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Abstract Recycling strategies for mixed plastics and textile blends currently aim for recycling only one of the components. Here, we demonstrate a water coupling strategy to co-hydrolyze polyester/cotton textile blends into polymer monomers and platform chemicals in gamma-valerolactone. The blends display a proclivity for achieving an augmented 5-hydroxymethylfurfural yield relative to the degradation of cotton alone. Controlled experiments and preliminary mechanistic studies underscore that the primary driver behind this heightened conversion rate lies in the internal water circulation. The swelling and dissolving effect of gamma-valerolactone on polyester enables a fast hydrolysis of polyester at much lower concentration of acid than the one in the traditional hydrolysis methods, effectively mitigating the excessive degradation of cotton-derived product and undesirable product formation. In addition, the system is also applicable to different kinds of blends and PET mixed plastics. This strategy develops an attractive path for managing end-of-life textiles in a sustainable and efficient way.

Introduction: As a soil amendment, Bamboo charcoal helps to contributes to the improvement of soil carbon sequestration, but its effect on the accumulation and transformation of different soil organic carbon in soil of karst forests is not clear.Methods: The research focused on three distinct forest land succession stages: virgin forest, secondary forest, and planted forest. A 60-day indoor constant temperature culture experiment was conducted, applying bamboo charcoal to the soil of the three forest lands at four different addition ratios: 0%, 1.0%, 2.0%, and 4.0%. The analysis aimed to study the characteristics of SOC mineralization, different carbon fractions of organic carbon, and soil enzyme activity.Results: The findings revealed that bamboo charcoal application led to an increase in the organic carbon (SOC) content within the three forest soils. Moreover, the organic carbon content showed an increase corresponding to the increased proportion of bamboo charcoal, with the highest SOC content observed in the planted forest land with 4.0% bamboo charcoal. The overall performance of the C0/SOC value in the three forest soils was ranked as follows: planted forest < secondary forest < virgin forest (C0: the mineralization potential of soil organic carbon). In both planted and secondary forest soils, the C0/SOC value increased after the application of bamboo charcoal. However, in the virgin forest soil, the application of 1.0% and 4.0% bamboo charcoal reduced the C0/SOC value, while the application of 2.0% bamboo charcoal increased the C0/SOC value. Particularly the C0/SOC value of the planted forest soil without bamboo charcoal was the smallest at 0.047, whereas that in the virgin forest soil with 2.0% bamboo charcoal had the largest value at 0.161.Discussion: Herein, appropriate human intervention can enhance the carbon sequestration potential of forest soil, in different succession stages within the karst area. However, the external application of bamboo charcoal does not significantly improve the carbon sequestration potential in the planted and secondary forest. Notably, applying a higher proportion (4.0%) of bamboo charcoal can enhance the organic carbon sequestration potential, particularly in the virgin forest soil, representing the climax community of forest succession.

This article combines (k,Θ)-Hilfer fractional calculus with glucose molecular graph, defines fractional differential and inclusion systems on each edge of a glucose molecular graph by the assumption that 0 or 1 marks the vertices, and studies the single-valued and multi-valued (k,Θ)-Hilfer type fractional boundary value problems on the glucose molecular graph. On the one hand, the existence and uniqueness of solutions in the single-valued case are proved by using several fixed point theorems. On the other hand, in the multi-valued case, we consider that the right side of the inclusion has convex valued and non-convex value. By applying Leray-Schauder nonlinear alternative method of multi-valued maps as well as Covitz-Nadler fixed point theorem of multi-valued contractions, two existence results are obtained respectively. On this basis, we also get the topological structure of the solution set, which is a pioneering work for (k,Θ)-Hilfer fractional differential inclusion on the glucose graph. Finally, several examples are provided to verify the reliability of our proposed results.

Tumors pose a significant global public health challenge, resulting in numerous fatalities annually. CD8+ T cells play a crucial role in combating tumors; however, their effectiveness is compromised by the tumor itself and the tumor microenvironment (TME), resulting in reduced efficacy of immunotherapy. In this dynamic interplay, extracellular vesicles (EVs) have emerged as pivotal mediators, facilitating direct and indirect communication between tumors and CD8+ T cells. In this article, we provide an overview of how tumor-derived EVs directly regulate CD8+ T cell function by carrying bioactive molecules they carry internally and on their surface. Simultaneously, these EVs modulate the TME, indirectly influencing the efficiency of CD8+ T cell responses. Furthermore, EVs derived from CD8+ T cells exhibit a dual role: they promote tumor immune evasion while also enhancing antitumor activity. Finally, we briefly discuss current prevailing approaches that utilize functionalized EVs based on tumor-targeted therapy and tumor immunotherapy. These approaches aim to present novel perspectives for EV-based tumor treatment strategies, demonstrating potential for advancements in the field.

