Visible-light photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamides with S-(difluoromethyl)sulfonium salt.

A facile and highly efficient visible-light photoredox-catalyzed protocol for aryldifluoromethylation of acrylamides was developed using S-(difluoromethyl)sulfonium salt as the difluoromethyl source. With this method, pharmaceutically interesting CF2H-containing oxindoles were readily accessed from N-arylacrylamides, and this method featured mild reaction conditions, a broad scope of substrates, good tolerance of functional groups, and good to excellent yields. Control experiments revealed that this protocol proceeded through a difluoromethylation/cyclization cascade process.

Lithium carbonate alleviates colon inflammation through modulating gut microbiota and Treg cells in a GPR43-dependent manner.

BACKGROUND: Recent evidence suggests that neuropsychiatric stabilizers have a place in resolving gastrointestinal disorders. Lithium carbonate (LC) is one of the most commonly used drugs for bipolar disorder clinically. Here, we estimate the therapeutic function of LC against colitis and investigate the mechanism of intestinal flora and metabolism modulation. METHODS: A colitis model was constructed by continuously administering 2.5% dextran sodium sulfate (DSS) solution daily for 7 days. Analysis of gut microbiota was carried out by 16S rRNA gene high-throughput sequencing. Spectrum antibiotic cocktail (ABX) and faecal microbiota transplantation (FMT) were employed to evaluate the protective effect of intestinal flora. Colonic Treg cells and related immune responses were detected by flow cytometry. RESULTS: LC treatment significantly alleviated colon inflammation by regulating gut microbial diversity and altering flora composition. Notably, LC treatment upregulated short-chain fatty acid (SCFA)-producing bacteria, especially Akkermansia muciniphila (A. muciniphila), and transformed metabolite SCFA profiles. LC activated anti-inflammatory Treg cell responses in colonic lamina propria (LP) in a G-protein coupled receptor 43 (GPR43)-dependent mechanism. ABX, FMT and single bacteria gavage experiments were conducted to confirm the above mechanism. CONCLUSIONS: As an intestinal microbiome and metabolite modulator, LC alleviates colon inflammation in a GPR43-dependent manner through activating Treg cell responses. Therefore, the therapeutic strategy of the microbiome-metabolite-immune axis, as observed in the A. muciniphila-SCFA-Treg cell axis in our study, might provide a new direction for the treatment of IBD.

Determination of Trimethylamine N-oxide and Betaine in Serum and Food by Targeted Metabonomics.

Trimethylamine N-oxide (TMAO), as a gut-derived metabolite, has been found to be associated with enhanced risk for atherosclerosis and cardiovascular disease. We presented a method for targeted profiling of TMAO and betaine in serum and food samples based on a combination of one-step sample pretreatment and proton nuclear magnetic resonance spectroscopy. The key step included a processing of sample preparation using a selective solid-phase extraction column for retention of basic metabolites. Proton signals at δ 3.29 and δ 3.28 were employed to quantify TMAO and betaine, respectively. The developed method was examined with acceptable linear relationship, precision, stability, repeatability, and accuracy. It was successfully applied to detect serum levels of TMAO and betaine in TMAO-fed mice and high-fructose-fed rats and also used to determine the contents of TMAO and betaine in several kinds of food, such as fish, pork, milk, and egg yolk.

[Preparation of hydrophilic Indigo Naturalis based on polyethylene glycol( PEG) surface film-forming method and evaluation].

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1ßand TNF-αin serum and IL-1ßand PGE_2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1ßlevel of the hydrophilic Indigo Naturalis group decreased (P<0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.

Multi-channel spin exchange relaxation free magnetometer towards two-dimensional vector magnetoencephalography.

