Efficacy of acupuncture for depression: a systematic review and meta-analysis.

Introduction: Depression is a pervasive mental health challenge with substantial global ramifications. Contemporary therapeutic strategies predominantly consist of psychological interventions and pharmacological treatments. Acupuncture, deeply rooted in ancient traditions and bolstered by a plethora of clinical trials, demonstrates considerable efficacy in depression. This study aims to elucidate the efficacy and safety of acupuncture as a standalone therapy for depression patients by reviewing randomized controlled trials that compare acupuncture treatment with conventional drug therapy. Methods: Comprehensive searches were conducted across six databases in both Chinese and English: CNKI, Wanfang, VIP, Embase, Medline, and CENTRAL. The literature search spanned from 1 July 2013, to 1 July 2023. Two researchers independently carried out literature screening and data extraction. Review Manager 5.4 was utilized for data analysis and bias risk assessment. A total of 20 randomized controlled trials were included in the qualitative synthesis, involving 1,376 participants and 43 relevant acupoints. Results: The Meta-analysis results, based on the HAMD scale scores, revealed that acupuncture regimens (RR: -1.63; 95% CI: -2.49 to -0.76; P = 0.0002; I2 = 86%; n = 1,668) were significantly more effective compared to standalone medication. Moreover, efficacy metrics from the HAMD highlighted a substantial advantage of acupuncture (RR: 2.6; 95% CI: 1.6 to 4.23; P = 0.0001; I2 = 0; n = 614). Further assessments utilizing SERS and TESS demonstrated a lower incidence of side effects and adverse outcomes in the acupuncture group. Conclusions: Acupuncture, when compared to conventional pharmacotherapy, exhibits significant efficacy as a standalone treatment after four weeks of intervention, with fewer side effects and adverse reactions. However, further investigation is needed to determine the most effective acupoints and appropriate types of acupuncture techniques for treating depression. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023443711.

NiFeB-assisted adsorption and activation of nitrogen to improve the photooxidation activity of zinc porphyrin.

This study effectively addresses the challenge of nitrogen adsorption and activation in photocatalytic nitrogen fixation by introducing an oxidizing co-catalyst, NiFeB hydroxides. The NiFeB hydroxides could provide reactive active sites and significantly enhance the nitrogen oxidation activity, offering a novel pathway for co-catalysts in nitrogen fixation reactions.

Factors associated with usage frequency and pricing of temporary anchorage devices among orthodontists.

Background/purpose: Temporary anchorage devices (TADs) are widely used in contemporary orthodontic treatments for anchorage purposes. This research aimed to investigate orthodontists' attitude toward temporary anchorage devices (TADs) by surveying their TAD usage frequency and pricing and to identify factors influencing TAD usage frequency and pricing. Materials and methods: A structured, self-administered questionnaire with a total of 26 questions was randomly distributed to members of the Taiwanese Association of Orthodontics at the annual orthodontic meeting. The questionnaire comprised 6 questions on demographics, 10 questions on work patterns and patient type, and 10 questions on orthodontic technique. Responses were analyzed using a Pearson chi-Square test to identify factors of interest. Results: Factors associated with TAD usage frequency included degree of income satisfaction, number of working hours per week, and proportion of extraction-based treatments in treatment plans. Factors associated with TAD pricing included orthodontist age, geographic region of practice, and adult treatment fee. Conclusion: More Taiwanese orthodontists use TADs compared with orthodontists in other countries. TADs have become universally accepted, but practitioners use them selectively. The main factor influencing TAD usage frequency was the proportion of extraction-based treatments in treatment plans, and those influencing TAD were orthodontist age, geographic region of practice, and adult treatment fee. These findings may be applicable to other parts of the world and should be investigated at an international level.

An innovative experimental apparatus for the analysis of natural gas hydrate cavitation erosion process using laser-induced cavitation.

