Modulation of copper sites in porphyrin metal-organic frameworks for electrochemical ascorbic acid sensing.

Two metal-organic frameworks (MOFs) with different Cu-centered coordination structures were synthesized. By introducing 4,4-bipyridine as a linker in the Cu-MOFs, we have discovered that Cu-O, instead of Cu-N, is the active site with higher electrocatalytical activity towards ascorbic acid, which is essential to understand and develop Cu-based ascorbic acid sensors.

Investigation of the biocontrol mechanism of a novel Pseudomonas species against phytopathogenic Fusarium graminearum revealed by multi-omics integration analysis.

Phytopathogenic Fusarium graminearum poses significant threats to crop health and soil quality. Although our laboratory-cultivated Pseudomonas sp. P13 exhibited potential biocontrol capacities, its effectiveness against F. graminearum and underlying antifungal mechanisms are still unclear. In light of this, our study investigated a significant inhibitory effect of P13 on F. graminearum T1, both in vitro and in a soil environment. Conducting genomic, metabolomic, and transcriptomic analyses of P13, we sought to identify evidence supporting its antagonistic effects on T1. The results revealed the potential of P13, a novel Pseudomonas species, to produce active antifungal components, including phenazine-1-carboxylate (PCA), hydrogen cyanide (HCN), and siderophores [pyoverdine (Pvd) and histicorrugatin (Hcs)], as well as the dynamic adaptive changes in the metabolic pathways of P13 related to these active ingredients. During the logarithmic growth stage, T1-exposed P13 strategically upregulated PCA and HCN biosynthesis, along with transient inhibition of the tricarboxylic acid (TCA) cycle. However, with growth stabilization, upregulation of PCA and HCN synthesis ceased, whereas the TCA cycle was enhanced, increasing siderophores secretion (Pvd and Hcs), suggesting that this mechanism might have caused continuous inhibition of T1. These findings improved our comprehension of the biocontrol mechanisms of P13 and provided the foundation for potential application of Pseudomonas strains in the biocontrol of phytopathogenic F. graminearum. IMPORTANCE: Pseudomonas spp. produces various antifungal substances, making it an effective natural biocontrol agent against pathogenic fungi. However, the inhibitory effects and the associated antagonistic mechanisms of Pseudomonas spp. against Fusarium spp. are unclear. Multi-omics integration analyses of the in vitro antifungal effects of novel Pseudomonas species, P13, against F. graminearum T1 revealed the ability of P13 to produce antifungal components (PCA, HCN, Pvd, and Hcs), strategically upregulate PCA and HCN biosynthesis during logarithmic growth phase, and enhance the TCA cycle during stationary growth phase. These findings improved our understanding of the biocontrol mechanisms of P13 and its potential application against pathogenic fungi.

Fe3O4/biochar modified with molecularly imprinted polymer as efficient persulfate activator for salicylic acid removal from wastewater: Performance and specific recognition mechanism.

In this study, a novel Fe3O4-based biochar coupled surface-imprinted polymer was constructed via simple hydrothermal route for salicylic acid recognition and degradation in advanced oxidation processes. The material exhibited excellent adsorption capability, up to 118.23 mg g-1, and efficient degradation performance, 87.44% removal rate within 240 min, based on integrating the advantages of both huge specific surface area as well as abundant functional groups from biochars and specific recognition sites from imprinted cavities. Moreover, high selectivity coefficient (11.67) showed stable recognition in single and binary systems. SO4•- and •OH were confirmed as reactive oxygen species in catalytic reaction according to quenching experiments and EPR analysis. The degradation mechanism and pathway were unraveled by DFT calculations and LC-MS. Furthermore, the results of toxicity evaluation, stability and reusability demonstrated application potential in the field of water environment restoration. This study confirmed that molecular imprinting provided a promising solution to targeted removal of emerging environmental pollutants by degrading after the enrichment of pollutants to the composites surface.

ß-Nicotinamide Mononucleotide Promotes Cell Proliferation and Hair Growth by Reducing Oxidative Stress.

