Regulatory roles of miRNA-530 in the post-transcriptional regulation of NF-κB signaling pathway through targeted modulation of IκBα in Sebastesschlegelii.

MicroRNAs (miRNAs) are a crucial type of non-coding RNAs involved in post-transcriptional regulation. The playing essential regulatory roles in the NF-κB signaling pathway and modulate the host immune response to diverse pathogens by targeting IκBα. However, the regulatory mechanism of miRNAs in relation with IκBα in Sebastes schlegelii remains unclear. In our study, we identified two copies of IkBα gene in black rockfish (Sebastes schlegelii), namely IkBα1 and IkBα2. Moreover, we have discovered that miRNA-530 can activate the NF-κB signaling pathway by inhibiting the expression of IκBα, thereby inducing the inflammatory response. This project comprehensively investigated the interactive regulatory roles of miRNA-530 in the NF-κB signaling pathway at both cellular and in vivo levels, while also elucidating the regulatory relationships between miRNA-530 and IκBα. In conclusion, our research confirmed that miRNA-530 can target the 3'UTR region of IκBα, resulting in a decrease in the expression of IκBα at the post-transcriptional level and inhibiting its translation. The findings contribute to the understanding of the regulatory network of non-coding RNA in teleosts and its subsequent regulation of the NF-κB signaling pathway by miRNAs.

Programmable Colloids with Analogous Hypercoordination Complex Architectures.

Colloidal molecule clusters (CMCs) are promising building blocks with molecule-like symmetry, offering exceptional synergistic properties for applications in plasmonics and catalysis. Traditional CMC fabrication has been limited to simple molecule-like structures utilizing isotropic particles. Here, we employ molecular dynamics simulation to investigate the co-assembly of anisotropic nanorods (NRs) and the stimulus-responsive polymer (SRP) via reversible adsorption. The results of the simulation show that it is possible to fabricate hypercoordination complex structures with high symmetry from the co-assembly of NRs and the SRP, even in analogy to the Th(BH4)4 structure. The coordination number of these CMCs can be precisely programmed by adjusting the shape and size of the ends of the NRs and the SRP cohesion energy. Furthermore, a finite-difference time-domain simulation indicates these hypercoordination structures exhibit significantly enhanced optical activity and plasmonic coupling effects. These findings introduce a new design approach for complex molecule-like structures utilizing anisotropic nanoparticles and may expand the applications of CMCs in photonics.

Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration.

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26RtdTomato mice to lethally irradiated Ackr1-/- mice (Ackr1-/- chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

Dynamic assessment of community resilience in China: empirical surveys from three provinces.

Background: Strengthening the construction of community resilience and reducing disaster impacts are on the agenda of the Chinese government. The COVID-19 pandemic could alter the existing community resilience. This study aims to explore the dynamic change trends of community resilience in China and analyze the primary influencing factors of community resilience in the context of COVID-19, as well as construct Community Resilience Governance System Framework in China. Methods: A community advancing resilience toolkit (CART) was used to conduct surveys in Guangdong, Sichuan, and Heilongjiang provinces in China in 2015 and 2022, with community resilience data and information on disaster risk awareness and disaster risk reduction behaviors of residents collected. The qualitative (in-depth interview) data from staffs of government agencies and communities (n = 15) were pooled to explore Community Resilience Governance System Framework in China. Descriptive statistics analysis and t-tests were used to investigate the dynamic development of community resilience in China. Hierarchical regression analysis was performed to explore the main influencing factors of residential community resilience with such socio-demographic characteristics as gender and age being controlled. Results: The results indicate that community resilience in China has improved significantly, presenting differences with statistical significance (p < 0.05). In 2015, connection and caring achieved the highest score, while disaster management achieved the highest score in 2022, with resources and transformative potential ranking the lowest in their scores in both years. Generally, residents presented a high awareness of disaster risks. However, only a small proportion of residents that were surveyed had participated in any "community-organized epidemic prevention and control voluntary services" (34.9%). Analysis shows that core influencing factors of community resilience include: High sensitivity towards major epidemic-related information, particular attention to various kinds of epidemic prevention and control warning messages, participation in epidemic prevention and control voluntary services, and formulation of epidemic response plans. In this study, we have constructed Community Resilience Governance System Framework in China, which included community resilience risk awareness, community resilience governance bodies, community resilience mechanisms and systems. Conclusion: During the pandemic, community resilience in China underwent significant changes. However, community capital was, is, and will be a weak link to community resilience. It is suggested that multi-stages assessments of dynamic change trends of community resilience should be further performed to analyze acting points and core influencing factors of community resilience establishment at different stages.

