Suillusgrevillei and Suillus luteus promote lead tolerance of Pinus tabulaeformis and biomineralize lead to pyromorphite.

Lead (Pb) is a hazardous heavy metal that accumulates in many environments. Phytoremediation of Pb polluted soil is an environmentally friendly method, and a better understanding of mycorrhizal symbiosis under Pb stress can promote its efficiency and application. This study aims to evaluate the impact of two ectomycorrhizal fungi (Suillus grevillei and Suillus luteus) on the performance of Pinus tabulaeformis under Pb stress, and the biomineralization of metallic Pb in vitro. A pot experiment using substrate with 0 and 1,000 mg/kg Pb2+ was conducted to evaluate the growth, photosynthetic pigments, oxidative damage, and Pb accumulation of P. tabulaeformis with or without ectomycorrhizal fungi. In vitro co-cultivation of ectomycorrhizal fungi and Pb shots was used to evaluate Pb biomineralization. The results showed that colonization by the two ectomycorrhizal fungi promoted plant growth, increased the content of photosynthetic pigments, reduced oxidative damage, and caused massive accumulation of Pb in plant roots. The structural characteristics of the Pb secondary minerals formed in the presence of fungi demonstrated significant differences from the minerals formed in the control plates and these minerals were identified as pyromorphite (Pb5(PO4)3Cl). Ectomycorrhizal fungi promoted the performance of P. tabulaeformis under Pb stress and suggested a potential role of mycorrhizal symbiosis in Pb phytoremediation. This observation also represents the first discovery of such Pb biomineralization induced by ectomycorrhizal fungi. Ectomycorrhizal fungi induced Pb biomineralization is also relevant to the phytostabilization and new approaches in the bioremediation of polluted environments.

Polysaccharides in fruits: Biological activities, structures, and structure-activity relationships and influencing factors-A review.

Fruits are a rich source of polysaccharides, and an increasing number of studies have shown that polysaccharides from fruits have a wide range of biological functions. Here, we thoroughly review recent advances in the study of the bioactivities, structures, and structure-activity relationships of fruit polysaccharides, especially highlighting the structure-activity influencing factors such as extraction methods and chemical modifications. Different extraction methods cause differences in the primary structures of polysaccharides, which in turn lead to different polysaccharide biological activities. Differences in the degree of modification, molecular weight, substitution position, and chain conformation caused by chemical modification can all affect the biological activities of fruit polysaccharides. Furthermore, we summarize the applications of fruit polysaccharides in the fields of pharmacy and medicine, foods, cosmetics, and materials. The challenges and perspectives for fruit polysaccharide research are also discussed.

The manufacturing process provides green teas with differentiated nonvolatile profiles and influences the deterioration of flavor during storage at room temperature.

Hundreds of green tea products are available on the tea market and exhibit different characteristics. In the present study, seven types of green tea were processed, and their nonvolatile profiles were analyzed by liquid chromatography-mass spectrometry. Non-spreading green tea contained higher concentrations of catechins and flavonoid glycosides, but lower concentrations of amino acids, caffeine, and theaflavins. Non-rolling green teas with a straight appearance contained higher concentrations of flavonoid glycosides and theaflavins. In contrast, leaf-rolling green teas contained much lower concentrations of flavonoid glycosides and catechins. These seven green tea qualities all decreased following prolonged storage, concurrent with increasing concentrations of proanthocyanidins, catechins dimers, theaflavins, and organic acids. The leaf-rolling green teas exhibited reduced levels of deterioration during storage in terms of their nonvolatile profile and sensory quality. Findings show that moderate destruction on tea leaves during green tea processing is beneficial to both tea flavor and quality maintenance during storage.

Detection and characterization of eravacycline heteroresistance in clinical bacterial isolates.

