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Abstract Colon adenocarcinoma (COAD) is one of the most common types of cancer. The interconnection between non-apoptotic cell death and COAD has not been adequately addressed. In our study, an integrative bioinformatics analysis was performed to explore non-apoptotic cell death-related biomarkers in COAD. ENO2 was determined as a potent biomarker for prognosis, drug response, immunity, and immunotherapy prediction. We used EdU and RT-qPCR assays to test our hypothesis and investigate how the ENO2 gene may influence or regulate cancer-related processes. ENO2 was expected to be a potential target in COAD.

Abstract Cerebral infarction (CI) is a common cerebrovascular disease worldwide, and the burden caused by the sequelae of CI has increased significantly. However, current treatment guidelines lack standardized recommendations for pharmacotherapy of sequelae of CI. This retrospective study collected and analyzed 1.98 million prescriptions concerning sequelae of CI from patients admitted to Zhiyun Health Internet Hospital in 2022. The mean age of patients was 66.2 ± 11.4 years, and 52.40% were male. 79.73% had one or more comorbidities. For treatment, the prescriptions of 1-, 2- and ≥ 3-drug accounted for 64.55%, 23.77% and 11.68% respectively. Chinese patent medicine (CPM) prescriptions, western medicine (WM) prescriptions, and CPM and WM combined (CPM + WM) prescriptions accounted for 53.81%, 27.33%, and 18.86% respectively. In CPM prescriptions, the most frequently prescribed medications were Salvia miltiorrhiza (34.81%), Ginkgo biloba (24.96%), Panax notoginseng (20.67%), Gastrodia (7.15%) and Ligusticum Wallichii (4.90%). For WM prescriptions, the most commonly prescribed agents were anti-hypertensive (32.82%), anti-thrombotic (16.06%), vasodilator (15.70%), anti-dementia (10.88%), and lipid-lowering (9.58%) drugs. Among CPM + WM prescriptions, 72.61% had CPM/WM = 1, 21.20% had CPM/WM 1. This research utilized real-world data extracted from internet hospitals in China to present valuable evidence of online prescription patterns among patients experiencing sequelae of CI.

Abstract Genomics-guided methodologies have revolutionized the discovery of natural products. However, a major challenge in the field of genome mining is determining how to selectively extract biosynthetic gene clusters (BGCs) for untapped natural products from numerous available genome sequences. In this study, we developed a fungal genome mining tool that extracts BGCs encoding enzymes that lack a detectable protein domain (i.e., domainless enzymes) and are not recognized as biosynthetic proteins by existing bioinformatic tools. We searched for BGCs encoding a homologue of Pyr4-family terpene cyclases, which are representative examples of apparently domainless enzymes, in approximately 2000 fungal genomes and discovered several BGCs with unique features. The subsequent characterization of selected BGCs led to the discovery of fungal onoceroid triterpenoids and unprecedented onoceroid synthases. Furthermore, in addition to the onoceroids, a previously unreported sesquiterpene hydroquinone, of which the biosynthesis involves a Pyr4-family terpene cyclase, was obtained. Our genome mining tool has broad applicability in fungal genome mining and can serve as a beneficial platform for accessing diverse, unexploited natural products.

ABSTRACT While in hospite Symbiodiniaceae dinoflagellates are essential for coral health, ambient free-living counterparts are crucial for coral recruitment and resilience. Comparing free-living and in hospite Symbiodiniaceae communities can potentially provide insights into endosymbiont acquisition and recurrent recruitment in bleaching recovery. In this study, we studied coral-endosymbiotic and ambient free-living Symbiodiniaceae communities in the South China Sea. We collected samples from 183 coral and ambient plankton samples and conducted metabarcoding to investigate the diversity distribution, driving factors, and assembly mechanisms of the two groups of Symbiodiniaceae. Results revealed Cladocopium C1 and Durusdinium D1 as dominant genotypes. We detected a higher genotypic diversity in free-living than in hospite symbiodiniacean communities, but with shared dominant genotypes. This indicates a genetically diverse pool of Symbiodiniaceae available for recruitment by corals. Strikingly, we found that the cooler area had more Symbiodiniaceae thermosensitive genotypes, whereas the warmer area had more Symbiodiniaceae thermotolerant genotypes. Furthermore, in hospite and free-living Symbiodiniaceae communities were similarly affected by environmental factors, but shaped by different assembly mechanisms. The in hospite communities were controlled mainly by deterministic processes, whereas the ambient communities by stochastic processes. This study sheds light on the genetic diversity of source environmental Symbiodiniaceae and differential assembly mechanisms influencing Symbiodiniaceae inside and outside corals.IMPORTANCESymbiodiniaceae dinoflagellates play a pivotal role as key primary producers within coral reef ecosystems. Coral-endosymbiotic Symbiodiniaceae communities have been extensively studied, but relatively little work has been reported on the free-living Symbiodiniaceae community. Conducting a comparative analysis between sympatric coral-endosymbiotic and free-living Symbiodiniaceae communities can potentially enhance the understanding of how endosymbiont communities change in response to changing environments and the mechanisms driving these changes. Our findings shed light on the genetic diversity of source environmental Symbiodiniaceae and differential assembly mechanisms shaping free-living and in hospite Symbiodiniaceae communities, with implications in evaluating the adaptive and resilient capacity of corals in response to future climate change.

Abstract Introduction Acute ischemic stroke (AIS) significantly contributes to severe disability and mortality among the elderly. This study aims to explore the association between longitudinal fluid balance (FB) trajectories and clinical outcomes in elderly patients with AIS. Our hypothesis posits the existence of multiple latent trajectories of FB in patients with AIS during the initial 7 days following ICU admission. Methods Patients (age ≥ 65 years) with AIS and continuous FB records were identified from two large databases. Group-based trajectory modeling identified latent groups with similar 7-day FB trajectories. Subsequently, multivariable logistic and quasi-Poisson regression were employed to evaluate the relationship between trajectory groups and outcomes. Additionally, nonlinear associations between maximum fluid overload (FO) and outcomes were analyzed using restricted cubic spline models. To further validate our findings, subgroup and sensitivity analysis were conducted. Results A total of 1146 eligible patients were included in this study, revealing three trajectory patterns were identified: low FB (84.8%), decreasing FB (7.2%), and high FB (7.9%). High FB emerged as an independent risk factor for in-hospital mortality. Compared with those without FO, patients with FO had a 1.57-fold increased risk of hospital mortality (adjusted odd ratio (OR) 1.57, 95% confidence interval (CI) 1.08–2.27), 2.37-fold increased risk of adverse kidney event (adjusted OR 2.37, 95% CI 1.56–3.59), and 1.33-fold increased risk of prolonged ICU stay (adjusted incidence rate ratio (IRR) 1.33, 95% CI 1.19–1.48). The risk of hospital mortality and adverse kidney event increased linearly with rising maximum FO (P for non-linearity = 0.263 and 0.563, respectively). Conclusion Daily FB trajectories were associated with adverse outcomes in elderly patients with AIS. Regular assessment of daily fluid status and restriction of FO are crucial for the recovery of critically ill patients.

