Uncoordinated amino groups of MIL-101 anchoring cobalt porphyrins for highly selective CO2 electroreduction.

Electrocatalytic carbon dioxide reduction reaction (CO2RR) presents a sustainable route to address energy crisis and environmental issues, where the rational design of catalysts remains crucial. Metal-organic frameworks (MOFs) with high CO2 capture capacities have immense potential as CO2RR electrocatalysts but suffer from poor activity. Herein we report a redox-active cobalt protoporphyrin grafted MIL-101(Cr)-NH2 for CO2 electroreduction. Material characterizations reveal that porphyrin molecules are covalently attached to uncoordinated amino groups of the parent MOF without compromising its well-defined porous structure. Furthermore, in situ spectroscopic techniques suggest inherited CO2 concentrate ability and more abundant adsorbed carbonate species on the modified MOF. As a result, a maximum CO Faradaic efficiency (FECO) up to 97.1% and a turnover frequency of 0.63 s-1 are achieved, together with FECO above 90% within a wide potential window of 300 mV. This work sheds new light on the coupling of MOFs with molecular catalysts to enhance catalytic performances.

Childhood psychological maltreatment and adolescent depressive symptoms: Exploring the role of social anxiety and maladaptive emotion regulation strategies.

BACKGROUND: Despite emerging evidence for the effect of childhood psychological maltreatment on adolescent depressive symptoms, the underlying processes for this effect are largely under-investigated. This study examined a conceptual framework for the effect of childhood psychological maltreatment on adolescent depressive symptoms through social anxiety disorder (SAD) and maladaptive emotion regulation strategies. METHODS: The participants were 1649 Chinese middle school students (751 girls and 898 boys) with a mean age of 16.29 ± 1.04 years old. A moderation-mediation model hypothesized that childhood psychological maltreatment predicts adolescent depressive symptoms, with SAD as a mediator and maladaptive emotion regulation strategies as a moderator. RESULTS: Childhood psychological maltreatment significantly positively predicted adolescent depressive symptoms, while SAD mediated the relation. Maladaptive emotion regulation strategies moderated the pathways from psychological maltreatment to depressive symptoms (but not from psychological maltreatment to SAD) and from SAD to adolescent depressive symptoms. LIMITATIONS: Subjective measures, and the cross-sectional design are the main limitations. CONCLUSIONS: SAD plays a mediating role in the relation between childhood psychological maltreatment and depressive symptoms. Maladaptive emotion regulation strategies exacerbate the relation between childhood psychological maltreatment and depressive symptoms, as well as the relation between SAD and depressive symptoms. These results highlight the importance of addressing social anxiety in reducing adolescent depressive symptoms by improving their cognitive emotion regulation strategies.

Effect of ferric ions on Cronobacter sakazakii growth, biofilm formation, and swarming motility.

Cronobacter sakazakii (C. sakazakii) is a common food-borne pathogen that induces meningitis, sepsis, and necrotizing enterocolitis, primarily in newborns and infants. Iron plays a pivotal role in the growth of cells and biofilm formation. However, the effects of hemin (ferric ion donor) on C. sakazakii cells are scarcely known. Here, we explored the effect of ferric ions on the growth of planktonic C. sakazakii, biofilm formation, and swarming motility by crystal violet staining (CVS), scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and swarming assay. Our study demonstrated that ferric ions facilitated the growth of planktonic C. sakazakii, while hemin at concentrations ranging from 50 to 800 µmol/L promoted biofilm formation and at concentrations between 50 and 200 µmol/L enhanced the swarming motility of C. sakazakii. Furthermore, high hemin concentrations (400-800 µmol/L) were found to reduce flagellar length, as confirmed by transmission electron microscopy (TEM). These findings indicated that ferric ions mediated the swarming motility of C. sakazakii by regulating flagellar assembly. Finally, transcriptomic analysis of C. sakazakii was performed at hemin concentrations of 0, 50, and 200 µmol/L, which revealed that several genes associated with iron transport and metabolism, and flagellar assembly were essential for the survival of C. sakazakii under hemin treatment. Our findings revealed the molecular basis of ferric ions on C. sakazakii growth and biofilm formation, thus providing a novel perspective for its prevention and control.

