Applications of Ene-Reductases in the Synthesis of Flavors and Fragrances.

Flavors and fragrances (F&F) are interesting organic compounds in chemistry. These compounds are widely used in the food, cosmetic, and medical industries. Enzymatic synthesis exhibits several advantages over natural extraction and chemical preparation, including a high yield, stable quality, mildness, and environmental friendliness. To date, many oxidoreductases and hydrolases have been used to biosynthesize F&F. Ene-reductases (ERs) are a class of biocatalysts that can catalyze the asymmetric reduction of α,ß-unsaturated compounds and offer superior specificity and selectivity; therefore, ERs have been increasingly considered an ideal alternative to their chemical counterparts. This review summarizes the research progress on the use of ERs in F&F synthesis over the past 20 years, including the achievements of various scholars, the differences and similarities among the findings, and the discussions of future research trends related to ERs. We hope this review can inspire researchers to promote the development of biotechnology in the F&F industry.

Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer's disease.

Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer's disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.

Self-Assembled MXene Supported on Carbonization-Free Wood for a Symmetrical All-Wood Eco-Supercapacitor.

As an emerging two-dimensional (2D) material, MXene has garnered significant interest in advanced energy storage systems, yet the stackable structure, poor mechanical stability, and lack of moldability limit its large-scale applications. To address this challenge, herein, the self-assembly of MXene on carbonization-free wood was obtained to serve as high-performance electrodes for symmetrical all-wood eco-supercapacitors by a steam-driven self-assembly method. This method can be implemented in a low-temperature environment, significantly simplifying traditional high-temperature annealing processes and generating minimal impact on the environment, human health, and resource consumption. The environmentally friendly steam-driven self-assembly strategy can be further extended into various wood-based electrodes, regardless of the types and structures of wood. As a typical platform electrode, the optimized MXene@delignified balsa wood (MDBW) achieves high areal capacitance and specific capacitance values of 2.99 F cm-2 and 580.55 F g-1 at an extensive mass loading of 5.16 mg cm-2, respectively, with almost loss-free capacitance after 10,000 cycles at 50 mA cm-2. In addition, an all-solid-state symmetrical all-wood eco-supercapacitor was further assembled based on MDBW-20 as both positive and negative electrodes to achieve a high energy density of 19.22 µWh cm-2 at a power density of 0.58 mW cm-2. This work provides an effective strategy to optimize wood-based electrodes for the practical application of biomass eco-supercapacitors.

Phase interface engineering enables state-of-the-art half-Heusler thermoelectrics.

In thermoelectric, phase interface engineering proves effective in reducing the lattice thermal conductivity via interface scattering and amplifying the density-of-states effective mass by energy filtering. However, the indiscriminate introduction of phase interfaces inevitably leads to diminished carrier mobility. Moreover, relying on a singular energy barrier is insufficient for comprehensive filtration of low-energy carriers throughout the entire temperature range. Addressing these challenges, we advocate the establishment of a composite phase interface using atomic layer deposition (ALD) technology. This design aims to effectively decouple the interrelated thermoelectric parameters in ZrNiSn. The engineered coherent dual-interface energy barriers substantially enhance the density-of-states effective mass across the entire temperature spectrum while preser carrier mobility. Simultaneously, the strong interface scattering on phonons is crucial for curtailing lattice thermal conductivity. Consequently, a 40-cycles TiO2 coating on ZrNi1.03Sn0.99Sb0.01 achieves an unprecedented zT value of 1.3 at 873 K. These findings deepen the understanding of coherent composite-phase interface engineering.

Novel diagnostic and prognostic approach for rapidly progressive dementias: Indicators based on amyloid/tau/neurodegeneration (ATN) framework.

AIMS: Apply established cerebrospinal fluid (CSF) and serum biomarkers and novel combined indicators based on the amyloid/tau/neurodegeneration (ATN) framework to improve diagnostic and prognostic power in patients with rapidly progressive dementias (RPDs). METHODS: CSF and serum biomarkers of Alzheimer's disease (AD) common neuropathology including Aß42, Aß40, p-Tau, and t-Tau were measured in cognitively normal (CN) controls (n = 33) and three RPD groups with rapidly progressive AD (rpAD, n = 23), autoimmune encephalitis (AE, n = 25), and Creutzfeldt-Jakob disease (CJD, n = 28). Logistic regression and multiple linear regression were used for producing combined indicators and prognostic assessment, respectively, including A&T, A&N, T&N, A&T&N, etc. RESULTS: Combined diagnostic indicator with A&T&N had the potential for differentiating AE from other types of RPDs, identifying 62.51% and 75% of AE subjects based on CSF and serum samples, respectively, compared to 39.13% and 37.5% when using autoantibodies. CSF t-Tau was associated with survival in the CJD group (adjusted R-Square = 0.16, p = 0.02), and its prognosis value improved when using combined predictors based on the ATN framework (adjusted R-Square = 0.273, p = 0.014). CONCLUSION: Combined indicators based on the ATN framework provide a novel perspective for establishing biomarkers for early recognition of RPDs due to treatment-responsive causes.

