The correlation between urinary iodine levels and gallstone risk: elevated iodine intake linked to gallstone occurrence.

Background: Essential trace elements are vital for human growth and development. Nevertheless, excessive intake can pose risks. As of yet, no research has looked at the possibility of a relationship between the prevalence of gallstones and urinary concentrations of nickel, molybdenum, and iodine. Objectives: The purpose of this study was to examine the correlation between urinary levels of iodine, molybdenum, and nickel and the occurrence of gallstones in a U.S. population and to verify whether excessive iodine intake is associated with the occurrence of gallstones. Methods: Data from 2,734 participants that were gathered between 2017 and 2020 were examined. Employing inductively coupled plasma mass spectrometry (ICP-MS), the levels of nickel (Ni), iodine (I), and molybdenum (Mo) in the urine were determined. Gallstones presence was determined using a standardized questionnaire. Restricted cubic spline analysis, subgroup analysis, and logistic regression analysis were used to evaluate the relationship between the occurrence of gallstones and urinary essential trace elements. Results: The logistic regression analysis indicated an increased risk of gallstone development in Quartiles 2, Quartiles 3, and Quartiles 4 groups in comparison to the Quartiles 1 group, based on urinary iodine levels (OR = 1.69, 95% CI: 1.11-2.56; OR = 1.68, 95% CI: 1.10-2.55; OR = 1.65, 95% CI: 1.09-2.51). Urinary iodine levels were nonlinearly positively linked with the development of gallstones, according to restricted cubic spline analysis (P-Nonlinear = 0.032). Subgroup analyses showed that high levels of urinary iodine were associated with a high risk of gallstones in different populations, and were more pronounced in adults aged 60 years and older, in women, with a BMI ≥ 25, and in diabetic patients. Conclusion: Our research revealed a correlation between an increased risk of gallstones and increasing urinary iodine levels. Urinary iodine levels serve as indicators of the body's iodine status, thus suggesting that excessive iodine intake may be linked to an elevated risk of gallstone formation.

Do bats' social vocalizations conform to Zipf's law and the Menzerath-Altmann law?

The study of vocal communication in non-human animals can uncover the roots of human languages. Recent studies of language have focused on two linguistic laws: Zipf's law and the Menzerath-Altmann law. However, whether bats' social vocalizations follow these linguistic laws, especially Menzerath's law, has largely been unexplored. Here, we used Asian particolored bats, Vespertilio sinensis, to examine whether aggressive vocalizations conform to Zipf's and Menzerath's laws. Aggressive vocalizations of V. sinensis adhere to Zipf's law, with the most frequent syllables being the shortest in duration. There was a negative association between the syllable number within a call and the average syllable duration, in agreement with Menzerath's law. A decrease in the proportion of some long syllables and a decrease in the duration of several syllable types in long-duration calls explain the occurrence of this law. Our results indicate that a general compression principle organizes aspects of bat vocal communication systems.

Validation of an AI-Powered Automated X-ray Bone Age Analyzer in Chinese Children and Adolescents: A Comparison with the Tanner-Whitehouse 3 Method.

INTRODUCTION: Automated bone age assessment (BAA) is of growing interest because of its accuracy and time efficiency in daily practice. In this study, we validated the clinical applicability of a commercially available artificial intelligence (AI)-powered X-ray bone age analyzer equipped with a deep learning-based automated BAA system and compared its performance with that of the Tanner-Whitehouse 3 (TW-3) method. METHODS: Radiographs prospectively collected from 30 centers across various regions in China, including 900 Chinese children and adolescents, were assessed independently by six doctors (three experts and three residents) and an AI analyzer for TW3 radius, ulna, and short bones (RUS) and TW3 carpal bone age. The experts' mean estimates were accepted as the gold standard. The performance of the AI analyzer was compared with that of each resident. RESULTS: For the estimation of TW3-RUS, the AI analyzer had a mean absolute error (MAE) of 0.48 ± 0.42. The percentage of patients with an absolute error of < 1.0 years was 86.78%. The MAE was significantly lower than that of rater 1 (0.54 ± 0.49, P = 0.0068); however, it was not significant for rater 2 (0.48 ± 0.48) or rater 3 (0.49 ± 0.46). For TW3 carpal, the AI analyzer had an MAE of 0.48 ± 0.65. The percentage of patients with an absolute error of < 1.0 years was 88.78%. The MAE was significantly lower than that of rater 2 (0.58 ± 0.67, P = 0.0018) and numerically lower for rater 1 (0.54 ± 0.64) and rater 3 (0.50 ± 0.53). These results were consistent for the subgroups according to sex, and differences between the age groups were observed. CONCLUSION: In this comprehensive validation study conducted in China, an AI-powered X-ray bone age analyzer showed accuracies that matched or exceeded those of doctor raters. This method may improve the efficiency of clinical routines by reducing reading time without compromising accuracy.

