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Peng Xie,1,* Hui-Qin Li,1,* Wan-Lin Peng,2 Hao Yang3 1People’s Hospital of Deyang City, Deyang City, Sichuan, 618000, People’s Republic of China; 2School of Nursing, Guangxi University of Chinese Medicine, Nanning, Guangxi, 530004, People’s Republic of China; 3West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui-Qin Li, People’s Hospital of Deyang City, Deyang City, Sichuan, 618000, People’s Republic of China, Tel + 86-0838-2208091, Email 874184073@qq.comIntroduction: Depression threatens people’s lives and imposes huge economic burden. Antidepressant therapy is the first-line treatment for depression, and patient adherence to medication is the key to successful treatment. Depression patients have poor medication adherence, which leads to failure of depression management and significantly poorer clinical outcomes. Incorporating patient preferences into clinical decisions can improve uptake rates, optimize treatment adherence. A discrete choice experiment (DCE) can elicit and quantify individual preferences. Previous DCE studies were conducted in developed countries and ignored the influences of factors other than the medication. This paper outlines an ongoing DCE that aims to (1) explore medication-management-related characteristics that may affect depression patients’ adherence to antidepressant, (2) elicit how depression patients consider the trade-offs among different medication managements.Methods: The six attributes and their levels were developed through a literature review, semi-structured interviews and experts and focus group discussions. A fractional factorial design in the software Ngene 1.2 version was used to generate 36 choice sets, and they were divided into 3 blocks. A mixed logit model will be used to explore the patients’ preferences, willingness to pay and uptake rate of depression patients for medication management attributes.Results: The final questionnaire consists of three parts. The first is the introduction, which introduces the purpose of the study and the requirements of completing the questionnaire. This was followed by a general information questionnaire, which included sociodemographic characteristics. The last part is DCE tasks, which include 13 DCE choice sets, and each choice set include two alternative and one “opt-out” option. The pilot-test results showed the questionnaire was easy to understand and could be used in formal surveys.Conclusion: Our study shows how the development process of the study can be conducted and reported systematically and rigorously according to the theoretical foundation and design principles in DCE.Keywords: depressive disorder, patient preferences, adherence, discrete choice experiment, protocol

Jin-Xiang Wang,1 Hui-Qiao Li,1 Fang Zhang,2 Wei Ning31Department of Pulmonary and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Pulmonary Function Test Room, Department of Pulmonary and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jin-Xiang WangDepartment of Pulmonary and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel +86 10 6954 3901 Ext. 1125Email wangjx0090@sina.comObjective: To evaluate patients with stable COPD for the presence of potentially pathogenic microorganisms (PPM), systemic inflammation and the effects of short-term antibiotic therapy in PPM positive patients.Methods: From January 2016 to June 2017, we enrolled 96 stable COPD patients. Bacterial cultures from sputum collections were quantitated, along with markers for systemic inflammation including serum C-reactive protein (CRP), interleukin-8 (IL-8) and plasma fibrinogen (FIB) in all patients. All enrolled patients were followed for 12 months. Forty patients were identified as PPM positive and were randomly divided into an antibiotic group and a control group. The antibiotic group was treated with moxifloxacin orally for 6 days. Lung function and markers for systemic inflammation were repeatedly measured at 30 days and 6 months in PPM positive subjects.Results: Binary logistic regression analysis showed that risk factors for PPM positive are bronchiectasis (OR 4.18, 95% CI 1.20–14.59; P=0.025), COPD assessment test (CAT) ≥20 (OR 17.55, 95% CI 2.82–109.18; P=0.002), spontaneous sputum (OR 15.09, 95% CI 1.36–168.02; P=0.027) and sputum purulence (OR 38.43, 95% CI 5.39–274.21; P=0.000). CRP and IL-8 were higher in PPM positive group than those in PPM negative group (P=0.001, P=0.007, respectively), but there were no differences of FIB between the two groups (P=0.086). Compared to the PPM negative group, the rate of acute exacerbation of COPD was higher (P=0.029) and time to next acute exacerbation was shorter (P=0.030) in PPM positive group. There were no differences in lung function and systemic inflammatory markers either in the control group or the antibiotic group at different time points of follow-up.Conclusion: PPM exists in stable COPD patients and can cause systemic inflammation and is associated with acute exacerbation of COPD. Short-term antibiotic therapy had no effect on systemic inflammation nor on acute exacerbation of COPD.China Clinical Trials Registry: ChiCTR-IOR-15006769Keywords: COPD, potentially pathogenic microorganisms, systemic inflammation, antibiotics, C-reactive protein, interleukin-8

Wen-Qin Guo, Lang Li, Qiang Su, Yu-Han Sun, Xian-Tao Wang, Wei-Ran Dai, Hong-Qing Li Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China Introduction: The optimal revascularization strategy for patients with ST-segment elevation myocardial infarction and multivessel disease is unclear. In this study, we performed a meta-analysis to determine the optimal revascularization strategy for treating these patients.Methods: Searches of PubMed, the Cochrane Library, clinicaltrial.gov, and the reference lists of relevant papers were performed covering the period between the year 2000 and March 20, 2017. A pairwise analysis and a Bayesian network meta-analysis were performed to compare the effectiveness of early complete revascularization (CR) during the index hospitalization, delayed CR, and culprit only revascularization (COR). The primary endpoint was the incidence of major adverse cardiac events (MACE), which were defined as the composite of recurrent myocardial infarction (MI), repeat revascularization, and all-cause mortality. The secondary endpoints were the rates of all-cause mortality, recurrent MI, and repeat revascularization. This study is registered at PROSPERO under registration number CRD42017059980.Results: Eleven randomized controlled trials including a total of 3,170 patients were identified. A pairwise meta-analysis showed that compared with COR, early CR was associated with significantly decreased risks of MACE (relative risk [RR] 0.47, 95% CI 0.39–0.56), MI (RR 0.55, 95% CI 0.37–0.83), and repeat revascularization (RR 0.35, 95% CI 0.27–0.46) but not of all-cause mortality (RR 0.78, 95% CI 0.52–1.16). These results were confirmed by trial sequential analysis. The network meta-analysis showed that early CR had the highest probability of being the first treatment option during MACE (89.2%), MI (83.3%), and repeat revascularization (80.4%).Conclusion: Early CR during the index hospitalization was markedly superior to COR with respect to reducing the risk of MACE, as CR significantly decreased the risks of MI and repeat revascularization compared with COR. However, further study is warranted to determine whether CR during the index hospitalization can improve survival in patients with concurrent ST-segment elevation myocardial infarction and multivessel disease. The optimal timing of CR remains inconclusive considering the small number of studies and patients included in the analysis comparing early and delayed CR. Keywords: ST-segment elevation myocardial infarction, multivessel disease, percutaneous coronary intervention, meta-analysis, trial sequential analysis