A novel strategy of integrating network pharmacology and transcriptome reveals antiapoptotic mechanisms of Buyang Huanwu Decoction in treating intracerebral hemorrhage.

ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Huanwu Decoction (BYHWD), as a traditional Chinese medical prescription, has been used to treat intracerebral hemorrhage (ICH) for hundreds of years, but the antiapoptotic properties have not yet been studied. AIM OF THE STUDY: This study aims to elucidate the antiapoptotic mechanism of BYHWD in ICH. MATERIALS AND METHODS: The therapeutic effect of BYHWD on ICH was assessed by modified neurological severity scores (mNSS), foot fault, and histopathological staining. Then, we used a modified comprehensive strategy by integrating transcriptome and network pharmacology to reveal the underlying mechanism. TUNEL assay, qRT-PCR, and western blot were further applied to evaluate the antiapoptotic effect of BYHWD on ICH. Dual-luciferase reporter assay and plasmid transfections were implemented to validate the potential competing endogenous RNAs (ceRNA) mechanism of Sh2b3. RESULTS: Network pharmacology analysis indicated that the regulation of the apoptotic process was the highest enriched GO term, and that MAP kinase activity, ERK1, and ERK2 cascade were strongly correlated. Transcriptome analysis screened 180 differentially expressed mRNAs, which were highly enriched in the immune system process and negative regulation of programmed cell death. By checking the literature, we found that Sh2b3 was of great importance to apoptosis by modulating MAPK cascades. TUNEL assay validated the anti-apoptotic effect of BYHWD. Moreover, BYHWD was proven to regulate the Sh2b3-mediated ERK1/2 signaling pathway in ICH mice by qRT-PCR and western blot. We further explored the lncRNA-miRNA-mRNA network underlying the therapeutic effect, among which 4933404O12Rik/miR-185-5p is the upstream regulatory mechanism of Sh2b3. CONCLUSIONS: We explored the antiapoptotic mechanism of BYHWD in treating ICH by a novel integrated strategy, which involved the 4933404O12Rik/miR-185-5p/Sh2b3 ceRNAs axis.

The multifaceted role of extracellular ATP in sperm function: From spermatogenesis to fertilization.

Extracellular adenosine 5'-triphosphate (ATP) is a vital signaling molecule involved in various physiological processes within the body. In recent years, studies have revealed its significant role in male reproduction, particularly in sperm function. This review explores the multifaceted role of extracellular ATP in sperm function, from spermatogenesis to fertilization. We discuss the impact of extracellular ATP on spermatogenesis, sperm maturation and sperm-egg fusion, highlighting the complex regulatory mechanisms and potential clinical applications in the context of male infertility. By examining the latest research, we emphasize the crucial role of extracellular ATP in sperm function and propose future research directions to further.

Triple microenvironment modulation of zeolite imidazolate framework (ZIF) nanocages for boosting dopamine electrocatalysis.

Multiple microenvironmental modulation of zeolite imidazole framework-8 (ZIF-8) is expected to solve the long-term intractable problem of low sensitivity in electrochemical sensing. Herein, the metal phthalocyanines with different central ions (PcM, M = Fe, Co, Ni and Cu) were introduced into ZIF-8 by in-situ synthesis method. Then, the hollow composite nanomaterials, HZIF-8/PcFe and HZIF-8@PcFe (HZIF-8, i.e., hollow ZIF-8) with different TA (tannic acid) coating thicknesses (∼11 nm and ∼33 nm) were successfully fabricated by carefully designed polyphenol-mediated modulation (PMM) strategy. Next, the HZIF-8@PcFe electrochemical sensor was constructed for selective and sensitive analysis by selecting dopamine (DA) as the analyte. The TA coating (superhydrophilic state), PcFe (redox properties) and hollow MOF cavity (faster mass transfer) was used as the triple microenvironment modulation of ZIF-8 to enhance the electrocatalytic performance. Under the optimum conditions (pH = 8.0), the linear correlations of 0.3 to 200 µmol/L was obtained for the peak current response, with a detection limit of 0.1 µmol/L (S/N = 3, i.e., Signal/Noise = 3). Meanwhile, the HZIF-8@PcFe electrochemical sensor exhibited excellent interference selectivity, reproducibility and stability, which enabled it to detect low abundance DA in real samples. And the F-test (homogeneity test of variance) and t-test (student's t test) statistical analyses were employed to enhance the accuracy of the actual samples' detection. This work will enlighten researchers working in the field of porous framework composites and open up new paths for the development of hollow MOFs hybrid materials in electrochemical sensing.