Abstract Objectives This study aimed to describe the temporal trends in age and gender burdens of rheumatic heart disease (RHD) in China from 1990 to 2019, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and to compare them with the global burden of the disease. Methods Using open data from the Global Burden of Disease (GBD) database from 1990 to 2019, this study analyzed the characteristics of RHD burden in China and worldwide, including changes in incidence, prevalence, mortality, and DALYs. Joinpoint was used to calculate the average annual percentage change (AAPC) and the corresponding 95% confidence interval (95% CI) to reflect the trends in the burden of RHD. A comprehensive comparative analysis of the differences in RHD burden between China and the rest of the world was conducted from multiple dimensions, including age, gender, and time periods. Results From 1990 to 2019, the age-standardized incidence rate (ASIR) of RHD in China decreased from 29.62/100,000 to 23.95/100,000, while the global ASIR increased from 32.69/100,000 to 37.40/100,000. The age-standardized prevalence rate (ASPR) in China decreased from 446.15/100,000 to 390.24/100,000, while the global ASPR increased from 451.56/100,000 to 513.68/100,000. The age-standardized rates of mortality (ASMR) in China decreased from 18.11/100,000 to 4.04/100,000, while the global ASMR decreased from 8.94/100,000 to 3.85/100,000. The age-standardized DALY rate (ASDR) in China decreased from 431.45/100,000 to 93.73/100,000, while the global ASDR decreased from 283.30/100,000 to 132.88/100,000. The AAPC of ASIR, ASPR, ASMR, and ASDR in China was − 0.73%, -0.47%, -5.10%, and − 5.21%, respectively, while the AAPC of the global burden of RHD was 0.48%, 0.45%, -2.87%, and − 2.58%, respectively. The effects of age and gender on the burden of RHD were different. ASIR generally decreased with increasing age, while ASPR increased first and then decreased. ASMR and ASDR increased with increasing age. Women had higher incidence and mortality rates of RHD than men. Conclusion From 1990 to 2019, the incidence, prevalence, mortality, and DALYs of RHD in China decreased, indicating a relative reduction in the burden of RHD in China. The burden of RHD is age-related, with a higher prevalence observed in the younger population, a peak incidence among young adults, and a higher mortality rate among the elderly population. Women are more susceptible to RHD and have a higher risk of mortality than men. Given China’s large population and aging population, RHD remains a significant public health challenge in China.

In order to study the effects of wildfires on soil carbon dioxide (CO2) emissions and microbial communities in planted forests, Pinus massoniana Lamb. and Cunninghamia lanceolata (Lamb.) Hook. forests were selected as the research subjects. Through a culture test with 60 days of indoor constant temperature, the soil physical and chemical properties, organic carbon mineralization, organic carbon components, enzyme activity, and microbial community structure changes of the two plantations after fire were analyzed. The results showed that wildfires significantly reduced soil CO2 emissions from the Pinus massoniana forests and Cunninghamia lanceolata forests by 270.67 mg·kg−1 and 470.40 mg·kg−1, respectively, with Cunninghamia lanceolata forests exhibiting the greatest reduction in soil CO2 emissions compared to unburned soils. Bioinformatics analysis revealed that the abundance of soil Proteobacteria in the Pinus massoniana and Cunninghamia lanceolata forests decreased by 6.00% and 4.55%, respectively, after wildfires. Additionally, redundancy analysis indicated a significant positive correlation between Proteobacteria and soil CO2 emissions, suggesting that the decrease in Proteobacteria may inhibit soil CO2 emissions. The Cunninghamia lanceolata forests exhibited a significant increase in soil available nutrients and inhibition of enzyme activities after the wildfire. Additionally, soil CO2 emissions decreased more, indicating a stronger adaptive capacity to environmental changes following the wildfire. In summary, wildfire in the Cunninghamia lanceolata forests led to the most pronounced reduction in soil CO2 emissions, thereby mitigating soil carbon emissions in the region.