Jiachen Luo,1 Liming Dai,1 Jianming Li,2 Jinlong Zhao,1 Zhiqiang Li,1 Xiaoming Qin,1 Hongqiang Li,1 Baoxin Liu,1 Yidong Wei1 1Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Cardiovascular Division, Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, USA Purpose: New-onset atrial fibrillation (NOAF) is a common finding in patients with myocardial infarction (MI), but few studies are available regarding the prediction model for its risk estimation. Although Global Registry of Acute Coronary Events (GRACE) risk score (RS) has been recognized as an effective tool for the risk evaluation of clinical outcomes in patients with MI, its usefulness in the prediction of post-MI NOAF remains unclear. In this study, we sought to validate the discrimination performance of GRACE RS in the prediction of post-MI NOAF and to make a comparison with that of the CHA2DS2-VASc score in patients with ST-segment elevation myocardial infarction (STEMI). Patients and methods: A total of 488 patients with STEMI who were admitted to our hospital between May 2015 and October 2016 without a history of atrial fibrillation were retrospectively evaluated in this study. GRACE and CHA2DS2-VASc scores were calculated for each patient. Patients were divided into low (GRACE RS≤125)-, intermediate (GRACE RS 126–154)-, and high (GRACE RS≥155)-risk groups. Receiver operating characteristic curve analyses were performed to evaluate the discrimination performance of both RSs. Model calibration was evaluated by using Hosmer–Lemeshow goodness-of-fit test (HLS). Results: Of the 488 eligible patients, 49 (10.0%) developed NOAF during hospitalization. In the overall cohort, the discrimination performance of GRACE RS (C-statistic: 0.76, 95% CI: 0.72–0.80) was significantly better than that of CHA2DS2-VASc score (C-statistic: 0.68, 95% CI: 0.64–0.72; comparison p=0.03). For subgroup analysis, GRACE RS tended to be better than the CHA2DS2-VASc score in all but the intermediate-risk group as evidenced by C-statistics of 0.60 and 0.65 for GRACE and CHA2DS2-VASc scores, respectively. Excellent calibration was achieved except for GRACE RS in females (HLS p=0.05). Conclusion: The diagnostic performance of GRACE RS is relatively high as well as better than that of the CHA2DS2-VASc score with respect to the prediction of post-MI NOAF. Keywords: myocardial infarction, atrial fibrillation, GRACE risk score, CHA2DS2-VASc score, risk prediction

Haiqin Li, Rong Tao, Jing Wang, Lingjie Xia Department of Clinical Pain, The People’s Hospital of Henan Province, Zhengzhou, People’s Republic of China Abstract: Several lines of evidence indicate that microRNAs (miRNAs) modulate tolerance to the analgesic effects of morphine via regulation of pain-related genes, making dysregulation of miRNA levels a clinical target for controlling opioid tolerance. However, the precise mechanisms by which miRNAs regulate opioid tolerance are unclear. In the present study, we noted that the miR-375 level was downregulated but the expression of Janus kinase 2 (JAK2) was upregulated in mouse dorsal root ganglia (DRG) following chronic morphine treatment. The miR-375 levels and JAK2 expression were correlated with the progression of morphine tolerance, and upregulation of miR-375 level could significantly hinder morphine tolerance. This was ameliorated by JAK2 knockdown. Prolonged morphine exposure induced the expression of brain-derived neurotrophic factor (BDNF) in a time-dependent manner in the DRG. This was regulated by the miR-375 and JAK2–signal transducer and activator of transcription 3 (STAT3) pathway, and inhibition of this pathway decreased BDNF production, and thus, attenuated morphine tolerance. More importantly, we found that miR-375 could target JAK2 and increase BDNF expression in a JAK2/STAT3 pathway-dependent manner. Keywords: morphine tolerance, miR-375, JAK2, BDNF

Qun Wang,1,2,* Jian-Ying Huang,2,* Hua-Qiong Li,3,4 Allan Zi-Jian Zhao,4 Yi Wang,4 Ke-Qin Zhang,2,5 Hong-Tao Sun,1 Yue-Kun Lai,2,5 1College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 2National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 3Institute of Biomaterials and Engineering, Wenzhou Medical University, 4Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou, 5Research Center of Cooperative Innovation for Functional Organic/Polymer Material Micro/Nanofabrication, Suzhou, People’s Republic of China *These authors contributed equally to this work Abstract: To address the limitations of traditional drug delivery, TiO2 nanotubes (TNTs) are recognized as a promising material for localized drug delivery systems. With regard to the excellent biocompatibility and physicochemical properties, TNTs prepared by a facile electrochemical anodizing process have been used to fabricate new drug-releasing implants for localized drug delivery. This review discusses the development of TNTs applied in localized drug delivery systems, focusing on several approaches to control drug release, including the regulation of the dimensions of TNTs, modification of internal chemical characteristics, adjusting pore openings by biopolymer coatings, and employing polymeric micelles as drug nanocarriers. Furthermore, rational strategies on external conditions-triggered stimuli-responsive drug release for localized drug delivery systems are highlighted. Finally, the review concludes with the recent advances on TNTs for controlled drug delivery and corresponding prospects in the future. Keywords: TiO2 nanotubes, electrochemical anodization, modification, stimulated drug delivery, drug-releasing implant

Qun Wang,1,2,* Jian-Ying Huang,1,* Hua-Qiong Li,3 Zhong Chen,4 Allan Zi-Jian Zhao,3 Yi Wang,3 Ke-Qin Zhang,1 Hong-Tao Sun,2 Salem S Al-Deyab,5 Yue-Kun Lai1 1National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou, 2College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, People’s Republic of China; 3Wenzhou Institute of Biomaterials and Engineering, Chinese Academy of Sciences, Wenzhou, People’s Republic of China; 4School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore; 5Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia *These authors contributed equally to this work Abstract: Titania nanotube (TNT) arrays are recognized as promising materials for localized drug delivery implants because of their excellent properties and facile preparation process. This review highlights the concept of localized drug delivery systems based on TNTs, considering their outstanding biocompatibility in a series of ex vivo and in vivo studies. Considering the safety of TNT implants in the host body, studies of the biocompatibility present significant importance for the clinical application of TNT implants. Toward smart TNT platforms for sustainable drug delivery, several advanced approaches were presented in this review, including controlled release triggered by temperature, light, radiofrequency magnetism, and ultrasonic stimulation. Moreover, TNT implants used in medical therapy have been demonstrated by various examples including dentistry, orthopedic implants, cardiovascular stents, and so on. Finally, a future perspective of TNTs for clinical applications is provided. Keywords: TiO2 nanotubes, anodization, drug delivery, orthopedic implant

