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Qing-Ren Liu,1 Yu-Chen Dai,2 Mu-Huo Ji,3 Pan-Miao Liu,4 Yong-Yan Dong,4 Jian-Jun Yang4 1Department of Anesthesiology, Xishan People’s Hospital of Wuxi City, Wuxi, 214105, People’s Republic of China; 2Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, People’s Republic of China; 3Department of Anesthesiology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, People’s Republic of China; 4Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, People’s Republic of ChinaCorrespondence: Jian-Jun Yang, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, NO. 1 East Jianshe Road, Zhengzhou, 450052, People’s Republic of China, Email yjyangjj@126.comAbstract: Acute postsurgical pain (APSP) has received growing attention as a surgical outcome. When poorly controlled, APSP can affect short- and long-term outcomes in patients. Despite the steady increase in awareness about postoperative pain and standardization of pain prevention and treatment strategies, moderate-to-severe APSP is frequently reported in clinical practice. This is possibly because pain varies widely among individuals and is influenced by distinct factors, such as demographic, perioperative, psychological, and genetic factors. This review investigates the risk factors for APSP, including gender, age, obesity, smoking history, preoperative pain history, pain sensitivity, preoperative anxiety, depression, pain catastrophizing, expected postoperative pain, surgical fear, and genetic polymorphisms. By identifying patients having an increased risk of moderate-to-severe APSP at an early stage, clinicians can more effectively manage individualized analgesic treatment protocols with a combination of pharmacological and non-pharmacological interventions. This would alleviate the transition from APSP to chronic pain and reduce the severity of APSP-induced chronic physical disability and social psychological distress.Keywords: acute postoperative pain, acute postsurgical pain, risk factors, predictors

Jing-Fan Gao,* Yue-Yan Dong,* Xin Jin, Li-Jun Dai, Jing-Rao Wang, Hong Zhang Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Zhang, Department of Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China, Email zhanghong@hrbmu.edu.cnObjective: Keratoconus is a commonly progressive and blinding corneal disorder. Iron metabolism and oxidative stress play crucial roles in both keratoconus and ferroptosis. However, the association between keratoconus and ferroptosis is currently unclear. This study aimed to analyze and verify the role of ferroptosis-related genes (FRGs) in the pathogenesis of keratoconus through bioinformatics.Methods: We first obtained keratoconus-related datasets and FRGs. Then, the differentially expressed FRGs (DE-FRGs) associated with keratoconus were screened through analysis, followed by analysis of their biological functions. Subsequently, the LASSO and SVM-RFE algorithms were used to screen for diagnostic biomarkers. GSEA was performed to explore the potential functions of the marker genes. Finally, the associations between these biomarkers and immune cells were analyzed. qRT‒PCR was used to detect the expression of these biomarkers in corneal tissues.Results: A total of 39 DE-FRGs were screened, and functional enrichment analysis revealed that the DE-FRGs were closely related to apoptosis, oxidative stress, and the immune response. Then, using multiple algorithms, 6 diagnostic biomarkers were selected, and the ROC curve was used to verify their risk prediction ability. In addition, based on CIBERSORT analysis, alterations in the immune microenvironment of keratoconus patients might be associated with H19, GCH1, CHAC1, and CDKN1A. Finally, qRT‒PCR confirmed that the expression of H19 and CHAC1 was elevated in the keratoconus group.Conclusion: This study identified 6 DE-FRGs, 4 of which were associated with immune infiltrating cells, and established a diagnostic model with predictive value for keratoconus.Keywords: keratoconus, ferroptosis, immune infiltration, machine learning

Qing Hu,1,2,* Xiao-Ling Fu,1,* Yi-Yan Dong,1,2 Ju Ma,1 Jian Hua,1 Jia-Ting Li,1 Kai-Xin Liu,1 Jian Yang,1,2 Chang-Xi Yu1,2 1School of Pharmacy, Fujian Medical University, Fuzhou, People’s Republic of China; 2Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-Xi Yu; Jian Yang, School of Pharmacy, Fujian Medical University, No. 1 Xuefu North Road, Fuzhou, 350122, People’s Republic of China, Tel +86-0591-22862016, Email changxiyu@mail.fjmu.edu.cn; fjmukent@mail.fjmu.edu.cnIntroduction: Koumine (KME) is the most abundant active ingredient separated from Gelsemium elegans Benth and exhibits a significant therapeutic effect on rheumatoid arthritis (RA). It is a lipophilic compound with poor aqueous solubility, and there is an urgent need to develop novel dosage forms of KME and promote its clinical application for the treatment of RA. The aim of this study was to design and develop KME-loaded microemulsions (KME-MEs) for the effective management of RA.Methods: The composition of the microemulsion was selected by carrying out a solubility study and generating pseudoternary phase diagrams, and further optimized by D-Optimal design. The optimized KME-MEs was evaluated for particle size, viscosity, drug release, storage stability, cytotoxicity, cellular uptake, Caco-2 cell transport and everted gut sac investigations. In vivo fluorescence imaging and the therapeutic effects of KME and KME-MEs on collagen-induced arthritis (CIA) rats were also evaluated.Results: The optimized microemulsion contained 8% oil, 32% Smix (surfactant/cosurfactant) and 60% water and was used for in vivo and in vitro studies. The optimal KME-MEs exhibited a small globule size of 18.5 ± 0.14 nm and good stability over 3 months, and the release kinetics followed a first-order model. These KME-MEs had no toxic effect on Caco-2 cells but were efficiently internalized into the cytoplasm. Compared to KME, the KME-MEs displayed significantly increased permeability and absorption in Caco-2 cell monolayer assay and ex vivo everted gut sac experiment. As expected, the KME-MEs attenuated the progression of RA in CIA rats and were more effective than free KME with a reduced frequency of administration.Conclusion: The KME-MEs improved the solubility and therapeutic efficacy of KME by employing formulation technology. These results provide a promising vehicle for the oral delivery of KME to treat RA and have attractive potential for clinical translation.Graphical Abstract: Keywords: rheumatoid arthritis, koumine, microemulsion, permeability, oral administration

Xing-Chen Li,1,* Yang-Yang Dong,1,* Yuan Cheng,1 Jing-Yi Zhou,1,2 Xiao Yang,1 Bo-Qiang Shen,1 Xiao-Tong Wu,1,2 Xiao-Ping Li,1 Jian-Liu Wang1,2 1Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing 100044, People’s Republic of China; 2Beijing Key Laboratory of Female Pelvic Floor Disorders Diseases, Beijing 100044, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Liu WangDepartment of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing 100044, People’s Republic of ChinaTel +86 10 8832 4474Email wangjianliu1203@163.comPurpose: The early predictive values of diagnostic markers for lymph node metastasis (LNM) in endometrial cancer (EC) are still unclear at present. The purpose of this study is to explore the relationship between serum calcium and LNM in EC.Methods: We identified all patients with EC who underwent surgery between January 2012 and December 2016. Patient characteristics and various preoperative clinicopathologic data were obtained from medical records and were reviewed retrospectively. These patients were divided into two groups according to the pathology of their lymph node. Logistic regression models analyzed the relationship between the ionized calcium and LNM of EC patients, while adjusting for the potential confounders.Results: A total of 448 patients were assessed. Univariate analysis showed that ionized calcium, CA125 level, tumor grade, peritoneal cytology, FIGO stage, histological type, LVSI, and myometrial invasion were positively correlated with LNM (all P< 0.05). The risk of LNM increased with the promotion of serum ionized calcium (P for trend < 0.01). Ionized calcium level was significant before and after the adjustment of cofounders (unadjusted: OR=11.9, 95% CI: 4.8– 29.6, P< 0.01; model I: OR=11.3, 95% CI: 4.5– 28.8, P< 0.01; model II: OR=5.2, 95% CI: 1.6– 17.2, P< 0.05). Additionally, the risk of ionized calcium was especially evident in patients whose age was older than 60, BMI< 28 kg/m2, grade 3, negative peritoneal cytology and endometrioid endometrial adenocarcinoma.Conclusion: Ionized calcium level was highly associated with LNM in EC and acted as a potential biomarker in predicting the risk of LNM in EC.Keywords: serum calcium level, EC, lymph node metastasis, stratification analysis