Natural gas hydrates (NGHs) are an emerging source of clean energy distributed in the pores of soil sediments in deep seabed and permafrost zones with abundant reserves. Cavitation contains enormous energy, thus allowing radial cavitation jets to improve drilling and production rates of NGHs. This paper presents an experimental apparatus that was developed to synthesize NGHs and generate cavitation bubbles by laser for the analysis of the erosion rules of NGHs by cavitation in a reservoir environment. The apparatus consists of a working fluid injection and pressure control system, a temperature control and circulation system, a laser-induced cavitation system, a visual reaction vessel, and a data acquisition and measurement system. The laser-induced cavitation erosion on NGHs and multi-bubble interaction experiments can be conducted over temperatures and pressures in the range of 0-20 °C and 0-12 MPa, respectively, in a visualized reaction vessel. Hydrophones and high-speed photography were utilized for monitoring and analyzing the erosion process within the visualized reaction vessel. In addition, bubble groups of different components in various environments can also be tested in this apparatus to obtain the interaction characteristics under different conditions. This paper discusses the basic structure and principle of the apparatus and conducts a series of experiments to verify the effect of cavitation erosion on hydrate and the feasibility of using cavitation to increase production in hydrate exploitation.

Recent Advances in Metal-Organic Framework (MOF)-Based Photocatalysts: Design Strategies and Applications in Heavy Metal Control.

The heavy metal contamination of water systems has become a major environmental concern worldwide. Photocatalysis using metal-organic frameworks (MOFs) has emerged as a promising approach for heavy metal remediation, owing to the ability of MOFs to fully degrade contaminants through redox reactions that are driven by photogenerated charge carriers. This review provides a comprehensive analysis of recent developments in MOF-based photocatalysts for removing and decontaminating heavy metals from water. The tunable nature of MOFs allows the rational design of composition and features to enhance light harvesting, charge separation, pollutant absorptivity, and photocatalytic activities. Key strategies employed include metal coordination tuning, organic ligand functionalization, heteroatom doping, plasmonic nanoparticle incorporation, defect engineering, and morphology control. The mechanisms involved in the interactions between MOF photocatalysts and heavy metal contaminants are discussed, including light absorption, charge carrier separation, metal ion adsorption, and photocatalytic redox reactions. The review highlights diverse applications of MOF photocatalysts in treating heavy metals such as lead, mercury, chromium, cadmium, silver, arsenic, nickel, etc. in water remediation. Kinetic modeling provides vital insights into the complex interplay between coupled processes such as adsorption and photocatalytic degradation that influence treatment efficiency. Life cycle assessment (LCA) is also crucial for evaluating the sustainability of MOF-based technologies. By elucidating the latest advances, current challenges, and future opportunities, this review provides insights into the potential of MOF-based photocatalysts as a sustainable technology for addressing the critical issue of heavy metal pollution in water systems. Ongoing efforts are needed to address the issues of stability, recyclability, scalable synthesis, and practical reactor engineering.

ATRA sensitized the response of hepatocellular carcinoma to Sorafenib by downregulation of p21-activated kinase 1.

BACKGROUND: Sorafenib resistance greatly reduces the efficacy of treatments in advanced hepatocellular carcinoma (HCC) patients, but the underlying mechanisms are not thoroughly understood. All-trans retinoic acid (ATRA), an anti-leukaemia agent, has attracted considerable attention due to its role in sensitizing cells to other anticancer treatments. We aimed to investigate the combined effect of ATRA and Sorafenib on HCC and the underlying mechanisms. METHODS: CCK-8, cell sphere formation, trans-well migration, and wound-healing assays were used to analyse the biological behaviours of HCC cells in vitro. Western blotting and qRT-PCR analysis were conducted to measure the expression of p21 activated kinase 1 (PAK1) and phospho-p21 activated kinase 1 (pPAK1). Xenograft models were established to confirm the synergistic effects of ATRA and Sorafenib in vivo. TUNEL assays and immunohistochemistry were utilized to determine apoptosis, proliferation, PAK1 and pPAK1 levels in tumour tissues. RESULTS: We observed that PAK1 was overexpressed in HCC, and its expression was negatively correlated with the survival of patients. PAK1 promoted the proliferation, self-renewal and epithelial-mesenchymal transition of HCC cells. Correlation analysis indicated that the IC50 of Sorafenib was positively correlated with the level of pPAK1 in HCC cell lines. ATRA inhibited the progression of HCC and sensitized HCC response to Sorafenib by downregulation of PAK1, as shown by the calculated coefficient of drug interaction and the data obtained from xenograft models. CONCLUSIONS: Our findings indicated that instead of treatment with Sorafenib alone, the combination of ATRA and Sorafenib provides a more effective treatment for HCC patients. Video Abstract.

Non-suicidal self-injury and professional psychological help-seeking among Chinese left-behind children: prevalence and influencing factors.

