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We study the interrelations between salt karst and landscape evolution at the Ze’elim and Hever alluvial fans, Dead Sea (DS), Israel, in an attempt to characterize the ongoing surface and subsurface processes and identify future trends. Using light detection and ranging, interferometric synthetic aperture radar, drone photography, time-lapse cameras, and direct measurements of floodwater levels, we document floodwater recharge through riverbed sinkholes, subsurface salt dissolution, groundwater flow, and brine discharge at shoreline sinkholes during the years 2011–2023. At the Ze’elim fan, most of the surface floodwater drains into streambed sinkholes and discharges at shoreline sinkholes, whereas at the Hever fan, only a small fraction of the floodwater drains into sinkholes, while the majority flows downstream to the DS. This difference is attributed to the low-gradient stream profiles in Ze’elim, which enable water accumulation and recharge in sinkholes and their surrounding depressions, in contrast with the higher-gradient Hever profiles, which yield high-energy floods capable of carrying coarse gravel that eventually fill the sinkholes. The rapid drainage of floodwater into sinkholes also involves slope failure due to pore-pressure drop and cohesion loss within hours after each drainage event. Surface subsidence lineaments detected by InSAR indicate the presence of subsurface dissolution channels between recharge and discharge sites in the two fans and in the nearby Lynch straits. Subsidence and streambed sinkholes occur in most other fans and streams that flow to the DS; however, with the exception of Ze’elim, all other streams show only minor or no recharge along their course. This is due to either the high-gradient profiles, the gravelly sediments, the limited floods, or the lack of conditions for sinkhole development in the other streambeds. Thus, understanding the factors that govern the flood-related karst formation is of great importance for predicting landscape evolution in the DS region and elsewhere and for sinkhole hazard assessment.

Studies the controlled grafting of poly(styrene-ran-n-butyl methacrylate) to isotactic polypropylene (PP) with nitroxide-mediated polymerization. Use of PP peroxides produced by gamma irradiation in air as macroinitiator for grafting; Analysis of molecular characteristics of grafted and free poly(styrene-ran-n-butyl methacrylate).

We study the interrelations between salt karst and landscape evolution at the Ze'elim and Hever alluvial fans, Dead Sea (DS), Israel, in an attempt to characterize the ongoing surface and subsurface processes and identify future trends. Using light detection and ranging, interferometric synthetic aperture radar, drone photography, time-lapse cameras, and direct measurements of floodwater levels, we document floodwater recharge through riverbed sinkholes, subsurface salt dissolution, groundwater flow, and brine discharge at shoreline sinkholes during the years 2011–2023. At the Ze'elim fan, most of the surface floodwater drains into streambed sinkholes and discharges at shoreline sinkholes, whereas at the Hever fan, only a small fraction of the floodwater drains into sinkholes, while the majority flows downstream to the DS. This difference is attributed to the low-gradient stream profiles in Ze'elim, which enable water accumulation and recharge in sinkholes and their surrounding depressions, in contrast with the higher-gradient Hever profiles, which yield high-energy floods capable of carrying coarse gravel that eventually fill the sinkholes. The rapid drainage of floodwater into sinkholes also involves slope failure due to pore-pressure drop and cohesion loss within hours after each drainage event. Surface subsidence lineaments detected by InSAR indicate the presence of subsurface dissolution channels between recharge and discharge sites in the two fans and in the nearby Lynch straits. Subsidence and streambed sinkholes occur in most other fans and streams that flow to the DS; however, with the exception of Ze'elim, all other streams show only minor or no recharge along their course. This is due to either the high-gradient profiles, the gravelly sediments, the limited floods, or the lack of conditions for sinkhole development in the other streambeds. Thus, understanding the factors that govern the flood-related karst formation is of great importance for predicting landscape evolution in the DS region and elsewhere and for sinkhole hazard assessment. [ABSTRACT FROM AUTHOR]

