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This work investigates the observer-based asynchronous boundary stabilization for a kind of stochastic Markovian reaction-diffusion neural networks with exogenous disturbances. Specifically, parameter uncertainties are considered in the drift item. First, a hidden Markov model is introduced that guarantees the observer modes run asynchronously with the system modes. It should be noted that the asynchronous observer constructed in this work only uses the boundary measurement information. Then a nonfragile asynchronous observer-based boundary controller is designed. Taking advantage of inequality techniques and stochastic analysis method, sufficient criterion is provided to satisfy input-to-state exponentially mean-square stability, and the asynchronous boundary observer/controller gains are further derived. As a special case, the synchronous observer-based boundary stabilization is also obtained. Finally, a numerical example is exploited to manifest the validity of the established results.

High strength-ductility synergy is difficult to achieve in Nb alloys. Although high strength has been achieved through severe plastic deformation (SPD) technology, led to low ductility in alloys. In this work, FSP technology was applied to treat Nb–5W–2Mo–1Zr-0.1C (Nb521) alloys in preparation of fine-grained (FG)/ultrafine-grained (UFG) Nb521 with excellent strength and ductility. The microstructure evolution and mechanical property improvement mechanism were systematically studied for Nb521 alloy through various characterization pathways. The research results indicated that UFG Nb521 alloy with a grain size of 0.63 ± 0.41 μm can be prepared using low shoulder plunge depth FSP (LPD-FSP), which is the first report of UFG Nb521 alloy. The main reason for the formation of onion rings structure in SZ is the periodic wear of the stirring tool, and the onion rings structure does not cause mechanical damage. The texture formed by Nb521 alloy under different processing parameters is off-axis shear texture, which matches the ideal shear texture of D2 (112‾)[111]after rotation. In addition, this study also elaborated on the refinement mechanism of the second phase particles (Nb, Zr) C in Nb521 alloy during FSP. This study also indicated that the increase in yield strength of FSP samples at room temperature is mainly determined by grain refinement. These findings provided new ideas for the development of high-performance niobium alloys.

Dual-comb spectroscopy (DCS) provides broadband, high-resolution, high-sensitivity amplitude and phase spectra within a short measurement time, thus holding promises for atmospheric spectroscopy. However, previous research has been limited to measuring over open-air paths of about 20 km. Here, by developing a bistatic set-up using time–frequency dissemination and high-power optical frequency combs, we implement DCS over a 113 km turbulent horizontal open-air path. We successfully measure the absorbance spectra of CO2and H2O with a 7 nm spectral bandwidth and a 10 kHz frequency accuracy, and achieve a sensing precision of <2 ppm in 5 min and <0.6 ppm in 36 min for CO2. We anticipate our system to find immediate applications in the monitoring of urban greenhouse gas and gaseous pollutants emission. Our technology may also be extended to satellite-based DCS for greenhouse gas monitoring and calibration measurements.

In industrial systems, cables are used to connect various pieces of equipment. Diagnosing soft faults in cables is a consistent step to ensure the system's stable operation. The bottleneck with existing diagnostic methods is locating and evaluating multiple faults in a cable with low error. In this article, a novel fault diagnosis method is proposed to locate multiple faults and estimate their reflection coefficients; the latter is used to assess the level of the fault. First, the reflection coefficient spectrum (RCS) (the data to be processed) is modeled, the relationship with faults is elaborated, and cable model parameters are estimated. Second, a matched filter matrix is constructed to analyze the RCS to locate faults. Third, the compensation model based on the cable transfer function is constructed to compensate for the attenuation of the signal and then estimate the reflection coefficients. Finally, sidelobe analysis is performed to improve detection accuracy, and multiple reflection analysis is performed to elaborate on the complex reflection phenomenon between multiple faults and filter out their interference in detecting real faults. Experimental results show that the proposed method locates multiple faults, estimates reflection coefficients with low error, and exhibits good robustness in the presence of noise.

