Transforming Adolescent Smiles: Correcting Skeletal Mandibular Retrusion and Bimaxillary Protrusion with Clear Aligners.

Maxillary protrusion combined with mandibular retraction is a highly prevalent but extremely complex maxillofacial deformity that can have a serious negative impact on patients' facial aesthetics and mental health. The traditional orthodontic treatment strategy often involves extracting 4 first premolars and conventional fixed techniques, combined with mini-implant screws, to retract the anterior teeth and improve facial protrusion. In recent years, an invisible orthodontic technique, without brackets, has become increasingly popular. However, while an invisible aligner has been used in some cases with reasonable results, there remain significant challenges in achieving a perfect outcome. This case report presents an adolescent patient with bimaxillary protrusion and mandibular retrognathia. Based on the characteristics of the invisible aligners and the growth characteristics of the adolescent's teeth and jawbone, we designed precise three-dimensional tooth movement and corresponding resistance/over-correction for each tooth, while utilizing the patient's jawbone growth potential to promote rapid development of the mandible, accurately and efficiently correcting bimaxillary protrusion and skeletal mandibular retrognathia. The patient's facial aesthetics, especially the lateral morphology, have been greatly improved, and various aesthetic indicators have also shown significant changes, and to the patient's great benefit, invasive mini-implant screws were not used during the treatment. This case highlights the advantages of using invisible aligners in adolescent maxillary protrusion combined with mandibular retraction patients. Furthermore, comprehensive and accurate design combined with good application of growth potential can also enable invisible orthodontic technology to achieve perfect treatment effects in tooth extractions, providing clinical guidance for orthodontists.

Synergistic antibacterial and antifouling wound dressings: Integration of photothermal-activated no release and zwitterionic surface modification.

Addressing the pervasive issue of bacteria and biofilm infections is crucial in the development of advanced antifouling wound dressings. In this study, a novel wound healing treatment using sulfobetaine (SBMA) decorated electrospun fibrous membrane based on polycaprolactone (PCL)/nitric oxide (NO) donors was developed. The fabrication involved a dual strategy, first integrating NO donors into mesoporous polydopamine (MPDA) and complexed with PCL/PEI to electrospin nanofibers. The fibrous membrane exhibited a potent antibacterial response upon irradiation at 808 nm, owing to a combination of NO and photothermal effect that effectively targets bacteria and disrupts biofilms. Surface functionalization of the membrane with PEI allowed for the attachment of SBMA via Michael addition, fabricating a zwitterionic surface, which significantly hinders protein adsorption and reduces biofilm formation on the wound dressing. In vitro and in vivo assessments confirmed the rapid bactericidal capabilities and its efficacy in biofilm eradication. Combining photothermal activity, targeted NO release and antifouling surface, this multifaceted wound dressing addresses key challenges in bacterial infection management and biofilm eradication, promoting efficient wound healing.

Research on the influence of power frequency magnetic field of pantograph on pacemaker wearers' health in high-speed EMU.

When the popular means of transportation-high-speed trains meet the increasing rate of pacemaker implantation year by year, the research on the magnetic field environment on the health of pacemaker wearers in the carriage becomes an urgent problem. In this work, models of an electric multiple unit carriage with a pantograph as well as passengers with pacemakers were built by using COMSOL Multiphysics software. The B, Ein and Jin of human heart and other tissues, and the induced voltage (Vin) at the pacemaker electrode were calculated under the pantograph operating condition, so as to assess the effect of its magnetic field on the health of pacemaker wearers. The results showed that Bmax in the carriage without passengers is 121.246 µT, occurs near the window. In the carriage, the Bmax, Ein max and Jin max of heart and body, Vin at the pacemaker electrode of the passenger next to the window are greater than that in the middle of the carriage. The Bmax, Ein max and Jin max of passengers' heart are 11.301µT, 1.613 mV/m and 139.030 µA/m2, respectively. The Bmax, Ein max and Jin max of passengers' body are 12.597µT, 0.788 mV/m and 75.299 µA/m2, respectively. The maximum value of Vin at the tip of the pacemaker electrode of the passengers' is 0.048 mV. The Bmax, Ein max in all tissues of passengers are much smaller than the basic limits of electromagnetic exposure to the public set by the International Commission on Non-Ionizing Radiation. Vin at the electrode tip of passengers' pacemakers are less than the perception sensitivity set by the International Organization for Standardization. This work illustrated that the magnetic field generated by the pantograph is within the recognized accepted limits for passengers with pacemakers, but we still recommended that passengers wearing pacemakers should stay as far away from windows as possible.