Optically pumped atomic magnetometers based on spin exchange relaxation free regime have recently become a powerful tool in the field of magnetoencephalography measurements. For this application of magnetometers, simultaneous multilocation magnetic field measurements are desired. To fulfill the requirement, we develop a multi-channel sensor module based on a single large vapor cell. The probe beam passes through the vapor cell twice by reflection and then records the two-dimensional spatial magnetic field distribution with two 2 × 2 photodiode matrixes. Comparing with the previous multi-channel tangential magnetic field measuring sensors, our magnetometer is sensitive to the normal magnetic field by operating in the longitudinal parametric modulation mode. Measuring the normal component is considered more suitable for magnetoencephalography, because the normal component provides more information. The sensitivities of the channels are approximately 10 fT/Hz1/2 in the normal direction. The auditory evoked magnetic fields of the four adjacent locations perpendicular to the scalp are detected simultaneously. Our magnetometer can measure the normal and tangential magnetic fields simultaneously. The dual-axis vector measurement of magnetic field is very important for magnetoencephalography.

Combination Therapy with Indigo and Indirubin for Ulcerative Colitis via Reinforcing Intestinal Barrier Function.

Indigo and indirubin, the active molecules of traditional Chinese medicine indigo naturalis, exert therapeutic activity for ulcerative colitis (UC). Indigo and indirubin are isomers and have distinctive profiles in anti-inflammation, immune regulation, intestinal microbiota regulation, oxidative stress regulation, and intestinal mucosal repair for UC treatment. Thus, exploring its combined administration's integrated advantages for UC is critical. This study is aimed at clarifying the effect and mechanisms of the combined administration of indigo and indirubin on colitis mouse models. The results showed that all the treatment groups could improve the disease symptoms, and the combined administration showed the best effect. Additionally, compared with indigo and indirubin alone, the combination group could significantly reinforce intestinal barrier function by increasing the expression of E-cadherin, occludin, ZO-1, and MUC2 and improving intestinal permeability. The treatment groups significantly improved the expression of cytokines, including TNF-α, IFN-γ, IL-12, IL-23, and IL-17A, and indirubin presented the most potent anti-inflammatory effect. Furthermore, all the treatment groups reduced the infiltration of the immune cells in intestinal lamina propria and the production of ROS/RNS. Notably, indigo exhibited a more substantial capacity to regulate natural killer (NK) cells, ILC3, neutrophils, and dendritic cells, followed by the combination group and indirubin alone. Finally, all the treatment groups modulated intestinal microbiota composition, increased the proportion of beneficial microbiota, and decreased the proportion of microbiota. Our results indicated that indigo and indirubin synergistically reinforced the intestinal barrier function, which may be associated with integrating the indirubin anti-inflammatory and intestinal microbiota regulating strength and indigo immune and ROS/RNS regulation advantage.

Lamiophlomis rotata attenuates rheumatoid arthritis by regulating sphingolipid and steroid hormone metabolism.

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease. Lamiophlomis rotata (L. rotata) (Benth.) Kudo, an essential medicinal plant in traditional Tibetan medicine, is useful in treating RA. The purpose of this study was to evaluate L. rotata's anti-RA effect and to analyze its serum metabolites and lipids to predict the possible action pathways. Female and male rats were immunized with CFA to induce arthritis. Paw volumes were measured, and arthritis index analysis and histological analysis were performed to check the effects of L. rotata. ELISA was used to measure the levels of inflammatory cytokines (IL-1ß, TNF-α, IL-6, and IL-10) and oxidative stress (MDA, SOD, GSH, and CAT). UPLC/Q-Orbitrap-MS was used to identify untargeted metabolites and lipids in serum. Metabolite validation was performed using UPLC/QQQ-MS. L. rotata application significantly reduced arthritis indices and paw swelling in AIA rats, and diminished inflammation and bone fractures in joint tissues. Sphingolipid (SP) and steroid hormone biosynthesis was found to be closely related to L. rotata's intervention in RA. In addition, our experiments also confirmed that females were more likely than males to develop RA. These findings provide clues and a scientific basis for the mechanism of L. rotata in treating RA.

Separation of nutrients and acetate from sewage sludge fermentation liquid in flow-electrode capacitive deionization system: Competitive mechanisms of ions and influence of activated carbon.

