Layer Hall effect in a 2D topological axion antiferromagnet.

Whereas ferromagnets have been known and used for millennia, antiferromagnets were only discovered in the 1930s1. At large scale, because of the absence of global magnetization, antiferromagnets may seem to behave like any non-magnetic material. At the microscopic level, however, the opposite alignment of spins forms a rich internal structure. In topological antiferromagnets, this internal structure leads to the possibility that the property known as the Berry phase can acquire distinct spatial textures2,3. Here we study this possibility in an antiferromagnetic axion insulator-even-layered, two-dimensional MnBi2Te4-in which spatial degrees of freedom correspond to different layers. We observe a type of Hall effect-the layer Hall effect-in which electrons from the top and bottom layers spontaneously deflect in opposite directions. Specifically, under zero electric field, even-layered MnBi2Te4 shows no anomalous Hall effect. However, applying an electric field leads to the emergence of a large, layer-polarized anomalous Hall effect of about 0.5e2/h (where e is the electron charge and h is Planck's constant). This layer Hall effect uncovers an unusual layer-locked Berry curvature, which serves to characterize the axion insulator state. Moreover, we find that the layer-locked Berry curvature can be manipulated by the axion field formed from the dot product of the electric and magnetic field vectors. Our results offer new pathways to detect and manipulate the internal spatial structure of fully compensated topological antiferromagnets4-9. The layer-locked Berry curvature represents a first step towards spatial engineering of the Berry phase through effects such as layer-specific moiré potential.

Dietary supplementation of vitamin B1 prevents the pathogenesis of osteoarthritis.

As the primary cause for chronic pain and disability in elderly individuals, osteoarthritis (OA) is one of the fastest-growing diseases due to the aging world population. To date, the impact of microenvironmental changes on the pathogenesis of OA remains poorly understood, greatly hindering the development of effective therapeutic approaches against OA. In this study, we profiled the differential metabolites in the synovial fluid from OA patients and identified the downregulation of vitamin B1 (VB1) as a metabolic feature in the OA microenvironment. In a murine destabilization of medial meniscus-induced OA model, supplementation of VB1 significantly mitigated the symptoms of OA. Cytokine array analysis revealed that VB1 treatment remarkably reduced the production of a pro-OA factor-C-C Motif Chemokine Ligand 2 (CCL2), in macrophages. Further evidence demonstrated that exogenous CCL2 counteracted the anti-OA function of VB1. Hence, our study unveils a unique biological function of VB1 and provides promising clues for the diet-based treatment of OA.

Shared and malignancy-specific functional plasticity of dynamic brain properties for patients with left frontal glioma.

The time-varying brain activity may parallel the disease progression of cerebral glioma. Assessment of brain dynamics would better characterize the pathological profile of glioma and the relevant functional remodeling. This study aims to investigate the dynamic properties of functional networks based on sliding-window approach for patients with left frontal glioma. The generalized functional plasticity due to glioma was characterized by reduced dynamic amplitude of low-frequency fluctuation of somatosensory networks, reduced dynamic functional connectivity between homotopic regions mainly involving dorsal attention network and subcortical nuclei, and enhanced subcortical dynamic functional connectivity. Malignancy-specific functional remodeling featured a chaotic modification of dynamic amplitude of low-frequency fluctuation and dynamic functional connectivity for low-grade gliomas, and attenuated dynamic functional connectivity of the intrahemispheric cortico-subcortical connections and reduced dynamic amplitude of low-frequency fluctuation of the bilateral caudate for high-grade gliomas. Network dynamic activity was clustered into four distinct configuration states. The occurrence and dwell time of the weakly connected state were reduced in patients' brains. Support vector machine model combined with predictive dynamic features achieved an averaged accuracy of 87.9% in distinguishing low- and high-grade gliomas. In conclusion, dynamic network properties are highly predictive of the malignant grade of gliomas, thus could serve as new biomarkers for disease characterization.

Concise Total Synthesis of (-)-Bipolarolide D.

