U-shaped association between fasting blood glucose and suicide attempts in Chinese patients with first-episode drug-naïve major depressive disorder.

BACKGROUND: Evidence regarding the relationship between fasting blood glucose (FBG) and suicide attempts (SA) in patients with major depressive disorder (MDD) was limited. Therefore, the objective of this research was to investigate whether FBG was independently related to SA in Chinese patients with first-episode drug-naïve (FEDN) MDD after adjusting for other covariates. METHODS: The present study was a cross-sectional study. A total of 1718 participants (average age: 34.9 ± 12.4 years, 65.8% females) with FEDN MDD were involved in a hospital in China from September 2016 to December 2018. Multiple logistic regression analysis and smooth curve fitting were used to estimate the association between FBG and the risk of SA. The threshold effect was examined by the two-piecewise linear regression model. Interaction and stratified analyses were conducted according to sex, education, marital status, comorbid anxiety, and psychotic symptoms. RESULTS: The prevalence of SA in patients with FEDN MDD was 20.1%. The result of fully adjusted binary logistic regression showed FBG was positively associated with the risk of SA (odds ratio (OR) = 1.62, 95% CI: 1.13-2.32). Smoothing plots also revealed a nonlinear relationship between FBG and SA, with the inflection point of FBG being 5.34 mmol/l. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 0.53 (0.32-0.88, P = 0.014) and 1.48 (1.04-2.10, P = 0.030), respectively. CONCLUSIONS: A U-shaped relationship between FBG and SA in FEDN MDD patients was found, with the lowest risk of SA at a FBG of 5.34 mmol/l, indicating that both the lower and higher FBG levels may lead to an increased risk of SA.

An antifouling epoxy coated metal surface containing silica-immobilized carbonic anhydrase supraparticles for CO2 capture through microalgae.

Carbonic anhydrase (CA) has a promising application as a green and efficient biocatalyst for CO2 capture, and many successful cases of immobilizing CA have been reported. However, CA antifouling coatings on metal for CO2 sequestration have rarely been reported. Herein, dimeric CA from Sulfurihydrogenibium azorense (SazCA) with a ferritin tag, which was prepared by low-speed centrifugation with high yield, was adopted as a free enzyme and encapsulated in the sol-gel silica. The silica-immobilized CAs were dispersed into the commercialized metal-antifouling epoxy resin paint to obtain CA coated nickel foams, which had excellent stability, with 90 % and 67 % residual activity after 28 days of incubation at 30 °C and 60 °C, respectively. The CA coated nickel foams remained 60 % original activity after 6 cycles of use within 28 days. Then, a CA-microalgae carbon capture device was constructed using the CA coated nickel foams and Chlorella. The growth rate of Chlorella was significantly increased and the biomass of Chlorella increased by 29 % compared with control after 7 days of incubation. Due to the simple and cost-effective preparation process, sustainable and efficient CO2 absorption, this easy-to-scale up CA coated nickel foam has great potential in CA assisted microalgae-based CO2 capture and carbon neutrality.

Deep Batch Integration and Denoise of Single-Cell RNA-Seq Data.

Numerous single-cell transcriptomic datasets from identical tissues or cell lines are generated from different laboratories or single-cell RNA sequencing (scRNA-seq) protocols. The denoising of these datasets to eliminate batch effects is crucial for data integration, ensuring accurate interpretation and comprehensive analysis of biological questions. Although many scRNA-seq data integration methods exist, most are inefficient and/or not conducive to downstream analysis. Here, DeepBID, a novel deep learning-based method for batch effect correction, non-linear dimensionality reduction, embedding, and cell clustering concurrently, is introduced. DeepBID utilizes a negative binomial-based autoencoder with dual Kullback-Leibler divergence loss functions, aligning cell points from different batches within a consistent low-dimensional latent space and progressively mitigating batch effects through iterative clustering. Extensive validation on multiple-batch scRNA-seq datasets demonstrates that DeepBID surpasses existing tools in removing batch effects and achieving superior clustering accuracy. When integrating multiple scRNA-seq datasets from patients with Alzheimer's disease, DeepBID significantly improves cell clustering, effectively annotating unidentified cells, and detecting cell-specific differentially expressed genes.

UFM1 inhibits hypoxia-induced angiogenesis via promoting proteasome degradation of HIF-1α.