Effective separation of volatile fatty acids (VFAs), ammonia (NH4+-N) and reactive phosphorous (RP) generated from anaerobic fermentation liquid is critically important for efficient resource recovery. Flow-electrode capacitive deionization (FCDI) is proven to be capable of efficient removal of ions, environmentally friendly and cost-effective in operation. The performances of FCDI system in the separation of NH4+-N, RP, and acetate and mechanism of pHs and activated carbon on their performances were investigated. Results showed that a pH of 5.0 promoted the removal of NH4+-N (53.1 %) and RP (39.5 %), and 72.0 % of acetate was retained in the solution, which revealed that removal of NH4+-N and RP, and retention of acetate were evidently affected by speciation of ions. Furthermore, the recovery of NH4+-N and RP was undermined by the adsorption of ions on activated carbon. This study provides a novel insight of ion selective mechanism during the operation of the FCDI system.

CircRNA circ_0023984 promotes the progression of esophageal squamous cell carcinoma via regulating miR-134-5p/cystatin-s axis.

Recent studies have shown that circRNAs can act as oncogenic factors or tumor suppressors by sponging microRNAs (miRNAs). The upregulation of circ_0023984 was reported in esophageal squamous cell carcinoma (ESCC). However, its functional role in ESCC remain unclear. In the present study, circ_0023984 expression in ESCC cells and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). Subcellular fraction experiment was performed to determine relative nuclear-cytoplasmic localization. The loss-of-function effects of circ_0023984 in ESCC cell lines were investigated by shRNA-mediated knockdown. Functional assays including cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EDU) incorporation, colony formation and Transwell migration assays were conducted to assess the malignant phenotype. The interaction between the two molecules was analyzed by RNA pull-down, luciferase reporter assay and RNA immunoprecipitation (RIP). The subcutaneous tumor model in nude mice was used to assess the role of circ-0023984 in tumorigenesis. We found that ESCC patients with high circ_0023984 expression was associated with a poor prognosis. The knockdown of circ_0023984 suppressed cell growth, invasion, and migration in ESCC cells. Circ_0023984 interacted with miR-134-5p and inhibited its activity, which promoted the expression of CST4 (Cystatin-S). Circ_0023984 also regulated tumorigenesis in a CST4-dependent manner. Together, our study indicates that the oncogenic role of Circ_0023984 is mediated by miR-134-5p/CST4 Axis in ESCC, which could serve as potential targets for future therapeutic strategies.

Immunotherapy for Sepsis Induced by Infections: Clinical Evidence and Potential Targets.

Sepsis is a life-threatening organ dysfunction caused by the maladjustment of the body's response to infection. Abnormal immune response plays an important role in the progression of sepsis, and immunomodulatory therapy is a promising therapeutic strategy for sepsis. Great efforts have been made recently to elucidate the mechanism by which immune dysfunction contributes to sepsis, and identify potential biomarkers and targets for the diagnosis and therapy of sepsis induced by emerging pathogens, especially for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19. In this review, we summarize recent progress on the understanding of immune dysregulation involved in sepsis, and highlight potential biomarkers and targets to evaluate immune status of the patients with sepsis for individualized and precise immunotherapy.

Rab31 promotes activation of hepatic stellate cells by accelerating TGF-ß receptor II complex endocytosis.

BACKGROUND & AIMS: Hepatic stellate cells activation is the key process of liver fibrosis, revealing the molecular mechanism of which is helpful to provide an effective target for inhibiting liver fibrosis. Rab31, a small GTPase, regulates the specificity of intracellular vesicular transport system, and is crucial for signal transduction. However, whether Rab31 is involved in hepatic stellate cells activation is unknown. METHODS & RESULTS: Analysis of the differences in gene expression between human healthy and fibrotic liver tissues by sequencing revealed that Rab31 was significantly upregulated in fibrotic tissues. Immunohistochemistry and immunofluorescence analysis confirmed that Rab31 positively correlated with hepatic fibrosis. Next, mouse primary hepatic stellate cells were prepared, and their continuous activation was accompanied by Rab31 expression increased. Interestingly, knockdown of Rab31 by lentivirus can significantly restrict those cell activation. Subsequently, the vary of signal transduction after Rab31 knockdown was detected, its presented that the TGF-ß/Smads signaling was obviously affected. Following experiments identified that Rab31 knockdown significantly inhibited the TGF-ß activation and led to the failure of hepatic stellate cells activation. Importantly, we revealed that Rab31 knockdown could inhibit TGF-ß receptor II complex endocytosis, a prerequisite for the activation of TGF-ß signaling. Finally, in a mouse CCl4 fibrosis model, we proved that Rab31 knockdown markedly inhibited hepatic fibrosis. CONCLUSIONS: Our study demonstrated that Rab31 could promote hepatic stellate cells activation by accelerating TGF-ß Receptor II complex endocytosis, suggesting that interfering with Rab31 could be an effectively strategy to inhibit hepatic fibrosis progression.

