Hyperactivation of mTOR/eIF4E Signaling Pathway Promotes the Production of Tryptophan-To-Phenylalanine Substitutants in EBV-Positive Gastric Cancer.

Although messenger RNA translation is tightly regulated to preserve protein synthesis and cellular homeostasis, chronic exposure to interferon-γ (IFN-γ) in several cancers can lead to tryptophan (Trp) shortage via the indoleamine-2,3-dioxygenase (IDO)- kynurenine pathway and therefore promotes the production of aberrant peptides by ribosomal frameshifting and tryptophan-to-phenylalanine (W>F) codon reassignment events (substitutants) specifically at Trp codons. However, the effect of Trp depletion on the generation of aberrant peptides by ribosomal mistranslation in gastric cancer (GC) is still obscure. Here, it is shows that the abundant infiltrating lymphocytes in EBV-positive GC continuously secreted IFN-γ, upregulated IDO1 expression, leading to Trp shortage and the induction of W>F substitutants. Intriguingly, the production of W>F substitutants in EBV-positive GC is linked to antigen presentation and the activation of the mTOR/eIF4E signaling pathway. Inhibiting either the mTOR/eIF4E pathway or EIF4E expression counteracted the production and antigen presentation of W>F substitutants. Thus, the mTOR/eIF4E pathway exposed the vulnerability of gastric cancer by accelerating the production of aberrant peptides and boosting immune activation through W>F substitutant events. This work proposes that EBV-positive GC patients with mTOR/eIF4E hyperactivation may benefit from anti-tumor immunotherapy.

Study on the interaction mechanism of whey protein isolate with phosphatidylcholine: By multispectral methods and molecular docking.

The elucidation of the interaction mechanism between phospholipids and milk proteins within emulsions is pivotal for comprehending the properties of infant formula fat globules. In this study, multispectral methods and molecular docking were employed to explore the relationship between phosphatidylcholine (PC) and whey protein isolate (WPI). Observations indicate that the binding constant, alongside thermodynamic parameters, diminishes as temperature ascends, hinting at a predominantly static quenching mechanism. Predominantly, van der Waals forces and hydrogen bonds constitute the core interactions between WPI and PC. This assertion is further substantiated by Fourier transform infrared spectroscopy, which verifies PC's influence on WPI's secondary structure. A detailed assessment of thermodynamic parameters coupled with molecular docking reveals that PC predominantly adheres to specific sites within α-lactalbumin, ß-lactoglobulin, and bovine serum albumin, propelled by a synergy of hydrophobic interactions, hydrogen bonding, and van der Waals forces, with binding energies noted at -5.59, -6.71, and -7.85 kcal/mol, respectively. An increment in PC concentration is observed to amplify the emulsification properties of WPI whilst concurrently diminishing the zeta potential. This study establishes a theoretical foundation for applying the PC-WPI interaction mechanism in food.

Effects of non-pharmacological interventions for adults with subjective cognitive decline: a network meta-analysis and component network meta-analysis.