Yuqing Mao,1 Jianbo Wang,2 Fujun Yu,1 Jian Cheng,1 Huanqing Li,1 Chuanyong Guo,3 Xiaoming Fan11Department of Gastroenterology and Hepatology, Jinshan Hospital of Fudan University, Shanghai, 2Department of Gastroenterology and Hepatology, The Central Hospital of Lishui City, Wenzhou Medical University, Zhejiang, 3Department of Gastroenterology and Hepatology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, People’s Republic of ChinaBackground and aims: Ghrelin is a 28-amino-acid gut hormone that was first discovered as a potent growth hormone secretagogue. Recently, it has been shown to exert a strong anti-inflammatory effect. The purpose of the study reported here was to explore the effect and mechanism of ghrelin on concanavalin (Con) A-induced acute hepatitis.Methods: Balb/C mice were divided into four groups: normal control (NC) (mice injected with vehicle [saline]); Con A (25 mg/kg); Con A + 10 µg/kg ghrelin; and Con A + 50 µg/kg ghrelin (1 hour before Con A injection). Pro-inflammatory cytokine levels were detected. Protein levels of phosphoinositide 3-kinase (PI3K); phosphorylated Akt (p-Akt); caspase 3, 8, and 9; and microtubule-associated protein 1 light chain 3 (LC3) were also detected. Perifosine (25 mM) (an Akt inhibitor) was used to investigate whether the protective effect of ghrelin was interrupted by an Akt inhibitor. Protein levels of p-AKT; Bcl-2; Bax; and caspase 3, 8, and 9 were also detected.Results: Aspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by ghrelin pretreatment in Con A-induced hepatitis. Inflammatory cytokines were significantly reduced by ghrelin pretreatment. Bcl-2; Bax; and caspase 3, 8, and 9 expression were also clearly affected by ghrelin pretreatment, compared with the Con A-treated group. However, the Akt kinase inhibitor reversed the decrease of Bax and caspase 3, 8, 9, and reduced the protein level of p-Akt and Bcl-2. Ghrelin activated the PI3K/Akt/Bcl-2 pathway and inhibited activation of autophagy.Conclusion: Our results demonstrate that ghrelin attenuates Con A-induced acute immune hepatitis by activating the PI3K/Akt pathway and inhibiting the process of autophagy, which might be related to inhibition of inflammatory cytokine release, and prevention of hepatocyte apoptosis. These effects could be interrupted by an Akt kinase inhibitor.Keywords: PI3K/Akt pathway, autophagy, inflammation, apoptosis

Youtao Xie, Hongqin Li, Chuanxian Ding, Xuebin Zheng, Kai Li Shanghai Institute of Ceramics, Key Laboratory of Inorganic Coating Materials, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: Calcium silicate (CS) ceramic is a good coating candidate for biomedical implants to improve biocompatibility and accelerate early osseo-integration. However, the poor fracture toughness and wear resistance of this ceramic material restricts the long-term performance of implants. In this study, graphene plates (GPs) were used as reinforcement to improve the mechanical properties of CS coating. Composite coating containing 1.5 weight % GPs was prepared by vacuum plasma spraying technology. The good survival of the GPs in the composite coating was demonstrated by Raman analysis, although the defects of the GPs were increased after plasma spraying. Effects of the GPs’ adoption on the microstructure of the coating were studied by scanning electron microscopy and transmission electron microscopy. Results showed that the GPs were homogenously distributed in the CS grains interface or enwrapped on the particles, and exhibited good wetting behavior with the CS matrix. The wear properties of the composite coating were obviously enhanced by the reinforcement of GPs. The reinforcement mechanism was attributed to the enhanced micro-hardness and interfacial bonding of the particles in the coating. In vivo experiments demonstrated that the composite coating possessed similarly good biocompatibility compared to pure CS coating. The bone-implant contact ratio reached 84.3%±7.4% for GPs/CS coating and 79.6%±9.4% for CS coating after 3 months’ implantation.Keywords: graphene plates, coating, microstructure, wear resistance, biocompatibility

Four lanthanide complexes with 8-hydroxyquinoline-2-aldehyde-2-hydrazinopyridine (H-L 1 ), 8-hydroxyquinoline-2-aldehyde-2-hydrazimidazole (H-L 2 ): [Sm(L 1 ) 2 ][Sm(L 1 )(NO 3 ) 3 ]·CHCl 3 ·2CH 3 OH (1), [Gd(L 1 ) 2 ][Gd(L 1 )(NO 3 ) 3 ]·CHCl 3 ·2CH 3 OH (2), [Sm(L 2 )(NO 3 ) 2 ] 2 ·CH 3 OH (3), and [Eu(L 2 )(NO 3 ) 2 ] 2 ·CH 3 OH (4) were synthesized and characterized. In vitro cytotoxicity evaluation showed that the ligands and four lanthanide complexes exhibited cytotoxicity to the five tested tumor cell lines. Among them, complex 1 showed the best antiproliferative activity against NCI-H460 tumor cells. Mechanistic studies demonstrated that complex 1 arrested the cell cycle of NCI-H460 cells in G1 phase and induced mitochondria-mediated apoptosis, which resulted in the loss of mitochondrial membrane potential, enhanced intracellular Ca 2+ levels and reactive oxygen species generation. In addition, complex 1 affected the expression levels of intracellular apoptosis-related proteins and activated the caspase-3/9 in NCI-H460 cells. Therefore, complex 1 is a potential anticancer agent., (© 2024 Wiley Periodicals LLC.)

Excessive fluoride ion (F - ) in the environment can affect health and even endanger life when ingested by the human body. However, most fluoride probes have the disadvantages of low sensitivity and long detection time. Herein, fluorescent probe 3a is successfully synthesized by linking two acetylenyltrimethylsilyl groups at both ends of the fluorinated benzothiadiazole core. After the addition of F - to 3a, the emission at 436 nm is significantly quenched and slightly blue-shifted. It is confirmed by electrospray ionization high-resolution mass spectrometry (ESI-HRMS) and density functional theory calculations (DFT) that these changes are due to the F - triggered Si-C bond cleavage and the subsequent inactivation of intramolecular charge transfer (ICT). The detection limit and response time of probe 3a for F - are 10 -8 mol/L and 25 s, respectively. Importantly, fluorescent material 3a can be processed into portable test tools for the visual detection of fluoride ion., 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 B.V. All rights reserved.)

