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Previous studies suggest that semantic concepts are characterized by high-dimensional neural representations and that language proficiency affects semantic processing. However, it is not clear whether language proficiency modulates the dimensional representations of semantic concepts at the neural level. To address this question, the present study adopted principal component analysis (PCA) and representational similarity analysis (RSA) to examine the differences in representational dimensionalities (RDs) and in semantic representations between words in highly proficient (Chinese) and less proficient (English) language. PCA results revealed that language proficiency increased the dimensions of lexical representations in the left inferior frontal gyrus, temporal pole, inferior temporal gyrus, supramarginal gyrus, angular gyrus, and fusiform gyrus. RSA results further showed that these regions represented semantic information and that higher semantic representations were observed in highly proficient language relative to less proficient language. These results suggest that language proficiency is associated with the neural representational dimensionality of semantic concepts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Various strategies are developed to engineer aligned hierarchical architectures in polymer hydrogels for enhanced mechanical performance. However, chain alignment remains impeded by the presence of hydrogen bonds between adjacent chains. Herein, a facile sacrificial micelle-assisted-alignment strategy is proposed, leading to well-aligned, strong and tough pure chitosan hydrogels. The sacrificial sodium dodecyl sulfate micelles electrostatically interact with the protonated chitosan chains, enabling chain sliding and alignment under uniaxial forces. Subsequently, sacrificial micelles can be easily removed via NaOH treatment, causing the reforming of H-bond in the chain networks. The strength of the pure chitosan hydrogels increases 140-fold, reaching 58.9 ± 3.4 MPa; the modulus increases 595-fold, reaching 226.4 ± 42.8 MPa. After drying-rehydration, the strength and modulus further rise to 70.3 ± 2.4 and 403.5 ± 76.3 MPa, marking a significant advancement in high-strength pure chitosan hydrogel films. Furthermore, the designed multiscale architectures involving enhanced crystallinity, well-aligned fibers, strong interfaces, robust multilayer Bouligand assembly contribute to the exact replica of lobster underbelly with impact resistance up to 6.8 ± 1.0 kJ m -1 . This work presents a promising strategy for strong, tough, stiff and impact-resistant polymer hydrogels via well-aligned hierarchical design., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The complex of natural organic matter (NOM) and iron minerals in sediment is the main host and source of groundwater iodine. However, the transformation pathways of the complex remain unclear. The groundwater and sediment from the Hetao Basin were collected in this study to analyze multi-isotopes, NOM molecular characteristics, and iron mineral phases. The results showed that high-iodine groundwater was mainly observed in the discharge area, where biodegradation of NOM, sulfate reduction and methanogenesis occurred. Compared to the shallow clayey sediments, the confined sandy sediments had lower iodine content, a lower fraction of crystalline iron oxides, and a higher fraction of carbonate associated Fe(II) minerals, suggesting that the release of sediment iodine in the aquifer is related to the transformation of sediment Fe(III) hydroxides/oxides. Moreover, the molecular features of high-iodine groundwater NOM and sandy sediment NOM were characterized by a higher proportion of refractory compounds, suggesting that the reductive transformation of sediment Fe(III) hydroxides/oxides is fueled by degradable organic compounds. The microbial Fe-reducing and/or sulfate-reducing processes cause the enrichment of groundwater iodine in the form of iodide via the transformation of iodine species. These findings provide new insights into the genesis of high-iodine groundwater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To investigate multi-dose and timings of COVID-19 vaccines in preventing antenatal infection., Design: Prospective observational study investigating primary vaccinations, boosters, antenatal COVID-19 infections, neutralizing antibody (Nab) durability, and cross-reactivity to Delta and Omicron variants of concern (VOCs)., Results: Ninety-eight patients completed primary vaccination prepregnancy (29.6%) and antenatally (63.3%), 24.2% of whom had antenatal COVID-19, while 7.1% were unvaccinated (28.6% had antenatal COVID-19). None had severe COVID-19. Prepregnancy vaccination resulted in vaccination-to-infection delay of 23.3 weeks, which extended to 45.2 weeks with a booster, compared to 16.9 weeks following antenatal vaccination (P < 0.001). Infections occurred at 26.2 weeks gestation in women vaccinated prepregnancy compared to 36.2 weeks gestation in those vaccinated during pregnancy (P < 0.007). The risk of COVID-19 infection was higher without antenatal vaccination (hazard ratio [HR] 14.6, P = 0.05) and after prepregnancy vaccination without a booster (HR 10.4, P = 0.002). Antenatal vaccinations initially led to high Nab levels, with mild waning but subsequent rebound. Significant Nab enhancement occurred with a third-trimester booster. Maternal-neonatal Nab transfer was efficient (transfer ratio >1), and cross-reactivity to VOCs was observed., Conclusion: Completing vaccination during any trimester delays COVID-19 infection and maintains effective neutralizing activity throughout pregnancy, with robust cross-reactivity to VOCs and efficient maternal-neonatal transfer., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The human gut microbiota is a complex ecosystem that plays a crucial role in promoting the interaction between the body and its environment. It has been increasingly recognized that the gut microbiota has diverse physiological functions. Recent studies have shown a close association between the gut microbiota and the development of certain tumors, including leukemia. Leukemia is a malignant clonal disease characterized by the uncontrolled growth of one or more types of blood cells, which is the most common cancer in children. The imbalance of gut microbiota is linked to the pathological mechanisms of leukemia. Probiotics, which are beneficial microorganisms that help maintain the balance of the host microbiome, play a role in regulating gut microbiota. Probiotics have the potential to assist in the treatment of leukemia and improve the clinical prognosis of leukemia patients. This study reviews the relationship between gut microbiota, probiotics, and the progression of leukemia based on current research. In addition, utilizing zebrafish leukemia models in future studies might reveal the specific mechanisms of their interactions, thereby providing new insights into the clinical treatment of leukemia. In conclusion, further investigation is still needed to fully understand the accurate role of microbes in leukemia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zhang, Zhao, Zhang, Zhang and Wei.)

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are reported to cause stress cardiomyopathy (SC). This study evaluated the association between SSRI/SNRI use and the occurrence of cardiomyopathy in the publicly available U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionate analysis and likelihood ratio tests were used to identify risk associated with SSRIs or SNRIs and the incidence of SC, using data from between from 2012 to 2022 acquired from the FAERS database. The study identified 132 individual case safety reports (ICSRs) of SC associated with SSRIs or SNRIs. Venlafaxine (48%) and fluoxetine (27%) were the most common antidepressants of the ICSRs. Approximately 80% of SC cases were reported in females, with individuals aged 45-65 years identified as a high-risk population. Both venlafaxine (ratio-scale information component [RSIC] 2.54, 95% CI 2.06-3.04) and fluoxetine (RSIC 3.20, 95% CI 2.31-4.47) were associated with SC, with likelihood ratio estimates of 3.55 (p = 0.02) for venlafaxine and 4.82 (p = 0.008) for fluoxetine. The median time to cardiomyopathy onset was 20 days, with hospitalization reported in 48.33% of patients. Venlafaxine and fluoxetine were associated with SC risk, particularly in middle-aged women. Caution should be exercised when using SSRIs or SNRIs combined with other serotonergic medications., (© 2024. The Author(s).)

