Photochemical α-selective radical ring-opening reactions of 1,3-disubstituted acyl bicyclobutanes with alkyl halides: modular access to functionalized cyclobutenes.

Although ring-opening reactions of bicyclobutanes bearing electron-withdrawing groups, typically with ß-selectivity, have evolved as a powerful platform for synthesis of cyclobutanes, their application in the synthesis of cyclobutenes remains underdeveloped. Here, a novel visible light induced α-selective radical ring-opening reaction of 1,3-disubstituted acyl bicyclobutanes with alkyl radical precursors for the synthesis of functionalized cyclobutenes is described. In particular, primary, secondary, and tertiary alkyl halides are all suitable substrates for this photocatalytic transformation, providing ready access to cyclobutenes with a single all-carbon quaternary center, or with two contiguous centers under mild reaction conditions.

Functional and structural brain reorganization in patients with ischemic stroke: a multimodality MRI fusion study.

Understanding how structural and functional reorganization occurs is crucial for stroke diagnosis and prognosis. Previous magnetic resonance imaging (MRI) studies focused on the analyses of a single modality and demonstrated abnormalities in both lesion regions and their associated distal regions. However, the relationships of multimodality alterations and their associations with poststroke motor deficits are still unclear. In this study, 71 hemiplegia patients and 41 matched healthy controls (HCs) were recruited and underwent MRI examination at baseline and at 2-week follow-up sessions. A multimodal fusion approach (multimodal canonical correlation analysis + joint independent component analysis), with amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV) as features, was used to extract the co-altered patterns of brain structure and function. Then compared the changes in patients' brain structure and function between baseline and follow-up sessions. Compared with HCs, the brain structure and function of stroke patients decreased synchronously in the local lesions and their associated distal regions. Damage to structure and function in the local lesion regions was associated with motor function. After 2 weeks, ALFF in the local lesion regions was increased, while GMV did not improve. Taken together, the brain structure and function in the local lesions and their associated distal regions were damaged synchronously after ischemic stroke, while during motor recovery, the 2 modalities were changed separately.

Acupuncture Alters Brain's Dynamic Functional Network Connectivity in Stroke Patients with Motor Dysfunction: A Randomised Controlled Neuroimaging Trial.

Objectives: Neuroimaging studies have confirmed that acupuncture can promote static functional reorganization in poststroke patients with motor dysfunction. But its effect on dynamic brain networks remains unclear. This study is aimed at investigating how acupuncture affected the brain's dynamic functional network connectivity (dFNC) after ischemic stroke. Methods: We conducted a single-center, randomised controlled neuroimaging study in ischemic stroke patients. A total of 53 patients were randomly divided into the true acupoint treatment group (TATG) and the sham acupoint treatment group (SATG) at a ratio of 2 : 1. Clinical assessments and magnetic resonance imaging (MRI) scans were performed on subjects before and after treatment. We used dFNC analysis to estimate distinct dynamic connectivity states. Then, the temporal properties and strength of functional connectivity (FC) matrix were compared within and between the two groups. The correlation analysis between dynamic characteristics and clinical scales was also calculated. Results: All functional network connectivity (FNC) matrices were clustered into 3 connectivity states. After treatment, the TATG group showed a reduced mean dwell time and found attenuated FC between the sensorimotor network (SMN) and the frontoparietal network (FPN) in state 3, which was a sparsely connected state. The FC between the dorsal attention network (DAN) and the default mode network (DMN) was higher after treatment in the TATG group in state 1, which was a relative segregated state. The SATG group preferred to increase the mean dwell time and FC within FPN in state 2, which displayed a local tightly connected state. In addition, we found that the FC value increased between DAN and right frontoparietal network (RFPN) in state 1 in the TATG group after treatment compared to the SATG group. Correlation analyses before treatment showed that the Fugl-Meyer Assessment (FMA) lower score was negatively correlated with the mean dwell time in state 3. FMA score showed positive correlation with FC in RFPN-SMN in state 3. FMA-lower score was positively correlated with FC in DAN-DMN and DAN-RFPN in state 1. Conclusions: Acupuncture has the potential to modulate abnormal temporal properties and promote the balance of separation and integration of brain function. True acupoint stimulation may have a more positive effect on regulating the brain's dynamic function. Clinical Trial Registration. This trial is registered with Chinese Clinical Trials Registry (ChiCTR1800016263).