The spine grapes (Vitis davidii Foëx.) are wild grape species that grow in southern China, and can be used for table grapes, juicing and winemaking. To systematically investigate the flavor profiles of spine grapes, flavonoids and volatile compounds were detected in five spine grape varieties (Seputao, Ziqiu, Miputao, Tianputao and Baiputao) using HPLC-QqQ-MS/MS and GC-MS. The content of flavonoids highly depended on the variety, such as the total concentrations of anthocyanins (91.43-328.85 mg/kg FW) and flavonols (33.90 to 83.16 mg/kg FW). The volatile compounds with higher odor active value were selected to describe the aroma of spine grapes. Hexanal, (E)-2-hexenal and (E, Z)-2,6-nonadienal contributed to the higher herbaceous flavor to Baiputao and Ziqiu. β-Damascenone and (E)-2-nonenal gave Baiputao a flavor with more floral, fruity and earthy. Their characteristic flavor compounds were subsequently revealed using multivariate statistical analysis. The results helped producers to further develop and utilize the spine grapes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cognitive deficits are long-lasting consequences of drug use, yet the convergent mechanism by which classes of drugs with different pharmacological properties cause similar deficits is unclear. We find that both phencyclidine and methamphetamine, despite differing in their targets in the brain, cause the same glutamatergic neurons in the medial prefrontal cortex of male mice to gain a GABAergic phenotype and decrease expression of their glutamatergic phenotype. Suppressing drug-induced gain of GABA with RNA-interference prevents appearance of memory deficits. Stimulation of dopaminergic neurons in the ventral tegmental area is necessary and sufficient to produce this gain of GABA. Drug-induced prefrontal hyperactivity drives this change in transmitter identity. Returning prefrontal activity to baseline, chemogenetically or with clozapine, reverses the change in transmitter phenotype and rescues the associated memory deficits. This work reveals a shared and reversible mechanism that regulates the appearance of cognitive deficits upon exposure to different drugs., (© 2024. The Author(s).)

The global surge in antibiotic resistance genes (ARGs) presents a serious public health challenge. While methods like metagenomic analysis and qPCR arrays have been instrumental in investigating ARG distributions and dynamics, the vast diversity of ARGs often complicates effective monitoring and risk assessment. Here, we developed a High-Risk ARGs (HRA) chip based on high-capacity quantitative PCR array targeting previously identified high-risk ARGs. These ARGs are known to be prevalent in human-related environments, exhibit gene mobility, and are present in ESKAPE pathogens. The HRA chip include 101 primer sets and the 16S rRNA gene as a reference. These primer sets consist of 34 obtained from previous studies, and 67 newly designed primer sets which were validated in silico and experimentally. Absolute quantification of targeted ARGs is accomplished by generating standard curves for all ARGs with serially ten-fold diluted mixed plasmids containing targeted ARG sequences. The amplification efficiencies of all ARGs exceed 99% via plasmid template dilution tests, suggesting high reliability in quantification. The performance of HRA chip is further evaluated by practical applications in environmental samples from wastewater treatment plants (WWTPs) and soils with various land use types and fertilization regimes. The results indicate the dynamics of high-risk ARGs during wastewater treatment process, and reveal the profiles of soil high-risk ARGs which is distinct from those derived via metagenomic approaches. These findings highlight the potentials of HRA Chip in the evaluation of anthropogenic impacts on the environmental resistome with a more focused spectrum of high-risk ARGs. Overall, the HRA Chip emerges as a powerful and efficient high-throughput tool for rapid detection and quantification of high-risk ARGs, facilitating comprehensive profiling of high-risk resistomes in environmental samples which is essential for human health risk assessment of ARGs., 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 Ltd. All rights reserved.)

This study aimed to clarify how microclimate diversity altered volatilomics in Cabernet Sauvignon grapes and wines. Four row-oriented vineyards were selected, and metabolites of grapes and wines were determined from separate canopy sides. Results showed that shaded sides received 59% of the solar radiation and experienced 55% of the high-temperature days compared to the exposed sides on average. Grape primary metabolites were slightly affected by the canopy side. Herbaceous aromas were consistently more abundant in grapes and wines from shaded clusters. Heat-stressed canopy sides accelerated terpenoid loss and increased norisoprenoid levels in grapes, while β-damascenone in north-side wines was 13%-32% higher than that in south-side wines of the east-west vineyard. The northeast-southwest vineyard showed the most notable variation in taste and aroma sensory scores, with four parameters significantly different. There were 32 aroma series identified in wines, and banana, pineapple, and strawberry odors were highly correlated with aroma sensory score., 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 Ltd. All rights reserved.)

Autism spectrum disorders (ASD) can be caused by environmental factors. These factors act early in the development of the nervous system and induce stereotyped repetitive behaviors and diminished social interactions, among other outcomes. Little is known about how these behaviors are produced. In pregnant women, delivery of valproic acid (VPA) (to control seizure activity or stabilize mood) or immune activation by a virus increases the incidence of ASD in offspring. We found that either VPA or Poly Inosine:Cytosine (which mimics a viral infection), administered at mouse embryonic day 12.5, induced a neurotransmitter switch from GABA to glutamate in PV- and CCK-expressing interneurons in the medial prefrontal cortex by postnatal day 10. The switch was present for only a brief period during early postnatal development, observed in male and female mice at postnatal day 21 and reversed in both males and females by postnatal day 30. At postnatal day 90, male mice exhibited stereotyped repetitive behaviors and diminished social interaction while female mice exhibited only stereotyped repetitive behavior. Transfecting GAD1 in PV- and CCK-expressing interneurons at postnatal day 10, to reintroduce GABA expression, overrode the switch and prevented expression of autistic-like behavior. These findings point to an important role of neurotransmitter switching in mediating the environmental causes of autism., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: This study was intended to investigate the correlation between depression and suicidal ideation among Chinese college students during the COVID-19 pandemic and the potential mediating roles of chronotype and sleep quality in this relationship ., Methods: A sample of 4,768 college students was selected from four institutions in Anhui Province, China, and the study was conducted during the COVID-19 pandemic (November to December 2020) using a stratified, cluster, multi-stage sampling method. This study used the two-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms, the Morningness-Eveningness Questionnaire 19 (MEQ-19) to determine individual sleep chronotypes (i.e., morning or evening preference), and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Participants were asked about suicidal ideation. MPLUS 8.3 software was used to analyze the mediating effect of chronotype and sleep quality on the relationship between depression and suicidal ideation., Results: During the COVID-19 pandemic, the prevalence of suicidal ideation among Chinese college students was 5.4%. Depression was inversely correlated with chronotype (beta = - 0.346, P < 0.01) and positively correlated with sleep quality (beta = 0.846, P < 0.001), indicating that students experiencing depressive symptoms were more likely to have a later chronotype and poor sleep quality. A later chronotype (beta = - 0.019, P < 0.05) and poor sleep quality (beta = 0.066, P < 0.01) predicted suicidal ideation. Depression emerged as a direct and significant risk factor for suicidal ideation (effect value = 0.535, 95% confidence interval: 0.449 ~ 0.622). Chronotype and sleep quality were found to have potential mediating effects on the relationship between depression and suicidal ideation; however, the chain-mediating effect of chronotype and sleep quality was not statistically significant., Conclusions: Our findings suggest that during the COVID-19 pandemic, depression can precipitate suicidal ideation through its influence on sleep chronotype and quality. These compelling findings highlight the urgency of early intervention strategies intended to mitigate suicidal thoughts, particularly among students exhibiting depressive symptoms, who experience disrupted sleep patterns and poor sleep quality., (© 2024. The Author(s).)