Abstract Purpose For patients with early-stage cervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. Patients and methods The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. Results A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rates were 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p

Fungal meroterpenoids are diverse structurally intriguing molecules with various biological properties. One large group within this compound class is derived from the aromatic precursor 3,5-dimethylorsellinic acid (DMOA). In this study, we constructed engineered metabolic pathways in the fungus Aspergillus oryzae to expand the molecular diversity of meroterpenoids. We employed the 5-methylorsellinic acid (5-MOA) synthase FncE and three additional biosynthetic enzymes for the formation of (6R,10′R)-epoxyfarnesyl-5-MOA methyl ester, which served as a non-native substrate for four terpene cyclases from DMOA-derived meroterpenoid pathways. As a result, we successfully generated six unnatural 5-MOA-derived meroterpenoid species, demonstrating the effectiveness of our approach in the generation of structural analogues of meroterpenoids.

Objective: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with an unclear pathogenetic mechanism in the labial gland. This study aims to investigate the cellular and molecular mechanisms contributing to the development of this disease. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on 32,337 cells of labial glands from three pSS patients and three healthy individuals. We analyzed all cell subsets implicated in pSS pathogenesis. Results: Our research revealed diminished differentiation among epithelial cells, concomitant with an enhancement of interferons (IFNs)-mediated signaling pathways. This indicates a cellular functional shift in reaction to inflammatory triggers. Moreover, we observed an augmentation in the population of myofibroblasts and endothelial cells, likely due to the intensified IFNs signaling, suggesting a possible reconfiguration of tissue structure and vascular networks in the impacted regions. Within the immune landscape, there was an apparent increase in immunosuppressive macrophages and dendritic cells (DCs), pointing to an adaptive immune mechanism aimed at modulating inflammation and averting excessive tissue harm. Elevated activation levels of CD4+T cells, along with a rise in regulatory T (Treg) cells, were noted, indicating a nuanced immune interplay designed to manage the inflammatory response. In the CD8+T cell subsests, we detected a notable increase in cells expressing granzyme K (GZMK), signaling an intensified cytotoxic activity. Additionally, the escalated presence of T cells with high levels of heat shock proteins (HSPs) suggests a cellular stress condition, possibly associated with persistent low-grade inflammation, mirroring the chronic aspect of the condition. Conclusions: Our research identified distinct stromal and immune cell populations linked to pSS, revealing new potential targets for its management. The activation of myeloid, B, and T cells could contribute to pSS pathogenesis, providing important guidance for therapeutic approaches.

BackgroundUnbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model.MethodsPatients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis.ResultsThe study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38+CD8+T cells, PD-1+NK cells, HLA-DR+CD8+T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1+ NK cells, while cluster 2 featured higher proportions of naïve CD4+T cells. Furthermore, the level of PD-1+NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, P

Abstract Acute respiratory distress syndrome (ARDS) is a major disease that threatens the life and health of neonates. Vitamin A (VA) can participate in early fetal lung development and affect lung immune function. Researches revealed that the serum VA level in premature infants with ARDS was lower than that in premature infants without ARDS of the same gestational age, and premature infants with VA deficiency (VAD) were more likely to develop ARDS. Moreover, the VA levels can be used as a predictor of the development and severity of neonatal ARDS. However, the critical question here is; Does ARDS develop due to VAD in these systemic diseases? Or does ARDS develop because these diseases cause VAD? We hypothesize that VAD may aggravate neonatal ARDS by affecting immunity, metabolism, barriers and other pathways. In this article, we used multiomics analysis to find that VAD may aggravate ARDS mainly through the Fc epsilon RI signaling pathway, the HIF-1 signaling pathway, glutathione metabolism, and valine, leucine and isoleucine degradation signaling pathways, which may provide the molecular pathogenic mechanism behind the pathology of VAD-aggravated ARDS and can also provide potential molecular targets for subsequent research on ARDS.

Abstract Hierarchical classification offers a more specific categorization of data and breaks down large classification problems into subproblems, providing improved prediction accuracy and predictive power for undefined categories, while also mitigating the impact of poor-quality data. Despite these advantages, its application in predicting primary cancer is rare. To leverage the similarity of cancers and the specificity of methylation patterns among them, we developed the Cancer Hierarchy Classification Tool (CHCT) using the idea of hierarchical classification, with methylation data from 30 cancer types and 8239 methylome samples downloaded from publicly available databases (The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO)). We used unsupervised clustering to divide the classification subproblems and screened differentially methylated sites using Analysis of variance (ANOVA) test, Tukey-kramer test, and Boruta algorithms to construct models for each classifier module. After validation, CHCT accurately classified 1568 out of 1660 cases in the test set, with an average accuracy of 94.46%. We further curated an independent validation cohort of 677 cancer samples from GEO and assigned a diagnosis using CHCT, which showed high diagnostic potential with generally high accuracies (an average accuracy of 91.40%). Moreover, CHCT demonstrates predictive capability for additional cancer types beyond its original classifier scope as demonstrated in the medulloblastoma and pituitary tumor datasets. In summary, CHCT can hierarchically classify primary cancer by methylation profile, by splitting a large-scale classification of 30 cancer types into ten smaller classification problems. These results indicate that cancer hierarchical classification has the potential to be an accurate and robust cancer classification method.

AbstractBackground Globally, the prevalence of hypertension and the accompanying burden of cardiovascular disease are increasing. Through drug utilization research, we can understand the prescription status of hypertension patients and promote rational drug use. The purpose of this retrospective study was to describe the current prescription pattern of antihypertensive drugs in Chinese patients and determine the compliance level of treatment guidelines.Materials and methods Around 11.1 million patients who received a prescription for antihypertensive therapy between January 2021 to December 2021 were obtained from a database of Hangzhou Kang Sheng Health Consulting CO., Ltd.Results The mean age of hypertensive patients was 54.75 ± 12.98 years. About 6.7 million (60.30%) were males. About 46.07% of patients had comorbidities. The most common classes of antihypertensive medications used were calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs). Around 78.33% of participants were on monotherapy. Diuretics + ARBs and Diuretics + CCBs + ARBs were the most commonly prescribed pattern in two-drug combination therapy and three-drug combination therapy, respectively.Conclusions CCBs and ARBs were the two most frequently prescribed for patients with hypertension. The prescription pattern of antihypertensive medications in the study largely complied with recommended Chinese hypertension guidelines.Key messagesCardiovascular disease is the most common complication of hypertension.Calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) are the two most commonly used drugs for hypertension patients in China.The proportion of combination prescription pattern in Chinese hypertensive patients is low.

We applied 24-h Holter monitoring to analyze the characteristics of arrhythmias and heart rate variability in Chinese patients with primary aldosteronism (PA) and compared them with age-, sex-, and blood pressure-matched primary hypertension (PH) patients. A total of 216 PA patients and 261 PH patients were enrolled. The nonstudy data were balanced using propensity score matching (PSM), and the risk variables for developing arrhythmias were then analyzed using logistic regression analysis. Before PSM, the proportion of PA patients with combined atrial premature beats and prolonged QT interval was higher than the corresponding proportion in the PH group. After PSM, the PA group had a larger percentage of transient atrial tachycardia and frequent atrial premature beats, and it had higher heart rate variability metrics. The proportion of unilateral PA combined with multiple ventricular premature beats was higher than that of bilateral PA. Older age, grade 3 hypertension, and hypokalemia were independent risk factors for the emergence of arrhythmias in PA patients. PA patients suffer from a greater prevalence of arrhythmias than well-matched PH patients.

