Genomic analyses provide insights into peach local adaptation and responses to climate change.

The environment has constantly shaped plant genomes, but the genetic bases underlying how plants adapt to environmental influences remain largely unknown. We constructed a high-density genomic variation map of 263 geographically representative peach landraces and wild relatives. A combination of whole-genome selection scans and genome-wide environmental association studies (GWEAS) was performed to reveal the genomic bases of peach adaptation to diverse climates. A total of 2092 selective sweeps that underlie local adaptation to both mild and extreme climates were identified, including 339 sweeps conferring genomic pattern of adaptation to high altitudes. Using genome-wide environmental association studies (GWEAS), a total of 2755 genomic loci strongly associated with 51 specific environmental variables were detected. The molecular mechanism underlying adaptive evolution of high drought, strong UVB, cold hardiness, sugar content, flesh color, and bloom date were revealed. Finally, based on 30 yr of observation, a candidate gene associated with bloom date advance, representing peach responses to global warming, was identified. Collectively, our study provides insights into molecular bases of how environments have shaped peach genomes by natural selection and adds candidate genes for future studies on evolutionary genetics, adaptation to climate changes, and breeding.

Efficacy difference of antipsychotics in Alzheimer's disease and schizophrenia: explained with network efficiency and pathway analysis methods.

Approximately 50% of Alzheimer's disease (AD) patients will develop psychotic symptoms and these patients will experience severe rapid cognitive decline compared with those without psychosis (AD-P). Currently, no medication has been approved by the Food and Drug Administration for AD with psychosis (AD+P) specifically, although atypical antipsychotics are widely used in clinical practice. These drugs have demonstrated modest efficacy in managing psychosis in individuals with AD, with an increased frequency of adverse events, including excess mortality. We compared the differences between the genetic variations/genes associated with AD+P and schizophrenia from existing Genome-Wide Association Study and differentially expressed genes (DEGs). We also constructed disease-specific protein-protein interaction networks for AD+P and schizophrenia. Network efficiency was then calculated to characterize the topological structures of these two networks. The efficiency of antipsychotics in these two networks was calculated. A weight adjustment based on binding affinity to drug targets was later applied to refine our results, and 2013 and 2123 genes were identified as related to AD+P and schizophrenia, respectively, with only 115 genes shared. Antipsychotics showed a significantly lower efficiency in the AD+P network than in the schizophrenia network (P < 0.001) indicating that antipsychotics may have less impact in AD+P than in schizophrenia. AD+P may be caused by mechanisms distinct from those in schizophrenia which result in a decreased efficacy of antipsychotics in AD+P. In addition, the network analysis methods provided quantitative explanations of the lower efficacy of antipsychotics in AD+P.

MADS-box protein PpDAM6 regulates chilling requirement-mediated dormancy and bud break in peach.

Bud dormancy is crucial for winter survival and is characterized by the inability of the bud meristem to respond to growth-promotive signals before the chilling requirement (CR) is met. However, our understanding of the genetic mechanism regulating CR and bud dormancy remains limited. This study identified PpDAM6 (DORMANCY-ASSOCIATED MADS-box) as a key gene for CR using a genome-wide association study analysis based on structural variations in 345 peach (Prunus persica (L.) Batsch) accessions. The function of PpDAM6 in CR regulation was demonstrated by transiently silencing the gene in peach buds and stably overexpressing the gene in transgenic apple (Malus × domestica) plants. The results showed an evolutionarily conserved function of PpDAM6 in regulating bud dormancy release, followed by vegetative growth and flowering, in peach and apple. The 30-bp deletion in the PpDAM6 promoter was substantially associated with reducing PpDAM6 expression in low-CR accessions. A PCR marker based on the 30-bp indel was developed to distinguish peach plants with non-low and low CR. Modification of the H3K27me3 marker at the PpDAM6 locus showed no apparent change across the dormancy process in low- and non-low- CR cultivars. Additionally, H3K27me3 modification occurred earlier in low-CR cultivars on a genome-wide scale. PpDAM6 could mediate cell-cell communication by inducing the expression of the downstream genes PpNCED1 (9-cis-epoxycarotenoid dioxygenase 1), encoding a key enzyme for ABA biosynthesis, and CALS (CALLOSE SYNTHASE), encoding callose synthase. We shed light on a gene regulatory network formed by PpDAM6-containing complexes that mediate CR underlying dormancy and bud break in peach. A better understanding of the genetic basis for natural variations of CR can help breeders develop cultivars with different CR for growing in different geographical regions.

