a placebo. The main outcome was the disease-free survival (DFS) rate 2 years after surgery. The secondary outcomes included DFS time, overall survival, annual cumulative recurrence and rate of metastasis after 1–3 years, cumulative annual survival after 1–3 years, fat distribution-related indicators, tumor markers, peripheral blood inflammatory indicators, prognostic nutritional index, symptoms and quality of life evaluation, medication compliance, and adverse reaction rate.DiscussionThere is a lack of effective therapy after the completion of adjuvant therapy during the postoperative period of watchful waiting. This study will be the first randomized clinical trial to evaluate whether complementary and alternative medical interventions can effectively prevent recurrence and metastasis during the watchful waiting period after GC surgery and to provide evidence for surveillance treatment management after GC surgery.Clinical trial registrationClinicalTrials.gov, identifier NCT05229809.

The suppressive tumour microenvironment significantly hinders the efficacy of immunotherapy in treating solid tumors. In this context, stromal cells, such as tumour-associated fibroblasts, undergo changes that include an increase in the number and function of immunosuppressive cells. Adenosine, a factor that promotes tumour growth, is produced from ATP breakdown and is markedly elevated in the tumour microenvironment. It acts through specific binding to adenosine receptors, with A2A and A2B adenosine receptor being primary drivers of immunosuppression. This paper presents the roles of various adenosine receptors in different tumour microenvironments. This review focus on the function of adenosine receptors in the stromal cells and non-cellular components of the tumour microenvironment. Additionally, we summarize and discuss recent advances and potential trends in using adenosine receptor antagonists combined with immunotherapy.

Malignant tumors are complex systemic chronic diseases and one of the major causes of human mortality. Targeted therapy, chemotherapy, immunotherapy, and radiotherapy are examples of mainstream allopathic medicine treatments that effective for intermediate and advanced malignant tumors. The ongoing use of conventional allopathic medicine has resulted in adverse responses and drug resistance, which have hampered its efficacy. As an important component of complementary and alternative medicine, Chinese medicine has been found to have antitumor effects and has played an important role in enhancing the therapeutic sensitivity of mainstream allopathic medicine, reducing the incidence of adverse events and improving immune-related functions. The combined application of adjuvant Chinese medicine and mainstream allopathic medicine has begun to gain acceptance and is gradually used in the field of antitumor therapy. Traditional natural medicines and their active ingredients, as well as Chinese patent medicines, have been proven to have excellent therapeutic efficacy and good safety in the treatment of various malignant tumors. This paper focuses on the mechanism of action and research progress of combining the above drugs with mainstream allopathic medicine to increase therapeutic sensitivity, alleviate drug resistance, reduce adverse reactions, and improve the body’s immune function. To encourage the clinical development and use of Chinese herb adjuvant therapy as well as to provide ideas and information for creating safer and more effective anticancer medication combinations, the significant functions of Chinese herb therapies as adjuvant therapies for cancer treatment are described in detail.

Backgrounds: Colorectal cancer (CRC) is one of the common malignant tumors, with a gradually increasing incidence. Due to late detection and poor sensitivity to chemotherapy, it has become a difficult problem in tumor prevention and treatment at present. Exploring or discovering new combinations is a significant strategy for the treatment of CRC. Compound kushen injection (CKI) is a traditional Chinese medicine injection extracted from Sophora flavescens Ait. and Smilax glabra Roxb., which is widely used in the comprehensive treatment of CRC in China. This systematic review is aimed to ascertain the clinical efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC based on available data. On this basis, the specific application of CKI in combination with chemotherapy in clinical practice is further discussed. Methods: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedicine Database Searches, the Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched systematically, from inception to April 20, 2024. We adopted the ROB2 tool to assess quality of the included trials, Stata 16 for data analysis, and evaluated the publication bias with the funnel plot and Egger’s test. The quality of the evidence was justified according to GRADE. We also used trial sequential analysis (TSA) to calculate the final required sample size in this meta-analysis and to verify whether the results present a reliable conclusion. The protocol for this systematic review was registered on PROSPERO (CRD42022380106) and has been published. Results: Sixteen trials that examined 1378 patients were included in this study. Meta-analysis revealed that compared with chemotherapy, objective response rate (ORR, RR = 1.30, 95% CI: 1.18-1.44), disease control rate (DCR, RR = 1.08, 95% CI: 1.03-1.13), and KPS score improvement rate were improved (RR = 1.18, 95% CI: 1.07-1.31) by the combination of CKI and chemotherapy in patients with advanced CRC. Additionally, CKI combined with chemotherapy was associated with lower adverse reactions such as leukopenia (RR = 0.74, 95% CI: 0.62-0.87), thrombocytopenia (RR = 0.68, 95% CI: 0.49-0.94), gastrointestinal reactions (RR = 0.72, 95% CI: 0.55-0.94), and liver damage (RR = 0.48, 95% CI: 0.30-0.79), higher CD4 + ratio (MD = 9.70, 95% CI:8.73-10.68) and CD4 + /CD8 + ratio (MD = 0.25, 95% CI: 0.22-0.28), and lower CD8 + T cell ratio (MD = −5.25, 95% CI: −5.94 to −4.56). Subgroup analysis demonstrated that ORR and DCR in patients with advanced CRC were improved when CKI combined with FOLFOX and 5Fu + L-OHP. Both 15 and 20 ml/day of CKI combined with FOLFOX provided a significant effect in ORR. Moreover, ORR was improved when the accumulated CKI dose reached 280 ml per course and 420 ml in total. 7 days/course as well as 14 days/course of CKI combined with FOLFOX were effective durations in ORR. As for DCR, 7 days/course of CKI combined with FOLFOX could improve efficacy. Furthermore, CKI + FOLFOX may be useful in ORR and DCR for at least 4 cycles of combination therapies. The TSA showed that firm results in ORR and DCR were established and additional trials were unlikely to change the results. Conclusion: CKI combined with chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, DCR, performance status, ADR reduction, and immune function in patients with CRC. However, more rigorously designed, large-scale, and multi-center RCTs are needed in the future.

