PLD3 affects axonal spheroids and network defects in Alzheimer's disease.

The precise mechanisms that lead to cognitive decline in Alzheimer's disease are unknown. Here we identify amyloid-plaque-associated axonal spheroids as prominent contributors to neural network dysfunction. Using intravital calcium and voltage imaging, we show that a mouse model of Alzheimer's disease demonstrates severe disruption in long-range axonal connectivity. This disruption is caused by action-potential conduction blockades due to enlarging spheroids acting as electric current sinks in a size-dependent manner. Spheroid growth was associated with an age-dependent accumulation of large endolysosomal vesicles and was mechanistically linked with Pld3-a potential Alzheimer's-disease-associated risk gene1 that encodes a lysosomal protein2,3 that is highly enriched in axonal spheroids. Neuronal overexpression of Pld3 led to endolysosomal vesicle accumulation and spheroid enlargement, which worsened axonal conduction blockades. By contrast, Pld3 deletion reduced endolysosomal vesicle and spheroid size, leading to improved electrical conduction and neural network function. Thus, targeted modulation of endolysosomal biogenesis in neurons could potentially reverse axonal spheroid-induced neural circuit abnormalities in Alzheimer's disease, independent of amyloid removal.

UB2/UB3/TSH4-anchored transcriptional networks regulate early maize inflorescence development in response to simulated shade.

Increasing planting density has been adopted as an effective means to increase maize (Zea mays) yield. Competition for light from neighbors can trigger plant shade avoidance syndrome, which includes accelerated flowering. However, the regulatory networks of maize inflorescence development in response to high-density planting remain poorly understood. In this study, we showed that shade-mimicking treatments cause precocious development of the tassels and ears. Comparative transcriptome profiling analyses revealed the enrichment of phytohormone-related genes and transcriptional regulators among the genes co-regulated by developmental progression and simulated shade. Network analysis showed that three homologous Squamosa promoter binding protein (SBP)-like (SPL) transcription factors, Unbranched2 (UB2), Unbranched3 (UB3), and Tasselsheath4 (TSH4), individually exhibited connectivity to over 2,400 genes across the V3-to-V9 stages of tassel development. In addition, we showed that the ub2 ub3 double mutant and tsh4 single mutant were almost insensitive to simulated shade treatments. Moreover, we demonstrated that UB2/UB3/TSH4 could directly regulate the expression of Barren inflorescence2 (BIF2) and Zea mays teosinte branched1/cycloidea/proliferating cell factor30 (ZmTCP30). Furthermore, we functionally verified a role of ZmTCP30 in regulating tassel branching and ear development. Our results reveal a UB2/UB3/TSH4-anchored transcriptional regulatory network of maize inflorescence development and provide valuable targets for breeding shade-tolerant maize cultivars.

The role of ncRNA regulatory mechanisms in diseases-case on gestational diabetes.

Non-coding RNAs (ncRNAs) are a class of RNA molecules that do not have the potential to encode proteins. Meanwhile, they can occupy a significant portion of the human genome and participate in gene expression regulation through various mechanisms. Gestational diabetes mellitus (GDM) is a pathologic condition of carbohydrate intolerance that begins or is first detected during pregnancy, making it one of the most common pregnancy complications. Although the exact pathogenesis of GDM remains unclear, several recent studies have shown that ncRNAs play a crucial regulatory role in GDM. Herein, we present a comprehensive review on the multiple mechanisms of ncRNAs in GDM along with their potential role as biomarkers. In addition, we investigate the contribution of deep learning-based models in discovering disease-specific ncRNA biomarkers and elucidate the underlying mechanisms of ncRNA. This might assist community-wide efforts to obtain insights into the regulatory mechanisms of ncRNAs in disease and guide a novel approach for early diagnosis and treatment of disease.

CircFOXO3 mediates hypoxia-induced autophagy of endometrial stromal cells in endometriosis.

