Injectable hydrogels based on biopolymers for the treatment of ocular diseases.

Injectable hydrogels based on biopolymers, fabricated utilizing diverse chemical and physical methodologies, exhibit exceptional physical, chemical, and biological properties. They have multifaceted applications encompassing wound healing, tissue regeneration, and across diverse scientific realms. This review critically evaluates their largely uncharted potential in ophthalmology, elucidating their diverse applications across an array of ocular diseases. These conditions include glaucoma, cataracts, corneal disorders (spanning from age-related degeneration to trauma, infections, and underlying chronic illnesses), retina-associated ailments (such as diabetic retinopathy, retinitis pigmentosa, and age-related macular degeneration (AMD)), eyelid abnormalities, and uveal melanoma (UM). This study provides a thorough analysis of applications of injectable hydrogels based on biopolymers across these ocular disorders. Injectable hydrogels based on biopolymers can be customized to have specific physical, chemical, and biological properties that make them suitable as drug delivery vehicles, tissue scaffolds, and sealants in the eye. For example, they can be engineered to have optimum viscosity to be injected intravitreally and sustain drug release to treat retinal diseases. Their porous structure and biocompatibility promote cellular infiltration to regenerate diseased corneal tissue. By accentuating their indispensable role in ocular disease treatment, this review strives to present innovative and targeted approaches in this domain, thereby advancing ocular therapeutics.

Seismic sedimentology response characteristics of nearshore terminal fan in the suning area of Raoyang Sag, Bohai Bay Basin, NE China.

A nearshore terminal fan is a special water system formed in arid environments. The characterisation of its thin-channel sand bodies has long been a challenge restricting oil and gas exploration. This study takes the Suning area of the Raoyang Sag as an example and uses the principles of seismic sedimentology to conduct seismic sedimentary research on the nearshore terminal fan of the first member of the Palaeogene Shahejie Formation (Es1) based on three-dimensional seismic, logging, and core analysis. Seven fourth-order sequences (SQV7) were identified within Es1, deposited by a fluvial river system terminating at the contracting bank of a lake. Prograding terminal fan sedimentary facies on a gentle slope zone were observed in the root mean square seismic attributes after spectral decomposition. We have successfully resolved the sandstone within the studied terminal fan system using a 90° phase conversion of the seismic data and red-green-blue (RGB) fusion of the various seismic attributes. The upper subsegment of the Shahejie Formation developed extensive nearshore terminal fan sedimentation, and the seismic sedimentological response characteristics were mainly channel-like and strip-shaped geomorphic systems deposited on gentle slope zones, indicating distributary channels and distal basin sedimentation. This study enriches our understanding of nearshore fans and provides ideas for predicting favourable sand bodies in this type of sedimentary facies.

Therapeutic potential of natural flavonoids in pulmonary arterial hypertension: A review.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease caused by pulmonary vascular remodeling, with a high incidence and mortality. At present, many clinical drugs for treating PAH mainly exert effects by relaxing the pulmonary artery, with limited therapeutic effects, so the search for viable therapeutic agents continues uninterrupted. In recent years, natural flavonoids have shown promising potential in the treatment of cardiovascular diseases. It is necessary to comprehensively elucidate the potential of natural flavonoids to combat PAH. PURPOSE: To evaluate the potential of natural flavonoids to hinder or slow down the occurrence and development of PAH, and to identify promising drug discovery candidates. METHODS: Literature was collected from PubMed, Science Direct, Web of science, CNKI databases and Google scholar. The search terms used included "pulmonary arterial hypertension", "pulmonary hypertension", "natural products", "natural flavonoids", "traditional chinese medicine", etc., and several combinations of these keywords. RESULTS: The resources, structural characteristics, mechanisms, potential and prospect strategies of natural flavonoids for treating PAH were summarized. Natural flavonoids offer different solutions as possible treatments for PAH. These mechanisms may involve various pathways and molecular targets related to the pathogenesis of PAH, such as inflammation, oxidative stress, vascular remodeling, genetic, ion channels, cell proliferation and autophagy. In addition, prospect strategies of natural flavonoids for anti-PAH including structural modification and nanomaterial delivery systems have been explored. This review suggests that the potential of natural flavonoids as alternative therapeutic agents in the prevention and treatment of PAH holds promise for future research and clinical applications. CONCLUSION: Despite displaying the enormous potential of flavonoids in PAH, some limitations need to be further explored. Firstly, using advanced drug discovery tools, including computer-aided design and high-throughput screening, to further investigate the safety, biological activity, and precise mechanism of action of flavonoids. Secondly, exploring the structural modifications of these compounds is expected to optimize their efficacy. Lastly, it is necessary to conduct well controlled clinical trials and a comprehensive evaluation of potential side effects to determine their effectiveness and safety.