α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata.

Nicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4ß2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into the lower hind leg, spinal nerve injury, chronic constriction injury, or chronic nicotine exposure. The analgesic effects of nAChR agonists were mimicked by optogenetic stimulation of cholinergic inputs from the pedunculopontine nucleus (PPN) to the SNr, but attenuated upon downregulation of α4 nAChRs on SNr GABAergic neurons and injection of dihydro-ß-erythroidine into the SNr. Chronic nicotine-induced hyperalgesia depended on α4 nAChRs in SNr GABAergic neurons and was associated with the reduction of ACh release in the SNr. Either activation of α4 nAChRs in the SNr or optogenetic stimulation of the PPN-SNr cholinergic projection mitigated chronic nicotine-induced hyperalgesia. Interestingly, mechanical stimulation-induced ACh release was significantly attenuated in mice subjected to either capsaicin injection into the lower hind leg or SNI. These results suggest that α4 nAChRs on GABAergic neurons mediate a cholinergic analgesic circuit in the SNr, and these receptors may be effective therapeutic targets to relieve hyperalgesia in acute and chronic pain, and chronic nicotine exposure.

The high-quality genome of Cryptotaenia japonica and comparative genomics analysis reveals anthocyanin biosynthesis in Apiaceae.

Cryptotaenia japonica, a traditional medicinal and edible vegetable crops, is well-known for its attractive flavors and health care functions. As a member of the Apiaceae family, the evolutionary trajectory and biological properties of C. japonica are not clearly understood. Here, we first reported a high-quality genome of C. japonica with a total length of 427 Mb and N50 length 50.76 Mb, was anchored into 10 chromosomes, which confirmed by chromosome (cytogenetic) analysis. Comparative genomic analysis revealed C. japonica exhibited low genetic redundancy, contained a higher percentage of single-cope gene families. The homoeologous blocks, Ks, and collinearity were analyzed among Apiaceae species contributed to the evidence that C. japonica lacked recent species-specific WGD. Through comparative genomic and transcriptomic analyses of Apiaceae species, we revealed the genetic basis of the production of anthocyanins. Several structural genes encoding enzymes and transcription factor genes of the anthocyanin biosynthesis pathway in different species were also identified. The CjANSa, CjDFRb, and CjF3H gene might be the target of Cjaponica_2.2062 (bHLH) and Cjaponica_1.3743 (MYB). Our findings provided a high-quality reference genome of C. japonica and offered new insights into Apiaceae evolution and biology.

Combination of omalizumab with allergen immunotherapy versus immunotherapy alone for allergic diseases: A meta-analysis of randomized controlled trials.

