A small molecule redistributes iron in ferroportin-deficient mice and patient-derived primary macrophages.

Deficiencies of the transmembrane iron-transporting protein ferroportin (FPN1) cause the iron misdistribution that underlies ferroportin disease, anemia of inflammation, and several other human diseases and conditions. A small molecule natural product, hinokitiol, was recently shown to serve as a surrogate transmembrane iron transporter that can restore hemoglobinization in zebrafish deficient in other iron transporting proteins and can increase gut iron absorption in FPN1-deficient flatiron mice. However, whether hinokitiol can restore normal iron physiology in FPN1-deficient animals or primary cells from patients and the mechanisms underlying such targeted activities remain unknown. Here, we show that hinokitiol redistributes iron from the liver to red blood cells in flatiron mice, thereby increasing hemoglobin and hematocrit. Mechanistic studies confirm that hinokitiol functions as a surrogate transmembrane iron transporter to release iron trapped within liver macrophages, that hinokitiol-Fe complexes transfer iron to transferrin, and that the resulting transferrin-Fe complexes drive red blood cell maturation in a transferrin-receptor-dependent manner. We also show in FPN1-deficient primary macrophages derived from patients with ferroportin disease that hinokitiol moves labile iron from inside to outside cells and decreases intracellular ferritin levels. The mobilization of nonlabile iron is accompanied by reductions in intracellular ferritin, consistent with the activation of regulated ferritin proteolysis. These findings collectively provide foundational support for the translation of small molecule iron transporters into therapies for human diseases caused by iron misdistribution.

Probing the salivary proteome for prognostic biomarkers in response to non-surgical periodontal therapy.

AIM: This prospective study investigated the salivary proteome before and after periodontal therapy. MATERIALS AND METHODS: Ten systemically healthy, non-smoking, stage III, grade C periodontitis patients underwent non-surgical periodontal treatment. Full-mouth periodontal parameters were measured, and saliva (n = 30) collected pre- (T0), and one (T1) and six (T6) months post-treatment. The proteome was investigated by label-free quantitative proteomics. Protein expression changes were modelled over time, with significant protein regulation considered at false discovery rate <0.05. RESULTS: Treatment significantly reduced bleeding scores, percentages of sites with pocket depth ≥5 mm, plaque and gingival indexes. One thousand seven hundred and thirteen proteins were identified and 838 proteins (human = 757, bacterial = 81) quantified (≥2 peptides). At T1, 80 (T1 vs. T0: 60↑:20↓), and at T6, 118 human proteins (T6 vs. T0: 67↑:51↓) were regulated. The salivary proteome at T6 versus T1 remained stable. Highest protein activity post- versus pre-treatment was observed for cellular movement and inflammatory response. The small proline-rich protein 3 (T1 vs. T0: 5.4-fold↑) and lymphocyte-specific protein 1 (T6 vs. T0: 4.6-fold↓) were the top regulated human proteins. Proteins from Neisseria mucosa and Treponema socranskii (T1 vs. T0: 8.0-fold↓, 4.9-fold↓) were down-regulated. CONCLUSIONS: Periodontal treatment reduced clinical disease parameters and these changes were reflected in the salivary proteome. This underscores the potential of utilizing saliva biomarkers as prognostic tools for monitoring treatment outcomes.

Production of bilirubin via whole-cell transformation utilizing recombinant Corynebacterium glutamicum expressing a ß-glucuronidase from Staphylococcus sp. RLH1.

Bilirubin, a key active ingredient of bezoars with extensive clinical applications in China, is produced through a chemical process. However, this method suffers from inefficiency and adverse environmental impacts. To address this challenge, we present a novel and efficient approach for bilirubin production via whole-cell transformation. In this study, we employed Corynebacterium glutamicum ATCC13032 to express a ß-glucuronidase (StGUS), an enzyme from Staphylococcus sp. RLH1 that effectively hydrolyzes conjugated bilirubin to bilirubin. Following the optimization of the biotransformation conditions, a remarkable conversion rate of 79.7% in the generation of bilirubin was obtained at temperate 40 °C, pH 7.0, 1 mM Mg2+ and 6 mM antioxidant NaHSO3 after 12 h. These findings hold significant potential for establishing an industrially viable platform for large-scale bilirubin production.

Laccase immobilization and its degradation of emerging pollutants: A comprehensive review.