For decades, implant-associated infections (IAIs) caused by pathogenic bacteria have been associated with high failure and mortality rates in implantation surgeries, posing a serious threat to global public health. Therefore, developing a functionalized biomaterial coating with anti-fouling and anti-bacterial functions is crucial for alleviating implant infections. Herein, a near-infrared-responsive anti-bacterial and anti-adhesive coating (Ti-PEG-Cu 2- x S) constructed on the surface of titanium (Ti) implants is reported. This coating is composed of nano-Cu 2- x S with anti-bacterial activity and super-hydrophilic polyethylene glycol (PEG). Under near-infrared irradiation, the nano-catalyst Cu 2- x S on the surface of Ti-PEG-Cu 2- x S induces bacterial death by catalyzing the production of singlet oxygen ( 1 O 2 ). The Ti-PEG-Cu 2- x S coating can effectively prevent bacterial adhesion and biofilm formation. This coating combines the antibacterial mechanisms of "active attack" and "passive defense", which can kill bacteria and inhibit biofilm formation. The results of in vitro and in vivo experiments have shown that Ti-PEG-Cu 2- x S exhibits excellent anti-bacterial properties under near-infrared irradiation and can effectively prevent implant-related infections caused by Escherichia coli ( E. coli ) ATCC 8739 and Staphylococcus aureus ( S. aureus ). The antibacterial efficiency of Ti-PEG-Cu 2- x S coatings against E. coli was 99.96% ± 0.058% and that of S. aureus was 99.66% ± 0.26%, respectively. In addition, the Ti-PEG-Cu 2- x S coating has good blood compatibility and excellent bactericidal ability. Therefore, this multifunctional coating combines a non-adhesive surface strategy and a near-infrared phototherapy sterilization method, effectively blocking the initial attachment and proliferation of bacteria on implants via photothermal/photodynamic effects and providing a promising method for preventing bacterium-induced IAIs.

The first example of rhodium-catalyzed nondirected C-H activation/annulation reactions for the construction of fused heterocyclic cations is reported herein with excellent regioselectivity. Deuterium-labeling experiments indicated that the C(sp 3 )-H bond cleavage of the N -methyl group might be the rate-limiting step during the reaction process. This protocol provides an opportunity to rapidly access highly π-conjugated fused heterocyclic cations, which opens up a new avenue for efficient screening of single-molecular white-light-emitting materials, pure red-light-emitting materials, and π-conjugated radical materials. Importantly, novel white-light-emitting materials exhibited distinct anti-Kasha dual-emission and could rapidly be fabricated into robust organic and low-cost white light-emitting diodes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Semantic processing, a core of language comprehension, involves the activation of brain regions dispersed extensively across the frontal, temporal, and parietal cortices that compose the semantic network. To comprehend the functional structure of this semantic network and how it prepares for semantic processing, we investigated its intrinsic functional connectivity (FC) and the relation between this pattern and semantic processing ability in a large sample from the Human Connectome Project (HCP) dataset. We first defined a well-studied brain network for semantic processing, and then we characterized the within-network connectivity (WNC) and the between-network connectivity (BNC) within this network using a voxel-based global brain connectivity (GBC) method based on resting-state functional magnetic resonance imaging (fMRI). The results showed that 97.73% of the voxels in the semantic network displayed considerably greater WNC than BNC, demonstrating that the semantic network is a fairly encapsulated network. Moreover, multiple connector hubs in the semantic network were identified after applying the criterion of WNC > 1 SD above the mean WNC of the semantic network. More importantly, three of these connector hubs (i.e., the left anterior temporal lobe, angular gyrus, and orbital part of the inferior frontal gyrus) were reliably associated with semantic processing ability. Our findings suggest that the three identified regions use WNC as the central mechanism for supporting semantic processing and that task-independent spontaneous connectivity in the semantic network is essential for semantic processing., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An analytical method was developed for the screening of 172 veterinary drugs in traditional Chinese medicine Galli Gigerii Endothelium Corneum by high-performance liquid chromatography tandem mass spectrometry. The samples were pretreated by a modified QuEChERS method. A Zorbax Eclipse plus C18 column (1.8 μm, 3.0 × 150 mm2, Agilent) was used for the separation of analytes by gradient elution. All analytes were detected by electrospray ionization mass spectrometry with multiple reaction monitoring mode. Good linearity with R ≥ 0.99 was exhibited for all analytes within the respective range. The recoveries of all monitored analytes ranged from 55.4 to 127.6% at three spiked levels (limit of quantitation-LOQ, 2-fold LOQ, 10-fold LOQ), with relative standard deviations <17.8%. The estimated LOQ levels were 0.2-20 μg/kg. The application of this method provides a reference for the safety control of traditional Chinese medicines., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Diabetic wounds are a significant clinical challenge. Developing effective antibacterial dressings is crucial for preventing wound ulcers caused by bacterial infections. In this study, a self-healing antibacterial hydrogel (polyvinyl alcohol (PVA)-polylysine-gum arabic, PLG hydrogels) with near-infrared photothermal response was prepared by linking PVA and a novel polysaccharide-amino acid compound (PG) through borate bonding combined with freeze-thaw cycling. Subsequently, the hydrogel was modified by incorporating inorganic nanoparticles (modified graphene oxide (GM)). The experimental results showed that the PLGM 3 hydrogels (PLG@GM hydrogels, 3.0 wt%) could effectively kill bacteria and promote diabetic wound tissue healing under 808-nm near-infrared laser irradiation. Therefore, this hydrogel system provides a new idea for developing novel dressings for treating diabetic wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Hypertension is one of the major public health problems in China. Limited evidence exists regarding sex differences in the association between hypertension and air pollutants, as well as the impact of dietary factors on the relationship between air pollutants and hypertension. The aim of this study was to investigate the sex-specific effects of dietary patterns on the association between fine particulate matter (PM 2.5 ), ozone(O 3 ) and hypertension in adults residing in Jiangsu Province of China., Methods: A total of 3189 adults from the 2015 China Adult Chronic Disease and Nutrition Surveillance in Jiangsu Province were included in this study. PM 2.5 and O 3 concentrations were estimated using satellite space-time models and assigned to each participant. Dietary patterns were determined by reduced rank regression (RRR), and multivariate logistic regression was used to assess the associations of the obtained dietary patterns with air pollutants and hypertension risk., Results: After adjusting for confounding variables, we found that males were more sensitive to long-term exposure to PM 2.5 (Odds ratio (OR) = 1.42 95%CI:1.08,1.87), and females were more sensitive to long-term exposure to O 3 (OR = 1.61 95%CI:1.15,2.23). Traditional southern pattern identified through RRR exhibited a protective effect against hypertension in males (OR = 0.73 95%CI: 0.56,1.00). The results of the interaction between dietary pattern score and PM 2.5 revealed that adherence to traditional southern pattern was significantly associated with a decreased risk of hypertension in males (P < 0.05), while no significant association was observed among females., Conclusions: Our findings suggested that sex differences existed in the association between dietary patterns, air pollutants and hypertension. Furthermore, we found that adherence to traditional southern pattern may mitigate the risk of long-term PM 2.5 exposure-induced hypertension in males., (© 2024. The Author(s).)

Bacterial infection is the most common risk factor that causes the failure of implantation surgery. Therefore, the development of biocompatible implants with excellent antibacterial properties is of utmost importance. In this study, NIR light-driven AgBiS 2 @ZIF-8 hybrid photocatalysts for rapid bacteria-killing were prepared. AgBiS 2 @ZIF-8 exhibited excellent photocatalytic activity due to the rapid transfer of photoelectrons from AgBiS 2 to ZIF-8, resulting in abundant reactive oxygen species (ROS) to kill bacteria. Meanwhile, AgBiS 2 @ZIF-8 exhibited a noteworthy photothermal effect, which could effectively convert NIR light into heat. Subsequently, the NIR light-driven antibacterial activity of AgBiS 2 @ZIF-8/Ti against S. aureus and E. coli was studied. The experimental results showed that AgBiS 2 @ZIF-8 displayed enhanced photodynamic therapy (PDT) and photothermal therapy (PTT) performance. Under irradiation with 808 nm NIR light for 10 min, AgBiS 2 @ZIF-8/Ti could effectively eliminate 98.55% of S. aureus in vitro , 99.34% of E. coli in vitro and 95% S. aureus in vivo . At the same time, AgBiS 2 @ZIF-8/Ti had good biocompatibility. Therefore, AgBiS 2 @ZIF-8/Ti showed potential as an antibacterial material, which provided a strategy to fight polymicrobial infections.

