A prediction model of dementia conversion for mild cognitive impairment by combining plasma pTau181 and structural imaging features.

AIMS: The early stages of Alzheimer's disease (AD) are no longer insurmountable. Therefore, identifying at-risk individuals is of great importance for precise treatment. We developed a model to predict cognitive deterioration in patients with mild cognitive impairment (MCI). METHODS: Based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we constructed models in a derivation cohort of 761 participants with MCI (138 of whom developed dementia at the 36th month) and verified them in a validation cohort of 353 cognitively normal controls (54 developed MCI and 19 developed dementia at the 36th month). In addition, 1303 participants with available AD cerebrospinal fluid core biomarkers were selected to clarify the ability of the model to predict AD core features. We assessed 32 parameters as candidate predictors, including clinical information, blood biomarkers, and structural imaging features, and used multivariable logistic regression analysis to develop our prediction model. RESULTS: Six independent variables of MCI deterioration were identified: apolipoprotein E ε4 allele status, lower Mini-Mental State Examination scores, higher levels of plasma pTau181, smaller volumes of the left hippocampus and right amygdala, and a thinner right inferior temporal cortex. We established an easy-to-use risk heat map and risk score based on these risk factors. The area under the curve (AUC) for both internal and external validations was close to 0.850. Furthermore, the AUC was above 0.800 in identifying participants with high brain amyloid-ß loads. Calibration plots demonstrated good agreement between the predicted probability and actual observations in the internal and external validations. CONCLUSION: We developed and validated an accurate prediction model for dementia conversion in patients with MCI. Simultaneously, the model predicts AD-specific pathological changes. We hope that this model will contribute to more precise clinical treatment and better healthcare resource allocation.

Vision-Centric BEV Perception: A Survey.

In recent years, vision-centric Bird's Eye View (BEV) perception has garnered significant interest from both industry and academia due to its inherent advantages, such as providing an intuitive representation of the world and being conducive to data fusion. The rapid advancements in deep learning have led to the proposal of numerous methods for addressing vision-centric BEV perception challenges. However, there has been no recent survey encompassing this novel and burgeoning research field. To catalyze future research, this paper presents a comprehensive survey of the latest developments in vision-centric BEV perception and its extensions. It compiles and organizes up-to-date knowledge, offering a systematic review and summary of prevalent algorithms. Additionally, the paper provides in-depth analyses and comparative results on various BEV perception tasks, facilitating the evaluation of future works and sparking new research directions. Furthermore, the paper discusses and shares valuable empirical implementation details to aid in the advancement of related algorithms.

Association of white matter hyperintensities with cognitive decline and neurodegeneration.

Background: The relationship between white matter hyperintensities (WMH) and the core features of Alzheimer's disease (AD) remains controversial. Further, due to the prevalence of co-pathologies, the precise role of WMH in cognition and neurodegeneration also remains uncertain. Methods: Herein, we analyzed 1803 participants with available WMH volume data, extracted from the ADNI database, including 756 cognitively normal controls, 783 patients with mild cognitive impairment (MCI), and 264 patients with dementia. Participants were grouped according to cerebrospinal fluid (CSF) pathology (A/T profile) severity. Linear regression analysis was applied to evaluate the factors associated with WMH volume. Modeled by linear mixed-effects, the increase rates (Δ) of the WMH volume, cognition, and typical neurodegenerative markers were assessed. The predictive effectiveness of WMH volume was subsequently tested using Cox regression analysis, and the relationship between WMH/ΔWMH and other indicators such as cognition was explored through linear regression analyses. Furthermore, we explored the interrelationship among amyloid-ß deposition, cognition, and WMH using mediation analysis. Results: Higher WMH volume was associated with older age, lower CSF amyloid-ß levels, hypertension, and smoking history (all p ≤ 0.001), as well as cognitive status (MCI, p < 0.001; dementia, p = 0.008), but not with CSF tau levels. These results were further verified in any clinical stage, except hypertension and smoking history in the dementia stage. Although WMH could not predict dementia conversion, its increased levels at baseline were associated with a worse cognitive performance and a more rapid memory decline. Longitudinal analyses showed that baseline dementia and positive amyloid-ß status were associated with a greater accrual of WMH volume, and a higher ΔWMH was also correlated with a faster cognitive decline. In contrast, except entorhinal cortex thickness, the WMH volume was not found to be associated with any other neurodegenerative markers. To a lesser extent, WMH mediates the relationship between amyloid-ß and cognition. Conclusion: WMH are non-specific lesions that are associated with amyloid-ß deposition, cognitive status, and a variety of vascular risk factors. Despite evidence indicating only a weak relationship with neurodegeneration, early intervention to reduce WMH lesions remains a high priority for preserving cognitive function in the elderly.