Abstract Background This study aimed to develop and validate an AI (artificial intelligence)-aid method in myocardial perfusion imaging (MPI) to differentiate ischemia in coronary artery disease. Methods We retrospectively selected 599 patients who had received gated-MPI protocol. Images were acquired using hybrid SPECT-CT systems. A training set was used to train and develop the neural network and a validation set was used to test the predictive ability of the neural network. We used a learning technique named “YOLO” to carry out the training process. We compared the predictive accuracy of AI with that of physician interpreters (beginner, inexperienced, and experienced interpreters). Results Training performance showed that the accuracy ranged from 66.20% to 94.64%, the recall rate ranged from 76.96% to 98.76%, and the average precision ranged from 80.17% to 98.15%. In the ROC analysis of the validation set, the sensitivity range was 88.9 ~ 93.8%, the specificity range was 93.0 ~ 97.6%, and the AUC range was 94.1 ~ 96.1%. In the comparison between AI and different interpreters, AI outperformed the other interpreters (most P-value

Etiology of hepatic steatosis and metabolic dysfunction-associated fatty liver disease (MAFLD) among acute coronary syndrome (ACS) remains unclear. Existing studies suggested the potential role of per- and polyfluoroalkyl substances (PFAS) in comorbidity of hepatic steatosis among ACS patients. Therefore, we conducted a cross-sectional study based on the ACS inpatients to assess the associations of plasma PFAS congeners and mixtures with hepatic steatosis and MAFLD. This study included 546 newly diagnosed ACS patients. Twelve PFAS were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. Hepatic steatosis was defined by hepatic steatosis index (HSI). MAFLD was defined as the combination of hepatic steatosis based on the risk factor calculation with metabolic abnormalities. Generalized linear model was used to examine the associations of PFAS congeners with HSI and MAFLD. Adaptive elastic net (AENET) was further used for PFAS congeners selection. Mixture effects were also assessed with Bayesian kernel machine regression model (BKMR). Congeners analysis observed significant greater percent change of HSI for each doubling in PFOS (1.82%, 95% CI: 0.87%, 2.77%), PFHxS (1.17%, 95% CI: 0.46%, 1.89%) and total PFAS (1.84%, 95% CI: 0.56%, 3.14%). Moreover, each doubling in PFOS (OR=1.42, 95% CI: 1.13, 1.81), PFHxS (OR=1.31, 95% CI: 1.09, 1.59) and total PFAS (OR=1.43, 95% CI: 1.06, 1.94) was associated with increased risk of MAFLD. In AENET regression, only PFOS presented significant positive associations with HSI. Mixture analysis indicated significant positive associations between PFAS mixtures and HSI. This is the first study to demonstrate associations of PFAS congeners and mixtures with hepatic steatosis and MAFLD among ACS patients, which provides hypothesis into the mechanisms behind comorbidity of hepatic steatosis among ACS patients, as well as tertiary prevention of ACS.

At present, the high energy consumption of data centers based on grid power supply not only brings huge direct cost of electricity, but also indirectly produces a lot of greenhouse gases, which affects the natural environment. Academia and industry are beginning to introduce clean renewable energy sources such as wind and solar power into data centers to reduce operating costs and environmental damage by building new green data centers. To solve this problem, this study considers the use of waste heat for refrigeration while taking natural gas power generation into account, and introduces wind energy as a green energy source. On the premise of considering the response level of data centers, the two resources are combined and deployed to improve resource utilization and reduce energy consumption costs. Aiming at the instability of wind power generation, a particle swarm energy scheduling optimization algorithm based on simulated annealing algorithm was proposed by combining simulated annealing algorithm and particle swarm optimization algorithm. The research shows that, considering the response level of data centers, the use of natural gas and wind energy as the main energy supply can effectively reduce the overall energy consumption of data centers.

BackgroundExisting evidence indicates that exposure to per- and polyfluoroalkyl substances (PFASs) may increase the risk of hypertension, but the findings are inconsistent. Therefore, we aimed to explore the relationship between PFASs and hypertension through this systematic review and meta-analysis.MethodsWe searched PubMed, Embase, and the Web of Science databases for articles published in English that examined the relationship between PFASs and hypertension before 13 August 2022. The random effects model was used to aggregate the evaluation using Stata 15.0 for Windows. We also conducted subgroup analyses by region and hypertension definition. In addition, a sensitivity analysis was carried out to determine the robustness of the findings.ResultsThe meta-analysis comprised 15 studies in total with 69,949 individuals. The risk of hypertension was substantially and positively correlated with exposure to perfluorooctane sulfonate (PFOS) (OR = 1.31, 95% CI: 1.14, 1.51), perfluorooctanoic acid (PFOA) (OR = 1.16, 95% CI: 1.07, 1.26), and perfluorohexane sulfonate (PFHxS) (OR = 1.04, 95% CI: 1.00, 1.09). However, perfluorononanoic acid (PFNA) exposure and hypertension were not significantly associated (OR = 1.08, 95% CI: 0.99, 1.17).ConclusionWe evaluated the link between PFASs exposure and hypertension and discovered that higher levels of PFOS, PFOA, and PFHxS were correlated with an increased risk of hypertension. However, further high-quality population-based and pathophysiological investigations are required to shed light on the possible mechanism and demonstrate causation because of the considerable variability.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/ PROSPERO, registration number: CRD 42022358142.