Accessing the spectrum of a single-photon by the Hong-Ou-Mandel interference.

We present and experimentally demonstrate a method for determining the spectral characterization of a single-photon state. This technique is based on the Hong-Ou-Mandel interference between a well-defined weak coherent state and a measured single-photon state. We estimate the spectrum of the single-photon state by fitting the measured interference dip with proposed model and least square method. Our method is particularly useful for characterising spectral property the single-photon state. It opens a way for robust and efficient on-line monitoring the single-photon emitters.

Predictors of futile recanalization after endovascular treatment of acute ischemic stroke.

OBJECTIVE: Endovascular therapy (EVT) is the most successful treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. However, futile recanalization (FR) seriously affects the prognosis of these patients. The aim of this study was to investigate predictors of FR after EVT in patients with AIS. METHOD: Patients diagnosed with AIS due to anterior circulation LVO and receiving EVT between June 2020 and October 2022 were prospectively enrolled. FR after EVT was defined as a poor 90-day prognosis (modified Rankin Scale [mRS] score ≥ 3) despite achieving successful reperfusion (modified Thrombolysis in Cerebral Infarction [mTICI] classification of 2b-3). All included patients were categorized into control group (mRS score < 3) and FR group (mRS score ≥ 3). Demographic characteristics, comorbidities (hypertension, diabetes, atrial fibrillation, smoking, etc.), stroke-specific data (NIHSS score, ASPECT score and site of occlusion), procedure data (treatment type [direct thrombectomy vs. bridging thrombectomy], degree of vascular recanalization [mTICI], procedure duration time and onset-recanalization time), laboratory indicators (lymphocytes count, neutrophils count, monocytes count, C-reactive protein, neutrophil-to-lymphocyte ratio [NLR], monocyte-to-high-density lipoprotein ratio [MHR], lymphocyte-to-monocyte ratio [LMR], lymphocyte-to-C-reactive protein ratio [LCR], lymphocyte-to-high-density lipoprotein ratio[LHR], total cholesterol and triglycerides.) were compared between the two groups. Multivariate logistic regression analysis was performed to explore independent predictors of FR after EVT. RESULTS: A total of 196 patients were included in this study, among which 57 patients were included in the control group and 139 patients were included in the FR group. Age, proportion of patients with hypertension and diabetes mellitus, median NIHSS score, CRP level, procedure duration time, neutrophil count and NLR were higher in the FR group than in the control group. Lymphocyte count, LMR, and LCR were lower in the FR group than in the control group. There were no significant differences in platelet count, monocytes count, total cholesterol, triglycerides, HDL, LDL, gender, smoking, atrial fibrillation, percentage of occluded sites, onset-recanalization time, ASPECT score and type of treatment between the two groups. Multivariate logistic regression analysis demonstrated that NLR was independently associated with FR after EVT (OR = 1.37, 95%CI = 1.005-1.86, P = 0.046). CONCLUSION: This study demonstrated that high NLR was associated with a risk of FR in patients with AIS due to anterior circulation LVO. These findings may help clinicians determine which patients with AIS are at higher risk of FR after EVT. Our study can provide a theoretical basis for interventions in the aforementioned population.

Enhancing post-traumatic stress disorder patient assessment: leveraging natural language processing for research of domain criteria identification using electronic medical records.

