High-quality integratable microlasers from scalable perovskite heterostructures enabled by solution-phase processing.

High-performance transferable and integratable microlasers hold great promise to construct the integrated photonics and optoelectronics. However, the qualified candidates are still being pursued. Herein, a mass-production of low-threshold and wavelength-tunable microlasers that is readily integratable with the optical fiber platform is realized by a two-step solution-phase approach. The demonstration is enabled by the formation of a novel semiconductor heterostructure from halide perovskites featuring the quasi-free-standing and highly emissive properties. Corroborated by the in-situ optical characterization, we reveal that the lateral perovskite heterostructures are constructed through a sequential reaction driven by the surface energy contrast. These perovskite heterostructures exhibit low-threshold and broadband tunable lasing action thanks to the efficient spatial light conversion nature and the facile composition tunability. Taking the merits together, the heterostructure microlasers can be the competitive applicants for photonic integration as demonstrated by the laser-on-fiber configuration.

Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) protect against diabetic cardiovascular diseases and nephropathy. However, their activity in diabetic retinopathy (DR) remains unclear. Our retrospective cohort study involving 1626 T2DM patients revealed superior efficacy of GLP-1 RAs in controlling DR compared to other glucose-lowering medications, suggesting their advantage in DR treatment. By single-cell RNA-sequencing analysis and immunostaining, we observed a high expression of GLP-1R in retinal endothelial cells, which was down-regulated under diabetic conditions. Treatment of GLP-1 RAs significantly restored the receptor expression, resulting in an improvement in retinal degeneration, vascular tortuosity, avascular vessels, and vascular integrity in diabetic mice. GO and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 RAs. Additionally, the treatment attenuated STING signaling activation in retinal endothelial cells, which is typically activated by leaked mitochondrial DNA. Expression of STING mRNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular membranes. Further investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1R signaling pathway on suppression of STING signaling. This study demonstrates a novel role of GLP-1 RAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

Impact of meteorological variability on diurnal and seasonal net ecosystem productivity in a desert riparian forest ecosystem.

The desert riparian forests are susceptible to meteorological changes and contribute significantly to the net ecosystem productivity (NEP) variations of arid ecosystems. However, the responsive patterns of their NEP variations to the meteorological variabilities remain inadequately comprehended. To address this gap, we utilized seven years of eddy covariance flux measurements in a representative desert riparian forest to investigate the NEP variations and its response to changing meteorological factors across diverse temporal scales. The results revealed significant periodic variations in half-hourly NEP, with dominant cycles spanning from five hours to one year, with a principal oscillation period of one day. Key meteorological factors including global solar radiation (Rg), relative humidity (RH), air temperature (Ta), soil temperature (Ts), and vapor pressure deficit (VPD) exhibited synchronization with NEP on daily scales. This synchronization, coupled with the observed one-day periodic NEP variations, provides robust evidence supporting the existence of a circadian rhythm in the ecosystem carbon exchange of desert riparian forest regulated by meteorological conditions. Seasonal patterns were significant in the impact of Rg phase, Ta diurnal amplitude, and VPD diurnal amplitude on NEP diurnal amplitude and phase. The NEP diurnal amplitude significantly, directly, and positively affected daily NEP in both the dormant and growing seasons, whereas its phase yielded significant negative effects (P< 0.05). The averages, amplitudes, and phases of diurnal meteorological conditions controlled the daily NEP by regulating NEP diurnal amplitude and phase. These findings provide evidence that the variability in circadian rhythms, caused by the increase in diurnal Ta and VPD, significantly impact the daily NEP at an ecosystem scale. This study enriches our comprehension of the meteorological mechanisms governing diurnal and seasonal carbon uptake dynamics within desert riparian forests, providing fresh insights into the direct and indirect roles of climate change in shaping patterns of ecosystem carbon exchange.

Cellular communication network factor 1 promotes retinal leakage in diabetic retinopathy via inducing neutrophil stasis and neutrophil extracellular traps extrusion.