The chronic lack of effective disposal of pollutants has resulted in the detection of a wide variety of EPs in the environment, with concentrations high enough to affect ecological health. Laccase, as a versatile oxidase capable of catalyzing a wide range of substrates and without producing toxic by-products, is a potential candidate for the biodegradation of pollutants. Immobilization can provide favorable protection for free laccase, improve the stability of laccase in complex environments, and greatly enhance the reusability of laccase, which is significant in reducing the cost of industrial applications. This study introduces the properties of laccase and subsequently elaborate on the different support materials for laccase immobilization. The research advances in the degradation of EDs, PPCPs, and PAHs by immobilized laccase are then reviewed. This review provides a comprehensive understanding of laccase immobilization, as well as the advantages of various support materials, facilitating the development of more economical and efficient immobilization systems that can be put into practice to achieve the green degradation of EPs.

Biogenic Solution Map Based on the Definition of the Metabolic Correlation Distance between 4-Dimensional Fingerprints.

Accurate discrimination and classification of unknown species are the basis to predict its characteristics or applications to make correct decisions. However, for biogenic solutions that are ubiquitous in nature and our daily lives, direct determination of their similarities and disparities by their molecular compositions remains a scientific challenge. Here, we explore a standard and visualizable ontology, termed "biogenic solution map", that organizes multifarious classes of biogenic solutions into a map of hierarchical structures. To build the map, a novel 4-dimensional (4D) fingerprinting method based on data-independent acquisition data sets of untargeted metabolomics is developed, enabling accurate characterization of complex biogenic solutions. A generic parameter of metabolic correlation distance, calculated based on averaged similarities between 4D fingerprints of sample groups, is able to define "species", "genus", and "family" of each solution in the map. With the help of the "biogenic solution map", species of unknown biogenic solutions can be explicitly defined. Simultaneously, intrinsic correlations and subtle variations among biogenic solutions in the map are accurately illustrated. Moreover, it is worth mentioning that samples of the same analyte but prepared by alternative protocols may have significantly different metabolic compositions and could be classified into different "genera".

Joint effects of depressive status and body mass index on the risk of incident hypertension in aging population: evidence from a nationwide population-based cohort study.

BACKGROUND: The impact of depressive status (DS) on hypertension incidence is still controversial and has not been studied in Chinese middle-aged and elderly population. This study aimed to explore the relationship between DS and incident hypertension and analyze the joint effects of DS and body mass index (BMI) on hypertension incidence. METHODS: We conducted a prospective cohort study using data from the China Health and Retirement Longitudinal Study (CHARLS), a nationwide population-based study. In 2013, DS was identified using scores from the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10) among eligible respondents from CHARLS, and hypertension occurrence was observed until 2018. The multiple Cox models were employed to calculate the associations between DS and hypertension incidence. In addition, we also computed the multiplicative interaction (MI) between DS and BMI of incident hypertension and assessed their additive interaction (AI) through relative excess risk due to interaction (RERI), attributable proportion (AP) or synthetic index (S). Positive AI was indicated by RERI > 0, AP > 0 or S > 1. RESULTS: Over the 5-year follow-up, depressive symptoms increased the risk of hypertension incidence by 19% (hazard ratio (HR) = 1.19, 95% confidence interval (CI): (1.01, 1.41)), while depression was associated with a 24% increased risk (HR = 1.24; 95% CI: (1.03, 1.50)). Significant MIs between DS and overweight or obesity were observed and almost all of AI indexes showed positive joint effects on incident hypertension, of which the depression-obesity combination had the largest joint effect (RERI = 4.47, 95%CI: (0.28, 8.66); AP = 0.67, 95%CI: (0.50, 0.85); S = 4.86,95%CI: (2.66, 8.86)). CONCLUSION: DS could lead to hypertension and this impact was amplified when coexisting with higher BMI. It highlighted a need for precise interventions targeting weight management and depression treatment in the aging population to prevent hypertension.

Secular trends in the incidence of major depressive disorder and dysthymia in China from 1990 to 2019.

