Rubisco and sucrose synthesis and translocation are involved in the regulation of photosynthesis in wheat with different source-sink relationships.

Source-sink relationships influence photosynthesis. So far, the limiting factors for photosynthesis of wheat cultivars with different source-sink relationships have not been determined. We aimed to determine the variation patterns of photosynthetic characteristics of wheat cultivars with different source-sink relationships. In this study, two wheat cultivars with different source-sink relationships were selected for photosynthetic physiological analyses. The results showed that YM25 (source-limited cultivar) had higher photosynthetic efficiency compared to YM1 (sink-limited cultivar). This is mainly due to a stronger photochemical efficiency, electron transfer capacity, and Rubisco carboxylation capacity of YM25. YM25 accumulated less soluble carbohydrates in flag leaves than YM1. This is mainly due to the stronger sucrose synthesis and transport capacity of YM25 by presenting higher sucrose-related enzyme activities and gene expression. A PCA analysis showed that Rubisco was the main factor limiting the photosynthetic capacity of YM25. The soluble sugar accumulation in flag leaves and sink limitation decreased the photosynthetic activity of YM1. Increased N application improved source-sink relationships and increased grain yield and source leaf photosynthetic capacity in both two wheat cultivars. Taken together, our findings suggest that Rubisco and sucrose synthesis and translocation are involved in the regulation of photosynthesis of wheat cultivars with different source-sink relationships and that source and sink limitation effects should be considered in photosynthesis.

Comparative study on the efficacy of PRP gel and UC-MSCs gel as adjuvant therapies in the treatment of DFU wounds.

BACKGROUND: Diabetic foot ulcer (DFU) is a common and serious complication of diabetes, and its treatment is challenging. Platelet-rich plasma (PRP) gel and umbilical cord mesenchymal stem cells (UC-MSCs) gel have been concerned as new therapies for DFU in recent years, and comparative studies on the efficacy and mechanisms of these methods, however, are rarely reported. METHODS: Thirty patients with DFU were selected and divided into the PRP group and the UC-MSCs group, and wound healing, foot blood vessels (ABI index), infection index (CRP), neuropathy symptoms (TCSS score), and foot skin temperature before and after treatment were compared between the two groups. SPSS 21.0 was used for statistical analysis. RESULTS: The results showed that the efficacy of the UC-MSCs gel group was significantly better than that of the PRP group in terms of wound healing rate, time to complete wound closure, ABI index, CRP level and TCSS score. No statistically significant difference in foot skin temperature was observed between the two groups. CONCLUSION: The efficacy of UC-MSCs gel is significantly superior to that of PRP gel in the treatment of DFU, with shortened time to complete wound closure, increased wound healing rate, better pain and infection control, and improved vascular and neurological symptoms.

Crystalline/Amorphous Mo-Ni(OH)2/FexNiy(OH)3x+2y hierarchical nanotubes as efficient electrocatalyst for overall water splitting.

The development of efficient bifunctional catalysts for overall water splitting is highly desirable and essential for the advancement of hydrogen technology. In this work, Mo-Ni(OH)2/FexNiy(OH)3x+2y with hierarchical nanotube structure is constructed on flexible carbon cloth (CC) through simple electrochemical deposition and hydrothermal method. The hollow tube-structure is in favor of both exposing active sites and enhancing mass transfer capability. Moreover, the doping of Mo can enhance the electronic conductivity of heterostructures. The interfacial interaction between amorphous and crystal can enhance effectively the charge transfer kinetics across the interface. Therefore, Mo-Ni(OH)2/FexNiy(OH)3x+2y can achieve a low overpotential of 57 mV for hydrogen evolution reaction (HER) and 229 mV for oxygen evolution reaction (OER) at 10 mA·cm-2. In addition, Mo-Ni(OH)2/FexNiy(OH)3x+2y needs a potential of only 1.54 V at 10 mA·cm-2 for overall water splitting, and retains for a long period of time (60 h) reliable. The work will provide a valuable approach to the construction of highly efficient electrocatalysts for overall water splitting.