The role and mechanism of pyroptosis and potential therapeutic targets in non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome characterized by the excessive accumulation of fat within liver cells, which can progress to end-stage liver disease in severe cases, posing a threat to life. Pyroptosis is a distinct, pro-inflammatory form of cell death, differing from traditional apoptosis. In recent years, there has been growing research interest in the association between pyroptosis and NAFLD, encompassing the mechanisms and functions of pyroptosis in the progression of NAFLD, as well as potential therapeutic targets. Controlled pyroptosis can activate immune cells, eliciting host immune responses to shield the body from harm. However, undue activation of pyroptosis may worsen inflammatory responses, induce cellular or tissue damage, disrupt immune responses, and potentially impact liver function. This review elucidates the involvement of pyroptosis and key molecular players, including NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome, gasdermin D (GSDMD), and the caspase family, in the pathogenesis and progression of NAFLD. It emphasizes the promising prospects of targeting pyroptosis as a therapeutic approach for NAFLD and offers valuable insights into future directions in the field of NAFLD treatment.

Surface modification prepared porous copper oxide/(Cu-S)n metal-organic framework/reduced graphene oxide hierarchical structure for highly selective electrochemical quercetin detection.

Electrochemical alkalization of (Cu-S)n metal-organic framework (MOF) and graphene oxide ((Cu-S)n MOF/GO) composite yields a new CuO/(Cu-S)n MOF/RGO (reduced GO) composite with porous morphology on screen printed carbon electrode (SPCE) which facilitated the electron transfer properties in electrochemical quercetin (QUE) detection. A selective QUE detection ability has been demonstrated by the constructed electrochemical sensor (CuO/(Cu-S)n MOF/RGO/SPCE), which also has a broad dynamic range of 0.5 to 115 µM in pH 3 by differential pulse voltammetry. The detection limit is 0.083 µM (S/N = 3). In this study, it was  observed that the real samples contained 0.34 mg mL-1 and 27.7 µg g-1 QUE in wine and onion, respectively.

Identification, expression, and characterization of a marine-derived chitinase Ce0303 from Chitiniphilus eburneus YS-30 with exo- and endo-hydrolytic properties.

N-acetyl-oligosaccharides exhibit antioxidant and antibacterial activities. However, the low catalytic efficiency of chitinase on crystalline chitin hinders the eco-friendly production of N-acetyl-oligosaccharides. A marine-derived chitinase-producing strain Chitiniphilus eburneus YS-30 was screened in this study. The genome of C. eburneus YS-30 spans 4,522,240 bp, with a G + C content of 63.96 % and 4244 coding genes. Among the chitinases secreted by C. eburneus YS-30, Ce0303 showed the highest content at 19.10 %, with a molecular weight of 73.5 kDa. Recombinant Ce0303 exhibited optimal activity at 50 °C and pH 5.0, maintaining stability across pH 4.0-10.0. Ce0303 demonstrated strict substrate specificity, with a specific activity toward colloidal chitin of 6.41 U mg-1, Km of 2.34 mg mL-1, and kcat of 3.27 s-1. The specific activity of Ce0303 toward α-chitin was 18.87 % of its activity on colloidal chitin. Ce0303 displayed both exo- and endo-hydrolytic properties, primarily producing (GlcNAc)1-3 from colloidal chitin. The structure of Ce0303 includes one catalytic domain and two chitin-binding domains. Docking results revealed that the GlcNAc at -1 subsite formed two hydrogen bonds with conserved Trp380. The hydrolytic properties of Ce0303 will provide technical support for the comprehensive utilization of crustacean raw materials.

Analytical performance evaluation of hemoglobin A1c on an ARKRAY HA-8160 analyzer with newly-developed mobile phase buffer.

