A clinical nomogram for predicting occult lymph node metastasis in patients with non-small cell lung cancer≤2 cm.

OBJECTIVES: Sublobar resection has been shown to be feasible for non-small cell lung cancers less than 2 cm in size based on several prospective studies. However, the prognosis of clinical N0 patients who experience an N-stage upgrade after surgery (known as occult lymph node metastasis) may be worse. The ability of predict occult lymph node metastasis in patients eligible for sublobar resection remains a controversial issue. METHODS: Patients with non-small cell lung cancer ≤2 cm in diameter and containing a solid component who underwent surgical treatment at the Affiliated Hospital of Qingdao University were retrospectively enrolled, and 1:1 case matching was performed. The risk factors were identified through logistic regression analyses and theoretical criteria, followed by the development of a nomogram that was evaluated using 200 iterations of 10-fold cross-validation. RESULTS: After case matching, 130 pairs of patients were selected for modelling. According to the multivariable logistic regression analysis, the carcinoembryonic antigen level, consolidation tumour ratio, mean computed tomography number and tumour margin were included in the nomogram. The cross-validated average area under the receiver operating characteristic curve was found to be 0.86. Furthermore, calibration curve and decision curve analyses demonstrated the excellent predictive accuracy and clinical utility of the nomogram respectively. CONCLUSIONS: By utilizing accessible characteristics, we developed a nomogram that predicts the probability of occult lymph node metastasis in patients with NSCLC ≤2 cm with a solid component. Risk stratification with this nomogram could aid in surgical method decision-making.

Antibacterial, Fatigue-Resistant, and Self-Healing Dressing from Natural-Based Composite Hydrogels for Infected Wound Healing.

The treatment of infected wounds faces substantial challenges due to the high incidence and serious infection-related complications. Natural-based hydrogel dressings with favorable antibacterial properties and strong applicability are urgently needed. Herein, we developed a composite hydrogel by constructing multiple networks and loading ciprofloxacin for infected wound healing. The hydrogel was synthesized via a Schiff base reaction between carboxymethyl chitosan and oxidized sodium alginate, followed by the polymerization of the acrylamide monomer. The resultant hydrogel dressing possessed a good self-healing ability, considerable compression strength, and reliable compression fatigue resistance. In vitro assessment showed that the composite hydrogel effectively eliminated bacteria and exhibited an excellent biocompatibility. In a model of Staphylococcus aureus-infected full-thickness wounds, wound healing was significantly accelerated without scars through the composite hydrogel by reducing wound inflammation. Overall, this study opens up a new way for developing multifunctional hydrogel wound dressings to treat wound infections.

Effects of Hericium erinaceus polysaccharide in porcine IPEC-J2 intestinal epithelial cells against apoptosis induced by oxidative stress.

This study was intended to investigate whether Hericium erinaceus polysaccharides (HEP) prevent oxidative stress and apoptosis of intestinal porcine epithelial cells from jejunum (IPEC-J2 cells) induced by hydrogen peroxide (H2O2). Crude HEP were extracted and purified by chromatography. The ultraviolet and infrared spectra and monosaccharide composition of HEP were analyzed. Reactive oxygen species (ROS) generation was quantified by flow cytometry method, and lactate dehydrogenase (LDH) and malondialdehyde (MDA) production were determined by TBARS. Also, apoptosis was analyzed by flow cytometry method and the apoptosis-related regulatory molecules were determined by microplate or western blotting method. Our results showed that pretreatment of IPEC-J2 cells with HEP significantly scavenged ROS and reduced LDH and MDA production. HEP also reduced apoptosis and kept polarity of the mitochondrial membrane potential. Moreover, HEP increased the content of caspase-3 and PARP, and protein expression of Bcl-2, while inhibited Bax and Bad and reduced the content of caspase-9 and release of CytC. Meanwhile, HEP inhibited the protein expression of TNFR1, FAS, and FASL, and decreased the content of caspase-8. The results indicated that HEP had a protective effect against oxidative stress in IPEC-J2 cells and the underlying mechanism was reducing apoptosis via mitochondrial and death receptor pathways.