BACKGROUND: Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities. METHODS: In our study, we created a natural language processing (NLP) workflow to analyze electronic medical record (EMR) data and identify and extract research of domain criteria using a pre-trained transformer-based natural language model, all-mpnet-base-v2. We subsequently built dictionaries from 100,000 clinical notes and analyzed 5.67 million clinical notes from 38,807 PTSD patients from the University of Pittsburgh Medical Center. Subsequently, we showcased the significance of our approach by extracting and visualizing RDoC information in two use cases: (i) across multiple patient populations and (ii) throughout various disease trajectories. RESULTS: The sentence transformer model demonstrated high F1 macro scores across all RDoC domains, achieving the highest performance with a cosine similarity threshold value of 0.3. This ensured an F1 score of at least 80% across all RDoC domains. The study revealed consistent reductions in all six RDoC domains among PTSD patients after psychotherapy. We found that 60.6% of PTSD women have at least one abnormal instance of the six RDoC domains as compared to PTSD men (51.3%), with 45.1% of PTSD women with higher levels of sensorimotor disturbances compared to men (41.3%). We also found that 57.3% of PTSD patients have at least one abnormal instance of the six RDoC domains based on our records. Also, veterans had the higher abnormalities of negative and positive valence systems (60% and 51.9% of veterans respectively) compared to non-veterans (59.1% and 49.2% respectively). The domains following first diagnoses of PTSD were associated with heightened cue reactivity to trauma, suicide, alcohol, and substance consumption. CONCLUSIONS: The findings provide initial insights into RDoC functioning in different populations and disease trajectories. Natural language processing proves valuable for capturing real-time, context dependent RDoC instances from extensive clinical notes.

Cobalt-based Co3Mo3N/Co4N/Co Metallic Heterostructure as a Highly Active Electrocatalyst for Alkaline Overall Water Splitting.

Alkaline water electrolysis holds promise for large-scale hydrogen production, yet it encounters challenges like high voltage and limited stability at higher current densities, primarily due to inefficient electron transport kinetics. Herein, a novel cobalt-based metallic heterostructure (Co3Mo3N/Co4N/Co) is designed for excellent water electrolysis. In operando Raman experiments reveal that the formation of the Co3Mo3N/Co4N heterointerface boosts the free water adsorption and dissociation, increasing the available protons for subsequent hydrogen production. Furthermore, the altered electronic structure of the Co3Mo3N/Co4N heterointerface optimizes ΔGH of the nitrogen atoms at the interface. This synergistic effect between interfacial nitrogen atoms and metal phase cobalt creates highly efficient active sites for the hydrogen evolution reaction (HER), thereby enhancing the overall HER performance. Additionally, the heterostructure exhibits a rapid OH- adsorption rate, coupled with great adsorption strength, leading to improved oxygen evolution reaction (OER) performance. Crucially, the metallic heterojunction accelerates electron transport, expediting the afore-mentioned reaction steps and enhancing water splitting efficiency. The Co3Mo3N/Co4N/Co electrocatalyst in the water electrolyzer delivers excellent performance, with a low 1.58 V cell voltage at 10 mA cm-2, and maintains 100 % retention over 100 hours at 200 mA cm-2, surpassing the Pt/C||RuO2 electrolyzer.

Active Enrichment of Nanoparticles for Ultra-Trace Point-of-Care COVID-19 Detection.