Endometriosis is a benign gynecological disease that shares some common features of malignancy. Autophagy plays vital roles in endometriosis and influences endometrial cell metastasis, and hypoxia was identified as the initiator of this pathological process through hypoxia inducible factor 1 alpha (HIF-1α). A newly discovered circular RNA FOXO3 (circFOXO3) is critical in cell autophagy, migration, and invasion of various diseases and is reported to be related to hypoxia, although its role in endometriosis remains to be elucidated up to now. In this study, a lower circFOXO3 expression in ectopic endometrium was investigated. Furthermore, we verified that circFOXO3 could regulate autophagy by downregulating the level of p53 protein to mediate the migration and invasion of human endometrial stromal cells (T HESCs). Additionally, the effects of HIF-1α on circFOXO3 and autophagy were examined in T HESCs. Notably, overexpression of HIF-1α could induce autophagy and inhibit circFOXO3 expression, whereas overexpressing of circFOXO3 under hypoxia significantly inhibited hypoxia-induced autophagy. Mechanistically, the direct combination between HIF-1α and HIF-1α-binding site on adenosine deaminase 1 acting on RNA (ADAR1) promoter increased the level of ADAR1 protein, which bind directly with circFOXO3 pre-mRNA to block the cyclization of circFOXO3. All these results support that hypoxia-mediated ADAR1 elevation inhibited the expression of circFOXO3, and then autophagy was induced upon loss of circFOXO3 via inhibition of p53 degradation, participating in the development of endometriosis.

Dietary antarctic krill improves antioxidant capacity, immunity and reduces lipid accumulation, insights from physiological and transcriptomic analysis of Plectropomus leopardus.

BACKGROUND: Due to its enormous biomass, Antarctic krill (Euphausia superba) plays a crucial role in the Antarctic Ocean ecosystem. In recent years, Antarctic krill has found extensive application in aquaculture, emerging as a sustainable source of aquafeed with ideal nutritional profiles. However, a comprehensive study focused on the detailed effects of dietary Antarctic krill on aquaculture animals, especially farmed marine fishes, is yet to be demonstrated. RESULTS: In this study, a comparative experiment was performed using juvenile P. leopardus, fed with diets supplemented with Antarctic krill (the krill group) or without Antarctic krill (the control group). Histological observation revealed that dietary Antarctic krill could reduce lipid accumulation in the liver while the intestine exhibited no obvious changes. Enzyme activity measurements demonstrated that dietary Antarctic krill had an inhibitory effect on oxidative stress in both the intestine and the liver. By comparative transcriptome analysis, a total of 1,597 and 1,161 differentially expressed genes (DEGs) were identified in the intestine and liver, respectively. Functional analysis of the DEGs showed multiple enriched terms significantly related to cholesterol metabolism, antioxidants, and immunity. Furthermore, the expression profiles of representative DEGs, such as dhcr7, apoa4, sc5d, and scarf1, were validated by qRT-PCR and fluorescence in situ hybridization. Finally, a comparative transcriptome analysis was performed to demonstrate the biased effects of dietary Antarctic krill and astaxanthin on the liver of P. leopardus. CONCLUSIONS: Our study demonstrated that dietary Antarctic krill could reduce lipid accumulation in the liver of P. leopardus, enhance antioxidant capacities in both the intestine and liver, and exhibit molecular-level improvements in lipid metabolism, immunity, and antioxidants. It will contribute to understanding the protective effects of Antarctic krill in P. leopardus and provide insights into aquaculture nutritional strategies.

Highly Crystalline Iridium-Nickel Nanocages with Subnanopores for Acidic Bifunctional Water Splitting Electrolysis.

Developing efficient bifunctional materials is highly desirable for overall proton membrane water splitting. However, the design of iridium materials with high overall acidic water splitting activity and durability, as well as an in-depth understanding of the catalytic mechanism, is challenging. Herein, we successfully developed subnanoporous Ir3Ni ultrathin nanocages with high crystallinity as bifunctional materials for acidic water splitting. The subnanoporous shell enables Ir3Ni NCs optimized exposure of active sites. Importantly, the nickel incorporation contributes to the favorable thermodynamics of the electrocatalysis of the OER after surface reconstruction and optimized hydrogen adsorption free energy in HER electrocatalysis, which induce enhanced intrinsic activity of the acidic oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Together, the Ir3Ni nanocages achieve 3.72 A/mgIr(η=350 mV) and 4.47 A/mgIr(η=40 mV) OER and HER mass activity, which are 18.8 times and 3.3 times higher than that of commercial IrO2 and Pt, respectively. In addition, their highly crystalline identity ensures a robust nanostructure, enabling good catalytic durability during the oxygen evolution reaction after surface oxidation. This work provides a new revenue toward the structural design and insightful understanding of metal alloy catalytic mechanisms for the bifunctional acidic water splitting electrocatalysis.