BACKGROUND: Non-pharmacological interventions have a myriad of available intervention options and contain multiple components. Whether specific components of non-pharmacological interventions or combinations are superior to others remains unclear. The main aim of this study is to compare the effects of different combinations of non-pharmacological interventions and their specific components on health-related outcomes in adults with subjective cognitive decline. METHODS: PubMed, Embase, Cochrane, CINAHL, PsycINFO, CENTRAL, Web of Science, and China's two largest databases, CNKI and Wanfang, were searched from inception to 22nd, January 2023. Randomized controlled trials using non-pharmacological interventions and reporting health outcomes in adults with subjective cognitive decline were included. Two independent reviewers screened studies, extracted data, and assessed risk of bias. Component network meta-analysis was conducted employing an additive component model for network meta-analysis. This study followed the PRISMA reporting guideline and the PRISMA checklist is presented in Additional file 2. RESULTS: A total of 39 trials with 2959 patients were included (range of mean ages, 58.79-77.41 years). Resistance exercise might be the optimal intervention for reducing memory complaints in adults with subjective cognitive decline; the surface under the cumulative ranking p score was 0.888, followed by balance exercise (p = 0.859), aerobic exercise (p = 0.832), and cognitive interventions (p = 0.618). Music therapy, cognitive training, transcranial direct current stimulation, mindfulness therapy, and balance exercises might be the most effective intervention components for improving global cognitive function (iSMD, 0.83; 95% CI, 0.36 to 1.29), language (iSMD, 0.31; 95% CI, 0.24 to 0.38), ability to perform activities of daily living (iSMD, 0.55; 95% CI, 0.21 to 0.89), physical health (iSMD, 3.29; 95% CI, 2.57 to 4.00), and anxiety relief (iSMD, 0.71; 95% CI, 0.26 to 1.16), respectively. CONCLUSIONS: The form of physical activity performed appears to be more beneficial than cognitive interventions in reducing subjective memory complaints for adults with subjective cognitive decline, and this difference was reflected in resistance, aerobic, and balance exercises. Randomized clinical trials with high-quality and large-scale are warranted to validate the findings. TRIAL REGISTRATION: PROSPERO registry number. CRD42022355363.

Adherence to therapeutic gastroscopy guidelines for acute esophageal food bolus impaction: Impact on adverse outcomes and length of stay.

Background and Aim: According to the European Society of Gastrointestinal Endoscopy (ESGE), gastroscopy should be conducted within 6 h for complete obstruction and 24 h for incomplete obstruction due to food bolus impaction. This study explores whether adults with acute esophageal food bolus (FB) impaction experience adverse outcomes when their time to esophagogastroduodenoscopy (EGD) deviates from the recommended guidelines. Methods: A retrospective review was performed on the records of 248 patients who presented at the study site between 2015 and 2022 with symptoms of FB impaction. Results: Two hundred and forty-eight patients underwent EGD for FB impaction. Grade 1 (erosion, ulceration), Grade 2 (tear), and Grade 3 (perforation) complications were present in 31.6%, 6.9%, and 0.8% of cases, respectively. Of the 134 (54.0%) patients with complete obstruction, 51 (38.1%) received EGD within the recommended 6 h. Of the 114 (46%) patients with incomplete obstructions, 93 (81.6%) received EGD within the recommended 24 h. There was no statistically significant correlation between length of stay (LOS) post-EGD and any of ingestion to presentation time, presentation to EGD time, or ingestion to EGD time. Age and complication level were greater predictors of longer LOS than presentation to EGD time. Patients who presented in hours were significantly more likely to receive EGD within the 6- and 24-h guidelines than those who presented out of hours (50.7% vs 22.0%). Conclusion: Neither time to EGD from ingestion of food bolus nor time to EGD from hospital presentation correlated with complication rate, complication severity, or length of stay post-EGD.

Clinicopathological significance and prognostic analysis of p21 and EGFR in colorectal cancer: a retrospective analysis on 12 319 cases in China.

AIMS: Colorectal cancer (CRC) is the third most common malignancy worldwide. Accurate pathological diagnosis and predictive abilities for treatment response and prognosis are crucial for patients with CRC. This study aims to analyse the expressions of p21 and EGFR in CRC and their relationships with clinicopathological characteristics and prognosis to enhance diagnostic and prognostic evaluations. METHODS: This study conducted a retrospective analysis of p21 and EGFR expressions in 12 319 Chinese patients with CRC using immunohistochemistry. The relationships between these expressions and clinicopathological characteristics and survival outcomes were explored through statistical and survival analyses. RESULTS: Differential expressions of p21 and EGFR in CRC were closely related to clinicopathological characteristics and significantly impacted overall survival (OS). p21 expression was associated with the primary tumour site, mucinous subtype, lymphovascular invasion, perineural invasion, circumferential resection margin, T stage, N stage, tumour, node, metastases (TNM) stage, and mismatch repair status. EGFR expression was related to mucinous subtype, tumour differentiation, lymphovascular invasion, perineural invasion, tumour size, T stage, N stage, TNM stage and BRAF gene mutation. p21 and EGFR expressions were positively correlated (r=0.11). High p21 expression correlated with favourable OS, whereas high EGFR expression predicted poorer OS. A prognostic nomogram incorporating these biomarkers and clinical variables demonstrated robust predictive power for patient survival rates. CONCLUSION: p21 and EGFR serve as potential indicators for pathological diagnosis, risk stratification, and predicting treatment efficacy and prognosis in patients with CRC. The study's findings provide valuable references for personalised treatment and prognosis evaluation in clinical practice.