Transglutaminase 2 (TGM2) is a versatile enzyme that modulates cell survival and differentiation. However, its role in terminal erythroid differentiation is poorly understood. In this study, we investigated the function of TGM2 in primary fetal liver erythroid differentiation. We predicted TGM2 as an upstream regulator via ingenuity pathway analysis (IPA), and found that its expression was increased at both RNA and protein level during terminal erythroid differentiation. TGM2 cross-linking activity inhibitors GK921 and Z-DON suppressed erythroid maturation and enucleation, while its GTPase inhibitor LDN27219 had no such effect. Z-DON treatment arrested differentiation at basophilic erythroblast stage, and interfered with cell cycle progression. RT-PCR demonstrated decreased GATA-1 and KLF1, and disarranged cyclin, CDKI and E2F family genes expression after Z-DON treatment. In conclusion, TGM2 regulates terminal erythroid differentiation through its cross-linking enzyme activity.

Abstract Colorectal cancer (CRC) is one of the most common malignancies that is usually detected late in the clinic. The currently available diagnostic tools for CRC are either invasive or insensitive to early lesions due to the dearth of reliable biomarkers. In this study, we discovered that the extracellular vesicles (EVs) in the faeces of CRC patients can act as a potent biomarker for the non‐invasive diagnosis and prognosis of CRC. This finding is based on the identification of two transmembrane proteins—CD147 and A33—on faeces‐derived EVs (fEVs) that are intrinsically associated with CRC. The detection results show that the levels of CD147 and A33 on fEVs were upregulated in the CRC patients (n = 48), dramatically distinguishing them from the healthy donors (n = 16). The CD147/A33‐enriched EVs offer a clinical sensitivity of 89%, much higher than that (40%) of carcinoembryonic antigen (CEA), a clinically‐established serum biomarker for CRC diagnosis. In addition, the analysis of longitudinal faeces samples (n = 29) demonstrated that the CD147/A33‐enriched fEVs can be utilized to track the prognosis of CRC. Due to the high compliance of faeces‐based detection, the CD147/A33‐enriched fEVs could serve as new‐generation CRC biomarkers for large‐scale, non‐invasive CRC screening as well as real‐time monitoring of patient outcomes during clinical interventions.

Continued exacerbation of ozone (O3) pollution in China has driven the urgent need for an emission control strategy that efficiently reduces O3 levels. Determining O3 precursor sensitivity (OPS) and its driving factors is a prerequisite for formulating effective O3 control strategies. In this study, we proposed an atmospheric oxidative capacity-based indicator, HO2/OH, and demonstrated its effectiveness in indicating OPS over the Yangtze River Delta (YRD) of China by applying a localized comprehensive air quality model with extensions (CAMx) coupled with the Weather Research and Forecasting (WRF) model. A strong correlation was discovered between HO2/OH and OPS, and HO2/OH showed the best performance in separating NOx- and VOC-limited regimes in comparison with other commonly used indicators. A comprehensive analysis with ensemble diagnostic tools revealed the spatial heterogeneity of NOx and VOC emissions and the impact of regional transport controlling the relationship between OPS variations and the HO2/OH indicator over the YRD. The process analysis results show that days with higher contributions from horizontal advection favored OPS transitions in Shanghai, Nanjing, Hefei, Suzhou, and Wuhu, while vertical advection caused OPS transitions in Hangzhou and Ningbo. O3 source apportionment technology analysis indicated that the regional contributions from Zhejiang and Jiangsu/Anhui corresponded well to the NOx-limited and VOC-limited regimes, respectively. Our results provide a better understanding of the underlying mechanisms of the relationship between OPS and the HO2/OH indicator and can help guide contingency control measures for O3 despiking over the YRD and other photochemically active regions worldwide.