ZoomQA: residue-level protein model accuracy estimation with machine learning on sequential and 3D structural features.

MOTIVATION: The Estimation of Model Accuracy problem is a cornerstone problem in the field of Bioinformatics. As of CASP14, there are 79 global QA methods, and a minority of 39 residue-level QA methods with very few of them working on protein complexes. Here, we introduce ZoomQA, a novel, single-model method for assessing the accuracy of a tertiary protein structure/complex prediction at residue level, which have many applications such as drug discovery. ZoomQA differs from others by considering the change in chemical and physical features of a fragment structure (a portion of a protein within a radius $r$ of the target amino acid) as the radius of contact increases. Fourteen physical and chemical properties of amino acids are used to build a comprehensive representation of every residue within a protein and grade their placement within the protein as a whole. Moreover, we have shown the potential of ZoomQA to identify problematic regions of the SARS-CoV-2 protein complex. RESULTS: We benchmark ZoomQA on CASP14, and it outperforms other state-of-the-art local QA methods and rivals state of the art QA methods in global prediction metrics. Our experiment shows the efficacy of these new features and shows that our method is able to match the performance of other state-of-the-art methods without the use of homology searching against databases or PSSM matrices. AVAILABILITY: http://zoomQA.renzhitech.com.

Tumour-associated and non-tumour-associated bacteria co-abundance groups in colorectal cancer.

BACKGROUND & AIMS: Gut microbiota is closely related to the occurrence and development of colorectal cancer (CRC). However, the differences in bacterial co-abundance groups (CAGs) between tumor tissue (TT) and normal tissue (NT), as well as their associations with clinical features, are needed to be clarified. METHODS: Bacterial 16 S rRNA sequencing was performed by using TT samples and NT samples of 251 patients with colorectal cancer. Microbial diversity, taxonomic characteristics, microbial composition, and functional pathways were compared between TT and NT. Hierarchical clustering was used to construct CAGs. RESULTS: Four CAGs were grouped in the hierarchical cluster analysis. CAG 2, which was mainly comprised of pathogenic bacteria, was significantly enriched in TT samples (2.27% in TT vs. 0.78% in NT, p < 0.0001). CAG 4, which was mainly comprised of non-pathogenic bacteria, was significantly enriched in NT samples (0.62% in TT vs. 0.79% in NT, p = 0.0004). In addition, CAG 2 was also significantly associated with tumor microsatellite instability (13.2% in unstable vs. 2.0% in stable, p = 0.016), and CAG 4 was positively correlated with the level of CA199 (r = 0.17, p = 0.009). CONCLUSIONS: Our research will deepen our understanding of the interactions among multiple bacteria and offer insights into the potential mechanism of NT to TT transition.

ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla formation in maize through regulating auxin signaling and ZmWOX3A expression.

Maize silk is a specialized type of stigma, covered with numerous papillae for pollen grain capture. However, the developmental process of stigmatic papillae and the underlying regulatory mechanisms have remained largely unknown. Here, we combined the cytological, genetic and molecular studies to demonstrate that three homologous genes ZmSPL10, ZmSPL14 and ZmSPL26 play a central role in promoting stigmatic papilla formation in maize. We show that their triple knockout mutants are nearly complete lack of stigmatic papilla, resulting in a severe reduction in kernel setting. Cellular examination reveals that stigmatic papilla is developed from a precursor cell, which is the smaller daughter cell resulting from asymmetric cell division of a silk epidermal cell. In situ hybridization shows that ZmSPL10, ZmSPL14 and their target genes SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A are preferentially expressed in the precursor cells of stigmatic papillae. Moreover, ZmSPL10, ZmSPL14 and ZmSPL26 directly bind to the promoters of SPI1, ZmPIN1b, ZmARF28 and ZmWOX3A and promote their expression. Further, Zmwox3a knockout mutants display severe defects in stigmatic papilla formation and reduced seed setting. Collectively, our results demonstrate that ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla development through regulating auxin signaling and ZmWOX3A expression.

