Flatband λ-Ti3O5 towards extraordinary solar steam generation.

Solar steam interfacial evaporation represents a promising strategy for seawater desalination and wastewater purification owing to its environmentally friendly character1-3. To improve the solar-to-steam generation, most previous efforts have focused on effectively harvesting solar energy over the full solar spectrum4-7. However, the importance of tuning joint densities of states in enhancing solar absorption of photothermal materials is less emphasized. Here we propose a route to greatly elevate joint densities of states by introducing a flat-band electronic structure. Our study reveals that metallic λ-Ti3O5 powders show a high solar absorptivity of 96.4% due to Ti-Ti dimer-induced flat bands around the Fermi level. By incorporating them into three-dimensional porous hydrogel-based evaporators with a conical cavity, an unprecedentedly high evaporation rate of roughly 6.09 kilograms per square metre per hour is achieved for 3.5 weight percent saline water under 1 sun of irradiation without salt precipitation. Fundamentally, the Ti-Ti dimers and U-shaped groove structure exposed on the λ-Ti3O5 surface facilitate the dissociation of adsorbed water molecules and benefit the interfacial water evaporation in the form of small clusters. The present work highlights the crucial roles of Ti-Ti dimer-induced flat bands in enchaining solar absorption and peculiar U-shaped grooves in promoting water dissociation, offering insights into access to cost-effective solar-to-steam generation.

LncRNA-SERB promotes vasculogenic mimicry (VM) formation and tumor metastasis in renal cell carcinoma.

A growing body of evidence shows that vasculogenic mimicry (VM) is closely related to the invasion and metastasis of many tumor cells. Although the estrogen receptor (ER) can promote initiation and progression of renal cell carcinoma (RCC), how the downstream biomolecules are involved, and the detailed mechanisms of how ER expression is elevated in RCC remain to be further elucidated. Here, we discovered that long noncoding RNA (LncRNA)-SERB is highly expressed in tumor cells of RCC patients. We used multiple RCC cells and an in vivo mouse model for our study, and results indicated that LncRNA-SERB could boost RCC VM formation and cell invasion in vitro and in vivo. Although a previous report showed that ERß can affect the VM formation in RCC, it is unclear which factor could upregulate ERß. This is the first study to show LncRNA-SERB can be the upstream regulator of ERß to control RCC progression. Mechanistically, LncRNA-SERB may increase ERß via binding to the promoter area, and ERß functions through transcriptional regulation of zinc finger E-box binding homeobox 1 (ZEB1) to regulate VM formation. These results suggest that LncRNA-SERB promotes RCC cell VM formation and invasion by upregulating the ERß/ZEB1 axis and that therapeutic targeting of this newly identified pathway may better inhibit RCC progression.

Permanent fluidic magnets for liquid bioelectronics.

Brownian motion allows microscopically dispersed nanoparticles to be stable in ferrofluids, as well as causes magnetization relaxation and prohibits permanent magnetism. Here we decoupled the particle Brownian motion from colloidal stability to achieve a permanent fluidic magnet with high magnetization, flowability and reconfigurability. The key to create such permanent fluidic magnets is to maintain a stable magnetic colloidal fluid by using non-Brownian magnetic particles to self-assemble a three-dimensional oriented and ramified magnetic network structure in the carrier fluid. This structure has high coercivity and permanent magnetization, with long-term magnetization stability. We establish a scaling theory model to decipher the permanent fluid magnet formation criteria and formulate a general assembly guideline. Further, we develop injectable and retrievable permanent-fluidic-magnet-based liquid bioelectronics for highly sensitive, self-powered wireless cardiovascular monitoring. Overall, our findings highlight the potential of permanent fluidic magnets as an ultrasoft material for liquid devices and systems, from bioelectronics to robotics.

Parafibromin governs cell polarity and centrosome assembly in Drosophila neural stem cells.