Objective: To evaluate the clinical effectiveness of antibiotic bone cement combined with the lobulated perforator flap based on the descending branch of the lateral circumflex femoral artery (d-LCFA) in the treatment of infected traumatic tissue defects in the foot, in accordance with the Enhanced Recovery after Surgery (ERAS) concept., Methods: From December 2019 to November 2022, 10 patients with infected traumatic tissue defects of the foot were treated with antibiotic bone cement combined with the d-LCFA lobulated perforator flap. The cohort comprised 6 males and 4 females, aged 21 to 67 years. Initial infection control was achieved through debridement and coverage with antibiotic bone cement, requiring one debridement in nine cases and two debridements in one case. Following infection control, the tissue defects were reconstructed utilizing the d-LCFA lobulated perforator flap, with the donor site closed primarily. The flap area ranged from 12 cm×6 cm to 31 cm×7 cm. Postoperative follow-up included evaluation of flap survival, donor site healing, and ambulatory function of the foot., Results: The follow-up period ranged from 7 to 24 months, averaging 14 months. Infection control was achieved successfully in all cases. The flaps exhibited excellent survival rates and the donor site healed by first intention. Based on the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale, pain and function were evaluated as excellent in 3 cases, good in 5 cases, and moderate in 2 cases., Conclusion: The application of antibiotic bone cement combined with the d-LCFA lobulated perforator flap is an effective treatment for infected traumatic tissue defects of the foot with the advantages of simplicity, high repeatability, and precise curative effects. The application of the d-LCFA lobulated perforator flap in wound repair causes minimal damage to the donor site, shortens hospital stays, lowers medical expenses, and accelerates patient rehabilitation, aligning with the ERAS concept. Therefore, it is a practice worth promoting in clinical use., (© 2024. The Author(s).)

Background: The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear., Results: Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism., Conclusions: In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments., (© 2024. The Author(s).)

Introduction: The P2Y 14 receptor (P2Y 14 R), a member of the G protein-coupled receptor family, is activated by extracellular nucleotides. Due to its involvement in inflammatory, immunological and other associated processes, P2Y 14 R has emerged as a promising therapeutic target. Despite lacking a determined three-dimensional crystal structure, the homology modeling technique based on closely related P2Y receptors' crystallography has been extensively utilized for developing active compounds targeting P2Y 14 R. Recent discoveries have unveiled numerous highly effective and subtype-specific P2Y 14 R inhibitors. This study presents an overview of the latest advancements in P2Y 14 R inhibitors., Areas Covered: This review presents an overview of the advancements in P2Y 14 R inhibitor research over the past five years, encompassing new patents, journal articles, and highlighting the therapeutic prospects inherent in these compounds., Expert Opinion: The recent revelation of the vast potential of P2Y 14 R inhibitors has led to the development of novel compounds that exhibit promising capabilities for the treatment of sterile inflammation of the kidney, potentially diabetes, and asthma. Despite being a relatively nascent class of compounds, certain members have already exhibited their capacity to surmount specific challenges posed by conventional P2Y 14 R inhibitors. Targeting P2Y 14 R through small molecules may present a promising therapeutic strategy for effectively managing diverse inflammatory diseases.

We present a novel solid form of monascin, an azaphilonoid derivative extracted from Monascus purpureus-fermented rice. The crystal structure, C 21 H 26 O 5 , was characterized by single-crystal X-ray diffraction and belongs to the orthorhombic space group P2 1 2 1 2 1 . To gain insight into the electronic properties of the short contacts in the crystalline state of monascin, we utilized the Experimental Library of Multipolar Atom Model 2 (ELMAM2) database to transfer the electron density of monascin in its crystalline state. Hirshfeld surface analysis, fingerprint analysis, electronic properties and energetic characterization reveal that intermolecular C-H...O hydrogen bonds play a crucial role in the noncovalent bonding interactions by connecting molecules into two- and three-dimensional networks. The molecular electrostatic potential (MEP) map of the monascin molecule demonstrates that negatively charged regions located at four O atoms are favoured binding sites for more positively charged amino acid residues during molecular recognition. In addition, powder X-ray diffraction confirms that no transformation occurs during the crystallization of monascin.

An efficient and operationally simple method for the synthesis of β-keto sulfones through the BF 3 ·OEt 2 -promoted reaction of alkynes and sodium sulfinates is developed. With its facile and selective access to the targets, it features good functional group compatibility, mild conditions, easily available starting materials, and good yields. Notably, the reaction does not require metal catalysts or chemical reagents with pungent odors.

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [ M ( Q 1 , Q 3 )] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P >0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P =0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference ( P =0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission ( OR =0.126, 95% CI : 0.025-0.629). FLT3 mutation was not conducive to morphological remission ( OR =5.832, 95% CI : 1.778-19.124) and negative MRD ( OR =4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

Objectives: To study the diagnosis, treatment, and complications of hypophosphatemic rickets (HR) in children, explore effectiveness evaluation indicators for the disease, and understand the pattern in height growth among these patients., Methods: A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022., Results: Among the 85 children with HR, there were 46 males (54%) and 39 females (46%). The age at initial diagnosis ranged from 6 months to 13 years and 9 months, with a median age of 2.75 years. The average height standard deviation score was -2.0±1.1. At initial diagnosis, children exhibited reduced blood phosphate levels and elevated alkaline phosphatase (ALP), with 99% (84/85) presenting with lower limb deformities. The positive rate for PHEX gene mutations was 93% (55/59). One year post-treatment, there was a significant reduction in ALP levels and the gap between the lower limbs ( P <0.05). The fastest height growth occurred in the first year after treatment, at 8.23 cm/year, with a peak height velocity (PHV) phase lasting about two years during puberty. The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children. Major complications included nephrocalcinosis and hyperparathyroidism. The incidence rate of nephrocalcinosis in the first year after treatment was 55% (22/40), which increased with the duration of the disease ( P <0.001); an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis ( OR =1.740, P <0.001). The incidence of hyperparathyroidism in the first year after treatment was 64% (27/42)., Conclusions: For children presenting with lower limb deformities, short stature, and slow growth, early testing for blood levels of phosphate, calcium, and ALP, along with imaging examinations of the lower limbs, can aid in the early diagnosis of HR. Genetic testing may be utilized for definitive confirmation when necessary. ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR. Compared to normal children, children with HR demonstrate a lower height increase during the PHV phase, necessitating close follow-up and timely adjustment of treatment plans Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 677-682 .

