Ribocentre-switch: a database of riboswitches.

Riboswitches are regulatory elements found in the untranslated regions (UTRs) of certain mRNA molecules. They typically comprise two distinct domains: an aptamer domain that can bind to specific small molecules, and an expression platform that controls gene expression. Riboswitches work by undergoing a conformational change upon binding to their specific ligand, thus activating or repressing the genes downstream. This mechanism allows gene expression regulation in response to metabolites or small molecules. To systematically summarise riboswitch structures and their related ligand binding functions, we present Ribocentre-switch, a comprehensive database of riboswitches, including the information as follows: sequences, structures, functions, ligand binding pockets and biological applications. It encompasses 56 riboswitches and 26 orphan riboswitches from over 430 references, with a total of 89 591 sequences. It serves as a good resource for comparing different riboswitches and facilitating the identification of potential riboswitch candidates. Therefore, it may facilitate the understanding of RNA structural conformational changes in response to ligand signaling. The database is publicly available at https://riboswitch.ribocentre.org.

Crystal structures of the NAD+-II riboswitch reveal two distinct ligand-binding pockets.

We present crystal structures of a new NAD+-binding riboswitch termed NAD+-II, bound to nicotinamide mononucleotide (NMN), nicotinamide adenine dinucleotide (NAD+) and nicotinamide riboside (NR). The RNA structure comprises a number of structural features including three helices, one of which forms a triple helix by interacting with an A5 strand in its minor-groove, and another formed from a long-range pseudoknot. The core of the structure (centrally located and coaxial with the triplex and the pseudoknot) includes two consecutive quadruple base interactions. Unusually the riboswitch binds two molecules of ligand, bound at distinct, non-overlapping sites in the RNA. Binding occurs primarily through the nicotinamide moiety of each ligand, held by specific hydrogen bonding and stacking interactions with the pyridyl ring. The mode of binding is the same for NMN, NR and the nicotinamide moiety of NAD+. In addition, when NAD+ is bound into one site it adopts an elongated conformation such that its diphosphate linker occupies a groove on the surface of the RNA, following which the adenine portion inserts into a pocket and makes specific hydrogen bonding interactions. Thus the NAD+-II riboswitch is distinct from the NAD+-I riboswitch in that it binds two molecules of ligand at separate sites, and that binding occurs principally through the nicotinamide moiety.

Ribocentre: a database of ribozymes.

Ribozymes are excellent systems in which to study 'sequence - structure - function' relationships in RNA molecules. Understanding these relationships may greatly help structural modeling and design of functional RNA structures and some functional structural modules could be repurposed in molecular design. At present, there is no comprehensive database summarising all the natural ribozyme families. We have therefore created Ribocentre, a database that collects together sequence, structure and mechanistic data on 21 ribozyme families. This includes available information on timelines, sequence families, secondary and tertiary structures, catalytic mechanisms, applications of the ribozymes together with key publications. The database is publicly available at https://www.ribocentre.org.

The regulation of chromatin configuration at AGAMOUS locus by LFR-SYD-containing complex is critical for reproductive organ development in Arabidopsis.

Switch defective/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes are evolutionarily conserved, multi-subunit machinery that play vital roles in the regulation of gene expression by controlling nucleosome positioning and occupancy. However, little is known about the subunit composition of SPLAYED (SYD)-containing SWI/SNF complexes in plants. Here, we show that the Arabidopsis thaliana Leaf and Flower Related (LFR) is a subunit of SYD-containing SWI/SNF complexes. LFR interacts directly with multiple SWI/SNF subunits, including the catalytic ATPase subunit SYD, in vitro and in vivo. Phenotypic analyses of lfr-2 mutant flowers revealed that LFR is important for proper filament and pistil development, resembling the function of SYD. Transcriptome profiling revealed that LFR and SYD shared a subset of co-regulated genes. We further demonstrate that the LFR and SYD interdependently activate the transcription of AGAMOUS (AG), a C-class floral organ identity gene, by regulating the occupation of nucleosome, chromatin loop, histone modification, and Pol II enrichment on the AG locus. Furthermore, the chromosome conformation capture (3C) assay revealed that the gene loop at AG locus is negatively correlated with the AG expression level, and LFR-SYD was functional to demolish the AG chromatin loop to promote its transcription. Collectively, these results provide insight into the molecular mechanism of the Arabidopsis SYD-SWI/SNF complex in the control of higher chromatin conformation of the floral identity gene essential to plant reproductive organ development.

