Resting state functional connectome in breast cancer patients with fear of cancer recurrence.

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.

E3 ligase Cul2 mediates Drosophila early germ cell differentiation through targeting Bam.

Drosophila ovary has been one of the most mature and excellent systems for studying the in vivo regulatory mechanisms of stem cell fate determination. It has been well-known that the bone morphogenetic protein (BMP) signaling released by the niche cells promotes the maintenance of germline stem cells (GSCs) through inhibiting the transcription of the bag-of-marbles (bam) gene, which encodes a key factor for GSC differentiation. However, whether Bam is regulated at the post-translational level remains largely unknown. Here we show that the E3 ligase Cullin-2 (Cul2) is involved in modulating Bam ubiquitination, which occurs probably at multiple lysine residues of Bam's C-terminal region. Genetic evidence further supports the notion that Cul2-mediated Bam ubiquitination and turnover are essential for GSC maintenance and proper germline development. Collectively, our data not only uncovers a novel regulatory mechanism by which Bam is controlled at the post-translational level, but also provides new insights into how Cullin family protein determines the differentiation fate of early germ cells.

The functional divergence of homologous GPAT9 genes contributes to the erucic acid content of Brassica napus seeds.

BACKGROUND: The early allopolyploid Brassica napus was a hybrid of two Brassica species, that had undergone a whole genome duplication event followed by genome restructuring, including deletions and small scale duplications. A large number of homologous genes appeared functional divergence during species domestication. Due to the high conservation of de novo glycerolipid biosynthesis, multiple homologues of glycerol-3-phosphate acyltransferases (GPATs) have been found in B. napus. Moreover, the functional variances among these homologous GPAT-encoding genes are unclear. RESULTS: In this study, four B. napus homologous genes encoding glycerol-3-phosphate acyltransferase 9 (BnaGPAT9) were characterized. Although a bioinformatics analysis indicated high protein sequence similarity, the homologues demonstrated tissue-specific expression patterns and functional divergence. Yeast genetic complementation assays revealed that BnaGPAT9-A1/C1 homologues but not BnaGPAT9-A10/C9 homologues encoded functional GPAT enzymes. Furthermore, a single nucleotide polymorphism of BnaGPAT9-C1 that occurred during the domestication process was associated with enzyme activity and contributed to the fatty acid composition. The seed-specific expression of BnGPAT9-C11124A increased the erucic acid content in the transformant seeds. CONCLUSIONS: This study revealed that BnaGPAT9 gene homologues evolved into functionally divergent forms with important roles in erucic acid biosynthesis.

Extranodal Extension at Pretreatment MRI and the Prognostic Value for Patients with Rectal Cancer.

Background Detection of extranodal extension (ENE) at pathology is a poor prognostic indicator for rectal cancer, but whether ENE can be identified at pretreatment MRI is, to the knowledge of the authors, unknown. Purpose To evaluate the performance of pretreatment MRI in detecting ENE using a matched pathologic reference standard and to assess its prognostic value in patients with rectal cancer. Materials and Methods This single-center study included a prospective development data set consisting of participants with rectal adenocarcinoma who underwent pretreatment MRI and radical surgery (December 2021 to January 2023). MRI characteristics were identified by their association with ENE-positive nodes (χ2 test and multivariable logistic regression) and the performance of these MRI features was assessed (area under the receiver operating characteristic curve [AUC]). Interobserver agreement was assessed by Cohen κ coefficient. The prognostic value of ENE detected with MRI for predicting 3-year disease-free survival was assessed by Cox regression analysis in a retrospective independent validation cohort of patients with locally advanced rectal cancer (December 2019 to July 2020). Results The development data set included 147 participants (mean age, 62 years ± 11 [SD]; 87 male participants). The retrospective cohort included 110 patients (mean age, 60 years ± 9; 79 male participants). Presence of vessel interruption and fusion (both P < .001), heterogeneous internal structure, and the broken-ring and tail signs (odds ratio range, 4.10-23.20; P value range, <.001 to .002) were predictors of ENE at MRI, and together achieved an AUC of 0.91 (95% CI: 0.88, 0.93) in detecting ENE. Interobserver agreement was moderate for the presence of vessel interruption and fusion (κ = 0.46 for both) and substantial for others (κ = 0.61-0.67). The presence of ENE at pretreatment MRI was independently associated with worse 3-year disease-free survival (hazard ratio, 3.00; P = .02). Conclusion ENE can be detected at pretreatment MRI, and its presence was associated with worse prognosis for patients with rectal cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Eberhardt in this issue.

