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Anticipated permafrost thaw in upcoming decades may exert significant impacts on forest soil nitrogen (N) dynamics. The rate of soil N mineralization (Nmin) plays a crucial role in determining soil N availability. Nevertheless, our understanding remains limited regarding how biotic and abiotic factors influence the Nmin of forest soil in response to permafrost thaw. In this study, we investigated the implications of permafrost thaw on Nmin within a hemiboreal forest based on a field investigation along the degree of permafrost thaw, having monitored permafrost conditions for eight years. The results indicate that permafrost thaw markedly decreased Nmin values. Furthermore, Nmin demonstrated positive associations with soil substrates (namely, soil organic carbon and soil total nitrogen), microbial biomass carbon and nitrogen, and soil moisture content. The decline in Nmin due to permafrost thaw was primarily attributed to the diminished quality and quantity of soil substrates rather than alterations in plant community composition. Collectively, our results underscore the pivotal role of soil substrate and microbial biomass in guiding forest soil N transformations in the face of climate-induced permafrost thaw.

Five new fusarin derivatives, steckfusarins A–E (1–5), and two known natural products (6, 7), were isolated and identified from the marine algicolous fungus Penicillium steckii SCSIO 41040. The new compounds, including absolute configurations, were determined by spectroscopic analyses and calculated electronic circular dichroism (ECD). All new compounds were evaluated for their antioxidant, antibacterial, antifungal, antiviral, cytotoxic, anti-inflammatory, antioxidant, cholesterol-lowering, acetyl cholinesterase (AChE) enzyme and 6-phosphofructo-2-kinase (PFKFB3) and phosphatidylinositol-3-kinase (PI3K) inhibitory activities. The biological evaluation results revealed that compound 1 exhibited radical scavenging activity against 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH), with an IC50 value of 74.5 µg/mL. In addition, compound 1 also showed weak anti-inflammatory activity at a concentration of 20 µM.

Abstract The COVID-19 restrictions in 2020 have led to distinct variations in NO2 and O3 concentrations in China. Here, the different drivers of anthropogenic emission changes, including the effects of the Chinese New Year (CNY), China’s 2018–2020 Clean Air Plan (CAP), and the COVID-19 lockdown and their impact on NO2 and O3 are isolated by using a combined model-measurement approach. In addition, the contribution of prevailing meteorological conditions to the concentration changes was evaluated by applying a machine-learning method. The resulting impact on the multi-pollutant Health-based Air Quality Index (HAQI) is quantified. The results show that the CNY reduces NO2 concentrations on average by 26.7% each year, while the COVID-lockdown measures have led to an additional 11.6% reduction in 2020, and the CAP over 2018–2020 to a reduction in NO2 by 15.7%. On the other hand, meteorological conditions from 23 January to March 7, 2020 led to increase in NO2 of 7.8%. Neglecting the CAP and meteorological drivers thus leads to an overestimate and underestimate of the effect of the COVID-lockdown on NO2 reductions, respectively. For O3 the opposite behavior is found, with changes of +23.3%, +21.0%, +4.9%, and −0.9% for CNY, COVID-lockdown, CAP, and meteorology effects, respectively. The total effects of these drivers show a drastic reduction in multi-air pollutant-related health risk across China, with meteorology affecting particularly the Northeast of China adversely. Importantly, the CAP’s contribution highlights the effectiveness of the Chinese government’s air-quality regulations on NO2 reduction.

Abstract Background Mesenchymal stem cells (MSCs) derived from different tissues have variant biological characteristics, which may induce different performances in the treatment of diseases. At present, it is difficult to know which type of MSC is most suitable for acute liver failure (ALF), and there is no parallel study to compare MSCs from different tissues of the same donor. Methods In this study, we derived MSCs from three different perinatal tissues of the same donor: cord lining (CL), cord–placenta junction (CPJ) and fetal placenta (FP), respectively, for compared gene expression profiles by transcriptome sequencing, and ability of proliferation and immune regulation in vitro. In addition, the therapeutic effects (e.g., survival rate, histological evaluation, biochemical analysis) of CL-MSCs, FP-MSCs and CPJ-MSCs on ALF mouse model were compared. Results The transcriptome analysis showed that FP-MSCs have significantly high expression of chemokines compared to CPJ-MSCs and CL-MSCs, similar to the q-PCR result. Of note, we found that CPJ-MSCs and FP-MSCs could improve the survival rate of mice with ALF induced by carbon tetrachloride, but CL-MSCs had no difference with Sham group. Moreover, we also found that biomarkers of ALF (e.g., MDA, SOD and GSH-px) significantly improved post-CPJ-MSCs and FP-MSCs treatment, but not CL-MSCs and Sham group. However, CL-MSCs treatment leads to inflammatory reaction in the early stage (day 3) of ALF treatment but not found with other groups. Conclusions It is important to select the MSCs derived from different tissues with variant performance for therapeutic purpose, and the CPJ-MSCs and FP-MSCs cells can significantly improve the syndrome of ALF which is highly recommended for a potential therapeutic options for ALF.

Abstract Background The aim of this study was to investigate the role of Vaspin on the chondrogenic differentiation of bone mesenchymal stem cells (BMSCs), and its effect on chondrocyte survival and ECM secretion. We also assessed whether the Akt activation participates in these processes. Methods In vivo, immunohistochemistry was used to examine the positive rate of the protein expressions of Akt in Wistar rat articular cartilage and subchondral bone after Vaspin intraperitoneal injection for 14 days. In vitro, we isolated and expanded BMSCs from Wistar rats, and further cultured BMSCs as pellets in a chondrogenic-differentiation medium supplemented with different concentrations of Vaspin. After 21 days, the pellets were processed for cell counting kit assay. The mRNA level of Akt, SOX9 and COL2A1 in the pellets were investigated using quantitative Real-Time polymerase chain reaction, and the protein level of COMP was detected using western blot. Results During the chondrogenic differentiation of BMSCs, Vaspin promoted the chondrogenic differentiation of BMSCs and chondrocyte survival by activating the Akt pathway. These effects were significantly reduced by treatment with an Akt inhibitor. Moreover, Vaspin promoted chondrogenic differentiation of BMSCs by increasing the expression of markers in cartilage formation and extracellular matrix secretion. Furthermore, our study also found that Vaspin could increase Akt expression in cartilage cavities and subchondral bone in vivo. Conclusion These findings demonstrate that Vaspin can promote the chondrogenic differentiation of BMSCs and chondrocyte survival via Akt activation. Our study provides new insights into the potential ability of Vaspin to ameliorate the chondrogenic differentiation of BMSCs and chondrocyte survival in OA.