Structure and mechanism of a methyltransferase ribozyme.

Known ribozymes in contemporary biology perform a limited range of chemical catalysis, but in vitro selection has generated species that catalyze a broader range of chemistry; yet, there have been few structural and mechanistic studies of selected ribozymes. A ribozyme has recently been selected that can catalyze a site-specific methyl transfer reaction. We have solved the crystal structure of this ribozyme at a resolution of 2.3 Å, showing how the RNA folds to generate a very specific binding site for the methyl donor substrate. The structure immediately suggests a catalytic mechanism involving a combination of proximity and orientation and nucleobase-mediated general acid catalysis. The mechanism is supported by the pH dependence of the rate of catalysis. A selected methyltransferase ribozyme can thus use a relatively sophisticated catalytic mechanism, broadening the range of known RNA-catalyzed chemistry.

Photocatalytic Degradation of Quinolones by Magnetic MOFs Materials and Mechanism Study.

With the rising incidence of various diseases in China and the constant development of the pharmaceutical industry, there is a growing demand for floxacin-type antibiotics. Due to the large-scale production and high cost of waste treatment, the parent drug and its metabolites constantly enter the water environment through domestic sewage, production wastewater, and other pathways. In recent years, the pollution of the aquatic environment by floxacin has become increasingly serious, making the technology to degrade floxacin in the aquatic environment a research hotspot in the field of environmental science. Metal-organic frameworks (MOFs), as a new type of porous material, have attracted much attention in recent years. In this paper, four photocatalytic materials, MIL-53(Fe), NH2-MIL-53(Fe), MIL-100(Fe), and g-C3N4, were synthesised and applied to the study of the removal of ofloxacin and enrofloxacin. Among them, the MIL-100(Fe) material exhibited the best photocatalytic effect. The degradation efficiency of ofloxacin reached 95.1% after 3 h under visible light, while enrofloxacin was basically completely degraded. The effects of different materials on the visible photocatalytic degradation of the floxacin were investigated. Furthermore, the photocatalytic mechanism of enrofloxacin and ofloxacin was revealed by the use of three trappers (▪O2-, h+, and ▪OH), demonstrating that the role of ▪O2- promoted the degradation effect of the materials under photocatalysis.

Aminopeptidase N-Responsive Conjugates with Tunable Charge-Reversal Properties for Highly Efficient Tumor Accumulation and Penetration.

Tumor enzyme-responsive charge-reversal carriers can induce efficient transcytosis and lead to efficient tumor infiltration and potent anticancer efficacy. However, the correlations of molecular structure with charge-reversal property, tumor penetration, and drug delivery efficiency are unknown. Herein, aminopeptidase N (APN)-responsive conjugates were synthesized to investigate these correlations. We found that the monomeric unit structure and the polymer chain structure determined the enzymatic hydrolysis and charge-reversal rates, and accordingly, the transcytosis and tumor accumulation and penetration of the APN-responsive conjugates. The conjugate with moderate APN responsiveness balanced the in vitro transcytosis and in vivo overall drug delivery process and achieved the best tumor delivery efficiency, giving potent antitumor efficacy. This work provides new insight into the design of tumor enzyme-responsive charge-reversal nanomedicines for efficient cancer drug delivery.

Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, phase 2 study.

Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD-1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II-IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1-3) of each 21-day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2-year progression-free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%-48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%-70.4%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 75.0%; grade 3, 10.7%; grade 4-5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2-year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long-term survival analyses.

The Role of Neuroglial Crosstalk and Synaptic Plasticity-Mediated Central Sensitization in Acupuncture Analgesia.