Water-use strategies and functional traits explain divergent linkages in physiological responses to simulated precipitation change.

As a part of global climate change, precipitation patterns in arid regions will change significantly, and the different responses of desert plants to these changes will lead to alterations in community composition, thereby impacting ecosystem stability. Thus, understanding the mechanism underlying the associations among physiological response variables considering changing precipitation is crucial. Here, water-use strategies, functional traits, and physiological processes (e.g., photosynthesis (An), transpiration (Tr), leaf water potential (Ψl), stomatal conductance (gs), and soil respiration (Rs)) were measured in a precipitation experiment with two coexisting desert riparian species to determine how water-use strategies and functional traits operate together in generating physiological response mechanisms. The results showed that the two species exhibited divergent response pathways of physiological processes following rainfall events, although both were identified as isohydric plants with stringent stomatal regulation. For the shallow-rooted species N. sphaerocarpa, gs was sensitive to changes in both surface soil moisture (Swc) and Ψl, and Swc was the primary factor influencing Rs. These results were supported by the preference for shallow water and predominance of functional traits associated with drought avoidance. For the deep-rooted species R. soongorica, variations in gs were decoupled from Swc and directly influenced by enhanced Ψl, An was the main factor affecting Rs, while Ψl negatively affected Rs. These correlations could be attributed to the preference for deep water and functional traits associated with drought tolerance. These findings suggest that R. soongorica had a stronger tolerance to environmental water deficits and may expand extensively under drier climatic conditions in the future.

Stabilization of organic carbon in top- and subsoil by biochar application into calcareous farmland.

Biochar is recognized for its role in carbon sequestration and emission mitigation in farmland topsoil. However, the mechanisms by which biochar affects soil organic carbon (SOC), its composition, and stability, in the topsoil (0-20 cm) and subsoil (140-160 cm) remain unclear. Applying biochar to the calcareous farmland topsoil significantly increased the topsoil SOC contents by 33 % after a decade, with a 5 % increase in dissolved organic carbon (DOC) contents (topsoil) and a substantial increase of 162 % in subsoil DOC contents. Additionally, humic substances showed an increase of 24 % (topsoil), while low-molecular-weight water-extracted DOC exhibited a remarkable increase of 142 % in the subsoil. The application of biochar significantly increases the contents of SOC, DOC, and microbial biomass carbon (MBC) in the topsoil, as well as SOC and DOC contents in the subsoil. However, a slight decrease is observed for MBC content in the subsoil. Biochar-amended soil significantly suppressed enzyme activity in the topsoil and decreased α diversity in topsoil and subsoil while increasing the content of mineral-associated soil organic matter (MAOM). These observed changes are conducive to stabilizing SOC, emphasizing MAOM formation as a primary mechanism for carbon sequestration in both topsoil and subsoils. This study provides evidence that biochar contributes to the long-term organic carbon sequestration in calcareous farmland, highlighting the importance of considering both topsoil and subsoil when evaluating the dynamic impacts of biochar on SOC.

Temporal changes of exposure to water on physic-chemical, stability, and transport characteristics of pyrogenic carbon colloids.

Understanding the effect of the aging process on the properties of pyrogenic carbon (PyC) is critical for predicting and evaluating its transport and fate. Water exposure is a common application scenario of PyC entering aquatic systems or flooded paddy fields, which might significantly affect the aging process. However, only some studies focused on the changes in PyC properties by water exposure treatment. In this study, the effect of water exposure on the mobility of PyC was investigated. Fresh PyC, PyC with 1.5 years and 3.5 years of water exposure were selected and named as CK, 1.5WA, and 3.5WA, respectively. Our results revealed that CK had the lowest intensity of surface functional groups (-OH, CO, and C-O-C) and the intensity of 3.5WA was higher than that of 1.5WA. There was no significant change in dissolved organic matter (DOM) content between fresh and aged PyC colloids. However, UV absorbance and its parameters (E2/E3, E4/E6, and SR) exhibited a comparable tendency to the abundance of functional groups (-OH, CO, and C-O-C). The fresh and aged PyC colloids showed high stability in Na+ and Ca2+ solutions at varying pH values (A/A0 > 85%), which was also observed in groundwater. The mobility of fresh and aged PyC colloids differed in Na+ (21.74%-57.19%), Ca2+ (14.30%-40.12%) solutions and groundwater (28.50%-44.24%), but exhibited similar order (3.5WA > 1.5WA > CK). The mechanism of the effect of water exposure on the property and mobility of PyC colloids was explored. This study provides the fundamental information to estimate PyC fate and transport after long-term water exposure.

