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Yu-Sen Feng,1,&ast; Zheng-Yun Sun,2,&ast; Fei Jiang,3 Peng-Cheng Ma,1 Xing-Rui Liu,1 Yuan-Yuan Meng,2 Cheng-De Liao,1 Gui-Fang Sun1 1Department of Radiology, Kunming Yan’an Hospital, Kunming, 650051, People’s Republic of China; 2Department of Radiology, Lincang First People’s Hospital, Lincang, 677000, People’s Republic of China; 3Department of Radiology, Wenshan First People’s Hospital, Wenshan, 663599, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui-Fang Sun, Department of Radiology, Kunming Yan’an Hospital, No. 245 Renmin East Road, Panlong District, Kunming, Yunnan, 650051, People’s Republic of China, Tel +86 13759518529, Email guifang_sun07@126.comObjective: This study aims to evaluate the relationship between the pericoronary fat attenuation index (FAI), derived from coronary artery computed tomography angiography, and post-lipid management levels of low-density lipoprotein cholesterol in patients with coronary artery disease (CAD). Additionally, the study investigates coronary inflammation across different lipid management strategies.Methods: We selected a cohort comprising 521 CAD patients who met the inclusion criteria. Patients were categorized into well-managed (LDL-C< 2.6 mmol/L) and poorly managed (LDL-C≥ 2.6 mmol/L) groups based on lipid management efficacy. We collected anthropometric measures (height, weight, body mass index, and body surface area) and clinical indicators, including Gensini score, and FAI-related parameters for coronary atherosclerotic lesions. We analyzed the interrelations along these parameters and lipid management using statistical methods and assessed diagnostic value via receiver operating characteristic (ROC) curve analysis of these parameters was assessed through.Results: The poorly managed group exhibited significantly higher levels of total cholesterol, triglycerides, and lower levels of high-density lipoprotein compared to the well-managed group (P < 0.05). Significant differences were observed between the groups in terms of lesion length in the proximal segment of the left anterior descending artery, FAI value in the proximal segment of lesions in the right coronary artery (RCA), volume thickness in the middle segment of RCA lesions, and lesion length in the distal segment of RCA (P < 0.05). ROC curve analysis revealed areas under the curve ranging from 0.484 to 0.660 for the parameters, indicating limited diagnostic efficacy.Conclusion: The FAI in the RCA varies with lipid management strategies, suggesting it as a valuable metric for monitoring both perivascular inflammation and lipid status in CAD patients. However, its current diagnostic efficacy is limited, indicating the need for further research to improve its clinical utility.Keywords: coronary artery CT angiography, coronary atherosclerotic heart disease, coronary inflammation, lipids, low-density lipoprotein cholesterol, pericoronary fat attenuation index

Meng Xiao,1,2,* Xin Fan,1–3,* Xin Hou,1,2,4,* Sharon CA Chen,5 He Wang,1,2 Fanrong Kong,5 Zi-Yong Sun,6,* Yun-Zhuo Chu,7 Ying-Chun Xu1,2 1Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, People’s Republic of China; 3Department of Infectious Diseases and Clinical Microbiology, Beijing Chaoyang Hospital, Beijing, People’s Republic of China; 4Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Center for Infectious Diseases and Microbiology Laboratory Services, ICPMR, New South Wales Health Pathology, Westmead Hospital, The University of Sydney, NSW, Australia; 6Department of Clinical Laboratory, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Clinical Laboratory, The First Affiliated Hospital of Chinese Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Abstract: Echinocandin antifungal agents have become the first-line therapy for invasive candidiasis (IC) in many countries. Despite their increasing use, resistance to this class of drug is, overall, still uncommon. Here, we report two patients from the People’s Republic of China with IC, one with infection caused by pan-echinocandin-resistant Candida tropicalis and the other by pan-echinocandin-resistant Candida glabrata. We also describe the mechanisms of drug resistance of these isolates. The echinocandin-resistant C. glabrata isolate was cultured from ascitic fluid of a 46-year-old male patient with intra-abdominal IC developing after surgery in 2012. This patient had had no prior antifungal exposure. The echinocandin-resistant C. tropicalis isolate was cultured from chest drainage fluid of a 60-year-old female patient with severe coronary disease and lung infection. Prior to culture and identification of the isolate, the patient had received micafungin treatment for 19 days. Both isolates were cross-resistant to micafungin, anidulafungin, and caspofungin, with minimum inhibitory concentration values of ≥2 µg/mL. The amino acid substitution E655K was found adjacent to the FKS2 HS1 region of the C. glabrata isolate, while the substitution S80P were found in the FKS1 HS1 region of the C. tropicalis isolate. This report highlights the emergence of echinocandin resistance in two important non-albicans Candida species. Although the overall prevalence of echinocandin resistance is low in the People’s Republic of China, monitoring of antifungal susceptibility trends in all Candida species is warranted. Keywords: Candida tropicalis, Candida glabrata, echinocandins, antifungal resistance, People’s Republic of China