Assessing bone age, or how developed a child's skeleton is, is important in medical care, but the standard method can be time-consuming. Using AI to automatically assess bone age from X-ray images may improve efficiency without reducing accuracy. In this study, we evaluated how well an AI-powered X-ray bone age analyzer performed compared to the established Tanner­Whitehouse 3 (TW-3) method. X-ray images from 900 Chinese children and adolescents were collected from 30 centers. Six doctors (three experts, three residents) and the AI system independently assessed the TW-3 radius, ulna, and short bones (RUS) and TW-3 carpal bone age. The experts' assessments were considered the gold standard. The AI analyzer had an average error of 0.48 years for TW3-RUS bone age, with 87% of assessments within 1 year of the experts. For TW3 carpal bone age, the AI had an average error of 0.48 years, with 89% within 1 year. These results were similar to or better than those of the resident raters. These findings show the AI-powered analyzer can assess bone age as accurately as human raters. This technology may improve clinical efficiency by reducing the time required for bone age assessments without compromising accuracy.

Redox-Responsive Hydrogels Loaded with an Antibacterial Peptide as Controlled Drug Delivery for Healing Infectious Wounds.

Infectious wounds occur when harmful microorganisms such as bacteria or viruses invade a wound site. Its problems associated include delayed healing, increased pain, swelling, and the potential for systemic infections. Therefore, developing new wound dressing materials with antibacterial effects is crucial for improving the healing process. Here a redox-degradable hydrogel loaded with an antibacterial peptide (vancomycin) in a straightforward gram-scale synthesis, is developed. The hydrogel structure consists of a disulfide bond-containing hyperbranched polyglycerol (SS-hPG) that is cross-linked by 4-arm polyethylene glycol-thiol (4-arm PEG-SH). The polymerization mechanism and full characterization of SS-hPG are described as this synthesis is reported for the first time. Rheology is used to ascertain the hydrogel's mechanical characteristics, such as stiffness, and self-healing, determining these properties for different ratios and concentrations of both gel components. The incorporation of disulfide bonds in the hydrogel is proved by conducting degradation experiments in reductive environments. Fluorescein isothiocyanate-albumin (FITC-BSA) and vancomycin both are loaded into the gel, and the guest release kinetics is assessed for both slow and on-demand releases. Finally, the in vitro and in vivo experiments prove that the vancomycin-loaded hydrogel acts as an antibacterial barrier for wound dressing and accelerates the healing of infectious wounds in a mouse model.

Applications of Ene-Reductases in the Synthesis of Flavors and Fragrances.

Flavors and fragrances (F&F) are interesting organic compounds in chemistry. These compounds are widely used in the food, cosmetic, and medical industries. Enzymatic synthesis exhibits several advantages over natural extraction and chemical preparation, including a high yield, stable quality, mildness, and environmental friendliness. To date, many oxidoreductases and hydrolases have been used to biosynthesize F&F. Ene-reductases (ERs) are a class of biocatalysts that can catalyze the asymmetric reduction of α,ß-unsaturated compounds and offer superior specificity and selectivity; therefore, ERs have been increasingly considered an ideal alternative to their chemical counterparts. This review summarizes the research progress on the use of ERs in F&F synthesis over the past 20 years, including the achievements of various scholars, the differences and similarities among the findings, and the discussions of future research trends related to ERs. We hope this review can inspire researchers to promote the development of biotechnology in the F&F industry.

Automated identification and segmentation of urine spots based on deep-learning.