BACKGROUND: Allergen immunotherapy (AIT)-associated adverse events (AEs) limit its usage in the management of allergic diseases. The monoclonal anti-IgE antibody (omalizumab) and AIT have complementary actions. However, no consensus has been reached on whether their combination could exert superior efficacy and safety. OBJECTIVE: To evaluate whether the combination of AIT with omalizumab is superior to AIT alone in treating allergic diseases. METHODS: The MEDLINE/PubMed, Embase, Scopus and Cochrane Library databases were searched to identify randomized control trials (RCTs) reporting the outcomes of omalizumab combined with AIT (omalizumab + AIT) versus AIT alone. A random-effect model was established to estimate outcomes with a 95% confidence interval (CI). RESULTS: A total of 11 eligible RCTs (involving 901 patients) were screened out for the meta-analysis. According to a pooled analysis, omalizumab + AIT significantly increased the number of patients achieving the target maintenance dose (TMD) and sustained unresponsiveness (SU) to allergens (odds ratio [OR] = 2.43; 95% CI: 1.33-4.44; p = 0.004; I2 = 35%, and OR = 6.77; 95% CI: 2.10-21.80; p = 0.001; I2 = 36%, respectively). Similarly, individuals receiving the combination therapy reported significantly fewer episodes of severe systemic AEs than AIT alone (OR = 0.32; 95% CI: 0.18-0.59; p = 0.0003; I2 = 0%). Meanwhile, the improvements in symptom severity score (mean difference [MD] = -0.26), rescue medication daily means score (MD = -0.14), and number of patients consuming epinephrine in AIT (OR = 0.20) were all more evident than those in AIT alone. CONCLUSION: Omalizumab + AIT can significantly enhance the efficacy and safety of AIT by increasing TMD and SU to allergens, while decreasing severe systemic AEs.

Exogenous Ang-(1-7) inhibits autophagy via HIF-1α/THBS1/BECN1 axis to alleviate chronic intermittent hypoxia-enhanced airway remodelling of asthma.

Obstructive sleep apnoea (OSA)-induced chronic intermittent hypoxia (CIH) has been considered a risk factor for severe asthma. Airway remodelling, which could be modulated by autophagy, plays a key role in severe asthma. However, the extent of autophagy's involvement in CIH-potentiated airway remodelling remains largely unexplored. Furthermore, we had found that angiotensin-(1-7) [Ang-(1-7)] has therapeutic effects on airway remodelling in asthma, but the underlying mechanism is either unclear. This study aimed to explore how CIH aggravates asthma and mechanism of protective effects of Ang-(1-7) on airway remodelling, with a focus on autophagy. We observed that CIH promoted epithelial-to-mesenchymal transition (EMT), indicated by elevated EMT and fibrotic markers such as Snail and Collagen IV, both in vitro and in vivo. CIH intensified cell autophagy, evident from increased LC3B expression and reduced p62 levels. Ang-(1-7) reversed the CIH-enhanced expression of Snail, Collagen IV, and LC3B. To explore how CIH enhanced autophagy in cellular and animal model of asthma, overexpression of hypoxia-inducible factor 1-alpha (HIF-1α) and Thrombospondin 1 (THBS1) were identified in CIH-exposure mice lung compared with normal mice lung tissues from the GEO database. Finally, through chromatin immunoprecipitation and immunoprecipitation assays, we verified that Ang-(1-7) inhibits CIH-induced binding of HIF-1α to the promoter of THBS1, and also disrupts the protein-protein interaction between THBS1 and the autophagy-associated protein Beclin 1 (BECN1), ultimately leading to autophagy inhibition. Our findings suggest that exogenous Ang-(1-7) can inhibit autophagy via HIF-1α/THBS1/BECN1 axis, thereby alleviating CIH-enhanced airway remodelling in asthma. These findings imply the potential therapeutic effect of Ang-(1-7) in asthma with OSA.

Mechanism Exploration of Euphorbia fischeriana Steud. for Liver Cancer Based on Aspartic Acid Identification in Metabolomics.