Fully semantic segmentation for rectal cancer based on post-nCRT MRl modality and deep learning framework.

PURPOSE: Rectal tumor segmentation on post neoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) has great significance for tumor measurement, radiomics analysis, treatment planning, and operative strategy. In this study, we developed and evaluated segmentation potential exclusively on post-chemoradiation T2-weighted MRI using convolutional neural networks, with the aim of reducing the detection workload for radiologists and clinicians. METHODS: A total of 372 consecutive patients with LARC were retrospectively enrolled from October 2015 to December 2017. The standard-of-care neoadjuvant process included 22-fraction intensity-modulated radiation therapy and oral capecitabine. Further, 243 patients (3061 slices) were grouped into training and validation datasets with a random 80:20 split, and 41 patients (408 slices) were used as the test dataset. A symmetric eight-layer deep network was developed using the nnU-Net Framework, which outputs the segmentation result with the same size. The trained deep learning (DL) network was examined using fivefold cross-validation and tumor lesions with different TRGs. RESULTS: At the stage of testing, the Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and mean surface distance (MSD) were applied to quantitatively evaluate the performance of generalization. Considering the test dataset (41 patients, 408 slices), the average DSC, HD95, and MSD were 0.700 (95% CI: 0.680-0.720), 17.73 mm (95% CI: 16.08-19.39), and 3.11 mm (95% CI: 2.67-3.56), respectively. Eighty-two percent of the MSD values were less than 5 mm, and fifty-five percent were less than 2 mm (median 1.62 mm, minimum 0.07 mm). CONCLUSIONS: The experimental results indicated that the constructed pipeline could achieve relatively high accuracy. Future work will focus on assessing the performances with multicentre external validation.

Formylpeptide receptor 1 contributes to epidermal barrier dysfunction-induced skin inflammation through NOD-like receptor C4-dependent keratinocyte activation.

BACKGROUND: Skin barrier dysfunction may both initiate and aggravate skin inflammation. However, the mechanisms involved in the inflammation process remain largely unknown. OBJECTIVES: We sought to determine how skin barrier dysfunction enhances skin inflammation and molecular mechanisms. METHODS: Skin barrier defect mice were established by tape stripping or topical use of acetone on wildtype mice, or filaggrin deficiency. RNA-Seq was employed to analyse the differentially expressed genes in mice with skin barrier defects. Primary human keratinocytes were transfected with formylpeptide receptor (FPR)1 or protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) small interfering RNA to examine the effects of these gene targets. The expressions of inflammasome NOD-like receptor (NLR)C4, epidermal barrier genes and inflammatory mediators were evaluated. RESULTS: Mechanical (tape stripping), chemical (acetone) or genetic (filaggrin deficiency) barrier disruption in mice amplified the expression of proinflammatory genes, with transcriptomic profiling revealing overexpression of formylpeptide receptor (Fpr1) in the epidermis. Treatment with the FPR1 agonist fMLP in keratinocytes upregulated the expression of the NLRC4 inflammasome and increased interleukin-1ß secretion through modulation of ER stress via the PERK-eIF2α-C/EBP homologous protein pathway. The activation of the FPR1-NLRC4 axis was also observed in skin specimens from old healthy individuals with skin barrier defect or elderly mice. Conversely, topical administration with a FPR1 antagonist, or Nlrc4 silencing, led to the normalization of barrier dysfunction and alleviation of inflammatory skin responses in vivo. CONCLUSIONS: In summary, our findings show that the FPR1-NLRC4 inflammasome axis is activated upon skin barrier disruption and may explain exaggerated inflammatory responses that are observed in disease states characterized by epidermal dysfunction. Pharmacological inhibition of FPR1 or NLRC4 represents a potential therapeutic target.