Novel methods to diagnose rotator cuff tear and predict post-operative Re-tear: Radiomics models.

Objective: To validated a classifier to distinguish the status of rotator cuff tear and predict post-operative re-tear by utilizing magnetic resonance imaging (MRI) markers. Methods: This retrospective study included patients with healthy rotator cuff and patients diagnosed as rotator cuff tear (RCT) by MRI. Radiomics features were identified from the pre-operative shoulder MRI and selected by using maximum relevance minimum redundancy (MRMR) methods. A radiomics model for diagnosis of RCT was constructed, based on the 3D volume of interest (VOI) of supraspinatus. Another model for the prediction of rotator re-tear after rotator cuff repair (Re-RCT) was constructed based on VOI of humerus, supraspinatus, infraspinatus and other clinical parameters. Results: The model for diagnosing the status of RCT produced an area under the receiver operating characteristic curve (AUC) of 0.989 in the training cohort and 0.979 for the validation cohort. The radiomics model for predicting Re-RCT produced an AUC of 0.923 ± 0.017 for the training dataset and 0.790 ± 0.082 for the validation dataset. The nomogram combining radiomics features and clinical factors yielded an AUC of 0.961 ± 0.020 for the training dataset and 0.808 ± 0.081 for the validation dataset, which displayed the best performance among all models. Conclusion: Radiomics models for the diagnosis of rotator cuff tear and prediction of post-operative Re-RCT yielded a decent prediction accuracy.

Gallic acid suppresses the progression of clear cell renal cell carcinoma through inducing autophagy via the PI3K/Akt/Atg16L1 signaling pathway.

Clear cell renal cell carcinoma (ccRCC), the most common type of renal cell carcinoma (RCC), is not sensitive to traditional radiotherapy and chemotherapy. The polyphenolic compound Gallic acid (GA) can be naturally found in a variety of fruits, vegetables and plants. Autophagy, an intracellular catabolic process, regulates the lysosomal degradation of organelles and portions in cytoplasm. It was reported that autophagy and GA could affect the development of several cancers. Therefore, the aim of the present study was to evaluate the effects of GA on ccRCC development and clarify the role of autophagy in this process. In the present study, the effects of GA on the proliferation, migration and invasion of ccRCC cells were investigated in vitro by Cell Counting Kit­8, colony formation, flow cytometry, wound healing and Transwell migration assays, respectively. Additionally, the effects of GA on ccRCC growth and metastasis were evaluated using hematoxylin­eosin and immunohistochemical staining in vivo. Moreover, it was sought to explore the underlying molecular mechanisms using transmission electron microscopy, western blotting and reverse transcription­quantitative PCR analyses. In the present study, it was revealed that GA had a more potent viability inhibitory effect on ccRCC cells (786­O and ACHN) than the effect on normal renal tubular epithelial cell (HK­2), which demonstrated that GA selectively inhibits the viability of cancer cells. Furthermore, it was identified that GA dose­dependently inhibited the proliferation, migration and invasion of ccRCC cells in vitro and in vivo. It was demonstrated that GA promoted the release of autophagy markers, which played a role in regulating the PI3K/Akt/Atg16L1 signaling pathway. All the aforementioned data provided evidence for the great potential of GA in the treatment of ccRCC.

Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults especially for females: a cross-sectional study.

BACKGROUND: Oral frailty is reported to increase the risk of new onset of mild cognitive impairment. Whereas, the association of oral frailty with cognition among older adults in both physical frail and non-physical frail status has not been sufficiently explored, and whether there are sex differences in the association is unclear. This study investigated the association of oral frailty and physical frailty with global cognitive function and executive function among older adults, as well as the sex differences in such association. METHODS: This cross-sectional study included 307 participants aged ≥ 60 years old from communities between June 2023 and August 2023, in Nanjing, China. Global cognitive function and executive function were assessed by using the Montreal Cognitive Assessment (MoCA) and Trail Making Tests A (TMT-A), respectively. Oral frailty was identified by the combination of natural tooth, Oral Frailty Index-8 (OFI-8), and oral diadochokinesis. Physical frailty was measured by using Fried phenotype model which contained 5 criteria: unintentional weight loss, weakness, exhaustion, slowness, and low physical activity. Multiple linear regression analyses for overall participants and stratified by sex and presence or absence of physical frailty were performed, respectively, to examine the association between oral frailty and cognitive functions. RESULTS: The median age of participants was 70 years old. The study included 158 (51.5%) females, 53 (17.3%) individuals with physical frailty, and 65 (21.2%) participants with oral frailty. After adjustment, the association between oral frailty and global cognitive function was observed in the physical frailty group (B = -2.67, 95% Confidence Interval [CI]: -5.27 to -0.07, p = 0.045) and the females with physical frailty (B = -4, 95% CI: -7.41 to -0.58, p = 0.024). Oral frailty was associated with executive function in overall participants (B = 0.12, 95% CI: 0.01 to 0.22, p = 0.037), physical frailty group (B = 23.68, 95% CI: 1.37 to 45.99, p = 0.038). In the adjusted models, oral frailty was significantly associated with executive function in all females (B = 0.21, 95% CI: 0.05 to 0.36, p = 0.009), in females without physical frailty (B = 0.19, 95% CI: 0.02 to 0.36, p = 0.027), and in females with physical frailty (B = 48.69, 95% CI: 7.17 to 90.21, p = 0.024). CONCLUSIONS: Physical frailty intensifies the positive association of oral frailty with poor global cognitive function and executive function among older adults, particularly among females. It is ponderable to consider sex differences and facilitate the management of physical frailty when it comes to promoting cognitive health based on the perspective of oral health among older adults.

The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery.

In this research, we delved into the predictive potential of three key markers - the neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and Onodera's prognostic nutritional index (OPNI), in assessing lymph node metastases in breast cancer patients who had internal mammary lymph node involvement following thoracoscopic surgery. Our study revealed notable pathological distinctions between the groups with and without metastases, while age, tumor size, and histological grade exhibited no significant differences. The analysis unveiled statistically significant variances in NLR, SII, and OPNI when comparing these two groups. Multivariate analysis pinpointed NLR (OR = 1.503), SII (OR = 1.987), and OPNI (OR = 0.612) as robust predictors of lymph node metastases. Remarkably, combining these markers (AUC: 0.897) substantially enhanced the precision of predicting lymph node metastases compared to individual measurements (NLR: 0.749, SII: 0.717, and OPNI: 0.787). In conclusion, this study underscores the pivotal role of NLR, SII, and OPNI in predicting lymph node metastasis among breast cancer patients with internal mammary lymph node involvement post-thoracoscopic surgery, affirming our utility as reliable independent predictors of this critical clinical outcome.

[Applications of Artificial Intelligence in Pancreatic Cystic Lesion Imaging].