OBJECTIVE: To investigate the anti-liver cancer effects and aspartic acid (Asp)-related action mechanism of Euphorbia fischeriana Steud. (Lang Du, LD). METHODS: The mice model of liver cancer was established by injection of H22 cells. After 5 days, mice were randomly divided into model group, sorafenib group (20 mg/kg), LD high-dose (LDH, 1.36 g/kg) group, LD medium-dose (LDM, 0.68 g/kg) group, and LD low-dose (LDL, 0.34 g/kg) group, 10 mice each group. Drugs were intragastrically administered to the mice once daily for 10 days, respectively. Body weight, tumor size and tumor weight were recorded. Hepatic index was calculated. Pathological changes of liver cancer tissues were evaluated by hematoxylin and eosin staining and TUNEL staining. Liquid chromatography-mass spectrometer was used to analyze different metabolites between the model and LDH groups. RESULTS: After LD treatment, tumor weight, tumor size and hepatic index were reduced compared with the model group. Necrocytosis and karyorrhexis of tumor cells were found. Moreover, 61 differential metabolites (18 up-regulated, 43 down-regulated) were affirmed and 20 pathways of KEGG (P<0.05) were gotten. In addition, Bel-7402, HepG2 and H22 cell viabilities were significantly increased after adding Asp into the medium. And then, the cell proliferation effect induced by Asp was ameliorated by LD. CONCLUSION: The anti-liver cancer efficacy of LD extract was validated in H22 mice model, and inhibition of Asp level might be the underlying mechanism.

Acylhydrazone-derived whole pectin-based hydrogel as an injectable drug delivery system.

Injectable hydrogel-based drug delivery systems have attracted more and more attention due to their sustained-release performance, biocompatibility, and 3D network. The present study showed whole pectin-based hydrogel as an injectable drug delivery system, which was developed from oxidized pectin (OP) and diacylhydrazine adipate-functionalized pectin (Pec-ADH) via acylhydrazone linkage. The as-prepared hydrogels were characterized by 1H NMR, FT-IR, and SEM techniques. The equilibrium swelling ratio of obtained hydrogel (i.e., sample gel 5) was up to 4306.65 % in the distilled water, which was higher than that in PBS with different pH values. Increasing the pH of the swelling media, the swelling ratio of all hydrogels decreased significantly. The results that involved the swelling properties indicated the salt- and pH-responsiveness of the as-prepared hydrogels. The drug release study presented that 5-FU can be persistently released for more than 12 h without sudden release. Moreover, the whole pectin-based hydrogel presented high cytocompatibility toward L929 cell lines, and the drug delivery system showed a high inhibitory effect on MCF-7 cell lines. All these results manifested that the acylhydrazone-derived whole pectin-based hydrogel was an excellent candidate for injectable drug delivery systems.

Tribulus terrestris L. induces cell apoptosis of breast cancer by regulating sphingolipid metabolism signaling pathways.

BACKGROUND: Tribulus terrestris L. (TT) was initially documented in Shen-Nong-Ben-Cao-Jing and has been used for thousands of years in China as a herb to calm liver, dispel melancholy and wind, promote blood circulation, improve eyesight, and relieve itching. Moreover, it was also used to treat breast cancer in ancient China. However, the pharmacological activities of TT extract on breast cancer have received little attention. PURPOSE: In this study, we investigated the anti-breast cancer effects and possible mechanisms of action of this herbal drug. METHODS: Network pharmacology analysis the study of network pharmacology was done to analyze the possibility of TT's anti-breast cancer effect. And then, molecular docking between TT7/TT8 and vascular endothelial growth factor receptor 2 (VEGFR2) were performed by Autodock software as well as the related protein expressions were analyzed by western blot to verify this effect. In vivo experiment: The mouse model of breast cancer was established by injection of 4T1 cells. Then drugs were intragastrically administered to the mice once daily for fourteen days. Body weight, tumor size, and tumor weight were recorded at the end of the experiment. Moreover, tumor inhibitory rate was calculated. Finally, pathological changes and apoptosis of breast cancer tissues were respectively evaluated by HE and Hoechst staining. Proteomics and metabonomics analyses: The tumor tissues were chosen to perform conjoint analysis. Firstly, differential proteins and metabolites were found. Furthermore, the functional analyses of them were analyzed by software. At the last, immunofluorescent staining of SGPP1, SPHK1 and p-SPHK1 in tumor tissue were done. RESULTS: 12 active ingredients of TT, 127 targets of active ingredients, 15,253 targets of breast cancer, 1,225 targets of Ru yan, and 123 overlapping genes were obtained in the network pharmacology study. There was firm conjunction between TT7/TT8 and VEGFR2. Besides, tumor size and weight were markedly reduced in TT groups compared to the model group. The tumor inhibitory rate was more than 26% in TTM group. After drug treatment, many adipocytes and cracks between tumor and apoptosis were discovered. The western blot results showed that TT aqueous extract lowered the levels of VEGFR2, ERK1/2, p-ERK1/2 (Thr202, Tyr204) and Bcl2, while increasing the levels of Bax and the ratio of Bax/Bcl2. Furthermore, 495 differential proteins and 76 differential metabolites were found between TTM and model groups with the sphingolipid metabolism pathway being enriched. At last, TT treatment significantly reduced the levels of SGPP1, SPHK1 and p-SPHK1 in tumor tissue. CONCLUSIONS: In conclusion, TT demonstrates therapeutic effects in a mouse model of breast cancer, and its mechanism of action involves the regulations of sphingolipid metabolism signaling pathways. This study lends credence to the pharmacological potential of TT extract as a breast cancer therapy.

