Altered regional brain activity and functional connectivity in primary intravaginal anejaculation patients revealed by resting-state fMRI.

ABSTRACT: Ejaculation is regulated by the central nervous system. However, the central pathophysiology of primary intravaginal anejaculation (PIAJ) is unclear. The present study aimed to examine the changes in regional brain activity and functional connectivity underlying PIAJ. A total of 20 PIAJ patients and 16 healthy controls (HCs) were enrolled from September 2020 to September 2022 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Magnetic resonance imaging data were acquired from all participants and then were preprocessed. The measures of fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) were calculated and compared between the groups. PIAJ patients showed increased fALFF values in the left precuneus compared with HCs. Additionally, PIAJ patients showed increased ReHo values in the left precuneus, left postcentral gyrus, left superior occipital gyrus, left calcarine fissure, right precuneus, and right middle temporal gyrus, and decreased ReHo values in the left inferior parietal gyrus, compared with HCs. Finally, brain regions with altered fALFF and ReHo values in PIAJ patients showed increased FC with widespread cortical regions, which included the frontal, parietal, temporal, and occipital regions, compared with HCs. In conclusion, increased regional brain activity in the parietal, temporal, and occipital regions, and increased FC between these brain regions, may be associated with PIAJ occurrence.

Effects of transcutaneous electrical acupoint stimulation on early postoperative pain and recovery: a comprehensive systematic review and meta-analysis of randomized controlled trials.

Background: Previous studies have indicated beneficial outcomes of transcutaneous electrical acupoint stimulation (TEAS), but high-quality and comprehensive meta-analyses are lacking. The aim was to quantitatively analyze the efficacy and safety of perioperative TEAS on postoperative pain and recovery. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched through July 2022. Randomized controlled trials (RCTs) that examined the perioperative application of TEAS in adults compared with sham-TEAS and/or non-TEAS were eligible. Cumulative analgesic consumption within 24 h and rest pain scores at 2, 6, 12, and 24 h postoperatively were the two co-primary outcomes. Results: Seventy-six RCTs (n = 9,665 patients) were included. Patients treated with TEAS experienced a reduction in clinical importance in cumulative analgesic (morphine equivalent) consumption (WMD: -14.60 mg, 97.5% CI: -23.60 to -5.60; p < 0.001) and a reduction in statistical importance in rest pain scores at multiple time points within the first 24 postoperative hours. The secondary outcome analysis also identified clinically significant recovery benefits to TEAS during the first 24 h after surgery. Furthermore, TEAS could effectively reduce opioid-related side effects and did not increase serious side effects. Conclusion: This article describes current evidence about TEAS intervention on early postoperative pain and recovery. The results support the effectiveness of TEAS, but more high-quality evidence of clinical applicability is also needed. Systematic review registration: PROSPERO (CRD42021249814).

Contrasting effects of music therapy and aromatherapy on perioperative anxiety: A systematic review and meta-analysis.

INTRODUCTION: Music therapy and aromatherapy have been demonstrated effective for perioperative anxiety. However, the available studies have indicated discordant results about which adjunct treatment is better for perioperative anxiety. Therefore, we conducted this meta-analysis to explore the contrasting effects between them. METHODS: Six electronic databases were searched for clinical trials evaluating the efficacy of music therapy compared with aromatherapy in alleviating perioperative anxiety. The primary outcome was the postintervention anxiety level. Secondary outcomes included differences in blood pressure and heart rate before and after the intervention as well as pain scores at intraoperative and postoperative time points. The study protocol was registered on PROSPERO (CRD42021249737). RESULTS: Twelve studies (894 patients) were included. The anxiety level showed no statistically significant difference (SMD, 0.28; 95% CI: -0.12, 0.68; P =.17). The analysis of blood pressure and heart rate also did not identify statistically significant differences. Notably, the pain scores at the intraoperative time point suggested that aromatherapy was superior to music therapy (WMD, 0.29 cm; 95% CI: 0.05, 0.52; P =.02), while those at 4 hours after surgery indicated the opposite results (WMD, -0.48 cm; 95% CI: -0.60, -0.36; P <.001). CONCLUSION: Low-to-moderate quality evidence suggests that music therapy and aromatherapy have similar potential to relieve perioperative anxiety. The potential data indicates that the two therapies have different benefits in intervention duration and age distribution. More direct high-quality comparisons are encouraged in the future to verify this point.