Enhanced muscle activity during interrupted sitting improves glycemic control in overweight and obese men.

The efficacy of interrupting prolonged sitting may be influenced by muscle activity patterns. This study examined the effects of interrupting prolonged sitting time with different muscle activity patterns on continuously monitored postprandial glycemic response. Eighteen overweight and obese men (21.0 ± 1.2 years; 28.8 ± 2.2 kg/m2) participated in this randomized four-arm crossover study, including uninterrupted sitting for 8.5 h (SIT) and interruptions in sitting with matched energy expenditure and duration but varying muscle activity: 30-min walking at 4 km/h (ONE), sitting with 3-min walking at 4 km/h (WALK) or squatting (SQUAT) every 45 min for 10 times. Net incremental area under the curve (netiAUC) for glucose was compared between conditions. Quadriceps, hamstring, and gluteal muscles electromyogram (EMG) patterns including averaged muscle EMG amplitude (aEMG) and EMG activity duration were used to predict the effects on glucose netiAUC. Compared with SIT (10.2 mmol/L/h [95%CI 6.3 to 11.7]), glucose netiAUC was lower during sitting interrupted with any countermeasure (ONE 9.2 mmol/L/h [8.0 to 10.4], WALK 7.9 mmol/L/h [6.4 to 9.3], and SQUAT 7.9 mmol/L/h [6.4 to 9.3], all p < 0.05). Furthermore, WALK and SQUAT resulted in a lower glucose netiAUC compared with ONE (both p < 0.05). Only increased aEMG in quadriceps (-0.383 mmol/L/h [-0.581 to -0.184], p < 0.001) and gluteal muscles (-0.322 mmol/L/h [-0.593 to -0.051], p = 0.022) was associated with a reduction in postprandial glycemic response. Collectively, short, frequent walking or squatting breaks effectively enhance glycemic control in overweight and obese men compared to a single bout of walking within prolonged sitting. These superior benefits seem to be associated with increased muscle activity intensity in the targeted muscle groups during frequent transitions from sitting to activity.

Cross-disease characterization of fibroblast heterogeneities and their pathogenic roles in skin inflammation.

Fibroblasts are critical pro-inflammatory regulators in chronic inflammatory and fibrotic skin diseases. However, fibroblast heterogeneity and the absence of a unified cross-disease taxonomy have hindered our understanding of the shared/distinct pathways in non-communicable skin inflammation. By integrating 10× single-cell data from 75 skin samples, we constructed a single-cell atlas across inflammatory and fibrotic skin diseases and identified 9 distinct subsets of skin fibroblasts. We found a shared subset of CCL19+ fibroblasts across these diseases, potentially attracting and educating immune cells. Moreover, COL6A5+ fibroblasts were a distinct subset implicated in the initiation and relapse of psoriasis, which tended to differentiate into CXCL1+ fibroblasts, inducing neutrophil chemotaxis and infiltration; while CXCL1+ fibroblasts exhibited a more heterogeneous response to certain inflammatory conditions. Differentiation trajectory and regulatory factors of these fibroblast subsets were also revealed. Therefore, our study presents a comprehensive atlas of skin fibroblasts and highlights pathogenic fibroblast subsets in skin disorders.

Wastewater treatment: A universal, scalable and recyclable catalyst with adjustable activity for diverse dyes degradation.

The growing concern over water shortage and pollution is propelling and accelerating the development of sewage treatment technologies. Among them, the catalytic hydrogenation method is highly recommended from a sustainable perspective, because it can turn toxic pollutants into valuable raw materials. The catalyst with excellent activity and stability plays a critical role in this "trash to treasure" approach. Herein, we proposed a novel economical, scalable and recyclable candidate catalyst, i.e., the copper nanoparticles supported on zinc oxide nanowire array (Cu-ZnO NWA), for realizing efficient and stable dye wastewater treatment. The salix argyracea-shaped Cu-ZnO NWA displays very outstanding universality and controllability towards the catalytic hydrogenation reactions of diverse dyes, owing to the fact that ZnO nanowire array not only offers a platform to realize stable and homogeneous dispersion of Cu nanoparticles, but also provides a large quantity of catalytically active sites. More attractively, its synthetic method can be facilely extended to various conductive substrates through combined electrodeposition and hydrothermal technique, showing its general applicability for the surface assembly of sewage treatment facilities. Benefiting from above advantages, this proposal offers an attractive approach for large-scale and continuous decolorization of dye wastewater, and presents a broad application prospect in the textile printing industry.