BACKGROUND: Diabetic retinopathy (DR) is a major cause of blindness and is characterized by dysfunction of the retinal microvasculature. Neutrophil stasis, resulting in retinal inflammation and the occlusion of retinal microvessels, is a key mechanism driving DR. These plugging neutrophils subsequently release neutrophil extracellular traps (NETs), which further disrupts the retinal vasculature. Nevertheless, the primary catalyst for NETs extrusion in the retinal microenvironment under diabetic conditions remains unidentified. In recent studies, cellular communication network factor 1 (CCN1) has emerged as a central molecule modulating inflammation in pathological settings. Additionally, our previous research has shed light on the pathogenic role of CCN1 in maintaining endothelial integrity. However, the precise role of CCN1 in microvascular occlusion and its potential interaction with neutrophils in diabetic retinopathy have not yet been investigated. METHODS: We first examined the circulating level of CCN1 and NETs in our study cohort and analyzed related clinical parameters. To further evaluate the effects of CCN1 in vivo, we used recombinant CCN1 protein and CCN1 overexpression for gain-of-function, and CCN1 knockdown for loss-of-function by intravitreal injection in diabetic mice. The underlying mechanisms were further validated on human and mouse primary neutrophils and dHL60 cells. RESULTS: We detected increases in CCN1 and neutrophil elastase in the plasma of DR patients and the retinas of diabetic mice. CCN1 gain-of-function in the retina resulted in neutrophil stasis, NETs extrusion, capillary degeneration, and retinal leakage. Pre-treatment with DNase I to reduce NETs effectively eliminated CCN1-induced retinal leakage. Notably, both CCN1 knockdown and DNase I treatment rescued the retinal leakage in the context of diabetes. In vitro, CCN1 promoted adherence, migration, and NETs extrusion of neutrophils. CONCLUSION: In this study, we uncover that CCN1 contributed to retinal inflammation, vessel occlusion and leakage by recruiting neutrophils and triggering NETs extrusion under diabetic conditions. Notably, manipulating CCN1 was able to hold therapeutic promise for the treatment of diabetic retinopathy.

Morphologies and magnetic properties of α-Fe2O3 nanoparticles calcined at different temperatures.

Different morphologies and sizes of α-Fe2O3 were prepared by a coprecipitation method using polyvinylpyrrolidone as a dispersant. In the preparation process, homogeneous and dispersed nanoscale FeOOH particles were first obtained by the coprecipitation method, and then the FeOOH particles were calcined at high temperature to form α-Fe2O3. The growth and aggregation of the α-Fe2O3 particles at different calcination temperatures resulted in α-Fe2O3 powders with diversiform morphologies (nanoscale microsphere, pinecone ellipsoidal, polyhedral, and quasi-spherical structures). By analyzing the SEM images, it was inferred that the polyhedral structure of α-Fe2O3 particles was formed by the accumulation of rhomboid sheet structures and high-temperature growth. In terms of the magnetic properties, the samples belonged to the class of canted antiferromagnetic materials, and the morphology, particle size, and crystallite size of the α-Fe2O3 particles were important factors affecting the coercivity. Among these, when the calcination temperature was increased from 700 °C to 800 °C, the growth rate of the particle size was significantly faster than that of the crystallite size, and the coercivity increased substantially from 1411 Oe to 2688 Oe.

Cholesterol-induced HRD1 reduction accelerates vascular smooth muscle cell senescence via stimulation of endoplasmic reticulum stress-induced reactive oxygen species.

Senescence of vascular smooth muscle cells (VSMCs) is a key contributor to plaque vulnerability in atherosclerosis (AS), which is affected by endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production. However, the crosstalk between ER stress and ROS production in the pathogenesis of VSMC senescence remains to be elucidated. ER-associated degradation (ERAD) is a complex process that clears unfolded or misfolded proteins to maintain ER homeostasis. HRD1 is the major E3 ligase in mammalian ERAD machineries that catalyzes ubiquitin conjugation to the unfolded or misfolded proteins for degradation. Our results showed that HRD1 protein levels were reduced in human AS plaques and aortic roots from ApoE-/- mice fed with high-fat diet (HFD), along with the increased ER stress response. Exposure to cholesterol in VSMCs activated inflammatory signaling and induced senescence, while reduced HRD1 protein expression. CRISPR Cas9-mediated HRD1 knockout (KO) exacerbated cholesterol- and thapsigargin-induced cell senescence. Inhibiting ER stress with 4-PBA (4-Phenylbutyric acid) partially reversed the ROS production and cell senescence induced by HRD1 deficiency in VSMCs, suggesting that ER stress alone could be sufficient to induce ROS production and senescence in VSMCs. Besides, HRD1 deficiency led to mitochondrial dysfunction, and reducing ROS production from impaired mitochondria partly reversed HRD1 deficiency-induced cell senescence. Finally, we showed that the overexpression of HDR1 reversed cholesterol-induced ER stress, ROS production, and cellular senescence in VSMCs. Our findings indicate that HRD1 protects against senescence by maintaining ER homeostasis and mitochondrial functionality. Thus, targeting HRD1 function may help to mitigate VSMC senescence and prevent vascular aging related diseases. TRIAL REGISTRATION: A real-world study based on the discussion of primary and secondary prevention strategies for coronary heart disease, URL:https://www.clinicaltrials.gov, the trial registration number is [2022]-02-121-01.

HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress.

Phenotypic change of vascular smooth muscle cells (VSMCs) is the main contributor of vascular pathological remodeling in atherosclerosis. The endoplasmic reticulum (ER) is critical for maintaining VSMC function through elimination of misfolded proteins that impair VSMC cellular function. ER-associated degradation (ERAD) is an ER-mediated process that controls protein quality by clearing misfolded proteins. One of the critical regulators of ERAD is HRD1, which also plays a vital role in lipid metabolism. However, the function of HRD1 in VSMCs of atherosclerotic vessels remains poorly understood. The level of HRD1 expression was analyzed in aortic tissues of mice fed with a high-fat diet (HFD). The H&E and EVG (VERHOEFF'S VAN GIESON) staining were used to demonstrate pathological vascular changes. IF (immunofluorescence) and WB (western blot) were used to explore the signaling pathways in vivo and in vitro. The wound closure and transwell assays were also used to test the migration rate of VSMCs. CRISPR gene editing and transcriptomic analysis were applied in vitro to explore the cellular mechanism. Our data showed significant reduction of HRD1 in aortic tissues of mice under HFD feeding. VSMC phenotypic change and HRD1 downregulation were detected by cholesterol supplement. Transcriptomic and further analysis of HRD1-KO VSMCs showed that HRD1 deficiency induced the expression of genes related to ER stress response, proliferation and migration, but reduced the contractile-related genes in VSMCs. HRD1 deficiency also exacerbated the proliferation, migration and ROS production of VSMCs induced by cholesterol, which promoted the VSMC dedifferentiation. Our results showed that HRD1 played an essential role in the contractile homeostasis of VSMCs by negatively regulating ER stress response. Thus, HRD1 in VSMCs could serve as a potential therapeutic target in metabolic disorder-induced vascular remodeling.

CRISPR screen identifies the role of RBBP8 in mediating unfolded protein response induced liver damage through regulating protein synthesis.

Unfolded protein response (UPR) maintains the endoplasmic reticulum (ER) homeostasis, survival, and physiological function of mammalian cells. However, how cells adapt to ER stress under physiological or disease settings remains largely unclear. Here by a genome-wide CRISPR screen, we identified that RBBP8, an endonuclease involved in DNA damage repair, is required for ATF4 activation under ER stress in vitro. RNA-seq analysis suggested that RBBP8 deletion led to impaired cell cycle progression, retarded proliferation, attenuated ATF4 activation, and reduced global protein synthesis under ER stress. Mouse tissue analysis revealed that RBBP8 was highly expressed in the liver, and its expression is responsive to ER stress by tunicamycin intraperitoneal injection. Hepatocytes with RBBP8 inhibition by adenovirus-mediated shRNA were resistant to tunicamycin (Tm)-induced liver damage, cell death, and ER stress response. To study the pathological role of RBBP8 in regulating ATF4 activity, we illustrated that both RBBP8 and ATF4 were highly expressed in liver cancer tissues compared with healthy controls and highly expressed in Ki67-positive proliferating cells within the tumors. Interestingly, overexpression of RBBP8 in vitro promoted ATF4 activation under ER stress, and RBBP8 expression showed a positive correlation with ATF4 expression in liver cancer tissues by co-immunostaining. Our findings provide new insights into the mechanism of how cells adapt to ER stress through the crosstalk between the nucleus and ER and how tumor cells survive under chemotherapy or other anticancer treatments, which suggests potential therapeutic strategies against liver disease by targeting DNA damage repair, UPR or protein synthesis.

