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Since higher education reforms were started in the mid-1980s, higher education in China has experienced significant transformations. Changes have not only been revealed by the increase in numbers of undergraduates, but also by a significant expansion in postgraduate education in mainland China. In order to enhance its global competitiveness, the Chinese government has tried very hard to internationalize universities with the strong conviction to transform a few universities in China into ‘world-class’ universities. It is against this context that Chinese universities have experienced significant restructuring and governance changes. In the quest for internationalization, academics and students are under tremendous pressure to compete with the global research-led universities, while internationalizing curriculum and promoting international academic exchanges have become an increasingly important trend in China. This article offers a practitioner's critical reflection on internationalization in universities in China. The author has worked in different universities and unesco in the last few decades and also got many opportunities to represent China in different international educational organizations. The critical reflections to be discussed in this article focuses on developing countries in Southeast Asia, at a time when many of them are under pressure to internationalize their universities.Higher Education Policy (2008) 21, 505–517. doi:10.1057/hep.2008.22 [ABSTRACT FROM AUTHOR]

Despite substantial research on foreign direct investment (FDI) in China, there have been few empirical studies on the strategic choice between the two major joint venture (JVs) types, equity joint ventures (EJVs) and contractual joint ventures (CJVs). This paper provides an in-depth analysis of the managerial choice between these two strategies. It also provides a critical test of two main theories, transaction cost economics (TCE) and resource-based view (RBV), in explaining the choice. Data from structured interviews with 55 Sino–Hong Kong JVs in Guangdong province showed that the choice of CJVs over EJVs largely mirrored transaction cost-saving rationale from both Hong Kong and Chinese perspectives. When choosing EJVs over CJVs, there was a larger variety of considerations between Hong Kong and Guangdong partners, and TCE and RBV intertwined in providing insights. The paper shows that transaction costs in setting up and running EJVs vs CJVs are dependent on firm-specific capabilities to negotiate and manage equity or non-equity-based alliance partnerships. While some Hong Kong and Chinese firms chose CJVs to exploit the contracting flexibility allowed in CJV non-equity alliances, others chose EJVs to avoid the same contract attribute, due to lack of ability to manage a flexible partnership.Asian Business & Management (2007) 6, 355–375. doi:10.1057/palgrave.abm.9200235 [ABSTRACT FROM AUTHOR]

Irinotecan, an anticancer drug, is associated with severe and potentially fatal diarrhea and neutropenia. The objective of this analysis was to evaluate the role of SN-38 exposure, the active metabolite of irinotecan, UGT1A1 genotypes, and baseline bilirubin on the maximum decrease (nadir) in absolute neutrophil counts following irinotecan. This analysis extended the work of a previous study that examined the effect of UGT1A1 genotypes on the incidence of severe neutropenia in 86 advanced cancer patients following irinotecan treatment. Regression analysis showed that the absolute neutrophil count nadir depended on SN-38 exposure (AUC) and UGT1A1*28 homozygous 7/7 genotype. An increased SN-38 AUC and the 7/7 genotype were significantly associated with a lower absolute neutrophil count nadir (R2 = .49). An alternate model suggested that higher baseline bilirubin and the 7/7 genotype were also significantly associated with a lower absolute neutrophil count nadir, although with a lower coefficient of determination (R2= .31). Based on these findings and other reports, the irinotecan label was modified to indicate the role of UGT1A1*28 polymorphism in the metabolism of irinotecan and the associated increased risk of severe neutropenia. The label modifications also included recommendations for lower starting doses of irinotecan in patients homozygous for the UGT1A1*28 (7/7) polymorphism. [ABSTRACT FROM AUTHOR]

A bimodal extended-release formulation of d-methylphenidate (d-MPH) has been developed to enable fast onset of action and once-daily administration in patients with attention deficit hyperactivity disorder. The authors studied the dose proportionality of extended-release d-MPH pharmacokinetics. Twenty-five healthy adult volunteers received 5, 10, 20, 30, and 40 mg d-MPH in a crossover study with 7 days between doses. All doses were well tolerated. Dose proportionality was shown for all dose-dependent pharmacokinetic parameters. Geometric means (%gCV) for the first C max peak, C max0-4, were 3.25 (29.0%), 6.05 (27.1%), 12.6 (31.9%), 18.5 (31.9%), and 25.2 ng/mL (29.3%) for d-MPH 5, 10, 20, 30, and 40 mg, respectively. Geometric means (%gCV) for C max4-10 were 3.18 (27.5%), 5.84 (27.7%), 12.5 (31.7%), 17.7 (31.6%), and 23.6 ng/mL (29.0%), respectively. Geometric means for AUC 0-∞were 24.3 (30.7%), 45.9 (30.2%), 96.4 (35.5%), 144 (33.3%), and 195 ng · h/mL (30.9%), respectively. The pharmacokinetics of once-daily extended-release d-MPH are proportional to the dose. [ABSTRACT FROM AUTHOR]

Empirical studies on contractual joint ventures (CJVs) in China are rare. Concentrated in Guangdong province, CJVs represent, rather than FDI, a long-term subcontracting alliance arrangement between Hong Kong and Guangdong firms. The quasi-market quasi-hierarchy nature of the alliance makes uncovering the ownership advantages of CJVs and dissecting the distribution of management control between CJV partners difficult. Drawing on data from cross-case studies, this paper identifies ownership advantages and their sources, and reveals how the pattern of non-equity contributions by CJV partners underpins CJV control structure. The findings show that the concept of ownership advantage can occur in a non-equity alliance, so long as there is a separate alliance organization. The transfer of ownership advantages from parent firms to CJVs takes place in the same way as in equity alliances. The overall design of the CJV control structure is based on the perceived value of non-equity contributions by each side, but as control rights are not clearly derived from equity ownership, power distribution is not always consistent with the pattern of non-equity resource contributions, particularly where trust between partners is lacking.Asian Business & Management (2006) 5, 379–398. doi:10.1057/palgrave.abm.9200192 [ABSTRACT FROM AUTHOR]