Perioperative outcomes and continence following robotic-assisted radical cystectomy with mainz pouch II urinary diversion in patients with bladder cancer.

PURPOSE: To present the widely unknown perioperative outcomes and continence status of bladder cancer patients following robotic-assisted radical cystectomy (RARC) with Mainz pouch II urinary diversion (UD). MATERIALS AND METHODS: From November 2020 to December 2023, 37 bladder cancer patients who underwent RARC with Mainz pouch II UD were retrospectively assessed (ChiCTR2300070279). The results, which included patient demographics, perioperative data, continence, and complications (early ≤ 30 days and late ≤ 30 days) were reported using the RC-pentafecta criteria. RC-pentafecta criteria included ≥ 16 lymph nodes removed, negative soft tissue surgical margins, absence of major (Grade III-IV) complication at 90 days, absence of clinical recurrence at ≤ 12 months, and absence of long-term UD-related sequelae. A numeric rating scale assessed patient satisfaction with urinary continence 30 days after surgery. The validated Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire was used to evaluate bowel function. The Kaplan-Meier curve was used to evaluate overall survival (OS). RESULTS: Of the 37 patients evaluated over a median (range) follow-up period of 23.0 (12.0-36.5) months. The median (range) age was 65 (40-81) years. The median (range) time to urinary continence after surgery was 2.3 (1.5-6) months. Of the 37 patients, 31 (83.8%) were continent both during the day and at night, 34 (91.9%) were continent during the day, 32 (86.5%) were continent at night, 35 (94.6%) were satisfied with their urinary continence status, and 21 (56.8%) were very satisfied. The mean (range) voiding frequency was 6 (4-10) during the day and 3 (2-5.5) at night. The mean (range) PAC-SYM total score was 9.50 (4.00-15.00). In 12 (32.4%) of the patients, RC-pentafecta was achieved, and achieving RC-pentafecta was linked to better satisfaction scores (7.3 vs. 5.5, p = 0.034). There was no significant difference between RC-pentafecta and No RC-pentafecta groups in terms of OS (25.6 vs. 21.5 months, p = 0.16). 7 (19.4%) patients experienced late complications. CONCLUSIONS: Mainz pouch II UD following RARC in bladder cancer patients results in a satisfactory continence rate. Achieving RC-pentafecta was correlated with better satisfaction scores. The intracorporeal approach to Mainz pouch II UD is beneficial for female patients due to its reduced invasiveness. TRIAL REGISTRATION: ChiCTR2300070279; Registration: 07/04/2023, Last updated version: 01/06/2023. Retrospectively registered.

Risk factors of high fluid absorption in patients treated with mini-PCNL: a single-center prospective study.

BACKGROUND: The factors influencing fluid absorption in mini-percutaneous nephrolithotripsy (mini-PCNL) are still unknown. We aim to investigate the factors that influence irrigation fluid absorption during mini-PCNL. METHODS: A total of 94 patients who underwent mini-PCNL were included in this prospective study. The endoscopic surgical monitoring system (ESMS) was used to measure the volume of irrigation fluid absorbed during the procedure. Irrigating time, the total volume of irrigation fluid, stone size, S.T.O.N.E. score, hemoglobin, electrolyte levels, and postoperative complications were recorded. RESULTS: A significant correlation was observed between fluid absorption and the presence of postoperative fever, and based on this phenomenon, patients were divided into low and high fluid absorption groups. The serum creatinine level in the high fluid absorption group was significantly high (7 vs. 16.5, p = 0.02). Significant differences were observed between the low and high fluid absorption groups in terms of mean stone size (21.70 mm vs. 26.78 mm), presence of stone burden ≥ 800 mm2 (4% vs. 23%), S.T.O.N.E. score > 8 (4% vs. 38%), the fluid used > 18,596 ml (19% vs. 78%), irrigation time (55.61 min vs. 91.28 min), and perfusion rate (24% vs. 45%) (all p < 0.05). The rates of postoperative fever and SIRS in the high fluid absorption group were significantly high (p < 0.05). CONCLUSIONS: Mean stone size, presence of stone burden ≥ 800 mm2, S.T.O.N.E. score > 8, the fluid used > 18596 mL, irrigation time, and perfusion rate are risk factors of intraoperative fluid absorption in mini-PCNL.