Kaempferol attenuates wear particle-induced inflammatory osteolysis via JNK and p38-MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Wear particle-induced inflammatory osteoclast activation is a master contributor to periprosthetic osteolysis, which can cause pathological bone loss and destruction. Hence, inhibiting inflammation and osteoclastogenesis is an important strategy for preventing wear particle-induced osteolysis. To date, there are no FDA-approved non-surgical pharmacotherapies for arresting periprosthetic osteolysis. Kaempferol (KAE), a natural flavonol abundant in many traditional Chinese herbal medicines, has been shown to have protective effects against inflammatory bone diseases such as rheumatoid arthritis, but no previous study has evaluated the effects of KAE on wear particle-induced osteolysis. AIM OF THE STUDY: The study aimed to investigate the effects of KAE on wear particle-induced inflammatory osteolysis and osteoclast activation, and further explore the underlying mechanisms. MATERIALS AND METHODS: TiAl6V4 metal particles (TiPs) were retrieved from the prosthesis of patients who underwent revision hip arthroplasty due to aseptic loosening. A mouse calvarial osteolysis model was used to investigate the effects of KAE on wear particle-induced inflammatory osteolysis in vivo. Primary bone marrow-derived macrophages (BMMs) were used to explore the effects of KAE on osteoclast differentiation and bone-resorbing activity as well as the underlying mechanisms in vitro. RESULTS: In the present study, we found that KAE alleviated wear particle-induced inflammatory bone loss in vivo and inhibited osteoclast differentiation and function in vitro. Furthermore, we revealed that KAE exerted anti-osteoclastogenic effects by downregulating JNK and p38-MAPK signaling as well as the downstream NFATc1 expression. CONCLUSIONS: KAE is an alternative therapeutic agent for preventing and treating periprosthetic osteolysis and aseptic loosening.

In-depth mass spectrometry analysis of rhGH administration altered energy metabolism and steroidogenesis.

Growth hormone, as a proteohormone, is primarily known of its dramatic effect on longitudinal growth. Recombinant DNA technology has provided a safe, abundant and comparatively cheap supply of human GH for growth hormone-deficient individuals. However, many healthy subjects, especially athletics, administrate GH for enhanced athletic performance or strength. A better and more comprehensive understanding of rhGH effect in healthy individuals is urgent and essential. In this study, we recruited 14 healthy young male and injected rhGH once. Untargeted LC-MS metabolomics profiling of serum and urine was performed before and after the rhGH injection. The GH-induced dysregulation of energy related pathways, such as amino acid metabolism, nucleotide metabolism, glycolysis and TCA cycle, was revealed. Moreover, individuals supplemented with micro-doses of rhGH exhibited significantly changed urinary steroidal profiles, suggesting a role of rhGH in both energy metabolism and steroidogenesis. We expect that our results will be helpful to provide new evidence on the effects of rhGH injection and provide potential biomarkers for rhGH administration.

Organic photodiodes with bias-switchable photomultiplication and photovoltaic modes.

The limited sensitivity of photovoltaic-type photodiodes makes it indispensable to use pre-amplifier circuits for effectively extracting electrical signals, especially when detecting dim light. Additionally, the photomultiplication photodiodes with light amplification function suffer from potential damages caused by high power consumption under strong light. In this work, by adopting the synergy strategy of thermal-induced interfacial structural traps and blocking layers, we develop a dual-mode visible-near infrared organic photodiode with bias-switchable photomultiplication and photovoltaic operating modes, exhibiting high specific detectivity (~1012 Jones) and fast response speed (0.05/3.03 ms for photomultiplication-mode; 8.64/11.14 µs for photovoltaic-mode). The device also delivers disparate external quantum efficiency in two optional operating modes, showing potential in simultaneously detecting dim and strong light ranging from ~10-9 to 10-1 W cm-2. The general strategy and working mechanism are validated in different organic layers. This work offers an attractive option to develop bias-switchable multi-mode organic photodetectors for various application scenarios.