As the detection rate of pancreatic cystic lesions(PCL)increases,artificial intelligence(AI)has made breakthroughs in the imaging workflow of PCL,including image post-processing,lesion detection,segmentation,diagnosis and differential diagnosis.AI-based image post-processing can optimize the quality of medical images and AI-assisted models for lesion detection,segmentation,diagnosis and differential diagnosis significantly enhance the work efficiency of radiologists.This article reviews the application progress of AI in PCL imaging and provides prospects for future research directions.

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

Quantifying cardiac dysfunction and valvular heart disease associated with subretinal drusenoid deposits in age-related macular degeneration.

BACKGROUND/AIMS: Demonstrate through objective multidisciplinary imaging that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to both coexistent valvular heart disease (VHD) and reduced systemic perfusion via cardiac index (CI). METHODS: Post-hoc analysis of cross-sectional study. 200 intermediate AMD (iAMD) subjects were assigned by masked readers to two groups: SDD (with or without drusen) and drusen (only) based on multimodal ophthalmic imaging. 65 transthoracic echocardiograms (TTEs) reports were available for cardiologist evaluation of VHD severity of the four cardiac valves and the presences of precursor lesions of aortic sclerosis (ASc) and mitral annular calcification (MAC). Necessary parameters to calculate CI were also obtained. Univariate testing was performed using Fisher's Exact test and t-test. RESULTS: 82.6% (19/23) of the iAMD subjects with at least one moderate/severe VHD had concurrent SDDs (p = 0.0040). All cases of aortic regurgitation (6/6, p = 0.0370) and mitral regurgitation (13/13, p = 0.0004) were found with coexisting SDDs. Stenotic VHD was not significantly associated with SDDs, however 70.7% of subjects with ASc (29/41, p = 0.0108) and 76.0% of subjects with MAC (19/25, 0.0377) had coexisting SDDs. CI was available in 48 subjects and was significantly below normal levels in the SDD cohort (mean CI SDD 1.95 ± 0.60 L/min/m2, non-SDD 2.71 ± 0.73 L/min/m2, p = 0.0004). CONCLUSIONS: Several specific VHDs have been found associated with the SDD form of AMD. Decreased systemic perfusion as measured by CI was also associated with SDDs, which supports a perfusion hypothesis of SDD pathogenesis. Further research is warranted to understand the relationship between cardiovascular disease and SDDs.

Eosinophilic Gastroenteritis Causing Pyloric Stenosis: A Rare Manifestation.

Eosinophilic gastritis is a gastrointestinal disorder characterized by eosinophilic infiltration in the gastric wall. We present a rare case of critical pyloric stenosis secondary to eosinophilic gastritis in a 16-year-old adolescent girl who presented with nausea, vomiting, early satiety, and abdominal pain. Abdominal computed tomography and subsequent esophagogastroduodenoscopy confirmed the anatomical diagnosis, but histological confirmation of the eosinophilic etiology was challenging. After an unsuccessful trial of high-dose systemic corticosteroids, a laparoscopic gastrojejunostomy was performed and long-term immunosuppression with mycophenolate mofetil was commenced.

Correlation between ellipsoid zone thickness and the presence of subretinal drusenoid deposits in age-related macular degeneration.

PURPOSE: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ) thickness, further evidence of hypoxic damage. METHODS: Post hoc analysis of a cross-sectional study. 165 AMD subjects (aged 51-100; 61% women). Spectral-domain optical coherence tomography was obtained in both eyes. Masked readers assigned subjects to three groups: drusen only, SDD+drusen (SDD+D) and SDD only. EZ thickness was measured subfoveally and 2000 µm nasally, temporally, superiorly and inferiorly from the fovea. Univariate testing was performed using two-tailed t-tests with Bonferroni correction. RESULTS: The mean EZ thickness differences between the SDD+D and drusen-only groups were (in µm) 1.10, 0.67, 1.21, 1.10 and 0.50 at the foveal, nasal, temporal, superior and inferior locations, respectively (p=0.08 inferiorly, otherwise p≤0.01); between the SDD-only and drusen-only groups, the differences were 3.48, 2.48, 2.42, 2.08 and 1.42 (p≤0.0002). Differences in EZ thicknesses across all subjects and between groups were not significantly different based on gender, race or age. CONCLUSION: Subjects with SDDs (±drusen) had thinner EZs than those with drusen only, and the inferior EZ was least affected. EZs were thinnest in SDD-only subjects. This thinning gradation is consistent with progressive destruction of highly oxygen-sensitive mitochondria in the EZ from hypoxia. These findings support the reduced ophthalmic perfusion hypothesis for the formation of SDDs secondary to high-risk systemic vasculopathy.