Angiogenesis is crucial for blood flow recovery and ischemic tissue repair of peripheral artery disease (PAD). Exploration of new mechanisms underlying angiogenesis will shed light on the treatment of PAD. Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule, has been discovered to be involved in various pathophysiological processes. However, the role of UFM1 in the pathogenesis of PAD, especially in endothelial angiogenesis remains obscure, and we aimed to clarify this issue in this study. We initially found UFM1 was significantly upregulated in gastrocnemius muscles of PAD patients and hind limb ischemia mice. And UFM1 was mainly colocalized with endothelial cells in ischemic muscle tissues. Further, elevated expression of UFM1 was observed in hypoxic endothelial cells. Subsequent genetic inhibition of UFM1 dramatically enhanced migration, invasion, adhesion, and tube formation of endothelial cells under hypoxia. Mechanistically, UFM1 reduced the stability of hypoxia-inducible factor-1α (HIF-1α) and promoted the von Hippel-Lindau-mediated K48-linked ubiquitin-proteasome degradation of HIF-1α, which in turn decreased angiogenic factor VEGFA expression and suppressed VEGFA related signaling pathway. Consistently, overexpression of UFM1 inhibited the angiogenesis of endothelial cells under hypoxic conditions, whereas overexpression of HIF-1α reversed this effect. Collectively, our data reveal that UFM1 inhibits the angiogenesis of endothelial cells under hypoxia through promoting ubiquitin-proteasome degradation of HIF-1α, suggesting UFM1 might serve as a potential therapeutic target for PAD.

Multi-strategy orthogonal enhancement and analysis of aldo-keto reductase thermal stability.

Given their outstanding efficiency and selectivity, enzymes are integral in various domains such as drug synthesis, the food industry, and environmental management. However, the inherent instability of natural enzymes limits their widespread industrial application. In this study, we underscore the efficacy of enhancing protein thermal stability through comprehensive protein design strategies, encompassing elements such as the free energy of protein folding, internal forces within proteins, and the overall structural design. We also demonstrate the efficiency and precision of combinatorial screening in the thermal stability design of aldo-keto reductase (AKR7-2-1). In our research, three single-point mutations and five combinatorial mutations were strategically introduced into AKR7-2-1, using multiple computational techniques. Notably, the E12I/S235I mutant showed a significant increase of 25.4 °C in its melting temperature (Tm). Furthermore, the optimal mutant, E12V/S235I, maintained 80 % of its activity while realizing a 16.8 °C elevation in Tm. Remarkably, its half-life at 50 °C was increased to twenty times that of the wild type. Structural analysis indicates that this enhanced thermal stability primarily arises from reduced oscillation in the loop region and increased internal hydrogen bonding. The promising results achieved with AKR7-2-1 demonstrate that our strategy could serve as a valuable reference for enhancing the thermal stability of other industrial enzymes.

Abnormal ambiguous facial expression recognition in Chinese patients with schizophrenia.

BACKGROUND: Patients with schizophrenia (SCZ) exhibit difficulties deficits in recognizing facial expressions with unambiguous valence. However, only a limited number of studies have examined how these patients fare in interpreting facial expressions with ambiguous valence (for example, surprise). Thus, we aimed to explore the influence of emotional background information on the recognition of ambiguous facial expressions in SCZ. METHODS: A 3 (emotion: negative, neutral, and positive) × 2 (group: healthy controls and SCZ) experimental design was adopted in the present study. The experimental materials consisted of 36 images of negative emotions, 36 images of neutral emotions, 36 images of positive emotions, and 36 images of surprised facial expressions. In each trial, a briefly presented surprised face was preceded by an affective image. Participants (36 SCZ and 36 healthy controls (HC)) were required to rate their emotional experience induced by the surprised facial expressions. Participants' emotional experience was measured using the 9-point rating scale. The experimental data have been analyzed by conducting analyses of variances (ANOVAs) and correlation analysis. RESULTS: First, the SCZ group reported a more positive emotional experience under the positive cued condition compared to the negative cued condition. Meanwhile, the HC group reported the strongest positive emotional experience in the positive cued condition, a moderate experience in the neutral cued condition, and the weakest in the negative cue condition. Second, the SCZ (vs. HC) group showed longer reaction times (RTs) for recognizing surprised facial expressions. The severity of schizophrenia symptoms in the SCZ group was negatively correlated with their rating scores for emotional experience under neutral and positive cued condition. CONCLUSIONS: Recognition of surprised facial expressions was influenced by background information in both SCZ and HC, and the negative symptoms in SCZ. The present study indicates that the role of background information should be fully considered when examining the ability of SCZ to recognize ambiguous facial expressions.