Accurate determination of pesticide residues is crucial for food safety. A self-calibration method was developed for dual-signal "naked-eye" detection of organophosphorus pesticides (OPs) using bifunctional gold nanozymes (AuNEs). OPs inhibit the cascade reaction of acetylcholinesterase/choline oxidase (AChE/CHO) to reduce hydrogen peroxide (H 2 O 2 ) production, which affects the AuNE-catalyzed color reaction and quenches the fluorescence of AuNEs with the assistance of Fe 2+ . The multi-enzyme cascade system can be integrated into hydrogel sheets for smartphone-assisted digital, quantitative, and onsite detection of OPs in real food samples by analyzing the linear changes in colorimetric and fluorometric signals, which closely match liquid chromatography-mass spectrometry (LC-MS) results. This method displays a lowest 'naked-eye' detection concentration of 7 ppb, a wide linear range (0-2000 ng/mL), and particularly the advantage of anti-interference via self-calibration when one of the signals is abnormal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Self-healing hydrogels have attracted significant attention in chronic diabetic wound healing due to their potential to minimize the risk of secondary infections caused by joint movement or dressing rupture. Herein, a multifunctional self-healing hydrogel mediated utilizing an enzyme-triggered cascade reaction based on dynamic imine bonds was designed. The hydrogel employs three enzymes: lysozyme (LYZ), glucose oxidase (GOx), and catalase (CAT), as building blocks. GOx catalyzes the conversion of glucose and 1-thio-β-d-glucose (β-GlcSH) into hydrogen peroxide (H 2 O 2 ), gluconic acid (GA), and hydrogen sulfide (H 2 S). Subsequently, CAT eliminates H 2 O 2 , protecting the imine bonds from oxidative damage. The acidic environment created by GA decreases the pH and regulates the crosslinking density of imine bonds, enhancing the self-healing capability and porosity of the hydrogel. This feature enables the sustained release of the drug rosuvastatin calcium (RCa) to promote endothelial cell migration and vascular regeneration. Combined with the antioxidative and anti-inflammatory effects of released H 2 S gas and the antibacterial properties of lysozyme, this hydrogel exhibits promising therapeutic efficacy for the synergistic treatment of chronic diabetic wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Ischemic stroke accounts for over 85 % of all stroke types. Acyl-CoA synthetase long chain family member 4 (ACSL4) is considered to promote myocardial and cerebral ischaemia/ reperfusion. However, up to now, no study focused on the role of ACSL4 in patients with post-stroke lower limb neurological sequelae., Objective: The present study aimed to investigate the predictive value of ACSL4 and collateral circulation for lower limb neurological sequelae of ischemic stroke patients after modified constraint-induced movement therapy (mCIMT)., Methods: This is a prospective cohort study which included 99 ischemic stroke patients with lower limb neurological sequelae who were admitted to our hospital during January 2021 to December 2022. All patients received mCIMT after the admission. Collateral circulation was evaluated by digital subtraction angiography (DSA) and graded by the American Society of Interventional and Therapeutic Neuroradiology/ Society of Interventional Radiology (ASITN/SIR) grading system. Enzyme linked immunosorbent assay (ELISA) was used to detect serum ACSL4. Basic characteristics were collected and lower limb motor function was measured by Fugl-Meyer score (FMS), modified Ashworth score (MAS) and Brunnstrom stage, as well as timed up and go (TUG) test, ten-Meter walk test (10MWT), and six-minute walk test (6MWT) before and after treatment., Results: Serum ACSL4 and percentage of patients with ASITN/SIR 0-1 decreased significantly after treatment compared with the values before treatment. Patients with higher baseline serum ACSL4 values at admission showed significantly lower FMS scores, higher TUG and 10MWT, as well as lower 6MWT. Patients with ASITN/SIR grade 0-1 at admission only showed significantly higher TUG and 10MWT, as well as lower 6MWT. Receiver operating characteristic (ROC) curves showed ACSL4 and ASITN/SIR grade could be used to predict the prognosis. Logistic regression found only national institutes of health stroke scores (NIHSS) was the independent risk factor for post-treatment motor impairment after mCIMT., Conclusion: Higher levels of ACSL4 and ASITN/SIR 0-1 are associated with poor recovery of motor functions of patients with post-stroke sequelae after mCIMT., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier B.V.)