Promoting liver cancer cell apoptosis effect of Tribulus terrestris L. via reducing sphingosine level was confirmed by network pharmacology with metabolomics.

Background: Tribulus terrestris L. (TT) is one of the most common Chinese herbs and distributes in various regions in China. TT was first documented to treat breast cancer in Shen-Nong-Ben-Cao-Jing. However, the pharmacological activities of TT extract on liver cancer have not been reported. In this study, we investigated its anti-liver cancer activity and underlying mechanism. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) and PharmMapper databases were used to obtain the active ingredients and the targets of TT. Genecards database was employed to acquire TT targets in liver cancer. Furthermore, Venny 2.1, Cytoscape 3.8.2, DAVID 6.8 software were utilized to analyze the relationship between TT and liver cancer. In vivo experiment: The animal model of liver cancer was established by injection of H22 cells into Balb/c mice. After five days, drugs were intragastrically administered to the mice daily for 10 days. Body weight, tumor size and tumor weight were recorded. Tumor inhibitory rate was calculated. Protein levels were examined by Western blotting. Pathological changes of liver cancer tissues were evaluated by HE and Tunel staining. Metabolomics study: LC-MS was used to analyze different metabolites between model and TTM groups. Results: 12 active ingredients of TT, 127 targets of active ingredients, 17,378 targets of liver cancer, and 125 overlapping genes were obtained. And then, 118 items of GO biological processes (BP), 54 items of GO molecular function (MF), 35 items of GO cellular component (CC) and 128 pathways of KEGG were gotten (P < 0.05). Moreover, 47 differential metabolites were affirmed and 66 pathways of KEGG (P < 0.05) were obtained. In addition, after TT and sorafenib treatment, tumor size was markedly reduced, respectively, compared with model group. Tumor weight was significantly decreased and tumor inhibitory rate was more than 44% in TTM group. After TT treatment, many adipocytes, cracks between tumor cells and apoptosis were found. The levels of pro-Cathepsin B, Cathepsin B, Bax, Bax/Bcl2, Caspase3 and Caspase7 were markedly increased, but the level of Bcl2 was significantly reduced after TT treatment. Conclusion: TT has a broad range of effects on various signaling pathways and biological processes, including the regulation of apoptosis. It exhibits antitumor activity in an animal model of liver cancer and activates the apoptotic pathway by decreasing Sph level. This study provides valuable information regarding the potential use of TT extract in the treatment of liver cancer and highlights the importance of investigating the underlying molecular mechanisms of traditional medicines for the development of new therapeutic drugs in liver cancer.

Identification of predictors of long-term survival and prognostic outcomes in thymic squamous cell carcinoma: A real-world study.