Diagnostic Performance of Modified Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Patients Without Risk Factors for Hepatocellular Carcinoma: Comparison With World Federation for Ultrasound in Medicine and Biology Guideline.

OBJECTIVE: The aim of this study was to assess the ability of the modified contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) to distinguish malignancy in patients without known hepatocellular carcinoma (HCC) risk factors and compare diagnostic accuracy with that of the World Federation for Ultrasound in Medicine and Biology (WFUMB) guideline across radiologists with different levels of CEUS experience. METHODS: A total of 848 individuals with no hepatitis infection presenting with 870 lesions in non-cirrhotic livers were included and divided into the Testing and Validation groups. The modified CEUS LI-RADS was proposed, including downgrading of focal nodular hyperplasia with typical features. Diagnostic performance of the modified CEUS LI-RADS was assessed in the Testing group. In the Validation group, two radiologists with more than 9 y of CEUS experience (Experts) and two radiologists with less than 6 mo of CEUS experience (Novices) used both the modified CEUS LI-RADS and the WFUMB guideline to evaluate performance in diagnosis of the lesions. RESULTS: LR-5 + M (combination of modified LR-5 and modified LR-M) revealed optimal performance with a sensitivity, specificity and area under the curve (AUC) of 99.3%, 81.6% and 0.904, respectively. Novices using the modified CEUS LI-RADS outperformed those using the WFUMB guideline (AUC: 0.858 vs. 0.767, p = 0.005). Additionally, the sensitivity, specificity and AUC of Novices were comparable to those of Experts using the modified CEUS LI-RADS (94.1%, 77.6% and 0.858 vs. 96.1%, 77.6% and 0.868 for experts, respectively). CONCLUSION: The modified CEUS LI-RADS is a valuable method for distinguishing hepatic malignancy in patients without HCC risk factors. This is particularly beneficial for radiologists with limited CEUS expertise.

Network pharmacology-based research on the effect of Radix Astragali on osteosarcoma and the underlying mechanism.

To explore the anti-tumor effects of Radix Astragali on osteosarcoma and its mechanism. We analyzed the PPI network of Radix Astragali's potential targets for treating osteosarcoma and got the hub targets. We used KM curves to screen hub targets that could prolong sarcoma patients' survival time. We performed GO and KEGG enrichment analysis of Radix Astragali's potential targets and predicted Radix Astragali's molecular mechanism and function in treating osteosarcoma. The binding process between the hub targets, which could prolong sarcoma patients' survival time, and Radix Astragali was simulated through molecular docking. PPI network analysis of potential therapeutic targets discriminated 25 hub targets. The KM curves of the hub targets showed there were 13 hub targets that were effective in improving the 5-year survival rate of sarcoma patients. GO and KEGG enrichment demonstrated that Radix Astragali regulates multiple signaling pathways of osteosarcoma. Molecular docking results indicated that Radix Astragali could bind freely to the hub target, which could prolong the sarcoma patient's survival time. Radix Astragali act on osteosarcoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways. Radix Astragali has the potential to become a drug for treating osteosarcoma and prolonging the sarcoma patient's survival time.

Thermal Interface Engineering in a 3D-Structured Carbon Framework for a Phase-Change Composite with High Thermal Conductivity.

Phase-change materials (PCMs) are promising thermal storage medium for thermal management due to their efficient thermal energy harvesting capabilities. However, the low thermal conductivity (TC) and poor shape stability of PCMs have hindered their practical applications. Construction of an interconnected three-dimensional (3D) heat-conductive structure is an effective way to build phonon conduits and provide PCM confinement. Phonon scattering at the interface is an unavoidable effect that undermines the TC improvement in the PCM composite and necessitates careful engineering. This study focuses on creating a highly thermally conductive 3D carbon-bonded graphite fiber (CBGF) network to enhance the TC of the PCM, with attention especially on thermal interface engineering considering both filler-matrix (F-M) and filler-filler (F-F) interfaces. The composite with an optimized proportion of F-M and F-F interface area achieves the highest TC of 45.48 W·m-1·K-1, which is 188.5 times higher than that of the pure PCM, and a high TC enhancement per volume fraction of the filler (TCEF) of 831% per 1 vol % loading. This also results in an enhanced spatial construction for PCM confinement during the phase change. The results emphasize the significance of interface engineering in creating high-TC and form-stable phase-change composites, providing insightful guidance for rational structural design.