Eravacycline (ERV) has emerged as a therapeutic option for the treatment of carbapenem-resistant pathogens. However, the advent of heteroresistance (HR) to ERV poses a challenge to these therapeutic strategies. This study aimed to investigate ERV HR prevalence among common clinical isolates and further characterize ERV HR in carbapenem-resistant Klebsiella pneumoniae (CRKP). A total of 280 clinical pathogens from two centers were selected for HR and analyzed using population analysis profiling (PAP) and modified E-tests. The PAP assay revealed an overall ERV HR prevalence of 0.7% (2/280), with intermediate heterogeneity observed in 24.3% (68/280) of strains. The proportion of heteroresistant strains was 18.3% according to modified E-test results. A time-killing assay demonstrated that CRKP CFU increased significantly after 10 h of ERV treatment, contributing to the reduced bactericidal effect of ERV in vitro. Interestingly, dual treatment with ERV and polymyxin B effectively inhibited the total CFU, simultaneously reducing the required polymyxin B concentration. Furthermore, fitness cost measurements revealed a growth trade-off in CRKP upon acquiring drug resistance, highlighting fitness costs as crucial factors in the emergence of ERV HR in CRKP. Overall, the findings of the current study suggest that ERV HR in clinical strains presents a potential obstacle in its clinical application.

PTCH1 mutation as a potential predictive biomarker for immune checkpoint inhibitors in gastrointestinal cancer.

Immune checkpoint inhibitors (ICIs) have become prominent therapies for gastrointestinal cancer (GC). However, it is urgent to screen patients who can benefit from ICIs. Protein patched homolog 1 (PTCH1) is a frequently altered gene in GC. We attempt to explore the association between PTCH1 mutation and immunotherapy efficacy. The Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 236) with GC (esophageal, gastric and colorectal cancers) patients receiving ICIs was used for discovery and the Peking University Cancer Hospital (PUCH) GC cohort (n = 92) was used for validation. Overall survival (OS) and tumor mutational burden (TMB) of the PTCH1 mutant-type (PTCH1-MUT) and PTCH1 wild-type (PTCH1-WT) groups were compared. Furthermore, GC data were collected from The Cancer Genome Atlas to assess the potential mechanisms. In the MSKCC cohort, PTCH1-MUT group showed significantly better OS (P = 0.017) and higher TMB. Multivariate analysis showed that PTCH1 mutation was associated with better OS. In the PUCH cohort, PTCH1-MUT group showed significantly longer OS (P = 0.036) and progression-free survival, and higher durable clinical benefit and TMB. Immune cell infiltration analysis revealed that PTCH1-MUT group had significantly higher distributions of CD8 T cells, CD4 T cells, NK cells, mast cells and M1 cells. The PTCH1-MUT group showed significantly higher expression of most immune-related genes. Gene set enrichment analysis showed that the PTCH1-MUT group had enriched INF-γ response, INF-α response, glycolysis and reactive oxygen species pathway gene sets. PTCH1 mutation may represent a potential biomarker for predicting ICIs response in GC. Nevertheless, prospective cohort studies should be performed to further validate our results.

Efficacy of Rituximab in the Treatment of Pemphigus Vulgaris: A Meta-analysis.

Background: Pemphigus vulgaris (PV) accounts for about 80% of all patients with pemphigus, and is the type with the most serious condition and the worst prognosis among autoimmune bullous diseases. Glucocorticoid and immunosuppressor are the main treatment method for PV. Methods: The computer retrieves four databases obtain controlled trials on the effects of Rituximab in patients with pemphigus vulgaris. After a rigorous literature quality evaluation, data analysis was performed using RevMan 5.3 software. Results: 7 studies were ultimately included in this meta-analysis. 6 studies reported the Remission rate of the test group and the control group, which was significantly higher (OR:2.26; 95% Cl: 1.80,2.82; P < .01) than the control group. Meta-analysis showed that the improvement of the Recurrence rate was significantly lower than the control group (OR:0.36; 95% Cl: 0.20,0.67; P < .01). Meta-analysis showed that the Adverse reactions was no significant statistical significance than the control group (OR:0.82; 95% Cl: 0.53,1.28; P = .383). Conclusion: The results of this study suggest that Rituximab may be effective in patients with pemphigus vulgaris, which will bring light for patients and doctors. And the above conclusions need to be verified by more high-quality studies.

α-Cyano-3-aminocinnamic acid: A novel reactive matrix for qualitative and quantitative analysis of plant N-glycans by MALDI-MS.

