Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis.

JOURNAL/nrgr/04.03/01300535-202502000-00029/figure1/v/2024-05-28T214302Z/r/image-tiff Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell-derived neural stem cell exosomes (hiPSC-NSC-Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism. Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits, enhanced blood-brain barrier integrity, and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage. Additionally, hiPSC-NSC-Exos decreased immune cell infiltration, activated astrocytes, and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α post-intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion, thereby improving blood-brain barrier integrity. Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In summary, our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity, in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

The ordered lattice host framework induced guest Li+ disordering in high performance cobalt-free Ni-rich cathode materials.

Recently, due to high price, resource shortage and unstable supply of cobalt, the development of low-cost cobalt-free Ni-rich cathodes has attracted extensive attention with the ever-increasing lithium-ion batteries (LIBs) industry. Selecting cost-effective elements to replace cobalt in Ni-rich cathodes is urgent. However, the principle of structural design of Ni-rich cathode remains unclear, hampering the selection of alternative elements. Herein, the cobalt-free cathodes of LiNi0.95Mg0.05O2 (NiMg) and LiNi0.95Mn0.05O2 (NiMn) are designed as alternatives to LiNi0.96Co0.04O2 (NiCo). NiMg has comparable cycle stability with NiCo, while NiMn has inferior cycle performance. Reverse Monte Carlo modelling was used to generate structural model and uncover local structure by fitting pair distribution function. It reveals Mn causes more severe Jahn-Teller distortions and disordered lattice host framework (Ni0.95M0.05O2, M = Co/Mn/Mg) than Co and Mg due to the strong size effect and coulomb interactions of Mn in Ni0.95Mn0.05O2 layer. The outstanding cycle stability of NiMg and NiCo originates from the ordered lattice host frameworks, which relieve stress and inhibit particle breakage during cycle. Meanwhile, the ordered lattice host framework induced guest Li+ disordering reduces Li+ diffusion energy barrier, improving the rate capability. This study provides a new perspective for the structural design of cobalt-free Ni-rich cathodes.

Increased indexed proximal aortic diameter is a predictor of poor prognosis in maintenance hemodialysis patients.

Background: Recent studies have shown that the baseline values of absolute aortic root diameter (ARD) and indexed diameter are associated with all-cause mortality and cardiovascular events in the general population, even in the absence of aneurysmal aortic disease. However, there is limited available data on the association between ARD and prognosis in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD). Accordingly, the purpose of this study is to investigate the predictive value of ARD for all-cause mortality and cardiovascular events in this specific population.Methods: ARD was measured by echocardiography at the level of the sinuses of Valsalva at end diastole and indexed to body surface area (BSA). The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiovascular events (MACE), including cardiovascular mortality, myocardial infarction and stroke. Cox proportional hazards models were conducted to evaluate the association between baseline ARD/BSA and clinical outcomes.Results: A total of 391 patients were included in this study. The primary endpoint occurred in 95 (24.3%) patients while the secondary endpoint occurred in 71 (18.2%) patients. Multivariate Cox regression analysis showed that ARD/BSA was an independent prognostic factor for all-cause mortality (HR, per 1-SD increase, 1.403; 95% CI, 1.118-1.761; p = 0.003) as well as MACE (HR, per 1-SD increase, 1.356; 95% CI, 1.037-1.772; p = 0.026).Conclusions: Our results show that ARD/BSA is predictive of all-cause mortality and MACE in MHD patients with ESRD and support the view that assessment of ARD/BSA may refine risk stratification and preventive strategies in this population.

Identification of toll-like receptor 2 as a key regulator of neuronal apoptosis in vascular dementia by bioinformatics analysis and experimental validation.

