Phase separation and transcriptional regulation in cancer development.

Liquid-liquid phase separation, a novel biochemical phenomenon, has been increasingly studied for its medical applications. It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes. During transcriptional regulation, dynamic condensates are formed through interactions between transcriptional elements, such as transcription factors, coactivators, and mediators. Cancer is a disease characterized by uncontrolled cell proliferation, but the precise mechanisms underlying tumorigenesis often remain to be elucidated. Emerging evidence has linked abnormal transcriptional condensates to several diseases, especially cancer, implying that phase separation plays an important role in tumorigenesis. Condensates formed by phase separation may have an effect on gene transcription in tumors. In the present review, we focus on the correlation between phase separation and transcriptional regulation, as well as how this phenomenon contributes to cancer development.

Amino acids-based deep eutectic solvents as additives for improved enantioseparation in capillary electrophoresis.

In this study, several amino acids deep eutectic solvents were prepared using L-valine and L-leucine as hydrogen bond acceptors, and L-lactic acid and glycerol as hydrogen bond donors. These amino acids' deep eutectic solvents were first used as buffer additives to construct several synergistic systems along with maltodextrin in capillary electrophoresis for the enantioseparations of four racemic drugs. Compared with single maltodextrin system, the separations of model drugs in the synergistic systems were significantly improved. Some key parameters affecting chiral separation such as maltodextrin concentration, deep eutectic solvent concentration, buffer pH, and applied voltage were optimized. In order to further understand the specific mechanism of the amino acids deep eutectic solvents in improving chiral separation, we first calculated the binding constants of maltodextrin with enantiomers using the capillary electrophoresis method in the two separation modes, respectively. We also used molecular simulation to calculate the binding free energy of maltodextrin with enantiomers. It is the first time that amino acids deep eutectic solvents were used for enantioseparation in capillary electrophoresis, which will greatly promote the development of deep eutectic solvents in the field of chiral separation.

Single-Port One Anastomosis Sleeve Gastrectomy with Transit Bipartition: Initial Experience and Technique.

BACKGROUND: Sleeve gastrectomy with transit bipartition (SG-TB) procedure has been gaining traction recently. While being a relatively novel procedure, it shows potentials to improve the standalone SG outcomes, such as diabetes remission and reflux. This article aims to show insights on performing SG-TB in one anastomosis fashion (SG-OATB) and single-port approach. METHODS: Three patients who underwent laparoscopic single-port SG-OATB at our hospital were included. The parameters included in this study comprised of age, gender, height, weight, body mass index (BMI), type 2 diabetes mellitus (T2DM) assessment, gastroesophageal reflux disease (GERD) assessment, length of the small bowel, the duration of the procedure, and 30-day readmission rate. RESULTS: The mean preoperative assessments for the three patients were as follows: two females vs. one male; age 38.7 ± 5.5 years old; weight 105.7 ± 5.4 kg; height 1.64 ± 0.11 m; BMI 39.3 ± 4.7 kg/m2; fasting blood glucose 6.7 ± 1.2 mmol/L; glycosylated hemoglobin level 7.1 ± 1.3%; GERD-Questionnaire score 6.3 ± 1.5; two patients with esophagitis grade A and B following endoscopy. The total duration of the procedure was 170.0 ± 26.5 min; there was no need for conversion to multiple-port in all patients. The 30-day readmission rate for all patients was 0%. CONCLUSION: In our small cases of patients, single-port SG-OATB is feasible and safe. We found the closure of the anastomosis defect to be most technically demanding. To understand better the outcome of single-port SG-OATB, studies with larger sample and longer follow-up will be needed in the future.

First Report of Anthracnose on Wurfbainia villosa var. villosa Caused by Colletotrichum gloeosporioides in China.