Recent advances in wearable medical diagnostic sensors and new therapeutic dosage forms for fever in children.

Fever in children is one of the most common symptoms of pediatric diseases and the most common complaint in pediatric clinics, especially in the emergency department. Diseases such as pneumonia, sepsis, and meningitis are leading causes of death in children, and the early manifestations of these diseases are accompanied by fever symptoms. Accurate diagnosis and real-time monitoring of the status of febrile children, rapid and effective identification of the cause, and treatment can have a positive impact on relieving their symptoms and improving their quality of life. In recent years, wearable diagnostic sensors have attracted special attention for their high flexibility, real-time monitoring, and sensitivity. Temperature sensors and heart rate sensors have provided new advances in detecting children's body temperature and heart rate. Furthermore, some novel formulations have also received wide attention for addressing bottlenecks in medication administration for febrile children, such as difficulty in swallowing and inaccurate dosing. In this context, the present review provides recent advances of novel wearable medical sensor devices for diagnosing fever. Moreover, the application progress of innovative dosage forms of classical antipyretic drugs for children is presented. Finally, challenges and prospects of wearable sensor-based diagnostics and novel agent-based treatment of fever in children are discussed in brief.

Insight into the incredible effects of microwave heating: Driving changes in the structure, properties and functions of macromolecular nutrients in novel food.

Microwave heating technology performs the characteristics of fast heating, high efficiency, green energy saving and easy control, which makes it deeply penetrate into the food industry and home cooking. It has the potential to alter the appearance and flavor of food, enhance nutrient absorption, and speed up the transformation of active components, which provides an opportunity for the development of innovation foods. However, the change of food driven by microwave heating are very complex, which often occurs beyond people's cognition and blocks the development of new food. It is thus necessary to explore the transformation mechanism and influence factors from the perspectives of microwave technology and food nutrient diversity. This manuscript focuses on the nutritional macromolecules in food, such as starch, lipid and protein, and systematically analyzes the change rule of structure, properties and function under microwave heating. Then, the flavor, health benefits, potential safety risks and bidirectional allergenicity associated with microwave heating are fully discussed. In addition, the development of new functional foods for health needs and future market based on microwave technology is also prospected. It aims to break the scientific fog of microwave technology and provide theoretical support for food science to understand the change law, control the change process and use the change results.

TLR4 regulates RORγt+ regulatory T-cell responses and susceptibility to colon inflammation through interaction with Akkermansia muciniphila.

BACKGROUND: Well-balanced interactions between gut microbiota and the immune system are essential to prevent chronic intestinal inflammation, as observed in inflammatory bowel diseases (IBD). Toll-like receptor 4 (TLR4) functions as a sensor mediating the crosstalk between the intestinal commensal microbiome and host immunity, but the influence of TLR4 on the shaping of intestinal microbiota and immune responses during colon inflammation remains poorly characterized. We investigated whether the different susceptibilities to colitis between wild-type (WT) and TLR4-/- mice were gut microbiota-dependent and aimed to identify the potential immunity modulation mechanism. METHODS: We performed antibiotic depletion of the microbiota, cohousing experiments, and faecal microbiota transplantation (FMT) in WT and TLR4-/- mice to assess the influence of TLR4 on intestinal microbial ecology. 16S rRNA sequencing was performed to dissect microbial discrepancies, and dysbiosis-associated immune perturbation was investigated by flow cytometry. Akkermansia muciniphila (A. muciniphila)-mediated immune modulation was confirmed through the T-cell transfer colitis model and bone marrow chimaera construction. RESULTS: TLR4-/- mice experienced enhanced susceptibility to DSS-induced colitis. 16S rRNA sequencing showed notable discrepancy in the gut microbiota between WT and TLR4-/- mice. In particular, A. muciniphila contributed most to distinguishing the two groups. The T-cell transfer colitis model and bone marrow transplantation (BMT) consistently demonstrated that A. muciniphila ameliorated colitis by upregulating RORγt+ Treg cell-mediated immune responses. Mucosal biopsies from human manifested parallel outcomes with colon tissue from WT mice, as evidenced by the positive correlation between TLR4 expression and intestinal A. muciniphila colonization during homeostasis. CONCLUSIONS: Our results demonstrate a novel protective role of TLR4 against intestinal inflammation, wherein it can modulate A. muciniphila-associated immune responses. These findings provide a new perspective on host-commensal symbiosis, which may be beneficial for developing potential therapeutic strategies. Video abstract.