The enzymatic depolymerization is a promising route to valorize the lignin polymers by turning the cross-linked polymers into monomers or oligomers. However, the lignin polymers cannot be effectively converted into small chemicals, as the oligomers are prone to polymerization, which is particularly challenging to monitor and thus regulate. Here, we develop a microstructured fiber Bragg grating (mFBG) sensor to probe the dynamic polymerization process of typical lignin oligomer surrogates─guaiacol (monomer) and guaiacylglycerol-β-guaiacyl ether (GBG, dimer)─catalyzed by laccase in an operandoway. The mFBG sensor was developed with its reliability well validated by control experiments at first. Further, operandomonitoring of the polymerization reaction process of the typical lignin monomer (i.e., guaiacol) and dimer (guaiacylglycerol-β-guaiacyl ether, GBG) was demonstrated under various conditions with the mFBG sensor. The GC-MS and UV–vis absorption measurements were carried out as a further check. Finally, the specific polymerization characteristics and reaction mechanism were studied. The mFBG sensor enables operandomonitoring of the heterogeneous polymerization process of lignin monomers and oligomers and can potentially be tailored to probe more complex lignin depolymerization processes and unveil enzymatic synergistic mechanisms for the biological transition of biomass.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/dbmice and potential mechanisms. Eight-week-old male db/dbmice were administered THBru (25, 50 mg·kg−1·d−1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/dbmice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 μM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

Different types of electron transfers (ETs) underlie the versatile use of various solid viologen-derived compounds, which is still insufficiently understood and difficult to control. Here, we demonstrate an effective strategy for modulating the key ET process in crystalline metalloviologen compounds (MVCs). By adjusting the coordinated transition metal ions bearing different electronic structures (e.g., d5, d7, d10), three MVCs (i.e., Mn-1, Co-2, and Cd-3) with highly consistent coordination environments have been synthesized successfully. Surprisingly, whether the photochromism (energy-induced ET mechanism) or the specific analyte recognition (molecule-induced ET mechanism), compound Cd-3exhibits obvious photochromic behavior and differential dimethylamine detection. Combined detailed structural analysis with theoretical calculations, such unique ion-dependent properties, were correlated to the fine modulation of the electron density of the bipyridinium cores by metal ions. Additionally, thanks to the delicate recognition of dimethylamine vapor, a convenient test strip Cd-3-PANwas prepared as a sensitive biogenic amine sensor for evaluating the real-time freshness of seafood.

As a promising material in the aircraft industry, 2A97 Al−Cu−Li alloy exhibits high corrosion susceptibility that may limit its application. In the present work, to illustrate the influences of precipitate and grain-stored energy on localized corrosion evolution in 2A97 Al−Cu−Li alloy, cold working and artificial aging were carried out to produce 2A97 Al−Cu−Li alloys under different thermomechanical conditions. Quasi-in-situ analysis, traditional immersion test and electrochemical measurement were then conducted to examine the corrosion behavior of 2A97 alloys. It is revealed that precipitate significantly affects Cu enrichment at corrosion fronts, which determines corrosion susceptibility of alloys, whereas grain-stored energy distribution is closely associated with localized corrosion propagation. It is also indicated that quasi-in-situ analysis exhibits a consistent corrosion evolution with traditional immersion tests, which is regarded as a proper method to explore localized corrosion mechanisms by providing local microstructural information with enhanced time and spatial resolutions.

[Display omitted] • Co-doping reduces g-C 3 N 4 photogenerated electron-hole complexation probability. • The introduction of diatomite improves the dispersion of g-C 3 N 4. • Co-g-C 3 N 4 /DE showed a 5.3 times higher degradation efficiency than pure g-C 3 N 4. • Co-g-C 3 N 4 /DE removed up to 98.7 % of 4-CP in 100 min. • Inferred ROS attack mechanism for 4-CP degradation using DFT calculations. The non-metallic photocatalyst g-C 3 N 4 is characterized by non-toxicity and straightforward preparation. Still, the drawbacks of low specific surface area and fast carrier complexation rate limit its practical application in photocatalysis. In this work, Co-doped g-C 3 N 4 was prepared on the surface of diatomite (DE) through a simple one-step calcination method and used to degrade 4-chlorophenol (4-CP). Photocatalytic experiments showed that Co-g-C 3 N 4 /DE removed up to 98.7% of 4-CP. The doping of Co could capture the photogenerated electrons, thereby reducing the recombination of photocarriers and accelerating the oxidation–reduction reaction of Co3+/Co2+ and H 2 O 2 , promoting the generation of OH. Introducing DE improved the aggregation of g-C 3 N 4 and expanded its surface area. Moreover, the Co-g-C 3 N 4 /DE composite material exhibited a low metal leaching rate and good reusability throughout the experiments. In addition, based on DFT calculations, the ROS attack mechanism of 4-CP degradation was speculated and calculated. The final product of 4-CP was found to pose a more minor environmental threat, according to the T.E.S.T. In short, the prepared Co-g-C 3 N 4 /DE composite realized the capture of photogenerated electrons and the acceleration of photocatalytic reactions, which are expected to solve the challenges in wastewater treatment. [ABSTRACT FROM AUTHOR]

