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Xiaomei Cui,1,2 Ting Zhang,2 Tao Xie,2 Fang-xi Guo,2 Yu-ying Zhang,2 Yuan-jia Deng,2 Qi Wang,1,2 Yi-xing Guo,1,2 Ming-hua Dong,1,2 Xiao-ting Luo1,3 1Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 2School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of General Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Xiao-ting Luo, Golden Campus of Gannan Medical University, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Tel +86 13677975578, Email xtluo76@163.comAbstract: Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut–brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations. Keywords: blood pressure, metabolites, gut-brain, treatment

Xin Liu,1,* Miao Tang,2,* Tian-Yi He,1 Shuang Zhao,1 Hui-Zhou Li,1 Zhao Li,1 Yue-Xian Guo,3 Xiu-Li Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiu-Li Wang, Department of Anesthesiology, The Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, Hebei, 050051, People’s Republic of China, Tel +86-13313019968, Email wangxl311@126.comObjective: This study aimed to investigate the effect of resveratrol (Res) on paclitaxel (PTX)-induced cognitive impairment and elucidate the underlying molecular mechanisms.Methods: Morris Water Maze (MWM) test was used to evaluate the mice’s spatial learning and memory abilities. Western blotting was applied to detect protein expression of receptor-interacting protein (RIP3), mixed lineage kinase domain-like protein (MLKL), silencing information regulator 2 related enzyme 1 (SIRT1), peroxisome proliferator activated receptor coactivator-1 (PGC-1α), NADPH oxidase 2 (NOX2), NOX4, postsynaptic density zone 95 (PSD95), arginase-1 (Arg-1) and inducible nitric oxide synthase (iNOS). Immunofluorescence of RIP3, MLKL, Arg-1, Iba-1 and iNOS was conducted to observe the apoptosis of hippocampal cells and the polarization of microglia. qRT-PCR was performed to detect BDNF mRNA expressions. DHE staining was used to assess the level of oxidative stress response. Golgi-Cox staining and dendritic spine counting were applied to visualize synaptic structural plasticity. Postsynaptic density was performed by transmission electron microscope. ELISA was used to detect the contents of tumour necrosis factor alpha (TNF-α), IL-1β, IL-4, and IL-10.Results: PTX-induced cognitive impairment model was constructed after the application of PTX, represented as longer latency to platform and less platform crossing times over the whole period in PTX group. After Res treatment, the above indicators were reversed, indicating that cognitive function was improved. Moreover, Res reduced neuronal apoptosis and oxidative stress through SIRT1/PGC-1α pathway in mice, manifesting as down-regulated expression of RIP3, MLKL, NOX2 and NOX4. Meanwhile, Res increased the density of dendritic spines and the expression of PSD95 and BDNF, thereby ameliorating the PTX induced synaptic damage. Besides, M2 microglia was in the majority, eliciting the expression of anti-inflammatory cytokines IL-4 and IL-10 after Res treatment in PTX+Res group, while immunofluorescence images results demonstrated an decrease in the proportion of M2 microglia a following SIRT1 inhibitor EX-527.Conclusion: Res improves PTX-induced cognitive impairment in mice by activating SIRT1/PGC-1α pathways to regulate neuronal state and microglia cell polarization.Keywords: resveratrol, paclitaxel, SIRT1/PGC-1α, microglia, M2 polarization

Yu-Xiong Guo,1,2,* Hong-Xia Ma,1– 3,* Yu-Xin Zhang,2 Zhi-Hong Chen,2 Qiong-Xiang Zhai1,2 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 2Department of Pediatrics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiong-Xiang ZhaiDepartment of Pediatrics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Second Road, Yuexiu District, Guangzhou, 510080, People’s Republic of ChinaTel +86-2083827812-76222Fax +86-20-8328480Email zhaiqx_241@163.comBackground: Intellectual developmental disorders (IDD) generally refers to the persistent impairment of cognitive activities and mental retardation caused by physical damage to the brain or incomplete brain development. We aimed to explore its genetic causes.Methods: In this study, 21 IDD patients were recruited. The Gesell developmental scales (GDS) and Wechsler intelligence scale for children (WISC) were used to assess the impaired level of intellectual development for all probands. A superconducting MRI scanner (Philips AcsNT 3.0 T Philips, Best, The Netherlands) was used to perform a plain MRI scan of the skull on the probands. The whole-exome sequencing was carried out using next-generation sequencing in all probands and their families.Results: Eight had seizures and four had typical characteristics of autism. Pregnancy and delivery were uneventful except for three patients. Moderate IDD (52.4%) accounted for the majority. The abnormal MRI results included ventriculomegaly, pachygyria, broadening external cerebral space, abnormal signal change and agenesis of corpus callosum. Eleven variants were identified, including the variant in CREBBP, MECP2, HCFC1, ATRX, RAB39B, CLCN4, DYRK1A and CASKgenes. The function areas result of gene-positive group were compared to that of gene-negative group. Not significant (p> 0.05) items were revealed after this analysis.Conclusion: Eleven variants were identified, including the variant in CREBBP, MECP2, HCFC1, ATRX, RAB39B, CLCN4, DYRK1A and CASK genes. The function areas result of gene-positive group were not significantly different from the gene-negative group.Keywords: intellectual developmental disorders, gene variant, whole-exome sequencing

Ya-Ting Li,1,* Li-Fen Yang,1,* Zhuang-Gui Chen,1,* Li Pan,1 Meng-Qi Duan,1 Yan Hu,2 Cheng-bin Zhou,3 Yu-Xiong Guo2 1Pediatric Intensive Care Unit, Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 2Pediatric Intensive Care Unit, Department of Pediatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 3Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Fulminant myocarditis (FM) is a life-threatening disease in children. With a rapid, progressive course of deterioration, it causes refractory cardiorespiratory failure even with optimal clinical intervention. We present the case of a 9-year-old girl with FM complicated by cardiogenic shock, malignant arrhythmia, and refractory cardiac arrest. She received effective cardiopulmonary resuscitation, therapeutic hypothermia, and other supportive treatments. However, the patient rapidly worsened into pulseless ventricular tachycardia and refractory cardiac arrest. Therefore, we performed extracorporeal membrane oxygenation (ECMO) to establish spontaneous circulation after the failure of standard resuscitation measures. The girl recovered with intact cardiac and neurocognitive functions after continued ECMO treatment for 221 hours. Therefore, ECMO is an effective rescue therapeutics for FM, especially when complicated with refractory cardiac arrest. Keywords: cardiac arrest, children, extracorporeal membrane oxygenation, fulminant myocarditis