Rivers are undergoing significant changes under the pressures of natural processes and human activities. However, characterizing and understanding these changes over the long term and from a spatial perspective have proven challenging. This paper presents a novel framework featuring twelve indicators that combine geometric and spatial structures for evaluating changes in river network patterns. Through global principal component analysis, these indicators were integrated into a comprehensive river network pattern index (RNP). Employing Pearson correlation analysis, geographically weighted regression, geographic detector models, and the Shapley Value, the study quantitatively analyzed various stressors' impacts and relative contributions on river network changes from the 1960s to 2015s. The results showed a clear trend of degradation over time, particularly with frequency and density declining by 57 % and 48 %, respectively. The changes across subbasins varied temporally and spatially, with the 1980s emerging as a significant temporal hotspot and six spatial hotspots identified among twenty subbasins. The analysis showed that agriculture was significantly negatively associated with RNP, while the relationship between urbanization and RNP was inverted N-shaped. To address the negative effects of human activities, a shift from uniform management approaches is crucial. In agricultural areas, adopting more intensive farming practices could help mitigate negative impacts on RNP. For highly urbanized regions, city planning should consider the interactions between urbanization and other factors affecting RNP. Overall, incorporating an understanding of RNP's spatial-temporal dynamics and driving factors into spatial planning is critical for creating effective and sustainable management strategies for human-river interactions., Competing Interests: Declaration of competing interest The author declares that there are no known competing financial interests or personal relationships that influenced the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The association between heme oxygenase-1 (HO-1) and asthma has been a subject of debate in both observational and experimental studies. We aimed to evaluate the potential causal relationship between HO-1 and asthma., Materials and Methods: A bidirectional two-sample Mendelian randomization (TSMR) study was conducted to examine the causal relationship between HO-1 and asthma. In the forward Mendelian randomization (MR) analyses, HO-1 was considered as the exposure, while asthma as the outcome. Conversely, in the reverse MR analyses, asthma was regarded as the exposure, and HO-1 as the outcome. Data for HO-1 and asthma were obtained from publicly accessible genome-wide association studies (GWAS). These causal relationships were identified through 5 MR methods, namely MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, and weighted mode. Additionally, sensitivity tests were conducted to assess the robustness of MR study. Finally, additional asthma datasets and childhood asthma were selected to validate the findings., Results: In the forward MR analyses, according to the IVW method, genetically predicted HO-1 displays a negative correlation with the risk of asthma (OR 0.947, 95% CI 0.905-0.990). It was not found any SNP overly sensitive or disproportionately responsible for the outcome. No evidence of heterogeneity and pleiotropy between SNPs was observed. Genetically predicted asthma was not associated with HO-1 in reverse MR analyses using the IVW method. The same results were validated in additional asthma datasets and in childhood asthma., Conclusion: The results of MR analysis revealed heme oxygenase-1 as a protective factor for asthma., Competing Interests: The author declares that there is no conflict of interest., (© 2024 The Author(s).)

Purpose of Review: Congenital myasthenia syndromes (CMS) are treatable, inherited disorders affecting neuromuscular transmission. We highlight that the involvement of an increasing number of proteins is making the understanding of the disease mechanisms and potential treatments progressively more complex., Recent Findings: Although early studies identified mutations of proteins directly involved in synaptic transmission at the neuromuscular junction, recently, next-generation sequencing has facilitated the identification of many novel mutations in genes that encode proteins that have a far wider expression profile, some even ubiquitously expressed, but whose defective function leads to impaired neuromuscular transmission. Unsurprisingly, mutations in these genes often causes a wider phenotypic disease spectrum where defective neuromuscular transmission forms only one component. This has implications for the management of CMS patients., Summary: Given the widening nonneuromuscular junction phenotypes in the newly identified forms of CMS, new therapies need to include disease-modifying approaches that address not only neuromuscular weakness but also the multisystem involvement. Whilst the current treatments for CMS are highly effective for many subtypes there remains, in a proportion of CMS patients, an unmet need for more efficacious therapies., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients., Patient Concerns: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation., Diagnoses: The child was diagnosed with CH with alpha thalassemia., Interventions: The patient was treated with levothyroxine sodium and anemia correction., Outcomes: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age., Conclusions: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia., Lesson: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.

Legumes account for a significant proportion of plants in the terrestrial ecosystems. Nitrogen (N)-fixing capability of certain legumes is a pivotal trait that contributes to their ecological dominance. Yet, the functional traits and trait relationships between N-fixer and non-N-fixer legumes are poorly understood. Here, we investigated 27 functional traits associated with morphology, nutrients, hydraulic conductance and photosynthesis in 42 woody legumes (19 N-fixers and 23 non-N-fixers) in a common garden. Our results showed that N-fixers had higher specific leaf area, photosynthetic phosphorus (P)-use efficiency, leaf N, and iron concentrations on both area and mass basis, N/P ratio, and carbon (C) to P ratio, but lower wood density, area-based maximum photosynthetic rate (Aa), photosynthetic N-use efficiency, leaf mass- and area-based P and molybdenum and area-based boron concentrations, and C/N ratio, compared with non-N-fixers. The mass-based maximum photosynthetic rate (Am), stomatal conductance (gs), intrinsic water-use efficiency (WUEi), mass- and area-based leaf potassium and mass-based boron concentrations, leaf hydraulic conductance (Kleaf), and whole-shoot hydraulic conductance (Kshoot) showed no difference between N-fixers and non-N-fixers. Significant positive associations between all hydraulic and photosynthetic trait pairs were found in N-fixers, but only one pair (Kshoot-Aa) in non-N-fixers, suggesting that hydraulic conductance plays a more important role in mediating photosynthetic capacity in N-fixers compared with non-N-fixers. Higher mass-based leaf N was linked to lower time-integrated gs and higher WUEi among non-N-fixer legumes or all legumes pooled after phylogeny was considered. Moreover, mass-based P concentration was positively related to Am and gs in N-fixers, but not in non-N-fixers, indicating that the photosynthetic capacity and stomatal conductance in N-fixers were more dependent on leaf P status than in non-N-fixers. These findings expand our understanding of the trait-based ecology within and across N-fixer and non-N-fixer legumes in tropics., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Excitatory amino acid transporters (EAATs) are important regulators of amino acid transport and in particular glutamate. Recently, more interest has arisen in these transporters in the context of neurodegenerative diseases. This calls for ways to modulate these targets to drive glutamate transport, EAAT2 and EAAT3 in particular. Several inhibitors (competitive and noncompetitive) exist to block glutamate transport; however, activators remain scarce. Recently, GT949 was proposed as a selective activator of EAAT2, as tested in a radioligand uptake assay. In the presented research, we aimed to validate the use of GT949 to activate EAAT2-driven glutamate transport by applying an innovative, impedance-based, whole-cell assay (xCELLigence). A broad range of GT949 concentrations in a variety of cellular environments were tested in this assay. As expected, no activation of EAAT3 could be detected. Yet, surprisingly, no biological activation of GT949 on EAAT2 could be observed in this assay either. To validate whether the impedance-based assay was not suited to pick up increased glutamate uptake or if the compound might not induce activation in this setup, we performed radioligand uptake assays. Two setups were utilized; a novel method compared to previously published research, and in a reproducible fashion copying the methods used in the existing literature. Nonetheless, activation of neither EAAT2 nor EAAT3 could be observed in these assays. Furthermore, no evidence of GT949 binding or stabilization of purified EAAT2 could be observed in a thermal shift assay. To conclude, based on experimental evidence in the present study GT949 requires specific assay conditions, which are difficult to reproduce, and the compound cannot simply be classified as an activator of EAAT2 based on the presented evidence. Hence, further research is required to develop the tools needed to identify new EAAT modulators and use their potential as a therapeutic target.