Alterations of serum neuropeptide levels and their relationship to cognitive impairment and psychopathology in male patients with chronic schizophrenia.

Serum neuropeptide levels may be linked to schizophrenia (SCZ) pathogenesis. This study aims to examine the relation between five serum neuropeptide levels and the cognition of patients with treatment-resistant schizophrenia (TRS), chronic stable schizophrenia (CSS), and in healthy controls (HC). Three groups were assessed: 29 TRS and 48 CSS patients who were hospitalized in regional psychiatric hospitals, and 53 HC. After the above participants were enrolled, we examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the blood serum levels of α-melanocyte stimulating hormone (α-MSH), ß-endorphin (BE), neurotensin (NT), oxytocin (OT) and substance.P (S.P). Psychiatric symptoms in patients with SCZ were assessed with the Positive and Negative Syndrome Scale. SCZ patients performed worse than HC in total score and all subscales of the RBANS. The levels of the above five serum neuropeptides were significantly higher in SCZ than in HC. The levels of OT and S.P were significantly higher in CSS than in TRS patients. The α-MSH levels in TRS patients were significantly and negatively correlated with the language scores of RBANS. However, the BE and NT levels in CSS patients were significantly and positively correlated with the visuospatial/constructional scores of RBANS. Moreover, the interaction effect of NT and BE levels was positively associated with the visuospatial/constructional scores of RBANS. Therefore, abnormally increased serum neuropeptide levels may be associated with the physiology of SCZ, and may cause cognitive impairment and psychiatric symptoms, especially in patients with TRS.

Ufmylation on UFBP1 alleviates non-alcoholic fatty liver disease by modulating hepatic endoplasmic reticulum stress.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease characterized by lipid accumulation and endoplasmic reticulum (ER) stress, while effective therapies targeting the specific characteristics of NAFLD are limited. Ufmylation is a newly found post-translational modification process that involves the attachment of the Ubiquitin-fold modifier 1 (UFM1) protein to its substrates via ufmylation modification system. Ufmylation regulates ER stress via modifying UFM1 binding protein 1 (UFBP1), suggesting a potential role for ufmylation in NAFLD pathogenesis. However, the precise role of ufmylation in NAFLD remains unclear. Herein, we aim to elucidate the impact of ufmylation on UFBP1 in NAFLD and explore the underlying mechanisms involved. We observed increased expression of UFM1-conjugated proteins and ufmylation modification system components in livers with steatosis derived from NAFLD patients and NAFLD models. Upregulation of ufmylation on hepatic proteins appeared to be an adaptive response to hepatic ER stress in NAFLD. In vitro, knocking down UFBP1 resulted in increased lipid accumulation and lipogenesis in hepatocytes treated with free fatty acids (FFA), which could be rescued by wild-type UFBP1 (WT UFBP1) but not by a mutant form of UFBP1 lacking the main ufmylation site lys267 (UFBP1 K267R). In vivo, ufmylation on UFBP1 ameliorated obesity, hepatic steatosis, hepatic lipogenesis, dyslipidemia, insulin resistance and liver damage in mice with NAFLD induced by a high fat diet (HFD). We also demonstrated that the downregulation of UFBP1 induced ER stress, whereas the reintroduction or overexpression of UFBP1 alleviated ER stress in a manner dependent on ufmylation in NAFLD. This mechanism could be responsible for the amelioration of aberrant hepatic lipogenesis and insulin resistance in NAFLD. Our data reveal a protective role of ufmylation on UFBP1 against NAFLD and offer a specific target for NAFLD treatment.

Specific coenzyme preference switching for an aldo-keto reductase that synthesizes the chiral intermediate of duloxetine.