Yu-Xiong Guo,1,* Zhao-Ni Wang,2,* Ya-Ting Li,2 Li Pan,2 Li-Fen Yang,2 Yan Hu,1 Yue-Yu Sun,1 Liang-Ming Cai,2 Zhuang-Gui Chen2 1Pediatric Intensive Care Unit, Department of Pediatrics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 2Pediatric Intensive Care Unit, Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background and purpose: Early or primary application of high-frequency oscillatory ventilation (HFOV) has been recently suggested not to offer benefit to patients with acute respiratory distress syndrome (ARDS). However, the rescue effects of HFOV on severe pediatric acute respiratory distress syndrome (PARDS) with hypoxemia refractory to conventional mechanical ventilation (CMV) remain unclear. This study aimed to determine whether severe PARDS children would benefit from HFOV when oxygenation deteriorated on CMV and to identify any potential risk factors related to mortality. Patients and methods: In a retrospective and observational study, 48 children with severe PARDS between January 2009 and July 2015 were divided into two groups: 26 in HFOV group and 22 in CMV group. Data regarding demographic, underlying conditions, arterial blood gases and clinical outcomes were collected and analyzed. Results: The arterial partial pressure of oxygen (PaO2)/fraction of inspiration oxygen (FiO2) ratio and PaO2 improved significantly during HFOV, whereas arterial partial pressure of carbon dioxide (PaCO2) and oxygenation index decreased. There was no statistical difference in the in-hospital mortality between the groups (P=0.367). The odds ratio of survival in HFOV group was 2.74 (95% confidence interval 0.52 to 14.58, P=0.237). The pediatric intensive care unit length of stay and total ventilation duration were longer in HFOV group (P=0.048 and P=0.000, respectively). Vasoactive agents were used more frequently in HFOV group (P=0.007). The incidence of new air leak was similar between the two groups (P=0.674). The presence of multiple organ dysfunction syndrome and heavier body weight were identified as predictors of mortality in the HFOV group (P=0.006 and P=0.020, respectively). Conclusion: HFOV as an efficient alternative therapy could significantly improve hypoxemia and promote CO2 removal in severe PARDS children when oxygenation progressively worsens on CMV. Keywords: pediatric acute respiratory distress syndrome, high-frequency oscillatory ventilation, mechanical ventilation, children

Geng Dou,1 Yu Zhang,1 Chunlin Zong,2 Yuanli Chen,2 Yuxuan Guo,2 Lei Tian2 1The First Brigade of Students, 2State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Cranio-facial Trauma and Orthognathic Surgery, School of Stomatology, The Fourth Military Medical University, Xi’an, People’s Republic of China Purpose: The present study aimed to evaluate the feasibility, accuracy, and clinical effect of intraoperative navigation for resection of elongated styloid process (ESP) in Eagle’s syndrome.Patients and methods: Twelve patients with Eagle’s syndrome with clinically and radiologically established diagnoses of ESP were included in this study. Preoperatively, all patients accepted three-dimensional computed tomography scan, and their skulls’ digital imaging and communications in medicine data were inputed into the navigation system workstation to make a virtual surgical plan in advance. During surgery, the intraoperative navigation was performed to excise the ESP accurately for both intraoral (without tonsillectomy) and extraoral approaches following the virtual plan. Postoperatively, the amount of bleeding, duration of operation and hospitalization, and the length of resected styloid process (SP) were measured and compared with those cases that had traditional styloidectomy without the help of surgical navigation (SN). A simple visual analog scale questionnaire was also used to assess patients’ satisfaction and the surgery effect after 3 months.Results: In total, 17 SPs from 12 patients were precisely resected by intraoral parapharyngeal approach and small cervical approach with the aid of SN. No severe complications occurred in any patients. The length of resected SPs was 21.93±14.26 mm. The average amount of bleeding and duration of operation were 22.50±8.54 mL and 40.35±11.81 minutes, respectively, which were all less than with traditional styloidectomy. The visual analog scale analysis showed that the discomfort in all patients was relieved, while ten patients’ symptoms were improved greatly, and two patients had some improvement.Conclusion: The higher accuracy of surgery, lesser amount of bleeding, decreased duration of surgery and hospitalization, absence of complications, and improved subjective symptoms indicated that SN is an effective and minimally invasive surgical procedure suitable for resection of ESP for treating Eagle’s syndrome. Keywords: elongation of styloid process, intraoperative navigation, oral and maxillofacial surgery, computer-aided surgery

Aim: Few studies have assessed the association between weight changes from childhood to adulthood and cardiometabolic factors in adulthood. The aim of this study was to explore the relationships between weight changes from childhood to adulthood and cardiometabolic factors in adulthood using national Chinese data., Methods: We included 649 participants from the China Health and Nutrition Survey from 1989 to 2009 and divided them into four groups by their body mass index from 6 to 37 years of age. They were selected using multistage random cluster sampling from 15 areas with large variations in economic and social development. Poisson regression models assessed associations between weight status changes and cardiometabolic outcomes in adulthood., Results: The risk of multiple abnormal cardiometabolic outcomes in adulthood was increased in the 126 subjects with normal weight in childhood but overweight or obesity in adulthood and the 28 with obesity at both ages, compared to the 462 with normal weight at both ages. There was insufficient evidence to demonstrate that the 33 who had weight issues as children, but not as adults, had an increased risk., Conclusion: Being overweight or obese in both childhood and adulthood or during adulthood only increased the risk of abnormal cardiometabolic outcomes in adulthood. Larger studies need to investigate whether weight problems in childhood, but not adulthood, increase the risk., (© 2024 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd.)

Background & Objective: Sex estimation is a critical aspect of forensic expertise. Some special anatomical structures, such as the maxillary sinus, can still maintain integrity in harsh environmental conditions and may be served as a basis for sex estimation. Due to the complex nature of sex estimation, several studies have been conducted using different machine learning algorithms to improve the accuracy of sex prediction from anatomical measurements., Material & Methods: In this study, linear data of the maxillary sinus in the population of northwest China by using Cone-Beam Computed Tomography (CBCT) were collected and utilized to develop logistic, K-Nearest Neighbor (KNN), Support Vector Machine (SVM) and random forest (RF) models for sex estimation with R 4.3.1. CBCT images from 477 samples of Han population (75 males and 81 females, aged 5-17 years; 162 males and 159 females, aged 18-72) were used to establish and verify the model. Length (MSL), width (MSW), height (MSH) of both the left and right maxillary sinuses and distance of lateral wall between two maxillary sinuses (distance) were measured. 80% of the data were randomly picked as the training set and others were testing set. Besides, these samples were grouped by age bracket and fitted models as an attempt., Results: Overall, the accuracy of the sex estimation for individuals over 18 years old on the testing set was 77.78%, with a slightly higher accuracy rate for males at 78.12% compared to females at 77.42%. However, accuracy of sex estimation for individuals under 18 was challenging. In comparison to logistic, KNN and SVM, RF exhibited higher accuracy rates. Moreover, incorporating age as a variable improved the accuracy of sex estimation, particularly in the 18-27 age group, where the accuracy rate increased to 88.46%. Meanwhile, all variables showed a linear correlation with age., Conclusion: The linear measurements of the maxillary sinus could be a valuable tool for sex estimation in individuals aged 18 and over. A robust RF model has been developed for sex estimation within the Han population residing in the northwestern region of China. The accuracy of sex estimation could be higher when age is used as a predictive variable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

