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Specific recognition and detoxification for copper is the key step for the early diagnosis and treatment of various diseases such as neurodegenerative disease and Wilson's disease. Herein, a Chlorella vulgaris‐inspired versatile theranostic nanoparticles is facilely and greenly prepared by assembling quercetin into poly(beta‐cyclodextrin) (PQNPs), which is further employed in the specific recognition and detoxification for Cu2+ in vitro and in vivo. PQNPs can be used in the detection of Cu2+ in aqueous solutions with fast response time (<5 s) and low detection limit (6.499 nM). The detection for Cu2+ in water and serum can be achieved by naked eye instantaneously on a PQNPs‐based paper sensor, and PQNPs can also act as a biological diagnostic agent for the Cu2+ imaging. Remarkably, PQNPs significantly enhance cell viability of the cell models induced by Cu2+ through the synergistic capacities of chelating Cu2+ and antioxidation. The detoxification of PQNPs for copper poisoning model is further ascertained in vivo, and it found that poly‐β‐cyclodextrin is capable of crossing the blood–brain barrier. Taken together, the as‐prepared versatile theranostic nanoparticles possess advantages of simple composition, significant theranostic efficacy, and novel treatment pattern, presenting an intriguing avenue to develop therapeutics for tackling abnormal copper metabolism in the clinic. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) is an inherited eye disease that causes progressive vision loss. Microglial activation and inflammation play essential roles in photoreceptor degeneration in RP, although the underlying mechanisms remain unclear. Here, we examined the progressive degeneration of photoreceptors in rd1 mice, a mouse model of RP. We investigated the molecular changes in various retinal cells in rd1 mice using single‐cell RNA sequencing and found that potentiation of JNK signaling is associated with photoreceptor degeneration in RP. Moreover, inflammation‐related molecules, which function downstream of JNK, are elevated in RP. Furthermore, inhibiting JNK alleviates microglial activation and rescues photoreceptor degeneration in rd1 mice. Thus, our findings suggest that targeting JNK is a promising approach for slowing RP progression. [ABSTRACT FROM AUTHOR]

Neutron production driven by intense lasers utilizing inverse kinematic reactions is explored self-consistently by a combination of particle-in-cell simulations for laser-driven ion acceleration and Monte Carlo nuclear reaction simulations for neutron production. It is proposed that laser-driven light-sail acceleration from ultrathin lithium foils can provide an energetic lithium-ion beam as the projectile bombarding a light hydrocarbon target with sufficiently high flux for the inverse p ( L i 7 , n) reaction to be efficiently achieved. Three-dimensional self-consistent simulations show that a forward-directed pulsed neutron source with ultrashort pulse duration 3 ns, small divergence angle 26°, and extremely high peak flux 3 × 1014n/(cm2⋅s) can be produced by petawatt lasers at intensities of 1021 W/cm2. These results indicate that a laser-driven neutron source based on inverse kinematics has promise as a novel compact pulsed neutron generator for practical applications, since the it can operate in a safe and repetitive way with almost no undesirable radiation. [ABSTRACT FROM AUTHOR]

Simple Summary: The addition of alternative feed sources such as Green Tea Powder to the feed of poultry, especially laying hens, has attracted attention due to its potential benefits. Therefore, the purpose of this study—with the addition of Green Tea Powder to the diet of laying hens—is, on the one hand, to explore the beneficial effects of Green Tea Powder on the production performance and physical function of laying hens and, on the other hand, to explore the utilization of Green Tea Powder and improve the utilization rate of biological resources. In conclusion, dietary supplementation of Green Tea Powder during the laying period can reduce the serum yolk weight of laying hens. The serum levels of immunoglobulin A and immunoglobulin M were increased, and the serum levels of malondialdehyde were decreased. Egg shell strength and shell thickness decreased, and egg yolk color deepened. Additionally, the percentage of amino acids in the eggs increased. It is beneficial to the health of laying hens to increase the diversity of intestinal flora and improve the structure of cecum flora. This study investigated the effects of Green Tea Powder supplementation on the performance and egg quality of laying hens and ultimately guided the development of more effective and scientific animal feeding strategies. This study was conducted to investigate the effects of different levels of Green Tea Powder on the performance, egg quality, serum immune and antioxidant indices, and cecal microflora of 300-day-old Chishui black-bone chickens during the peak laying period. A total of 360 Chishui black-bone chickens were selected as the experimental animals. They were randomly allocated into four groups: the control group (CON), trial group I (T1), trial group II (T2), and trial group III (T3), each group with six replicates and 15 hens in each replicate. The control group was fed a basal diet, and the experimental groups were fed a basal diet supplemented with 0.8%, 1.6%, and 2.4% Green Tea Powder, respectively. The accommodation period was 14 d, and the experimental period was 60 d. The statistical software SPSS was used to perform a one-way analysis of variance (ANOVA) on the experimental data, and Duncan's method was used to perform multiple comparisons among groups. The results showed the following: compared with those of the control group, the average daily gain of the laying hens significantly decreased in the 1.6% Green Tea Powder group (p < 0.05); adding Green Tea Powder significantly reduced the content of malondialdehyde in the serum (p < 0.05), and the addition of 0.8% tea leaves significantly increased the immunoglobulin M and immunoglobulin A contents (p < 0.05); the egg yolk weight, eggshell thickness, eggshell strength, and yolk color of the laying hens significantly decreased in the 1.6% Green Tea Powder group (p < 0.05), and the addition of Green Tea Powder at the level of 2.4% significantly increased the percentage of umami, essential, and total amino acids (p < 0.05); and the structure of intestinal microorganisms was improved, and the abundance of Bacteroidetes and Bacteroidaceae significantly increased, while the abundance of Firmicutes and Lachnospiraceae significantly decreased (p < 0.05). [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the influence of ferroptosis on an oxygen-glucose deprivation/reoxygenation (OGD/R) model in primary rat microglia. Methods: Primary microglia were extracted from rats and cultured in vitro. The cells were subjected to a hypoxic environment for 6 h in a glucose-free medium, and then re-oxygenated for 24 h in DMEM/F12. Rat microglia were pretreated with the ferroptosis activator erastin and the ferroptosis inhibitor ferrostatin 1 for 24 h, followed by detection of cell cycle progression and apoptosis by flow cytometry. Intracellular total iron levels were measured. In addition, the relative levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were determined using enzyme-linked immunosorbent assay. The protein levels of 15-lox2, GPX4, SLC7A11, ACSL4, and TFR1 were examined by western blotting. Results: Compared with rat microglia subjected to OGD/R, pretreatment with erastin did not influence cell apoptosis but significantly enhanced total iron levels, MDA, and ROS levels, whereas it reduced SOD levels. Moreover, it upregulated ACSL4, TFR1, and 15-lox2 and downregulated GPX4 and SLC7A11. Pretreatment with ferrostatin 1 significantly inhibited cell apoptosis and cell cycle arrest in the G0/G1 phase. It significantly reduced total iron levels, MDA, and ROS levels and enhanced SOD levels, which also downregulated ACSL4, TFR1, and 15-lox2, and upregulated GPX4 and SLC7A11. Conclusion: Our study showed that inhibition of ferroptosis is favorable against potential OGD/R-induced damage in rat microglia. [ABSTRACT FROM AUTHOR]

