Association of geriatric nutritional risk index with bone mineral density and osteoporosis in postmenopausal elderly women with T2DM.

BACKGROUND AND OBJECTIVES: To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). METHODS AND STUDY DESIGN: A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T1, T2, T3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. RESULTS: Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the nor-mal BMD group [(103±5.46) vs. (105±5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae (L) were gradually increased, which were higher in the T3 group than in the T1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L1, L2, L3, L4, and L1-L4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). CONCLUSIONS: In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP.

Optimal conditions and nitrogen removal performance of aerobic denitrifier Comamonas sp. pw-6 and its bioaugmented application in synthetic domestic wastewater treatment.

To assess the possibility of using aerobic denitrification (AD) bacteria with high NO2--N accumulation for nitrogen removal in wastewater treatment, conditional optimization, as well as sole and mixed nitrogen source tests involving AD bacterium, Comamonas sp. pw-6 was performed. The results showed that the optimal carbon source, pH, C/N ratio, rotational speed, and salinity for this strain were determined to be succinate, 7, 20, 160 rpm, and 0%, respectively. Further, this strain preferentially utilized NH4+-N, NO3--N, and NO2--N, and when NO3--N was its sole nitrogen source, 92.28% of the NO3--N (150 mg·L-1) was converted to NO2--N. However, when NH4+-N and NO3--N constituted the mixed nitrogen source, NO3--N utilization by this strain was significantly lower (p < 0.05). Therefore, a strategy was proposed to combine pw-6 bacteria with traditional autotrophic nitrification to achieve the application of pw-6 bacteria in NH4+-N-containing wastewater treatment. Bioaugmented application experiments showed significantly higher NH4+-N removal (5.96 ± 0.94 mg·L-1·h-1) and lower NO3--N accumulation (2.52 ± 0.18 mg·L-1·h-1) rates (p < 0.05) than those observed for the control test. Thus, AD bacteria with high NO2--N accumulation can also be used for practical applications, providing a basis for expanding the selection range of AD strains for wastewater treatment.

Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. METHODS: High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. RESULTS: Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. CONCLUSIONS: These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.

MiR-30b-5p attenuates neuropathic pain by the CYP24A1-Wnt/ß-catenin signaling in CCI rats.

MicroRNAs (miRNAs) has been reported to act as key regulators of neuronal function. Increasing evidence has showed that miRNAs exert significant effects in neuropathic pain. We explored the role of miR-30b-5p in neuropathic pain by establishing a rat model of chronic constrictive injury (CCI). The sciatic nerve of CCI rats was used to induce chronic neuropathic pain. The expression and cellular distribution of miR-30b-5p were determined by RT-qPCR and FISH. The mRNA level, protein level, and cellular distribution of CYP24A1 were detected by RT-qPCR, western blot, and immunofluorescence staining assays, respectively. The interaction between miR-30b-5p and CYP24A1 was examined by a luciferase reporter assay. The behavioral effects of miR-30b-5p were assessed after intrathecal administration. Mechanical stimuli and radiant heat were applied to assess mechanical allodynia and thermal hyperalgesia of rats. ELISA was performed to measure the concentration of inflammatory cytokines. MiR-30b-5p expression was significantly downregulated in the spinal cord tissues and of CCI rats. Overexpression of miR-30b-5p attenuated symptoms of neuropathic pain, including mechanical allodynia and thermal hyperalgesia. Additionally, miR-30b-5p overexpression suppressed neuroinflammation by reducing the levels of IL-6, TNF-α and COX2 and elevating the levels of IL-10 in CCI rats. Mechanistically, CYP24A1 was a target of miR-30b-5p, and its expression was negatively regulated by miR-30b-5p. Moreover, CYP24A1 expression was upregulated in CCI rats and knockdown of CYP24A1 attenuated neuropathic pain and neuroinflammation. Furthermore, miR-30b-5p reduced the levels of the Wnt pathway-related genes in CCI rats by downregulating CYP24A1. Rescue assays showed that overexpression of CYP24A1 or activation of Wnt pathway reduced the alleviative effects of miR-30b-5p overexpression on neuropathic pain in CCI rats. Overall, miR-30b-5p inhibits neuropathic pain progression in CCI rats by inhibiting the CYP24A1-Wnt/ß-catenin pathway.

Association between hemoglobin A1c and asymptomatic carotid intima-media thickness in middle-aged and elderly populations without diabetes.