It is commonly accepted that exposure to stress may cause overactivity in the orofacial muscles, leading to consistent muscle pain, which is the main symptom of temporomandibular disorders. The central neural mechanism underlying this process, however, remains unclear. The locus coeruleus is considered to play an important role in stress-related behavioral changes. Therefore, the present study was designed to examine the role of locus coeruleus neurons in masseter overactivity induced by stress. C57BL/6 mice were subjected to chronic restraint stress for 14 days to establish an animal model. The behavioral changes and the electromyography of the masseter muscle in mice were measured. The expression of Fos in locus coeruleus was observed by immunofluorescence staining to assess neuronal activation. A chemogenetic test was used to inhibit locus coeruleus neuronal activity, and the behavioral changes and electromyography of the masseter muscle were observed again. The results exhibited that chronic restraint stress could induce anxiety-like behavior, overactivity of the masseter muscle, and significant activation of locus coeruleus neurons in mice. Furthermore, inhibition of noradrenergic neuron activity within the locus coeruleus could alleviate stress-induced anxiety behavior and masseter muscle overactivity. Activation of noradrenergic neurons in locus coeruleus induced by stress may be one of the central regulatory mechanisms for stress-induced anxiety-like behaviors and overactivity of masseter muscles., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To observe the genetic variation of SH2B3 in patients with myeloid neoplasms., Methods: The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology, Xuanwu Hospital, Capital Medical University from November 2017 to November 2022 were retrospectively analyzed, and the patients with SH2B3 gene mutations were identified. The demographic and clinical data of these patients were collected, and characteristics of SH2B3 gene mutation, co-mutated genes and their correlations with diseases were analyzed., Results: The sequencing results were obtained from 1 005 patients, in which 19 patients were detected with SH2B3 gene mutation, including 18 missense mutations (94.74%), 1 nonsense mutation (5.26%), and 10 patients with co-mutated genes (52.63%). Variant allele frequency (VAF) ranged from 0.03 to 0.66. The highest frequency mutation was p.Ile568Thr (5/19, 26.32%), with an average VAF of 0.49, involving 1 case of MDS/MPN-RS (with SF3B1 mutation), 1 case of MDS-U (with SF3B1 mutation), 1 case of aplastic anemia with PNH clone (with PIGA and KMT2A mutations), 2 cases of MDS-MLD (1 case with SETBP1 mutation). The other mutations included p.Ala567Thr in 2 cases (10.53%), p.Arg566Trp, p.Glu533Lys, p.Met437Arg, p.Arg425Cys, p.Glu314Lys, p.Arg308*, p.Gln294Glu, p.Arg282Gln, p.Arg175Gln, p.Gly86Cys, p.His55Asn and p.Gln54Pro in 1 case each., Conclusion: A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms, among of them, p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

Background: Large cell neuroendocrine carcinoma (LCNEC) of the bladder is a rare non-urothelial tumor of the bladder. The treatment of LCNEC of the bladder is different from that of urothelial carcinoma (UC); therefore, early and accurate diagnosis is particularly important. As LCNEC of the bladder is rare and its clinical symptoms and radiographic features are similar to those of urothelial tumors, the clinical diagnosis of the disease remains challenging., Case Summary: We report a 72-year-old female patient who presented with gross hematuria for 3 mo. A solitary tumor located in the anterior wall of the bladder was found by cystoscopy. Pathological examination after biopsy suggested UC of the bladder in the absence of immunohistochemical assessment. The patient underwent partial cystectomy and was finally diagnosed with LCNEC (pT2bN0M0) based on the results of postoperative immunohistochemical examination. During the 10-mo follow-up, no signs of tumor recurrence or metastasis were found., Conclusion: Immunohistochemical examination is essential for diagnosing LCNEC of the bladder. Accurate diagnosis and multidisciplinary treatment in the early stage of the disease are crucial for improving the prognosis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Depression manifests as a mental disorder characterized by a low mood, suicidal tendencies, disturbances in sleep-wake cycles, psychomotor agitation, and pronounced feelings of hopelessness and anhedonia. Baicalin, a natural flavonoid compound, shows significant promise in alleviating depressive symptoms in animals. This study aims to assess the impact of baicalin on experimental models of depression., Methods: A systematic search of electronic databases was conducted using the search terms "baicalin" AND "depression" OR "depressed" OR "anti-depression". Preclinical animal models representing experimental depression were included in the analysis. The risk of bias in the included studies was evaluated using the CAMARADES tools., Results: Baicalin significantly increased sucrose preference test (SPT) [SMD= 21.31, 95%CI (16.32, 26.31), P < 0.00001]. mThe tail suspension test (TST) duration significantly decreased in the baicalin group compared to the model group [SMD = -39.3, 95%CI (-49.71, -28.89), P < 0.0001]. Furthermore, baicalin reduced immobility time in rats subjected to the forced swim test (FST) [SMD = -39.73, 95%CI (-48.77, -30.69) P < 0.0001]. Compared to the model group, baicalin treatment also significantly increased the frequency of crossings in the open field test (OFT) [SMD = 32.44, 95%CI (17.74, 47.13), P < 0.00001]., Conclusion: Baicalin significantly improves the manifestations of depressive symptoms. The effect of baicalin against depression is exerted through its anti-inflammatory actions, inhibition of oxidative stress, regulation of the HPA axis, and restoration of neuroplasticity. Future studies will be needed to further explore how these promising preclinical findings can be translated into clinical treatment for depression., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472181., 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 Wang, Ren, Guo, Zhang, Sui and Zhang.)

Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objectives: To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence., Methods: A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed., Results: Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group ( P >0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage ( n =62, 42.5%) and the early stage ( n =46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene ( HR =4.177, 95% CI : 2.086-8.364, P <0.001) and minimal residual disease≥0.01% on day 46 ( HR =2.013, 95% CI : 1.163-3.483, P =0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol., Conclusions: There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

The comorbidity of anxiety and depression frequently occurs in patients with neuropathic pain. The ventrolateral orbital cortex (VLO) plays a critical role in mediating neuropathic pain and anxiodepression in rodents. Previous studies suggested that 5-HT 6 receptors in the VLO are involved in neuropathic pain. Strong evidence supports a close link between 5-HT 6 receptors and affective disorders such as depression and anxiety disorders. However, it remains unclear whether the 5-HT 6 receptors in the VLO are involved in neuropathic pain-induced anxiodepression. Using a rat neuropathic pain model of spared nerve injury (SNI), we demonstrated that rats exhibited significant anxiodepression-like behaviors and the expression of VLO 5-HT 6 receptors obviously decreased four weeks after SNI surgery. Microinjection of the 5-HT 6 receptor agonist EMD-386088 into the VLO or overexpression of VLO 5-HT 6 receptors alleviated anxiodepression-like behaviors. These effects were blocked by pre-microinjection of a selective 5-HT 6 receptor antagonist (SB-258585) or inhibitors of AC (SQ-22536), PKA (H89), and MEK1/2 (U0126) respectively. Meanwhile, the expression of p-ERK, p-CREB, and BDNF in the VLO decreased four weeks after SNI surgery. Furthermore, administration of EMD-386088 upregulated the expression of BDNF, p-ERK, and p-CREB in the VLO of SNI rats, which were reversed by pre-injection of SB-258585. These findings suggest that activating 5-HT 6 receptors in the VLO has anti-anxiodepressive effects in rats with neuropathic pain via activating AC-cAMP-PKA-MERK-CREB-BDNF signaling pathway. Accordingly, 5-HT 6 receptor in the VLO could be a potential target for the treatment of the comorbidity of neuropathic pain and anxiodepression., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiple sclerosis (MS) is a class of autoimmune diseases mainly caused by the immune system attacking the myelin sheath of the axons in the nervous system. Although the pathogenesis of MS is complex, studies have shown that dendritic cells (DCs) play a vital role in the pathogenesis of MS. Quercetin (QU) has a unique advantage in clinical application, especially for treating autoimmune diseases. However, the mechanism of QU in the treatment of experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we explore the potential role of QU in EAE. Finally, we find that QU has anti-inflammatory activities and neural protective effects in EAE. The experimental results suggest that the cellular basis for QU's function is to inhibit the activation of DCs while modulating the Th17 cell differentiation in the co-culture system. Further, QU may target STAT4 to inhibit its activation in DCs. This work will be of great significance for the future development and utilization of QU., 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.)

Spirotryprostatins are representative members of medicinally interesting bioactive molecules of the spirooxindole natural products. In this communication, we present a novel enantioselective total synthesis of the spirooxindole alkaloid dihydrospirotryprostatin B. The synthesis takes advantage of copper-catalyzed tandem reaction of o -iodoanilide chiral sulfinamide derivatives with alkynone to rapidly construct the key quaternary carbon stereocenter of the natural product dihydrospirotryprostatin B.

HIV-1 reverse transcriptase (RT) inhibitors play a crucial role in the treatment of HIV by preventing the activity of the enzyme responsible for the replication of the virus. The HIV-1 Tat protein binds to transactivation response (TAR) RNA and recruits host factors to stimulate HIV-1 transcription. We have created a small library consisting of 4 × 6 polypyridyl Ru(II) complexes that selectively bind to TAR RNA, with targeting groups specific to HIV-1 TAR RNA. The molecule design was conducted by introducing hydroxyl or methoxy groups into an established potent TAR binder. The potential TAR binding ability was analysis from nature charge population and electrostatic potential by quantum chemistry calculations. Key modifications were found to be R 1 and R 3 groups. The most potent and selective TAR RNA binder was a3 with R 1  = OH, R 2  = H and R 3  = Me. Through molecular recognition of hydrogen bonds and electrostatic attraction, they were able to firmly and selectively bind HIV-1 TAR RNA. Furthermore, they efficiently obstructed the contact between TAR RNA and Tat protein, and inhibited the reverse transcription activity of HIV-1 RT. The polypyridyl Ru(II) complexes were chemical and photo-stable, and sensitive and selective spectroscopic responses to TAR RNA. They exhibited little toxicity towards normal cells. Hence, this study might offer significant drug design approaches for researching AIDS and other illnesses associated with RT, including HCV, EBOV, and SARS-CoV-2. Moreover, it could contribute to fundamental research on the interactions of inorganic transition metal complexes with biomolecules., 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.)

Background: Etomidate can induce myoclonus with an incidence of 50 ~ 85% during anesthesia induction. Dexamethasone, as a long-acting synthetic glucocorticoid, has neuroprotective effects. However, the effects of dexamethasone on the etomidate-induced myoclonus remain uncertain., Methods: Adult male Sprague-Dawley rats were randomly assigned to receive etomidate (1.5 mg/kg) plus dexamethasone (4 mg/kg) (etomidate plus dexamethasone group) or etomidate (1.5 mg/kg) plus the same volume of normal saline (NS) (etomidate plus NS group). The mean behavioral scores, local field potentials and muscular tension were recorded to explore the effects of dexamethasone on etomidate-induced myoclonus. Liquid chromatography coupled with tandem mass spectrometric system (LC-MS/MS), quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting were applied to analyze the levels of glutamate and γ -aminobutyric acid (GABA), the mRNA and protein expression of excitatory amino acid transporters (EAATs), and plasma corticosterone levels at different time points after anesthesia., Results: Compared with the etomidate plus NS treatment, the etomidate plus dexamethasone treatment significantly decreased the mean behavioral score at 1, 3, 4, and 5 min after administration; the peak power spectral density (PSD) ( p  = 0.0197) in the analysis of ripple waves; and the glutamate level ( p  = 0.0139) in the neocortex. However, compared with etomidate plus NS, etomidate plus dexamethasone increased the expression of the neocortical proteins of EAAT1 ( p  = 0.0207) and EAAT2 ( p  = 0.0022) and aggravated the inhibition of corticosterone at 4 h ( p  = 0.0019), 5 h ( p  = 0.0041), and 6 h ( p  = 0.0009) after administration., Conclusion: Dexamethasone can attenuate the myoclonus, inhibit the glutamate accumulation, and reverse the suppression of EAATs in the neocortex induced by etomidate following myoclonus, while conversely aggravating etomidate-induced adrenal suppression., 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 Feng, Zhang, Jia, Guo and Jia.)