Recent work putatively linked a rare genetic variant of the chaperone Resistant to Inhibitors of acetylcholinesterase (RIC3) (NM&#95;024557.4:c.262G > A, NP&#95;078833.3:p.G88R) to a unique ability to speak backwards, a language skill that is associated with exceptional working memory capacity. RIC3 is important for the folding, maturation, and functional expression of α7 nicotinic acetylcholine receptors (nAChR). We compared and contrasted the effects of RIC3G88R on assembly, cell surface expression, and function of human α7 receptors using fluorescent protein tagged α7 nAChR and Förster resonance energy transfer (FRET) microscopy imaging in combination with functional assays and 125 I-α-bungarotoxin binding. As expected, the wild-type RIC3 protein was found to increase both cell surface and functional expression of α7 receptors. In contrast, the variant form of RIC3 decreased both. FRET analysis showed that RICG88R increased the interactions between RIC3 and α7 protein in the endoplasmic reticulum. These results provide interesting and novel data to show that a RIC3 variant alters the interaction of RIC3 and α7, which translates to decreased cell surface and functional expression of α7 nAChR., (© 2024. The Author(s).)

Gastric cancer (GC) is a major global health concern with poor outcomes. Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a multifunctional protein that participates in pre-mRNA packaging, alternative splicing regulation, and chromatin remodeling. Its potential role in GC remains unclear. In this study, the expression characteristics of HNRNPU were analyzed by The Cancer Genome Atlas data, Gene Expression Omnibus data, and then further identified by real-time quantitative PCR and immunohistochemistry using tissue specimens. From superficial gastritis, atrophic gastritis, and hyperplasia to GC, the in situ expression of HNRNPU protein gradually increased, and the areas under the curve for diagnosis of GC and its precancerous lesions were 0.911 and 0.847, respectively. A nomogram integrating HNRNPU expression, lymph node metastasis, and other prognostic indicators exhibited an area under the curve of 0.785 for predicting survival risk. Knockdown of HNRNPU significantly inhibited GC cell proliferation, migration, and invasion and promoted apoptosis in vitro. In addition, RNA-sequencing analysis showed that HNRNPU could affect alternative splicing events in GC cells, with functional enrichment analysis revealing that HNRNPU may exert malignant biological function in GC progression through alternative splicing regulation. In summary, the increased expression of HNRNPU was significantly associated with the development of GC, with a good performance in diagnosing and predicting the prognostic risk of GC. Functionally, HNRNPU may play an oncogenic role in GC by regulating alternative splicing., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

A new disaccharide glycoside, franchoside A ( 1 ), and 17 known compounds were isolated from the tubers of Arisaema franchetianum Engler. The chemical structure of the previously undescribed compound 1 was elucidated on the basis of detailed spectroscopic analyses. Compounds 1 , 2 , 6 , 10 , 14 and 18 showed significant cytotoxic activities at varying IC 50 values in the range of 4.0-10.6  μ M against five cancer cell lines. Compounds 8 , 10 , 13 and 17 (10  μ M) exhibited moderate anti-inflammatory activities by inhibiting the NF- κ B signaling pathway and the release of NO from RAW264.7 macrophages induced by lipopolysaccharide (LPS), while compounds 1 , 9 , 14 , 15 and 16 showed weak anti-inflammatory activities.

Introduction: Muscle specific kinase (MuSK) antibody positive myasthenia gravis (MG) often presents with a severe disease course and resistance to treatment. Treatment-refractory patients may respond to B cell depleting treatment methods. Our aim was to investigate whether inhibition of Fc receptor-like B (FCRLB) could effectively suppress autoimmunity without diminishing B cell counts in animal model of MG, a classical antibody-mediated autoimmune disease., Methods: Experimental autoimmune MG was induced in Balb/C mice with two s.c. immunizations with recombinant human MuSK in complete Freund's adjuvant. FCRLB was silenced with a lentiviral particle transported shRNA in myasthenic mice with a single i.p. injection during second MuSK-immunization. Control immunized mice received scrambled shRNA or saline. Mice were observed for clinical parameters for 28 days and at termination, anti-MuSK IgG, neuromuscular junction (NMJ) deposits, muscle AChR expression and lymph node B and T cell ratios were assessed by ELISA, immunofluorescence, immunoblotting and flow cytometry, respectively., Results: FCRLB shRNA-treated mice showed no muscle weakness or weight loss at termination. Also, they exhibited higher grip strength and muscle AChR levels, lower anti-MuSK IgG and NMJ IgG/C3 levels than control mice. Flow cytometry analysis showed that ratios of major effector lymph node B and T cell populations were not altered by FCRLB silencing. However, regulatory T and CD19 + CD5+ B cell ratios were decreased in FCRLB shRNA-group., Conclusion: Our results provide evidence regarding involvement and therapeutic value of FCRLB in MuSK-MG. Silencing of FCRLB appears to substantially inhibit antibody production without interfering with survival of major lymphocyte populations., Competing Interests: Declaration of Competing Interest The authors declare no disclosures of any financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Postpartum depression (PPD) is a prevalent public health issue. Although ketamine has prophylactic effects on PPD in women undergoing cesarean section, the effects of esketamine on PPD remain unclear. This trial aimed to evaluate the efficacy of perioperative esketamine infusion on PPD risk by assessing Edinburgh Postnatal Depression Scale (EPDS) scores and blood biomarkers., Methods: A total of 150 participants undergoing elective cesarean section were randomly allocated to receive either esketamine or normal saline. Since 27 participants were excluded due to consent withdrawal or loss to follow-up, 123 patients were included. The primary outcome was the prevalence of PPD risk. Secondary outcomes included the prevalence of postpartum anxiety (PPA) risk, levels of biomarkers, postoperative pain intensity, and cumulative sufentanil consumption., Results: The prevalence of PPD and PPA risk at 3 days, 42 days, 3 months, and 6 months postpartum did not differ between the two groups. Furthermore, EPDS scores, pain intensity at rest, and during coughing on postoperative days (POD) 1 and 2 did not differ between the two groups. Sufentanil consumption during 0-12 h, 12-24 h, 0-24 h, and 0-48 h postoperatively were significantly lower in the esketamine group compared to the control group. Blood biomarkers did not differ between the two groups on POD 3., Limitations: The sample size was small. PPD risk was simply screened, not diagnosed., Conclusions: Perioperative administration of esketamine did not decrease the incidence of PPD risk in women after elective cesarean section. However, esketamine reduced opioid consumption., Competing Interests: Declaration of competing interest Dr. Hashimoto is the inventor of filed patent applications on “The use of R-Ketamine in the treatment of psychiatric diseases”, “(S)-norketamine and salt thereof as pharmaceutical”, “R-Ketamine and derivative thereof as a prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder”, “Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases”, and “R-Ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder” by the Chiba University. Dr. Hashimoto has also received speakers' honoraria, consultant fees, or research support from Abbott, Boehringer-Ingelheim, Daiichi-Sankyo, Meiji Seika Pharma, Seikagaku Corporation, Dainippon-Sumitomo, Taisho, Otsuka, Murakami Farm, and Perception Neuroscience. The other authors have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The dynamics and processes underlying the codiversification of plant-pollinator interactions are of great interest to researchers of biodiversity and evolution. Cospeciation is generally considered a key process driving the diversity of figs and their pollinating wasps. Groups of closely related figs pollinated by separate wasps occur frequently and represent excellent opportunities to study ongoing diversification in this textbook mutualism. We study two closely related sympatric dioecious figs ( Ficus heterostyla and Ficus squamosa ) in Xishuangbanna, southwest China, and aim to document what is likely to be the final stages of speciation between these species using a combination of trait data and experimental manipulation. Volatile profiles at the receptive phase, crucial for attracting pollinators, were analyzed. In total, 37 and 29 volatile compounds were identified from receptive F. heterostyla and F. squamosa figs, respectively. Despite significant interspecific dissimilarity, 25 compounds were shared. Ovipositor lengths lie well within range required for access to heterospecific ovules, facilitating hybridization. Cross introduction of wasps into figs was conducted and hybrid seeds were generated for all donor/recipient combinations. F. heterostyla wasps produce adult offspring in F. squamosa figs. While F. squamosa wasps induce gall development in F. heterostyla figs and their offspring fail to mature in synchrony with their novel host. We record limited geographic barriers, minimal volatile dissimilarity, compatible morphology, complementary reproductive phenologies, and the production of hybrid seeds and wasp offspring. These findings suggest ongoing wasp specialization and reproductive isolation, potentially applicable to other related fig species., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Society for the Study of Evolution (SSE) and European Society for Evolutionary Biology (ESEN).)