Ground-level O3 pollution has been continuously worsening in China despite gradual improvement in other major pollutant levels. Understanding the sensitivity of O3 production to its precursors (OPS) is a prerequisite for formulating effective O3 control measures, but this has been hampered by significant discrepancies in OPS produced by traditional identification approaches using observation-based models (OBM) and emission-based models (EBM). In this study, by applying OBM and EBM in parallel within a month having significant O3 pollution in Shanghai, China, we demonstrated that a lack of carbonyl input, overestimation in NO2 monitoring data, and differences in simulation period and emission reduction area were the core factors leading to OPS discrepancies, and that a reliable OPS cannot be obtained unless these factors are reconciled. By collectively addressing these factors, the number of days with a consistent OPS from both models increased from 6–7 to 20–21 in a month, and the R value defined to quantify the discrepancy decreased by ∼55%. The contributions of these factors to OPS discrepancy differed greatly in urban and suburban settings, mainly caused by differences in pollutant emission and transport characteristics. Overall, OPS identified solely by OBM or EBM is associated with great uncertainty, while reliable OPS estimation can be achieved by a collective application of OBM and EBM with consensus on the above factors. The method demonstrated here could be applied to other photo-chemically active regions worldwide as part of efforts to address ozone pollution.

Objective Heart failure (HF) and atrial fibrillation (AF) are often coexisting. They have common risk factors and pathophysiologic mechanisms. Sacubitril/valsartan has shown efficacy and tolerability in patients with HF. Thus, the study was performed to evaluate the impact of sacubitril/valsartan on AF occurrence in patients with HF. Methods The Embase and PubMed were searched from their inception date to June 2021 for all relevant randomized controlled trials (RCTs) evaluating the efficacy of sacubitril/valsartan in HF. The outcome of interest was the AF occurrence during the follow-up. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results Six trials involving a total of 15,512 patients were included (7,750 randomized to sacubitril/valsartan and 7,762 to control). All trials were randomized, double-blind, and active-control. There was no significant difference in the prevention of AF occurrence between the sacubitril/valsartan group and the control group (enalapril or valsartan) in patients with HF (RR 1.07, 95%CI 0.95 to 1.19; I2 4%). Conclusions Sacubitril/valsartan was similar to either enalapril or valsartan in preventing the occurrence of AF in patients with HF.

Energy consumption is the key factor leading to high operating costs in data center. In this paper, considering the data center service level under the premise of using electricity and gas as energy supply of energy supply and energy consumption from two angles, the data center energy scheduling model is built. The lower model is calculation scheduling model for the data center, and the upper model is data center energy supply scheduling model. Then the particle swarm algorithm is used to simulate the schedule. The results show that using natural gas as supplementary energy supply can effectively reduce the overall energy consumption of data center in considering the service delay level of data center.

Lung cancer is one of the most common cancers worldwide. TRPV4 belongs to the ‘transient receptor potential' (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation, and inflammation. Unlike other TRP superfamily channels, its roles in cancers are unknown. Here, we elucidated the effects of TRPV4 and molecular mechanisms in human lung cancer cells. The levels of TRPV4 were detected in human lung cancer tissues and the paired paracarcinoma tissues by real-time PCR and western blotting analysis. The proliferation of human lung cancer cells was determined by MTT assay. Cell apoptosis was determined by FACS assay. The results demonstrated that low levels of TRPV4 were detected in clinical lung carcinoma specimens. Over-expression of TRPV4 induced cell death and inhibited cell proliferation and migration in A549 cells and H460 cells. Moreover, over-expression of TRPV4 enhanced the activation of p38 MAPK signal pathway. Inhibition of p38 MAPK abolished the effects of TRPV4 on cell proliferation, apoptosis, and migration in A549 cells. Collectively, our findings indicated that TRPV4 induced apoptosis via p38 MAPK in human lung cancer cells and suggested that TRPV4 was a potential target for therapy of human lung cancers.

Abstract Introduction The traditional treatment of myocardial infarction with ventricular septal rupture is surgical treatment. For the elderly patients with cardiac insufficiency, surgical treatment is very risky. The successful treatment of this case by interventional occlusion is a new method. No relevant literature reports have been found. Case A 77-year-old man with a past medical history of old myocardial infarction presented to the physician with sudden onset of palpitation and shortness of breath. Echocardiography showed thinning of the interventricular septum near the apex and bulging toward the right ventricular side with “paradoxical motion”, on which a rupture of about 8 mm in diameter was seen. CDFI: left ventricular blood shunted to the right ventricle through the rupture.Echocardiographic diagnosis: old left ventricular anteroseptal myocardial infarction with ventricular septal rupture. Due to the older age of the patient and reduced left ventricular function, surgical repair of the ventricular septal rupture site was more difficult. After multidisciplinary discussion, it was agreed that the patient could not afford thoracotomy and was not suitable for thoracotomy, and echocardiography guided interventional occlusion of the ruptured interventricular septum could be performed. Conclusion Transesophageal echocardiography-guided interventional occlusion of myocardial infarction with ventricular septal rupture in elderly patients with cardiac insufficiency is a new attempt, the successful treatment of this case shows that this method is feasible, for some patients is an appropriate treatment.