Active enrichment can detect nucleic acid at ultra-low concentrations without relatively time-consuming polymerase chain reaction (PCR), which is an important development direction for future rapid nucleic acid detection. Here, we reported an integrated active enrichment platform for direct hand-held detection of nucleic acid of COVID-19 in nanoliter samples without PCR. The platform consists of a capillary-assisted liquid-carrying system for sampling, integrated circuit system for ultrasound output, and cell-phone-based surface-enhanced Raman scattering (SERS) system. Considering the acoustic responsiveness and SERS-enhanced performance, gold nanorods were selected for biomedical applications. Functionalized gold nanorods can effectively capture and enrich biomarkers under ultrasonic aggregation. Such approaches can actively assemble gold nanorods in 1-2 s and achieved highly sensitive (6.15 × 10-13 M) SERS detection of COVID-19 biomarkers in nanoliter (10-7 L) samples within 5 min. We further demonstrated the high stability, repeatability, and selectivity of the platform, and validated its potential for the detection of throat swab samples. This simple, portable, and ultra-trace integrated active enrichment detection platform is a promising diagnostic tool for the direct and rapid detection of COVID-19.

Characterization of two-photon interference between a weak coherent state and a heralded single photon state.

We experimentally investigate two-photon interference between a weak coherent state and a heralded single-photon state, producing from a spontaneous parametric down conversion. Both the unequal spectrum linewidth and average photon number ratio in a given time interval are considered in our model. We obtained excellent agreement between our experimental data and prediction from our model. Furthermore, the range of observing high visibility two-photon interference is significantly extended by isolating coincidence events from two-photon contributions in the weak coherent state. These results may throw some new light on quantum information technology when the two-photon interference with independent sources is required.

Identification of orbital angular momentum using atom-based spatial self-phase modulation.

Optical vortex orbital angular momentum modes, namely the twists number of the light does in one wavelength, play a critical role in quantum-information coding, super-resolution imaging, and high-precision optical measurement. Here, we present the identification of the orbital angular momentum modes based on spatial self-phase modulation in rubidium atomic vapor. The refractive index of atomic medium is spatially modulated by the focused vortex laser beam, and the resulted nonlinear phase shift of beam directly related to the orbital angular momentum modes. The output diffraction pattern carries clearly distinguishable tails, whose number and rotation direction correspond to the magnitude and sign of the input beam orbital angular momentum, respectively. Furthermore, the visualization degree of orbital angular momentums identification is adjusted on-demand in the terms of incident power and frequency detuning. These results show that the spatial self-phase modulation of atomic vapor can provide a feasible and effective way to rapidly readout the orbital angular momentum modes of vortex beam.

Geometric pattern evolution of photonic graphene in coherent atomic medium.

The photonic graphene in atoms not only has the typical photonic band structures but also exhibits controllable optical properties that are difficult to achieve in the natural graphene. Here, the evolution process of discrete diffraction patterns of a photonic graphene, which is constructed through a three-beam interference, is demonstrated experimentally in a 5S1/2 - 5P3/2 - 5D5/2 85Rb atomic vapor. The input probe beam experiences a periodic refractive index modulation when traveling through the atomic vapor, and the evolution of output patterns with honeycomb, hybrid-hexagonal, and hexagonal geometric profiles is obtained by controlling the experimental parameters of two-photon detuning and the power of the coupling field. Moreover, the Talbot images of such three kinds of periodic structure patterns at different propagating planes are observed experimentally. This work provides an ideal platform to investigate manipulation the propagation of light in artificial photonic lattices with tunable periodically varying refractive index.

5.32 W ultraviolet laser generation at 266†nm using sum-frequency method with CsB3O5 crystal.

Ultraviolet (UV) beam generation at 266 nm using the sum-frequency (SFG) method with CsB3O5 (CBO) crystals was first suggested in 1997 [Opt. Lett.22, 1840 (1997).10.1364/OL.22.001840]; however, there has been no further research in the past 25 years. Herein, by sum-frequency mixing in CBO crystals, we obtained a high conversion efficiency picosecond (ps) and a high-power nanosecond (ns) 266 nm UV beam output. First, a ps laser device with simultaneously radiated wavelengths of 1064 and 355 nm and repetition frequency of 10 Hz was used as the fundamental laser source, and the conversion efficiency from 1064 + 355 nm to 266 nm reached 20.35%. We then used a 1064 nm ns laser with a high output power and repetition frequency of 10 kHz as the pump source. We accurately modified the optimal phase matching direction of the CBO crystal, and the achieved output power at 266 nm reached 5.32 W.