Identification of novel biomarkers and immune infiltration characteristics of ischemic stroke based on comprehensive bioinformatic analysis and machine learning.

Background: Ischemic stroke (IS) is one of most common causes of disability in adults worldwide. However, there is still a lack of effective and reliable diagnostic markers and therapeutic targets in IS. Furthermore, immune cell dysfunction plays an important role in the pathogenesis of IS. Hence, in-depth research on immune-related targets in progressive IS is urgently needed. Methods: Expression profile data from patients with IS were downloaded from the Gene Expression Omnibus (GEO) database. Then, differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to identify the significant modules and differentially expressed genes (DEGs). Key genes were obtained and used in functional enrichment analyses by overlapping module genes and DEGs. Next, hub candidate genes were identified by utilizing three machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE). Subsequently, a diagnostic model was constructed based on the hub genes, and receiver operating characteristic (ROC) curves were constructed to validate the performances of the predictive models and candidate genes. Finally, the immune cell infiltration landscape of IS was explored with the CIBERSORT deconvolution algorithm. Results: A total of 40 key DEGs were identified based on the intersection of the DEGs and module genes, and we found that these genes were mainly enriched in the regulation of lipolysis in adipocytes, neutrophil extracellular trap formation and complement and coagulation cascades. Based on the results from three advanced machine learning algorithms, we obtained 7 hub candidate genes (ABCA1, ARG1, C5AR1, CKAP4, HMFN0839, SDCBP and TLN1) as diagnostic biomarkers of IS and developed a reliable nomogram with high predictive performance (AUC = 0.987). In addition, immune cell infiltration dysregulation was implicated in IS, and compared with those in the normal group, IS patients had increased fractions of gamma delta T cells, monocytes, M0 macrophages, M2 macrophages and neutrophils and clearly lower percentages of naive B cells, CD8 T cells, CD4+ memory T cells, follicular helper T cells, regulatory T cells (Tregs) and resting dendritic cells. Furthermore, correlation analysis indicated a significant correlation between the hub genes and immune cells in progressive IS. Conclusion: In conclusion, our study identified 7 hub genes as diagnostic biomarkers and established a reliable model to predict the occurrence of IS. Meanwhile, we explored the immune cell infiltration pattern and investigated the relationship between candidate genes and immune cells in the pathogenesis of IS. Hence, our study provides new insights into the diagnosis and treatment of IS.

Relationship Between Systemic Immune-Inflammation Index and Risk of Respiratory Failure and Death in COPD: A Retrospective Cohort Study Based on the MIMIC-IV Database.

Purpose: Chronic obstructive pulmonary disease (COPD) concurrent with respiratory failure (RF) is devastating, and may result in death and disability. Systemic immune-inflammation index (SII) is a new prognostic biomarker linked to unfavorable outcomes of acute coronary syndrome, ischemic stroke, and heart failure. Nonetheless, its role in COPD is rarely investigated. Consequently, this study intends to assess the accuracy of SII in predicting the prognosis of COPD. Patients and Methods: The clinical information was retrospectively acquired from the Medical Information Mart for Intensive Care-IV database. The outcomes encompassed the incidence of RF and mortality. The relationship between different SII and outcomes was examined utilizing the Cox proportional-hazards model and restricted cubic splines. Kaplan-Meier analysis was employed for all-cause mortality. Results: The present study incorporated 1653 patients. During hospitalization, 697 patients (42.2%) developed RF, and 169 patients (10.2%) died. And 637 patients (38.5%) died during long-term follow-up. Higher SII increased the risk of RF (RF: HR: 1.19, 95% CI 1.12-1.28, P<0.001), in-hospital mortality (HR: 1.22, 95% CI 1.07-1.39, P=0.003), and long-term follow-up mortality (HR: 1.12, 95% CI 1.05-1.19, P<0.001). Kaplan-Meier analysis suggested a significantly elevated risk of all-cause death (log-rank P<0.001) in patients with higher SII, especially during the short-term follow-up period of 21 days. Conclusion: SII is closely linked to an elevated risk of RF and death in COPD patients. It appears to be a potential predictor of the prognosis of COPD patients, which is helpful for the risk stratification of this population. However, more prospective studies are warranted to consolidate our conclusion.