Launching and recovering human-occupied vehicles (HOVs) has always been a challenging problem. The current recovery process requires staff to manually complete the tethering task, which is inefficient and endangers the lives of staff. This paper suggests moving the recovery position from the surface to underwater at approximately half the wavelength of the water depth (30–50 m underwater), where the HOV experiences less environmental disturbance. An ROV equipped with a ultra-short baseline beacon (USBL) and a manipulator was used to complete the tethering operation. Additionally, a shackle customized to the shape of the manipulator’s gripper is fitted to the end of the cable to simplify the tethering process. To investigate the dynamic response of recovering the HOV using this suggested method, a comprehensive numerical model is developed in this research. The effects of wind, surface waves, ocean currents, and nonlinear interaction between the installation vessel and the HOV are quantitatively examined. The results show that the proposed recovery method can reduce the motion amplitude of the HOV and that the wave has the greatest influence on the dynamic response of the HOV during the recovery process. This model provides better insight into the proposed HOV recovery method and confirms the effectiveness of the heave compensation system. The proposed approach aims to enhance safety and operational efficiency by reducing direct human involvement in the recovery process and mitigating potential dangers. This finding holds particular significance, especially in environmentally sensitive areas, where reducing the impact on the surrounding ecosystem is crucial.

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN and LMN) innervating the muscles of the trunk, extremities, head, neck and face in cerebrum, brain stem and spinal cord, which results in the progressive weakness, atrophy and fasciculation of muscle innervated by the related UMN and LMN, accompanying with the pathological signs leaded by the cortical spinal lateral tract lesion. The pathogenesis about ALS is not fully understood, and no specific drugs are available to cure and prevent the progression of this disease at present. In this review, we reviewed the structure and associated functions of copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 is crucial to the pathogenesis of ALS, and outline the pathogenic mechanisms of SOD1 in ALS that have been identified at recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, axonal transport disruption, prion-like propagation, and the non-cytologic toxicity of glial cells. This review will help us to deeply understand the current progression in this field of SOD1 pathogenic mechanisms in ALS.

Eucryptorrhynchus scrobiculatus(Motschulsky) (Coleoptera: Curculionidae) is a notorious pest of Ailanthus altissima(Mill.) Swingle (Sapindales: Simaroubaceae). E. scrobiculatusadults typically aggregate under leaves and in soil crevices at the base of A. altissimain the field. We hypothesize that the environmental factors and conspecific signals determine their aggregation behavior. To test this, we investigated adult numbers in light-exposed and shaded areas of the sample trees and conducted experiments in both field and lab settings. Results revealed that (i) greater adult distribution in shaded areas; (ii) significant influence of temperature and illumination on aggregation tendency in the field; (iii) no gender-based difference in aggregation degree and maximum aggregation between light and dark; (iv) the host plant triggering the aggregation tendency, negatively affected in the absence; (v) the aggregation tendency of E. scrobiculatusweakened with the temperature gradually changing to ordinary temperature; and (vi) mutual attraction and chemical attraction between males and females. Thus, the aggregation behavior was influenced by factors including temperature, light intensity, host plant, and conspecific signals, but light’s role was not obvious in the lab.10.1093/ee/nvae035_video1Video Abstractnvae035_video16352459126112