Abstract Eigenvector‐based SPIRiT (ESPIRiT) can estimate multiple sets of coil sensitivity maps from the calibration matrix constructed from the auto‐calibration data. Recently, the L1 norm and total variation were combined with the ESPIRiT model to improve the reconstruction quality of magnetic resonance (MR) images. To further improve the reconstruction performance, the non‐local low‐rank regularisation term is incorporated into the ESPIRiT model (NLR‐ESPIRiT) is proposed. The proposed NLR‐ESPIRiT model takes full advantage of the non‐local self‐similarity features of MR images. The resulting optimisation problem can be transformed into a gradient problem and a denoising problem with low‐rank constraints using the operator splitting technique. The weighted nuclear norm (WNN) is applied as a surrogate of the rank. Then the denoising subproblem with the WNN can be effectively solved by using the alternating direction method of multipliers technique. For practical applications, a parameter‐selecting method is proposed to obtain almost optimal parameters for the same kind of MR images. Simulation experiments on in vivo data sets demonstrate that the proposed NLR‐ESPIRiT outperforms all competing traditional model‐based algorithms in terms of three objective metrics and visual comparison.

Voice user interface (VUI) is widely used in developing intelligent products due to its low learning cost. However, most of such products do not consider the cognitive and language ability of elderly people, which leads to low interaction efficiency, poor user experience, and unfriendliness to them. Firstly, the paper analyzes the factors which influence the voice interaction behavior of elderly people: speech rate of elderly people, dialog task type, and feedback word count. And then, the voice interaction simulation experiment was designed based on the wizard of Oz testing method. Thirty subjects (M = 61.86 years old, SD = 7.16; 15 males and 15 females) were invited to interact with the prototype of a voice robot through three kinds of dialog tasks and six configurations of the feedback speech rate. Elderly people’s speech rates at which they speak to a person and to a voice robot, the feedback speech rates they expected for three dialog tasks were collected. The correlation between subjects’ speech rate and the expected feedback speech rate, the influence of dialog task type, and feedback word count on elderly people’s expected feedback speech rate were analyzed. The results show that elderly people speak to a voice robot with a lower speech rate than they speak to a person, and they expected the robot feedback speech rate to be lower than the rate they speak to the robot. There is a positive correlation between subjects’ speech rate and the expected speech rate, which implies that elderly people with faster speech rates expected a faster feedback speech rate. There is no significant difference between the elderly people’s expected speech rate for non-goal-oriented and goal-oriented dialog tasks. Meanwhile, a negative correlation between the feedback word count and the expected feedback speech rate is found. This study extends the knowledge boundaries of VUI design by investigating the influencing factors of voice interaction between elderly people and VUI. These results also provide practical implications for developing suitable VUI for elderly people, especially for regulating the feedback speech rate of VUI.

Abstract Background Hirschsprung's disease (HSCR) is a relatively common congenital disability. Accumulating extracellular matrix (ECM) prompts intestinal fibrosis remodelling in the aganglionic segments of HSCR. The contributions of various cellular subsets in the fibrogenesis of HSCR segments are poorly understood. Methods Single‐cell transcriptomics from 8 aganglionic segments and 5 normal segments of 7 HSCR subjects and 26 healthy segments of seven healthy donors were analysed. Fibrotic phenotype and alterations were explored using differential expression analysis and single‐cell trajectory analysis. Fibrosis‐related transcription factors were inferred through single‐cell regulatory network inference. Bulk transcriptomic data, proteomic data, immunohistochemistry (IHC) and real‐time polymerase chain reaction were used to validate the alterations in the HSCR intestine. Results Various collagen, fibronectin and laminin protein‐coding genes expression were up‐regulated in the stromal and glial cells of the HSCR intestine. The number of fibroblasts and myofibroblasts in the aganglionic segments increased, and more myofibroblasts were activated at an earlier stage in HSCR segments, which infers that there is an intestinal fibrosis phenotype in HSCR segments. The fibrotic regulators POSTN, ANXA1 and HSP70 were highly expressed in the ECM‐related cellular subsets in the transitional segments and aganglionic segments. The transcription factor regulatory network revealed that fibrosis‐related and megacolon‐related NR2F1 in the fibroblasts and glial subsets was up‐regulated in the aganglionic segment. Conclusions This work identifies intestinal fibrosis and related regulators in aganglionic segments of HSCR; hence, anti‐fibrotic therapy may be considered to prevent HSCR‐associated enterocolitis (HAEC), relieve intestinal stricture and improve cell therapy.

We report on the discovery of a rare case of spatially and kinematically resolved galactic-scale outflow at intermediate redshift based on VLT/MUSE optical integral field spectroscopic observation of the quasar HE 0238–1904. This classical non–broad absorption line quasar at z = 0.631 remains underexplored in its optical emission lines, though its UV absorption lines are well studied. We identify a superbubble driven by HE 0238−1904 from the emission line morphology, line ratio diagnostics, and kinematics showing a one-sided outflow reaching a projected distance of R ∼ 55 kpc from the nucleus. The bulk of the ionized gas, with a characteristic mass M ∼ 10 ^8 M _⊙ , is blueshifted by v ≈ 700 km s ^−1 with respect to the quasar systemic velocity. The outflows detected using the absorption and emission lines are likely stratified components of different spatial scale and velocity in the ionized phase outflow. Although feedback in HE 0238–1904 is taking place on kiloparsec scales, the kinetic power of the outflow at 55 kpc (≪0.1% L _bol ) implies that it is inadequate to effectively regulate the evolution of the host galaxy at this large scale.

Whether N6-methyladenosine (m6A) is involved in biliary atresia (BA) remains undefined. Herein, we comprehensively evaluated the m6A profile in BA. When compared with normal controls, BA had an elevated m6A level with upregulated m6A writers. The m6A level was correlated with liver function, stage of fibrosis and jaundice clearance in BA. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) demonstrated an altered m6A topology in BA. MeRIP-seq and RNA sequencing filtered out 130 m6A-modified genes, which were enriched in fibrogenetic pathways. MeRIP-qPCR in vivo and interventions of LX-2 and primary HSCs in vitro validated the regulatory role of m6A on COL1A1 and THY1. THY1+ myofibroblasts expanded in portal area of BA, and highly expressed profibrogenic genes (COL1A1, MMP2, PDGFRA, and DCN). THY1 was correlated with liver fibrosis and jaundice clearance in BA. Bulk array (GSE46960, GSE15235), single-cell RNA sequencing (GSE136103), primary HSC interventions, and co-immunoprecipitation revealed that THY1 was correlated with extracellular matrix organization, promoted HSC activation, showed higher interactions with integrins on myeloid cells in cholestatic fibrosis, and was correlated with native liver survival in BA. Our study highlights the significance of m6A in BA-induced liver fibrogenesis by regulating THY1, shedding new light on the novel therapies to alleviate liver fibrosis by targeting m6A/THY1 axis in BA.