Comparative Analysis of Phytohormone Biosynthesis Genes Responses to Long-Term High Light in Tolerant and Sensitive Wheat Cultivars.

Phytohormones are vital for developmental processes, from organ initiation to senescence, and are key regulators of growth, development, and photosynthesis. In natural environments, plants often experience high light (HL) intensities coupled with elevated temperatures, which pose significant threats to agricultural production. However, the response of phytohormone-related genes to long-term HL exposure remains unclear. Here, we examined the expression levels of genes involved in the biosynthesis of ten phytohormones, including gibberellins, cytokinins, salicylic acid, jasmonic acid, abscisic acid, brassinosteroids, indole-3-acetic acid, strigolactones, nitric oxide, and ethylene, in two winter wheat cultivars, Xiaoyan 54 (XY54, HL tolerant) and Jing 411 (J411, HL sensitive), when transferred from low light to HL for 2-8 days. Under HL, most genes were markedly inhibited, while a few, such as TaGA2ox, TaAAO3, TaLOG1, and TaPAL2, were induced in both varieties. Interestingly, TaGA2ox2 and TaAAO3 expression positively correlated with sugar content but negatively with chlorophyll content and TaAGP expression. In addition, we observed that both varieties experienced a sharp decline in chlorophyll content and photosynthesis performance after prolonged HL exposure, with J411 showing significantly more sensitivity than XY54. Hierarchical clustering analysis classified the phytohormone genes into the following three groups: Group 1 included six genes highly expressed in J411; Group 2 contained 25 genes drastically suppressed by HL in both varieties; and Group 3 contained three genes highly expressed in XY54. Notably, abscisic acid (ABA), and jasmonic acid (JA) biosynthesis genes and their content were significantly higher, while gibberellins (GA) content was lower in XY54 than J411. Together, these results suggest that the differential expression and content of GA, ABA, and JA play crucial roles in the contrasting responses of tolerant and sensitive wheat cultivars to leaf senescence induced by long-term HL. This study enhances our understanding of the mechanisms underlying HL tolerance in wheat and can guide the development of more resilient wheat varieties.

Distribution characteristics of sulfonamide antibiotics between water and extracellular polymeric substances in municipal sludge.

The interaction between extracellular polymeric substances (EPS) in municipal sludge and antibiotics in wastewater is critical in wastewater treatment, resource recovery, and sludge management. Therefore, it is increasingly urgent to investigate the distribution coefficient (Log K) of sulfonamide antibiotics (SAs) in EPS, particularly in sludge-derived dissolved organic carbon (DOC) and aqueous phase systems. Herein, through balance experiments, the concentrations of SAs were determined using alkaline extraction EPS (AEPS) and alginate-like extracellular polymer (ALE) systems, and the Log KDOC values were determined. The results showed that the Log KDOC of AEPS was higher than that of ALE, which exhibited a negative KDOC value, indicating an inhibitory effect on dissolution. For the three SAs studied, the Log KDOC values were in the following order: sulfamethoxazole > sulfapyridine > sulfadiazine. This order can be attributed to the differing physicochemical properties, such as polarity, of the SAs. Three-dimensional excitation-emission matrix fluorescence spectra and fitting results indicated a lack of aromatic proteins dominated by tryptophan and humus-like substances in ALE. Meanwhile, the hydrophobic interaction of aromatic proteins dominated by tryptophan was the main driving force in the binding process between AEPS and SAs.