Wurfbainia villosa var. villosa is a traditional Chinese herbal medicine under the family Zingiberaceae, and its ripe fruits (called Fructus Amomi) are widely used clinically for the treatment of gastrointestinal disorders (Yang et al. 2023; Chen et al. 2023). In September 2023, plants of W. villosa var. villosa exhibited anthracnose-like symptoms on leaf with a disease incidence of 35% (n = 100 investigated plants) in an approximately 90 m2 field in Guangning, China (N23°42'51.70″, E112°26'35.75″). Light yellowish-green spots (~2 mm diameter) initially appeared on the infected leaves, gradually formed sub-circular or irregular spots, then fused and expanded, resulting in wilting of the leaves. To identify the causal agent, 10 symptomatic leaves were collected and transferred to the laboratory. The symptomatic leaf samples were surface sterilized in 0.5% NaClO for 2 min, and in 70% ethanol for 30 s, then washed three times with sterile water and air-dried on sterile filter paper. The leaf tissues were placed on potato dextrose agar (PDA) medium containing 100 µg mL-1 of ampicillin (Sigma-Aldrich, St. Louis, MO) and incubated for 7 days at 28°C in darkness. Nine isolates with similar colony morphology were isolated from the 10 plated leaves. Three representative isolates (GNAF03, GNAF06, GNAF09 with approximately 3.5 cm in diameter after 3 days of incubation) appeared gray to dark brown with dense aerial hyphae at the front and gray to black colonies on the reverse of the plates. Conidia were cylindrical and measured 21.2 to 29.3 µm long × 7.1 to 9.6 µm wide (n = 50). Appressoria were formed by the tips of germ tubes or hyphae and were brown, ellipsoid, thick-walled, and smooth-margined, measuring 10.2 to 12.3 µm long × 6.4 to 8.2 µm wide (n = 50). Morphologically, the fungal isolates resembled Colletotrichum sp. (Weir et al. 2012). For molecular analysis, genomic DNA was extracted from fresh mycelia of the three isolates, and the primers ACT-512F/ACT-783R, CL1/CL2A, GDF/GDR, and ITS1/ITS4 were used to amplify partial regions of rDNA-ITS, actin (ACT), calmodulin (CAL), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) regions, respectively (Weir et al. 2012). The resulting sequences with more than 99% nucleotide identity to C. gloeosporioides were submitted to GenBank (accession numbers PP552725, PP552726, and OR827444 for ACT; PP552727, PP552728, and OR827443 for CAL; PP552729, PP552730, and OR827445 for GAPDH; PP549996, PP549999, and OR841394 for ITS). A phylogenetic tree was generated by the maximum likelihood method using the concatenated sequences of ACT, CAL, GADPH, and ITS by Polysuite software (Damm et al. 2020). Based on morphological and molecular analysis, the three isolates were characterized as C. gloeosporioides. The pathogenicity of the GNAF09 isolate was assessed on W. villosa var. villosa seedling leaves inoculated by spraying with 40 µL of conidial suspension at 106 conidia mL-1 or wounded with a sterile toothpick then inoculated with mycelial agar plugs (5 mm diameter). Control leaves were inoculated with 40 µL of sterile distilled water or agar plugs without mycelia. The inoculated plants were placed in a humid chamber at 28°C with 80% humidity and a 12 h light-dark photoperiod. Symptoms similar to those seen on naturally infected leaves were observed on all inoculated leaves after 7 days inoculation. Re-isolation was performed from 80% of the inoculated leaves and isolates were confirmed as C. gloeosporioides morphologically, confirming Koch's postulates, and by sequencing the ACT, CAL, GADPH, and ITS regions. The control groups remained asymptomatic. In previous studies, C. gloeosporioides has also caused anthracnose on Chinese medicinal plants, including Baishao (Radix paeoniae alba) (Zhang et al. 2017) and Rubia cordifolia L. (Tang et al. 2020). To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on W. villosa var. villosa in China. The results of our report serve as valuable references for further research on this disease.

Interfacial Engineering of MoS2@CoS2 Heterostructure Electrocatalysts for Effective pH-Universal Hydrogen Evolution Reaction.

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

Activation of Pink1/Parkin-mediated mitochondrial autophagy alleviates exertional heat stroke-induced acute lung injury in rats.