Unlike thermoplastic petroleum-based materials, starch-based materials rely on aqueous systems but are incapable of hot melting, resulting in low processing efficiency and limited large-scale industrial applications. In this study, the combination of α-amylase liquefaction and urea plasticization was used for the first time to obtain enzymatic thermoplastic starch (ETPS) for hot melting by changing the molecular chain of starch. ETPS showed an apparent hot melting phenomenon when heated below 200 °C. Differential scanning calorimetry revealed that heat absorption peaks were obviously reduced, and the hot melting phenomenon occurred easily depending on the combination of enzymatic hydrolysis and plasticization. Dynamic mechanical analysis indicated that the combined modification effectively increased the number of freely movable chains. The red shift of -OH stretching vibration peaks indicated the formation of strengthened hydrogen bonds in ETPS. X-ray diffraction showed that the crystallinity of ETPS was reduced to 5.68 %, effectively reducing the regenerative phenomenon. Gel permeation chromatography revealed that the molecular weight of ETPS decreased, and the entanglements between molecular chains were reduced. A tensile test showed that the elongation at break of ETPS was as high as 235.29 %, which was much higher than those of enzymatic hydrolysis starch and thermoplastic starch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Consistent retention time (t R ) of metabolites is vital for identification in metabolomic analysis with ultrahigh-performance liquid-chromatography (UPLC). To minimize inter-experimental t R variations from the reversed-phase UPLC-MS, we developed an endogenous retention-index (endoRI) using in-sample straight-chain acylcarnitines with different chain-length (L C , C0-C26) without additives. The endoRI-corrections reduced the t R variations caused by the combined changes of mobile phases, gradients, flow-rates, elution time, columns and temperature from up to 5.1 min-0.2 min for most metabolites in a model metabolome consisting of 91 metabolites and multiple biological matrices including human serum, plasma, fecal, urine, A549 cells and rabbit liver extracts. The endoRI-corrections also reduced the inter-batch and inter-platform t R variations from 1.5 min to 0.15 min for 95 % of detected features in the above biological samples. We further established a quantitative model between t R and L C for predicting t R values of acylcarnitines when absent in samples. This makes it possible to compare metabolites' t R from different t R databases and the UPLC-based metabolomic data from different batches., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0-C26) within 10-min with good sensitivity (limit of detection < 0.7 fmol), linearity (correlation coefficient > 0.992), accuracy (relative error < 20%), precision (coefficient of variation (CV), CV < 15%), stability (CV < 15%), and inter-technician consistency (CV < 20%, n  = 6). We also established a quantitative structure-retention relationship (goodness of fit > 0.998) for predicting retention time ( t R ) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters ( t R , ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Efficient quantification of fatty-acid (FA) composition (fatty-acidome) in biological samples is crucial for understanding physiology and pathophysiology in large population cohorts. Here, we report a rapid GC-FID/MS method for simultaneous quantification of all FAs in numerous biological matrices. Within eight minutes, this method enabled simultaneous quantification of 50 FAs as fatty-acid methyl esters (FAMEs) in femtomole levels following the efficient transformation of FAs in all lipids including FFAs, cholesterol-esters, glycerides, phospholipids and sphingolipids. The method showed satisfactory inter-day and intra-day precision, stability and linearity (R 2 > 0.994) within a concentration range of 2-3 orders of magnitude. FAs were then quantified in typical multiple biological matrices including human biofluids (urine, plasma) and cells, animal intestinal content and tissue samples. We also established a quantitative structure-retention relationship (QSRR) for analytes to accurately predict their retention time and aid their reliable identification. We further developed a novel no-additive retention index (NARI) with endogenous FAMEs reducing inter-batch variations to 15 seconds; such NARI performed better than the alkanes-based classical RI, making meta-analysis possible for data obtained from different batches and platforms. Collectively, this provides an inexpensive high-throughput analytical system for quantitative phenotyping of all FAs in 8-minutes multiple biological matrices in large cohort studies of pathophysiological effects., Competing Interests: Pinghui Liu, Qinsheng Chen, Lianglong Zhang, Chengcheng Ren, Biru Shi, Jingxian Zhang, Shuaiyao Wang, Ziliang Chen, Qi Wang, Hui Xie, Qingxia Huang and Huiru Tang declare that they have no conflict of interest., (© The Author(s) 2023.)

Androst-4-ene-3,17-dione (AD) and 22-hydroxy-23,24-bisnorchol-4-ene-3-one (4-HBC) are important drug intermediates that can be biosynthesized from phytosterols. However, the C9 hydroxylation of steroids via 3-ketosteroid 9α-hydroxylase (KSH) limits AD and 4-HBC accumulation. Five active KshAs, the oxidation component of KSH, were identified in Mycobacterium fortuitum ATCC 35855 for the first time. The deletion of kshAs indicated that the five KshA genes were jointly responsible for C9 hydroxylation during phytosterol biotransformation. MFKDΔkshA, the five KshAs deficient strain, blocked C9 hydroxylation and produced 5.37 g/L AD and 0.55 g/L 4-HBC. The dual function reductase Opccr knockout and 17β-hydroxysteroid dehydrogenase Hsd4A enhancement reduced 4-HBC content from 8.75 to 1.72% and increased AD content from 84.13 to 91.34%, with 8.24 g/L AD being accumulated from 15 g/L phytosterol. In contrast, hsd4A and thioesterase fadA5 knockout resulted in the accumulation of 5.36 g/L 4-HBC from 10 g/L phytosterol. We constructed efficient AD (MFKDΔkshAΔopccr&#95;hsd4A) and 4-HBC (MFKDΔkshAΔhsd4AΔfadA5) producers and provided insights for further metabolic engineering of the M. fortuitum ATCC 35855 strain for steroid productions. KEY POINTS: • Five active KshAs were first identified in M. fortuitum ATCC 35855. • Deactivation of all five KshAs blocks the steroid C9 hydroxylation reaction. • AD or 4-HBC production was improved by Hsd4A, FadA5, and Opccr modification., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The implantation of medical devices is frequently accompanied by the invasion of bacteria, which may lead to implant failure. Therefore, an intelligent and responsive coating seems particularly essential in hindering implant-associated infections. Herein, a self-defensive antimicrobial coating, accompanied by silk fibroin as a valve, was successfully prepared on the titanium (Ti-Cu@SF) for pH-controlled release of Cu 2+ . The results showed that the layer could set free massive Cu 2+ to strive against E. coli and S. aureus for self-defense when exposed to a slightly acidic condition. By contrary, a little Cu 2+ was released in the physiological situation, which could avoid damage to the normal cells and showed excellent in vitro pH-dependent antibiosis. Besides, in vivo experiment confirmed that Ti-Cu@SF could work as an antibacterial material to kill S. aureus keenly and display negligible toxicity in vivo. Consequently, the design provided support for endowing the layer with outstanding biocompatibility and addressing the issue of bacterial infection during the implantation of Ti substrates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Chinese/Mandarin language instruction to undergraduate students from non-Chinese speaking countries has become a topic of increasing interest, driven by China's influential role in global political and economic dynamics. With Mandarin being the language spoken by approximately 70% of Chinese speakers, it is not only taught within China but also in institutions around the world. While teaching any second or foreign language presents unique challenges, the specific challenges faced in Mandarin language education have not received comprehensive scrutiny, prompting the need for further investigation., Objectives: The primary objective of this study was to explore the challenges associated with teaching and learning Mandarin from the perspectives of non-native Mandarin language teachers. By adopting a qualitative (phenomenological) research approach, we aimed to uncover the multifaceted challenges that confront both educators and learners in the context of Mandarin language instruction., Methodology: The research methodology employed for this study involved the use of semi-structured interviews conducted with 15 Mandarin language teachers, who were chosen through theoretical sampling. These interviews were transcribed into text files and subsequently subjected to qualitative data analysis, which was facilitated by the use of MAQDA software. This approach allowed us to identify and categorize the various challenges and problems encountered in the teaching and learning of Mandarin., Findings: The research findings revealed a range of challenges and problems experienced in Mandarin language education. These challenges were grouped into two primary thematic categories: psycho-linguistic and educational challenges. The linguistic challenges are deeply rooted in the distinctive features of the Mandarin language, presenting obstacles that necessitate innovative teaching strategies and materials. Educational challenges extend beyond native speaker proficiency, emphasizing the requirement for a comprehensive pedagogical skill set among instructors., Implications: The implications of this research extend to various stakeholders in the field of Chinese/Mandarin language education, including policymakers, educators, curriculum designers, and learners. Understanding the linguistic, educational, and psychological challenges can inform the development of more effective teaching methods, curriculum design, and motivation-enhancing strategies, ultimately promoting a more successful and engaging Mandarin language learning experience for non-native speakers., (© 2023. The Author(s).)