Activation of endogenous neural stem cells (NSC) is one of the most potential measures for neural repair after spinal cord injury. However, methods for regulating neural stem cell behavior are still limited. Here, we investigated the effects of nicotinamide riboside promoting the proliferation of endogenous neural stem cells to repair spinal cord injury. Nicotinamide riboside promotes the proliferation of endogenous neural stem cells and regulates their differentiation into neurons. In addition, nicotinamide riboside significantly restored lower limb motor dysfunction caused by spinal cord injury. Nicotinamide riboside plays its role in promoting the proliferation of neural stem cells by activating the Wnt signaling pathway through the LGR5 gene. Knockdown of the LGR5 gene by lentivirus eliminates the effect of nicotinamide riboside on the proliferation of endogenous neural stem cells. In addition, administration of Wnt pathway inhibitors also eliminated the proliferative effect of nicotinamide riboside. Collectively, these findings demonstrate that nicotinamide promotes the proliferation of neural stem cells by targeting the LGR5 gene to activate the Wnt pathway, which provides a new way to repair spinal cord injury., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Yan-Chun Shan, Zhao-Chuan Yang, Liang Ma, Ni Ran, Xue-Ying Feng, Xiao-Mei Liu, Peng Fu, Ming-Ji Yi Department of Child Health Care, Pediatric Center, Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaCorrespondence: Ming-Ji YiDepartment of Child Health Care, Pediatric Center, Affiliated Hospital of Qingdao University, No. 16 of Jiangsu Road, Shinan District, Qingdao, 266003, People’s Republic of ChinaTel +86 532 82911223Email ymj1042_dryi@163.comObjective: This study aims to explore the clinical features and molecular diagnosis of FBN1-related acromelic dysplasia in Chinese patients.Methods: The clinical and genetic features of three FBN1-related acromicric dysplasia (AD)/geleophysic dysplasia (GD) Chinese patients from two families were reviewed, and comprehensive medical evaluations were performed. Targeted next-generation sequencing was used to detect genetic mutations associated with short statures, including FBN1. Sanger sequencing was used to determine the de novo mutation origin.Results: Patient 1 presented with short stature, short and stubby hands and feet, mild facial dysmorphism, hepatomegaly, delayed bone age and beak-like femoral heads. Patient 2 and this patient’s father merely presented with short stature, wide and short hands, and beak-like femoral heads. One novel mutation, c.5272G>T(p.D1758Y), and one known mutation, c.5183C>T(p.A1728V), were identified in these patients.Conclusion: The clinical features varied among these patients. The variant c.5272G>T(p.D1758Y) is a novel mutation.Keywords: FBN1, acromelic dysplasia, acromicric dysplasia, geleophysic dysplasia, short stature

Single-component electrocatalysts generally lead to unbalanced adsorption of OH - and urea during urea oxidation reaction (UOR), thus obtaining low activity and selectivity especially when oxygen evolution reaction (OER) competes at high potentials (>1.5 V). Herein, a cross-alignment strategy of in situ vertically growing Ni(OH) 2 nanosheets on 2D semiconductor g-C 3 N 4 is reported to form a hetero-structured electrocatalyst. Various spectroscopy measurements including in situ experiments indicate the existence of enhanced internal electric field at the interfaces of vertical Ni(OH) 2 and g-C 3 N 4 nanosheets, favorable for balancing adsorption of reaction intermediates. This heterojunction electrocatalyst shows high-selectivity UOR compared to pure Ni(OH) 2 , even at high potentials (>1.5 V) and large current density. The computational results show the vertical heterojunction could steer the internal electric field to increase the adsorption of urea, thus efficiently avoiding poisoning of strongly adsorbed OH - on active sites. A membrane electrode assembly (MEA)-based electrolyzer with the heterojunction anode could operate at an industrial-level current density of 200 mA cm -2 . This work paves an avenue for designing high-performance electrocatalysts by vertical cross-alignments of active components., (© 2024 Wiley‐VCH GmbH.)