The blue electroluminescence from titania nanotubes doped into poly(2-methoxy-5-(2-ethylhexyloxy)-p-phenylene vinylene) (MEH-PPV) was studied. The results of absorption andphotoluminescence demonstrated that the observed blue electroluminescence in thenanocomposites comes directly from band-to-band transitions of titania nanotubes. Therelative intensity of the blue electroluminescence was enhanced by increasing the content oftitania nanotubes. Moreover, polymer light-emitting diodes doped with titania nanotubesshowed higher carrier transport ability and lower onset voltages. Electroluminescence fromone-dimensional materials has potential applications in nanoscale electrical andoptoelectronic devices. [ABSTRACT FROM AUTHOR]

Ag/cross-linked poly(vinyl alcohol) (PVA) cable-like nanostructureswere synthesized with control in an aqueous solution of a hydrolysableamphiphilic block polymer, poly(vinyl acetone) (PVKA) (ketalization degreeDH = 0.533)under γ-ray irradiation, via one-step in situ reduction ofAg+ and cross-linking of alcohol units. In the present approach, we try to control the speed ofthe cross-linking reaction of PVA chains (alcohol units), which are yielded from thehydrolysed PVKA, utilizing the low hydrolysis rate of the PVKA in dilute acidic solution. [ABSTRACT FROM AUTHOR]

We demonstrate irreversible blocking of ion channels using single-wall carbon nanotubes(SWNTs) functionalized with 2-aminoethylmethane thiosulfonate (MTSET). Incontrast, as-produced and purified SWNTs exhibit reversible blocking, indicatingthat the MTSET molecule attached to SWNTs chemically interacts with thecysteine groups in the ion channels. Functionalization of SWNTs with MTSET isinferred from Fourier transform infrared (FTIR) spectroscopy, which clearly showsabsorptions due to –CH stretching and deformation modes, and decrease in intensity ofthe –COOH line due to reaction of acid functionalized SWNTs with the basicN–CH3 end of the MTSET molecule. [ABSTRACT FROM AUTHOR]

We report here a low-temperature approach which is simple and catalyst free to synthesize aligned ZnO nanorods on flat substrates, i.e. decomposing zinc acetate (C4H6O4Zn) in air at ∼250 °C. The ZnO nanorods prepared by this method exhibited strong photoluminescence at ∼377 nm, ∼387 nm and ∼401 nm. Thermal annealing experiments suggested that the emission at ∼401 nm might be due to the defects in the ZnO nanorods which can be removed by low-temperature annealing, and that the near band-edge emissions at ∼377 and ∼387 nm might be caused by the difference in the diameter of the nanorods. [ABSTRACT FROM AUTHOR]

Silver flowerlike and dendritic nanostructures were synthesized in an aqueous solution of ahydrolysable amphiphilic block copolymer polyvinylacetone (PVKA) via in situ reduction ofAg+ and hydrolysis of PVKA at room temperature. Compared with a previous result, thecomplete hydrolysis time of PVKA is greatly shortened in this process. [ABSTRACT FROM AUTHOR]

Background: Spontaneous thought is a universal, complex, and heterogeneous cognitive activity that significantly impacts mental activity and strongly correlates with mental disorders., Methods: Utilizing the think-aloud method, we captured spontaneous thoughts during rest from 38 diagnosed with depression, alongside 36 healthy controls and 137 healthy individuals. Through a comprehensive assessment of various dimensions of thought content, we compared thought content between individuals with depression and healthy controls, and between healthy women and men. Finally, we employed natural language processing (NLP) to develop regression models for multidimensional content assessment and a classification model to differentiate between individuals with and without depression., Results: Compared to healthy controls, individuals with depression had more internally oriented and less externally oriented spontaneous thoughts. They focused more on themselves and negative things, and less on positive things, experiencing higher levels of negative emotions and lower levels of positive emotions. Besides, we found that compared to healthy men, healthy women's spontaneous thoughts focus more on interoception, the self, past events, and negative events, and they experience higher levels of negative emotions. Meanwhile, we identified the potential application of the think-aloud method to collect spontaneous thoughts and integrate NLP in the field of depression., Conclusions: This study offers direct insights into the stream of thought during individuals' resting state, revealing differences between individuals with depression and healthy controls, as well as sex differences in the content of spontaneous thoughts. It enhances our understanding of spontaneous thought and offers a new perspective for preventing, diagnosing, and treating depression., Competing Interests: Declaration of competing interest All the authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Second primary cancer (SPC) risks after breast cancer (BC) in BRCA1/BRCA2 pathogenic variant (PV) carriers are uncertain. We estimated relative and absolute risks using a novel linkage of genetic testing data to population-scale National Disease Registration Service and Hospital Episode Statistics electronic health records., Methods: We followed 25,811 females and 480 males diagnosed with BC and tested for germline BRCA1/BRCA2 PVs in NHS Clinical Genetics centers in England between 1995 and 2019 until SPC diagnosis, death, migration, contralateral breast/ovarian surgery plus 1 year, or the 31st of December 2020. We estimated standardized incidence ratios (SIRs) using English population incidences, hazard ratios (HRs) comparing carriers to noncarriers using Cox regression, and Kaplan-Meier 10-year cumulative risks., Results: There were 1,840 BRCA1 and 1,750 BRCA2 female PV carriers. Compared with population incidences, BRCA1 carriers had elevated contralateral BC (CBC; SIR, 15.6 [95% CI, 11.8 to 20.2]), ovarian (SIR, 44.0 [95% CI, 31.4 to 59.9]), combined nonbreast/ovarian (SIR, 2.18 [95% CI, 1.59 to 2.92]), colorectal (SIR, 4.80 [95% CI, 2.62 to 8.05]), and endometrial (SIR, 2.92 [95% CI, 1.07 to 6.35]) SPC risks. BRCA2 carriers had elevated CBC (SIR, 7.70 [95% CI, 5.45 to 10.6]), ovarian (SIR, 16.8 [95% CI, 10.3 to 26.0]), pancreatic (SIR, 5.42 [95% CI, 2.09 to 12.5]), and combined nonbreast/ovarian (SIR, 1.68 [95% CI, 1.24 to 2.23]) SPC risks. Compared with females without BRCA1/BRCA2 PVs on testing, BRCA1 carriers had elevated CBC (HR, 3.60 [95% CI, 2.65 to 4.90]), ovarian (HR, 33.0 [95% CI, 19.1 to 57.1]), combined nonbreast/ovarian (HR, 1.45 [95% CI, 1.05 to 2.01]), and colorectal (HR, 2.93 [95% CI, 1.53 to 5.62]) SPC risks. BRCA2 carriers had elevated CBC (HR, 2.40 [95% CI, 1.70 to 3.40]), ovarian (HR, 12.0 [95% CI, 6.70 to 21.5]), and pancreatic (HR, 3.56 [95% CI, 1.34 to 9.48]) SPC risks. Ten-year cumulative CBC, ovarian, and combined nonbreast/ovarian cancer risks were 16%/6.3%/7.8% ( BRCA1 carriers), 12%/3.0%/6.2% ( BRCA2 carriers), and 3.6%/0.4%/4.9% (noncarriers). Male BRCA2 carriers had higher CBC (HR, 13.1 [95% CI, 1.19 to 146]) and prostate (HR, 5.61 [95% CI, 1.96 to 16.0]) SPC risks than noncarriers., Conclusion: Survivors of BC carrying BRCA1 and BRCA2 PVs are at high SPC risk. They may benefit from enhanced surveillance and risk-reduction measures.