BACKGROUND: Non-suicidal self-injury (NSSI) is a risk factor for suicide. This study aimed to investigate the prevalence of NSSI and professional psychological help-seeking status and influencing factors among left-behind children (LBC) in China. METHODS: We implemented a population-based cross-sectional study in participants aged 10-18 years. Sociodemographic characteristics, NSSI, help-seeking status and coping style were measured by self-reported questionnaires. A total of 16,866 valid questionnaires were collected, including 6096 LBC. Binary logistic regression models were used to analyze the factors influencing NSSI and professional psychological help-seeking. RESULTS: The incidence of NSSI among LBC was 4.6%, significantly higher than that of non-left-behind children (NLBC). This incidence was higher among girls. Moreover, 53.9% of LBC with NSSI did not receive any treatment and only 22.0% sought professional psychological help. LBC often adopt emotion-oriented coping styles, specifically, those with NSSI. LBC with NSSI who seek professional help tend to adopt problem-oriented coping styles. Logistic regression analysis revealed that girls, learning stage, single-parent, remarried families, patience, and emotional venting were risk factors for NSSI in LBC, while problem-solving and social support seeking were protective factors. Moreover, problem-solving was also a predictor for seeking professional psychological help, patience will prevent it. LIMITATIONS: This was an online survey. CONCLUSIONS: The prevalence of NSSI in LBC is high. Gender, grade, family structure, and coping style affect the occurrence of NSSI among LBC. Only a few LBC with NSSI seek professional psychological help, while the coping style will affect the help-seeking behavior.

METTL3 facilitates multiple myeloma tumorigenesis by enhancing YY1 stability and pri-microRNA-27 maturation in m6A-dependent manner.

Multiple myeloma (MM) is a pernicious plasma cell disorder and has a poor prognosis. N6-methyladenosine (m6A) is an abundant epigenetic RNA modification and is important in cancer progression. Nevertheless, the function of m6A and its regulator METTL3 in MM are rarely reported. Here, we identified the m6A "writers", METTL3, was enhanced in MM and found that Yin Yang 1 (YY1) and primary-miR-27a-3p were the potential target for METTL3. METTL3 promoted primary-miR-27a-3p maturation and YY1 mRNA stability in an m6A manner. YY1 also was found to facilitate miR-27a-3p transcription. METTL3 affected the growth, apoptosis, and stemness of MM cells through accelerating the stability of YY1 mRNA and the maturation of primary-miR-27a-3p in vitro and in vivo. Our results reveal the key function of the METTL3/YY1/miR-27a-3p axis in MM and may provide fresh insights into MM therapy.

Environmentally relevant concentrations of F-53B induce eye development disorders-mediated locomotor behavior in zebrafish larvae.

The perfluorooctane sulfonate alternative, F-53B, induces multiple physiological defects but whether it can disrupt eye development is unknown. We exposed zebrafish to F-53B at four different concentrations (0, 0.15, 1.5, and 15 µg/L) for 120 h post-fertilization (hpf). Locomotor behavior, neurotransmitters content, histopathological alterations, morphological changes, cell apoptosis, and retinoic acid signaling were studied. Histology and morphological analyses showed that F-53B induced pathological changes in lens and retina of larvae and eye size were significantly reduced as compared to control. Acridine orange (AO) staining revealed a dose-dependent increase in early apoptosis, accompanied by upregulation of p53, casp-9 and casp-3 genes. Genes related to retinoic acid signaling (aldh1a2), lens developmental (cryaa, crybb, crygn, and mipa) and retinal development (pax6, rx1, gant1, rho, opn1sw and opn1lw) were significantly downregulated. In addition, behavioral responses (swimming speed) were significantly increased, while no significant changes in the neurotransmitters (dopamine and acetylcholine) level were observed. Therefore, in this study we observed that exposure to F-53B inflicted histological and morphological changes in zebrafish larvae eye, induced visual motor dysfunctions, perturbed retinoid signaling and retinal development and ultimately triggering apoptosis.

Molecular network strategy in multi-omics and mass spectrometry imaging.

Human physiological activities and pathological changes arise from the coordinated interactions of multiple molecules. Mass spectrometry (MS)-based multi-omics and MS imaging (MSI)-based spatial omics are powerful methods used to investigate molecular information related to the phenotype of interest from homogenated or sliced samples, including the qualitative, relative quantitative and spatial distributions. Molecular network strategy provides efficient methods to help us understand and mine the biological patterns behind the phenotypic data. It illustrates and combines various relationships between molecules, and further performs the molecule identification and biological interpretation. Here, we describe the recent advances of network-based analysis and its applications for different biological processes, such as, obesity, central nervous system diseases, and environmental toxicology.