Th22 is the effector cell of thymosin ß15-induced hair regeneration in mice.

BACKGROUND: Thymosin beta family has a significant role in promoting hair regeneration, but which type of T cells play a key role in this process has not been deeply studied. This research aimed to find out the subtypes of T cell that play key role in hair regeneration mediated by thymosin beta 15 (Tß15). METHODS: Ready-to-use adenovirus expressing mouse Tmsb15b (thymosin beta 15 overexpression, Tß15 OX) and lentivirus-Tß15 short hairpin RNA (Tß15 sh) were used to evaluate the role of Tß15 in hair regeneration and development. The effect of Th22 cells on hair regeneration was further studied by optimized Th22-skewing condition medium and IL-22 binding protein (IL-22BP, an endogenous antagonist of IL-22, also known as IL-22RA2) in both ex vivo culture C57BL/6J mouse skin and BALB/c nude mice transplanted with thymus organoid model. RESULTS: The results show that Tß15, the homologous of Tß4, can promote hair regeneration by increasing the proliferation activity of hair follicle cells. In addition, high-level expression of Tß15 can not only increase the number of Th22 cells around hair follicles but also accelerate the transformation of hair follicles to maturity. Consistent with the expected results, when the IL-22BP inhibitor was used to interfere with Th22, the process of hair regeneration was blocked. CONCLUSIONS: In conclusion, Th22 is the key effector cell of Tß15 inducing hair regeneration. Both Tß15 and Th22 may be the potential drug targets for hair regeneration.

Macrophage Activation in Synovitis and Osteoarthritis of Temporomandibular Joint and Its Relationship with the Progression of Synovitis and Bone Remodeling.

This study investigates the regulatory mechanisms of synovial macrophages and their polarization in the progression of temporomandibular joint osteoarthritis (TMJOA). Macrophage depletion models were established by intra-articular injection of clodronate liposomes and unloaded liposomes. TMJOA was induced by intra-articular injection of 50 µL Complete Freund's Adjuvant and the surgery of disc perforation. The contralateral joint was used as the control group. The expression of F4/80, CD86, and CD206 in the synovium was detected by immunofluorescence staining analysis. Hematoxylin and eosin staining and TMJOA synovial score were detected to show the synovial changes in rat joints after TMJOA induction and macrophage depletion. Changes in rat cartilage after TMJOA induction and macrophage depletion were shown by safranin fast green staining. The bone-related parameters of rats' joints were evaluated by micro-computed tomography analysis. The TMJOA model induced by Complete Freund's Adjuvant injection and disc perforation aggravated synovial hyperplasia and showed a significant up-regulation of expression of F4/80-, CD86-, and CD206-positive cells. F4/80, CD86, and CD206 staining levels were significantly decreased in macrophage depletion rats, whereas the synovitis score further increased and cartilage and subchondral bone destruction was slightly aggravated. Macrophages were crucially involved in the progression of TMJOA, and macrophage depletion in TMJOA synoviocytes promoted synovitis and cartilage destruction.

The role of WWP1 and WWP2 in bone/cartilage development and diseases.