Dietary Supplementation of Aspirin Promotes Drosophila Defense against Viral Infection.

Aspirin, also known as acetylsalicylic acid, is widely consumed as a pain reliever and an anti-inflammatory as well as anti-platelet agent. Recently, our studies using the animal model of Drosophila demonstrated that the dietary supplementation of aspirin renovates age-onset intestinal dysfunction and delays organismal aging. Nevertheless, it remains probable that aspirin plays functional roles in other biological activities, for instance antiviral defense reactions. Intriguingly, we observed that the replications of several types of viruses were drastically antagonized in Drosophila macrophage-like S2 cells with the addition of aspirin. Further in vivo experimental approaches illustrate that adult flies consuming aspirin harbor higher resistances to viral infections with respect to flies without aspirin treatment. Mechanistically, aspirin positively contributes to the Drosophila antiviral defense largely through mediating the STING (stimulator of interferon genes) but not the IMD (immune deficiency) signaling pathway. Collectively, our studies uncover a novel biological function of aspirin in modulating Drosophila antiviral immunity and provide theoretical bases for exploring new antiviral treatments in clinical trials.

Dichlorodiphenyltrichloroethane for Malaria and Agricultural Uses and Its Impacts on Human Health.

Pesticides are widely used in agriculture and disease control, and dichlorodiphenyltrichloroethane (DDT) is one of the most used pesticides in human history. Besides its significant contributions in pest control in agriculture, DDT was credited as having saved millions of human lives for controlling malaria and other deadly insect-transmitted diseases. Even today, the use of DDT in some countries for malaria control cannot be replaced without endangering people who live there. The recent COVID-19 pandemic has changed our lives and reminded us of the challenges in dealing with infectious diseases, especially deadly ones including malaria. However, DDT and its metabolites are stable, persist long, are found in almost every corner of the world, and their persistent effects on humans, animals, and the environment must be seriously considered. This review will focus on the history of DDT use for agriculture and malaria control, the pathways for the spread of DDT, benefits and risks of DDT use, DDT exposure to animals, humans, and the environment, and the associated human health risks. These knowledge and findings of DDT will benefit the selection and management of pesticides worldwide.

[Research Progress in Pathogenesis of Hypertension in Acute Intermittent Porphyria].

Acute intermittent porphyria (AIP) has complicated clinical manifestations and is often accompanied by hypertension.AIP may cause hypertension through adrenergic effect,heme deficiency,inflammation,inappropriate secretion of antidiuretic hormone,toxicity of delta-aminolevulinic acid(ALA,aporphyrin precursor),and elevated serum glucose level.The prevention and treatment strategies for AIP accompanied with hypertension mainly include the controlling of porphyria attacks,application of antihypertensive drugs,lifestyle intervention,and management of latent AIP patients.

Activating PIK3CA postzygotic mutations in segmental overgrowth of muscles with bone involvement in the body extremities.