Introduction: Workplace violence against healthcare workers has become a serious global public health problem. The incidence of workplace violence towards Psychiatric nurses is higher than in all other medical institutions, up to 84.2% per year. It not only negatively affects many aspects of healthcare workers' lives, but also destroys the harmony of the nurse-patient relationship and reduces the quality of nursing care. The number of psychiatric nurses in China was approximately 96,000, far lower than most other countries and unable to meet the growing demand for mental health. However, the increase in workplace violence has future exacerbates the current shortage of nurses. Therefore, it is necessary to develop effective strategies to prevent psychiatric nurses from suffering from workplace violence, thereby to reduce nurse turnover and improve the quality of nursing care. A comprehensive understanding of psychiatric nurses' preferences and priorities for preventing workplace violence is an important prerequisite before formulating strategies and taking measures. Unfortunately, to date, no research has investigated the psychiatric nurses' preferences. Therefore, a discrete choice experiment (DCE) is conducting to explore the psychiatric nurses' preferences for workplace violence prevention. This article reports on methodological details of the DCE., Methods and Analysis: Six attributes were developed through a literature review, one-on-one interviews and focus group discussions. D-efficient design in NGENE was used to generate choice sets. SPSS 24.0 will be used for descriptive analysis of social Demography, and Stata 16.0 will be used for analysis of DCE data. A multinomial logit model will be used to preliminarily explore trade-offs between workplace violence prevention characteristics included in the choice tasks. Then, in a mixed logit model, we plan to choose some arbitrarily defined base violence prevention program and will use the nlcom command to evaluate the probability of an alternative violence prevention program., Ethics and Dissemination: The study was approved by the relevant ethics committees. Our findings will emphasize priority intervention areas based on the preferences of psychiatric nurses and provide references for hospitals to develop and improve workplace violence prevention strategies. The results will be shared through seminars, policy briefs, peer-reviewed journal articles and online blogs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xie, Li, Tao and Yang.)

Aims: Apply established cerebrospinal fluid (CSF) and serum biomarkers and novel combined indicators based on the amyloid/tau/neurodegeneration (ATN) framework to improve diagnostic and prognostic power in patients with rapidly progressive dementias (RPDs)., Methods: CSF and serum biomarkers of Alzheimer's disease (AD) common neuropathology including Aβ42, Aβ40, p-Tau, and t-Tau were measured in cognitively normal (CN) controls (n = 33) and three RPD groups with rapidly progressive AD (rpAD, n = 23), autoimmune encephalitis (AE, n = 25), and Creutzfeldt-Jakob disease (CJD, n = 28). Logistic regression and multiple linear regression were used for producing combined indicators and prognostic assessment, respectively, including A&T, A&N, T&N, A&T&N, etc. RESULTS: Combined diagnostic indicator with A&T&N had the potential for differentiating AE from other types of RPDs, identifying 62.51% and 75% of AE subjects based on CSF and serum samples, respectively, compared to 39.13% and 37.5% when using autoantibodies. CSF t-Tau was associated with survival in the CJD group (adjusted R-Square = 0.16, p = 0.02), and its prognosis value improved when using combined predictors based on the ATN framework (adjusted R-Square = 0.273, p = 0.014)., Conclusion: Combined indicators based on the ATN framework provide a novel perspective for establishing biomarkers for early recognition of RPDs due to treatment-responsive causes., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

To introduce the modified pharyngeal flap of bilateral muscular rings (BMR), and to discuss the clinical effect of this operation in the correction of moderate and severe velopharyngeal insufficiency. The clinical data of 18 patients who underwent BMR surgery in the Department of Craniofacial Plastic and Aesthetic Surgery, School of Stomatology, The Fourth Military Medical University from May 2019 to July 2021 were retrospectively analyzed. There were 10 males and 8 females, with a median age of 8.5 years (aged from 5 to 34 years). The patients were diagnosed preoperatively with moderate to severe velopharyngeal insufficiency (velopharyngeal closure ratio<0.7). The results of nasopharyngoscopy and speech assessment were compared and analyzed before operation and at the follow-up 6 months after the operation to evaluate the changes in velopharyngeal function and speech. Eighteen patients underwent BMR, 4 patients had snoring (the symptom disappeared after a few weeks in 3 cases), and 2 patients had local erosion of the wound, which delayed healing. Postoperative nasopharyngoscopy showed that all patients achieved comparatively complete velopharyngeal closure, some patients got enhanced lateral pharyngeal wall motility, and all patients got active motility of posterior pharyngeal wall flap. The postoperative speech assessment was significantly improved compared with that before the operation. The preoperative median score was 9 (range 7-12), and the postoperative median score was 2 (range 0-4). The statistical analysis was performed by paired non-parametric Wilcoxon signed rank test, and the difference was statistically significant ( P <0.001). BMR is a reliable method for the treatment of moderate and severe velopharyngeal insufficiency. This technique can achieve functional contraction of the full circumference of the ventilator while preserving the obstructive effect of the posterior pharyngeal wall flap, which is helpful to balance nasal ventilation and velopharyngeal closure and improve the velopharyngeal function of patients.

Background: Androgenetic alopecia (AGA) is a prevalent type of hair loss that impacts individuals of both genders. Platelet-rich plasma (PRP) and minoxidil have been employed as therapeutic interventions for AGA, yet the efficacy of their concurrent use remains ambiguous., Objective: To perform a comprehensive review and meta-analysis aimed at evaluating the effectiveness of platelet-rich plasma (PRP) in combination with minoxidil for the treatment of androgenetic alopecia (AGA)., Methods: We conducted a comprehensive search of the databases PubMed, Embase, Web of Science, and Cochrane Library, encompassing their complete records up until December 2023. Eligible studies were randomized controlled trials that compared the combination of PRP and minoxidil with minoxidil or PRP alone in patients with AGA. The primary outcome measure was the change in hair growth as assessed by the hair density or hair thickness. Secondary outcome measures included patient satisfaction, and global photographic assessment., Results: A total of 6 studies involving 343 participants were included in this meta-analysis. The results showed that PRP combined with minoxidil significantly improved hair growth compared to minoxidil or PRP alone. The pooled analysis demonstrated a significant increase in hair density (weighted mean difference [WMD] = 9.14; 95% confidence interval [CI]: 6.57-11.70) and hair diameter (WMD = 4.72; 95% CI 3.21-6.23) in the PRP combined with minoxidil group. Moreover, patients receiving PRP combined with minoxidil reported higher satisfaction rates compared to those using minoxidil or PRP alone., Conclusions: This meta-analysis suggests that PRP combined with minoxidil is an effective treatment for AGA, providing significant improvement in hair growth and patient satisfaction., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Most of the materials studied as catalysts in the electro-Fenton system are variants of iron oxide or iron hydroxide. However, iron-based catalysts often exhibit weak catalytic capabilities under neutral and alkaline conditions. In this work, we synthesized three cobalt based bimetallic oxides, Co 2 CuOx, Co 2 AlOx, and Co 2 NiOx, using hydrothermal method and evaluated them as catalysts for the heterogeneous electro-Fenton system to remove 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP) and Methylisothiazolinone [2-methyl-4-isothiazolin-3-one] (MIT). Co 2 NiOx has the highest catalytic degradation activity for HEDP, and Co 2 CuOx has the best catalytic degradation effect for MIT. Based on characterization results of the catalysts, the reasons for the differences in the pollutant removal efficiency were analysed, and the optimal pH for the three cobalt based oxides to remove HEDP and MIT was investigated. The results showed that the optimal pH values of the three cobalt based bimetallic oxides are not only influenced by the second metal type, but also by the properties of pollutants. Therefore, suitable cobalt based catalysts can be selected based on the different properties of pollutants, or the composition of cobalt based catalysts can be adjusted to meet the different pH requirements of target wastewater. The three cobalt based bimetallic oxides exhibited good degradation of HEDP and MIT under neutral conditions, which to some extent solved the problem of narrow pH range in the practical application of the electro-Fenton process.