Neural stem cells (NSCs) divide asymmetrically to balance their self-renewal and differentiation, an imbalance in which can lead to NSC overgrowth and tumor formation. The functions of Parafibromin, a conserved tumor suppressor, in the nervous system are not established. Here, we demonstrate that Drosophila Parafibromin/Hyrax (Hyx) inhibits ectopic NSC formation by governing cell polarity. Hyx is essential for the asymmetric distribution and/or maintenance of polarity proteins. hyx depletion results in the symmetric division of NSCs, leading to the formation of supernumerary NSCs in the larval brain. Importantly, we show that human Parafibromin rescues the ectopic NSC phenotype in Drosophila hyx mutant brains. We have also discovered that Hyx is required for the proper formation of interphase microtubule-organizing center and mitotic spindles in NSCs. Moreover, Hyx is required for the proper localization of 2 key centrosomal proteins, Polo and AurA, and the microtubule-binding proteins Msps and D-TACC in dividing NSCs. Furthermore, Hyx directly regulates the polo and aurA expression in vitro. Finally, overexpression of polo and aurA could significantly suppress ectopic NSC formation and NSC polarity defects caused by hyx depletion. Our data support a model in which Hyx promotes the expression of polo and aurA in NSCs and, in turn, regulates cell polarity and centrosome/microtubule assembly. This new paradigm may be relevant to future studies on Parafibromin/HRPT2-associated cancers.

α-Synuclein reduces acetylserotonin O-methyltransferase mediated melatonin biosynthesis by microtubule-associated protein 1 light chain 3 beta-related degradation pathway.

Previous studies have demonstrated that α-synuclein (α-SYN) is closely associated with rapid eye movement sleep behavior disorder (RBD) related to several neurodegenerative disorders. However, the exact molecular mechanisms are still rarely investigated. In the present study, we found that in the α-SYNA53T induced RBD-like behavior mouse model, the melatonin level in the plasma and pineal gland were significantly decreased. To elucidate the underlying mechanism of α-SYN-induced melatonin reduction, we investigated the effect of α-SYN in melatonin biosynthesis. Our findings showed that α-SYN reduced the level and activity of melatonin synthesis enzyme acetylserotonin O-methyltransferase (ASMT) in the pineal gland and in the cell cultures. In addition, we found that microtubule-associated protein 1 light chain 3 beta (LC3B) as an important autophagy adapter is involved in the degradation of ASMT. Immunoprecipitation assays revealed that α-SYN increases the binding between LC3B and ASMT, leading to ASMT degradation and a consequent reduction in melatonin biosynthesis. Collectively, our results demonstrate the molecular mechanisms of α-SYN in melatonin biosynthesis, indicating that melatonin is an important molecule involved in the α-SYN-associated RBD-like behaviors, which may provide a potential therapeutic target for RBD of Parkinson's disease.

Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy.

The treatment for trastuzumab-resistant breast cancer (BC) remains a challenge in clinical settings. It was known that CD47 is preferentially upregulated in HER2+ BC cells, which is correlated with drug resistance to trastuzumab. Here, we developed a novel anti-CD47/HER2 bispecific antibody (BsAb) against trastuzumab-resistant BC, named IMM2902. IMM2902 demonstrated high binding affinity, blocking activity, antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and internalization degradation effects against both trastuzumab-sensitive and trastuzumab-resistant BC cells in vitro. The in vivo experimental data indicated that IMM2902 was more effective than their respective controls in inhibiting tumor growth in a trastuzumab-sensitive BT474 mouse model, a trastuzumab-resistant HCC1954 mouse model, two trastuzumab-resistant patient-derived xenograft (PDX) mouse models and a cord blood (CB)-humanized HCC1954 mouse model. Through spatial transcriptome assays, multiplex immunofluorescence (mIFC) and in vitro assays, our findings provided evidence that IMM2902 effectively stimulates macrophages to generate C-X-C motif chemokine ligand (CXCL) 9 and CXCL10, thereby facilitating the recruitment of T cells and NK cells to the tumor site. Moreover, IMM2902 demonstrated a high safety profile regarding anemia and non-specific cytokines release. Collectively, our results highlighted a novel therapeutic approach for the treatment of HER2+ BCs and this approach exhibits significant anti-tumor efficacy without causing off-target toxicity in trastuzumab-resistant BC cells.