BACKGROUND: Vascular dementia (VaD), the second most prevalent type of dementia, lacks a well-defined cause and effective treatment. Our objective was to utilize bioinformatics analysis to discover the fundamental disease-causing genes and pathological mechanisms in individuals diagnosed with VaD. METHODS: To identify potential pathogenic genes associated with VaD, we conducted weighted gene co-expression network analysis (WGCNA), differential expression analysis, and protein-protein interaction (PPI) analysis. The exploration of potential biological mechanisms involved the utilization of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Moreover, a bilateral common carotid artery stenosis (BCAS) mouse model of VaD was established, and the expression of the hub gene, its relationship with cognitive function and its potential pathogenic mechanism were verified by cognitive behavior tests, cerebral blood flow measurement, Western blotting, and immunofluorescence experiments. RESULTS: This study identified 293 DEGs from the brain cortex of VaD patients and healthy controls, among these genes, the Toll-like receptor 2 (TLR2) gene was identified as hub gene, and it was associated with the apoptosis-related pathway PI3K/AKT.The BCAS model demonstrated that the use of TLR2 inhibitors greatly enhanced the cognitive function of the mice (p < 0.05). Additionally, there was a notable decrease in the number of apoptotic cells in the brain cortex of the mice (p < 0.01). Moreover, significant alterations in the levels of proteins related to the PI3K/AKT pathway and cleaved-caspase3 proteins were detected (p < 0.05). CONCLUSIONS: TLR2 plays a role in the pathophysiology of VaD by enhancing the neuronal apoptotic pathway, suggesting it could be a promising therapeutic target.

Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline.

Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood-brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

CSF1R blockade slows progression of cerebral hemorrhage by reducing microglial proliferation and increasing infiltration of CD8 + CD122+ T cells into the brain.

Microglia play a pivotal role in the neuroinflammatory response after brain injury, and their proliferation is dependent on colony-stimulating factors. In the present study, we investigated the effect of inhibiting microglia proliferation on neurological damage post intracerebral hemorrhage (ICH) in a mouse model, an aspect that has never been studied before. Using a colony-stimulating factor-1 receptor antagonist (GW2580), we observed that inhibition of microglia proliferation significantly ameliorated neurobehavioral deficits, attenuated cerebral edema, and reduced hematoma volume after ICH. This intervention was associated with a decrease in pro-inflammatory factors in microglia and an increased infiltration of peripheral regulatory CD8 + CD122+ T cells into the injured brain tissue. The CXCR3/CXCL10 axis is the mechanism of brain homing of regulatory CD8 + CD122+ T cells, and the high expression of IL-10 is the hallmark of their synergistic anti-inflammatory effect with microglia. And activated astrocytes around the insult site are a prominent source of CXCL10. Thus, inhibition of microglial proliferation offers a new perspective for clinical translation. The cross-talk between multiple cells involved in the regulation of the inflammatory response highlights the comprehensive nature of neuroimmunomodulation.

Effects of dissolved organic matter and halogen ions on phototransformation of pharmaceuticals and personal care products in aquatic environments.

Photochemical reactions contribute to the attenuation and transformation of pharmaceuticals and personal care products (PPCPs) in surface natural waters. Nevertheless, effects of DOM and halogen ions on phototransformation of PPCPs remain elusive. This work selected disparate PPCPs as target pollutants to investigate their aquatic phototransformation processes. Results show that PPCPs containing multiple electron-donating groups (-OH, -NH2, -OR, etc.) are more reactive with photochemically produced reactive intermediates (PPRIs) such as triplet DOM (3DOM*), singlet oxygen (1O2), and reactive halogen species (RHSs), relative to PPCPs containing electron-withdrawing groups (-NOR, -COOR, -OCR, etc.). The generation of RHSs as a result of the coexistance of DOM and halide ions changed the contribution of PPRIs to the photochemical conversion of PPCPs during their migration from fresh water to seawater. For PPCPs (AMP, SMZ, PN, NOR, CIP, etc) with highly reactive groups toward RHSs, the generation of RHSs facilitated their photolysis in halide ion-rich waters, where Cl- plays a critical role in the photochemical transformation of PPCPs. Density functional theory (DFT) calculations showed that single electron transfer and H-abstraction are main reaction pathways of RHSs with the PPCPs. These results demonstate the irreplaceable roles of PPRIs and revealing the underlying reaction mechanisms during the phototransformation of PPCPs, which contributes to a better understanding of the environmental behaviors of PPCPs in complex aquatic environments.