Micturition serves an essential physiological function that allows the body to eliminate metabolic wastes and maintain water-electrolyte balance. The urine spot assay (VSA), as a simple and economical assay, has been widely used in the study of micturition behavior in rodents. However, the traditional VSA method relies on manual judgment, introduces subjective errors, faces difficulty in obtaining appearance time of each urine spot, and struggles with quantitative analysis of overlapping spots. To address these challenges, we developed a deep learning-based approach for the automatic identification and segmentation of urine spots. Our system employs a target detection network to efficiently detect each urine spot and utilizes an instance segmentation network to achieve precise segmentation of overlapping urine spots. Compared with the traditional VSA method, our system achieves automated detection of urine spot area of micturition in rodents, greatly reducing subjective errors. It accurately determines the urination time of each spot and effectively quantifies the overlapping spots. This study enables high-throughput and precise urine spot detection, providing important technical support for the analysis of urination behavior and the study of the neural mechanism underlying urination.

A dual-function mixed-culture biofilm for sulfadiazine removal and electricity production using bio-electrochemical system.

Sulfadiazine (SDZ) is frequently detected in environmental samples, arousing much concern due to its toxicity and hard degradation. This study investigated the electricity generation capabilities, SDZ removal and microbial communities of a highly efficient mixed-culture system using repeated transfer enrichments in a bio-electrochemical system. The mixed-culture biofilm (S160-T2) produced a remarkable current density of 954.12 ± 15.08 µA cm-2 with 160 mg/L SDZ, which was 32.9 and 1.8 times higher than that of Geobacter sulfurreducens PCA with 40 mg/L SDZ and without additional SDZ, respectively. Especially, the impressive SDZ removal rate of 98.76 ± 0.79% was achieved within 96 h using the further acclimatized mixed-culture. The removal efficiency of this mixed-culture for SDZ through the bio-electrochemical system was 1.1 times higher than that using simple anaerobic biodegradation. Furthermore, the current density and removal efficiency in this system gradually decreased with increasing SDZ concentrations from 0 to 800 mg/L. In addition, community diversity data demonstrated that the dominant genera, Geobacter and Escherichia-Shigella, were enriched in mixed-culture biofilm, which might be responsible for the current production and SDZ removal. This work confirmed the important roles of acclimatized microbial consortia and co-substrates in the simultaneous removal of SDZ and electricity generation in an electrochemical system.

METTL14-mediated upregulation of lncRNA HOTAIR represses PP1α expression by promoting H3K4me1 demethylation in oxycodone-treated mice.

N6-methyladenosine (m6A) methylation is a vital epigenetic mechanism associated with drug addiction. However, the relationship between m6A modification and oxycodone rewarding is less well explored. Based on an open field test, the present study evaluated oxycodone rewarding using chromatin immunoprecipitation PCR, immunofluorescence, and RNA sequencing. A marked increase in METTL14 protein and a decrease in PP1α protein due to oxycodone abundance in the striatal neurons were observed in a dose- and time-dependent manner. Oxycodone markedly increased LSD1 expression, and decreased H3K4me1 expression in the striatum. In the open field test, intra-striatal injection of METTL14 siRNA, HOTAIR siRNA, or LSD1 shRNA blocked oxycodone-induced increase in locomotor activity. The downregulation of PP1α was also inhibited after treatment with METTL14/HOTAIR siRNA and LSD1 shRNA. Enhanced binding of LSD1 with CoRest and of CoRest with the PP1α gene induced by oxycodone was also reversed by LSD1 shRNA. In addition, H3K4me1 demethylation was also blocked by the treatment. In summary, the investigation confirmed that METTL14-mediated upregulation of HOTAIR resulted in the repression of PP1α, which in turn facilitated the recruitment of LSD1, thus catalyzing H3K4me1 demethylation and promoting oxycodone addiction.

Clinical, Imaging, and Pathological-Molecular Characteristics Associated with Stage IA Invasive Lung Adenocarcinoma Recurrence After Sub-lobar Resection.