Mixed lineage kinase 3 and CD70 cooperation sensitize trastuzumab-resistant HER2+ breast cancer by ceramide-loaded nanoparticles.

Trastuzumab is the first-line therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancer, but often patients develop acquired resistance. Although other agents are in clinical use to treat trastuzumab-resistant (TR) breast cancer; still, the patients develop recurrent metastatic disease. One of the primary mechanisms of acquired resistance is the shedding/loss of the HER2 extracellular domain, where trastuzumab binds. We envisioned any new agent acting downstream of the HER2 should overcome trastuzumab resistance. The mixed lineage kinase 3 (MLK3) activation by trastuzumab is necessary for promoting cell death in HER2+ breast cancer. We designed nanoparticles loaded with MLK3 agonist ceramide (PPP-CNP) and tested their efficacy in sensitizing TR cell lines, patient-derived organoids, and patient-derived xenograft (PDX). The PPP-CNP activated MLK3, its downstream JNK kinase activity, and down-regulated AKT pathway signaling in TR cell lines and PDX. The activation of MLK3 and down-regulation of AKT signaling by PPP-CNP induced cell death and inhibited cellular proliferation in TR cells and PDX. The apoptosis in TR cells was dependent on increased CD70 protein expression and caspase-9 and caspase-3 activities by PPP-CNP. The PPP-CNP treatment alike increased the expression of CD70, CD27, cleaved caspase-9, and caspase-3 with a concurrent tumor burden reduction of TR PDX. Moreover, the expressions of CD70 and ceramide levels were lower in TR than sensitive HER2+ human breast tumors. Our in vitro and preclinical animal models suggest that activating the MLK3-CD70 axis by the PPP-CNP could sensitize/overcome trastuzumab resistance in HER2+ breast cancer.

Hepatocyte estrogen sulfotransferase inhibition protects female mice from concanavalin A-induced T cell-mediated hepatitis independent of estrogens.

Autoimmune hepatitis (AIH) is a typical T cell-mediated chronic liver disease with a higher incidence in females. However, the molecular mechanism for the female predisposition is poorly understood. Estrogen sulfotransferase (Est) is a conjugating enzyme best known for its function in sulfonating and deactivating estrogens. The goal of this study is to investigate whether and how Est plays a role in the higher incidence of AIH in females. Concanavalin A (ConA) was used to induce T cell-mediated hepatitis in female mice. We first showed that Est was highly induced in the liver of ConA-treated mice. Systemic or hepatocyte-specific ablation of Est, or pharmacological inhibition of Est, protected female mice from ConA-induced hepatitis regardless of ovariectomy, suggesting the effect of Est inhibition was estrogen independent. In contrast, we found that hepatocyte-specific transgenic reconstitution of Est in the whole-body Est knockout (EstKO) mice abolished the protective phenotype. Upon the ConA challenge, EstKO mice exhibited a more robust inflammatory response with elevated production of proinflammatory cytokines and changed liver infiltration of immune cells. Mechanistically, we determined that ablation of Est led to the hepatic induction of lipocalin 2 (Lcn2), whereas ablation of Lcn2 abolished the protective phenotype of EstKO females. Our findings demonstrate that hepatocyte Est is required for the sensitivity of female mice to ConA-induced and T cell-mediated hepatitis in an estrogen-independent manner. Est ablation may have protected female mice from ConA-induced hepatitis by upregulating Lcn2. Pharmacological inhibition of Est might be a potential strategy for the treatment of AIH.

Expanding and improving nanobody repertoires using a yeast display method: Targeting SARS-CoV-2.