The synthesis of chiral intermediates for the traditional antidepressant duloxetine has gained significant attention as the number of depressed patients continues to grow. S-N, N-Dimethyl-3-hydroxy-3-(2-thienyl)-1-propanamide (S-DHTP) is a critical intermediate in the synthesis of duloxetine, and the chemical synthesis process is complex and environmentally unfriendly. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a major cost driver in the biocatalytic production of S-DHTP from N, N-Dimethyl-3-keto-3-(2-thienyl)-1-propanamide (DKTP). Here, we successfully modified the coenzyme preference of an aldo-keto reductase (AKR7-2-1) to use the cheaper reduced nicotinamide adenine dinucleotide (NADH) through a coenzyme preference modification approach. We utilized protein engineering to create a superior mutant, Y53F, which increased the coenzyme specificity of AKR7-2-1 by 875-fold and improved its thermal stability, enhancing its potential for industrial applications. Molecular dynamics simulations were performed to demonstrate the effect of mutations at key sites on the protein, revealing the altered coenzyme preference and increased thermal stability from structural and energetic changes. This study validates the viability of the coenzyme preference modification strategy for aldo-keto reductase, offering valuable insights for fellow researchers and guiding future investigations.

Efficacy and safety of Transcranial Direct Current Stimulation (tDCS) on cognitive function in chronic schizophrenia with Tardive Dyskinesia (TD): a randomized, double-blind, sham-controlled, clinical trial.

OBJECTIVE: Previous studies have shown that transcranial direct current stimulation(tDCS) led to an improvement of cognitive function in patients with schizophrenia, but rare study has explored the effect of tDCS on long-term hospitalized chronic schizophrenia with tardive dyskinesia (TD). The present research explored if cognitive function in patients with long-term hospitalized chronic schizophrenia with TD could be improved through tDCS. METHODS: This study is a randomized, double-blind, sham-controlled clinical trial. Of the 52 patients, 14 dropped out, and 38 completed the experiment. Thirty-eight patients on stable treatment regimens were randomly assigned to receive active tDCS(n = 21) or sham stimulation(n = 17) on weekdays of the first, third, and fifth weeks of treatment. Patients performed the Pattern Recognition Memory (PRM) and the Intra/Extradimensional Set Shift (IED) from the Cambridge Neuropsychological Test Automated Battery (CANTAB) at baseline and the end of week 3, week 5. Clinical symptoms were also measured at the baseline and the fifth week using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS). Side effects of tDCS were assessed with an experimenter-administered open-ended questionnaire during the whole experiment. RESULTS: There were no significant differences in PRM and IED performance metrics, SANS total score and PANSS total score between active and sham tDCS groups at the end of week 5 (p > 0.05). Furthermore, there was a significant difference in the adverse effects of the tingling sensation between the two groups (p < 0.05), but there was no significant difference in other side effects (p > 0.05). CONCLUSION: According to these findings, no evidence supports using anodal stimulation over the left dorsolateral prefrontal cortex to improve cognitive function in patients with long-term hospitalized chronic schizophrenia with TD.

Sex-differential association of suicide attempts with thyroid dysfunction in first-episode and drug-naïve young major depressive disorder patients with comorbid anxiety.

This study aimed to explore sex differences in the relationship between thyroid function indicators and suicide attempts in first-episode and drug-naïve young major depressive disorder (MDD) patients with comorbid anxiety (MDA). A total of 917 MDD patients (aged 18-35 years) were recruited. The Hamilton depression rating scale (HAMD-17), Hamilton anxiety rating scale (HAMA), positive and negative syndrome scale (PANSS) positive subscale and clinical global impression of severity scale (CGI-S) were used. 467 patients were classified as MDA. The prevalence of suicide attempts was 31.3% in MDA patients, which was significantly higher than that (7.3%) in MDD patients without anxiety. Compared with MDA patients without suicide attempts, MDA patients with suicide attempts were older, had a later age of onset, higher HAMD-17, HAMA, and PANSS positive symptom subscale scores, as well as higher TSH, TgAb and TPOAb levels. For male patients, TSH and TPOAb levels were independently associated with suicide attempts. For female patients, HAMA, PANSS positive symptom scores, CGI-S score and TPOAb levels were independently associated with suicide attempts. Our results suggest that the indicators of thyroid function which can predict suicide attempts in male and female MDA patients have sex differences.

Prevalence and clinical correlates of psychotic symptoms in first-episode untreated female chinese patients with major depressive disorder.