Nanobubbles have been increasingly used in various applications involving porous media, such as groundwater remediation and irrigation. However, the fundamental scientific knowledge regarding the interactions between nanobubbles and the media is still limited. The interactions can be repulsive, attractive, or inert, and can involve reversible or irreversible attachment as well as destructive mechanisms. Specifically, the stability and mobility of nanobubbles in porous media is expected to be dependent on the dynamic conditions and the physicochemical properties of the porous media, solutions, and nanobubbles themselves. In this study, we investigated how changes in solution chemistry (pH, ionic strength, and valence) and media characteristics (size and wettability) affect the size and concentration of nanobubbles under dynamic conditions using column experiments. Quartz crystal microbalance with dissipation monitoring provided a deeper understanding of irreversible and elastic nanobubbles' interactions with silica-coated surfaces. Our findings suggest that nanobubbles are less mobile in solutions of higher ionic strength and valence, acidic pH and smaller porous media sizes, while the wettability of porous media has a negligible influence on the retention of nanobubbles. Overall, our findings provide insights into the underlying mechanisms of nanobubble interactions and suggest potential strategies to optimize their delivery in various applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Spinal cord injury (SCI) is a devastating condition for which effective clinical treatment is currently lacking. During the acute phase of SCI, myriad pathological changes give rise to subsequent secondary injury. The results of our previous studies indicated that treating rats post-SCI with nafamostat mesilate (NM) protected the blood-spinal cord barrier (BSCB) and exerted an antiapoptotic effect. However, the optimal dosage for mice with SCI and the underlying mechanisms potentially contributing to recovery, especially during the acute phase of SCI, have not been determined. In this study, we first determined the optimal dosage of NM for mice post-SCI (5 mg/kg/day). Subsequently, our RNA-seq findings revealed that NM has the potential to inhibit pyroptosis after SCI. These findings were further substantiated by subsequent Western blot (WB) and Immunofluorescence (IF) analyses in vivo. These results indicate that NM can alleviate NLRP3 (NOD-like receptor thermal protein domain associated protein 3)-mediated pyroptosis by modulating the NF-κB signaling pathway and reducing the protein expression levels of NIMA-related kinase 7 (NEK7) and cathepsin B (CTSB). In vitro experimental results supported our in vivo findings, revealing the effectiveness of NM in suppressing pyroptosis induced by adenosine triphosphate (ATP) and lipopolysaccharide (LPS) in BV2 cells. These results underscore the potential of NM to regulate NLRP3-mediated pyroptosis following SCI. Notably, compared with other synthetic compounds, NM exhibits greater versatility, suggesting that it is a promising clinical treatment option for SCI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

We developed an optofluidic surface-enhanced Raman scattering chip capable of online fabrication, online molecular detection, and online self-cleaning. In this chip, we harnessed UV light to successfully reduce an AgNO 3 solution, resulting in the formation of Ag nanoparticles on carbon fiber cloth coated with titanium dioxide (TiO 2 ). This innovative approach enabled the online fabrication of AgNPs@TiO 2 -CFC SERS structures. By introducing target molecules into our optofluidic SERS chip, we achieved online molecular Raman detection. Furthermore, by leveraging the UV light-induced self-cleaning properties of TiO 2 , we achieved continuous online self-cleaning of the molecules. To verify the feasibility and stability of our method, we conducted multiple experiments for online detection and self-cleaning. Experimental results demonstrated impressively low detection limits of 10 -8 mol/L for crystal violet and 10 -9 mol/L for rhodamine 6G, with an enhancement factor as high as 1.4 × 10 6 . Additionally, we successfully applied our method to polycyclic aromatic hydrocarbons like pyrene.