A new formulation of dezocine, Cyc-dezocine, reduces oxycodone self-administration in female and male rats.

Dezocine is a partial mu opioid receptor agonist previously used as an analgesic for perioperative acute pain in the US and is now the most used perioperative analgesic in China. In general, dezocine is well-tolerated, with relatively minimal risk of fatal respiratory depression. To our knowledge, there are no reports of dezocine addiction, which suggests that the abuse liability of dezocine is low. The overarching goal of this study was to determine the efficacy of a novel formulation of dezocine (Cyc-dezocine), developed for intraperitoneal or intranasal administration, to reduce voluntary opioid taking in rats. One cohort of male rats self-administered intravenous oxycodone on a fixed-ratio 5 schedule of reinforcement. Once oxycodone taking stabilized, rats were pretreated with systemic injections of vehicle or Cyc-dezocine. Cyc-dezocine dose-dependently reduced intravenous oxycodone self-administration. A second cohort of male and female rats self-administered oral oxycodone from drinking water. Once oxycodone taking stabilized, rats were pretreated with intra-nasal Cyc-dezocine. Consistent with the effects of i.p. Cyc-dezocine in our intravenous oxycodone studies, intra-nasal Cyc-dezocine attenuated oral oxycodone self-administration. Together, these findings support the need for further studies investigating the therapeutic potential of Cyc-dezocine for treating opioid use disorder.

Preparation of Phillygenin-Hyaluronic acid composite milk-derived exosomes and its anti-hepatic fibrosis effect.

Liver fibrosis remains a serious problem affecting the health of millions of people worldwide. Hepatic stellate cells (HSCs) are the main effector cells in liver fibrosis and their activation could lead to extracellular matrix deposition, which may aggravate the development of liver fibrosis and inflammation. Previous studies have reported the potential of Phillygenin (PHI) as a hepatoprotective agent to inhibit HSCs activation and fibrosis development. However, the poor water solubility of PHI hinders its clinical application as a potential anti-liver fibrosis therapy. Milk-derived exosomes (mEXO) serve as scalable nanocarriers for delivering chemotherapeutic agents due to their excellent biocompatibility. Here, we developed a PHI-Hyaluronic acid (HA) composite mEXO (PHI-HA-mEXO) drug delivery system, in which DSPE-PEG2000-HA was conjugated to the surface of mEXO to prepare HA-mEXO, and PHI was encapsulated into HA-mEXO to form PHI-HA-mEXO. As a specific receptor for HA, CD44 is frequently over-expressed during liver fibrosis and highly expressed on the surface of activated HSCs (aHSCs). PHI-HA-mEXO can bind to CD44 and enter aHSCs through endocytosis and release PHI. PHI-HA-mEXO drug delivery system can significantly induce aHSCs death without affecting quiescent HSCs (qHSCs) and hepatocytes. Furthermore, we carried out in vitro and in vivo experiments and found that PHI-HA-mEXO could alleviate liver fibrosis through aHSCs-targeted mechanism. In conclusion, the favorable biosafety and superior anti-hepatic fibrosis effects suggest a promising potential of PHI-HA-mEXO in the treatment of hepatic fibrosis. However, detailed pharmokinetics and dose-responsive experiments of PHI-HA-mEXO and the mechanism of mEXO loading drugs are still required before PHI-HA-mEXO can be applied clinically.

PECAM-1 drives ß-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression, although the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives ß-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer. METHODS: The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3ß/ß-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests. RESULTS: DM promoted the progression and EndMT occurrence of colon cancer (CC). Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted ß-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3ß signaling was enhanced to inhibit the degradation of ß-catenin, which regulates the process of EndMT. CONCLUSIONS: PECAM-1 defects and/or internalization are key events for ß-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3ß signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC. Video Abstract.