Although pain is regarded as a global public health priority, analgesic therapy remains a significant challenge. Pain is a hypersensitivity state caused by peripheral and central sensitization, with the latter considered the culprit for chronic pain. This study summarizes the pathogenesis of central sensitization from the perspective of neuroglial crosstalk and synaptic plasticity and underlines the related analgesic mechanisms of acupuncture. Central sensitization is modulated by the neurotransmitters and neuropeptides involved in the ascending excitatory pathway and the descending pain modulatory system. Acupuncture analgesia is associated with downregulating glutamate in the ascending excitatory pathway and upregulating opioids, 𝛾-aminobutyric acid, norepinephrine, and 5-hydroxytryptamine in the descending pain modulatory system. Furthermore, it is increasingly appreciated that neurotransmitters, cytokines, and chemokines are implicated in neuroglial crosstalk and associated plasticity, thus contributing to central sensitization. Acupuncture produces its analgesic action by inhibiting cytokines, such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α, and upregulating interleukin-10, as well as modulating chemokines and their receptors such as CX3CL1/CX3CR1, CXCL12/CXCR4, CCL2/CCR2, and CXCL1/CXCR2. These factors are regulated by acupuncture through the activation of multiple signaling pathways, including mitogen-activated protein kinase signaling (e.g., the p38, extracellular signal-regulated kinases, and c-Jun-N-terminal kinase pathways), which contribute to the activation of nociceptive neurons. However, the responses of chemokines to acupuncture vary among the types of pain models, acupuncture methods, and stimulation parameters. Thus, the exact mechanisms require future clarification. Taken together, inhibition of central sensitization modulated by neuroglial plasticity is central in acupuncture analgesia, providing a novel insight for the clinical application of acupuncture analgesia.

LFR is functionally associated with AS2 to mediate leaf development in Arabidopsis.

Leaves are essential organs for plants. We previously identified a functional gene possibly encoding a component of the SWI/SNF complex named Leaf and Flower Related (LFR) in Arabidopsis thaliana. Loss-of-function mutants of LFR displayed obvious defects in leaf morphogenesis, indicating its vital role in leaf development. Here an allelic null mutant of ASYMMETRIC LEAVES2 (AS2), as2-6, was isolated as an enhancer of lfr-1 in petiole length, vasculature pattern and leaf margin development. The lfr as2 double-mutants showed enhanced ectopic expression of BREVIPEDICELLUS (BP) compared with each of the single-mutants, which is consistent with their synergistic genetic enhancement in multiple BP-dependent development processes. Moreover, LFR and several putative subunits of the SWI/SNF complex interacted physically with AS2. LFR associated with BP chromatin in an AS1-AS2-dependent manner to promote the nucleosome occupancy for appropriate BP repression in leaves. Taken together, our findings reveal that LFR and the SWI/SNF complex play roles in leaf development at least partly by repressing BP transcription as interacting factors of AS2, which expounds our understanding of BP repression at the chromatin structure level in leaf development.

Restless legs syndrome in end stage renal disease patients undergoing hemodialysis.

BACKGROUND: The prevalence of Restless legs syndrome (RLS) in End Stage Renal Disease (ESRD) patients is higher than that in the general population. However, the associations of RLS within the ESRD population are inconsistent and RLS is usually neglected in dialysis centers, although it impairs the life quality among ESRD patients. We aim to investigate the prevalence of RLS in patients with ESRD undergoing maintenance hemodialysis and evaluate the risk factors of developing RLS and the effect of RLS on quality of life among ESRD patients. METHODS: ESRD patients undergoing maintenance hemodialysis in Shanghai General Hospital dialysis unit from July 2016 to October 2016 were enrolled in the study. RLS was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group (IRLSSG). IRLSSG Severity Scale was used to evaluate the severity of RLS. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and Hospital Anxiety and Depression Scale (HADS) was used to estimate anxiety and depression. Serologic and historic variables were analyzed to determine predictors of RLS in the ESRD population. RESULTS: A total of 137 ESRD patients were enrolled. The prevalence of RLS among the ESRD patients was 20.44%. The risk of RLS was increased significantly in females (OR = 2.729, p = 0.032) and daily alcohol drinkers (OR = 4.716, p = 0.022). RLS increased the risks of sleep disorders (25/28, 89.3% vs 73/109, 67.0%, p = 0.02) and sedative hypnotics intake (7/28, 25.0% vs 10/109, 9.2%, p = 0.047) and impaired the sleep quality (7/109 vs 11/28, p = 0.001) according to PSQI sum scores. CONCLUSION: A high RLS prevalence among the ESRD patients undergoing hemodialysis was confirmed. ESRD patients who are women and drinking alcohol have a higher risk of RLS. The sleep quality was significantly impaired and sleeping medication use was more common among the ESRD patients with RLS.

Effect of dendritic cell-cytokine-induced killer cells in patients with advanced colorectal cancer combined with first-line treatment.