Recent Advances in Preparation and Structure of Polyurethane Porous Materials for Sound Absorbing Application.

Various acoustic materials are developed to resolve noise pollution problem in many industries. Especially, materials with porous structure are broadly used to absorb sound energy in civil construction and transportation area. Polyurethane (PU) porous materials possess excellent damping properties, good toughness, and well-developed pore structures, which have a broad application prospect in sound absorption field. This work aims to summarize the recent progress of fabrication and structure for PU porous materials in sound absorption application. The sound absorption mechanisms of porous materials are introduced. Different kinds of structure for typical PU porous materials in sound absorption application are covered and highlighted, which include PU foam, modified PU porous materials, aerogel, templated PU, and special PU porous materials. Finally, the development direction and existing problems of PU material in sound absorption application are briefly prospected. It can be expected that porous PU with high sound absorption coefficient can be obtained by using some facile methods. The design and accurate regulation of porous structures or construction of multilayer sound absorption structure is favorably recommended to fulfill the high demand of industrial and commercial applications in the future work.

[Banxia Xiexin Decoction inhibiting colitis-associated colorectal cancer infected with Fusobacterium nucleatum by regulating Wnt/ß-catenin pathway].

This paper investigates the intervention effect and mechanism of Banxia Xiexin Decoction(BXD) on colitis-associated colorectal cancer(CAC) infected with Fusobacterium nucleatum(Fn). C57BL/6 mice were randomly divided into a control group, Fn group, CAC group [azoxymethane(AOM)/dextran sulfate sodium salt(DSS)](AOM/DSS), model group, and BXD group. Except for the control and AOM/DSS groups, the mice in the other groups were orally administered with Fn suspension twice a week. The AOM/DSS group, model group, and BXD group were also injected with a single dose of 10 mg·kg~(-1) AOM combined with three cycles of 2.5% DSS taken intragastrically. The BXD group received oral administration of BXD starting from the second cycle until the end of the experiment. The general condition and weight changes of the mice were monitored during the experiment, and the disease activity index(DAI) was calculated. At the end of the experiment, the colon length and weight of the mice in each group were compared. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the colon tissue. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin(IL)-2, IL-4, and IL-6 inflammatory factors in the serum. Immunohistochemistry(IHC) was used to detect the expression of Ki67, E-cadherin, and ß-catenin in the colon tissue. Western blot was used to detect the protein content of Wnt3a, ß-catenin, E-cadherin, annexin A1, cyclin D1, and glycogen synthase kinase-3ß(GSK-3ß) in the colon tissue. The results showed that compared with the control group, the Fn group had no significant lesions. The mice in the AOM/DSS group and model group had decreased body weight, increased DAI scores, significantly increased colon weight, and significantly shortened colon length, with more significant lesions in the model group. At the same time, the colon histology of the model group showed more severe adenomas, inflammatory infiltration, and cellular dysplasia. The levels of IL-4 and IL-6 in the serum were significantly increased, while the IL-2 content was significantly decreased. The IHC results showed low expression of E-cadherin and high expression of Ki67 and ß-catenin in the model group, with a decreased protein content of E-cadherin and GSK-3ß and an increased protein content of Wnt3a, ß-catenin, annexin A1, and cyclin D1. After intervention with BXD, the body weight of the mice increased; the DAI score decreased; the colon length increased, and the tumor decreased. The histopathology showed reduced tumor proliferation and reduced inflammatory infiltration. The levels of IL-6 and IL-4 in the serum were significantly decreased, while the IL-2 content was increased. Meanwhile, the expression of E-cadherin was upregulated, and that of Ki67 and ß-catenin was downregulated. The protein content of E-cadherin and GSK-3ß increased, while that of Wnt3a, ß-catenin, annexin A1, and cyclin D1 decreased. In conclusion, BXD can inhibit CAC infected with Fn, and its potential mechanism may be related to the inhibition of Fn binding to E-cadherin, the decrease in annexin A1 protein level, and the regulation of the Wnt/ß-catenin pathway.

[Characteristics and Source Apportionment of VOCs Initial Mixing Ratio in Beijing During Summer].