N-glycans have a diversity of crucial biological roles in organisms. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has become an indispensable analytical instrument for biomolecules. However, due to the inherent low abundance, high structural heterogeneity, and poor ionization efficiency of N-glycans, as well as the extremely inhomogeneous co-crystal property using traditional matrices, the qualitation and quantitation of N-glycans by MALDI-MS remains challenging. In the present study, α-cyano-3-aminocinnamic acid (3-CACA) was reasonably designed and synthesized as a novel reactive matrix for N-glycan analysis. Combining with traditional matrix α-cyano-4-hydroxycinnamic acid (CHCA) as an acidic catalyst, a combinational matrix 3-CACA/CHCA was obtained with homogeneous co-crystallization and high derivatization efficiency, achieving the sensitive qualitation with the limits of detection low to femtomole and reproducible quantitation with good linearity (R2 > 0.998). As a result, the established method was successfully applied to the on-target derivatization and high-throughput quantification of N-glycans in eight varieties of the peach complex system, indicating that N-glycan has the potential to become a new biomarker for food allergy, and elucidating the prospective correlation between N-glycan epitopes and allergic reactions.

Manufacturing process differences give Keemun black teas their distinctive aromas.

Traditional Keemun black tea is also known as Congou black tea (CF). Over the last three decades, three other types of Keemun black tea (Jinzhen, JZ; Maofeng, MF; Xiangluo, XL) made by different processing have been introduced into the tea market. Total CF volatile concentrations ranged from 1666.3 to 2185.7 µg/L, followed by XL (1193.5-1916.1 µg/L), JZ (1058.9-1811.0 µg/L), and MF (987.5-1518.0 µg/L) tea infusions. A total of 79 volatiles in tea infusions was identified by two methods, among which fourteen with OAVs > 1 were identified and OAVs proportion of volatiles with flowery, fruity, or sweet notes to those with other notes differed in four Keemun black teas (CF = 6.58:1, MF = 5.16:1, JZ = 4.04:1, XL = 5.11:1). Phenylethyl alcohol oxidation resulted in phenylacetaldehyde formation which is the characteristic odorant in Keemun black tea. We clearly show that changes in tea processing gives the distinctive aroma to different Keemun black teas.

Radical-Induced Dissociation for Oligonucleotide Sequencing by TiO2/ZnAl-Layered Double Oxide-Assisted Laser Desorption/Ionization Mass Spectrometry.

De novo sequencing of oligonucleotides remains challenging, especially for oligonucleotides with post-transcriptional or synthetic modifications. Mass spectrometry (MS) sequencing can reliably detect and locate all of the modification sites in oligonucleotides via m/z variance. However, current MS-based sequencing methods exhibit complex spectra and low ion abundance and usually require coupled instrumentation. Herein, we demonstrate a method of oligonucleotide sequencing using TiO2/ZnAl-layered double oxide (LDO)-assisted laser desorption/ionization (LDI)-MS based on radical-induced dissociation (RID). ·CH2OH radicals can be produced on the surface of a TiO2/ZnAl-LDO matrix via ultraviolet light, inducing an attack on the active site of the oligonucleotide phosphate skeleton to create typical "a-, a-B-, c·-, d-, w-, and y"-type fragments. Compared with the spectra obtained via collision-based methods, such as collision-induced dissociation and higher-energy collisional dissociation, the LDI-MS spectra based on RID exhibit single-charged signals, fewer types of fragments, and a lower proportion of unknown noise peaks. We demonstrate full sequence coverage for a 6-mer 2'-O-methyl-modified oligonucleotide and a 21-mer small interfering RNA and show that RID can sequence oligonucleotides with modifications. Importantly, the mechanism responsible for the RID of the oligonucleotide phosphate skeleton was investigated through offline experiments, demonstrating consistent results with density functional theory calculations.

POTEE mutation as a potential predictive biomarker for immune checkpoint inhibitors in lung adenocarcinoma.