Genetic causal association between varicella-zoster virus infection and psychiatric disorders: A 2-sample Mendelian randomization study.

BACKGROUND: Psychiatric disorders, such as schizophrenia (SCZ), major depressive (MDD), and bipolar disorder (BD) have a profound impact on millions of individuals worldwide. The critical step toward developing effective preventive and treatment strategies lies in comprehending the causal mechanisms behind these diseases and identifying modifiable risk factors associated with them. METHODS: In this study, we conducted a 2-sample Mendelian randomization analysis to explore the potential links between chickenpox(varicella-zoster virus infection) and three major psychiatric disorders(SCZ, MDD, BD). RESULTS: In our MR study, among the three major psychiatric disorders, chickenpox was shown to be causally related to BD, indicating that infection with chickenpox may increase the risk of developing BD (IVW: OR = 1.064, 95% CI =1.025-1.104, P=0.001; RAPS: OR=1.066, 95% CI=1.024-1.110, P=0.002), while there was no causal relationship between SCZ and MDD. Similar estimated causal effects were observed consistently across the various MR models. The robustness of the identified causal relationship between chickenpox and BD holds true regardless of the statistical methods employed, as confirmed by extensive sensitivity analyses that address violations in model assumptions. The MR-Egger regression test failed to reveal any signs of directional pleiotropy (intercept = -0.042, standard error (SE) = 0.029, p = 0.236). Similarly, the MR-PRESSO analysis revealed no evidence of directional pleiotropy or outliers among the chickenpox-related instrumental variables (global test p = 0.653). Furthermore, a leave-one-out sensitivity analysis yielded consistent results, further underscoring the credibility and stability of the causal relationship. CONCLUSIONS: Our findings provide compelling evidence of a causal effect of chickenpox on the risk of BD. To gain a more comprehensive understanding of this association and its underlying mechanisms, additional research is needed. Such investigations are pivotal in identifying effective interventions for promoting BD prevention.

Evaluating the Impact of Cl2•- Generation on Antibiotic-Resistance Contamination Removal via UV/Peroxydisulfate.

The removal of antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs) using sulfate anion radical (SO4•-)-based advanced oxidation processes has gained considerable attention recently. However, immense uncertainties persist in technology transfer. Particularly, the impact of dichlorine radical (Cl2•-) generation during SO4•--mediated disinfection on ARB/ARGs removal remains unclear, despite the Cl2•- concentration reaching levels notably higher than those of SO4•- in certain SO4•--based procedures applied to secondary effluents, hospital wastewaters, and marine waters. The experimental results of this study reveal a detrimental effect on the disinfection efficiency of tetracycline-resistant Escherichia coli (Tc-ARB) during SO4•--mediated treatment owing to Cl2•- generation. Through a comparative investigation of the distinct inactivation mechanisms of Tc-ARB in the Cl2•-- and SO4•--mediated disinfection processes, encompassing various perspectives, we confirm that Cl2•- is less effective in inducing cellular structural damage, perturbing cellular metabolic activity, disrupting antioxidant enzyme system, damaging genetic material, and inducing the viable but nonculturable state. Consequently, this diminishes the disinfection efficiency of SO4•--mediated treatment owing to Cl2•- generation. Importantly, the results indicate that Cl2•- generation increases the potential risk associated with the dark reactivation of Tc-ARB and the vertical gene transfer process of tetracycline-resistant genes following SO4•--mediated disinfection. This study underscores the undesired role of Cl2•- for ARB/ARGs removal during the SO4•--mediated disinfection process.

Entropy-Driven Enhancement of the Conductivity and Phase Purity of Na4Fe3(PO4)2P2O7 as the Superior Cathode in Sodium-Ion Batteries.