OBJECTIVE: To investigate the role of Pink1/Parkin-mediated mitochondrial autophagy in exertional heat stroke-induced acute lung injury in rats. METHODS: Sixty SD rats were divided into four groups: normal group (CON group), normal Parkin overexpression group (CON + Parkin group), exertional heat stroke group (EHS group), and exertional heat stroke Parkin overexpression group (EHS + Parkin group). Adeno-associated virus carrying the Parkin gene was intravenously injected into the rats to overexpress Parkin in the lung tissue. An exertional heat stroke rat model was established, and survival curves were plotted. Lung micro-CT was performed, and lung coefficient and pulmonary microvascular permeability were measured. RESULTS: Compared with the EHS group, the survival rate of rats in the EHS + Parkin overexpression group was significantly increased, lung coefficient and pulmonary microvascular permeability were reduced, and pathological changes such as exudation and consolidation were significantly reduced. The levels of inflammatory factors IL-6, IL-1ß, TNF- α, and ROS were significantly decreased; the degree of mitochondrial swelling in type II alveolar epithelial cells was reduced, and no vacuolization was observed. Lung tissue apoptosis was reduced, and the colocalization fluorescence of Pink1 and Parkin, as well as LC3 and Tom20, were increased. The expression of Parkin and LC3-II/LC3-I ratio in lung tissue were both increased, while the expression of P62, Pink1, MFN2, and PTEN-L was decreased. CONCLUSION: Impairment of Pink1/Parkin-mediated mitochondrial autophagy function is one of the mechanisms of exertional heat stroke-induced acute lung injury in rats. Activation of the Pink1/Parkin pathway can alleviate acute lung injury caused by exertional heat stroke.

Three-dimensional analysis of the positional relationship between the dentition and basal bone region in patients with skeletal Class I and Class II malocclusion with mandibular retrusion.

Objective: This study aimed to determine the maxillary and mandibular basal bone regions and explore the three-dimensional positional relationship between the dentition and basal bone regions in patients with skeletal Class I and Class II malocclusions with mandibular retrusion. Methods: Eighty patients (40 each with Class I and Class II malocclusion) were enrolled. Maxillary and mandibular basal bone regions were determined using cone-beam computed tomography images. To measure the relationship between the dentition and basal bone region, the root position and root inclination were calculated using the coordinates of specific fixed points by a computer program written in Python. Results: In the Class II group, the mandibular anterior teeth inclined more labially (P < 0.05), with their apices positioned closer to the external boundary. The apex of the maxillary anterior root was positioned closer to the external boundary in both groups. Considering the molar region, the maxillary first molars tended to be more lingually inclined in females (P = 0.037), whereas the mandibular first molars were significantly more labially inclined in the Class II group (P < 0.05). Conclusions: Mandibular anterior teeth in Class II malocclusion exhibit a compensatory labial inclination trend with the crown and apex relative to the basal bone region when mandibular retrusion occurs. Moreover, as the root apices of the maxillary anterior teeth are much closer to the labial side in Class I and Class II malocclusion, the range of movement at the root apex should be limited to avoid extensive labial movement.

Inflammation-based lung adenocarcinoma molecular subtype identification and construction of an inflammation-related signature with bulk and single-cell RNA-seq data.

The role of inflammation is increasingly understood to have a central influence on therapeutic outcomes and prognosis in lung adenocarcinoma (LUAD). However, the detailed molecular divisions involved in inflammatory responses are yet to be fully elucidated. Our study identified two main inflammation-oriented LUAD grades: the inflammation-low (INF-low) and the inflammation-high (INF-high) subtypes. Both presented with unique clinicopathological features, implications for prognosis, and distinctive tumor microenvironment profiles. Broadly, the INF-low grade, marked by its dominant immunosuppressive tumor microenvironment, was accompanied by less favorable prognostic outcomes and a heightened prevalence of oncogenic mutations. In contrast, the INF-high grade exhibited more optimistic clinical trajectories, underscored by its immune-active environment. In addition, our efforts led to the conceptualization and empirical validation of an inflammation-centric predictive model with considerable predictive potency. Our study paves the way for a refined inflammation-centric LUAD classification and fosters a deeper understanding of tumor microenvironment intricacies.

Examining the transformation of postindustrial land in reversing the lack of urban vitality: A paradigm spanning top-down and bottom-up approaches in urban planning studies.