NOX2 oxidase inhibitor GSK2795039 possess antiviral activity against H1N1 influenza A virus in vitro and vivo.

The continuous zoonotic circulation and reassortment potential of influenza A viruses (IAV) in nature represents an enormous public health threat to humans. Beside vaccination antivirals are needed to efficiently control spreading of the disease. The previous research has shown that NOX2 involved in IAV replication, but the detailed mechanism has not been reported. In the present study we investigated the roles of NOX2 in host inflammatory response and IAV replication using a novel inhibitor GSK2795039. The drug significantly reduced H1N1 virus induced NOX2 activity and ROS release in human lung epithelial cells. The results of time course experiments suggested that GSK2795039 inhibited an early post-entry step of viral infection. Concomitantly, there was a decreased expression of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-ß and interleukin (IL)-6) in NOX2 suppressed cells. In vivo, compared with control groups, suppression of NOX2 improved the survival rate of mice infected with H1N1 virus (42.9% in GSK2795039 treated mice versus >0% of control mice) and viral burden also decreased in the GSK2795039 treated group. Thus, our data demonstrated a critical role for NOX2 in the establishment of H1N1 infection and subsequent inflammatory reactions, which suggest that GSK2795039 may be a potential therapeutic drug for IAV infection.

Three-dimensional location system based on an L-shaped array of Rydberg atomic receivers.

The Rydberg atomic receiver, sensing microwave electric field with high sensitivity and broad bandwidth, possesses the potential to be the staple for precise navigation and remote sensing. In this Letter, a Ku-band three-dimensional location system using an L-shaped array of Rydberg atomic receivers is theoretically proposed and experimentally demonstrated, and the proof of principle results show excellent consistency between the location-derived and the setting coordinates. The novel L-shaped array, together with the triangulation method, gives both phase difference and angle of arrival, achieving location of the horn for a signal microwave field in three-dimensional space. The concluded validity of this location system in the testing scene remains at approximately 90% with a theoretical maximum location tolerance of 5.7 mm. Furthermore, the estimation of two different spatiotemporal coordinates for the moving target confirms the velocity measurement capability of the system with errors less than 0.5 mm/s. The proposed location system using a Rydberg atomic receiver array is a verification for the most basic element and can be extended through repetition or nesting to a multi-input-multi-output system as well as multi-channel information processing.

Spatial mapping of the polarization-resolved spectrum based on vector-beam-assisted nondegenerate four-wave mixing.

The introduction of vector beams (VBs), with space-variant polarization, into the polarization-resolved spectrum, provides a convenient and rapid pathway for revealing micro-structure. Here, we realize the spatial mapping of the polarization-resolved spectrum based on VB-assisted nondegenerate four-wave mixing (FWM) in a diamond atomic system of 85Rb. The 780 nm radial VB and 776 nm linearly polarized Gaussian beam serve as the probe and pump beams in the FWM process, respectively. The generated 420 nm coherent blue light (CBL) possesses a space-variant intensity profile due to the spatially polarized atomic medium. Accordingly, the polarization-resolved spectrum can be directly mapped from a single CBL profile and the polarization information of the input 776 nm beam can be accurately extracted. In particular, such nondegenerate FWM based on VB provides a proof of principle for rapid and visual polarization-related detection by converting to a frequency domain where efficient detectors are readily available.

A novel approach to quantify calcifications of thyroid nodules in US images based on deep learning: predicting the risk of cervical lymph node metastasis in papillary thyroid cancer patients.