Exposure to ultrafine particles and childhood obesity: A cross-sectional analysis of the Seven Northeast Cities (SNEC) Study in China.

BACKGROUND: Studies on the obesogenic effect of air pollution on children have been mixed and sparse. Moreover, due to insufficient air monitoring, few studies have investigated the role of more tiny but unregulated particles (ambient particles with a diameter of 0.1 µm or less, ultrafine particles). OBJECTIVE: We sought to explore the associations between long-term exposure to ambient ultrafine particles (UFPs) and childhood obesity in Chinese children. METHODS: In this cross-sectional study, we randomly recruited 47,990 children, aged 6-18 years, from seven cities in Northeastern China between 2012 and 2013. Child age- and sex-specific z-scores for body mass index (BMI Z-score) and weight status were generated using the World Health Organization growth reference. Four-year average concentrations of UFPs and airborne particulates of diameter ≤ 1 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10) were estimated at home, using neural network simulated WRF-Chem model and spatiotemporal model, respectively. Confounder-adjusted generalized linear mixed models examined the associations between air pollution and BMI Z-score and the prevalence of childhood obesity. RESULT: We found that UFPs exposure was associated with greater childhood BMI Z-score and a higher likelihood of obesity. Compared with the lowest quartile, higher quartiles of UFPs were associated with greater odds for obesity prevalence in children (i.e., the adjusted OR was 1.25; 95 % CI, 1.12-1.39; 1.43; 95 % CI, 1.27-1.61; and 1.41; 95 % CI, 1.25-1.58 for the second, third, and fourth quartile, respectively). Similar associations were observed for PM1, PM2.5, and PM10, and were greater in boys and children living close to roadways. CONCLUSIONS: Long-term UFPs exposure was associated with a greater likelihood of childhood obesity, and stronger associations on BMI Z-score were observed in boys and children living close to roadways. This study indicates that more attention should be paid to the health effects of UFPs, and routinely monitoring of UFPs should be considered.

Sirtuin Type 1 Mediates the Antidepressant Effect of S-Ketamine in a Chronic Unpredictable Stress Model.

Background: Major depressive disorder (MDD) refers to a mental disease with complex pathogenesis and treatment mechanism. S-ketamine exhibited high effectiveness in treating MDD. However, the pharmacological activity of S-ketamine has not been reported yet. Materials and Methods: In this study, depression-like characteristics were induced by chronic unpredictable stress (CUS). After S-ketamine (15 mg/kg) was intraperitoneally injected, the behaviors of mice were tested by conducting open-field test, elevated plus maze test, tail suspension test, and forced swimming test. Bilateral injection of sirtuin type 1 (SIRT1) inhibitor EX-527 was injected into the medial prefrontal cortex (mPFC) to upregulate the SIRT1 expression. The expression of SIRT1 and brain-derived neurotrophic factor (BDNF) was detected by conducting Western blot and immunofluorescence assays. Meanwhile, the synaptic ultrastructure was detected by transmission electron microscopy. Results: In this study, the mice showed depression-like behavior in a series of behavioral tests. After the treatment with S-ketamine, the depression-like behavior stopped. Further, the synaptic ultrastructure in mPFC, including the decreased curvature of the post synaptic density and thinning of the postsynaptic density, improved after the S-ketamine treatment. Moreover, we found that S-ketamine had the possibility of spontaneous binding with SIRT1 at the molecular level and reversed CUS-induced SIRT1 reduction. Meanwhile, a positive relationship between SIRT1 and BDNF expression in mPFC and SIRT1 inhibitor limited the role of S-ketamine in reducing the depression-like behavior and increasing the BDNF level. Conclusion: S-ketamine upregulated the SIRT1-mediated BDNF in mPFC and reversed the synaptic structural defects caused by CUS. SIRT1 is a mediator of S-ketamine in alleviating depression-like behavior.

Per- and perfluoroalkyl substances alternatives, mixtures and liver function in adults: A community-based population study in China.

Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: -0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.

Perfluorooctane sulfonates induces neurobehavioral changes and increases dopamine neurotransmitter levels in zebrafish larvae.

