Search

Objective: To evaluate the association of human papilloma virus (HPV) infection with prognosis, specifically overall survival (OS) and disease‐free survival (DFS), in laryngeal squamous cell carcinoma (LSCC) patients. Method: A systematic review and meta‐analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. LSCC was confirmed on the basis of histopathology, whereas HPV status was confirmed by polymerase chain reaction. Results: A total of 6539 articles were initially searched from 8 databases, of which 11 studies were eligible for our review. A total of 1442 LSCC cases were included in this analysis. Eight studies examined 3‐year OS for LSCC. The pooled hazard ratio (HR) from the 8 studies was 0.29 (95% CI: 0.25‐0.33). There was a statistically significant difference in 3‐year OS between the HPV‐negative and ‐positive groups, with the latter having a better survival. There was no statistically significant differences in 5‐ and 10‐year OS. Five studies examined 3‐ and 5‐year DFS for LSCC, whereas only 3 studies examined 10‐year DFS. There was no statistically significant difference in 3‐, 5‐, and 10‐year DFS between the HPV groups. Conclusion: This study evaluated the survival impact of HPV infection in LSCC patients. The OS of the HPV‐positive group was better than that of the HPV‐negative group in terms of short‐term survival. Compared with the HPV‐negative group, the HPV‐positive group had a better trend of DFS, suggesting that a larger sample size and further exploration of the pathology and local control of HPV‐positive tumors are needed. [ABSTRACT FROM AUTHOR]

Neurotrophins are a family of growth factors that regulate neural survival, development, function and plasticity in the central and the peripheral nervous system. There are four neurotrophins: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and NT-4. Among them, BDNF is the most studied due to its high expression in the brain. Over the past two decades, BDNF and its receptor tropomyosin receptor kinase B (TrkB) have been reported to be upregulated in a wide range of tumors. This activated signal stimulates a series of downstream pathways, including phosphoinositide 3-kinase/protein kinase B, Ras-Raf-mitogen activated protein kinase kinase-extracellular signal-regulated kinases, the phospholipase-C-γ pathway and the transactivation of epidermal growth factor receptor. Activation of these signaling pathways induces oncogenic effects by increasing cancer cell growth, proliferation, survival, migration and epithelial to mesenchymal transition, and decreasing anoikis, relapse and chemotherapeutic sensitivity. The present review summarizes recent findings to discuss the role of BDNF in tumors, the underlying molecular mechanism, targeting Trk receptors for treatment of cancers and its potential risk. [ABSTRACT FROM AUTHOR]

Carbon Capture, Utilization and Storage, also referred to as Carbon Capture, Utilization and Sequestration (CCUS), is one of the novel climate mitigation technologies by which CO2 emissions are captured from sources, such as fossil power generation and industrial processes, and further either reused or stored with more attention being paid on the utilization of captured CO2. In the whole CCUS process, the dominant migration pathway of CO2 after being injected underground becomes very important information to judge the possible storage status as well as one of the essential references for evaluating possible environmental affects. Interferometric Synthetic Aperture Radar (InSAR) technology, with its advantages of extensive coverage in surface deformation monitoring and all-weather traceability of the injection processes, has become one of the promising technologies frequently adopted in worldwide CCUS projects. In this study, taking the CCUS sequestration area in Shizhuang Town, Shanxi Province, China, as an example, unmanned aerial vehicle (UAV) photography measurement technology with a 3D surface model at a resolution of 5.3 cm was applied to extract the high-resolution digital elevation model (DEM) of the study site in coordination with InSAR technology to more clearly display the results of surface deformation monitoring of the CO2 injection area. A 2 km surface heaving dynamic processes before and after injection from June 2020 to July 2021 was obtained, and a CO2 migration pathway northeastward was observed, which was rather consistent with the monitoring results by logging and micro-seismic studies. Additionally, an integrated monitoring scheme, which will be the trend of monitoring in the future, is proposed in the discussion. [ABSTRACT FROM AUTHOR]