Absolute Structures of a Mirror Pair of Infinite Na(H2O)4 + -Connected ε-Keggin-Al13 Species.

The absolute structures of a pair of infinite Na(H2O)4+-connected ε-Keggin-Al13 species (Na-ε-K-Al13) that were inversion structures and mirror images of each other were determined. Single crystals obtained by adding A2SO4 (A = Li, Na, K, Rb, or Cs) solution to NaOH-hydrolyzed AlCl3 solution were subjected to X-ray structure analyses. The statistical results for 36 single crystals showed that all the crystals had almost the same unit cell parameter, belonged to the same F4̅3m space group, and possessed the same structural formula [Na(H2O)4AlO4Al12(OH)24(H2O)12](SO4)4·10H2O. However, the crystals had two inverse absolute structures (denoted A and B), which had a crystallization ratio of 1:1. From Li+ to Cs+, with increasing volume of the cation coexisting in the mother solution, the degree of disorder of the four H2O molecules in the Na(H2O)4+ hydrated ion continuously decreased; they became ordered when the cation was Cs+. Absolute structures A and B are the first two infinite aluminum polycations connected by statistically occupied [(Na1/4)4(H2O)4]+ hydrated ions. The three-dimensional structure of the infinite Na-ε-K-Al13 species can be regarded as the assembly of finite ε-K-Al13 species linked by [(Na1/4)4(H2O)4]+ in a 1:1 ratio. In this assembly, each [(Na1/4)4(H2O)4]+ is connected to four ε-K-Al13 and each ε-K-Al13 is also connected to four [(Na1/4)4(H2O)4]+ in tetrahedral orientations to form a continuous rigid framework structure, which has an inverse spatial orientation between absolute structure A and B. This discovery clarifies that the ε-K-Al13 (or ε-K-GaAl12) species in Na[MO4Al12(OH)24(H2O)12](XO4)4·nH2O (M = Al, Ga; X = S, Se; n = 10-20) exists as discrete groups and deepens understanding of the formation and evolution process of polyaluminum species in forcibly hydrolyzed aluminum salt solution. The reason why Na+ statistically occupies the four sites was examined, and a formation and evolution mechanism of the infinite Na-ε-K-Al13 species was proposed.

A Study on the Maximum Reliability of Multi-UAV Cooperation Relay Systems.

This paper studies the maximum reliability of multi-hop relay UAVs, in which UAVs provide wireless services for remote users as a coded cooperative relay without an end-to-end direct communication link. In this paper, the analytical expressions of the total power loss and total bit error rate are derived as reliability measures. First, based on the environmental statistical parameters, a LOS probability model is proposed. Then, the problem of minimizing the bit error rate of static and mobile UAVs is studied. The goal is to minimize the total bit error rate by jointly optimizing the height, elevation, power and path loss and introducing the maximum allowable path loss constraints, transmission power allocation constraints, and UAV height and elevation constraints. At the same time, the total path loss is minimized to achieve maximum ground communication coverage. However, the formulated joint optimization problem is nonconvex and generally difficult to solve. Therefore, we decomposed the problem into two subproblems and proposed an effective joint optimization iteration algorithm. Finally, the simulation results are given, and the analysis shows that the optimal height of different reliability measures is slightly different; thus, using the mobility of UAVs can improve the reliability of communication performance.

Correction to "Diterpenoid Tanshinones Can Inhibit Lung Cancer Progression by Improving the Tumor Microenvironment and Downregulation of NF-κB Expression".

[This corrects the article DOI: 10.1021/acsomega.3c09667.].

The Clinical Application of Double Taylor Spatial Frame in Segmental Tibial Fracture.