Objective: This study aimed to investigate vitamin A and vitamin D conditions and related factors among children and adolescents aged 6-17 years in Jiangsu Province of China., Methods: All the data were derived from China Nutrition and Health Surveillance of Children and Lactating Mothers in 2016-2017. By applying multiple stage stratified cluster random sampling method, 3244 children aged 6-17 years were selected from 12 survey sites in Jiangsu Province. Face to face interview, physical measurements and 6 mL blood sample were used to collect the general information, anthropometric information and blood nutritional indexes of the participants. Multivariate Logistic analysis was used for vitamin A and vitamin D conditions to test related factors., Results: The prevalence of vitamin A deficiency and marginal deficiency was 0.8% and 15.8%, respectively.23.2% of the participants had vitamin D deficiency, 54.2% had vitamin D insufficiency and 4.8% had vitamin A insufficiency combined with vitamin D deficiency. Age group, weight levels, screen time and mother&apos;s education levels are the relevant factors of vitamin A insufficiency in children and adolescents. The related factors of vitamin D deficiency among children and adolescents are gender, age group, residence, physical activity level, screen time and mother&apos;s education levels. Gender, residence, weight levels, screen time and mother&apos;s education levels are the related factors of vitamin A insufficiency combined with vitamin D deficiency., Conclusion: Vitamin A insufficiency and vitamin D deficiency are at high epidemic levels among children and adolescents in Jiangsu Province in 2016-2017.

Ammonia (NH 3 ) synthesis at mild conditions by electrocatalytic nitrogen reduction (eNRR) has received more attention and has been regarded as a promising alternative to the traditional Haber-Bosch process. Lewis acid-base pairs (LPs) can chemisorb and react with nitrogen by electronic interaction, while the tuning of the microenvironment near electrode can hinder hydrogen evolution reaction (HER) thus improving the selectivity of the eNRR. Herein, the FeOOH nanorod coupled with LPs on the surface (i.e., Fe, Fe-O) was synthesized, which could effectively drive eNRR. Meanwhile, polyethylene glycol (PEG) was introduced to serve as a local non-aqueous electrolyte system to inhibit HER. The prepared FeOOH-150 catalyst achieved outstanding eNRR performance with an NH 3 yield rate of 118.07 μg h -1 mg cat -1 and a Faradaic efficiency of 51.4 % at -0.6 V vs. RHE in 0.1 M LiClO 4  + 20 % PEG. Both the experiment and DFT calculations revealed that the interaction of PEG with Lewis base sites could optimize nitrogen adsorption configuration and activation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Environmental protection and social obligation fulfillment have become hot subjects as the "dual carbon" approach has been developed and deepened. The ESG system is consistent with China's current policies, abandoning the traditional business philosophy of economic supremacy in favor of comprehensively measuring corporate social responsibility and sustainable development capability across three dimensions: environmental (E), social (S), and corporate governance (G), which receive widespread attention from all sectors of society. Based on observational data from A-share listed businesses in Shanghai and Shenzhen from 2011 to 2020, this study empirically evaluates the influence and mechanism of ESG on government subsidies. The research results indicate that enterprises can receive more government subsidies by improving ESG performance. Mechanism analysis found that corporate transparency plays a positive mediating role in the process of ESG affecting government subsidies. Further research on political affiliation and property rights has found that companies without political affiliation are more inclined to receive more government subsidies by improving ESG performance, and the impact of political affiliation and ESG performance on government subsidies is mutually complementary. Enterprises with different property rights have different strengths of motivation to increase government subsidies by improving ESG performance. State owned enterprises (excluding central enterprises) are the strongest, followed by non-state-owned enterprises, and central enterprises are the weakest. Therefore, enterprises should be further encouraged to strengthen ESG construction, improve the quality of ESG information disclosure, improve resource allocation efficiency, and promote high-quality development of enterprises., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography-mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up-regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe 2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA-induced hepatotoxicity by reversing the occurrence of ferroptosis., (© 2023 Wiley Periodicals LLC.)

Pheretima, also called "earthworms", is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines (CPMs) in Chinese Pharmacopoeia (2020 edition). However, its zoological origin is unclear, both in the herbal market and CPMs. In this study, a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing algorithms (restricted search, open search, and de novo) was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima, including Pheretima aspergillum (PA), Pheretima   vulgaris (PV), and Metaphire magna (MM). We identified 10,477 natural peptides in the PA, 7,451 in PV, and 5,896 in MM samples. Five specific signature peptides were screened and then validated using synthetic peptides; these demonstrated robust specificity for the authentication of PA, PV, and MM. Finally, all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills, revealing the inconsistent Pheretima species used in these CPMs. In conclusion, our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines, especially non-model species with poorly annotated protein databases., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 The Authors.)

Background: The current progressive increase in the cancer burden of prostate cancer requires the exploration of new diagnostic and therapeutic approaches. Nanobodies are single-domain antibodies with the advantages of small size, high stability, easy processing and modification, which are increasingly used in the treatment of many types of cancer., Methods: This review analyzed the relevant literature in PubMed and other databases., Result: In the retrieved literature, nanobodies are widely used in the treatment of prostate cancer. The preparation of nanobodies targeting PSA or PSMA is straightforward. For diagnostic purposes, nanobodies can be used in the preparation of biosensors for more sensitive identification of prostate cancer; for therapeutic purposes, nanobodies are used in the preparation of immunotoxic and ADC drugs. Preclinical in vivo and in vitro experiments have shown that this therapeutic approach is feasible. This article is a review of the above to provide new ideas for the treatment of prostate cancer., Conclusion: Compared with traditional antibodies, nano-antibodies have the advantages of small size, high stability, and high penetration. These advantages make nano-antibodies worthy to be widely used. Current studies have shown that nanobodies have advantages and future in the diagnosis and treatment of prostate cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety, particularly concerning the composition and content levels of trace ingredients. Panax notoginseng Saponins Injection (PNSI), widely used in China for treating acute cardiovascular diseases, contains low-abundance (10%-25%) and trace saponins in addition to its five main constituents (notoginsenoside R 1 , ginsenoside Rg 1 , ginsenoside Re, ginsenoside Rb 1 , and ginsenoside Rd). This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types. To achieve this, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method employing multiple ions monitoring (MIM) was developed. A "post-column valve switching" strategy was implemented to eliminate highly abundant peaks (NR 1 , Rg 1 , and Re) at 26 min. A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards, with digoxin as the internal standard. This study evaluated 119 batches of PNSI from seven vendors, revealing significant variability in trace saponin levels among different vendors and formulation types. These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety. Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases., (Copyright © 2023 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Chronic wounds cause a number of unnecessary amputations due to a delay in proper treatment. To expedite timely treatment, this paper presents an algorithm which uses a logistic regression classifier to predict whether the wound will heal or not within a specified time. The prediction is made at three time-points: one month, three months, and six months from the first visit of the patient to the healthcare facility. This prediction is made using a systematically collected chronic wound registry and is based entirely on data collected during patients' first visit. The algorithm achieves an area under the receiver operating characteristic curve (AUC) of 0.75, 0.72, and 0.71 for the prediction at the three time-points, respectively.Clinical relevance- Using the proposed prediction model, the clinicians will have an early estimate of the time taken to heal thereby providing appropriate treatments. We hope this will ensure timely treatments and reduce the number of unnecessary amputations.