Six ionone glycosides ( 1 - 3 and 5 - 7 ), including three new ones, named capitsesqsides A-C ( 1 - 3 ), together with an eudesmane sesquiterpenoid glycoside ( 4 ) and three known triterpenoid saponins ( 8 - 10 ) were isolated from Rhododendron capitatum . The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.

Biofilms attached to submerged macrophytes play an important role in improving the water quality of the water environment supplemented with reclaimed water. In order to explore the effects of reclaimed water quality and submerged macrophyte species on the characteristics of an epiphytic bacterial community, different types of submerged macrophytes were selected as research objects in this study. 16S rRNA high-throughput sequencing technology was used on the epiphytic bacteria and the surrounding environmental samples to analyze the bacterial community structure and functional genes. The results showed that approximately 20%-35% of the nitrogen and phosphorus nutrients were absorbed and utilized in the water environment supplemented with reclaimed water. However, the COD, turbidity, and chroma of the downstream water were significantly increased. The bacterial community of the biofilms attached to submerged macrophytes was significantly different from that in the surrounding environment (soil, sediment, and water body) and in the activated sludge that was treated by reclaimed water. In terms of bacterial community diversity, the richness and diversity were significantly lower than those of soil and sediment but higher than those of plankton bacteria in water. In terms of bacterial community composition, dominant genera and corresponding abundances were also different from those of other samples. The main dominant bacterial genera were Sphingomonas , Aeromonas , Pseudomonas, and Acinetobacter , accounting for 7%-40%, respectively. Both macrophyte species and the quality of reclaimed water (BOD 5 , TN, NH 4 + -N, and TP) could affect the bacterial community. However, the effect of water quality of the bacterial community was greater than that of macrophytes species. Additionally, the quality of reclaimed water also affected the abundance of functional genes in the bacterial community, and the relative abundance of nitrogen and phosphorus cycling functional genes was higher in areas with higher nitrogen and phosphorus concentrations.

Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer.

The mitochondrial (mt) genome can provide data for phylogenetic analyses and evolutionary biology. Herein, we sequenced and annotated the complete mt genome of Ergasilus anchoratus. This mt genome was 13852 bp long and comprised 13 protein-coding genes (PCGs), 22 tRNAs and 2 rRNAs. All PCGs used the standard ATN start codons and complete TAA/TAG termination codons. A majority of tRNA genes exhibited standard cloverleaf secondary structures, with the exception of one tRNA that lacked the TψC arm (trnC), and three tRNAs that lacked the DHU arm (trnR, trnS1 and trnS2). Phylogenetic analyses conducted using Bayesian inference (BI) and maximum likelihood (ML) methods both supported Ergasilidae as a monophyletic family forming a sister group to Lernaea cyprinacea and Paracyclopina nana. It also supported the monophyly of orders Calanoida, Cyclopoida, and Siphonostomatoida; and the monophyly of families Harpacticidae, Ergasilidae, Diaptomidae, and Calanidae. The gene orders of E. anchoratus and Sinergasilus undulatus were identical, which represents the first instance of two identical gene orders in copepods. More mt genomes are needed to better understand the phylogenetic relationships within Copepoda in the future., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Weed control is essential for agricultural floor management in vineyards and the inter-row mulching is an eco-friendly practice to inhibit weed growth via filtering out photosynthetically active radiation. Besides weed suppression, inter-row mulching can influence grapevine growth and the accumulation of metabolites in grape berries. However, the complex interaction of multiple factors in the field challenges the understanding of molecular mechanisms on the regulated metabolites. In the current study, black geotextile inter-row mulch (M) was applied for two vintages (2016-2017) from anthesis to harvest. Metabolomics and transcriptomics analysis were conducted in two vintages, aiming to provide insights into metabolic and molecular responses of Cabernet Sauvignon grapes to M in a semi-arid climate., Results: Upregulation of genes related to photosynthesis and heat shock proteins confirmed that M weakened the total light exposure and grapes suffered heat stress, resulting in lower sugar-acid ratio at harvest. Key genes responsible for enhancements in phenylalanine, glutamine, ornithine, arginine, and C 6 alcohol concentrations, and the downward trend in ε-viniferin, anthocyanins, flavonols, terpenes, and norisoprenoids in M grapes were identified. In addition, several modules significantly correlated with the metabolic biomarkers through weighted correlation network analysis, and the potential key transcription factors regulating the above metabolites including VviGATA11, VviHSFA6B, and VviWRKY03 were also identified., Conclusion: This study provides a valuable overview of metabolic and transcriptomic responses of M grapes in semi-arid climates, which could facilitate understanding the complex regulatory network of metabolites in response to microclimate changes., (© 2024. The Author(s).)

Stable matching of neurotransmitters with their receptors is fundamental to synapse function and reliable communication in neural circuits. Presynaptic neurotransmitters regulate the stabilization of postsynaptic transmitter receptors. Whether postsynaptic receptors regulate stabilization of presynaptic transmitters has received less attention. Here, we show that blockade of endogenous postsynaptic acetylcholine receptors (AChR) at the neuromuscular junction destabilizes the cholinergic phenotype in motor neurons and stabilizes an earlier, developmentally transient glutamatergic phenotype. Further, expression of exogenous postsynaptic gamma-aminobutyric acid type A receptors (GABA A receptors) in muscle cells stabilizes an earlier, developmentally transient GABAergic motor neuron phenotype. Both AChR and GABA A receptors are linked to presynaptic neurons through transsynaptic bridges. Knockdown of specific components of these transsynaptic bridges prevents stabilization of the cholinergic or GABAergic phenotypes. Bidirectional communication can enforce a match between transmitter and receptor and ensure the fidelity of synaptic transmission. Our findings suggest a potential role of dysfunctional transmitter receptors in neurological disorders that involve the loss of the presynaptic transmitter., Competing Interests: Competing interests statement:The authors declare no competing interest.