OBJECTIVES: Multi-planar external fixation has been used for the management of segmental tibial fractures with severe soft tissue injuries. However, fewer specialized studies have been reported. The primary aim of this study was to describe our experience of treating fractures of this type using the Taylor Spatial Frame and Ilizarov external fixation methods. METHODS: We retrospectively analyzed 33 patients with segmental tibial fracture treated at our institution between January 2016 and December 2020. The patients were divided into double Taylor Spatial Frame (D-TSF) and Ilizarov groups based on the external fixation structure. Baseline demographic data included sex, age, injury side and cause, open or closed fracture, time from injury to surgery, complications, and external frame removal and fracture healing time. The hip-knee-ankle angle (HKA) was measured from preoperative, immediate postoperative, and final follow-up full-length X-rays of bilateral lower limbs. We determined the degree of deviation in the HKA by calculating the difference between the measured angle and the ideal value of 180°; the absolute value was used to assess recovery of the lower limb force line. At the final follow-up, Johner-Wruhs tibial fracture outcome criteria (J-W TFOC) were used to classify the postoperative function of the affected limb as excellent, good, moderate, or poor. Count data were analyzed with the chi-square test or Fisher's exact test; the Mann-Whitney U test was used for rank data. RESULTS: No statistically significant differences were observed between the two groups in terms of sex, age, side of injury, cause of injury, closed or open fracture, or time between injury and surgery, which indicates that the groups were comparable (p > 0.05). A statistically significant difference was observed in external frame removal and fracture healing time between the D-TSF and Ilizarov groups (36.24 ± 8.34 vs 45.42 ± 10.21 weeks, p = 0.009; 33.33 ± 8.21 vs 42.00 ± 9.78 weeks, p = 0.011). The Johner-Wruhs criteria were used to assess the function of the affected limb, the D-TSF group performed better in correcting the lower limb force line than the Ilizarov group. A statistically significant difference in terms of excellent ratings was observed between the two groups (18/2/1/0 vs 5/5/1/1, p = 0.010). Postoperative follow-up X-rays demonstrated a significant improvement in the HKA in both groups immediately after surgery and at the final follow-up compared to the angle before surgery. At the final follow-up, a statistically significant difference was observed in the degree of deviation in the HKA between the two groups (1.58° ± 0.84° vs 2.37° ± 1.00°, p = 0.023). CONCLUSION: The D-TSF treatment is associated with minimal secondary damage to soft tissue, a straightforward and minimally invasive procedure, multiplanar stable fracture fixation, and optimization of fracture alignment and lower limb force lines, therefore, it is highly effective therapeutic option for segmental tibial fracture.

Assessing multidisciplinary follow-up pattern efficiency and cost in follow-up care for patients in cervical spondylosis surgery: a non-randomized controlled study.

Background: The use of multidisciplinary treatment programs in out-of-hospital healthcare is a new area of research. Little is known about the benefits of this method in the management of discharged patients undergoing cervical spondylosis surgery. Objective: This study aimed to explore the effect of a contracted-based, multidisciplinary follow-up plan in patients after cervical spondylosis surgery. Methods: This non-blinded non-randomized controlled study was conducted with 88 patients (44 in the intervention group, 44 in the control group). The clinical outcomes, including Neck Disability Index (NDI), pain score (VAS), Self-Efficacy for Managing Chronic Disease 6-item Scale (SECD-6), and 12-Item Short-Form Health Survey (SF-12) score were assessed at the time of discharge, 24-72 h, 1 month, and 3 months post-discharge. The complications, patient satisfaction, and economic indicators were assessed at the final follow-up (3 months). Results: Patients who received contracted follow-up showed greater improvement in neck dysfunction at 24-72 h, 1 month, and 3 months after discharge compared to those who received routine follow-up (p < 0.001). At 1 month after discharge, the intervention group exhibited better self-efficacy (p = 0.001) and quality of life (p < 0.001) than the control group, and these improvements lasted for 3 months. The intervention group reported lower pain scores at 24-72 h and 1 month (p = 0.008; p = 0.026) compared to the control group. The incidence of complications was significantly lower in the intervention group (11.4%) compared to the control group (40.9%). The total satisfaction score was significant difference between the two groups (p < 0.001). Additionally, the intervention group had lower direct medical costs (p < 0.001), direct non-medical costs (p = 0.035), and total costs (p = 0.04) compared to the control group. However, there was no statistically significant difference in indirect costs between the two groups (p = 0.59). Conclusion: A multidisciplinary contract follow-up plan has significant advantages regarding neck disability, self-efficacy, quality of life, postoperative complications, patient satisfaction, and direct costs compared with routine follow-up.

Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine.

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

Metabolic risks remain a serious threat to cardiovascular disease: findings from the Global Burden of Disease Study 2019.

