Immuno-oncological role of 20S proteasome alpha-subunit 3 in aggravating the progression of esophageal squamous cell carcinoma.

PSMA3, a member of the proteasome subunit, has been shown to play a major player in protein degradation. Reportedly, PSMA3 functions as a negative regulator in various cancers including colon, pancreatic and gastric cancers. However, the contributions of PSMA3 to the progression of esophageal squamous cell carcinoma (ESCC) and the underlying mechanism remain unclear. Therefore, in this study, we investigated whether PSMA3 is involved in ESCC progression and the potential underlying mechanism. The results revealed that PSMA3 was highly expressed in the ESCC tumor tissues and functioned as a negative indicator according to the data from The Cancer Genome Atlas (TCGA)/Gene Expression Omnibus (GEO) datasets and clinical patients' samples. Pathway enrichment analysis showed that PSMA3 was closely correlated with ESCC cancer stemness and the inflammatory response; however, this correlation was absent after knockdown of PSMA3 in vitro. We further demonstrated that PSMA3 suppressed CD8+ T-cells infiltration depending on the C-C motif chemokine ligand 3 (CCL3)/C-C motif chemokine receptor 5 (CCR5) axis. Collectively, these results demonstrate the role of PSMA3 in ESCC cancer stemness and the negative regulation of CD8 T-cells infiltration mediated by PSMA3. The results of this study may provide a potential target for the immuno-oncology effect of PSMA3 in ESCC therapy.

Ultra-Stretchable, Self-Healing, Conductive, and Transparent PAA/DES Ionic Gel.

A deep eutectic solvent (DES) ionic gel is fabricated rapidly under mild conditions. The acrylic acid monomer is polymerized based on a dual self-catalytic system between Vitamin C (VC) and metal ions, such as Fe3+ in the presence of ammonium persulfate in the DES of betaine and ethylene glycol. The as-obtained PAA/DES ionic gel possesses excellent conductivity between 0.1 and 1.3 S m-1 in a wide range of temperatures from 0 to 90 °C. Moreover, it also shows an ultra-stretchable performance with stretch more than 200 times its original length even under a stretching rate of 100 mm min-1 . Besides, it can operate in harsh conditions because of its anti-freezing and anti-drying properties. The ionic gel is self-healing, and the stretching and conductive performance can be recovered after it is broken. These superior properties of the DES ionic gel provide new insights into the design of novel gels in various applications, such as tissue engineering, sensing, and wearable electronics.

Novel dual-target FAAH and TRPV1 ligands as potential pharmacotherapeutics for pain management.

Dual-acting drugs that simultaneously inhibit fatty acid amide hydrolase (FAAH) and antagonize the transient receptor potential vanilloid 1 (TRPV1) is a promising stronger therapeutic approach for pain management without side effects associated with single-target agents. Here, several series of dual FAAH/TRPV1 blockers were designed and synthesized through rational molecular hybridization between the pharmacophore of classical TRPV1 antagonists and FAAH inhibitors. The studies resulted in compound 2r, which exhibited strong dual FAAH/TRPV1 inhibition/antagonism in vitro, exerted powerful analgesic effects in formalin-induced pain test (phase II, in mice), desirable anti-inflammatory activity in carrageenan-induced paw edema in rats, no TRPV1-related hyperthermia side effect, and favorable pharmacokinetic properties. Meanwhile, the contributions of TRPV1 and FAAH to its antinociceptive effects were verified by target engagement and molecular docking studies. Overall, compound 2r can serve as a new scaffold for developing FAAH/TRPV1 dual-activie ligands to counteract pain.

Effect of Simultaneous Multiplane Surgery on Cardiopulmonary Function in Patients with Moderate to Severe Obstructive Sleep Apnea-Hypopnea Syndrome and Its Curative Effect.