Spinal cord injury (SCI) has no effective treatment modalities. It faces a significant global therapeutical challenge, given its features of poor axon regeneration, progressive local inflammation, and inefficient systemic drug delivery due to the blood-spinal cord barrier (BSCB). To address these challenges, a new nano complex that achieves targeted drug delivery to the damaged spinal cord is proposed, which contains a mesoporous silica nanoparticle core loaded with microRNA and a cloaking layer of human umbilical cord mesenchymal stem cell membrane modified with rabies virus glycoprotein (RVG). The nano complex more readily crosses the damaged BSCB with its exosome-resembling properties, including appropriate size and a low-immunogenic cell membrane disguise and accumulates in the injury center because of RVG, where it releases abundant microRNAs to elicit axon sprouting and rehabilitate the inflammatory microenvironment. Culturing with nano complexes promotes axonal growth in neurons and M2 polarization in microglia. Furthermore, it showed that SCI mice treated with this nano complex by tail vein injection display significant improvement in axon regrowth, microenvironment regulation, and functional restoration. The efficacy and biocompatibility of the targeted delivery of microRNA by nano complexes demonstrate their immense potential as a noninvasive treatment for SCI., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The Geological Survey of Israel has upgraded and expanded the national Israeli Seismic Network (ISN), with more than 110 stations country-wide, as part of the implementation of a governmental decision to build a national Earthquake Early Warning (EEW) system named TRUAA. This upgraded seismic network exhibits a high station density and fast telemetry. The stations are distributed mainly along the main fault systems, the Dead Sea Transform, and the Carmel-Zfira Fault, which may potentially produce Mw 7.5 earthquakes. The system has recently entered a limited operational phase, allowing for initial performance estimation. Real-time performance during eight months of operation (41 earthquakes) matches expectations. Alert delays (interval between origin-time and Earthquake Early Warning alert time) are reduced to as low as 3 s, and source parameter errorstatistics are within expected values found in previous works using historical data playbacks. An evolutionary alert policy is implemented based on a magnitude threshold of Mw 4.2 and peak ground accelerations exceeding 2 cm/s2. A comparison between different ground motion prediction equations (GMPE) is presented for earthquakes from Israel and California using median ground motion prediction equations values. This analysis shows that a theoretical GMPE produced the best agreement with observed ground motions, with less bias and lower uncertainties. The performance of this GMPE was found to improve when an earthquake specific stress drop is implemented.

The in situ characterization of the heterostructure active sites during the hydrogen evolution reaction (HER) process and the direct elucidation of the corresponding catalytic structure-activity relationships are essential for understanding the catalytic mechanism and designing catalysts with optimized activity. Hence, exploring the underlying reasons behind the exceptional catalytic performance necessitates a detailed analysis. Herein, we employed scanning electrochemical microscopy (SECM) to in situ image the topography and local electrocatalytic activity of 1T/2H MoS 2 heterostructures on mixed-phase molybdenum disulfide (MoS 2 ) with 20 nm spatial resolution. Our measurements provide direct data about HER activity, enabling us to differentiate the superior catalytic performance of 1T/2H MoS 2 heterostructures compared to other active sites on the MoS 2 surface. Combining this spatially resolved electrochemical information with density functional theory calculations and numerical simulations enables us to reveal the existence of hydrogen spillover from the 1T MoS 2 surface to 1T/2H MoS 2 heterostructures. Furthermore, it has been verified that hydrogen spillover can significantly enhance the electrocatalytic activity of the heterostructures, in addition to its strong electronic interaction. This study not only contributes to the future investigation of electrochemical processes at nanoscale active sites on structurally complex electrocatalysts but also provides new design strategies for improving the catalytic activity of 2D electrocatalysts.

Density functional theory (DFT) calculations demonstrate neighboring Pt atoms can enhance the metal activity of NiCoP for hydrogen evolution reaction (HER). However, it remains a great challenge to link Pt and NiCoP. Herein, we introduced curvature of bowl-like structure to construct Pt/NiCoP interface by adding a minimal 1 ‰-molar-ratio Pt. The as-prepared sample only requires an overpotential of 26.5 and 181.6 mV to accordingly achieve the current density of 10 and 500 mA cm -2 in 1 M KOH. The water dissociation energy barrier (E a ) has a ~43 % decrease compared with NiCoP counterpart. It also shows an ultrahigh stability with a small degradation rate of 10.6 μV h -1 at harsh conditions (500 mA cm -2 and 50 °C) after 3000 hrs. X-ray photoelectron spectroscopy (XPS), soft X-ray absorption spectroscopy (sXAS), and X-ray absorption fine structure (XAFS) verify the interface electron transfer lowers the valence state of Co/Ni and activates them. DFT calculations also confirm the catalytic transition step of NiCoP can change from Heyrovsky (2.71 eV) to Tafel step (0.51 eV) in the neighborhood of Pt, in accord with the result of the improved H ads at the interface disclosed by in situ electrochemical impedance spectroscopy (EIS) and scanning electrochemical microscopy (SECM) tests., (© 2024 Wiley-VCH GmbH.)