Precise selection of patients who could benefit from immune checkpoint inhibitors (ICIs) is an important challenge for immunotherapy in lung cancer. POTEE (POTE Ankyrin Domain Family Member E) is a member of one primate-specific gene family which have been identified as cancer-related antigens and potential target for immunotherapy of cancer. Here, we investigated the correlation between POTEE mutation and the clinical outcome of ICIs treatment in non-small cell lung cancer (NSCLC). We merged three NSCLC cohorts (n = 165) to assess predictive value of POTEE mutation of immunotherapy efficacy in NSCLC. The prognostic analysis and the potential molecular mechanism exploration were conducted based on the data from The Cancer Genome Atlas (TCGA) database. In the merged cohort, patients with POTEE-mutation (POTEE-Mut) had a significantly higher objective response rate (ORR) (100% vs 27.7%; P < 0.001) and longer progression-free survival (PFS) (P = 0.001; HR 0.08; 95% CI 0.01 - 0.54) compared to patients with POTEE wild-type (POTEE-WT) in NSCLC. Also, patients with POTEE-Mut showed higher ORR (100% vs 27.2%; P < 0.001) and longer PFS (P = 0.001; HR 0.07; 95% CI 0.01 - 0.52) in lung adenocarcinoma (LUAD). POTEE mutation was significantly associated with higher tumor mutational burden (TMB) and higher neoantigen load (NAL), but not with PD-L1 expression in LUAD. Gene set enrichment analyses (GSEA) analysis revealed prominent enrichment of signatures related to DNA repair in POTEE-Mut group (P < 0.001) in LUAD. Our results indicate that POTEE mutation could serve as a potential predictive biomarker for ICIs in LUAD. However, prospective cohort studies are still needed for further validation.

A PdPt nanoparticle-decorated thiol-functionalized MOF with high peroxidase-like activity for colorimetric sensing of D-glucose and chlorophenol isomers.

The peroxidase (POD)-like catalytic activity of various nanozymes was extensively applied in many significant fields. In this study, a thiol-functionalized MOF-loaded PdPt nanocomposite (UiO-66-(SH)2@PdPt) was fabricated, which possesses superior and selective POD-like activity with strong affinity towards H2O2 and 3,3',5,5'-tetramethylbenzidine under mild conditions. The POD-like property of UiO-66-(SH)2@PdPt was used to sensitively detect the concentration of D-glucose under near-neutral (pH = 6.5) conditions. The detection limit of D-glucose was as low as 2.7 µM, and the linear range of D-glucose was 5-700 µM. In addition, UiO-66-(SH)2@PdPt could accelerate the oxidative coupling chromogenic reaction of chlorophenol (CP) and 4-aminoantipyrine (4-AAP) in the presence of H2O2. Based on this phenomenon, a simple and visualized sensing array for the identification of chlorophenol contaminant isomers was further constructed to finally achieve the effective differentiation of three monochlorophenol isomers and six dichlorophenol isomers. Furthermore, a colorimetric detection method for 2-chlorophenol and 2,4-dichlorophenol was established. This work provides an effective means to improve the catalytic activity and selectivity of nanozymes by introducing an ideal carrier, which will be of significant value for the design of efficient nanozymes.

Blood-Glucose-Depleting Hydrogel Dressing as an Activatable Photothermal/Chemodynamic Antibacterial Agent for Healing Diabetic Wounds.

Poorly healing and nonhealing diabetic wounds are challenging to treat as the rapid growth of bacteria due to the high local glucose content can lead to persistent inflammation and poor angiogenesis. Herein, a smart hydrogel dressing composed of 3,3',5,5'-tetramethylbenzidine/ferrous ion/Pluronic F-127/glucose oxidase (TMB/Fe2+/PF127/GOx) is designed and demonstrated to consume blood glucose while accelerating wound healing by generating antibacterial agents in situ. The loaded GOx degrades blood glucose to provide hydrogen peroxide (H2O2) and gluconic acid to support the Fe2+-based Fenton reaction, and the generated hydroxyl radical (·OH) facilitates the oxidation of TMB. The color change from colorless to green caused by the oxidation of TMB in the blood glucose range between 1 and 10 mM can be monitored visually. Simultaneously, this process induced chemodynamic therapy (CDT) by the specific generation of hydroxyl radical (·OH) for killing bacteria. Moreover, the oxidized TMB shows strong absorption in the near infrared (NIR) region so that NIR light can be converted into heat efficiently for photothermal therapy (PTT). As a result, nearly 100% of Staphylococcus aureus and Escherichia coli are killed by synergistic PTT/CDT, and the infected skin wounds undergo complete repair along with downregulation of interleukin-6 (IL-6) and upregulation of the vascular endothelial growth factor (VEGF) and matrix metallopeptidase-2 (MMP-2). Different from traditional wound dressings that can give rise to secondary injury, the excellent thermosensitive properties arising from the sol/gel phase transition render the hydrogel dressing materials injectable, self-reparable, and removable on demand. The multifunctional hydrogel with hypoglycemic, chemodynamic, photothermal, antibacterial, and on-demand thermosensitive properties has immense potential in the treatment of diabetic wounds.