Identification of candidate SNPs and genes associated with resistance to nervous necrosis virus in leopard coral grouper (Plectropomus leopardus) using GWAS.

The leopard coral grouper (Plectropomus leopardus), which has become increasingly popular in consumption due to its bright body color and great nutritional, holds a high economic and breeding potential. However, in recent years, the P.leopardus aquaculture industry has been impeded by the nervous necrosis virus (NNV) outbreak, leading to widespread mortality among fry and juvenile grouper. However, the genetic basis of resistance to NNV in P. leopardus remains to be investigated. In the present study, we conducted a genome-wide association analysis (GWAS) on 100 resistant and 100 susceptible samples to discover variants and potential genes linked with NNV resistance. For this study, 157,926 high-quality single nucleotide polymorphisms (SNPs) based on whole genome resequencing were discovered, and eighteen SNPs loci linked to disease resistance were discovered. We annotated six relevant candidate genes, including sik2, herc2, pip5k1c, npr1, mybpc3, and arhgap9, which showed important roles in lipid metabolism, oxidative stress, and neuronal survival. In the brain tissues of resistant and susceptible groups, candidate genes against NNV infection showed significant differential expression. The results indicate that regulating neuronal survival or pathways involved in lipid metabolism may result in increased resistance to NNV. Understanding the molecular mechanisms that lead to NNV resistance will be beneficial for the growth of the P. leopardus breeding sector. Additionally, the identified SNPs could be employed as biomarkers of disease resistance in P. leopardus, which will facilitate the selective breeding of grouper.

ENPP1 inhibits the transcription activity of the hepatitis B virus pregenomic promoter by upregulating the acetylation of LMNB1.

Current therapies for hepatitis B virus (HBV) infection can slow disease progression but cannot cure the infection, as it is difficult to eliminate or permanently silence HBV covalently closed circular DNA (cccDNA). The interaction between host factors and cccDNA is essential for their formation, stability, and transcriptional activity. Here, we focused on the regulatory role of the host factor ENPP1 and its interacting transcription factor LMNB1 in HBV replication and transcription to better understand the network of host factors that regulate HBV, which may facilitate the development of new antiviral drugs. Overexpression of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) in Huh7 cells decreased HBV pregenomic RNA (pgRNA) and hepatitis B core antigen (HBcAg) expression levels, whereas knockdown of ENPP1 increased them. A series of HBV promoter and mutant plasmids were constructed, and a luciferase reporter assay showed that overexpression of ENPP1 caused inhibition of the HBV promoter and its mutants. A DNA pull-down assay showed that lamin B1 (LMNB1), but not ENPP1, interacts directly with the HBV enhancer II/ basic core promoter (EnhII/BCP). ZDOCK and PyMOL software were used to predict the interaction of ENPP1 with LMNB1. Overexpression of LMNB1 inhibited the activity of the HBV promoter and its mutant. The acetylation levels at the amino acids 111K, 261K, and 483K of LMNB1 were reduced compared to the control, and an LMNB1 acetylation mutant containing 111R, 261Q, 261R, 483Q, and 483R showed increased promoter activity. In summary, ENPP1 together with LMNB1 increased the acetylation level at 111K and 261K, and LMNB1 inhibited the activity of HBV promoter and downregulated the expression of pregenomic RNA and HBcAg. Our follow-up studies will investigate the expression, clinical significance, and relevance of ENPP1 and LMNB1 in HBV patient tissues, explore the effect of LMNB1 on post-transcriptional progression, and examine whether ENPP1 can reduce cccDNA levels in the nucleus.

