C-terminal glutamine acts as a C-degron targeted by E3 ubiquitin ligase TRIM7.

The exposed N-terminal or C-terminal residues of proteins can act, in cognate sequence contexts, as degradation signals (degrons) that are targeted by specific E3 ubiquitin ligases for proteasome-dependent degradation by N-degron or C-degron pathways. Here, we discovered a distinct C-degron pathway, termed the Gln/C-degron pathway, in which the B30.2 domain of E3 ubiquitin ligase TRIM7 (TRIM7B30.2) mediates the recognition of proteins bearing a C-terminal glutamine. By determining crystal structures of TRIM7B30.2 in complexes with various peptides, we show that TRIM7B30.2 forms a positively charged binding pocket to engage the "U"-shaped Gln/C-degron. The four C-terminal residues of a substrate play an important role in C-degron recognition, with C-terminal glutamine as the principal determinant. In vitro biochemical and cellular experiments were used to further analyze the substrate specificity and selective degradation of the Gln/C-degron by TRIM7.

Optimum Baseline Clinical Severity Scale Cut Points for Prognosticating Intracerebral Hemorrhage: INTERACT Studies.

BACKGROUND: The optimal cut point of baseline National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale scores for prognosticating acute intracerebral hemorrhage (ICH) is unknown. METHODS: Secondary analyses of participant data are from the INTERACT (Intensive Blood Pressure Reduction in Acute Intracerebral Hemorrhage Trials) 1 and 2 studies. Receiver operating characteristic analyses were used to compare the predictive performance of baseline NIHSS and Glasgow Coma Scale scores, ICH score, and max-ICH score. Optimal cut points for predicting 90-day clinical outcomes (death or major disability [defined as modified Rankin Scale scores 3-6], major disability [defined as modified Rankin Scale scores 3-5], and death alone) were determined using the Youden index. Logistic regression models were adjusted for age, sex, hematoma volume, and other known risk factors for poor prognosis. We validated our findings in the INTERACT1 database. RESULTS: There were 2829 INTERACT2 patients (age, 63.5±12.9 years; male, 62.9%; ICH volume, 10.96 [5.77-19.49] mL) included in the main analyses. The baseline NIHSS score (area under the curve, 0.796) had better prognostic utility for predicting death or major disability than the Glasgow Coma Scale score (area under the curve, 0.650) and ICH score (area under the curve, 0.674) and was comparable to max-ICH score (area under the curve, 0.789). Similar findings were observed when assessing the outcome of major disability. A cut point of 10 on baseline NIHSS optimally (sensitivity, 77.5%; specificity, 69.2%) predicted death or major disability (adjusted odds ratio, 4.50 [95% CI, 3.60-5.63]). The baseline NIHSS cut points that optimally predicted major disability and death alone were 10 and 12, respectively. The predictive effect of NIHSS≥10 for poor functional outcomes was consistent in all subgroups including age and baseline hematoma volume. Results were consistent when analyzed in the independent INTERACT1 validation database. CONCLUSIONS: In patients with mild-to-moderate ICH, a baseline NIHSS score of ≥10 was optimal for predicting poor outcomes at 90 days. Prediction based on baseline NIHSS is better than baseline Glasgow Coma Scale score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00226096 and NCT00716079.

Huperzine alkaloids: forty years of total syntheses.

Covering: up to 2023Huperzine alkaloids are a group of natural products belonging to the Lycopodium alkaloids family. The representative member huperzine A has a unique structure and exhibits potent inhibitory activity against acetylcholine esterase (AChE). This subfamily of alkaloids provides a great opportunity for developing synthetic methodologies and asymmetric synthesis. The efforts towards the synthesis of huperzine A have cultivated dozens of total syntheses and a rich body of new chemistry. Impressive progress has also been made in the synthesis of other huperzine alkaloids. The total syntheses of huperzines B, U, O, Q and R, structure reassignment and total syntheses of huperzines K, M and N have been reported in the past decade. This review focuses on the synthetic organic chemistry and the biosynthesis and medicinal chemistry of huperzines are also covered briefly.

The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial.

BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

Sucrose promotes cone enlargement via the TgNGA1-TgWRKY47-TgEXPA2 module in Torreya grandis.