Novel compound heterozygous mutations in the hemojuvelin gene in a juvenile hemochromatosis patient: A case report.

BACKGROUND: Juvenile hemochromatosis (JH) is an early-onset, rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs. Pathogenic mutations in the hemojuvelin (HJV) gene are the major cause of JH. CASE SUMMARY: A 34-year-old male Chinese patient presented with liver fibrosis, diabetes, hypogonadotropic hypogonadism, hypophysis hypothyroidism, and skin hyperpigmentation. Biochemical test revealed a markedly elevated serum ferritin level of 4329 µg/L and a transferrin saturation rate of 95.4%. Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A (p.R288Q) in the HJV gene which was transmitted from his father, and two known mutations, c.18G>C (p.Q6H) and c.962_963delGCinsAA (p.C321*) in cis, which were inherited from his mother. The p.R288W mutation was previously reported to be pathogenic for hemochromatosis, which strongly supported the pathogenicity of p.R288Q reported for the first time in this case. After 72 wk of intensive phlebotomy therapy, the patient achieved a reduction in serum ferritin to 160.5 µg/L. The patient's clinical symptoms demonstrated a notable improvement. CONCLUSION: This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism. It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH.

The invertase gene PWIN1 confers chilling tolerance of rice at the booting stage via mediating pollen development.

Pollen fertility is a primary regulator of grain yield and is highly susceptible to cold and other environmental stress. We revealed the roles of rice cell wall invertase gene PWIN1 in pollen development and chilling tolerance. We uncovered its preferential expression in microspores and bicellular pollen and identified its knock-down and knock-out mutants. pwin1 mutants produced a higher proportion of abnormal pollen than wild-type plants. The contents of sucrose, glucose, and fructose were increased, while ATP content and primary metabolism activity were reduced in the mutant pollen. Furthermore, the loss of function of PWIN1 coincided with an increase in SnRK1 activity and a decrease in TOR activity. Under chilling conditions, pwin1 mutants displayed significantly reduced pollen viability and seed-setting rate, while overexpressing PWIN1 notably increased pollen viability and seed-setting rate as compared with the wild-type, indicating that PWIN1 is essential for rice pollen development and grain yield under cold stress. This study provides insights into the molecular mechanisms underlying rice pollen fertility during chilling stress, and a new module to improve chilling tolerance of rice at the booting stage by molecular design.

Whole-genome landscape of histone H3K4me3 modification during sperm cell lineage development in tomato.

BACKGROUND: During male gametogenesis of flowering plants, sperm cell lineage (microspores, generative cells, and sperm cells) differentiated from somatic cells and acquired different cell fates. Trimethylation of histone H3 on lysine 4 (H3K4me3) epigenetically contributes to this process, however, it remained unclear how H3K4me3 influences the gene expression in each cell type. Here, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) to obtain a genome-wide landscape of H3K4me3 during sperm cell lineage development in tomato (Solanum lycopersicum). RESULTS: We show that H3K4me3 peaks were mainly enriched in the promoter regions, and intergenic H3K4me3 peaks expanded as sperm cell lineage differentiated from somatic cells. H3K4me3 was generally positively associated with transcript abundance and served as a better indicator of gene expression in somatic and vegetative cells, compared to sperm cell lineage. H3K4me3 was mutually exclusive with DNA methylation at 3' proximal of the transcription start sites. The microspore maintained the H3K4me3 features of somatic cells, while generative cells and sperm cells shared an almost identical H3K4me3 pattern which differed from that of the vegetative cell. After microspore division, significant loss of H3K4me3 in genes related to brassinosteroid and cytokinin signaling was observed in generative cells and vegetative cells, respectively. CONCLUSIONS: Our results suggest the asymmetric division of the microspore significantly reshapes the genome-wide distribution of H3K4me3. Selective loss of H3K4me3 in genes related to hormone signaling may contribute to functional differentiation of sperm cell lineage. This work provides new resource data for the epigenetic studies of gametogenesis in plants.