Astrocytes, the predominant glial cells in the central nervous system, play essential roles in maintaining brain function. Reprogramming induced pluripotent stem cells (iPSCs) to become astrocytes through overexpression of the transcription factors, NFIB and SOX9, is a rapid and efficient approach for studying human neurological diseases and identifying therapeutic targets. However, the precise differentiation path and molecular signatures of induced astrocytes remain incompletely understood. Accordingly, we performed single-cell RNA sequencing analysis on 64,736 cells to establish a comprehensive atlas of NFIB/SOX9-directed astrocyte differentiation from human iPSCs. Our dataset provides detailed information about the path of astrocyte differentiation, highlighting the stepwise molecular changes that occur throughout the differentiation process. This dataset serves as a valuable reference for dissecting uncharacterized transcriptomic features of NFIB/SOX9-induced astrocytes and investigating lineage progression during astrocyte differentiation. Moreover, these findings pave the way for future studies on neurological diseases using the NFIB/SOX9-induced astrocyte model. [ABSTRACT FROM AUTHOR]

Blackbody‐sensitive uncooled infrared photodetectors with ultra‐broadband and ultrafast photoresponse have a profound impact on many areas of modern science and technology. However, it is a big challenge for both traditional photodetectors and emerging low‐dimensional ones to simultaneously have all the above characteristics. Here, this challenge is addressed by establishing a Te/WTe2 heterostructure photodetector. The built‐in field of the heterostructure and the crossing conduction and valence bands of WTe2 jointly result in a high responsivity and a visible‐to‐long‐wavelength‐infrared photoresponse range. The peak responsivity (at the 3.3 µm wavelength) reaches 914 mA W−1 at zero bias and 8.51 A W−1 at 2 V bias. Further, the joint action coupled with the high mobility of Te and WTe2 promotes the 3‐dB bandwidth to 153 kHz. The self‐powered blackbody responsivity and specific detectivity reach 235.7 mA W−1 and 1.1 × 108 cm Hz1/2 W−1, respectively. The former increases to 5.82 A W−1 at 1 V bias. Moreover, this device is polarization‐sensitive with a contrast ratio of 2. This work reveals the potential of the Te/WTe2 heterostructure for high‐performance room‐temperature infrared photodetectors. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence has highlighted that lncRNA ABHD11-AS1 plays an essential role in tumorigenesis and is expected to become a new predictive biomarker and ideal target for cancer therapy, whereas some of their findings are conflicting due to the relatively small sample size of individual studies. Thus, this meta-analysis aimed to quantitatively ascertain the association of ABHD11-AS1 with diverse human malignancies. Methods: Eight databases were comprehensively screened for relevant articles on January 1, 2024. The significance of ABHD11-AS1 in malignancies was determined by odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were applied to verify the reliability and robustness of the pooled results. Simultaneously, the GEPIA2021 and UCSC Xena databases were applied to further strengthen the results. Results: Fourteen clinical studies comprising eight kinds of malignancies and 1215 malignancy cases were enrolled into this meta-analysis. The pooled results showed that increased ABHD11-AS1 expression was remarkably associated with lymph node metastasis (OR = 2.73, 95%CI [1.97, 3.77], I2 = 0%, p < 0.00001), advanced tumor stage (OR = 3.14, 95%CI [2.34, 4.21], I2 = 39%, p < 0.00001), and unfavorable overall survival (OS) (HR = 1.81, 95%CI [1.58, 2.06], I2 = 0%, p < 0.00001). Subgroup analyses and sensitivity analyses indicated that the pooled results were reliable and robust. Additionally, ABHD11-AS1 was significantly increased in eight kinds of malignancies according to the validation of the GEPIA2021 database. Meanwhile, the UCSC Xena databases further revealed that elevated ABHD11-AS1 expression was significantly associated with poor prognosis as assessed by progression free interval (PFI), disease free interval (DFI), disease specific survival (DSS), and OS. Conclusions: Current evidence supports the association of elevated ABHD11-AS1 expression with poor prognosis. Thereby, ABHD11-AS1 may be considered as a promising biomarker to screen cancer and predict malignancy prognosis. Also, there is a necessity for larger-scale multicenter studies with uniform study protocols from different countries to further validate the conclusions. [ABSTRACT FROM AUTHOR]