Diagnostic suspicion bias and machine learning: Breaking the awareness deadlock for sepsis detection.

Many early warning algorithms are downstream of clinical evaluation and diagnostic testing, which means that they may not be useful when clinicians fail to suspect illness and fail to order appropriate tests. Depending on how such algorithms handle missing data, they could even indicate "low risk" simply because the testing data were never ordered. We considered predictive methodologies to identify sepsis at triage, before diagnostic tests are ordered, in a busy Emergency Department (ED). One algorithm used "bland clinical data" (data available at triage for nearly every patient). The second algorithm added three yes/no questions to be answered after the triage interview. Retrospectively, we studied adult patients from a single ED between 2014-16, separated into training (70%) and testing (30%) cohorts, and a final validation cohort of patients from four EDs between 2016-2018. Sepsis was defined per the Rhee criteria. Investigational predictors were demographics and triage vital signs (downloaded from the hospital EMR); past medical history; and the auxiliary queries (answered by chart reviewers who were blinded to all data except the triage note and initial HPI). We developed L2-regularized logistic regression models using a greedy forward feature selection. There were 1164, 499, and 784 patients in the training, testing, and validation cohorts, respectively. The bland clinical data model yielded ROC AUC's 0.78 (0.76-0.81) and 0.77 (0.73-0.81), for training and testing, respectively, and ranged from 0.74-0.79 in four hospital validation. The second model which included auxiliary queries yielded 0.84 (0.82-0.87) and 0.83 (0.79-0.86), and ranged from 0.78-0.83 in four hospital validation. The first algorithm did not require clinician input but yielded middling performance. The second showed a trend towards superior performance, though required additional user effort. These methods are alternatives to predictive algorithms downstream of clinical evaluation and diagnostic testing. For hospital early warning algorithms, consideration should be given to bias and usability of various methods.

Single-cell transcriptomics reveals the brain evolution of web-building spiders.

Spiders are renowned for their efficient capture of flying insects using intricate aerial webs. How the spider nervous systems evolved to cope with this specialized hunting strategy and various environmental clues in an aerial space remains unknown. Here we report a brain-cell atlas of >30,000 single-cell transcriptomes from a web-building spider (Hylyphantes graminicola). Our analysis revealed the preservation of ancestral neuron types in spiders, including the potential coexistence of noradrenergic and octopaminergic neurons, and many peptidergic neuronal types that are lost in insects. By comparing the genome of two newly sequenced plesiomorphic burrowing spiders with three aerial web-building spiders, we found that the positively selected genes in the ancestral branch of web-building spiders were preferentially expressed (42%) in the brain, especially in the three mushroom body-like neuronal types. By gene enrichment analysis and RNAi experiments, these genes were suggested to be involved in the learning and memory pathway and may influence the spiders' web-building and hunting behaviour. Our results provide key sources for understanding the evolution of behaviour in spiders and reveal how molecular evolution drives neuron innovation and the diversification of associated complex behaviours.

An education-based telehealth group improves the management and clinical outcomes of patients with inflammatory bowel disease in China (THEIM study).

BACKGROUND: Although poor medication adherence has a negative impact on disease prognosis in patients with inflammatory bowel disease (IBD), finding proven solutions remains a challenge. In this study, we developed a telehealth management model based on education and patient-centered medical care (PCEB) using the social media platform WeChat. OBJECTIVE: To investigate the effect of PCEB on adherence and clinical outcomes. METHODS: In this retrospective cohort, 543 IBD patients (274 in the PCEB group and 269 in the routine group) at the IBD center of Renmin Hospital (Wuhan University, Wuhan, China) were enrolled between January 2020 and September 2022. The routine group received routine follow-up and management, while for PCEB patients, a comprehensive IBD education program and PCEB were conducted. Medication adherence and clinical outcomes were also evaluated. RESULTS: There were no differences between the PCEB and routine groups in terms of patient demographics and clinical characteristics, including disease classification, duration, biological treatment, and educational background at baseline. Compared with routine treatment, PCEB greatly improved patient medication adherence, as assessed by compliance with oral medication, enteral nutrition, biological infusion, and scheduled endoscopic assessment. Clinical and endoscopic remission in patients with PCEB increased during short-term (month 4) and long-term (month 12) follow-ups, along with a decrease in relapse rates for CD (13.3% vs. 31.8%) and UC (19.8% vs. 37.2%). CONCLUSION: The telehealth model applied to the PCEB group improved medication adherence and clinical outcomes in patients with IBD. This is a new and powerful solution for the long-term management of this chronic and progressive disease.