ß-Nicotinamide mononucleotide (NMN) has shown promising effects on intestinal health, and it is extensively applied as an anti-aging and Alzheimer's disease therapeutic, due to its medicinal properties. The effects of NMN on the growth of mouse hair were observed after hair removal. The results indicated that NMN can reverse the state of hair follicle atrophy, hair thinning, and hair sparsity induced by dihydrotestosterone (DHT), compared to that of minoxidil. In addition, the action mechanisms of NMN promoting hair growth in cultured human dermal papilla cells (HDPCs) treated with DHT were investigated in detail. The incubation of HDPCs with DHT led to a decrease in cell viability and the release of inflammatory mediators, including interleukin-6 (IL-6), interleukin-1Beta (IL-1ß) and tumor necrosis factor Alpha (TNF-α). It was found that NMN can significantly lower the release of inflammatory factors induced by DHT in HDPCs. HDPCs cells are protected from oxidative stress damage by NMN, which inhibits the NF-κB p65 inflammatory signaling pathway. Moreover, the levels of androgen receptor (AR), dickkopf-1 (DKK-1), and ß-catenin in the HDPCs were assessed using PCR, indicating that NMN can significantly enhance the expression of VEGF, reduced IL-6 levels and suppress the expression of AR and DKK-1, and notably increase ß-catenin expression in DHT-induced HDPCs.

Plasmon-Switched Kinetics for Formic Acid Dehydrogenation: Selective Adsorption Driven by Local Field and Hot Carriers.

Understanding illumination-mediated kinetics is essential for catalyst design in plasmon catalysis. Here we prepare Pd-based plasmonic catalysts with tunable electronic structures to reveal the underlying illumination-enhanced kinetic mechanisms for formic acid (HCOOH) dehydrogenation. We demonstrate a kinetic switch from a competitive Langmuir-Hinshelwood adsorption mode in dark to a non-competitive type under irradiation triggered by local field and hot carriers. Specifically, the electromagnetic field induces a spatial-temporal separation of dehydrogenation-favorable configurations of reactant molecule HCOOH and HCOO- due to their natural different polarities. Meanwhile, the generated energetic carriers can serve as active sites for selective molecular adsorption. The hot electrons act as adsorption sites for HCOOH, while holes prefer to adsorb HCOO- . Such unique non-competitive adsorption kinetics induced by plasmon effects serves as another typical characteristic of plasmonic catalysis that remarkably differs from thermocatalysis. This work unravels unique adsorption transformations and a kinetic switching driven by plasmon nonthermal effects.

Unipolar Solution Flow in Calcium-Organic Frameworks for Seawater-Evaporation-Induced Electricity Generation.

Seawater-flow- and -evaporation-induced electricity generation holds significant promise in advancing next-generation sustainable energy technologies. This method relies on the electrokinetic effect but faces substantial limitations when operating in a highly ion-concentrated environment, for example, natural seawater. We present herein a novel solution using calcium-based metal-organic frameworks (MOFs, C12H6Ca2O19·2H2O) for seawater-evaporation-induced electricity generation. Remarkably, Ca-MOFs show an open-circuit voltage of 0.4 V and a short-circuit current of 14 µA when immersed in seawater under natural conditions. Our experiments and simulations revealed that sodium (Na) ions selectively transport within sub-nanochannels of these synthetic superhydrophilic MOFs. This selective ion transport engenders a unipolar solution flow, which drives the electricity generation behavior in seawater. This work not only showcases an effective Ca-MOF for electricity generation through seawater flow/evaporation but also contributes significantly to our understanding of water-driven energy harvesting technologies and their potential applications beyond this specific context.

Photo-enhanced dehydrogenation of formic acid on Pd-based hybrid plasmonic nanostructures.