Abstract Introduction Current therapies for autoimmune rheumatic diseases (ARDs) have limited efficacy in certain patients, highlighting the need for the development of novel treatment approaches. This meta-analysis aims to assess the efficacy and safety of low-dose interleukin-2 (LD-IL-2) and evaluate the alterations in lymphocyte subsets in various rheumatic diseases following administration of different dosages of LD-IL-2. Methods A comprehensive search was conducted in PubMed, Web of Science, the Cochrane Library, Embase databases and CNKI to identify relevant studies. A total of 31 trials were included in this meta-analysis. The review protocols were registered on PROSPERO (CRD42022318916), and the study followed the PRISMA guidelines. Results Following LD-IL-2 treatment, patients with ARDs exhibited a significant increase in the number of Th17 cells and Tregs compared to their pre-treatment levels [standardized mean difference (SMD) = 0.50, 95% confidence interval (CI) (0.33, 0.67), P

Introduction: Compound Kushen Injection (CKI) is a traditional Chinese medicine extracted from Sophora flavescens Aiton and Heterosmilax japonica Kunth. Widely utilized in China for the comprehensive treatment of colorectal cancer (CRC), this study aims to systematically assess the efficacy and safety of CKI when combined with chemotherapy for the treatment of advanced CRC, based on available data. Methods: Randomized controlled trials investigating the efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC will be comprehensively searched from databases, including PubMed, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang, Chinese Biomedicine Database Searches, Chinese Clinical Trial Registry, and ClinicalTrials.gov until November 2022. Two independent reviewers will screen the studies, assess the risk of bias, and extract data in duplicate. The ROB2 tool will be employed to assess the quality of included studies. Stata 16 will be used for data analysis, and publication bias will be assessed using funnel plots and Egger's test. The quality of evidence will be evaluated according to GRADE, and trial sequence analysis (TSA) will be utilized to calculate the final total sample size required for the meta-analysis. The results of this systematic review will be published in a peer-reviewed journal. The proposed review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022380106). Discussion: This systematic review will integrate current evidence on CKI in advanced CRC and analyze the clinical efficacy and safety of CKI combined with different chemotherapy regimens, providing valuable guidance on the use of CKI in CRC patients.

Abstract It has recently been argued that half degrees of freedom could emerge in Lorentz and parity invariant field theories, using a non-linear Proca field theory dubbed Proca-Nuevo as a specific example. We provide two proofs, using the Lagrangian and Hamiltonian pictures, that the theory possesses a pair of second class constraints, leaving D − 1 degrees of freedom in D spacetime dimensions, as befits a consistent Proca model. Our proofs are explicit and straightforward in two dimensions and we discuss how they generalize to an arbitrary number of dimensions. We also clarify why local Lorentz and parity invariant field theories cannot hold half degrees of freedom.

BackgroundThe question of whether flexible sigmoidoscopy (FS) for colorectal cancer (CRC) affects incidence or mortality remains unclear. In this study, we conducted a meta-analysis and systematic review to explore this issue.MethodsA systematic search of PubMed, EMBASE, and ClinicalTrials.gov was performed for cohort studies (CS), case–control studies, and randomized controlled trials (RCTs) of people who underwent FS and reported mortality or incidence of CRC until 11 December 2022. Relative risk (RR) was applied as an estimate of the effect of interest. To combine the RRs and 95% confidence intervals, a random-effects model was used. The quality of the included studies and evidence was assessed by the Newcastle-Ottawa quality assessment scale, the Jadad scale, and the “Grading of Recommendations Assessment, Development and Evaluation System.”ResultsThere were a total of six RCTs and one CS, comprising 702,275 individuals. FS was found to be associated with a 26% RR reduction in CRC incidence (RR, 0.74; 95% CI, 0.66–0.84) and a 30% RR reduction in CRC mortality (RR, 0.70; 95% CI, 0.58–0.85). In the incidence subgroup analysis, FS significantly reduced the incidence of CRC compared with non-screening, usual care, and fecal immunochemical testing. Significance was also shown in men, women, distal site, stages III–IV, ages 55–59, and age over 60. In terms of the mortality subgroup analysis, the results were roughly the same as those of incidence.ConclusionAccording to this study, FS might reduce the incidence and mortality of CRC. To confirm this finding, further prospective clinical studies should be conducted based on a larger-scale population.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023388925.