ER stress aggravates diaphragm weakness through activating PERK/JNK signaling in obesity hypoventilation syndrome.

OBJECTIVE: Obesity hypoventilation syndrome is associated with diaphragmatic dysfunction. This study aimed to explore the role of endoplasmic reticulum (ER) stress in mediating obesity-induced diaphragmatic dysfunction. METHODS: A pulmonary function test and ultrasound were applied to evaluate diaphragmatic function and magnetic resonance imaging was applied to measure diaphragmatic lipid deposition in human patients. For the mechanistic study, obese mice were introduced to a high-fat diet for 24 weeks, followed by diaphragmatic ultrasound measurement, transcriptomic sequencing, and respective biochemical analysis. Automatic force mapping was applied to measure the mechanical properties of C2C12 myotubes. RESULTS: People with obesity showed significant diaphragm weakness and lipid accumulation, which was further confirmed in obese mice. Consistently, diaphragms from obese mice showed altered gene expression profile in lipid metabolism and activation of ER stress response, indicated by elevated protein kinase R-like ER kinase (PERK) and c-Jun NH2 -terminal kinase (JNK) activation. In C2C12 myotubes, inhibition of PERK or JNK signaling abrogated lipotoxicity-induced intracellular lipid deposition and insulin resistance. Inhibition of JNK signaling reversed lipotoxicity-induced impairment of elasticity in C2C12 myotubes. CONCLUSIONS: These data suggest that ectopic lipid deposition impairs the diaphragmatic function of people with obesity. Activation of PERK/JNK signaling is involved in the pathogenesis of lipotoxicity-induced diaphragm weakness in obesity hypoventilation syndrome.

Multilevel resistive switching in stable all-inorganic n-i-p double perovskite memristor.

Memristors are promising information storage devices for commercial applications because of their long endurance and low power consumption. Particularly, perovskite memristors have revealed excellent resistive switching (RS) properties owing to the fast ion migration and solution fabrication process. Here, an n-i-p type double perovskite memristor with "ITO/SnO2/Cs2AgBiBr6/NiOx/Ag" architecture was developed and demonstrated to reveal three resistance states because of the p-n junction electric field coupled with ion migration. The devices exhibited reliable filamentary with an on/off ratio exceeding 50. The RS characteristics remained unchanged after 1000 s read and 300 switching cycles. The synaptic functions were examined through long-term depression and potentiation measurements. Significantly, the device still worked after one year to reveal long-term stability because of the all-inorganic layers. This work indicates a novel idea for designing a multistate memristor by utilizing the p-n junction unidirectional conductivity during the forward and reverse scanning.

Secreted MUP1 that reduced under ER stress attenuates ER stress induced insulin resistance through suppressing protein synthesis in hepatocytes.

Disturbed endoplasmic reticulum (ER) stress response driven by the excessive lipid accumulation in the liver is a characteristic feature in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Restoring metabolic homeostasis by targeting ER stress is a potentially therapeutic strategy for NAFLD. Here we aim to identify novel proteins or pathways involved in regulating ER stress response and therapeutic targets for alleviating NAFLD. Proteomic and transcriptomic analysis demonstrated that major urinary proteins (MUPs) were significantly reduced in the livers from NAFLD mouse models. Then we confirmed that MUP1, the major secreted form of MUPs, was reduced at mRNA and protein expression levels in hepatocytes both in vivo and in vitro under ER stress. We further illustrated that MUP1 protein levels in the urine were reduced in mice with NAFLD, which was reversed by GLP-1 receptor agonist treatment. To study the relationship between ER stress and MUP1 biology, our analysis demonstrated that MUP1 was misfolded and trapped in the ER under ER stress in vivo. Interestingly, we discovered that recombinant MUP1 treatment in hepatocytes increased calcium efflux from the ER, which resulted in transient ER stress response, including reduced protein synthesis. These responses facilitated the alleviation of chemical induced ER stress in hepatocytes, which was suggested as "pre-adaptive ER stress". Besides, recombinant MUP1 pretreatment also improved ER stress-induced insulin resistance in hepatocytes. Our findings revealed a novel and critical role of MUP1, and recombinant MUP1 or its potential derivates may serve as a promising therapeutic target for alleviating NAFLD.