Flavin-dependent halogenase (FDH) is highly prized in pharmaceutical and chemical industries for its exceptional capacity to produce halogenated aromatic compounds with precise regioselectivity. This study has devised a multi-enzyme self-assembly strategy to construct an effective and reliable in vitro coenzyme cycling system tailored for FDHs. Initially, tri-enzyme self-assembling nanoclusters (TESNCs) were developed, comprising glucose dehydrogenase (GDH), flavin reductase (FR) and FDH. The TESNCs exhibited enhanced thermal stability and conversion efficiency compared to free triple enzyme mixtures during the conversion of L-Trp to 6-Cl-L-Trp, resulting in a 2.1-fold increase in yield. Subsequently, an ordered co-immobilization of GDH, FR, and FDH was established, further amplifying the stability and catalytic efficiency of the FDH coenzyme cycle system. Compared to the free TESNCs, the immobilized TESNCs demonstrated a 4.2-fold increase in catalytic efficiency in a 5 mL reaction system. This research provides an effective strategy for developing a robust and efficient coenzyme recycling system for FDHs., (© 2024 Wiley Periodicals LLC.)

Adenomyosis involves the infiltration of endometrial glands and stroma deep into the uterine tissue, causing disruption to the endometrial-myometrial interface (EMI). The role of interleukin-17 (IL-17) has been extensively studied in endometriosis, but its involvement in adenomyosis remains unclear. This study aimed to investigate the expression of IL-17 in eutopic and ectopic endometrium (adenomyosis) of individuals with adenomyosis at the level of EMI. Paired tissues of eutopic endometrium and adenomyoma were collected from 16 premenopausal women undergoing hysterectomy due to adenomyosis. The IL-17 system was demonstrated in paired tissue samples at the level of EMI by the immunochemistry study. Gene expression levels of IL-17A and IL-17 receptor (IL-17R) were assessed through quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Comparative gene transcript amounts were calculated using the delta-delta Ct method. By immunohistochemical staining, CD4, IL-17A, and IL-17R proteins were detected in both eutopic endometrium and adenomyosis at the level of EMI. IL-17A and IL-17R were expressed mainly in the glandular cells, and the expression of both IL-17A and IL-17R was found to be stronger in adenomyosis than in endometrium. 3-Diaminobenzidine (DAB) staining revealed greater IL-17A expression in adenomyosis compared to eutopic endometrium. Quantitative RT-PCR showed 7.28-fold change of IL-17A and 1.99-fold change of IL-17R, and the fold change level of both IL-17A and IL-17R is significantly higher in adenomyosis (IL-17A: p = 0.047, IL-17R: p = 0.027) versus eutopic endometrium. We found significantly higher IL-17 levels in adenomyosis compared to eutopic endometrium at the level of EMI. The results showed that the IL-17 system may play a role in adenomyosis.