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

Properties of atomic van der Waals heterostructures are profoundly influenced by interlayer coupling, which critically depends on stacking of the proximal layers. Rotational misalignment or lattice mismatch of the layers gives rise to a periodic modulation of the stacking, the moiré superlattice. Provided the superlattice period extends over many unit cells, the coupled layers undergo lattice relaxation, leading to the concentration of strain at line defects - solitons - separating large area commensurate domains. We visualize such long-range periodic superstructures in thin crystals of hexagonal boron nitride using atomic-force microscopy and nano-infrared spectroscopy. The solitons form sub-surface hexagonal networks with periods of a few hundred nanometers. We analyze the topography and infrared contrast of these networks to obtain spatial distribution of local strain and its effect on the infrared-active phonons of hBN.

The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2 1/2 years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.

Non-Hodgkin's Lymphoma (NHL) remains a significant challenge in hematology, with chemotherapy and radiation therapy as conventional treatment options, albeit with limitations such as adverse effects. Immunotherapy, particularly bispecific antibodies (BsAbs) T cell engagers (TCEs), has emerged as a promising approach. Despite their potential, TCEs pose challenges, including adverse events like cytokine release syndrome. Understanding the structural details of TCEs and their interactions with target proteins is crucial for optimizing their therapeutic efficacy and toxicity. In this study, we further developed our protocol MCCS-Docker for protein-protein interactions and applied it to investigate the structural intricacies of CD3 interactions with therapeutic antibodies such as OKT3, UCHT1, Mosunetuzumab, Odronextumab, Glofitamab, and Epcoritamab using computational modeling techniques. Our analysis not only approved the effectiveness of our updated MCCS-Docker protocol but also revealed detailed binding interactions between the BsAbs and CD3, elucidating key residues of Tyrosine and Asparagine in the antibodies involved in the binding interface. Molecular dynamics simulations validated the stability of these interactions over time, confirming the reliability of the binding poses generated from docking studies. Overall, our study offered a novel method to predict critical residues in protein-protein interactions and enhanced the understanding of the structural determinants governing BsAb interactions with target proteins, offering valuable insights for designing and optimizing immunotherapeutic agents for NHL and related hematologic malignancies., 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 Ltd.)

We perform molecular dynamics simulations to study deposition patterns of linear diblock copolymer solution nanodroplets on a solid surface (a wall). The current work mainly investigates the influence of the polymer concentration, chain length, and solvent-wall interactions. Polymer block-wall interaction strengths ( ε Pa(Pb)W ) are modified to simulate polymer blocks with different adsorption behaviors, such as weak adsorbable ( ε Pa(Pb)W = 0.6), moderate adsorbable ( ε Pa(Pb)W = 1.0), and strong adsorbable ( ε Pa(Pb)W = 1.2) polymer blocks. The deposition patterns are summarized into diagrams, including penetrating and nonpenetrating ridge-like structures, penetrating and nonpenetrating coffee-ring structures, and multilayer structures with and without defects. We determine factors that influence the deposition structure of the droplet and unveil the mechanism of the formation process of the pattern. This work helps in understanding the deposition pattern of linear diblock copolymer solution nanodroplets, which is beneficial for potential applications involving nanodroplet evaporation.

Composting is an effective method for recycling resources in waste management. However, significant nitrogen loss can hinder the overall effectiveness of the composting process. Biofiltration is a promising method for conserving nitrogen in composting owing to its ability to efficiently trap and convert gaseous emissions. This study investigated the efficiency and mechanisms of a composting-biofiltration system to enhance nitrogen retention in distilled grain waste (DGW) compost using pre-composted DGW as biofilter media. The DGW composting-biofiltration system exhibited a lower nitrogen loss (24.9%) than the mono-composting system (40.1%). Additionally, this DGW system achieved a high NH 3 removal efficiency of 94.7%-97.7%, while NO 3 - concentration continuously increased in the biofilter, indicating that biofiltration mainly conserved nitrogen through the conversion of NH 3 emitted from the composter. The analysis of the microbial community and key functional enzymes involved in nitrogen metabolism revealed a significant increase in both nitrification and ammonia assimilation within the biofilter. This resulted in the accumulation of NO 3 - and the formation of organic nitrogen, thereby facilitating nitrogen retention. Genera such as Chryseolinea, Anseongella, Parapusillimonas, Bacillus, and Urebacillus mainly contributed to the generation of NO 3 - and organic nitrogen. The structural equation model analysis revealed that nitrogen retention in DGW compost was mainly facilitated by enhanced nitrification and ammonia assimilation in the biofilter. These results provide insights into underlying mechanisms for enhancing nitrogen retention through a composting-biofiltration approach and present guidance for improving compost quality., 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.)

