Migraine after stellate ganglion block: A case report.

Stellate ganglion block-induced ipsilateral migraines are rare. We present a typical case detailing its developmental process. Abnormalities in the autonomic nervous system control and vascular and neural mechanisms may play crucial roles in the manifestation of these migraines. Postprocedural migraines necessitate anesthesiologists' awareness during stellate ganglion blocks.

Discovery of NLRP3 inhibitors using machine learning: Identification of a hit compound to treat NLRP3 activation-driven diseases.

NLRP3 is vital in developing many human diseases as one of the most critical inflammasomes. Developing related inhibitors has been instrumental in advancing the development of therapies for associated diseases. To date, there are no NLRP3 inhibitors on the market. This study identified a series of NLRP3 inhibitors using the self-developed machine learning model. Among them, CSC-6 was validated as the hit molecule with optimal activity and significantly inhibited IL-1ß secreted by PMA-THP-1 cells (IC50 = 2.3 ± 0.38 µM). The results show that CSC-6 specifically binds NLRP3 and inhibits NLRP3 activation by blocking ASC oligomerization during NLRP3 assembly. In vivo experiments have demonstrated that CSC-6 effectively reduces the symptoms of NLRP3 overactivation-mediated sepsis and Gout in mouse models. Importantly, CSC-6 has lower cytotoxicity and exhibits better stability in human-derived liver microsomes, which is more favorable for the drug to maintain its efficacy in vivo for longer. The discovery of CSC-6 may contribute to the design and discovery of related NLRP3 inhibitors.

An Organic Coordination Manganese Complex as Cathode for High-Voltage Aqueous Zinc-metal Battery.

Aqueous Zn-Mn battery has been considered as the most promising scalable energy-storage system due to its intrinsic safety and especially ultralow cost. However, the traditional Zn-Mn battery mainly using manganese oxides as cathode shows low voltage and suffers from dissolution/disproportionation of the cathode during cycling. Herein, for the first time, a high-voltage and long-cycle Zn-Mn battery based on a highly reversible organic coordination manganese complex cathode (Manganese polyacrylate, PAL-Mn) was constructed. Benefiting from the insoluble carboxylate ligand of PAL-Mn that can suppress shuttle effect and disproportionationation reaction of Mn3+ in a mild electrolyte, Mn3+ /Mn2+ reaction in coordination state is realized, which not only offers a high discharge voltage of 1.67 V but also exhibits excellent cyclability (100 % capacity retention, after 4000 cycles). High voltage reaction endows the Zn-Mn battery high specific energy (600 Wh kg-1 at 0.2 A g-1 ), indicating a bright application prospect. The strategy of introducing carboxylate ligands in Zn-Mn battery to harness high-voltage reaction of Mn3+ /Mn2+ well broadens the research of high-voltage Zn-Mn batteries under mild electrolyte conditions.

NSD3: Advances in cancer therapeutic potential and inhibitors research.

Nuclear receptor-binding SET domain 3, otherwise known as NSD3, is a member of the group of lysine methyltransferases and is involved in a variety of cellular processes, including transcriptional regulation, DNA damage repair, non-histone related functions and several others. NSD3 gene is mutated or loss of function in a variety of cancers, including breast, lung, pancreatic, and osteosarcoma. These mutations produce dysfunction of the corresponding tumor tissue proteins, leading to tumorigenesis, progression, chemoresistance, and unfavorable prognosis, which suggests that the development of NSD3 probe molecules is important for understanding the specific role of NSD3 in disease and drug discovery. In recent years, NSD3 has been increasingly reported, demonstrating that this target is a very hot epigenetic target. However, the number of NSD3 inhibitors available for cancer therapy is limited and none of the drugs that target NSD3 are currently available on the market. In addition, there are very few reviews describing NSD3. Within this review, we highlight the role of NSD3 in tumorigenesis and the development of NSD3 targeted small-molecule inhibitors over the last decade. We hope that this publication can serve as a guide for the development of potential drug candidates for various diseases in the field of epigenetics, especially for the NSD3 target.

Recent advances in gout drugs.

Gout is an autoinflammatory disease caused by the deposition of urate crystals. As the most common inflammatory arthritis, gout has a high incidence and can induce various severe complications. At present, there is no effective cure method in the world. With the deepening of medical research, gout treatment drugs continue to progress. In this review, we provide a landscape view of the current state of the research on gout treatment drugs, including the research progress of anti-inflammatory and analgesic drugs, drugs that promote uric acid excretion, and drugs that inhibit uric acid production. We mainly emphasize the understanding of gout as an auto-inflammatory disease and the discovery strategy of related gout drugs to provide a systematic and theoretical basis for the new exploration of gout drug discovery.