Here we report the first and concise total synthesis of a complex ophiobolin-derived sesterterpene, bipolarolide D, which hinges on two strategic applications of pentafulvene: (1) enantioselective pentafulvene-involved [6+2] cycloaddition; (2) regioselective and diastereoselective pentafulvene-involved Heck cyclization. Late-stage selective allylic addition to the ketone moiety facilitates the successful installation of the side chain. This strategy enabled the accomplishment of its first enantioselective total synthesis through a modular approach. This synthesis will facilitate the investigation of relevant biological activities and provide a synthetic blueprint for utilizing fulvenes as versatile synthons in other complex natural product synthesis.

Three-Motif Molecular Junction Type Covalent Organic Frameworks for Efficient Photocatalytic Aerobic Oxidation.

Covalent organic frameworks (COFs), with the features of flexible structure regulation and easy introduction of functional groups, have aroused broad interest in the field of photocatalysis. However, due to the low light absorption intensity, low photoelectron conversion efficiency, and lack of suitable active sites, it remains a great challenge to achieve efficient photocatalytic aerobic oxidation reactions. Herein, based on reticular chemistry, we rationally designed a series of three-motif molecular junction type COFs, which formed dual photosensitizer coupled redox molecular junctions containing multifunctional COF photocatalysts. Significantly, due to the strong light adsorption ability of dual photosensitizer units and integrated oxidation and reduction features, the PY-BT COF exhibited the highest activity for photocatalytic aerobic oxidation. Especially, it achieved a photocatalytic benzylamine conversion efficiency of 99.9% in 2.5 h, which is much higher than that of the two-motif molecular junctions with only one photosensitizer or redox unit lacking COFs. The mechanism of selective aerobic oxidation was studied through comprehensive experiments and density functional theory calculations. The results showed that the photoinduced electron transfer occurred from PY and then through triphenylamine to BT. Furthermore, the thermodynamics energy for benzylamine oxidation on PY-BT COF was much lower than that for others, which confirmed the synergistic effect of dual photosensitizer coupled redox molecular junction COFs. This work provided a new strategy for the design of functional COFs with three-motif molecular junctions and also represented a new insight into the multifunctional COFs for organic catalytic reactions.

Axion optical induction of antiferromagnetic order.

Using circularly polarized light to control quantum matter is a highly intriguing topic in physics, chemistry and biology. Previous studies have demonstrated helicity-dependent optical control of chirality and magnetization, with important implications in asymmetric synthesis in chemistry; homochirality in biomolecules; and ferromagnetic spintronics. We report the surprising observation of helicity-dependent optical control of fully compensated antiferromagnetic order in two-dimensional even-layered MnBi2Te4, a topological axion insulator with neither chirality nor magnetization. To understand this control, we study an antiferromagnetic circular dichroism, which appears only in reflection but is absent in transmission. We show that the optical control and circular dichroism both arise from the optical axion electrodynamics. Our axion induction provides the possibility to optically control a family of [Formula: see text]-symmetric antiferromagnets ([Formula: see text], inversion; [Formula: see text], time-reversal) such as Cr2O3, even-layered CrI3 and possibly the pseudo-gap state in cuprates. In MnBi2Te4, this further opens the door for optical writing of a dissipationless circuit formed by topological edge states.

Multi-pool chemical exchange saturation transfer MRI in glioma grading, molecular subtyping and evaluating tumor proliferation.