Artemisia argyi H.Lév. & Vaniot, a traditional Chinese medicine with a history spanning over two millennia, has been extensively used in folk medicine to treat dysmenorrhea, uterine bleeding and inflammation. Recent studies have demonstrated that the essential oil extracted from Artemisia argyi H.Lév. & Vaniot, known as AAEO, exhibits significant anti-tumor properties against liver and lung cancers. There is a scarcity of research on the potential impact of AAEO on pancreatic cancer (PC) cells. In this study, UPLC-MS/MS-based metabolomics method was established to evaluate the effect of AAEO on the proliferation of PC cells. The differential compounds included 5-oxoproline, glutamate, γ-glutamylcysteine, glutathione, arachidonic acid, adrenal acid and linoleic acid were detected by metabolomics, enriching in the γ-glutamyl cycle and polyunsaturated fatty acid metabolism, which were closely related to ferroptosis. Meanwhile, AAEO dramatically increased the levels of intracellular iron ion via up-regulation of TFR1, augmented reactive oxygen species and malondialdehyde in a dose-dependent manner by down-regulation of γ-glutamyl cycle through decreasing expressions of SLC7A11. Additionally, β-caryophyllene oxide, one of the main components of AAEO, could covalently bind to Cys in SW1990 cells to form a conjugate Cpo-Cys, resulting in the inhibition of glutathione synthesis. Importantly, the ferroptosis inhibitor deferoxamine significantly blocked the inhibitory effect of AAEO on SW1990 cells. Meanwhile, β-caryophyllene oxide, dihydro-β-ionone and α-bisabolol had strong binding force with GPX4, SLC7A11 and TFR1, respectively. These findings showed that AAEO induced ferroptosis via regulation of γ-glutamyl cycle by SLC7A11 and iron disorders by TFR1. Our study discovered AAEO as a potential therapeutic approach to induce ferroptosis to prevent or treat PC., Competing Interests: Declaration of Competing Interest The authors declare no potential conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

A new oxyphenisatin analogue was detected from a processed plum claiming to be a weight loss product without any side effects during the daily inspecting and monitoring of illegal adulterants in health supplements. An abundant peak caused our interest firstly owing to its identical fragments of m/z 224 and 196 in the MS/MS experiments with those of oxyphenisatin acetate. The chemical structure of the unknown compound was characterized by ultra-high performance liquid chromatography equipped with diode array detector and quadrupole time-of-flight tandem mass spectrometry (UHPLC-DAD-Q-TOF/MS), followed by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy experiments. Based on the data, it was defined that the two symmetrical acetyl groups in oxyphenisatin acetate were replaced by two propionyl groups for the unknown structure. Finally, the new oxyphenisatin analogue was identified as 3,3-bis[4'-(propionyloxy)phenyl]-1,3-dihydroindole-2-one and designated as oxyphenisatin propionate. Thereafter, the content of the new analogue was quantitatively determined to be 681 mg/kg, which would inevitably cause adverse health effect because there was not specification for daily consumption of this product. To the best of our knowledge, this is the first report for identification of oxyphenisatin propionate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: A novel vardenafil analogue was detected from a health wine claimed to be anti-impotence during a special inspection in an online store., Methods: The unknown compound was found by using ultra-high performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC/Q-TOF MS). The characteristic product ions were similar to those of vardenafil. The UV spectrum of the compound closely mirrored that of vardenafil. The analogue underwent purification by semi-preparative HPLC and structurally identified by FT-IR and NMR analysis., Results: Based on the data, The structure of the analogue was characterized as 2-[2-propyloxy-5-(4-ethylpiperazin-1-yl)sulfonylphenyl]-5-methyl-7-propyl-3H-imidazo [5,15,1-f] [1,2,4]triazin-4-one, simplified as propoxy-vardenafil., Conclusion: To the best of our knowledge, the analogue has not been reported and is even only ninth vardenafil analogue, which was confirmed that a n-propyloxy group had replaced the ethoxy group on the aromatic ring of vardenafil. Therefore, It is essential to pay more attention to vardenafil analogues in the routine inspection of health supplements., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Pt-based alloys with precise structure and composition design have been considered to be effective and robust novel electrocatalysts for fuel cells. Whereas, the sluggish kinetics of oxygen reduction reaction (ORR) and low intrinsic activity of Pt limited their real application on a large scale. Herein, a novel ternary PtZrNi nanorods (PtZrNi NRs) was synthesized via a facile wet-chemical method to achieve high electrocatalytic performance for both ORR and alcohol oxidation reaction owing to the synergism of chosen three elements and prominent one-dimensional morphology. Specifically, the PtZrNi NRs show enhanced mass and specific activities of 0.755 A mg Pt -1 and of 0.97 mA/cm 2 at 0.9 V RHE towards ORR in acidic media, which are 4.7 and 4.4 times of those of commercial Pt/C, respectively. Additionally, in alkaline media, the PtZrNi NRs also exhibit superior ORR mass and specific activities of 3.216 A mg Pt -1 and 4.13 mA/cm 2 , enhanced by 34.6 and 31.3 times compared with those of commercial Pt/C, respectively. The PtZrNi NRs retain the nanorod shape well without agglomeration after an accelerated durability test (20000 cycles). This work may offer a new perspective for engineering high-performance Pt-based electrocatalysts for commercial fuel cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Titanium (Ti) was an excellent medical metal material, but the lack of good antibacterial activity confined its further practical application. To solve this dilemma, a coating containing graphene oxide (GO) and copper (Cu) was prepared on the surface of Ti sheet (Ti/APS/GO/Cu). First, physical sterilization could be carried out through the sharp-edged sheet structure of GO. Second, the oxygen-containing functional group on the surface of GO and the released Cu 2+ would generate reactive oxygen species for chemical sterilization. The synergistic effect of GO and Cu substantially enhanced the in vitro and in vivo antibacterial property of Ti sheet, thereby reducing bacterial-related inflammation. Quantitatively, the antibacterial rate of Ti/APS/GO/Cu against E. coli or S. aureus reached over 99%. Besides, Ti/APS/GO/Cu showed excellent biocompatibility and no toxicity to cell. Such work developed multiple sterilization avenues to design non-antibiotic, safe and efficient antibacterial implant material for the biomedical domain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Biocompatible coatings that can protect metal implants have great potential in tissue engineering. In this work, MWCNT/chitosan composite coatings with hydrophobic-hydrophilic asymmetric wettability were facilely prepared by one-step in situ electrodeposition. The resultant composite coating exhibits excellent thermal stability and mechanical strength (0.76 MPa), benefiting from the compact internal structure. The thickness of the coating can be controlled precisely by the amounts of transferred charges. The MWCNT/chitosan composite coating demonstrates a lower corrosion rate due to its hydrophobicity and compact internal structure. Compared with exposed 316 L stainless steel, its corrosion rate is reduced by two orders of magnitude from 3.004 × 10 -1 mm/yr to 5.361 × 10 -3 mm/yr. The content of iron released from 316 L stainless steel into the simulated body fluid drops to 0.1 mg/L under the protection of the composite coating. In addition, the composite coating enables efficient calcium enrichment from simulated body fluids and promotes the formation of bioapatite layers on the coating surface. This study contributes to furthering the practical application of chitosan-based coatings in implant anticorrosion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Mycobacterium neoaurum DSM 1381 originated from Mycobacterium neoaurum ATCC 25790 by mutagenesis screening is a strain of degrading phytosterols and accumulating important C22 steroid intermediates, including 22-hydroxy-23, 24-bisnorchola-4-en-3-one (4-HP) and 22-hydroxy-23, 24-bisnorchola-1,4-dien-3-one (HPD). However, the metabolic mechanism of these C22 products in M. neoaurum DSM 1381 remains unknown. Therefore, the whole-genome sequencing and comparative genomics analysis of M. neoaurum DSM 1381 and its parent strain M. neoaurum ATCC 25790 were performed to figure out the mechanism. As a result, 28 nonsynonymous single nucleotide variants (SNVs), 17 coding region Indels, and eight non-coding region Indels were found between the genomes of the two strains. When the wild-type 3-ketosteroid-9α-hydroxylase subunit A1 (KshA1) and β-hydroxyacyl-CoA dehydrogenase (Hsd4A) were overexpressed in M. neoaurum DSM 1381, the steroids were transformed into the 4-androstene-3, 17- dione (AD) and 1,4-androstadiene-3,17-dione (ADD) instead of C22 intermediates. This result indicated that 173N of KshA1 and 171K of Hsd4A are indispensable to maintaining their activity, respectively. Amino acid sequence alignment analysis show that both N173D in KshA1 and K171E in Hsd4A are conservative sites. The 3D models of these two enzymes were predicted by SWISS-MODEL and AlphaFold2 to understand the inactivation of the two key enzymes. These results indicate that K171E in Hsd4A may destroy the inaction between the NAD+ with the NH3+ and N173D in KshA1 and may disrupt the binding of the catalytic domain to the substrate. A C22 steroid intermediates-accumulating mechanism in M. neoaurum DSM 1381 is proposed, in which the K171E in Hsd4A leads to the enzyme's inactivation, which intercepts the C19 sub-pathways and accelerates the C22 sub-pathways, and the N173D in KshA1 leads to the enzyme's inactivation, which blocks the degradation of C22 intermediates. In conclusion, this study explained the reasons for the accumulation of C22 intermediates in M. neoaurum DSM 1381 by exploring the inactivation mechanism of the two key enzymes.