The role of Angiogenesis and remodeling (AR) associated signature for predicting prognosis and clinical outcome of immunotherapy in pan-cancer.

Background: Angiogenesis and remodeling (AR) is necessary for the growth and metastasis of cancers. Although AR related genes involved in this process are reported, the correlation between AR and clinical outcome, immune cell infiltration, and immunotherapy is still unknown in diverse cancers. This study aimed to investigate the role of AR in the tumor immune microenvironment (TIME) in pan-cancer, and explore its values in prognostic prediction and therapeutic responses. Methods: Firstly, AR genes (including angiogenesis genes and blood vessel remodeling genes) are collected from MsigDB database. The differential expression, and prognostic value of AR genes were studied in 33 tumor types based on TCGA and GTEx data. The AR score of each sample was calculated using the "ssGSEA" function of R package "GSVA" in pan-cancer. The correlation of the AR score with TIME index, such as the amount of stromal and immune components and the immune cell infiltration, was evaluated via integrating multiple computational methods. And we also utilized IMvigor210 and GSE78220 data to explore the prediction value of the AR score on the immunotherapy response. Results: Significant differences in AR gene expression between tumors and adjacent normal tissues were found in most cancer types. The AR score varied depending on the types of tumors, and high score was related to worse survival in various tumors, such as pancreatic and stomach adenocarcinoma and so on. Moreover, the AR score was further explored to be positively correlated with proportions and pathways of immune and stromal in TIME. And the AR score was positively correlated with immunosuppressive cells, including TAMs and iTregs, while negatively with CD8+ T cells. Further analysis revealed that patients with high AR had worse therapy efficacy and survival status in bladder cancer and melanomas. Conclusions: Our systematic analysis revealed that AR is closely associated TIME, and prognosis, and clinical characteristics in multiple cancers. Targeting AR genes may activate immune microenvironment and increase the efficacy of immunotherapy.

Mn2+/I- Hybrid Cathode with Superior Conversion Efficiency for Ultrahigh-Areal-Capacity Aqueous Zinc Batteries.

Aqueous Zn-Mn2+ electrolysis batteries utilizing the two-electron-transfer reaction between Mn2+ and MnO2 attract great attention because of their superior theoretical capacity (616 mAh g-1). However, the low conductivity of deposited MnO2 and the poor conversion efficiency of Mn2+/MnO2 inevitably result in limited areal capacity and unsatisfied cycling stability, which have become the main hurdles of aqueous Zn-Mn2+ batteries' applications. Herein, we propose a novel Mn2+/I- hybrid cathode that couples the triiodide/iodide redox with the Mn2+/MnO2 redox to optimize the electrolysis kinetics. Because of the synergistically enhanced conversion reaction between Mn2+/I- and the promoter effect of I- to the dissolution of MnO2, this hybrid cathode not only exhibits fast reaction kinetics, thus demonstrating ultrahigh rate capability (100 mA cm-2), but also displays observably enhanced conversion efficiency up to 96.0% with excellent reversibility of 2000 cycles. Especially the superhigh areal capacity of 20 mAh cm-2 with more than 100 cycles among the reported static Zn-Mn2+ electrolysis batteries is demonstrated. The excellent battery performance as well as the facile electrode hybridization approach designed here paves the way for the practical applications of aqueous Zn batteries.

Perioperative management of malignant hyperthermia during general anesthesia: A report of two cases.

Malignant hyperthermia (MH) is a lethal complication associated with general anesthesia characterized by sudden onset, rapid progression, and high mortality. We present two seemingly typical cases of intraoperative MH development, with details on perioperative assessment and rescue. Postoperative genetic test showed mutations in the ryanodine receptor type 1 gene.

Trends in insulin resistance: insights into mechanisms and therapeutic strategy.