RATIONALE AND OBJECTIVES: This study aimed to investigate the association of clinical, imaging, and pathological-molecular characteristics with the prediction of patient prognosis with stage IA invasive lung adenocarcinoma (ILADC) after sub-lobar resection. MATERIALS AND METHODS: This study assessed 360 patients, including 91 and 269 with and without recurrence 3 years postoperatively, respectively, with stage IA ILADC undergoing preoperative chest computed tomography (CT) scans and subsequent sub-lobar resection at our institution. Their clinical and CT features and histological subtypes and gene mutation status were compared. Binary logistic regression analysis was conducted to identify the independent risk factors for recurrence. An external validation cohort included 113 patients, used to test the model's efficiency. RESULTS: For clinical features, old age, male gender, smokers, and high age-adjusted Charlson comorbidity index (ACCI) were frequently observed in patients with recurrence than those without (all p < 0.05). For CT features, large tumor size, solid-predominant density, spiculation, peripheral fibrosis, type II pleural tag, and pleural adhesion were more common in recurrent patients than non-recurrent ones (all p < 0.05). The regression model revealed old age, large tumor size, solid-predominant density, spiculation, type II pleural tag, and pleural adhesion as independent risk factors for recurrence, with an area under the curve (AUC) of 0.942. The external validation cohort obtained an AUC of 0.958. For phological-molecular features, micropapillary/solid-predominant growth pattern, KRAS, ALK, and NRAS mutation or fusion were more common in the recurrent group, whereas EGFR mutation was more frequent in the non-recurrent group (all p < 0.05). CONCLUSION: Clinical and CT features help predict the prognosis of patients with stage IA ILADC after sub-lobar resection and decide for individualized treatment. Moreover, patients with different prognosis demonstrated different pathological-molecular features.

Ubiquitin-induced RNF168 condensation promotes DNA double-strand break repair.

Rapid accumulation of repair factors at DNA double-strand breaks (DSBs) is essential for DSB repair. Several factors involved in DSB repair have been found undergoing liquid-liquid phase separation (LLPS) at DSB sites to facilitate DNA repair. RNF168, a RING-type E3 ubiquitin ligase, catalyzes H2A.X ubiquitination for recruiting DNA repair factors. Yet, whether RNF168 undergoes LLPS at DSB sites remains unclear. Here, we identified K63-linked polyubiquitin-triggered RNF168 condensation which further promoted RNF168-mediated DSB repair. RNF168 formed liquid-like condensates upon irradiation in the nucleus while purified RNF168 protein also condensed in vitro. An intrinsically disordered region containing amino acids 460-550 was identified as the essential domain for RNF168 condensation. Interestingly, LLPS of RNF168 was significantly enhanced by K63-linked polyubiquitin chains, and LLPS largely enhanced the RNF168-mediated H2A.X ubiquitination, suggesting a positive feedback loop to facilitate RNF168 rapid accumulation and its catalytic activity. Functionally, LLPS deficiency of RNF168 resulted in delayed recruitment of 53BP1 and BRCA1 and subsequent impairment in DSB repair. Taken together, our finding demonstrates the pivotal effect of LLPS in RNF168-mediated DSB repair.

Multispectral Image Stitching via Global-Aware Quadrature Pyramid Regression.

Image stitching is a critical task in panorama perception that involves combining images captured from different viewing positions to reconstruct a wider field-of-view (FOV) image. Existing visible image stitching methods suffer from performance drops under severe conditions since environmental factors can easily impair visible images. In contrast, infrared images possess greater penetrating ability and are less affected by environmental factors. Therefore, we propose an infrared and visible image-based multispectral image stitching method to achieve all-weather, broad FOV scene perception. Specifically, based on two pairs of infrared and visible images, we employ the salient structural information from the infrared images and the textual details from the visible images to infer the correspondences within different modality-specific features. For this purpose, a multiscale progressive mechanism coupled with quadrature correlation is exploited to improve regression in different modalities. Exploiting the complementary properties, accurate and credible homography can be obtained by integrating the deformation parameters of the two modalities to compensate for the missing modality-specific information. A global-aware guided reconstruction module is established to generate an informative and broad scene, wherein the attentive features of different viewpoints are introduced to fuse the source images with a more seamless and comprehensive appearance. We construct a high-quality infrared and visible stitching dataset for evaluation, including real-world and synthetic sets. The qualitative and quantitative results demonstrate that the proposed method outperforms the intuitive cascaded fusion-stitching procedure, achieving more robust and credible panorama generation. Code and dataset are available at https://github.com/Jzy2017/MSGA.