Purpose: To inform better asthma management in China, this study aimed to comprehensively investigate clinical characteristics, treatment patterns, asthma control status, exacerbations, and humanistic burden among adult patients seeking hospital-based asthma care by analyzing data from Adelphi Asthma Disease Specific Program conducted in China. Patients and Methods: All information was collected on survey date (August–December 2018) from medical records, physicians, or patients, without follow-up being conducted. Results are summarized descriptively for the overall population as well as subgroups defined by GINA 2018 treatment step. Results: Of the included 765 patients, 46.0%, 40.4%, and 29.2% had undergone lung function, blood eosinophil count, and specific immunoglobulin E/radioallergosorbent testing, and 17.2%, 24.1%, and 58.7% were managed at GINA Steps 1– 2, 3, and 4– 5, respectively. Asthma was not well controlled in 57.3% of patients based on definitions adapted from the ERS/ATS and 10.7% of patients had experienced ≥ 1 severe exacerbation in the preceding year. According to patient self-reporting (n=603), the mean (SD) was 0.9 (0.1) for utility on EQ-5D-3L and was 7.8% (10.4%), 36.9% (20.0%), 40.8% (22.2%), and 37.9% (22.3%) for absenteeism, presenteeism, work productivity loss, and activity impairment, respectively, on WPAI. Both asthma control and humanistic burden worsened with progressive GINA treatment steps. Conclusion: In patients seeking hospital-based asthma care in China, lung function and biomarker tests were underutilized, impairment in productivity and quality of life was observed, and more than half did not achieve well-controlled asthma despite approximately 60% being managed at GINA treatment Steps 4– 5. These findings highlight the urgent need for optimizing asthma management in China. [ABSTRACT FROM AUTHOR]

The compound p-Nitrophenol (p-NP) is widely recognized as a highly toxic nitro-aromatic substance that urgently requires emission control. Reducing p-NP to p-aminophenol (p-AP) not only decreases its toxicity and mineralization properties in nature but also provides a key raw material for the chemical and pharmaceutical industries. The study used coal fly ash (CFA) as a catalyst carrier for synthesizing the p-NP reduction catalyst. Using CFA as an alternative option not only reduces costs but also achieves the objective of treating waste with waste compared to utilizing commercial solid materials for synthesizing catalysts. By employing hydrochloric acid and sodium hydroxide pretreatment methods, the physicochemical properties of CFA are significantly improved, enhancing the dispersion of palladium (Pd) nanoparticles. The structural features of the prepared samples were characterized using various surface analysis techniques, and both intermittent and continuous modes were experimentally tested for the model catalytic reaction involving the sodium borohydride (NaBH4)-mediated reduction of p-NP. The results demonstrate that CFA has potential in wastewater treatment. [ABSTRACT FROM AUTHOR]

The load transfer mechanism of laterally loaded pile groups is very complicated, and the analysis method is affected by many factors. This paper presents a field test study on lateral responses of large diameter cast-in-place isolated single piles with free head and pile groups with fixed head to investigate the pile group effect. Boreholes are drilled, and relevant field and laboratory tests are carried out to obtain main physical mechanical parameters and the soil profile of the site. Results of lateral loads, lateral displacements and bending moments measured in the field are reported and discussed. A group efficiency factor-based calculation method applicable to laterally loaded pile groups is derived according to a series of full scale and centrifuge tests. An existing group efficiency factor-based calculation method is compared with the proposed method. And three other measured test results are used to verify the calculated results. The comparison results show that the proposed method provides good predictions of load–displacement responses of pile groups. [ABSTRACT FROM AUTHOR]

The absolute stereochemical configurations of acremolides A and B were predicted by a biochemistry-based rule and unambiguously confirmed through their total syntheses. The features of the total syntheses include sequential Krische's Ir-catalyzed crotylation, Brown's borane-mediated crotylation, Mitsunobu esterification reaction, and cross-metathesis reaction. The efficient total synthesis enabled clear validation of the predicted stereochemistry for acremolides A and B. [ABSTRACT FROM AUTHOR]