Metabolic reprogramming is a hallmark of human cancer. Cancer cells exhibit enhanced glycolysis, which allows glycolytic intermediates to be diverted into several other biosynthetic pathways, such as serine synthesis. Here, we explored the anti-cancer effects of the pyruvate kinase (PK) M2 inhibitor PKM2-IN-1 alone or in combination with the phosphoglycerate dehydrogenase (PHGDH) inhibitor NCT-503 in human NSCLC A549 cells in vitro and in vivo. PKM2-IN-1 inhibited proliferation and induced cell cycle arrest and apoptosis, with increased glycolytic intermediate 3-phosphoglycerate (3-PG) level and PHGDH expression. The combination of PKM2-IN-1 and NCT-503 further suppressed cancer cell proliferation and induced G2/M phase arrest, accompanied by the reduction of ATP, activation of AMPK and inhibition of its downstream mTOR and p70S6K, upregulation of p53 and p21, as well as downregulation of cyclin B1 and cdc2. In addition, combined treatment triggered ROS-dependent apoptosis by affecting the intrinsic Bcl-2/caspase-3/PARP pathway. Moreover, the combination suppressed glucose transporter type 1 (GLUT1) expression. In vivo, co-administration of PKM2-IN-1 and NCT-503 significantly inhibited A549 tumor growth. Taken together, PKM2-IN-1 in combination with NCT-503 exhibited remarkable anti-cancer effects through induction of G2/M cell cycle arrest and apoptosis, in which the metabolic stress induced ATP reduction and ROS augmented DNA damage might be involved. These results suggest that the combination of PKM2-IN-1 and NCT-503 might be a potential strategy for the therapy of lung cancer.

Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are widely used in the treatment of lung cancer, especially in the first-line treatment of advanced NSCLC, and EGFR-TKIs monotherapy has achieved better efficacy and tolerability compared with standard chemotherapy. However, acquired resistance to EGFR-TKIs and associated adverse events pose a significant obstacle to targeted lung cancer therapy. Therefore, there is an urgent need to seek effective interventions to overcome these limitations. Natural medicines have shown potential therapeutic advantages in reversing acquired resistance to EGFR-TKIs and reducing adverse events, bringing new options and directions for EGFR-TKIs combination therapy. In this paper, we systematically demonstrated the resistance mechanism of EGFR-TKIs, the clinical strategy of each generation of EGFR-TKIs in the synergistic treatment of NSCLC, the treatment-related adverse events of EGFR-TKIs, and the potential role of traditional Chinese medicine in overcoming the resistance and adverse reactions of EGFR-TKIs. Herbs and active compounds have the potential to act synergistically through multiple pathways and multiple mechanisms of overall regulation, combined with targeted therapy, and are expected to be an innovative model for NSCLC treatment.

Abstract Background Epigenetic reprogramming is involved in multiple steps of human cancer evolution and is mediated by a variety of chromatin-modifying enzymes. Specifically, the histone lysine methyltransferase KMT2D is among the most frequently mutated genes in oral squamous cell carcinoma (OSCC). However, the mechanisms by which KMT2D affects the development of OSCC remain unclear. Results In the present study, we found that the expression of KMT2D was elevated in OSCC compared to paracancerous specimens and was correlated with a more advanced tumor grade. More importantly, knockdown of KMT2D impaired their reconstitution in patient-derived organoids and decreased the expression of CD133 and β-catenin in OSCC cells. In in vitro and in vivo models, knockdown of KMT2D reduced the colony formation, migration and invasion abilities of OSCC cells and delayed tumor growth. Mechanistically, the dual-luciferase reporter and co-immunoprecipitation assays in two individual OSCC cell lines indicated that KMT2D may cooperate with MEF2A to promote the transcription activity of CTNNB1, thereby enhancing WNT signaling. Conclusion The upregulation of KMT2D contributes to stem-like properties in OSCC cells by sustaining the MEF2A-mediated transcriptional activity of CTNNB1.

Abstract Background Diabetic kidney disease (DKD) is a significant complication of diabetes and has garnered considerable attention. Our previous retrospective study indicated that Shenzhuo formula (SZF) potentially reduces macroalbuminuria secondary to DKD. Methods This trial is a 24-week, randomized, multicentric, double-blinded, double-dummy clinical trial. A total of 120 patients with DKD will be equally and randomly divided into two groups: SZF+ irbesartan simulator or irbesartan + SZF simulator. The 24-h urinary protein change from baseline to week 24 is the primary outcome measure. The secondary outcome measures include serum creatinine, estimated glomerular filtration rate, urinary albumin excretion rate, improvement in traditional Chinese medicine symptoms, fasting blood glucose, 2-h postprandial plasma glucose, hemoglobin A1c, cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, blood pressure, albumin to creatinine ratio, and the Audit of Diabetes-Dependent Quality of Life 19. Our recruitment began in May 2015; currently, we have recruited 100 participants, with a designed maximum sample size of 120. The interim results were reviewed at N = 60, and continuing recruitment was recommended. This statistical analysis plan includes our approach to missing data imputation, primary and secondary outcomes analyses, and safety endpoints. Discussion This statistical analysis plan will standardize the clinical trial’s statistical analysis and avoid outcome selective reporting bias and data-driven analysis. This trial will provide further clinical evidence regarding the effectiveness of SZF in managing macroalbuminuria secondary to DKD. Trial registration Chinese Clinical Trial Registry ChiCTR-ICR-15006311. Registered on 26 May 2013. http://www.chictr.org.cn/showproj.aspx?proj=10862

Rapid urbanization considerably changes the urban–rural landscape, soil environment, and soil ecosystem functions. Within terrestrial ecosystems, microorganisms play key roles in soil ecosystem functions and are highly vulnerable to the effects of rapid urbanization. However, research on the effects of changing environment along urban–rural gradient on the composition, diversity, and network structure of soil microbial community remains limited. In this study, we analyzed the effects of land use pattern, human activities, and soil properties on soil bacterial community in urban, peri-urban, and rural areas. Results revealed substantial differences in soil bacterial composition, diversity, and network structure among urban, peri-urban, and rural soils. Peri-urban areas emerged as hotspots of soil microbial diversity compared with urban and rural areas. The results of a co-occurrence network analysis demonstrated that bacterial community in rural soils exhibited a complicated and stable network, whereas soil bacterial network in urban and peri-urban soils were unstable, especially in urban soils. The intensity of human activity on the land surface and proportion of forestland were the key factors affecting soil bacterial community. Human activity and land use may not only directly affect soil bacterial community but also indirectly affect soil bacterial composition and diversity by changing soil properties. This study can enhance our understanding of the influence of urbanization pattern on soil microbial community and their potential consequences on soil ecosystem and human health.