Segmental overgrowth of the skeletal muscles with bone involvement in body extremities, predominantly affecting the upper limb, is an extremely rare condition with only 40-50 affected children described clinically. The molecular pathogenesis of this disorder remains largely unclear except for the identification of a somatic PIK3CA mutation in each of the six patients genetically tested, all restricted to upper limbs in the literature. This study aimed to further characterize the molecular defects for patients affected with segmental overgrowth of the skeletal muscles by analyzing a 9-gene panel selected from the PI3K/AKT/mTOR pathway and genes associated with other related conditions. Nineteen unrelated patients were chosen for this study, comprising ten upper limb (nine unilateral and one bilateral) and nine lower limb (eight unilateral and one bilateral) cases with variable bone involvement. In each case, an activating PIK3CA mutation (p.E110del, p.N345K, p.E542K, p.E545K, p.H1047R, or p.H1047L) was identified in the affected muscle tissue with variant allele frequencies ranging from 13.88 to 30.43%, while no mutation was detected in the paired peripheral blood sample, indicating somatic mosaicism. All detected mutations were limited to PIK3CA and were previously reported in other overgrowth syndromes currently categorized under the PIK3CA-Related Overgrowth Spectrum (PROS). Our study provides strong molecular evidence that isolated segmental overgrowth of the skeletal muscle with bone involvement is a subtype of PROS. Our findings expand the PROS clinical presentations with a newly molecularly classified condition and can provide guidance in clinical and molecular diagnosis and treatment for patients with this condition.

Contrast-enhanced MRI for T Restaging of Locally Advanced Rectal Cancer Following Neoadjuvant Chemotherapy and Radiation Therapy.

Background Accurate restaging of rectal cancer is crucial in the selection of candidates for local excision after neoadjuvant chemotherapy and radiation therapy (NCRT). The conventional approach of combined T2-weighted imaging and diffusion-weighted imaging (DWI) at MRI has been found to have limitations in restaging. Purpose To determine the diagnostic performance of contrast-enhanced MRI in distinguishing between pathologic stage ypT0-1 and ypT2-4 rectal cancer after NCRT compared with T2-weighted imaging and DWI by using surgical pathologic specimens as the reference standard. Materials and Methods This retrospective study evaluated MRI scans in all consecutive patients with locally advanced rectal cancer who underwent total mesorectal excision after NCRT in Peking University Cancer Hospital (Beijing, China) from January 2014 to October 2018. All MRI features obtained before and after NCRT were evaluated by two experienced radiologists, independently and blinded to personal, clinical, and histopathologic information. The post-NCRT yT stage was assigned based on high b value (b = 1000 sec/mm2) DWI with T2-weighted imaging (protocol 1) in the first round and on contrast-enhanced MRI scans (protocol 2) in a second round. The diagnostic accuracies for the differentiation of pathologic stage ypT0-1 from ypT2-4 tumors with the two protocols were compared. Multivariable regression analysis was used to explore the independent predictors of pathologic stage ypT0-1 tumors. Results A total of 328 patients (mean age, 57 years ± 10 [SD]; 227 men; 69%) were enrolled. The area under the receiver operating characteristic curve of the contrast-enhanced MRI protocol in predicting pathologic stage ypT0-1 tumors was 0.81 (95% CI: 0.77, 0.85), which was better than that of the T2-weighted DWI protocol (0.66; 95% CI: 0.60, 0.71; P < .001). Multivariable logistic regression analysis showed that yT stage after NCRT on contrast-enhanced MRI scans was the only independent predictor of pathologic stage ypT0-1 tumors (P < .001). Conclusion Contrast-enhanced MRI provides accurate differentiation of ypT0-1 from ypT2-4 tumors after neoadjuvant chemotherapy and radiation therapy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Zins and Santiago in this issue.

Engineering a CRISPR interference system targeting AcrAB-TolC efflux pump to prevent multidrug resistance development in Escherichia coli.

OBJECTIVES: We engineered a CRISPR interference (CRISPRi) system targeting the AcrAB-TolC efflux pump to prevent MDR development in Escherichia coli. METHODS: Nine specific single-guide RNAs (sgRNAs) were designed to target the components of the AcrAB-TolC efflux pump, namely AcrA, AcrB and TolC. A total of thirteen CRISPRi recombinant plasmids were constructed with single or clustered sgRNAs. The transcriptional levels of the target genes, MICs of multiple antibiotics and biofilm formation in each CRISPRi strain were tested. RESULTS: The CRISPRi system expressing sgRNA clusters targeting acrB and tolC simultaneously exhibited the highest inhibitory effect on AcrAB-TolC efflux pump activity in E. coli HB101, with 78.3%, 90.0% and 65.4% inhibition rates on the transcriptional levels of acrA, acrB and tolC, respectively. The CRISPRi system resulted in ∼2-, ∼8- and 16-fold increased susceptibility to rifampicin, erythromycin and tetracycline, respectively. In addition, the constructed CRISPRi system reduced biofilm formation with inhibition rates in the range of 11.2% to 58.2%. CONCLUSIONS: To the best of our knowledge, this is the first report on the construction of an inducible CRISPRi system targeting the AcrAB-TolC efflux pump to prevent MDR development in E. coli. This study provides insights for future regulation and manipulation of AcrAB-TolC activity and bacterial MDR by a CRISPRi system.