Objective To assess the association between the systemic inflammation response index (SIRI) and the prognosis in patients with sepsis-associated acute kidney injury (SA-AKI). Methods In this observational study, adult patients with SA-AKI were categorized into three groups based on SIRI tertiles. Survival outcomes were compared across the three groups using Kaplan–Meier survival curves. Various Cox proportional hazards regression models were developed to determine the association between the SIRI and mortality in patients with SA-AKI. Subgroup analyses were also performed to explore the association between different SIRI tertiles and all-cause mortality. Results After adjusting for several confounders, the second SIRI tertile (2.5

Abstract There has been an increase in cardiovascular morbidity and mortality over the past few decades, making cardiovascular disease (CVD) the leading cause of death worldwide. However, the pathogenesis of CVD is multi-factorial, complex, and not fully understood. The gut microbiome has long been recognized to play a critical role in maintaining the physiological and metabolic health of the host. Recent scientific advances have provided evidence that alterations in the gut microbiome and its metabolites have a profound influence on the development and progression of CVD. Among the trillions of microorganisms in the gut, bifidobacteria, which, interestingly, were found through the literature to play a key role not only in regulating gut microbiota function and metabolism, but also in reducing classical risk factors for CVD (e.g., obesity, hyperlipidemia, diabetes) by suppressing oxidative stress, improving immunomodulation, and correcting lipid, glucose, and cholesterol metabolism. This review explores the direct and indirect effects of bifidobacteria on the development of CVD and highlights its potential therapeutic value in hypertension, atherosclerosis, myocardial infarction, and heart failure. By describing the key role of Bifidobacterium in the link between gut microbiology and CVD, we aim to provide a theoretical basis for improving the subsequent clinical applications of Bifidobacterium and for the development of Bifidobacterium nutritional products.

ABSTRACTIn this work, Ta2O5 films were first deposited on Si substrates by reactive magnetron sputtering of a Ta metal target at various substrate temperatures, RF powers and sputtering pressures. The crystal characteristics of these films can be effectively tailored by controlling the sputtering process. Based on the optimized process parameters, tantalum oxide (TaOx) films with different oxygen component content were sputtered on ITO buffered Si substrates and comparatively investigated. The results show that the film with Ta/TaOx/ITO structure has a resistance switching (RS) behavior and its conduction mechanism is closely related to the O2-/O concentration related to the oxygen partial pressure at the dielectric layer and electrode interface. This study provides an in-depth understanding of the component/structure design and structure-activity relationship for high-performance TaOx-based resistive memory.

Background: With the rise of targeted treatments for asthma, treatment with omalizumab is a new option. Objectives: To assess the improvement of pulmonary function with additional omalizumab treatment in patients (⩾6 years old) with moderate-to-severe allergic asthma. Data sources and methods: Observational studies of randomized controlled trials of add-on omalizumab for the treatment of patients with moderate-to-severe allergic asthma, published from the establishment till August 2022, were retrieved from WAN FANG DATA, PubMed, CNKI, Embase, Cochrane, and Web of Science databases. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria, using RevMan 5.3 to analyze the data. Results: A total of 11 randomized controlled clinical trials were included, involving a total of 3578 patients with asthma, 1856 patients in the omalizumab group, and 1722 patients in the control group. The improvement in Forced expiratory volume in 1 s as a percentage of predicted normal and Forced expiratory volume in 1 s was more pronounced in the omalizumab-treated group [MD = 3.91, 95% confidence interval (CI): 1.89–5.94, p = 0.0002; MD = 0.09, 95% CI: 0.05–0.13, p

ObjectiveThis study aims to analyze the efficacy of anti-syphilis treatment and the impact of syphilis events on HIV virology and immunology in HIV/syphilis co-infected patients on long-term antiretroviral therapy (ART) and to investigate the incidence and factors of syphilis recurrence/re-infection/serofast state. The insights derived from this investigation can potentially guide strategies for preventing and managing syphilis and AIDS.MethodsA retrospective case–control study was conducted at the AIDS clinic of Peking Union Medical College Hospital from January 2003 to December 2022. The study involved 86 HIV/syphilis co-infected patients and 86 HIV mono-infected patients matched based on age, baseline CD4 + T cell counts, and viral load. We examined the clinical characteristics of HIV/syphilis co-infected patients, evaluated the efficacy of anti-syphilis treatment, and analyzed the dynamic changes in HIV virology and immunology. The Generalized Estimating Equations (GEE) model investigated the factors associated with HIV/syphilis co-infection and syphilis recurrence/reinfection/serofast state.ResultsSyphilis serofast state was observed in 11.6% (10/86) of HIV/syphilis co-infected patients after treatment, and 33.7% (29/86) had syphilis recurrence or re-infection. The overall effectiveness of syphilis treatment stood at 76.8% (63/82). Notably, the effectiveness of syphilis treatment displayed a significant correlation with baseline syphilis titers exceeding 1:128 (p = 0.003). Over the 10-year follow-up period on ART, the HLA-DR + CD8+/CD8 + % levels in the HIV/syphilis co-infected group were markedly higher than those in the HIV mono-infected group (p 0.05). GEE analysis model revealed that elevated HLA-DR + CD8+/CD8 + % levels were associated with HIV/syphilis co-infection (OR = 1.026, 95% CI = 1.007–1.046; p = 0.007) and syphilis recurrence/reinfection/serofast state (OR = 1.036, 95% CI = 1.008–1.065; p = 0.012).ConclusionWhile HIV/syphilis co-infected patients typically receive adequate treatment, the incidence of syphilis recurrence and reinfection remain notably elevated. A heightened HLA-DR + CD8+/CD8+ % is a notable risk factor for HIV/syphilis co-infection and syphilis recurrence/reinfection/serofast state. Therefore, it is advisable to reinforce health education efforts and ensure regular follow-ups for people living with HIV undergoing ART to monitor syphilis infection or increased risk of syphilis infection.

BackgroundSkull fracture can lead to significant morbidity and mortality, yet the development of effective predictive tools has remained a challenge. This study aimed to establish and validate a nomogram to evaluate the 28-day mortality risk among patients with skull fracture.Materials and methodsData extracted from the Medical Information Mart for Intensive Care (MIMIC) database were utilized as the training set, while data from the eICU Collaborative Research Database were employed as the external validation set. This nomogram was developed using univariate Cox regression, best subset regression (BSR), and the least absolute shrinkage and selection operator (LASSO) methods. Subsequently, backward stepwise multivariable Cox regression was employed to refine predictor selection. Variance inflation factor (VIF), akaike information criterion (AIC), area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) were used to assess the model's performance.ResultsA total of 1,527 adult patients with skull fracture were enrolled for this analysis. The predictive factors in the final nomogram included age, temperature, serum sodium, mechanical ventilation, vasoactive agent, mannitol, extradural hematoma, loss of consciousness and Glasgow Coma Scale score. The AUC of our nomogram was 0.857, and C-index value was 0.832. After external validation, the model maintained an AUC of 0.853 and a C-index of 0.829. Furthermore, it showed good calibration with a low Brier score of 0.091 in the training set and 0.093 in the external validation set. DCA in both sets revealed that our model was clinically useful.ConclusionA nomogram incorporating nine features was constructed, with a good ability in predicting 28-day mortality in patients with skull fracture.