Background: Most glycated hemoglobin A1c (HbA1c) analytical reagents used were obtained from the analyzer's manufacturer. However, clinical laboratories need more choices for HbA1c analytical reagents to overcome the limitations of dedicated reagents for special analyzers. We developed new mobile phase buffers as HbA1c diagnostic reagents and evaluated their analytical performance for the HbA1c assay. Methods: Different mobile phase buffers used as HbA1c diagnostic reagents were prepared using different concentrations of sodium salts. According to the Clinical and Laboratory Standards Institute (CLSI) recommendation guidelines, the analytical performances of the newly developed mobile phase buffers were evaluated on an ARKRAY HA-8160 Analyzer. Both quality controls and clinical blood samples were used in these experiments. To assess the quality of the newly developed mobile phase buffers, precision, accuracy, linearity, carryover, interference, bias, correlation with commercial reagents, and stability were analyzed. Results: The CVs of intra-assay precision and interassay precision of quality control and clinical.There were fewer than 1.00 % blood sample assays using the newly developed mobile phase buffer. The RDs of accuracy were less than 1.00 %. Linearity: R2 = 0.9998 in the concentration range of 4.40%-17.30 %. Carryover: 0.00 %. Reagent comparison revealed that the Pearson regression equation was Y = 0.9884x+0.05692 (R2 = 0.9977), and the Bland-Altman mean difference was -0.02650 % (CI: -0.2121 %-0.1591 %) between the two analytical reagents. Stability was also acceptable within 12 months. This mobile phase buffer showed good anti-interference ability. Conclusion: The newly developed mobile phase buffers demonstrated good analytical performance and were suitable for clinical HbA1c assays on an ARKRAY HA-8160 Analyzer.

The Etiology of Rapidly Progressive Dementia: A 3-Year Retrospective Study in a Tertiary Hospital in China.

Background: Rapidly progressive dementia (RPD), characterized by a rapid cognitive decline leading to dementia, comprises a diverse range of disorders. Despite advancements in diagnosis and treatment, research on RPD primarily focuses on Western populations. Objective: This study aims to explore the etiology and demographics of RPD in Chinese patients. Methods: We retrospectively analyzed 323 RPD inpatients at Huashan Hospital from May 2019 to March 2023. Data on sociodemographic factors, epidemiology, clinical presentation, and etiology were collected and analyzed. Results: The median onset age of RPD patients was 60.7 years. Two-thirds received a diagnosis within 6 months of symptom onset. Memory impairment was the most common initial symptom, followed by behavioral changes. Neurodegenerative diseases accounted for 47.4% of cases, with central nervous system inflammatory diseases at 30.96%. Autoimmune encephalitis was the leading cause (16.7%), followed by Alzheimer's disease (16.1%), neurosyphilis (11.8%), and Creutzfeldt-Jakob disease (9.0%). Alzheimer's disease, Creutzfeldt-Jakob disease, and frontotemporal dementia were the primary neurodegenerative causes, while autoimmune encephalitis, neurosyphilis, and vascular cognitive impairment were the main non-neurodegenerative causes. Conclusions: The etiology of RPD in Chinese patients is complex, with neurodegenerative and non-neurodegenerative diseases equally prevalent. Recognizing treatable conditions like autoimmune encephalitis and neurosyphilis requires careful consideration and differentiation.

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation.

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.

AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases.

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.

Temporal trends in disparities in COVID-19 seropositivity among Canadian blood donors.

BACKGROUND: In Canada's largest COVID-19 serological study, SARS-CoV-2 antibodies in blood donors have been monitored since 2020. No study has analysed changes in the association between anti-N seropositivity (a marker of recent infection) and geographic and sociodemographic characteristics over the pandemic. METHODS: Using Bayesian multi-level models with spatial effects at the census division level, we analysed changes in correlates of SARS-CoV-2 anti-N seropositivity across three periods in which different variants predominated (pre-Delta, Delta and Omicron). We analysed disparities by geographic area, individual traits (age, sex, race) and neighbourhood factors (urbanicity, material deprivation and social deprivation). Data were from 420 319 blood donations across four regions (Ontario, British Columbia [BC], the Prairies and the Atlantic region) from December 2020 to November 2022. RESULTS: Seropositivity was higher for racialized minorities, males and individuals in more materially deprived neighbourhoods in the pre-Delta and Delta waves. These subgroup differences dissipated in the Omicron wave as large swaths of the population became infected. Across all waves, seropositivity was higher in younger individuals and those with lower neighbourhood social deprivation. Rural residents had high seropositivity in the Prairies, but not other regions. Compared to generalized linear models, multi-level models with spatial effects had better fit and lower error when predicting SARS-CoV-2 anti-N seropositivity by geographic region. CONCLUSIONS: Correlates of recent COVID-19 infection have evolved over the pandemic. Many disparities lessened during the Omicron wave, but public health intervention may be warranted to address persistently higher burden among young people and those with less social deprivation.