Background: The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) has stimulated work to identify biomarkers and develop effective treatments. Metabolomics is an emerging tool that has been widely applied to discover biomarkers and simultaneously uncover pathological mechanisms. Here, we aim to optimize metabolomic acquisition with the goal of obtaining a systemic metabolic profile to unravel the potential link between dysregulated metabolism and NAFLD. Methods: We analyzed serum samples collected from healthy subjects (n = 8) and NAFLD patients (n = 8) via an integrative analytical workflow using two orthogonal separation modes with T3 and amide columns and two ionization polarity modes on a UPLC-ESI-Q/TOF. Data dependent acquisition was employed for data acquisition. Differentially expressed metabolites and lipids were identified by comparing the collected metabolic and lipidomic profiles between the healthy subjects and NAFLD patients. Results: The integrative LC-MS/MS analytical workflow employed here features an improved coverage of metabolites and lipids, which leads to the identification of 20 potential biomarkers of NAFLD, including lipids, acylcarnitines, and organic acids. Conclusions: This pilot study has identified potential biomarkers for NAFLD and revealed corresponding dysregulated metabolic pathways related to NAFLD's occurrence and progression, establishing a molecular basis for NAFLD diagnosis and therapeutic intervention.

Introduction Metformin (MET) can regulate glucose and lipid levels, and the gut microbiota may be involved in the control of metabolism. We hypothesized that MET alleviates glucolipid metabolism disorder by modulating gut microbiota and microbial metabolites.Research design and methods A total of 24 male C57BL/6 J mice were equally divided into three groups (normal control, model control (MC), and MET-treated groups). Model mice were established by feeding a high-fat diet for 6 weeks. The MET-treated group was administered MET solution (2.5 g/100 mL, 250 mg/kg). Fecal samples were collected to characterize the microbiota system using metagenomic shotgun sequencing and gas chromatography–time of flight–mass spectrometry analysis. Phenotypic and biochemical indices were obtained for further correlation analysis.Results Compared with the MC group, MET reduced the levels of weight, glucose, areas under the glucose curve in the glucose tolerance test, triglyceride (TG), and total cholesterol (TC). A decreasing abundance of bacteria, including Parabacteroides distasonis, and an increasing abundance of bacteria, including Bacteroides vulgatus, were observed in the MET-treated group. The 2-deoxytetronic acid declined after MET intervention and was positively correlated with species over-represented in the MC group and negatively correlated with species enriched in the MET-treated group. Additionally, species enriched in the MET-treated group negatively correlated with glucose, areas under the glucose curve in the glucose tolerance test, and TGs. Further, the correlation between the differential metabolites, which decreased after MET intervention, and the phenotypic indices was positive.Conclusions MET-induced restoration of intestinal homeostasis correlates with the amelioration of host glucolipid metabolism.

Cancer has become one of the major causes of human death. Several anticancer drugs are available; howeve their use and efficacy are limited by the toxic side effects and drug resistance caused by their continuous application. Many natural products have antitumor effects with low toxicity and fewer adverse effects. Moreover, they play an important role in enhancing the cytotoxicity of chemotherapeutic agents, reducing toxic side effects, and reversing chemoresistance. Consequently, natural drugs are being applied as potential therapeutic options in the field of antitumor treatment. As natural medicinal plants, some components of ginseng have been shown to have excellent efficacy and a good safety profile for cancer treatment. The pharmacological activities and possible mechanisms of action of ginseng have been identified. Its broad range of pharmacological activities includes antitumor, antibacterial, anti-inflammatory, antioxidant, anti-stress, anti-fibrotic, central nervous system modulating, cardioprotective, and immune-enhancing effects. Numerous studies have also shown that throuth multiple pathways, ginseng and its active ingredients exert antitumor effects on gastrointestinal (GI) tract tumors, such as esophageal, gastric, colorectal, liver, and pancreatic cancers. Herein, we introduced the main components of ginseng, including ginsenosides, polysaccharides, and sterols, etc., and reviewed the mechanism of action and research progress of ginseng in the treatment of various GI tumors. Futhermore, the pathways of action of the main components of ginseng are discussed in depth to promote the clinical development and application of ginseng in the field of anti-GI tumors.