Fabrication and Oxidation Resistance of a Novel MoSi2-ZrB2-Based Coating on Mo-Based Alloy.

To enhance the oxidation resistance of Mo-based TZM alloy (Mo-0.5Ti-0.1Zr-0.02C, wt%), a novel MoSi2-ZrB2 composite coating was applied on the TZM substrate by a two-step process comprising the in situ reaction of Mo, Zr, and B4C to form a ZrB2-MoB pre-layer followed by pack siliconizing. The as-packed coating was composed of a multi-layer structure, consisting of a MoB diffusion layer, an MoSi2-ZrB2 inner layer, and an outer layer of mixture of MoSi2 and Al2O3. The composite coating could provide excellent oxidation-resistant protection for the TZM alloy at 1600 °C. The oxidation kinetic curve of the composite coating followed the parabolic rule, and the weight gain of the coated sample after 20 h of oxidation at 1600 °C was only 5.24 mg/cm2. During oxidation, a dense and continuous SiO2-baed oxide scale embedded with ZrO2 and ZrSiO4 particles showing high thermal stability and low oxygen permeability could be formed on the surface of the coating by oxidation of MoSi2 and ZrB2, which could hinder the inward diffusion of oxygen at high temperatures. Concurrently, the MoB inner diffusion layer played an important role in hindering the diffusion of Si inward with regard to the TZM alloy and could retard the degradation of MoSi2, which could also improve the long life of the coating.

Silicon mediated redox homeostasis in the root-apex transition zone of rice plays a key role in aluminum tolerance.

The supply of silicon (Si) mitigates the aluminum (Al) toxicity on plant root growth, while the underlying mechanism remains unknown. Transition zone (TZ) emerges as the Al-toxicity target of plant root apex. The objective of the study was to evaluate the effect of Si on redox homeostasis in root-apex TZ of rice seedlings under Al stress. Si alleviated Al toxicity as revealed by promotion of root elongation and less Al accumulation. In Si-deprived plants, treatment with Al altered the normal distribution of superoxide anion (O2·-) and hydrogen peroxide (H2O2) in root tip. Al induced a significant increase of reactive oxygen species (ROS) in root-apex TZ, resulting in the peroxidation of membrane lipid and loss of plasma membrane integrity in root-apex TZ. However, Si greatly increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and enzymes involved in ascorbate-glutathione (AsA-GSH) cycle in root-apex TZ under Al stress, and enhanced AsA and GSH contents, which reduced ROS and callose contents, thereby reducing malondialdehyde (MDA) content and Evans blue uptake. These results allow to precise the changes of ROS in root-apex TZ after exposure to Al, and the positive role of Si in maintaining redox balance in root-apex TZ.

The protective effect of forsythiaside A on 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestatic liver injury in mice: Based on targeted metabolomics and molecular biology technology.

Cholestasis is a disorder of bile secretion and excretion caused by a variety of etiologies. At present, there is a lack of functional foods or drugs that can be used for intervention. Forsythiaside A (FTA) is a natural phytochemical component isolated from the medicinal plant Forsythia suspensa (Thunb.) Vahl, which has a significant hepatoprotective effect. In this study, we investigated whether FTA could alleviate liver injury induced by cholestasis. In vitro, FTA reversed the decrease in viability of human intrahepatic bile duct epithelial cells, the decrease in antioxidant enzymes (SOD1, CAT and GSH-Px), and cell apoptosis induced by lithocholic acid. In vivo, FTA protected mice from 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury, abnormal serum biochemical indexes, abnormal bile duct hyperplasia, and inflammatory infiltration. Furthermore, FTA treatment alleviated liver fibrosis by inhibiting collagen deposition and HSC activation. The metabonomic results showed that DDC-induced bile acid disorders in the liver and serum were reversed after FTA treatment, which may benefit from the activation of the FXR/BSEP axis. In addition, FTA treatment increased the levels of antioxidant enzymes in the serum and liver. Meanwhile, FTA treatment inhibited ROS and MDA levels and cleaved caspase 3 protein expression, thereby reducing DDC-induced hepatic oxidative stress and apoptosis. Further studies showed that the antioxidant effects of FTA were dependent on the activation of the BRG1/NRF2/HO-1 axis. In a word, FTA has a significant hepatoprotective effect on cholestatic liver injury, and can be further developed as a functional food or drug to prevent and treat cholestatic liver injury.