Liquid biopsy using cell-free DNA in the early diagnosis of hepatocellular carcinoma.

Hepatocellular carcinoma ranks fourth in cancer-related causes of death worldwide and second in China. Patients with hepatocellular carcinoma (HCC) at the early stage have a better prognosis compared to HCC patients at the late stage. Therefore, early screening for HCC is critical for clinical treatment decisions and improving the prognosis of patients. Ultrasound (US), computed tomography (CT), and serum alpha fetoprotein (AFP) have been used to screen HCC, but HCC is still difficult to be diagnosed in the early stage due to the low sensitivity of the above methods. It is urgent to find a method with high sensitivity and specificity for the early diagnosis of HCC. Liquid biopsy is a noninvasive detection method using blood or other bodily fluids. Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) are important biomarkers for liquid biopsy. Recently, HCC screening methods using the application of cfDNA and ctDNA have become the hot spot of early HCC diagnostics. In this mini review, we summarize the latest research progress of liquid biopsy based on blood cfDNA in early screening of HCC.

Toward a New Era of Coral Reef Monitoring.

Coral reefs host some of the highest concentrations of biodiversity and economic value in the oceans, yet these ecosystems are under threat due to climate change and other human impacts. Reef monitoring is routinely used to help prioritize reefs for conservation and evaluate the success of intervention efforts. Reef status and health are most frequently characterized using diver-based surveys, but the inherent limitations of these methods mean there is a growing need for advanced, standardized, and automated reef techniques that capture the complex nature of the ecosystem. Here we draw on experiences from our own interdisciplinary research programs to describe advances in in situ diver-based and autonomous reef monitoring. We present our vision for integrating interdisciplinary measurements for select "case-study" reefs worldwide and for learning patterns within the biological, physical, and chemical reef components and their interactions. Ultimately, these efforts could support the development of a scalable and standardized suite of sensors that capture and relay key data to assist in categorizing reef health. This framework has the potential to provide stakeholders with the information necessary to assess reef health during an unprecedented time of reef change as well as restoration and intervention activities.

Quantitative N-Glycomic and N-Glycoproteomic Profiling of Peach [Prunus persica (L.) Batsch] during Fruit Ripening.

Being part of the human diet, peach is an important fruit consumed worldwide. In the present study, a systematic first insight into the N-glycosylation of peach fruit during ripening was provided. First, N-glycome by reactive matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry indicated that 6 of 24 N-glycans of peach were differentially expressed. Second, a comparative N-glycoproteome was characterized via 18O-tagged N-glycosylation site labeling followed by nano-liquid chromatography-electrospray ionization-tandem mass spectrometry (nLC-ESI-MS/MS). Totally 1464 N-glycosites on 881 N-glycoproteins were identified, among which 291 N-glycosites on 237 N-glycoproteins were expressed differentially with a fold change value of 1.5 or 0.67. The enrichment analysis of GO and KEGG revealed that four pathways including other glycan degradation, phenylpropanoid biosynthesis, amino sugar and nucleotide sugar metabolism, and protein processing in endoplasmic reticulum were mainly enriched, in which several important N-glycoproteins with dynamic change during fruit ripening were further screened out. Our findings on a large scale for N-glycosylation analysis of peach fruit during ripening may provide new molecular insights for comprehending N-glycoprotein functions, which should be of great interest to both glycobiologists and analytical chemists.

Newly revealed variants of SERPINA3 in generalized pustular psoriasis attenuate inhibition of ACT on cathepsin G.