Mitogenomic phylogeny, biogeography, and cryptic divergence of the genus Silurus (Siluriformes: Siluridae).

The genus Silurus, an important group of catfish, exhibits heterogeneous distribution in Eurasian freshwater systems. This group includes economically important and endangered species, thereby attracting considerable scientific interest. Despite this interest, the lack of a comprehensive phylogenetic framework impedes our understanding of the mechanisms underlying the extensive diversity found within this genus. Herein, we analyzed 89 newly sequenced and 20 previously published mitochondrial genomes (mitogenomes) from 13 morphological species to reconstruct the phylogenetic relationships, biogeographic history, and species diversity of Silurus. Our phylogenetic reconstructions identified eight clades, supported by both maximum-likelihood and Bayesian inference. Sequence-based species delimitation analyses yielded multiple molecular operational taxonomic units (MOTUs) in several taxa, including the Silurus asotus complex (four MOTUs) and Silurus microdorsalis (two MOTUs), suggesting that species diversity is underestimated in the genus. A reconstructed time-calibrated tree of Silurus species provided an age estimate of the most recent common ancestor of approximately 37.61 million years ago (Ma), with divergences among clades within the genus occurring between 11.56 Ma and 29.44 Ma, and divergences among MOTUs within species occurring between 3.71 Ma and 11.56 Ma. Biogeographic reconstructions suggested that the ancestral area for the genus likely encompassed China and the Korean Peninsula, with multiple inferred dispersal events to Europe and Central and Western Asia between 21.78 Ma and 26.67 Ma and to Japan between 2.51 Ma and 18.42 Ma. Key factors such as the Eocene-Oligocene extinction event, onset and intensification of the monsoon system, and glacial cycles associated with sea-level fluctuations have likely played significant roles in shaping the evolutionary history of the genus Silurus.

Advancing Detectivity and Stability of Near-Infrared Organic Photodetectors via a Facile and Efficient Cathode Interlayer.

Near-infrared (NIR) organic photodetectors (OPDs) are pivotal in numerous technological applications due to their excellent responsivity within the NIR region. Polyethylenimine ethoxylated (PEIE) has conventionally been employed as an electron transport layer (hole-blocking layer) to suppress dark current (JD) and enhance charge transport. However, the limitations of PEIE in chemical stability, processing conditions, environmental impact, and absorption range have spurred the development of alternative materials. In this study, we introduced a novel solution: a hybrid of sol-gel zinc oxide (ZnO) and N,N'-bis(N,N-dimethylpropan-1-amine oxide)perylene-3,4,9,10-tetracarboxylic diimide (PDINO) as the electron transport layer for NIR-OPDs. Our fabricated OPD exhibited significantly improved responsivity, reduced internal traps, and enhanced charge transfer efficiency. The detectivity, spanning from 400 to 1100 nm, surpassed ∼5 × 1012 Jones, reaching ∼1.1 × 1012 Jones at 1000 nm, accompanied by an increased responsivity of 0.47 A/W. Also, the unpackaged OPD remarkedly demonstrated stable JD and external quantum efficiency (EQE) over 1000 h under dark storage conditions. This innovative approach not only addresses the drawbacks of conventional PEIE-based OPDs but also offers promising avenues for the development of high-performance OPDs in the future.

Do Weather Conditions Still Have an Impact on the COVID-19 Pandemic? An Observation of the Mid-2022 COVID-19 Peak in Taiwan.