PURPOSE: To evaluate the performance of multi-pool Chemical exchange saturation transfer (CEST) MRI in prediction of glioma grade, isocitrate dehydrogenase (IDH) mutation, alpha-thalassemia/mental retardation syndrome X-linked (ATRX) loss and Ki-67 labeling index (LI), based on the fifth edition of the World Health Organization classification of central nervous system tumors (WHO CNS5). METHODS: 95 patients with adult-type diffuse gliomas were analyzed. The amide, direct water saturation (DS), nuclear Overhauser enhancement (NOE), semi-solid magnetization transfer (MT) and amine signals were derived using Lorentzian fitting, and asymmetry-based amide proton transfer-weighted (APTwasym) signal was calculated. The mean value of tumor region was measured and intergroup differences were estimated using student-t test. The receiver operating curve (ROC) and area under the curve (AUC) analysis were used to evaluate the diagnostic performance of signals and their combinations. Spearman correlation analysis was performed to evaluate tumor proliferation. RESULTS: The amide and DS signals were significantly higher in high-grade gliomas compared to low-grade gliomas, as well as in IDH-wildtype gliomas compared to IDH-mutant gliomas (all p < 0.001). The DS, MT and amine signals showed significantly differences between ATRX loss and retention in grade 2/3 IDH-mutant gliomas (all p < 0.05). The combination of signals showed the highest AUC in prediction of grade (0.857), IDH mutation (0.814) and ATRX loss (0.769). Additionally, the amide and DS signals were positively correlated with Ki-67 LI (both p < 0.001). CONCLUSION: Multi-pool CEST MRI demonstrated good potential to predict glioma grade, IDH mutation, ATRX loss and Ki-67 LI.

Can good neighbourhood perception magnify the positive effect of favourable built environment on recreational walking in China?

BACKGROUND: It remains unknown whether good neighbourhood perception can enhance the benefits of favourable built environment to physical activity. Moreover, the moderation pattern is less understood in developing countries. OBJECTIVES: This work aims to examine the moderation effects of perceived neighbourhood safety and aesthetics on the relationship between built environment and time for recreational walking. METHODS: We performed the examination using a sample of 760 residents in Fuzhou City, China. The Negative Binomial Regression Model was developed to examine the moderation roles of neighbourhood safety and aesthetics on the impact of built environment, adjusting for the effects of location, socioeconomic, personal preferences and social environment factors. Moreover, two sensitivity analyses were performed to test whether the moderators found are robust to the control of residential self-selection, and differential measures of conceptually-comparable aspects of built environment. RESULTS: We found stronger associations of time for recreational walking with road density and proportion of parks and squares POIs for residents with high perception of neighbourhood safety, compared to those with low perception of neighbourhood safety. There was a greater effect of the proportion of parks and squares POIs, when perceived aesthetics was high than when perceived aesthetics was low. The findings of neighbourhood safety and aesthetics as moderator, were robust in the two sensitivity analyses. No significant moderation effect was found for land use diversity. CONCLUSIONS: High perceived neighbourhood safety can magnify the positive effects of road connectivity and accessibility to parks and squares. Neighbourhood aesthetics positively moderates the association of time for recreational walking with accessibility to parks and squares. The findings emphasize the need to consider safety- and aesthetics-specific differences in estimates of built environment effects. Improvements in neighbourhood safety and aesthetics are key to effective interventions in built environment to better promote physical activity.

Genotoxicity of bisphenol AF in rats: Detrimental to male reproductive system and probable stronger micronucleus induction potency than BPA.

Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28-day multi-endpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF-treated groups (0.5, 5, and 50 µg/kg·bw/d), BPA group (10 µg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high-dose recovery group (BPAF-HR), oil recovery group (oil-R), ENU recovery group (ENU-R), and PBS recovery group (PBS-R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood-testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA.

Exploring the characteristics of Burkholderia gladioli pathovar cocovenenans: Growth, bongkrekic acid production, and potential risks of food contamination in wet rice noodles and vermicelli.

This research investigated the presence of Burkholderia gladioli pathovar cocovenenans (BGC) in wet rice and starch products, Tremella, and Auricularia auricula in Guangzhou, China. It examined BGC growth and bongkrekic acid (BA) production in wet rice noodles and vermicelli with varying rice flour, edible starch ratios, and oil concentrations. A qualitative analysis of 482 samples revealed a detection rate of 0.62%, with three positive for BGC. Rice flour-based wet rice noodles had BA concentrations of 13.67 ± 0.64 mg/kg, 2.92 times higher than 100% corn starch samples (4.68 ± 0.54 mg/kg). Wet rice noodles with 4% soybean oil had a BA concentration of 31.72 ± 9.41 mg/kg, 5.74 times higher than those without soybean oil (5.53 ± 1.23 mg/kg). The BA concentration correlated positively (r = 0.707, P < 0.05) with BGC contamination levels. Low temperatures (4 °C and -18 °C) inhibited BGC growth and BA production, while higher storage temperatures (26 °C and 32 °C) promoted BGC proliferation and increased BA production. Reducing edible oil use and increasing edible starch can mitigate the risk of BGC-related food poisoning in wet rice noodles and vermicelli production. Further research is needed to find alternative oils that do not enhance BA production. Strengthening prevention and control measures is crucial across the entire production chain to address BGC contamination and BA production.

