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BackgroundThe growth of secondary hair follicles (SHFs) in cashmere goats has periodic changes, including telogen, anagen, and catagen, during which proteins play important roles as the executor of life activities.ResultsIn this study, the skin tissues of cashmere goats at three different growth stages of SHFs were collected for proteome sequencing and validation experiments. Through protein differential expression analysis and time series analysis, FKBP prolyl isomerase 10 (FKBP10) and fibrillin 2 (FBN2) were screened as the key proteins for SHF cycle growth of cashmere goats, and albumin (ALB), collagen type I alpha 1 chain (COL1A1) and elastin (ELN) were predicted to be their interacting proteins. The results of quantitative real-time PCR (qRT-PCR), western blot, and immunohistochemistry experiments showed that the mRNA and protein expression levels of FKBP10, FBN2, COL1A1, ELN and ALB were higher in anagen and lower in telogen. They were all highly expressed in the outer root sheath of SHFs in anagen.ConclusionFKBP10, FBN2, COL1A1, ELN, and ALB can promote the growth of SHFs in cashmere goats. This study lays the foundation for analyzing the growth cycle regulatory mechanism of SHFs in cashmere goats, and provides new ideas for further improving cashmere yield and quality.

Emerging evidence suggests that proline metabolism is important for regulating the survival and death of different types of cancer cells. Proline dehydrogenase (PRODH), an enzyme catalyzing proline catabolism, and the degradation products of proline by PRODH, such as ATP and ROS, are known to play critical roles in cancer progression. Notably, the role of PRODH in cancer is still complicated and unclear, and primarily depends on the cancer type and tumor microenvironment. For instance, PRODH induces apoptosis and senescence through ROS signaling in different types of cancers, while as a protumor factor, PRODH promotes malignant phenotypes of certain tumors under stresses such as hypoxia. In order to assess whether PRODH can serve as a novel target for cancer therapy, we will provide an overview of the biological functions of PRODH and its double-edged role in cancer in this article.

BackgroundAlthough the study of the neuroanatomical correlates of depression in Parkinson’s Disease (PD) is gaining increasing interest, up to now the cortical gyrification pattern of PD-related depression has not been reported. This study was conducted to investigate the local gyrification index (LGI) in PD patients with depression, and its associations with the severity of depression.MethodsLGI values, as measured using FreeSurfer software, were compared between 59 depressed PD (dPD), 27 non-depressed PD (ndPD) patients and 43 healthy controls. The values were also compared between ndPD and mild-depressed PD (mi-dPD), moderate-depressed PD (mo-dPD) and severe-depressed PD (se-dPD) patients as sub-group analyses. Furthermore, we evaluated the correlation between LGI values and depressive symptom scores within dPD group.ResultsCompared to ndPD, the dPD patients exhibited decreased LGI in the left parietal, the right superior-frontal, posterior cingulate and paracentral regions, and the LGI values within these areas negatively correlated with the severity of depression. Specially, reduced gyrification was observed in mo-dPD and involving a larger region in se-dPD, but not in mi-dPD group.ConclusionThe present study demonstrated that cortical gyrification is decreased within specific brain regions among PD patients with versus without depression, and those changes were associated with the severity of depression. Our findings suggested that cortical gyrification might be a potential neuroimaging marker for the severity of depression in patients with PD.

This study investigated alterations in degree centrality (DC) in different motor subtypes of Parkinson’s disease (PD) and analyzed its clinical significance during disease occurrence. A total of 146 subjects were recruited in the study, including 90 patients with PD [51 and 39 with tremor dominant (TD) and akinetic-rigid dominant (ARD) disease, respectively] and 56 healthy controls (HCs). The resting-state functional magnetic resonance imaging data of all the subjects were obtained by 3.0 T magnetic resonance scans. The DC values, an indicator of whole brain synchronization, were calculated and compared among the TD, ARD, and HC groups. Disparities in DC values among the three groups were evaluated by analysis of variance and post hoc two-sample t-tests. Correlation between brain regions with DC differences and clinical variables were performed using partial correlation analysis after controlling for age, gender, and disease duration. Compared to the HCs, both TD and ARD groups demonstrated increased DC values bilaterally in the cerebellum; DC values were decreased in the left putamen and paracentral lobule in the TD group and in the left anterior cingulate gyrus and right supplementary motor area in the ARD group. Compared to the ARD group, the TD group showed decreased DC values in bilateral cerebellar hemispheres and increased DC values in the left anterior cingulate gyrus and right supplementary motor area. The DC of the whole brain showed inconsistencies and shared neural bases among patients with the two subtypes of PD. The differences between brain regions with abnormal DC values may be closely related to different clinical presentations of the two motor subtypes. Our findings provide new insights into the clinical heterogeneity of PD with respect to different motor subtypes.

