A new simplified risk assessment model enhances postoperative prophylaxis of venous thromboembolism in Chinese adult patients with inguinal hernia (CHAT-3): A prospective, multicenter, randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) significantly affects the prognosis of surgical patients with inguinal hernia. The complex Caprini score, commonly used for postoperative VTE risk assessment, poses practical challenges for surgeons in clinical settings. METHODS: The CHAT-3 trial, a prospective, multicenter, randomized controlled trial, compared a simple three-factor model to assess VTE risk against routine practices in post-inguinal hernia surgery (IHS) patients. The patients were randomly assigned (1:1) to the intervention or control arm. The intervention group used the three-factor model to identify patients at moderate or high risk of VTE for subsequent prophylaxis according to clinical guidelines. Both groups were followed for four weeks, with randomization implemented using computer-generated sequences. The primary outcome measured was the rate of VTE prophylaxis. Secondary outcomes included time spent on VTE risk assessment (surgeon self-reported), postoperative D-dimer trends, perioperative VTE occurrence, bleeding events, and the net clinical benefit. RESULTS: Of the 1,109 participants, 508 in the experimental group and 601 in the control group completed follow-up. The three-factor model showed higher VTE prophylaxis rates in all patients (pharmacologic prophylaxis: 26.2% vs. 6.00%, P<0.001) and particularly in those at high risk (pharmacologic prophylaxis: 57.3% vs. 9.50%, P<0.001). The experimental group significantly reduced VTE risk assessment time compared to the Caprini score (1.39±0.55 min vs. 5.73±1.35 min, P<0.001). The experimental group had lower D-dimer levels (0.26±0.73 mg/L vs. 0.35±0.55 mg/L, P=0.028). In the experimental group, the patients did not experience an increased risk of VTE (0% vs. 1.66%, P=0.268) and bleeding (1.18% vs. 0.67%, P=0.558) compared to the controls. There was no significant difference in net clinical benefit, which combined VTE and bleeding events, between the experimental and control groups (1.18% vs. 0.83%, P=0.559). CONCLUSION: Applying the simple three-factor model in perioperative VTE management could quickly identify the patient with a high risk of VTE and improve the prophylaxis rate of perioperative VTE. TRIAL REGISTRATION: XXX. TRIAL REGISTRATION: ChiCTR2000033769.

Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis.

OBJECTIVE: Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion. Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis. In this study, we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition. METHODS: Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls. A systematic analysis of clinical characteristics and prognostic factors was also conducted. Cell growth was assessed using the Cell Counting Kit-8 (CCK-8) assay, and apoptosis and cell cycle progression were evaluated by flow cytometry. Moreover, RNA pull-down was performed to identify target microRNAs, and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets. RESULTS: Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival (OS) (hazard ratio: 2.357; 95% confidence interval 1.258-4.415). The circ_0012152 knockdown reduced cell growth, increased apoptosis, and inhibited cell cycle progression in AML cell lines. RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152. Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors. We suggested that miR-652-3p targeted SOX4, as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells. CONCLUSION: Circ_0012152 is an independent poor prognostic factor for OS in AML, and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

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.

Association of Life's Essential 8 with all-cause mortality and risk of cancer: a prospective cohort study.

BACKGROUND: No study has concentrated on the association of LE8 with cancer risk and death. We aim to examine the association of LE8 with death and cancer. METHODS: A total of 94733 adults aged 51.42 ± 12.46 years and 77551 participants aged 54.09±12.06 years were enrolled in longitudinal and trajectory analysis respectively. Baseline LE8 was divided into three groups based on the American Heart Association criteria and three trajectory patterns by latent mixture models. We reviewed medical records and clinical examinations to confirm incident cancer during the period from 2006 to 2020. Death information was collected from provincial vital statistics offices. Cox models were used. RESULTS: 12807 all-cause deaths and 5060 cancers were documented during a 14-year follow-up. Relative to participants with high LE8 at baseline, participants with lower levels of LE8 have a significantly increased risk of mortality and incident cancer. All these risks have an increasing trend with LE8 level decreasing. Meanwhile, the trajectory analysis recorded 7483 all-cause deaths and 3037 incident cancers after approximately 10 years. The associations of LE8 with death and cancer were identical to the longitudinal study. In the subtype cancer analysis, LE8 has a strong effect on colorectal cancer risk. Moreover, the cut point is 56.67 in the association between LE8 and death, while the cut point altered to 64.79 in the association between LE8 and incident cancers. These associations were enhanced among younger adults. CONCLUSIONS: There was a significant association of LE8 with death and cancer risk, especially for the young population.

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.

Ventricular Netrin-1 deficiency leads to defective pyramidal decussation and mirror movement in mice.

The corticospinal tract (CST) is the principal neural pathway responsible for conducting voluntary movement in the vertebrate nervous system. Netrin-1 is a well-known guidance molecule for midline crossing of commissural axons during embryonic development. Families with inherited Netrin-1 mutations display congenital mirror movements (CMM), which are associated with malformations of pyramidal decussation in most cases. Here, we investigated the role of Netrin-1 in CST formation by generating conditional knockout (CKO) mice using a Gfap-driven Cre line. A large proportion of CST axons spread laterally in the ventral medulla oblongata, failed to decussate and descended in the ipsilateral spinal white matter of Ntn1Gfap CKO mice. Netrin-1 mRNA was expressed in the ventral ventricular zone (VZ) and midline, while Netrin-1 protein was transported by radial glial cells to the ventral medulla, through which CST axons pass. The level of transported Netrin-1 protein was significantly reduced in Ntn1Gfap CKO mice. In addition, Ntn1Gfap CKO mice displayed increased symmetric movements. Our findings indicate that VZ-derived Netrin-1 deletion leads to an abnormal trajectory of the CST in the spinal cord due to the failure of CST midline crossing and provides novel evidence supporting the idea that the Netrin-1 signalling pathway is involved in the pathogenesis of CMM.

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.

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.

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.].

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.

Reproductive factors and cardiovascular health in post-menopausal women: a special focus on natural menopause.

Female-specific reproductive factors might contribute to increased risk of cardiovascular disease, and the American Heart Association (AHA) recently proposed Life's Essential 8 (LE8) score to quantify cardiovascular health (CVH). The study aimed to examine the relationships between reproductive factors and the LE8 score among post-menopause women in the United States. We enrolled 3223 post-menopause women from National Health and Nutrition Examination Survey (NHANES). CVH groups based on LE8 score were low (0-49), moderate (50-79), and high good CVH levels (80-100). Multivariate ordinal logistic regressions were applied to estimate the associations between reproductive factors and the LE8 score. In multivariate model, early menarche (OR: 0.69, 95 percent CI: 0.51-0.93) and early menopause (OR: 0.57, 95 percent CI: 0.43-0.77) were associated with LE8 score compared with normal menarche and menopause; Meanwhile, ages at menarche and menopause were positively correlated with LE8 score. The number of pregnancies and full-term pregnancies were negatively associated with LE8 (OR for per pregnancy increase and 95 percent CI, 0.93 (0.88, 0.98), 0.93 (0.87, 0.99), separately). Overall, natural menopausal women with early age at menarche and menopause, and a higher number of pregnancies may have a high risk of lower CVH, and need to focus on their CVH.

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

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.

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.

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.

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.

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.