Objective: To investigate the changes in cardiopulmonary function in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) by one-stage multiplane surgery. Methods: 70 patients with moderate and severe OSAHS underwent nasal in our hospital from July 2017 to February 2021, palatopharyngeal, and/or tongue operations simultaneously and were followed up for 6 months. The Epworth Sleeping Scale (ESS) scores of patients before and after surgery were compared to observe the surgical efficacy, and the changes in the cardiopulmonary function of patients before and after surgery were detected. The static and dynamic indexes of cardiopulmonary function, respiratory disturbance index (AHI), and blood oxygen saturation (SaO2) were compared before and after the operation. Results: After surgery, all patients' indexes of static lung function were improved compared with that before surgery. After surgery, the percentage of maximal oxygen uptake peak to the predicted value, percentage of oxygen pulse to the predicted value, the ratio of oxygen uptake power, anaerobic threshold, and maximum ventilatory capacity per minute/maximum exercise volume were increased compared with that before surgery, and AHI and SaO2 were improved compared with that before surgery. Conclusion: This study suggests that it is feasible for patients with OSAHS who are unable to tolerate or unwilling to undergo noninvasive assisted ventilation to undergo simultaneous surgery for multiplane stenosis. It can reduce clinical symptoms and improve cardiopulmonary function.

Efficient preparation of high-quality graphene via anodic and cathodic simultaneous electrochemical exfoliation under the assistance of microwave.

Currently, the electrochemical exfoliation of graphene stands out as an efficient, scalable approach to access high-quality products, due to its simplicity, low cost, and environmental friendliness. Here we have proposed an electrochemical method for preparing graphene at both the anode and cathode simultaneously. Graphite was first subjected to ion intercalation sufficiently on the anode and cathode and then expanded ultrafast under the assistance of microwave irradiation. With plenty of ion intercalation and proper microwave irradiation, graphene would be successfully exfoliated. The as-prepared graphene flakes from anode and cathode behave few-layer feature (more than 80% ≤ 4 layers) and large sizes (about 94% are larger than 1 µm), possess low oxygen content and little defects (6.1% and 1.9% oxygen for anodic and cathodic graphene, respectively). In addition, the high yields in our method (the maximum yields for anode and cathode were 81% and 76%, respectively) and the recycling of electrolytes suggest that our method owns great potential for large-scale production and provide an important reference for the commercial preparation of green and low-cost graphene.

Prediction of the potential geographical distribution of Betula platyphylla Suk. in China under climate change scenarios.

Climate is a dominant factor affecting the potential geographical distribution of species. Understanding the impact of climate change on the potential geographic distribution of species, which is of great significance to the exploitation, utilization, and protection of resources, as well as ecologically sustainable development. Betula platyphylla Suk. is one of the most widely distributed temperate deciduous tree species in East Asia and has important economic and ecological value. Based on 231 species distribution data points of Betula platyphylla Suk. in China and 37 bioclimatic, soil, and topography variables (with correlation coefficients < 0.75), the potential geographical distribution pattern of Betula platyphylla Suk. under Representative Concentration Pathway (RCP) climate change scenarios at present and in the 2050s and 2070s was predicted using the MaxEnt model. We analyzed the main environmental variables affecting the distribution and change of suitable areas and compared the scope and change of suitable areas under different climate scenarios. This study found: (1) At present, the main suitable area for Betula platyphylla Suk. extends from northeastern to southwestern China, with the periphery area showing fragmented distribution. (2) Annual precipitation, precipitation of the warmest quarter, mean temperature of the warmest quarter, annual mean temperature, and precipitation of the driest month are the dominant environmental variables that affect the potential geographical distribution of Betula platyphylla Suk. (3) The suitable area for Betula platyphylla Suk. is expected to expand under global warming scenarios. In recent years, due to the impact of diseases and insect infestation, and environmental damage, the natural Betula platyphylla Suk. forest in China has gradually narrowed. This study accurately predicted the potential geographical distribution of Betula platyphylla Suk. under current and future climate change scenarios, which can provide the scientific basis for the cultivation, management, and sustainable utilization of Betula platyphylla Suk. resources.

Indoleamine 2,3-Dioxygenase 1 Inhibitor-Loaded Nanosheets Enhance CAR-T Cell Function in Esophageal Squamous Cell Carcinoma.

In chimeric antigen receptor (CAR)-T cell therapy, the role and mechanism of indoleamine 2, 3 dioxygenase 1 (IDO1) in enhancing antitumor immunity require further study. IDO1 is one of the most important immunosuppressive proteins in esophageal squamous cell carcinoma (ESCC). However, the IDO1 inhibitor, epacadostat, has failed in phase III clinical trials; its limited capacity to inhibit IDO1 expression at tumor sites was regarded as a key reason for clinical failure. In this study, we innovatively loaded the IDO1 inhibitor into hyaluronic acid-modified nanomaterial graphene oxide (HA-GO) and explored its potential efficacy in combination with CAR-T cell therapy. We found that inhibition of the antitumor effect of CAR-T cells in ESCC was dependent on the IDO1 metabolite kynurenine. Kynurenine could suppress CAR-T cell cytokine secretion and cytotoxic activity. Inhibiting IDO1 activity significantly enhanced the antitumor effect of CAR-T cells in vitro and in vivo. Our findings suggested that IDO1 inhibitor-loaded nanosheets could enhance the antitumor effect of CAR-T cells compared with free IDO1 inhibitor. Nanosheet-loading therefore provides a promising approach for improving CAR-T cell therapeutic efficacy in solid tumors.

