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Abstract Without intervention, a considerable proportion of patients with metabolism‐associated fatty liver disease (MAFLD) will progress from simple steatosis to metabolism‐associated steatohepatitis (MASH), liver fibrosis, and even hepatocellular carcinoma. However, the molecular mechanisms that control progressive MAFLD have yet to be fully determined. Here, we unraveled that the expression of the N6-methyladenosine (m6A) methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD, whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation, liver injury, and fibrosis. Conversely, hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet (HFD). Notably, in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner, which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1 + Ccr2 + monocyte-derived macrophages (Mo-macs). In detail, Cx3cr1 + Ccr2 + Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells (HSCs) to promote liver fibrosis. Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1 + Ccr2 + Mo-macs. Restoration of METTL14 or GLS2, or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis. Taken together, these findings indicate potential therapies for the treatment of MAFLD progression.

The “Broadband China” has enabled China to achieve leapfrog development in the construction of its high-speed broadband networks, thereby accelerating the development of digital infrastructure and unleashing the potential for financial sector growth. This has created a strong impetus for economy to shift towards high-quality development. An in-depth understanding of the empirical correlation between the development of digital infrastructure and financial progress is absent, leaving an unexplored domain of research concerning the impact of the “Broad China” strategy on financial agglomeration (Finagg), financial scale (Finscal), and digital finance (Digfina). In order to evaluate the dynamic impacts of this policy on financial development, this research builds a multi-period difference in differences (DID) model using panel data from 269 prefecture-level cities between 2011 and 2020. The study concludes that the “Broadband China” policy significantly fosters the growth of Finagg, Finscal, and Digfina, in China, and found that the “Broadband China” policy has a significant impact on the regional heterogeneity of financial agglomeration and digital finance. There are significant variations in the effects of this policy on different regions, while the regional heterogeneity differences in the impact on financial scale are relatively small. Additionally, the three mediating variables of technological innovation, fund support, and talent agglomeration play a mediating role in the mechanism of digital infrastructure on financial development.

High salinity inhibits microbial activity in the bioremediation of saline wastewater. To alleviate osmotic stress, glycine betaine (GB), an osmoprotectant, is added to enhance the secretion of extracellular polymeric substances (EPS). These EPS are pivotal in withstanding environmental stressors, yet the intricate interplay between GB supplementation and microbial responses through EPS modifications—encompassing composition, molecular architecture, and electrochemical features—remains elusive in hypersaline conditions. Here we show microbial strategies for salinity endurance by investigating the impact of GB on the dynamic alterations of EPS properties. Our findings reveal that GB supplementation at 3.5% salinity elevates the total EPS (T-EPS) content from 12.50 ± 0.05 to 24.58 ± 0.96 mg per g dry cell weight. The observed shift in zeta potential from −28.95 to −6.25 mV at 0% and 3.5% salinity, respectively, with GB treatment, indicates a reduction in electrostatic repulsion and compaction. Notably, the EPS protein secondary structure transition from β-sheet to α-helix, with GB addition, signifies a more compact protein configuration, less susceptible to salinity fluctuations. Electrochemical analyses, including cyclic voltammetry (CV) and differential pulse voltammetry (DPV), reveal GB's role in promoting the release of exogenous electron shuttles, such as flavins and c-type cytochromes (c-Cyts). The enhancement in DPV peak areas (QDPV) with GB addition implies an increase in available extracellular electron transfer sites. This investigation advances our comprehension of microbial adaptation mechanisms to salinity through EPS modifications facilitated by GB in saline habitats.

Abstract The presence of light absorption and scattering in underwater conditions results in underwater images with missing details, low contrast, and color bias. The current deep learning-based methods bring unlimited potential for underwater image restoration (UIR) tasks. These methods, however, do not adequately take into account the inconsistency of the attenuation of different color channels and spatial regions when performing image restoration. To solve these gaps, we propose a dual information modulation network (DIMN) for accurate UIR tasks. To be specific, we design a multi-information enhancement module (MIEM), empowered by spatial-aware attention block (SAAB) and multi-scale structural Transformer block (MSTB), to guide the inductive bias of image degradation processes under nonhomogeneous media distributions. SAAB focuses on different spatial locations, capturing more spatial-aware cues to correct color deviations and recover details. MSTB utilizes the difference and complementarity between features at different scales to effectively complement the network’s structural and global perceptual capabilities, enhancing image sharpness and contrast further. Experimental results reveal that the proposed DIMN exceeds most state-of-the-art UIR methods. Our code and results are available at: https://github.com/wwaannggllii/DIMN .