Ectoine and its derivative 5-hydroxyectoine are compatible solutes initially found in the hyperhalophilic bacterium Ectothiorhodospira halochloris, which inhabits the desert in Egypt. The habitat of ectoine producers implies the primary function of ectoine as a cytoprotectant against harsh conditions such as high salinity, drought, and high radiation. More extensive and in-depth studies have revealed the multiple functions of ectoine in its native producer bacterial cells and other types of cells and its biomolecular components (such as proteins and DNA) as a general protective agent. Its chemical properties as a bio-based amino acid derivative make it attractive for basic scientific research and related industries, such as the food/agricultural industry, cosmetic manufacturing, biologics, and therapeutic agent preparation. This article first discusses the functions and applications of ectoine and 5-hydroxyectoine. Subsequently, more emphasis was placed on advances in bio-based ectoine and/or 5-hydroxyectoine production. Strategies for developing more robust cell factories for highly efficient ectoine and/or 5-hydroxyectoine production are further discussed. We hope this review will provide a valuable reference for studies on the bio-based production of ectoine and 5-hydroxyectoine. [ABSTRACT FROM AUTHOR]

The epidermal barrier is vital for protecting the skin from environmental stressors and ultraviolet (UV) radiation. Filaggrin-2 (FLG2), a critical protein in the stratum corneum, plays a significant role in maintaining skin barrier homeostasis. However, the precise role of FLG2 in mitigating the adverse effects of UV-induced barrier disruption and photoaging remains poorly understood. In this study, we revealed that UVB exposure resulted in a decreased expression of FLG2 in HaCaT keratinocytes, which correlated with a compromised barrier function. The administration of recombinant filaggrin-2 (rFLG2) enhanced keratinocyte differentiation, bolstered barrier integrity, and offered protection against apoptosis and oxidative stress induced by UVB irradiation. Furthermore, in a UV-induced photodamage murine model, the dermal injection of rFLG2 facilitated the enhanced restoration of the epidermal barrier, decreased oxidative stress and inflammation, and mitigated the collagen degradation that is typical of photoaging. Collectively, our findings suggested that targeting FLG2 could be a strategic approach to prevent and treat skin barrier dysfunction and combat the aging effects associated with photoaging. rFLG2 emerges as a potentially viable therapy for maintaining skin health and preventing skin aging processes amplified by photodamage. [ABSTRACT FROM AUTHOR]

DNA replication and transcription generate DNA supercoiling, which can cause topological stress and intertwining of daughter chromatin fibers, posing challenges to the completion of DNA replication and chromosome segregation. Type II topoisomerases (Top2s) are enzymes that relieve DNA supercoiling and decatenate braided sister chromatids. How Top2 complexes deal with the topological challenges in different chromatin contexts, and whether all chromosomal contexts are subjected equally to torsional stress and require Top2 activity is unknown. Here we show that catalytic inhibition of the Top2 complex in interphase has a profound effect on the stability of heterochromatin and repetitive DNA elements. Mechanistically, we find that catalytically inactive Top2 is trapped around heterochromatin leading to DNA breaks and unresolved catenates, which necessitate the recruitment of the structure specific endonuclease, Ercc1-XPF, in an SLX4- and SUMO-dependent manner. Our data are consistent with a model in which Top2 complex resolves not only catenates between sister chromatids but also inter-chromosomal catenates between clustered repetitive elements. Here the authors show that the catalytic inhibition of the Top2 complex in interphase has an effect on the stability of heterochromatin and repetitive DNA elements. [ABSTRACT FROM AUTHOR]

All-solid-state batteries, renowned for their enhanced safety and high energy density, have garnered broad interest. Oxide solid electrolytes are highly anticipated for their balanced performance. However, their high Young's modulus and inadaptability to volume change during cycling lead to poor contact and eventual battery failure. In this work, Young's modulus of Li1+x(OH)xCl samples is lowered to a level comparable to that of sulfide by regulating the–OH content. As the–OH content increases, Young's modulus of Li1+x(OH)xCl samples decreases significantly. This may be due to the local aggregation of–OH groups, forming cavities similar to LiOH structure, which reduces the bonding of the structure. On the premise of high Li-ion conductivity and electrochemical stability, the lowered Young's modulus improves the contact between the solid electrolyte and the electrodes, forming a strong and stable interfacial layer, thereby improving interfacial and cycling stability. The symmetrical lithium metal cell shows excellent cycle performance of 600 h, and the assembled LiFePO4∣Li2.4(OH)1.4Cl∣Li cell shows significantly enhanced cycling endurance with 80% capacity retention after 150 cycles. This work not only emphasizes the crucial importance of Young's modulus in improving interface issues but also offers innovative approaches to advance the mechanical properties of solid electrolytes. [ABSTRACT FROM AUTHOR]

Detecting pathogenic bacteria and their phenotypes including microbial resistance is crucial for preventing infection, ensuring food safety, and promoting environmental protection. Raman spectroscopy offers rapid, seamless, and label-free identification, rendering it superior to gold-standard detection techniques such as culture-based assays and polymerase chain reactions. However, its practical adoption is hindered by issues related to weak signals, complex spectra, limited datasets, and a lack of adaptability for detection and characterization of bacterial pathogens. This review focuses on addressing these issues with recent Raman spectroscopy breakthroughs enabled by machine learning (ML), particularly deep learning methods. Given the regulatory requirements, consumer demand for safe food products, and growing awareness of risks with environmental pathogens, this study emphasizes addressing pathogen detection in clinical, food safety, and environmental settings. Here, we highlight the use of convolutional neural networks for analyzing complex clinical data and surface enhanced Raman spectroscopy for sensitizing early and rapid detection of pathogens and analyzing food safety and potential environmental risks. Deep learning methods can tackle issues with the lack of adequate Raman datasets and adaptability across diverse bacterial samples. We highlight pending issues and future research directions needed for accelerating real-world impacts of ML-enabled Raman diagnostics for rapid and accurate diagnosis and surveillance of pathogens across critical fields. [ABSTRACT FROM AUTHOR]