Comparative visual outcomes of the first versus second eye following small-incision lenticule extraction (SMILE).

BACKGROUND: This study aimed to compare the visual outcomes of the first operated eyes with those of the second operated eyes following small-incision lenticule extraction (SMILE). METHODS: A total of 202 patients (404 eyes) underwent SMILE using the tear film mark centration method for myopia and myopic astigmatism correction. Baseline characteristics, objective optical quality, decentered displacement, induced corneal aberrations, and modulation transfer function (MTF) values were assessed. Linear regression analyzed the relationship between decentration and visual quality parameters, including corneal aberrations and MTF values. RESULTS: No significant difference was observed in objective visual quality, efficacy, and safety indexes between the two groups (all P > 0.05). The average decentered displacement for the first and second surgical eyes was 0.278 ± 0.17 mm and 0.315 ± 0.15 mm, respectively (P = 0.002). The horizontal coma in the first surgical eyes were notably lower than in the second (P = 0.000). MTF values at spatial frequencies of 5, 10, 15, and 20 cycles/degree (c/d) were higher in the first surgical eyes compared to the second (all P < 0.05). Linear regression indicated that high-order aberrations (HOAs), root mean square (RMS) coma, spherical aberration, horizontal coma, vertical coma, and eccentric displacement were all linearly correlated. Furthermore, MTF values exhibited a linear relationship with eccentric displacement across these spatial frequencies. CONCLUSIONS: There was no discernible difference in visual acuity, efficacy, or safety between the two operated eyes. Nonetheless, the first operated eyes exhibited reduced decentered displacement and demonstrated superior outcomes in terms of horizontal coma and MTF values compared to the second operated eyes following SMILE. The variations in visual quality parameters were linearly correlated with decentered displacement.

Intermittent hypoxia induces myofibroblast differentiation and extracellular matrix production of MRC5s via HIF-1α-TGF-ß/Smad pathway.

PURPOSE: To investigate whether or not intermittent hypoxia (IH), the main characteristic of obstructive sleep apnea (OSA) may affect the myofibroblast differentiation and extracellular matrix (ECM) production of lung fibroblast through the HIF-1α-TGF-ß/Smad pathway and assess the interventional role of a HIF-1α inhibitor, 2-methoxyestradiol (2-ME2). METHOD: The human lung fibroblast MRC5 cells were exposed to normoxia or IH conditions, and the expression of myofibroblast differentiation marker α-smooth muscle actin (α-SMA) and ECM protein collagen I were evaluated. To clarify the underlying mechanism, the expression level of HIF-1α, TGF-ß, and p-Smads/Smads were measured and the effects of inhibiting HIF-1α with 2-ME2 on the α-SMA expression level and ECM production through the TGF-ß/Smad pathway were assessed. Si HIF-1α was applied to genetically inhibit HIF-1α in MRC5 cells, and the related proteins were assessed. RESULTS: IH increased the protein and mRNA expression of Collagen I and α-SMA of MRC5 cells in a time-dependent manner. IH activated the protein and mRNA level of HIF-1α and TGF-ß and increased the phosphorylation of Smad2/Smad3 of MRC5 cells in a time-dependent manner. 2-ME2 inhibited the activation of HIF-1α induced by IH and decreased overexpression of TGF-ß, p-Smad2/Smad2, and p-Smad3/Smad3, which in turn partially reversed the upregulation of α-SMA and Collagen I induced by IH in MRC5 cells. When HIF-1α was successfully silenced by si-HIF-1α, upregulation of TGF-ß induced by intermittent hypoxia was partially decreased. CONCLUSIONS: This study showed that IH contributes to myofibroblast differentiation and excessive ECM production of MRC5 cells through activation of the HIF-1α-TGF-ß/Smad pathway. 2-ME2 partially attenuated myofibroblast differentiation induced by IH by inhibiting the HIF-1α-TGF-ß/Smad pathway.