ObjectiveThree-dimensionally (3D) printed patient-specific instrumentation (PSI) might help in this regard with individual design and more accurate osteotomy, but whether the utility of such instrumentations minimizes the variability of patellar height in total knee arthroplasty (TKA) and the reasons for this effect are unknown. Our aim is to compare and analyze the variability of patellar height with PSI and conventional instrumentation (CI) in TKA.MethodsBetween March 2018 and November 2021, 215 patients with severe knee osteoarthritis who were treated with primary unilateral TKA were identified for this observational study. The patients were divided into the CI-TKA group and PSI-TKA group according to the osteotomy tools used in TKA. Preoperative and postoperative radiographic parameters including hip–knee–ankle angle (HKA), posterior tibial slope (PTS), Insall–Salvati ratio, modified Caton–Deschamps (mCD) ratio, anterior condylar offset (ACO), and posterior condylar offset (PCO) were evaluated.ResultsThe groups were similar in patients' demographic data, clinical scores, and radiographic parameters preoperatively. Overall, according to the results of the Insall–Salvati ratio, postoperative patellar height reduction was noted in 140 patients (65.1%). Interestingly, the variability of patellar height was smaller in the PSI-TKA group. Radiographic evaluation revealed that the Insall–Salvati ratio after TKA had a minor change in the PSI-TKA group (p = 0.005). Similarly, the mCD ratio after TKA also had a minor change in the PSI-TKA group (p

This work designed and prepared a novel heterojunction composite NiO/BaTiO3 through a method of photodeposition and used it in piezocatalytic dye removal for the first time. Results of the piezocatalytic test indicated that the NiO/BaTiO3 composite presented superior efficiency and stability in the RhB degradation under the vibration of ultrasonic waves. The best NiO/BaTiO3 sample synthesized under light irradiation for 2 h displayed an RhB degradation rate of 2.41 h−1, which was 6.3 times faster than that of pure BaTiO3. By optimizing the piezocatalytic reaction conditions, the degradation rate constant of NiO/BaTiO3 can further reach 4.14 h−1 A variety of systematic characterizations were executed to determine the reason for the excellent piezocatalytic performance of NiO/BaTiO3. The band potentials of NiO and BaTiO3 are found to coincide, and at their contact interface, they may create a type-II p-n heterojunction structure. Driven by the potential difference and the built-in electric field, piezoelectrically enriched charge carriers can migrate between NiO and BaTiO3, resulting in improved efficiency in charge separation and an increase in the piezoelectric catalytic performance. This study may provide a potential composite catalyst and a promising idea for the design of highly efficient catalysts in the field of piezoelectric catalysis.

The repair of critical-sized bone defects (CSBD) remains a significant challenge in clinical practice. Personalized 3D porous scaffolding is generally considered an ideal approach for directed regeneration of CSBD, which usually has irregular and complex 3D geometry. In this study, we designed a customized porous scaffold rabbit radius based on a body-centered cubic unit. Borate bioactive glass/polycaprolactone (BBG/PCL) composite scaffolds with different BBG contents (0%, 5%, 10%, 20%, and 40%) were fabricated using selective laser sintering. The pore geometry, porosity, mechanical strength, hydrophilicity, protein absorption, degradation behavior, in vitro cytocompatibility, and osteogenesis differentiation of the composite scaffolds were systematically characterized. The in vivo biological properties of the BBG/PCL composite scaffold for CSBD repair were assessed using a rabbit foreleg radius defect model. The results indicate that the BBG/PCL composite scaffold with 20% BBG content effectively promoted the proliferation of osteoblasts and repaired the rabbit radius defects. The mechanical strength of the scaffold was sufficient to maintain the integrity of the scaffold structure during a relatively long CSBD repair. Our results indicate that the BBG/PCL composite scaffold can be anticipated to be a promising biomaterial for CSBD repair.

Summary: Influenza A virus poses a constant challenge to human health. The highly conserved influenza matrix-2 (M2) protein is an attractive target for the development of a universal antibody-based drug. However, screening using antigens with subphysiological conformation in a nonmembrane environment significantly reduces the generation of efficient antibodies. Here, M2(1-46) was incorporated into nanodiscs (M2-nanodiscs) with M2 in a membrane-embedded tetrameric conformation, closely resembling its natural physiological state in the influenza viral envelope. M2-nanodisc generation, an antigen, was followed by Chiloscyllium plagiosum immunization. The functional vNARs were selected by phage display panning strategy from the shark immune library. One of the isolated vNARs, AM2H10, could specifically bind to tetrameric M2 instead of monomeric M2e (the ectodomain of M2 protein). Furthermore, AM2H10 blocked ion influx through amantadine-sensitive and resistant M2 channels. Our findings indicated the possibility of developing functional shark nanobodies against various influenza viruses by targeting the M2 protein.

Treatment of wastewater from natural-pigment-manufacturing process is a challenge due to its complex composition and recalcitrance. This study investigated the use of biological method to degrade high-concentration gardenia-yellow-manufacturing wastewater (GYMW) in a laboratory and then applied the anaerobic-aerobic (A/O) process in pilot- and full-scale plants. The maximum anaerobic volume load reached 6 kg chemical oxygen demand (COD) m-3 d in laboratory and 5.5 kg COD m-3 d in full-scale reactor, while the COD removal efficiency was consistently above 90%. Singlefactor control experiments were conducted in sequencing batch reactors to examine the factors that have an influence on the anaerobic treatment, which is responsible for the majority of COD removal. After adjusting the operating temperature, pH, and influent COD, the effluent COD further decreased by 300 mg L-1. In addition, high-performance liquid chromatography, which was used to analyze the main contaminants in GYMW, confirmed that the toxic geniposide was considerably reduced. The high-throughput sequencing analysis illustrated that, under the selective pressure from GYMW, the microbial community structure can degrade biorefractory pollutants enriched in the A/O reactors and contributed to the satisfactory performance of GYMW treatment. [ABSTRACT FROM AUTHOR]