Background: The disruption of intracranial fluid dynamics due to large unruptured cerebral arteriovenous malformation (AVM) commonly triggers a domino effect within the central nervous system. This phenomenon is frequently overlooked in prior clinic and may lead to catastrophic misdiagnoses. Our team has documented the world's first case of so-called AVM Pentalogy (AVMP) induced by a AVM. Clinical presentation and result: A 30-year-old female was first seen 9years ago with an occasional fainting, at which time a huge unruptured AVM was discovered. Subsequently, due to progressive symptoms, she sought consultations from several prestigious neurosurgical departments in China, where all consulting neurosurgeons opted for conservation treatment due to perceived surgical risks. During the follow-up period, the patient gradually presented with hydrocephalus, empty sella, secondary Chiari malformation, syringomyelia, and scoliosis (we called as AVMP). When treated in our department, she already displayed numerous symptoms, including severe intracranial hypertension. Our team deduced that the hydrocephalus was the primary driver of her AVMP symptoms, representing the most favorable risk profile for intervention. As expected, a ventriculoperitoneal shunt successfully mitigated all symptoms of AVMP at 21-months post-surgical review. Conclusion: During the monitoring of unruptured AVM, it is crucial to remain vigilant for the development or progression of AVMP. When any component of AVMP is identified, thorough etiological studies and analysis of cascade reactions are imperative to avert misdiagnosis. When direct AVM intervention is not viable, strategically addressing hydrocephalus as part of the AVMP may serve as the critical therapeutic focus. [ABSTRACT FROM AUTHOR]

The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic–pituitary–gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives. [ABSTRACT FROM AUTHOR]

Mortality in patients with infective endocarditis (IE) remains high. The existing risk scores are relatively complex with limited clinical application. This study was conducted to establish a new risk model to predict in-hospital and 6-month mortality in IE patients. A total of 1549 adult patients with definite IE admitted to Guangdong Provincial People's Hospital (n=1354) or Xiamen Cardiovascular Hospital (n=195) were included. The derivation cohort consisted of 1141 patients. The score was developed using the multivariate stepwise logistic regression analysis for in-hospital death. Bootstrap analysis was used for validation. Discrimination and calibration were evaluated by the receiver operating characteristic curve and the Hosmer–Lemeshow goodness-of-fit test. Six risk factors were used as score parameters (1 point for each): aortic valve affected, previous valve replacement surgery, severe heart failure, elevated serum direct bilirubin, moderate–severe anemia and acute stage. The predictive value and calibration of the ASSESS-IE score for in-hospital death were excellent in the derivation (area under the curve [AUC]=0.781, p<0.001; Hosmer–Lemeshow p=0.948) and validation (AUC=0.779, p<0.001; Hosmer–Lemeshow p=0.520) cohorts. The score remained excellent in bootstrap validation (AUC=0.783). The discriminatory ability of the ASSESS-IE score for in-hospital (AUC: 0.781 vs. 0.799, p=0.398) and 6-month mortality (AUC: 0.778 vs. 0.814, p=0.040) were similar with that of Park's score which comprised 14 variables. The ASSESS-IE risk score is a new and robust risk-stratified tool for patients with IE, which might further facilitate clinical decision-making. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a progressive neurodegeneration disease that causes photoreceptor demise and vision impairments. In AMD pathogenesis, the primary death of retinal neurons always leads to the activation of resident microglia. The migration of activated microglia to the ongoing retinal lesion and their morphological transformation from branching to ameboid-like are recognized as hallmarks of AMD pathogenesis. Activated microglia send signals to Müller cells and promote them to react correspondingly to damaging stimulus. Müller cells are a type of neuroglia cells that maintain the normal function of retinal neurons, modulating innate inflammatory responses, and stabilize retinal structure. Activated Müller cells can accelerate the progression of AMD by damaging neurons and blood vessels. Therefore, the crosstalk between microglia and Müller cells plays a homeostatic role in maintaining the retinal environment, and this interaction is complicatedly modulated. In particular, the mechanism of mutual regulation between the two glia populations is complex under pathological conditions. This paper reviews recent findings on the crosstalk between microglia and Müller glia during AMD pathology process, with special emphasis on its therapeutic potentials. [ABSTRACT FROM AUTHOR]