A distinct rise of global interest in the role of cultural and creative industries in post-industrial urban development calls for the transformation of our industrial heritage into creative clusters. Despite many factories being removed in deindustrialization, some enterprises still preserve and reuse the former industrial lands. However, the inconclusive judgments on the performances of creative clusters call for an in-depth examination of the underlying mechanism of transforming dilapidated urban industrial spaces. In addition, few empirical studies have revealed the commonalities and differences of market entities employing both the top-down and bottom-up approaches during the redevelopment. In this article, a multilevel transformation, and the consequent spatial performance in three postindustrial lands in Beijing have been examined based on big data analysis, field observation and in-depth interviews. We reached three conclusions. First, in addition to the angle of participatory planning, the deep exploration of specific market entities as an intermediate joint among different parties in protecting and reusing the postindustrial lands uncovers a distinct perspective of urban revitalization. Second, the finding of the enterprises' role in mitigating the conflicts between bottom-up and top-down approaches further testifies to a less-dichotomous perspective in urban regeneration studies. Last, though the examination of the multilevel transformation mechanism reflecting the difference between state and nonstate enterprises in property-led management, a generic paradigm behind the trend of relying on enterprises in revitalizing the large-scale postindustrial lands is revealed.

Haplotype-resolved genomes of octoploid species in Phyllanthaceae family reveal a critical role for polyploidization and hybridization in speciation.

The Phyllanthaceae family comprises a diverse range of plants with medicinal, edible, and ornamental value, extensively cultivated worldwide. Polyploid species commonly occur in Phyllanthaceae. Due to the rather complex genomes and evolutionary histories, their speciation process has been still lacking in research. In this study, we generated chromosome-scale haplotype-resolved genomes of two octoploid species (Phyllanthus emblica and Sauropus spatulifolius) in Phyllanthaceae family. Combined with our previously reported one tetraploid (Sauropus androgynus) and one diploid species (Phyllanthus cochinchinensis) from the same family, we explored their speciation history. The three polyploid species were all identified as allopolyploids with subgenome A/B. Each of their two distinct subgenome groups from various species was uncovered to independently share a common diploid ancestor (Ancestor-AA and Ancestor-BB). Via different evolutionary routes, comprising various scenarios of bifurcating divergence, allopolyploidization (hybrid polyploidization), and autopolyploidization, they finally evolved to the current tetraploid S. androgynus, and octoploid S. spatulifolius and P. emblica, respectively. We further discuss the variations in copy number of alleles and the potential impacts within the two octoploids. In addition, we also investigated the fluctuation of metabolites with medical values and identified the key factor in its biosynthesis process in octoploids species. Our study reconstructed the evolutionary history of these Phyllanthaceae species, highlighting the critical roles of polyploidization and hybridization in their speciation processes. The high-quality genomes of the two octoploid species provide valuable genomic resources for further research of evolution and functional genomics.

Analysis of clinical features of heart failure in children with cardiomyopathy and improved ejection fraction.

Background: The prognosis of children with heart failure varies considerably. After treatment, left ventricular ejection fraction (LVEF) can be improved in some children. The aim of this study was to analyze the clinical features of children with heart failure accompanied by cardiomyopathy and recovered ejection fraction [heart failure with recovered ejection fraction (HFrecEF)] and to identify the predictors of improved LVEF. Methods: Children diagnosed with heart failure in Beijing Anzhen Hospital Affiliated to Capital Medical University from 2018 to 2021 were retrospectively enrolled. According to the baseline and change of LVEF, the patients were divided into two groups: a reduced ejection fraction (HFrEF) group and an HFrecEF group. The t-test was used to evaluate the difference between the two groups. The predictive factors of ejection fraction improvement were analyzed with a logistic regression model. Results: A total of 72 children were included in this study, including 31 (43.1%) in the HFrEF group and 41 (56.9%) in the HFrecEF group. Compared with children in the HFrEF group, children in the HFrecEF group were younger and had faster resting heart rates, lower creatinine, lower suppression of tumorigenicity 2 (ST2) expression, a lower platelet-to-lymphocyte (PLT:LYM) ratio, and smaller left atrial diameter. After a mean follow-up of 35.87 months, 26 cases returned to normal ejection fraction. In the HFrEF group, sudden cardiac death occurred in two cases, and four cases received heart transplantation. Logistic analysis showed that virus infection [odds ratio (OR) =1.279; 95% confidence interval (CI): 0.374-4.379; P=0.007], low ST2 expression (cutoff value =1.89 ng/mL: OR =1.042; 95% CI: 1.007-1.082; P=0.032), and treatment with intravenous immunoglobulin (IVIG) (OR =5.077; 95% CI: 1.458-17.684; P=0.011) were predictors of improvement in LVEF in patients with heart failure after treatment. Conclusions: In some patients with HFrecEF, LVEF eventually returned to normal. The combination of viral infection, low ST2 expression, and the application of IVIG therapy were found to be independent predictors of LVEF improvement in patients with heart failure after treatment.