Generalized pustular psoriasis (GPP) is an autoinflammatory skin disease whose pathogenesis has not yet been fully elucidated. Alpha-1-antichymotrypsin(ACT) is a protein encoded by the SERPINA3 gene and an inhibitor of cathepsin G. One study of a European sample suggested that the loss of ACT function caused by SERPINA3 mutation is implicated in GPP. However, the role of SERPINA3 in the pathogenesis of GPP in other ethnic populations is unclear. To explore this, seventy children with GPP were performed next-generation sequencing to identify rare variants in the SERPINA3 gene. Bioinformatic analysis and functional tests were used to determine the effects of the variants, and a comprehensive analysis was performed to determine the pathogenicity of the variants and whether they are associated with GPP. One rare deletion and three rare missense variants were identified in the SERPINA3 gene in GPP. The deletion variant c.1246_1247del was found to result in a mutant protein with an extension of 10 amino acids and a C-terminal of 20 amino acids that was completely different from the wild-type. This mutant was found to impede secretion of ACT, thus failing to function as an inhibitor of cathepsin G. Two missense variants were found to reduce the ability of ACT to inhibit cathepsin G enzymatic activity. The association analysis suggested that the deletion variant is associated with GPP. This study identified four rare novel mutations of SERPINA3 and demonstrated that three of these mutations result in loss of function, contributing to the pathogenesis of pediatric-onset GPP in the Asian population.

2-Hydrazinoterephthalic Acid as a Novel Negative-Ion Matrix-Assisted Laser Desorption/Ionization Matrix for Qualitative and Quantitative Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Analysis of N-Glycans in Peach Allergy Research.

Glycans recently attracted considerable attention as the proposal of cross-reactive carbohydrate determinants for food allergy. Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) is powerful in analyzing biomolecules, while its applications in glycans are still challenging. Herein, a novel reactive matrix-assisted laser desorption/ionization (MALDI) matrix, 2-hydrazinoterephthalic acid, was rationally designed and synthesized. It provides uniform co-crystallization with glycans and only produces deprotonated ions with high intensities in the negative-ion mode. In combination with sinapic acid, a rapid and high-throughput method was established for on-target analysis of glycans with a superior limit of detection at the femtomole level and a good linearity (R2 > 0.999). Furthermore, the established method was successfully applied to quantify N-glycans in different cultivars and tissues of peach [Prunus persica (L.) Batsch]. Our work suggests the potential role of N-glycans as biomarkers for food-borne allergy and lays a methodological foundation for the elucidation of the possible relationship between carbohydrate epitopes and food allergy.

Quorum sensing regulates heteroresistance in Pseudomonas aeruginosa.

The prevalence and genetic mechanism of antibiotic heteroresistance (HR) have attracted significant research attention recently. However, non-genetic mechanism of HR has not been adequately explored. The present study aimed to evaluate the role of quorum sensing (QS), an important mechanism of behavioral coordination in different subpopulations and consequent heteroresistance. First, the prevalence of HR to 7 antibiotics was investigated in 170 clinical isolates of P. aeruginosa using population analysis profiles. The results showed that P. aeruginosa was significantly heteroresistant to meropenem (MEM), amikacin (AMK), ciprofloxacin (CIP), and ceftazidime (CAZ). The observed HR was correlated with down-regulation of QS associated genes lasI and rhlI. Further, loss-of-function analysis results showed that reduced expression of lasI and rhlI enhanced HR of P. aeruginosa to MEM, AMK, CIP, and CAZ. Conversely, overexpression of these genes or treatment with 3-oxo-C12-HSL/C4-HSL lowered HR of P. aeruginosa to the four antibiotics. Additionally, although downregulation of oprD and upregulation of efflux-associated genes was evident in heteroresistant subpopulations, their expression was not regulated by LasI and RhlI. Moreover, fitness cost measurements disclosed higher growth rates of PAO1ΔlasI and PAO1ΔrhlI in the presence of sub-MIC antibiotic as compared with that of wild-type PAO1. Our data suggest that under temporary antibiotic pressure, downregulation of QS might result in less fitness cost and promote HR of P. aeruginosa.