Anaerobic digestion (AD) frequently encounters disturbances due to variations in organic loading rates (OLRs), which can result in the failure of the sludge treatment process. However, there is a lack of comprehensive studies on the robustness of AD systems against OLR disturbances and the underlying mechanisms. In this study, the responses of reactor performance and active microbial communities in mesophilic AD were investigated and compared under conditions of OLR shock and OLR fluctuation. Statistical analysis confirmed that all reactors recovered from both types of OLR disturbance, indicating both functional and structural robustness of the mesophilic community. Based on metagenomics and metatranscriptomics analyses, it was observed that high diversity within the microbial community led to functional redundancy, which appears to be a key mechanism contributing to the robustness against OLR disturbances. Additionally, for the first time, the potential metabolic diversity of aerobic autotrophy bacteria in AD reactors was identified, including their roles in the utilization of glucose and acetate. Furthermore, the analysis of topological properties within the microbial interaction network was conducted, and the robustness of the community network was verified through the application of random node deletion attacks. The findings from this study provide valuable information for the effective regulation of microbial communities and the design of practical AD systems., 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.)

Background: Hypoxic pulmonary vasoconstriction (HPV) is a reflex constriction of vascular smooth muscle. This study aims to investigate the role of Salidroside (Sal) in pulmonary arterial dilatation and the potential mechanism of Sal regulating hypoxic pulmonary hypertension in vitro and in vivo., Methods: A rat model of hypoxic pulmonary hypertension (HPH) was constructed using hypoxic chamber. The effect of Sal on HPH were evaluated using vascular ring, whole cell patch-clamp, WGA staining, HE staining, and Sirius Scarlet staining assays., Results: Sal treatment alleviated the injury of acute hypoxia on pulmonary circulation in SD rats. Meanwhile, Sal treatment reduced the pulmonary vascular tone of acute hypoxia in a concentration-dependent manner, which was involved in the TWIK-related acid-sensitive potassium channel 1 (TASK-1) mediating diastolic effect. We found that Sal treatment significantly increased the TASK-1 current of pulmonary artery smooth muscle cells (PASMCs) in a concentration-dependent manner, as well as reversed the inhibitory effect of acute hypoxia on the TASK-1 current. Moreover, Sal treatment improved the TASK-1 current density, suppressed the proliferation, and enhanced the apoptosis of PASMCs in SD rats under continuous hypoxic condition. In addition, we found that the electrophysiological remodeling and pulmonary vascular remodeling of PASMCs were improved by the treatment of Sal through the regulation of TASK-1 channel., Conclusions: Sal could alleviate HPH by restoring the function of TASK-1 channel, which may provide a novel method for the treatment of HPH., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Shenghui Yizhi Decoction (SHYZD) has exhibited the capacity to enhance cognitive function and learning abilities in individuals diagnosed with Alzheimer's disease (AD) while ameliorating pre-existing neuroinflammation. Nevertheless, the precise mechanism underlying its therapeutic effects on AD remains to be elucidated., Methods: Twenty-four male SAMP8 mice were randomly divided into three groups, and eight male SAMR1 mice were used as a blank control, to examine their learning and spatial memory abilities. The expression of amyloid β1-42 (Aβ1-42) was detected by immunohistochemical staining of hippocampal tissue. ELISA was used to detect the interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) expressions. Real time PCR was used to detect NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteine protease-1 (Caspase-1), and IL-1β mRNA expression. Western blot was used to detect nuclear factor kappa-B (NF-κB), inhibitor of NF-κB α (IκBα), IκB kinase α (IKKα), NLRP3, Caspase-1, and IL-1β protein expression., Results: In this study, SAMP8 mice, employed as an AD model, displayed markedly diminished abilities in terms of spatial localization, navigation, and spatial exploration when compared to the blank control group. Additionally, there was a substantial upregulation of Aβ1-42 expression in the hippocampus of these mice, along with a significant increase in the levels of inflammation-associated factors, including IL-1β, IL-6, TNF-α, NLRP3, Caspase-1, as well as the NF-κB pathway-related proteins, namely, NF-κB, IκBα, and IKKα. Moreover, after treatment with positive drugs (donepezil hydrochloride) and SHYZD, the learning abilities of the mice exhibited significant improvements. Furthermore, the hallmark AD protein Aβ1-42, inflammatory factors, and NF-κB/NLRP3 signalling pathway proteins were significantly reduced. These findings collectively suggest that SHYZD exerts a therapeutic effect on AD., Conclusion: In summary, the specific molecular mechanisms through which SHYZD alleviates AD and the potential role for SHYZD in the NF-κB/NLRP3 signalling pathway are identified in this study.