Characterization of dietary and herbal sourced natural compounds that modulate SEL1L-HRD1 ERAD activity and alleviate protein misfolding in the ER.

Dysregulated production of peptide hormones is the key pathogenic factor of various endocrine diseases. Endoplasmic reticulum (ER) associated degradation (ERAD) is a critical machinery in maintaining ER proteostasis in mammalian cells by degrading misfolded proteins. Dysfunction of ERAD leads to maturation defect of many peptide hormones, such as provasopressin (proAVP), which results in the occurrence of Central Diabetes Insipidus. However, drugs targeting ERAD to regulate the production of peptide hormones are very limited. Herbal products provide not only nutritional sources, but also alternative therapeutics for chronic diseases. Virtual screening provides an effective and high-throughput strategy for identifying protein structure-based interacting compounds extracted from a variety of dietary or herbal sources, which could be served as (pro)drugs for preventing or treating endocrine diseases. Here, we performed a virtual screening by directly targeting SEL1L of the most conserved SEL1L-HRD1 ERAD machinery. Further, we analyzed 58 top-ranked compounds and demonstrated that Cryptochlorogenic acid (CCA) showed strong affinity with the binding pocket of SEL1L with HRD1. Through structure-based docking, protein expression assays, and FACS analysis, we revealed that CCA enhanced ERAD activity and promoted the degradation of misfolded proAVP, thus facilitated the secretion of well-folded proAVP. These results provide us with insights into drug discovery strategies targeting ER protein homeostasis, as well as candidate compounds for treating hormone-related diseases.

Hyperlipidemia induces proinflammatory responses by activating STING pathway through IRE1α-XBP1 in retinal endothelial cells.

Diabetic retinopathy (DR) is one of the most prevalent microvascular complications caused by diabetes mellitus. Previous studies demonstrate that microvascular endothelial inflammation caused by chronic hyperglycemia and hyperlipidemia plays a key role in the pathogenesis of DR. However, the detailed mechanisms on how endothelial inflammation contributes to DR are not fully understood. The STING pathway is an important innate immune signaling pathway. Although STING has been implicated in multiple autoimmune and metabolic diseases, it is not clear whether STING is involved in the pathogenesis of DR. Thus, re-analysis of the public single cell RNA sequencing (sc-RNAseq) data demonstrated that STING was highly expressed in mouse retinal vessels. Moreover, our results demonstrated that STING and p-TBK1 protein levels in retinal endothelial cells are significantly increased in mice fed with high fat diet compared with chow diet. In vitro, palmitic acid treatment on HRVECs induced mitochondrial DNA leakage into the cytosol, and augmented p-TBK1 protein and IFN-ß mRNA levels. As STING is localized to the ER, we analyzed the relation between STING activation and ER stress. In HRVECs, STING pathway was shown to be activated under chemical-induced ER stress, but attenuated when IRE1α was abolished by genetic deletion or pharmacological inhibition. Taken together, our findings revealed that STING signaling plays an important role in mediating lipotoxicity-induced endothelial inflammatory and injury, and IRE1α-XBP1 signaling potentiated STING signaling. Thus, targeting the IRE1α or STING pathways to alleviate endothelial inflammation provides candidate therapeutic target for treating DR as well as other microvascular complications.

Ferroelectric polarization effect on the photocatalytic activity of Bi0.9Ca0.1FeO3/CdS S-scheme nanocomposites.

BiFeO3 (BFO), as a kind of narrow band-gap semiconductor material, has gradually emerged advantages in the application of photocatalysis. In this paper, Ca doped BFO nanoparticles Bi0.9Ca0.1FeO3 (BCFO) were prepared by sol-gel method. And BCFO and CdS nanocomposites with two morphologies were obtained by controlling the time of loading CdS under a low temperature liquid phase process. It is found that the band gap becomes narrower after doping Ca into BFO, which is conducive to the absorption of visible light. Among all the samples, the composite of CdS nanowires and BCFO nanoparticles obtained by reaction time of 10 min has the best photocatalytic performance. The degradation rate of Methyl Orange solution was 94% after 90 min under visible light irradiation, which was much higher than that of pure BCFO and CdS. Furthermore, significant enhancement in the degradation rate (100% degradation in 60 min) can be achieved in poled samples after electric polarization process. The highest degradation rate is due to the promoted separation of photogenerated carriers induced by the internal polarization field and the formation of S-scheme heterostructure between BCFO and CdS. Such BCFO-CdS nanocomposites may bring new insights into designing highly efficient photocatalyst.