Coupling visible light with Pd-based hybrid plasmonic nanostructures has effectively enhanced formic acid (FA) dehydrogenation at room temperature. Unlike conventional heating to achieve higher product yield, the plasmonic effect supplies a unique surface environment through the local electromagnetic field and hot charge carriers, avoiding unfavorable energy consumption and attenuated selectivity. In this minireview, we summarized the latest advances in plasmon-enhanced FA dehydrogenation, including geometry/size-dependent dehydrogenation activities, and further catalytic enhancement by coupling local surface plasmon resonance (LSPR) with Fermi level engineering or alloying effect. Furthermore, some representative cases were taken to interpret the mechanisms of hot charge carriers and the local electromagnetic field on molecular adsorption/activation. Finally, a summary of current limitations and future directions was outlined from the perspectives of mechanism and materials design for the field of plasmon-enhanced FA decomposition.

SPA, a Stigma-style-transmitting tract Physical microenvironment Assay for investigating mechano-signaling in pollen tubes.

Accurate sensing and responding to physical microenvironment are crucial for cell function and survival, but the underlying molecular mechanisms remain elusive. Pollen tube (PT) provides a perfect single-cell model for studying mechanobiology since it's naturally subjected to complex mechanical instructions from the pistil during invasive growth. Recent reports have revealed discrepant PT behaviors between in vivo and flat, two-dimensional in vitro cultures. Here, we established the Stigma-style-transmitting tract (TT) Physical microenvironment Assay (SPA) to recapitulate pressure changes in the pistil. This biomimetic assay has enabled us to swiftly identify highly redundant genes, GEF8/9/11/12/13, as new regulators for maintaining PTs integrity during style-to-TT emergence. In contrast to normal growth on solid medium, SPA successfully phenocopied gef8/9/11/12/13 PT in vivo growth-arrest deficiency. Our results suggest the existence of distinct signaling pathways regulating in vivo and in vitro PT integrity maintenance, underscoring the necessity of faithfully mimicking the physical microenvironment for studying plant cell biology.

Induced Resistance Mechanism of Bacillus velezensis S3-1 Against Pepper Wilt.

In recent years, pepper wilt has emerged as a pivotal constraint on pepper yield augmentation. Bacillus velezensis S3-1, with a wide array of hosts, can be used as both a biocontrol agent and biofertilizer. Nonetheless, the precise mechanisms underpinning its employment in combating pepper wilt remain cloaked in ambiguity. In our study, we found that B. velezensis S3-1 could significantly inhibit Fusarium sp. F1T that caused pepper wilt. S3-1 could effectively inhibit both the growth and germination of F1T conidia, leading to a reduction in the spore germination percentage from 83.2 to 37.1% in vitro experiments. Additionally, leaf detachment experiments revealed that the volatile compounds produced by S3-1 could inhibit the spread of pepper leaf spot area. Moreover, we observed a significant decrease in the content of malondialdehyde (MDA) in pepper treated with S3-1, along with a significant increase in the content of soluble protein, polyphenol oxidase (PPO), peroxidase (POD), and phenylalanine ammonia-lyase (PAL) in pepper. Furthermore, RT-PCR analysis showed that the expression of the defense genes CaPR 1 and CaPIN II in pepper after treatment with S3-1 was significantly upregulated, suggesting that S3-1 had the potential to induce systemic resistance in pepper, thereby enhancing its disease resistance. Hence, our findings suggest that S3-1 can be a promising biocontrol agent for managing pepper wilt in modern agriculture.

The Factor beyond Schmidt's Criteria Impacting the Photo-Induced [2+2] Cycloaddition Reactivity and Photoactuation of Molecular Crystals Based on Cyclic Chalcone Analogues.