BACKGROUND: Recent studies have reported that psychotic symptoms are common in patients with major depressive disorder (MDD). However, few studies have reported the relationship between thyroid function, lipid metabolism and clinical profiles in female MDD patients. Thus, this study aimed to investigate the prevalence of psychotic depression (PD) and its risk factors in first-episode and drug naive (FEDN) depression among the female population in China. METHODS: This was a cross-sectional study involving a representative probability sample of 1,130 FEDN female outpatients with MDD (aged 18 years or older) in China. We collected information relating to socio-demographic characteristics, clinical data and blood samples. The Hamilton Depression Rating Scale 17-item version (HAMD-17), Hamilton Anxiety Rating Scale 14-item version (HAMA-14), and Positive and Negative Syndrome Scale (PANSS) were used to evaluate depressive, anxiety, and psychotic symptoms. RESULTS: The prevalence of psychotic symptoms in female MDD patients was 10.97%. The findings revealed significant differences between MDD female patients with psychotic symptoms and non-PD female patients in the following areas: higher HAMD scores, higher HAMA scores, more severe anxiety and an increased risk of suicide attempts. Further logistic regression analysis showed that psychotic symptoms were associated with higher thyroid-stimulating hormone (TSH) levels and an odds ratio of 1.168. CONCLUSIONS: Our findings supported the hypothesis that higher TSH levels were correlated with psychotic symptoms in female MDD patients. Therefore, serum TSH levels may be a potential biomarker of PD in female MDD patients. In addition, we found that PD was closely associated with suicide attempts and lipid levels, but did not reach statistical significance.

Association between body mass index and suicide attempts in Chinese patients of a hospital in Shanxi district with first-episode drug-naïve major depressive disorder.

OBJECTIVE: In patients with major depressive disorder (MDD), the relationship between body mass index (BMI) and risk of suicide attempts (SA) remains unclear, and findings are controversial. The aim of this study was to investigate the relationship between BMI and SA in a Chinese population with first-episode drug-naïve (FEDN) MDD. METHODS: A total of 1718 patients with FEDN MDD were enrolled in this cross-sectional study. Their socio-demographic characteristics as well as anthropometric data were collected. The 17-item Hamilton Rating Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA) were used to assess the severity of depression and anxiety symptoms in all participants. Thyroid hormones, lipid profile, and fasting blood glucose (FBG) were measured. A history of suicide attempts was verified based on medical records and interviews with patients and their family members. Multiple logistic regression analysis was used to estimate the association between BMI and the risk of SA. Threshold effects were examined by a two-piecewise logistic regression model. RESULTS: Multiple logistic regression analysis showed that BMI was independently and negatively correlated with SA (OR = 0.91, 95%CI: 0.85 to 0.98, P = 0.01) in patients with FEDN MDD after adjusting for covariates. Smoothing plots also revealed a non-linear (L-shaped) relationship between BMI and SA, and a two-piecewise logistic regression model was used to calculate the inflection point of BMI as 22.1 kg/m2. On the left of the inflection point, a negative association between BMI and SA was detected (OR = 0.54, 95%CI: 0.42 to 0.70, P < 0.001), while no significant association was observed on the right side of the inflection point (OR = 1.01, 95%CI: 0.93 to 1.10, P = 0.75). CONCLUSIONS: Our results suggest that lower BMI is associated with a higher risk of recent SA in Chinese patients with FEDN MDD, especially in those with BMI below 22.1 kg/m2.

A novel self-purified auxiliary protein enhances the lichenase activity towards lichenan for biomass degradation.

Due to the complex composition of lichenan, lichenase alone cannot always hydrolyze it efficiently. Carbohydrate-binding modules (CBMs) and lytic polysaccharide monooxygenases (LPMOs) have been confirmed to increase the hydrolysis efficiency of lichenases. However, their practical application was hampered by the complex and costly preparation procedure, as well as the poor stability of LPMOs. Herein, we discovered a novel and stable auxiliary protein named SCE to boost the hydrolysis efficiency. SCE was composed of SpyCatcher (SC) and elastin-like polypeptides (ELPs) and could be easily and cheaply prepared. Under the optimal conditions, the boosting degree for SCE/lichenase was 1.45, and the reducing sugar yield improved by nearly 45%. The results of high-performance liquid chromatography (HPLC) indicated that SCE had no influence on the hydrolysis pattern of lichenase. Through the experimental verification and bioinformatics analysis, we proposed the role of SCE in promoting the interaction between the lichenase and substrates. These findings endow SC with a novel function in binding to insoluble lichenan, paving the way for biomass degradation and biorefinery. KEY POINTS: • A novel self-purification auxiliary protein that could boost the hydrolysis efficiency of lichenase has been identified. • The protein is highly produced, simple to prepare, well stable, and does not require any external electron donor. • The novel function of SpyCatcher in binding to insoluble lichenan was first demonstrated.