BACKGROUND: Depression is increasingly recognized as a worldwide serious, public health concern. A better understanding of depression is important for advancing its management and learning the difference between major depressive disorder (MDD) and dysthymia. Our aim is to conduct a concurrent analysis of the trends of both MDD and dysthymia in China. METHODS: The data on depression from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 (GBD 2019). To determine the average annual percent changes (AAPC) and relative risks (RRs), joinpoint regression and the age-period-cohort models were employed, respectively. RESULTS: The incidence number of MDD and dysthymia continuously increased in China from 1990 to 2019, however, the age-standardized rates (ASR) had a decreasing trend in both men and women. The results from joinpoint regression showed that a declining trend was presented in young people (< 50 years) but an increased trend in the elderly (≥ 50 years) both in men and women, during 1990-2019. Age is the most influential factor for MDD and dysthymia. Age RRs for MDD incidence had an overall increasing trend with age. Period RR in MDD presented a U-shaped pattern, while Cohort RRs presented an inverted U-shaped pattern. On the other hand, RRs in dysthymia for period and cohort effects had no statistical significance, only the age effect presented an inverted U-shaped pattern. CONCLUSIONS: The disparities in trends observed between MDD and dysthymia during the period of 1990-2019 indicated the significance of distinguishing between these two disorders. The age, period and cohort effects all had a greater impact on MDD than on dysthymia, and age effects presented different influential patterns in these two. To alleviate the burden of depressive disorders in China, proactive measures need to be implemented, with particular attention to the elderly population.

H-Dot Mediated Nanotherapeutics Mitigate Systemic Toxicity of Platinum-Based Anticancer Drugs.

Platinum-based anticancer agents have revolutionized oncological treatments globally. However, their therapeutic efficacy is often accompanied by systemic toxicity. Carboplatin, recognized for its relatively lower toxicity profile than cisplatin, still presents off-target toxicities, including dose-dependent cardiotoxicity, neurotoxicity, and myelosuppression. In this study, we demonstrate a delivery strategy of carboplatin to mitigate its off-target toxicity by leveraging the potential of zwitterionic nanocarrier, H-dot. The designed carboplatin/H-dot complex (Car/H-dot) exhibits rapid drug release kinetics and notable accumulation in proximity to tumor sites, indicative of amplified tumor targeting precision. Intriguingly, the Car/H-dot shows remarkable efficacy in eliminating tumors across insulinoma animal models. Encouragingly, concerns linked to carboplatin-induced cardiotoxicity are effectively alleviated by adopting the Car/H-dot nanotherapeutic approach. This pioneering investigation not only underscores the viability of H-dot as an organic nanocarrier for platinum drugs but also emphasizes its pivotal role in ameliorating associated toxicities. Thus, this study heralds a promising advancement in refining the therapeutic landscape of platinum-based chemotherapy.

HSA-ZW800-PEG for Enhanced Optophysical Stability and Tumor Targeting.

Small molecule fluorophores often face challenges such as short blood half-life, limited physicochemical and optical stability, and poor pharmacokinetics. To overcome these limitations, we conjugated the zwitterionic near-infrared fluorophore ZW800-PEG to human serum albumin (HSA), creating HSA-ZW800-PEG. This conjugation notably improves chemical, physical, and optical stability under physiological conditions, addressing issues commonly encountered with small molecules in biological applications. Additionally, the high molecular weight and extinction coefficient of HSA-ZW800-PEG enhances biodistribution and tumor targeting through the enhanced permeability and retention effect. The unique distribution and elimination dynamics, along with the significantly extended blood half-life of HSA-ZW800-PEG, contribute to improved tumor targetability in both subcutaneous and orthotopic xenograft tumor-bearing animal models. This modification not only influences the pharmacokinetic profile, affecting retention time and clearance patterns, but also enhances bioavailability for targeting tissues. Our study guides further development and optimization of targeted imaging agents and drug-delivery systems.

Production of marine bacterial metalloprotease A69 and evaluation of its potential in preparing soybean peptides with angiotensin-converting enzyme-inhibitory activity.

BACKGROUND: Marine bacteria secrete a variety of proteases, which are a good source to explore proteases with application value. However, only a few marine bacterial proteases with a potential in bioactive peptides preparation have been reported. RESULTS: The metalloprotease A69 from the marine bacterium Anoxybacillus caldiproteolyticus 1A02591 was successfully expressed in the food safe bacterium Bacillus subtilis as a secreted enzyme. A technique to efficiently produce protease A69 in a 15-L bioreactor was established, with a production of 8988 U mL-1 . Based on optimizing the hydrolysis parameters of A69 on soybean protein, a process for soybean protein peptides (SPs) preparation was set up, in which soybean protein was hydrolyzed by A69 at 4000 U g-1 and 60 °C for 3 h. The prepared SPs had a high content (> 90%) of peptides with a molecular mass less than 3000 Da and contained 18 amino acids. The prepared SPs showed high angiotensin-converting enzyme (ACE)-inhibitory activity, with an IC50 value of 0.135 mg mL-1 . Moreover, three ACE-inhibitory peptides, RPSYT, VLIVP and LAIPVNKP, were identified from the SPs using liquid chromatography-mass spectrometry analysis. CONCLUSION: The marine bacterial metalloprotease A69 has a promising potential for preparing SPs with good nutritional and potential antihypertensive effects, laying a good foundation for its industrial production and application. © 2023 Society of Chemical Industry.