Background: Currently, a paramount issue in nursing education is to motivate nursing undergraduate interns to develop self-directed learning skills and improve their practice satisfaction and professional identity, so as to meet the growing demands in healthcare., Objectives: This study aimed to examine the effectiveness of a motivational programme based on the Existence-Relatedness-Growth (ERG) theory in developing self-directed learning skills, improving practice satisfaction and promoting the professional identity of nursing undergraduate interns in China., Design: A quasi-experimental study design., Setting: A government-funded tertiary teaching hospital in Guangzhou, Guangdong province, China., Methods: This study was conducted with 99 nursing undergraduate interns in a hospital between June 2020 and April 2022. The interns in the experimental group (n = 50) participated in the motivational programme based on ERG theory, while those in the control group (n = 49) underwent a traditional training programme. The interns in the two groups were compared in terms of their degree of self-directed learning, practice satisfaction and professional identity after the training, using independent samples t-test., Results: After the internship, interns in the experimental group showed a statistically significantly higher level of self-directed learning and practice satisfaction than those in the control group (p < 0.05). However, no significant difference was observed in professional identity between the two groups after the internship., Conclusions: The motivational programme based on ERG theory was shown to be effective in improving self-directed learning and practice satisfaction in nursing undergraduate interns. A large-scale randomized controlled trial is warranted to confirm the results., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Automatic modulation classification (AMC) is an essential part in a cognitive radio receiver. Benefited from the discriminative constellation characteristics among most modulations, AMC methods based on constellation diagrams usually achieve pleasant performance. However, in noncooperation communication systems, constellation diagrams expressing modulations explicitly are difficult to obtain via blind symbol timing synchronization, especially in complicated wireless channels. Therefore, this article proposes a novel constellation diagram-based AMC architecture called attentive Siamese networks (ASNs) by considering multitiming constellation diagrams (MCDs) and selecting the proper symbol timings at the feature level, which is a more robust way than the conventional signal-level symbol timing synchronization. In detail, convolutional neural networks sharing the same parameters first extract deep feature vectors for MCDs. Then, an attention inference module weights all the deep feature vectors. Finally, AMC is realized based on the weighted feature vectors. Moreover, the ASN architecture can be trained end-to-end. Comparing with the state-of-the-art methods that take diverse representations of received baseband signals as input, experimental results based on the RadioML 2018.01A dataset and non-Gaussian noise dataset demonstrate that ASN achieves a remarkable improvement, whose classification accuracy goes over 99% when the signal-to-noise ratio (SNR) > 10 dB.

Constructing ecological security pattern and identifying ecological important areas are the focus of current research on regional ecological security. With Ningbo City as a case study area, we identified ecological sources by remote sensing ecological index, the ecological corridors and pinch point by circuit theory model, and the minimum spanning tree and cuts by graph theory algorithm. The results showed that there were 203 ecological sources in Ningbo, and that the main type of land cover was forest, including a small amount of paddy fields and flooded vegetation. There were 368 ecological corridors with a total length of 573.42 km, being dense in the southwest and sparse in the northeast. There were 91 ecological pinch points, which mainly distributed between coastal areas and closely related ecological sources. According to current situation, we put forward the optimization strategy with 187 primary corridors, 181 secondary corridors, 50 ecological restoration priority areas and 59 long-term ecological restoration areas. The optimization strategy combined with graph theory and circuit theory model would provide a refe-rence for the constructing of ecological security pattern.

Objectives: To explore the characteristics of postmortem examination, chemical examination and scene investigation of deaths caused by oral diphenidol hydrochloride poisoning, and so as to provide a reference for proper settlement and prevention of such deaths., Methods: The data of 22 deaths caused by oral diphenidol hydrochloride poisoning in a city from January 2018 to August 2020 were collected, including case details, scene investigations, autopsies, chemical examinations and digital evidence. Thirty-one cases of deaths caused by oral diphenidol hydrochloride poisoning reported in previous literature were also collected., Results: In the 53 oral diphenidol hydrochloride poisoning death cases, 50 cases were suicide, 2 cases were accidental, while 1 case was undetermined. Fifty-two cases were found in the medical records or crime scene investigation reports with doses ranging from 775 mg to 12 500 mg, and 23 deceased were detected with postmortem blood concentrations ranging from 2.71 mg/L to 83.1 mg/L. Clinical symptoms were recorded in 6 patients, including conscious disturbance and convulsion. Among the 45 cases which were performed with external examination, 23 cases autopsied., Conclusions: Most of the deceased of oral diphenidol hydrochloride poisoning were suicide. No significant correlation was found between dose and blood concentration through the retrospective analysis of cases.

To study the characteristics of heart rate rhythm in pregnant women at different trimester of pregnancy, and to explore the relationship between the basic rhythm of heart rate and pregnancy complications. Thirteen pregnant women who were diagnosed with normal early pregnancy in the Reproductive Center of the Second Affiliated Hospital of Soochow University from June 2018 to December 2019 were prospectively selected. Personal files were created and the heart rate data of pregnancy women was collected 24 hours a day by wearable devices until delivery. Prenatal examination and pregnancy outcomes were surveyed at follow-up. The cosine analysis method and the designed statistical module were used to analyze the long-term rhythm of pregnant women's heart rate. The heart rate of pregnant women showed a significant rhythm at different gestational weeks. Compared with the gestational week of 12, the midline-estimating statistic of rhythm(MESOR) increased significantly at the gestational week of 28 and 32 ( t =-2.751, P =0.013; t =-2.314, P =0.032).The phase of rhythm shifted from 14∶00 pm in the first trimester of pregnancy (12 weeks) to 16∶00 pm in the second trimester (24 weeks) ( t =2.613, P =0.018) and returned to 14∶00 pm at the third trimester (32 weeks) ( t =-2.176, P =0.046). Season had no significant effect on the changes of MESOR, amplitude and phase of maternal heart rate in the first trimester ( t =-0.356, P =0.729; t =-0.777, P =0.464; t =-0.434, P =0.673), while season had no significant effect on the changes of MESOR, amplitude and phase in the third trimester ( t =-0.663, P =0.532; t =-0.209, P =0.841; t =0.625, P =0.592). The heart rate of one pregnant woman with natural delivery had rhythm disorder from the start of labor to delivery. The heart rate of one pregnant woman with premature rupture of membranes showed rhythm disorder before and after the rupture of membranes, and smaller amplitude. Rhythm disturbance may play a suggestive role in preterm delivery and labor initiation. In conclusion, pregnancy may cause changes in the internal heart rate rhythm. Maternal internal rhythm disturbance may occur when delivery or premature rupture of membranes occurs. The heart rate rhythm of pregnant women may be related to some common complications of pregnancy such as premature rupture of membranes.