The prevalence of cadmium (Cd) contamination has emerged as a significant global concern. Exposure to Cd during pregnancy is associated with adverse pregnancy outcomes, including miscarriage. However, there is currently a lack of comprehensive summaries on Cd-induced miscarriage. Therefore, it is imperative to further strengthen research into in vivo studies, clinical status, pathological mechanisms, and pharmacological interventions for Cd-induced miscarriage. This study systematically presents the current knowledge on animal models and clinical trials investigating Cd exposure-induced miscarriage. The underlying mechanisms involving oxidative stress, inflammation, endocrine disruption, and placental dysfunction caused by Cd-induced miscarriage are also extensively discussed. Additionally, potential drug interventions such as melatonin, vitamin C, and vitamin E are highlighted for their pharmacological role in mitigating adverse pregnancy outcomes induced by Cd., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene., Methods: Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing., Results: All of the six patients had presented with severe short stature (< 3s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c.5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c.5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c.5156G>T (p.C1719F) missense variant in exon 42, which was de novo in origin. Patient 6 had harbored a c.5272G>T (p.D1758Y) missense variant in exon 43, which was also de novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c.5156G>T was rated as a pathogenic variant (PS2+PM1+PM2&#95;Supporting +PM5+PP3)., Conclusion: All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.

Fas apoptotic signaling regulates diverse physiological processes. Acute activation of Fas signaling triggers massive apoptosis in liver. Upon Fas receptor stimulation, the BH3-only protein Bid is cleaved into the active form, tBid. Subsequent tBid recruitment to mitochondria, which is facilitated by its receptor MTCH2 at the outer mitochondrial membrane (OMM), is a critical step for commitment to apoptosis via the effector proteins Bax or Bak. MOAP-1 is a Bax-binding protein enriched at the OMM. Here, we show that MOAP-1-deficient mice are resistant to Fas-induced hepatocellular apoptosis and lethality. In the absence of MOAP-1, mitochondrial accumulation of tBid is markedly impaired. MOAP-1 binds to MTCH2, and this interaction appears necessary for MTCH2 to engage tBid. These findings reveal a role for MOAP-1 in Fas signaling in the liver by promoting MTCH2-mediated tBid recruitment to mitochondria.

Objective: Hepatitis B virus (HBV) infection causes substantial harm to mitochondrial activity, which hinders the development of effective treatments for chronic hepatitis B (CHB). The discovery of the mitochondrial-derived short peptide MOTS-c, which possesses multiple bioactivities, offers a promising new approach in treating HBV infection. This study aims to explore the diagnostic and therapeutic potential of MOTS-c in HBV-related diseases and its molecular mechanism., Design: In total, 85 healthy subjects and 404 patients with HBV infection, including 20 clinical treatment cohorts, were recruited for this study. MOTS-c levels were measured by ELISA and its diagnostic value was evaluated by receiving operating characteristic curve analysis. The therapeutic effect of MOTS-c was observed in multiple HBV-infected mice and cells through various techniques, including transcriptomic sequencing, flow cytometry, immunofluorescence and electron microscopy. Additionally, MOTS-c's potential interaction with myosin-9 (MYH9) and actin was predicted using immunoprecipitation, proteomics and target prediction software., Results: MOTS-c negatively correlates with HBV DNA expression (R=-0.71), and its AUC (the area under the curve) for distinguishing CHB from healthy controls is 0.9530, and IA (immune reactive) from IC (inactive HBV carrier) is 0.8689. Inhibition of HBV replication (with a 50-70% inhibition rate) was observed alongside improved liver function without notable toxicity in vitro or in vivo. MOTS-c was found to promote mitochondrial biogenesis and enhance the MAVS (mitochondrial antiviral signalling protein) signalling pathway. The impact is dependent on MOTS-c's ability to regulate MYH9-actin-mediated mitochondrial homeostasis., Conclusion: MOTS-c has the potential to serve as a biomarker for the progression of HBV infection while also enhancing antiviral efficacy. These findings present a promising innovative approach for effectively treating patients with CHB. Furthermore, our research uncovers a novel role for MOTS-c in regulating MYH9-actin-mediated mitochondrial dynamics and contributing to mitochondrial biogenesis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: High-throughput sequencing was used to screen expressing differences of miRNA, lncRNA, and mRNA in CD19+ B peripheral blood samples of newly diagnosed immune thrombocytopenia (ITP) patients and healthy controls. The study aimed to explore the regulatory role of ceRNA network in the pathogenesis of dysfunctional CD19 + B lymphocytes of ITP patients., Methods: CD19+ B lymphocytes were isolated from peripheral blood samples of ITP patients and their healthy counterparts. High-throughput sequencing was used to screen for the expression of miRNA, lncRNA, and mRNA of ITP patients and healthy controls, which were analysed by the ceRNA network. Moreover, qPCR was used to verify the differential expression of miRNA, lncRNA, and mRNA in ITP patients and healthy controls. The correlation between differentially expressed miRNA, lncRNA, mRNA, and B lymphocyte subsets was also analysed., Results: The CD19+ B lymphocytes of 4 newly diagnosed ITP patients and 4 healthy controls were sequenced and analysed. There were 65 differentially expressed lncRNA and 149 mRNA forming a ceRNA network showed that 12 lncRNA and 136 differentially expressed mRNA were closely associated. Similarly, miR-144-3p, miR-374c-3p, and miR-451a were highly expressed in ITP patients, as confirmed by qPCR, which was consistent with the high-throughput sequence results. LOC102724852 and CCL20 were highly expressed in ITP patients, while LOC105378901, LOC112268311, ALAS2, and TBC1D3F were not as compared to healthy controls, which was consistent with the high-throughput sequence results. In addition, the expression of miR-374c-3p, LOC112268311, LOC105378901, and CXCL3 were correlated with the percentage of B lymphocyte subsets., Conclusions: The ceRNA network of miRNA, lncRNA, and mRNA in peripheral CD19 + B lymphocytes plays an essential role in the pathogenesis of ITP.