Roxarsone (ROX) as a feed additive in livestock industry could be transported and migrated with manure in soil and aquatic environments, which pose a serious environmental problem due to the long-term accumulation and exposure of arsenic (As). In this study, sodium alginate (SA) loaded micro-scale zerovalent iron (ZVI) was chosen as one macromolecular polymer adsorbent in order to remove residual ROX from synthetic livestock wastewater. The results showed that the maximum adsorption capacity of SA-ZVI for ROX were about 156.4mg ROX g-1.The possible adsorptive mechanism is mainly due to the reaction of hydrogen bonding and electrostatic interactions. Furthermore, the results documented that about 93% of total As sequestrated by SA-ZVI could be recovered and the content of As in the recovered product was 105.64±1.58 mg As g-1. [ABSTRACT FROM AUTHOR]

Abstract Advanced gastric cancer (GCa) remains highly lethal due to the lack of effective therapies. Identifying promising therapeutic targets and developing effective treatment against GCa are urgently needed. Through mRNA and protein analysis of GCa clinical tumor samples, we found that autophagy-related gene 4B (ATG4B) was overexpressed in GCa tumors and that its high expression was associated with patients’ poor prognosis. Knockdown of ATG4B significantly inhibited GCa cell survival and tumor growth. To further probe the role of ATG4B in GCa by pharmacological means, we screened an in-house marine natural compound library against ATG4B and identified Azalomycin F4a (Am-F4a) as a novel and potent ATG4B inhibitor. Am-F4a directly bound to ATG4B with high affinity and effectively suppressed GCa cell autophagy via inhibition of ATG4B both in vitro and in vivo. Moreover, Am-F4a or ATG4B knockdown significantly suppressed tumor growth as well as GCa cell migration and invasion. Am-F4a effectively blocked the metastatic progression of primary GCa and sensitized tumors to chemotherapy. Taken together, our findings indicate that ATG4B is a potential therapeutic target against GCa and the natural product Am-F4a is a novel ATG4B inhibitor that can be further developed for the treatment of GCa.

In mitochondria, the major subunits of oxidative phosphorylation complexes are translated by the mitochondrial ribosome (mito-ribosome). The correct insertion and assembly of these subunits into the inner mitochondrial membrane (IMM) are facilitated by mitochondrial oxidase assembly protein 1 (Oxa1) during the translation process. This co-translational insertion process involves an association between the mito-ribosome and the C-terminus of Oxa1 (Oxa1-CTD) Nuclear magnetic resonance (NMR) methods were mainly used to investigate the structural characterization of yeast Oxa1-CTD and its mode of interaction with the E. coli 70S ribosome. Oxa1-CTD forms a transient α-helical structure within the residues P342–Q385, which were reported to form an α-helix when combining with the ribosome. Two conserved contact sites that could interact with the ribosome were further identified. The first site was located on the very end of the N-terminus (V321–I327), and the second one encompassed a stretch of amino acid residues I348–Q370. Based on our discoveries and previous reports, a model has been proposed in which Oxa1-CTD interacts with ribosomes, accompanied by transient-to-stable transitions at the second contact site. These observations may enhance our understanding of the potential role of Oxa1-CTD in facilitating the assembly of oxidative phosphorylation complexes and provide insight into the structural characteristics of Oxa1-CTD.

Soil water infiltration is a key mechanism for meeting plant water demand and groundwater recharge cycles; however, unreasonable land use practices cause reduced infiltration capacity and greater soil erosion. To date, differences in the properties of aeolian sandy soil and Pisha sandstone soil under different utilization methods as well as in soil properties, aggregates, and infiltration among kind of soil types, remain poorly understood. In this work, 54 soil samples of cropland and grassland were selected to identify the unique characteristics of soil infiltration processes under transition from cropland to grassland and contributions of soil properties to soil infiltrability in the Loess Plateau of China. The results showed that converting cropland to grassland could enhance the stable infiltration capacity of shallow soils of aeolian sandy soil and loess soil by 43.6% and 35.7%, respectively. Compared with cropland, the root properties and soil aggregate formation of the three soil types increased during grassland use, with the largest increase in soil organic matter content (32.14%) and total porosities (6.4%). As determined by the ring knife method, the saturated infiltration capacity of Pisha sandstone soil was significantly lower than in aeolian sandy soil and loess soil (p < 0.5). Moreover, its saturated infiltration capacity of cropland was better than grassland. Spearman’s correlation analysis and structural equation modeling (SEM) revealed that soil infiltration capacity appeared to be the most influenced by soil organic matter, and aggregate structure. These results highlight that fifteen years of returning cropland to grassland is not enough to affect the infiltration ability of deep soil (≥20 cm), and this improvement requires longer term maintenance.

The performance of the underwater acoustic (UWA) orthogonal frequency division multiplexing (OFDM) system is often restrained by time-varying channels with large delays. The existing frequency domain equalizers do not work well because of the high complexity and difficulty of finding the real-time signal-to-noise ratio. To solve these problems, we propose a low-complexity neural network (NN)-based scheme for joint equalization and detection. A simple NN structure is built to yield the detected symbols with the joint input of the segmented channel response and received symbol. The coherence bandwidth is investigated to find the optimal hyperparameters. By being completely trained offline with real channels, the proposed detector is applied independently in both simulations and sea trials. The results show that the proposed detector outperforms the ZF and MMSE equalizers and extreme learning machine (ELM)-based detectors in both the strongly reflected channels of the pool and time-variant channels of the shallow sea. The complexity of the proposed network is lower than the MMSE and ELM-based receiver.

Waste cement, a common by-product of urban construction, is often wasted in huge quantities and is worthless. However, some studies have confirmed that waste cement can be used as an alternative heavy metal immobilizing agent. Waste cements, derived from hydrated cement mortar products, were evaluated for soil Cd bioavailability by DTPA extraction and for their efficacy in ameliorating the toxicity of cadmium to soil enzymes and plant antioxidant enzymes. Soil incubation and pot experiments were conducted on three types of waste cement (OPC (ordinary Portland cement), FAC (fly ash cement) and ZEC (zeolite cement)) with an application rate of 1%, 2%, and 3%. The addition of OPC, FAC, and ZEC significantly increased the pH and cation exchange capacity of the soil (p < 0.05). The concentration of DTPA-extractable Cd significantly reduced with a consequential decrease in Cd uptake and transport in lettuce. OPC, FAC, and ZEC application significantly (p < 0.05) enhanced FDA hydrolysis and soil urease activity, except for catalase activity. OPC, FAC, and ZEC, when applied to soil, enhanced the total dry biomass (shoots and roots). Furthermore, the activities of guaiacol peroxidase (POD), catalase (CAT) and superoxide dismutase (SOD) declined in lettuce treated with OPC, FAC, and ZEC. With the addition OPC, FAC, and ZEC, the content of MDA in lettuce leaves displayed a remarkable decrease. In conclusion, the waste cements effectively reduced Cd bioavailability and enhanced the antioxidant system of lettuce.