Generally, the potential reactive "olefin pairs" in the molecular crystals satisfying Schmidt's criteria could undergo topological [2+2] cycloaddition. In this study, another factor that affects the photodimerization reactivity of chalcone analogues was found. The cyclic chalcone analogues of (E)-2-(2,4-dichlorobenzylidene)-2,3-dihydro-1H-inden-1-one (BIO), (E)-2-(naphthalen-2-ylmethylene)-2,3-dihydro-1H-inden-1-one (NIO), (Z)-2-(2,4-dichlorobenzylidene)benzofuran-3(2H)-one (BFO), and (Z)-2-(2,4-dichlorobenzylidene)benzo[b]thiophen-3(2H)-one (BTO) have been synthesized. While the geometrical parameters for the molecular packing of the above four compounds did not exceed Schmidt's criteria, [2+2] cycloaddition did not occur in the crystals of BIO and BTO. The single crystal structures and Hirshfeld surface analyses revealed that interactions of C=O⋅⋅⋅H (CH2 ) existed between adjacent molecules in the crystal of BIO. Therefore, the carbonyl and methylene groups linked with one carbon atom in carbon-carbon double bond were tightly confined in the lattice, acting as a tweezer to inhibit free movement of the double bond and suppressing [2+2] cycloaddition. In the crystal of BTO, similar interactions of Cl⋅⋅⋅S and C=O⋅⋅⋅H (C6 H4 ) prevented free movement of the double bond. In contrast, the intermolecular interaction of C=O⋅⋅⋅H only exists around the carbonyl group in the crystals of BFO and NIO, leaving the C=C double bonds to move freely and allowing the occurrence of [2+2] cycloaddition. Driven by photodimerization, the needle-like crystals of BFO and NIO displayed evident photo-induced bending behavior. This work demonstrates that the intermolecular interactions around carbon-carbon double bond affect the [2+2] cycloaddition reactivity except for Schmidt's criteria. These findings provide valuable insights into the design of photomechanical molecular crystalline materials.

Real-Time Image-Guided Navigation in the Management of Alveolar Cleft Repair.

Objectives: To present the use of dynamic navigation system in the repair of alveolar cleft. Patients and Participants: A total of three non-syndromic patients with unilateral alveolar cleft were involved in this study. Real-time computer-aided navigation were used to achieve restoration and reconstruction with standardized surgical technique. Methods: With the individual virtual 3-dimensional (3-D) modeling based on computed tomography (CT) data, preoperative planning and surgical simulation were carried out with the navigation system. During preoperative virtual planning, the defect volume or the quantity of graft is directly assessed at the surgical region. With the use of this system, the gingival periosteum flap incision can be tracked in real-time, and the bone graft can be navigated under the guidance of the 3-D views until it matches the preoperatively planned position. Results: Three patients with alveolar cleft were successfully performed under navigation guidance. Through the model alignment procedure, accurate matches between the actual intraoperative position and the CT images were achieved within the systematic error of 0.3 mm. The grafted bone was implanted according to the preoperative plan with the aid of instrument- and probe-based navigation. All the patients were healed well without serious complications. Conclusions: These findings suggest that image-guided surgical navigation, including preoperative planning, surgical simulation, postoperative assessment, and computer-assisted navigation was feasible and yielded good clinical outcomes. Clinical relevance: This dynamic navigation could be proved to be a valuable option for this complicated surgical procedure in the management of alveolar cleft repair.

Comprehensive Analysis of Ubiquitously Expressed Genes in Humans from A Data-driven Perspective.

Comprehensive characterization of spatial and temporal gene expression patterns in humans is critical for uncovering the regulatory codes of the human genome and understanding the molecular mechanisms of human diseases. Ubiquitously expressed genes (UEGs) refer to the genes expressed across a majority of, if not all, phenotypic and physiological conditions of an organism. It is known that many human genes are broadly expressed across tissues. However, most previous UEG studies have only focused on providing a list of UEGs without capturing their global expression patterns, thus limiting the potential use of UEG information. In this study, we proposed a novel data-driven framework to leverage the extensive collection of ∼ 40,000 human transcriptomes to derive a list of UEGs and their corresponding global expression patterns, which offers a valuable resource to further characterize human transcriptome. Our results suggest that about half (12,234; 49.01%) of the human genes are expressed in at least 80% of human transcriptomes, and the median size of the human transcriptome is 16,342 genes (65.44%). Through gene clustering, we identified a set of UEGs, named LoVarUEGs, which have stable expression across human transcriptomes and can be used as internal reference genes for expression measurement. To further demonstrate the usefulness of this resource, we evaluated the global expression patterns for 16 previously predicted disallowed genes in islet beta cells and found that seven of these genes showed relatively more varied expression patterns, suggesting that the repression of these genes may not be unique to islet beta cells.