Neuroimaging mechanisms of acupuncture on functional reorganization for post-stroke motor improvement: a machine learning-based functional magnetic resonance imaging study.

Objective: Motor recovery is crucial in stroke rehabilitation, and acupuncture can influence recovery. Neuroimaging and machine learning approaches provide new research directions to explore the brain functional reorganization and acupuncture mechanisms after stroke. We applied machine learning to predict the classification of the minimal clinically important differences (MCID) for motor improvement and identify the neuroimaging features, in order to explore brain functional reorganization and acupuncture mechanisms for motor recovery after stroke. Methods: In this study, 49 patients with unilateral motor pathway injury (basal ganglia and/or corona radiata) after ischemic stroke were included and evaluated the motor function by Fugl-Meyer Assessment scores (FMA) at baseline and at 2-week follow-up sessions. Patients were divided by the difference between the twice FMA scores into one group showing minimal clinically important difference (MCID group, n = 28) and the other group with no minimal clinically important difference (N-MCID, n = 21). Machine learning was performed by PRoNTo software to predict the classification of the patients and identify the feature brain regions of interest (ROIs). In addition, a matched group of healthy controls (HC, n = 26) was enrolled. Patients and HC underwent magnetic resonance imaging examination in the resting state and in the acupuncture state (acupuncture at the Yanglingquan point on one side) to compare the differences in brain functional connectivity (FC) and acupuncture effects. Results: Through machine learning, we obtained a balance accuracy rate of 75.51% and eight feature ROIs. Compared to HC, we found that the stroke patients with lower FC between these feature ROIs with other brain regions, while patients in the MCID group exhibited a wider range of lower FC. When acupuncture was applied to Yanglingquan (GB 34), the abnormal FC of patients was decreased, with different targets of effects in different groups. Conclusion: Feature ROIs identified by machine learning can predict the classification of stroke patients with different motor improvements, and the FC between these ROIs with other brain regions is decreased. Acupuncture can modulate the bilateral cerebral hemispheres to restore abnormal FC via different targets, thereby promoting motor recovery after stroke. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=37359, ChiCTR1900022220.

Effects of sulfated polysaccharides from Laminaria japonica on regularating the gut microbiotan and alleviating intestinal inflammation in obese mice.

Due to their known health-enhancing properties, Laminaria japonica polysaccharides (LJP) may alleviate obesity via unknown mechanisms. This study aimed to investigate beneficial LJP effects and mechanism(s) of action using an animal obesity model (ICR mice fed a high-fat diet). First, LJP were confirmed to consist of sulfated polysaccharides via infrared spectroscopy. Next, LJP administration to mice was found to induce weight loss, reduce liver fat accumulation, and support healthy obesity-related blood serum indicator levels. Notably, LJP treatment significantly reduced TC and LDL levels and significantly increased HDL, LPL, UCP-2, and PPAR-α levels. Furthermore, examinations of tissues of LJP-treated mice revealed significantly reduced intestinal tissue inflammation as compared to corresponding results obtained for untreated obese controls. Additionally, LJP treatment relieved colonic shortening and reduced colonic levels of inflammatory factors TNF-α and IL-6. Further exploration of LJP treatment effects on mouse gut microbiota conducted via fecal 16S rRNA gene sequence-based gut microbiome profiling analysis revealed that LJP treatment increased the Bacteroidetes/Firmicutes ratio and increased gut abundances of probiotics Bacteroides acidifaciens, s_Lactobacillus intestinalis, and s_Lactobacillus murinus. In conclusion, these results collectively suggest that LJP use as a food supplement may alleviate obesity and related gut microbiota dysbiosis and intestinal inflammatory disorders.

Discovery of Potent Small-Molecule USP8 Inhibitors for the Treatment of Breast Cancer through Regulating ERα Expression.