Objectives: To explore burden and its related factors among primary caregivers of patients with cancer., Sample & Setting: This study was conducted in an oncology ward at a medical center in southern Taiwan. A total of 137 dyads of patients with cancer and their primary caregivers were recruited., Methods & Variables: This cross-sectional correlational study used a structured questionnaire to assess the burden of primary caregivers. Data on patients' basic characteristics and disease profiles were extracted from medical records from January to June 2019. Linear regression analysis was used to identify factors associated with the burden of primary caregivers., Results: The majority of primary caregivers were female (70%) and aged younger than 65 years (85%). Overall, the mean primary caregiver burden score was 38.83 (SD = 12.86), with spiritual burden ranking highest among the four domains assessed. Factors related to overall primary caregiver burden included psychiatric symptoms, daily care hours, patient age, and the lack of rotational support., Implications for Nursing: Hospice and oncology nurses can actively identify psychiatric symptoms in primary caregivers, targeting high-risk groups to provide timely resources or psychiatric referrals, aiming to alleviate future caregiver burden.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Two coumarin derivatives SWJT-33 and SWJT-34 were synthesized as probes for the detection of cadaverine (Cad). Among them, SWJT-34 exhibits high selectivity and low detection limits for Cad using fluorescence or UV-vis spectrum. The detection limits for Cad were calculated to be 0.018 μM by fluorescence spectrum and 0.34 μM by UV-vis spectrum, which was much lower than those of most of reported probes. The probe could realize colorimetric and ratiometric detection of Cad because an aza-Michael addition reaction occurred between SWJT-34 and Cad to form the Schiff base compound as a product. In addition, SWJT-34 could be fabricated as portable test strips for the selective detection of Cad in vapor, and the corresponding detection limits were calculated to be 1.88 ppm in the fluorescent mode and 57 ppm in UV-vis mode, respectively. Additionally, these test strips could be used to test the freshness of Rottweiler shrimp and pork at different temperatures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Deep and extensive wounds usually cannot be closed directly by suturing or skin grafting. Flap transplantation is typically used to reconstruct large wounds clinically. The flap survival is based on a stable blood perfusion. It is established that estrogen promotes wound healing and angiogenesis, and regulates the inflammatory response, leading to enhanced flap survival after transplantation. However, estrogen concentrations administered in previous studies were significantly higher than physiological levels, potentially causing systemic side effects. Estrogen-sustained-release silastic capsules can maintain blood serum estrogen closer to physiological levels. This study aimed to investigate whether administering estrogen at a lower concentration, closer to physiological levels, could still enhance flap survival., Materials and Methods: This study was performed in a random skin flap model in ovariectomized (OVX) mice. Sustained-release estrogen silastic capsules were implanted into OVX mice to determine the functional role of estrogen in wound healing after flap transplantation. Flap blood perfusion was analysed using a colour laser Doppler scanner. Immunohistochemical staining of CD31, hypoxia-inducible factor 1 alpha (HIF-1α), alpha-smooth muscle actin (α-SMA), cleaved caspase 3 and apoptotic terminal dUTP nick end-labelling stain was used to investigate flap angiogenesis, tissue hypoxia, wound healing and cell death in the flap tissue, respectively., Results: We observed that administering estrogen at a lower concentration enhanced superficial blood perfusion while reducing the flap's ischemic area and tissue necrosis. HIF-1α expression was significantly decreased in the dermis layer but not in the fascia, whereas cleaved caspase 3 levels decreased in the fascia but remained unchanged in the dermis. Additionally, there was no significant difference in CD31and α-SMA expression between the groups., Conclusion: In summary, the study showed that an estrogen silastic capsule maintained physiological estrogen levels and improved superficial perfusion, thereby reducing dermal hypoxia, and cell death in a mouse random pattern skin flap model. Although no significant promotion of angiogenesis was observed, the study suggests that appropriate estrogen supplements could enhance flap wound recovery., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Higher serum cholesterol levels have been associated with an increased risk of dry eye disease (DED). The relationship between statin (HMG-CoA reductase inhibitor) use and DED in patients with hyperlipidemia remains unclear. To investigate the association between statin use and the risk of DED in patients with hyperlipidemia, we conducted a population-based retrospective cohort study utilizing data from Taiwan's Longitudinal Generation Tracking Database. Patients were categorized into statin users and nonusers, with a 5-year follow-up period. The study identified patients with newly diagnosed hyperlipidemia, excluding those with prior DED diagnoses. Matching and adjustments for covariates resulted in 41,931 individuals in each group. Patients receiving statin therapy were compared with those unexposed. Cumulative exposure doses were also evaluated to assess dose-response relationships. The primary outcome was the incidence of DED diagnosed during the follow-up period. Cox proportional hazards regression models estimated the risk of DED, and conditional logistic regression analyzed the dose-response effect of statin exposure. Among 41,931 matched pairs, statin users exhibited a slightly increased risk of developing DED compared with nonusers (adjusted hazard ratio, 1.06; 95% CI, 1.02-1.11; p < 0.01). However, no dose-response relationship was observed between statin exposure and DED risk. Statin use among patients with hyperlipidemia is associated with a marginally higher risk of DED. These findings underscore the importance of regular eye examinations in this patient population to facilitate early detection and management of DED., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background/purpose: In Taiwan, there are very few dental radiology curricula in medical radiation education system. This study assessed the participants' learning outcomes after finishing the dental radiology course for the continuing education of medical radiation technologists in Taiwan., Materials and Methods: This study used the questionnaire survey to evaluate the participants' learning outcomes after finishing the dental radiology course for the continuing education of medical radiation technologists in Taiwan., Results: In this study, 85 participants filled out the questionnaires completely after finishing the dental radiology course. The majority of participants agreed that dental radiology courses were rare in the medical radiation school curricula and the continuing education courses of medical radiation technologists. Moreover, most of participants found this course to be helpful in raising their basic knowledge about the dental radiology, their attitude towards the dental radiology, and their interest in further learning of the dental radiology. They were satisfied with the courses. The degree of agreement for each question was high with all the mean scores for each question being between 3.87 and 4.61. The numbers (rates) of respondents who answered as agree were between 58 (68.24%) and 84 (98.82%)., Conclusion: The dental radiology course for the continuing education of medical radiation technologists is found to increase the participants' basic knowledge about the dental radiology, and their awareness and understanding of the radiation protection in dental radiography. Thus, this model can be further used for the dental radiology course for the continuing education of medical radiation technologists in Taiwan., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Gasotransmitters are endogenous gaseous signaling molecules that can freely pass through cell membranes and transmit signals between cells, playing multiple roles in cell signal transduction. Due to extensive and ongoing research in this field, we have successfully identified many gasotransmitters so far, among which nitric oxide, carbon monoxide, and hydrogen sulfide are best studied. Gasotransmitters are implicated in various diseases related to necroptosis, such as cardiovascular diseases, inflammation, ischemia-reperfusion, infectious diseases, and neurological diseases. However, the mechanisms of their effects on necroptosis are not fully understood. This review focuses on endogenous gasotransmitter synthesis and metabolism and discusses their roles in necroptosis, aiming to offer new insights for the therapeutic approaches to necroptosis-associated diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Long-term use of rhubarb (RH) can cause adverse gastrointestinal reactions (such as diarrhea), whereas RH steaming with wine (PRH) can alleviate RH-induced diarrhea. However, the potential material basis and mechanisms by which wine steaming alleviates diarrhea caused by RH remain unclear., Purpose: To reveal the potential material basis and underlying mechanisms of wine steaming in alleviating diarrhea caused by RH from the perspective of small intestinal flora and immune function., Methods: The major anthraquinone/anthrone components were detected using high-performance liquid chromatography (HPLC). Constipation model mice were replicated using loperamide hydrochloride and were administered RH and PRH for six consecutive weeks. Histopathological observation (duodenum, jejunum, and ileum) was performed using hematoxylin-eosin (HE) staining, and the serum levels of inflammatory cytokines, immunoglobulin G (IgG), and immunoglobulin A (IgA) were examined. CD4 + , CD8 + , and Treg cells counts in peripheral blood were determined using flow cytometry; The protein expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa-B (NF-κB) was determined using immunohistochemistry (IHC) and western blot (WB). The small intestine contents and feces were analyzed by 16 S rRNA sequencing and the contents of short chain fatty acids (SCFAs) in feces were determined using gas chromatography-mass spectrometry (GC-MS). Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the blood absorption compounds and endogenous metabolites., Results: The levels of the major anthraquinone/anthrone components were decreased in PRH. RH and PRH both increased the wet fecal weight at 12 h (WFW-12) and fecal water rate (FWR), alleviated the dry and black fecal morphology, and relieved small intestine injuries in the second week. In the fourth week, although RH and PRH alleviated the abnormal levels of indicators in the model mice (fecal water rate, immune cells percentage, and TLR4/NF-κB expression), minor small intestinal damage was observed. Compared to that at the fourth week, RH and PRH increased the levels of WFW-12, FWR, inflammatory cytokines, and TLR4/NF-κB expression, and decreased the levels of IgG/IgA and immune cells with extended administration (sixth week). Further, damage to the small intestine worsened (severe ileal damage) and different degrees of loose stools were observed in RH- and PRH-administered mice in the sixth week. Compared with those in the control group, the levels of WFW-12, FWR, inflammatory cytokines, TLR4/NF-κB expression, IgG/IgA, and immune cell percentage were significantly different in the RH-H and PRH-H mice at the sixth week (except for CD8 + in PRH-H). Further, RH and PRH disturbed the gut microbiota (GM) (Lactobacillus and Dubosiella decreased, Aerococcus and Corynebacterium increased) and obviously reduced the content of SCFAs (acetic acid, butyric acid, and isobutyric acid). However, almost all the results indicated a lower impact of PRH than that of RH. Metabolic pathways mainly involved in glycerophospholipid metabolism were identified along with a total of 21 blood absorption components, including anthraquinones, anthrones, flavanols, and tannins. The correlation analysis showed a positive correlation of pathogenic bacteria (Aerococcus and Corynebacterium) with inflammatory cytokines, TLR4/NF-κB, LysoPC(20:0/0:0), and PE (16:0/20:4(8Z,11Z,14Z,17Z)) and a negative correlation with immune cells and SCFAs (acetic acid and isobutyric acid); however, the opposite results were observed for beneficial bacteria (Lactobacillus and Dubosiella)., Conclusion: Overall, PRH can alleviate RH-induced diarrhea by recovering the GM imbalance and abnormal levels of GM-mediated SCFAs, alleviating the decrease in cellular immune function and abnormal expression of TLR4/NF-κB, thereby suppressing the release of inflammatory factors, possibly, through its lower content of anthraquinones. This study explored for the first time the processing mechanism of wine steaming in alleviating RH-induced diarrhea from the aspects of small intestinal flora and small intestinal immune function., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Tumour immunotherapy represented by immune checkpoint inhibitors (ICIs) has greatly improved the overall prognosis of patients with malignant tumours, and is regarded as an important breakthrough in the field of medicine in recent years. ICIs have gradually become the core of tumour therapy and are increasingly used in the clinic. In order to achieve early clinical prediction and management of immune-related adverse events (irAEs), it is still necessary to perform further research on the mechanisms, risk factors, and predictors of irAE occurrence in the future. Zhou et al describe the consultation of a patient with advanced gastric cancer combined with chronic plaque psoriasis. This case provides an important reference for the use of programmed cell death protein-1 (PD-1) inhibitors in patients of tumours combined with chronic plaque psoriasis. This case also highlights that screening of high-risk groups for irAEs is critical before applying PD-1 inhibitors to patients with chronic psoriasis combined with tumours. PD-1 inhibitors are new and potent antineoplastic agents that can cause serious immune-related adverse events such as toxic epidermal necrolysis release and psoriasis. Glucocorticosteroids are the first-line agents for irAEs. The incidence of rheumatic irAEs may be higher in reality, which will inevitably become a new challenge for rheumatologists and dermatologists., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Zebrafish sex differentiation is a complicated process and the detailed mechanism has not been fully understood. Here we characterized a transcription factor, Foxl2l, which participates in female oogenesis. We show that it is expressed specifically in proliferating germ cells in juvenile gonads and mature ovaries. We have used CRISPR-Cas9 to generate zebrafish deficient in foxl2l expression. Zebrafish with foxl2l -/- are all males, and this female-to-male sex reversal cannot be reversed by tp53 mutation, indicating this sex reversal is unrelated to cell death. We have generated transgenic fish expressing GFP under the control of foxl2l promoter to track the development of foxl2l + -germ cells; these cells failed to enter meiosis and accumulated as cystic cells in the foxl2l -/- mutant. Our RNA-seq analysis also showed the reduced expression of genes in meiosis and oogenesis among other affected pathways. All together, we show that zebrafish Foxl2l is a nuclear factor controlling the expression of meiotic and oogenic genes, and its deficiency leads to defective meiotic entry and the accumulation of premeiotic germ cells., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Design-Thinking Intergenerational Service-Learning Model (DTISLM), rooted in the biopsychosocial model, aims to empower older adults to improve their chronic-disease management behavior through tailored programs addressing their specific healthcare needs. This study, conducted in Taiwan, used a convenience sampling method ( n = 172) to evaluate the impact of DTISLM on Taiwan's adult day center participants' perception of self-care behaviors, feelings of happiness, depression, and perceived social support using pretest-posttest surveys. The results indicated a significant enhancement in participants' perception of self-care behaviors, reduction in depression score, and improvements in perceived social support following the completion of the program. The findings underscore the efficacy of applying a design-thinking framework in an intergenerational context. Future studies should investigate how the DTISLM can be scaled to various demographics and healthcare settings to enhance its applicability and understand its long-term effects., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cancer metastasis is the leading cause of cancer-related deaths, underscoring the importance of understanding its underlying mechanisms. Hepatocellular carcinoma (HCC), a highly malignant type of cancer, was selected as our research model., Material and Methods: We aimed to develop high-metastatic cell lines using in vitro and in vivo selection strategies and identify critical metastasis-related genes through microarray analyses by comparing them with parental cells., Results: Our results showed that the high-metastatic cell lines exhibited significantly stronger invasion abilities than parental cells. Microarray analyses identified cytidine deaminase (CDA), a gene associated with systemic chemotherapy resistance, as one of the overexpressed genes in the high-metastatic cells. Data analysis from The Cancer Genome Atlas Program revealed that while CDA is downregulated in HCC, patients with high CDA expression tend to have poorer prognoses. Cell models confirmed that CDA overexpression enhances cell migration and invasion, whereas CDA knockdown inhibits these abilities. Investigating the key molecules involved in the epithelial-mesenchymal transition (EMT), we found that CDA overexpression increases the expression of fascin, N-cadherin, β-catenin, and snail while decreasing E-cadherin expression. Conversely, CDA knockdown produced opposite results. Additionally, we discovered that CDA regulates NF-κB signaling, which controls the expression of N-cadherin, thereby promoting the invasion capability of HCC cells., Conclusions: We isolated highly metastatic cells and identified potential HCC metastasis-related genes. CDA promotes cell invasion by regulating EMT through the NF-κB pathway. Future studies are warranted to explore the potential of CDA as a biomarker for prognosis and therapeutic decision-making., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The nonlinear susceptibility in the terahertz region is expected to have a non-negligible imaginary part originating from the momentum-dependent scattering time of free carriers, but it has been scarcely reported. By utilizing an intense 4 THz beam from a terahertz free electron laser, we investigated the azimuth angle dependence of the third harmonic generation (THG) from semiconductors. The observed angular anisotropy of THG revealed the contribution of the imaginary part of the nonlinear susceptibility originating from the momentum-scattering time relation in addition to its real part originating from the band nonparabolicity. The results provide a deeper understanding of nonlinear optics in the terahertz region.