BACKGROUND: Surgical resection combined with adjuvant chemotherapy is considered as the gold-standard treatment for advanced colorectal cancer patients. These patients have a poor 5-year survival rate of 5% or less. Furthermore, a large dose of chemotherapy can produce adverse side effects and severe toxicity. Therefore, this retrospective study aimed to evaluate the efficacy of dendritic cell-cytokine-induced killer (DC-CIK) cell infusion as an adjuvant therapy in patients with advanced colorectal cancer combined with first-line treatment. METHODS: A total of 142 patients with stage III/IV colorectal carcinoma who had been treated with first-line therapy were included in this study. Among these patients, 71 patients received first-line treatment only (non-DC-CIK group), while the other 71 patients who had similar demographic and clinical characteristics received a DC-CIK cell infusion combined with first-line treatment (DC-CIK group). These patients were followed up until August 2014. Data were analyzed by Kaplan-Meier and Cox regression. RESULTS: Our results showed that the 5-year overall survival (OS) rate for the DC-CIK group versus the non-DC-CIK group was 41.3 versus 19.4% (p = 0.001) and the 5-year progression-free survival (PFS) rate for the DC-CIK group versus the non-DC-CIK group was 57.4 versus 33.6% (p = 0.022). CONCLUSIONS: Our results showed that patients with advanced colorectal cancer might benefit from DC-CIK immunotherapy combined with first-line therapy by significantly prolonging 5-year OS and PFS.

A review on traditional Chinese medicine natural products and acupuncture intervention for Alzheimer's disease based on the neuroinflammatory.

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset and progressive development. It is clinically characterized by cognitive impairment, memory impairment and behavioral change. Chinese herbal medicine and acupuncture are important components of traditional Chinese medicine (TCM), and are commonly used in clinical treatment of AD. This paper systematically summarizes the research progress of traditional Chinese medicine natural products and acupuncture treatment of AD, which combined with existing clinical and preclinical evidence, based on a comprehensive review of neuroinflammation, and discusses the efficacy and potential mechanisms of traditional Chinese medicine natural products and acupuncture treatment of AD. Resveratrol, curcumin, kaempferol and other Chinese herbal medicine components can significantly inhibit the neuroinflammation of AD in vivo and in vitro, and are candidates for the treatment of AD. Acupuncture can alleviate the memory and cognitive impairment of AD by improving neuroinflammation, synaptic plasticity, nerve cell apoptosis and reducing the production and aggregation of amyloid ß protein (Aß) in the brain. It has the characteristics of early, safe, effective and benign bidirectional adjustment. The purpose of this paper is to provide a basis for improving the clinical strategies of TCM for the treatment of AD.

Babaodan inhibits cell proliferation and metastasis and enhances anti-tumor effects of camrelizumab by inhibiting M2 phenotype macrophages in hepatocellular carcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: Babaodan (BBD) is a unique Chinese medication utilized in traditional Chinese medicine. It can eliminate toxins, induce diuresis, and eliminate yellowish hue. In addition to treating acute and chronic viral hepatitis, cholecystitis, cholangitis, and urinary tract infections, BBD has garnered popularity as a substitution treatment for several malignant cancers, particularly hepatocellular carcinoma (HCC). AIM OF THE STUDY: To elucidate the efficacy and mechanism of BBD alone and combined with camrelizumab (CLM) for treating HCC. METHODS: We investigated the effects of BBD on the HCC tumor microenvironment in vivo. Furthermore, we evaluated its effects on tumor growth and metastasis induced by M2 macrophages in vitro. RESULTS: In a mouse model of orthotopic HCC, BBD decreased tumor growth. Furthermore, it increased the M1/M2 macrophage ratio and CD8+ T-cell abundance in mice. In addition, BBD reversed HCC cell proliferation and metastasis induced by M2 macrophages, increased the anti-HCC effect of low-dose CLM, and attenuated organ damage induced by high-dose CLM. Lastly, BBD enhanced the efficacy of CLM via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: BBD increases the antitumor effect of CLM by modulating the tumor immune microenvironment and attenuating its the toxic side effects of CLM.

Revealing the clinical effect and biological mechanism of acupuncture in COPD: A review.