As the cleanest energy source, hydrogen energy is regarded as the most promising fuel. Water electrolysis, as the primary means of hydrogen production, has constantly been the focus of attention in the energy conversion field. Developing eco-friendly, cheap, safe and efficient catalysts for electrochemical water splitting (EWS) is the key challenge. Herein, the intermetallic silicide alloy is first synthesized via a facile magnesiothermic reduction and employed as bifunctional electrocatalysts for EWS. Ferric-nickel silicide (denoted as FeNiSi) alloy is designed and shows a good electrocatalytic performance for EWS. The lattice distortions of FeNiSi enhance the electrocatalytic activity. Besides, the porous structure affords more active sites and improves the reaction kinetics. As a consequence, FeNiSi delivers an excellent performance with overpotential of 308 mV for oxygen evolution reaction (OER) and 386 mV for hydrogen evolution reaction (HER) at 10 mA·cm−2 in 1 M KOH. The stability structure of intermetallic silicide achieves an outstanding durability with an unchanged potential of 1.66 V for overall water splitting at 10 mA·cm−2 for 15 h. This work not only provides a facile method for the synthesis of intermetallic silicide with considerable porous structures, but also develops the potential of intermetallic silicide alloy as bifunctional electrocatalysts for EWS, which opens up a new avenue for the design and application of intermetallic silicide alloy.

Rational design of oxygen evolution reaction (OER) catalysts at low cost would greatly benefit the economy. Taking advantage of earth-abundant elements Si, Co and Ni, we produce a unique-structure where cobalt-nickel silicate hydroxide [Co2.5Ni0.5Si2O5(OH)4] is vertically grown on a reduced graphene oxide (rGO) support (CNS@rGO). This is developed as a low-cost and prospective OER catalyst. Compared to cobalt or nickel silicate hydroxide@rGO (CS@rGO and NS@rGO, respectively) nanoarrays, the bimetal CNS@rGO nanoarray exhibits impressive OER performance with an overpotential of 307 ​mV@10 ​mA ​cm−2. This value is higher than that of CS@rGO and NS@rGO. The CNS@rGO nanoarray has an overpotential of 446 ​mV@100 ​mA ​cm−2, about 1.4 times that of the commercial RuO2 electrocatalyst. The achieved OER activity is superior to the state-of-the-art metal oxides/hydroxides and their derivatives. The vertically grown nanostructure and optimized metal-support electronic interactions play an indispensable role for OER performance improvement, including a fast electron transfer pathway, short proton/electron diffusion distance, more active metal centers, as well as optimized dual-atomic electron density. Taking advantage of interlay chemical regulation and the in-situ growth method, the advanced-structural CNS@rGO nanoarrays provide a new horizon to the rational and flexible design of efficient and promising OER electrocatalysts.

The metabolic disorders caused by diabetes can lead to various complications, including male spermatogenesis dysfunction. Exploring effective therapeutics that attenuate diabetes mellitus (DM)-induced male subfertility is of great importance. Pharmaceuticals targeting PPARα activation such as bezafibrate have been regarded as an important strategy for patients with diabetes. In this study, we use streptozocin (STZ) injection to establish a type 1 DM mice model and use bezafibrate to treat DM mice and evaluate the effects of bezafibrate on the spermatogenic function of the DM male mice. Bezafibrate treatment exhibited protective effects on DM-induced spermatogenesis deficiency, as reflected by increased testis weight, improved histological morphology of testis, elevated sperm parameters, increased serum testosterone concentration as well as increased mRNA levels of steroidogenesis enzymes. Meanwhile, testicular cell apoptosis, inflammation accumulation and oxidative stress status were also shown to be alleviated by bezafibrate compared with the DM group. In vivo and in vitro studies, PPARα specific inhibitor and PPARα knockout mice were further used to investigate the role of PPARα in the protective effects of bezafibrate on DM-induced spermatogenesis dysfunction. Our results indicated that the protection of bezafibrate on DM-induced spermatogenesis deficiency was abrogated by PPARα inhibition or deletion. Our study suggested that bezafibrate administration could ameliorate DM-induced spermatogenesis dysfunction and may represent a novel practical strategy for male infertility.

Background: Contrast retention (CR) is an important predictor of left atrial appendage thrombus (LAAT) and stroke in patients with non-valvular atrial fibrillation (AF). We sought to explore the underlying mechanisms of CR using computational fluid dynamic (CFD) simulations. Methods: A total of 12 patients with AF who underwent both cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) before left atrial appendage occlusion (LAAO) were included in the study. The patients were allocated into the CR group or non-CR group based on left atrial appendage (LAA) angiography. Patient-specific models were reconstructed to evaluate time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and endothelial cell activation potential (ECAP). Additionally, the incidence of thrombosis was predicted using residence time (RT) at different time-points. Results: TAWSS was lower [median (Interquartile Range) 0.27 (0.19–0.47) vs 1.35 (0.92–1.79), p