Objective: To explore clinical efficacy of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures by Meta analysis., Methods: Controlled clinical studies on autogenous bone transplantation and bone substitutes in treating tibial plateau fractures published on PubMed,Web of Science,CNKI,Wanfang and other databases from January 2005 to August 2022 were searched by computer. Literature screening and data extraction were performed according to randomized controlled trial(RCT),and the quality of RCT were evaluated by using intervention meta-analysis criteria in Cochrane manual. Meta-analysis of joint depression,secondary collapse rate of articular surface,blood loss,operative time and infection rate between two methods were performed by Rev Man 5.3 software., Results: Seven RCT studies (424 patients) were included,296 patients in bone replacement group and 128 patients in autograft group. Operative time [ MD =-16.79,95% CI (-25.72,-7.85), P =0.000 2] and blood loss[ MD =-70.49,95% CI (-79.34,-61.65), P <0.000 01] between two groups had statistically differences,while joint depression[ MD =-0.17,95% CI (-0.91,0.58), P =0.66],secondary collapse rate of joint surface[ RR =-0.74, 95% CI (0.35,1.57), P =0.43],infection rate [ RR =1.21,95% CI (0.31,4.70), P =0.78] between two groups had no differences., Conclusion: The effects of bone substitute and autograft for the treatment of tibial plateau fracture have similar effects in terms of joint depression,secondary articular surface collapse rate and infection rate. However,compared with autologous bone transplantation,bone replacement could reduce blood loss and shorten operation time.

Overgeneralization of fear to harmless situations is a core feature of anxiety disorders resulting from acute stress, yet the mechanisms by which fear becomes generalized are poorly understood. In this study, we show that generalized fear in mice results from a transmitter switch from glutamate to γ-aminobutyric acid (GABA) in serotonergic neurons of the lateral wings of the dorsal raphe. Similar change in transmitter identity was found in the postmortem brains of individuals with posttraumatic stress disorder (PTSD). Overriding the transmitter switch in mice prevented the acquisition of generalized fear. Corticosterone release and activation of glucocorticoid receptors mediated the switch, and prompt antidepressant treatment blocked the cotransmitter switch and generalized fear. Our results provide important insight into the mechanisms involved in fear generalization.

Despite the previous preparation of aconine hydrochloride monohydrate (AHM), accurate determination of the crystal's composition was hindered by severely disordered water molecules within the crystal. In this study, we successfully prepared a new dihydrate form of the aconine hydrochloride [C 25 H 42 NO 9 + Cl - ·2(H 2 O), aconine hydrochloride dihydrate (AHD)] and accurately refined all water molecules within the AHD crystal. Our objective is to elucidate both water-chloride and water-water interactions in the AHD crystal. The crystal structure of AHD was determined at 136 K using X-ray diffraction and a multipolar atom model was constructed by transferring charge-density parameters to explore the topological features of key short contacts. By comparing the crystal structures of dihydrate and monohydrate forms, we have observed that both AHD and AHM exhibit identical aconine cations, except for variations in the number of water molecules present. In the AHD crystal, chloride anions and water molecules serve as pivotal connecting hubs to establish three-dimensional hydrogen bonding networks and one-dimensional hydrogen bonding chain; both water-chloride and water-water interactions assemble supramolecular architectures. The crystal packing of AHD exhibits a complete reversal in the stacking order compared to AHM, thereby emphasizing distinct disparities between them. Hirshfeld surface analysis reveals that H···Cl - and H···O contacts play a significant role in constructing the hydrogen bonding network and chain within these supramolecular architectures. Furthermore, topological analysis and electrostatic interaction energy confirm that both water-chloride and water-water interactions stabilize supramolecular architectures through electrostatic attraction facilitated by H···Cl - and H···O contacts. Importantly, these findings are strongly supported by the existing literature evidence. Consequently, navigating these water-chloride and water-water interactions is imperative for ensuring storage and safe processing of this pharmaceutical compound., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Calcium sulfate and calcium sulfate-based biomaterials have been widely used in non-load-bearing bone defects for hundreds of years due to their superior biocompatibility, biodegradability, and non-toxicity. However, lower compressive strength and rapid degradation rate are the main limitations in clinical applications. Excessive absorption causes a sharp increase in sulfate ion and calcium ion concentrations around the bone defect site, resulting in delayed wound healing and hypercalcemia. In addition, the space between calcium sulfate and the host bone, resulting from excessively rapid absorption, has adverse effects on bone healing or fusion techniques. This issue has been recognized and addressed. The lack of sufficient mechanical strength makes it challenging to use calcium sulfate and calcium sulfate-based biomaterials in load-bearing areas. To overcome these defects, the introduction of various inorganic additives, such as calcium carbonate, calcium phosphate, and calcium silicate, into calcium sulfate is an effective measure. Inorganic materials with different physical and chemical properties can greatly improve the properties of calcium sulfate composites. For example, the hydrolysis products of calcium carbonate are alkaline substances that can buffer the acidic environment caused by the degradation of calcium sulfate; calcium phosphate has poor degradation, which can effectively avoid the excessive absorption of calcium sulfate; and calcium silicate can promote the compressive strength and stimulate new bone formation. The purpose of this review is to review the poor properties of calcium sulfate and its complications in clinical application and to explore the effect of various inorganic additives on the physicochemical properties and biological properties of calcium sulfate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Lun, Li, Li, Mou, Li, Zhu, Li and Hu.)

Objective. Dynamic functional network connectivity (dFNC), based on data-driven group independent component (IC) analysis, is an important avenue for investigating underlying patterns of certain brain diseases such as schizophrenia. Canonical polyadic decomposition (CPD) of a higher-way dynamic functional connectivity tensor, can offer an innovative spatiotemporal framework to accurately characterize potential dynamic spatial and temporal fluctuations. Since multi-subject dFNC data from sliding-window analysis are also naturally a higher-order tensor, we propose an innovative sparse and low-rank CPD (SLRCPD) for the three-way dFNC tensor to excavate significant dynamic spatiotemporal aberrant changes in schizophrenia. Approach. The proposed SLRCPD approach imposes two constraints. First, the L 1 regularization on spatial modules is applied to extract sparse but significant dynamic connectivity and avoid overfitting the model. Second, low-rank constraint is added on time-varying weights to enhance the temporal state clustering quality. Shared dynamic spatial modules, group-specific dynamic spatial modules and time-varying weights can be extracted by SLRCPD. The strength of connections within- and between-IC networks and connection contribution are proposed to inspect the spatial modules. K-means clustering and classification are further conducted to explore temporal group difference. Main results. 82 subject resting-state functional magnetic resonance imaging (fMRI) dataset and opening Center for Biomedical Research Excellence (COBRE) schizophrenia dataset both containing schizophrenia patients (SZs) and healthy controls (HCs) were utilized in our work. Three typical dFNC patterns between different brain functional regions were obtained. Compared to the spatial modules of HCs, the aberrant connections among auditory network, somatomotor, visual, cognitive control and cerebellar networks in 82 subject dataset and COBRE dataset were detected. Four temporal states reveal significant differences between SZs and HCs for these two datasets. Additionally, the accuracy values for SZs and HCs classification based on time-varying weights are larger than 0.96. Significance. This study significantly excavates spatio-temporal patterns for schizophrenia disease., (© 2024 IOP Publishing Ltd.)