Calcitonin receptor signaling in nucleus accumbens D1R- and D2R-expressing medium spiny neurons bidirectionally alters opioid taking in male rats.

The high rates of relapse associated with current medications used to treat opioid use disorder (OUD) necessitate research that expands our understanding of the neural mechanisms regulating opioid taking to identify molecular substrates that could be targeted by novel pharmacotherapies to treat OUD. Recent studies show that activation of calcitonin receptors (CTRs) is sufficient to reduce the rewarding effects of addictive drugs in rodents. However, the role of central CTR signaling in opioid-mediated behaviors has not been studied. Here, we used single nuclei RNA sequencing (snRNA-seq), fluorescent in situ hybridization (FISH), and immunohistochemistry (IHC) to characterize cell type-specific patterns of CTR expression in the nucleus accumbens (NAc), a brain region that plays a critical role in voluntary drug taking. Using these approaches, we identified CTRs expressed on D1R- and D2R-expressing medium spiny neurons (MSNs) in the medial shell subregion of the NAc. Interestingly, Calcr transcripts were expressed at higher levels in D2R- versus D1R-expressing MSNs. Cre-dependent viral-mediated miRNA knockdown of CTRs in transgenic male rats was then used to determine the functional significance of endogenous CTR signaling in opioid taking. We discovered that reduced CTR expression specifically in D1R-expressing MSNs potentiated/augmented opioid self-administration. In contrast, reduced CTR expression specifically in D2R-expressing MSNs attenuated opioid self-administration. These findings highlight a novel cell type-specific mechanism by which CTR signaling in the ventral striatum bidirectionally modulates voluntary opioid taking and support future studies aimed at targeting central CTR-expressing circuits to treat OUD.

Orthogonal Experimental Optimization of Preparation and Microstructural Properties of a Diffusion Barrier for Tantalum-Based Silicide Coatings.

To solve the problem of silicide coatings on tantalum substrates failing due to elemental diffusion under high-temperature oxidation environments and to find diffusion barrier materials with excellent effects of impeding Si elemental spreading, TaB2 and TaC coatings were prepared on tantalum substrates by the encapsulation and infiltration methods, respectively. Through orthogonal experimental analysis of the raw material powder ratio and pack cementation temperature, the best experimental parameters for the preparation of TaB2 coatings were selected: powder ratio (NaF:B:Al2O3 = 2.5:1:96.5 (wt.%)) and pack cementation temperature (1050 °C). After diffusion treatment at 1200 °C for 2 h, the thickness change rate of the Si diffusion layer prepared using this process was 30.48%, which is lower than that of non-diffusion coating (36.39%). In addition, the physical and tissue morphological changes of TaC and TaB2 coatings after siliconizing treatment and thermal diffusion treatment were compared. The results prove that TaB2 is a more suitable candidate material for the diffusion barrier layer of silicide coatings on tantalum substrates.

Accelerating the solar-thermal energy storage via inner-light supplying with optical waveguide.

Solar-thermal storage with phase-change material (PCM) plays an important role in solar energy utilization. However, most PCMs own low thermal conductivity which restricts the thermal charging rate in bulk samples and leads to low solar-thermal conversion efficiency. Here, we propose to regulate the solar-thermal conversion interface in spatial dimension by transmitting the sunlight into the paraffin-graphene composite with side-glowing optical waveguide fiber. This inner-light-supply mode avoids the overheating surface of the PCM, accelerates the charging rate by 123% than that of the traditional surface irradiation mode and increases the solar thermal efficiency to ~94.85%. Additionally, the large-scale device with inner-light-supply mode works efficiently outdoors, indicating the potential of this heat localization strategy in practical application.