Soybean is one of the most widely grown oilseed crops worldwide. Several unfavorable factors, including salt and salt-alkali stress caused by soil salinization, affect soybean yield and quality. Therefore, exploring the molecular basis of salt tolerance in plants and developing genetic resources for genetic breeding is important. Sucrose non-fermentable protein kinase 1 (SnRK1) belongs to a class of Ser/Thr protein kinases that are evolutionarily highly conserved direct homologs of yeast SNF1 and animal AMPKs and are involved in various abiotic stresses in plants. The GmPKS4 gene was experimentally shown to be involved with salinity tolerance. First, using the yeast two-hybrid technique and bimolecular fluorescence complementation (BiFC) technique, the GmSNF1 protein was shown to interact with the GmPKS4 protein. Second, the GmSNF1 gene responded positively to salt and salt-alkali stress according to qRT-PCR analysis, and the GmSNF1 protein was localized in the nucleus and cytoplasm using subcellular localization assay. The GmSNF1 gene was then heterologously expressed in yeast, and the GmSNF1 gene was tentatively identified as having salt and salt-alkali tolerance function. Finally, the salt-alkali tolerance function of the GmSNF1 gene was demonstrated by transgenic Arabidopsis thaliana , soybean hairy root complex plants overexpressing GmSNF1 and GmSNF1 gene-silenced soybean using VIGS. These results indicated that GmSNF1 might be useful in genetic engineering to improve plant salt and salt-alkali tolerance.

Objective: The aim of this study was to create a predictive nomogram that can accurately identify the risk factors of venous thromboembolism (VTE) in hospitalized patients exhibiting hemoptysis., Patients and Methods: The present study gathered clinical and demographic data of 1,052 hospitalized patients with hemoptysis at Dongyang Hospital between January 2016 and January 2021 through the Lejiu database. The patients were categorized into two groups: the thrombotic event group (n=123) and the non-thrombotic event group (n=929), based on the presence of VTE before discharge. The study utilized univariable and multivariable logistic regression analyses to identify the independent risk factors for VTE, with the occurrence of thrombotic events serving as the dependent variable. Furthermore, a nomogram prediction model was formulated to verify the findings., Results: In hospitalized patients with hemoptysis, the risk of VTE was found to be independently associated with the administration of tranexamic acid (TXA), the presence of D-dimer, and the Charlson Comorbidity Index (CCI) score (p<0.05)., Conclusions: A nomogram model was constructed to evaluate the probability of VTE in patients hospitalized with hemoptysis. This model allows for the timely detection of early VTE warning signs, which may ultimately reduce its occurrence.

Background: Lymph node metastasis (LNM) is an important factor affecting endometrial cancer (EC) prognosis. Current controversy exists as to how to accurately assess the risk of lymphatic metastasis. Metabolic syndrome has been considered a risk factor for endometrial cancer, yet its effect on LNM remains elusive. We developed a nomogram integrating metabolic syndrome indicators with other crucial variables to predict lymph node metastasis in endometrial cancer., Methods: This study is based on patients diagnosed with EC in Peking University People's Hospital between January 2004 and December 2020. A total of 1076 patients diagnosed with EC and who underwent staging surgery were divided into training and validation cohorts according to the ratio of 2:1. Univariate and multivariate logistic regression analyses were used to determine the significant predictive factors., Results: The prediction nomogram included MSR, positive peritoneal cytology, lymph vascular space invasion, endometrioid histological type, tumor size >  = 2 cm, myometrial invasion >  = 50%, cervical stromal invasion, and tumor grade. In the training group, the area under the curve (AUC) of the nomogram and Mayo criteria were 0.85 (95% CI: 0.81-0.90) and 0.77 (95% CI: 0.77-0.83), respectively (P < 0.01). In the validation group (N = 359), the AUC was 0.87 (95% CI: 0.82-0.93) and 0.80 (95% CI: 0.74-0.87) for the nomogram and the Mayo criteria, respectively (P = 0.01). Calibration plots revealed the satisfactory performance of the nomogram. Decision curve analysis showed a positive net benefit of this nomogram, which indicated clinical value., Conclusion: This model may promote risk stratification and individualized treatment, thus improving the prognosis., (© 2023. The Author(s).)

This study takes Cushing's syndrome, a rare disease, as a model, and adopts the path of "Plan, Do, Check, Action" (PDCA) to explore new methods to optimize the clinical path, can improve the quality and efficiency of diagnosis and treatment of rare diseases. After sorting out the problems existing in the previous diagnosis and treatment mode, our team optimizes the path in various ways and establishes a standard operation procedure (SOP) for the new path. In the evaluation of the optimized mode, 55 patients with Cushing's syndrome were admitted to the Department of Endocrinology, Peking Union Medical College Hospital, including 19 males and 36 females, aged (41.8±14.4) years (6-68 years). The pathway group (28 cases) and the control group (27 cases) were divided according to whether they were included in the new path management at the time of admission, and the effect of path optimization was assessed in terms of time, efficacy, safety and cost. The results showed that compared with the control group, the pathway group had a shorter time of hospitalization in the Department of Endocrinology and critical tests, such as blood cortisol rhythm, low-dose dexamethasone inhibition test, and bilateral inferior petrosal sinus sampling (all P <0.05). There was no significant differences in the decrease of total cortisol after operation, the incidence of postoperative complications, and hospitalization expenses (all P >0.05). The optimized path improves the medical efficiency while ensuring medical quality, safety and no increase in cost. This study proposes PDCA path optimization for complex diseases and establishes SOP process, which provides experience in management optimization for the patient-centered and clinical path-oriented diagnosis and treatment mode of rare diseases.