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (Ratio Hep/Port , Ratio Peri/Hep , and Ratio Port/Peri ) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher Ratio Peri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher Ratio Port/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

MiRNA-21 is recognized as an important biological marker for the diagnosis, treatment, and prognosis of breast cancer. Here, we have created a nanochannel biosensor utilizing the duplex-specific nuclease (DSN) signal amplification strategy to achieve the detection of miRNAs. In this system, DNA as the capture probe was covalently immobilized on the surface of nanochannels, which hybridized with the target miRNA and forms RNA/DNA duplexes. DSN could cleave the probe DNA in RNA/DNA duplexes, recycling target miRNA, which may again hybridized with other DNA probes. After N cycles, most of the DNA probes had been cleaved, and the content of miRNA could be quantified by detecting changes in surface charge density. This biosensor can distinguish miR-21 from non-complementary miRNAs and one-base mismatched miRNAs, with reliable detection limits as low as 1 fM in PBS. In addition, we had successfully applied this method to analysis of total RNA samples in MCF-7 cells and HeLa cells, and the nanochannels had also shown excellent responsiveness and strong anti-interference ability. This new method is expected to contribute to miRNA detection in clinical diagnostics, providing a unique approach to detecting and distinguishing disease-associated molecules., 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.)

Mechanochromic functionality realized via the force-responsive mechanophores in polymers has great potential for damage sensing and information storage. Mechanophores with the ability to recognize multiple stimuli for tunable chromic characteristics are highly sought after for versatile sensing ability and color programmability. Nevertheless, the majority of mechanophores are based on single-component chromophores with limited sensitivity, or require additional fabrication technology for multi-modal chromism. Here, we report a novel multifunctional mechanophore capable of vividly detectable and tunable mechanochromism in polymers. This synergistic optical coupling relies on strategically fusing rhodamine and spiropyran (Rh-SP), and tethering polymer chains on both subunits. The mechanochromic behaviors of the Rh-SP-linked polymers under sonication and compression are thoroughly evaluated in response to changes in force and the light-controlled relaxation process. Non-sequential ring-opening of the two subunits under force is identified, endowing high-contrast mechanochromism. Light-induced differential ring-closing reactions of the two subunits, together with the acidichromism of the SP moiety, are employed to engineer elastomers with programmable and wide-spectrum colors. Our work presents an effective strategy for highly appreciable and regulable mechanochromic functionality, and also provides new insights into the rupture mechanisms of π-fused mechanophores, as well as how the stimuli history controls stress accumulation in polymers., (© 2024 Wiley-VCH GmbH.)

Objectives: Long-term follow-up is essential for type 1 autoimmune pancreatitis (AIP) patients due to high relapse rates. The cumulative radiation dose from repeated CT scans during follow-up should not be ignored. We aim to investigate the cumulative radiation dose in AIP patients undergoing CT surveillance and the diagnostic performance of CT in detecting disease relapse. The diagnostic performance of MRI from a secondary cohort during the same period was also investigated., Methods: This retrospective single-institutional study included 247 type 1 AIP patients with one or more follow-up CT scans, and 120 patients with MR follow-ups. Four metrics were utilized to report the radiation dose, including the volume computed tomography dose index, the dose length product, size-specific dose estimate and effective dose. The diagnostic performance for AIP relapse was assessed, taking the final clinical diagnosis in retrospect as the reference standard., Results: With a median 2.3-year follow-up period, AIP patients followed up with CT exhibited a median cumulative radiation dose of 37.5 mSv. 11.3% of patients have accumulated doses exceeding 100 mSv. For the 169 patients followed over a year, 30.8% sustained an average annual radiation dose surpassing 20 mSv. The sensitivity/specificity/accuracy of CT for detecting abdominal organ relapse was 64.1%/99.6%/97.0%. For AIP patients followed up with MRI, the sensitivity for detecting disease relapse was 90.5%., Conclusion: Considering the accumulation of radiation dose in AIP patients and the insufficient sensitivity in detecting disease relapse with CT, safer and more sensitive imaging follow-up strategies should be explored., Key Points: Question CT, as the primary imaging modality for autoimmune pancreatitis (AIP) follow-up, raises concerns regarding radiation exposure and lacks reported diagnostic performance in detecting AIP relapse. Findings CT in AIP follow-up causes significant cumulative radiation exposure and exhibits insufficient sensitivity in relapse detection. Clinical relevance Type 1 AIP necessitates long-term imaging follow-up, yet current guidelines lack consensus regarding the prioritization of CT or MRI for such follow-up. CT is widely used but has radiation concerns and limited sensitivity, calling for safer, efficient strategies., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