Large plants enhance aboveground biomass in arid natural forest and plantation along differential abiotic and biotic conditions.

Big-sized trees, species diversity, and stand density affect aboveground biomass in natural tropical and temperate forests. However, these relationships are unclear in arid natural forests and plantations. Here, we hypothesized that large plants (a latent variable of tall-stature and big-crown, which indicated the effect of big-sized trees on ecosystem function and structure) enhance aboveground biomass in both arid natural forests and plantations along the gradients of climate water availability and soil fertility. To prove it, we used structural equation modeling (SEM) to test the influences of large plants located in 20% of the sequence formed by individual size (a synthetical value calculated from tree height and crown) on aboveground biomass in natural forests and plantations while considering the direct and indirect influences of species diversity as well as climatic and soil conditions, using data from 73 natural forest and 30 plantation plots in the northwest arid region of China. The results showed that large plants, species diversity, and stand density all increased aboveground biomass. Soil fertility declined aboveground biomass in natural forest, whereas it increased biomass in plantation. Although climatic water availability had no direct impact on aboveground biomass in both forests, it indirectly controlled the change of aboveground biomass via species diversity, stand density, and large plants. Stand density negatively affects large plants in both natural forests and plantations. Species diversity positively affects large plants on plantations but not in natural forests. Large plants increased slightly with increasing climatic water availability in the natural forest but decreased in plantation, whereas soil fertility inhibited large plants in plantation only. This study highlights the extended generality of the big-sized trees hypothesis, scaling theory, and the global importance of big-sized tree in arid natural forests and plantations.

Uterine rupture after previous caesarean section with hysterotomy above the lower uterine segment.

Background Spontaneous uterine rupture is a severe pregnancy complication. Several risk factors have been described, especially for women with a previous caesarean section. Method We reported two cases of uterine rupture (UR) occurring outside of labour in patients with a history of caesarean section (CS) due to placenta previa. Results: The current study evaluates how a higher hysterotomy, combined with some risk factors, can increase the prevalence of UR in the subsequent pregnancy. Conclusion This study supports that a careful evaluation of risk factors can identify patients who need a specific follow up to early diagnose and treat UR and thus improve the maternal-fetal outcome.

LASSO Regression-Based Diagnosis of Acute ST-Segment Elevation Myocardial Infarction (STEMI) on Electrocardiogram (ECG).

Electrocardiogram (ECG) is an important tool for the detection of acute ST-segment elevation myocardial infarction (STEMI). However, machine learning (ML) for the diagnosis of STEMI complicated with arrhythmia and infarct-related arteries is still underdeveloped based on real-world data. Therefore, we aimed to develop an ML model using the Least Absolute Shrinkage and Selection Operator (LASSO) to automatically diagnose acute STEMI based on ECG features. A total of 318 patients with STEMI and 502 control subjects were enrolled from Jan 2017 to Jun 2019. Coronary angiography was performed. A total of 180 automatic ECG features of 12-lead ECG were input into the model. The LASSO regression model was trained and validated by the internal training dataset and tested by the internal and external testing datasets. A comparative test was performed between the LASSO regression model and different levels of doctors. To identify the STEMI and non-STEMI, the LASSO model retained 14 variables with AUCs of 0.94 and 0.93 in the internal and external testing datasets, respectively. The performance of LASSO regression was similar to that of experienced cardiologists (AUC: 0.92) but superior (p < 0.05) to internal medicine residents, medical interns, and emergency physicians. Furthermore, in terms of identifying left anterior descending (LAD) or non-LAD, LASSO regression achieved AUCs of 0.92 and 0.98 in the internal and external testing datasets, respectively. This LASSO regression model can achieve high accuracy in diagnosing STEMI and LAD vessel disease, thus providing an assisting diagnostic tool based on ECG, which may improve the early diagnosis of STEMI.