Na4Fe3(PO4)2(P2O7) (NFPP) is regarded as a promising cathode material for sodium-ion batteries (SIBs) owing to its low cost, easy manufacture, environmental purity, high structural stability, unique three-dimensional Na-ion diffusion channels, and appropriate working voltage. However, for NFPP, the low conductivity of electrons and ions limits their capacity and power density. The generation of NaFeP2O7 and NaFePO4 inhibits the diffusion of sodium ions and reduces reversible capacity and rate performance during the manufacturing process in synthesis methods. Herein, we report an entropy-driven approach to enhance the electronic conductivity and, concurrently, phase purity of NFPP as the superior cathode in sodium-ion batteries. This approach was realized via Ti ions substituting different ratios of Fe-occupied sites in the NFPP lattice (denoted as NTFPP-X, T is the Ti in the lattice, X is the ratio of Ti-substitution) with the configurational entropic increment of the lattice structures from 0.68 R to 0.79 R. Specifically, 5% Ti-substituted lattice (NTFPP-0.05) inducing entropic augmentation not only improves the electronic conductivity from 7.1 × 10-2 S/m to 8.6 × 10-2 S/m but also generates the pure-phase of NFPP (suppressing the impure phases of the NaFeP2O7 and NaFePO4) of the lattice structure, which is validated by a series of characterizations, including powder X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR), X-ray photoelectron spectroscopy (XPS), and density functional theory (DFT). Benefiting from the Ti replacement in the lattice, the optimal NTFPP-0.05 composite shows a high first discharge capacity (118.5 mAh g-1 at 0.1 C), superior rate performance (70.5 mAh g-1 at 10 C), and excellent long cycling life (1200 cycles at 10 C with capacity retention of 86.9%). This research proposes a new entropy-driven approach to improve the electrochemical performance of NFPP and reports a low-cost, ultrastable, and high-rate cathode material of NTFPP-0.05 for SIBs.

o-Semiquinone Radical and o-Benzoquinone Selectively Degrade Aniline Contaminants in the Periodate-Mediated Advanced Oxidation Process.

Advanced oxidation processes (AOPs) often employ strong oxidizing inorganic radicals (e.g., hydroxyl and sulfate radicals) to oxidize contaminants in water treatment. However, the water matrix could scavenge the strong oxidizing radicals, significantly deteriorating the treatment efficiency. Here, we report a periodate/catechol process in which reactive quinone species (RQS) including the o-semiquinone radical (o-SQ•-) and o-benzoquinone (o-Q) were dominant to effectively degrade anilines within 60 s. The second-order reaction rate constants of o-SQ•- and o-Q with aniline were determined to be 1.0 × 108 and 4.0 × 103 M-1 s-1, respectively, at pH 7.0, which accounted for 21% and 79% of the degradation of aniline with a periodate-to-catechol molar ratio of 1:1. The major byproducts were generated via addition or polymerization. The RQS-based process exhibited excellent anti-interference performance in the degradation of aniline-containing contaminants in real water samples in the presence of diverse inorganic ions and organics. Subsequently, we extended the RQS-based process by employing tea extract and dissolved organic matter as catechol replacements as well as metal ions [e.g., Fe(III) or Cu(II)] as periodate replacements, which also exhibited good performance in aniline degradation. This study provides a novel strategy to develop RQS-based AOPs for the highly selective degradation of aniline-containing emerging contaminants.

High Chaos Induced Multiple-Anion-Rich Solvation Structure Enabling Ultrahigh Voltage and Wide Temperature Lithium-Metal Batteries.