Metabolic factors are major and controllable risk factors for cardiovascular diseases (CVD), and few studies have described this burden. We aim to assess it from 1990 to 2019 and predict the trends through 2034. Global Burden of Disease (GBD) provides data on sex, age, and socio-demographic index (SDI) levels. Numbers, age-standardized death rates (ASDR) and estimated annual percentage change (EAPC) were used. Future trends were estimated by NORDPRED model. The deaths cases of metabolic-related CVD increased from 8.61 million (95% UI: 7.91-9.29) to 13.71 million (95% UI: 12.24-14.94) globally. The ASDR continued to decline globally (EAPC = -1.36). The burden was heavier in male and middle-aged people and elderly people. CVD-related ASDR caused by high systolic blood pressure (SBP) had a downward trend globally (EAPC = -1.45), while trends of high body mass index (BMI) (EAPC = 1.29, 1.97, 0.92) and fasting plasma glucose (FPG) (EAPC = 0.95, 1.08, 0.46) were increasing in the middle, low-middle, and low SDI regions, respectively. Compared to 2015-2019, cumulative deaths will increase by 27.85% from 2030 to 2034, while ASDR will decrease 10.47%. The metabolic-related CVD burden remained high globally and deaths will continue to rise in the future. Men, middle-aged and elderly people were focus of concern. High SBP was globally well-managed over the past 30 years, but the CVD burden due to high BMI and FPG remained high. Exceptional initiatives are needed to regarding interventions targeting high BMI and FPG in middle and lower SDI regions.

Glutamatergic neurons in the paraventricular nucleus of the hypothalamus participate in the regulation of visceral pain induced by pancreatic cancer in mice.

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice. Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer. Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain.

Understanding healthcare providers' preferred attributes of pediatric pneumococcal conjugate vaccines in the United States.

As higher-valent pneumococcal conjugate vaccines (PCVs) become available for pediatric populations in the US, it is important to understand healthcare provider (HCP) preferences for and acceptability of PCVs. US HCPs (pediatricians, family medicine physicians and advanced practitioners) completed an online, cross-sectional survey between March and April 2023. HCPs were eligible if they recommended or prescribed vaccines to children age <24 months, spent ≥25% of their time in direct patient care, and had ≥2 y of experience in their profession. The survey included a discrete choice experiment (DCE) in which HCPs selected preferred options from different hypothetical vaccine profiles with systematic variation in the levels of five attributes. Relative attribute importance was quantified. Among 548 HCP respondents, the median age was 43.2 y, and the majority were male (57.9%) and practiced in urban areas (69.7%). DCE results showed that attributes with the greatest impact on HCP decision-making were 1) immune response for the shared serotypes covered by PCV13 (31.4%), 2) percent of invasive pneumococcal disease (IPD) covered by vaccine serotypes (21.3%), 3) acute otitis media (AOM) label indication (20.3%), 4) effectiveness against serotype 3 (17.6%), and 5) number of serotypes in the vaccine (9.5%). Among US HCPs, the most important attribute of PCVs was comparability of immune response for PCV13 shared serotypes, while the number of serotypes was least important. Findings suggest new PCVs eliciting high immune responses for serotypes that contribute substantially to IPD burden and maintaining immunogenicity against serotypes in existing PCVs are preferred by HCPs.

Shell Modulation of Hollow Metal Sulfide Nanocomposite for Stable Potassium Storage at Room and High Temperature.

The large size of K-ion makes the pursuit of stable high-capacity anodes for K-ion batteries (KIBs) a formidable challenge, particularly for high temperature KIBs as the electrode instability becomes more aggravated with temperature climbing. Herein, we demonstrate that a hollow ZnS@C nanocomposite (h-ZnS@C) with a precise shell modulation can resist electrode disintegration to enable stable high-capacity potassium storage at room and high temperature. Based on a model electrode, we identify an interesting structure-function correlation of the h-ZnS@C: with an increase in the shell thickness, the cyclability increases while the rate and capacity decreases, shedding light on the design of high-performance h-ZnS@C anodes via engineering the shell thickness. Typically, the h-ZnS@C anode with a shell thickness of 60 nm can deliver an impressive comprehensive performance at room temperature; the h-ZnS@C with shell thickness increasing to 75 nm can achieve an extraordinary stability (88.6% capacity retention over 450 cycles) with a high capacity (450 mAh g-1) and a superb rate even at an extreme temperature of 60 ℃, which is much superior than those reported anodes. This contribution envisions new perspectives on rational design of functional metal sulfides composite toward high-performance KIBs with insights into the significant structure-function correlation.