OBJECTIVE: Based on ultrasound (US) images, this study aimed to detect and quantify calcifications of thyroid nodules, which are regarded as one of the most important features in US diagnosis of thyroid cancer, and to further investigate the value of US calcifications in predicting the risk of lymph node metastasis (LNM) in papillary thyroid cancer (PTC). METHODS: Based on the DeepLabv3+ networks, 2992 thyroid nodules in US images were used to train a model to detect thyroid nodules, of which 998 were used to train a model to detect and quantify calcifications. A total of 225 and 146 thyroid nodules obtained from two centers, respectively, were used to test the performance of these models. A logistic regression method was used to construct the predictive models for LNM in PTCs. RESULTS: Calcifications detected by the network model and experienced radiologists had an agreement degree of above 90%. The novel quantitative parameters of US calcification defined in this study showed a significant difference between PTC patients with and without cervical LNM (p < 0.05). The calcification parameters were beneficial to predicting the LNM risk in PTC patients. The LNM prediction model using these calcification parameters combined with patient age and other US nodular features showed a higher specificity and accuracy than the calcification parameters alone. CONCLUSIONS: Our models not only detect the calcifications automatically, but also have value in predicting cervical LNM risk of PTC patients, thereby making it possible to investigate the relationship between calcifications and highly invasive PTC in detail. CLINICAL RELEVANCE STATEMENT: Due to the high association of US microcalcifications with thyroid cancers, our model will contribute to the differential diagnosis of thyroid nodules in daily practice. KEY POINTS: • We developed an ML-based network model for automatically detecting and quantifying calcifications within thyroid nodules in US images. • Three novel parameters for quantifying US calcifications were defined and verified. • These US calcification parameters showed value in predicting the risk of cervical LNM in PTC patients.

Predictive role of pre-thrombolytic hs-CRP on the safety and efficacy of intravenous thrombolysis in acute ischemic stroke.

PURPOSE: To investigate the predictive role of pre-thrombolytic high sensitivity C-reactive protein (hs-CRP) on the safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Patients with AIS who underwent intravenous thrombolysis with recombinant plasminogen activator (rtPA) or urokinase without endovascular therapy from June 2019 to June 2022 were retrospectively analysed. All patients were grouped into two groups (high or low hs-CRP group) according to the median value of hs-CRP before intravenous thrombolysis. The baseline NIHSS, NIHSS changes before and after thrombolysis (ΔNIHSS), the rate of good thrombolysis response (NIHSS decreased ≥ 2 points from baseline), the rate of any intracranial hemorrhage, age, sex, hypertension, diabetes, uric acid and platelet count were compared between the two groups. Logistic regression analysis was performed to identify possible prognostic factors for a good thrombolysis response. RESULTS: A total of 212 patients were included in the analysis, with a mean age of 66.3 ± 12.5 years. In total, 145 patients received rtPA, and 67 patients received urokinase. Patients were divided into a high hs-CRP group (> 1.60 mg/L) and a low hs-CRP group (≤ 1.60 mg/L) according to the median hs-CRP level (1.60 mg/L). The ΔNIHSS of the high hs-CRP group was significantly smaller than that of the low hs-CRP group (0 [-1 ~ 0] vs. -1 [-2 ~ 0], P < 0.05). The good rate of thrombolysis response in the high hs-CRP group was significantly lower than that in the low hs-CRP group (21.9% vs. 36.5%, P < 0.05). Similar results were shown in the rtPA subgroup between the high and low hs-CRP groups but not in the urokinase subgroup. Logistic regression analysis showed that hs-CRP > 1.60 mg/L was negatively correlated with a good thrombolysis response rate (OR = 0.496, 95% CI = 0.266-0.927, P = 0.028). CONCLUSION: hs-CRP > 1.6 mg/L may serve as a poor prognosis predictive factor for patients with AIS receiving intravenous thrombolysis. However, due to the small sample size of this study, further studies are needed to verify our results.

Ideal topological Weyl complex phonons in two dimensions.