In this study, enhanced pyridine bio-photodegradation with assistance of electricity was achieved. Meanwhile, photoelectron-hole played a vital role in accelerating pyridine biomineralization. The significant separation of photoelectron-hole was achieved with an external electric field, which provided sufficient electron donors and acceptors for pyridine biodegradation. The enhanced electron transport system activity also revealed the full utilization of photoelectron-hole by microbes at semiconductor-microbe interface with assistance of electricity. Microbial community analysis confirmed the enrichment of functional species related to pyridine biodegradation and electron transfer. Microbial function analysis and microbial co-occurrence networks analysis indicated that upregulated functional genes and positive interactions of different species were the important reasons for enhanced pyridine bio-photodegradation with external electric field. A possible mechanism of enhanced pyridine biodegradation was proposed, i.e., more photoelectrons and holes of semiconductors were utilized by microbes to accelerate reduction and oxidation of pyridine with the assistance of electrical stimulation. The excellent performance of the photoelectrical biodegradation system showed a potential alternative for recalcitrant organic wastewater treatment.

Abstract Community-acquired pneumonia (CAP) is one of the main reasons of mortality and morbidity in elderly population, causing substantial clinical and economic impacts. However, clinically available score systems have been shown to demonstrate poor prediction of mortality for patients aged over 65. Especially, no existing clinical model can predict morbidity and mortality for CAP patients among different age stages. Here, we aimed to understand the impact of age variable on the establishment of assessment model and explored prognostic factors and new biomarkers in predicting mortality. We retrospectively analyzed elderly patients with CAP in Minhang Hospital, Fudan University. We used univariate and multiple logistic regression analyses to study the prognostic factors of mortality in each age-based subgroup. The prediction accuracy of the prognostic factors was determined by the Receiver Operating Characteristic curves and the area under the curves. Combination models were established using several logistic regressions to save the predicted probabilities. Four factors with independently prognostic significance were shared among all the groups, namely Albumin, BUN, NLR and Pulse, using univariate analysis and multiple logistic regression analysis. Then we built a model with these 4 variables (as ABNP model) to predict the in-hospital mortality in all three groups. The AUC value of the ABNP model were 0.888 (95% CI 0.854–0.917, p

Abstract Background Children under five are the vulnerable population most at risk of being infected with Plasmodium parasites, especially in the Sahel region. Seasonal malaria chemoprevention (SMC) recommended by World Health Organization (WHO), has proven to be a highly effective intervention to prevent malaria. Given more deaths reported during the COVID-19 pandemic than in previous years due to the disruptions to essential medical services, it is, therefore, necessary to seek a more coordinated and integrated approach to increasing the pace, coverage and resilience of SMC. Towards this end, fully leverage the resources of major players in the global fight against malaria, such as China could accelerate the SMC process in Africa. Methods We searched PubMed, MEDLINE, Web of Science, and Embase for research articles and the Institutional Repository for Information Sharing of WHO for reports on SMC. We used gap analysis to investigate the challenges and gaps of SMC since COVID-19. Through the above methods to explore China’s prospective contribution to SMC. Results A total of 68 research articles and reports were found. Through gap analysis, we found that despite the delays in the SMC campaign, 11.8 million children received SMC in 2020. However, there remained some challenges: (1) a shortage of fully covered monthly courses; (2) lack of adherence to the second and third doses of amodiaquine; (3) four courses of SMC are not sufficient to cover the entire malaria transmission season in areas where the peak transmission lasts longer; (4) additional interventions are needed to consolidate SMC efforts. China was certified malaria-free by WHO in 2021, and its experience and expertise in malaria elimination can be shared with high-burden countries. With the potential to join the multilateral cooperation in SMC, including the supply of quality-assured health commodities, know-how transfer and experience sharing, China is expected to contribute to the ongoing scale-up of SMC. Conclusions A combination of necessary preventive and curative activities may prove beneficial both for targeted populations and for health system strengthening in the long run. More actions are entailed to promote the partnership and China can be one of the main contributors with various roles.

Lactobacillus fermentum (L. fermentum) was first evaluated as a potential advanced glycation end-product (AGE) formation inhibitor by establishing a bovine serum albumin (BSA) + glucose (glu) glycation model in the present study. The results showed that the highest inhibition rates of pentosidine and total fluorescent AGEs by L. fermentum were approximately 51.67% and 77.22%, respectively, which were higher than that of aminoguanidine (AG). Mechanistic analysis showed that L. fermentum could capture methylglyoxal and glyoxal, inhibit carbonyl and sulfhydryl oxidation, reduce the binding of glucose and amino groups, increase total phenolic content and antioxidant activity, and release intracellular substances to scavenge free radicals; these abilities were the basis of the antiglycation mechanism of L. fermentum. In addition, L. fermentum significantly prevented conformational changes in proteins during glycation, reduced protein cross-linking by 35.67%, and protected the intrinsic fluorophore. Therefore, the inhibition of L. fermentum on glycation mainly occurs through antioxidation, the capture of dicarbonyl compounds, and the protection of the BSA structure. These findings collectively suggest that Lactobacillus is an inhibitor of protein glycation and AGE formation and has the potential for nutraceutical applications.