COVID-19, caused by the coronavirus SARS-CoV-2, represents a serious worldwide health issue, with continually emerging new variants challenging current therapeutics. One promising alternate therapeutic avenue is represented by nanobodies, small single-chain antibodies derived from camelids with numerous advantageous properties and the potential to neutralize the virus. For identification and characterization of a broad spectrum of anti-SARS-CoV-2 Spike nanobodies, we further optimized a yeast display method, leveraging a previously published mass spectrometry-based method, using B-cell complementary DNA from the same immunized animals as a source of VHH sequences. Yeast display captured many of the sequences identified by the previous approach, as well as many additional sequences that proved to encode a large new repertoire of nanobodies with high affinities and neutralization activities against different SARS-CoV-2 variants. We evaluated DNA shuffling applied to the three complementarity-determining regions of antiviral nanobodies. The results suggested a surprising degree of modularity to complementarity-determining region function. Importantly, the yeast display approach applied to nanobody libraries from immunized animals allows parallel interrogation of a vast number of nanobodies. For example, we employed a modified yeast display to carry out massively parallel epitope binning. The current yeast display approach proved comparable in efficiency and specificity to the mass spectrometry-based approach, while requiring none of the infrastructure and expertise required for that approach, making these highly complementary approaches that together appear to comprehensively explore the paratope space. The larger repertoires produced maximize the likelihood of discovering broadly specific reagents and those that powerfully synergize in mixtures.

Integrated evolutionary pattern analyses reveal multiple origins of steroidal saponins in plants.

Steroidal saponins are a class of specialized metabolites essential for plant's response to biotic and abiotic stresses. They are also important raw materials for the industrial production of steroid drugs. Steroidal saponins are present in some monocots, such as Dioscorea and Paris, but their distribution, origin, and evolution in plants remain poorly understood. By reconstructing the evolutionary history of the steroidal saponin-associated module (SSAM) in plants, we reveal that the steroidal saponin pathway has its origin in Asparagus and Dioscorea. Through evaluating the distribution and evolutionary pattern of steroidal saponins in angiosperms, we further show that steroidal saponins originated multiple times in angiosperms, and exist in early diverged lineages of certain monocot lineages including Asparagales, Dioscoreales, and Liliales. In these lineages, steroidal saponins are synthesized through the high copy and/or high expression mechanisms of key genes in SSAM. Together with shifts in gene evolutionary rates and amino acid usage, these molecular mechanisms shape the current distribution and diversity of steroidal saponins in plants. Consequently, our results provide new insights into the distribution, diversity and evolutionary history of steroidal saponins in plants, and enhance our understanding of plants' resistance to abiotic and biotic stresses. Additionally, fundamental understanding of the steroidal saponin biosynthesis will facilitate their industrial production and pharmacological applications.

Assessing thresholds of resistance prevalence at which empiric treatment of gonorrhea should change among men who have sex with men in the US: A cost-effectiveness analysis.

BACKGROUND: Since common diagnostic tests for gonorrhea do not provide information about susceptibility to antibiotics, treatment of gonorrhea remains empiric. Antibiotics used for empiric therapy are usually changed once resistance prevalence exceeds a certain threshold (e.g., 5%). A low switch threshold is intended to increase the probability that an infection is successfully treated with the first-line antibiotic, but it could also increase the pace at which recommendations are switched to newer antibiotics. Little is known about the impact of changing the switch threshold on the incidence of gonorrhea, the rate of treatment failure, and the overall cost and quality-adjusted life-years (QALYs) associated with gonorrhea. METHODS AND FINDINGS: We developed a transmission model of gonococcal infection with multiple resistant strains to project gonorrhea-associated costs and loss in QALYs under different switch thresholds among men who have sex with men (MSM) in the United States. We accounted for the costs and disutilities associated with symptoms, diagnosis, treatment, and sequelae, and combined costs and QALYs in a measure of net health benefit (NHB). Our results suggest that under a scenario where 3 antibiotics are available over the next 50 years (2 suitable for the first-line therapy of gonorrhea and 1 suitable only for the retreatment of resistant infections), changing the switch threshold between 1% and 10% does not meaningfully impact the annual number of gonorrhea cases, total costs, or total QALY losses associated with gonorrhea. However, if a new antibiotic is to become available in the future, choosing a lower switch threshold could improve the population NHB. If in addition, drug-susceptibility testing (DST) is available to inform retreatment regimens after unsuccessful first-line therapy, setting the switch threshold at 1% to 2% is expected to maximize the population NHB. A limitation of our study is that our analysis only focuses on the MSM population and does not consider the influence of interventions such as vaccine and common use of rapid drugs susceptibility tests to inform first-line therapy. CONCLUSIONS: Changing the switch threshold for first-line antibiotics may not substantially change the health and financial outcomes associated with gonorrhea. However, the switch threshold could be reduced when newer antibiotics are expected to become available soon or when in addition to future novel antibiotics, DST is also available to inform retreatment regimens.