In Situ Formation of "Dimethyl Sulfoxide/Water-in-Salt"-Based Chitosan Hydrogel Electrolyte for Advanced All-Solid-State Supercapacitors.

Biodegradable hydrogel electrolytes are particularly attractive in the fabrication of all-solid-state supercapacitors due to environmental benignity and avoiding of leakage. The introduction of "water-in-salt" (WIS) electrolytes into hydrogels will further broaden the electrochemical stability window of aqueous supercapacitors significantly. Meanwhile, the addition of an organic co-solvent can effectively overcome the inevitable salt precipitation and extend the temperature adaptability. Herein, an in situ cross-linking approach was demonstrated without any extra binder to obtain a "dimethyl sulfoxide/water-in-salt"-based (DWIS) chitosan hydrogel electrolyte. Interestingly, the addition of 4-7 mol L-1 of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salts not only conforms to the criterion of WIS, but also promoted the successful gelation through the supramolecular complexation between Li+ -solvated complexes and chitosan chains. A hydrogel-based all-solid-state supercapacitor was fabricated using the DWIS chitosan hydrogel as the electrolyte and separator while nitrogen-doped graphene hydrogel (NG) was used as the electrode. The optimized supercapacitor with a wide operating voltage of 2.1 V showed a high specific capacitance of 107.6 F g-1 at 1 A g-1 , remarkable capacitance retention of 80.1 % after 5000 cycles, a superior energy density of 62.9 Wh kg-1 at a power density of 1025.5 W kg-1 , and excellent temperature stability in the range of -20 to 70 °C. These findings suggest that the as-prepared hydrogel electrolyte holds great potential in the practical application of high-performance solid-state energy storage devices.

A high-voltage quasi-solid-state flexible supercapacitor with a wide operational temperature range based on a low-cost "water-in-salt" hydrogel electrolyte.

Recently, "water-in-salt" electrolytes have provided a huge boost to the realization of high energy density for water-based supercapacitors by broadening the electrochemical stability window. However, the high cost and low conductivity of high concentration LiTFSI greatly restrict the possibility of practical application. Herein, we adopt a new strategy to develop a low-cost and quasi-solid-state polyelectrolyte hydrogel accommodating a superhigh concentration of CH3COOK through in situ polymerization, avoiding the problem that many conventional polymers cannot accommodate ultra-high ion concentration. The polyelectrolyte hydrogel with 24 M CH3COOK exhibits a conductivity of up to 35.8 mS cm-1 and a stretchability of 950%. With advanced N-doped graphene hydrogel electrodes, the assembled supercapacitor yields a voltage window of 2.1 V with an energy density of 33.0 W h kg-1 and superior cyclability with 88.2% capacitance retention at 4 A g-1 after 6000 cycles comparable to those supercapacitors using high-cost LiTFSI salts. Besides, the supercapacitor with excellent temperature stability in the range of -20 to 70 °C can light an LED for more than one minute. The assembled flexible device with the PAAK/CMC-24 M gel film sandwiched in between demonstrates excellent bendability from 0° to 180° and shows great potential for flexible/wearable electronic devices. Our feasible approach provides a new route for assembling quasi-solid-state flexible high-energy storage devices with "water-in-salt" electrolytes.

PD-1 Affects the Immunosuppressive Function of Group 2 Innate Lymphoid Cells in Human Non-Small Cell Lung Cancer.