The optimal electrolyte for ultrahigh energy density (>400 Wh/kg) lithium-metal batteries with a LiNi0.8Co0.1Mn0.1O2 cathode is required to withstand high voltage (≥4.7 V) and be adaptable over a wide temperature range. However, the battery performance is degraded by aggressive electrode-electrolyte reactions at high temperature and high voltage, while excessive growth of lithium dendrites usually occurs due to poor kinetics at low temperature. Accordingly, the development of electrolytes has encountered challenges in that there is almost no electrolyte simultaneously meeting the above requirements. Herein, a high chaos electrolyte design strategy is proposed, which promotes the formation of weak solvation structures involving multiple anions. By tailoring a Li+-EMC-DMC-DFOB--PO2F2--PF6- multiple-anion-rich solvation sheath, a robust inorganic-rich interphase is obtained for the electrode-electrolyte interphase (EEI), which is resistant to the intense interfacial reactions at high voltage (4.7 V) and high temperature (45 °C). In addition, the Li+ solvation is weakened by the multiple-anion solvation structure, which is a benefit to Li+ desolventization at low temperature (-30 °C), greatly improving the charge transfer kinetics and inhibiting the lithium dendrite growth. This work provides an innovative strategy to manipulate the high chaos electrolyte to further optimize solvation chemistry for high voltage and wide temperature applications.

Superb microvascular imaging for evaluation of microvascularity in breast nodules compared with conventional Doppler imaging.

Background: Neovascularity visualization in breast nodules is challenging due to the limitations of conventional Doppler imaging methods. This study aims to assess the performance of superb microvascular imaging (SMI) in evaluating the microvascularity of breast nodules (diameter ≤2 cm). The comparison of performances of SMI with color Doppler flow imaging (CDFI) and power Doppler imaging (PDI) was made by using a three-factor scoring system of vascularity. This study also investigated the common features of microvascularity in small malignant nodules on SMI for early differentiating from benign nodules. Methods: Ninety-one female patients (with 125 breast nodules) were enrolled in this retrospective study. All the breast nodules were examined by grayscale ultrasonography (US), CDFI, PDI, and SMI. The number, morphologic features, and distribution of blood vessels were scored to evaluate the nodular vascularity in light of the three-factor scoring system. The diagnostic value of SMI for microvascularity in breast nodules was analyzed and compared with CDFI and PDI. Results: Histological analysis showed 53 malignant and 72 benign nodules. The vascularity grades detected by SMI were significantly different from those of CDFI and PDI (P<0.05). SMI detected 47 grade-IV nodules of the total 125 nodules (37.6%), which was more than those detected by CDFI (10.4%, 13/125) and PDI (12.8%, 16/125), while more grade-I nodules were detected by CDFI (42.4%, 53/125) and PDI (36.8%, 46/125) compared with SMI (21.6%, 27/125). Differences in the vessel number, morphologic features, and distribution between benign and malignant breast nodules were significant on SMI (P<0.05). The vessel number ≥6, penetrating vessels, and a mixed distribution of vessels in peripheral and central nodular tissues were the common features of microvascularity in the grade-IV malignant nodules on SMI, whereas the blood vessels in the benign nodules were straight and branching and peripherally distributed. Conclusions: In comparison with CDFI and PDI, SMI enhances microvascularity detection, depicts the microvascular architecture in breast nodules and has potential in the differential diagnosis of malignant nodules from benign nodules.

Electrolyte Salts for Sodium-Ion Batteries: NaPF6 or NaClO4?

NaClO4 and NaPF6, the most universally adopted electrolyte salts in commercial sodium-ion batteries (SIBs), have a decisive influence on the interfacial chemistry, which is closely related to electrochemical performance. The complicated and ambiguous interior mechanism of microscopic interfacial chemistry has prevented reaching a consensus regarding the most suitable sodium salt for high-performance SIB electrolytes. Herein, we reveal that the solvation structure induced by different sodium salt anions determines the Na+ desolvation kinetics and interfacial film evolution process. Specifically, the weak interaction between Na+ and PF6- promoted sodium desolvation and storage kinetics. The solvation structure involving PF6- induced the anion's preferential decomposition, generating a thin, inorganic compound-rich cathode-electrolyte interphase that ensured interface stability and inhibited solvent decomposition, thereby guaranteeing electrode stability and promoting the charge transfer kinetics. This study provides clear evidence that NaPF6 is not only more compatible with industrial processes but also more conducive to battery performance. Commercial electrolyte design employing NaPF6 will undoubtedly promote the industrialization of SIBs.

Determination of excited triplet states of dissolved organic matter using chemical probes: A comparative and mechanistic study.