To clarify the characteristics and source apportionment of the VOCs initial mixing ratio in Beijing in summer, continuous monitoring of VOCs was conducted in the Beijing urban area from May to August 2022, and the initial mixing ratio was calculated using the photochemical ratio method. The results showed that:① during the study period, initial φ(TVOCs) in the Beijing urban area were (30.0 ±11.5)×10-9, in which the proportion of VOCs and alkanes containing oxygen reached 34.2% and 33.2%, respectively. The species with high volume fractions were low carbon substances such as acetone, ethane, acetaldehyde, and propane. ② The initial TVOCs mixing ratio in Beijing showed a slightly unimodal trend, reaching the peak at 11:00 and slightly decreasing in the afternoon. ③ Isoprene, acetaldehyde, n-butanal, and ethylene were the major contributors to the generation of O3, whereas toluene, isoprene, m-paraxylene, and ethylbenzene were the major contributors to the generation of secondary organic aerosols. ④ Based on the initial mixing ratio of PMF analysis, it was found that aging background and secondary sources (30%) contributed the most to VOCs in Beijing, and motor vehicle sources (25%) were the main primary human sources. In addition, solvent and fuel volatile sources contributed 16%, combustion sources contributed 11%, industrial process sources contributed 9%, and natural sources contributed 9%. ⑤ The anthropogenic sources of Beijing were mainly from the eastern and southern regions, whereas the natural sources were from the western and northwestern regions. This research showed that vehicle emissions should be further reduced, and regional joint prevention and control to reduce VOCs in the whole region is an effective means to control VOCs in Beijing.

[Tongxie Yaofang regulates tumor-associated macrophage polarization in colorectal cancer under chronic stress].

This study aims to investigate the intervention effect and mechanism of Tongxie Yaofang in regulating tumor-associated macrophage polarization on colorectal cancer under chronic stress. BALB/C mice were randomized into blank, control, model, mifepristone, and low-, medium-, and high-dose Tongxie Yaofang groups. The other groups except the blank and model groups were subjected to chronic restraint stress and subcutaneous implantation of colon cancer cells for the modeling of colon cancer under stress. Du-ring this period, the body mass and tumor size of each group of mice were recorded. The degree of depression in mice was assessed by behavioral changes. Enzyme-linked immunosorbent assay was employed to determine the levels of cortisol(CORT), 5-hydroxytryptamine(5-HT), norepinephrine(NE), M1-associated inflammatory cytokines [interleukin(IL)-1ß, IL-12, and tumor necrosis factor(TNF)-α], and M2-associated inflammatory cytokines(IL-4 and IL-10) in the serum. The tumor growth of mice in each group was regularly monitored by in vivo imaging. The histopathological changes of tumors in each group of mice were observed by hematoxylin-eosin staining. The proportions of CD86 and CD206 in the tumor tissue were detected by flow cytometry and immunofluorescence staining. Western blot was employed to determine the protein levels of Janus kinase(JAK)1, JAK2, JAK3, signal transducer and activator of transcription(STAT)3, and STAT6 in the tumor tissue. The results showed that chronic stress increased the immobility time of mice, elevated the serum levels of CORT, IL-4, and IL-10, lowered the levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and promoted the growth of subcutaneous tumors. The tumor cells in the tumor tissue grew actively, with obvious atypia and up-regulated protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and down-regulated protein level of CD86. The treatment with Tongxie Yaofang shortened the immobility time of mice, lowered the serum levels of CORT, IL-4, and IL-10, elevated the serum levels of 5-HT, NE, IL-1ß, IL-12, and TNF-α, and inhibited the growth of subcutaneous tumors in mice. Moreover, the treatment caused different degrees of necrosis in the tumor tissues, down-regulated the protein levels of CD206, JAK1, JAK2, JAK3, STAT3, and STAT6, and up-regulated the protein level of CD86. In summary, Tongxie Yaofang can promote the transformation of M2 macrophages to M1 macrophages and change the tumor microenvironment under chronic stress to inhibit the development of colorectal cancer, which may be related to the JAK/STAT signaling pathway.

A case report and literature review of rectal lipoma.