TREML4: a Potential Target for Immunotherapy of Sepsis.

Sepsis is a serious syndrome with a series of abnormalities caused by dysfunctional host response to infection. Toll-like receptor 4 (TLR-4) has been considered as a key regulator of inflammatory response and immune cell apoptosis in lipopolysaccharides (LPS) challenged models. However, in clinical trials, monoclonal antibodies of TLR-4 have not shown therapeutic effects as expected. Moreover, clinical trials based on immunotherapy by regulating inflammatory cytokines during the acute phase of sepsis have also failed. Recent evidence indicates that the fast-acting innate immune system plays a bigger role in blocking the fast progression of sepsis upon infection than the adaptive immune system. Consequently, the strategies for clinical management of sepsis should be shifted from targeting adaptive immune system to targeting innate immune system. In this review, we summarize our understanding of the role of TREML4 in sepsis, and highlight potential value of TREML4 in clinical management of sepsis. Further mechanistic studies on TREML4 such as the identification of its ligand will provide more clues on the development of novel and effective approaches to the prevention and therapy of sepsis.

Hsa_circ_0008537 facilitates liver carcinogenesis by upregulating MCL1 and Snail1 expression via miR­153­3p.

The biological functions of circular RNAs in liver tumorigenesis have been well demonstrated by a number of studies. Nevertheless, to the best of our knowledge, the role and mechanism of action of hsa_circ_0008537 (circ_0008537) in liver cancer pathogenesis remain undetermined. In the present study, circ_0008537 expression was associated with the GLI3 gene and was markedly increased in liver cancer tissue specimens and cells. High expression levels of circ_0008537 exhibited a poor prognosis. In addition, circ_0008537 overexpression resulted in an increased proliferation, migration and invasion of liver cancer cells, whereas circ_0008537 knockdown exhibited opposite effects. circ_0008537 acted as a sponge of microRNA­153­3p (miR­153­3p), and a negative correlation was observed between circ_0008537 and miR­153­3p expression in liver cancer. Transfection with miR­153­3p further abolished the effects of circ_0008537 on the malignant behavior of liver cancer cells. Furthermore, circ_0008537 indirectly affected the expression levels of pro­survival protein myeloid cell leukemia 1 (MCL1) and snail family zinc finger 1 (Snail1) via miR­153­3p in liver cancer cells. In conclusion, the data indicated that circ_0008537 facilitated liver carcinogenesis by indirectly regulating miR­153­3p and leading to the release of MCL1 and Snail1.

Danggui-Shaoyao-San Improves Gut Microbia Dysbiosis and Hepatic Lipid Homeostasis in Fructose-Fed Rats.