Background: 9α-hydroxyandrost-4-ene-3,17-dione (9-OHAD) is a significant intermediate for the synthesis of glucocorticoid drugs. However, in the process of phytosterol biotransformation to manufacture 9-OHAD, product degradation, and by-products restrict 9-OHAD output. In this study, to construct a stable and high-yield 9-OHAD producer, we investigated a combined strategy of blocking Δ 1 ‑dehydrogenation and regulating metabolic flux., Results: Five 3-Ketosteroid-Δ 1 -dehydrogenases (KstD) were identified in Mycobacterium fortuitum ATCC 35855. KstD2 showed the highest catalytic activity on 3-ketosteroids, followed by KstD3, KstD1, KstD4, and KstD5, respectively. In particular, KstD2 had a much higher catalytic activity for C9 hydroxylated steroids than for C9 non-hydroxylated steroids, whereas KstD3 showed the opposite characteristics. The deletion of kstDs indicated that KstD2 and KstD3 were the main causes of 9-OHAD degradation. Compared with the wild type M. fortuitum ATCC 35855, MFΔkstD, the five kstDs deficient strain, realized stable accumulation of 9-OHAD, and its yield increased by 42.57%. The knockout of opccr or the overexpression of hsd4A alone could not reduce the metabolic flux of the C22 pathway, while the overexpression of hsd4A based on the knockout of opccr in MFΔkstD could remarkably reduce the contents of 9,21 ‑dihydroxy‑20‑methyl‑pregna‑4‑en‑3‑one (9-OHHP) by-products. The inactivation of FadE28-29 leads to a large accumulation of incomplete side-chain degradation products. Therefore, hsd4A and fadE28-29 were co-expressed in MFΔkstDΔopccr successfully eliminating the two by-products. Compared with MFΔkstD, the purity of 9-OHAD improved from 80.24 to 90.14%. Ultimately, 9‑OHAD production reached 12.21 g/L (83.74% molar yield) and the productivity of 9-OHAD was 0.0927 g/L/h from 20 g/L phytosterol., Conclusions: KstD2 and KstD3 are the main dehydrogenases that lead to 9-OHAD degradation. Hsd4A and Opccr are key enzymes regulating the metabolic flux of the C19- and C22-pathways. Overexpression of fadE28-29 can reduce the accumulation of incomplete degradation products of the side chains. According to the above findings, the MF-FA5020 transformant was successfully constructed to rapidly and stably accumulate 9-OHAD from phytosterols. These results contribute to the understanding of the diversity and complexity of steroid catabolism regulation in actinobacteria and provide a theoretical basis for further optimizing industrial microbial catalysts., (© 2023. The Author(s).)

C22 steroid drug intermediates are suitable for corticosteroids synthesis, and the production of C22 steroids is unsatisfactory due to the intricate steroid metabolism. Among the C22 steroids, 21-hydroxy-20-methyl-pregna-1,4-dien-3-one (1,4-HP) could be used for Δ 1 -steroid drug synthesis, such as prednisolone. Nevertheless, the production of 1,4-HP remains unsatisfactory. In this study, an ideal 1,4-HP producing strain was constructed. By the knockout of 3-ketosteroid-9-hydroxylase (KshA) genes and 17β-hydroxysteroid dehydrogenase (Hsd4A) gene, the steroid nucleus degradation and the accumulation of C19 steroids in Mycolicibacterium neoaurum were blocked. The mutant strain could transform phytosterols into 1,4-HP as the main product and 21-hydroxy-20-methyl-pregna-4-ene-3-one as a by-product. Subsequently, the purity of 1,4-HP improved to 95.2% by the enhancement of 3-ketosteroid-Δ 1 -dehydrogenase (KSTD) activity, and the production of 1,4-HP was improved by overexpressing NADH oxidase (NOX) and catalase (KATE) genes. Consequently, the yield of 1,4-HP achieved 10.5 g/L. The molar yield and the purity of 1,4-HP were optimal so far, and the production of 1,4-HP provides a new intermediate for the pharmaceutical steroid industry. KEY POINTS: • A third 3-ketosteroid-9-hydroxylase was identified in Mycolicibacterium neoaurum. • An 1,4-HP producer was constructed by KshA and Hsd4A deficiency. • The production of 1,4-HP was improved by KSTD, NOX, and KATE overexpression., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Heavy metals are common environmental contaminants that are toxic, non-biodegradable, and bioaccumulative. They can bioaccumulate through the food chain and present a risk to both public health and ecology. Therefore, this study takes the mangrove wetland of Dongzhai Harbor as an example. The concentrations of heavy metals such as As, Cd, Cr, Cu, Ni, Pb, and Zn in the surface sediments of mangrove wetlands were measured to reveal their distribution, the contamination level was assessed, and the sources of contamination were analyzed. The distribution of Cr, Zn, Ni, Pb, Cu, and Cd concentrations are: Yanfeng East River > Sanjiang River > Yanzhou River > Yanfeng West River, while the As concentration in the Yanfeng West River is greater than that in the Yanfeng East River. According to the correlation analysis, the concentrations of Cr, Zn, Ni, Cu, and Cd are significantly and positively correlated with total organic carbon (TOC), total phosphorus (TP), total nitrogen (TN), and salinity (SAL) and shared a significantly negative correlation with pH. There is moderate contamination risk of As and slight contamination risk of Cd, Cr, Cu, Ni, Pb, and Zn in most regions within the study area. Cd, Cr, Cu, Ni, Pb, and Zn exhibit the same sources, which are mainly influenced by human sources such as aquaculture, agricultural cultivation, and livestock farming, while the source of As comes from aquaculture.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease around the world. However, no specific medicine has been approved for NAFLD treatment. Our study was conducted to explore the role and mechanism of TRIM59 in NAFLD, aiming to provide a novel target for NAFLD treatment. Here, the expression of TRIM family members was detected in 10 mild and severe NAFLD tissues as well as 10 normal tissues. TRIM59 expression was verified in 10 normal tissues and 25 mild and severe NAFLD tissues. Palmitic acid and high-fatty diet were used for the construction of NAFLD models. Oil Red O staining was used to detect the level of steatosis. The content of TNF-α, IL-6, and IL-8 was measured to reflect the level of inflammation. Lipid reactive oxygen species was estimated by flow cytometry. We found that TRIM59 was highly expressed in NAFLD tissues compared with normal liver tissues. The inhibition of TRIM59 could inhibit the steatosis and inflammation in NAFLD, whereas its overexpression exhibited reversed effects. The application of ferroptosis inhibitor, deferoxamine, could markedly ameliorate steatosis and inflammation, which was mediated by overexpressed TRIM59. Besides, TRIM59 was demonstrated to interact with GPX4 and promoted its ubiquitination. The overexpression of GPX4 could significantly reverse the pathogenic effects of TRIM59 in NAFLD. Additionally, the inhibition of TRIM59 appeared to be a promising strategy to ameliorate NAFLD in mice model. In summary, our study revealed that TRIM59 could promote steatosis and ferroptosis in NAFLD via enhancing GPX4 ubiquitination. TRIM59 could be a potential target for NAFLD treatment., (© 2022. The Author(s).)