Cystathionine β-synthase (CBS) occupies a key position as the initiating and rate-limiting enzyme in the sulfur transfer pathway and plays a vital role in health and disease. CBS is responsible for regulating the metabolism of cysteine, the precursor of glutathione (GSH), an important antioxidant in the body. Additionally, CBS is one of the three enzymes that produce hydrogen sulfide (H 2 S) in mammals through a variety of mechanisms. The dysregulation of CBS expression in cancer cells affects H 2 S production through direct or indirect pathways, thereby influencing cancer growth and metastasis by inducing angiogenesis, facilitating proliferation, migration, and invasion, modulating cellular energy metabolism, promoting cell cycle progression, and inhibiting apoptosis. It is noteworthy that CBS expression exhibits complex changes in different cancer models. In this paper, we focus on the CBS synthesis and metabolism, tissue distribution, potential mechanisms influencing tumor growth, and relevant signaling pathways. We also discuss the impact of pharmacological CBS inhibitors and silencing CBS in preclinical cancer models, supporting their potential as targeted cancer therapies., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous observational studies have suggested that there appears to be a close association between mitochondrial function and psychiatric disorders, but whether a causal role exists remains unclear., Methods: We extracted genetic instruments for 67 mitochondrial-related proteins and 10 psychiatric disorders from publicly available genome-wide association studies, and employed five distinct MR methods and false discovery rate correction to detect causal associations between them. Additionally, we conducted a series of sensitivity tests and additional model analysis to ensure the robustness of the results. For potential causal associations, we further performed reverse MR analyses to assess the impact of reverse causality., Results: We identified a total of 2 significant causal associations and 24 suggestive causal associations. Specifically, Phenylalanine-tRNA ligase was found to increase the risk of Alzheimer's disease, while Mitochondrial glutamate carrier 2 decreased the risk of autism spectrum disorder. Furthermore, there was no evidence of significant pleiotropy, heterogeneity, or reverse causality., Limitations: This study was limited to individuals of European ancestry, and the conclusions drawn are merely revelatory., Conclusion: This study provides novel insights into the relationship between mitochondria and psychiatric disorders, as well as the pathogenesis and treatment strategies for psychiatric disorders., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A bioinspired total synthesis of 3- epi -junipercedrol, which contains a strained tricyclo[5.2.2.0 3,7 ]undecane allo -cedrane framework and five stereocenters, was accomplished via an effective anionic semipinacol rearrangement of a tricyclic cedrane mesylate. The corresponding cedrane precursor was synthesized efficiently by employing the reductive oxy-Nazarov cyclization and an intramolecular aldol condensation as the key steps. This synthetic approach provided a further evidence for the biogenetic relationship between the typical cedrane and allo -cedrane sesquiterpenoids.