Network pharmacology-based research on the effect of angelicin on osteosarcoma and the underlying mechanism.

To explore the antitumor effects of angelicin on osteosarcoma and the underlying mechanism. We aimed to elucidate the mechanism by network pharmacology, molecular docking, and in vitro experiments. We analyzed a PPI network of potential angelicin targets in the treatment of osteosarcoma and identified hub targets. We systematically performed GO and KEGG enrichment analyses of the potential targets of angelicin, and we predicted it function in osteosarcoma treatment and the underlying molecular mechanism. Through molecular docking, the interactions between hub targets and angelicin were simulated, and then, the hub targets of angelicin were identified. Based on these results, we validated the effects of angelicin on osteosarcoma cells by conducting in vitro experiments. The PPI network analysis of potential therapeutic targets identified four apoptosis-related hub targets, namely, BCL-2, Casp9, BAX and BIRC 2. GO and KEGG enrichment analyses demonstrated that angelicin regulates osteosarcoma cell apoptosis. Molecular docking results indicated that angelicin can freely bind to the hub targets listed above. In vitro experiments showed that angelicin promoted osteosarcoma cell apoptosis in a dose-dependent manner and inhibited osteosarcoma cell migration and proliferation in a time- and dose-dependent manner. The RT-PCR results showed that angelicin simultaneously promoted the mRNA expression of Bcl-2 and Casp9 and inhibited the mRNA expression of BAX and BIRC 2. Angelicin promotes osteosarcoma cell apoptosis and inhibits osteosarcoma cell proliferation and migration by activating a signaling network that is composed of hub targets that link multiple signaling pathways. Angelicin could become an alternative drug for the treatment of osteosarcoma.

Celastrol as an emerging anticancer agent: Current status, challenges and therapeutic strategies.

Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicine Tripterygium wilfordii Hook F., which has multiple pharmacological activities. In particular, modern pharmacological studies have demonstrated that celastrol exhibits significant broad-spectrum anticancer activities in the treatment of a variety of cancers, including lung cancer, liver cancer, colorectal cancer, hematological malignancies, gastric cancer, prostate cancer, renal carcinoma, breast cancer, bone tumor, brain tumor, cervical cancer, and ovarian cancer. Therefore, by searching the databases of PubMed, Web of Science, ScienceDirect and CNKI, this review comprehensively summarizes the molecular mechanisms of the anticancer effects of celastrol. According to the data, the anticancer effects of celastrol can be mediated by inhibiting tumor cell proliferation, migration and invasion, inducing cell apoptosis, suppressing autophagy, hindering angiogenesis and inhibiting tumor metastasis. More importantly, PI3K/Akt/mTOR, Bcl-2/Bax-caspase 9/3, EGFR, ROS/JNK, NF-κB, STAT3, JNK/Nrf2/HO-1, VEGF, AR/miR-101, HSF1-LKB1-AMPKα-YAP, Wnt/ß-catenin and CIP2A/c-MYC signaling pathways are considered as important molecular targets for the anticancer effects of celastrol. Subsequently, studies of its toxicity and pharmacokinetic properties showed that celastrol has some adverse effects, low oral bioavailability and a narrow therapeutic window. In addition, the current challenges of celastrol and the corresponding therapeutic strategies are also discussed, thus providing a theoretical basis for the development and application of celastrol in the clinic.

An estrogen response-related signature predicts response to immunotherapy in melanoma.