ABSTRACT Innate lymphoid cells (ILCs) play a crucial role in mucosal protection and tissue homeostasis. However, the early mucosal defense mechanisms against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have not been fully understood to date. This knowledge gap has motivated us to develop a coronavirus disease 2019-like mouse model to investigate the interactions between the virus, its receptor, and ILCs. In our study, we conducted intranasal challenges using pseudovirus expressing Spike (PSV-S) to examine the expression patterns of humanized ACE2 (chiACE2) and the transduction of PSV-S in lung and ileum tissues over a specified time period. Within a span of 72 hours, we observed an intense viral transduction induced by the spike protein, which was detected from the central bronchus to the bronchiole and alveolus in the lung (levels 3 to 8). Similarly, we observed the transduction of PSV-S in the villi and crypts of the ileum. Interestingly, our precise three-dimensional colocalization analysis revealed that only 73.74% ± 1.76% of the PSV-S transduction depended on chiACE2. Furthermore, type 2 innate lymphoid cells (ILC2s) exhibited the most pronounced activation in the gut mucosa. This finding indicates the significant role of ILC2s as contributors to the mucosal defense against viral infections. Our data shed light on the critical involvement of ILC2s and their intricate three-dimensional regulatory network in combating SARS-CoV-2 within the mucosa. IMPORTANCE Our study revealed the spatial interaction between humanized ACE2 and pseudovirus expressing Spike, emphasizing the role of type 2 innate lymphoid cells during the initial phase of viral infection. These findings provide a foundation for the development of mucosal vaccines and other treatment approaches for both pre- and post-infection management of coronavirus disease 2019.

The content and distribution of adipocytes is an important factor that affects meat quality. Previous studies showed that circRNAs are involved in various physiological processes. Nevertheless, more research is needed to investigate the function of circRNAs in adipogenesis. The present study examines the effects of circRNF111 on adipogenesis of bovine preadipocyte and aims to elucidate the underlying molecular mechanisms. In our study, the sequence signature of circRNF111 was identified using bioinformatics, RNA-FISH, and sequencing. Mechanistically, knockdown or exogenous expression of circRNF111 in preadipocytes was done to prove the functional significance of circRNF111. Combined with bioinformatics, a dual fluorescein reporter system, and immunoprecipitation, the interaction between circRNF111, miR-27a-3p, and the target gene PPARγ was verified. The results reveal that circRNF111 is positively correlated with adipocyte differentiation. The newly identified bovine circRNF111 functions as a miR-27a-3p sponge to rescue the inhibitory effect of miR-27a-3p on the PPARγ gene, thereby promoting adipogenesis.

With the continuous acceleration of the global construction industry, many structural infrastructure structures in China have been put into use for decades. They are very prone to damage due to fatigue. The modal parameter identification of civil engineering construction can evaluate the safety status of infrastructure structures. In view of this, an identification system of civil engineering structure modal parameters is proposed based on improved wavelet transform. In the process, the mode shape was chosen as the method of wavelet transform. The data was discretized by selecting the actual data of a high-speed railway station combined with sensors and wavelet transform. Finally, the correct identification of the modal parameters of civil engineering structures is realized. The data shows that under normal conditions where there is only white noise interference, the waveform of the structure is relatively stable, and the amplitude fluctuation is in the [-2,3] interval. At the same time, the average amplitude of the structure is in the [2.2, −1.5] interval under normal conditions. In addition, the positive and negative extreme points are 3.7 and −2.3, respectively. This indicates that the structure amplitude fluctuation is in a dynamic and stable state under normal circumstances. The optimized wavelet transform method identifies a total of four orders in the first six natural frequencies. The minimum error is 0.11%, the maximum error is 1.50%, and the average error of the first four natural frequencies is 0.578%. In addition, based on the comparison of theoretical and identification values of longitudinal vibration shapes, the proposed method can successfully detect abnormal values at the 10th and 18th nodes. From the above results, it shows that the wavelet transform method has high accuracy and small error in frequency identification. It meets the requirements of identifying the natural frequency parameters of the structure. From the calculation, the method proposed in the experiment can realize the real-time health detection of the structure, which is of great significance.

Using S-band dual-polarization radar data and other observation data, a supercell storm that caused a large hail in Changsha, Hunan Province on 10 May, 2021 was analyzed. The results show as below. (1) This process takes place under the synoptic condition of low-level warm advection, high energy, and convective instability. Besides, wet bulb 0 ℃ (WBZ) is obviously lower than the height of 0℃, which provided favorable conditions for the formation and maintenance of large hail supercell storms. (2) The area of strong center (horizontal reflectivity (Zh) ≥60 dBz) and the maximum horizontal reflectivity increase significantly. The vertical integrated liquid water content increases significantly, and the height of mass center develops to reach the effective growth layer of hail, which can be used as a criterion of major hail formation and development. (3) The evolution of differential reflectivity (Zdr) column, correlation coefficient (CC), and specific differential phase (Kdp) provides the important basis for distinguishing the changes in the cloud physical process of hail. In the early stage of storm development, the appearance of Zdr column corresponds to the updraft zone, which extends above WBZ. The supercooled raindrops in the Zdr column provide hail embryos for the development of hail. The Zdr-hole (< 0 dB) corresponds to the downdraft area and expands to near the ground. Small CC and Kdp-hole indicate the appearance of dry large hail. (4) The dual-polarization monitoring and identification model of hail supercell is constructed and which shows that due to the occlusion of precipitation echo, Zh does not show the characteristics of three body scatter spike (TBSS). The polarization TBSS characteristics of significantly negative Zdr and small CC and non-uniform beam filling can be used as an important criteria for identifying hail and hail scales.

Abstract Colorectal cancer (CRC) has high incidence and mortality rates and is one of the most common cancers of the digestive tract worldwide. Metastasis and drug resistance are the main causes of cancer treatment failure. Studies have recently suggested extracellular vesicles (EVs) as a novel mechanism for intercellular communication. They are vesicular particles, which are secreted and released into biological fluids, such as blood, urine, milk, etc., by a variety of cells and carry numerous biologically active molecules, including proteins, nucleic acids, lipids, metabolites, etc. EVs play a crucial part in the metastasis and drug resistance of CRC by delivering cargo to recipient cells and modulating their behavior. An in-depth exploration of EVs might facilitate a comprehensive understanding of the biological behavior of CRC metastasis and drug resistance, which might provide a basis for developing therapeutic strategies. Therefore, considering the specific biological properties of EVs, researchers have attempted to explore their potential as next-generation delivery systems. On the other hand, EVs have also been demonstrated as biomarkers for the prediction, diagnosis, and presumed prognosis of CRC. This review focuses on the role of EVs in regulating the metastasis and chemoresistance of CRC. Moreover, the clinical applications of EVs are also discussed. Graphical Abstract

Abstract Depression is a common mental illness, which is related to monoamine neurotransmitters and the dysfunction of the cholinergic, immune, glutamatergic, and neuroendocrine systems. The hypothesis of monoamine neurotransmitters is one of the commonly recognized pathogenic mechanisms of depression; however, the drugs designed based on this hypothesis have not achieved good clinical results. A recent study demonstrated that depression and inflammation were strongly correlated, and the activation of alpha7 nicotinic acetylcholine receptor (α7 nAChR)-mediated cholinergic anti-inflammatory pathway (CAP) in the cholinergic system exhibited good therapeutic effects against depression. Therefore, anti-inflammation might be a potential direction for the treatment of depression. Moreover, it is also necessary to further reveal the key role of inflammation and α7 nAChR in the pathogenesis of depression. This review focused on the correlations between inflammation and depression as well-discussed the crucial role of α7 nAChR in the CAP.