Synergistic chemo-photothermal therapy using gold nanorods supported on thiol-functionalized mesoporous silica for lung cancer treatment.

Cancer therapy necessitates the development of novel and effective treatment modalities to combat the complexity of this disease. In this project, we propose a synergistic approach by combining chemo-photothermal treatment using gold nanorods (AuNRs) supported on thiol-functionalized mesoporous silica, offering a promising solution for enhanced lung cancer therapy. To begin, mesoporous MCM-41 was synthesized using a surfactant-templated sol-gel method, chosen for its desirable porous structure, excellent biocompatibility, and non-toxic properties. Further, thiol-functionalized MCM-41 was achieved through a simple grafting process, enabling the subsequent synthesis of AuNRs supported on thiol-functionalized MCM-41 (AuNR@S-MCM-41) via a gold-thiol interaction. The nanocomposite was then loaded with the anticancer drug doxorubicin (DOX), resulting in AuNR@S-MCM-41-DOX. Remarkably, the nanocomposite exhibited pH/NIR dual-responsive drug release behaviors, facilitating targeted drug delivery. In addition, it demonstrated exceptional biocompatibility and efficient internalization into A549 lung cancer cells. Notably, the combined photothermal-chemo therapy by AuNR@S-MCM-41-DOX exhibited superior efficacy in killing cancer cells compared to single chemo- or photothermal therapies. This study showcases the potential of the AuNR@S-MCM-41-DOX nanocomposite as a promising candidate for combined chemo-photothermal therapy in lung cancer treatment. The innovative integration of gold nanorods, thiol-functionalized mesoporous silica, and pH/NIR dual-responsive drug release provides a comprehensive and effective therapeutic approach for improved outcomes in lung cancer therapy. Future advancements based on this strategy hold promise for addressing the challenges posed by cancer and transforming patient care.

Tumor mutational burden as a predictive biomarker for non-small cell lung cancer treated with immune checkpoint inhibitors of PD-1/PD-L1.

BACKGROUND: The significant clinical benefits of PD-1/PD-L1 immune checkpoint inhibitors (ICIP) in non-small cell lung cancer (NSCLC) have been widely recognized, emphasizing the urgent need for a reliable biomarker. In this study, we find the remarkable capacity of tumor mutational burden (TMB) to serve as an accessible and streamlined indicator. PATIENTS AND METHODS: We designed a retrospective cohort study, consisting of 600 NSCLC patients treated with ICIP. Association between TMB and overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) has been explored. RESULTS: A strong positive correlation between TMB levels and OS, PFS rates, clinical benefit has been found when TMB > = 16(TMB > = 16 mutations/megabase (mut/Mb)). However, when TMB < 16, increasing TMB values did not exhibit a gradual stepwise increase in OS and PFS rates. The median months of OS in the TMB > = 16 and < 16 are 35.58, and 10.71 months respectively with average 12.39 months (p < 0.0001). The median months of PFS in the TMB > = 16 and < 16 are not-obtained, and 2.79 months respectively with an average of 3.32 months (p < 0.0001). The DCR in the TMB > = 16 and < 16 are 71.4% and 44.2% respectively with an average of 47.7% (p < 0.0001). The ORR in the TMB > = 16 and < 16 are 49.4% and 20.8% respectively with an average of 24.5% (p < 0.0001). CONCLUSION: The TMB > = 16 shows significantly associated with optimal ICIP treatment outcomes, including higher patient survival rates, delayed disease progression, and significant clinical benefits. These results present the potential of TMB as a promising biomarker candidate for NSCLC patients undergoing ICIP treatment.

Regulatory effects of natural products on N6-methyladenosine modification: A novel therapeutic strategy for cancer.