Gerstmann-Sträussler-Scheinker (GSS) disease is an autosomal dominant neurodegenerative disease, and it is characterized by progressive cerebellar ataxia. Up to now, GSS cases with the p.P102L mutation have mainly been reported in Caucasian, but rarely in Asian populations. A 54-year-old female patient presented with an unstable gait in the hospital. Last year, she was unable to walk steadily and occasionally choked, could not even walk independently gradually. After taking her medical history, we found that she was misdiagnosed with schizophrenia before the gait problems. The patient's father showed similar symptoms and was diagnosed with brain atrophy at the age of 56, but her daughter showed no similar symptoms at present. On arrival at the Neurology Department, the patient's vital signs and laboratory examinations showed no abnormality. As the proband presented with cerebellar ataxia and had an obvious family history, we were sure that she had hereditary cerebellar ataxia. Then, patient's brain MRI showed an abnormal signal in the right parietal cortex and bilateral small ischaemic lesions in the frontal lobe. A gene panel (including 142 ataxia-related genes) was performed, and a heterozygous mutation PRNP Exon2 c.305C>T p. (Pro102Leu) was identified. Her daughter had the same heterozygous mutation. The patient was diagnosed with GSS with mental disorders as initial symptoms. After 2 months of TCM treatment, the patient's walking instability decreased, and her emotional fluctuations were less than before. In conclusion, we have reported a rare case of GSS in Sichuan, China, and the family with mental disorder as the first symptom was finally confirmed with GSS PRNP P102L mutation.

Cereals grains are the prime component of the human diet worldwide. To promote food security and sustainability, new approaches to non-chemical weed control are needed. Early vigor cultivars with enhanced weed-competitiveness ability are a potential tool, nonetheless, the introduction of such trait in breeding may be a long and labor-intensive process. Here, two image-driven plant phenotyping methods were evaluated to facilitate effective and accurate selection for early vigor in cereals. For that purpose, two triticale genotypes differentiating in vigor and growth rate early in the season were selected as model plants: X-1010 (high) and Triticale1 (low). Two modeling approaches, 2-D and 3-D, were applied on the plants offering an evaluation of various morphological growth parameters for the triticale canopy development, under controlled and field conditions. The morphological advantage of X-1010 was observed only at the initial growth stages, which was reflected by significantly higher growth parameter values compared to the Triticale1 genotype. Both modeling approaches were sensitive enough to detect phenotypic differences in growth as early as 21 days after sowing. All growth parameters indicated a faster early growth of X-1010. However, the 2-D related parameter [projected shoot area (PSA)] is the most available one that can be extracted via end user-friendly imaging equipment. PSA provided adequate indication for the triticale early growth under weed-competition conditions and for the improved weed-competition ability. The adequate phenotyping ability for early growth and competition was robust under controlled and field conditions. PSA can be extracted from close and remote sensing platforms, thus, facilitate high throughput screening. Overall, the results of this study may improve cereal breeding for early vigor and weed-competitiveness.