A Dual-Stream-Modulated Learning Framework for Illuminating and Super-Resolving Ultra-Dark Images.

Enhancement of image resolution for scenes captured under extremely dim conditions represents a practical yet challenging problem that has received little attention. In such low-light scenarios, the limited lighting and minimal signal clarity tend to intensify issues such as diminished detail visibility and altered color accuracy, which are often more severe during the image enhancement process than in scenarios with adequate lighting. Consequently, standard methods for enhancing low-light images or improving their resolution, whether implemented independently or through a combined approach, generally face challenges in effectively restoring luminance, preserving color integrity, and detailing intricate features. To conquer these issues, this article introduces an innovative dual-stream (DS) modulated learning framework designed to tackle the real-world coupled degradation issues in super-resolution (SR) under low-light conditions. Leveraging natural image color characteristics, we introduce a self-regularized luminance constraint to specifically target uneven illumination. We develop illumination-semantic dual modulator (ISDM), a refinement middleware embedded in the decoding stage to bridge illumination and semantic features concurrently, aimed at safeguarding the integrity of lighting and color details at the feature level. Our approach replaces simple upsampling methods with the resolution-sensitive merging upsampler (RSMU) module, which integrates diverse sampling techniques to effectively reduce artifacts and halo effects. Comprehensive experiments on three benchmarks showcase the applicability and generalizability of our approach to diverse and challenging ultra-poorly lit settings, outperforming state-of-the-art methods with a notable improvement. The code and benchmark are publicly available at https://github.com/moriyaya/UltraIS.

Distribution and spread of tigecycline resistance gene tet(X4) in Escherichia coli from different sources.

Tigecycline serves as a last-resort antimicrobial agent against severe infections caused by multidrug-resistant bacteria. Tet(X) and its numerous variants encoding flavin-dependent monooxygenase can confer resistance to tigecycline, with tet(X4) being the most prevalent variant. This study aims to investigate the prevalence and characterize tigecycline resistance gene tet(X) in E. coli isolates from various origins in Yangzhou, China, to provide insights into tet(X) dissemination in this region. In 2022, we tested the presence of tet(X) in 618 E. coli isolates collected from diverse sources, including patients, pig-related samples, chicken-related samples, and vegetables in Yangzhou, China. The antimicrobial susceptibility of tet(X)-positive E. coli isolates was conducted using the agar dilution method or the broth microdilution method. Whole genome sequencing was performed on tet(X)-positive strains using Illumina and Oxford Nanopore platforms. Four isolates from pig or pork samples carried tet(X4) and exhibited resistance to multiple antimicrobial agents, including tigecycline. They were classified as ST542, ST10, ST761, and ST48, respectively. The tet(X4) gene was located on IncFIA8-IncHI1/ST17 (n=2), IncFIA18-IncFIB(K)-IncX1 (n=1), and IncX1 (n=1) plasmids, respectively. These tet(X4)-carrying plasmids exhibited high similarity to other tet(X4)-bearing plasmids with the same incompatible types found in diverse sources in China. They shared related genetic environments of tet(X4) associated with ISCR2, as observed in the first identified tet(X4)-bearing plasmid p47EC. In conclusion, although a low prevalence (0.65%) of tet(X) in E. coli strains was observed in this study, the horizontal transfer of tet(X4) among E. coli isolates mediated by pandemic plasmids and the mobile element ISCR2 raises great concerns. Thus, heightened surveillance and immediate action are imperative to curb this clinically significant resistance gene and preserve the efficacy of tigecycline.

Changes in bulbar conjunctival microcirculation and microvasculature during short-term scleral lens wearing and their associated factors.