The Stevens law, S = kIn, is commonly accepted as a landmark achievement in the field of sensory psychophysics and has been widely applied in food sensory research. The theory effectively links the two parameters of very different nature, the intensity of sensory perception (S) and the intensity of physical stimulus (I). However, the Stevens law suffers from two major drawbacks. The equation was self-inconsistent in terms of the units, which makes equation questionable in principle. The Stevens law was also found inapplicable when multiple physical stimuli are involved in the perception of a sensory attribute. To solve the first drawback, we propose to replace the absolute stimulation intensity in the Stevens law with a relative intensity, S = k(I/I0)n. The modified Stevens law becomes self-consistent when both sides of the equation are dimensionless and the theory is applicable regardless of the unit of the physical stimulus. To solve the second drawback, a concept of sensory derivation is introduced and so sensory properties can be categorized as primary sensory and derived sensory. The former can be described effectively by the Stevens law, while description of the latter is beyond the applicability of the Stevens law because of the involvement of multiple sensory stimuli or multi level sensory derivation. Furthermore, a sensory hierarch is constructed with sensory perception of different nature at different levels, including the primary sensory at the basic level and derived sensory perception at progressing levels. The modified Stevens law provides a self-consistent model for psychophysical analysis of sensory perception. The proposed sensory hierarchy helps to streamline sensory terms and attributes and may be used as a useful guide in establishing instrumental analysis of sensory perception.

BackgroundCurrently, gastric cancer (GC) and colorectal cancer (CRC) are the most common causes of cancer-related mortality worldwide. Gut microbiota is closely related to the occurrence of GC and CRC and the efficacy of chemotherapy. This study is aimed at evaluating the efficacy and safety of herbal formulas with the function of gut microbiota regulation (HFGMR) in the treatment of GC and CRC and to assess the quality of the synthesized evidence.MethodsA comprehensive search was performed on eight electronic databases, PubMed, EMBASE, CENTRAL, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and two registries, Chinese Clinical Trial Registry and ClinicalTrials.gov, from their initiation to January 2022. Randomized controlled trials (RCTs) studying the therapeutic effects of HFGMR were included. We used Stata 16 for data synthesis and Risk of Bias 2 (RoB 2) for methodological quality evaluation and assessed the quality of the synthesized evidence in the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.ResultsFifty-three RCTs involving 4,478 patients were included. These trials involve seven herbal formulas that could regulate the gut microbiota of Bifidobacterium, Lactobacillus, Escherichia coli, Bacteroides, and Enterococcus faecalis. The meta-analysis results were subgrouped to three different stages in GC and CRC. 1) For the perioperative stage, HFGMR combined with conventional therapy could shorten the time to bowel sound recovery by 1.63 h [mean difference (MD) = −1.63, 95% confidence interval (CI) (−2.62, −0.65)], the time to first flatus by 9.69 h [MD = −9.69, 95% CI (−10.89, −8.48)], and the duration of hospitalization by 2.91 days [MD = −2.91, 95% CI (−4.01, −1.80)] in GC. There were no significant differences in outcomes of gastrointestinal function recovery and adverse events in CRC. 2) For postoperative patients, combined with adjuvant chemotherapy, HFGMR could decrease the incidence of diarrhea, nausea and vomiting, anorexia, and peripheral neurotoxicity in GC; boost Karnofsky performance status (KPS) improvement rate [risk ratio (RR) = 1.96, 95% CI (1.38, 2.79)]; and decrease the incidence of leucopenia and nausea and vomiting in CRC. 3) For advanced stage, HFGMR can significantly improve the objective response rate (ORR) [RR = 1.35, 95% CI (1.19~1.53)], disease control rate (DCR) [RR = 1.14, 95% CI (1.05~1.23)], and KPS improvement rate [RR = 1.56, 95% CI (1.17, 2.09)] and decrease the incidence of leucopenia, neutropenia, anemia, nausea and vomiting, diarrhea, and fatigue in GC. There were no significant differences in ORR [RR = 1.32, 95% CI (0.94~1.86)] and DCR [RR = 1.22, 95% CI (0.99~1.50)], but they can improve the KPS response rate [RR = 1.62, 95% CI (1.13, 2.32)] and decrease the incidence of myelosuppression, nausea and vomiting, diarrhea, and hepatic and renal dysfunction in CRC.ConclusionThis study indicates that herbal formulas that could regulate the composition and proportion of gut microbiota have a positive effect in three stages (perioperative, postoperative, and advanced) of GC and CRC. They could promote the recovery of postoperative gastrointestinal function, increase tumor response, improve performance status, and reduce the incidence of adverse events. Herbal formulas exerted anti-cancer efficacy through multiple mechanisms and pathways; among them, the regulation of gut microbiota has not been paid enough attention. To further support the conclusion and better understand the role of gut microbiota in the treatment of GC and CRC, more rigorously designed, large-scale, and multicenter RCTs that focus on herbal formulas and gut microbiota are needed in the future.