Influencing factors of death in patients with MDR-TB based on Bayesian Cox regression model. / 基于贝叶斯Coxå›žå½’æ¨¡åž‹åˆ†æžè€å¤šè¯è‚ºç»“æ ¸æ‚£è€ æ­»äº¡çš„å½±å“å› ç´ .

OBJECTIVES: Multidrug-resistant tuberculosis (MDR-TB) has a high mortality and is always one of the major challenges in global TB prevention and control. Analyzing the factors that may impact the adverse outcomes of MDR-TB patients is helpful for improving the systematic management and optimizing the treatment strategies for MDR-TB patients. For follow-up data, the Cox proportional hazards regression model is an important multifactor analysis method. However, the method has significant limitations in its application, such as the fact that it is difficult to deal with the impacts of small sample sizes and other practical issues on the model. Therefore, Bayesian and conventional Cox regression models were both used in this study to analyze the influencing factors of death in MDR-TB patients during the anti-TB therapy, and compare the differences between these 2 methods in their application. METHODS: Data were obtained from 388 MDR-TB patients treated at Lanzhou Pulmonary Hospital from November 1, 2017 to March 31, 2021. Survival analysis was employed to analyze the death of MDR-TB patients during the therapy and its influencing factors. Conventional and Bayesian Cox regression models were established to estimate the hazard ratios (HR) and their 95% confidence interval (95% CI) for the factors affecting the death of MDR-TB patients. The reliability of parameter estimation in these 2 models was assessed by comparing the parameter standard deviation and 95% CI of each variable. The smaller parameter standard deviation and narrower 95% CI range indicated the more reliable parameter estimation. RESULTS: The median survival time (1st quartile, 3rd quartile) of the 388 MDR-TB patients included in the study was 10.18 (4.26, 18.13) months, with the longest survival time of 31.90 months. Among these patients, a total of 12 individuals died of MDR-TB and the mortality was 3.1%. The median survival time (1st quartile, 3rd quartile) for the deceased patients was 4.78(2.63, 6.93) months. The majority of deceased patients, accounting for 50%, experienced death within the first 5 months of anti-TB therapy, with the last mortality case occurring within the 13th month of therapy. The results of the conventional Cox regression model showed that the risk of death in MDR-TB patients with comorbidities was approximately 6.96 times higher than that of patients without complications (HR=6.96, 95% CI 2.00 to 24.24, P=0.002) and patients who received regular follow-up had a decrease in the risk of death by approximately 81% compared to those who did not receive regular follow-up (HR=0.19, 95% CI 0.05 to 0.77, P=0.020). In the results of Bayesian Cox regression model, the iterative history plot and Blue/Green/Red (BGR) plot for each parameter showed the good model convergence, and parameter estimation indicated that the risk of death in patients with a positive first sputum culture was lower than that of patients with a negative first sputum culture (HR=0.33, 95% CI 0.08 to 0.87). Additionally, compared to patients without complications, those with comorbidities had an approximately 6.80-fold increase in the risk of death (HR=7.80, 95% CI 1.90 to 21.91). Patients who received regular follow-up had a 90% reduction in the risk of death compared to those who did not receive regular follow-up (HR=0.10, 95% CI 0.01 to 0.30). The comparison between these 2 models showed that the parameter standard deviations and corresponding 95% CI ranges of other variables in the Bayesian Cox model were significantly smaller than those in the conventional model, except for parameter standard deviations of receiving regular follow-up (Bayesian model was 0.77; conventional model was 0.72) and pulmonary cavities (Bayesian model was 0.73; conventional model was 0.73). CONCLUSIONS: The first year of anti-TB therapy is a high-risk period for mortality in MDR-TB patients. Complications are the main risk factors of death in MDR-TB patients, while patients who received regular follow-up and had positive first sputum culture presented a lower risk of death. For data with a small sample size and low incidence of outcome, the Bayesian Cox regression model provides more reliable parameter estimation than the conventional Cox model.