BACKGROUND: Although thymic squamous cell carcinoma (TSCC) is among the most prevalent forms of thymic carcinoma, there are relatively few studies on this tumor type, and its staging, optimal treatment strategies, and relevant prognostic factors remain controversial. METHODS: The present study analyzed 79 patients diagnosed with TSCC between January 2008 and January 2021. Kaplan-Meier curves and Cox univariate and multivariate regression analyses were used to explore factors associated with overall survival (OS) and progression-free survival (PFS) in the overall patient cohort and patient subgroups stratified according to the TNM stage. Time-dependent receiver operating characteristic (ROC) analyses were used to compare the TNM and Masaoka systems as predictors of patient prognosis. RESULTS: The 5- and 10-year OS rates in this study were 65.5% and 49.4%, respectively, with corresponding 5- and 10-year PFS rates of 52.3% and 37.9%. Survival outcomes were better for patients with early-stage disease (p < 0.001) and patients that underwent surgical treatment (p < 0.001). Neither extent of resection (p = 0.820) nor the surgical approach (p = 0.444) influenced patient survival. In individuals with advanced disease, all forms of adjuvant therapy including radiotherapy (p = 0.021), chemotherapy (p = 0.035), and chemoradiation (p = 0.01) significantly improved patient PFS, but only adjuvant chemoradiotherapy improved patient OS (p = 0.035). When predicting the patient survival outcomes, the TNM system was slightly superior to the Masaoka system (area under the ROC curve [AUC] at 5 years: OS, 0.742 vs. 0.723; PFS, 0.846 vs. 0.816). CONCLUSION: TSCC is an orphan malignancy with a poor prognosis. TNM staging may be superior to Masaoka staging as a predictor of TSCC patient prognosis. Surgery is the mainstay of TSCC treatment. Video-assisted thoracoscopy (VATS) should be considered for selected patients. Multimodal therapy was associated with excellent results for patients with advanced TNM stage, particularly when surgery was accompanied by adjuvant chemoradiation.

Low light intensity elongates period and defers peak time of photosynthesis: a computational approach to circadian-clock-controlled photosynthesis in tomato.

Photosynthesis is involved in the essential process of transforming light energy into chemical energy. Although the interaction between photosynthesis and the circadian clock has been confirmed, the mechanism of how light intensity affects photosynthesis through the circadian clock remains unclear. Here, we propose a first computational model for circadian-clock-controlled photosynthesis, which consists of the light-sensitive protein P, the core oscillator, photosynthetic genes, and parameters involved in the process of photosynthesis. The model parameters were determined by minimizing the cost function ( [Formula: see text]), which is defined by the errors of expression levels, periods, and phases of the clock genes (CCA1, PRR9, TOC1, ELF4, GI, and RVE8). The model recapitulates the expression pattern of the core oscillator under moderate light intensity (100 µmol m -2 s-1). Further simulation validated the dynamic behaviors of the circadian clock and photosynthetic outputs under low (62.5 µmol m-2 s-1) and normal (187.5 µmol m-2 s-1) intensities. When exposed to low light intensity, the peak times of clock and photosynthetic genes were shifted backward by 1-2 hours, the period was elongated by approximately the same length, and the photosynthetic parameters attained low values and showed delayed peak times, which confirmed our model predictions. Our study reveals a potential mechanism underlying the circadian regulation of photosynthesis by the clock under different light intensities in tomato.

Theoretical Study on Zigzag Boron Nitride Nanowires.

In this work, two kinds of BN-nanowires (BNnws): a-BNnw and d-BNnw, respectively composed of azo (N-N) and diboron (B-B) bonds, are proposed with the aid of the first-principles simulations. Their structural stabilities are carefully verified from the energetics, lattice dynamics, and thermodynamic perspectives. Similar to the other common boron nitride polymorph, the a-BNnw and d-BNnw are semiconductors with relatively wide band gaps of 3.256 and 4.631 eV at the HSE06 level, respectively. The corresponding projected DOS patterns point out that their band edges are composed of different atomic species, which can help with the separation of their excitons. The band gaps can be manipulated monotonically by axial strains within the elastic ranges. The major charge carriers are electron holes. Significantly, a-BNnw possesses very high carrier mobilities around 0.44×104  cm2 V-1 s-1 .