Background: Bacterial fruit blotch (BFB), known as the 'cancer' of cucurbits, is a seed-borne disease of melons caused by Acidovorax citrulli. Traditional chemical treatments for BFB are ineffective and adversely affect the environment. Using dielectric barrier discharge (DBD) nanosecond-pulsed plasma technology, melon seeds were treated to promote germination and growth and to control BFB., Results: Based on the evaluation parameters of seed germination, seedling growth, leaf yellowing and bacterial infection after seed plasma treatments, 9 min at 20 kV was selected as the optimal plasma discharge parameter. In this study, seedling growth was significantly improved after treating melon seeds carrying A. citrulli using this discharge parameter. The number of first true leaves measured on the eighth day was 2.3 times higher and the disease index was reduced by 60.5% compared to the control group. Attenuated total reflectance-Fourier transform infrared measurements show that plasma treatments penetrate the seed coat and denature polysaccharides and proteins in the seed kernel, affecting their growth and sterilization properties., Conclusion: Pre-sowing treatment of melon seeds carrying A. citrulli using nanosecond-pulsed plasma technology can effectively control seedling BFB disease and promote melon seedling growth by optimizing DBD parameters. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

A dual-emission ratio-fluorescent sensing nanohybrid based on Radix Hedysari green-synthesized carbon quantum dots (CDs) and glutathione-functionalized gold nanoclusters (GSH-AuNCs) had been developed for the determination of cefodizime sodium (CDZM). The designed fluorescence nanohybrid had two significant fluorescence emission peaks at 458 nm and 569 nm when excited at 360 nm, which was attributed to the CDs and GSH-AuNCs. With the addition of CDZM, the fluorescence at 458 nm was slightly weakened while the fluorescence at 569 nm was enhanced obviously. Based on the relationship between the I 569 /I 458 fluorescence intensity ratio and the concentration of CDZM, the designed nanohybrid exhibited a good linearity range of 1.0-1000.0 μM and the limit of detection (LOD) was 0.19 μM. The method was finally applied in the detection of CDZM in urine, showing the potential applications in complicated biological samples.

Background: Active vitamin D analog eldecalcitol is clinically applied in treatment of postmenopausal osteoporosis. This study aims to determine the role of eldecalcitol in the protection of osteocytes from senescence and the associated ferroptosis., Methods: The MLO-Y4 osteocytes were exposed to D-gal inducing senescence. The ovariectomized (OVX) mice treated with D-gal using as an aging inducer were intraperitoneally injected with eldecalcitol. The multiplexed confocal imaging, fluorescence in situ hybridization and transmission electron microscopy were applied in assessing osteocytic properties. Immunochemical staining and immunoblotting were carried out to detect abundance and expression of molecules., Results: The ablation of vitamin D receptor led to a reduction in amounts of osteocytes, a loss of dendrites, an increase in mRNA expression of SASP factors and in protein expression of senescent factors, as well as changes in mRNA expression of ferroptosis-related genes (PTGS2 & RGS4). Eldecalcitol reversed senescent phenotypes of MLO-Y4 cells shown by improving cell morphology and density, decreasing β-gal-positive cell accumulation, and down-regulating protein expression (P16, P21 & P53). Eldecalcitol reduced intracellular ROS and MDA productions, elevated JC-1 aggregates, and up-regulated expression of Nrf2 and GPX4. Eldecalcitol exhibited osteopreserve effects in D-gal-induced aging OVX mice. The confocal imaging displayed its improvement on osteocytic network organization. Eldecalcitol decreased the numbers of senescent osteocytes at tibial diaphysis by SADS assay and attenuated mRNA expression of SASP factors as well as down-regulated protein expression of senescence-related factors and restored levels of ferroptotic biomarkers in osteocytes-enriched bone fraction. It reduced 4-HNE staining area, stimulated Nrf2-positive staining, and promoted nuclear translocation of Nrf2 in osteocytes of mice as well as inhibited and promoted protein expression of 4-HNE and Nrf2, respectively, in osteocytes-enriched bone fraction., Conclusions: The present study revealed the ameliorative effects of eldecalcitol on senescence and the associated ferroptosis of osteocytes, contributing to its preservation against osteoporosis of D-gal-induced senescent ovariectomized mice., 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. Published by Elsevier Inc.)

We report the synthesis of functionalized cycloheptanes by thermal electrocyclization of heptatrienyl anions under mild conditions. In addition, we disclose the first examples of this electrocyclization manifold conducted under catalytic conditions. Previously, electrocyclization of heptatrienyl systems required formation of anions with a strong base, resulting in limited functional group compatibility. We demonstrate that polarization of heptatrienyl anions using strategically positioned electron-withdrawing groups lowers the energy landscape of the reaction by stabilizing both the acyclic heptatrienyl anion and cycloheptadienyl product. Divergent reactivity is observed between aliphatic and aromatic substrates, with the latter requiring only catalytic amounts of base for complete conversion. This can be rationalized by the relative stability of the acyclic and cyclic anions and their ability to participate in a chain reaction process., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: To investigate the application value of combining the Demirjian's method with machine learning algorithms for dental age estimation in northern Chinese Han children and adolescents., Methods: Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected. The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method. Various machine learning algorithms, including support vector regression (SVR), gradient boosting regression (GBR), linear regression (LR), random forest regression (RFR), and decision tree regression (DTR) were employed. Age estimation models were constructed based on total, female, and male samples respectively using these algorithms. The fitting performance of different machine learning algorithms in these three groups was evaluated., Results: SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples, while GBR showed the best performance in male samples. The mean absolute error (MAE) of the optimal age estimation model was 1.246 3, 1.281 8 and 1.153 8 years in the total, female and male samples, respectively. The optimal age estimation model exhibited varying levels of accuracy across different age ranges, which provided relatively accurate age estimations in individuals under 18 years old., Conclusions: The machine learning model developed in this study exhibits good age estimation efficiency in northern Chinese Han children and adolescents. However, its performance is not ideal when applied to adult population. To improve the accuracy in age estimation, the other variables can be considered.