Strategy for Identifying a Robust Metabolomic Signature Reveals the Altered Lipid Metabolism in Pituitary Adenoma.

Despite the well-established connection between systematic metabolic abnormalities and the pathophysiology of pituitary adenoma (PA), current metabolomic studies have reported an extremely limited number of metabolites associated with PA. Moreover, there was very little consistency in the identified metabolite signatures, resulting in a lack of robust metabolic biomarkers for the diagnosis and treatment of PA. Herein, we performed a global untargeted plasma metabolomic profiling on PA and identified a highly robust metabolomic signature based on a strategy. Specifically, this strategy is unique in (1) integrating repeated random sampling and a consensus evaluation-based feature selection algorithm and (2) evaluating the consistency of metabolomic signatures among different sample groups. This strategy demonstrated superior robustness and stronger discriminative ability compared with that of other feature selection methods including Student's t-test, partial least-squares-discriminant analysis, support vector machine recursive feature elimination, and random forest recursive feature elimination. More importantly, a highly robust metabolomic signature comprising 45 PA-specific differential metabolites was identified. Moreover, metabolite set enrichment analysis of these potential metabolic biomarkers revealed altered lipid metabolism in PA. In conclusion, our findings contribute to a better understanding of the metabolic changes in PA and may have implications for the development of diagnostic and therapeutic approaches targeting lipid metabolism in PA. We believe that the proposed strategy serves as a valuable tool for screening robust, discriminating metabolic features in the field of metabolomics.

Luminescence-Based Infrared Thermal Sensors: Comprehensive Insights.

Recent chronological breakthroughs in materials innovation, their fabrication, and structural designs for disparate applications have paved transformational ways to subversively digitalize infrared (IR) thermal imaging sensors from traditional to smart. The noninvasive IR thermal imaging sensors are at the cutting edge of developments, exploiting the abilities of nanomaterials to acquire arbitrary, targeted, and tunable responses suitable for integration with host materials and devices, intimately disintegrate variegated signals from the target onto depiction without any discomfort, eliminating motional artifacts and collects precise physiological and physiochemical information in natural contexts. Highlighting several typical examples from recent literature, this review article summarizes an accessible, critical, and authoritative summary of an emerging class of advancement in the modalities of nano and micro-scale materials and devices, their fabrication designs and applications in infrared thermal sensors. Introduction is begun covering the importance of IR sensors, followed by a survey on sensing capabilities of various nano and micro structural materials, their design architects, and then culminating an overview of their diverse application swaths. The review concludes with a stimulating frontier debate on the opportunities, difficulties, and future approaches in the vibrant sector of infrared thermal imaging sensors.

All-Scale Hierarchical Structuring, Optimized Carrier Concentration, and Band Manipulation Lead to Ultra-High Thermoelectric Performance in Eco-Friendly MnTe.

MnTe emerges as an enormous potential for medium-temperature thermoelectric applications due to its lead-free nature, high content of Mn in the earth's crust, and superior mechanical properties. Here, it is demonstrate that multiple valence band convergence can be realized through Pb and Ag incorporations, producing large Seebeck coefficient. Furthermore, the carrier concentration can be obviously enhance by Pb and Ag codoping, contributing to significant enhancement of power factor. Moreover, microstructural characterizations reveal that PbTe nanorods can be introduced into MnTe matrix by alloying Pb. This can modify the microstructure into all-scale hierarchical architectures (including PbTe nanorods, enhances point-defect scattering, dense dislocations and stacking faults), strongly lowering lattice thermal conductivity to a record low value of 0.376 W m-1 K-1 in MnTe system. As a result, an ultra-high ZT of 1.5 can be achieved in MnTe thermoelectric through all-scale hierarchical structuring, optimized carrier concentration, and valence band convergence, outperforming most of MnTe-based thermoelectric materials.