Bone and cartilage diseases are often associated with trauma and senescence, manifested as pain and limited mobility. The repair of bone and cartilage lesion by mesenchymal stem cells is regulated by various transcription factors. WW domain-containing protein 1 (WWP1) and WW domain-containing protein 2 (WWP2) are named for WW domain which recognizes PPXY (phono Ser Pro and Pro Arg) motifs of substrate. WWP1and WWP2 are prominent components of the homologous to the E6-AP carboxyl terminus (HECT) subfamily, a group of the ubiquitin ligase. Recently, some studies have found that WWP1 and WWP2 play an important role in the pathogenesis of bone and cartilage diseases and regulate the level and the transactivation of various transcription factors through ubiquitination. Therefore, this review summarizes the distribution and effects of WWP1 and WWP2 in the development of bone and cartilage, discusses the potential mechanism and therapeutic drugs in bone and cartilage diseases such as osteoarthritis, fracture, and osteoporosis.

Effects of intravenous rtPA in patients with minor stroke.

BACKGROUND: Whether minor ischemic stroke (MIS) patients can benefit from intravenous thrombolysis (IVT) remains controversial. The association between the efficacy of IVT and baseline National Institute of Health Stroke Scale (NIHSS) score is unclear in MIS, while the association in moderate and severe stroke is known. This study aimed to explore the effect of IVT in patients with MIS and analyze its efficacy in patients with different baseline NIHSS scores. METHODS: Patients with a NIHSS score ≤5 within 4.5 h of stroke onset were screened in 32 centers. Patients with and without IVT were matched to a ratio of 1:1 with propensity scores. An excellent outcome was defined as a modified Rankin Scale (mRS) score ≤1 at three months after stroke onset. Safety outcomes included mortality and symptomatic intracranial hemorrhage (sICH). Multivariate analysis was used to compute the adjusted odds ratio (OR) for excellent outcomes. The effect of IVT was further analyzed in subgroups according to the baseline NIHSS score. RESULTS: Of the 23,853 screened, 3336 patients with MIS who arrived at the hospital within 4.5 h of onset were included. The 1163 patients treated with IVT were matched with 1163 patients without IVT. IVT in minor strokes generated an adjusted OR of 1.38 (95% CI: 1.09-1.75, p = 0.009) for excellent outcomes. There were no significant differences in mortality (0.17% vs. 0.09%, p = 1.000) and sICH (0.69% vs. 0.86%, p = 0.813) between patients with and without IVT. Subgroup analysis showed that there was no significant effect of IVT in the baseline NIHSS 0-1 or 2-3 subgroups, with adjusted OR of 0.816 (95% CI 0.437-1.53, p = 0.525) and1.22 (95% CI 0.845-1.77, p = 0.287), respectively. In patients with NIHSS score of 4-5, IVT was significantly effective, with an adjusted OR of 1.53 (95% CI 1.02-2.30, p = 0.038). CONCLUSION: IVT can improve MIS outcomes. The risks of sICH and mortality did not increase, especially in patients with NIHSS scores 4 to 5, who could benefit from IVT significantly.

Overall, intravenous thrombolysis can improve the outcomes of patients with minor stroke.Minor stroke patients with a baseline NIHSS score of 4-5 can benefit the most from intravenous thrombolysis.

Electrodeposition of paracetamol oxide for intelligent portable ratiometric detection of nicotine and ethyl vanillin ß-D-glucoside.

Herein, the electrodeposition of paracetamol oxide (PA ox) for the intelligent portable ratiometric detection of nicotine (NIC) and ethyl vanillin ß-D-glucoside (EVG) is reported. PA ox electrodeposited on a screen-printed carbon electrode (SPCE) was used as a new fixed state ratiometric reference probe. A portable electrochemical workstation combined with a smart phone was applied as an intelligent portable electrochemical sensing platform. The sensor was studied by scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FT-IR), ultraviolet-visible spectrophotometry (UV-vis), theoretical calculation, chronoamperometry, cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and square wave voltammetry (SWV). Under optimized conditions, the detection range of NIC is 10-200 µmol L-1, and the detection limit is 0.256 µmol L-1. The detection range of EVG was 10-180 µmol L-1, and the detection limit was 0.058 µmol L-1. The sensor can realize the real-time detection of NIC and EVG concentration in cigarette samples quickly and accurately, and has good anti-interference, repeatability and stability.