Thermal modification can increase the physical stability and impact the mechanical strength of wood. It is necessary to understand the effects of modifications on the compressive stress of wood. In this study, Douglas fir (Pseudotsuga menziessi) blocks were modified at 180 °C (TM-180 °C) and 210 °C (TM-210 °C). The compressive stress of pure earlywood (EW), pure latewood (LW), and combined earlywood and latewood (ELW) specimens was measured. The specimens were compressed at 30% of their original thickness, and during the compression test the strain distribution of the ELW was recorded. In addition, the microstructures before and after compression were investigated, complemented with SEM to understand the structural changes taking place. The results showed that the compressive stress of the TM-180 °C specimens was the highest because the thermal modification increased the stiffness of cell walls and the homogenized strain distribution in the ELW specimens. The control specimens had a higher compression set recovery rate than the thermally modified specimens. The tracheid cell walls in the EW and LW specimens were flattened and buckled, respectively, due to compression. In the thermally modified materials, cell wall fissures and wood ray fractures in the EW and LW specimens, respectively, were observed. For the ELW specimens, the structural changes in the latewood were not obvious and the structural changes in the earlywood were less significant than in the full EW specimens. Compared to the EW specimens, the earlywood in the ELW specimens showed higher compression set recovery rates. It seems that structural failure in earlywood is limited when used in combination with latewood, resulting from the homogenized strain distribution in earlywood.

Abstract Iron–sulfur clusters are essential cofactors found in all kingdoms of life and play essential roles in fundamental processes, including but not limited to respiration, photosynthesis, and nitrogen fixation. The chemistry of iron–sulfur clusters makes them ideal for sensing various redox environmental signals, while the physics of iron–sulfur clusters and its host proteins have been long overlooked. One such protein, MagR, has been proposed as a putative animal magnetoreceptor. It forms a rod-like complex with cryptochromes (Cry) and possesses intrinsic magnetic moment. However, the magnetism modulation of MagR remains unknown. Here in this study, iron–sulfur cluster binding in MagR has been characterized. Three conserved cysteines of MagR play different roles in iron–sulfur cluster binding. Two forms of iron–sulfur clusters binding have been identified in pigeon MagR and showed different magnetic properties: [3Fe–4S]-MagR appears to be superparamagnetic and has saturation magnetization at 5 K but [2Fe–2S]-MagR is paramagnetic. While at 300 K, [2Fe–2S]-MagR is diamagnetic but [3Fe–4S]-MagR is paramagnetic. Together, the different types of iron–sulfur cluster binding in MagR attribute distinguished magnetic properties, which may provide a fascinating mechanism for animals to modulate the sensitivity in magnetic sensing.

Abstract A new type of piecewise negative stiffness (NS) mechanism is designed and the relationship between the force and displacement is studied. At first, the prototype of the piecewise NS mechanism is established, and the stiffness characteristic of this mechanism is analyzed. Then, the piecewise NS mechanism is applied to dynamic vibration absorber (DVA) system to establish a dynamic model with the piecewise linearity. The differential motion equations are derived according to Newton's law of mechanics. The approximate analytical solution and the amplitude frequency curve of the system with the piecewise NS are obtained by means of the averaging method. The correctness of the analytical solution is proved by comparing with the numerical solution. In the end, the comparisons with two other traditional DVAs show that the system in this paper has better vibration reduction effect under the condition of harmonic excitation and random excitation.

Abstract Background Polygonatum kingianum Coll. et Hemsl. is an important plant in Traditional Chinese Medicine. The extracts from its tubers are rich in polysaccharides and other metabolites such as saponins. It is a well-known concept that growing medicinal plants in semi-arid (or drought stress) increases their natural compounds concentrations. This study was conducted to explore the morpho-physiological responses of P. kingianum plants and transcriptomic signatures of P. kingianum tubers exposed to mild, moderate, and severe drought and rewatering. Results The stress effects on the morpho-physiological parameters were dependent on the intensity of the drought stress. The leaf area, relative water content, chlorophyll content, and shoot fresh weight decreased whereas electrolyte leakage increased with increase in drought stress intensity. A total of 53,081 unigenes were obtained; 59% of which were annotated. We observed that 1352 and 350 core genes were differentially expressed in drought and rewatering, respectively. Drought stress driven differentially expressed genes (DEGs) were enriched in phenylpropanoid biosynthesis, flavonoid biosynthesis, starch and sucrose metabolism, and stilbenoid diarylheptanoid and gingerol biosynthesis, and carotenoid biosynthesis pathways. Pathways such as plant-pathogen interaction and galactose metabolism were differentially regulated between severe drought and rewatering. Drought reduced the expression of lignin, gingerol, and flavonoid biosynthesis related genes and rewatering recovered the tubers from stress by increasing the expression of the genes. Increased expression of carotenoid biosynthesis pathway related genes under drought suggested their important role in stress endurance. An increase in starch and sucrose biosynthesis was evident from transcriptomic changes under drought stress. Rewatering recovered the drought affected tubers as evident from the contrasting expression profiles of genes related to these pathways. P. kingianum tuber experiences an increased biosynthesis of sucrose, starch, and carotenoid under drought stress. Drought decreases the flavonoids, phenylpropanoids, gingerol, and lignin biosynthesis. These changes can be reversed by rewatering the P. kingianum plants. Conclusions These results provide a transcriptome resource for P. kingianum and expands the knowledge on the effect of drought and rewatering on important pathways. This study also provides a large number of candidate genes that could be manipulated for drought stress tolerance and managing the polysaccharide and secondary metabolites’ contents in P. kingianum.

A red-black (RB) tree is a data structure with red and black nodes coloration. The red and black color of nodes make up the principal component for balancing a RB tree. A balanced tree has an equal number of black nodes on any simple path. But when a black leaf node is deleted, a double-black (DB) node is formed, thus, causing a reduction in black heights and the tree becomes unbalanced. Rebalancing a RB tree with a DB node is a fairly complex process. Teaching and learning the removal of DB nodes is also challenging. This paper introduces a simplified novel method which is a symbolic-algebraic arithmetic procedure for the removal of DB nodes and the rebalancing of black heights in RB trees. This simplified approach has enhanced student learning of the DB node removal in RB trees. Feedback from students showed the learnability, workability and acceptance of the symbolic-algebraic method in balancing RB trees after a delete operation.