Residual protein in chitosan-based biomaterials may cause inflammation, allergy, and immune rejection after surgery, impeding their clinical application. Facile production of chitosan with ultra-low protein content (residual protein <0.2 %) is yet to be addressed. Herein, we proposed a one-step method for preparing chitosan with residue protein content <0.2 % by using hydrogen peroxide and sodium dodecyl sulfate, which is simple, time-saving, cost-effective, and acid/alkali-free. Notably, the molecular weight of chitosan can be reduced simultaneously. The effects of experimental parameters (i.e. hydrogen peroxide concentration (0.01 %-1 %), SDS concentration (5 %-20 %), and reaction temperature (50 °C-70 °C)) on the protein removal and molecular weight decrease were systematically analyzed by response surface methodology. The results show that temperature and H 2 O 2 concentration are the main parameters affecting the deproteinization of chitosan. Further characterizations on the resulting ultra-low protein residue chitosan revealed unchanged chemical structure, enhanced crystallinity, and reduced thermal stability. The proposed one-step deproteination method may have great potential for industrial mass production of ultra-low protein residue chitosan., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, financial or otherwise., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Pheretima vulgaris has been prescribed for the treatment of cardiovascular diseases in China for several hundred years in the form of dried powder in the clinic. However, the peptides with the potential antithrombotic activity of this source have never been reported. The total active proteins from Pheretima vulgaris were hydrolyzed by eight different commercial proteases and the alcalase hydrolysate showed the strongest thrombolytic activity. Four original thrombolytic peptides were isolated and characterized using bioactivity-directed fractionation of the active hydrolysate. The amino acid sequences were identified as HEPLPEP (m/z 818.40076), EYPLPEP (m/z 844.39648), LGEPSVP (m/z 698.39648), and LLAPP (m/z 510.28043) by nanoLC-ESI-Orbitrap mass spectrometry with PEAKS software. HEPLPEP and EYPLPEP, containing the common -PLPEP residue, showed superior thrombolytic activity in plasmin assay and fibrinogen-thrombin time assay. This research confirmed that Pheretima vulgaris was a potential source of active peptides with thrombolytic activities and provided novel candidates for the thrombolytic agents. PRACTICAL APPLICATIONS: Thrombosis has become the leading cause of mortality as it was the common underlying pathology of cardiovascular diseases, such as ischemic heart disease, and stroke. The demand for thrombolytics has increased gradually as the incidence trends of thrombosis-related diseases raise with the aging of the population. Four novel thrombolytic peptides were characterized from Pheretima vulgaris proteins hydrolysates, among which HEPLPEP and EYPLPEP could prevent the formation of thrombus and degrade existing thrombus in vitro. These peptides are promising to be meritorious templates for developing thrombolytic agents. The structure-function relationship of peptides resulting from the presence of specific residues in these sequences may contribute to extending the knowledge about their thrombolytic activity, which may be useful in designing novel thrombolytic agents. The present research based on a bioactivity-directed isolation strategy could also be applied to other animal-derived traditional Chinese medicines with proteins or peptides as their function basis., (© 2022 Wiley Periodicals LLC.)

Steroid drug precursors, including C19 and C22 steroids, are crucial to steroid drug synthesis and development. However, C22 steroids are less developed due to the intricacy of the steroid metabolic pathway. In this study, a C22 steroid drug precursor, 9-hydroxy-3-oxo-4,17-pregadiene-20-carboxylic acid methyl ester (9-OH-PDCE), was successfully obtained from Mycolicibacterium neoaurum by 3-ketosteroid-Δ 1 -dehydrogenase and enoyl-CoA hydratase ChsH deficiency. The production of 9-OH-PDCE was improved by the overexpression of 17β-hydroxysteroid dehydrogenase Hsd4A and acyl-CoA dehydrogenase ChsE1-ChsE2 to reduce the accumulation of by-products. The purity of 9-OH-PDCE in fermentation broth was improved from 71.7% to 89.7%. Hence, the molar yield of 9-OH-PDCE was improved from 66.7% to 86.7%, with a yield of 0.78 g/L. Furthermore, enoyl-CoA hydratase ChsH1-ChsH2 was identified to form an indispensable complex in Mycolicibacterium neoaurum DSM 44704. IMPORTANCE C22 steroids are valuable precursors for steroid drug synthesis, but the development of C22 steroids remains unsatisfactory. This study presented a strategy for the one-step bioconversion of phytosterols to a C22 steroid drug precursor, 9-hydroxy-3-oxo-4,17-pregadiene-20-carboxylic acid methyl ester (9-OH-PDCE), by 3-ketosteroid-Δ 1 -dehydrogenase and enoyl-CoA hydratase deficiency with overexpression of 17β-hydroxysteroid dehydrogenase acyl-CoA dehydrogenase in Mycolicibacterium . The function of the enoyl-CoA hydratase ChsH in vivo was revealed. Construction of the novel C22 steroid drug precursor producer provided more potential for steroid drug synthesis, and the characterization of the function of ChsH and the transformation of steroids further revealed the steroid metabolic pathway.

High-performance low-cost catalysts are in high demand for the hydrogen evolution reaction (HER). In the present study, we reported that V 1.11 S 2 materials with flower-like, flake-like, and porous morphologies were successfully synthesized by hydrothermal synthesis and subsequent calcination. The effects of morphology on hydrogen evolution performance were studied. Results show that flower-like V 1.11 S 2 exhibits the best electrocatalytic activity for HER, achieving both high activity and preferable stability in 0.5 M H 2 SO 4 solution. The main reason can be ascribed to the abundance of catalytically active sites and low charge transfer resistance.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a new definition for the evidence of hepatic steatosis and metabolic dysfunctions. The specific role of the dietary factors in the development and progress of the disease are not well illuminated. Thus, we conducted this study on the associations between dietary quality assessed by five dietary quality indexes (Dietary Inflammatory Index, DII; Mediterranean diet, MED; Dietary Approach to Stop Hypertension, DASH; Alternate Healthy Eating Index diet, AHEI; Healthy Eating Indices, HEI) and MAFLD phenotypes. This study was extracted from the latest NHANES 2017-2018 wave. Demographic information, health status, lifestyles, and dietary habits were reported in the questionnaire. Multivariate logistic regression and multivariate ordinal logistic regression methods were applied to explore the associations between dietary quality indexes and MAFLD or MAFLD with liver fibrosis. The weighted prevalence of Non-MAFLD, MAFLD without fibrosis, and MAFLD with fibrosis were 47.05%, 36.67%, and 16.28%, respectively, at the cutoff value of a median Controlled Attenuation Parameter (CAP) 248 dB/m and a median Liver Stiffness Measurement (LSM) 6.3 kPa. When the diagnostic cutoff values of CAP changed to 285 dB/m, the weighted prevalence of Non-MAFLD, MAFLD without liver fibrosis, and MAFLD with fibrosis turned to 64.62%, 22.08%, and 13.30%, respectively. All five dietary quality indexes, including DII, HEI-2015, AHEI, DASH, and MED, were all significantly associated with MAFLD phenotypes. DII was positively associated with MAFLD phenotypes, while other four dietary quality indexes, including HEI-2015, AHEI, DASH, and MED, were significantly associated with lower risk of MAFLD phenotypes. MAFLD is becoming a threatening public health concern among adult Americans and dietary quality is markedly associated with MAFLD phenotypes., Competing Interests: The authors declare no conflict of interest.