Since the onset of the COVID-19 pandemic in 2019, the role of weather conditions in influencing transmission has been unclear, with results varying across different studies. Given the changes in border policies and the higher vaccination rates compared to earlier conditions, this study aimed to reassess the impact of weather on COVID-19, focusing on local climate effects. We analyzed daily COVID-19 case data and weather factors such as temperature, humidity, wind speed, and a diurnal temperature range from 1 March to 15 August 2022 across six regions in Taiwan. This study found a positive correlation between maximum daily temperature and relative humidity with new COVID-19 cases, whereas wind speed and diurnal temperature range were negatively correlated. Additionally, a significant positive correlation was identified between the unease environmental condition factor (UECF, calculated as RH*Tmax/WS), the kind of Climate Factor Complex (CFC), and confirmed cases. The findings highlight the influence of local weather conditions on COVID-19 transmission, suggesting that such factors can alter environmental comfort and human behavior, thereby affecting disease spread. We also introduced the Fire-Qi Period concept to explain the cyclic climatic variations influencing infectious disease outbreaks globally. This study emphasizes the necessity of considering both local and global climatic effects on infectious diseases.

A comparative study on the age, growth, and mortality of Gobio huanghensis (Luo, Le & Chen, 1977) in the Gansu and Ningxia sections of the upper Yellow River, China.

BALKGROUND: Gobio huanghensis is a small economic fish endemic to the Yellow River at the junction of the Tibetan Plateau and the Huangtu Plateau in China. To understand the impact of environmental changes and human activities on the ecological structure of the G. huanghensis population, a comparative study was conducted on the age composition, growth characteristics, mortality rate, and exploitation rate of the G. huanghensis populations in the Gansu and Ningxia sections of the upper Yellow River. RESULTS: During the investigation, a total of 1147 individuals were collected, with 427 individuals collected from the Gansu section and 720 individuals from the Ningxia section. The results showed that G. huanghensis in the Gansu section exhibited a total length ranging from 5.00 to 22.80 cm, with an average of 12.68 ± 4.03 cm. In the Ningxia section, the total length of G. huanghensis ranged from 2.15 to 20.65 cm, with an average of 9.48 ± 3.56 cm. The age composition of G. huanghensis in the Gansu section ranged from 1 to 7 years, where female fish were observed between 1 and 7 years old, and male fish between 1 and 6 years old. In the Ningxia section, both female and male fish ranged from 1 to 5 years old. The relationships between total length and body weight were (Gansu section, R2 = 0.9738) and (Ningxia section, R2 = 0.9686), indicating that fish in the Gansu section exhibit positive allometric growth, while fish in the Ningxia section exhibit negative allometric growth. The von Bertalanffy growth equation revealed that G. huanghensis in the Gansu section exhibited an asymptotic total length L∞ of 27.426 cm with a growth coefficient K of 0.225 yr-1, while in the Ningxia section, the asymptotic total length L∞ was 26.945 cm with a growth coefficient K of 0.263 yr-1. The total mortality rate (Z) values of G. huanghensis were 0.7592 yr and 1.1529 yr in the Gansu section and Ningxia section, respectively. The average natural mortality rate (M), estimated by three different methods, in the Gansu section was 0.4432 yr, while it was 0.5366 yr in the Ningxia section. The exploitation rate (E) of G. huanghensis was 0.4163 in the Gansu section and 0.5345 in the Ningxia section, indicating that the population in the Ningxia section may have been overexploited. CONCLUSION: Prolonged fishing pressures and environmental changes may have led to variations in the ecological parameters of the G. huanghensis population between the Gansu and Ningxia sections.

Effect of robbing intensity on reproductive success of Symphytum officinale (Boraginaceae).