Background: The ubiquitin-proteasome pathway (UPP) has been proven to play important roles in cancer., Aim: To investigate the prognostic significance of genes involved in the UPP and develop a predictive model for liver cancer based on the expression of these genes., Methods: In this study, UPP-related E1, E2, E3, deubiquitylating enzyme, and proteasome gene sets were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, aiming to screen the prognostic genes using univariate and multivariate regression analysis and develop a prognosis predictive model based on the Cancer Genome Atlas liver cancer cases., Results: Five genes (including autophagy related 10, proteasome 20S subunit alpha 8, proteasome 20S subunit beta 2, ubiquitin specific peptidase 17 like family member 2, and ubiquitin specific peptidase 8) were proven significantly correlated with prognosis and used to develop a prognosis predictive model for liver cancer. Among training, validation, and Gene Expression Omnibus sets, the overall survival differed significantly between the high-risk and low-risk groups. The expression of the five genes was significantly associated with immunocyte infiltration, tumor stage, and postoperative recurrence. A total of 111 differentially expressed genes (DEGs) were identified between the high-risk and low-risk groups and they were enriched in 20 and 5 gene ontology and KEGG pathways. Cell division cycle 20, Kelch repeat and BTB domain containing 11 , and DDB1 and CUL4 associated factor 4 like 2 were the DEGs in the E3 gene set that correlated with survival., Conclusion: We have constructed a prognosis predictive model in patients with liver cancer, which contains five genes that associate with immunocyte infiltration, tumor stage, and postoperative recurrence., Competing Interests: Conflict-of-interest statement: All authors declare that they have no competing interests to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The ventrolateral orbital cortex (VLO) is identified as an integral component of the endogenous analgesic system comprising a spinal cord - thalamic nucleus submedius - VLO - periaqueductal gray (PAG) - spinal cord loop. The present study investigates the effects of 5-HT 5A receptor activation in the VLO on allodynia induced by spared nerve injury and formalin-evoked flinching behavior and spinal c-Fos expression in male SD rats, and further examines whether GABAergic modulation is involved in the effects evoked by VLO 5-HT 5A receptor activation. We found an upregulation of 5-HT 5A receptor expression in the VLO during neuropathic and inflammatory pain states. Microinjection of the non-selective 5-HT 5A receptor agonist 5-CT into the VLO dose dependently alleviated allodynia, and flinching behavior and spinal c-Fos expression, which were blocked by the selective 5-HT 5A receptor antagonist SB-699551. Moreover, application of the GABA A receptor antagonist bicuculline in the VLO augmented the analgesic effects induced by 5-CT in neuropathic and inflammatory pain states, whereas the GABA A receptor agonist muscimol attenuated these analgesic effects. Additionally, the 5-HT 5A receptors were found to be colocalized with GABAergic neurons in the VLO. These results provide new evidence for the involvement of central 5-HT 5A receptors in the VLO in modulation of neuropathic and inflammatory pain and support the hypothesis that activation of 5-HT 5A receptors may inhibit the inhibitory effect of GABAergic interneurons on output neurons projecting to the PAG (GABAergic disinhibitory mechanisms), consequently activating the brainstem descending inhibitory system that depresses nociceptive transmission at the spinal cord level., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Sex estimate is a key stage in forensic science for identifying individuals. Some anatomical structures may be useful for sex estimation since they retain their integrity even after highly severe events. However, few studies are focusing on the Chinese population. Some researchers used teeth for sex estimation, but comparison with maxillary sinus were lack. As a result, the objective of this research is to develop a sex estimation formula for the northwestern Chinese population by the volume of the maxillary sinus and compare with the accuracy of sex estimation based on teeth through cone-beam computed tomography (CBCT)., Methods: CBCT images from 349 samples were used to establish and verify the formula. The volume of both the left and right maxillary sinuses was measured and examined for appropriate formula coefficients. To create the formula, we randomly picked 80% of the data as the training set and 20% of the samples as the testing set. Another set of samples, including 20 males and 20 females, were used to compare the accuracy of maxillary sinuses and teeth., Results: Overall, sex estimation accuracy by volume of the left maxillary sinus can reach 78.57%, while by the volume of the right maxillary sinus can reach 74.29%. The accuracy for females, which can reach 91.43% using the left maxillary sinus, was significantly higher than that for males, which was 65.71%. The result also shows that maxillary sinus volume was higher in males. The comparison with the available results using measurements of teeth for sex estimation performed by our group showed that the accuracy of sex estimation using canines volume was higher than the one using maxillary sinus volume, the accuracies based on mesiodistal diameter of canine and first molar were the same or lower than the volume of maxillary sinus., Conclusions: The study demonstrates that measurement of maxillary sinus volume based on CBCT scans was an available and alternative method for sex estimation. And we established a method to accurately assess the sex of the northwest Chinese population. The comparison with the results of teeth measurements made the conclusion more reliable., (© 2024. The Author(s).)

Seeking novel high-performance elastocaloric materials with low critical stress plays a crucial role in advancing the development of elastocaloric refrigeration technology. Here, as a first attempt, the elastocaloric effect of TiZrNbAl shape memory alloy at both room temperature and finite temperatures ranging from 245 K to 405 K, is studied systematically. Composition optimization shows that Ti-19Zr-14Nb-1Al (at.%), possessing excellent room-temperature superelasticity with a critical stress of around 100 MPa and a small stress hysteresis of around 70 MPa and outstanding fracture resistance with a compressive strain of 20% and stress of 1.7 GPa, demonstrates a substantial advantage as an elastocaloric refrigerant. At room temperature, a large adiabatic temperature change (ΔTad) of -6.7 K is detected, which is comparable to the highest value reported in the Ti-based alloys. A high elastocaloric cyclic stability, with almost no degradation of ΔTad after 4000 cycles, is observed. Furthermore, the sizeable elastocaloric effect can be steadily expanded from 255 K to 395 K with a temperature window of as large as 140 K. A maximum ΔTad of -7.9 K appears at 355 K. The present work demonstrates a promising potential of TiZrNbAl as a low critical stress and low hysteresis elastocaloric refrigerant.

Bananas (Musa spp.) are one of the world's most important fruit crops and play a vital role in food security for many developing countries. Most banana cultivars are triploids derived from inter- and intraspecific hybridizations between the wild diploid ancestor species Musa acuminate (AA) and M. balbisiana (BB). We report two haplotype-resolved genome assemblies of the representative AAB-cultivated types, Plantain and Silk, and precisely characterize ancestral contributions by examining ancestry mosaics across the genome. Widespread asymmetric evolution is observed in their subgenomes, which can be linked to frequent homologous exchange events. We reveal the genetic makeup of triploid banana cultivars and verify that subgenome B is a rich source of disease resistance genes. Only 58.5% and 59.4% of Plantain and Silk genes, respectively, are present in all three haplotypes, with >50% of genes being differentially expressed alleles in different subgenomes. We observed that the number of upregulated genes in Plantain is significantly higher than that in Silk at one-week post-inoculation with Fusarium wilt tropical race 4 (Foc TR4), which confirms that Plantain can initiate defense responses faster than Silk. Additionally, we compared genomic and transcriptomic differences among the genes related to carotenoid synthesis and starch metabolism between Plantain and Silk. Our study provides resources for better understanding the genomic architecture of cultivated bananas and has important implications for Musa genetics and breeding., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote., Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T)., Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital., Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included., Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CR V ) rate was 67.9%, and the cumulative complete hematological response (CR H ) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CR V rate (median time from diagnosis to CR V  = 130 days) and 66.7% CR H rate (median time from diagnosis to CR H  = 218 days). In addition, the VEGF response was less than the partial remission (PR V ) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor., Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3'UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases., (© 2024. The Author(s).)