Cone enlargement is a crucial process for seed production and reproduction in gymnosperms. Most of our knowledge of cone development is derived from observing anatomical structure during gametophyte development. Therefore, the exact molecular mechanism underlying cone enlargement after fertilization is poorly understood. Here, we demonstrate that sucrose promotes cone enlargement in Torreya grandis, a gymnosperm species with relatively low rates of cone enlargement, via the TgNGA1-TgWRKY47-TgEXPA2 pathway. Cell expansion plays a significant role in cone enlargement in T. grandis. 13C labeling and sucrose feeding experiments indicated that sucrose-induced changes in cell size and number contribute to cone enlargement in this species. RNA-sequencing analysis, transient overexpression in T. grandis cones, and stable overexpression in tomato (Solanum lycopersicum) suggested that the expansin gene TgEXPA2 positively regulates cell expansion in T. grandis cones. The WRKY transcription factor TgWRKY47 directly enhances TgEXPA2 expression by binding to its promoter. Additionally, the NGATHA transcription factor TgNGA1 directly interacts with TgWRKY47. This interaction suppresses the DNA-binding ability of TgWRKY47, thereby reducing its transcriptional activation on TgEXPA2 without affecting the transactivation ability of TgWRKY47. Our findings establish a link between sucrose and cone enlargement in T. grandis and elucidate the potential underlying molecular mechanism.

Transcription factors TgbHLH95 and TgbZIP44 cotarget terpene biosynthesis gene TgGPPS in Torreya grandis nuts.

Terpenes are volatile compounds responsible for aroma and the postharvest quality of commercially important xiangfei (Torreya grandis) nuts, and there is interest in understanding the regulation of their biosynthesis. Here, a transcriptomics analysis of xiangfei nuts after harvest identified 156 genes associated with the terpenoid metabolic pathway. A geranyl diphosphate (GPP) synthase (TgGPPS) involved in production of the monoterpene precursor GPP was targeted for functional characterization, and its transcript levels positively correlated with terpene levels. Furthermore, transient overexpression of TgGPPS in tobacco (Nicotiana tabacum) leaves or tomato (Solanum lycopersicum) fruit led to monoterpene accumulation. Analysis of differentially expressed transcription factors identified one basic helix-loop-helix protein (TgbHLH95) and one basic leucine zipper protein (TgbZIP44) as potential TgGPPS regulators. TgbHLH95 showed significant transactivation of the TgGPPS promoter, and its transient overexpression in tobacco leaves led to monoterpene accumulation, whereas TgbZIP44 directly bound to an ACGT-containing element in the TgGPPS promoter, as determined by yeast 1-hybrid test and electrophoretic mobility shift assay. Bimolecular fluorescence complementation, firefly luciferase complementation imaging, co-immunoprecipitation, and GST pull-down assays confirmed a direct protein-protein interaction between TgbHLH95 and TgbZIP44 in vivo and in vitro, and in combination these proteins induced the TgGPPS promoter up to 4.7-fold in transactivation assays. These results indicate that a TgbHLH95/TgbZIP44 complex activates the TgGPPS promoter and upregulates terpene biosynthesis in xiangfei nuts after harvest, thereby contributing to its aroma.

Theoretical and Experimental Aspects of Electrocatalysts for Oxygen Evolution Reaction.

Scientists are increasingly paying attention to using theoretical design as a guide combined with modern in-situ characterization techniques to develop catalysts with high activity, low cost, and long-term life. The review discusses the progress of catalyst theoretical design and corresponding experiments based on three typical oxygen evolution catalytic mechanisms, including the adsorbate evolution, lattice oxygen-mediated, and unconventional bifunctional mechanisms. This work briefly describes the commonly used tools and descriptors in theory as well as the electrochemical techniques and characterizations in experiments. Our purpose is to sort out the ways to closely integrate the theoretical method and experimental verification from the perspective of reaction mechanism, and to provide some experience reference for the future development of theoretical tools and experimental technologies.

Opinions over targets for blood pressure control after mechanical thrombectomy in patients with acute ischemic stroke: baseline survey for the ENCHANTED2/MT trial in China.