OBJECTIVE: To explore the changes in microcirculation and microvasculature of the bulbar conjunctiva during the short-term wearing of the scleral lenses (ScCL). And investigate the factors affecting the microcirculation and microvasculature of the bulbar conjunctiva. METHODS: In this prospective cross-sectional study, functional slit lamp biomicroscopy (FSLB) was used to image the ocular surface microcirculation and microvascular images at two different sites (under the area of ScCL and outside of the area of ScCL) before (baseline) and during the wearing of ScCL at 0 h, 1 h, 2 h and 3 h. Anterior segment optical coherence tomography (AS-OCT) (RTVue, Optovue Inc, USA) was also used to image central post-lens tear film (PoLTF) and the morphology changes of the conjunctiva under the landing zone at the same time period. The semi-automatic quantification of microcirculation and microvasculature including vessel density (Dbox), vessel diameter (D), axial blood flow velocity (Va) and blood flow volume (Q). And the morphological changes of conjunctiva and PoLTF fogging grading were evaluated manually. The changes in the microcirculation and microvasculature of the ocular surface, PoLTF fogging grade and conjunctival morphology were compared before and during the ScCL wearing at different time periods, and the relationship between them was analyzed. RESULTS: Nineteen eyes (11 right eyes, 8 left eyes) were analyzed in this study. Outside of the area of ScCL, the Dbox before wearing lenses was less than that at 0 h (P = 0.041). The Q at baseline was greater than that after 1 h ScCL wearing (P = 0.026). Under the area of the ScCL, the Q at 1 h was less than that at baseline and 3 h. During the ScCL wearing, statistically significant conjunctival morphology changes were found among different time stages (baseline (0 µm), 0 h (113.18 µm), 2 h (138.97 µm), 3 h (143.83 µm) (all P ＜0.05). Outside the area of the ScCL, the morphology changes of the conjunctiva were negatively correlated with the changes of Va (P＜0.001,r = -0.471) and Q (P = 0.003,r = -0.348),but positively correlated with the Dbox (P = 0.001,r = 0.386). Under the area of ScCL, the morphology changes of the conjunctiva were negatively correlated with the Q (P = 0.012, r = -0.291). The fogging grade was positively correlated with the Q under the area of the ScCL (P = 0.005, r = 0.331). CONCLUSIONS: The microcirculation and microvasculature of the ocular surface and conjunctival morphology were changed after wearing ScCL in wearers, which indicated that the microvascular responses happened in the ScCL wearers and the severity of microvascular responses of the ocular surface related to the morphology changes of the conjunctiva. The quantification methods and findings in this study provide clues for the safety of ScCL wearing and may supervise the health of the wearer's ocular surface.

Wintersweet-like Nanohybrids of Titanium-doped Cerium Vanadate Loaded with Polypyrrole for Tumor Theranostic.

Compromises between enhanced on-targeting reactivity and precise real-time monitoring in the tumor microenvironment (TME) are the main roadblocks for catalytic cancer therapy. The hallmark of a high level of hydrogen peroxide (H2O2) and acidic extracellular environment of the hypoxia solid tumor can underpin therapeutic and tracking performance. Herein, this work provides an activatable wintersweet-like nanohybrid consisting of titanium (Ti) doped cerium vanadate nanorods with the modification of polypyrrole (PPy) nanoparticles (CeVO4-Ti@PPy) for combinatorial therapies of breast carcinoma. The Ti dopants in the size-controllable CeVO4 nanorods lower the energy barrier (0.5 eV) of the rate-determining steps and elaborate peroxidase-like (POD-like) activities to improve the generation of toxic hydroxyl radical (·OH) according to the density functional theory (DFT) calculation. The multiple enzyme-like activities, including the intrinsic glutathione peroxidase (GPx) and catalase (CAT), achieve a record-high therapeutic efficiency. Coupling this oxidative stress with the photothermal effects of PPy enables enhanced catalytic tumor necrosis. The exterior PPy heterogeneous structure can be further doped with protons in the local acidic environment to intensify photoacoustic signals, allowing the non-invasive accurate tracking of tumors. The theranostic performance displayed negligible attenuated signals in near-infrared (NIR) windows. This organic-inorganic nanohybrid with a heterogeneous structure provides the potential to improve the overall outcomes of catalytic therapy.

A novel MYC-ZNF706-SLC7A11 regulatory circuit contributes to cancer progression and redox balance in human hepatocellular carcinoma.