During the past three decades, the Dead Sea (DS) water level has dropped at an average rate of ~1 m/year, resulting in the formation of thousands of sinkholes along its coastline that severely affect the economy and infrastructure of the region. The sinkholes are associated with gradual land subsidence, preceding their collapse by periods ranging from a few days to about five years. We present the results of over six years of systematic high temporal and spatial resolution interferometric synthetic aperture radar (InSAR) observations, incorporated with and refined by detailed Light Detection and Ranging (LiDAR) measurements. The combined data enable the utilization of interferometric pairs with a wide range of spatial baselines to detect minute precursory subsidence before the catastrophic collapse of the sinkholes and to map zones susceptible to future sinkhole formation. We present here four case studies that illustrate the timelines and effectiveness of our methodology as well as its limitations and complementary methodologies used for sinkhole monitoring and hazard assessment. Today, InSAR-derived subsidence maps have become fundamental for sinkhole early warning and mitigation along the DS coast in Israel and are incorporated in all sinkhole potential maps which are mandatory for the planning and licensing of new infrastructure.

Formulas containing intact cow milk protein are appropriate alternatives when human milk (HM) is not feasible. However, for babies with a physician-diagnosed cow milk protein allergy (CMPA), hydrolyzed formulas are needed. We conducted a 3-month, open-label, nonrandomized concurrent controlled trial (ChiCTR2100046909) between June 2021 and October 2022 in Qingdao City, China. In this study, CMPA toddlers were fed with a partially hydrolyzed formula containing synbiotics (pHF, n  = 43) and compared with healthy toddlers fed a regular intact protein formula (IF, n  = 45) or HM ( n  = 21). The primary endpoint was weight gain; the secondary endpoints were changes in body length and head circumference of both CMPA and healthy toddlers after 3-month feeding; and the exploratory outcomes were changes in gut microbiota composition. After 3 months, there were no significant group differences for length-for-age, weight-for-age, or head circumference-for-age Z scores. In the gut microbiota, pHF feeding increased its richness and diversity, similar to those of IF-fed and HM-fed healthy toddlers. Compared with healthy toddlers, the toddlers with CMPA showed an increased abundance of phylum Bacteroidota, Firmicutes, class Clostridia, and Bacteroidia, and a decreased abundance of class Negativicutes, while pHF feeding partly eliminated these original differences. Moreover, pHF feeding increased the abundance of short-chain fatty acid producers. Our data suggested that this pHF partly simulated the beneficial effects of HM and shifted the gut microbiota of toddlers with CMPA toward that of healthy individuals. In conclusion, this synbiotic-containing pHF might be an appropriate alternative for toddlers with CMPA., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Maintaining the integrity of the blood-spinal cord barrier is critical for the recovery of spinal cord injury. Ferroptosis contributes to the pathogenesis of spinal cord injury. We hypothesized that ferroptosis is involved in disruption of the blood-spinal cord barrier. In this study, we administered the ferroptosis inhibitor liproxstatin-1 intraperitoneally after contusive spinal cord injury in rats. Liproxstatin-1 improved locomotor recovery and somatosensory evoked potential electrophysiological performance after spinal cord injury. Liproxstatin-1 maintained blood-spinal cord barrier integrity by upregulation of the expression of tight junction protein. Liproxstatin-1 inhibited ferroptosis of endothelial cell after spinal cord injury, as shown by the immunofluorescence of an endothelial cell marker (rat endothelium cell antigen-1, RECA-1) and ferroptosis markers Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase. Liproxstatin-1 reduced brain endothelial cell ferroptosis in vitro by upregulating glutathione peroxidase 4 and downregulating Acyl-CoA synthetase long-chain family member 4 and 15-lipoxygenase. Furthermore, inflammatory cell recruitment and astrogliosis were mitigated after liproxstatin-1 treatment. In summary, liproxstatin-1 improved spinal cord injury recovery by inhibiting ferroptosis in endothelial cells and maintaining blood-spinal cord barrier integrity., Competing Interests: None