Picosecond alexandrite laser treatment of nevus of Ota in children.

BACKGROUND: The picosecond alexandrite laser has been safely and effectively used to treat the nevus of Ota in adults. However, limited data are available for children. OBJECTIVE: To investigate the efficacy, safety, and correlative influencing factors of a 755nm picosecond alexandrite laser in the treatment of nevus of Ota in children. METHODS: We retrospectively analyzed Chinese children with nevus of Ota who received a 755nm picosecond alexandrite laser treatment in a tertiary dermatological hospital. RESULT: A total of 305 pediatric patients received an average of two treatments achieving an average of 79% pigment clearance. After the first treatment, 22 patients achieved complete clearance (95%-100%), and 72 patients achieved excellent response (75%-94%), with an average initial efficacy of 63% lesion clearance. Treatment at an early age achieved better initial efficacy (0- to 12-month group >1- to 6-year group, 6- to 12-year group). And 0- to 12-month group achieved better final efficacy. More treatment sessions also increased the final efficacy. Both initial efficacy and final efficacy were better when treating a darker lesion. The incidence of complications was 12.1%, with 10.8% being post-inflammatory hyperpigmentation and 1.3% being hypopigmentation. The rate of recurrence was 6.6%. LIMITATION: Retrospective study. CONCLUSION: A 755nm picosecond alexandrite laser is safe and effective in treating nevus of Ota in children. Younger to initiate treatment, darker lesions, and more treatments are positively associated with better pigmentation clearance.

Effectiveness of Roy Adaptation Model-Based Cognitive Stimulation Therapy in Elderly Patients with Non-Small Cell Lung Cancer Undergoing Curative Resection.

This study aimed to investigate the effects of a Roy adaptation model (RAM)-based cognitive stimulation therapy (CST) intervention on elderly patients diagnosed with primary non-small cell lung cancer (NSCLC) undergoing curative resection. A total of 280 patients diagnosed with primary NSCLC were randomized into RAM-based CST group and control group. Outcomes were assessed at three intervals: pre-surgery, discharge, and one-month post-discharge. Cognitive function was evaluated using Mini-Cognitive test. Postoperative delirium prevalence was determined within 48 hours post-surgery using Nursing Delirium Screening Scale. The Hospital Anxiety and Depression Scale evaluated anxiety and depression symptoms, while Quality of Life (QoL) was assessed via Short Form-36 (SF36) Health Survey. The RAM-based CST group demonstrated significantly higher Mini-Cog test scores than the control group upon discharge and post-intervention. Patients with RAM-based CST exhibited a decrease in postoperative delirium compared to the control group. The RAM-based CST intervention yielded an improvement in anxiety and depression at discharge and 1-month post-discharge compared to preoperative levels. Additionally, the RAM-based CST group exhibited substantial enhancements in SF36 subcategory scores at 1-month post-discharge compared to pre-surgery. At post-intervention, the RAM-based CST group demonstrated significantly higher scores than the control group across various health-related domains, including role limitations due to emotional problems, mental health, general health perception, bodily pain, and role limitations due to physical problems. The RAM-based CST intervention in elderly NSCLC patients undergoing curative resection yielded significant enhancements in cognitive function, reduced delirium incidence, improved emotional well-being, and better QoL postoperatively.

Progress on metabolites of Astragalus medicinal plants and a new factor affecting their formation: Biotransformation of endophytic fungi.

It is generally believed that the main influencing factors of plant metabolism are genetic and environmental factors. However, the transformation and catalysis of metabolic intermediates by endophytic fungi have become a new factor and resource attracting attention in recent years. There are over 2000 precious plant species in the Astragalus genus. In the past decade, at least 303 high-value metabolites have been isolated from the Astragalus medicinal plants, including 124 saponins, 150 flavonoids, two alkaloids, six sterols, and over 20 other types of compounds. These medicinal plants contain abundant endophytic fungi with unique functions, and nearly 600 endophytic fungi with known identity have been detected, but only about 35 strains belonging to 13 genera have been isolated. Among them, at least four strains affiliated to Penicillium roseopurpureum, Alternaria eureka, Neosartorya hiratsukae, and Camarosporium laburnicola have demonstrated the ability to biotransform four saponin compounds from the Astragalus genus, resulting in the production of 66 new compounds, which have significantly enhanced our understanding of the formation of metabolites in plants of the Astragalus genus. They provide a scientific basis for improving the cultivation quality of Astragalus plants through the modification of dominant fungal endophytes or reshaping the endophytic fungal community. Additionally, they open up new avenues for the discovery of specialized, green, efficient, and sustainable biotransformation pathways for complex pharmaceutical intermediates.