Long-Term Results and Risk Factors of Treatment for Post-Infarction Ventricular Septal Rupture: A Single-Center Experience.

BACKGROUND: Ventricular septal rupture (VSR) following myocardial infarction (MI) is a rare but lethal complication. We analyzed the long-term results and risk factors for survival in the treatment of VSR. METHODS: From January 2012 to December 2021, 115 consecutive patients with post-MI VSR were admitted to our hospital. Depending on different treatment methods patients were divided into following three groups: medical, transcatheter intervention, and surgical repair. During the study, relevant clinical data, operation-related conditions, and follow-up data were analyzed. The Kaplan-Meier method and log-rank test were used to determine the cumulative incidence of mortality. The independent risk factors for patient mortality were evaluated by multivariate logistic regression. RESULTS: The mean follow-up time was 43.4 ± 34.7 months. The overall in-hospital, 30-day, and long-term mortality rates were 24.3%, 38.3%, and 51.3%, respectively. In the medical group, the in-hospital and 30-day mortality rates were 46.7 % (21/45) and 82.2 % (37/45), respectively, with only three patients alive at follow-up. In the transcatheter intervention group, 30-day and long-term mortality rates were 12% and 28%, respectively. In the surgical repair group, 30-day and long-term mortality rates were 8.9% and 22.2%, respectively. Compared with the surgery-group patients, patients with transcatheter intervention had a longer time from VSR to intervention. Logistic regression analysis revealed that age, previous infarction, Killip class, serum creatinine, Troponin T, N-terminal pro-B-type natriuretic peptide, and medical strategy were risk factors for all-cause mortality. CONCLUSIONS: The 30-day and long-term outcomes of patients treated with surgical repair and transcatheter intervention were significantly better than medically treated patients.

IgE directly affects eosinophil migration in CRSwNP through CCR3 and predicts the efficacy of omalizumab.

BACKGROUND: Whether IgE affects eosinophil migration in chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unclear. Moreover, our understanding of local IgE, eosinophils and omalizumab efficacy in CRSwNP remains limited. OBJECTIVE: To investigate whether IgE acts directly on eosinophils and determine its role in omalizumab therapy. METHODS: Eosinophils and their surface receptors were detected by hematoxylin-eosin staining and flow cytometry. IgE and its receptors, EPX, ECP, and CCR3 were detected by immunohistochemistry and immunofluorescence. Functional analyses were performed on blood eosinophils and polyp tissues. Logistic regression was performed to screen for risk factors. Receiver operating characteristic curve was generated to evaluate the accuracy. RESULTS: Both FcɛRI and CD23 were expressed on eosinophils. The expression of FcɛRI and CD23 on eosinophil in nasal polyp tissue was higher than that in peripheral blood (both P < 0.001). IgE and EPX co-localized in CRSwNP. IgE directly promoted eosinophil migration by upregulating CCR3 in CRSwNP but not in healthy controls. Omalizumab and lumiliximab were found to be effective in restraining this migration, indicating CD23 was involved in IgE-induced eosinophil migration. Both IgE+, EPX+ cells were significantly reduced after omalizumab treatment in responders (IgE+ cells, P = 0.001; EPX+ cells, P = 0.016) but not in non-responders (IgE+ cells, P = 0.060; EPX+ cells, P = 0.151). Baseline IgE+ cell levels were higher in responders than in non-responders (P = 0.024). The baseline local IgE+ cell count predicted omalizumab efficacy with an accuracy of 0.811. CONCLUSIONS: IgE directly promotes eosinophil migration and baseline local IgE+ cell counts are predictive of omalizumab efficacy in CRSwNP.

An end-to-end platform for digital pathology using hyperspectral autofluorescence microscopy and deep learning based virtual histology.