Ubiquitin-specific protease 8 (USP8), belonging to the deubiquitinase family, has been implicated to be closely related to the occurrence of many malignant tumors, but only a few USP8-targeting inhibitors have been reported to date. In this study, we present virtual screening to discover novel hit candidates that inhibit the catalytic activity of USP8. Exploration of the structure-activity relationship led to the identification of compound DC-U4106, which binds to USP8 with a KD value of 4.7 µM and is selective over USP2 and USP7. Western blotting and immunoprecipitation showed that DC-U4106 could target the ubiquitin pathway and facilitate the degradation of ERα. In a xenograft tumor model, DC-U4106 also significantly inhibited tumor growth with minimal toxicity. Overall, our findings suggest that DC-U4106 is a promising drug candidate and targeting the USP8-ERα complex could be a new approach to treat ER-positive or drug-resistant breast cancer.

Sensorimotor Responses in Post-Stroke Hemiplegic Patients Modulated by Acupuncture at Yanglingquan (GB34): A fMRI Study Using Intersubject Functional Correlation (ISFC) Analysis.

Motor dysfunction is common in patients with stroke. Acupuncture has become an acceptable alternative method for stroke rehabilitation. Previous studies have shown various functional connectivity changes activated by acupuncture. We introduced intersubject correlation (ISC) and intersubject functional correlation (ISFC) analyses into the functional magnetic resonance imaging (fMRI) for ischemic stroke to seek a common activation and suppression pattern triggered by acupuncture. In this study, 63 ischemic stroke patients with motor dysfunction and 42 normal controls were analyzed. Three functional scans were conducted during the resting state, motor task, and acupuncture at Yanglingquan (GB34) task. Twenty-two sensory, motor, and movement-imagination cortices in the bilateral hemispheres were selected as the region of interest (ROI). We performed ISC and ISFC analyses among these ROIs in three fMRI runs on patients and controls. Subgroup analyses by course or severity were also conducted. The results showed that acupuncture at GB34 triggered ISFC among upper limb motor, upper limb/hand/face, lower limb, tongue/larynx sensory, and movement imagination regions in the patient group. Subgroup ISC and ISFC analyses showed that patients tended to have increasing responses in the early stage of stroke (within 1 month) and decreasing responses afterward (1-3 months). Patients with mild clinical functional damage (NIHSS 2-4) tended to generate more responses via acupuncture than those with moderate damage (NIHSS 5-15). Our findings may help understand the clinical effects and modulatory features of acupuncture based on the group-level post-stroke neuroplasticity.

Physical Therapies for Psychosomatic Symptoms and Quality of Life Induced by Aromatase Inhibitors in Breast Cancer Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effects of Physical Therapies (PTs) on improvement in psychosomatic symptoms and quality of life (QOL) in breast cancer patients. DATA SOURCES: Seven databases (MEDLINE, EMBASE, Cochrane CENTRAL, China National Knowledge Infrastructure, Wangfang, VIP, and China Biology Medicine disc databases) were systematically searched from the database inception through May 18, 2021. STUDY SELECTION: Randomized controlled trials (RCTs) which compared acupuncture or exercise with a sham control or usual care for the treatment of aromatase inhibitors (AIs)-related psychosomatic symptoms and QOL. DATA EXTRACTION AND SYNTHESIS: Data were screened and extracted independently using predesigned forms. The quality of RCTs was assessed with the Cochrane Handbook for Systematic Reviews of Interventions. The effect size was calculated via random-effects modeling. The quality of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. MAIN OUTCOMES AND MEASURES: The score of pain was measured with BPI scale and Western Ontario and the McMaster Universities Index (WOMAC) scale. Emotional state was measured with Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS-A), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). The QOL score was measured by self-reported measurements, including the Functional Assessment of Cancer Therapy-General (FACT-G) scale and 36-Item Short Form Survey (SF-36) scale. RESULTS: Eleven RCTs (with 830 patients) were included in the systematic review, and data from 10 RCTs (with 798 patients) were used in the meta-analysis. Results showed acupuncture significantly reduced worst pain scores (P < 0.00001, I 2 = 83.5%) [SMD = -0.81, 95% CI (-1.51, -0.11)], but the effect of exercise therapies was not significant in overall change in worst pain scores (P =0.006, I 2 = 72.3%) [SMD = -0.30, 95% CI (-0.76, 0.16)]. Both acupuncture and exercise resulted in little to no difference in overall change in HADS-A subscale (P = 0.026<0.05, I 2 = 79.8%) [WMD = -0.21, 95% CI (-3.44, 3.03)], PSQI subscale (P = 0.488, I 2 = 0%) [WMD = 0.98, 95% CI (-0.57, 2.53)], and FACIT-Fatigue subscale (P = 0.022<0.05, I 2 = 81.0%) [WMD = 1.6, 95% CI (-5.75, 8.94)]. Exercise (compared with usual care) was associated with improving overall change in health-related QOL (subscales of SF-36 tool) (P = 0, I 2 = 72.1%) [WMD = 7.97, 95% CI (5.68, 10.25)] and cancer-specific QOL (subscales of FACT-G tool) (P = 0.304, I 2 = 16%) [WMD = 1.16, 95% CI (0.34, 1.97)]. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis suggested that based on moderate-level evidence, acupuncture was associated with significant reductions in pain intensity, and exercise might improve QOL in breast cancer patients treated with AIs. However, in psychosomatic symptoms such as anxiety, sleep disturbance, and fatigue, acupuncture and exercise training did not result in significant improvements.