The oncogenic potential of chromosome 8q22 copy number gain in liver cancer remains to be depicted. Here, we report that ZNF706, encoded by a gene mapped to chromosome 8q22, is a C2H2-type zinc finger protein. However, the biological function and mechanism of ZNF706 have been poorly investigated. Clinically, ZNF706 expression was elevated in hepatocellular carcinoma (HCC), and high ZNF706 expression was associated with unfavorable survival in HCC patients. Functional experiments revealed that ZNF706 knockdown inhibited HCC progression both in vitro and in vivo. RNA sequencing (RNA-seq) and chromatin immunoprecipitation-based deep sequencing (ChIP-seq) revealed that mechanistically, ZNF706 is a crucial ferroptosis regulator and that SLC7A11 is a critical target of ZNF706. In addition, ZNF706 knockdown inhibited SLC7A11 expression, increased lipid peroxidation, and promoted ferroptosis. Further analysis revealed that ZNF706 is a novel direct target transcriptionally activated by MYC in HCC cells. Importantly, MYC depletion reduced SLC7A11-mediated redox homeostasis, and this effect was reversed by ZNF706 reexpression. Collectively, our data demonstrate that ZNF706 is a potential oncogene in liver cancer and functions as a ferroptosis regulator by modulating SLC7A11 expression, constituting a potential therapeutic target for HCC.

Pan-drug resistance and hypervirulence in a human fungal pathogen are enabled by mutagenesis induced by mammalian body temperature.

The continuing emergence of invasive fungal pathogens poses an increasing threat to public health. Here, through the China Hospital Invasive Fungal Surveillance Net programme, we identified two independent cases of human infection with a previously undescribed invasive fungal pathogen, Rhodosporidiobolus fluvialis, from a genus in which many species are highly resistant to fluconazole and caspofungin. We demonstrate that R. fluvialis can undergo yeast-to-pseudohyphal transition and that pseudohyphal growth enhances its virulence, revealed by the development of a mouse model. Furthermore, we show that mouse infection or mammalian body temperature induces its mutagenesis, allowing the emergence of hypervirulent mutants favouring pseudohyphal growth. Temperature-induced mutagenesis can also elicit the development of pan-resistance to three of the most commonly used first-line antifungals (fluconazole, caspofungin and amphotericin B) in different Rhodosporidiobolus species. Furthermore, polymyxin B was found to exhibit potent activity against the pan-resistant Rhodosporidiobolus mutants. Collectively, by identifying and characterizing a fungal pathogen in the drug-resistant genus Rhodosporidiobolus, we provide evidence that temperature-dependent mutagenesis can enable the development of pan-drug resistance and hypervirulence in fungi, and support the idea that global warming can promote the evolution of new fungal pathogens.

Molecular engineering of PETase for efficient PET biodegradation.

The widespread utilization of polyethylene terephthalate (PET) has caused a variety of environmental and health problems. Compared with traditional thermomechanical or chemical PET cycling, the biodegradation of PET may offer a more feasible solution. Though the PETase from Ideonalla sakaiensis (IsPETase) displays interesting PET degrading performance under mild conditions; the relatively low thermal stability of IsPETase limits its practical application. In this study, enzyme-catalysed PET degradation was investigated with the promising IsPETase mutant HotPETase (HP). On this basis, a carbohydrate-binding module from Bacillus anthracis (BaCBM) was fused to the C-terminus of HP to construct the PETase mutant (HLCB) for increased PET degradation. Furthermore, to effectively improve PET accessibility and PET-degrading activity, the truncated outer membrane hybrid protein (FadL) was used to expose PETase and BaCBM on the surface of E. coli (BL21with) to develop regenerable whole-cell biocatalysts (D-HLCB). Results showed that, among the tested small-molecular weight ester compounds (p-nitrophenyl phosphate (pNPP), p-Nitrophenyl acetate (pNPA), 4-Nitrophenyl butyrate (pNPB)), PETase displayed the highest hydrolysing activity against pNPP. HP displayed the highest catalytic activity (1.94 µM(p-NP)/min) at 50 °C and increased longevity at 40 °C. The fused BaCBM could clearly improve the catalytic performance of PETase by increasing the optimal reaction temperature and improving the thermostability. When HLCB was used for PET degradation, the yield of monomeric products (255.7 µM) was ∼25.5 % greater than that obtained after 50 h of HP-catalysed PET degradation. Moreover, the highest yield of monomeric products from the D-HLCB-mediated system reached 1.03 mM. The whole-cell catalyst D-HLCB displayed good reusability and stability and could maintain more than 54.6 % of its initial activity for nine cycles. Finally, molecular docking simulations were utilized to investigate the binding mechanism and the reaction mechanism of HLCB, which may provide theoretical evidence to further increase the PET-degrading activities of PETases through rational design. The proposed strategy and developed variants show potential for achieving complete biodegradation of PET under mild conditions.