BACKGROUND: To provide new ideas for the clinical and mechanism research of acupuncture in the treatment of chronic obstructive pulmonary disease (COPD), this study systematically reviews clinical research and the progress of basic research of acupuncture in the treatment of COPD. METHODS: PubMed and Web of Science databases were searched using acupuncture and COPD as keywords in the last 10 years, and the included literature was determined according to exclusion criteria. FINDINGS: Acupuncture can relieve clinical symptoms, improve exercise tolerance, anxiety, and nutritional status, as well as hemorheological changes (blood viscosity), reduce the inflammatory response, and reduce the duration and frequency of COPD in patients with COPD. Mechanistically, acupuncture inhibits M1 macrophage activity, reduces neutrophil infiltration, reduces inflammatory factor production in alveolar type II epithelial cells, inhibits mucus hypersecretion of airway epithelial cells, inhibits the development of chronic inflammation in COPD, and slows tissue structure destruction. Acupuncture may control pulmonary COPD inflammation through the vagal-cholinergic anti-inflammatory, vagal-adrenomedullary-dopamine, vagal-dual-sensory nerve fiber-pulmonary, and CNS-hypothalamus-orexin pathways. Furthermore, acupuncture can increase endogenous cortisol levels by inhibiting the HPA axis, thus improving airway antioxidant capacity and reducing airway inflammation in COPD. In conclusion, the inhibition of the chronic inflammatory response is the key mechanism of acupuncture treatment for COPD.

Electroacupuncture pre-treatment exerts a protective effect on LPS-induced cardiomyopathy in mice through the delivery of miR-381 via exosomes.

OBJECTIVE: This study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. METHODS AND RESULTS: Pre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. CONCLUSIONS: Our research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381.

TRPA1 Ion Channel Mediates the Analgesic Effects of Acupuncture at the ST36 Acupoint in Mice Suffering from Arthritis.

Purpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia. Patients and Methods: We injected complete Freund's adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1-/- mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1. Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1-/- ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated. Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.

Coordination measure for coupling system of digital economy and rural logistics: An evidence from China.

As an important engine for high-quality economic development, the digital economy is gradually integrating with the rural logistics industry. This trend is contributing to making rural logistics a fundamental, strategic, and pioneering industry. However, some valuable topics remain unstudied, such as whether they are coupled and whether there is variability in the coupling system across the provinces. Therefore, this article takes system theory and coupling theory as the analytical framework, aiming to better elaborate the subject's logical relationship and operational structure of the coupled system, which is composed of a digital economy subsystem and a rural logistics subsystem. Furthermore, 21 provinces are seen as the research object in China, and the coupling coordination model is constructed, aiming to verify the coupling and coordination relationship between the two subsystems. The results suggest that two subsystems are coupled and coordinated in the same direction, and they feed back and influence each other. During the same period, four echelons are divided and there is variability in the coupling and coordination between the digital economy and rural logistics, according to the coupling degree (CD) and coupling coordination degree (CCD). Findings presented can serve as a useful reference for the evolutionary laws of the coupled system. The findings presented here can serve as a useful reference for the evolutionary laws of coupled systems. Moreover, it further provides ideas for the development between rural logistics and the digital economy.

Abnormal tryptophan catabolism in diabetes mellitus and its complications: Opportunities and challenges.

In recent years, the incidence rate of diabetes mellitus (DM), including type 1 diabetes mellitus(T1DM), type 2 diabetes mellitus(T2DM), and gestational diabetes mellitus (GDM), has increased year by year and has become a major global health problem. DM can lead to serious complications of macrovascular and microvascular. Tryptophan (Trp) is an essential amino acid for the human body. Trp is metabolized in the body through the indole pathway, kynurenine (Kyn) pathway and serotonin (5-HT) pathway, and is regulated by intestinal microorganisms to varying degrees. These three metabolic pathways have extensive regulatory effects on the immune, endocrine, neural, and energy metabolism systems of the body, and are related to the physiological and pathological processes of various diseases. The key enzymes and metabolites in the Trp metabolic pathway are also deeply involved in the pathogenesis of DM, playing an important role in pancreatic function, insulin resistance (IR), intestinal barrier, and angiogenesis. In DM and its complications, there is a disruption of Trp metabolic balance. Several therapy approaches for DM and complications have been proven to modify tryptophan metabolism. The metabolism of Trp is becoming a new area of focus for DM prevention and care. This paper reviews the impact of the three metabolic pathways of Trp on the pathogenesis of DM and the alterations in Trp metabolism in these diseases, expecting to provide entry points for the treatment of DM and its complications.