Objective: To investigate the relationship between the long-non-coding RNA LINC00342 expression and the clinicopathological parameters of head and neck squamous cell carcinoma (HNSCC) and the biological function of LINC00342 in HNSCC cells. Methods: The expression level of LINC00342 in the HNSCC was analyzed using transcriptome sequencing data from TCGA (The Cancer Genome Atlas) database, and the expressions of LINC00342 in laryngeal squamous cell carcinoma tissues (LSCC) of 27 patients in the First Hospital of Shanxi Medical University were detected by transcriptome sequencing. The expression levels of LINC00342 in human embryonic lung diploid cells 2BS, HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 were determined by real-time quantitative polymerase chain reaction (qPCR). RNAi (RNA interference) was used for LINC00342 knockdown in HNSCC cell lines, and the changes of malignant phenotype in the tumor cells after LINC00342 knockdown were examined by cell counting kit-8 (CCK-8), colony formation, flow cytometry, transwell invasion and migration assays. Bioinformatics analysis was performed to construct a LINC00342 -centered competing endogenous RNA (ceRNA) regulatory network, and GO (Gene Ontology) enrichment analysis was performed. Statistical analysis and graphing were performed using SPSS 25.0 software and GraphPad Prism 6 software. Results: Mean LINC00342 levels in HNSCC tissues and TCGA database were higher than that in normal control tissues, but with no significantly statistical difference ( P= 0.522). LINC00342 expression levels were positively correlated with cervical lymph node metastasis and pathological grade in patients with HNSCC, with higher expression in male patients than in female patients ( P< 0.05). Transcriptome sequencing analysis showed that mean expression level of LINC00342 in LSCC tissues of 27 patients was significantly higher than that in the paired adjacent normal mucosa tissues ( t= 1.56, P= 0.036). LINC00342 expression was significantly upregulated in HNSCC cell lines FD-LSC-1, CAL-27 and Detroit562 ( t -values of -12.17, -23.26 and -388.57, respectively; all P< 0.001). Knockdown of LINC00342 by transfecting si- LINC00342 -1 and si- LINC00342 -2 inhibited HNSCC cell proliferation ( t -values of 8.95 and 4.84, 2.70 and 5.55, 2.02 and 3.70, respectively), colony formation ( t -values of 6.66 and 6.17, 7.38 and 11.65, 4.90 and 5.79, respectively), migration ( t -values of 8.21 and 7.19, 5.76 and 6.46, 6.28 and 9.92, respectively) and invasion abilities ( t -values of 9.29 and 10.25, 11.30 and 11.36, 8.02 and 8.66, respectively), but promoting apoptosis in cell lines FD-LSC-1 and CAL-27 ( t -values of -2.21 and -5.83, -3.05 and -5.25 respectively) (all P -values<0.05). The LINC00342 -centered ceRNA network consists of 10 downregulated microRNA and 647 upregulated mRNA nodes. GO analysis results indicated that LINC00342 -regulated mRNAs were enriched in 22 biological processes, 32 molecular functions, and 12 cellular components. Conclusion: High level of LINC00342 is associated with the malignant progression of HNSCC. LINC00342 promotes the proliferation, migration, invasion, and antagonizes apoptosis of HNSCC cells, which serves as a potential molecular marker in HNSCC.

In this study, we investigated the effect of type 1 diabetes mellitus on the modulation of the activities of CYP450s in dynamics by a UHPLC-MS/MS method. The diabetic rat model was constructed by an intraperitoneal single injection of streptozotocin. Fasting blood glucose levels > 16.7 mmol/L were considered as diabetic. The rats were given a cocktail of four probe drugs (10 mg/kg phenacetin, 1 mg/kg tolbutamide, 10 mg/kg metoprolol, and 10 mg/kg midazolam) by oral administration for the pharmacokinetic study. Thereafter, the metabolic ratio (MR) of the metabolites to probe substrates were determined. The results indicated that two weeks after diabetes was induced, diabetes increased the MRs of acetaminophen/phenacetin (CYP1A2) and 4-hydroxyl tolbutamide/tolbutamide (CYP2C9); however, it decreased the MRs of α-hydroxy metoprolol/metoprolol (CYP2D6) and 1-hydroxy midazolam/midazolam (CYP3A4). Two months after diabetes was induced, diabetes increased the MRs of acetaminophen/phenacetin and 4-hydroxyl tolbutamide/tolbutamide. The MR of α-hydroxy metoprolol/metoprolol was decreased and the MR of 1-hydroxy midazolam/midazolam was increased but the difference was not significant. According to the results, CYP1A2 and CYP2C9 activities were enhanced in the diabetic rats. and CYP2D6 activity was inhibited in a short period of diabetes; however, the decrease in CYP2D6 activity was not significant in the long period. CYP3A4 activity was decreased in a short period of diabetes and increased in a long period of diabetes but was not significant in the two periods. This study suggests the activity change rule of the CYP450 enzyme system in diabetes mellitus, which can provide a reference for precise clinical medication., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The cathodic product Li 2 CO 3 , due to its high decomposition potential, has hindered the practical application of rechargeable Li-CO 2 /O 2 batteries. To overcome this bottleneck, a Pt/FeNC cathodic catalyst is fabricated by dispersing Pt nanoparticles (NPs) with a uniform size of 2.4 nm and 8.3 wt % loading amount into a porous microcube FeNC support for high-performance rechargeable Li-CO 2 /O 2 batteries. The FeNC matrix is composed of numerous two-dimensional (2D) carbon nanosheets, which is derived from an Fe-doping zinc metal-organic framework (Zn-MOF). Importantly, using Pt/FeNC as the cathodic catalyst, the Li-CO 2 /O 2 ( V CO 2 / V O 2 = 4:1) battery displays the lowest overpotential of 0.54 V and a long-term stability of 142 cycles, which is superior to batteries with FeNC (1.67 V, 47 cycles) and NC (1.87 V, 23 cycles) catalysts. The FeNC matrix and Pt NPs can exert a synergetic effect to decrease the decomposition potential of Li 2 CO 3 and thus enhance the battery performance. In situ Fourier transform infrared (FTIR) spectroscopy further confirms that Li 2 CO 3 can be completely decomposed under a low potential of 3.3 V using the Pt/FeNC catalyst. Impressively, Li 2 CO 3 exhibits a film structure on the surface of the Pt/FeNC catalysts by scanning electron microscopy (SEM), and its size can be limited by the confined space between the carbon sheets in Pt/FeNC, which enlarges the better contacting interface. In addition, density functional theory (DFT) calculations reveal that the Pt and FeNC catalysts show a higher adsorption energy for Li 2 CO 3 and Li 2 CO 4 intermediates compared to the NC catalyst, and the possible discharge pathways are deeply investigated. The synergetic effect between the FeNC support and Pt active sites makes the Li-CO 2 /O 2 battery achieve optimal performance.

Objective: Understanding factors for prolonged operative time is essential for surgery. This study aims at identifying the factors related to prolonged ileostomy closure operation time., Patients and Methods: The data of 88 patients who underwent ileostomy reversal in the Department of Gastrointestinal Surgery of Jiaxing First Hospital between January 2018 and October 2021 were retrospectively analyzed. Prolonged operation time was defined as operative time >65 minutes. The Chi-square test was used to compare data between patients with normal operative time (≤65 minutes) and patients with prolonged operative time. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with prolonged ileostomy closure operation time., Results: Among the 88 patients (mean age: 62.78 years), median ileostomy retention time was 127.50 (range: 61.00-1,192.00) days. The operation time ranged from 35.00 minutes to 125.00 minutes. Prolonged ileostomy closure time occurred in 41 (46.6%) patients. In univariate analysis, the factors associated with prolonged operation time were body mass index (BMI) ≥25 kg/m2, previous history of abdominal surgery, and manual suture. History of serious complications after the primary operation was associated with shorter operation time. In multivariate analysis, the independent risk factors for prolonged operation time were BMI ≥25 kg/m2 (OR = 4.552, 95% CI: 1.369-15.136, p = 0.013), previous history of abdominal surgery (OR = 4.377, 95% CI: 1.394-13.739, p = 0.011), and manual suture (OR = 3.941, 95% CI: 1.181-13.154, p = 0.026)., Conclusions: Overweight, previous history of abdominal surgery, and manual suture appear to be risk factors for prolonged operative time for ileostomy closure.