A variety of systemic chemotherapy regimens have been used for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, most guidelines have been derived from a single clinical trial, and no studies have comprehensively compared their efficacy and safety. We systematically searched PubMed, Embase, Web of Science, and Cochrane Library databases. Eligible studies reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and ≥ 3 adverse events rate (AEs). Eighteen eligible trials involving 4930 patients and 15 treatment regimens were included. The results suggest that patients with R/M HNSCC exhibit better tumor response with the cetuximab/platinum/5-FU, pembrolizumab/platinum/5-FU or pembrolizumab alone, accompanied by a low AE rate. Nivolumab also showed better efficacy than other single agents. Immunotherapy has achieved better efficacy. [Display omitted] • Immunotherapy combined with chemotherapy showed better efficacy in R/M HNSCC. • Nivolumab and pembrolizumab are two immunotherapeutic agents with high efficacy and low AE. • Methotrexate is the least efficient method recommended and should be minimized. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a challenging cancer with poor prognosis. The classical standard for treatment is safe resection, followed by concurrent chemoradiotherapy with subsequent adjuvant temozolomide (TMZ). Despite several attempts at different treatments, the 5-year survival rate remains poor. In recent years, with the continuous progress of treatment technology, tumor treating fields (TTFields) were preferable. The device could generate an intermediate frequency alternating electric field and induce apoptosis of some specific types of cancer cells with few toxic and side effects. TTFields induced apoptosis through multiple activations of the pathway. TTFields have been Food and Drug Administration (FDA)-approved for diagnosis and recurrent GBM as additional clinical trial results are revealed. This study reviewed the current status, mechanisms, correlations with immune pathways, the prospects of applying TTFields for GBM, and the adverse events. [Display omitted] • Tumor treating fields (TTFields) is an emerging therapy for glioblastoma patients. • TTFields was delivered continuously (> 18 h/day) via 4 transducer arrays. • TTFields has many landmark experiments: EF-2, EF-7, EF-11, EF-14. • Adverse events of TTFields includes contact dermatitis, ulcers, and infections. [ABSTRACT FROM AUTHOR]

Leakage and compression of blood vessels may result in deprivation of blood flow to a large number of tumor tissues, which can lead to tumor hypoxia. Hypoxia induces an increase in the expression of hypoxia-inducible factor 1 in tumor cells, which induces angiogenesis in tumors through the high expression of vascular endothelial growth factor, thereby forming a positive feedback vicious circle. Improving hypoxia by normalizing blood vessels and improving radiosensitivity by immunotherapy has emerged as a new application of combined immunotherapy and radiotherapy. Interferon γ produced by CD4 + /CD8 + T cells, induced by immune checkpoint inhibitors, plays an important role in the normalization of blood vessels; tumor-associated eosinophils also play a role in the process of immunotherapy-induced blood vessel normalization. In addition, the reduction in regulatory T cells induced by immune checkpoint inhibitors can increase eosinophil levels, which promotes the further development of vascular normalization mechanisms. This review focuses on the mechanism of immunotherapy to normalize blood vessels, and proposes a good prospect for improving hypoxia. Due to the narrow vascular normalization window of anti-angiogenesis therapy, discovery of the vascular normalization effect of immunotherapy provides a new idea for the combined application of immunotherapy and radiotherapy. The enlarged vascular normalization window and improved hypoxia provide a good opportunity for the subsequent implementation of radiotherapy. The above sorting and analysis may pave the way for a promising strategy for cancer treatment via combined immunotherapy and radiotherapy. [Display omitted] • Immune checkpoint inhibitors can normalize blood vessels just like anti-angiogenesis therapy. • IFNγplay an important role in the vascular normalization of immune checkpoint inhibitors. • The normalization of blood vessels by ICIs can improve tumor hypoxia. [ABSTRACT FROM AUTHOR]