A colorimetric sensor with dual-ratio and dual-mode for detection of nicotine in tobacco samples.

Nicotine (NIC) is a harmful substance, drug, pesticide and chemical that is widely found in tobacco. It has carcinogenic, teratogenic and neurotoxic effects that have raised serious concerns. Herein, a colorimetric sensor with dual-ratio and dual-mode for the detection of NIC in tobacco samples was reported. The localized surface plasmon resonance signals of gold nanoparticles (AuNPs) and AuNPs-NIC are used as dual-ratio signals. The absorbance ratio of NIC to AuNPs or the absorbance ratio of NIC to AuNPs-NIC and the wavelength shift value of AuNPs-NIC are applied as dual-mode. Transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering spectroscopy, ultraviolet-visible spectrophotometry, cyclic voltammetry, and potentiostatic methods were used to characterize the sensor. Further analysis of NIC was conducted through morphological fitting and theoretical calculations. Under optimal conditions, the sensor shows a wide linear range of 5-500 µM. The detection limits for NIC are 2.48 µM, 1.63 µM and 1.34 µM, respectively. The experimental result shows that the dual-ratio signal of AuNPs and AuNPs-NIC has good selectivity and sensitivity, and can effectively reduce the interference of impurities on NIC detection. And the dual-mode of detection for NIC improves the accuracy and comparability of the result significantly. In addition, the proposed sensor was also applied to test NIC in tobacco samples with satisfactory recovery.

Age-related hearing loss and its potential drug candidates: a systematic review.

BACKGROUND: Age-related hearing loss (ARHL) is one of the main illnesses afflicting the aged population and has a significant negative impact on society, economy, and health. However, there is presently no appropriate therapeutic treatment of ARHL due to the absence of comprehensive trials. OBJECTIVES: The goal of this review is to systematically evaluate and analyze recent statistics on the pathologic classifications, risk factors, treatment strategies, and drug candidates of ARHL, including that from traditional Chinese medicine (TCM), to provide potential new approaches for preventing and treating ARHL. METHODS: Literature related to ARHL was conducted in databases such as PubMed, WOS, China National Knowledge Infrastructure (CNKI), and Wanfang from the establishment of the database to Jan, 2023. The pathology, causal factor, pathophysiological mechanism, treatment strategy, and the drug candidate of ARHL were extracted and pooled for synthesis. RESULTS: Many hypotheses about the etiology of ARHL are based on genetic and environmental elements. Most of the current research on the pathology of ARHL focuses on oxidative damage, mitochondrial dysfunction, inflammation, cochlear blood flow, ion homeostasis, etc. In TCM, herbs belonging to the kidney, lung, and liver meridians exhibit good hearing protection. Seven herbs belonging to the kidney meridian, 9 belonging to the lung meridian, and 4 belonging to the liver meridian were ultimately retrieved in this review, such as Polygonum multiflorum Thunb., Panax ginseng C.A. Mey, and Pueraria lobata (Willd.) Ohwi. Their active compounds, 2,3,4',5-Tetrahydroxystilbene-2-O-D-glucoside, ginsenoside Rb1, and puerarin, may act as the molecular substance for their anti-ARHL efficacy, and show anti-oxidative, neuroprotective, anti-inflammatory, anti-apoptotic, or mitochondrial protective effects. CONCLUSION: Anti-oxidants, modulators of mitochondrial function, anti-inflammation agents, vasodilators, K+ channel openers, Ca2+ channel blockers, JNK inhibitors, and nerve growth factors/neurotrophic factors all contribute to hearing protection, and herbs are an important source of potential anti-ARHL drugs.

Mitochondrial transplantation ameliorates doxorubicin-induced cardiac dysfunction via activating glutamine metabolism.