Comprehensive quality control of Qingjin Yiqi granule based on UHPLC-Q-Orbitrap-MS and UPLC-QQQ-MS.

INTRODUCTION: Qingjin Yiqi granule (QYG) is a prescription medicine of traditional Chinese medicine which is widely used clinically for the recovery of coronavirus patients. However, there is currently limited research on the quality control of QYG. OBJECTIVE: To evaluate the quality of QYG qualitatively and quantitatively by making full use of advanced chromatography-mass spectrometry techniques. METHODS: Firstly, a multicomponent characterisation of QYG was performed by ultrahigh-performance liquid chromatography coupled with a Q Exactive™ hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap-MS) system using a rapid negative/positive switching mode. Secondly, the co-condition fingerprint analysis of constituted herbal medicines of QYG was performed to unveil active ingredients as the quality markers of QYG. Thirdly, the marker compounds in 10 batches of QYG were quantified by ultrahigh-performance liquid chromatography coupled with a Waters Xevo TQ-S triple quadrupole mass spectrometry (UPLC-QQQ-MS) system. RESULTS: A comprehensive method that combined the inclusion list and data-dependent acquisition (DDA) to achieve a systematic characterisation of QYG was established by UHPLC-Q-Orbitrap-MS. After analysis based on Compound Discoverer software and Global Natural Products Social (GNPS) platform, a total of 332 compounds were detected. Eleven Q-markers were determined for the quality evaluation of QYG by comparison with the fingerprint of nine constituted herbal medicines. An adjusted multiple reaction monitoring (MRM) quantification method was further established to simultaneously determine the 11 Q-markers for holistic quality evaluation of QYG. CONCLUSION: This is the first study to report comprehensive multicomponent characterisation, identification, and quality assessment of QYG, which could be used for effective guarantee of the quality of QYG.

High incidence of EDNRB gene mutation in seven southern Chinese familial cases with Hirschsprung's disease.

PURPOSE: Hirschsprung's disease (HSCR) is the leading cause of neonatal functional intestinal obstruction, which has been identified in many familial cases. HSCR, a multifactorial disorder of enteric nervous system (ENS) development, is associated with at least 24 genes and seven chromosomal loci, with RET and EDNRB as its major genes. We present a genetic investigation of familial HSCR to clarify the genotype-phenotype relationship. METHODS: We performed whole exome sequencing (WES) on Illumina HiSeq X Ten platform to investigate genetic backgrounds of core family members, and identified the possibly harmful mutation genes. Mutation carriers and pedigree relatives were validated by Sanger sequencing for evaluating the gene penetrance. RESULTS: Four familial cases showed potential disease-relative variants in EDNRB and RET gene, accounting for all detection rate of 57.1%. Three familial cases exhibited strong pathogenic variants as frameshift or missense mutations in EDNRB gene. A novel c.367delinsTT mutation of EDNRB was identified in one family member. The other two EDNRB mutations, c.553G>A in family 2 and c.877delinsTT in family 5, have been reported in previous literatures. The penetrance of EDNRB variants was 33-50% according mutation carries. In family 6, the RET c.1858T>C (C620R) point mutation has previously been reported to cause HSCR, with 28.5% penetrance. CONCLUSION: We identified a novel EDNRB (deleted C and inserted TT) mutation in this study using WES. Heterozygote variations in EDNRB gene were significantly enriched in three families and RET mutations were identified in one family. EDNRB variants showed an overall higher incidence and penetrance than RET in southern Chinese families cases.