Background: Gastric cancer (GC) is a common malignant tumor with a poor prognosis. Combination treatments may prolong the survival of patients with GC. Acacetin, which is a flavonoid, exerts potent inhibitory effects on several types of cancer cells; however, the mechanisms of action remain poorly understood.Methods: Network pharmacology and RNA sequencing were used to predict the targets of acacetin, which were then verified by drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and molecular docking. The biological functions of acacetin in MKN45 and MGC803 cells were investigated using TUNEL assays, crystal staining and colony formation assays. The pathways affected by acacetin were verified through reverse experiments. The in vivo antitumor efficacy of acacetin was assessed in a subcutaneous xenotransplanted tumor model.Results: In this study, we identified EGFR from more than a dozen predicted targets as a protein that directly binds to acacetin. Moreover, acacetin affected the level of phosphorylated EGFR. In vitro, acacetin promoted the apoptosis of GC cells. Importantly, EGFR agonists reversed the inhibitory effects of acacetin on the STAT3 and ERK pathways. In vivo, acacetin decreased the protein levels of pEGFR in tumors, resulting in increased GC xenograft tumor regression without obvious toxicity.Conclusion: Our findings highlight EGFR as one of the direct targets of acacetin in GC cells. Acacetin inhibited the phosphatase activity of EGFR in vitro and in vivo, which played a role in the antitumor effects of acacetin. These studies provide new evidence for the use of acacetin as a potential reagent for the treatment of GC.

Background: The recurrence of colorectal adenomas (CRAs) after endoscopy predisposes patients to a risk of colorectal cancer. Guided by the traditional Chinese medicine (TCM), patients with colorectal diseases usually manifest with spleen deficiency syndrome (SDS) and are treated with Sijunzi decoction (SJZD). Therefore, this trial aims to explore the efficacy and safety of SJZD in the prevention and treatment of CRAs recurrence.Methods: SJZD on prevention and treatment of CRAs recurrence after resection: a multicenter, randomized, double-blind, placebo-controlled trial was designed. Patients who undergo polypectomy of CRAs will be recruited and randomized into a SJZD group and a placebo group in a 1:1 ratio. The intervention phase will be 12 months. The follow-up period will last 24 months. The primary outcome is the CRA recurrence rate after intervention. The secondary outcomes include the CRA recurrence rate at the second year post-polypectomy, the pathological type of adenoma and the alterations in SDS scores after intervention.Discussion: Previous clinical practice has observed the sound effect of SJZD in the context of gastrointestinal diseases. A number of experiments have also validated the active components in SJZD. This trial aims to provide tangible evidence for the usage of SJZD, hoping to reduce the recurrence of CRAs.

Gastrointestinal (GI) cancer includes a variety of cancers with high incidence that seriously threaten the lives of people worldwide. Although treatment strategies continue to improve, patient benefits are still very limited, and the ongoing search for new treatment strategies remains a priority. Cell senescence is closely related to the occurrence and development of tumors. For GI cancer, cell senescence may not only promote cancer but also bring new opportunities for treatment. Combined with relevant studies, we review the dual role of cell senescence in GI cancer, including the mechanism of inducing cell senescence, biomarkers of senescent cells, and potential of targeted senescence therapy for GI cancer.

ObjectiveThe purpose of this study is to look into the altered functional connectivity of brain networks in Early-Onset Parkinson’s Disease (EOPD) and Late-Onset Parkinson’s Disease (LOPD), as well as their relationship to clinical symptoms.MethodsA total of 50 patients with Parkinson’ disease (28 EOPD and 22 LOPD) and 49 healthy controls (25 Young Controls and 24 Old Controls) were admitted to our study. Employing independent component analysis, we constructed the brain networks of EOPD and Young Controls, LOPD and Old Controls, respectively, and obtained the functional connectivity alterations in brain networks.ResultsCerebellar network (CN), Sensorimotor Network (SMN), Executive Control Network (ECN), and Default Mode Network (DMN) were selected as networks of interest. Compared with their corresponding health controls, EOPD showed increased functional connectivity within the SMN and ECN and no abnormalities of inter-network functional connectivity were found, LOPD demonstrated increased functional connectivity within the ECN while decreased functional connectivity within the CN. Furthermore, in LOPD, functional connectivity between the SMN and DMN was increased. The functional connectivity of the post-central gyrus within the SMN in EOPD was inversely correlated with the Unified Parkinson’s Disease Rating Scale Part III scores. Age, age of onset, and MMSE scores are significantly different between EOPD and LOPD (p < 0.05).ConclusionThere is abnormal functional connectivity of networks in EOPD and LOPD, which could be the manifestation of the associated pathological damage or compensation.