Heracles Ⅱ rapid electronic odor analyzer has been gradually applied in the study on the &quot;odor&quot; of Chinese medicine because of its ability to associate volatile substances in the sample with &quot;odor&quot;, but its applicability is not clear. In this article, processed ginger products--dried ginger, roasted ginger, and carbonized ginger were chosen as examples to study the volatile chemical components, and the applied scope and accuracy of Heracles Ⅱ rapid electronic odor analyzer were verified by gas chromatography-mass spectrometry(GC-MS). Components in ten batches of ginger from different producing places were detected by GC-MS and Heracles Ⅱ rapid electronic odor analyzer. Principal component analysis(PCA) and discriminant factor analysis(DFA) were performed to investigate the effects of producing place and processing degree on dried ginger, roasted ginger, and carbonized ginger. The results showed that the processing degree had significant impact on the processed ginger products, while producing place was not significant to the processed ginger products. At the same time, 42 and 45 compounds were detected by Heracles Ⅱ rapid electronic odor analyzer and GC-MS, respectively, of which 29 compounds were common detected, with a coincidence rate of 64.4%. This result indicated that compared with GC-MS, Heracles Ⅱ rapid electronic odor analyzer had certain referential value in the qualitative analysis. Heracles Ⅱ rapid electronic odor analyzer, with the characteristics of convenience, high efficiency, and accuracy in processing data, has certain advantages in the &quot;odor&quot; research aiming to comprehensively evaluate volatile substances, and has a good application prospect in the quality control of Chinese medicine and its processed products.

Background and Aims: Abnormal expression of lncRNAs is relevant to the occurrence and development of gastric cancer (GC), but the significance remains inconclusive. We performed a diagnostic meta-bioinformatics analysis to elucidate the association between lncRNA expression and GC risk., Methods: Published datasets were selected from PubMed, Embase, CNKI, and Web of Science, up to 1st December 2021. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the diagnostic value. RNA sequencing data were downloaded for validation., Results: 54 studies with 4671 patients and 4652 matched controls were included in the meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC were 0.71, 0.76, 2.9, 0.39, 8, and 0.79, respectively. Subgroup analyses showed that the DOR and AUC of intergenic lncRNAs, circulating lncRNAs, larger sample size (>200), and high-quality (NOS score ≥ 7) groups were superior to antisense lncRNAs, tissue lncRNAs, smaller sample size (≤200), and low-quality (NOS score < 7) groups, respectively. However, only circulating lncRNAs had significantly higher diagnostic utility than that tissue lncRNAs. Nine differentially expressed lncRNAs in the meta-analysis were verified in TCGA-STAD. PVT1 was the most effective single lncRNA, with AUC of 0.949, SEN of 0.808, and SPE of 0.969, while PVT1 and C5orf66-AS1 were the most effective combination, with AUC of 0.972, SEN of 0.941, and SPE of 0.937., Conclusion: Abnormally expressed lncRNAs, especially circulating lncRNAs, might be potential diagnostic biomarkers for GC risk. A novel combined model of lncRNAs might achieve better GC diagnosis performance., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Ying-ying Dong et al.)

Four undescribed flavonoid glucosides (iridins B-C, tectoridin A and ampelopsinin A); one undescribed phenolic glucoside (diplostephioside B); one undescribed phenolic compound (phenanthrenetriol A); and seventeen known compounds were isolated from the rhizomes of Iris domestica. The chemical structures of the undescribed compounds were established by spectroscopic/spectrometric data interpretation using HRESIMS, NMR, and ECD. Tectoridin A, nigricin A and naringenin exhibited anti-inflammatory activities with inhibition rates of 53.71%, 57.68% and 88.71%, respectively, against the NF-κB signaling pathway at a concentration of 10 μM. 4'-O-methylnyasol (10 μM) exhibited 84.91% antiproliferative activity against the K562 human leukemia cell line with an IC 50 value of 4.20 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

PTFE/Al reactive material is an energetic material that releases energy under impact conditions, resulting in a wide range of application prospects. In order to improve its damage ability-considering the higher heat of the reaction per unit mass when Ni 2 O 3 is involved in the aluminothermic reaction-we designed and studied PTFE/Al/Ni 2 O 3 , a reaction material based on polytetrafluoroethylene (PTFE). We also designed two other kinds (PTFE/Al, PTFE/Al/CuO) for comparative study, with the mass fraction of the metal oxides added at 10%, 20%, and 30%, respectively. The quasi-static compression properties and impact initiation behavior of the material were investigated by a universal material testing machine and a drop hammer test. The reaction process of different materials under a high strain rate was recorded using a high-speed camera. The results show that with the increase in Ni 2 O 3 content, the strength of the PTFE/Al/Ni 2 O 3 reactive material shows an increasing trend followed by a decreasing trend. Among the three reactive materials, when the content of Al/Ni 2 O 3 reaches 30 wt.%, the reaction duration is the longest (at 4 ms) and the reaction fireball is the largest. The addition of Ni 2 O 3 is helpful to improve the reactivity and reaction duration of the PTEF/Al reactive material.

In the past decade, selenocyclization has been extensively exploited for the preparation of a wide range of selenylated heterocycles with versatile activities. Previously, selenium electrophile-based and FeCl 3 -promoted methods were employed for the synthesis of selenylated benzoxazines. However, these methods are limited by starting material availability and low atomic economy, respectively. Inspired by the recent catalytic selenocyclization approaches based on distinctive pathways, we rationally constructed an efficient and greener double-redox catalytic system for the access to diverse selenylated benzoxazines. The coupling of I 2 /I - and Fe 3+ /Fe 2+ catalytic redox cycles enables aerial O 2 to act as the driving force to promote the selenocyclization. Control and test redox experiments confirmed the roles of each component in the catalytic system, and a PhSeI-based pathway is proposed for the selenocyclization process.

Background: Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown., Methods: We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes., Results: We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii -derived butyrate were through the GPR (G protein-coupled receptor)-43., Conclusions: Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.

Gut microbiota is well-established to regulate host blood pressure. Diosgenin is a natural steroid sapogenin with documented anti-inflammatory, antioxidant and antihypertensive properties. We aimed to investigate whether the antihypertensive effects of diosgenin are mediated by the microbiota-gut-brain axis in spontaneously hypertensive rats (SHR). 15-Week-old male Wistar Kyoto rats (WKY) and age-matched SHR were randomly distributed into three groups: WKY, SHR treated with a vehicle, and SHR treated with diosgenin (100 mg kg -1 ). Our results showed that diosgenin prevented elevated systolic blood pressure (SBP) and ameliorated cardiac hypertrophy in SHR. Moreover, the gut microbiota composition and intestinal integrity were improved. Furthermore, increased butyrate-producing bacteria and plasma butyrate and decreased plasma lipopolysaccharides were observed in SHR treated with diosgenin. These findings were associated with reduced microglial activation and neuroinflammation in the paraventricular nucleus. Our findings suggest that diosgenin attenuates hypertension by reshaping the gut microbiota and improving the gut-brain axis.

Researchers have reported that zinc finger CCHC domain containing 12 gene (ZCCHC12) plays a role in the progression and tumorigenesis of papillary thyroid cancer. However, the biological role of ZCCHC12 in osteosarcoma (OS) remains unknown. ZCCHC12 was highly upregulated in OS cell lines according to our present study. Also, our subsequent assays demonstrated that ZCCHC12 enhanced the proliferation, tumor growth and migration of OS cells. Moreover, the epithelial-mesenchymal transition (EMT) of OS cells was also promoted by ZCCHC12. In addition, downregulation of ZCCHC12 induced apoptosis and S-phase arrest in OS cells. Then, our study indicated that ZCCHC12 exerts its oncogenic function in OS cells by activating the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway greatly limits the oncogenic function of ZCCHC12 in OS cells. Also, overexpression of ZCCHC12 promotes tumor growth in vivo . Altogether, our study suggests ZCCHC12 promotes OS cells progression by activating the PI3K/AKT pathway. The ZCCHC12 gene may be a novel diagnostic and therapeutic target for OS.