Conventional histopathology involves expensive and labor intensive processes that often consume tissue samples, rendering them unavailable for other analysis. We present a novel end-to-end workflow for pathology powered by hyperspectral microscopy and deep learning. First, we developed a custom hyperspectral microscope to non-destructively image the autofluorescence of unstained tissue sections. We then trained a deep learning model to use the autofluorescence to generate virtual histological stains, which avoids the cost and variability of chemical staining procedures and conserves tissue samples. We showed that the virtual images reproduce the histological features present in the real stained images using a randomized nonalcoholic steatohepatitis (NASH) scoring comparison study where both real and virtual stains are scored by pathologists. The test showed moderate to good concordance between pathologists' scoring on corresponding real and virtual stains. Finally, we developed deep learning-based models for automated NASH Clinical Research Network (NASH CRN) score prediction. We showed that the end-to-end automated pathology platform is comparable to pathologists for NASH CRN scoring when evaluated against the expert pathologist consensus scores. This study provides proof of concept for this virtual staining strategy, which could improve cost, efficiency, and reliability in pathology, and enable novel approaches to spatial biology research.

Low-temperature photothermal-induced alkyl radical release facilitates dihydroartemisinin-triggered "valve-off" starvation therapy.

The high nutrient and energy demand of tumor cells compared to normal cells to sustain rapid proliferation offer a potentially auspicious avenue for implementing starvation therapy. However, conventional starvation therapy, such as glucose exhaustion and vascular thrombosis, can lead to systemic toxicity and exacerbate tumor hypoxia. Herein, we developed a new "valve-off" starvation tactic, which was accomplished by closing the valve of glucose transporter protein 1 (GLUT1). Specifically, dihydroartemisinin (DHA), 2,20-azobis [2-(2-imidazolin-2-yl) propane] dihydrochloride (AI), and Ink were co-encapsulated in a sodium alginate (ALG) hydrogel. Upon irradiation with the 1064 nm laser, AI rapidly disintegrated into alkyl radicals (R•), which exacerbated the DHA-induced mitochondrial damage through the generation of reactive oxygen species and further reduced the synthesis of adenosine triphosphate (ATP). Simultaneously, the production of R• facilitated DHA-induced starvation therapy by suppressing GLUT1, which in turn reduced glucose uptake. Systematic in vivo and in vitro results suggested that this radical-enhanced "valve-off" strategy for inducing tumor cell starvation was effective in reducing glucose uptake and ATP levels. This integrated strategy induces tumor starvation with efficient tumor suppression, creating a new avenue for controlled, precise, and concerted tumor therapy.

Rapid migration of Mongolian oak into the southern Asian boreal forest.

The migration of trees induced by climatic warming has been observed at many alpine treelines and boreal-tundra ecotones, but the migration of temperate trees into southern boreal forest remains less well documented. We conducted a field investigation across an ecotone of temperate and boreal forests in northern Greater Khingan Mountains of northeast China. Our analysis demonstrates that Mongolian oak (Quercus mongolica), an important temperate tree species, has migrated rapidly into southern boreal forest in synchrony with significant climatic warming over the past century. The average rate of migration is estimated to be 12.0 ± 1.0 km decade-1 , being slightly slower than the movement of isotherms (14.7 ± 6.4 km decade-1 ). The migration rate of Mongolian oak is the highest observed among migratory temperate trees (average rate 4.0 ± 1.0 km decade-1 ) and significantly higher than the rates of tree migration at boreal-tundra ecotones (0.9 ± 0.4 km decade-1 ) and alpine treelines (0.004 ± 0.003 km decade-1 ). Compared with the coexisting dominant boreal tree species, Dahurian larch (Larix gmelinii), temperate Mongolian oak is observed to have significantly lower capacity for light acquisition, comparable water-use efficiency but stronger capacity to utilize nutrients especially the most limiting nutrient, nitrogen. In the context of climatic warming, and in addition to a high seed dispersal capacity and potential thermal niche differences, the advantage of nutrient utilization, reflected by foliar elementomes and stable nitrogen isotope ratios, is also likely a key mechanism for Mongolian oak to coexist with Dahurian larch and facilitate its migration toward boreal forest. These findings highlight a rapid deborealization of southern Asian boreal forest in response to climatic warming.