BACKGROUND: Although guidelines recommend a target blood pressure 185-180/105-110 mmHg after mechanical thrombectomy for acute ischemic stroke (AIS), there is limited randomized evidence to support this level. We surveyed candidate institutions about the approach to blood pressure management in this patient group in preparation for inviting them to participate in the Enhanced Blood Pressure Control after Endovascular Thrombectomy for the Acute Ischemic Stroke Trial (ENCHANTED2/MT). METHODS: Physicians from a professional network of institutions that met mechanical thrombectomy qualification requirements were invited to participate in an online questionnaire covering basic clinical information as well as questions on blood pressure management. RESULTS: We invited 88 sites to participate with 44 (50%) ultimately joining the trial, and a total of 88 physicians finished the survey. The median number of annual mechanical thrombectomy cases performed per site was 89 [IQR 65-150]. Only 38 (43%) institutions strictly adhere to guidelines when managing the blood pressure of mechanical thrombectomy patients. The most popular blood pressure target for reperfusion patients was 140-160 mmHg (n=47, 53%), and <120 mmHg (n=28, 32%). Fewer hospital stroke beds (40 [21-57] vs. 60 [39-110], p = 0.01) and lower proportion of elevated blood pressure after mechanical thrombectomy (25% [10%-50%] vs. 50% [20%-70%], p = 0.02) were related to a more aggressive blood pressure target (<120 mmHg). Urapidil (n=82, 93%) and calcium channel blockers (CCBs) (n = 87, 99%), were the most widely used antihypertensive drugs, respectively. CONCLUSIONS: According to the survey, unstandardized blood pressure management protocols are performed in mechanical thrombectomy patients at institutions across China, which is different from prior survey from another country. More high-quality studies are needed to guide clinical practice.

Predictors of Early versus Delayed Neurological Deterioration after Thrombolysis for Ischemic Stroke.

INTRODUCTION: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with the functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: END and DND (without END) were defined as scores of a ≥2-point increase on the National Institutes of Health Stroke Scale (NIHSS) or a ≥1-point decrease on the Glasgow coma scale or death, from baseline to 24 h and 24-72 h, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2-6 vs. 0-1 and 3-6 vs. 0-2 and death). RESULTS: Of 4,496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large-artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 h were all independent predictors for both END (all p ≤ 0.01) and DND (all p ≤ 0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), higher diastolic BP variability within 24 h (OR 1.07, 95% CI 1.04-1.09), patients from Asia (OR 1.25, 95% CI 1.03-1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47-0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 h were the key predictors of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all p < 0.001). CONCLUSION: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for AIS. Both END and DND predict unfavorable outcomes at 90 days.

Statistical Analysis Plan for the INTEnsive Ambulance-Delivered Blood Pressure Reduction in Hyper-ACute Stroke Trial.

INTRODUCTION: Recruitment is complete in the fourth INTEnsive ambulance-delivered blood pressure Reduction in hyper-ACute stroke Trial (INTERACT4), a multicenter, prospective, randomized, open-label, blinded endpoint assessed trial of prehospital blood pressure (BP) lowering initiated in the ambulance for patients with a suspected acute stroke and elevated BP in China. According to the registered and published trial protocol and developed by the blinded trial Steering Committee and Operations team, this manuscript outlines a detailed statistical analysis plan for the trial prior to database lock. METHODS: Patients were randomized (1:1) to intensive (target systolic BP 130-140 mm Hg within 30 min) or guideline-recommended BP management (BP lowering only considered if systolic BP >220 mm Hg) group. Primary outcome is an ordinal analysis of the full range of scores on the modified Rankin scale at 90 days. A modified sample size of 2,320 was estimated to provide 90% power to detect a 22% reduction in the odds (common odds ratio of 0.78) of a worse functional outcome using ordinal logistic regression, on the assumption of 5% patients with missing outcome and 6% patients with a stroke mimic. CONCLUSION: The statistical analysis plan for the trial has been developed to ensure transparent, verifiable, and prespecified analysis and to avoid potential bias in the evaluation of the trial intervention.

Intensive blood pressure lowering and renal function in ischemic stroke patients: secondary analysis of ENCHANTED trial.