The intervention of nectar robbers in plant pollination systems will cause some pollinators to modify their foraging behavior to act as secondary robbers, consequently adopting a mixed foraging strategy. The influence of nectar robbing on pollinator behavior may be affected by spatio-temporal difference of robbing intensity, and consequently, may have different effects on the pollination of host plants. However, whether and how the nectar robbing might influence pollinators under different robbing intensity still needs further investigation. In this study, Symphytum officinale was used to detect the effect of nectar robbers on pollinators under different robbing intensity as well as their effects on plant reproductive success. Six robbing levels and three bumblebees with mixed foraging behaviors were used to evaluate the effect of different robbing intensity on pollinator behavior, visitation rate, flower longevity and pollen deposition. Our results indicated that the robbing rate increased gradually with the proportion of robbed flowers, but which did not affect the frequency of legitimate visits. The increase of robbing rate promoted the corolla abscission, and then enhanced the self-pollen deposition, but which had no significant effect on cross-pollen deposition. These results indicate that the overall fitness of S. officinale was improved by combined self and cross-pollination modes when visited by both pollinators and nectar robbers simultaneously. Although nectar robbing is not uncommon, its consequences for pollination in the interaction web have not been well studied. Our results emphasize the significance of indirect impacts in mediating the adaptive outcomes of species interactions.

The complete mitochondrial genome of Gobio huanghensis (Cypriniformes: Cyprinidae) in the Yellow River, China.

Gobio huanghensis, a member of the eponymous genus within the Cyprinidae, family of the Cypriniformes order, is an endemic fish species found exclusively in the upper reaches of the Yellow River, spanning from Yinchuan to Lanzhou. This study presents the first comprehensive report of the complete mitochondrial genome sequence of G. huanghensis, encompassing 16,604 base pairs (bp) with a nucleotide composition of 26.3% cytosine (C), 17.6% guanine (G), 29.4% adenine (A), and 26.7% thymine (T). In congruence with other species in the Gobio genus, its mitochondrial genome comprises 37 genes, including two ribosomal RNA genes, 13 protein-coding genes (PCGs), and 22 transfer RNA genes. Notably, COX1 initiates with the start codon GTG, distinct from the typical ATG start codon of other PCGs. The mitogenome exhibits four types of stop codons: TAA, TAG, TA-, and T--. Phylogenetic analyses, grounded in complete mitochondrial sequences, position G. huanghensis at the forefront of one of two major clusters within the genus Gobio, corroborating existing morphological classifications. These findings offer valuable theoretical insights for the taxonomic classification, conservation, and population genetics of G. huanghensis.

Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice.

BACKGROUND: CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longevity and ameliorates an age-related skin phenotype in transgenic mice. Here we translate the genetic evidence into a pharmaceutical application using a potent CISD2 activator, hesperetin, which enhances CISD2 expression in HEK001 human keratinocytes from an older person. We also treated naturally aged mice in order to study the activator's anti-aging efficacy. METHODS: We studied the biological effects of hesperetin on aging skin using, firstly, a cell-based platform, namely a HEK001 human keratinocyte cell line established from an older person. Secondly, we used a mouse model, namely old mice at 21-month old. In the latter case, we investigate the anti-aging efficacy of hesperetin on ultraviolet B (UVB)-induced photoaging and naturally aged skin. Furthermore, to identify the underlying mechanisms and potential biological pathways involved in this process we carried out transcriptomic analysis. Finally, CISD2 knockdown HEK001 keratinocytes and Cisd2 knockout mice were used to study the Cisd2-dependent effects of hesperetin on skin aging. RESULTS: Four findings are pinpointed. Firstly, in human skin, CISD2 is mainly expressed in proliferating keratinocytes from the epidermal basal layer and, furthermore, CISD2 is down-regulated in the sun-exposed epidermis. Secondly, in HEK001 human keratinocytes from an older person, hesperetin enhances mitochondrial function and protects against reactive oxygen species-induced oxidative stress via increased CISD2 expression; this enhancement is CISD2-dependent. Additionally, hesperetin alleviates UVB-induced damage and suppresses matrix metalloproteinase-1 expression, the latter being a major indicator of UVB-induced damage in keratinocytes. Thirdly, transcriptomic analysis revealed that hesperetin modulates a panel of differentially expressed genes that are associated with mitochondrial function, redox homeostasis, keratinocyte function, and inflammation in order to attenuate senescence. Intriguingly, hesperetin activates two known longevity-associated regulators, namely FOXO3a and FOXM1, in order to suppress the senescence-associated secretory phenotype. Finally, in mouse skin, hesperetin enhances CISD2 expression to ameliorate UVB-induced photoaging and this occurs via a mechanism involving CISD2. Most strikingly, late-life treatment with hesperetin started at 21-month old and lasting for 5 months, is able to retard skin aging and rejuvenate naturally aged skin in mice. CONCLUSIONS: Our results reveal that a pharmacological elevation of CISD2 expression at a late-life stage using hesperetin treatment is a feasible approach to effectively mitigating both intrinsic and extrinsic skin aging and that hesperetin could act as a functional food or as a skincare product for fighting skin aging.