The centenary of insulin discovery represents an important opportunity to transform diabetes from a fatal diagnosis into a medically manageable chronic condition. Insulin is a key peptide hormone and mediates the systemic glucose metabolism in different tissues. Insulin resistance (IR) is a disordered biological response for insulin stimulation through the disruption of different molecular pathways in target tissues. Acquired conditions and genetic factors have been implicated in IR. Recent genetic and biochemical studies suggest that the dysregulated metabolic mediators released by adipose tissue including adipokines, cytokines, chemokines, excess lipids and toxic lipid metabolites promote IR in other tissues. IR is associated with several groups of abnormal syndromes that include obesity, diabetes, metabolic dysfunction-associated fatty liver disease (MAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), and other abnormalities. Although no medication is specifically approved to treat IR, we summarized the lifestyle changes and pharmacological medications that have been used as efficient intervention to improve insulin sensitivity. Ultimately, the systematic discussion of complex mechanism will help to identify potential new targets and treat the closely associated metabolic syndrome of IR.

An electrochemically stable homogeneous glassy electrolyte formed at room temperature for all-solid-state sodium batteries.

All-solid-state sodium batteries (ASSSBs) are promising candidates for grid-scale energy storage. However, there are no commercialized ASSSBs yet, in part due to the lack of a low-cost, simple-to-fabricate solid electrolyte (SE) with electrochemical stability towards Na metal. In this work, we report a family of oxysulfide glass SEs (Na3PS4-xOx, where 0 < x ≤ 0.60) that not only exhibit the highest critical current density among all Na-ion conducting sulfide-based SEs, but also enable high-performance ambient-temperature sodium-sulfur batteries. By forming bridging oxygen units, the Na3PS4-xOx SEs undergo pressure-induced sintering at room temperature, resulting in a fully homogeneous glass structure with robust mechanical properties. Furthermore, the self-passivating solid electrolyte interphase at the Na|SE interface is critical for interface stabilization and reversible Na plating and stripping. The new structural and compositional design strategies presented here provide a new paradigm in the development of safe, low-cost, energy-dense, and long-lifetime ASSSBs.

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China.

BACKGROUND: Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative HCC patients to allow for improved clinical management and prognostication of the disease. METHODS: This study observed a cohort of HCC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods. RESULTS: Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child-Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR). CONCLUSIONS: The are significant differences in clinical pathologic characteristics between AFP positive and negative HCC patients which may be helpful for the management and prognostication of the disease.

Cyclic Ether-Water Hybrid Electrolyte-Guided Dendrite-Free Lamellar Zinc Deposition by Tuning the Solvation Structure for High-Performance Aqueous Zinc-Ion Batteries.

The serious zinc dendrites and poor cyclability at high cathode loading owing to the strong solvation effect of traditional aqueous electrolytes are the main bottlenecks to the development of aqueous rechargeable zinc-ion batteries (ARZIBs). Here, we design an ether-water hybrid zinc-ion electrolyte with bifunctional roles of not only unplugging the dendrites bottleneck at the Zn anode but also extending the cycle life at high cathode loading. A cyclic ether (1,4-dioxane (DX)) is incorporated into traditional ZnSO4-based electrolytes to finely tune the solvation sheath of Zn2+. DX is found to guide the deposition orientation of zinc along the (002) plane, leading to not a dendritic structure but distinctively dense lamellar deposition due to the stronger affinity of the cyclic DX molecules toward Zn(002) than that of water, which is proven by density functional theory calculations. The cycling lifespan of the Zn anode extends up to over 600 h at 5.0 mA cm-2 and maintains extremely high Coulombic efficiency of 99.8%, thereby further enabling the Zn-MnO2 full cells to stably cycle at an ultrahigh mass loading of 9.4 mg cm-2, paving the way to their practical applications. This work also provides a novel electrolyte regulating solution for other aqueous multivalent metal-ion batteries.

Ultrastable Zinc Anodes Enabled by Anti-Dehydration Ionic Liquid Polymer Electrolyte for Aqueous Zn Batteries.

The side reaction and dendrite of a zinc anode in an aqueous electrolyte represent a huge obstacle for the development of rechargeable aqueous Zn batteries. An electrolyte with confined water is recognized to fundamentally stabilize the zinc anode. This work proposes acetamide/zinc perchlorate hexahydrate (AA/ZPH) ionic liquid (IL)-polyacrylamide (PAM) polymer electrolytes, here defined as IL-PAM. The novel Zn2+-conducting IL is able to accommodate trace water and can achieve both high conductivity (15.02 mS cm-1) and alleviation of side reactions (>90% reduction). Cross-linked PAM acts as the three-dimensional framework to suppress dendrites and obtain flexibility. As a result, the Zn anode with IL-PAM can cycle stably over 2000 h with a record highest cumulative capacity of 3000 mAh cm-2 and well-preserved morphology. Based on IL-PAM, the flexible LFP|Zn hybrid batteries can be successfully assembled and operate normally in series and parallel conditions. Moreover, the low volatility of IL and binding forces exerted by the PAM network endues IL-PAM with an anti-dehydration property. In a 50 °C unsealed environment, the weight loss of IL-PAM is about two-fifths of PAM hydrogel and an aqueous electrolyte, and the corresponding hybrid battery with IL-PAM can also prolong a 4 times longer lifespan.