Long-term exposure to arsenic can lead to functional damage to many organs and can be life-threatening. It is of great significance to analyze the distribution characteristics of arsenic in water and evaluate its potential risk for preventing and controlling human health hazards caused by water-derived arsenic. Based on the published data from 2000 to 2022, the geographical distribution characteristics of arsenic in drinking water across China were systematically analyzed in detail, and the health risk of arsenic in drinking water was quantitatively assessed using disability-adjusted life years (DALYs), which represent the burden of disease. The results showed that the average concentration of arsenic in drinking water in China was (2.88 ±0.33) μg·L -1 , which was lower than the limit of 10 μg·L -1 set by the standard for drinking water quality (GB 5749-2022). Nevertheless, the arsenic in drinking water in some provinces, including Shanxi, Inner Mongolia, and Ningxia, was still higher than the limit. The arsenic concentration in drinking water in northern China was higher than that in southern China, and that in rural areas was higher than that in cities. The estimated health risk of arsenic in drinking water (1.63×10 -6 DALYs per person-year) was higher than the acceptable risk level of waterborne exposure of 1.0×10 -6 DALYs per person-year set by the World Health Organization. The personal health risks related to arsenic in drinking water in the six geographical regions were ranked as follows:North China &gt; Northeast China &gt; Central South China &gt; Northwest China &gt; Southwest China &gt; East China. Almost all (99.4%) of the health burden associated with water arsenic was attributable to skin and lung cancer, which caused 2 905.25 and 1 513.96 DALYs per year, respectively. Most (78.0%) of the health burden was borne by people aged 45 years or older. In addition, given the proportion of each age group in the total population, older persons over the age of 60 bear a higher drinking-water-associated arsenic burden at the individual level than others, and attention should be consequently paid to them when controlling the risk of arsenic in water.

Roselle is rich in an extensive diversity of beneficial substances, including phenolic acids, amino acids, anthocyanins, vitamins, and flavonoids. Herein, the chemical constituents in Roselle extract (RE) were identified by UPLC-DAD-QTOF-MS. Besides, its inhibitory effects on three digestive enzymes, i.e. α-amylase, α-glucosidase, and pancreatic lipase, were investigated in both in vitro and in vivo. Thirty-three constituents including hibiscus acid, 18 phenolic acids, 2 anthocyanins and 12 flavonoids were identified. The anthocyanins content in RE was 21.44 ± 0.68 %, while the contents of chlorogenic acids, rutin and quercetin were 17.76 ± 2.28 %, 0.31 ± 0.01 % and 0.32 ± 0.01 %, respectively. RE inhibited pancreatic lipase in a non-competitive way with an IC 50 value of 0.84 mg/mL. Besides, it demonstrated a mixed-type inhibition on both α-glucosidase and α-amylase with IC 50 values of 0.59 mg/mL and 1.93 mg/mL, respectively. Fluorescence quenching assays confirmed the binding of RE to the enzyme proteins. Furthermore, rats pre-treated with RE at doses of 50 and 100 mg/kg body weight (bwt) exhibited significant reductions in fat absorption and improvements in fat excretion through feces. Additionally, the in vivo study revealed that RE was effective in suppressing the increase of blood glucose after starch consumption, while its effects on maltose and sucrose consumption were relatively weak., 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 © 2023 Elsevier B.V. All rights reserved.)