Upadacitinib for the management of bullous pemphigoid coexisting with psoriasis vulgaris: a case report and literature review.

Both bullous pemphigoid (BP) and psoriasis are common immune-related dermatological conditions in clinical practice, but the co-occurrence of these two diseases is rare. Currently, there is no consensus on the long-term safe and effective treatment for patients with both BP and psoriasis. JAK inhibitors are emerging as targeted therapeutic drugs that act by inhibiting Janus kinase activity, regulating the JAK/STAT pathway, blocking the transduction pathway of key proinflammatory cytokines, and influencing T-cell differentiation. These cytokines upstream of the JAK/STAT pathway play a pivotal role in the pathogenesis of numerous inflammatory and autoimmune disorders. Upadacitinib, a second-generation JAK inhibitor with high selectivity, demonstrates promising potential.This case report aims to provide a description of the successful treatment of bullous pemphigoid (BP) and psoriasis vulgaris by using upadacitinib, highlighting significant clinical outcomes. Additionally, we aim to analyze the underlying mechanism of upadacitinib in treating these two comorbidities by reviewing relevant literature from both domestic and international sources. Based on our clinical observations, upadacitinib appears to be a promising and well-tolerated therapeutic option for patients with concurrent BP and psoriasis, offering valuable insights for developing appropriate treatment strategies in clinical practice.

Relationship between ideal cardiovascular health score and perioperative acute kidney injury: A case-control study.

BACKGROUND: Maintaining ideal cardiovascular health scores (CHS) may indirectly contribute to reducing the risk of perioperative acute kidney injury (AKI), which has never been explored previously. In this study, we aimed to explore the relationship between CHS and AKI and provide new ideas for AKI prevention and treatment. METHODS: We examined the effects of CHS on the occurrence of AKI among 2783 participants from the Kailuan study, who received general anesthesia during noncardiac surgery from 2016 to 2020. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for AKI were calculated by using the logistic regression. RESULTS: Among 2783 participants 187 were diagnosed with perioperative AKI. We found an inverse relationship between the CHS scores and the risk of AKI. Participants with CHS score ≥ 10 had 57% decreased risk of AKI (OR = 0.43, 95% CI = 0.23, 0.79), compared with participants with CHS score ≤ 7, especially in men (OR = 0.39, 95% CI: 0.20, 0.76). In addition, participants who never smoked, exercised frequently, and had normal blood pressure had decreased risk of AKI, with corresponding ORs (95% CIs) of 0.66 (0.47, 0.91), 0.73 (0.60, 0.92), and 0.46 (0.28, 0.75), respectively. CONCLUSIONS: CHS was strongly associated with the risk of perioperative AKI, and higher CHS scores were associated with a lower risk of AKI. Further research is needed to explore the long-term effects of achieving and maintaining an ideal CHS on AKI risk.

Design and Fabrication of Enzymatic Potentiometric Biosensor Based on Flexible Printed Circuit Board for Glucose Detection.