Factorization machine (FM) is an effective model for feature-based recommendation that utilizes inner products to capture second-order feature interactions. However, one of the major drawbacks of FM is that it cannot capture complex high-order interaction signals. A common solution is to change the interaction function, such as stacking deep neural networks on the top level of FM. In this work, we propose an alternative approach to model high-order interaction signals at the embedding level, namely generalized embedding machine (GEM). The embedding used in GEM encodes not only the information from the feature itself but also the information from other correlated features. Under such a situation, the embedding becomes high-order. Then we can incorporate GEM with FM and even its advanced variants to perform feature interactions. More specifically, in this paper, we utilize graph convolution networks (GCN) to generate high-order embeddings. We integrate GEM with several FM-based models and conduct extensive experiments on two real-world datasets. The results demonstrate significant improvement of GEM over the corresponding baselines.

The effects of sodium–glucose co-transporter-2 (SGLT2) inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population.Further research is warranted to investigate the potential benefit of SGLT2 inhibitors in AF.

Oxychalcogenides are increasingly attracting wide attention because they contain multiple anions that may combine the advantages of oxides and chalcogenides. In this work, two new pentanary oxythiogermanates, Ba3MGe3O2S8[M = Ca (1), Zn (2)], were synthesized by a high-temperature solid-state reaction. They crystallize in the orthorhombic space group Pnma, and their structures contain isolated [Ge3O2S8]8–units constructed by one [GeO2S2] and two [GeOS3] tetrahedra that link with M2+ions to build the {[MGe3O2S8]6–}8chain, representing a new type of oxythiogermanate. Notably, a [ZnS5] square pyramid exists in 2. Their structural chemistry and relationship with relevant structures are analyzed. 1and 2exhibit wide band gaps of 3.93 and 2.63 eV, birefringences of 0.100 and 0.089 at 2100 nm, respectively, and also obvious photocurrent responses. This work may be extended to a family of AE3MIIMIV3O2Q8(AE = alkali-earth metal; MII= Ca, Zn, Cd, Hg; MIV= Si, Ge, Sn; Q = S, Se), and further systematic survey on them can be performed to enrich the study of multifunctional oxychalcogenides.

Histamine, found abundantly in salt-fermented foods, poses a risk of food poisoning. Natronobeatus ordinarius, a halophilic archaeon isolated from a salt lake, displayed a strong histamine degradation ability. Its histamine oxidase (HOD) gene was identified (hodNbs). This is the first report of an archaeal HOD. The HODNbsprotein was determined to be a tetramer with a molecular weight of 307 kDa. HODNbsdisplayed optimum activity at 60–65 °C, 1.5–2.0 M NaCl, and pH 6.5. Notably, within the broad NaCl range between 0.5 and 2.5 M, HODNbsretained above 50% of its maximum activity. HODNbsexhibited good thermal stability, pH stability, and salinity tolerance. HODNbswas able to degrade various biogenic amines. The Vmaxof HODNbsfor histamine was 0.29 μmol/min/mg, and the Kmwas 0.56 mM. HODNbsexhibited high efficiency in histamine removal from fish sauce, namely, 100 μg of HODNbsdegraded 5.63 mg of histamine (37.9%) in 10 g of fish sauce within 24 h at 50 °C. This study showed that HODNbswith excellent enzymatic properties has promising application potentials to degrade histamine in high-salt foods.

Efficient and stable green emission of perovskite light-emitting diodes (PeLEDs) is an essential element for their potential applications in full-color displays and solid-state lighting, aspiring to become a new generation of light-emitting devices. Rational manipulation of the entire electroluminescence process is expected to prepare high-performance devices. Hence, to generate effective green PeLEDs that simultaneously reduce energy loss during electron–photon conversion and increase light outcoupling, a simple device architecture is suggested. Consequently, in our research, we utilized thermally activated delayed fluorescent materials DTC-mBPSB and BTBC-DPS to modify the hole transport layer. Employing efficient interfacial engineering to modulate the growth of perovskite crystals resulted in dense perovskite films and effectively reduced the density of defective states by providing lone electron pairs to neutralize unsaturated Pb2+via oxygen atoms in the passivation group of the S═O bond. Furthermore, this approach increases the carrier transport abilities and thus facilitates the occurrence of more radiative recombination. Hence, this approach contributes to the realization of EQE of 11.04% (DTC-mBPSB) and 13.97% (BTBC-DPS), respectively, for green PeLEDs emitted at 512 nm and enhances the operational stability, establishing a foundation for subsequent studies.