• Radiation-induced carotid injury (RICI) is a potentially lethal clinical complication of head and neck radiotherapy. • The mechanisms of RICI include inflammatory, atherosclerosis, intimal proliferation, media necrosis, and peri-adventitial fibrosis. • CAS is mainly treated with carotid endarterectomy or carotid angioplasty and stent implantation. • BMSCs are advantageous in RICI treatment and reduce carotid inflammation, oxidative stress, and delaying atherosclerosis. Radiotherapy has significantly improved the survival of cancer patients but is also associated with several adversities, including radiation-induced carotid injury (RICI). The RICI mechanisms are complex, including vessel inflammatory injury, carotid atherosclerosis, intimal proliferation, media necrosis, and peri-adventitial fibrosis. The main manifestation and adverse consequence of RICI is carotid artery stenosis (CAS), which can lead to stroke and transient ischemic attack. Currently, carotid artery injury is primarily diagnosed via color-coded duplex sonography. Early detection of traumatic changes in the carotid artery depends on measurements of carotid intima-media thickness; serum biomarker testing also shows great potential. CAS is mainly treated with carotid endarterectomy or carotid angioplasty and stent implantation. Notably, bone marrow mesenchymal stem cells are advantageous in RICI treatment and reduce carotid inflammation, oxidative stress, and delaying atherosclerosis. This review summarizes the mechanisms, examination methods, and latest treatments for RICI to provide data for its clinical prevention and treatment. [ABSTRACT FROM AUTHOR]

Neuroblastoma is the most common extracranial solid tumor, arising from primitive sympathetic ganglion cells, in pediatric patients. The unique features of neuroblastoma include variable clinical behaviors, such as rapid progression to death and maturation to benign ganglioneuroma, followed by regression. Radiation therapy (RT) is usually administered to both the primary tumor bed and persistent metastatic sites after induction chemotherapy for high-risk neuroblastoma. RT to the tumor bed after surgical resection contributes significantly to local disease control and prevention of local relapse, confirming the role of RT. Palliative radiotherapy for metastatic neuroblastoma is also effective and safe and mainly provides symptomatic relief. The late side effects of RT in neuroblastoma patients include growth and developmental failure, hypothyroidism, gastrointestinal dysfunction, neurocognitive defects, pulmonary and cardiac abnormalities, infertility, and secondary cancers. In this article, we reviewed the role and toxicity of RT in neuroblastoma patients. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment, yet the roles and mechanisms of TAMs in inflammation-associated oncogenesis remain enigmatic. We report that protein canopy homolog 2 (CNPY2) functions as a novel TLR4 regulator, promoting cytokine production in macrophages. CNPY2 binds directly to TLR4. Cnpy2 deficiency reduces cell surface expression of TLR4, nuclear translocation of NFκB and cytokine production in macrophages. Macrophage-specific CNPY2 deficiency significantly decreases cytokine production in macrophages and reduces hepatocarcinogenesis in a diethylnitrosamine (DEN)-induced liver cancer model. RNA-sequencing analysis revealed Cnpy2 knockout decreased the mRNA level and cell surface expression of two VEGF receptors, Flt1 and Kdr, compared to those in WT counterparts, resulting in inhibition of macrophage tumor infiltration. Cnpy2 knockout inhibits NFκB2/p52-mediated transcription of Flt1 and Kdr in macrophages. These findings demonstrate that CNPY2 regulates macrophages in both inflammation and hepatocarcinogenesis and may serve as a therapeutic target for cancer., Competing Interests: Declaration of competing interest, (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Genitourinary (GU) malignancies are common and associated with significant morbidity and mortality. In patients with localized GU cancers, surgical resection or definitive radiation remain the mainstays of treatment. Despite definitive treatment, many patients with high-risk localized disease experience recurrence. There is growing interest in using neoadjuvant immunotherapy to improve outcomes. This narrative review summarizes the current evidence for neoadjuvant immunotherapy in patients with localized high-risk GU cancers including renal cell carcinoma, urothelial carcinoma, prostate cancer, penile squamous cell carcinoma, and testicular germ cell tumors. We also discuss ongoing clinical trials and candidate biomarkers to optimize patient selection and improve treatment outcomes.