Proactive consultation of laboratory medicine increased diagnostic rate of multiple myeloma: One single center's 12-year experience.

Multiple myeloma (MM) was one of the hardest cancers to diagnose because of numerous nonspecific symptoms, leading to diagnostic delay. Proactive consultation of laboratory medicine (PCLM) could help timely diagnosis of blood cancers, avoiding diagnostic delay. This study aimed to evaluate the effect of PCLM on diagnosis and outcomes in MM. This retrospective study was conducted in newly diagnosed MM patients from 2011 to 2022. Implementation of PCLM initiated in 2015 with a laboratory-oriented algorithm. The annual diagnostic rate, patient demographics, the time intervals from symptom onset to diagnosis and to treatment, and clinical outcomes were analyzed. A total of 134 patients were newly diagnosed during the study interval. The diagnostic rate increased from 4.65 ±â€…1.59 to 7.43 ±â€…1.52 per million patient-visits after implementation of PCLM. The median time interval from symptom onset to diagnosis was significantly shortened after implementation of PCLM (50 days with interquartile range [IQR]: 24-136 days vs 150 days with IQR: 41-385 days, P = .003). Besides, the 1-year survival was significantly higher in patients diagnosed as MM after implementation of PCLM (72.4% vs 51.7%, P = .035). Implementation of PCLM not only increased diagnostic rate of MM and improved outcomes, but also raise awareness for MM and promote multidisciplinary collaboration in healthcare.

Risk factors for invasive pulmonary aspergillosis in patients with severe fever with thrombocytopenia syndrome: A multicenter retrospective study.

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.

Self-reporting electroswitchable colorimetric platform for smart ammonium recovery from wastewater.

Recovery of ammonium from wastewater represents a sustainable strategy within the context of global resource depletion, environmental pollution and carbon neutralization. The present study developed an advanced self-reporting electroswitchable colorimetric platform (SECP) to realize smart ammonium recovery based on the electrically stimulated transformation of Prussian blue/Prussian white (PB/PW) redox couple. The key to SECP was the selectivity of ammonium adsorption, sensitivity of desorption to electric signals and visualability of color change during switchable adsorption/desorption transformation. The results demonstrated the electrochemical intercalation-induced selective adsorption of NH4+ (selectivity coefficient of 3-19 versus other cations) and deintercalation-induced desorption on the PB-film electrode. At applied voltage of 1.2 V for 20 min, the negatively charged PB-film electrode achieved the maximum adsorption capacity of 3.2 mmol g-1. Reversing voltage to -0.2 V for 20 min resulted in desorption efficiency as high as 99%, indicating high adsorption/desorption reversibility and cyclic stability. The Fe(III)/Fe(II) redox dynamics were responsible for PB/PW transformation during reversible intercalation/deintercalation of NH4+. Based on the blue/transparence color change of PB/PW, the quantitative relationship was established between amounts of NH4+ adsorbed and extracted RGB values by multiple linear regression (R2 = 0.986, RMSE = 0.095). Then, the SECP was created upon the unique capability of real-time monitoring and feedback of color change of electrode to realize the automatic control of NH4+ adsorption/desorption. During five cycles of tests, the adsorption process consistently peaked at an average value of 3.15±0.04 mmol g-1, while desorption reliably approached the near-zero average of 0.06±0.04 mmol g-1. The average time of duration was 19.6±1.67 min for adsorption and 18.8±1.10 min for desorption, respectively. With electroswitchability, selectivity and self-reporting functionalities, the SECP represents a paradigm shift in smart ammonium recovery from wastewater, making wastewater treatment and resource recovery more efficient, more intelligent and more sustainable.

[Advances in clinical management of neonatal sepsis]. / 新生儿败血症的临床管理进展.

Neonatal sepsis, as a significant cause of various complications and adverse outcomes in neonates, remains a serious health burden both domestically and internationally. Strategies such as antibiotic prophylaxis during delivery, the utilization of early-onset sepsis risk calculators, and quality improvement initiatives in neonatal wards are beneficial in alleviating the disease burden of neonatal sepsis. This paper provides a review of the epidemiology, risk factors, and recent advances in clinical management of neonatal sepsis.