Doxorubicin is a wildly used effective anticancer agent. However, doxorubicin use is also related to cardiotoxic side effect in some patients. Mitochondrial damage has been shown to be one of the pathogeneses of doxorubicin-induced myocardial injury. In this study, we demonstrated that mitochondrial transplantation could inhibit doxorubicin-induced cardiotoxicity by directly supplying functional mitochondria. Mitochondrial transplantation improved contractile function and respiratory capacity, reduced cellular apoptosis and oxidative stress in cardiomyocytes. Mitochondria isolated from various sources, including mouse hearts, mouse and human arterial blood, and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), all exerted similar cardioprotective effects. Mechanically, mitochondrial transplantation activates glutamine metabolism in doxorubicin-treated mice heart and blocking glutamine metabolism attenuated the cardioprotective effects of mitochondrial transplantation. Overall, our study demonstrates that mitochondria isolated from arterial blood could be used for mitochondrial transplantation, which might serve as a feasible promising therapeutic option for patients with doxorubicin-induced cardiotoxicity.

Strontium alleviated the growth inhibition and toxicity caused by cadmium in rice seedlings.

Cadmium (Cd) contamination of rice is an urgent ecological and agricultural problem. Strontium (Sr) has been shown to promote plant growth. However, the effect of Sr on rice seedlings under Cd stress is currently unclear. In this work hydroponic experiments were used to assess the impact of Sr on rice seedling growth under Cd stress. The findings demonstrated that foliar application of 0.5 mg L-1 Sr had no discernible impact on the development of rice seedlings. However, Sr significantly alleviated growth inhibition and toxicity in rice seedlings when threatened by Cd. Compared with the Cd treatment (Cd, 2.5 mg L-1), the root length, shoot height, and whole plant length of rice seedlings in the Cd + Sr treatment (Cd, 2.5 mg L-1; Sr, 0.5 mg L-1) increased by 4.96 %, 12.47 % and 9.60 %, respectively. The content of Cd in rice decreased by 23.34 % (roots) and 5.79 % (shoots). Sr lessened the degree of membrane lipid peroxidation damage (lower MDA concentration) among the seedlings of rice under Cd stress by controlling the activities of antioxidant enzymes and GSH content. By changing the expression of antioxidant enzyme-encoding genes and downregulating the heavy metal transporter gene (OsNramp5), Sr reduced accumulation and the detrimental effects of Cd on rice seedlings. Our study provides a new solution to the problem of Cd contamination in rice, which may promote the safe production of rice and benefit human health.

Association of survival with adjuvant radiotherapy for pN0 esophageal cancer.

INTRODUCTION: This study was conducted to elucidate the link between adjuvant radiotherapy and survival in pathologic node-negative (pN0) esophageal cancer patients with upfront esophagectomy. METHODS: From 2000 to 2016, patients with pN0 esophageal cancer who underwent upfront esophagectomy were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The association of high-risk covariates with survival after adjuvant radiotherapy was evaluated using propensity score matching and multivariate analysis. RESULTS: We identified 3197 patients, 321 (10.0%) underwent postoperative radiotherapy and 2876 (90.0%) underwent esophagectomy alone. In the unmatched cohort, postoperative radiotherapy was associated with a statistically significant but modest absolute decrease in survival outcomes (P < 0.001). In the matched cohort, the survival differences disappeared. Additionally, adjuvant radiotherapy was linked to a 5-year overall survival (OS) benefit for patients with the pT3-4N0 disease (34.8% vs. 27.7%; P = 0.008). Adjuvant radiotherapy for pT3-4N0 disease with tumor length ≥3 cm, adenocarcinoma, and evaluated lymph node count <12 was shown to independently function as a risk factor for improved OS, as per a multivariate analysis (P < 0.01). CONCLUSIONS: This population-based trial showed that high-risk patients with pT3-4N0 esophageal cancer had better OS following upfront esophagectomy followed by radiotherapy therapy. This discovery may have major significance in the use of adjuvant radiotherapy following upfront esophagectomy in patients with pN0 esophageal cancer.

Understanding the Influence of Li7La3Zr2O12 Nanofibers on Critical Current Density and Coulombic Efficiency in Composite Polymer Electrolytes.