BACKGROUND: Renal failure is a major safety concern of intensive systolic blood pressure (SBP) lowering. We aimed to determine the effect of this treatment on early change in renal function in participants of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: Post-hoc analysis of the ENCHANTED BP-arm in which thrombolyzed patients with acute ischemic stroke (AIS) were randomized to intensive (target 130-140 mm Hg within 1 h) or guideline-recommended (target <180 mm Hg) management within 6 h of symptom onset. Primary outcome is early change in renal function, defined by a difference in estimated glomerular filtration rate (∆eGFR = 24 h - baseline eGFR), analyzed using linear regression with adjustment for clinical variables. Key SBP parameters were attained (mean), variability (standard deviation [SD]) and magnitude of reduction within 24 h. RESULTS: Of 2151 participants (mean age 66.9 years; 38% female) included with available baseline eGFR, there were significant differences in attained 144.3±10.2 vs 149.8±12.0 [5.5 mm Hg]; P<0.0001), variation (15.1±5.4 vs 14.0±5.6 mm Hg; P<0.0001) and magnitude of reduction (44.6±16.2 vs 38.7±17.6 mm Hg; P<0.0001) in SBP within 24 hours. 1718 (79.9%) participants with complete follow-up eGFR were included in the primary analysis, and there was no significant difference in ∆eGFR (adjusted mean difference -1.10, 95% confidence interval [CI] -3.14 to -0.94; P=0.29) between the intensive and guideline groups, respectively. The neutral effect on ∆eGFR was consistent in patients with different baseline eGFR stages and in sensitivity analysis after multiple imputation for missing follow-up eGFR. SBP variability was significantly associated with decreasing ∆eGFR (per 5 mm Hg increase by category: adjusted mean difference -1.35, 95%CI -2.43 to -0.28; P for trend=0.01). CONCLUSIONS: Intensive SBP lowering with a target of 130-140 mm Hg had no impact on early renal function in thrombolyzed AIS patients. Wide SBP variability was associated with a larger decline in eGFR. CLINICAL TRIAL REGISTRATION: ENCHANTED is registered at ClinicalTrials.gov (NCT01422616).

Implementation of low-intensity thrombolysis monitoring care in routine practice: process evaluation of the Optimal Post rtPA-IV Monitoring in Acute Ischemic Stroke (OPTIMISTmain) study in the United States.

INTRODUCTION: The ongoing OPTIMISTmain study, an international, multicenter, stepped-wedge cluster randomized trial, aims to determine effectiveness and safety of low-intensity versus standard monitoring in thrombolysis-treated patients with mild-to-moderate acute ischemic stroke (AIS). An embedded process evaluation explored integration and impact of the intervention on care processes at participating US sites. METHODS: A mixed-methods approach with quantitative and qualitative data were collected between September 2021 and November 2022. Implementer surveys were undertaken at pre- and post-intervention phases to understand the perceptions of low-intensity monitoring strategy. A sample of stroke care nurses were invited to participate in semi-structured interviews at an early stage of post-intervention. Qualitative data were analyzed deductively using the normalization process theory; quantitative data were tabulated. RESULTS: Interviews with 21 nurses at 8 hospitals have shown low-intensity monitoring was well accepted, as there were less time constraints and reduced workload for each patient. There were initial safety concerns over missing deteriorating patients and difficulties in changing established routines. Proper training, education, and communication, and changing the habits and culture of care, were key elements to successfully adopting the new monitoring care into routine practice. Similar results were found in the post-intervention survey (42 nurses from 13 hospitals). Nurses reported time being freed up to provide patient education (56%), daily living care (50%), early mobilization (26%), mood/cognition assessment (44%), and other aspects (i.e. communication, family support). CONCLUSIONS: Low-intensity monitoring for patients with mild-to-moderate acute ischemic stroke, facilitated by appropriate education and organizational support, appears feasible and acceptable at US hospitals.

Physical symptoms and anxiety and depression in older patients with advanced cancer in China: a network analysis.