There were two rare 6 cm hailstones under the background of low-level warm advection forcing in Huaihua of Hunan Province on March 21 and May 4, 2020. Based on the meteorological stational data and the Doppler weather radar data, the structures of intensity and dynamic fields of the supercell storms for these two events are analyzed. Results are showed below. (1) Both cases occur under the background of low-level warm advection forcing. Moderate-intensity convective effective potential energy, large deep vertical wind shear, and high energy helicity favored the organizational development and maintenance of storms, and the ground convergence line is the main trigger factor of severe convection weather. (2) The 6-cm hails in the two cases both occurred in the early mature stage of supercell storm, which are caused by the "supercell-like" storm without the characteristics of mesocyclone, but with the characteristics of hook echoes, sidelobe echoes, three-body scattering spike, and echo overhangs. (3) In the intense development stage, the vertical dynamic fields of the storms are both featured by the structure of low-level convergence, the double-vortex-tube rotating structure of cyclonic rotation and anticyclonic rotation in the middle level (referred to as double vortex) and high-level divergence. (4) The maximum reflectivity and the cells-vertical integrated liquid both reach 67 dBz and 69 kg·m-2.The decrease of height top and the strongest-shear height reflect hail falling.

Extreme precipitation occurred in northern Hubei,with the maximum precipitation of 518.5 mm in 24 hours and 117.9 mm in 1 hour,causing serious disasters from 20:00 BT on August 11 to 20:00 BT on August 12,2021. Based on conventional meteorological observation data and ERA5 reanalysis data,the characteristics and synoptic causes of extreme precipitation for the event are preliminarily analyzed using statistical methods and synoptic diagnostic analysis methods. The results are shown below. (1) Although the characteristics of rain are different in different regions,the extreme rainstorm has the characteristics of large accumulated rainfall,strong short-term rainfall,concentrated precipitation period,strong disaster possibility,and extreme rainfall. (2) The rapid development,long duration and slow eastward movement of β-Mesoscale Convective System (MβCS) are the main reasons for the extreme precipitation. (3) The main influence systems are the high level South Asia High (SAH),the upper jet,the middle level West Pacific Subtropical High (WPSH) and the low trough. The direct participants are the mid- low level wind shear,mesoscale vortex and easterly jet. (4) The abnormal strength and maintenance of 850-925 hPa mesoscale vortex and easterly jet lead to the formation of strong dynamic convergence center and strong water vapor convergence center in the lower layer,providing continuous vertical upward movement below 700 hPa. The jet also favors the strengthening of energy front and the establishment of high-energy region and low-level instability,which leads to the occurrence and development of convective heavy rain. (5) The precipitable water in the whole layer and the vorticity and the vertical velocity and specific humidity at 925-850 hPa show relatively abnormal extreme characteristics. In addition,its anomaly evolution trend is basically consistent with the evolution trend of rainfall intensity.

Background: The objective was to explore the impact of different delivery methods on maternal and infant outcomes in women with a prolonged second stage of labor and a fetus with a persistent occipital posterior position. Methods: 60 women with a fetus in the occipital posterior position who underwent obstetric low forceps-assisted delivery were selected as the study group according to the order of delivery, and 40 women who underwent cesarean section during the same period were selected as study group 1 according to the order of delivery. We compared the maternal-related indicators and neonatal outcome-related indicators of the two groups. Then, we selected women in chronological order during the same period to be included in control group 2 (60 primiparous women with a fetus in the occipital anterior position who underwent low forceps-assisted delivery during the same period) for comparison with the study group. Results: The time of fetal head delivery, postpartum hemorrhage rate, hospitalization time, average hospitalization cost, and number of cases of postpartum infection in the group with a fetus in the occipital posterior position and low forceps-assisted delivery were significantly lower than those in the cesarean section group (p < 0.05). There was no statistically significant difference in the 1-minute Apgar score, umbilical artery blood gas pH value, or number of neonatal injuries between the cesarean section group and the group with a fetus in the occipital posterior position with forceps-assisted delivery (p > 0.05). There were also no statistically significant differences in the complication-related indicators between the group with a fetus in the occipital posterior position with forceps-assisted delivery and the group with a fetus in the occipital anterior position with forceps-assisted delivery. The two groups had second-degree lacerations, cervical lacerations, vaginal wall lacerations, and vaginal wall hematomas. There was no statistically significant difference in the comparison of urinary retention (p > 0.05), and there was no statistically significant difference between the group with a fetus in the occipital posterior position and forceps-assisted delivery and the group with a fetus in the occipital anterior position and forceps-assisted delivery in the comparison of related indicators of neonatal outcomes and pelvic floor reexamination at the Aa and Ap points 42 days after delivery (p > 0.05). Conclusions: The use of low forceps for women with a prolonged second stage of labor and a fetus in a persistent occipital posterior position can effectively shorten the time of fetal head delivery, reduce postpartum bleeding, reduce the incidence of postpartum infection, shorten the hospitalization time, and reduce average hospitalization costs and does not increase adverse neonatal outcomes.

Coupling land use and climate change under shared socioeconomic pathway and representative concentration pathway (SSP–RCP) scenarios can provide more accurate predictions of water supply risks, thereby supporting decision-making for spatial planning with a focus on climate adaptation. Climate change exhibits spatial and temporal differences. To meet the requirements of spatial planning, further research is needed to assess water supply risks at different basin or regional scales. In this study, we selected four SSP–RCP scenarios for analysis, considering the temporal scale of spatial planning. The climate modeling capabilities of five global climate models (GCMs) and a multi-model ensemble (MME) were evaluated using a Taylor diagram, which assesses the performance of climate element simulations. The modeling framework that consisted of system dynamics (SD), patch-generating land-use simulations (PLUS), and Soil and Water Assessment Tool (SWAT) was employed to analyze synergistic changes in climate, land use, and water supply. The Ganjiang River Basin (GRB) serves as a case study for climate-adaptive planning at the basin scale, given its characteristics of high agricultural water demand and vulnerability to droughts and floods. The study aims to provide decision-making support for such planning. In our projections, precipitation in the GRB showed a slightly increasing trend from 2021 to 2050. Monthly precipitation increases during the flood season in August and decreases during the dry season from October to December. The maximum and minimum temperatures showed an increasing trend on both the yearly and monthly scales, with slightly higher increases during fall and winter. During the planning phase, the land use quantities of SSP126 and SSP245 showed similar variations. SSP370 experienced the most significant reduction in farmland, while SSP585 displayed a more scattered and punctuated layout of construction land. The annual water supply in the GRB showed a slightly decreasing trend from 2021 to 2035 and 2036–2050, and the largest reduction was found in SSP370. The trend of variation in the monthly water supply was complex. There was a consistent trend of decreasing water supply during the dry season, whereas the changes during the flood season were more complex. Seasonal variations in water supply are a major water security concern for the basin’s future. It is necessary to strengthen the agricultural water security planning in the northern region of the basin and enhance its ability to adapt to droughts and floods.