Correlations of disease severity and age with hematology parameter variations in patients with COVID-19 pre- and post-treatment.

BACKGROUND: For better understanding of the pathological changes of COVID-19, benefiting clinical management of the disease and the preparation for future waves of similar pandemics. METHODS: Hematology parameters from a total of 52 cases of COVID-19 admitted for treatment in a designated hospital were retrospectively analyzed. Data were analyzed by SPSS statistical software. RESULTS: Pre-treatment T-cell subsets, total lymphocytes, red blood cell distribution width (RDW), eosinophils, and basophils were significantly lower than that of post-treatment, while the inflammatory indexes neutrophils, neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP) levels, as well as red blood cell (RBC) and hemoglobin, were significantly reduced after treatment. The T-cell subsets, total lymphocytes, and basophils in severely and critically ill patients were significantly lower than those in moderately ill patients. Neutrophils, NLR, eosinophils, procalcitonin (PCT), and CRP was significantly higher in severely and critically ill patients than in moderately ill patients. CD3+, CD8+, total lymphocytes, platelets, and basophils in patients older than 50 were lower than that of those younger than 50, while neutrophils, NLR, CRP, and RDW in patients older than 50 were higher than that of younger than 50. There was a positive correlation among prothrombin time (PT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in severely and critically ill patients. CONCLUSIONS: T-cell subsets, lymphocyte count, RDW, neutrophils, eosinophils, NLR, CRP, PT, ALT, and AST are important indicators in the management especially for severely and critically ill patients with COVID-19.

An Ultrastable Na-Zn Solid-State Hybrid Battery Enabled by a Robust Dual-Cross-linked Polymer Electrolyte.

This work proposes a dual-cross-linked gel solid electrolyte (SE), here defined as Zn-re-inforced sodium alginate-polyacrylamide SE (Zn-reinforced SA-PAM SE), in which Na+ and Zn2+ coexist. The SE shows a high conductivity of 19.74 mS cm-1. Compared to the pure PAM gel, the tensile strength and compressive strength of Zn-reinforced SA-PAM SE are significantly enhanced to be 674.28 kPa and 16.29 MPa, respectively, because of the strengthening mechanism of Zn2+ cross-linked SA. Based on such a robust electrolyte, a novel hybrid cell is developed by involving Na0.5FeFe(CN)6-carbon nanotube composites (PB@CNT) as the Na+ intercalation-type cathode and metallic Zn as the plating anode. The hybrid cell shows an extremely high stability for 10,000 cycles with a record little capacity loss of 0.0027% per cycle, as Zn-reinforced SA-PAM SE successfully inhibits free water molecules from occupying low-spinning metallic sites (Fe-C) in Na0.5FeFe(CN)6. Ex situ X-ray photoelectron spectroscopy reveals that the dissolution of Na0.5FeFe(CN)6 is highly reduced by 79.5%. It is further noted that the corrosion and dendrites at the Zn2+/Zn plating anode are greatly hindered for the robust electrolyte. This work gives a pathway for the development of new aqueous ion batteries.

The association of serum vitamin D-binding protein and 25-hydroxyvitamin D in pre-operative and post-operative colorectal cancer.

BACKGROUND: The association between vitamin D-binding protein (VDBP) and 25-hydroxyvitamin D (25 (OH)D) with colorectal cancer (CRC) is still ambiguous. This study was to further investigate the relationship between serum VDBP, 25 (OH)D levels and the clinical and pathological features of patients with CRC. METHODS: Enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay were used to analyze the VDBP and 25(OH)D concentrations in serum. Pearson's correlation analysis was applied to evaluate the association between serum VDBP and 25(OH)D levels in CRC. Conditional logistic regression was performed to analyze the prediction value of serum VDBP or 25(OH)D as a risk factor for CRC. RESULTS: The serological levels of 25(OH)D in patients were significantly lower than in healthy individuals, while VDBP levels were significantly higher than in healthy controls. The serum VDBP in pre-operative was significantly lower than in post-operative samples, while the serum 25(OH)D from pre-operative patients was significantly higher than post-operative patients. Patients with tumors with higher stage and increased lymph node involvement had lower serum post-operative VDBP levels. In addition, our results showed that the pre-operative VDBP level is a risk factor of CRC. CONCLUSIONS: The levels of serum 25(OH)D and VDBP were both associated with CRC. Thus, serum 25(OH)D and VDBP levels might be of value in evaluating the pathogenesis and risk of CRC in the future. Moreover, serum VDBP or 25(OH)D levels were associated with patient's clinical and pathological features providing data for risk and prognostic prediction.