Programmable and printable formaldehyde dehydrogenase as an excellent catalyst for biodegradation of formaldehyde.

As an environmental pollutant, formaldehyde can cause serious harm to the human body. Among many degradation methods, formaldehyde dehydrogenase from Pseudomonas putida (PFDH) exhibits broad potential because of its strong catalytic specificity and high degradation efficiency. However, the real application of PFDH in industry is limited by its instability and difficulties in recycling. In this work, the suitable printing conditions for immobilizing PFDH by three-dimensional (3D) printing technology were studied: the concentration of sodium alginate (SA) was 1.635 wt%, the concentration of CaCl2 was 7.4 wt%, the crosslinking time with CaCl2 was 8 min, and the temperature of the reaction was 31.5°C. 3D-printed PFDH/calcium alginate (CA) microspheres have 210% relative enzyme activity after seven repeated uses. Dried PFDH/CA particles were characterized by scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR), EDS elemental mapping, and thermogravimetric analysis (TGA) which proved that the enzyme was immobilized by the material. In addition, the recycling ability of 3D printing to immobilize different objects was explored and different shapes were designed by computer-aided design (CAD). In conclusion, 3D printing technology was applied to immobilize PFDH in this work, which provides a new idea to biodegrade formaldehyde in a green way.

Association between childhood trauma and white matter deficits in first-episode schizophrenia.

OBJECTIVE: This study aimed to investigate the relationship between childhood trauma (ChT) and white matter (WM) deficits in first-episode schizophrenia (FES). METHODS: A total of 103 individuals with FES and 206 healthy control individuals (HCs) were enrolled and assessed based on ChT Questionnaire (CTQ) and Positive and Negative Symptoms Scale (PANSS). Diffusion tensor imaging was acquired on a Signa 3.0 T scanner. Map of fractional anisotropy (FA) was analyzed using Tract-Based Spatial Statistics. Hierarchical logistic regression analyses were used to examine associations of sociodemographic characteristics, total CTQ scores, and WM deficits. RESULTS: Compared with the HCs group, the FES group showed significantly lower FA in several WM bundles (left anterior thalamic radiation, left inferior frontal-occipital fasciculus, left cingulum, forceps major, and forceps minor), and the mean FA value in these WM bundles was inversely related to the total CTQ score. In addition, a higher CTQ score may increase the risk of schizophrenia, while higher FA values may decrease the risk of schizophrenia. CONCLUSION: This study demonstrates that individuals with FES evince widespread cerebral WM abnormalities and that these abnormalities were associated with ChT. These results provide clues about the neural basis and potential biomarkers of schizophrenia.

Green synthesis of silica-coated magnetic nanocarriers for simultaneous purification-immobilization of ß-1,3-xylanase.

Tailoring magnetic nanocarriers with tunable properties is of great significance for the development of multifunctional candidate materials in numerous fields. Herein, we report a one-pot biomimetic silicification-based method for the synthesis of silica-coated magnetic nanoparticles. The synthesis process was mild, low cost, and highly efficient, which took only about 21 min compared with 4.5-120 h in other literature. Then, the carriers had been characterized by VSM, SEM, TEM, XRD, FT-IR, and EDS to confirm their function. To evaluate the usefulness of the carriers, they were adopted to couple the purification and immobilization of ß-1,3-xylanase from the cell lysate in a single step with high immobilization yield (92.8 %) and high activity recovery (82.4 %). The immobilized enzyme also retained 58.4 % of the initial activity after 10 cycles and displayed good storage properties, and improved thermal stability, which would be promising in algae biomass bioconversion as well as other diverse applications.

Biomimetic one-pot preparation of surface biofunctionalized silica-coated magnetic composites for dual enzyme oriented immobilization without pre-purification.