To elucidate the mechanism of biochar addition on carbon and nitrogen retention during distilled grain (DGW) composting, this study investigated the losses of carbon and nitrogen and functional genes related to carbon and nitrogen metabolisms between biochar-treated and control composts. The addition of biochar significantly increased carbon and nitrogen retention by 13.5% and 33.8%, respectively. The difference in core carbon metabolism genes indicated that biochar addition inhibited CO 2 release and promoted carbon fixation during the later composting phase, leading to improved carbon retention. Nitrogen metabolism analysis indicated that biochar addition suppressed early-phase ammoniation and late-phase denitrification and promoted nitrification and ammonia assimilation during the later stages of composting, thereby preserving nitrogen. During the later composting phase, biochar addition enhanced carbon-nitrogen coupling metabolism activity, leading to the synchronous retention of carbon and nitrogen. These findings elucidate the mechanism of biochar addition on carbon and nitrogen retention during DGW composting., 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 Ltd.)

The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H 2 O 2 -treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

IL-1β represents an important inflammatory factor involved in the host response against GBS infection. Prior research has suggested a potential involvement of IL-1β in the process of ferroptosis. However, the relationship between IL-1β and ferroptosis in the context of anti-GBS infection remains uncertain. This research demonstrates that the occurrence of ferroptosis is essential for the host's defense against GBS infection in a mouse model of abdominal infection, with peritoneal macrophages identified as the primary cells undergoing ferroptosis. Further research indicates that IL-1β induces lipid oxidation in macrophages through the upregulation of pathways related to lipid oxidation. Concurrently, IL-1β is not only involved in the initiation of ferroptosis in macrophages, but its production is intricately linked to the onset of ferroptosis. Ultimately, we posit that ferroptosis acts as a crucial initiating factor in the host response to GBS infection, with IL-1β playing a significant role in the resistance to infection by serving as a key inducer of ferroptosis., (© 2024. The Author(s).)

To gain a deeper understanding of the pollution status and influencing factors of fine particles （PM 2.5 ） and their water-soluble ions （WSI） in Dalian and to implement precise control of pollution events such as haze and acid rain, PM 2.5 samples were collected in Dalian from June 2021 to May 2022. Then, the mass concentrations of PM 2.5 and WSI were determined using the weight method and ion chromatography, respectively, and the pollution characteristics and sources were analyzed. Furthermore, the causes of the high acidity of PM 2.5 in spring were discussed. The results showed that the annual average mass concentrations of PM 2.5 and WSI in Dalian during the sampling period were （33.24 ±28.87） μg·m -3 and （18.66 ±20.52） μg·m -3 , respectively, and the secondary ions （SNA, including SO 4 2- , NO 3 - , and NH 4 + ） accounted for the highest proportion of WSI [（86.2 ±9.3）%]. The order of ion concentration levels from highest to lowest was： NO 3 - &gt;SO 4 2- &gt;NH 4 + &gt;Cl - &gt;K + &gt;Ca 2+ &gt;Na + &gt;Mg 2+ &gt;F - . Due to the influence of meteorological conditions and coal combustion emissions during the concentrated heating period from late autumn to early spring, the seasonal variation in PM 2.5 and WSI was winter&gt;spring&gt;autumn&gt;summer, whereas SNA was the highest in spring and the lowest in summer. The results of correlation and principal component analysis showed that WSI in PM 2.5 was mainly from the secondary transformation of atmospheric SO 2 and NO 2 （contributing to the majority of SNA）, mixed sources of combustion and dust （characterized by K + , Mg 2+ , Cl - , and F - ）, and sources of sand and sea salt （characterized by Na + , Ca 2+ , and Mg 2+ ）. In summer, the main combustion source was biomass burning, whereas in autumn, winter, and spring, coal combustion emissions were predominant. The change in wind direction from autumn to winter brought by a shift from the source of sea salt to soil dust； additionally, the external pollution transported by northwest winds contributed to the complexity of the sources of WSI in PM 2.5 during spring in Dalian. ISORROPIA-II model simulations suggested NH 4 NO 3 as the most present solid aerosol form in PM 2.5 in Dalian, followed by CaSO 4 and （NH 4 ） 2 SO 4 ； compared to that in solid aerosols, more SNA existed in liquid aerosols. The annual average pH of PM 2.5 in Dalian was 5.65 ±3.00, with pH values close to neutral in summer, autumn, and winter but significantly acidic in spring （2.03 ±3.18）. The high acidity observed in spring was attributed to the combination of low temperature, high humidity, and high SNA concentrations. These conditions resulted in higher aerosol water content and increased gas-to-particle conversion rates, ultimately leading to an ammonia-deficient environment. The backward trajectory and PSCF results indicated that the external transport of high acidity PM 2.5 in spring mainly came from the northwest （45.0%） and southwest （40.8%） directions. Mobile source emissions made the most significant contribution to the transportation of pollutants in the former, forming high-pollution source areas in the Beijing-Tianjin-Hebei Region, which may have been mainly related to urban motor vehicle and port vessel emissions； the latter was influenced by relatively strong stationary sources and showed higher SO 2 emissions in the southern part of Henan Province and the central part of Jiangsu Province.