RATIONALE: Colonic lipomas are uncommon benign submucosal adipose tumors that are usually asymptomatic. In principle, large lipomas can cause symptoms that require further treatment. Here, we report a case of prolapsed giant rectal lipoma and transanal mass resection. PATIENT CONCERNS: A 65-year-old male developed rectal mass prolapse with bloody stool for 1 day. DIAGNOSES: The pathological findings were rectal lipoma. INTERVENTION: After resection of the anal tumor, the patient postoperative symptoms quickly disappeared. OUTCOMES: No recurrence of the condition was observed after 6 months of follow-up after surgery. LESSONS: It is safe and feasible for us to perform transanal mass resection for giant rectal lipomas that protrude outside the anus.

Behavioural Variant Frontotemporal Dementia due to CCNF Gene Mutation: A Case Report.

BACKGROUND: Frontal, temporal lobe dementia (FTD) and amyotrophic lateral sclerosis (ALS) are fatal neurodegenerative diseases. Studies have found that CCNF mutations have been found in patients with familial and sporadic ALS and FTD. Behavioural variant frontotemporal dementia (bvFTD) is a clinical syndrome characterized by progressive deterioration of personality, social behaviour, and cognitive function, which is most closely related to genetic factors. As the early symptoms of bvFTD are highly heterogeneous, the condition is often misdiagnosed as Alzheimer's disease or psychiatric disorders. In this study, a bvFTD patient had a CCNF gene mutation, which led to ubiquitinated protein accumulation and ultimately caused neurodegenerative disease. Genetic detection should be improved urgently for bvFTD patients and family members to provide a clinical reference for early diagnosis of frontotemporal dementia. CASE PRESENTATION: In this case, the patient was 65 years old with an insidious onset, early-onset memory loss, a significant decline in the episodic memory, an early AD diagnosis, and oral treatment with donepezil hydrochloride for 3 years with poor efficacy, followed by a change to oral memantine hydrochloride tablets, which controlled the condition for several months. His medication was switched to sodium oligomannate capsules, and his condition was gradually controlled, but no significant improvement was observed. After spontaneous drug withdrawal, the patient's condition progressed rapidly; therefore, he visited our hospital and underwent neuropsychological tests for moderate to severe cognitive impairment. AD cerebrospinal fluid markers showed no significant abnormalities, and cranial MRI revealed frontotemporal lobe atrophy and decreased hippocampal volume. Genetic testing for the presence of the CCNF gene revealed a c.1532C > A (p. T511N) heterozygous variant, which might be a diagnostic criterion for bvFTD. Therefore, the patient's symptoms recurred after transient improvement with the combination of donepezil, oral memantine hydrochloride tablets, and sodium oligomannate, but his overall condition was improved compared to that before, and this treatment regimen was continued to observe changes during the follow-up. CONCLUSION: The early clinical manifestations of bvFTD are complex and variable, and the condition is easily misdiagnosed, thus delaying treatment. Therefore, for patients with a high clinical suspicion of FTD, in addition to a detailed understanding of their medical history and family history and improvement of relevant examinations, genetic testing should be performed as early as possible to help confirm the diagnosis. For diseases closely related to genes, genetic testing of other family members should be optimised as much as possible to allow early diagnosis and intervention and guide fertility in the next generation.

Characteristics of Shisa Family Genes in Zebrafish.

Shisa represents a type of single-transmembrane adaptor protein containing an N-terminal cysteine-rich domain and a proline-rich C-terminal region. Nine shisa subfamily genes have been proposed in most vertebrates; however, some might be species-specific. The number of shisa genes present in zebrafish remains unclear. This study aimed to investigate the evolutionary relationships among shisa family genes in zebrafish (TU strain) using phylogenetic and syntenic analyses. The function of shisa-2 was preliminarily examined via CRISPR/Cas13d-mediated knockdown. Following identification in zebrafish, 10 shisa family genes, namely shisa-1, 2, 3, 4, 5, 6, 7, 8, 9a, and 9b, were classified into three main clades and six subclades. Their encoding proteins contained a cysteine-rich N-terminal domain and a proline-rich C-terminal region containing different motifs. A specific syntenic block containing atp8a2 and shisa-2 was observed to be conserved across all species. Furthermore, all these genes were expressed during embryogenesis. Shisa-2 was expressed in the presomitic mesoderm, somites, and so on. Shisa-2 was identified as a regulator of the expression of the somite formation marker mesp-ab. Overall, our study provides new insights into the evolution of shisa family genes and the control of shisa-2 over the convergent extension cells of somitic precursors in zebrafish.