While single-modal visible light images or infrared images provide limited information, infrared light captures significant thermal radiation data, whereas visible light excels in presenting detailed texture information. Combining images obtained from both modalities allows for leveraging their respective strengths and mitigating individual limitations, resulting in high-quality images with enhanced contrast and rich texture details. Such capabilities hold promising applications in advanced visual tasks including target detection, instance segmentation, military surveillance, pedestrian detection, among others. This paper introduces a novel approach, a dual-branch decomposition fusion network based on AutoEncoder (AE), which decomposes multi-modal features into intensity and texture information for enhanced fusion. Local contrast enhancement module (CEM) and texture detail enhancement module (DEM) are devised to process the decomposed images, followed by image fusion through the decoder. The proposed loss function ensures effective retention of key information from the source images of both modalities. Extensive comparisons and generalization experiments demonstrate the superior performance of our network in preserving pixel intensity distribution and retaining texture details. From the qualitative results, we can see the advantages of fusion details and local contrast. In the quantitative experiments, entropy (EN), mutual information (MI), structural similarity (SSIM) and other results have improved and exceeded the SOTA (State of the Art) model as a whole. [ABSTRACT FROM AUTHOR]

Background: Hemorrhage is a common complication of nephrostomy and percutaneous nephrolithotripsy, and it is caused by surgical factors. Here we report a rare case of hemorrhage caused by sepsis-related coagulation dysfunction. Case presentation: A 72-years-old male patient with bilateral ureteral calculi accompanied by hydronephrosis and renal insufficiency developed sepsis and hemorrhage on the third day after bilateral nephrostomy. After vascular injury was excluded by DSA, the hemorrhage was considered to be sepsis-associated coagulopathy(SAC/SIC), finally the patient recovered well after active symptomatic treatment. Conclusions: In patients with sepsis and hemorrhage, SAC/SIC cannot be excluded even if coagulation function is slightly abnormal after surgical factors are excluded. For urologists who may encounter similar cases in their general urology practice, it is important to be aware of these unusual causes of hemorrhage. [ABSTRACT FROM AUTHOR]

The Jishishan Ms 6.2 earthquake occurred at 23:59 on December 18, 2023 in Gansu Province, China. We conducted a field survey to assess the hazards and damages caused by the earthquake and its associated geo-activities. Subsequently, we organized a seminar to discuss the possible causes of the destruction of a prehistoric site—Lajia Settlement—dated back to four thousand years B.P. and located only several kilometers away from the epicenter of the Jishishan earthquake. The Jishishan earthquake was unique for its hazard and disaster process, which featured ground shaking and a series of complex geological and geomorphological activities: sediment and soil spray piles, liquefaction, collapse, landslide, and mudflow along water channels. We define this phenomenon as the Jishishan earthquake ripple hazard (JERH). The most recent evidence from the JERH suggests that a prehistoric earthquake similar to the JERH, instead of riverine floods or earthquake-induced landslide dam outburst flood, as previously hypothesized, destroyed the Lajia Settlement. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. Method: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. Results: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. Conclusion: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Objective: To compare the clinical efficacy of febuxostat combined with a low‐purine diet versus allopurinol combined with a low‐purine diet in the treatment of gout. Method s : In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low‐purine diet) and the control group (allopurinol combined with a low‐purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor‐a (TNF‐a), cytokine interleukin‐1beta (IL‐1β), and interleukin (IL)‐18 (IL‐18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. Results: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p =.027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 μmol/L ± 17.23 μmol/L vs. S198.32 μmol/L ± 18.34 μmol/L, p <.001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p =.014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p <.001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p <.001) compared to the control group, with statistically significant differences (p <.05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p <.05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p =.025). Conclusion: Febuxostat combined with a low‐purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). ATP‐binding cassette protein G1 (ABCG1) is crucial in mediating the outflow of cholesterol, phosphatidylcholine and sphingomyelin and reducing intracellular lipid accumulation. Objective: This study aimed to evaluate whether ABCG1 participates in the abnormal adipogenesis of chondrocytes in osteoarthritic cartilage of temporomandibular joint. Methods: Eight‐week‐old female rats were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical (IHC) staining, and qRT–PCR were performed. Primary condylar chondrocytes of rats were transfected with ABCG1 shRNA or overexpression lentivirus and then stimulated with fluid flow shear stress (FFSS). Cells were collected for oil red O staining, immunofluorescence staining, and qRT–PCR analysis. Results: Abnormal adipogenesis, characterized by increased expression of Adiponectin, CCAAT/enhancer‐binding protein α (Cebpα), fatty acid binding protein 4 (Fabp4) and Perilipin1, was enhanced in the degenerative cartilage of TMJ OA in rats with UAC, accompanied by decreased expression of ABCG1. After FFSS stimulation, we observed lipid droplets in the cytoplasm of cultured cells with increased expression of Adiponectin, Cebpα, Fabp4 and Perilipin1 and decreased expression of ABCG1. Knockdown of Abcg1 induced abnormal adipogenesis and differentiation of condylar chondrocytes. Overexpression of ABCG1 alleviated the abnormal adipogenesis and differentiation of condylar chondrocytes induced by FFSS. Conclusions: Abnormal adipogenesis of chondrocytes and decreased ABCG1 expression were observed in degenerative cartilage of TMJ OA. ABCG1 overexpression effectively inhibits the adipogenesis of chondrocytes and thus alleviates TMJ condylar cartilage degeneration. [ABSTRACT FROM AUTHOR]