Genotoxic mode of action and threshold exploration of 2-methyl furan under 120-day sub-chronic exposure in male Sprague-Dawley rats.

2-Methylfuran (2-MF) is an important member of the furan family generated during food thermal processing. An in-vivo multiple endpoint genotoxicity assessment system was applied to explore the genotoxic mode of action and threshold of 2-MF. Male Sprague-Dawley rats received 2-MF by oral gavage at doses of 0.16, 0.625, 2.5, and 10 mg/kg.bw/day for 120 days. An additional 15 days were granted for recovery. The Pig-a gene mutation frequency of RET and RBC showed significant increases among the 2-MF groups on day 120. After a 15-day recovery period, the Pig-a gene mutation frequency returned to levels similar to those in the vehicle control. The tail intensity (TI) values of peripheral blood cells at a dose of 10 mg/kg.bw/day significantly increased from day 4 and remained at a high level after the recovery period. No statistical difference was found in the micronucleus frequency of peripheral blood between any 2-MF dose group and the corn oil group at any timepoint. 2-MF may not induce the production of micronuclei, but it could cause DNA breakage. It could not be ruled out that 2-MF may accumulate in vivo and cause gene mutations. Hence, DNA, other than the spindle, may be directly targeted. The mode of action of 2-MF may be that it was metabolized by EPHX1 to more DNA-active metabolites, thus leading to oxidative and direct DNA damage. The point of departure (PoD) of 2-MF-induced genotoxicity was derived as 0.506 mg/kg bw/day.

Nano-immuno-conjugates inspired by hydrophilic perovskite fluorescent spheres and magnetic assisted for detection of hepatitis B surface antigen.

The rampant hepatitis B virus (HBV) seriously endangers human health, and hepatitis B surface antigen (HBsAg) is its early diagnostic marker. Therefore, it is crucial to construct a fast and highly sensitive HBsAg detection method. Based on high-efficiency magnetic separation technology and fluorescent composite material labelling technology, an accurate, fast and sensitive fluorescent immunosensing system for HBsAg detection was developed. Immunomagnetic beads constructed from carboxyl-functionalized Fe3O4 nanoparticles (Fe3O4-COOH) with excellent magnetic response performance were used as efficient capture carriers for HBsAg. Immunofluorescence composite microspheres constructed based on ultra-stable polystyrene-coated CsPbBr3 perovskite nanocrystals (CPB@PSAA) with high hydrophilic properties, were excellent fluorescent markers for HBsAg. Using this sensitive sandwich fluorescence sensing system a good linear relationship within the range of 0.2-15 ng/mL was established between HBsAg concentration and fluorescence intensity with a limit of detection (LOD) of  0.05 ng/mL. The system obtained satisfactory results when tested on real human serum samples. The magnetic-assisted fluorescence immune-sandwich sensor system has broad application prospects in biomedicine such as rapid and early diagnosis and effective prevention of infectious diseases.

Robust Attitude Estimation for Low-Dynamic Vehicles Based on MEMS-IMU and External Acceleration Compensation.