Introduction: Glucose and lipid metabolism disturbances has become the third major disease after cancer and cardio-cerebrovascular diseases. Emerging evidence shows that berberine can effectively intervene glucose and lipid metabolism disturbances, but the underlying mechanisms of this remain unclear. To investigate this issue, we performed metagenomic and metabolomic analysis in a group of normal mice (the NC group), mice with disturbances in glucose and lipid metabolism (the MC group) and mice with disturbances in glucose and lipid metabolism after berberine intervention (the BER group).Result: Firstly, analysis of the clinical indicators revealed that berberine significantly improved the blood glucose and blood lipid of the host. The fasting blood glucose level decreased by approximately 30% in the BER group after 8 weeks and the oral glucose tolerance test showed that the blood glucose level of the BER group was lower than that of the MC group at any time. Besides, berberine significantly reduced body weight, total plasma cholesterol and triglyceride. Secondly, compared to the NC group, we found dramatically decreased microbial richness and diversity in the MC group and BER group. Thirdly, LDA effect size suggested that berberine significantly altered the overall gut microbiota structure and enriched many bacteria, including Akkermansia (p < 0.01), Eubacterium (p < 0.01) and Ruminococcus (p < 0.01). Fourthly, the metabolomic analysis suggested that there were significant differences in the metabolomics signature of each group. For example, isoleucine (p < 0.01), phenylalanine (p < 0.05), and arbutin (p < 0.05) significantly increased in the MC group, and berberine intervention significantly reduced them. The arbutin content in the BER group was even lower than that in the NC group. Fifthly, by combined analysis of metagenomics and metabolomics, we observed that there were significantly negative correlations between the reduced faecal metabolites (e.g., arbutin) in the BER group and the enriched gut microbiota (e.g., Eubacterium and Ruminococcus) (p < 0.05). Finally, the correlation analysis between gut microbiota and clinical indices indicated that the bacteria (e.g., Eubacterium) enriched in the BER group were negatively associated with the above-mentioned clinical indices (p < 0.05).Conclusion: Overall, our results describe that the changes of gut microbiota and metabolites are associated with berberine improving glucose and lipid metabolism disturbances.

The serine/threonine kinase Akt, also known as protein kinase B (PKB), is one of the key factors regulating glucose and lipid energy metabolism, and is the core focus of current research on diabetes and metabolic diseases. Akt is mostly expressed in key metabolism-related organs and it is activated in response to various stimuli, including cell stress, cell movement, and various hormones and drugs that affect cell metabolism. Genetic and pharmacological studies have shown that Akt is necessary to maintain the steady state of glucose and lipid metabolism and a variety of cellular responses. Existing evidence shows that metabolic syndrome is related to insulin resistance and lipid metabolism disorders. Based on a large number of studies on Akt-related pathways and reactions, we believe that Akt can be used as a potential drug target to effectively treat metabolic syndrome.

Background: Gastric cancer (GC) is one of the most common digestive tract cancers and ranks fifth in the incidence of malignant tumors worldwide. Brucea javanica oil emulsion injection (BJOEI), a Chinese patent medicine extracted from Brucea javanica (Yadanzi in Chinese Pinyin), is widely used as an adjuvant treatment for GC in China. This systematic review and meta-analysis aimed to evaluate the available data on the efficacy and safety of BJOEI in the treatment of GC and assess the quality of the synthesized evidence.Methods: A comprehensive search was performed on PubMed, EMBASE, CENTRAL, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and Chinese Scientific Journals Database (VIP database), and other potential resources, such as the Chinese Clinical Trial Registry (ChiCTR) and ClinicalTrials.gov from their inception to July 31, 2021. Randomized controlled trials (RCTs) comparing the therapeutic effects of BJOEI combined with conventional therapy to those of conventional therapy alone were included. We used RevMan 5.3 for data analysis and quality evaluation of the included studies and assessed the evidence quality based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.Results: Eighteen RCTs involving 1,210 patients were included, and the meta-analysis results demonstrated that compared with the control group (conventional therapy), the experimental group (BJOEI combined with conventional therapy) showed a significantly improved overall response rate (ORR) (risk ratio [RR] = 1.52, 95% CI: 1.36–1.69, P < 0.00001), clinical benefit rate (CBR) (RR = 1.17, 95% CI: 1.11–1.23, P < 0.00001), performance status (RR = 1.72, 95% CI: 1.46–2.01, P < 0.00001), and reduced incidence of the following adverse drug reactions (ADRs): neutropenia, leukopenia, nausea and vomiting, diarrhea, liver damage, hand-foot syndrome, and peripheral sensory nerve toxicity. Subgroup analysis showed that the BJOEI intervention could significantly improve the ORR and CBR in patients with GC when combined with FOLFOX4, XELOX, and other chemotherapeutics.Conclusion: The evidence presented in this study supports the fact that BJOEI combined with conventional chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, CBR, performance status, and ADR reduction in patients with GC. To further support this conclusion, more rigorously designed, large-scale, and multicenter RCTs are needed in the future.

Background: Kanglaite injection (KLTI) is a traditional Chinese medicine (TCM) preparation with anti-tumor activity, which has been used to treat malignant tumors in China. The purpose of this study was to evaluate the efficacy and safety of intrapleural infusion with KLTI in the treatment of malignant pleural effusion (MPE).Methods: Randomized controlled trials (RCTs) on the efficacy and safety of intrathoracic infusion with KLTI in the treatment of MPE were searched from the PubMed, EMBASE, the Cochrane Library, CNKI, VIP, Wanfang and CBM databases. The primary outcome was objective remission rate (ORR). Secondary outcomes included quality of life (QOL) and incidence of adverse events (AEs). The Stata15.1 software and RevMan5.3 software were used to calculate risk ratios (RR) at 95% confidence intervals (CI) and conduct the meta-analysis.Results: This meta-analysis included 20 RCTs, involving 1,291 patients. The ORR of intrapleural infusion with KLTI + chemotherapy drugs in the treatment of MPE was higher than that of chemotherapy alone (RR) 1.23; 95%CI; 1.11–1.36, I2 = 0%, z = 3.876, p = 0.000]. When KLTI is combined with cisplatin or KLTI 200 ml is used in every time, it is more advantageous to improve ORR. Moreover, compared with intrapleural infusion of chemotherapy drugs alone, KLTI combined with chemotherapy drugs significantly improved the QOL of patients with MPE (RR 1.28; 95%CI; 1.70–1.53, I2 = 0%, z = 2.70, p = 0.007). In addition, the participation of KLTI reduced the gastrointestinal reaction (RR 0.79; 95% CI; 0.66–0.96; I2 = 0%, z = 2.37, p = 0.018) and renal damage (RR 0.468; 95% CI; 0.23–0.945, I2 = 0%, z = 2.11, p = 0.035) caused by chemotherapy drugs, but did not increase other adverse reactions (p > 0.05).Conclusion: The efficacy and safety of traditional chemotherapy drugs plus KLTI was superior to traditional chemotherapy drugs alone via intrapleural injection in controlling MPE, which suggested that KLTI can be used to treat MPE. However, a more rigorous RCT should be designed and completed before it is widely recommended.