Abstract Background Professor Xinfang Wang first introduced the clinical application of trans nose pharynx esophagus echocardiography (TNPEE) in 2014. Subsequently, we developed the technology. In the present study we assess the feasibility of TNPEE in the ultrasonic diagnosis. Methods Select patients suitable for TNPEE examination. After obtaining written consent of patients or their families, oral dacronin hydrochloride gel local anesthesia was given 10–15 min before examination. The nostrils were disinfected and then smeared with tetracaine hydrochloride gel, which acted as local anesthesia and lubrication. The probe was inserted gently through the nostrils and entered the esophagus through the nasal cavity and pharynx. TNPEE is similar to transoral esophagus echocardiography (TOEE) after the probe reaches the esophagus. Results TNPEE was performed in 103 patients. Forty-five patients (43.7%) underwent the examination successfully, 46 patients (44.7%) failed because of objective reasons, 12 patients midway refused to accept the examination and cancelled the examination, accounting for 11.6%, 11 patients (12.1%) suffered from epistaxis. Of all the patients with epistaxis, 9 had taken anticoagulant drugs, accounting for 82% of the patients with epistaxis. The vital signs of all patients were stable and no serious complications occurred. Conclusion Compared with TOEE, TNPEE can cause less nausea and vomiting reaction, and patients take longer time to undergo examination, which is conducive to more detailed examination. However, TNPEE has a high requirement for the probe, and its success rate is relatively low. It is easy to cause nasal bleeding in patients, so its wide clinical application is limited.

The winged helix superfamily comprises a large number of structurally related nucleic acid-binding proteins. While these proteins are often shown to bind dsDNA, few are known to bind ssDNA. Here, we report the identification and characterization of Sul7s, a novel winged-helix single-stranded DNA binding protein family highly conserved in Sulfolobaceae. Sul7s from Sulfolobus islandicus binds ssDNA with an affinity approximately 15-fold higher than that for dsDNA in vitro. It prefers binding oligo(dT)30 over oligo(dC)30 or a dG-rich 30-nt oligonucleotide, and barely binds oligo(dA)30. Further, binding by Sul7s inhibits DNA strand annealing, but shows little effect on the melting temperature of DNA duplexes. The solution structure of Sul7s determined by NMR shows a winged helix-turn-helix fold, consisting of three α-helices, three β-strands, and two short wings. It interacts with ssDNA via a large positively charged binding surface, presumably resulting in ssDNA deformation. Our results shed significant light on not only non-OB fold single-stranded DNA binding proteins in Archaea, but also the divergence of the winged-helix proteins in both function and structure during evolution.

Objective Huang-Lian-Jie-Du-Tang (HLJDT), a traditional Chinese medicine, improves cognitive ability in rat models of Alzheimer’s disease (AD). The objective of this study was to evaluate the protective effects of HLJDT on learning and memory impairment that are caused by Aβ 25–35 . Methods Rats were randomly assigned to the following groups: control (water), Aβ 25–35 , donepezil hydrochloride 1.05 mg/kg, HLJDT 6 g/kg, HLJDT 3 g/kg, and HLJDT 1.5 g/kg and the corresponding drugs were administered for 28 days by oral gavage. HLJDT for the prevention of Aβ 25–35 -induced injury in rats and the underlying mechanisms were assessed. Aβ 25–35 and amyloid precursor protein (APP) levels were measured in the hippocampal specimens. Total superoxide dismutase (T-SOD), glutathione (GSH), and malondialdehyde (MDA) levels in the hippocampus were also measured. The ultrastructure of CA1 hippocampal region was observed using electron microscopy. Results HLJDT treatment ameliorated impaired learning and memory significantly, decreased Aβ 25–35 , and APP levels in the hippocampus, increased T-SOD and GSH activity and decreased the MDA concentration, and alleviated the nuclear and cytoplasmic abnormalities of the hippocampal CA 1 region that were induced by Aβ 25–35 injection. Conclusions HLJDT might decrease hippocampal vulnerability to Aβ 25–35 , suggesting its potential neuroprotective effect in AD.