Currently, the desired research focus in energy storage technique innovation has been gradually shifted to next-generation aqueous batteries holding both high performance and sustainability. However, aqueous Zn–I2batteries have been deemed to have great sustainable potential, owing to the merits of cost-effective and eco-friendly nature. However, their commercial application is hindered by the serious shuttle effect of polyiodides during reversible operations. In this work, a Janus functional binder based on chitosan (CTS) molecules was designed and prepared; the polar terminational groups impart excellent mechanical robustness to hybrid binders; meanwhile, it can also deliver isochronous enhancement on physical adsorption and redox kinetics toward I2species. By feat of highly effective remission to shuttle effect, the CTS cell exhibits superb electrochemical storage capacities with long-term robustness, specifically, 144.1 mAh g–1, at a current density of 0.2 mA g–1after 1500 cycles. Simultaneously, the undesired self-discharging issue could be also well-addressed; the Coulombic efficiency could remain at 98.8 % after resting for 24 h. More importantly, CTS molecules endow good biodegradability and reusable properties; after iodine species were reloaded, the recycled devices could also deliver specific capacities of 73.3 mAh g–1, over 1000 cycles. This Janus binder provides a potential synchronous solution to realize high comprehensive performance with high iodine utilization and further make it possible for sustainable Zn–I2batteries.

C28H34FNO4, monoclinic, C2/c(no. 15), a= 21.7795(12) Å, b= 5.9103(4) Å, c= 39.830(2) Å, β= 100.866(3)°, V= 5035.1(5) Å3, Z= 8, Rgt(F) = 0.0487, wRref(F2) = 0.1376, T= 170 K.

Since sodium-ion batteries (SIBs) have become increasingly commercialized in recent years, Na3V2(PO4)2O2F (NVPOF) offers promising economic potential as a cathode for SIBs because of its high operating voltage and energy density. According to reports, NVPOF performs poorly in normal commercial poly(vinylidene fluoride) (PVDF) binder systems and performs best in combination with aqueous binder. Although in line with the concept of green and sustainable development for future electrode preparation, aqueous binders are challenging to achieve high active material loadings at the electrode level, and their relatively high surface tension tends to cause the active material on the electrode sheet to crack or even peel off from the collector. Herein, a cross-linkable and easily commercial hybrid binder constructed by intermolecular hydrogen bonding (named HPP) has been developed and utilized in an NVPOF system, which enables the generation of a stable cathode electrolyte interphase on the surface of active materials. According to theoretical simulations, the HPP binder enhances electronic/ionic conductivity, which greatly lowers the energy barrier for Na+migration. Additionally, the strong hydrogen-bond interactions between the HPP binder and NVPOF effectively prevent electrolyte corrosion and transition-metal dissolution, lessen the lattice volume effect, and ensure structural stability during cycling. The HPP-based NVPOF offers considerably improved rate capability and cycling performance, benefiting from these benefits. This comprehensive binder can be extended to the development of next-generation energy storage technologies with superior performance.

Objective: Human adenovirus (HAdV) infection is common and can develop to serious conditions with high mortality, yet the mechanism of HAdV infection remains unclear. In the present study, the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection (URTI) were explored. Methods: In total, 35 patients were enrolled in the study following an outbreak of HAdV-7 in the army, of whom 14 had pneumonia and 21 had URTI. Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics. Results: Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules, including glycerophospholipids, fatty acyls, and sphingolipids. The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways, including sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients, but not between the acute and recovery stages for the URTI patients. Ceramide and lactosylceramide, involved in sphingolipid metabolism, were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities [area under curve (AUC) 0.742 and 0.716, respectively; combination AUC 0.801]. Conclusion: Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia, especially the sphingolipid metabolism involving ceramide and lactosylceramide, which might thus be a potential intervention target in the treatment of HAdV infection.