The adsorption of polymer-grafted nanoparticles at interfaces is a problem of fundamental interest in physics and soft materials. This adsorption behavior is governed by the interplay between interaction potentials and entropic effects. Here, we use molecular dynamics simulations and umbrella sampling methods to study the adsorption behavior of a Janus-like homopolymer-grafted nanoparticle at fluid-fluid interfaces. By calculating the potential of the mean force as the particle moves from fluid A to the interface, the adsorption energy Ea can be obtained. When two homopolymer chains with types A and B are grafted to the opposite poles of the particle, Ea shows a scaling behavior with respect to chain length N: Ea ∝ N0.598. This is determined by the interactions between polymers and fluids. The enthalpy dominates, and the entropy effects mainly come from the rotational entropy loss of the polymer-grafted nanoparticle at interfaces, which disfavors the stabilization of particles at interfaces. When the grafted polymer number m is large, the adsorption energy exhibits a linear dependence on m. While the enthalpy dominates the behavior, the entropy becomes significant at a larger chain length of N = 15, where the configurational entropy of the polymer chains dominates the entropy of the system. The globule-coil transition occurs when polymers move from poor solvents to good solvents, increasing the configurational entropy and favoring the stabilization of particles at interfaces. Our study provides novel insights into the stabilization mechanism of polymer-grafted nanoparticles at interfaces and reveals the stabilization mechanism favored by the configurational entropy of grafted polymer chains., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

This study aimed to investigate the therapeutic potential of human adipose-derived mesenchymal stem cells (hADSCs) modified with recombinant adeno-associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate-buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control-hADSCs group), or rAAV VEGF165 vector (VEGF165-hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium-binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165-hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV-VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Objective: To evaluate the clinical effectiveness of antibiotic bone cement combined with the lobulated perforator flap based on the descending branch of the lateral circumflex femoral artery (d-LCFA) in the treatment of infected traumatic tissue defects in the foot, in accordance with the Enhanced Recovery after Surgery (ERAS) concept., Methods: From December 2019 to November 2022, 10 patients with infected traumatic tissue defects of the foot were treated with antibiotic bone cement combined with the d-LCFA lobulated perforator flap. The cohort comprised 6 males and 4 females, aged 21 to 67 years. Initial infection control was achieved through debridement and coverage with antibiotic bone cement, requiring one debridement in nine cases and two debridements in one case. Following infection control, the tissue defects were reconstructed utilizing the d-LCFA lobulated perforator flap, with the donor site closed primarily. The flap area ranged from 12 cm×6 cm to 31 cm×7 cm. Postoperative follow-up included evaluation of flap survival, donor site healing, and ambulatory function of the foot., Results: The follow-up period ranged from 7 to 24 months, averaging 14 months. Infection control was achieved successfully in all cases. The flaps exhibited excellent survival rates and the donor site healed by first intention. Based on the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, pain and function were evaluated as excellent in 3 cases, good in 5 cases, and moderate in 2 cases., Conclusion: The application of antibiotic bone cement combined with the d-LCFA lobulated perforator flap is an effective treatment for infected traumatic tissue defects of the foot with the advantages of simplicity, high repeatability, and precise curative effects. The application of the d-LCFA lobulated perforator flap in wound repair causes minimal damage to the donor site, shortens hospital stays, lowers medical expenses, and accelerates patient rehabilitation, aligning with the ERAS concept. Therefore, it is a practice worth promoting in clinical use., (© 2024. The Author(s).)