Esophageal cancer (EC) is the sixth leading cause of cancer-related deaths worldwide. Western medicine has played a leading role in its treatment, but its prognosis remains unsatisfactory. Therefore, the development of effective therapies is important. Traditional Chinese medicine (TCM) has been practiced for thousands of years, and involves taking measures before diseases occur, deteriorate, and recur. Interestingly, there is growing evidence that TCM can improve the therapeutic effects in reversing precancerous lesions, inhibiting the recurrence and metastasis of EC. In this article, we review traditional Chinese herbs and formulas that have preventive and therapeutic effects on EC, summarize the application and research status of TCM in patients with EC, and discuss its shortcomings and prospects in the context of translational, evidence-based, and precision medicine.

Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats induced by a single intraperitoneal injection of streptozotocin after 4 weeks of high-fat diet feeding. The T2DM rats were randomly allocated to receive GQD, metformin (Met), or saline for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota was analyzed using 16S rRNA gene sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats. GQD administration decreased the levels of blood glucose and inflammatory cytokines, and increased the levels of tight junction proteins. Besides, GQD had a protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation, as evidenced by increases in the levels of serum C-peptide, occludin, and claudin-1 in the colon, and also improved the expression of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype. Overall, these findings suggest that GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota.

Phenolipids such as alkyl gallates (A-GAs) have been approved by the food industry as non-toxic antioxidant additives, which are also regarded as an emerging source of functional food ingredients. However, comprehensive understanding of their digestive absorption is needed. Thus, the models of live mice and anaerobic fermentation were used to clarify the distribution and microbial hydrolysis characteristics of A-GAs in the gastrointestinal tract. HPLC-UV results demonstrated that A-GAs could be hydrolyzed by intestinal lipases and gut microorganisms including Lactobacillus to produce free gallic acid (GA). Through regulating the chain length of the lipid part in A-GAs, the sustained and controllable release of the GA can be easily achieved. Furthermore, A-GAs were also able to reach the colon and the cecum, which would lead to potential gastrointestinal protective effects. Therefore, A-GAs may be applied as possible ingredient for functional foods.

As a novel family of 2D materials, MXenes are supposed to play a vital role in optoelectronic devices and systems due to their high conductivity, good optical properties, and favorable compatibility with water and organic solvents. However, the application of MXenes in highly sensitive photodetection is far scarcely investigated. Here, we demonstrate high-quality Ti3C2Tx/GaAs Schottky junction by simply dripping Ti3C2Tx MXene solution on a pre-patterned GaAs substrate. Owing to the wide absorption of MXene and the good quality junction, the self-driven Ti3C2Tx/GaAs Schottky junction photodetector with an impressive performance is realized. The assembled photodetector exhibits a high sensitivity over a wide waveband with a good responsivity of ~1.46 A/W, a large specific detectivity of ~1.23 × 1013 Jones, and a high Ilight/Idark ratio of 5.6 × 105. Significantly, the photodetector is capable of sensing infrared light signal up to 980 nm which exceeds the absorption edge of GaAs (874 nm) due to the generation of hot electrons in Ti3C2Tx MXene film. Given the superior device performance along with a simple and facile fabrication method, the Ti3C2Tx/GaAs Schottky junction photodetector may find the great potential in high performance broadband, self-driven photodetection applications.

Weakened capability of eating and swallowing is common among elderly population, affecting negatively on their health and well-being. This work measured occlusal force and tongue muscle strength of elderly patients and then assessed whether correlations existed between oral physiological properties and the eating and swallowing capability. A total of 26 elderly patients with potential swallow disorder were recruited in this work. Participants’ denture status and daily diet texture were determined by a pre-questionnaire analysis. Their swallowing capability was assessed and rated by water drinking test. Maximum tongue pressure, incisor occlusal force and hand gripping force were measured for each subject. It was observed that participating subjects have on average a significantly lower biting force and maximum tongue pressure than that of normal adults. The swallowing grades assessed by water drinking test showed significant correlations with both the biting force (r = −0.498, P

Abstract Chronic kidney disease (CKD) is associated with accelerated atherosclerosis progression and high incidence of cardiovascular events, hinting that atherosclerotic plaques in CKD may be vulnerable. However, its cause and mechanism remain obscure. Here, it is shown that apolipoprotein E‐deficient (ApoE−/−) mouse with CKD (CKD/ApoE−/− mouse) is a useful model for investigating the pathogenesis of plaque vulnerability, and premature senescence and phenotypic switching of vascular smooth muscle cells (VSMCs) contributes to CKD‐associated plaque vulnerability. Subsequently, VSMC phenotypes in patients with CKD and CKD/ApoE−/− mice are comprehensively investigated. Using multi‐omics analysis and targeted and VSMC‐specific gene knockout mice, VSMCs are identified as both type‐I‐interferon (IFN‐I)‐responsive and IFN‐I‐productive cells. Mechanistically, mitochondrial damage resulting from CKD‐induced oxidative stress primes the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway to trigger IFN‐I response in VSMCs. Enhanced IFN‐I response then induces VSMC premature senescence and phenotypic switching in an autocrine/paracrine manner, resulting in the loss of fibrous cap VSMCs and fibrous cap thinning. Conversely, blocking IFN‐I response remarkably attenuates CKD‐associated plaque vulnerability. These findings reveal that IFN‐I response in VSMCs through immune sensing of mitochondrial damage is essential for the pathogenesis of CKD‐associated plaque vulnerability. Mitigating IFN‐I response may hold promise for the treatment of CKD‐associated cardiovascular diseases.