N6-methyladenosine (m6A) is considered to be the most common and abundant epigenetics modification in messenger RNA (mRNA) and noncoding RNA. Abnormal modification of m6A is closely related to the occurrence, development, progression, and prognosis of cancer. m6A regulators have been identified as novel targets for anticancer drugs. Natural products, a rich source of traditional anticancer drugs, have been utilized for the development of m6A-targeting drugs. Here, we review the key role of m6A modification in cancer progression and explore the prospects and structural modification mechanisms of natural products as potential drugs targeting m6A modification for cancer treatment.

Development of an impedimetric sensor for susceptible detection of melatonin at picomolar concentrations in diverse pharmaceutical and human specimens.

Our investigation aimed to create and manufacture an electrochemical impedance sensor with the purpose of improving the detection efficiency of melatonin (ME). To achieve this objective, we employed gold nanoparticles coated on polydopamine formed in glassy carbon electrodes (AuNPs/PDA/GCE) as a means to enhance the sensor's capabilities. A novel approach employing the signal-off strategy and electrochemical impedance spectroscopy (EIS) technique was utilized to determine ME. When the AuNPs/PDA/GCE electrode was immersed in a buffered solution containing ME, and the oxidation current of AuNPs was recorded, it was observed that the oxidation current of AuNPs decreased upon the introduction of ME molecules. The decrease in electrical current can be ascribed to the inhibitory impact of ME molecule adsorption on the electrode surface with applying -0.2 V for 150 s in acetate buffer solution (ABS) (pH, 5) through various mechanisms, which hinders the electron transfer process crucial for AuNPs oxidation. Consequently, by utilizing EIS, various concentrations of ME were quantified spanning from 1 to 18 pM. Moreover, the ME sensor achieved an impressive detection limit of 0.32 pM, indicating its remarkable sensitivity in detecting low concentrations of ME. Importantly, these novel sensors demonstrated exceptional attributes in terms of sensitivity, specificity, stability, and repeatability. The outstanding performance of these sensors, coupled with their desirable attributes, establishes their considerable potential for a wide range of practical applications. These applications encompass various fields such as clinical diagnostics, pharmaceutical analysis, environmental monitoring, and industrial quality control, where accurate and sensitive detection of ME is of utmost importance.

Recapitulating Antioxidant and Antibacterial Compounds into a Package for Tissue Regeneration: Dual Function Materials with Synergistic Effect.

Oxidative damage and infection can prevent or delay tissue repair. Moreover, infection reinforces reactive oxygen species (ROS) formation, which makes the wound's condition even worse. Therefore, the need for antioxidant and antibacterial agents is felt for tissue regeneration. There are emerging up-and-coming biomaterials that recapitulate both properties into a package, offering an effective solution to turn the wound back into a healing state. In this article, the principles of antioxidant and antibacterial activity are summarized. The review starts with biological aspects, getting the readers to familiarize themselves with tissue barriers against infection. This is followed by the chemistry and mechanism of action of antioxidant and antibacterial materials (dual function). Eventually, the outlook and challenges are underlined to provide where the dual-function biomaterials are and where they are going in the future. It is expected that the present article inspires the designing of dual-function biomaterials to more advanced levels by providing the fundamentals and comparative points of view and paving the clinical way for these materials.

Effects of Rotations With Legume on Soil Functional Microbial Communities Involved in Phosphorus Transformation.

Including legumes in the cereal cropping could improve the crop yield and the uptake of nitrogen (N) and phosphorus (P) of subsequent cereals. The effects of legume-cereal crop rotations on the soil microbial community have been studied in recent years, the impact on soil functional genes especially involved in P cycling is raising great concerns. The metagenomic approach was used to investigate the impacts of crop rotation managements of soybean-wheat (SW) and maize-wheat (MW) lasting 2 and 7years on soil microbial communities and genes involved in P transformation in a field experiment. Results indicated that SW rotation increased the relative abundances of Firmicutes and Bacteroidetes, reduced Actinobacteria, Verrucomicrobia, and Chloroflexi compared to MW rotation. gcd, phoR, phoD, and ppx predominated in genes involved in P transformation in both rotations. Genes of gcd, ppa, and ugpABCE showed higher abundances in SW rotation than in MW rotation, whereas gadAC and pstS showed less abundances. Proteobacteria, Acidobacteria, and Gemmatimonadetes played predominant roles in microbial P cycling. Our study provides a novel insight into crop P, which requires strategy and help to understand the mechanism of improving crop nutrient uptake and productivity in different rotations.