Genome-wide DNA methylation analysis of peripheral blood cells derived from patients with first-episode schizophrenia in the Chinese Han population.

Schizophrenia is a severe neuropsychiatric disorder with core features including hallucinations, delusions, and cognition deficits. Accumulating evidence has implicated abnormal DNA methylation in the development of schizophrenia. However, the mechanisms by which DNA methylation changes alter the risk for schizophrenia remain largely unknown. We recently carried out a DNA methylome study of peripheral blood samples from 469 first-episode patients with schizophrenia and 476 age- and gender-matched healthy controls of Han Chinese origin. Genomic DNA methylation patterns were quantified using an Illumina Infinium Human MethylationEPIC BeadChip. We identified multiple differentially methylated positions (DMPs) and regions between patients and controls. The most significant DMPs were annotated to genes C17orf53, THAP1 and KCNQ4 (KV7.4), with Bonferroni-adjusted P values of [Formula: see text], [Formula: see text], and [Formula: see text], respectively. In particular, KCNQ4 encodes a voltage-gated potassium channel of the KV7 family, which is linked to neuronal excitability. The genes associated with top-ranked DMPs also included many genes involved in nervous system development, such as LIMK2 and TMOD2. Gene ontology analysis of the differentially methylated genes further identified strong enrichment of neuronal networks, including neuron projection extension, axonogenesis and neuron apoptotic process. Finally, we provided evidence that schizophrenia-associated epigenetic alterations co-localize with genetic susceptibility loci. By focusing on first-episode schizophrenia patients, our investigation lends particularly strong support for an important role of DNA methylation in schizophrenia pathogenesis unconfounded by the effects of long-term antipsychotic medication or disease progression. The observed DNA methylation aberrations in schizophrenia patients could potentially provide a valuable resource for identifying diagnostic biomarkers and developing novel therapeutic targets to benefit schizophrenia patients.

Spectrum of Spondyloarthritis Among Chinese Populations.

PURPOSE OF REVIEW: This review aims to emphasize interesting and important new findings with a focus on the spectrum of spondyloarthritis (SpA) in China. RECENT FINDINGS: Over the past decade, significant advances have been made in the investigation of SpA epidemiology, the exploration of genetic and environmental risk factors, the identification of clinical features, and the updating of treatment protocols in the Chinese population. The prevalence of ankylosing spondylitis (AS) in China is 0.20-0.42%, and the prevalence of HLA-B27 in AS patients is 88.8-89.4%. HLA-B*2704 is the most common subtype in Chinese AS patients, followed by HLA-B*2705. HLA-A*01, more precisely HLA-A*01:01, may be associated with psoriatic arthritis (PsA). Tumor necrosis factor inhibitors and IL-17A inhibitors have been shown to be effective and safe for AS patients in China. Juvenile-onset AS is relatively rare, accounting for only 9.1% of the AS population. The prevalence of arthritis related to inflammatory bowel disease is 6.9 to 7.2%. A Chinese study showed that the most frequently prescribed medication was methotrexate (66.4%). Biological agents were prescribed in only16.4% of patients with PsA. This review summarizes the latest research in the epidemiology, pathogenesis, clinical manifestations, and management of SpA among Chinese populations. Multiple HLA associations with SpA have also been described, and it is hoped that discoveries of such ethnic-specific risk factor(s) and understanding of their pathological mechanisms may potentially lead to newer targeted therapies for the Chinese populations worldwide.

Improving the color and functional properties of seabuckthorn seed protein with phytase treatment combined with alkaline solubilization and isoelectric precipitation.