CwJAZ4/9 negatively regulates jasmonate-mediated biosynthesis of terpenoids through interacting with CwMYC2 and confers salt tolerance in Curcuma wenyujin.

Plant JASMONATE ZIM-DOMAIN (JAZ) genes play crucial roles in regulating the biosynthesis of specialized metabolites and stressful responses. However, understanding of JAZs controlling these biological processes lags due to numerous JAZ copies. Here, we found that two leaf-specific CwJAZ4/9 genes from Curcuma wenyujin are strongly induced by methyl-jasmonate (MeJA) and negatively correlated with terpenoid biosynthesis. Yeast two-hybrid, luciferase complementation imaging and in vitro pull-down assays confirmed that CwJAZ4/9 proteins interact with CwMYC2 to form the CwJAZ4/9-CwMYC2 regulatory cascade. Furthermore, transgenic hairy roots showed that CwJAZ4/9 acts as repressors of MeJA-induced terpenoid biosynthesis by inhibiting the terpenoid pathway and jasmonate response, thus reducing terpenoid accumulation. In addition, we revealed that CwJAZ4/9 decreases salt sensitivity and sustains the growth of hairy roots under salt stress by suppressing the salt-mediated jasmonate responses. Transcriptome analysis for MeJA-mediated transgenic hairy root lines further confirmed that CwJAZ4/9 negatively regulates the terpenoid pathway genes and massively alters the expression of genes related to salt stress signaling and responses, and crosstalks of multiple phytohormones. Altogether, our results establish a genetic framework to understand how CwJAZ4/9 inhibits terpenoid biosynthesis and confers salt tolerance, which provides a potential strategy for producing high-value pharmaceutical terpenoids and improving resistant C. wenyujin varieties by a genetic approach.

Psilostachyin C reduces malignant properties of hepatocellular carcinoma cells by blocking CREBBP-mediated transcription of GATAD2B.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally. Many herbal medicines and their bioactive compounds have shown anti-tumor properties. This study was conducted to examine the effect of psilostachyin C (PSC), a sesquiterpenoid lactone isolated from Artemisia vulgaris L., in the malignant properties of HCC cells. CCK-8, flow cytometry, wound healing, and Transwell assays revealed that 25 µM PSC treatment significantly suppressed proliferation, cell cycle progression, migration, and invasion of two HCC cell lines (Hep 3B and Huh7) while promoting cell apoptosis. Bioinformatics prediction suggests CREB binding protein (CREBBP) as a promising target of PSC. CREBBP activated transcription of GATA zinc finger domain containing 2B (GATAD2B) by binding to its promoter. CREBBP and GATAD2B were highly expressed in clinical HCC tissues and the acquired HCC cell lines, but their expression was reduced by PSC. Either upregulation of CREBBP or GATAD2B restored the malignant properties of HCC cells blocked by PSC. Collectively, this evidence demonstrates that PSC pocessess anti-tumor functions in HCC cells by blocking CREBBP-mediated transcription of GATAD2B.

Recent advances in nucleic acid signal amplification-based aptasensors for sensing mycotoxins.

Mycotoxin contamination in food products may cause serious health hazards and economic losses. The effective control and accurate detection of mycotoxins have become a global concern. Even though a variety of methods have been developed for mycotoxin detection, most conventional methods suffer from complicated operation procedures, low sensitivity, high cost, and long assay time. Therefore, the development of simple and sensitive methods for mycotoxin assay is highly needed. The introduction of nucleic acid signal amplification technology (NASAT) into aptasensors significantly improves the sensitivity and facilitates the detection of mycotoxins. Herein, we give a comprehensive review of the recent advances in NASAT-based aptasensors for assaying mycotoxins and summarize the principles, features, and applications of NASAT-based aptasensors. Moreover, we highlight the challenges and prospects in the field, including the simultaneous detection of multiple mycotoxins and the development of portable devices for field detection.

Inhibition of USP7 enhances CD8+ T cell activity in liver cancer by suppressing PRDM1-mediated FGL1 upregulation.

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.

Two pairs of bioactive cyclohexene alkaloid enantiomers from the roots of Piper nigrum.

Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice.

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.