Melamine Polymerization Promotes Compact Phosphorus/Carbon Composite for High-Performance and Safe Lithium Storage.

Phosphorus is regarded as a promising material for high-performance lithium-ion batteries (LIBs) due to its high theoretical capacity, appropriate lithiation potential, and low lithium-ion diffusion barrier. Phosphorus/carbon composites (PC) are engineered to serve as high-capacity high-rate anodes; the interaction between phosphorus and carbon, long-term capacity retention, and safety problems are important issues that must be well addressed simultaneously. Herein, an in situ polymerization approach to fabricate a poly-melamine-hybridized (pMA) phosphorus/carbon composite (pMA-PC) is employed. The pMA hybridization enhances the density and electrical conductivity of the PC, improves the structural integrity, and facilitates stable electron transfer within the pMA-PC composite. Moreover, the pMA-PC composite exhibits efficient adsorption of lithium polysulfides, enabling stable transport of Li+ ions. Therefore, the pMA-PC anode demonstrates a high specific charging capacity of 1,381 mAh g-1 at 10 A g-1, and a great capacity retention of 86.7% at 1 A g-1 over 500 cycles. The synergistic effect of phosphorus and nitrogen further confers excellent flame retardant properties to the pMA-PC anode, including self-extinguishing in 2.5 s, and a much lower combustion temperature than PC. The enhanced capacity and safety performance of pMA-PC show potential in future high-capacity and high-rate LIBs.

Icariin Ameliorates D-galactose-induced Cell Injury in Neuron-like PC12 Cells by Inhibiting MPTP Opening.

OBJECTIVE: Icariin (ICA) has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats. Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases. Abnormal opening of the mitochondrial permeability transition pore (mPTP) is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy. This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose (D-gal)-induced cell injury model. METHODS: A cell model of neuronal injury was established in rat pheochromocytoma cells (PC12 cells) treated with 200 mmol/L D-gal for 48 h. In this cell model, PC12 cells were pre-treated with different concentrations of ICA for 24 h. MTT was used to detect cell viability. Senescence associated ß-galactosidase (SA-ß-Gal) staining was used to observe cell senescence. Western blot analysis was performed to detect the expression levels of a senescence-related protein (p21), autophagy markers (LC3B, p62, Atg7, Atg5 and Beclin 1), mitochondrial fission and fusion-related proteins (Drp1, Mfn2 and Opa1), and mitophagy markers (Pink1 and Parkin). The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus. The intracellular ultrastructure was observed by transmission electron microscopy. Immunofluorescence was used to detect mPTP, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS) and ROS levels. ROS and apoptosis levels were detected by flow cytometry. RESULTS: D-gal treatment significantly decreased the viability of PC12 cells, and markedly increased the SA-ß-Gal positive cells as compared to the control group. With the D-gal stimulation, the expression of p21 was significantly up-regulated. Furthermore, D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 expression. Meanwhile, autophagosomes and autolysosomes were significantly increased, indicating abnormal activation of autophagy levels. In addition, in this D-gal-induced model of cell injury, the mPTP was abnormally open, the ROS generation was continuously increased, the MMP was gradually decreased, and the apoptosis was increased. ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis. It strongly inhibited excessive autophagy by blocking the opening of the mPTP. Cotreatment with ICA and an mPTP inhibitor (cyclosporin A) did not ameliorate mitochondrial dysfunction. However, the protective effects were attenuated by cotreatment with ICA and an mPTP activator (lonidamine). CONCLUSION: ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.