Background: Patients with recurrent implantation failure (RIF) may have more uterine contractions. Several observational studies suggested that atosiban administration around embryo transfer resulted in higher pregnancy rates in RIF patients. This study aimed to evaluate the effect of atosiban given before fresh embryo transfer on pregnancy outcomes of women with RIF., Methods: A prospective, randomized, double-blind controlled clinical trial was performed in IVF center of Shanghai First Maternity and Infant Hospital. According to a computer-generated randomization list, 194 infertile women with RIF received fresh embryo transfer between July 2017 and December 2019 were randomly allocated into the atosiban (n = 97) and the placebo (n = 97) groups. Women in the treatment group received atosiban intravenously about 30 min before embryo transfer with a bolus dose of 6.75 mg over one minute. Those in the placebo group received only normal saline infusion for the same duration., Results: There was no significant difference in the live birth rate between the atosiban and placebo groups (42.3% vs 35.1%, P = 0.302, RR = 1.206 (0.844-1.723)). No significant differences were found between the two groups in the positive pregnancy test, clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and implantation rates. Similar results were found when stratified by the number of embryos previously transferred, number of previous failed embryo transfers, frequency of endometrial peristalsis on embryo transfer day (≥ 3 waves/min) or serum estradiol (E 2 ) on the day of hCG above the median level. And, there was no correlation between the serum E 2 level on the day of hCG and the frequency of endometrial peristalsis on embryo transfer day. The frequency of endometrial peristalsis on embryo transfer day, total FSH/HMG dosage and duration were the significant factors which independently predicted the likelihood of a live birth., Conclusions: These results suggested that atosiban treatment before fresh embryo transfer might not improve the live birth rate in RIF patients., Trial Registration: The study had been approved by the Institutional Review Board of the hospital (2017 ethics No.43) and was registered under Clinicaltrials.gov with an identifier NCT02893722., (© 2022. The Author(s).)

The CDK4/6-Rb axis is a crucial target of cancer therapy and several selective inhibitors of it have been approved for clinical application. However, current therapeutic efficacy evaluation mostly relies on anatomical imaging, which cannot directly reflect changes in drug targets, leading to a delay in the selection of optimal treatment. In this study, we constructed a novel fluorescent probe, CPP30-Lipo/CDKACT4, for real-time monitoring of CDK4 activity and the therapeutic efficacy of its inhibitor in HR + /HER2 - breast cancer. CPP30-Lipo/CDKACT4 exhibited good optical stability and targetability. The signal of the probe in living cells decreased after CDK4 knockdown or palbociclib treatment. Moreover, the fluorescence intensity of the tumors after 7 days of palbociclib treatment was significantly lower than that before treatment, while no significant change in tumor diameter was observed under magnetic resonance imaging. Overall, we developed an innovative fluorescent probe that can monitor CDK4 activity and the early therapeutic response to CDK4 inhibitors in living cells and in vivo . It may provide a new strategy for evaluating antitumor therapeutic efficacy in a clinical context and for drug development., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

This paper has aimed to review the available evidence on the association between Interleukin (IL) -10 -1082G/A, -592C/A gene polymorphisms and the risk of human immunodeficiency virus-1(HIV-1) infection. The data of PubMed updated in May 2021 were retrieved. The HIV infection risks were estimated in allelic, recessive, dominant, homozygous, heterozygous, over-dominant models of IL-10-1082G/A and-592C/A gene locus as odds ratio (OR) with the corresponding 95% confidence interval (95% CI). The correlation was not significant between -1082G/A polymorphism and HIV-1 susceptibility (allelic model (G vs. A: OR (95% CI)=0.968 (0.878-1.067)); recessive model (GG vs. AA+AG: OR (95% CI)=0.940, (0.771-1.146)); dominant model (GG+AG vs. AA: OR (95% CI)=0.967(0.846-1.106)); homozygous model (GG vs. AA: OR (95% CI)=0.971(0.780-1.209)); heterozygous model (AG vs. AA: OR (95% CI)=0.988(0.797-1.224)) and over-dominant model (GG+AA vs. AG: OR (95% CI)=0.969(0.781-1.201)). IL-10-592C/A polymorphism might be related to HIV-1 in allelic model, dominant model, homozygous model and heterozygous model (OR (95% CI)(0.796-0.965); OR (95% CI)=0.793(0.664-0.948); OR (95% CI)=0.755,(0.612-0.930); OR (95% CI)=0.820(0.679-0.991), respectively), but not to recessive model and over-dominant model (OR (95% CI)=0.882(0.770-1.010) and OR (95% CI)=1.009(0.897-1.148)).

Hafnium(IV) triflate (Hf(OTf) 4 ) has been identified as a potent catalyst for the direct three-component synthesis of β-carbamate ketones. This new method, featuring a low catalyst loading, fast reaction rate, and solvent-free conditions, provided facile access to a diversity of carbamate-protected Mannich bases. A mechanistic investigation indicated that the three-component reaction proceeds via sequential aldol condensation and aza-Michael addition, but not the Mannich-type pathway.

5-Hydroxymethyl-2'-deoxycytidine (5hmdC) phosphoramidite and triphosphate are important building blocks in 5hmdC-containing DNA synthesis for epigenetic studies. However, efficient and practical methods for the synthesis of these compounds are still limited. The current research provides an intensively improved synthetic method that enables the preparation of commercially available cyanoethyl-protected 5hmdC phosphoramidite with an overall yield of 39% on 5 g scale. On the basis of facile and efficient accesses to cyanoethyl protected-5hmdU and 5hmdC intermediates, two efficient synthetic routes for 5hmdC triphosphate were also developed.

Inulae Flos was widely distributed throughout Europe, Africa, and Asia, and was commonly used as a folk medicine in clinic for treating various respiratory diseases, including cough, asthma, bronchitis, pulmonary fibrosis, and pneumonia. However, the ingredients responsible for the pharmacology effects of I. Flos and the underlying mechanisms remain unclear. In this study, the effects of 16 known sesquiterpene lactones and flavonoids from I. Flos on TGF-β1-induced fibroblast activation were assessed by phenotypic high-content screening. Among those sixteen compounds, 1β-hydroxy alantolactone (HAL), the main characteristic sesquiterpene lactone from I. Flos, exhibited remarkable inhibitory activity. The further studies showed that HAL significantly inhibited the proliferation and induced the apoptosis of human fibroblast cell lines HELF and MRC-5 in a concentration-dependent manner. It also reduced intracellular ROS production, suppressed the mRNA expressions of E-cad, TGF-β1, Smad3, Col I, α-SMA and TNF-α, and downregulated protein expressions of α-SMA and F-actin. Furthermore, HAL significantly reduced the levels of HA, LN, PC-III and IV-C in serum, TNF-α and IL-6 in BALF, and TGF-β1, HYP and Col I in lung tissues of bleomycin (BLM)-treated rats. HAL significantly downregulated the expressions of p-JNK, FOXO1, p-p65, α-SMA, p-smad3 and Col I but upregulated p-FOXO1, which could be reversed by JNK agonist anisomycin. These results demonstrated that HAL induced the apoptosis of lung fibroblast cells activated by TGF-β1 and improved BLM-induced lung fibrosis in rats via inhibiting JNK/FOXO1/NF-κB pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)