ObjectiveThe aim of this study is to explore the neural network mechanism of Parkinson’s disease (PD) with different degrees of depression using independent component analysis (ICA) of the functional connectivity changes in the forehead, limbic system, and basal ganglia regions.MethodsA total of 106 patients with PD were divided into three groups: PD with moderate-severe depression (PDMSD, n = 42), PD with mild depression (PDMD, n = 29), and PD without depression (PDND, n = 35). Fifty gender- and age-matched healthy subjects were recruited as a control group (HC). Three-dimensional T1-weighted image and resting-state functional magnetic resonance imaging (RS-fMRI) data were collected.ResultsDifferent functional connectivity was observed in the left precentral gyrus, right precuneus, right inferior frontal gyrus, right medial and paracingulate gyrus, left supplementary motor area, right brain insula, and the inferior frontal gyrus of the left orbit among the four groups (ANOVA, P < 0.05, Voxel size > 5). Both PDMD and PDMSD exhibited increased functional connectivity in the superior-posterior default-mode network (spDMN) and left frontoparietal network (LFPN); they also exhibited a decreased functional connectivity in the interior Salience Network (inSN) when compared with the PDND group. The functional connectivity within the inSN network was decreased in the PDMSD group when compared with the PDMD group (Alphasim correction, P < 0.05, voxel size > 5).ConclusionPD with different degrees of depression has abnormal functional connectivity in multiple networks, which is an important neurobiological basis for the occurrence and development of depression in PD. The degree of decreased functional connectivity in the inSN network is related to the degree of depression in patients with PD-D, which can be an imaging marker for PD to judge the severity of depression.

Colorectal cancer (CRC) is one of the most common malignant carcinomas. CRC is characterized by asymptomatic onset, and most patients are already in the middle and advanced stages of disease when they are diagnosed. Inflammatory bowel disease (IBD) and the inflammatory-cancer transformation of advanced colorectal adenoma are the main causes of CRC. There is an urgent need for effective prevention and intervention strategies for CRC. In recent years, rapid research progress has increased our understanding of gut microbiota. Meanwhile, with the deepening of research on the pathogenesis of colorectal cancer, gut microbiota has been confirmed to play a direct role in the occurrence and treatment of colorectal cancer. Strategies to regulate the gut microbiota have potential value for application in the prevention and treatment of CRC. Regulation of gut microbiota is one of the important ways for natural products to exert pharmacological effects, especially in the treatment of metabolic diseases and tumours. This review summarizes the role of gut microbiota in colorectal tumorigenesis and the mechanism by which natural products reduce tumorigenesis and improve therapeutic response. We point out that the regulation of gut microbiota by natural products may serve as a potential means of treatment and prevention of CRC.

BackgroundExcessive daytime sleepiness (EDS) is one of the most important non-motor symptoms of Parkinson's disease (PD), and its neuropathologic basis is still unclear.ObjectiveThis study investigated the changes of neuronal activity in PD patients with EDS (PD-EDS) in the resting state.MethodsForty-three PD patients were recruited and divided into the PD-EDS group (n = 21) and PD-NEDS group (PD patients without excessive daytime sleepiness, n = 22) according to the Epworth sleepiness scale (ESS) scores. Patients in both groups received resting-state functional magnetic resonance imaging (rs-fMRI). The differences in fractional amplitude of low-frequency fluctuation (fALFF) between the two groups, correlations between fALFF and ESS, and functional connection (FC) between the brain regions with different fALFF values and the whole brain were analyzed.ResultsPD-EDS patients exhibited a decreased fALFF in the Cingulum-Ant-R, but an increased fALFF in the Putamen-R and Thalamus-L when compared with PD-NEDS patients; an increased functional connectivity between these three seed regions with different fALFF values and the right medial frontal gyrus, bilateral superior temporal gyrus, left insular, and right precuneus was observed (p < 0.05), but a deceased functional connectivity between these three seed regions and the right cerebellum anterior lobe/right brainstem, right middle temporal gyrus and inferior temporal gyrus, right hippocampus/parahippocampal gyrus, right medial cingulate gyrus and bilateral middle occipital gyrus was observed (p < 0.05). The value of fALFF was negatively correlated with the ESS score in the Cingulum-Ant-R, but positively correlated with the ESS score in the Putamen-R and Thalamus-L.ConclusionsEDS in PD patients may be associated with changes in brain neuron activity and functional connectivity.