BACKGROUND AND AIMS: Carotid atherosclerosis, including carotid artery intima-media thickness, plaques, and stenosis, is an important risk factor for stroke. However, the association between hemoglobin A1c (HbA1c) and carotid intima-media thickness (cIMT) was inconsistent. The aim of this study was to explore the association between HbA1c and the risk of increased cIMT among the Chinese population aged ≥40 years without diabetes. METHODS AND RESULTS: A total of 3528 participants without diabetes from the China National Stroke Screen Survey program were enrolled in this study. cIMT was measured using duplex ultrasound examination. Logistic regression models were used to assess the association between HbA1c level and the risk of increased cIMT. A total of 565 (16.0%) participants had increased cIMT. After adjustment for other potential confounding factors, higher levels of HbA1c increased the risk of increased cIMT compared with the lowest level, and the odds ratios for quartile 2, quartile 3, and quartile 4 were 1.58, 1.67, and 1.98, respectively. Age had an interaction impact on the association between HbA1c level and the risk of increased cIMT. CONCLUSION: In this large-scale and cross-sectional study, high-normal HbA1c was associated with the risk of increased asymptomatic cIMT in a rural Chinese population without diabetes, especially in individuals aged <60 years.

Hemodynamic response varies across tactile stimuli with different temporal structures.

Tactile stimuli can be distinguished based on their temporal features (e.g., duration, local frequency, and number of pulses), which are fundamental for vibrotactile frequency perception. Characterizing how the hemodynamic response changes in shape across experimental conditions is important for designing and interpreting fMRI studies on tactile information processing. In this study, we focused on periodic tactile stimuli with different temporal structures and explored the hemodynamic response function (HRF) induced by these stimuli. We found that HRFs were stimulus-dependent in tactile-related brain areas. Continuous stimuli induced a greater area of activation and a stronger and narrower hemodynamic response than intermittent stimuli with the same duration. The magnitude of the HRF increased with increasing stimulus duration. By normalizing the characteristics into topographic matrix, nonlinearity was obvious. These results suggested that stimulation patterns and duration within a cycle may be key characters for distinguishing different stimuli. We conclude that different temporal structures of tactile stimuli induced different HRFs, which are essential for vibrotactile perception and should be considered in fMRI experimental designs and analyses.

Pneumatical-Mechanical Tactile Stimulation Device for Somatotopic Mapping of Body Surface During fMRI.

BACKGROUND: There is a need for devices that allow reproducible stimulation of skin areas of humans for investigating somatosensory mapping of the whole-body surface. However, their design is not simple, due to the magnetic field of MRI scanners. PURPOSE: To accurately characterize the mapping of somatosensory presentation of the whole-body surface of subjects during functional (f)MRI scans. STUDY TYPE: Prospective. POPULATION: A water phantom and six healthy participants (age 23-27 years; two males) were recruited for the fMRI experiment. FIELD STRENGTH/SEQUENCE: T1 -weighted magnetization-prepared rapid acquisition gradient-echo, T2 *-weighted gradient echo sequence at 3T. ASSESSMENT: The stimulation device for somatotopic mapping was composed of three units: an air-generating unit, a control unit, and an execution unit. The fMRI in response to tactile stimulation was measured to characterize somatotopic mapping of the right-side body consisting of hand, arm, and leg in six healthy subjects. STATISTICAL TESTS: Pared-samples t-test for the conditions in SII. RESULTS: The pneumatical-mechanical tactile stimulation offered a wide range of stimulation intensities (0-400 g) in each channel. The predetermined physical pressure was successfully reached within ~5 msec and returned to baseline within 5 msec after the end of stimulation. With this tactile device, the digressive rate of the signal-to-noise ratio (SNR) (271.44 without the device, 269.68 with the device) was 0.65% in the magnetic field environment. For the fMRI experiment, the primary somatosensory activation contralateral to the stimulation site was detected in response to spatial task and attentive task. DATA CONCLUSION: This stimulation device characterized the mapping of somatosensory representation of the whole-body surface in individual participants during fMRI scans. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 1. J. Magn. Reson. Imaging 2020;52:1093-1101.

17ß-Estradiol via Orai1 activates calcium mobilization to induce cell proliferation in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal estrogen-sensitive gynecological cancer. Studies have reported that estrogen induces rapid cellular calcium mobilization in cells and can determine the fate of a cell. We found that estrogen increased the calcium release-activated calcium channel modulator 1 (Orai1) protein expression levels in SK-OV-3 cells. However, to date, there has been no research on the functional relationship and molecular mechanism of estrogen-regulating Orai1 during EOC development. In our study, Orai1 had a high expression level in high-grade serous ovarian tumor tissues and SK-OV-3 cells. Estrogen promoted cell proliferation and migration while inhibiting cell apoptosis in SK-OV-3 cells. Orai1 silencing suppressed estrogen-induced cell migration and proliferation. Overexpression of Orai1, however, enhanced the ability of 17ß-estradiol (E2) to exert its function. Estrogen induced rapid calcium influx in SK-OV-3 cells. Knockdown of Orai1 in SK-OV-3 cells blocked E2-induced stored-operated Ca2+ influx. The messenger RNA expression of caspase 3, matrix metallopeptidase 1, and cyclin-dependent kinase 6 were regulated via Orai1 under E2 treatment. Our results suggest that estrogen, by regulating Orai1, induced calcium influx to determine cell fate.