Background: Estrogen/estrogen receptor signaling influences the tumor microenvironment and affects the efficacy of immunotherapy in some tumors, including melanoma. This study aimed to construct an estrogen response-related gene signature for predicting response to immunotherapy in melanoma. Methods: RNA sequencing data of 4 immunotherapy-treated melanoma datasets and TCGA melanoma was obtained from open access repository. Differential expression analysis and pathway analysis were performed between immunotherapy responders and non-responders. Using dataset GSE91061 as the training group, a multivariate logistic regression model was built from estrogen response-related differential expression genes to predict the response to immunotherapy. The other 3 datasets of immunotherapy-treated melanoma were used as the validation group. The correlation was also examined between the prediction score from the model and immune cell infiltration estimated by xCell in the immunotherapy-treated and TCGA melanoma cases. Results: "Hallmark Estrogen Response Late" was significantly downregulated in immunotherapy responders. 11 estrogen response-related genes were significantly differentially expressed between immunotherapy responders and non-responders, and were included in the multivariate logistic regression model. The AUC was 0.888 in the training group and 0.654-0.720 in the validation group. A higher 11-gene signature score was significantly correlated to increased infiltration of CD8+ T cells (rho=0.32, p=0.02). TCGA melanoma with a high signature score showed a significantly higher proportion of immune-enriched/fibrotic and immune-enriched/non-fibrotic microenvironment subtypes (p<0.001)-subtypes with better response to immunotherapy-and significantly better progression-free interval (p=0.021). Conclusion: In this study, we identified and verified an 11-gene signature that could predict response to immunotherapy in melanoma and was correlated with tumor-infiltrating lymphocytes. Our study suggests targeting estrogen-related pathways may serve as a combination strategy for immunotherapy in melanoma.

Improving the Encapsulation Efficiency of Lipase in Molecular Cages and Its Application.

Here, lipase encapsulation is constructed by locking enzyme molecules in nanomolecular cages on the surface of SH-PEI@PVAC magnetic microspheres. To improve the encapsulation efficiency in enzyme loading, the thiol group is efficiently modified on the grafted polyethyleneimine (PEI) using 3-mercaptopropionic acid. N2 adsorption-desorption isotherms reveal the existence of mesoporous molecular cages on the microsphere surface. The robust immobilizing strength of carriers to lipase demonstrates the successful encapsulation of enzymes in nanomolecular cages. The encapsulated lipase shows high enzyme loading (52.9 mg/g) and high activity (51.4 U/mg). Different sizes of molecular cages are established, and the cage size showed important effects on lipase encapsulation. It shows that enzyme loading is low at a small size of molecular cages, which is attributed to that the nanomolecular cage is too small to house lipase. The investigation in lipase conformation suggests that the encapsulated lipase retains its active conformation. Compared with the adsorbed lipase, the encapsulated lipase shows higher thermal stability (4.9 times) and higher resistance to denaturants (5.0 times). Encouragingly, the encapsulated lipase shows high activity and reusability in lipase-catalyzed synthesis of propyl laurate, suggesting the potential application value of encapsulated lipase.

Fabrication of a corn stalk derived cellulose-based bio-adsorbent to remove Congo red from wastewater: Investigation on its ultra-high adsorption performance and mechanism.

A cellulose-based bio-absorbent with various and plenty of amino groups was successfully prepared from corn stalk to achieve quantitative removal of Congo red from wastewater with wide pH values (5 ≤ pH ≤ 10). The maximum removal amount was 8.0 mmol·g-1 (5572 mg·g-1) under pH = 6.0 and 45 °C, which was obviously higher than reported absorbents. Investigation on dynamic adsorption and recyclability in authentic wastewater found that the removal efficiency of Congo red was >98 % within 180 min and decreased slightly in industrial water after five cycles, denoting this adsorbent with great potential for environmental application. The characterization results proved that 7.58 mmol·g-1 of different amino groups (-NH2, -NH- and -NR2) were introduced on adsorbent surface by two steps of modification and were the major functional groups for adsorption of Congo red. The inferred adsorption mechanism revealed that Congo red could be adsorbed equivalently on the amino groups by strong electrostatic interactions or hydrogen bonds. Different amino groups played different roles in adsorption due to great differences in protonation ability in 5 ≤ pH ≤ 10. The study was expected to high-efficiently remove Congo red from acidic or alkaline wastewater, and offered an alternative strategy for biowaste treatment of corn stalks in a high value-added manner.