Attitude determination based on a micro-electro-mechanical system inertial measurement unit (MEMS-IMU) has attracted extensive attention. The non-gravitational components of the MEMS-IMU have a significant effect on the accuracy of attitude estimation. To improve the attitude estimation of low-dynamic vehicles under uneven soil conditions or vibrations, a robust Kalman filter (RKF) was developed and tested in this paper, where the noise covariance was adaptively changed to compensate for the external acceleration of the vehicle. The state model for MEMS-IMU attitude estimation was initially constructed using a simplified direction cosine matrix. Subsequently, the variance of unmodeled external acceleration was estimated online based on filtering innovations of different window lengths, where the acceleration disturbance was addressed by tradeoffs in time-delay and prescribed computation cost. The effectiveness of the RKF was validated through experiments using a three-axis turntable, an automatic vehicle, and a tractor tillage test. The turntable experiment demonstrated that the angle result of the RKF was 0.051° in terms of root mean square error (RMSE), showing improvements of 65.5% and 29.2% over a conventional KF and MTi-300, respectively. The dynamic attitude estimation of the automatic vehicle showed that the RKF achieves smoother pitch angles than the KF when the vehicle passes over speed bumps at different speeds; the RMSE of pitch was reduced from 0.875° to 0.460° and presented a similar attitude trend to the MTi-300. The tractor tillage test indicated that the RMSE of plough pitch was improved from 0.493° with the KF to 0.259° with the RKF, an enhancement of approximately 47.5%, illustrating the superiority of the RKF in suppressing the external acceleration disturbances of IMU-based attitude estimation.

Aqueous Sol-Gel Synthesis and Shaping of Covalent Organic Frameworks.

The intrinsic fragility and insoluble nature of covalent organic frameworks (COFs) have strongly impeded their processability for practical applications. Herein, an aqueous-based sol-gel synthetic strategy is reported for the synthesis and shaping of COFs with task-specific applications that satisfy the principles of green chemistry for gram-scale production of crystalline materials. Our successful approach involves three pivotal aspects: the "prodrug mimic" design of water-soluble monomers, the utilization of hydrolyzable bonds, and the manipulation of reaction kinetics. The generality of the method is demonstrated by the successful preparation of representative high-surface area two-dimensional (2D) COFs with several commonly used amines. By virtue of this strategy, a COF colloidal dispersion is achieved and can be formulated into processable fluids, structured films, and COF monoliths. Remarkably, the obtained lightweight (∼0.020 g cm-3) and robust aerogels displayed outstanding adsorption capacity (exceeding 57 times its own weight) toward a variety of organic solvents and exhibited superior thermal insulating properties compared to the widely used sponge and cotton. This work demonstrates a versatile strategy for the synthesis and shaping of processable COF materials in water that will contribute to the development of COF monoliths for advanced applications.

Causal effects of COVID-19 on structural changes in specific brain regions: a Mendelian randomization study.

BACKGROUND: Previous studies have found a correlation between coronavirus disease 2019 (COVID-19) and changes in brain structure and cognitive function, but it remains unclear whether COVID-19 causes brain structural changes and which specific brain regions are affected. Herein, we conducted a Mendelian randomization (MR) study to investigate this causal relationship and to identify specific brain regions vulnerable to COVID-19. METHODS: Genome-wide association study (GWAS) data for COVID-19 phenotypes (28,900 COVID-19 cases and 3,251,161 controls) were selected as exposures, and GWAS data for brain structural traits (cortical thickness and surface area from 51,665 participants and volume of subcortical structures from 30,717 participants) were selected as outcomes. Inverse-variance weighted method was used as the main estimate method. The weighted median, MR-Egger, MR-PRESSO global test, and Cochran's Q statistic were used to detect heterogeneity and pleiotropy. RESULTS: The genetically predicted COVID-19 infection phenotype was nominally associated with reduced cortical thickness in the caudal middle frontal gyrus (ß = - 0.0044, p = 0.0412). The hospitalized COVID-19 phenotype was nominally associated with reduced cortical thickness in the lateral orbitofrontal gyrus (ß = - 0.0049, p = 0.0328) and rostral middle frontal gyrus (ß = - 0.0022, p = 0.0032) as well as with reduced cortical surface area of the middle temporal gyrus (ß = - 10.8855, p = 0.0266). These causal relationships were also identified in the severe COVID-19 phenotype. Additionally, the severe COVID-19 phenotype was nominally associated with reduced cortical thickness in the cuneus (ß = - 0.0024, p = 0.0168); reduced cortical surface area of the pericalcarine (ß = - 2.6628, p = 0.0492), superior parietal gyrus (ß = - 5.6310, p = 0.0408), and parahippocampal gyrus (ß = - 0.1473, p = 0.0297); and reduced volume in the hippocampus (ß = - 15.9130, p = 0.0024). CONCLUSIONS: Our study indicates a suggestively significant association between genetic predisposition to COVID-19 and atrophy in specific functional regions of the human brain. Patients with COVID-19 and cognitive impairment should be actively managed to alleviate neurocognitive symptoms and minimize long-term effects.