It has been reported that exposure to perfluorooctane sulfonates (PFOS) causes behavioral abnormalities in zebrafish larvae, but the possible mechanisms underlying these changes remain unexplored. In this study, zebrafish embryos (2 h postfertilization, 2-hpf) were exposed to PFOS at different concentrations (0, 0.032, 0.32 and 3.2 mg/L) for 120 h. Developmental endpoints and the locomotion behavior of larvae were evaluated. Reactive oxygen species (ROS) levels, dopamine contents, several genes and proteins related to neurodevelopment and dopamine signaling were examined. Our results indicate that increased ROS levels in the zebrafish larvae heads may be causally associated with neurodevelopment damage. Meanwhile, brain-derived neurotrophic factor (BDNF) and alpha1-Tubulin (α1-Tubulin) protein contents were significantly increased, which may be a compensatory mechanism for the impaired central nervous system. PFOS-induced locomotor hyperactivity was observed in the first light phase and dark phase at the 0.32 and 3.2 mg/L of PFOS. Upregulation of dopamine-related genes tyrosine hydroxylase (th) and dopamine transporter (dat) associated with increased dopamine contents in the 3.2 mg/L of PFOS. In addition, protein expression of TH and DAT were noted at the 0.32 and 3.2 mg/L of PFOS concentrations. Our results suggested that PFOS induces neurobehavioral changes in zebrafish larvae, possibly by perturbing a dopamine signaling pathway. In addition, PFOS induced development damage, such as increased malformation rate and shorter body length.

Clinical Efficacy and Safety of Non-Cross-Linked Hyaluronic Acid Combined with L-carnosine for Horizontal Neck Wrinkles Treatment.

Background Horizontal neck wrinkle formation is gaining more attention among cosmetic practitioners and clients. To date, hyaluronic acid products are one of the most common treatment options for this aesthetic concern. However, different therapeutic strategies should be given to solve the problem due to multiple etiological reasons. Given that oxidative damage plays a critical role in neck wrinkle formation, anti-oxidative compounds are now considered by physicians when making a treatment plan. Aims To evaluate the efficacy and safety of a non-cross-linked hyaluronic acid filler in combination with L-carnosine in treating horizontal neck wrinkles. Methods Thirteen patients with a Wrinkle Assessment Scale (WAS) of 2-5 for horizontal neck wrinkles were treated with L-carnosine-containing non-cross-linked hyaluronic acid. Participants were followed-up for 3 months after treatment. The post-treated WAS scores evaluated by physicians were collected when patient satisfaction was surveyed. Any post-treatment adverse events were recorded. Results With a single injection of the above filler, the physician-evaluated WAS scores improved by at least one score at one month and the improvement kept consistent as far as three months after injection. According to the last follow-up visit, 11/13 patients were satisfied with the treatment effect of their neck wrinkle. Moreover, adverse events were rare after filler injection, except for local complications that were considered common reactions to the filler injection procedure. Conclusion The non-cross-linked hyaluronic acid filler containing L-carnosine is safe and effective for treating horizontal neck wrinkles.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Organoid Cultures Derived From Patients With Papillary Thyroid Cancer.

CONTEXT: Papillary thyroid cancer (PTC) has been one of the most frequent endocrine malignancies around the world. Although most PTC patients have a favorable prognosis, a subgroup of patients die, especially when disease recurrence occurs. There is a pressing need for clinically relevant preclinical thyroid cancer models for personalized therapy because of the lack of in vitro models that faithfully represent the biology of the parental tumors. OBJECTIVE: To understand thyroid cancer and translate this knowledge to clinical applications, patient-derived PTC organoids as a promising new preclinical model were established. METHODS: Surgically resected PTC primary tissues were dissociated and processed for organoid derivation. Tumor organoids were subsequently subjected to histological characterization, DNA sequencing, drug screen, and cell proliferation assay, respectively. RESULTS: We describe a 3-dimensional culture system for the long-term expansion of patient-derived PTC organoid lines. Notably, PTC organoids preserve the histopathological profiles and genomic heterogeneity of the originating tumors. Drug sensitivity assays of PTC organoids demonstrate patient-specific drug responses, and large correlations with the respective mutational profiles. Estradiol was shown to promote cell proliferation of PTC organoids in the presence of estrogen receptor α (ERα), regardless of the expression of ERß and G protein-coupled ER. CONCLUSION: These data suggest that these newly developed PTC-derived organoids may be an excellent preclinical model for studying clinical response to anticancer drugs in a personalized way, as well as provide a potential strategy to develop prevention and treatment options for thyroid cancer with ERα-specific antagonists.