Guiding and dynamically modulating topological defects are critical challenges in defect engineering of liquid crystals. Here, we employ molecular dynamics simulations to investigate the transition dynamics and relative kinetic stability of defect patterns in two-dimensional nematic Gay-Berne liquid crystals confined within rectangular geometries. We observe the formation of various defect patterns including long-axis, diagonal, X-shaped, composite, and bend configurations under different confinement conditions. The competition between boundary effects and the uniformity of nematic orientation induces the continuous realignment of liquid crystal molecules, facilitating the spatially continuous transformation of defect patterns over time. This transition involves changes in both defect types and their locations, typically initiating from defect regions. Furthermore, we demonstrate that the relative stability of these defect patterns can be effectively controlled by adjusting confinement parameters and external field conditions. Our findings provide fundamental insights into the transition kinetics of defect patterns in confined nematic liquid crystals, thereby enhancing our ability to manipulate topological defects for advanced applications., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Thermophilic semi-continuous composting (TSC) is effective for kitchen waste (KW) treatment, but large amounts of NH 3 -rich odorous gas are generated. This study proposes a TSC-biofiltration (BF) two-stage process. Compost from the front-end TSC was used as the packing material in the BF to remove NH 3 from the exhaust gas. The BF process was effective in removing up to 83.7 % of NH 3 , and the NH 3 content was reduced to < 8 ppm. Seven days of BF improved the quality of the product from TSC by enhancing the germination index to 134.6 %, 36.5 % higher than that in the aerated-only group. Microbial community analysis revealed rapid proliferation and eventual dominance in the BF of members related to compost maturation and the nitrogen cycle from Actinobacteria, Proteobacteria, Chloroflexi, and Bacteroidetes. The results suggest that the TSC-BF two-stage process is effective in reducing NH 3 emissions from TSC and improving compost quality., 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.)

Therapeutic antibody design has garnered widespread attention, highlighting its interdisciplinary importance. Advancements in technology emphasize the critical role of designing nanobodies and humanized antibodies in antibody engineering. However, current experimental methods are costly and time-consuming. Computational approaches, while progressing, faced limitations due to insufficient structural data and the absence of a standardized protocol. To tackle these challenges, our lab previously developed IsAb1.0, an in silico antibody design protocol. Yet, IsAb1.0 lacked accuracy, had a complex procedure, and required extensive antibody bioinformation. Moreover, it overlooked nanobody and humanized antibody design, hindering therapeutic antibody development. Building upon IsAb1.0, we enhanced our design protocol with artificial intelligence methods to create IsAb2.0. IsAb2.0 utilized AlphaFold-Multimer (2.3/3.0) for accurate modeling and complex construction without templates and employed the precise FlexddG method for in silico antibody optimization. Validated through optimization of a humanized nanobody J3 (HuJ3) targeting HIV-1 gp120, IsAb2.0 predicted five mutations that can improve HuJ3-gp120 binding affinity. These predictions were confirmed by commercial software and validated through binding and neutralization assays. IsAb2.0 streamlined antibody design, offering insights into future techniques to accelerate immunotherapy development., (© The Author(s) 2024. Published by Oxford University Press.)

Real-time assessment of ecological environment quality in arid and semi-arid regions is crucial for the sustainable development of ecological environments in China. In this study, we constructed a topsoil remote sensing ecological index (TRSEI) by coupling five indicators, greenness, wetness, dryness, topsoil grain size, and heat, with the Google Earth Engine (GEE). With the index, we evaluated the ecological environment quality of Wuchuan County from 1990 to 2020, and examined the spatio-temporal variations of ecological environment quality and its driving factors by using univariate linear regression, multiple regression residual analysis, and Hurst index. Results showed that the first principal component of the TRSEI in the study area contributed over 70%, with a mean eigenvalue of 0.148, indicating the effective integration of various ecological indicators by TRSEI. The topsoil grain size index was essential for the assessment of ecological environment quality in arid and semi-arid regions. From 1990 to 2020, the fluctuation range of TRSEI in the study area was between 0.289 and 0.458, showing an overall slight deterioration trend. The ecological environment quality of cropland and de-farming region had improved, with the improved area accounting for 47.9% of the total area. The grassland, barren land, and construction land areas had deteriorated, with the deteriorated area accounting for 52.1% of the total area. In the future, 36.9% of the regions would experience continuous improvement in ecological environment quality, while 41.4% might continue to dete-riorate. Human activities were the primary driving factor for the changes in ecological environment quality in arid and semi-arid regions, accounting for 88.6% of the total area. Climate change also had a significant impact, accounting for 11.4% of the total area. The TRSEI could effectively assess the ecological environment quality of arid and semi-arid regions, providing a scientific basis for ecological conservation and construction in these areas.