Patients with RET fusions represent 1-2% of all cases of non-small cell lung cancer (NSCLC), the majority of whom are younger, and are extremely rare in the elderly. As a selective RET inhibitor, pralsetinib has been shown to be efficacious and well-tolerated in patients with RET-fusion NSCLC. Nevertheless, there are currently insufficient data available for assessing the activity and safety of pralsetinib in elderly patients with NSCLC. Herein, we report an 81-year-old NSCLC patient with KIF5B-RET fusion, who achieved stable disease for more than 9 months at a low-dose of pralsetinib as second-line therapy. Of particular note, during pralsetinb therapy, his clinical course was complicated by cryptococcal pneumonia and staphylococcus aureus lung abscess. Our study demonstrates that pralsetinib is an effective therapeutic option that provides survival benefits for elderly NSCLC patients harboring RET fusion. However, during pralsetinb therapy, treating physicians should maintain particular vigilance for the increased risk of infection, especially in elderly patients.

Biofilms play a crucial role in microbial-induced concrete corrosion (MICC), although their growth and composition vary depending on different environment. However, limited studies have been conducted on the corrosion process of MICC in tropical coastal sewer systems, specifically on the spatial microbial distribution within the concrete corrosion layer. This study utilized scanning electron microscopy, element mapping, and fluorescence microscopy to characterize the micro-morphology of biofilm and corrosion products, the element distribution in concretes using element mapping, and the spatial distribution of microorganisms inside deteriorated concretes, respectively. The results demonstrate that compared with the freshwater group, the seawater group with a high salt content is more favorable for biofilm adhesion to the concrete surface and induces more serious corrosion owing to the biological sulfur cycle reaction. The biological sulfuric acid produced by microbial metabolism corrodes concrete to produce gypsum and other corrosion products. Moreover, the surface and internal corrosion layers of concrete contain an abundance of Fe, a crucial element for microbial survival. Furthermore, fluorescence staining reveals a considerable number of microorganisms in concrete, and free proteins are widely distributed in the degraded hydration products, leading to microbial activity. This implies that microorganisms infiltrate the concrete through cracks and pores and proliferate within the concrete, hence aggravating bio-deterioration. Importantly, the combination of morphological observation and fluorescence analysis can provide a deeper understanding of the MICC process in seawater-containing sewage conditions.

Super absorbent polymers, expansion agents, and shrinkage reduction agents have been used to improve the self-shrinkage of ultra-high-performance concrete (UHPC), but they may degrade the mechanical properties of concrete. Sulfoaluminate cement (SAC) has been proven to improve the compressive strength and self-shrinkage of UHPC. However, few studies have focused on the role of SAC in the tensile strength and pore structure of reactive powder concrete (RPC), a type of UHPC. In our study, we used compressive strength and splitting tensile strength tests, isothermal calorimetry, X-ray diffraction (XRD), thermogravimetric analysis (TG-DTA), mercury intrusion porosimetry (MIP), and scanning electron microscopy (SEM) to determine the mechanical properties and microstructure of RPC modified by SAC. The results showed that the addition of SAC effectively enhanced the strength of RPC, especially the early strength. Specifically, using an 8 wt% SAC caused an 871.4 % increase in compressive strength and 600% improvement in tensile strength after 8 h of curing. The tensile strength exhibited a strong positive linear correlation with the compressive strength. The rapid hydration of SAC promoted the generation of ettringite in RPC, which significantly increased the cumulative heat release and improved the strength of RPC at an early age; however, its effect was not significant on the later strength. The key reasons for the improvement in the mechanical properties of RPC by SAC modification were pore refinement and aggregate-paste interface improvement. Thus, incorporating SAC into RPC significantly enhance its early-age compressive and tensile strengths, which contributes to accelerate the formwork turnover of RPC components and operational efficiency of the stacking area.

The fundamental understanding of metal-organic frameworks (MOFs) is crucial since the relationship between the macroscopic properties of these materials and their molecular-level structures allows for the development of technological applications and improvements in current performance. The metal centers and attached functional groups dictate MOFs' dynamics, structure, and porosity. The development of the solid-state nuclear magnetic resonance (SSNMR) technique, capable of providing atomic-level information, enables the non-destructive characterization of the structure and dynamics of MOFs have become essential step in ameliorating our understanding and are often complementary to traditional methods. This review aims to briefly introduce the concepts of SSNMR and the methods employed when investigating the dynamics, structure, and mapping of functional groups of microporous materials, including MOFs. This review highlights the best experimental practices when working with these complex systems. The article scrutinizes the information on framework structures, active center, surface position, host-guest interaction, and intermediate interaction through different SSNMR spectrums. Despite all the recent technological advancements, the SSNMR still faces the challenges of large sample quantities, long experimental measurements and data analyses, and complex isotopic labeling, which are enlightened in this review.

As nano-drug carriers, small extracellular vesicles (sEVs) have shown unique advantages, but their drug loading and encapsulation efficiency are far from being satisfied, especially for the loading of hydrophilic small-molecule drugs. Inspired by the strategies of active loading of liposomal nanomedicines, pre-drug design and immobilization enzyme, here we developed a new platform, named “Esterase-responsive Active Loading” (EAL), for the efficient and stable drug encapsulation of sEVs. Widely used ferulic acid ester derivatives were chosen as prodrugs based on the EAL of engineered sEVs to establish a continuous transmembrane ion gradient for achieving efficient loading of active molecule ferulic acid into sEVs. The EAL showed that the drug loading and encapsulation efficiency were around 6-fold and 5-fold higher than passive loading, respectively. Moreover, characterization by nano-flow cytometry and Malvern particle size analyzer showed that differential ultracentrifugation combined with multiple types of membrane filtration methods can achieve large-scale and high-quality production of sEVs. Finally, extracellular and intracellular assessments further confirmed the superior performance of the EAL-prepared sEVs-loaded ferulic acid preparation in terms of slow release and low toxicity. Taken together, these findings will provide an instructive insight into the development of sEV-based delivery systems.