Background: It is controversial whether there is a survival difference between open esophagectomy (OE) and thoracoscopic esophagectomy (TE) for esophageal cancer (EC). Therefore, this study aimed to compare the differences in survival and safety between two surgical approaches in patients with node-negative esophageal squamous cell carcinoma (ESCC). Methods: This ambispective cohort study included 1104 patients with node-negative ESCC who received OE or TE treatment at a Grate-A tertiary hospital in Henan Province between January 2015 and December 2016. The primary endpoint was 5-year overall survival (OS) and disease-free survival (DFS), and the secondary endpoint was surgical safety. Multivariable Cox regression analysis was used to analyze the effect of surgical approaches on OS and DFS, and propensity score matching (PSM) was performed to match confounding factors between two groups. Results: Patients were followed up ranged from 1.03 to 91.60 months, with a median follow-up time of 67.37 months. Kaplan–Meier survival analysis showed statistically significant differences between OE and TE in OS (70.05% vs 83.73%, P&lt; 0.001) and DFS (67.15% vs 77.76%, P&lt; 0.001). Furthermore, multivariate Cox regression analysis also demonstrated significant differences in long-term survival between the two groups (OS, HR (95% CI): 0.54 (0.41, 0.70); DFS, HR (95% CI): 0.68 (0.54, 0.86)). TE was associated with a reduction in intraoperative bleeding (median: 100 ml vs. 200 ml, P&lt; 0.001), and an increase in the number of lymph nodes dissection (median: 23 vs. 28, P&lt; 0.001). Similar results were found after PSM. Conclusion: In a selected cohort of patients with node-negative ESCC, TE surgical treatment was safer and had better long-term survival outcomes compared to OE. This provided corresponding clinical guidance to enhance survival benefits for patients. In the future, we hope to further explore the reasons for TE achieving higher survival rates. Graphical abstract:

The TRacing Etiology of Non-communicable Diseases (TREND) cohort is a prospective longitudinal cohort and biobank that is mainly based in Ma’anshan, Anhui Province, China. The primary aim of the study is to decipher comprehensive molecular characterization and deep phenotyping for a broad spectrum of chronic non-communicable diseases (NCDs), which focuses on providing mechanistic insights with diagnostic, prognostic and therapeutic implications. The recruitment was initiated in 2023 and is expected to complete in 2025 with 20,000 participants originated from urban and rural area. In the first phase, 3360 participants were recruited. Follow-up visits are scheduled annually and intervally for a total of 30 years. The cohort includes individuals aged over 18 years. Two participants with first-degree linkage were recruited from a household. The age distribution of recruited participants was stratified into four categories: 18–45, 45–55, 55–65, and ≥65 years, aligning with the population proportions of Ma’anshan. Meanwhile, the gender distribution was controlled by pairing men and women from the same household. Data collected at baseline includes socio-economic information, medical history, lifestyle and nutritional habits, anthropometrics, blood oxygen, electrocardiogram (ECG), heart sound, as well as blood, urine and feces tests results. Molecular profiling includes genome, proteome, metabolome, microbiome and extracellular vesicles -omics. Blood, urine and fecal samples are collected and stored at −80 °C in a storage facility for future research.