Epidemiology and risk factors of oral frailty among older people: an observational study from China.

OBJECTIVES: This study aimed to compare the prevalence of oral frailty among community-dwelling older people in Nanjing, China with the usage of different measurements, and to investigate the potential risk factors of oral frailty. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 338 community-dwelling older people in Nanjing, China were recruited. METHODS: Oral frailty was measured based on the Oral Frailty Index-8 (OFI-8) scale and other measurement methods including the number of natural teeth (TN), repetitive saliva-swallowing test (RSST), and oral diadochokinesis (ODK). The chi-square test and the binary logistic regression analysis were performed to identify potential risk factors for oral frailty. RESULTS: There were 310 participants included in the analysis. Prevalence of oral frailty by using the OFI-8, OFI-8 + TN, OFI-8 + ODK, OFI-8 + TN + ODK and RSST measurement methods were 69.0%, 27.4%, 51.9%, 21.0% and 2.9%, respectively. Passive smoking (OR = 2.04; 95%CI 1.03-4.03), being widowed/unmarried (OR1 = 2.53; 95%CI 1.25-5.10; OR2 = 2.94; 95%CI 1.12-7.77), pre-frailty (OR = 1.76; 95%CI 1.03-3.01), frailty (OR = 3.01; 95%CI 1.39-6.54), and aged 80 years and above (OR = 3.99; 95%CI 1.35-11.81) were found to be risk factors of oral frailty by the usage of the four kinds of measurement methods. CONCLUSIONS AND IMPLICATIONS: The definition and diagnostic criteria of oral frailty are strongly needed to be unified in future research. Only subjective assessment is not enough for assessing oral frailty. Among objective indicators, RSST is not suitable as a screening method for oral frailty. In addition, objective indicators including TN and ODK should be valued for early screening and preventive interventions. The risk factors of oral frailty include physical frailty, passive smoking, and being widowed.

Internal Carotid Artery Stenosis and Ipsilateral Subretinal Drusenoid Deposits.

Purpose: Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are strongly associated with vasculopathies such as myocardial infarction and ischemic stroke. This study evaluates ischemic stroke subjects for SDDs to determine whether ocular hypoperfusion from internal carotid artery (ICA) stenosis is associated with ipsilateral SDDs. Methods: A cross-sectional study at Mount Sinai Hospital recruited 39 subjects with ischemic stroke (aged 52-90; 18 women, 21 men); 28 completed all study procedures. Computed tomography (CT) of the head and neck evaluated 54/56 ICAs for stenosis criteria: none (n = 33), mild (n = 12), moderate (n = 3), severe (n = 3), and complete (n = 3). Spectral-domain optical coherence tomography (SD-OCT) scans were read to consensus by two masked graders for soft drusen, SDDs and choroidal thickness (CTh; choroidal thinning = CTh < 250 µm). Univariate testing was done with Fisher's exact test. Multivariate logistic regression models tested age, gender, and ICA stenosis as covariates. Results: Moderate or more ICA stenosis (≥50%-69%) was significantly associated with ipsilateral choroidal thinning (P = 0.021) and ipsilateral SDDs (P = 0.005); the latter were present distal to six of nine stenosed ICAs versus five of 33 normal ICAs. Mild ICA stenosis (≥1%-49%) was not significantly associated with ipsilateral SDDs. Multivariate regression found that older age (P = 0.015) and moderate or more ICA stenosis (P = 0.011) remained significant independent risks for ipsilateral SDDs. Conclusions: At least moderate ICA stenosis (≥50%-69%) is strongly associated with ipsilateral SDDs and choroidal thinning, supporting downstream ophthalmic artery and choroidal hypoperfusion from ICA stenosis as the mechanism for SDD formation. SDDs may thus serve as sensitive biomarkers for ischemic stroke and other vascular diseases.