There is increasing concern regarding the impact of compound agroclimatic extreme events on crop yield, particularly in the context of projected increases in their frequency and intensity due to climate change. While previous studies have generally focused on compound hot and dry events in maize and wheat using growing-season relative thresholds, the time-variant physiological sensitivity of crops to climate extremes has not been sufficiently considered. We determined the spatiotemporal variations of compound climate extremes (CEs) for single- and late-rice in southern China during 1980–2014 and their underlying drivers using growth-stage specific physiological thresholds. Specifically, we carefully distinguished between concurrent compound events (CCEs) and consecutive compound events (CSEs). Our results indicated an increasing trend of compound hot-dry events for single-rice, but a decreasing trend of compound chilling-rainy events for late-rice. Spatially, the hotspots of compound hot-dry events for single-rice shifted from the lower Yangtze River Basin to its upper stream, and were dominated by the spatial differences in phenology rather than the occurrence of extreme events. The hotspots of compound chilling-rainy events for late-rice remained concentrated near the northwest edges of late-rice growing areas, indicating the limitation of thermal conditions. The occurrence and duration of CCEs was closely related to local temperature-moisture coupling (negative correlation). A path analysis suggested that temperature was the dominant factor influencing the changes in compound hot-dry events for single-rice. For the changes in compound chilling-rainy events for late-rice, the effect of temperature was only slightly larger than that of moisture. Our study has improved the understanding of compound climate extremes in China's rice production system, and the results provide important information for risk management and adaptation strategies under climate change. [ABSTRACT FROM AUTHOR]

Synthetic glucocorticoids (GC), such as dexamethasone, are extensively used to treat chronic inflammation and autoimmune disorders. However, long-term treatments are limited by various side effects, including muscle atrophy. GC activities are mediated by the glucocorticoid receptor (GR), that regulates target gene expression in various tissues in association with cell-specific co-regulators. Here we show that GR and the lysine-specific demethylase 1 (LSD1) interact in myofibers of male mice, and that LSD1 connects GR-bound enhancers with NRF1-associated promoters to stimulate target gene expression. In addition, we unravel that LSD1 demethylase activity is required for triggering starvation- and dexamethasone-induced skeletal muscle proteolysis in collaboration with GR. Importantly, inhibition of LSD1 circumvents muscle wasting induced by pharmacological levels of dexamethasone, without affecting their anti-inflammatory activities. Thus, our findings provide mechanistic insights into the muscle-specific GC activities, and highlight the therapeutic potential of targeting GR co-regulators to limit corticotherapy-induced side effects. Even though glucocorticoids are potent anti-inflammatory agents, they can cause muscle wasting. Here, the authors show that targeting the glucocorticoid receptor coactivator LSD1 limits muscle loss without reducing the drugs' efficiency on the immune system. [ABSTRACT FROM AUTHOR]

Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single‐cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV‐releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification. [ABSTRACT FROM AUTHOR]

Accepted by: Aris Syntetos Management-led productivity improvements are crucial for achieving sustainable development, and the Malmquist productivity index is known to be useful in relevant contexts. This study aims to extend such index by using non-parametric mathematical modelling of production processes. Specifically, and in the spirit of the existing index, we introduce the directional distance function to develop a new one applicable to the joint production of desirable and undesirable outputs. Furthermore, we decompose the new index into two constituent components to provide more intuitive explanations when revealing the root sources of productivity changes over time. Under the cost minimization assumption, the new index is applicable when producers implement resource allocation management, and the input–output quantities and the micro-level input prices are known. The index emphasizes that the allocative efficiency should be regarded as an important aspect of productivity assessment like the technical efficiency. As a practical benchmarking tool, it can offer valuable information and provide appropriate strategies for managerial decision-making. The index's application and usefulness is demonstrated in the commercial bank sector in China. [ABSTRACT FROM AUTHOR]

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The first total synthesis of incarnatapeptins A and B, two novel marine natural products, was accomplished from readily available (S)‐1‐benzyloxycarbonylhexahydropyridazine‐3‐carboxylic acid. This route, whose longest linear sequence was 12 steps, provided the incarnatapeptins A and B in yields of 26.5 % and 19.7 %, respectively, and enabled the structure and stereochemistry of both natural products to be unambiguously confirmed. Highlights of our synthesis include the photoredox‐mediated decarboxylative 1,4‐addition reaction and a novel and practical N‐acylation paradigm promoted by silver carbonate. The unusual facile atropisomerism of some linear peptidic intermediates was also observed by TLC analysis in the course of this work. [ABSTRACT FROM AUTHOR]

The first total synthesis of incarnatapeptins A and B, two novel marine natural products, was accomplished from readily available (S)‐1‐benzyloxycarbonylhexahydropyridazine‐3‐carboxylic acid. This route, whose longest linear sequence was 12 steps, provided the incarnatapeptins A and B in yields of 26.5 % and 19.7 %, respectively, and enabled the structure and stereochemistry of both natural products to be unambiguously confirmed. Highlights of our synthesis include the photoredox‐mediated decarboxylative 1,4‐addition reaction and a novel and practical N‐acylation paradigm promoted by silver carbonate. The unusual facile atropisomerism of some linear peptidic intermediates was also observed by TLC analysis in the course of this work. [ABSTRACT FROM AUTHOR]

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury. Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues. These proteins initiate inflammatory dysfunction, such as neurogenic heterotopic ossification. This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies. Accordingly, a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues. Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis. The relationships among brain-derived extracellular vesicles, fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo. The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury. [ABSTRACT FROM AUTHOR]