As a major contributor to neonatal death and neurological sequelae, hypoxic-ischemic encephalopathy (HIE) lacks a viable medication for treatment. Oxidative stress induced by hypoxic-ischemic brain damage (HIBD) predisposes neurons to ferroptosis due to the fact that neonates accumulate high levels of polyunsaturated fatty acids for their brain developmental needs but their antioxidant capacity is immature. Ferroptosis is a form of cell death caused by excessive accumulation of iron-dependent lipid peroxidation and is closely associated with mitochondria. Mitophagy is a type of mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. In this study we employed mitophagy agonists and inhibitors to explore the mechanisms by which mitophagy exerted ferroptosis resistance in a neonatal rat HIE model. Seven-days-old neonatal rats were subjected to ligation of the right common carotid artery, followed by exposure to hypoxia for 2 h. The neonatal rats were treated with a mitophagy activator Tat-SPK2 peptide (0.5, 1 mg/kg, i.p.) 1 h before hypoxia, or in combination with mitochondrial division inhibitor-1 (Mdivi-1, 20 mg/kg, i.p.), and ferroptosis inhibitor Ferrostatin-1 (Fer-1) (2 mg/kg, i.p.) at the end of the hypoxia period. The regulation of ferroptosis by mitophagy was also investigated in primary cortical neurons or PC12 cells in vitro subjected to 4 or 6 h of OGD followed by 24 h of reperfusion. We showed that HIBD induced mitochondrial damage, ROS overproduction, intracellular iron accumulation, lipid peroxidation and ferroptosis, which were significantly reduced by the pretreatment with Tat-SPK2 peptide, and aggravated by the treatment with Mdivi-1 or BNIP3 knockdown. Ferroptosis inhibitors Fer-1 and deferoxamine B (DFO) reversed the accumulation of iron and lipid peroxides caused by Mdivi-1, hence reducing ferroptosis triggered by HI. We demonstrated that Tat-SPK2 peptide-activated BNIP3-mediated mitophagy did not alleviate neuronal ferroptosis through the GPX4-GSH pathway. BNIP3-mediated mitophagy drove the P62-KEAP1-NRF2 pathway, which conferred ferroptosis resistance by maintaining iron and redox homeostasis via the regulation of FTH1, HO-1, and DHODH/FSP1-CoQ10-NADH. This study may provide a new perspective and a therapeutic drug for the treatment of neonatal HIE.

Langerhans cell histiocytosis (LCH) lacks a standardized first-line therapy. This single-center, phase 2 prospective study (NCT04121819) enrolled 61 newly diagnosed adult LCH patients with multisystem or multifocal single system disease from October 2019 to June 2022. Subcutaneous cytarabine (100 mg/m2 for 5 days) was administered in 35-day cycles for 12 total cycles. The primary endpoint was event-free survival (EFS). The median age was 33 years (range 18–66). Twelve patients (19.7%) had liver involvement, of which 2 also had spleen involvement. Among 43 patients undergoing next-generation sequencing, BRAF alterations (44.2%) were most frequent, followed by TP53 (16.3%), MAP2K1 (14.0%) and IDH2 (11.6%). MAPK pathway alterations occurred in 28 patients (65.1%). The overall response rate was 93.4%, with 20 (32.7%) achieving complete response and 37 (60.7%) partial response. After a median 30 months follow-up, 21 (34.4%) relapsed without deaths. Estimated 3-year OS and EFS were 100.0% and 58.5%, respectively. Multivariate analysis identified ≥3 involved organs (P= 0.007; HR 3.937, 95% CI: 1.456–9.804) and baseline lung involvement (P= 0.028; HR 2.976, 95% CI: 1.126–7.874) as poor prognostic factors for EFS. The most common grade 3–4 toxicities were neutropenia (27.9%), thrombocytopenia (1.6%), and nausea (1.6%). In conclusion, cytarabine monotherapy is an effective and safe regimen for newly diagnosed adults, while baseline lung or ≥3 involved organs confers poor prognosis.

Herein, a novel ratiometric sensor for fluorimetric and smartphone-assisted visual detection of Al3+in environmental water was developed based on the target-regulated formation of Eu metal–organic frameworks (Eu MOFs). By employing 2-[4-(2-hydroxyethyl) piperazin-1-yl] ethanesulfonic acid (Hepes), Eu3+and tetracycline (TC) as raw materials, Eu MOFs with red emission were facilely synthesized through the coordination of Eu3+with Hepes and TC. However, upon the introduction of Al3+, a higher affinity of TC towards Al3+resulted in the formation of a TC–Al3+complex with green fluorescence and inhibited the generation of Eu MOFs. This led to an increase in green fluorescence and a decrease in red fluorescence accompanied by the fluorescence color of the solution changing from red to green under the illumination of the UV lamp. Thus, a ratiometric sensor for fluorimetric and the smartphone-assisted visual detection of Al3+was established. The ratiometric sensor exhibited high sensitivity for Al3+detection with a detection limit of 0.14 μM for fluorescence detection and 1.21 μM for visual detection. Additionally, the proposed strategy was successfully applied to detect Al3+in the environmental water samples with satisfactory results, indicating great application prospects for environmental monitoring.