Dissolved organic matter (DOM) plays an important role in the biogeochemical cycle in natural waters. The determination and characterization of the excited triplet state of DOM (3DOM*) have attracted much attention recently. However, the underlying differences of determined 3DOM* through different pathways are not yet fully understood. In this study, the differences and underlying mechanisms of the determined 3DOM* using 2,4-hexadien-1-ol (HDO) through an energy transfer pathway and 2,4,6-trimethylphenol (TMP) through an electron transfer pathway, were investigated. The results showed that the determined quantum yields of 3DOM* (Φ3DOM*) for four commercial and four isolated local DOMs are different using HDO ((0.04 ± 0.00) × 10-2 to (2.9 ± 0.17) × 10-2)) and TMP ((0.08 ± 0.01) × 10-2 to (1.2 ± 0.17) × 10-2), respectively. For 17 DOM-analogs, significant differences were also observed with the quantum yields of their 3DOM* determined using HDO (ΦHDO) and the triplet-state quantum yield coefficients determined using TMP (fTMP). It indicates the different reactivity of TMP and HDO with the excited triplet of the chromophores with different structures within the isolated DOM. Based on the experimental and predicted values of fTMP and ΦHDO for different DOM-analogs, the impact of substituents on differences in 3DOM* values were further revealed. These results demonstrated that the levels of 3DOM* depended on the chemical functionalities present in the DOM-analogs.

Clinical characteristics and outcome correlates of Chinese patients with takotsubo syndrome: Results from the first Chinese takotsubo syndrome registry.

OBJECTIVE: To investigate clinical features and outcomes of Chinese patients with Takotsubo syndrome (TTS). METHODS: We established the first Chinese Registry of Takotsubo Syndrome (ChiTTS Registry) and analyzed demographic, clinical, therapeutical, and outcome data to characterize clinical and outcome features of Chinese TTS patients. RESULTS: In 112 enrolled patients in the ChiTTS registry from 02/01/2016 to 12/28/2021, the mean age was 59.4 ± 18.7 years old, and 27.7% were men. A total of 41.1% patients experienced respiratory and circulatory complications during hospitalization, and 17.3% patients developed cardiogenic shock. Physical triggers, dyspnea, tachycardia, and younger age (< 70 years old) predicted in-hospital complications. The MACCE rate during follow up was 13.9% per patient per year and the rate of all-cause death was 12.8% per patient per year. TTS patients with in-hospital complications developed more long-term MACCE (24.6% vs. 6.6% per patient-year, P < 0.001) and higher all-cause mortality (21.9% vs. 6.6% per patient-year, P = 0.001) than those without. The Kaplan-Meier survival analysis showed that more MACCE occurred in TTS patients with tachycardia during 3-year follow-up (HR 4.18; 95% CI 1.80-9.74; log-rank test P < 0.001). Among all medications at discharge, only beta-blocker was associated with reduced long-term MACCE (HR: 0.35; 95% CI: 0.12-0.996; P = 0.049). CONCLUSION: We investigated clinical and outcome features of patients in the first Chinese TTS Registry. Tachycardiac TTS patients developed more inpatient and long-term adverse cardiovascular events.

Detecting representative characteristics of different genders using intraoral photographs: a deep learning model with interpretation of gradient-weighted class activation mapping.