Synergistic Combination of Fermi Level Equilibrium and Plasmonic Effect for Formic Acid Dehydrogenation.

Developing an efficient catalyst for formic acid (FA) dehydrogenation is a promising strategy for safe hydrogen storage and transportation. Herein, we successfully developed trimetallic NiAuPd heterogeneous catalysts through a galvanic replacement reaction and a subsequent chemical reduction process to boost hydrogen generation from FA decomposition at room temperature by coupling Fermi level engineering with plasmonic effect. We demonstrated that Ni worked as an electron reservoir to donate electrons to Au and Pd driven by Fermi level equilibrium whereas plasmonic Au served as an optical absorber to generate energetic hot electrons and a charge-redistribution mediator. Ni and Au worked cooperatively to promote the charge heterogeneity of surface-active Pd sites, leading to enhanced chemisorption of formate-related intermediates and eventually outstanding activity (342 mmol g-1 h-1 ) compared with bimetallic counterpart. This work offers excellent insight into the rational design of efficient catalysts for practical hydrogen energy exploitation.

Leukemia Inhibitory Factor Facilitates Self-Renewal and Differentiation and Attenuates Oxidative Stress of BMSCs by Activating PI3K/AKT Signaling.

Objective: Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) remains a hopeful therapeutic approach for bone defect reconstruction. Herein, we investigated the effects and mechanisms of leukemia inhibitory factor (LIF) in the function and viability of hypoxic BMSCs as well as bone defect repair. Methods: The effects of LIF on apoptosis (flow cytometry, TUNEL staining), mitochondrial activity (JC-1 staining), proliferation (colony formation, EdU staining), and differentiation (CD105, CD90, and CD29 via flow sorting) were examined in hypoxic BMSCs. LIF, LIFR, gp130, Keap1, Nrf2, antioxidant enzymes (SOD1, catalase, GPx-3), bone-specific matrix proteins (ALP, BSP, OCN), PI3K, and Akt were detected via immunoblotting or immunofluorescent staining. BMSCs combined with biphasic calcium phosphate scaffolds were implanted into calvarial bone defect mice, and the therapeutic effect of LIF on bone defect was investigated. Results: Hypoxic BMSCs had increased apoptosis and oxidative stress and reduced mitochondrial activity. Additionally, LIF, LIFR, and gp130 were upregulated and PI3K/Akt activity was depressed in hypoxic BMSCs. Upregulated LIF alleviated apoptosis and oxidative stress and heightened mitochondrial activity and PI3K/Akt signaling in hypoxic BMSCs. Additionally, LIF overexpression promoted self-renewal and osteogenic differentiation of BMSCs with hypoxic condition. Mechanically, LIF facilitated self-renewal and differentiation as well as attenuated oxidative stress of BMSCs through enhancing PI3K/AKT signaling activity. Implantation of LIF-overexpressed BMSC-loaded BCP scaffolds promoted osteogenesis as well as alleviated oxidative stress and apoptosis through PI3K/Akt signaling. Conclusion: Our findings demonstrate that LIF facilitates self-renewal and differentiation and attenuates oxidative stress of BMSCs by PI3K/AKT signaling.

Analysis of prognostic and therapeutic values of drug resistance-related genes in the lung cancer microenvironment.