Major depressive disorder (MDD) is a chronic relapsing psychiatric disorder. Conventional antidepressants usually require several weeks of continuous administration to exert clinically significant therapeutic effects, while about two-thirds of the patients are prone to relapse of symptoms or are completely ineffective in antidepressant treatment. The recent success of the N-methyl-D-aspartic acid (NMDA) receptor antagonist ketamine as a rapid-acting antidepressant has propelled extensive research on the action mechanism of antidepressants, especially in relation to its role in synaptic targets. Studies have revealed that the mechanism of antidepressant action of ketamine is not limited to antagonism of postsynaptic NMDA receptors or GABA interneurons. Ketamine produces powerful and rapid antidepressant effects by affecting α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors, adenosine A1 receptors, and the L-type calcium channels, among others in the synapse. More interestingly, the 5-HT2A receptor agonist psilocybin has demonstrated potential for rapid antidepressant effects in depressed mouse models and clinical studies. This article focuses on a review of new pharmacological target studies of emerging rapid-acting antidepressant drugs such as ketamine and hallucinogens (e.g., psilocybin) and briefly discusses the possible strategies for new targets of antidepressants, with a view to shed light on the direction of future antidepressant research.

Abstract All‐inorganic metal halide perovskite CsPbBr3 crystal is regarded as an attractive alternative to high purity Ge and CdZnTe for room temperature γ‐ray detection. However, high γ‐ray resolution is only observable in small CsPbBr3 crystal; more practical and deployable large crystal exhibits very low, and even no detection efficiency, thereby thwarting prospects for cost‐effective room temperature γ‐ray detection. The poor performance of large crystal is attributed to the unexpected secondary phase inclusion during crystal growth, which traps the generated carriers. Here, the solid–liquid interface during crystal growth is engineered by optimizing the temperature gradient and growth velocity. This minimizes the unfavorable formation of the secondary phase, leading to industrial‐grade crystals with a diameter of 30 mm. This excellent‐quality crystal exhibits remarkably high carrier mobility of 35.4 cm2 V−1 s−1 and resolves the peak of 137Cs@ 662 keV γ‐ray at an energy resolution of 9.91%. These values are the highest among previously reported large crystals.

Introduction Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a variable clinical course, ranging from mild to severe forms. It mainly occurs in women, especially those of fertile age. The aim of the study was to systematically analyze the associations of perinatal disease activity with adverse outcomes of Chinese patients with SLE and their off-spring. Material and methods Data of prenatal SLE patients and healthy pregnant woman admitted to our hospital during the period October 2001 to January 2018 were retrospectively collected, and the status of offspring of SLE patients was followed up in March 2020. Disease activity was evaluated by SLE disease activity index 2000 (SLEDAI-2k), and those with scores > 6 were defined as having active disease. Results In total, 198 deliveries of 194 SLE patients and 199 deliveries of healthy women were documented. Maternal and fetal adverse outcomes occurred in 74 (37.4%) and 90 (45.5%) deliveries of SLE patients, respectively, which were significantly higher than those of healthy subjects. Among SLE patients, the active group had higher rates of gestational hypertension (p < 0.001), reeclampsia/eclampsia (p < 0.001), low birth weight (p < 0.001), premature birth (p < 0.001) and fetal growth restriction (FGR) (p < 0.01) than the inactive group. Multivariate logistic analysis revealed that perinatal renal activity was associated with gestational hypertension (OR 4.43, p < 0.001), preeclampsia/ eclampsia (OR 9.14, p < 0.001), low birth weight (OR 2.24, p < 0.05) and premature birth (OR 4.20, p < 0.001). Compared with the general population, offspring of SLE patients had relatively high rates of eczema (50/142, 35.2%) and congenital heart disease (6/142, 4.2%), which were irrelevant to perinatal disease activity, but related to specific antibodies. Conclusions For perinatal women with SLE, renal activity is associated with a variety of adverse pregnancy outcomes. However, maternal perinatal dis�ease activity does not seem to affect the growth of their offspring

BackgroundElevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). However, low adherence to medication and lifestyle management has limited the benefits of lowering lipid levels. Cognitive behavioral therapy (CBT) has been proposed as a promising solution. ObjectiveThis trial aimed to evaluate the efficacy of mobile-based CBT interventions in lowering LDL-C levels in patients with ASCVD. MethodsThis multicenter, prospective, randomized controlled trial enrolled 300 patients with ASCVD, who were randomly assigned to the mobile-based CBT intervention group and the control group in a ratio of 1:1. The intervention group received CBT for ASCVD lifestyle interventions delivered by WeChat MiniApp: “CBT ASCVD.” The control group only received routine health education during each follow-up. The linear regression and logistic regression analyses were used to determine the effects of a mobile-based CBT intervention on LDL-C, triglyceride, C-reactive protein, the score of General Self-Efficacy Scale (GSE), quality of life index (QL-index), and LDL-C up-to-standard rate (

ObjectivesWe aimed to determine a method to identify normal cerebrospinal fluid (CSF) glucose levels by examining the correlation between blood and CSF glucose levels in patients with normal and abnormal glucose metabolism.MethodsOne hundred ninety-five patients were divided into two groups according to their glucose metabolism. The glucose levels were obtained from CSF and fingertip blood at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. SPSS 22.0 software was used for the statistical analysis.ResultsIn both the normal and abnormal glucose metabolism groups, CSF glucose levels increased with blood glucose levels at 6, 5, 4, 3, 2, 1, and 0 h before lumbar puncture. In the normal glucose metabolism group, the CSF/blood glucose ratio range was 0.35–0.95 at 0–6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.43–0.74. In the abnormal glucose metabolism group, the CSF/blood glucose ratio range was 0.25–1.2 at 0–6 h before lumbar puncture, and the CSF/average blood glucose ratio range was 0.33–0.78.ConclusionThe CSF glucose level is influenced by the blood glucose level 6 h before lumbar puncture. In patients with normal glucose metabolism, direct measurement of the CSF glucose level can be used to determine whether the CSF level is normal. However, in patients with abnormal or unclear glucose metabolism, the CSF/average blood glucose ratio should be used to determine whether the CSF glucose level is normal.

This article demonstrates the capability of imaging micro-ellipsometry in the investigation of ordered plasmonic nanostructures on different substrates. The difference of the resonances of similar square lattices of plasmonic nanoparticles on a dielectric substrate and in a metal-insulator-metal configuration is analyzed. The influence of the surface plasmon on interparticle interactions becomes clearly apparent. Comparison of the obtained data with dark-field scattering spectra proves the consistency of the measured results as well as the complementary information received from both methods.

As a well-known pseudo-persistent environmental pollutant, oxybenzone (BP-3) and its related organic ultraviolet (UV) filters have been verified to directly contribute to the increasing mortality rate of coral reefs. Previous studies have revealed the potential role of symbiotic Symbiodiniaceae in protecting corals from the toxic effects of UV filters. However, the detailed protection mechanism(s) have not been explained. Here, the impacts of BP-3 on the symbiotic Symbiodiniaceae Cladocopium goreaui were explored. C. goreaui cells exhibited distinct cell growth at different BP-3 doses, with increasing growth at the lower concentration (2 mg L–1) and rapid death at a higher concentration (20 mg L–1). Furthermore, C. goreaui cells showed a significant BP-3 uptake at the lower BP-3 concentration. BP-3 absorbing cells exhibited elevated photosynthetic efficiency, and decreased cellular carbon and nitrogen contents. Besides, the derivatives of BP-3 and aromatic amino acid metabolism highly responded to BP-3 absorption and biodegradation. Our physiological and metabolic results reveal that the symbiotic Symbiodiniaceae could resist the toxicity of a range of BP-3 through promoting cell division, photosynthesis, and reprogramming amino acid metabolism. This study provides novel insights into the influences of organic UV filters to coral reef ecosystems, which urgently needs increasing attention and management.