Objectives: To investigate community health centers' (CHCs) health literacy., Design: A cross-sectional study., Sample: A total of 374 CHCs were surveyed and 258 CHCs responded, with an effective questionnaire response rate of 69.0%., Measurements: Data were collected by using a self-developed health literacy assessment tool to survey CHCs' health literacy throughout Taiwan from January to December 2019., Results: The item of organizational health literacy (OHL) with the highest proportion of CHCs not implementing them was "Design of easy-to-use computer applications and new media" (47.3% not yet achieved), followed by "Involving target audiences in document and service development" (34.9% not yet achieved). CHCs located in northern Taiwan had higher health literacy achievement scores than those in other regions, and those in urban areas had higher health literacy achievement scores than those in general and remote areas., Conclusions: This study identified items with poor implementation of OHL and found regional differences in health literacy among CHCs. The findings can inform the development of targeted interventions to improve health literacy in underperforming CHCs and guide policymakers in allocating resources to regions and areas in need of., (© 2024 Wiley Periodicals LLC.)

Objectives: Campylobacter is a significant zoonotic pathogen primarily transmitted through poultry. Our study aimed to assess antimicrobial resistance and genetic relationships among Campylobacter isolates from retail chicken meat and humans in Taiwan., Methods: Campylobacter isolates were analysed using whole-genome sequencing to investigate their antimicrobial resistance, genetic determinants of resistance, and genotypes., Results: Campylobacter coli and Campylobacter jejuni accounted for 44.9% and 55.1% of chicken meat isolates, and 11.4% and 88.6% of human isolates, respectively. C. coli displayed significantly higher resistance levels. Furthermore, isolates from chicken meat exhibited higher levels of resistance to most tested antimicrobials compared to isolates from humans. Multidrug resistance was observed in 96.3% of C. coli and 43.3% of C. jejuni isolates from chicken meat and 80.6% of C. coli and 15.8% of C. jejuni isolates from humans. Macrolide resistance was observed in 85.5% of C. coli isolates, primarily attributed to the erm(B) rather than the A2075G mutation in 23S rRNA. Among the 511 genomes, we identified 133 conventional MLST sequence types, indicating significant diversity among Campylobacter strains. Notably, hierarchical Core-genome multilocus sequence typing clustering, including HC0, HC5, and HC10, revealed a significant proportion of closely related isolates from chicken meat and humans., Conclusions: Our research highlights significant associations in antimicrobial resistance and genetic relatedness between Campylobacter isolates from chicken meat and humans in Taiwan. The genetic analysis data suggest that campylobacteriosis outbreaks may occur more frequently in Taiwan than previously assumed. Our study emphasizes the need for strategies to control multidrug-resistant strains and enhance outbreak prevention., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this study, based on the self-assembly strategy, we fused CipA with carbonyl reductase LXCAR S154Y derived from Leifsonia xyli by gene coding, and successfully performed the carrier-free immobilization of LXCAR S154Y . The immobilized enzyme was then characterized using scanning electron microscope (SEM), dynamic light scattering (DLS) and fourier transform infrared spectroscopy (FTIR). Compared with the free enzyme, the immobilized LXCAR S154Y exhibited a 2.3-fold improvement in the catalytic efficiency k cat /k m for the synthesis of a chiral pharmaceutical intermediate (R)-3,5-bis(trifluoromethyl)phenyl ethanol ((R)-BTPE) by reducing 3,5-bis(trifluoromethyl)acetophenone (BTAP). Moreover, the immobilized enzyme showed the enhanced stability while maintaining over 61 % relative activity after 18 cycles of batch reaction. Further, when CipA-fused carbonyl reductase was employed for (R)-BTPE production in a continuous flow reaction, almost complete yield (97.0 %) was achieved within 7 h at 2 M (512.3 g/L) of BTAP concentration, with a space-time yield of 1717.1 g·L -1 ·d -1 . Notably, we observed the retention of cofactor NADH by CipA-based enzyme aggregates, resulting in a higher total turnover number (TTN) of 4815 to facilitate this bioreductive process. This research developed a concise strategy for efficient preparation of chiral intermediate with cofactor self-sufficiency via continuous flow biocatalysis, and the relevant mechanism was also explored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Interleukin (IL)-37, a unique member of the IL-1 family, is known for its anti-inflammatory properties. However, its effects on immune-mediated liver diseases, such as primary biliary cholangitis (PBC) and acute immune-mediated hepatitis, remain unclear. Using mouse models of autoimmune cholangitis and hepatitis induced by 2-OA-OVA and concanavalin A (Con A) respectively, we introduced the human IL-37 gene via a liver-preferred adeno-associated virus vector (AAV-IL-37) to mice, as mice lack endogenous IL-37. Our findings reveal that IL-37 did not affect autoimmune cholangitis. Surprisingly, IL-37 exacerbated inflammation in Con A-induced hepatitis rather than mitigating it. Mechanistic insights suggest that this exacerbation involves the interferon (IFN)-γ pathway, supported by elevated serum IFN-γ levels in AAV-IL-37-treated Con A mice. Specifically, IL-37 heightened the number of hepatic NK and NKT cells, increased the production of the NK cell chemoattractant CCL5, and elevated the frequency of hepatic NK and NKT cells expressing IFN-γ. Moreover, IL-37 enhanced IFN-γ secretion from NK cells when combined with other proinflammatory cytokines, highlighting its synergistic effect in promoting IFN-γ production. These unexpected outcomes underscore a novel role for IL-37 in exacerbating liver inflammation during immune-mediated liver diseases, implicating its influence on NK cells and the production of IFN-γ by these cells., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Abstract: A 54-year-old woman with a history of end-stage renal disease was found to have infiltrative cardiomyopathy by echocardiography. 99m Tc-pyrophosphate ( 99m Tc-PYP) scintigraphy was positive with a remarkable myocardial uptake. Gene test found a mutation of AGXT , confirming a final diagnosis of primary hyperoxaluria. Radiotracer uptake was due to high myocardial oxalate deposition. This case illustrates false positivity of the 99m Tc-PYP scan caused by hyperoxaluria-associated cardiomyopathy, which raises awareness for other conditions apart from amyloid cardiomyopathy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients. Trauma patients with moderate to severe TBI were included in this retrospective study. rs8104571 genotyping and admission plasma TRPM4 and SUR1 quantification was performed with real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Adequate plasma for TRPM4 and SUR1 ELISA quantification was available for 289 patients, 54 of whom were African American (AA). Plasma TRPM4 concentration was increased in those with a variant rs8104571 allele compared to wild type when controlling for demographics and injury characteristics in the overall cohort (P = 0.04) and within the AA subgroup (P = 0.01). There was no significant association between plasma TRPM4 or SUR1 and clinical outcome (each P > 0.05). Plasma TRPM4 abundance increased with acute kidney injury severity (P = 0.02). The association between increased plasma TRPM4 and variant rs810457 supports an underlying mechanism involving increased neuroinflammation with a subsequent increase in the leakage of TRPM4 from the central nervous system into circulation. Alternative sources of plasma TRPM4 including the kidney cannot be excluded and may play a significant role in the pathophysiology of trauma as well., Competing Interests: Funding and Conflicts of Interest: This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health (T32GM008792). Additional funding was provided by the William Stamps Farish Fund, the Howell Family Foundation, and the James H. "Red" Duke Professorship. Dr. Cox reports additional support from the National Institutes of Health; Department of Defense-Medical Technology Enterprise Consortium; State of Texas Emerging Technology Fund; Generate Life Sciences, Inc.; Athersys, Inc.; Celgene Cellular Therapeutics; Cellvation, Inc.; Cellularity, Inc.; Hope Biosciences, Inc.; The Bentsen Foundation; Mission Connect; Let's Cure CP; Ladybug Foundation; Evelyn Griffin Foundation; Glassell Family Foundation; The George and Cynthia Mitchell Foundation; Grace R. Walls Endowment; Brown Foundation; Cellvation, Inc.; Coagulex, Inc.; EMIT Corporation. No other authors report funding or conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: Hydroxylamine (HA) is vital industrial raw material and pharmaceutical intermediate. In addition, HA is an important cellular metabolite, which is intermediate in the formation of nitric oxide and nitroxide. However, excessive amounts of HA are toxic to both animals and plants. Conventional methods for the detection of HA are cumbersome and complicated. The detection of HA with fluorescent probes is convenient and sensitive. There are few probes available for the detection of hydroxylamine. Therefore, a fluorescent probe for the sensitive and selective detection of HA was developed in this work., Results: A coumarin derivative SWJT-22 was synthesized as a colorimetric fluorescent probe to detect hydroxylamine (HA), with high sensitivity and selectivity. The detection limit of the probe to HA was 0.15 μM, which was lower than most probes of HA. Upon the addition of HA to aqueous solution containing SWJT-22, the color of the solution changed from orange to yellow, and the fluorescence color also changed from orange to green. The reaction mechanism of SWJT-22 to HA was confirmed by 1 H NMR titrations, mass spectrometry and round bottom flask experiments. Moreover, SWJT-22 had been fabricated into portable test strips for the detection of HA. SWJT-22 had been successfully used in cellular imaging and could detect both endogenous and exogenous HA in HeLa cells and RAW 264.7 cells., Significance: Due to the physiological role of hydroxylamine in organisms, it is crucial to detect hydroxylamine selectively and sensitively. This work provided a convenient tool for the detection of hydroxylamine, not only to detect endogenous and exogenous HA in cells, but also made into portable test strips. The HA fluorescent probe SWJT-22 is expected to promote the study of HA in physiological processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD., (© 2024. The Author(s).)