The deficiency of Maged1 attenuates Parkinson's disease progression in mice.

Melanoma-associated antigen D1 (Maged1) has critical functions in the central nervous system in both developmental and adult stages. Loss of Maged1 in mice has been linked to depression, cognitive disorder, and drug addiction. However, the role of Maged1 in Parkinson's disease (PD) remains unclear. In this study, we observed that Maged1 was expressed in the dopaminergic (DA) neurons of the substantia nigra in mice and humans, which could be upregulated by the in vivo or in vitro treatment with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-Methyl-4-phenylpyridinium iodide (MPP+). Genetic ablation of Maged1 in mice attenuated motor deficits, the loss of DA neurons, and disease progression induced by MPTP. Moreover, Maged1 deficiency protected DA neurons against MPP+-induced toxicity in primary cultured cells. Mechanistically, loss of Maged1 upregulated the Akt signaling pathway and downregulated the mTOR signaling pathway in SH-SY5Y cells, which may in turn attenuate the cell apoptosis and impairment of autophagy. Consistent with it, the degeneration of midbrain and striatum among elderly Maged1 knockout mice was relatively mild compared to those in wild-type mice under physiological conditions. Taken together, this study suggested that Maged1 deficiency inhibited apoptosis and enhanced autophagy, which may provide a new potential target for the therapy of PD.

Interventions for improving self-efficacy in patients after stroke based on self-efficacy-related principles of Bandura's cognition theory: a systematic review and meta-analysis.

BACKGROUND: Interventional approaches based on Bandura's cognition theory are effective in improving self-efficacy poststroke. However, a systematical investigation for identifying effectives therapeutic components of the intervention has not yet been conducted. OBJECTIVE: This meta-analysis was conducted to systematically investigated the effects of interventions with different principles on improving self-efficacy after stroke. METHODS: Searches were conducted in PubMed, EMBASE, CINAHL, PsycINFO, MEDLINE, Cochrane Library, and two randomized controlled trials registration websites for randomized controlled trials from inception to 18th January 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The meta-analysis was performed using Review Manager and Stata software. RESULTS: In total, 36 RCTs were included. Interventions using any one of the self-efficacy principles - principle 1 (Mastery), principle 2 (Modeling), principle 3 (Social persuasion), and principle 4 (Understanding), were more effective in improving self-efficacy in patients with stroke at post-training and follow-up, compared with the control group. Psycho-educational interventions might significantly improve self-efficacy in both post-intervention and follow-up stages, compared with control group. Meta-regression revealed time since stroke onset was significantly associated with effect sizes. CONCLUSION: Interventions developed based on Bandura's cognition theory are beneficial to the improvement of self-efficacy. This review highlights principles of Bandura's cognition theory are worth considering to be integrated to interventions targeted at improving self-efficacy. The application of self-efficacy principles with Bandura's cognitive theory could be encouraged in clinical practice in the future. PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42020154984.

Novel strategies to reverse chemoresistance in colorectal cancer.

Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients. Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis of patients. To overcome chemoresistance in CRC, many strategies are being investigated. Here, we review the common and novel measures to combat the resistance, including drug repurposing (nonsteroidal anti-inflammatory drugs, metformin, dichloroacetate, enalapril, ivermectin, bazedoxifene, melatonin, and S-adenosylmethionine), gene therapy (ribozymes, RNAi, CRISPR/Cas9, epigenetic therapy, antisense oligonucleotides, and noncoding RNAs), protein inhibitor (EFGR inhibitor, S1PR2 inhibitor, and DNA methyltransferase inhibitor), natural herbal compounds (polyphenols, terpenoids, quinones, alkaloids, and sterols), new drug delivery system (nanocarriers, liposomes, exosomes, and hydrogels), and combination therapy. These common or novel strategies for the reversal of chemoresistance promise to improve the treatment of CRC.