The oxygen evolution reaction (OER) is a key reaction in hydrogen production through water splitting and in fuel cells. Nickel nanoalloys are potential low-cost OER electrocatalysts, but their catalytic activity and stability need to be improved. The doping of nickel catalysts with anionic elements combined with partial amorphization can improve their electrocatalytic activity. In this study, we report a ternary B-, P- and O-doped amorphous nickel nanoalloy (BPO-Ni) as an effective electrocatalyst for the OER. Compared with binary boron–oxygen-doped nickel (BO-Ni) and phosphorus–oxygen-doped nickel (PO-Ni), ternary BPO-Ni has higher OER catalytic activity and better durability under alkaline conditions. Our results reveal that the high catalytic activity of the B-, P- and O-doped Ni nanoalloy is derived from the synergistic effects between the ternary heteroatoms and the Ni atoms, thereby increasing their catalytic activity. This work produces a new non-metal doped amorphous nickel nanoalloy structure, and offers a way of studying novel inexpensive and efficient OER catalysts. Keywords: Amorphous, Ni nanoalloy, Boron, Phosphorus, Oxygen evolution reaction

Abstract Background Previous studies showed that the majority of developmental genes are devoid of DNA methylation at promoters even when they are repressed. Such hypomethylated regions at developmental genes are unusually large and extend well beyond proximal promoters, forming DNA methylation valleys (DMVs) or DNA methylation canyons. However, it remains elusive how most developmental genes can evade DNA methylation regardless of their transcriptional states. Results We show that DMVs are hypomethylated in development and are highly conserved across vertebrates. Importantly, DMVs are hotspots of regulatory regions for key developmental genes and show low levels of deamination mutation rates. By analyzing a panel of DNA methylomes from mouse tissues, we identify a subset of DMVs that are dynamically methylated. These DMVs are strongly enriched for Polycomb-deposited H3K27me3 when the associated genes are silenced, and surprisingly show elevated DNA methylation upon gene activation. 4C-seq analyses indicates that Polycomb-bound DMVs form insulated and self-interacting chromatin domains. Further investigations show that DNA hypomethylation is better correlated with the binding of Polycomb than with H3K27me3. In support of a role of Polycomb in DMV hypomethylation, we observe aberrant methylation in DMVs in mouse embryonic stem cells deficient in the EED protein. Finally, we show that Polycomb regulates hypomethylation of DMVs likely through ten-eleven translocation (TET) proteins. Conclusions We show that Polycomb promotes the hypomethylation of DMVs near key developmental genes. These data reveal a delicate interplay between histone modifiers and DNA methylation, which contributes to their division at distinct gene targets, allowing lineage-specifying genes to largely maintain DNA methylation-free at regulatory elements.

New Delhi metallo-β-lactamases (NDMs) hydrolyze almost all β-lactam antibiotics and pose a major public health threat. Here, the authors study the mechanism of NDM-1 catalyzed carbapenem hydrolysis and present the crystal structures of the enzyme-intermediate and product complexes, which is important for drug design.

Abstract NZ17074 (N1), an arenicin-3 derivative isolated from the lugworm, has potent antibacterial activity and is cytotoxic. To reduce its cytotoxicity, seven N1 analogues with different structures were designed by changing their disulfide bonds, hydrophobicity, or charge. The “rocket” analogue-N2 and the “kite” analogue-N6 have potent activity and showed lower cytotoxicity in RAW264.7 cells than N1. The NMR spectra revealed that N1, N2, and N6 adopt β-sheet structures stabilized by one or two disulfide bonds. N2 and N6 permeabilized the outer/inner membranes of E. coli, but did not permeabilize the inner membranes of S. enteritidis. N2 and N6 induced E. coli and S. enteritidis cell cycle arrest in the I-phase and R-phase, respectively. In E. coli and in S. enteritidis, 18.7–43.8% of DNA/RNA/cell wall synthesis and 5.7–61.8% of DNA/RNA/protein synthesis were inhibited by the two peptides, respectively. Collapsed and filamentous E. coli cells and intact morphologies of S. enteritidis cells were observed after treatment with the two peptides. Body weight doses from 2.5–7.5 mg/kg of N2 and N6 enhanced the survival rate of peritonitis- and endotoxemia-induced mice; reduced the serum IL-6, IL-1β and TNF-α levels; and protected mice from lipopolysaccharide-induced lung injury. These data indicate that N2 and N6, through multiple selective actions, may be promising dual-function candidates as novel antimicrobial and anti-endotoxin peptides.