The aim of this study was to examine the association between dietary patterns and high blood glucose in Jiangsu province of China by using structural equation modelling (SEqM). Methods: Participants in this cross-sectional study were recruited through the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance Program in Jiangsu province using a multistage stratified cluster random sampling method. Dietary patterns were defined by exploratory factor analysis (EFA). Confirmatory factor analysis (CFA) was used to test the fitness of EFA. SEqM was used to investigate the association between dietary patterns and high blood glucose. Results: After exclusion, 3137 participants with complete information were analysed for this study. The prevalence of high blood glucose was 9.3% and 8.1% in males and females, respectively. Two dietary patterns: the modern dietary pattern (i.e., high in red meats and its products, vegetables, seafood, condiments, fungi and algae, main grains and poultry; low in other grains, tubers and preserves), and the fruit−milk dietary pattern (i.e., high in milk and its products, fruits, eggs, nuts and seeds and pastry snacks, but low in vegetable oils) were established. Modern dietary pattern was found to be positively associated with high blood glucose in adults in Jiangsu province (multivariate logistic regression: OR = 1.561, 95% CI: 1.025~2.379; SEqM: β = 0.127, p < 0.05). Conclusion: The modern dietary pattern—high intake of red meats—was significantly associated with high blood glucose among adults in Jiangsu province of China, while the fruit−milk dietary pattern was not significantly associated with high blood glucose.

Introduction: A well-validated diagnostic assay with curated biomarkers complements clinicopathological factors to facilitate early diagnosis and ensure timely treatment delivery. This study focuses on an Asian-centric cancer diagnostic assay designed and thoroughly validated against commercially available standard references and a cohort of over 200 clinical specimens spanning 12 diverse Asian-centric cancer types. Methods: The assay uses hybrid-capture probes capable of profiling DNA aberrations from 572 cancer-related genes and 91 RNA fusion partners. The panel can detect clinically-tractable biomarkers such as microsatellite instability (MSI) and tumor mutation burden (TMB). Results: Analytical evaluation demonstrated 100% specificity and 99.9% sensitivity within a ≥5% VAF limit of detection (LoD) for SNV/Indels. RNA-based fusion features an LoD of ≥5 copies per nanogram input when evaluated against commercial references. Excellent linearity and concordance were observed when benchmarking against orthogonal methods in identifying MSI status, TMB scores and RNA fusions. Actionable genetic alterations were identified in 65% of the clinical samples. Conclusion: These results demonstrate a molecular diagnostic assay that accurately detects genomic alterations and complex biomarkers. The data also supports an excellent performance of this assay for making critical diagnoses and well-informed therapeutic decisions in Asian prevalent cancers., Competing Interests: M-HT and YC are employees of and hold stock ownership in Lucence Diagnostics Pte Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ng, Lim, Lim, Md Nasir, Zhang, Rajasegaran, Lee, Kok, Thike, Lim, Weng, Yee, Choudhury, Chan, Tan, Tan and Teh.)

Background: Consumer-grade wearable devices enable detailed recordings of heart rate and step counts in free-living conditions. Recent studies have shown that summary statistics from these wearable recordings have potential uses for longitudinal monitoring of health and disease states. However, the relationship between higher resolution physiological dynamics from wearables and known markers of health and disease remains largely uncharacterized., Objective: We aimed to derive high-resolution digital phenotypes from observational wearable recordings and to examine their associations with modifiable and inherent markers of cardiometabolic disease risk., Methods: We introduced a principled framework to extract interpretable high-resolution phenotypes from wearable data recorded in free-living conditions. The proposed framework standardizes the handling of data irregularities; encodes contextual information regarding the underlying physiological state at any given time; and generates a set of 66 minimally redundant features across active, sedentary, and sleep states. We applied our approach to a multimodal data set, from the SingHEART study (NCT02791152), which comprises heart rate and step count time series from wearables, clinical screening profiles, and whole genome sequences from 692 healthy volunteers. We used machine learning to model nonlinear relationships between the high-resolution phenotypes on the one hand and clinical or genomic risk markers for blood pressure, lipid, weight and sugar abnormalities on the other. For each risk type, we performed model comparisons based on Brier scores to assess the predictive value of high-resolution features over and beyond typical baselines. We also qualitatively characterized the wearable phenotypes for participants who had actualized clinical events., Results: We found that the high-resolution features have higher predictive value than typical baselines for clinical markers of cardiometabolic disease risk: the best models based on high-resolution features had 17.9% and 7.36% improvement in Brier score over baselines based on age and gender and resting heart rate, respectively (P<.001 in each case). Furthermore, heart rate dynamics from different activity states contain distinct information (maximum absolute correlation coefficient of 0.15). Heart rate dynamics in sedentary states are most predictive of lipid abnormalities and obesity, whereas patterns in active states are most predictive of blood pressure abnormalities (P<.001). Moreover, in comparison with standard measures, higher resolution patterns in wearable heart rate recordings are better able to represent subtle physiological dynamics related to genomic risk for cardiometabolic disease (improvement of 11.9%-22.0% in Brier scores; P<.001). Finally, illustrative case studies reveal connections between these high-resolution phenotypes and actualized clinical events, even for borderline profiles lacking apparent cardiometabolic risk markers., Conclusions: High-resolution digital phenotypes recorded by consumer wearables in free-living states have the potential to enhance the prediction of cardiometabolic disease risk and could enable more proactive and personalized health management., (©Weizhuang Zhou, Yu En Chan, Chuan Sheng Foo, Jingxian Zhang, Jing Xian Teo, Sonia Davila, Weiting Huang, Jonathan Yap, Stuart Cook, Patrick Tan, Calvin Woon-Loong Chin, Khung Keong Yeo, Weng Khong Lim, Pavitra Krishnaswamy. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.07.2022.)

Titanium (Ti) is an excellent medical metal material, but the absence of good antibacterial property restricts its widespread application. To overcome this, we thus conducted a series of modifications for Ti. First, a titanium dioxide (TiO 2 ) nanorod array was generated on the Ti surface by hydrothermal treatment (TiO 2 /Ti). With the polymer-mediated self-assembly method, a continuous copper (Cu) shell structure on the surface of the nanorod was then generated to form a TiO 2 @Cu core-shell nanorod array as coating for Ti (TiO 2 @Cu/Ti). Using pure Ti as the control group, the antibacterial properties of TiO 2 /Ti and TiO 2 @Cu/Ti were appraised. The results manifested that the mechanical and chemical dual function of the released Cu 2+ and TiO 2 nanorod array could effectively kill bacteria on the surface of Ti. Besides, the obtained coating exhibited no cytotoxicity and favorable biocompatibility. In this work, we found an antibacterial strategy based on multiple sterilization pathways, which made Ti have good antibacterial property and further improved its biocompatibility.

Due to mechanical instability, surface wrinkles form spontaneously in plants, animals and human beings for propagation and enhanced surface functionality. However, there remains tremendous challenge in mimicking such exquisite structure at a micro/nanoscale in lab. Herein, we report an approach to converting an electrodeposited chitosan hydrogel film into a hollow tube with controllable wrinkle wavelength and amplitude via soaking the film in acidic sodium dodecyl sulfate (SDS). Notably, wrinkled pattern can be controlled by a self-design device through modulating the shrinkage ratio. The resultant wrinkled hydrogel tube with adjustable wall thickness, outer diameter shows excellent mechanical strength, anti-fatigue ability, recoverability and flexibility. It is demonstrated that 2D/3D complicated hollow framework with wrinkled pattern can be customized on demand. This facile strategy not only provides a feasible approach to preparing hydrogel tube with wrinkles, but also points to possible pathways for bioengineering more complicated materials from natural polymers., (Copyright © 2022 Elsevier Ltd. All rights reserved.)