Co-augmentation of a transport gene mfsT1 in Mycolicibacterium neoaurum with genome engineering to enhance ergothioneine production.

Ergothioneine (EGT) is a rare thiohistidine derivative with exceptional antioxidant properties. The blood level of EGT is considered highly reliable predictors for cardiovascular diseases and mortality, yet animals lack the ability to synthesize this compound. Free plasmids have been previously used to overexpress genes involved in the EGT biosynthetic pathway of Mycolicibacterium neoaurum. Here, we tentatively introduced a putative transporter gene mfsT1 into high-copy plasmids and sharply increased the ratio of extracellular EGT concentration from 18.7% to 44.9%. Subsequently, an additional copy of egtABCDE, hisG, and mfsT1 was inserted into the genome with a site-specific genomic integration tool of M. neoaurum, leading a 2.7 times increase in EGT production. Co-enhancing the S-adenosyl-L-methionine regeneration pathway, or alternatively, the integration of three copies of egtABCDE, hisG and mfsT1 into the genome further increased the total EGT yield by 16.1% (64.6 mg/L) and 21.7% (67.7 mg/L), respectively. After 168-h cultivation, the highest titer reached 85.9 mg/L in the latter strain with three inserted copies. This study provided a solid foundation for genome engineering to increase the production of EGT in M. neoaurum.

Subretinal drusenoid deposits, age-related macular degeneration, and cardiovascular disease.

Decades of studies on age-related macular degeneration (AMD), cardiovascular disease and stroke have not found consistent associations between AMD and systemic vascular disease. This study suggests that there is in fact no general relationship, but instead a strong, specific association between only the subretinal drusenoid deposit (SDD) phenotype of AMD on retinal imaging and certain co-existent vascular diseases that are high risk for compromised cardiac output or internal carotid artery stenosis. Future screening initiatives for these high -risk vascular diseases (HRVDs) with fast, inexpensive retinal imaging could make a significant contribution to public health and save lives. Likewise, screening patients with known HRVDs for unrecognized AMD of the SDD form could enable needed treatment and save vision.

Organohydrogel-based transparent terahertz absorber via ionic conduction loss.

The fast-growing terahertz technologies require high-performance terahertz absorber for suppressing electromagnetic interference. Since the dissipation mechanism in terahertz band usually focuses on electronic conduction loss, almost all terahertz absorbers are constructed with electronically conducting materials being opaque, which limits their applications in scenarios requiring high visible transmittance. Here, we demonstrate a transparent terahertz absorber based on permittivity-gradient elastomer-encapsulated-organohydrogel. Our organohydrogel-based terahertz absorber exhibits a high absorbing property (average reflection loss of 49.03 dB) in 0.5-4.5 THz band with a thin thickness of 700 µm and a high average visible transmittance of 85.51%. The terahertz absorbing mechanism mainly derives from the ionic conduction loss of the polar liquid in organohydrogel. Besides, the hydrophobic and adhesive elastomer coating endows this terahertz absorber high absorbing stability and interfacial adhesivity. This work paves a viable way to designing transparent terahertz absorbers.

Correction: An E-selectin targeting and MMP-2-responsive dextran-curcumin polymeric prodrug for targeted therapy of acute kidney injury.

Correction for 'An E-selectin targeting and MMP-2-responsive dextran-curcumin polymeric prodrug for targeted therapy of acute kidney injury' by Jing-Bo Hu et al., Biomater. Sci., 2018, 6, 3397-3409, https://doi.org/10.1039/C8BM00813B.