Neddylation of PTEN regulates its nuclear import and promotes tumor development.

PTEN tumor suppressor opposes the PI3K/Akt signaling pathway in the cytoplasm and maintains chromosomal integrity in the nucleus. Nucleus-cytoplasm shuttling of PTEN is regulated by ubiquitylation, SUMOylation and phosphorylation, and nuclear PTEN has been proposed to exhibit tumor-suppressive functions. Here we show that PTEN is conjugated by Nedd8 under high glucose conditions, which induces PTEN nuclear import without effects on PTEN stability. PTEN neddylation is promoted by the XIAP ligase and removed by the NEDP1 deneddylase. We identify Lys197 and Lys402 as major neddylation sites on PTEN. Neddylated PTEN accumulates predominantly in the nucleus and promotes rather than suppresses cell proliferation and metabolism. The nuclear neddylated PTEN dephosphorylates the fatty acid synthase (FASN) protein, inhibits the TRIM21-mediated ubiquitylation and degradation of FASN, and then promotes de novo fatty acid synthesis. In human breast cancer tissues, neddylated PTEN correlates with tumor progression and poor prognosis. Therefore, we demonstrate a previously unidentified pool of nuclear PTEN in the Nedd8-conjugated form and an unexpected tumor-promoting role of neddylated PTEN.

Nedd8-activating enzyme inhibitor MLN4924 (Pevonedistat), inhibits miR-1303 to suppress human breast cancer cell proliferation via targeting p27Kip1.

MLN4924/Pevonedistat, a Nedd8-activating enzyme (NAE, E1) inhibitor, has shown notable anti-cancer effect in pre-clinical trials, but it still faces tolerance resistance risk. Combination target therapy indicates a much better clinical effect than single target, and miRNAs are beneficial for easy detection in bodily fluids and tissues. Up to now, MLN4924 and miRNA-targeting combination approaching to treat breast cancer patients remains largely unknown. Here, microRNA-seq analysis showed that the expression of miR-1303 was significantly decreased after MLN4924 treatment in breast cancer cells. Moreover, miR-1303 was abnormally high in breast cancer tissues, and breast cancer patients with high miR-1303 showed poor prognosis. Functionally, excessive miR-1303 promoted the malignant phenotypes of breast cancer cells. Excessive miR-1303 accelerated cell cycle progression by promoting G2/M arrest. Furthermore, we revealed that miR-1303 targeted p27Kip1 to release G2/M arrest. Notably, excessive miR-1303 partially disturbed the anti-cancer effect of MLN4924. These findings provide potential evidences for combined anti-cancer target therapy of breast cancer patients in the future.

Alterations of cerebral perfusion and functional brain connectivity in medication-naïve male adults with attention-deficit/hyperactivity disorder.

AIMS: Functional brain abnormalities, including altered cerebral perfusion and functional connectivities, have been illustrated in adults with attention-deficit/hyperactivity disorder (aADHD). The present study attempted to explore the alterations of cerebral blood flow (CBF) and resting-state functional connectivity (RSFC) simultaneously to understand the neural mechanisms for adults with ADHD comprehensively. METHODS: Resting-state arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) data were acquired for 69 male aADHD and 69 matched healthy controls (HCs). The altered CBFs associated with aADHD were explored based on both categorical (aADHD vs HCs) and dimensional (correlation with aADHD core symptoms) perspectives. Then, the seed-based RSFC analyses were developed for the regions showing significant alterations of CBF. RESULTS: Significantly decreased CBF in the large-scale resting-state networks regions (eg, ventral attentional network, somatomotor network, limbic network) and subcortical regions was indicated in aADHD compared with HCs. The correlation analyses indicated that the hypoperfusion in left putamen/global pallidum and left amygdala/hippocampus was correlated with ADHD inattentive and total symptoms, respectively. Further, weaker negative functional connectivity between left amygdala and bilateral supplementary motor area, bilateral superior frontal gyrus, and left medial frontal gyrus was found in adults with ADHD. CONCLUSION: The present findings suggested alterations of both cerebral perfusion and functional connectivity for the left amygdala in aADHD. The combination of CBF and RSFCs may help to interpret the neuropathogenesis of ADHD more comprehensively.