BACKGROUND: Reducing anti-nutritional factors like phytates in seed protein products requires an ongoing effort. This study was the first to investigate the phytic acid content in seabuckthorn seed protein (SSP) and its reduction by an exogenous phytase during protein isolation from seabuckthorn seed meal through the common alkaline solubilization-isoelectric precipitation process. RESULTS: The additional phytase treatment could reduce the content of phytic acid from 22.46 to 13.27 g kg-1 , leading to SSP products with lighter color (lower ΔE* ), higher protein solubility, higher in vitro digestibility, but lower phenolic antioxidant content (including flavonoids and procyanidins) and some beneficial ions like Ca, Fe, Mg, and Zn. The Fourier transform infrared (FTIR) results indicated that the secondary structure of protein changed under the treatment with phytase. Correlation analysis showed that L* was significantly negatively correlated with TP, TPC and TF (P < 0.001), while a* and b* were significantly positively correlated with them (P < 0.001). CONCLUSIONS: There may be a trade-off between protein functionalities and other health-promoting components when a phytase treatment is included in SSP isolation. © 2021 Society of Chemical Industry.

Switching metabolic flux by engineering tryptophan operon-assisted CRISPR interference system in Klebsiella pneumoniae.

One grand challenge for bioproduction of desired metabolites is how to coordinate cell growth and product synthesis. Here we report that a tryptophan operon-assisted CRISPR interference (CRISPRi) system can switch glycerol oxidation and reduction pathways in Klebsiella pneumoniae, whereby the oxidation pathway provides energy to sustain growth, and the reduction pathway generates 1,3-propanediol and 3-hydroxypropionic acid (3-HP), two economically important chemicals. Reverse transcription and quantitative PCR (RT-qPCR) showed that this CRISPRi-dependent switch affected the expression of glycerol metabolism-related genes and in turn improved 3-HP production. In shake-flask cultivation, the strain coexpressing dCas9-sgRNA and PuuC (an aldehyde dehydrogenase native to K. pneumoniae for 3-HP biosynthesis) produced 3.6 g/L 3-HP, which was 1.62 times that of the strain only overexpressing PuuC. In a 5 L bioreactor, this CRISPRi strain produced 58.9 g/L 3-HP. When circulation feeding was implemented to alleviate metabolic stress, biomass was substantially improved and 88.8 g/L 3-HP was produced. These results indicated that this CRISPRi-dependent switch can efficiently reconcile biomass formation and 3-HP biosynthesis. Furthermore, this is the first report of coupling CRISPRi system with trp operon, and this architecture holds huge potential in regulating gene expression and allocating metabolic flux.

Regional anesthetics versus analgesia for stopping the persistent postsurgical pain: A meta-analysis.

INTRODUCTION: Regional anesthesia might moderate the risk of persistent postsurgical pain, but its effect compared to systemic analgesia is still conflicting. This meta-analysis study was performed to assess the relationship between the efficiency of regional anesthesia versus systemic analgesia in reducing pain persisting longer than 3 months after surgery. METHODS: Through a systematic literature search up to August 2020, 31 studies included 2975 subjects who underwent surgery at baseline and reported a total of 1471 subjects using regional anesthesia and 1319 subjects using conventional anesthesia were found recording relationships between efficiency of regional anesthesia versus systemic analgesia in reducing pain persisting longer than 3 months after surgery. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated between regional anesthesia versus systemic analgesia in reducing pain persisting longer than 3 months after surgery using the dichotomous methods with a random or fixed-effect model. RESULTS: Number of subjects reporting persistent pain 3 months postsurgery was significantly lower in regional anesthesia compared to systemic analgesia in thoracotomy (OR, 0.44; 95% CI, 0.29-0.65, P < .001); breast surgery (OR, 0.46; 95% CI, 0.29-0.72, P < .001); and cesarean section (OR, 0.44; 95% CI, 0.27-0.72, P < .001). CONCLUSIONS: Regional anesthesia might have an independent relationship with lower pain persisting longer than 3 months after thoracotomy, breast surgery, and cesarean section. Further studies are required to validate these findings.