Characterizing advanced heart failure risk and hemodynamic phenotypes using interpretable machine learning.

BACKGROUND: Although previous risk models exist for advanced heart failure with reduced ejection fraction (HFrEF), few integrate invasive hemodynamics or support missing data. This study developed and validated a heart failure (HF) hemodynamic risk and phenotyping score for HFrEF, using Machine Learning (ML). METHODS: Prior to modeling, patients in training and validation HF cohorts were assigned to 1 of 5 risk categories based on the composite endpoint of death, left ventricular assist device (LVAD) implantation or transplantation (DeLvTx), and rehospitalization in 6 months of follow-up using unsupervised clustering. The goal of our novel interpretable ML modeling approach, which is robust to missing data, was to predict this risk category (1, 2, 3, 4, or 5) using either invasive hemodynamics alone or a rich and inclusive feature set that included noninvasive hemodynamics (all features). The models were trained using the ESCAPE trial and validated using 4 advanced HF patient cohorts collected from previous trials, then compared with traditional ML models. Prediction accuracy for each of these 5 categories was determined separately for each risk category to generate 5 areas under the curve (AUCs, or C-statistics) for belonging to risk category 1, 2, 3, 4, or 5, respectively. RESULTS: Across all outcomes, our models performed well for predicting the risk category for each patient. Accuracies of 5 separate models predicting a patient's risk category ranged from 0.896 +/- 0.074 to 0.969 +/- 0.081 for the invasive hemodynamics feature set and 0.858 +/- 0.067 to 0.997 +/- 0.070 for the all features feature set. CONCLUSION: Novel interpretable ML models predicted risk categories with a high degree of accuracy. This approach offers a new paradigm for risk stratification that differs from prediction of a binary outcome. Prospective clinical evaluation of this approach is indicated to determine utility for selecting the best treatment approach for patients based on risk and prognosis.

MiR-3680-3p is a novel biomarker for the diagnosis and prognosis of liver cancer and is involved in regulating the progression of liver cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that can actively participate in post-transcriptional regulation of genes. A number of studies have shown that miRNAs can serve as important regulators of cancer cell growth, differentiation, and apoptosis. They can also act as markers for the diagnosis and prognosis of certain cancers. To explore the potential prognosis-related miRNAs in liver cancer patients, to provide theoretical basis for early diagnosis and prognosis of liver cancer, as well as to provide a new direction for the targeted therapy of liver cancer. The miRNA expression profiles of liver cancer patients in the the Cancer Genome Atlas database were comprehensively analyzed and various prognostic-related miRNAs of liver cancer were screened out. The data was further subjected to survival analysis, prognostic analysis, gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis, microenvironment analysis, and drug sensitivity analysis by R Language version 4.2.0. Finally, the screened miRNAs were further validated by different experiments. Thus, miNRAs involved in liver cancer diagnosis and prognosis were identified. MiRNA-3680-3p was found to be significantly different in 10 different cancers, including liver cancer, and was significantly associated with the microenvironment, survival, and prognosis of liver cancer patients. In addition, drug sensitivity analysis revealed that miRNA-3680-3p can provide a useful reference for drug selection in targeted therapy for liver cancer. MiRNA-3680-3p can serve as a biomarker for the diagnosis and prognosis of liver cancer patients and down-regulation of miRNA-3680-3p could significantly inhibit both the proliferation and migration of liver cancer cells.

Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.

Outcomes of Patients Transferred to Tertiary Care Centers for Treatment of Cardiogenic Shock: A Cardiogenic Shock Working Group Analysis.