On-Chip Investigation of Electrocatalytic Oxygen Reduction Reaction of 2D Materials.

The on-chip electrocatalytic microdevice (OCEM) is an emerging platform specialized in the electrochemical investigation of single-entity nanomaterials, which is ideal for probing the intrinsic catalytic properties, optimizing performance, and exploring exotic mechanisms. However, the current catalytic applications of OCEMs are almost exclusively in electrocatalytic hydrogen/oxygen evolution reactions with minimized influence from the mass transfer. Here, an OCEM platform specially tailored to investigate the electrocatalytic oxygen reduction reaction (ORR) at a microscopic level by introducing electrolyte convection through a microfluidic flow cell is reported. The setup is established on gold microelectrodes and later successfully applied to investigate how Ar-plasma treatment affects the ORR activities of 2H MoS2 . This study finds that Ar-plasma treatment significantly enhances the ORR performance of MoS2 nanosheets owing to the introduction of surface defects. This study paves the way for highly efficient microscopic investigation of diffusion-controlled electrocatalytic reactions.

Reversal of genetic brain iron accumulation by N,N'-bis(2-mercaptoethyl)isophthalamide, a lipophilic metal chelator, in mice.

N,N'-bis(2-mercaptoethyl)isophthalamide (NBMI) is a novel lipophilic metal chelator and antioxidant used in mercury poisoning. Recent studies have suggested that NBMI may also bind to other metals such as lead and iron. Since NBMI can enter the brain, we evaluated if NBMI removes excess iron from the iron-loaded brain and ameliorates iron-induced oxidative stress. First, NBMI exhibited preferential binding to ferrous (Fe2+) iron with a negligible binding affinity to ferric (Fe3+) iron, indicating a selective chelation of labile iron. Second, NBMI protected SH-SY5Y human neuroblastoma cells from the cytotoxic effects of high iron. NBMI also decreased cellular labile iron and lessened the production of iron-induced reactive oxygen species in these cells. Deferiprone (DFP), a commonly used oral iron chelator, failed to prevent iron-induced cytotoxicity or labile iron accumulation. Next, we validated the efficacy of NBMI in Hfe H67D mutant mice, a mouse model of brain iron accumulation (BIA). Oral gavage of NBMI for 6 weeks decreased iron accumulation in the brain as well as liver, whereas DFP showed iron chelation only in the liver, but not in the brain. Notably, depletion of brain copper and anemia were observed in BIA mice treated with DFP, but not with NBMI, suggesting a superior safety profile of NBMI over DFP for long-term use. Collectively, our study demonstrates that NBMI provides a neuroprotective effect against BIA and has therapeutic potential for neurodegenerative diseases associated with BIA.

Fungal diversity notes 1512-1610: taxonomic and phylogenetic contributions on genera and species of fungal taxa.