Aerogels exhibit poor adhesion to wet tissue surfaces, which is a significant factor that limits their hemostatic properties. In this work, we propose a new method for investigating aerogel hemostatic materials by introducing the concept of the 'rapid tissue hydration layer-triggered property' into the hemostatic material. A chitosan derivative ( Csde ) with a "swollen property" was prepared via an amide reaction, followed by the incorporation of the extracted bletilla striata complex ( Bscai ) into the chitosan derivative to fabricate the Bscai/Csde hemostatic material. The research results indicated that the Bscai/Csde hemostatic material exhibited a rapid tissue hydration layer-triggered response, outstanding hemostasis ability, as well as excellent hemocompatibility, antibacterial properties, and cytocompatibility. Additionally, the preparation method for the Bscai/Csde hemostatic material is straightforward, and the raw materials are readily available. Therefore, this study presents a novel method for developing a hemostatic material method, and the composite aerogel hemostatic material demonstrates considerable potential for future applications.

Biochar prepared from crop straw is an economical method for adsorbing bromocresol green (BCG) from textile industrial wastewater. However, there is limited research on the adsorption mechanism of biochar for the removal of BCG. This study utilized cucumber straw as raw material to prepare biochar with good adsorption potential and characterized its physicochemical properties. Through adsorption experiments, the effects of solution pH, biochar dosage, and initial dye concentration on adsorption performance were examined. The adsorption mechanism of cucumber straw biochar (CBC) for BCG was elucidated at the molecular level using adsorption kinetics, adsorption isotherm models, and density functional theory (DFT) calculations. Results show that the specific surface area of the CBC is 101.58 m 2 /g, and it has a high degree of carbonization, similar to the structure of graphite crystals. The presence of aromatic rings, -OH groups, and -COOH groups in CBC provides abundant adsorption sites for BCG. The adsorption process of CBC for BCG is influenced by both physical and chemical adsorption, and can be described by the Langmuir isotherm model, indicating a monolayer adsorption process. The theoretical maximum monolayer adsorption capacity (q m ) of BCG at 298 K was calculated to be 99.18 mg/g. DFT calculations reveal interactions between BCG and CBC involving electrostatic interactions, van der Waals forces, halogen-π interactions, π-π interactions, and hydrogen bonds. Additionally, the interaction of hydrogen bonds between BCG and the -COOH group of biochar is stronger than that between BCG and the -OH group. These findings provide valuable insights into the preparation and application of efficient organic dye adsorbents.

Background and Purpose: Amyloid-β (Aβ) peptide is one of the more important pathological markers in Alzheimer's disease (AD). The development of AD impairs autophagy, which results in an imbalanced clearance of Aβ. Our previous research demonstrated that AdipoRon, an agonist of adiponectin receptors, decreased the deposition of Aβ and enhanced cognitive function in AD. However, the exact mechanisms by which AdipoRon affects Aβ clearance remain unclear., Experimental Approach: We studied how AdipoRon affects autophagy in HT22 cells and APP/PS1 transgenic mice. We also investigated the signalling pathway involved and used pharmacological inhibitors to examine the role of autophagy in this process., Key Results: AdipoRon promotes Aβ clearance by activating neuronal autophagy in the APP/PS1 transgenic mice. Interestingly, we found that AdipoRon induces the nuclear translocation of GAPDH, where it interacts with the SIRT1/DBC1 complex. This interaction then leads to the release of DBC1 and the activation of SIRT1, which in turn activates autophagy. Importantly, we found that inhibiting either GAPDH or SIRT1 to suppress the activity of SIRT1 counteracts the elevated autophagy and decreased Aβ deposition caused by AdipoRon. This suggests that SIRT1 plays a critical role in the effect of AdipoRon on autophagic induction in AD., Conclusion and Implications: AdipoRon promotes the clearance of Aβ by enhancing autophagy through the AdipoR1/AMPK-dependent nuclear translocation of GAPDH and subsequent activation of SIRT1. This novel molecular pathway sheds light on the modulation of autophagy in AD and may lead to the development of new therapeutic strategies targeting this pathway., (© 2024 British Pharmacological Society.)

Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1/PD-L1 to boost tumor-specific T lymphocyte immunity have opened up new avenues for the treatment of various histological types of malignancies, with the possibility of durable responses and improved survival. However, the development of acquired resistance to ICI therapy over time after an initial response remains a major obstacle in cancer therapeutics. The potential mechanisms of acquired resistance to ICI therapy are still ambiguous. In this review, we focused on the current understanding of the mechanisms of acquired resistance to ICIs, including the lack of neoantigens and effective antigen presentation, mutations of IFN-γ/JAK signaling, and activation of alternate inhibitory immune checkpoints, immunosuppressive tumor microenvironment, epigenetic modification, and dysbiosis of the gut microbiome. Further, based on these mechanisms, potential therapeutic strategies to reverse the resistance to ICIs, which could provide clinical benefits to cancer patients, are also briefly discussed., (© 2023. The Author(s).)

Apatinib is a novel antiangiogenic agent that targets vascular endothelial growth factor 2. The aim of our study was to explore the efficacy and safety of apatinib in the treatment of patients with recurrence or metastasis (R/M) inoperable head and neck squamous cell carcinoma (HNSCC). This multi-center retrospective study analyzed 53 cases of recurrent or metastatic inoperable HNSCC who had progressed or recurred after undergoing standard radiotherapy, chemotherapy, and immunotherapy treated with apatinib from March 2017 to August 2021. Patients continued apatinib until the time of disease progression or onset of intolerable adverse events. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR) and incidence of adverse events. Univariable and multivariable analyses were performed to determine prognostic factors. The main adverse events were counted, and the severity of the adverse reactions was evaluated. Fifty-three patients with recurrent or metastatic inoperable R/M HNSCC who had progressed or recurred after standard radiotherapy, chemotherapy, and immunotherapy were included. The ORR was 15.1%, and the DCR was 86.8%. The median PFS was 4.4 months (95% confidence interval [CI] 3.7-5.0 months) and the median OS was 6.6 months (95% CI 5.3-7.9 months). The number of apatinib lines was an influencing factor for both PFS and OS, and the Eastern Cooperative Oncology Group (ECOG) score, tumor differentiation, and apatinib duration were only the influencing factors for OS. Of these, only the ECOG score was an independent predictor of OS. The most common adverse reactions were hypertension (39.6%), hand-foot syndrome (32.1%), fatigue (32.1%), oral ulcers (28.3%), and nausea and vomiting (20.8%). Most adverse reactions were grade 1 or 2. Apatinib mesylate has good efficacy for recurrent/metastatic inoperable HNSCC as second-line and above-line treatment. ECOG score was an independent prognostic factors of OS in patients who were treated with apatinib. In addition, the adverse effects of apatinib mesylate were relatively mild., (© 2022. The Author(s).)