Enhancing the Sound and Thermal Insulation Properties of Polypropylene Foam by Preparing High Melt Strength Polypropylene.

High-performance polypropylene (PP) foam is a vital polymer product in industrial areas. However, the poor melt strength of ordinary PP homopolymer limits its foaming molding. In this work, high melt strength polypropylene (HMSPP) is prepared by using styrene (St) and tripropylene glycol diacrylate (TPGDA) as comonomers, and then PP foams are prepared by mold foaming method. The results show that adding St in the grafting process of TPGDA will obviously improve the melt strength of the PP matrix, and its melt strength (28 184 Pa.s) is 7.4 times higher than that of pure PP. HMSPP foam has more regular and uniform cells and higher cell density, which significantly improves the sound and thermal insulation properties of PP foam. Compared with pure PP foam, the average sound transmission loss (52.9 dB) of HMSPP foam with a low foaming ratio increased by 64%, and the thermal conductivity (0.0867 W mK-1 ) decreased by 46%. Therefore, the obtained HMSPP foam can be used in sound insulation or thermal insulation area. This work provides an available route for the high-performance utilization of PP foam.

A high-gain dual-band shared-aperture array integrating zero-order-resonance patch and higher-order metasurface antenna.

This letter proposes a high-gain shared-aperture array for vehicular communications which integrates the hybrid zeroth-order-resonance (ZOR) patch and the higher-order metasurface antenna (MA). In terms of each array element, four hybrid ZOR patches with shorting pins form a metasurface which is fed by slot coupling. Different from some reported designs which have more high-frequency elements than low-frequency ones, the whole array is composed of 4 [Formula: see text] 4 hybrid ZOR patches operating in C band (4.74-5.12 GHz) and 2 [Formula: see text] 2 MAs working in Ku band (13.0-14.0 GHz). Such a layout brings that the designed array has the benefit to reduce Ku-band loss. Measure results validate the dual-band operation and show that the antenna has its peak gains of 12.7 dBi and 17.2 dBi in these two bands, respectively, which can support vehicle-to-base station and vehicle-to-satellite communications.

Electroactive Microorganisms in Advanced Energy Technologies.

Large-scale production of green and pollution-free materials is crucial for deploying sustainable clean energy. Currently, the fabrication of traditional energy materials involves complex technological conditions and high costs, which significantly limits their broad application in the industry. Microorganisms involved in energy production have the advantages of inexpensive production and safe process and can minimize the problem of chemical reagents in environmental pollution. This paper reviews the mechanisms of electron transport, redox, metabolism, structure, and composition of electroactive microorganisms in synthesizing energy materials. It then discusses and summarizes the applications of microbial energy materials in electrocatalytic systems, sensors, and power generation devices. Lastly, the research progress and existing challenges for electroactive microorganisms in the energy and environment sectors described herein provide a theoretical basis for exploring the future application of electroactive microorganisms in energy materials.

[Decursin affects proliferation, apoptosis, and migration of colorectal cancer cells through PI3K/Akt signaling pathway].

We investigated the effects of decursin on the proliferation, apoptosis, and migration of colorectal cancer HT29 and HCT116 cells through the phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway. Decursin(10, 30, 60, and 90 µmol·L~(-1)) was used to treat HT29 and HCT116 cells. The survival, colony formation ability, proliferation, apoptosis, wound hea-ling area, and migration of the HT29 and HCT116 cells exposed to decursin were examined by cell counting kit-8(CCK8), cloning formation experiments, Ki67 immunofluorescence staining, flow cytometry, wound healing assay, and Transwell assay, respectively. Western blot was employed to determine the expression levels of epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, B-cell lymphoma/leukemia-2(Bcl-2), Bcl-2-associated X protein(Bax), tumor suppressor protein p53, PI3K, and Akt. Compared with the control group, decursin significantly inhibited the proliferation and colony number and promoted the apoptosis of HT29 and HCT116 cells, and it significantly down-regulated the expression of Bcl-2 and up-regulated the expression of Bax. Decursin inhibited the wound healing and migration of the cells, significantly down-regulated the expression of N-cadherin and vimentin, and up-regulated the expression of E-cadherin. In addition, it significantly down-regulated the expression of PI3K and Akt and up-regulated that of p53. In summary, decursin may regulate epithelial-mesenchymal transition(EMT) via the PI3K/Akt signaling pathway, thereby affecting the proliferation, apoptosis, and migration of colorectal cancer cells.