Composite polymer electrolytes (CPEs) are attractive materials for solid-state lithium metal batteries, owing to their high ionic conductivity from ceramic ionic conductors and flexibility from polymer components. As with all lithium metal batteries, however, CPEs face the challenge of dendrite formation and propagation. Not only does this lower the critical current density (CCD) before cell shorting, but the uncontrolled growth of lithium deposits may limit Coulombic efficiency (CE) by creating dead lithium. Here, we present a fundamental study on how the ceramic components of CPEs influence these characteristics. CPE membranes based on poly(ethylene oxide) and lithium bis(trifluoromethanesulfonyl)imide (PEO-LiTFSI) with Li7La3Zr2O12 (LLZO) nanofibers were fabricated with industrially relevant roll-to-roll manufacturing techniques. Galvanostatic cycling with lithium symmetric cells shows that the CCD can be tripled by including 50 wt % LLZO, but half-cell cycling reveals that this comes at the cost of CE. Varying the LLZO loading shows that even a small amount of LLZO drastically lowers the CE, from 88% at 0 wt % LLZO to 77% at just 2 wt % LLZO. Mesoscale modeling reveals that the increase in CCD cannot be explained by an increase in the macroscopic or microscopic stiffness of the electrolyte; only the microstructure of the LLZO nanofibers in the PEO-LiTFSI matrix slows dendrite growth by presenting physical barriers that the dendrites must push or grow around. This tortuous lithium growth mechanism around the LLZO is corroborated with mass spectrometry imaging. This work highlights important elements to consider in the design of CPEs for high-efficiency lithium metal batteries.

The macrophage polarization in inflammatory dermatosis and its potential drug candidates.

Inflammatory dermatosis is characterized by persistent inflammatory infiltration and hard repair of diseased skin. As a member of the human innate immune cells, macrophages usually show different phenotypes in different diseases. The macrophage phenotype (M1/M2) imbalance caused by the increase of M1 macrophages or the decrease of M2 macrophages is common in inflammatory dermatosis. In recent years, with the deepening research on inflammatory skin diseases, more and more natural medicines/traditional Chinese medicines (TCMs), represented by Shikonin and Angelica Dahurica, have shown their therapeutic effects by affecting the polarization of macrophages. This review introduced macrophage polarization in different inflammatory dermatosis, such as psoriasis. Then summarized the natural medicines/TCMs that have potential therapeutic effects so far and introduced their mechanisms of action and the proteins/signal pathways involved. We found that the TCMs with therapeutic effects listed in this review are closely related to the theory of five flavors and four properties of Chinese medicinal, and most of them are bitter, acrid and sweet. Bitter TCMs have antipyretic, anti-inflammatory and antibacterial effects, which may improve the persistent inflammation of M1 macrophage infiltration. Acrid TCMs have the effect of promoting blood circulation, while sweet TCMs have the effect of nourishing. These 2 flavors may accelerate the repair of skin lesions of inflammatory dermatosis by affecting M2 macrophages. In conclusion, we hope to provide sufficient knowledge for natural medicine research and the development of inflammatory dermatosis related to macrophage phenotype imbalance.

Thymosin α1 and Its Role in Viral Infectious Diseases: The Mechanism and Clinical Application.

Thymosin α1 (Tα1) is an immunostimulatory peptide that is commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C, and acquired immune deficiency syndrome (AIDS). Tα1 can influence the functions of immune cells, such as T cells, B cells, macrophages, and natural killer cells, by interacting with various Toll-like receptors (TLRs). Generally, Tα1 can bind to TLR3/4/9 and activate downstream IRF3 and NF-κB signal pathways, thus promoting the proliferation and activation of target immune cells. Moreover, TLR2 and TLR7 are also associated with Tα1. TLR2/NF-κB, TLR2/p38MAPK, or TLR7/MyD88 signaling pathways are activated by Tα1 to promote the production of various cytokines, thereby enhancing the innate and adaptive immune responses. At present, there are many reports on the clinical application and pharmacological research of Tα1, but there is no systematic review to analyze its exact clinical efficacy in these viral infectious diseases via its modulation of immune function. This review offers an overview and discussion of the characteristics of Tα1, its immunomodulatory properties, the molecular mechanisms underlying its therapeutic effects, and its clinical applications in antiviral therapy.