Protein phosphatase 2A deficiency in hippocampal CA1 inhibits priming effect of morphine on conditioned place preference in mice.

Studies have shown that protein phosphorylation plays an important role in morphine abuse. However, the neurobiological mechanism of protein phosphatase 2A (PP2A) underlying the morphine-priming process is still unclear. Here we constructed T29-2-Cre; PP2Afl/fl conditional knockout mice (KO) and investigated the role of hippocampal PP2A in morphine priming. We observed that the deficit of PP2A inhibited the priming behavior of morphine and blocked the priming-induced long-term potentiation (LTP) in the hippocampus of KO mice. Moreover, the expression levels of Rack1 and the membrane GluN2B were significantly reduced in the nucleus accumbens of KO mice compared with those in the control mice, which may be attributed to the decreased HDAC4 in the hippocampus of KO mice. Consistent with it, the similar inhibited priming effects were also observed in the wild-type mice treated with sodium butyrate (NaB)-a nonspecific inhibitor of histone deacetylases-3 h after morphine administration. Taken together, our results suggest that hippocampal PP2A may be involved in morphine priming through the PP2A/HDAC4/Rack1 pathway.

Peripheral Treg Levels and Transforming Growth Factor-ß (TGFß) in Patients with Psoriatic Arthritis: A Systematic Review Meta-Analysis.

INTRODUCTION: Studies on the level of regulatory T (Treg) cells in psoriatic arthritis (PsA) have been controversial, leading to disagreement regarding the role Treg cells play in the pathogenesis of the disease. To clarify the status of Treg cells in patients with PsA, we performed a meta-analysis to determine the levels of Treg cells and serum Treg-associated cytokines in PsA patients. METHODS: According to published data from PubMed, Web of Science, Embase, Clinical Trials.gov, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, we determined the Treg and Treg cytokine levels in patients with PsA. The effect estimates were pooled using a random-effects model. RESULTS: This meta-analysis included 12 studies. Compared to healthy controls (HCs), the proportions of Treg cells had no significant difference in patients with PsA (based on standardized means[SMD] = - 1.038, 95% confidence intervals[CI] = - 2.165 to 0.089, p = 0.071). On the basis of subgroup analysis, patients with PsA had a lower percentage of CD4+ Treg cells (SMD = - 1.501, 95% CI - 2.799 to - 0.202, p = 0.023) than OKT8+ Treg (SMD = 0.568, 95% CI - 2.127 to 3.263, p = 0.679). Besides, CD4+CD25+FoxP3+ Treg cells and CD4+CD25highCD127low Treg cells were both significantly decreased on the levels of PBMCs in patients with PsA (SMD = - 0.764, 95% CI - 1.404 to - 0.125, p = 0.019; SMD = - 5.184, 95% CI - 6.955 to - 3.412, p < 0.001). CD4+CD25+FoxP3+ Treg cells were particularly more abundant in the synovial fluid thanin peripheral blood (SMD = 3.288, 95% CI 2.127 to 4.449, p < 0.001). No significant difference was observed in the proportion of CD4+CD25+ Treg cells in peripheral blood and CD4+CD25+FoxP3+ Treg cells in CD4+ T cells (SMD = - 2.498, 95% CI - 7.720 to 2.725, p = 0.349; SMD = - 0.719, 95% CI - 2.525 to 1.086, p = 0.435). PsA patients had decreased cytokines such as transforming growth factor-ß (TGFß) (SMD = - 2.199, 95% CI - 3.650 to - 0.749, p = 0.003). CONCLUSIONS: Treg definition markers influence the scale of Treg cells in patients with PsA. Pathogenesis of PsA may be attributed to an insufficient or malfunctioning Treg population.