Inverse correlation between serum irisin and cardiovascular risk factors among Chinese overweight/obese population.

BACKGROUND: Irisin is a novel myokine associated with obesity, which is a traditional cardiovascular risk factor (CVRF). The present study aimed to investigate the association between serum irisin and a single CVRF as well as the clustering of CVRFs among Chinese overweight/obese population. METHODS: A total of 98 overweight and 93 obese subjects without clinical treatments were enrolled in this study. Subjects were then divided into two groups, based on the serum irisin level: a low irisin group (1.10-13.44 ng/ml) and a high irisin group (13.49-29.9 ng/ml). The clustering of CVRFs, smoking, diabetes mellitus, dyslipidemia and hypertension, was classified as 0, 1, 2 and ≥ 3 CVRFs. The demographic and baseline clinical characteristics of all participants were collected and serum irisin was measured. RESULTS: The high serum irisin group had significantly higher high-density lipoprotein cholesterol but lower fasting plasma glucose than the low serum irisin group. Additionally, the high serum irisin group had a significantly lower prevalence of smoking, diabetes mellitus and dyslipidemia than the low serum irisin group. Increased serum irisin was significantly associated with a reduced risk of smoking and dyslipidemia in both the unadjusted and adjusted models. Furthermore, high serum irisin significantly reduced the risk of the prevalence of 1, 2 and ≥ 3 CVRFs. CONCLUSIONS: among the Chinese overweight/obese populations, high serum irisin is negatively associated with smoking, dyslipidemia and the clustering of CVRFs. Thus, high serum irisin is potentially associated with a low risk of cardiovascular diseases in the Chinese overweight/obese population.

Association of serum irisin concentration with thyroid autoantibody positivity and subclinical hypothyroidism.

OBJECTIVE: This study evaluated the association of serum irisin level with thyroid autoantibody (TAA) positivity and subclinical hypothyroidism (SH). METHODS: In this cross-sectional study, 334 participants were assigned to one of the following four age- and sex-matched groups: TAA plus SH (84 patients), isolated TAA (83 patients), isolated SH (83 patients), or healthy controls (84 individuals). Irisin and creatine kinase (CK) were measured in serum samples. RESULTS: Patients with TAA plus SH, isolated TAA, and isolated SH had higher irisin levels compared with the controls. There was a significant increase in the irisin level in the TAA plus SH group compared with the control group. Among all participants, the irisin levels were positively associated with thyroglobulin and thyroid peroxidase antibody titers and high-density lipoprotein cholesterol levels, but negatively associated with waist circumference, glycated hemoglobin levels, and fasting plasma glucose levels. The irisin level was not associated with the thyroid-stimulating hormone, free thyroxine, or CK levels. Irisin levels were independently associated with TAA, with or without SH, but they were not associated with SH alone. CONCLUSIONS: Irisin level may help to predict the risk of developing TAA with or without SH.

Irisin plays an important role in the outcomes of newly diagnosed prediabetes in adults in Guiyang, China.