The advent of topological phonons has been attracting tremendous attention. However, studies in two-dimensional (2D) systems are limited. Here, we reveal a 2D novel combination of Weyl phonons - a Weyl complex composed of two linear Weyl nodes and one quadratic Weyl node. This Weyl complex consists of crossing points of two specific branches. We show that the coexistence of threefold symmetry - rotation symmetry, inversion symmetry, and time-reversal symmetry - could lead to the presence of the Weyl complex. Based on the symmetry requirement, we further construct the tight-binding model and effective k·p model for characterizing the Weyl complex. Moreover, due to the presence of the spacetime inversion symmetry, the linear and quadratic Weyl nodes feature a quantized (π and 2π) Berry phase, thus defining the corresponding topological charge. Furthermore, Weyl complexes consisting of Weyl points possess an emergent chiral symmetry, an integer topological charge is thus defined. Then, distinguished phenomena for the Weyl complex are studied, in particular, the edge states with three terminals. Our work predicts the presence of this novel 2D topological phase, and provides the symmetry guidance to realize it. Based on the first-principles calculations, we identify an existing material Cu2Si, as a concrete example to demonstrate the presence of the Weyl complex, and also study the phase transition under symmetry breaking.

Drumhead surface states promoted hydrogen evolution reactions in type-II nodal-line topological catalyst Mg3Bi2.

An excellent catalyst generally meets three indicators: high electron mobility, high surface density of states and low Gibbs free energy (ΔG) [H. Luo et al. Nat. Rev. Phys., 2022, 4, 611-624]. Recent studies have confirmed that topological materials exhibit more advantages than conventional precious metals with regard to the above-mentioned indicators. Herein, based on DFT calculations and symmetry analysis, we discovered for the first time that the topological surface states of Mg3Bi2 with a Kagome lattice promote hydrogen evolution reactions (HERs). In particular, there exists a snake-like type-II nodal loop (NL), located on kz = 0 plane in Mg3Bi2. Besides, the NL forms a topologically protected drumhead surface state on the (001) surface. It was found that the ΔG (0.176 eV) value of the (001) surface is comparable to that of the precious metal Pt. Then, through hole doping and strain regulation, it was found that the catalytic activity of Mg3Bi2 is closely related to the drumhead surface state formed by NL. With the above-mentioned results, this study not only provides a promising candidate material for hydrogen electrolysis, but also deepens our understanding of the dominant factors of NL semimetals for the catalytic activity.

Nontargeted metabolomics integrated with 1 H NMR and LC-Q-TOF-MS/MS methods to depict a more comprehensive metabolic profile in response to chrysosplenetin and artemisinin co-treatment against artemisinin-sensitive and -resistant Plasmodium berghei K173.

Our previous work revealed mutual and specific metabolites/pathways in artemisinin-sensitive and -resistant Plasmodium berghei K173-infected mice. In this study, we further investigated whether chrysosplenetin, a candidate chemical to prevent artemisinin resistance, can regulate these metabolites/pathways by integrating nontargeted metabolomics with 1 H NMR and LC-Q-TOF-MS/MS spectrum. The nuclear magnetic resonance method generated specifically altered metabolites in response to co-treatment with chrysosplenetin, including: the products of glycolysis such as glucose, pyruvate, lactate and alanine; taurine, closely associated with liver injury; arginine and proline as essential amino acids for parasites; TMAO, a biomarker for dysbacteriosis and renal function; and tyrosine, which is used to generate levodopa and dopamine and may improve the torpor state of mice. Importantly, we noticed that chrysosplenetin might depress the activated glycolysis induced by sensitive parasites, but oppositely promoted the inhibited glycolysis to generate more lactate, which suppresses the proliferation of resistant parasites. Moreover, chrysosplentin possibly disturbs the heme biosynthetic pathway in mitochondria. The MS method yielded changed coenzyme A, phosphatidylcholine and ceramides, closely related to mitochondria ß-oxidation, cell proliferation, differentiation and apoptosis. These two means shared no overlapped metabolites and formed a more broader metabolic map to study the potential mechanisms of chrysosplenetin as a promising artemisinin resistance inhibitor.