Background: There is increasing evidence that group 2 innate lymphoid cells (ILC2s) play an essential role in allergy and parasitic infection. However, the role of ILC2s in human lung cancer remains unclear. Methods: ILC2s from peripheral blood mononuclear cells (PBMCs) obtained from healthy donors (HDs) and non-small cell lung cancer (NSCLC) patients, and NSCLC tumor tissues were analyzed via multicolor flow cytometry. ILC2s or CD14+ cells were sorted by fluorescence-activated cell sorting. qPCR and flow cytometry were performed to assess the gene and protein expression of the indicated molecules. M1-like and M2-like macrophages were induced from CD14+ monocytes in vitro. Results: ILC2s were significantly more enriched in PBMCs and tumor tissues from NSCLC patients than in HDs. After screening for the main immune checkpoint molecules, we found that PD-1 was upregulated in ILC2s in NSCLC patients. Functionally, PD-1high ILC2s from tumor tissues expressed higher levels of IL-4 and IL-13 regarding both mRNA and protein levels than PD-1low ILC2s. Furthermore, PD-1high ILC2s robustly boosted M2-like macrophage polarization in vitro, by secreting IL-4 and IL-13, while neutralization of IL-4 and IL-13 by antibodies abrogated M2-like macrophage polarization. Conclusion: ILC2s are enriched in NSCLC patients and upregulate PD-1 expression. Upregulation of PD-1 facilitates the immunosuppressive function of ILC2s. PD-1high ILC2s enhance M2-like macrophage polarization by secreting IL-4 and IL-13. PD-1 acts as a positive regulator of the immunosuppressive function of ILC2s in human NSCLC.

Dynamic Changes, Spatiotemporal Differences and Factors Influencing the Urban Eco-Efficiency in the Lower Reaches of the Yellow River.

The measurement of eco-efficiency is an important tool to evaluate the level of urban sustainable development. Therefore; improving urban eco-efficiency in the lower reaches of the Yellow River ensures the implementation of ecological protection and high-quality development strategies in the Yellow River Basin. In this study; the dynamic changes of urban eco-efficiency and spatiotemporal differences in the lower reaches of the Yellow River were investigated using the Super-SBM (Super-Slack measure model) model with undesirable outputs and standard deviation ellipse. The STIRPAT (Stochastic Impacts by Regression Population; Affluence and Technology) model was introduced to analyze the factors affecting the change in urban eco-efficiency. The results showed that the overall urban eco-efficiency in the lower reaches of the Yellow River has not reached the optimal level. The overall eco-efficiency in the lower reaches of the Yellow River in Shandong Province was higher than that in Henan Province but the gap is narrowing. The spatial differentiation of urban eco-efficiency in the lower reaches of the Yellow River showed the following trends: "blooming in the middle and reverse development at both ends" in the high-value area and gradual decrease in the low-value area. From 2007 to 2018; a direction was notable with respect to the development of urban eco-efficiency in the lower reaches of the Yellow River; with the centripetal force weakening. Although the mean center of urban eco-efficiency located in Shandong Province; it notably shifted to the west during the study period. In terms of driving factors; affluence and technological progress play positive roles in driving eco-efficiency; while investment intensity; industrial structure; and foreign investment intensity hindered the optimization and improvement of urban eco-efficiency in the lower reaches of the Yellow River. The results of this study show that urban eco-efficiency in the lower reaches of the Yellow River is improving; but the regional coordination is poor. The main methods promoting the sustainable development in the study area include changing the mode of extensive investments and the introduction of foreign capital; which improve the energy efficiency and promote faster and better economic development.

Ternary PtFeCo alloys on graphene with high electrocatalytic activities for methanol oxidation.

Ternary PtFeCo alloys as alternatives to conventional Pt electrocatalysts are highly important in the field of the methanol oxidation reaction. In this study, we demonstrate a one-pot two-step reduction method for the synthesis of graphene supported PtFeCo alloy nanocomposites as an integrated binder-free catalyst. The synergistic effect of alloying with Fe and Co as well as graphene decorating contributes to an increase in the utilization of the noble metal, namely, reducing the amount of Pt in the nanocomposites to 7%. After tailoring the elemental composition of the alloys, Pt52Fe29Co19@G-7% exhibits a mass activity/specific activity of 1758.2 mA mg-1Pt/3.42 mA cm-2 that is 3.13/3.45 times that of commercial Pt/C in an acidic medium. Impressively, it showed a superior mass current density of 9356.1 mA mg-1Pt at 60 °C which is close to the operating temperature of direct methanol fuel cells. Moreover, the as-obtained Pt52Fe29Co19@G-7% also exhibited excellent CO tolerance and reliable stability compared to commercial Pt/C. The structural characterization further verifies that the surface strain and electronic effect play a critical role in determining the electrocatalytic properties of PtFeCo@G nanocomposites for the methanol oxidation reaction.