Background: The interaction between cancer cells and stromal cells has a significant contribution in tumorigenesis and tumor development, and plays an anti-tumor immune effect under the regulation of drug resistance-related genes, which affects the outcome of patients. Coiled-coil domain-containing protein 73 (CCDC73), DLG associated protein 1 (DLGAP1), dermatan sulfate epimerase like (DSEL), estrogen receptor 1 (ESR1), and SEC14-like 5 (SEC14L5) were identified as drug resistance-related genes in lung cancer. However, these genes have no clear value in lung cancer in terms of expression and prognosis. Methods: ONCOMINE, GEPIA, UALCAN, cBioPortal, GeneMANIA, STRING, and TIMER were utilized in this study. Results: The transcriptional expression level of DLGAP1 was remarkably decreased in lung cancer tissues, while the transcriptional level of SEC14L5 was significantly increased. The pathological stage of lung adenocarcinoma (LUAD) was tightly correlated with the expression of SEC14L5. The lung cancer patients with high transcription level of CCDC73 gene tended to have a good prognosis. The function of drug resistance-related genes is mainly related to RNA polymerization. Our results showed that infiltration of six types of immune cells (dendritic cells, macrophages, neutrophils, B cells, CD4+ T cells, and CD8+ T cells) significantly correlated with the expression of these drug resistance-related genes. Conclusions: Novel screening for immunotherapy targets and prognostic biomarkers in lung cancer may draw inspiration from our results.

Lymphocyte activation gene-3 is associated with programmed death-ligand 1 and programmed cell death protein 1 in small cell lung cancer.

BACKGROUND: In recent years, immunotherapy has achieved notable success in cancer treatment. Indeed, the novel immune checkpoint lymphocyte activation gene-3 (LAG3) has shown promising therapeutic efficacy in non-small cell lung cancer. However, it is unclear about the role of LAG3 in immunotherapy and survival in small cell lung cancer (SCLC). METHODS: The expression of LAG3 in SCLC was evaluated in four public datasets. The association of LAG3 with programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and overall survival (OS) was investigated. The LAG3-related biological processes and pathways were identified by functional analyses. RESULTS: LAG3 expression was detected in SCLC tumor tissues. In the cBioPortal dataset with 81 clinical SCLC samples, LAG3 expression was markedly associated with PD-1 and PD-L1 expression (both P<0.050). In addition, Patients with high LAG3 expression had a trend toward a better OS (P=0.073). A similar survival trend was also observed in the GSE60052 dataset. Significantly, LAG3 expression was related to immune-related biological processes, such as immune response, antigen processing and presentation, and T cell co-stimulation (all P<0.001). CONCLUSIONS: This study demonstrated that LAG3 is an important immune checkpoint that is closely associated with PD-1/PD-L1. LAG3 may be a promising novel immunotherapy target for SCLC.

TMK-based cell-surface auxin signalling activates cell-wall acidification.

The phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion1. The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for five decades, but the mechanism that underlies auxin-induced cell-wall acidification is poorly characterized. Auxin induces the phosphorylation and activation of the plasma membrane H+-ATPase that pumps protons into the apoplast2, yet how auxin activates its phosphorylation remains unclear. Here we show that the transmembrane kinase (TMK) auxin-signalling proteins interact with plasma membrane H+-ATPases, inducing their phosphorylation, and thereby promoting cell-wall acidification and hypocotyl cell elongation in Arabidopsis. Auxin induced interactions between TMKs and H+-ATPases in the plasma membrane within seconds, as well as TMK-dependent phosphorylation of the penultimate threonine residue on the H+-ATPases. Our genetic, biochemical and molecular evidence demonstrates that TMKs directly phosphorylate plasma membrane H+-ATPase and are required for auxin-induced H+-ATPase activation, apoplastic acidification and cell expansion. Thus, our findings reveal a crucial connection between auxin and plasma membrane H+-ATPase activation in regulating apoplastic pH changes and cell expansion through TMK-based cell surface auxin signalling.

DNA Damage Response and Repair Gene Alterations Increase Tumor Mutational Burden and Promote Poor Prognosis of Advanced Lung Cancer.