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world and is a typical inflammatory tumor. In recent years, the incidence of CRC has been increasing year by year. There is evidence that the intake of high-fat diet and overweight are associated with the incidence of CRC, among which bile acids play a key role in the pathogenesis of the disease. Studies on the relationship between bile acid metabolism and the occurrence of CRC have gradually become a hot topic, improving the understanding of metabolic factors in the etiology of colorectal cancer. Meanwhile, intestinal flora also plays an important role in the occurrence and development of CRC In this review, the classification of bile acids and their role in promoting the occurrence of CRC are discussed, and we highlights how a high-fat diet affects bile acid metabolism and destroys the integrity of the intestinal barrier and the effects of gut bacteria.

BackgroundPoststroke fatigue (PSF) is a dynamic process over time. Current evidence for interventions for PSF is limited. Our study investigated the effects of selective serotonin reuptake inhibitors (SSRIs) on the time course of PSF.MethodsThe patients with acute ischaemic stroke were enrolled in this study. All patients were scored with the Fatigue Severity Scale (FSS) at baseline and 6, 12, and 24 months after the index stroke. The time course of PSF was classified as non-PSF, incident PSF, recovered PSF and persistent PSF according to the PSF status at baseline and the 24-month follow-up. Multivariate logistic regression analysis and generalized mixed model were applied to explore the relationships between SSRIs and the time course of PSF.ResultsEight hundred forty-seven patients were analyzed in this study. No significant association between SSRIs and the time course of PSF was observed in all patients (p = 0.076). The subgroup analyses indicated that SSRI antidepressants reduced the risk of incident PSF [Odds Ratio (OR) 0.23; 95% confidence interval (CI) 0.05–0.96, p = 0.044] and persistent PSF (OR 0.28; 95% CI 0.09–0.90, p = 0.033) in the PSD subgroup, but not in the non-PSD group. In the longitudinal analysis, generalized logistical mixed-effect models indicated that early administration of SSRIs reduced the risk (OR 0.955; 95% CI 0.928–0.984, p = 0.002) and severity (β = −0.018, p = 0.041) of PSF in the PSD subgroup.ConclusionNo relationship was identified between the use of SSRIs and the time course of PSF in all patients. However, these drugs might be effective in PSF patients with depression.

Empirical evidence has accumulated showing that smartphone use at work has the double-edged sword impacts on work-related attitudes and behaviors, but little is known about how its effects transmit and spill over from the workplace to the family domain. Drawing upon compensatory ethics theory, we hypothesize positive associations of employees’ daily private smartphone use at work with their family role performance after work through feeling of guilt. Using an experience sampling methodology, we test our hypotheses in a sample of 101 employees who completed surveys across 10 consecutive workdays. Multilevel path analysis results showed that excessive smartphone use at work triggered experienced guilt, and had a positive indirect effect on family role performance via feeling of guilt. Furthermore, employees with high ability of emotion regulation can be better resolve own painful emotion by engaging in family role performance. Theoretical and practical implications, limitations, and propose future research directions are discussed.

Background: Although the study of the neuroanatomical correlates of depression in Parkinson's Disease (PD) is gaining increasing interest, up to now the cortical gyrification pattern of PD-related depression has not been reported. This study was conducted to investigate the local gyrification index (LGI) in PD patients with depression, and its associations with the severity of depression. Methods: LGI values, as measured using FreeSurfer software, were compared between 59 depressed PD (dPD), 27 non-depressed PD (ndPD) patients and 43 healthy controls. The values were also compared between ndPD and milddepressed PD (mi-dPD), moderate-depressed PD (mo-dPD) and severe-depressed PD (se-dPD) patients as sub-group analyses. Furthermore, we evaluated the correlation between LGI values and depressive symptom scores within dPD group. Results: Compared to ndPD, the dPD patients exhibited decreased LGI in the left parietal, the right superior-frontal, posterior cingulate and paracentral regions, and the LGI values within these areas negatively correlated with the severity of depression. Specially, reduced gyrification was observed in mo-dPD and involving a larger region in se-dPD, but not in mi-dPD group. Conclusion: The present study demonstrated that cortical gyrification is decreased within specific brain regions among PD patients with versus without depression, and those changes were associated with the severity of depression. Our findings suggested that cortical gyrification might be a potential neuroimaging marker for the severity of depression in patients with PD. [ABSTRACT FROM AUTHOR]