Frizzled receptors (FZDs) in Wnt signaling: potential therapeutic targets for human cancers.

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.

Effects of narrow-wide row planting patterns on canopy photosynthetic characteristics, bending resistance and yield of soybean in maize‒soybean intercropping systems.

With the improvements in mechanization levels, it is difficult for the traditional intercropping planting patterns to meet the needs of mechanization. In the traditional maize‒soybean intercropping, maize has a shading effect on soybean, which leads to a decrease in soybean photosynthetic capacity and stem bend resistance, resulting in severe lodging, which greatly affects soybean yield. In this study, we investigated the effects of three intercropping ratios (four rows of maize and four rows of soybean; four rows of maize and six rows of soybean; six rows of maize and six rows of soybean) and two planting patterns (narrow-wide row planting pattern of 80-50 cm and uniform-ridges planting pattern of 65 cm) on soybean canopy photosynthesis, stem bending resistance, cellulose, hemicellulose, lignin and related enzyme activities. Compared with the uniform-ridge planting pattern, the narrow-wide row planting pattern significantly increased the LAI, PAR, light transmittance and compound yield by 6.06%, 2.49%, 5.68% and 5.95%, respectively. The stem bending resistance and cellulose, hemicellulose, lignin and PAL, TAL and CAD activities were also significantly increased. Compared with those under the uniform-ridge planting pattern, these values increased by 7.74%, 3.04%, 8.42%, 9.76%, 7.39%, 10.54% and 8.73% respectively. Under the three intercropping ratios, the stem bending resistance, cellulose, hemicellulose, lignin content and PAL, TAL, and CAD activities in the M4S6 treatment were significantly greater than those in the M4S4 and M6S6 treatments. Compared with the M4S4 treatment, these variables increased by 12.05%, 11.09%, 21.56%, 11.91%, 18.46%, 16.1%, and 16.84%, respectively, and compared with the M6S6 treatment, they increased by 2.06%, 2.53%, 2.78%, 2.98%, 8.81%, 4.59%, and 4.36%, respectively. The D-M4S6 treatment significantly improved the lodging resistance of soybean and weakened the negative impact of intercropping on soybean yield. Therefore, based on the planting pattern of narrow-wide row maize‒soybean intercropping planting pattern, four rows of maize and six rows of soybean were more effective at improving the lodging resistance of soybean in the semiarid region of western China.

LINC01133 regulates MARCKS expression via sponging miR-30d-5p to promote the development of lung squamous cell carcinoma.

LncRNAs are vital regulators for lung squamous cell carcinoma (LUSC). However, the detailed role that LINC01133 plays in LUSC is unclear. This work sought to explore the potential function of LINC01133.Levels of LINC01133, miR-30d-5p, and MARCKS were separately tested in both tissues and cells using qRT-PCR. Proliferation was assessed through MTT experiment and apoptosis was detected upon flow cytometry. Transwell experiments were implemented to evaluate migratory and invasive abilities. The interaction between two genes was affirmed through luciferase reporter assay and RNA pull-down experiment. Western blotting measured the protein level of MARCKS. Animal models were established and tissues were taken for IHC analysis of MARCKS and Ki67.LINC01133 was elevated in LUSC and its downregulation could suppress proliferation, migration and invasion but induced apoptosis. LINC01133 interacted with and regulated the binding of miR-30d-5p to MARCKS. LINC01133/miR-30d-5p axis mediated proliferation, apoptosis, migration and invasion in LUSC cells, as well as modulated tumor growth in animal models. LINC01133 interacted with miR-30d-5p to modulate MARCKS expression, contributes to promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. These findings could provide possible therapeutic targets in view of LUSC treatment in the future.

Language development beyond the here-and-now: Iconicity and displacement in child-directed communication.

Most language use is displaced, referring to past, future, or hypothetical events, posing the challenge of how children learn what words refer to when the referent is not physically available. One possibility is that iconic cues that imagistically evoke properties of absent referents support learning when referents are displaced. In an audio-visual corpus of caregiver-child dyads, English-speaking caregivers interacted with their children (N = 71, 24-58 months) in contexts in which the objects talked about were either familiar or unfamiliar to the child, and either physically present or displaced. The analysis of the range of vocal, manual, and looking behaviors caregivers produced suggests that caregivers used iconic cues especially in displaced contexts and for unfamiliar objects, using other cues when objects were present.