Aims: Cardiovascular disease (CVD) is the leading cause of death worldwide. Inflammation and oxidative stress are the primary factors underlying angiotensin II (Ang II)-induced aortic damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important antioxidative stress factor. Sulforaphane (SFN), which is naturally found in cruciferous vegetables, is an Nrf2 agonist that is safe for oral administration. Here, we aimed to explore the potential of SFN in protecting against Ang II-induced aortic damage by upregulating Nrf2 expression via the extracellular signal-regulated kinase (ERK)/glycogen synthase kinase-3 beta (GSK-3β)/Fyn pathway., Main Methods and Key Findings: Wild-type (WT) C57BL/6J and Nrf2-knockout (Nrf2-KO) mice were injected with Ang II to induce aortic inflammation, oxidative stress, and cardiac remodeling (increased fibrosis and wall thickness). SFN treatment prevented aortic damage via Nrf2 activation in the WT mice. However, the protective effect of SFN on Ang II-induced aortic damage and upregulation of genes downstream of Nrf2 were not observed in Nrf2-KO mice. SFN induced the upregulation of aortic Nrf2 and inhibited the accumulation of ERK, GSK-3β, and Fyn in the nuclei., Significance: These results revealed that Nrf2 plays a central role in protecting against Ang II-induced aortic injury. Furthermore, SFN prevented Ang II-induced aortic damage by activating Nrf2 through the ERK/GSK-3β/Fyn pathway., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Radiotherapy (RT) is an effective treatment for head and neck cancer (HNC). Radiation-induced temporal lobe injury (TLI) is a serious complication of RT. Late symptoms of radiation-induced TLI are irreversible and manifest as memory loss, cognitive impairment, and even temporal lobe necrosis (TLN). It is currently believed that the mechanism of radiation-induced TLI involves microvascular injury, neuron and neural stem cell injury, glial cell damage, inflammation, and the production of free radicals. Significant RT-related structural changes and dose-dependent changes in gray matter (GM) and white matter (WM) volume and morphology were observed through computed tomography (CT) and magnetic resonance imaging (MRI) which were common imaging assessment tools. Diffusion tensor imaging (DTI), dispersion kurtosis imaging (DKI), susceptibility-weighted imaging (SWI), resting-state functional magnetic resonance (rs-fMRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET) can be used for early diagnosis and prognosis evaluation according to functional, molecular, and cellular processes of TLI. Early diagnosis of TLI is helpful to reduce the incidence of TLN and its related complications. This review summarizes the clinical features, mechanisms, and imaging of radiation-induced TLI in HNC patients. KEY POINTS: • Radiation-induced temporal lobe injury (TLI) is a clinical complication and its symptoms mainly include memory impairment, headache, and cognitive impairment. • The mechanisms of TLI include microvascular injury, cell injury, and inflammatory and free radical injury. Significant RT-related structural changes and dose-dependent changes in TL volume and morphology were observed through CT and MRI. • SWI, MRS, DTI, and DKI and other imaging examinations can detect anatomical and functional, molecular, and cellular changes of TLI., (© 2021. European Society of Radiology.)