AIMS/INTRODUCTION: To explore the potential role of irisin in the outcomes of newly diagnosed prediabetes. MATERIALS AND METHODS: Data were obtained from the Guiyang subcenter of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. A total of 2,530 participants had newly diagnosed prediabetes at baseline and completed follow up. The nested 1:1 case-control study included 161 participants who developed diabetes mellitus at follow up, and 161 age- and sex-matched controls. The follow-up study included 86 matched case-control pairs. Fasting serum irisin levels were measured using enzyme-linked immunosorbent assay. RESULTS: Baseline serum irisin levels were higher in the cases than in the controls (P = 0.002); high baseline serum irisin levels were an independent risk factor for the development of diabetes (odds ratio 1.235, 95% confidence interval 1.025-1.488). After adjustment for age, sex, body mass index, glycated hemoglobin (HbA1c), smoking, exercise, and family history of diabetes, subjects in the highest quartile of irisin levels had a higher risk of diabetes than those in the lowest quartile (odds ratio 3.065, 95% confidence interval 1.511-6.218). The extent of decrease in irisin levels during follow-up was greater in the cases than in the controls (P < 0.001). Baseline serum irisin levels were positively correlated with the extent of decrease in irisin during follow-up (r = 0.773, P < 0.001). After adjustment for confounding factors, subjects with a decrease of irisin above the median had much higher risk for diabetes (odds ratio 5.077, 95% confidence interval 2.112-12.206). CONCLUSIONS: Irisin might play an important role in the outcomes of newly diagnosed prediabetes in adults in Guiyang, and can predict the risk for developing diabetes in these individuals.

Higher Baseline Serum Irisin Decreases Risk for Body Mass Index Increment in Chinese Populations: A 3.2-Year Cohort Study.

INTRODUCTION: Irisin, a newly discovered myokine, exerts beneficial effects on energy metabolism. However, published results from studies examining the relationship between irisin concentration and obesity have been conflicting. The aim of our study was to investigate the association between serum irisin level and obese individuals with different body mass index (BMI) values and to explore the question of whether serum irisin can predict the risk of increases in the BMI. METHODS: This study based on the data collected in the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION). The cross-sectional cohort study was carried out from May 2011 to August 2011, and a longitudinal cohort study was conducted from July 2014 to October 2014 to complete the first 3.2-year follow-up. We enrolled 93 low-weight subjects (BMI < 18.5 kg/m2), 94 normal-weight subjects (BMI 18.5-23.9 kg/m2), 98 overweight subjects (BMI 24.0-27.9 kg/m2) and 93 obese subjects (BMI ≥ 28 kg/m2). Subjects in the normal-weight, overweight and obese groups were selected to match low-weight subjects by age and sex. Serum samples were obtained from all subjects to determine the irisin level. RESULTS: Subjects with a higher serum irisin level tended to have significantly lower changes in BMI and body fat percentage and higher baseline high-density lipoprotein cholesterol level (p < 0.05). No significant correlation was observed between serum irisin level and the baseline obesity index. Serum irisin level was positively correlated to an active lifestyle (i.e. physical activity; ß = 1.138, p = 0.032) and negatively correlated to fasting plasma glucose level (ß = - 0.996, p = 0.023), changes in BMI (ß = - 0.533, p = 0.002), waist circumference (ß = - 0.102, p = 0.018), body fat percentage (ß = - 0.457, p = 0.001) and Chinese visceral adiposity index (ß = - 0.280, p = 0.028). After adjustment for cofactors, higher baseline serum irisin was an independent factor for a decreased BMI increment (baseline serum irisin: odds ratio 0.747, 95% confidence interval 0.652-0.949, p = 0.002). CONCLUSIONS: Higher serum irisin at baseline independently predicted a lower BMI increment in Chinese populations.

{1-[(3,5-Dimethyl-4H-1,2,4-triazol-4-yl)imino]eth-yl}ferrocene.

In the title compound, [Fe(C(5)H(5))(C(11)H(13)N(4))], the triazolyl and Cp ring form a dihedral angle of 76.6 (3)°. In the crystal structure, there are both intra- and inter-molecular C-H⋯π inter-actions, forming a one-dimensional chain structure along [010].