The structure of a representative pyrazolo[3,4]pyran derivative was determined by 1D and 2D NMR techniques. Complete 1H and 13C chemical shifts for this compound are reported. Careful analysis of the HMBC (Heteronuclear Multi-Bond Correlation) spectrum helped to elucidate the configuration of the derivative around C7 and C8. The results showed that the characteristic double-strong and double-weak cross peak pattern in the HMBC spectrum for C7 and C8 might be useful for establishing the structures of other pyrazolo[3,4]pyran derivatives.

In the present study, the wastewater sample collected from the Dongming discharging river in Shijiazhuang city was analysed using both chemical analysis and biological assays including the Salmonella mutagenicity test, micronucleus test and single-cell gel electrophoresis. Chemical analysis of the sample was performed using gas chromatography mass spectrometry and inductively coupled plasma mass spectrometry. The Salmonella mutagenicity test was performed on Salmonella typhimurium TA97, TA98, TA100 and TA102 strains with and without S9 mixture. The mice received the wastewater in natura through drinking water at concentrations of 25%, 50%, and 100%. One group of mice was exposed for 2 consecutive days, and the other group of mice was exposed for 15 consecutive days. To establish the levels of primary DNA damage, single-cell gel electrophoresis was performed on treated mouse liver cell. The concentrations of chromium and lead in the sample exceeded the national standard (GB20922-2007) by 0.78 and 0.43-fold, respectively. More than 30 organic compounds were detected, and some of the detected compounds were mutagens, carcinogens and environmental endocrine disrupters. A positive response for Salmonella typhimurium TA98 strain was observed. Mouse exposure via drinking water containing 50% and 100% of wastewater for 15 consecutive days caused a significant increase of MN frequencies in a dose-response manner. Mouse exposure via drinking water containing 50% and 100% of wastewater for 15 consecutive days caused a significant increase of the Olive tail moments in a dose-response manner. All the results indicated that the sample from the Dongming discharging river in Shijiazhuang city exhibited genotoxicity and might pose harmful effects on the local residents.

Tumors pose a significant global public health challenge, resulting in numerous fatalities annually. CD8+ T cells play a crucial role in combating tumors; however, their effectiveness is compromised by the tumor itself and the tumor microenvironment (TME), resulting in reduced efficacy of immunotherapy. In this dynamic interplay, extracellular vesicles (EVs) have emerged as pivotal mediators, facilitating direct and indirect communication between tumors and CD8+ T cells. In this article, we provide an overview of how tumor-derived EVs directly regulate CD8+ T cell function by carrying bioactive molecules they carry internally and on their surface. Simultaneously, these EVs modulate the TME, indirectly influencing the efficiency of CD8+ T cell responses. Furthermore, EVs derived from CD8+ T cells exhibit a dual role: they promote tumor immune evasion while also enhancing antitumor activity. Finally, we briefly discuss current prevailing approaches that utilize functionalized EVs based on tumor-targeted therapy and tumor immunotherapy. These approaches aim to present novel perspectives for EV-based tumor treatment strategies, demonstrating potential for advancements in the field. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze trends in the burden of myocarditis in the Chinese population during 1990-2019. Methods: The Global Burden of Disease (GBD) database aims to assess the burden of various diseases and injuries on a global scale, and the contribution of relevant risk factors to the burden of disease was also included. In this study, we collected age-standardized incidence and mortality rates for myocarditis in China from 1990 to 2019 using GBD 2019. The age-period-cohort model was utilized to calculate local drift, longitudinal age patterns, as well as the ratios of period and cohort. Results: The age-standardized incidence and mortality rates of myocarditis in both men and women presented a decreasing trend during 1990-2019 [average annual percentage change (AAPC) of men = -0.202 (95% CI: -0.213 to -0.191); AAPC of women = -0.263 (95% CI: -0.27 to -0.256) for incidence; AAPC of men = -0.233 (95% CI: -0.371 to -0.094); AAPC of women = -0.872 (95% CI: -1.112 to -0.631) for mortality]. Longitudinal age curves showed that myocarditis incidence and mortality rates elevated with age among individuals aged 15-95+ years, with a higher growth rate in men than in women. The period and cohort ratios for both men and women showed similar decreasing trends. Local drift values for the incidence and mortality rates of myocarditis showed an increasing trend among individuals aged 70-75 years and above. Conclusion: Although the overall burden of myocarditis in China presented a decreasing trend during 1990-2019, the male and elderly populations still have a higher risk of incidence and mortality. Therefore, it is essential for the health-care system to introduce effective prevention and treatment measures for myocarditis. [ABSTRACT FROM AUTHOR]