This article is the 14th in the Fungal Diversity Notes series, wherein we report 98 taxa distributed in two phyla, seven classes, 26 orders and 50 families which are described and illustrated. Taxa in this study were collected from Australia, Brazil, Burkina Faso, Chile, China, Cyprus, Egypt, France, French Guiana, India, Indonesia, Italy, Laos, Mexico, Russia, Sri Lanka, Thailand, and Vietnam. There are 59 new taxa, 39 new hosts and new geographical distributions with one new combination. The 59 new species comprise Angustimassarina kunmingense, Asterina lopi, Asterina brigadeirensis, Bartalinia bidenticola, Bartalinia caryotae, Buellia pruinocalcarea, Coltricia insularis, Colletotrichum flexuosum, Colletotrichum thasutense, Coniochaeta caraganae, Coniothyrium yuccicola, Dematipyriforma aquatic, Dematipyriforma globispora, Dematipyriforma nilotica, Distoseptispora bambusicola, Fulvifomes jawadhuvensis, Fulvifomes malaiyanurensis, Fulvifomes thiruvannamalaiensis, Fusarium purpurea, Gerronema atrovirens, Gerronema flavum, Gerronema keralense, Gerronema kuruvense, Grammothele taiwanensis, Hongkongmyces changchunensis, Hypoxylon inaequale, Kirschsteiniothelia acutisporum, Kirschsteiniothelia crustaceum, Kirschsteiniothelia extensum, Kirschsteiniothelia septemseptatum, Kirschsteiniothelia spatiosum, Lecanora immersocalcarea, Lepiota subthailandica, Lindgomyces guizhouensis, Marthe asmius pallidoaurantiacus, Marasmius tangerinus, Neovaginatispora mangiferae, Pararamichloridium aquisubtropicum, Pestalotiopsis piraubensis, Phacidium chinaum, Phaeoisaria goiasensis, Phaeoseptum thailandicum, Pleurothecium aquisubtropicum, Pseudocercospora vernoniae, Pyrenophora verruculosa, Rhachomyces cruralis, Rhachomyces hyperommae, Rhachomyces magrinii, Rhachomyces platyprosophi, Rhizomarasmius cunninghamietorum, Skeletocutis cangshanensis, Skeletocutis subchrysella, Sporisorium anadelphiae-leptocomae, Tetraploa dashaoensis, Tomentella exiguelata, Tomentella fuscoaraneosa, Tricholomopsis lechatii, Vaginatispora flavispora and Wetmoreana blastidiocalcarea. The new combination is Torula sundara. The 39 new records on hosts and geographical distribution comprise Apiospora guiyangensis, Aplosporella artocarpi, Ascochyta medicaginicola, Astrocystis bambusicola, Athelia rolfsii, Bambusicola bambusae, Bipolaris luttrellii, Botryosphaeria dothidea, Chlorophyllum squamulosum, Colletotrichum aeschynomenes, Colletotrichum pandanicola, Coprinopsis cinerea, Corylicola italica, Curvularia alcornii, Curvularia senegalensis, Diaporthe foeniculina, Diaporthe longicolla, Diaporthe phaseolorum, Diatrypella quercina, Fusarium brachygibbosum, Helicoma aquaticum, Lepiota metulispora, Lepiota pongduadensis, Lepiota subvenenata, Melanconiella meridionalis, Monotosporella erecta, Nodulosphaeria digitalis, Palmiascoma gregariascomum, Periconia byssoides, Periconia cortaderiae, Pleopunctum ellipsoideum, Psilocybe keralensis, Scedosporium apiospermum, Scedosporium dehoogii, Scedosporium marina, Spegazzinia deightonii, Torula fici, Wiesneriomyces laurinus and Xylaria venosula. All these taxa are supported by morphological and multigene phylogenetic analyses. This article allows the researchers to publish fungal collections which are important for future studies. An updated, accurate and timely report of fungus-host and fungus-geography is important. We also provide an updated list of fungal taxa published in the previous fungal diversity notes. In this list, erroneous taxa and synonyms are marked and corrected accordingly.

Fast and Durable Intraoperative Near-infrared Imaging of Ovarian Cancer Using Ultrabright Squaraine Fluorophores.

The residual tumor after surgery is the most significant prognostic factor of patients with epithelial ovarian cancer. Near-infrared (NIR) fluorescence-guided surgery is actively utilized for tumor localization and complete resection during surgery. However, currently available contrast-enhancing agents display low on-target binding, unfavorable pharmacokinetics, and toxicity, thus not ideal for clinical use. Here we report ultrabright and stable squaraine fluorophores with optimal pharmacokinetics by introducing an asymmetric molecular conformation and surface charges for rapid transporter-mediated cellular uptake. Among the tested, OCTL14 shows low serum binding and rapid distribution into cancer tissue via organic cation transporters (OCTs). Additionally, the charged squaraine fluorophores are retained in lysosomes, providing durable intraoperative imaging in a preclinical murine model of ovarian cancer up to 24 h post-injection. OCTL14 represents a significant departure from the current bioconjugation approach of using a non-targeted fluorophore and would provide surgeons with an indispensable tool to achieve optimal resection.

CRB-SWATH: A Method for Enhancing Untargeted Precursor Ion Extraction and Automatically Constructing Their Tandem Mass Spectra from SWATH Datasets by Chromatographic Retention Behaviors.