Aim: VDJ001 is a novel recombinant humanized monoclonal antibody against the anti-interleukin-6 receptor. As an analog of tocilizumab, it exhibited improved affinity and in vitro activity. Based on preclinical studies, a first-in-human clinical study was conducted to evaluate the safety, tolerability, and pharmacokinetics of VDJ001. Methods: This is a single-center, randomized, double-blinded, placebocontrolled phase I dose-escalation study conducted in healthy Chinese volunteers. Four cohorts were designed with dosages ranging from 1 to 8 mg/kg. There were equal numbers of female and male volunteers in each cohort. Enrolled subjects randomly received a single intravenous administration of VDJ001 or placebo (VDJ001: placebo = 4:1 in both female and male volunteers). Three sentinel volunteers in the 1 mg/kg cohort were first administered, and the treatment of the other seven volunteers was carried out after a safety assessment on D15. The following cohort was conducted only when the safety profile was evaluated as acceptable on D29 of the previous cohort. Samples for pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity were collected at specified time points and analyzed through validated methods. Adverse events and the results of the examination and laboratory were analyzed to assess the safety profile. Results: All cohorts were carried out according to the protocol. With the escalation of dosage, Cmax increased linearly, and AUC0-t and AUC0-8 increased in a non-linear manner, while clearance decreased and t1/2 prolonged. Six volunteers who received VDJ001 tested ADA-positive, among whom one participant tested Nab-positive on D57. One volunteer in the placebo group tested ADA-positive but Nab-negative. CRP concentrations were not found to be correlated with the dosage. Both IL-6 and sIL-6R concentrations increased after the administration of VDJ001. All adverse events were mild to moderate in severity. No serious adverse events were reported in this study. No unexpected or clinically significant safety issues were found. Conclusion: The safety and tolerability of VDJ001 are acceptable with a single intravenous dosage of 1~8 mg/kg. Further clinical trials are warranted. [ABSTRACT FROM AUTHOR]

Aims: Phosphorus (P) deficiency-induced mobilization of rare earth elements (REEs) in the rhizosphere contributes to REE accumulation in the hyperaccumulator Phytolacca americana, but a lack of in situ methods for visualization of the root-soil interface limits our understanding of the underlying processes. Methods: Diffusive gradients in thin-films (DGT) devices were used for probing root exudates, REEs and P in the P. americana rhizosphere. Desorption electrospray ionization mass spectrometry and laser-ablation inductively coupled mass spectrometry were used for in situ imaging of root exudates, REEs and P sorbed on the DGT. Results: The novel approach demonstrated here is capable of synchronously and quantitatively characterizing the distribution of root exudates and labile elements in the rhizosphere. The secretion fluxes of citrate and oxalate in the rhizosphere under P deficiency were three times higher than under P sufficient condition; and the lanthanum (La) fluxes in the rhizosphere under P deficiency were ten times greater than at P sufficiency condition. The enrichment of P and La under P deficiency and depletion under P sufficient conditions in the rhizosphere suggests that P deficiency-induced organic acid secretion is crucial for the mobilization of soil REEs and subsequent REE accumulation in P. americana. Conclusion: The combination of DGT devices with mass spectrometry imaging is technically feasible for in situ synchronous imaging of root exudates, REEs and labile elements at the root-soil interface. Our study shed light on processes of mobilization of mineral elements in the rhizosphere induced as a side-effect of the P acquisition mechanism. [ABSTRACT FROM AUTHOR]

The zero-inflated count data model has long been viewed as an important research topic owing to its enormously different disciplines. As early classical statistical models of linear and logarithmic mean transformation are difficult to be consistent with reality, an enhanced hurdle model based on machine learning methods is proposed. The decision tree, random forest, support vector, and XGBoost methods are introduced in the two stages of the hurdle model. This framework allows to capture the decision-making behavior and predict the count more flexibly and accurately. The generalized hurdle model consists of traditional discrete distributions, which can fit under-dispersed, equi-dispersed, or over-dispersed count data. The extended hurdle models are utilized to fit health care data and compare their performance with traditional count models. The results show that the generalized hurdle model with random forest performs best. Variable importance, break-down plots, and partial plots provide better interpretability for the extended model, which makes the results more reliable and transparent. To the best of our knowledge, this is the first study to generalize the hurdle model with interpretable machine learning methods in count data. [ABSTRACT FROM AUTHOR]

Reliable lithology spatial distribution directly reflects the geological situation of the reservoir, which is the basis of stratigraphic correlation, sedimentary modeling, and other geological research. Under the condition of limited reservoir data, it is a challenging task to accurately depict the lithology spatial distribution and provide a quantitative reliability analysis of the results. In this study, we propose a flexible spatial distribution prediction and model reliability analysis method. Firstly, the method develops a spatially dependent deep Kriging technology to fit the heterogeneous characteristics of the reservoir lithology, and adopts the extracted spatial key information and related reservoir attributes to invert lithology spatial distribution intelligently. Then, it focuses on the real-time assimilation of non-Gaussian data in the reliability modeling and quantitatively analyzes the reliability of the prediction system under the non-Gaussian hypothesis. Finally, the method is applied to the actual heterogeneous reservoir, good results are achieved in the prediction accuracy, model fitting degree, model reliability, and time performance compared with other methods. The method is conducive to finding future mineral deposits locations and reducing exploration costs. [ABSTRACT FROM AUTHOR]