BACKGROUND: Little is understood about the association between psychosomatic symptoms and advanced cancer among older Chinese patients. METHODS: This secondary analysis was part of a multicenter cross-sectional study based on an electronic patient-reported outcome platform. Patients with advanced cancer were included between August 2019 and December 2020 in China. Participants (over 60 years) completed the MD Anderson Symptom Inventory (MDASI) and Hospital Anxiety and Depression Scale (HADS) to measure symptom burden. Network analysis was also conducted to investigate the network structure, centrality indices (strength, closeness, and betweenness) and network stability. RESULTS: A total of 1022 patients with a mean age of 66 (60-88) years were included; 727 (71.1%) were males, and 295 (28.9%) were females. A total of 64.9% of older patients with advanced cancer had one or more symptoms, and up to 80% had anxiety and depression. The generated network indicated that the physical symptoms, anxiety and depression symptom communities were well connected with each other. Based on an evaluation of the centrality indices, 'distress/feeling upset' (MDASI 5) appears to be a structurally important node in all three networks, and 'I lost interest in my own appearance' (HADS-D4) had the lowest centrality indices. The network stability was relatively high (> 0.7). CONCLUSION: The symptom burden remains high in older patients with advanced cancer in China. Psychosomatic symptoms are highly interactive and often present as comorbidities. This network can be used to provide targeted interventions to optimize symptom management in older patients with advanced cancer in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024957), registered on 06/12/2020.

First Report of Aspergillus niger causing rot of Morchella sextelata in China.

As an important edible mushroom, morel mushroom (Morchella spp.) has been widely spread and cultivated in China. However, between 2022 and 2023, a rot disease with a natural incidence of 28% occurred in morel mushroom farms in the Qingpu district of Shanghai (N30°97', E121°06'), China. High temperatures (>20℃) and high humidity (>70%) provide conditions conducive to the spread of this disease. First, a small white mold-like symptoms appeared on the surface or the pinnacle of pileus. The tissues in the infected parts stop growing and developing.Then the lesion developed to encircle the pileus and spread gradually to the stipe, seriously affecting its yield and quality. The infected tissue of morel fruiting body at the edge of the lesions was isolated and cultivated on potato dextrose agar (PDA) at 28℃ in the dark. After 3 days, monospore cultures formed black cottony colonies. In order to reliably identify, isolates were transferred to Czapek Yeast Autolysate agar (CYA) (Samson et al, 2014). On CYA fungal colonies consisted of a white mycelium, covered by a layer of black conidiophores. Scanning electron microscope analysis revealed that mature mycelia produced conidiophores ended with numerous metula and phialides. The phialides showed the number of conidia bearing rounded spores, which coincides with previous research(Silva et al, 2020). To confirm the identity of the pathogen, the genomic fragments for the internal transcribed spacer (ITS), beta-microtubulin (BenA), calmodulin (CaM), and RNA polymerase II second largest subunit (RPB2) gene of the isolate were amplified by PCR (White et al. 1990; Glass et al. 1995; Hong et al. 2005; Liu et al. 1999). The resulting sequence was deposited in GenBank with accession OQ931346.1, OR393310, OR393311, and OR393312, respectively. PCR results and morphological observations indicated the isolated strain was a pure culture and the strain was designated as MOR02. Comparison results indicated that the sequences with accession numbers KF305756.1, MK450794.1, HQ285594.1, and HQ285594.1 have high identity with the molecular sequences of A. niger MOR02, which is 99%, 98%, 98%, 99%, respectively. Phylogenetic analysis with ITS and RBP2 genes of the isolated strain and 9 Aapergillus spp. strains were performed using MEGAX software with Neighbor-Joining (NJ) method. Based on the results of growth habits, morphological observations, and phylogenetic analysis, the pathogen was identified as A. niger. A spore suspension of the A. niger strain MOR02 (1 x107 conidia/mL) was inoculated back to healthy morel mushrooms. Five healthy fruit bodies of M. sextelata were injected, and another five healthy morels were treated with potato dextrose broth（PDB） medium as controls. Morels were incubated for 7 days at 20℃ and 85% to 90% relative humidity. The pathogen successfully infected the morel showing a similar white mold-like lesion as the natural occurrence disease. The controls remained healthy without any symptoms. The pathogen was reisolated from the affected lesions and identified as A. niger MOR02 based on its morphological characteristics and phylogenetic marker genes. To our knowledge, this is the first report of A. niger causing rot disease of M. sextelata. This study confirms that A. niger is the pathogenic fungus causing morel rot on the Qingpu farm in Shanghai. The disease occurs under conditions of high humidity and high-temperature conditions. Better production management is the most important to prevent the disease.