High-resolution on-chip spatial heterodyne Fourier transform spectrometer based on artificial neural network and PCSBL reconstruction algorithm.

A novel compact on-chip Fourier transform (FT) spectrometer has been proposed based on the silicon-on-insulator (SOI) platform with wide operating bandwidth and high resolution. The spectrometer consists of a 16-channel power splitter and a Mach-Zehnder interferometer (MZI) array of 16 MZIs with linearly increasing optical path length (OPL) difference. We have also developed a spectral retrieval algorithm based on the pattern-coupled sparse Bayesian learning (PCSBL) algorithm and artificial neural network (ANN). The experimental results show that the designed spectrometer has a flat transmission characteristic in the wavelength range between 1500 nm and 1600 nm, indicating that the device has a wide operating bandwidth of 100 nm. In addition, with the assistance of the spectral retrieval algorithm, our spectrometer has the ability to reconstruct narrowband signals with full width at half maximum (FWHM) of 0.5 nm and a triple-peaked signal separated by a 3-nm distance.

PIC-integrable high-responsivity germanium waveguide photodetector in the C + L band.

We report the demonstration of a germanium waveguide p-i-n photodetector (PD) for the C + L band light detection. Tensile strain is transferred into the germanium layer using a SiN stressor on top surface of the germanium. The simulation and experimental results show that the trenches must be formed around the device, so that the strain can be transferred effectively. The device exhibits an almost flat responsivity with respect to the wavelength range from 1510 nm to 1630 nm, and high responsivity of over 1.1 A/W is achieved at 1625 nm. The frequency response measurement reveals that a high 3 dB bandwidth (f3dB) of over 50 GHz can be obtained. The realization of the photonic-integrated circuits (PIC)-integrable waveguide Ge PDs paves the way for future telecom applications in the C + L band.

Nomogram model and risk score to predict 5-year risk of progression from prediabetes to diabetes in Chinese adults: Development and validation of a novel model.

AIM: To develop a personalized nomogram and risk score to predict the 5-year risk of diabetes among Chinese adults with prediabetes. METHODS: There were 26 018 participants with prediabetes at baseline in this retrospective cohort study. We randomly stratified participants into two cohorts for training (n = 12 947) and validation (n = 13 071). The least absolute shrinkage and selection operator (LASSO) model was applied to select the most significant variables among candidate variables. And we further established a stepwise Cox proportional hazards model to screen out the risk factors based on the predictors chosen by the LASSO model. We presented the model with a nomogram. The model's discrimination, clinical use and calibration were assessed using the area under the receiver operating characteristic (ROC) curve, decision curve and calibration analysis. The associated risk factors were also categorized according to clinical cut-points or tertials to create the diabetes risk score model. Based on the total score, we divided it into four risk categories: low, middle, high and extremely high. We also evaluated our diabetes risk score model's performance. RESULTS: We developed a simple nomogram and risk score that predicts the risk of prediabetes by using the variables age, triglyceride, fasting blood glucose, body mass index, alanine aminotransferase, high-density lipoprotein cholesterol and family history of diabetes. The area under the ROC curve of the nomogram was 0.8146 (95% CI 0.8035-0.8258) and 0.8147 (95% CI 0.8035-0.8259) for the training and validation cohort, respectively. The calibration curve showed a perfect fit between predicted and observed diabetes risks at 5 years. Decision curve analysis presented the clinical use of the nomogram, and there was a wide range of alternative threshold probability spectrums. A total risk score of 0 to 2.5, 3 to 4.5, 5 to 7.5 and 8 to 13.5 is associated with low, middle, high and extremely high diabetes risk status, respectively. CONCLUSIONS: We developed and validated a personalized prediction nomogram and risk score for 5-year diabetes risk among Chinese adults with prediabetes, identifying individuals at a high risk of developing diabetes. Doctors and other healthcare professionals can easily and quickly use our diabetes score model to assess the diabetes risk status in patients with prediabetes. In addition, the nomogram model and risk score we developed need to be validated in a prospective cohort study.