IntroductionThe vestibular system is anatomically connected to extensive regions of the cerebral cortex, hippocampus, and amygdala. However, studies focusing on the impact of vestibular impairment on visuospatial cognition ability are limited. This study aimed to develop a mobile tablet-based vestibular cognitive assessment system (VCAS), enhance the dynamic and three-dimensional (3D) nature of the test conditions, and comprehensively evaluate the visuospatial cognitive ability of patients with vestibular dysfunction.Materials and methodsFirst, the VCAS assessment dimensions (spatial memory, spatial navigation, and mental rotation) and test content (weeding, maze, card rotation, and 3D driving tests) were determined based on expert interviews. Second, VCAS was developed based on Unity3D, using the C# language and ILruntime hot update framework development technology, combined with the A* algorithm, prime tree algorithm, and dynamic route rendering. Further, the online test was built using relevant game business logic. Finally, healthy controls (HC) and 78 patients with vertigo (VP) were recruited for the VCAS test. The validity of VCAS was verified using the test results of random controls.ResultsIn the weeding test, the HC group had a significantly longer span and faster velocity backward than did the VP group. In the 12 × 12 maze, statistically significant differences in step and time were observed between the two groups, with VP taking longer time and more steps. In the mental rotation task, no significant difference was observed between the two groups. Similarly, no significant difference was found in the performance of the two groups on maps 2, 3, and 4 in the 3D driving task.DiscussionThus, impaired visuospatial cognition in patients with vestibular dysfunction is primarily related to spatial memory and navigation. VCAS is a clinically applicable visuospatial cognitive ability test for VP.

In 2020, the National Center for Cardiovascular Diseases with National Committee on Hypertension Management in Primary Health Care in China issued revised national clinical practice guidelines on the management of hypertension in primary health care based on the 2018 Chinese guidelines for the management of hypertension. To evaluate adherence to the guidelines, this retrospective study assessed the real-world status of antihypertensive drug prescribing for Chinese patients with hypertension, classified by comorbidity: coronary heart disease, diabetes mellitus, heart failure, stroke, and renal disease. About 1088212 hypertensive patients who received their first prescription for antihypertensive therapy between January 2021 to June 2021, were obtained from a database of Hangzhou Kang Sheng Health Consulting CO., Ltd. Calcium channel blockers (CCBs) and angiotensin II receptor blockers (ARBs) were the most common drugs prescribed for each comorbidity subgroup. Whereas diabetes mellitus or renal disease is a compelling indication for use of renin–angiotensin system inhibitors, CCBs were often administered in these subgroups. The treatment pattern for patients with coronary heart disease was closely similar to that for the overall patient population. Beta-blockers (BBs) were prescribed more frequently for patients with heart failure than for those with other comorbidities. Although antihypertensive drug prescription varied by comorbidity, pharmacological decisions were largely made under Chinese recommendations while physicians could select antihypertensive drugs based on the patients’ comorbidities. However, educational initiatives are still necessary to inspire clinicians to better familiarize themselves with the guidelines and manage hypertension comorbid diseases.

Abstract Background Precision medicine aims to address the demand for precise therapy at the gene and pathway levels. We aimed to design software to allow precise treatment of osteoporosis (OP) with Chinese medicines (CMs) at the gene and pathway levels. Methods PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP database), and the Wanfang database were searched to identify studies treating osteoporosis with CMs. The TCMSP was used to identify bioactive ingredients and related genes for each CM. Gene expression omnibus (GEO) database and the limma package were used to identify differentially expressed genes in osteoporosis. Perl software was used to identify the shared genes between the bioactive components in CM and osteoporosis. R packages and bioconductor packages were used to define the target relationship between shared genes and their related pathways. Third-party Python libraries were used to write program codes. Pyinstaller library was used to create an executable program file. Results Data mining: a total of 164 CMs were included, but Drynariae Rhizoma (gusuibu) was used to present this process. We obtained 44 precise relationships among the bioactive ingredients of Drynariae Rhizoma, shared genes, and pathways. Python programming: we developed the software to show the precise relationship among bioactive ingredients, shared genes, and pathways for each CM, including Drynariae Rhizoma. Conclusions This study could increase the precision of CM, and could provide a valuable and convenient software for searching precise relationships among bioactive ingredients, shared genes, and pathways.

NaX is an atypical member of the voltage-gated sodium channel family that may contribute to Na+ homeostasis. Here, the authors describe the structural and functional attributes of the human NaX channel to reveal new insights into its physiology.

A large number of studies have provided evidence regarding the factors that influence commuting time. However, few studies have explored such effects in the context of considering spatial heterogeneity across cities, which limits the generalizability of the findings. This study addresses this gap by utilizing a dataset of 113 cities in China across the years 2014, 2016, 2018, and 2020. A two-level hierarchical linear model (HLM) was developed to explore the combined effects of city-level and individual-level factors on commuting time by constructing a nested “city-individual” relationship. The results show that (1) built environments at the city level significantly impact commuting time; (2) a non-linear association between population density and commuting time (U-shaped relationship) was identified, as well as between the number of buses and commuting time (inverted U-shaped relationship); (3) the urban construction land area and road area per capita exert negative effects on commuting time; (4) the impacts of individuals’ jobs–housing balance, travel allowances, and education on commuting time vary across cities. These findings might contribute to optimizing the design of a built environment, addressing the challenge posed by longer commuting times, and providing a better understanding of the effects of individuals’ characteristics on commuting time while considering the inherent differences across cities.

Although stochastic gradient algorithm can identify linear systems with high efficiency. It is inefficient for nonlinear systems for the difficulty in the step-size designing. To overcome this dilemma, this paper proposes a fractional stochastic gradient algorithm for systems with piece-wise linear input. First, the nonlinear system is transformed into a polynomial nonlinear model, then the parameters and time-delay are estimated iteratively based on the fractional stochastic gradient algorithm and self-organizing maps method. In addition, to increase the convergence rates of the fractional stochastic gradient algorithm, a multi-innovation fractional stochastic gradient algorithm is developed. Convergence analysis and simulation examples are introduced to show the effectiveness of the proposed algorithms.

Abstract Actinobacillus pleuropneumoniae (APP) is the major pathogen of porcine contagious pleuropneumoniae (PCP). The QseB/QseC two-component system (TCS) consists of the regulator QseB and the kinase QseC, which relates to quorum sensing (QS) and virulence in some bacteria. Here, we investigated the role of QseB/QseC in apf gene cluster (apfABCD) expression of APP. Our results have showed that QseB/QseC TCS can potentially regulate the expression of apf gene cluster. The ΔqseBC, ΔapfA, ΔapfB, ΔapfC and ΔapfD strains are more sensitive to acidic and osmotic stressful conditions, and exhibite lower biofilm formation ability than wild-type (WT) strain, whereas the complemented strains show similar phenotype to the WT strain. In additon, the mutants have defective anti-phagocytosis, adhesion and invasion when they come into contact with the host cells. In experimental animal models of infection, mice infected with ΔqseBC, ΔapfA, ΔapfB, ΔapfC and ΔapfD strains showed lower mortality and bacterial loads in the lung and the blood than those infected with WT strain. In conclusion, our results suggest that QseB/QseC TCS contributes to stress resistance, biofilm formation, phagocytosis, adhesion, invasion and virulence by downregulating expression of apf gene cluster in A. pleuropneumoniae.