Metabolic syndrome (MetS) is a multifarious metabolic disorder that could severely damage multiple organs. The emergence of MetS has markedly increased medical burden for patients. The treatment of MetS involves multitarget regulation, which is the advantage of traditional Chinese medicine (TCM). Many high-quality studies related to TCM for MetS have been conducted in recent years; however, no overall efficacy analysis has been reported. To evaluate the efficacy and safety of TCM against MetS, we reviewed randomized controlled trials of MetS published in the past decade and then selected and analyzed 16 high-quality articles from over 800 papers. The results showed that TCM might be beneficial in improving body weight as well as in regulating glucose and lipid metabolisms; thus, TCM might be an ideal alternative therapy for MetS management. Treatment safety was also estimated in our analysis. A more elaborately designed and long-term observation of TCM for MetS should be performed in the future.

Diabetic nephropathy (DN) is not only an important microvascular complication of diabetes but also the main cause of end-stage renal disease. Studies have shown that the occurrence and development of DN are closely related to morphological and functional changes in podocytes. A series of morphological changes after podocyte injury in DN mainly include podocyte hypertrophy, podocyte epithelial-mesenchymal transdifferentiation, podocyte detachment, and podocyte apoptosis; functional changes mainly involve podocyte autophagy. More and more studies have shown that multiple signaling pathways play important roles in the progression of podocyte injury in DN. Here, we review research progress on the pathological mechanism of morphological and functional changes in podocytes associated with DN, to provide a new target for delaying the occurrence and development of this disorder.

Dopamine (DA), a catecholamine neurotransmitter, is known to for its diverse roles on hematopoiesis, yet its function in thrombopoiesis remains poorly understood. This study shows that DA stimulation can directly induce platelet production from megakaryocytes (MKs) in the final stages of thrombopoiesis via a reactive oxygen species (ROS)-dependent pathway. The mechanism was suggested by the results that DA treatment could significantly elevate the ROS levels in MKs, and time-dependently activate oxidative stress-mediated signaling, including p38 mitogen-activated protein kinase, c-Jun NH2-terminal kinase, and caspase-3 signaling pathways, while the antioxidants N-acetylcysteine and L-glutathione could effectively inhibit the activation of these signaling pathways, as well as the ROS increase and platelet production triggered by DA. Therefore, our data revealed that the direct role and mechanism of DA in thrombopoiesis, which provides new insights into the function recognition of DA in hematopoiesis.

Background. Diabetes mellitus (DM) belongs to the progressive and irreversible disease. With the development of the disease, the function of beta cells declines significantly. Current treatments cannot reverse the course of the disease. The role of traditional Chinese medicine (TCM) in the DM treatment has been recognized widely, while there are few long-term observation reports. In this study, we introduced a case of DM treated by classical prescription alone for 10 years, which would provide the reference for clinical practice. Case Presentation. A 64-year-old male complained of a 2-month history of dry mouth, frequent urination, and blurred vision and found increased blood glucose for 3 days. The patient’s glycated hemoglobin was 14.2%, fasting plasma glucose fluctuated at 12-15 mmol/L, and urinary albumin excretion rate (UAER) was 32.9 μg/min. The male was treated with 10 years of continuous classical prescription alone. After 3 months of TCM treatment, the patient’s blood glucose level decreased significantly and blurred vision symptoms improved. With continued TCM treatment, his UAER normalized. Subsequently, he continued outpatient consultation, and his TCM prescription was adjusted according to clinical symptoms. After 10 years of continuous TCM treatment, his blood glucose remained stable, urinary microalbumin quantitation showed no abnormalities, and blurred vision disappeared. Conclusions. This case provides specific treatment plans and effective references for long-term control of blood glucose, prevention and treatment of diabetes complications, delay of disease progression, and protection of impaired islet function in the treatment of diabetes with TCM. TCM may become a meaningful alternative DM treatment in the future.

Diabetes mellitus (DM) is one of the most familiar chronic diseases threatening human health. Recent studies have shown that the development of diabetes is closely related to an imbalance of the gut microbiota. Accordingly, there is increasing interest in how changes in the gut microbiota affect diabetes and its underlying mechanisms. Immunomodulatory cells play important roles in maintaining the normal functioning of the human immune system and in maintaining homeostasis. Intestinal immunomodulatory cells (IICs) are located in the intestinal mucosa and are regarded as an intermediary by which the gut microbiota affects physiological and pathological properties. Diabetes can be regulated by IICs, which act as a bridge linking the gut microbiota and DM. Understanding this bridge role of IICs may clarify the mechanisms by which the gut microbiota contributes to DM. Based on recent research, we summarize this process, thereby providing a basis for further studies of diabetes and other similar immune-related diseases.