Abstract Background Biliary atresia (BA) is a devastating inflammatory and fibrosing cholangiopathy of neonates with unknown aetiology. We aim to investigate the relationship between these two main characteristics. Methods Single‐cell RNA sequencing and spatial transcriptomics were performed on liver samples from a cohort of 14 objects (BA: n = 6; control: n = 8). We conducted data integration and cell‐type annotation based on gene expression profiling. Furthermore, we identified fibrosis‐related immune cells according to their spatial locations, GO and KEGG analysis. Finally, SPOTlight and CIBERSORTx were used to deconvolute ST data and microarray data of the GSE46960 cohorts, respectively. Results Immune subpopulations inhabiting the ‘fibrotic niche’ (areas of scarring), comprising ‘intermediate’ CD14++CD16+ monocytes, scar‐associated macrophages, natural killer T cells, transitional B cells and FCN3+ neutrophils were identified. GO and KEGG analyses showed that pathways including ‘positive regulation of smooth muscle cell/fibroblast proliferation’ and ‘positive regulation of/response to VEGFR/VEGF/EGFR/FGF’ were enriched in these cell types. Interactions analysis showed that communication among ‘FGF_FGFR’, ‘RPS19‐C5AR1’, ‘CD74_COPA/MIF/APP’ and ‘TNFRSF1A/B_GRN’ was extensive. Finally, the results of deconvolution for ST data and microarray data validated that the proportions of certain identified fibrosis‐related cell types we identified were increased in BA. Discussion Fibrosis is an important feature of BA, in which the immune system plays an important role. Our work reveals the subpopulations of immune cells enriched in the fibrotic niche of BA liver, as well as key related pathways and molecules; some are highlighted for the first time in liver fibrosis. These newly identified interactions might partly explain why the rate of liver fibrosis occurs much faster in BA than in other liver diseases. Conclusion Our study revealed the molecular, cellular and spatial immune microenvironment of the fibrotic niche of BA.

ObjectiveTo curb the unreasonable growth of pharmaceutical expenditures, Beijing implemented the zero markup drug policy (ZMDP) in public hospitals in 2017, which focused on separating drug sales from hospital revenue. The purpose of this study is to evaluate the impacts of ZMDP on healthcare expenditures and utilization for inpatients.MethodsThe Beijing claims data of inpatients diagnosed with ischemic heart disease (IHD), chronic renal failure (CRF), and lung cancer (LC) was extracted from the China Health Insurance Research Association (CHIRA) database. The study employed an interrupted time series to evaluate the impacts of ZMDP on healthcare expenditures and utilization.ResultsThe changes in total hospitalization expenses, health insurance expenses, and out-of-pocket expenses were not statistically significant neither in level change nor in trend change for inpatients diagnosed with IHD, CRF, or LC after implementing ZMDP (all P > 0.05). The Western medicine expenses for the treatment of inpatients diagnosed with IHD significantly decreased by 1,923.38 CNY after the reform (P < 0.05). The Chinese medicine expenses of inpatients diagnosed with CRF instantaneously increased by 1,344.89 CNY (P < 0.05). The service expenses of inpatients diagnosed with IHD and LC instantaneously increased by 756.52 CNY (p > 0.05) and 2,629.19 CNY (p < 0.05), respectively. However, there were no significant changes (P > 0.05) in out-of-pocket expenses, medical consumables, imaging, and laboratory test expenses of inpatients diagnosed with IHD, CRF, or LC. The initiation of the intervention immediately increased the number of inpatient admissions with LC by 2.293 per month (p < 0.05).ConclusionsThe ZMDP was effective in reducing drug costs, and the effects on healthcare utilization varied across diseases type. However, the increase in medical service and Chinese medicine expenses diminished the effect of containing healthcare expenses and relieving the financial burdens of patients. Policymakers are advised to take multiple and long-lasting measures, such as provider payment methods reform, volume-based drug procurement, and drug price negotiation to improve the affordability of patients thoroughly.

Iron-sulfur proteins play essential roles in a wide variety of cellular processes such as respiration, photosynthesis, nitrogen fixation and magnetoreception. The stability of iron-sulfur clusters varies significantly between anaerobic and aerobic conditions due to their intrinsic sensitivity to oxygen. Iron-sulfur proteins are well suited to various practical applications as molecular redox sensors or molecular “wires” for electron transfer. Various technologies have been developed recently using one particular iron-sulfur protein, MagR, as a magnetic tag. However, the limited protein stability and low magnetic sensitivity of MagR hindered its wide application. Here in this study, the iron-sulfur binding site of pigeon clMagR was rationally re-designed. One such mutation, T57C in pigeon MagR, showed improved iron-sulfur binding efficiency and higher iron content, as well as prolonged thermostability. Thus, clMagRT57C can serve as a prototype for further design of more stable and sensitive magnetic toolbox for magnetogenetics in the future.

Evidence suggests that increased microRNA-155 (miR-155) expression in immune cells enhances antitumor immune responses. However, given the reported association of miR-155 with tumorigenesis in various cancers, a debate is provoked on whether miR-155 is oncogenic or tumor suppressive. We aimed to interrogate the impact of tumor miR-155 expression, particularly that of cancer cell–derived miR-155, on antitumor immunity in breast cancer. We performed bioinformatic analysis of human breast cancer databases, murine experiments, and human specimen examination. We revealed that higher tumor miR-155 levels correlate with a favorable antitumor immune profile and better patient outcomes. Murine experiments demonstrated that miR-155 overexpression in breast cancer cells enhanced T cell influx, delayed tumor growth, and sensitized the tumors to immune checkpoint blockade (ICB) therapy. Mechanistically, miR-155 overexpression in breast cancer cells upregulated their CXCL9/10/11 production, which was mediated by SOCS1 inhibition and increased phosphorylated STAT1 (p-STAT1)/p-STAT3 ratios. We further found that serum miR-155 levels in breast cancer patients correlated with tumor miR-155 levels and tumor immune status. Our findings suggest that high serum and tumor miR-155 levels may be a favorable prognostic marker for breast cancer patients and that therapeutic elevation of miR-155 in breast tumors may improve the efficacy of ICB therapy via remodeling the antitumor immune landscape.