Background: The prognostic value of different KRAS (Kirsten rat sarcoma viral oncogene) mutation subtypes and their association with programmed death ligand 1 (PD-L1) expression in lung adenocarcinoma (LADC) remain unclear. We examined the association of KRAS mutation subtypes with clinical outcomes and PD-L1 expression status., Patients and Methods: Patients diagnosed with KRAS-mutated LADC were evaluated for PD-L1 expression, cancer staging, overall survival (OS), and relapse-free survival., Results: A cohort of 254 KRAS-mutated LADC patients (median follow-up, 17 months) was studied. The 3 major subtypes of KRAS mutations were G12C (46.1%), G12V (21.7%), and G12D (15.7%). We found that all these subtypes had no impact on cancer stages, brain metastasis at diagnosis, OS, and relapse-free survival. Among this cohort, 33% of 94 patients who had PD-L1 staining data available had PD-L1-positive disease (≥ 1% of tumor cells). PD-L1 expression status was not significantly different among the 3 major mutation subtypes. Of interest, among patients with G12C mutation, positive PD-L1 expression was associated with significantly shorter OS (median survival, 5.7 vs. 12.8 months, P = .007). In multivariable analysis, PD-L1 positivity remained as an adverse factor for OS, with hazard ratio of 4.44 (P = .0007). PD-L1 status did not affect OS in other subtypes of mutations., Conclusion: KRAS mutation subtype is not associated with patient clinical outcomes or PD-L1 expression status. However, PD-L1 positivity appears to negatively affect OS in LADC patients with G12C mutation. Further study is needed to confirm our observation and to determine if programmed cell death 1/PD-L1 antagonist may affect the clinical outcome of patients with different KRAS mutation subtypes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Type 2 diabetes is the fastest-growing metabolic disease in the world. Many clinical studies have found that type 2 diabetes patients have metabolic disorders and chronic inflammatory states accompanied by disturbances in the gut microbiota. The gut microbiota plays an important role in body metabolism and immune regulation, and disturbances in the gut microbiota in conjunction with destruction of the intestinal barrier in type 2 diabetes patients causes damage to multiple organs. Therefore, the gut microbiota may be a new therapeutic target for treating type 2 diabetes and related diseases. In this review, we introduce the characteristics of the gut microbiota in type 2 diabetes and related diseases, as well as highlight the potential molecular mechanisms of their effects on intestinal barrier disruption, metabolic disorders, and chronic inflammation. Finally, we summarize an intestinal microecological therapeutic strategy, with a focus on shaping the intestinal bacteria, to improve the malignant progress of type 2 diabetes and related diseases. AUTHOR SUMMARY: Type 2 diabetes (T2D) is the fastest-growing metabolic disease in the world. Many clinical studies have found that T2D patients have metabolic disorders and chronic inflammatory states, accompanied by disturbances of the gut microbiota and increased intestinal permeability. The number of human gut microbiota is more than 10 times of human cells, and they play an important role in the body's metabolism and immune regulation. The abnormal intestinal metabolites and intestinal barrier disruption caused by the gut microbiota dysbiosis in the T2D facilitate intestinal bacteria and their harmful metabolites entering the circulatory system. The abnormal entering will cause the damage to multiple organs through disturbing insulin sensitivity, glucose metabolism, and immune homeostasis. Therefore, the gut microbiota may be a new therapeutic target for improving T2D and its related diseases. In this review, we introduce the compositional characteristics of the gut microbiota in T2D, and highlight some new molecular mechanisms of their effects on intestinal barrier disruption, metabolic disorders and chronic inflammation in T2D and its related diseases. Finally, we summarize an intestinal microecological therapeutic strategy, with a focus on shaping the intestinal bacteria, to improve the malignant progress of T2D and related diseases., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of this study was to develop a derivative of chitosan as pharmaceutical excipient used in sustained-release matrix tablets of poorly soluble drugs. A water-soluble quaternary ammonium carboxymethylchitosan was synthesized by a two-step reaction with carboxymethylchitosan (CMCTS), decylalkyl dimethyl ammonium and epichlorohydrin. The elemental analysis showed that the target product with 10.27% of the maximum grafting degree was obtained. To assess the preliminary safety of this biopolymer, cell toxicity assay was employed. In order to further investigate quaternary ammonium carboxymethylchitosan application as pharmaceutical excipient, aspirin was chosen as model drug. The effect of quaternary ammonium CMCTS on aspirin release rate from sustained-release matrix tablets was examined by in-vitro dissolution experiments. The results showed that this biopolymer had a great potential in increasing the dissolution of poorly soluble drug. With the addition of CMCTS-CEDA, the final cumulative release rate of drug rose up to 90%. After 12 h, at the grade of 10, 20 and 50 cps, the drug release rate increased from 58.1 to 90.7%, from 64.1 to 93.9%, from 69.3 to 96.1%, respectively. At the same time, aspirin release rate from sustainedrelease model was found to be related to the amount of quaternary ammonium CMCTS employed. With the increase of CMCTS-CEDA content, the accumulated release rate increased from 69.1% to 86.7%. The mechanism of aspirin release from sustained-release matrix tablets was also preliminary studied to be Fick diffusion. These data demonstrated that the chitosan derivative has positive effect on drug release from sustained-release matrix tablets.

This paper studied the effects of different ramets adjustment measures on the growth and seed generation of Quercus liaotungensis shrub in the upper reach of Minjiang River. The results showed that artificially adjusting ramets number largely affected the growth of plant height and sexual reproduction of Q. liaotungensis. The adjustment had little effect on the basal diameter of remained ramets, but obviously affected their height if 2 or 3 ramets per shrub were remained. The number, total length, and total biomass of new branches of adjusted shrub had more increase than those of unadjusted one, especially for the shrub of remaining 2 ramets. In adjusted shrub, the number and total biomass of leaves increased obviously, and the leaf area decreased gradually with increasing number of remained ramets. The shrub with three remained ramets generated most seed, while natural shrub had the biggest weight of single seed.