This study investigated the development and optimization of a flexible printed circuit board-based glucose biosensor with an emphasis on high sensitivity, selectivity, and overall performance. Advances in glucose biosensing have highlighted its importance in medical diagnostics, especially diabetes management. The fabrication process involves depositing a RuO2 sensing film on a flexible printed circuit board (FPCB) by radio frequency sputtering. Enzyme-based modification using glucose oxidase (GOx), (3-aminopropyl) triethoxysilane (APTES), and glutaraldehyde (GA) to enhance selectivity and catalytic reactions. And through Scanning Electron Microscopy and electrochemical impedance spectroscopy, the sensing film, and the effect of modification on the charge transfer rate and performance improvement were analyzed. This glucose biosensor has excellent linearity, sensitivity, and reproducibility. The study also assessed response time and selectivity. The response time efficiency of the biosensor solidified its utility in point-of-care monitoring, while selectivity experiments validated its ability to distinguish glucose from interfering substances, ensuring accuracy in practical applications. According to the experimental results, the enzymatic glucose biosensor has the best average sensitivity and linearity of 44.42 mV/mM and 0.999 with a response time of 6 seconds.

Joint L2,p-norm and random walk graph constrained PCA for single-cell RNA-seq data.

The development and widespread utilization of high-throughput sequencing technologies in biology has fueled the rapid growth of single-cell RNA sequencing (scRNA-seq) data over the past decade. The development of scRNA-seq technology has significantly expanded researchers' understanding of cellular heterogeneity. Accurate cell type identification is the prerequisite for any research on heterogeneous cell populations. However, due to the high noise and high dimensionality of scRNA-seq data, improving the effectiveness of cell type identification remains a challenge. As an effective dimensionality reduction method, Principal Component Analysis (PCA) is an essential tool for visualizing high-dimensional scRNA-seq data and identifying cell subpopulations. However, traditional PCA has some defects when used in mining the nonlinear manifold structure of the data and usually suffers from over-density of principal components (PCs). Therefore, we present a novel method in this paper called joint L2,p-norm and random walk graph constrained PCA (RWPPCA). RWPPCA aims to retain the data's local information in the process of mapping high-dimensional data to low-dimensional space, to more accurately obtain sparse principal components and to then identify cell types more precisely. Specifically, RWPPCA combines the random walk (RW) algorithm with graph regularization to more accurately determine the local geometric relationships between data points. Moreover, to mitigate the adverse effects of dense PCs, the L2,p-norm is introduced to make the PCs sparser, thus increasing their interpretability. Then, we evaluate the effectiveness of RWPPCA on simulated data and scRNA-seq data. The results show that RWPPCA performs well in cell type identification and outperforms other comparison methods.

Investigation of corneal epithelial thickness and irregularity by optical coherence tomography after transepithelial photorefractive keratectomy.

CLINICAL RELEVANCE: Corneal epithelial healing after refractive surgery is a clinically significant issue, especially for surface ablation procedures, and this can be monitored using optical coherence tomography (OCT). BACKGROUND: The aim of this work is to investigate the corneal epithelial thickness and irregularity by OCT after transepithelial photorefractive keratectomy (t-PRK) and analyse its correlation with visual and refractive outcomes. METHODS: Patients aged ≥18 years with myopia, with or without astigmatism, who underwent t-PRK between May 2020 and August 2021 were included. All participants were subjected to complete ophthalmic examinations and OCT pachymetry at every follow-up visit. Patients were followed up at 1 week and 1, 3, and 6 months postoperatively. RESULTS: A total of 67 patients (126 eyes) were enrolled in this study. One month postoperatively, spherical equivalent refraction and visual acuity achieved preliminary stability. However, central corneal epithelial thickness (CCET) and standard deviation of the corneal epithelial thickness (SDcet) took 3-6 months to progressive recovery. Patients with higher baseline spherical equivalent refraction were associated with slower epithelial recovery. At every follow-up time point, a significant superior-inferior difference in the minimum corneal epithelial thickness area was observed. Higher stromal haze was correlated with higher spherical equivalent refraction (both baseline and residual) but had no relation with visual outcomes. There was a significant correlation between higher CCET with a better uncorrected distance visual acuity and lower corneal epithelial thickness irregularity. CONCLUSIONS: CCET and SDcet measured by OCT seem to be a good auxiliary indicator for reflecting the status of corneal wound recovery after t-PRK surgery. However, a well-designed randomised control study is needed to confirm the study results.