Comparison of 68Ga-PSMA-11 PET-CT with mpMRI for preoperative lymph node staging in patients with intermediate to high-risk prostate cancer.

BACKGROUND: To evaluate the diagnostic value of 68Ga-PSMA-11 PET-CT with multiparametric magnetic resonance imaging (mpMRI) for lymph node (LN) staging in patients with intermediate- to high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP) with pelvic lymph node dissection (PLND). METHODS: We retrospectively identified 42 consecutive patients with intermediate- to high-risk PCa according to D'Amico and without concomitant cancer. Preoperative 68Ga-PSMA-11 PET-CT, pelvic mpMRI and subsequent robot assisted laparoscopic RP with PLND were performed in all patients. RESULTS: Among 42 patients assessed, the preoperative PSA value, Gleason score, pT stage and intraprostatic PCa volume of patients with LN metastases were all significantly higher than those without metastases (P = 0.029, 0.028, 0.004, respectively). The average maximum standardized uptake value (SUV) of 68Ga-PSMA-11 PET-CT positive PCa of patients with or without LN metastases were 13.10 (range 6.12-51.75) and 7.22 (range 5.4-11.2), respectively (P < 0.001). 68Ga-PSMA-11 PET-CT and pelvic mpMRI had the ability of succeed on preoperative definite accurate diagnosis and accurate localization of primary PCa in all 42 patients. Fifteen patients (35.71%) had a pN1 stage. 51 positive LN were found. Both 68Ga-PSMA-11 PET-CT and pelvic mpMRI displayed brillient patient-based and region-based sensitivity, specificity, negative predictive value and positive predictive value. There was no statistical difference for the detection of LNMs according to the diameter of the LNMs between 68Ga-PSMA-11 PET-CT and mpMRI in this study. CONCLUSIONS: Both 68Ga-PSMA-11 PET-CT and mpMRI performed great value for LN staging in patients with intermediate- to high-risk PCa undergoing RP with PLND. However, despite excellent performance of 68Ga-PSMA-11 PET-CT, it cannot replace mpMRI that remains excellent for lymph node staging.

Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment.

BACKGROUND: The cognitive impairment in type 2 diabetes mellitus (T2DM) is a multifaceted and advancing state that requires further exploration to fully comprehend. Neuroinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease. AIM: To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment. METHODS: To identify differentially expressed genes (DEGs) between T2DM and controls, we used data from the Gene Expression Omnibus database GSE125387. To identify T2DM module genes, we used Weighted Gene Co-Expression Network Analysis. All the genes were subject to Gene Set Enrichment Analysis. Protein-protein interaction network construction and machine learning were utilized to identify three hub genes. Immune cell infiltration analysis was performed. The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis. Validation experiments including reverse transcription quantitative real-time PCR, Western blotting and immunohistochemistry were conducted both in vivo and in vitro. To identify potential drugs associated with hub genes, we used the Comparative Toxicogenomics Database (CTD). RESULTS: A total of 576 DEGs were identified using GSE125387. By taking the intersection of DEGs, T2DM module genes, and immune-related genes, a total of 59 genes associated with the immune system were identified. Afterward, machine learning was utilized to identify three hub genes (H2-T24, Rac3, and Tfrc). The hub genes were associated with a variety of immune cells. The three hub genes were validated in GSE152539. Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro, consistent with the bioinformatics analysis. Additionally, 11 potential drugs associated with RAC3 and TFRC were identified based on the CTD. CONCLUSION: Immune-related genes that differ in expression in the hippocampus are closely linked to microglia. We validated the expression of three hub genes both in vivo and in vitro, consistent with our bioinformatics results. We discovered 11 compounds associated with RAC3 and TFRC. These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.

Efficacy and safety of the Latarjet procedure for the treatment of athletes with glenoid bone defects ≥ 20%: a single-arm meta-analysis.