Organic synaptic transistors are a promising technology for advanced electronic devices with simultaneous computing and memory functions and for the application of artificial neural networks. In this study, the neuromorphic electrical characteristics of organic synaptic electrolyte-gated transistors are correlated with the microstructural and interfacial properties of the active layers. This is accomplished by utilizing a semiconducting/insulating polyblend-based pseudobilayer with embedded source and drain electrodes, referred to as PB-ESD architecture. Three variations of poly(3-hexylthiophene) (P3HT)/poly(methyl methacrylate) (PMMA) PB-ESD-based organic synaptic transistors are fabricated, each exhibiting distinct microstructures and electrical characteristics, thus serving excellent samples for exploring the critical factors influencing neuro-electrical properties. Poor microstructures of P3HT within the active layer and a flat active layer/ion-gel interface correspond to typical neuromorphic behaviors such as potentiated excitatory postsynaptic current (EPSC), paired-pulse facilitation (PPF), and short-term potentiation (STP). Conversely, superior microstructures of P3HT and a rough active layer/ion-gel interface correspond to significantly higher channel conductance and enhanced EPSC and PPF characteristics as well as long-term potentiation behavior. Such devices were further applied to the simulation of neural networks, which produced a good recognition accuracy. However, excessive PMMA penetration into the P3HT conducting channel leads to features of a depressed EPSC and paired-pulse depression, which are uncommon in organic synaptic transistors. The inclusion of a second gate electrode enables the as-prepared organic synaptic transistors to function as two-input synaptic logic gates, performing various logical operations and effectively mimicking neural modulation functions. Microstructure and interface engineering is an effective method to modulate the neuromorphic behavior of organic synaptic transistors and advance the development of bionic artificial neural networks.

Background and Aims: Primary biliary cholangitis (PBC) is an autoimmune disease often accompanied by multisystem damage. This study aimed to explore the causal association between genetically predicted PBC and diabetes, as well as multiple cardiovascular diseases (CVDs)., Methods: Genome-wide association studies (GWAS) summary data of PBC in 24,510 individuals of European ancestry from the European Association for the Study of the Liver was used to identify genetically predicted PBC. We conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to estimate the impacts of PBC on diabetes (N = 17,685 to 318,014) and 20 CVDs from the genetic consortium (N = 171,875 to 1,030,836)., Results: SVMR provided evidence that genetically predicted PBC is associated with an increased risk of type 1 diabetes (T1D), type 2 diabetes (T2D), myocardial infarction (MI), heart failure (HF), hypertension, atrial fibrillation (AF), stroke, ischemic stroke, and small-vessel ischemic stroke. Additionally, there was no evidence of a causal association between PBC and coronary atherosclerosis. In the MVMR analysis, PBC maintained independent effects on T1D, HF, MI, and small-vessel ischemic stroke in most models., Conclusion: Our findings revealed the causal effects of PBC on diabetes and 7 CVDs, and no causal relationship was detected between PBC and coronary atherosclerosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to this study., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Brain biological age, which measures the aging process in the brain using neuroimaging data, has been used to assess advanced brain aging in neurodegenerative diseases, including Parkinson disease (PD). However, assuming that whole brain degeneration is uniform may not be sufficient for assessing the complex neurodegenerative processes in PD. In this study we constructed a multiscale brain age prediction models based on structural MRI of 1240 healthy participants. To assess the brain aging patterns using the brain age prediction model, 93 PD patients and 91 healthy controls matching for sex and age were included. We found increased global and regional brain age in PD patients. The advanced aging regions were predominantly noted in the frontal and temporal cortices, limbic system, basal ganglia, thalamus, and cerebellum. Furthermore, region-level rather than global brain age in PD patients was associated with disease severity. Our multiscale brain age prediction model could aid in the development of objective image-based biomarkers to detect advanced brain aging in neurodegenerative diseases., 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.)

Psychological stress affects the neuroendocrine regulation, which modulates mental status and behaviors. Melatonin, a hormone synthesized primarily by the pineal gland, regulates many brain functions, including circadian rhythms, pain, sleep, and mood. Selective pharmacological melatonin agonist ramelteon has been clinically used to treat mood and sleep disorders. Posttraumatic stress disorder (PTSD) is a psychiatric condition associated with severe trauma; it is generally triggered by traumatic events, which lead to severe anxiety and uncontrollable trauma recall. We recently reported that repeated social defeat stress (RSDS) may induce robust anxiety-like behaviors and social avoidance in mice. In the present study, we investigated whether melatonin receptor activation by melatonin and ramelteon regulates RSDS-induced behavioral changes. Melatonin treatment improved social avoidance and anxiety-like behaviors in RSDS mice. Moreover, treatment of the non-selective MT 1 /MT 2 receptor agonist, ramelteon, markedly ameliorated RSDS-induced social avoidance and anxiety-like behaviors. Moreover, activating melatonin receptors also balanced the expression of monoamine oxidases, glucocorticoid receptors, and endogenous antioxidants in the hippocampus. Taken together, our findings indicate that the activation of both melatonin and ramelteon regulates RSDS-induced anxiety-like behaviors and PTSD symptoms. The current study also showed that the regulatory effects of neuroendocrine mechanisms and cognitive behaviors on melatonin receptor activation in repeated social defeat stress., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

A new chemodosimeter SWJT-31 with an aggregation-induced emission (AIE) effect was designed and constructed. Upon increasing the water fraction in the solution, it exhibited typical AIE, which showed bright red fluorescence at 610 nm. SWJT-31 could sensitively and specifically recognize hydrazine by the TICT effect with an LOD of 33.8 nM, which was much lower than the standard of the USEPA. A portable test strip prepared using SWJT-31 was also developed for the visual detection of hydrazine. Eventually, it was successfully used for the detection of hydrazine in water samples and HeLa cells.