BACKGROUND: Consensus recommendations for cardiogenic shock (CS) advise transfer of patients in need of advanced options beyond the capability of "spoke" centers to tertiary/"hub" centers with higher capabilities. However, outcomes associated with such transfers are largely unknown beyond those reported in individual health networks. OBJECTIVES: To analyze a contemporary, multicenter CS cohort with the aim of comparing characteristics and outcomes of patients between transfer (between spoke and hub centers) and nontransfer cohorts (those primarily admitted to a hub center) for both acute myocardial infarction (AMI-CS) and heart failure-related HF-CS. We also aim to identify clinical characteristics of the transfer cohort that are associated with in-hospital mortality. METHODS: The Cardiogenic Shock Working Group (CSWG) registry is a national, multicenter, prospective registry including high-volume (mostly hub) CS centers. Fifteen U.S. sites contributed data for this analysis from 2016-2020. RESULTS: Of 1890 consecutive CS patients enrolled into the CSWG registry, 1028 (54.4%) patients were transferred. Of these patients, 528 (58.1%) had heart failure-related CS (HF-CS), and 381 (41.9%) had CS related to acute myocardial infarction (AMI-CS). Upon arrival to the CSWG site, transfer patients were more likely to be in SCAI stages C and D, when compared to nontransfer patients. Transfer patients had higher mortality rates (37% vs 29%, < 0.001) than nontransfer patients; the differences were driven primarily by the HF-CS cohort. Logistic regression identified increasing age, mechanical ventilation, renal replacement therapy, and higher number of vasoactive drugs prior to or within 24 hours after CSWG site transfer as independent predictors of mortality among HF-CS patients. Conversely, pulmonary artery catheter use prior to transfer or within 24 hours of arrival was associated with decreased mortality rates. Among transfer AMI-CS patients, BMI > 28 kg/m2, worsening renal failure, lactate > 3 mg/dL, and increasing numbers of vasoactive drugs were associated with increased mortality rates. CONCLUSION: More than half of patients with CS managed at high-volume CS centers were transferred from another hospital. Although transfer patients had higher mortality rates than those who were admitted primarily to hub centers, the outcomes and their predictors varied significantly when classified by HF-CS vs AMI-CS.

Prognostic Implications of Quantifying Vasoactive Medications in Cardiogenic Shock.

None.

Heterografting enhances chrysanthemums resistance to Alternaria alternata via jasmonate-mediated increases in trichomes and terpenoids.

Trichomes, specialized hair-like structures in the epidermal cells of the aboveground parts of plants, protect plants from pests and pathogens and produce valuable metabolites. Chrysanthemum morifolium, used in tea products, has ornamental and medicinal value. However, it is susceptible to Alternaria alternata fungal infection, posing a threat to its production and use, resulting in substantial economic losses. Increasing the density of glandular trichomes enhances disease resistance and improves the production of medicinal metabolites in chrysanthemums. Jasmonate (JA), promotes the formation of glandular trichomes in various plants. However, it remains unclear whether glandular trichome in chrysanthemums are regulated by JA. Grafting, a technique to improve plant resistance to biotic stresses, has been insufficiently explored in its impact on glandular trichomes, terpenoids, and disease resistance. In this study, we demonstrated that grafting with Artemisia vulgaris rootstocks improves the resistance of chrysanthemum scions to A. alternata. Heterografted chrysanthemums exhibited higher trichome density and terpenoid content compared to self-grafted counterparts. Transcriptome analysis highlighted the significant role of CmJAZ1-like in disease resistance in heterografted chrysanthemums. Overexpressing CmJAZ1-like lines exhibited sensitivity to A. alternate, characterized by reduced glandular trichome density and limited terpenoids. Conversely, silencing lines exhibited resistance to A. alternata showcasing increased glandular trichome density and abundant terpenoids. Higher JA content was confirmed in heterografted chrysanthemum scions compared to self-grafted ones. Furthermore, we established that JA promotes the development of glandular trichomes and the synthesis of terpenoids while inducing the degradation of CmJAZ1-like proteins in chrysanthemums. These findings suggest that higher JA increases trichome density and terpenoid content, enhancing resistance to A. alternata by regulating CmJAZ1-like in heterografted chrysanthemums.