Sudden deafness as an initial presentation of varicella: case report and literature review.

Varicella, or chickenpox, is a highly contagious disease transmitted by the varicella zoster virus (VZV). Idiopathic sudden sensorineural hearing loss (ISSNHL) has been defined as a loss of at least 30 dB over at least three frequencies on audiogram within three days and with an uncertain cause. Deafness caused by varicella-zoster virus occasionally occurred in Ramsey hunter syndrome but associated with chickenpox is rare. We present a case of an adult varicella infection with sudden deafness as the first symptom. The patient begins with a sudden hearing loss in his left ear and developed fever 12 days later and skin rash 13 days later. He was diagnosed as chickenpox and received treatment of oral famciclovir capsule 250 mg administrated three times daily. After 2 weeks, at an outpatient follow-up the patient reported that while his scabs had fallen off and he felt well, the sudden deafness in the left ear had not improved. This kind of cases are rare and suggest the relationship between VZV and sudden deafness. Sudden deafness can be the first symptom of chickenpox. In this study, we also reviewed pathogenesis, clinical feature and the epidemiological character of chickenpox, the neurological complications of varicella zoster and the etiology of sudden deafness.

Correlation between serum lipid and prognosis of idiopathic sudden sensorineural hearing loss: a prospective cohort study.

BACKGROUND: To investigate the correlation between blood lipids and the prognosis of idiopathic sudden sensorineural hearing loss (ISSNHL). METHODS: We included 232 patients with ISSNHL at the Second Affiliated Hospital of Shanghai University from June 2015 to March 2017 using a prospective cohort study design. We collected information including age, gender, hypertension, diabetes, mellitus, vertigo, as well as the levels of blood total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL-C). We also recorded the ratio between the levels of low-density lipoproteins and the levels of high-density lipoproteins (LDL-C/HDL-C ratio). Correlations between the prognosis of ISSNHL and TC, TG, LDL-C, and LDL-C/HDL-C ratio were analyzed by univariable and multivariable logistic regression analyses. RESULTS: The clinical effectiveness rate of patients with TC ranging from 5.2 to 6.2 mmol/L was significantly higher than that of patients with TC <5.2 mmol/L (P<0.001). No notable difference was found between patients with TC <5.2 mmol/L and patients with TC ≥6.2 mmol/L. The clinical effectiveness rate of patients in TG ranging from 1.7 mmol/L to 2.3 mmol/L was markedly higher than those in TG <1.7 mmol/L (P<0.001). No significant difference was found between patients with TG ranging from 2.3 to 5.6 mmol/L, TG ≥5.6 mmol/L, and TG <1.7 mmol/L. The clinical effectiveness rate of patients in LDL-C/HDL-C <1.5 was considerably higher than those in LDL-C/HDL-C ranging from 1.5 to 2.5, 2.5 to 3.5, and ≥3.5 (P<0.001). CONCLUSIONS: Our findings indicated that TC, TG, and the LDL-C/HDL-C ratio are strongly associated with the prognosis of ISSNHL. These three indices could be recommended as independent markers to predict outcomes.

4D-Printed Dynamic Materials in Biomedical Applications: Chemistry, Challenges, and Their Future Perspectives in the Clinical Sector.

Most of the biomedical materials printed using 3D bioprinting are static and are unable to alter/transform with dynamic changes in the internal environment of the body. The emergence of four-dimensional (4D) printing addresses this problem. By preprogramming dynamic polymer materials and their nanocomposites, 4D printing is able to produce the desired shapes or transform functions under specific conditions or stimuli to better adapt to the surrounding environment. In this review, the current and potential applications of 4D-printed materials are introduced in different aspects of the biomedical field, e.g., tissue engineering, drug delivery, and sensors. In addition, the existing limitations and possible solutions are discussed. Finally, the current limitations of 4D-printed materials along with their future perspective are presented to provide a basis for future research.

Transplantation of bFGF-expressing neural stem cells promotes cell migration and functional recovery in rat brain after transient ischemic stroke.