Metabolic syndrome (MetS) is a pathological state of many abnormal metabolic sections. These abnormalities are closely related to diabetes, heart pathologies and other vascular diseases. Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine formula that has been used as a therapy for Alzheimer's disease. DSS has rarely been reported in the application of MetS and its mechanism of how it improves gut microbia dysbiosis and hepatic lipid homeostasis. In this study, three extracts of DSS were obtained using water, 50% methanol in water and methanol as extracting solvents. Their chemical substances were analyzed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass (UPLC-Q/TOF-MS). Pharmacodynamic effect of the extracts were evaluated by comparison of biochemical factors, 16S rRNA sequencing test for gut microbiota analysis, as well as metabonomic and transcriptomic assessments on liver tissues from fructose-fed rats. This study aimed at investigating DSS's mechanism of regulating blood lipid, anti-inflammation and reducing blood glucose. The results showed that the 50% methanol extract (HME) was more effective. It was worth noting that hydroxysteroid 17ß-dehydrogenase 13 (HSD17ß13) as a critical element of increasing blood lipid biomarker-triglyceride (TG), was decreased markedly by DSS. The influence from upgraded hydroxysteroid 17ß-dehydrogenase 7 (HSD17ß7) may be stronger than that from downgraded Lactobacillus in the aspect of regulating back blood lipid biomarker-total cholesterol (TC). The differential down-regulation of tumornecrosis factor alpha (TNF-α) and the significant up-regulation of Akkermansia showed the effective effect of anti-inflammation by DSS. The declining glycine and alanine induced the lowering glucose and lactate. It demonstrated that DSS slowed down the reaction of gluconeogenesis to reduce the blood glucose. The results demonstrated that DSS improved pathological symptoms of MetS and some special biochemical factors in three aspects by better regulating intestinal floras and improving hepatic gene expressions and metabolites.

Pharmacological and clinical application of heparin progress: An essential drug for modern medicine.

Heparin is the earliest and most widely used anticoagulant and antithrombotic drug that is still used in a variety of clinical indications. Since it was discovered in 1916, after more than a century of repeated exploration, heparin has not been replaced by other drugs, but a great progress has been made in its basic research and clinical application. Besides anticoagulant and antithrombotic effects, heparin also has antitumor, anti-inflammatory, antiviral, and other pharmacological activities. It is widely used clinically in cardiovascular and cerebrovascular diseases, lung diseases, kidney diseases, cancer, etc., as the first anticoagulant medicine in COVID-19 exerts anticoagulant, anti-inflammatory and antiviral effects. At the same time, however, it also leads to a lot of adverse reactions, such as bleeding, thrombocytopenia, elevated transaminase, allergic reactions, and others. This article comprehensively reviews the modern research progress of heparin compounds; discusses the structure, preparation, and adverse reactions of heparin; emphasizes the pharmacological activity and clinical application of heparin; reveals the possible mechanism of the therapeutic effect of heparin in related clinical applications; provides evidence support for the clinical application of heparin; and hints on the significance of exploring the wider application fields of heparin.

Laboratory Biomarkers for the Diagnosis and Management of Patients with COVID-19: an Updated Review.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global crisis due to strong infectivity and fast transmission speed. Some patients with Coronavirus Disease 2019 (COVID-19) progress rapidly and may develop fatal complications, which brings serious challenges in disease assessment and treatment. Recent progress in the understanding of the molecular biology of SARS-CoV-2 has led to the identification of a variety of laboratory biomarkers that could be potentially applied to clinical practice for the diagnosis, treatment, and prognosis of patients with COVID-19. In this review we summarize the updated status on the identification of COVID-19 related laboratory markers, and propose further direction on the application of these markers to clinical diagnosis and management of patients with COVID-19.

Advances in the Application of Natural Products and the Novel Drug Delivery Systems for Psoriasis.

Psoriasis, an incurable autoimmune skin disease, is one of the most common immune-mediated disorders. Presently, numerous clinical research studies are underway, and treatment options are available. However, these treatments focus on improving symptoms of the disease and fail to achieve a radical cure; they also have certain toxic side effects. In recent years, natural products have increasingly gained attention because of their high efficiency and low toxicity. Despite their obvious therapeutic effects, natural products' biological activity was limited by their instability, poor solubility, and low bioavailability. Novel drug delivery systems, including liposomes, lipospheres, nanostructured lipid carriers, niosomes, nanoemulsions, nanospheres, microneedles, ethosomes, nanocrystals, and foams could potentially overcome the limitations of poor water solubility and permeability in traditional drug delivery systems. Thus, to achieve a therapeutic effect, the drug can reach the epidermis and dermis in psoriatic lesions to interact with the immune cells and cytokines.