Surface functioned magnetic silica particles are efficient carriers to achieve facilitated separation and recycling of biocatalysts. However, traditional methods of modifying magnetic silica particles required time-costly sequential coating and surface modification steps and toxic solvents. Herein, a green and efficient routine was proposed to prepare the surface modified silica-coated magnetic microspheres (SCEs@SiO2 @Fe3O4) in one-pot. The elastin-like polypeptides (ELPs)-SpyCatcher chimera (SCEs) were purified by inverse transition cycling with high yield (275 mg/L) and incorporated into the magnetic silica spheres based on the biomimetic silicification capability of ELPs as proved by the EDS and SEM mapping. No SCEs leaked was observed within 48 h, indicating excellent stability in buffer. Then, the biofunctionalized carriers were used to purify and immobilize the target dual enzymes (xylanase-linker-SpyTag-linker-lichenase, bienzymes) directly from the crude cell lysis solution by the spontaneous isopeptide bond reaction between SpyCatcher and SpyTag. The immobilized bienzymes were sphere-like magnetic silica particles with uniform size, which had good magnetic responsiveness. The immobilization yield, immobilization efficiency and activity recovery for xylanase were 86%, 84 % and 72 %, while for lichenase was 92 %, 86 % and 79 %, respectively. Besides, the immobilized bienzymes showed good reusability (>60 %, 10 times for xylanase, >95 %, 8 times for lichenase). The SCEs modified silica-coated magnetic microspheres are expected to provide versatile platforms for single-step of purification and immobilization of multienzymes, offering great potentials in the field of biocatalysis.

Revealing the role of tunable amino acid residues in elastin-like polypeptides (ELPs)-mediated biomimetic silicification.

Elastin-like polypeptides (ELPs) are attractive materials for the green preparation of silica nanoparticles via biomimetic silicification. However, the critical factors affecting the ELP-mediated silicification remain unclear. Herein, the role of tunable amino acid residues of ELPs in silicification was studied using three ELPs (ELPs[V9F-40], ELPs[KV8F-40], and ELPs[K5V4F-40]) and their fusion proteins (ELPs[V9F-40]-SpyCatcher, ELPs[KV8F-40]-SpyCatcher, and ELPs[K5V4F-40]-SpyCatcher) with different contents of lysine residues. Bioinformatics methods were employed for the first time to reveal the key physicochemical parameters correlated with silicification. The specific activity of ELPs was increased with the promotion of lysine content with a high correlation coefficient (R = 0.899). Furthermore, exogenous acidic protein SpyCatcher would hinder the interactions between the silica precursors and ELPs, leading to the significantly decrease in specific activity. The isoelectric point (pI) of ELPs presented the highest correlation to silicification with a coefficient of 0.963. The charges of the ELPs [K5V4F-40] at different pH were calculated based on the sequence or structure. Interestingly, the excellent correlation between charges based on structure and specific activity was obtained. Collectively, the novel methods developed here may pave a new way for rational design of ELPs or other peptides for efficient and green preparation of silica nanomaterials for biomedicine, biocatalysis, and biosensor.

Early Efficacy of Antipsychotic Medications at Week 2 Predicts Subsequent Responses at Week 6 in a Large-scale Randomized Controlled Trial.

BACKGROUND: Since the early clinical efficacy of antipsychotics has not yet been well perceived, this study sought to decide whether the efficacy of antipsychotics at week 2 can predict subsequent responses at week 6 and identify how such predictive capacities vary among different antipsychotics and psychotic symptoms. METHODS: A total of 3010 patients with schizophrenia enrolled in a randomized controlled trial (RCT) and received a 6-week treatment with one antipsychotic drug randomly chosen from five atypical antipsychotics (risperidone 2-6 mg/d, olanzapine 5-20 mg/d, quetiapine 400-750 mg/d, aripiprazole 10-30 mg/d, and ziprasidone 80-160 mg/d) and two typical antipsychotics (perphenazine 20-60 mg/d and haloperidol 6-20 mg/d). Early efficacy was defined as the reduction rate using the Positive and Negative Syndrome Scale (PANSS) total score at week 2. With cut-offs at 50% reduction, logistic regression, receiver operating characteristic (ROC) and random forests were adopted. RESULTS: The reduction rate of PANSS total score and improvement of psychotic symptoms at week 2 enabled subsequent responses to 7 antipsychotics to be predicted, in which improvements in delusions, lack of judgment and insight, unusual thought content, and suspiciousness/ persecution were endowed with the greatest weight. CONCLUSION: It is robust enough to clinically predict treatment responses to antipsychotics at week 6 using the reduction rate of PANSS total score and symptom relief at week 2. Psychiatric clinicians had better determine whether to switch the treatment plan by the first 2 weeks.