Cerebrovascular disease such as stroke is one of the most common diseases in the aging population, and neural stem cells (NSCs) transplantation may provide an alternative therapy for cerebral ischemia. However, a hostile microenvironment in the ischemic brain offers is challenging for the survival of the transplanted cells. Considering the neuroprotective role of basic fibroblast growth factor (bFGF), the present study investigated whether bFGF gene-modified NSCs could improve the neurological function deficit after transient middle cerebral artery occlusion (MCAO) in adult male Sprague-Dawley rats. These rats were intravenously injected with modified NSCs (5×106/200 µL) or vehicle 24 h after MCAO. Histological analysis was performed on days 7 and 28 after tMCAO. The survival, migration, proliferation, and differentiation of the transplanted modified C17.2 cells in the brain were improved. In addition, the intravenous infusion of NSCs and bFGF gene-modified C17.2 cells improved the functional recovery as compared to the control. Furthermore, bFGF promoted the C17.2 cell growth, survival, and differentiation into mature neurons within the infarct region. These data suggested that bFGF gene-modified NSCs have the potential to be a therapeutic agent in brain ischemia.

Comparison of the more than 5-year clinical outcomes of cervical disc arthroplasty versus anterior cervical discectomy and fusion: A protocol for a systematic review and meta-analysis of prospective randomized controlled trials.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) was almost the "golden standard" technique in treatment of symptomatic cervical degenerative disc disease, however, it cause motion loss of the indexed level, increase the intradiscal pressure and motion of the adjacent levels, and may accelerate the degeneration of adjacent level. Cervical disc arthroplasty (CDA) was designed to preserve the motion of index level, avoid the over-activity of adjacent levels and reduce the degeneration of adjacent disc levels, the process of degeneration of adjacent level is very slowly, long term follow up studies should be conducted, this study aim to compare the more than 5 years' long-term clinical outcomes and safety between CDA and ACDF. METHODS: A systematic review and meta-analysis that will be performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The electric database of Medline, Embase, and Cochrane library will be systematic search. A standard data form will be used to extract the data of included studies. We will assess the studies according to the Cochrane Handbook for Systematic Reviews of Interventions, and perform analysis in software STATA 12.0. Fixed-effects models will be used for homogeneity data, while random-effects will be used for heterogeneity data. The overall effect sizes will be determined as weighted mean difference (WMD) for continuous outcomes and Relative risk (RR) for dichotomous outcomes. RESULTS: The results of study will be disseminated via both international conference and peer-review journal. CONCLUSION: The conclusion of our study will provide the long-term and updated evidence of clinical outcomes and safety between CDA and ACDF, and help surgeon to change better surgical technique for patients.

[Study on the chemical constituents of Viscum ovalifolium].

OBJECTIVE: To study the chemical constituents of Viscum ovalifolium. METHODS: The chemical constituents from Viscum ovalifolium were isolated and purified by silica gel column chromatography, polyamide column chromatography and recrystallization methods. Their structures were elucidated by physicochemical properties and spectral analysis. RESULTS: Twelve compounds were isolated and their structures were identified as 1-octadecene (1), ethyl palmitate (2), 28-hydrxy-amyrone (3), betulinic acid (4), rutin (5), quercetin (6), beta-amyrinpalmitate (7), lupeol acetate (8), beta-amyrin (9), beta-sitosterol (10), lupeol (11) and oleanolic acid (12). CONCLUSION: Compounds 1 - 6 are obtained from this plant for the first time.

[Morphological identification of 20 medicinal species in Hypericum].

OBJECTIVE: To provide anatomical evidences for the morphological and histological identification of 20 medicinal species in Hypericum. METHOD: Morphological and anatomical study on the organs of 20 medicinal species in Hypericum using tissue clearing, paraffin sectioning and thin sectioning. RESULT: According to their anatomical characteristics, the secretory structures can be divided into nodules, secretory cavities (canals) and tiny secretory tubes of 20 medicinal species in Hypericum. Hypericin was produced and stored in the nodules, while the volatile oil was produced and stored in the secretory cavities (canals) and tiny secretory tubes. The types differed markedly from each other in location, diameter and distributional density of leaf, and the anatomical structures differed from each other of stem, calyx, petal, anther and fruit among the 20 species in Hypericum. CONCLUSION: The secretory structures may be as anatomical evidences for the morphological and histological identification of 20 medicinal species in Hypericum.