Ultrathin Cobalt-Based Prussian Blue Analogue Nanosheet-Assembled Nanoboxes Interpenetrated with Carbon Nanotubes as a Fast Electron/Potassium-Ion Conductor for Superior Potassium Storage.

Rechargeable potassium-ion batteries (PIBs) are regarded as potential substitutes for industrial lithium-ion batteries in large scale energy storage systems due to the world's abundant potassium supplies. Althogh cobalt hexacyanocobaltate (CoHCC) exhibits broad potential as a PIB anode material, its performance is currently unsatisfactory. Herein, novel 5 nm scale ultrathin CoHCC nanosheet-assembled nanoboxes with interspersed carbon nanotubes (CNTs/CoHCC nanoboxes) are fabricated to realize a highly reactive PIB anode. The ultrathin CoHCC layers substantially accelerate electron conduction and provide numerous active sites, while the connected CNTs provide fast axial electron transport. Consequently, the optimized anode exhibits a remarkable discharge capacity of 580.9 mAh g-1 at 0.1 A g-1 and long-term stability with 71.3% retention over 1000 cycles. In situ and ex situ characterizations and density functional theory calculations are further employed to elucidate the K+ storage process and the reason for the enhanced performance of the CNTs/CoHCC nanoboxes.

Gas Chromatography-Mass Spectrometry Metabolites and Transcriptome Profiling Reveal Molecular Mechanisms and Differences in Terpene Biosynthesis in Two Torrya grandis Cultivars during Postharvest Ripening.

Terpene aroma compounds are key quality attributes of postharvest Torreya grandis nuts, contributing to their commercial value. However, terpene biosynthesis and regulatory networks in different T. grandis cvs. are still poorly understood. Here, chief cvs. 'Xi Fei' and 'Xiangya Fei' were investigated for their differences in terpene biosynthesis and gene expression levels during postharvest ripening using headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) and transcriptomic datasets. A total of 28 and 22 aroma compounds were identified in 'Xi Fei' and 'Xiangya Fei', respectively. Interestingly, differences in aroma composition between the two cvs. were mostly attributed to D-limonene and α-pinene levels as key determinants in Torreya nuts' flavor. Further, transcriptome profiling, correlation analysis, and RT-qPCR annotated two novel genes, TgTPS1 in 'Xi Fei' and TgTPS2 in 'Xiangya Fei', involved in terpene biosynthesis. In addition, six transcription factors (TFs) with comparable expression patterns to TgTPS1 and four TFs to TgTPS2 were identified via correlation analysis of a volatile and transcriptome dataset to be involved in terpene biosynthesis. Our study provides novel insight into terpene biosynthesis and its regulation at the molecular level in T. grandis nut and presents a valuable reference for metabolic engineering and aroma improvement in this less explored nut.

Serum Metabolomic Profiles for Distinguishing Lung Cancer From Pulmonary Tuberculosis: Identification of Rapid and Noninvasive Biomarker.

BACKGROUND: Pulmonary tuberculosis (PTB) and lung cancer (LC) have similar clinical symptoms and atypical imaging findings, which are easily misdiagnosed. There is an urgent need for a noninvasive and accurate biomarker to distinguish LC from PTB. METHODS: A total of 694 subjects were enrolled and divided into discovery set (n = 122), identification set (n = 214), and validation set (n = 358). Metabolites were identified by multivariate and univariate analyses. Receiver operating characteristic curve were used to evaluate the diagnostic efficacy of biomarkers. RESULTS: Seven metabolites were identified and validated. Phenylalanylphenylalanine for distinguishing LC from PTB yielded an area under the curve of 0.89, sensitivity of 71%, and specificity of 92%. It also showed good diagnostic abilities in discovery set and identification set. Compared with that in healthy volunteers (median [interquartile range], 1.57 [1.01, 2.34] µg/mL), it was elevated in LC (4.76 [2.74, 7.08] µg/mL; ratio of median, [ROM] = 3.03, P < .01) and reduced in PTB (1.06 [0.51, 2.09] µg/mL; ROM = 0.68, P < .05). CONCLUSIONS: The metabolomic profile of LC and PTB was described and a key biomarker identified. We produced a rapid and noninvasive method to supplement existing clinical diagnostic examinations for distinguishing LC from PTB.