Host-pathogen interactions (HPIs) are vital in numerous biological activities and are intrinsically linked to the onset and progression of infectious diseases. HPIs are pivotal in the entire lifecycle of diseases: from the onset of pathogen introduction, navigating through the mechanisms that bypass host cellular defenses, to its subsequent proliferation inside the host. At the heart of these stages lies the synergy of proteins from both the host and the pathogen. By understanding these interlinking protein dynamics, we can gain crucial insights into how diseases progress and pave the way for stronger plant defenses and the swift formulation of countermeasures. In the framework of current study, we developed a web-based R/Shiny app, Deep-HPI-pred, that uses network-driven feature learning method to predict the yet unmapped interactions between pathogen and host proteins. Leveraging citrus and C Las bacteria training datasets as case study, we spotlight the effectiveness of Deep-HPI-pred in discerning Protein-protein interaction (PPIs) between them. Deep-HPI-pred use Multilayer Perceptron (MLP) models for HPI prediction, which is based on a comprehensive evaluation of topological features and neural network architectures. When subjected to independent validation datasets, the predicted models consistently surpassed a Matthews correlation coefficient (MCC) of 0.80 in host-pathogen interactions. Remarkably, the use of Eigenvector Centrality as the leading topological feature further enhanced this performance. Further, Deep-HPI-pred also offers relevant gene ontology (GO) term information for each pathogen and host protein within the system. This protein annotation data contributes an additional layer to our understanding of the intricate dynamics within host-pathogen interactions. In the additional benchmarking studies, the Deep-HPI-pred model has proven its robustness by consistently delivering reliable results across different host-pathogen systems, including plant-pathogens (accuracy of 98.4% and 97.9%), human-virus (accuracy of 94.3%), and animal-bacteria (accuracy of 96.6%) interactomes. These results not only demonstrate the model's versatility but also pave the way for gaining comprehensive insights into the molecular underpinnings of complex host-pathogen interactions. Taken together, the Deep-HPI-pred applet offers a unified web service for both identifying and illustrating interaction networks. Deep-HPI-pred applet is freely accessible at its homepage: https://cbi.gxu.edu.cn/shiny-apps/Deep-HPI-pred/ and at github: https://github.com/tahirulqamar/Deep-HPI-pred., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Background: The COVID-19 pandemic has a heavy impact on the mental health of elderly surgical patients worldwide. In particular, the elderly patients faced considerable psychological stress due to various environmental and medical factors during the outbreak. This study aims to examine changes in mental health trends among non-cardiac surgical patients aged 65 and above in China during the COVID-19 pandemic., Methods: This multi-center, convenient sampling, longitudinal observational study was conducted from April 1, 2020 to April 30, 2022. Primary outcome was the prevalence of postoperative depression. Secondary outcome was the prevalence of postoperative anxiety. Follow-up was conducted separately at 7 days and 30 days after surgery. Depression symptoms were assessed using the Patient Health Questionnaire 9 (PHQ-9) scale. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (GAD-7) scale, with scores of ≥5 defining positive depression or anxiety symptoms. Multivariate logistic regression analysis was used to investigate risk factors of mental health status in more elderly patients undergoing non-cardiac surgery., Results: A total of 4639 patients were included, of whom 2279 (46.0 %) were male, 752 (15.2 %) were over the age of 75, and 4346 (93.7 %) were married. The monthly prevalence trends demonstrated that compared to the outbreak period, a significant reduction in the prevalence of depression and anxiety symptoms in elderly patients who underwent surgery during the post-pandemic period. In post-pandemic period, a statistically significant decrease in the prevalence of all severity depression and anxiety patients was noted at the 7-day follow-up, but no significant decrease was observed for severe depression and anxiety in the 30-day follow-up. In COVID-19 low-risk area, a significant overall decrease in prevalence of mental health was observed during the post-pandemic period compared to the outbreak period, including 7-day depression, 7-day anxiety, 30-day depression, and 30-day anxiety (all with P < 0.001). Female and patients with ≥2 comorbidities appeared to be more susceptible to postoperative depression and anxiety during the pandemic., Limitation: The absence of data from the early days of the COVID-19 outbreak., Conclusions: This study analyzed the prevalence of depression and anxiety in elderly non-cardiac patients during and after the COVID-19 pandemic, focusing on dimensions such as severity, risk-areas, gender, and comorbidity. Our findings revealed a significant decrease in the prevalence of depression and anxiety in elderly surgery patients during the post-pandemic period., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Developing novel nanoscale carriers for drug delivery is of great significance for improving treatment efficiency and reducing side effects of antitumor drugs. In view of the good biocompatibility and special affinity of porphyrin (PP) molecule to cancer cells, it was used to construct a series of metal-doped M@PP (M = Ca ∼ Zn) materials for the delivery of anticancer drug 5-fluorouracil (5-Fu) in this work. Our results reveal that 5-Fu is tightly adsorbed on M@PP (M = Ca ∼ V, Mn ∼ Co, and Zn) by chemisorption, but is physically adsorbed by M@PP (M = Cr, Ni, and Cu). The calculated electronic properties show that all these 5-Fu@[M@PP] (M = Ca ∼ Zn) complexes have both high stability and solubility. Among these 5-Fu@[M@PP] complexes, the chemical bond formed between 5-Fu and Ti@PP has the strongest covalent characteristic, resulting in the largest adsorption energy of -19.93 kcal/mol for 5-Fu@[Ti@PP]. In particular, 5-Fu@[Ti@PP] has the proper recovery time under the near-infrared light at body temperature, which further suggests that Ti@PP is the best drug carrier for 5-Fu. This study not only reveals the interaction strength and nature between 5-Fu and M@PP, but also confirmed the intriguing potential of Ti@PP as nano-carrier for drug delivery. However, further experimental research should be conducted to verify the conclusion obtained in this work., 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 © 2023 Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide with an increasing number of new cases each year. Apolipoprotein (APOL) isoforms have been explored for their associations with HCC.The GSE14520 cohort was used for training data; The Cancer Genome Atlas (TCGA) database was used for validated data. Diagnostic, prognostic significance and mechanisms were explored using these cohorts. Risk score models and nomograms were constructed using prognosis-related isoforms and clinical factors for survival prediction. Oncomine and HCCDB databases were further used for validation of diagnostic, prognostic significance. APOL1, 3, and 6 were differentially expressed in two cohorts (all P ≤ 0.05). APOL1 and APOL6 had diagnostic capacity whereas APOL3 and APOL6 had prognostic capacity in two cohorts (areas under curves [AUCs] > 0.7, P ≤ 0.05). Mechanism studies demonstrated that APOL3 and APOL6 might be involved in humoral chemokine signaling pathways (all P ≤ 0.05). Risk score models and nomograms were constructed and validated for survival prediction of HCC. Moreover, diagnostic values of APOL1 and weak APOL6 were validated in Oncomine database (AUC > 0.700, 0.694); prognostic values of APOL3 and APOL6 were validated in HCCDB database (all P < 0.05). Differentially expressed APOL1 and APOL6 might be diagnostic biomarkers; APOL3 and APOL6 might be prognostic biomarkers of RFS and OS for HCC via chemokine signaling pathways., (© 2023. The Author(s).)

Objectives: To investigate the current application status and implementation difficulties of extracorporeal cardiopulmonary resuscitation (ECPR) in children with sudden cardiac arrest. Methods: This cross-sectional survey was conducted in 35 hospitals. A Children's ECPR Information Questionnaire on the implementation status of ECPR technology (abbreviated as the questionnaire) was designed, to collect the data of 385 children treated with ECPR in the 35 hospitals. The survey extracted the information about development of ECPR, the maintenance of extracorporeal membrane oxygenation (ECMO) machine, the indication of ECPR, and the difficulties of implementation in China. These ECPR patients were grouped based on their age, the hospital location and level, to compare the survival rates after weaning and discharge. The statistical analysis used Chi-square test and one-way analysis of variance for the comparison between the groups, LSD method for post hoc testing, and Bonferroni method for pairwise comparison. Results: Of the 385 ECPR cases, 224 were males and 161 females. There were 185 (48.1%) survival cases after weaning and 157 (40.8%) after discharge. There were 324 children (84.2%) receiving ECPR for cardiac disease and 27 children (7.0%) for respiratory failure. The primary cause of death in ECPR patients was circulatory failure (82 cases, 35.9%), followed by brain failure (80 cases, 35.0%). The most common place of ECPR was intensive care unit (ICU) (278 cases, 72.2%); ECPR catheters were mostly inserted through incision (327 cases, 84.9%). There were 32 hospitals (91.4%) had established ECMO emergency teams, holding 125 ECMO machines in total. ECMO machines mainly located in ICU (89 pieces, 71.2%), and the majority of hospitals (32 units, 91.4%) did not have pre-charged loops. There were no statistically significant differences in the post-withdrawal and post-discharge survival rates of ECPR patients among different age groups, regions, and hospitals (all P >0.05). The top 5 difficulties in implementing ECPR in non-ICU environments were lack of ECMO machines (16 times), difficulty in placing CPR pipes (15 times), long time intervals between CPR and ECMO transfer (13 times), lack of conventional backup ECMO loops (10 times), and inability of ECMO emergency teams to quickly arrive at the site (5 times). Conclusion: ECPR has been gradually developed in the field of pediatric critical care in China, and needs to be further standardized. ECPR in non-ICU environment remains a challenge.