This study proposes a fractional gradient descent (FGD) algorithm for FIR models with missing data. By using the auxiliary model method, the missing data can be obtained. Then, the FGD algorithm is applied to update the parameters of the FIR models. Because of the fractional term in the conventional GD algorithm, the convergence rates of the GD algorithm can be increased. In addition, to avoid the step-size calculation, an Aitken FGD-based auxiliary model algorithm is also introduced. The convergence analysis and simulation examples are provided to show the effectiveness of the proposed algorithms.

Abstract Background Postoperative delirium (POD) is a common phenomenon after spinal surgery. Intraoperative fluid management may affect POD. The aim of this study was to compare the effects of restrictive fluid therapy (RF) with those of goal-directed fluid therapy (GDT) on POD. Methods A total of 195 patients aged ≥ 50 years who underwent spinal surgery were randomly divided into two groups: the RF group and the GDT group. In group RF, a bolus of lactated Ringer’s solution was administered at a dose of 5 mL·kg-1 before the induction of anesthesia, followed by a dose of 5 mL·kg-1·h-1 until the end of surgery. For patients in the GDT group, in addition to the initial administration of lactated Ringer’s solution at 5 mL·kg-1, the subsequent fluid therapy was adjusted by using a continuous noninvasive arterial pressure (CNAP) monitoring system to maintain pulse pressure variation (PPV) ≤ 14%. The primary endpoint was the incidence of POD, assessed once daily with the Confusion Assessment Method-Chinese Reversion (CAM-CR) scale at 1–3 days postoperatively. The secondary endpoints were intraoperative fluid infusion volume, urine volume, mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), regional cerebral oxygen saturation (rSO2) value, lactic acid value, and visual analog scale (VAS) pain score at 1–3 days after surgery. Moreover, postoperative complications and the length of hospital stay were recorded. Results The incidence of POD was lower in the GDT group than in the RF group (12.4% vs 4.1%; P = 0.035) in the first 3 days after spine surgery. Compared to group RF, group GDT exhibited a significantly increased volume of intraoperative lactated Ringer’s solution [1500 (interquartile range: 1128 to 1775) mL vs 1000 (interquartile range: 765 to 1300) mL, P < 0.001] and urine volume [398 (interquartile range: 288 to 600) mL vs 300 (interquartile range: 200 to 530) mL, P = 0.012]. Intraoperative MAP, CI and rSO2 values were higher in the GDT group than in the RF group (P < 0.05). Moreover, the length of hospital stay [17.0 (14 to 20) days versus 14.5 (13 to 17.0) days, P = 0.001] was shorter in the GDT group than in the RF group. Conclusions GDT reduced the incidence of POD in middle- and old-aged patients undergoing spinal surgery possibly by stabilizing perioperative hemodynamic and improving the supply and demand of oxygen. Trial registration ChiCTR2000032603 ; Registered on May 3, 2020.

A chemical investigation on Sporormiella sp. led to the isolation and structural elucidation of tripodalsporormielones A–C (1–3), a new class of polyketide possessing unprecedented cage-like skeletons with polyvdent bridged and fused ring systems. These polyketides with cage-like skeletons were characterized as a high non-protonated carbon-containing system, which resulted in few HMBC correlations observed and made the accurate structures hard to be obtained by NMR. Especially, some signals of non-protonated sp2 carbons are weak and even unobservable in compound 1. In order to establish the structure of 1, the calculated NMR with DP4 evaluation was applied to determine the structure from the plausible structure candidates obtained from the detailed NMR analysis. Based on NMR experiments and calculated NMR, the structures of isolated compounds were established and confirmed by X-ray technology. Through chiral isolation, the optically pure enantiomers of 1 and 3 were obtained, and their absolute configurations were determined based on ECD quantum chemical calculation. Based on the isolated compounds and our previous work, 1–3 would be derived from 3-methylorcinaldehyde, and their plausible biosynthetic mechanism was proposed. Furthermore, 1 exhibited obvious short-term memory improvement activity on an Alzheimer's disease fly model.

ObjectiveInvestigating the causal relationship between rheumatoid arthritis (RA) and atlantoaxial subluxation (AAS) and identifying and quantifying the role of C-reactive protein (CRP) as a potential mediator.MethodsUsing summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of genetically predicted rheumatoid arthritis (14,361 cases, and 43,923 controls) and AAS (141 cases, 227,388 controls) was performed. Furthermore, we used two-step MR to quantitate the proportion of the effect of c-reactive protein-mediated RA on AAS.ResultsMR analysis identified higher genetically predicted rheumatoid arthritis (primary MR analysis odds ratio (OR) 0.61/SD increase, 95% confidence interval (CI) 1.36-1.90) increased risk of AAS. There was no strong evidence that genetically predicted AAS had an effect on rheumatoid arthritis risk (OR 1.001, 95% CI 0.97-1.03). The proportion of genetically predicted rheumatoid arthritis mediated by C-reactive protein was 3.7% (95%CI 0.1%−7.3%).ConclusionIn conclusion, our study identified a causal relationship between RA and AAS, with a small proportion of the effect mediated by CRP, but a majority of the effect of RA on AAS remains unclear. Further research is needed on additional risk factors as potential mediators. In clinical practice, lesions of the upper cervical spine in RA patients need to be given more attention.

ObjectiveThis study aims to analyze the gene expression profile of peripheral blood in different stages of myocardial infarction (MI) by transcriptome sequencing, and to study the gene expression characteristics of peripheral blood after MI.MethodsDifferentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify genes and modules associated with old myocardial infarction (OMI). Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation were applied to analyze the potential functions of genes. Hub genes were identified by Random Forest Classifier. CIBERSORT was used to provide an estimate of the abundance of 22 immune cells in peripheral blood. Quantitative polymerase chain reaction (qPCR) was used to detect gene expression levels in clinical samples. The cellular components (CC) of peripheral blood were counted by an automatic hematology analyzer.ResultsThrough differential gene analysis and co-expression network analysis, 11 candidate genes were obtained. A random forest classifier identified 10 hub genes. Immune cell distribution of peripheral blood was found that T cell CD4 memory resting, NK cells resting, Dendritic cells activated, Mast cells resting, Monocytes and Neutrophils were correlated with OMI. Spearman correlation analysis found that PFKFB2 is related to the above immune cells. Low expression of PFKFB2 in peripheral blood of OMI was detected in clinical samples, and the relationship between PFKFB2 and peripheral blood immune cell counts was analyzed, which showed monocytes were associated with PFKFB2 in our study.ConclusionPFKFB2 was low expressed in OMI, and related to the distribution of immune cells. PFKFB2 may play a key role in reflecting the transition from AMI to OMI, and predicting the distribution of immune cells, which provided a new perspective for improving myocardial fibrosis and adverse remodeling.