Does the last 20 years paradigm of clinical research using volatile organic compounds to non-invasively diagnose cancer need to change? Challenges and future direction.

PURPOSE: Volatile organic compounds (VOCs) have shown great potential as novel biomarkers for cancer detection; however, comprehensive quantitative analysis is lacking. In this study, we performed a bibliometric analysis of non-invasive cancer diagnosis using VOCs to better characterise international trends and to predict future hotspots in this field, and then we focussed on human studies to analyse clinical characteristics for presenting the current controversies and future perspectives of further clinical work. METHODS: Publications, from 2002 to 2022, were retrieved from the Web of Science Core Collection database. CiteSpace and VOSviewer were used to generate network maps and identify the annual publications, top countries, authors, institutions, journals, references, and keywords. Then, we further screened clinical trials, and the key information was extracted into Microsoft Excel for further systematical analysis. RESULTS: Six hundred and forty-one articles were identified to evaluate research trends, of which 301 clinical trials were selected for further systematical analysis. Overall, the annual publications in this area increased, with an overall upward trend, while the quality of clinical research remains remarkably uneven. CONCLUSION: The study of non-invasive cancer diagnosis using VOCs would continue to be an active field. However, without stringent clinical design criteria, most suitable acquisition and analysis devices and statistical approaches, a list of exclusive, specific, reliable and reproducible VOCs to identify a disease and these VOCs appearing in a breath at detectable levels at early stage disease, the clinical utility of VOC tests will be difficult to have any breakthroughs.

Patient-derived organoids of lung cancer based on organoids-on-a-chip: enhancing clinical and translational applications.

Lung cancer is one of the most common malignant tumors worldwide, with high morbidity and mortality due to significant individual characteristics and genetic heterogeneity. Personalized treatment is necessary to improve the overall survival rate of the patients. In recent years, the development of patient-derived organoids (PDOs) enables lung cancer diseases to be simulated in the real world, and closely reflects the pathophysiological characteristics of natural tumor occurrence and metastasis, highlighting their great potential in biomedical applications, translational medicine, and personalized treatment. However, the inherent defects of traditional organoids, such as poor stability, the tumor microenvironment with simple components and low throughput, limit their further clinical transformation and applications. In this review, we summarized the developments and applications of lung cancer PDOs and discussed the limitations of traditional PDOs in clinical transformation. Herein, we looked into the future and proposed that organoids-on-a-chip based on microfluidic technology are advantageous for personalized drug screening. In addition, combined with recent advances in lung cancer research, we explored the translational value and future development direction of organoids-on-a-chip in the precision treatment of lung cancer.

Whole-brain CT Perfusion at Admission and During Delayed Time-window Detects the Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: To evaluate the utility of computed tomography perfusion (CTP) both at admission and during delayed cerebral ischemia time-window (DCITW) in the detection of delayed cerebral ischemia (DCI) and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage. METHODS: Eighty patients underwent CTP at admission and during DCITW. The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group, and comparisons were also made between admission and DCITW within each group. The qualitative color-coded perfusion maps were recorded. Finally, the relationship between CTP parameters and DCI was assessed by receiver operating characteristic (ROC) analyses. RESULTS: With the exception of cerebral blood volume (P=0.295, admission; P=0.682, DCITW), there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW. In the DCI group, the extreme parameters were significantly different between admission and DCITW. The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps. For the detection of DCI, mean transit time to the center of the impulse response function (Tmax) at admission and mean time to start (TTS) during DCITW had the largest area under curve (AUC), 0.698 and 0.789, respectively. CONCLUSION: Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW. The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.

Research progress of indole-fused derivatives as allosteric modulators: Opportunities for drug development.

Allosteric modulation is a direct and effective method for regulating the function of biological macromolecules, which play vital roles in various cellular activities. Unlike orthosteric modulators, allosteric modulators bind to sites distant from the protein's orthosteric/active site and can have specific effects on the protein's function or activity without competing with endogenous ligands. Compared to traditional orthosteric modulators, allosteric modulators offer several advantages, including reduced side effects, greater specificity, and lower toxicity, making them a promising strategy for developing novel drugs. Indole-fused architectures are widely distributed in natural products and bioactive drug leads, displaying diverse biological activities that attract the interest of both chemists and biologists in drug discovery. Currently, an increasing number of indole-fused compounds have exhibited potent activities in allosteric modulation. In this review, we provide a brief summary of examples of allosteric modulators based on the indole-fused complex architecture, highlighting the strategies for drug design/discovery and the structure-activity relationships of allosteric modulators from the perspective of medicinal chemistry.