Differed Growth Stage Dynamics of Root-Associated Bacterial and Fungal Community Structure Associated with Halophytic Plant Lycium ruthenicum.

Lycium ruthenicum, a halophytic shrub, has been used to remediate saline soils in northwest China. However, little is known about its root-associated microbial community and how it may be affected by the plant's growth cycle. In this study, we investigate the microbial community structure of L. ruthenicum by examining three root compartments (rhizosphere, rhizoplane, and endosphere) during four growth stages (vegetative, flowering, fruiting, and senescence). The microbial community diversity and composition were determined by Illumina MiSeq sequencing of the 16S V3-V4 and 18S ITS regions. Proteobacteria, Actinobacteria, Bacteroidetes, Planctomycetes, and Acidobacteria were the dominant bacterial phyla, while Ascomycota, Basidiomycota, and Mortierellomycota were the most dominant fungal phyla. The alpha diversity of the bacterial communities was highest in the rhizosphere and decreased from the rhizosphere to the endosphere compartments; the fungal communities did not show a consistent trend. The rhizosphere, rhizoplane, and endosphere had distinct bacterial community structures among the three root compartments and from the bulk soil. Additionally, PERMANOVA indicated that the effect of rhizocompartments explained a large proportion of the total community variation. Differential and biomarker analysis not only revealed that each compartment had unique biomarkers and was enriched for specific bacteria, but also that the biomarkers changed with the plant growth cycle. Fungi were also affected by the rhizocompartment, but to a much less so than bacteria, with significant differences in the community composition along the root compartments observed only during the vegetative and flowering stages. Instead, the growth stages appear to account for most of the fungal community variation as demonstrated by PCoA and NMDS, and supported by differential and biomarker analysis, which revealed that the fungal community composition in the rhizosphere and endosphere were dynamic in response to the growth stage. Many enriched OTUs or biomarkers that were identified in the root compartments were potentially beneficial to the plant, meanwhile, some harmful OTUs were excluded from the root, implying that the host plant can select for beneficial bacteria and fungi, which can promote plant growth or increase salt tolerance. In conclusion, the root compartment and growth stage were both determinant factors in structuring the microbial communities of L. ruthenicum, but the effects were different in bacteria and fungi, suggesting that bacterial and fungal community structures respond differently to these growth factors.

Deep learning assessment of left ventricular hypertrophy based on electrocardiogram.

Background: Current electrocardiogram (ECG) criteria of left ventricular hypertrophy (LVH) have low sensitivity. Deep learning (DL) techniques have been widely used to detect cardiac diseases due to its ability of automatic feature extraction of ECG. However, DL was rarely applied in LVH diagnosis. Our study aimed to construct a DL model for rapid and effective detection of LVH using 12-lead ECG. Methods: We built a DL model based on convolutional neural network-long short-term memory (CNN-LSTM) to detect LVH using 12-lead ECG. The echocardiogram and ECG of 1,863 patients obtained within 1 week after hospital admission were analyzed. Patients were evenly allocated into 3 sets at 3:1:1 ratio: the training set (n = 1,120), the validation set (n = 371) and the test set 1 (n = 372). In addition, we recruited 453 hospitalized patients into the internal test set 2. Different DL model of each subgroup was developed according to gender and relative wall thickness (RWT). Results: The LVH was predicted by the CNN-LSTM model with an area under the curve (AUC) of 0.62 (sensitivity 68%, specificity 57%) in the test set 1, which outperformed Cornell voltage criteria (AUC: 0.57, sensitivity 48%, specificity 72%) and Sokolow-Lyon voltage (AUC: 0.51, sensitivity 14%, specificity 96%). In the internal test set 2, the CNN-LSTM model had a stable performance in predicting LVH with an AUC of 0.59 (sensitivity 65%, specificity 57%). In the subgroup analysis, the CNN-LSTM model predicted LVH by 12-lead ECG with an AUC of 0.66 (sensitivity 72%, specificity 60%) for male patients, which performed better than that for female patients (AUC: 0.59, sensitivity 50%, specificity 71%). Conclusion: Our study established a CNN-LSTM model to diagnose LVH by 12-lead ECG with higher sensitivity than current ECG diagnostic criteria. This CNN-LSTM model may be a simple and effective screening tool of LVH.