Sequential window acquisition of all theoretical spectra (SWATH) as a typical data-independent acquisition (DIA) strategy is favorable for untargeted metabolomics. It could theoretically acquire product ions of all precursor ions, including precursor ions showing chromatographic peaks of rather poor qualities. However, existing data processing methods present limited capabilities in capturing poor-quality peaks of precursor ions. Thus, although their product ions could be acquired, their precursor ions are absent. Here, we present a new strategy, chromatographic retention behavior-SWATH (CRB-SWATH), that could unbiasedly capture poor-quality peaks and provide high resolutions of multiplexed mass spectroscopy (MS/MS) spectra in SWATH datasets. CRB-SWATH monitors CRBs of SWATH-MS signals under a series of altered elution gradients. As signals of compounds differ from noise by showing CRBs, both the precursor and fragment ions are captured, while ignoring their peak qualities. Moreover, CRB-SWATH offers good chances to resolve highly multiplexed MS/MS spectra in SWATH datasets because precursor ions coeluted in a single elution gradient often present different CRBs. In the untargeted metabolic analysis of Hela cell extracts, CRB-SWATH showed the advantage in exclusively capturing 2645 ions of poor-quality peaks (i.e., tiny peaks, discontinuous ion traces, tailing peaks, zigzag peaks, etc.), accounting for 34.4% of all the untargeted precursor ions extracted. Therein, it is noteworthy that among 2116 negative ions detected in hydrophilic interaction liquid chromatography (HILIC) mode, 1284 poor-quality ion peaks (>60%) were exclusively captured by CRB-SWATH. As CRB-SWATH automatically captures a large sum of true ion peaks of poor qualities, extracts MS/MS spectra of high purities, and provides chromatographic retention behaviors of untargeted metabolites for identification and classification, it could be a useful metabolomics tool for understanding biological phenomena better.

Grating-enabled high-speed high-efficiency surface-illuminated silicon photodiodes.

High-speed, high-efficiency silicon photodetectors play important roles in the optical communication links that are used increasingly in data centers to handle the increasing volumes of data traffic and higher bandwidths required as use of big data and cloud computing continues to grow exponentially. Monolithic integration of the optical components with signal processing electronics on a single silicon chip is of paramount importance in the drive to reduce costs and improve performance. Here we report grating-enhanced light absorption in a silicon photodiode. The absorption efficiency is determined theoretically to be as high as 77% at 850 nm for the optimal structure, which has a thin intrinsic absorption layer with a thickness of 220 nm. The fabricated devices demonstrate a high bandwidth of 11.3 GHz and improved radio-frequency output power of more than 14 dB, thus making them suitable for use in data center optical communications.

Metaproteome and metabolome of oral microbial communities.

The emergence of high-throughput technologies for the comprehensive measurement of biomolecules, also referred to as "omics" technologies, has helped us gather "big data" and characterize microbial communities. In this article, we focus on metaproteomic and metabolomic approaches that support hypothesis-driven investigations on various oral biologic samples. Proteomics reveals the working units of the oral milieu and metabolomics unveils the reactions taking place; and so these complementary techniques can unravel the functionality and underlying regulatory processes within various oral microbial communities. Current knowledge of the proteomic interplay and metabolic interactions of microorganisms within oral biofilm and salivary microbiome communities is presented and discussed, from both clinical and basic research perspectives. Communities indicative of, or from, health, caries, periodontal diseases, and endodontic lesions are represented. Challenges, future prospects, and examples of best practice are given.

Design, synthesis and anticancer activity of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as microtubule-destabilizing agents.

Hereby, we report our efforts on discovery and optimization of a new series of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as new microtubule-destabilizing agents along our previous study. Guided by docking model analysis, we introduced the 1,2,3-thiadiazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. Extensive structure modifications were performed to investigate the detailed structure and activity relationships (SARs). Some compounds exhibited potent antiproliferative activities against three human cancer cell lines (SGC-7901, A549 and HeLa). The compound 5m exhibited the highest potency against the three cancer cell lines. The tubulin polymerization experiments indicated that compound 5m effectively inhibited the tubulin polymerization, and immunostaining assay revealed that it significantly disrupted microtubule dynamics. Moreover, cell cycle studies revealed that compound 5m dramatically arrested cell cycle progression at G2/M phase.

Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers.

A series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key intermediates ethyl 1-aryl-1H-tetrazole-5-carboxylates 10 can be simply and efficiently prepared via a microwave-assisted continuous operation process. Among the compounds synthesised, compound 6-31 showed noteworthy potency against SGC-7901, A549 and HeLa cell lines. In mechanism studies, compound 6-31 inhibited tubulin polymerisation and disorganised microtubule in SGC-7901 cells by binding to tubulin. Moreover, compound 6-31 arrested SGC-7901cells in G2/M phase. This study provided a new perspective for development of antitumor agents that target tubulin.