BACKGROUND: Sexual dimorphism is obvious not only in the overall architecture of human body, but also in intraoral details. Many studies have found a correlation between gender and morphometric features of teeth, such as mesio-distal diameter, buccal-lingual diameter and height. However, it's still difficult to detect gender through the observation of intraoral photographs, with accuracy around 50%. The purpose of this study was to explore the possibility of automatically telling gender from intraoral photographs by deep neural network, and to provide a novel angle for individual oral treatment. METHODS: A deep learning model based on R-net was proposed, using the largest dataset (10,000 intraoral images) to support the automatic detection of gender. In order to reverse analyze the classification basis of neural network, Gradient-weighted Class Activation Mapping (Grad-CAM) was used in the second step, exploring anatomical factors associated with gender recognizability. The simulated modification of images based on features suggested was then conducted to verify the importance of characteristics between two genders. Precision (specificity), recall (sensitivity) and receiver operating characteristic (ROC) curves were used to evaluate the performance of our network. Chi-square test was used to evaluate intergroup difference. A value of p < 0.05 was considered statistically significant. RESULTS: The deep learning model showed a strong ability to learn features from intraoral images compared with human experts, with an accuracy of 86.5% and 82.5% in uncropped image data group and cropped image data group respectively. Compared with hard tissue exposed in the mouth, gender difference in areas covered by soft tissue was easier to identify, and more significant in mandibular region than in maxillary region. For photographs with simulated removal of lips and basal bone along with overlapping gingiva, mandibular anterior teeth had similar importance for sex determination as maxillary anterior teeth. CONCLUSIONS: Deep learning method could detect gender from intraoral photographs with high efficiency and accuracy. With assistance of Grad-CAM, the classification basis of neural network was deciphered, which provided a more precise entry point for individualization of prosthodontic, periodontal and orthodontic treatments.

Dark repair of sunlight-inactivated tetracycline-resistant bacteria: Mechanisms and important role of bacteria in viable but non-culturable state.

The spread of antibiotic resistant bacteria (ARB) in the environment poses a potential threat to human health, and the reactivation of inactivated ARB accelerated the spread of ARB. However, little is known about the reactivation of sunlight-inactivated ARB in natural waters. In this study, the reactivation of sunlight-inactivated ARB in dark conditions was investigated with tetracycline-resistant E. coli (Tc-AR E. coli) as a representative. Results showed that sunlight-inactivated Tc-AR E. coli underwent dark repair to regain tetracycline resistance with dark repair ratios increasing from (0.124 ± 0.012)‱ within 24 h dark treatment to (0.891 ± 0.033)‱ within 48 h. The presence of Suwannee River fulvic acid (SRFA) promoted the reactivation of sunlight-inactivated Tc-AR E. coli and tetracycline inhibited their reactivation. The reactivation of sunlight-inactivated Tc-AR E. coli is mainly attributed to the repair of the tetracycline-specific efflux pump in the cell membrane. Tc-AR E. coli in a viable but non-culturable (VBNC) state was observed and dominated the reactivation as the inactivated ARB remain present in the dark for more than 20 h. These results explained the reason for distribution difference of Tc-ARB at different depths in natural waters, which are of great significance for understanding the environmental behavior of ARB.

Sestrin2-mediated disassembly of stress granules dampens aerobic glycolysis to overcome glucose starvation.

Sestrins are a small gene family of pleiotropic factors whose actions promote cell adaptation to a range of stress conditions. In this report we disclose the selective role of Sestrin2 (SESN2) in dampening aerobic glycolysis to adapt to limiting glucose conditions. Removal of glucose from hepatocellular carcinoma (HCC) cells inhibits glycolysis associated with the downregulation of the rate-limiting glycolytic enzyme hexokinase 2 (HK2). Moreover, the accompanying upregulation of SESN2 through an NRF2/ATF4-dependent mechanism plays a direct role in HK2 regulation by destabilizing HK2 mRNA. We show SESN2 competes with insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) for binding with the 3'-UTR region of HK2 mRNA. Interactions between IGF2BP3 and HK2 mRNA result in their coalescence into stress granules via liquid-liquid phase separation (LLPS), a process which serves to stabilize HK2 mRNA. Conversely, the enhanced expression and cytoplasmic localization of SESN2 under glucose deprivation conditions favors the downregulation of HK2 levels via decreases in the half-life of HK2 mRNA. The resulting dampening of glucose uptake and glycolytic flux inhibits cell proliferation and protect cells from glucose starvation-induced apoptotic cell death. Collectively, our findings reveal an intrinsic survival mechanism allowing cancer cells to overcome chronic glucose shortages, also providing new mechanistic insights into SESN2 as an RNA-binding protein with a role in reprogramming of cancer cell metabolism.