Dual inhibition of MYC and SLC39A10 by a novel natural product STAT3 inhibitor derived from Chaetomium globosum suppresses tumor growth and metastasis in gastric cancer.

Gastric cancer remains one of the most common deadly diseases and lacks effective targeted therapies. In the present study, we confirmed that the signal transducer and activator of transcription 3 (STAT3) is highly expressed and associated with a poor prognosis in gastric cancer. We further identified a novel natural product inhibitor of STAT3, termed XYA-2, which interacts specifically with the SH2 domain of STAT3 (Kd= 3.29 µM) and inhibits IL-6-induced STAT3 phosphorylation at Tyr705 and nuclear translocation. XYA-2 inhibited the viability of seven human gastric cancer cell lines with 72-h IC50 values ranging from 0.5 to 0.7 µΜ. XYA-2 at 1 µΜ inhibited the colony formation and migration ability of MGC803 (72.6% and 67.6%, respectively) and MKN28 (78.5% and 96.6%, respectively) cells. In the in vivo studies, intraperitoneal administration of XYA-2 (10 mg/kg/day, 7 days/week) significantly suppressed 59.8% and 88.8% tumor growth in the MKN28-derived xenograft mouse model and MGC803-derived orthotopic mouse model, respectively. Similar results were obtained in a patient-derived xenograft (PDX) mouse model. Moreover, XYA-2 treatment extended the survival of mice bearing PDX tumors. The molecular mechanism studies based on transcriptomics and proteomics analyses indicated that XYA-2 might exert its anticancer activity by synergistically inhibiting the expression of MYC and SLC39A10, two downstream genes of STAT3 in vitro and in vivo. Together, these findings suggested that XYA-2 may be a potent STAT3 inhibitor for treating gastric cancer, and dual inhibition of MYC and SLC39A10 may be an effective therapeutic strategy for STAT3-activated cancer.

Galangin alleviated myocardial ischemia-reperfusion injury by enhancing autophagic flux and inhibiting inflammation.

Autophagy is critically involved in myocardial ischemia-reperfusion (I/R). Autophagy inhibition exacerbates myocardial I/R injury. Few effective agents target autophagy to prevent myocardial I/R injury. Effective drugs that promote autophagy in myocardial I/R warrant further investigation. Galangin (Gal) enhances autophagy and alleviates I/R injury. Here we conducted both in vivo and in vitro experiments to observe the changes in autophagy after galangin treatment and investigated the cardioprotective effects of galangin on myocardial I/R. METHODS: After 45-min occlusion of the left anterior descending coronary artery, myocardial I/R was induced by slipknot release. One day before surgery and immediately after surgery, the mice were injected intraperitoneally with the same volume of saline or Gal. The effects of Gal were evaluated using echocardiography, 2,3,5-triphenyltetrazolium chloride staining (TTC staining), western blotting, and transmission electron microscopy. Primary cardiomyocytes and bone marrow-derived macrophages were extracted in vitro to measure the cardioprotective effects of Gal. RESULTS: Compared with the saline-treated group, Gal significantly improved cardiac function and limited infarct enlargement after myocardial I/R. In vivo and in vitro studies demonstrated that Gal treatment promoted autophagy during myocardial I/R. The anti-inflammatory effects of Gal were validated in bone marrow-derived macrophages. These results strongly suggest that Gal treatment can attenuate myocardial I/R injury. CONCLUSION: Our data demonstrated that Gal could improve left ventricular ejection fraction and reduce infarct size after myocardial I/R by promoting autophagy and inhibiting inflammation.