Rational design of GDP­D­mannose mannosyl hydrolase for microbial L­fucose production.

BACKGROUND: L­Fucose is a rare sugar that has beneficial biological activities, and its industrial production is mainly achieved with brown algae through acidic/enzymatic fucoidan hydrolysis and a cumbersome purification process. Fucoidan is synthesized through the condensation of a key substance, guanosine 5'­diphosphate (GDP)­L­fucose. Therefore, a more direct approach for biomanufacturing L­fucose could be the enzymatic degradation of GDP­L­fucose. However, no native enzyme is known to efficiently catalyze this reaction. Therefore, it would be a feasible solution to engineering an enzyme with similar function to hydrolyze GDP­L­fucose. RESULTS: Herein, we constructed a de novo L­fucose synthetic route in Bacillus subtilis by introducing heterologous GDP­L­fucose synthesis pathway and engineering GDP­mannose mannosyl hydrolase (WcaH). WcaH displays a high binding affinity but low catalytic activity for GDP­L­fucose, therefore, a substrate simulation­based structural analysis of the catalytic center was employed for the rational design and mutagenesis of selected positions on WcaH to enhance its GDP­L­fucose­splitting efficiency. Enzyme mutants were evaluated in vivo by inserting them into an artificial metabolic pathway that enabled B. subtilis to yield L­fucose. WcaHR36Y/N38R was found to produce 1.6 g/L L­fucose during shake­flask growth, which was 67.3% higher than that achieved by wild­type WcaH. The accumulated L­fucose concentration in a 5 L bioreactor reached 6.4 g/L. CONCLUSIONS: In this study, we established a novel microbial engineering platform for the fermentation production of L­fucose. Additionally, we found an efficient GDP­mannose mannosyl hydrolase mutant for L­fucose biosynthesis that directly hydrolyzes GDP­L­fucose. The engineered strain system established in this study is expected to provide new solutions for L­fucose or its high value­added derivatives production.

Association between preoperative serum sodium and postoperative 30-day mortality in adult patients with tumor craniotomy.

BACKGROUND: Limited data exist regarding preoperative serum sodium (Na) and 30-day mortality in adult patients with tumor craniotomy. Therefore, this study investigates their relationship. METHODS: A secondary retrospective analysis was performed using data from the ACS NSQIP database (2012-2015). The principal exposure was preoperative Na. The outcome measure was 30-day postoperative mortality. Binary logistic regression modeling was conducted to explore the link between them, and a generalized additive model and smooth curve fitting were applied to evaluate the potential association and its explicit curve shape. We also conducted sensitivity analyses and subgroup analyses. RESULTS: A total of 17,844 patients (47.59% male) were included in our analysis. The mean preoperative Na was 138.63 ± 3.23 mmol/L. The 30-day mortality was 2.54% (455/17,844). After adjusting for covariates, we found that preoperative Na was negative associated with 30-day mortality. (OR = 0.967, 95% CI:0.941, 0.994). For patients with Na ≤ 140, each increase Na was related to a 7.1% decreased 30-day mortality (OR = 0.929, 95% CI:0.898, 0.961); for cases with Na > 140, each increased Na unit was related to a 8.8% increase 30-day mortality (OR = 1.088, 95% CI:1.019, 1.162). The sensitivity analysis and subgroup analysis indicated that the results were robust. CONCLUSIONS: This study shows a positive and nonlinear association between preoperative Na and postoperative 30-day mortality in adult patients with tumor craniotomy. Appropriate preoperative Na management and maintenance of serum Na near the inflection point (140) may reduce 30-day mortality.