Expression characteristics of Hsd3b7 in the gonads of Paralichthys olivaceus.

Steroidogenesis is an important biological process for gonadal differentiation and development. In mammals, 3ß-hydroxysteroid dehydrogenase 7 (HSD3B7) could convert 3ß-hydroxy of 7α-hydroxycholesterol into a ketone and form 7α-hydroxy-4-cholesten-3-one, which may affect steroidogenesis. However, in fish, the study of Hsd3b7 is still lacking. In this study, Hsd3b7 was identified in the olive flounder Paralichthys olivaceus, an important mariculture fish. According to bioinformatics analysis, Hsd3b7 belongs to a Rossmann-fold NAD(P)(+)-binding protein and can interact in a predictable manner with Hsd17b2, -3, and - 4, which play a role in steroidogenesis. In the adult flounder, Hsd3b7 was expressed in various tissues, at particularly high level in male muscle. The expression levels of Hsd3b7 at gonadal development stages I-V initially increased and then decreased, with an inflection point in the ovary at stage III and in the testis at stage IV. At stage III, the expression level of Hsd3b7 was significantly higher in the ovary than in the testis (P < 0.01). The results of in situ hybridization (ISH) revealed that it was mainly expressed in oocytes of phases I-IV or around oocytes of phases IV-V in the ovaries and around spermatid lobules at stages IV-V in the testes. Three regulatory sites of SRY-box transcription factor 9 (Sox9), a transcription factor involved in steroidogenesis and gonadal differentiation, were predicted in the promoter of Hsd3b7. After intraperitoneal injection with the recombination flounder Sox9a, the expression of Hsd3b7 was significantly up-regulated (P < 0.01). During the flounder gonadal differentiation, 17ß-estradiol (E2, 5 µg/g feed) and 17α-methyltestosterone (T, 5 µg/g feed) were used to obtain the phenotypic female or male flounder, and the results showed that in the E2 group, Hsd3b7 expression was highest at 2 cm TL, the primordial gonad stage, which was significantly higher than that at 12 cm TL (P < 0.05). In the T group, Hsd3b7 expression level was also highest at 2 cm TL and significantly higher than at 10 and 12 cm TL (P < 0.05). Moreover, Hsd3b7 was detected to be localized mainly around oogonia and spermatogonia during the differentiated gonads with ISH. These findings first introduce the expression characteristics of Hsd3b7 and the effect of Sox9a on its expression, which contribute to our understanding of the function of Hsd3b7 in fish gonads.

Establishment and application of four long-term culture cell lines of the olive flounder Paralichthys olivaceus blastocysts.

Four new embryonic cell lines derived from blastocysts of the olive flounder Paralichthys olivaceus, an important commercial marine fish, were established and characterized. They were designated as PoEFCI, PoEFCII, PoEFCIII, and PoEFCIV and were all fibroblastic cells. The cells were cultured in DMEM/F-12 medium supplemented with antibiotics, FBS, and growth factors at temperature of 25 °C and subcultured for >100 passages over 18 months. The origin of the cell lines was confirmed by examining the partial sequences of the cytochrome oxidase c subunit I (COI) gene of the flounder mitochondrial DNA (mtDNA). The four cell lines showed different growth curve patterns. According to the results of gene and protein expression and enzyme activity, the cell lines PoEFCI, PoEFCII, and PoEFC III could be pluripotent. The cells of all four cell lines were also successfully transfected with the green fluorescent protein (GFP) reporter gene, suggesting that they could be used to study gene function in the flounder or other fish. More importantly, PoEFCI-III were sensitive to chromium (Cr) and red sea bream Pagrus major iridovirus (RSIV), so they could be used as a powerful tool for the study of the toxicological investigation of heavy metals and RSIV in fish. Therefore, these cell lines would be useful for biotechnological and toxicological research on marine fish as an in vitro biological system.