A P2/P3 Biphasic Layered Oxide Composite as a High-Energy and Long-Cycle-Life Cathode for Potassium-Ion Batteries.

Layered transition metal oxides are extensively considered as appealing cathode candidates for potassium-ion batteries (PIBs) due to their abundant raw materials and low cost, but their further implementations are limited by slow dynamics and impoverished structural stability. Herein, a layered composite having a P2 and P3 symbiotic structure is designed and synthesized to realize PIBs with large energy density and long-term cycling stability. The unique intergrowth of P2 and P3 phases in the obtained layered oxide is plainly characterized by X-ray diffraction refinement, high-angle annular dark field and annular bright field-scanning transmission electron microscopy at atomic resolution, and Fourier transformation images. The synergistic effect of the two phases of this layered P2/P3 composite is well demonstrated in K+ intercalation/extraction process. The as-prepared layered composite can present a large discharge capacity with the remarkable energy density of 321 Wh kg-1 and also manifest excellent capacity preservation after 600 cycles of K+ uptake/removal.

Heat-Resistant Carbon-Coated Potassium Magnesium Hexacyanoferrate Nanoplates for High-Performance Potassium-Ion Batteries.

Metal hexacyanoferrates (HCFs) are regarded as promising cathode materials for potassium-ion batteries (PIBs) on account of their low cost and high energy density. However, the difficult-to-remove [Fe(CN)6] vacancies and crystal water lead to structural instability and capacity deterioration as well as the stereotype of poor thermostability of conventional HCFs. Herein, we report (100) face-oriented potassium magnesium hexacyanoferrate (KMgHCF) nanoplates with low [Fe(CN)6] vacancies and high crystallinity, enabling thermostability up to 550 °C, high-temperature carbon coating and crystal water elimination. The as-obtained KMgHCF/C nanoplates exhibit superior potassium storage properties, including a large reversible capacity of 84.6 mAh g-1, a high voltage plateau of 3.87 V, excellent long-term cycling performance over 15000 cycles and high rate capability at 5 A g-1. The unprecedented cycling stability of KMgHCF/C is attributed to the synergistic effect of a highly reversible two-phase reaction, low [Fe(CN)6] vacancies and no crystal water, a specially exposed steady (100) surface, and a protective carbon coating. This work provides a new material selection and modification strategy for the practical application of HCFs in PIBs.

Tunable Interfacial Electric Field-Mediated Cobalt-Doped FeSe/Fe3Se4 Heterostructure for High-Efficiency Potassium Storage.

The interfacial electric field (IEF) in the heterostructure can accelerate electron transport and ion migration, thereby enhancing the electrochemical performance of potassium-ion batteries (PIBs). Nevertheless, the quantification and modulation of the IEF for high-efficiency PIB anodes currently remains a blank slate. Herein, we achieve for the first time the quantification and tuning of IEF via amorphous carbon-coated undifferentiated cobalt-doped FeSe/Fe3Se4 heterostructure (denoted UN-CoFe4Se5/C) for efficient potassium storage. Co doping can increase the IEF in FeSe/Fe3Se4, thereby improving the electron transport, promoting the potassium adsorption capacity, and lowering the diffusion barrier. As expected, the IEF magnitude in UN-CoFe4Se5/C is experimentally quantified as 62.84 mV, which is 3.65 times larger than that of amorphous carbon-coated FeSe/Fe3Se4 heterostructure (Fe4Se5/C). Benefiting from the strong IEF, UN-CoFe4Se5/C as a PIB anode exhibits superior rate capability (145.8 mAh g-1 at 10.0 A g-1) and long cycle lifespan (capacity retention of 95.1 % over 3000 cycles at 1.0 A g-1). Furthermore, this undifferentiated doping strategy can universally regulate the IEF magnitude in CoSe2/Co9Se8 and FeS2/Fe7S8 heterostructures. This work can provide fundamental insights into the design of advanced PIB electrodes.