Summary: Background: Non-AIDS-defining cancers (NADCs) are now becoming a rising cause of morbidity among people living with HIV (PLHIV) in the highly active antiretroviral therapy (HAART) era. We conducted a systematic review and meta-analysis to estimate the summary risk of incidence and mortality of a wide range of NADCs among PLHIV compared with the general population. Methods: This systematic review and meta-analysis was registered in the PROSPERO (registration number CRD42020222020). We searched PubMed, EMBASE, Cochrane library, and Web of Science for relevant studies published before Jan 24, 2022. Cohort or registry linkage studies comparing the incidence or mortality of individual NADCs in PLHIV with that in the general population were included. Studies simply reporting outcomes of cancer precursor lesions or combined NADCs were excluded. We calculated pooled standardised incidence (SIRs) and standardised mortality ratios (SMRs) and their 95% confidence intervals (CIs) using random-effects models, and used robust variance estimation to account for non-independence in study-level effect sizes. Findings: We identified 92 publications arising from 46 independent studies including 7 articles out of 7 studies from developing countries. Among the 40 types of NADCs investigated, all of the 20 infection-related NADCs, cancers related with human papillomavirus infection in particular, and half of the 20 non-infection-related NADCs occurred in excess in PLHIV compared with the general population. This risk pattern was consistent in most WHO regions and in both high-income and low-and middle-income countries. The increased SIRs for various NADCs were more evident among PLHIV with advanced immunodeficiency, and was explored by HIV transmission route, and use of HAART. PLHIV had increased mortality for anal cancer (SMR 124·07, 95% CI 27·31-563·72), Hodgkin lymphoma (41·03, 2·91−577·88), liver cancer (8·36, 3·86−18·11), lung cancer (3·95, 1·52-10·26), and skin melanoma (3·95, 1·28−12·2). Interpretation: PLHIV had increased incidence and mortality for a wide spectrum of NADCs. Primary prevention and effective treatment for NADCs in this population is urgently needed. Funding: Natural Science Foundation of China Excellent Young Scientists Fund, Natural Science Foundation of China International/Regional Research Collaboration Project, National Science and Technology Major Project of China, Sanming Project of Medicine in Shenzhen, High Level Project of Medicine in Longhua, Shenzhen, Shenzhen Science and Technology Innovation Commission Basic Research Program, Special Support Plan for High-Level Talents of Guangdong Province, the Guangzhou Basic Research Program on People's Livelihood Science and Technology, the National Natural Science Foundation of China.

ImportanceThe number of infections and deaths caused by the global epidemic of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) invasion is steadily increasing daily. In the early stages of outbreak, approximately 15%–20% of patients with coronavirus disease 2019 (COVID-19) inevitably developed severe and critically ill forms of the disease, especially elderly patients and those with several or serious comorbidities. These more severe forms of disease mainly manifest as dyspnea, reduced blood oxygen saturation, severe pneumonia, acute respiratory distress syndrome (ARDS), thus requiring prolonged advanced respiratory support, including high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), and invasive mechanical ventilation (IMV).ObjectiveThis study aimed to propose a safer and more practical tracheotomy in invasive mechanical ventilated patients with COVID-19.DesignThis is a single center quality improvement study.ParticipantsTracheotomy is a necessary and important step in airway management for COVID-19 patients with prolonged endotracheal intubation, IMV, failed extubation, and ventilator dependence. Standardized third-level protection measures and bulky personal protective equipment (PPE) may hugely impede the implementation of tracheotomy, especially when determining the optimal pre-surgical positioning for COVID-19 patients with ambiguous surface position, obesity, short neck or limited neck extension, due to vision impairment, reduced tactile sensation and motility associated with PPE. Consequently, the aim of this study was to propose a safer and more practical tracheotomy, namely percutaneous dilated tracheotomy (PDT) with delayed endotracheal intubation withdrawal under the guidance of bedside ultrasonography without the conventional use of flexible fiberoptic bronchoscopy (FFB), which can accurately determine the optimal pre-surgical positioning, as well as avoid intraoperative damage of the posterior tracheal wall and prevent the occurrence of tracheoesophageal fistula (TEF).

BackgroundCoronary artery disease (CAD) is a progressive disease of the blood vessels supplying the heart, which leads to coronary artery stenosis or obstruction and is life-threatening. Early diagnosis of CAD is essential for timely intervention. Imaging tests are widely used in diagnosing CAD, and artificial intelligence (AI) technology is used to shed light on the development of new imaging diagnostic markers.ObjectiveWe aim to investigate and summarize how AI algorithms are used in the development of diagnostic models of CAD with imaging markers.MethodsThis scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guideline. Eligible articles were searched in PubMed and Embase. Based on the predefined included criteria, articles on coronary heart disease were selected for this scoping review. Data extraction was independently conducted by two reviewers, and a narrative synthesis approach was used in the analysis.ResultsA total of 46 articles were included in the scoping review. The most common types of imaging methods complemented by AI included single-photon emission computed tomography (15/46, 32.6%) and coronary computed tomography angiography (15/46, 32.6%). Deep learning (DL) (41/46, 89.2%) algorithms were used more often than machine learning algorithms (5/46, 10.8%). The models yielded good model performance in terms of accuracy, sensitivity, specificity, and AUC. However, most of the primary studies used a relatively small sample (n < 500) in model development, and only few studies (4/46, 8.7%) carried out external validation of the AI model.ConclusionAs non-invasive diagnostic methods, imaging markers integrated with AI have exhibited considerable potential in the diagnosis of CAD. External validation of model performance and evaluation of clinical use aid in the confirmation of the added value of markers in practice.Systematic review registration[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022306638], identifier [CRD42022306638].

The antiferromagnetic topological insulator MnBi2Te4 exhibits Chern and axion insulator phases at low magnetic field; however, its behaviour in high magnetic field has remained unexplored. Here, using transport measurements at high magnetic field, the authors report a zero Hall plateau composed of two counter-propagating edge channels.

ObjectivesLung cancer (LC) is the largest single cause of death from cancer worldwide, and the lack of effective screening methods for early detection currently results in unsatisfactory curative treatments. We herein aimed to use breath analysis, a noninvasive and very simple method, to identify and validate biomarkers in breath for the screening of lung cancer.Materials and methodsWe enrolled a total of 2308 participants from two centers for online breath analyses using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS). The derivation cohort included 1007 patients with primary LC and 1036 healthy controls, and the external validation cohort included 158 LC patients and 107 healthy controls. We used eXtreme Gradient Boosting (XGBoost) to create a panel of predictive features and derived a prediction model to identify LC. The optimal number of features was determined by the greatest area under the receiver‐operating characteristic (ROC) curve (AUC).ResultsSix features were defined as a breath-biomarkers panel for the detection of LC. In the training dataset, the model had an AUC of 0.963 (95% CI, 0.941–0.982), and a sensitivity of 87.1% and specificity of 93.5% at a positivity threshold of 0.5. Our model was tested on the independent validation dataset and achieved an AUC of 0.771 (0.718–0.823), and sensitivity of 67.7% and specificity of 73.0%.ConclusionOur results suggested that breath analysis may serve as a valid method in screening lung cancer in a borderline population prior to hospital visits. Although our breath-biomarker panel is noninvasive, quick, and simple to use, it will require further calibration and validation in a prospective study within a primary care setting.