Causal relationship of obesity and adiposity distribution on risk of ventral hernia.

PURPOSE: Ventral hernia (VH) is a common surgical disease. Previous studies suggested that obesity is an important risk factor for VH. However, the causal relationship between fat distribution and the risk of VH is still unclear. This study used Mendelian randomization (MR) to evaluate their causal relationship. METHODS: We used the body mass index (BMI), body fat percentage, and body fat mass to represent general obesity and utilized the volume of abdominal subcutaneous adiposity tissue, visceral adiposity tissue, waist circumference, hip circumference, and waist-to-hip ratio to represent abdominal adiposity. The data were extracted from the large-scale genome-wide association study of European ancestry. We used two-sample MR to infer causality, using multivariate MR to correct the effects of confounding factors. RESULTS: Increased BMI, body fat percentage, body fat mass, visceral adiposity tissue, waist circumference, and hip circumference rather than subcutaneous adiposity tissue or waist-to-hip ratio, were causally associated with a higher risk of VH. The results of multivariate MR suggested that body fat percentage was causally associated with a higher risk of VH after adjusting for body mass index, diabetes, and smoking. CONCLUSION: General obesity, increased visceral adiposity tissue, waist circumference, and hip circumference rather than subcutaneous adiposity tissue or the waist-to-hip ratio were causally associated with a higher risk of VH. These findings provided a deeper understanding of the role that the distribution of adiposity plays in the mechanism of VH.

Risk Factor Analysis and Nomogram for Early Progression of COVID-19 Pneumonia in Older Adult Patients in the Omicron Era.

Background and Objective: Timely recognition of risk factors for early progression in older adult patients with COVID-19 is of great significance to the following clinical management. This study aims to analyze the risk factors and create a nomogram for early progression in older adult patients with COVID-19 in the Omicron era. Methods: A total of 272 older adults infected with COVID-19 admitted from December 2022 to February 2023 were retrospectively recruited. Risk factor selection was determined using the logistic and the least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then created to predict early progression, followed by the internal validation and assessment of its performance through plotting the receiver operating characteristic (ROC), calibration, and decision curves. Results: A total of 83 (30.5%) older adult patients presented an early progression on chest CT after 3-5 days of admission under standard initiate therapy. Six independent predictive factors were incorporated into the nomogram to predict the early progression, including CRP > 10 mg/L, IL-6 > 6.6 pg/mL, LDH > 245 U/L, CD4+ T-lymphocyte count <400/µL, the Activities of Daily Living (ADL) score ≤40 points, and the Mini Nutritional Assessment Scale-Short Form (MNA-SF) score ≤7 points. The area under the curve (AUC) of the nomogram in discriminating older adult patients who had risk factors in the training and validation cohort was 0.857 (95% CI 0.798, 0.916) and 0.774 (95% CI 0.667, 0.881), respectively. The calibration and decision curves demonstrated a high agreement in the predicted and observed risks, and the acceptable net benefit in predicting the early progression, respectively. Conclusion: We created a nomogram incorporating highly available laboratory data and the Comprehensive Geriatric Assessment (CGA) findings that effectively predict early-stage progression in older adult patients with COVID-19 in the Omicron era.

Evaluation of the Correlation Between Distribution Location and Vulnerability of Carotid Plaque in Patients with Transient Ischemic Attack.