The evaporation-induced deposition pattern of the linear diblock copolymer solution has attracted attention in recent years. Given its critical applications, we study deposition patterns of the linear diblock copolymer solution nanodroplet on a solid surface (the wall) by molecular dynamics simulations. This study focuses on the influence of the nonbonded interaction strength, including the interaction between the wall and polymer blocks (ɛAW and ɛBW), the interaction between the solvent and the wall (ɛSW), and the interaction between polymer blocks (ɛAB). Conditions leading to diverse deposition patterns are explored, including the coffee-ring and the volcano-like structures. The formation of the coffee-ring structure is attributed to receding interfaces, the heterogeneity inside the droplet, and the self-assembly of polymer chains. This study contributes to the establishment of guidelines for designing deposition patterns of the linear diblock copolymer solution nanodroplet, which facilitates practical applications such as inkjet printing., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Anaerobic digestion (AD) is an effective and applicable technology for treating organic wastes to recover bioenergy, but it is limited by various drawbacks, such as long start-up time for establishing a stable process, the toxicity of accumulated volatile fatty acids and ammonia nitrogen to methanogens resulting in extremely low biogas productivities, and a large amount of impurities in biogas for upgrading thereafter with high cost. Microbial electrolysis cell (MEC) is a device developed for electrosynthesis from organic wastes by electroactive microorganisms, but MEC alone is not practical for production at large scales. When AD is integrated with MEC, not only can biogas production be enhanced substantially, but also upgrading of the biogas product performed in situ. In this critical review, the state-of-the-art progress in developing AD-MEC systems is commented, and fundamentals underlying methanogenesis and bioelectrochemical reactions, technological innovations with electrode materials and configurations, designs and applications of AD-MEC systems, and strategies for their enhancement, such as driving the MEC device by electricity that is generated by burning the biogas to improve their energy efficiencies, are specifically addressed. Moreover, perspectives and challenges for the scale up of AD-MEC systems are highlighted for in-depth studies in the future to further improve their performance., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The gas diffusion layer (GDL), as the bridge to reactants and electrons in PEMFC, is a carbon-based porous component and would be deformed under compression to induce changes in the distributions of reactants and the corresponding performances of PEMFC; therefore, unmasking the impacts of assembly pressure on the distribution of the reactants in GDL is significant to improve the performance of PEMFC. In the present article, the structural response of GDL to assembly pressure was first studied; the variations in transport properties of GDL and the reactant distributions induced by assembly pressure were then discussed; the impacts on the dynamic performances of PEMFC were finally investigated. From the results, assembly pressure was found to have different effects on the regions of GDL under the rib and channel, significant gaps in GDL porosity and/or GDL permeability existed near the rib/channel transition region to worsen the inhomogeneity of reactants. Suffering assembly pressure, the distribution of current density became uneven, and the current density near the rib-channel border seriously rose to the aggravated risk of MEA thermal damage. Furthermore, the power density at specific efficiencies was raised under certain assembly pressures, which meant suitable assembly pressure(s) existed for better output performances of PEMFC., Competing Interests: 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., (© 2024 The Authors.)

The central sulcus divides the primary motor and somatosensory cortices in many anthropoid primate brains. Differences exist in the surface area and depth of the central sulcus along the dorso-ventral plane in great apes and humans compared to other primate species. Within hominid species, there are variations in the depth and aspect of their hand motor area, or knob, within the precentral gyrus. In this study, we used post-image analyses on magnetic resonance images to characterize the central sulcus shape of humans, chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), and orangutans (Pongo pygmaeus and Pongo abelii). Using these data, we examined the morphological variability of central sulcus in hominids, focusing on the hand region, a significant change in human evolution. We show that the central sulcus shape differs between great ape species, but all show similar variations in the location of their hand knob. However, the prevalence of the knob location along the dorso-ventral plane and lateralization differs between species and the presence of a second ventral motor knob seems to be unique to humans. Humans and orangutans exhibit the most similar and complex central sulcus shapes. However, their similarities may reflect divergent evolutionary processes related to selection for different positional and habitual locomotor functions., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)