Significantly increased anti-tumor activity of carcinoembryonic antigen-specific chimeric antigen receptor T cells in combination with recombinant human IL-12.

BACKGROUND AIMS: Chimeric antigen receptor T cells (CAR-T cells) have been successfully used in treatments of hematological tumors, however, their anti-tumor activity in solid tumor treatments was limited. As IL-12 increases T-cell immune functions, we designed carcinoembryonic antigen (CEA) specific CAR-T (CEA-CAR-T) cells and, for the first time, used them in combination with recombinant human IL-12 (rhIL-12) to treat several types of solid tumors. METHODS: In vitro anti-tumor activity of CEA-CAR-T cells in combination with rhIL-12 was confirmed by evaluation of CEA-CAR-T cell activation, proliferation, and cytotoxicity after co-incubation with CEA-positive or CEA-negative human tumor cells. In vivo anti-tumor activity of CEA-CAR-T cells in combination with rhIL-12 was confirmed in a xenograft model in nude mice for treatments of several types of solid tumors. RESULTS: In vitro experiments confirmed that rhIL-12 significantly increased the activation, proliferation, and cytotoxicity of CEA-CAR-T cells. Similarly, in vivo experiments found that CEA-CAR-T cells in combination with rhIL-12 had significantly enhanced anti-tumor activity than CEA-CAR-T cells in growth inhibition of newly colonized colorectal cancer cell HT-29, pancreatic cancer cell AsPC-1, and gastric cancer cell MGC803. CONCLUSIONS: These works confirmed that simultaneous use of cytokines, for example, rhIL-12, can increase the anti-tumor activity of CAR-T cells, especially for treatments of several types of solid tumors.

Metal-organic framework-derived hierarchical Co3O4@MnCo2O4.5 nanocubes with enhanced electrocatalytic activity for Na-O2 batteries.

The Na-O2 battery system is attracting increasing attention due to its superiority in specific capacity and cost. However, its practical implementation is hindered by many issues, such as high charge-discharge overpotential, limited cycling life, and poor reversibility, all of which result from the mediocre O2 electrode. Herein, to surmount these critical challenges, hierarchical Co3O4@MnCo2O4.5 nanocubes (h-Co3O4@MnCo2O4.5 Ns) with a yolk-shell structure are designed for the first time as the novel O2 electrode. h-Co3O4@MnCo2O4.5 Ns are synthesized from a metal-organic framework via a template-assisted method, which is demonstrated to be helpful in creating a high specific surface area of 130.4 m2 g-1, a hierarchical macro- and mesoporous structure, and synergistic yolk-shelled Co3O4@MnCo2O4.5 active sites. These unique structural properties endow h-Co3O4@MnCo2O4.5 Ns with remarkably enhanced electrocatalytic activity towards both the ORR and OER. The Na-O2 battery based on h-Co3O4@MnCo2O4.5 Ns displays an ultrahigh initial discharge capacity of 8400 mA h g-1, ultralow charge-discharge overpotential of 0.45 V, long cycling life of 135 cycles, and excellent rate capability.

Stabilizing the Interface between Sodium Metal Anode and Sulfide-Based Solid-State Electrolyte with an Electron-Blocking Interlayer.

Sulfide-based Na-ion conductors are promising electrolytes for all-solid-state sodium batteries (ASSSBs) because of high ionic conductivity and favorable formability. However, no effective strategy has been reported for long-duration Na cycling with sulfide-based electrolytes because of interfacial challenges. Here we demonstrate that a cellulose-poly(ethylene oxide) (CPEO) interlayer can stabilize the interface between sulfide electrolyte (Na3SbS4) and Na by shutting off the electron pathway of the electrolyte decomposition reaction. As a result, we achieved stable Na plating/stripping for 800 cycles at 0.1 mA cm-2 in all-solid-state devices at 60 °C.