Purpose: To analyze the relationship among distribution location, characteristics, and vulnerability of carotid plaque using CTA and provide more information on the risk factors of carotid atherosclerotic plaque. Patients and Methods: We retrospectively analyzed the CTA images of the head and neck of 93 patients with carotid atherosclerosis. Atherosclerosis was developed in 148 carotid arteries. The plaques were divided into a high-risk plaque group and a low-risk plaque group according to whether the plaques had high-risk characteristics. The maximum cross-sectional area of carotid artery bifurcation plaque on the axial image was selected, and the cross-sectional lumen was equally divided into four 90-degree sectors, ventral side wall, dorsal side wall, inner side wall, and outer side wall. The differences in the characteristics and distribution locations of the plaques in the two groups were analyzed. The characteristic parameters of the cross-sectional plaques at the bifurcation of the carotid artery. The logistic regression analysis was used to further analyze the risk factors associated with plaque vulnerability. Results: Among 148 carotid arteries,80 were classified as high-risk and 68 as low-risk groups. There were significant differences between the two groups concerning the thickness, length, maximum cross-sectional area, burden, and cross-sectional distribution of the plaques (P < 0.05). The plaque distribution on the dorsal side wall of the carotid bifurcation was higher in the high-risk group than that in the low-risk group (P < 0.05), dorsal side wall plaque-independent risk factors for the development of vulnerability of plaques in transient ischemic attack (TIA) patients (95% CI:1.522~6.991, P<0.05). Conclusion: High-risk plaques tend to occur on the dorsal side wall of the carotid bifurcation, whereas low-risk plaques tend to occur on the outer side wall of the carotid bifurcation.

Role of Platelet/Lymphocyte, Neutrophil/Lymphocyte, and Interleukin-37/Interleukin-17 Ratios in the Occurrence and Treatment of Rheumatoid Arthritis.

This study was designed to investigate the correlation of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and interleukin (IL)-37/IL-17 ratio with the incidence/treatment of rheumatoid arthritis (RA). Firstly, fifty-eight patients with RA treated at the first affiliated hospital of Xinjiang Medical University from January 2018 to January 2019 were selected as the RA group; forty-nine healthy volunteers were enrolled in the control group. RA patients were treated with disease-modifying anti-rheumatic drugs (DMARDs). Next, the NLR, PLR, IL-37, IL-17 and 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) were deleted in two groups. Subsequently, Spearman correlation analysis was adopted for the correlations of various indicators before and after treatment in two groups. According to the analysis results, the levels of NLR, PLR, IL-37, and IL-17 before treatment in the RA group were higher than those in the control group (P < .05), but the difference in the IL-37/IL-17 level between the two groups was not significant (P > .05). After treatment, NLR, PLR, and IL-37/IL-17 levels were significantly reduced in RA patients (P < .05). NLR and PLR were significantly positively correlated with DAS28-ESR, ESR and C-reactive protein (CRP), of which represented the disease activity of RA. NLP was strongly correlated with IL-37/IL-17. Collectively, NLR, PLR, IL-37, and IL-17 are closely related to the occurrence of RA. In addition, NLR and IL-37/IL-17 are more suitable than PLR in reflecting the therapeutic effect. Therefore, IL-37/IL-17 can be considered as a new indicator for reflecting the treatment effectiveness of RA.

Sacral Neural Crest-Independent Origin of the Enteric Nervous System in Mouse.

BACKGROUND & AIMS: The enteric nervous system (ENS), the gut's intrinsic nervous system critical for gastrointestinal function and gut-brain communication, is believed to mainly originate from vagal neural crest cells (vNCCs) and partially from sacral NCCs (sNCCs). Resolving the exact origins of the ENS is critical for understanding congenital ENS diseases but has been confounded by the inability to distinguish between both NCC populations in situ. Here, we aimed to resolve the exact origins of the mammalian ENS. METHODS: We genetically engineered mouse embryos facilitating comparative lineage-tracing of either all (pan-) NCCs including vNCCs or caudal trunk and sNCCs (s/tNCCs) excluding vNCCs. This was combined with dual-lineage tracing and 3-dimensional reconstruction of pelvic plexus and hindgut to precisely pinpoint sNCC and vNCC contributions. We further used coculture assays to determine the specificity of cell migration from different neural tissues into the hindgut. RESULTS: Both pan-NCCs and s/tNCCs contributed to established NCC derivatives but only pan-NCCs contributed to the ENS. Dual-lineage tracing combined with 3-dimensional reconstruction revealed that s/tNCCs settle in complex patterns in pelvic plexus and hindgut-surrounding tissues, explaining previous confusion regarding their contributions. Coculture experiments revealed unspecific cell migration from autonomic, sensory, and neural tube explants into the hindgut. Lineage tracing of ENS precursors lastly provided complimentary evidence for an exclusive vNCC origin of the murine ENS. CONCLUSIONS: sNCCs do not contribute to the murine ENS, suggesting that the mammalian ENS exclusively originates from vNCCs. These results have immediate implications for comprehending (and devising treatments for) congenital ENS disorders, including Hirschsprung's disease.