DNA damage response and repair (DDR) gene alterations increase tumor-infiltrating lymphocytes, genomic instability, and tumor mutational burden (TMB). Whether DDR-related alterations relate to therapeutic response and prognosis in lung cancer lacking oncogenic drivers remains unknown. Pretherapeutic cancer samples of 122 patients [86 non-small cell lung cancer and 36 small cell lung cancer (SCLC)] harboring no EGFR/ALK alterations were collected. Through whole-exome sequencing, we outlined DDR mutational landscape and determined relationships between DDR gene alterations and TMB or intratumoral heterogeneity. Then, we evaluated the impacts of DDR gene alterations on therapeutic response and prognosis and established a DDR-based model for prognosis prediction. In addition, we investigated somatic interactions of DDR genes and immunomodulatory genes, immune expression patterns, immune microenvironment, and immune infiltration characteristics between DDR-deficient and DDR-proficient samples. Samples from cBioportal datasets were utilized for verification. We found that deleterious DDR gene alterations were closely associated with higher TMB than proficient-types (p < 0.001). DDR mechanisms attach great importance to the determination of patients' prognosis after chemotherapy, and alterations of base excision repair pathway in adenocarcinoma, nucleotide excision repair in squamous carcinoma, and homologous recombination pathway in SCLC tend to associate with worse progression-free survival to first-line chemotherapy (all p < 0.05). A predictive nomogram model was constructed incorporating DDR-related alterations, clinical stage, and smoking status, with the area under curve values of 0.692-0.789 for 1- and 2-year receiver operating characteristic curves in training and testing cohorts. Furthermore, DDR-altered tumors contained enhanced frequencies of alterations in various genes of human leukocyte antigen (HLA) class I pathway including TAP1 and TAP2 than DDR-proficient samples. DDR-deficient types had lower expressions of STING1 (p = 0.01), CD28 (p = 0.020), HLA-DRB6 (p = 0.014) in adenocarcinoma, lower TNFRSF4 (p = 0.017), and TGFB1 expressions (p = 0.033) in squamous carcinoma, and higher CD40 (p = 0.012) and TNFRSF14 expressions (p = 0.022) in SCLC. DDR alteration enhanced activated mast cells in adenocarcinoma (p = 0.044) and M2 macrophage in squamous carcinoma (p = 0.004) than DDR-proficient types. Collectively, DDR gene alterations in lung cancer without oncogenic drivers are positively associated with high TMB. Specific DDR gene alterations tend to associate with worse progression-free survival to initial chemotherapy.

Mutational Profile Evaluates Response and Survival to First-Line Chemotherapy in Lung Cancer.

Evaluating the therapeutic response and survival of lung cancer patients receiving first-line chemotherapy has always been difficult. Limited biomarkers for evaluation exist and as a result histology represents an empiric tool to guide therapeutic decision making. In this study, molecular signatures associated with response and long-term survival of lung cancer patients receiving first-line chemotherapy are discovered. Whole-exome sequencing is performed on pretherapeutic tissue samples of 186 patients [145 non-small cell lung cancer (NSCLC) and 41 small cell lung cancer (SCLC)]. On the basis of genomic alteration characteristics, NSCLC patients can be classified into four subtypes (C1-C4). The long-term survival is similar among different subtypes. SCLC patients are also divided into four subtypes and significant difference in their progression free survival is revealed (P < 0.001). NSCLC patients can be divided into three subtypes (S1-S3) based on TMB. A trend of worse survival associated with higher TMB in subtype S3 than in S1+S2 is found. In contrast, no significant correlations between molecular subtype and therapeutic response are observed. In conclusion, this study identifies several molecular signatures associated with response and survival to first-line chemotherapy in lung cancer.

[Application of immobilized glycosidase in the synthesis of glycoside compounds].

Glycoside compounds are widely used in medicine, food, surfactant, and cosmetics. The glycosidase-catalyzed synthesis of glycoside can be operated at mild reaction conditions with low material cost. The glycosidase-catalyzed processes include reverse hydrolysis and transglycosylation, appropriately reducing the water activity in both processes may effectively improve the catalytic efficiency of glucosidase. However, glucosidase is prone to be deactivated at low water activity. Thus, glucosidase was immobilized to maintain its activity in the low water activity environment, and even in neat organic solvent system. This article summarizes the advances in glycosidase immobilization in the past 30 years, including single or comprehensive immobilization techniques, and immobilization techniques combined with genetic engineering, with the aim to provide a reference for the synthesis of glycosides using immobilized glycosidases.