BACKGROUND: The shoulder joint is the most commonly dislocated joint in the human body, and the recurrence rate exceeds 50% after nonsurgical treatment. Although surgical treatment reduces the recurrence rate, there is controversy regarding the optimal surgical approach. Previous studies suggest that the Latarjet procedure yields favourable outcomes for specific populations at risk of recurrence, such as competitive athletes with significant glenoid defects. However, most of the existing related research consists of nonrandomized controlled trials with small sample sizes, and there is a lack of strong evidence regarding the efficacy and safety of the Latarjet procedure. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched. Athletes with ≥ 20% glenoid defects were selected for inclusion. The following data were extracted: general patient information, instability rates, return to sports (RTS) rates, imaging features (graft positioning rate and graft healing rate), functional assessments [Rowe score, Athletic Shoulder Outcome Scoring System(ASOSS), visual analogue scale (VAS), forward flexion function, and external rotation function], and complications. RESULTS: After excluding suspected duplicate cases, a total of 5 studies were included in this meta-analysis. The studies involved a total of 255 patients, including 237 males (93%) and 18 females (7%). The average age at the time of surgery was 25.4 ± 8.5 years. All the studies had a minimum follow-up period of 2 years, with an average follow-up time of 48.7 ± 18.9 months. The pooled rate of return to sport (RTS) was 94.3% (95% CI: 87.3%, 98.8%), and 86.1% (95% CI: 78.2%, 92.5%) of patients returned to their preoperative level of activity. The pooled redislocation rate was 1.1% (95% CI: 0%, 3.8%). Regarding the imaging results, the combined graft retention rate was 92.1% (95% CI: 88.1%, 95.5%), and the graft healing rate was 92.1% (95% CI: 88%, 95.4%). Postoperative functional evaluation revealed that the combined Rowe score, ASOSS score, and VAS score were 93.7 ± 6.5 points, 88.5 ± 4.4 points, and 1.1 ± 10 points, respectively. The forward flexion and external rotation angles were 170.9 ± 6.9 degrees and 65.6 ± 4.5 degrees, respectively. After excluding one study with unclear complications, the combined complication rate was 9.4% (95% CI: 1.0%, 23.6%). CONCLUSION: For athletes with shoulder instability and a total of ≥ 20% glenoid bone defects, the Latarjet procedure can achieve excellent functional outcomes, with the majority of patients returning to preoperative levels of sports activity. This procedure also leads to a low recurrence rate. Therefore, the Latarjet procedure has been proven to be a safe and effective treatment.

A study on the spatial differences between the tourism network attention and tourism flow in Shanghai, China.

The tourism network attention as a reflection of tourism demand is closely related to the tourism flow, the differences between the two has become an important criterion for judging the efficiency of destination tourism demand conversion, as well as a manifestation of the balance and coordination of destination tourism industry. Against the background of insufficient release of tourism demand in China, research on the development differences between tourism network attention and tourism flow can provide a basis for demand-side management and high-quality development. Based on the theory of spatial mismatch, this research analyzes the spatial development difference between the tourism network attention and the tourism flow in Shanghai from 2012 to 2021 using methods such as center of gravity model, spatial mismatch index, and two-dimensional combination matrix. The results show: (1) According to the analysis of the center of gravity model, there was a shift of the center of gravity of tourism network attention with the direction of "south-north", while the tourism flow shifted "west-east"; the center of gravity between tourism network attention and tourism flow began to diverge from 2012 to 2016, gradually converged from 2016 to 2019, and then gradually deviated again after 2020. (2) According to the spatial mismatch index, the spatial mismatch types between tourism network attention and tourism flow in various Districts of Shanghai are mainly negative and low mismatch, with high mismatch areas mainly distributed in the eastern and southwestern parts of Shanghai. (3) Combining the two-dimensional combination matrix, it can be observed that the spatial development difference between tourism network attention and tourism flow in Shanghai show a characteristic of "enlarging-shrinking-enlarging". From 2012 to 2016, the spatial development difference between tourism network attention and tourism flow in Shanghai continuously expanded; from 2017 to 2019, the spatial development difference continuously shrank; and from 2020 to 2021, the spatial differences expanded again. (4) The analysis results of the panel data model show that the development of tourism resources and the level of tourism services have a positive promoting effect on the evolution of spatial mismatch, while the social basic development environment has a negative effect. The research results not only meet the needs of evaluating the high-quality development of the tourism industry in the current economic restructuring, providing direction for the high-quality development of the regional tourism industry, but also enrich the research content of network attention as a tourism element participating in the evaluation of tourism industry development quality, and deepen the relationship research between network attention and tourism flow.

Treatment of Atrophic Acne Scarring with Fractional Microplasma Radiofrequency: A Multicentric Experience.

Background: Atrophic scarring is a severe form-disfiguring sequela of acne, which can lead to negative effect on patients' life. Fractional microplasma radiofrequency (RF) has emerged as a promising modality, leveraging dermal fibroblast remodeling to enhance aesthetic results for scars and hyperpigmentation. This study evaluates the efficacy and safety of high-power fractional microplasma RF for atrophic acne scars, considering patient tolerance to procedural discomfort. Methods: In this prospective study, 95 Chinese patients with atrophic facial acne scars underwent three sessions of fractional microplasma RF treatment, with assessments at 1, 3, and 6 months post-treatment. Patients were categorized based on treatment power: Group A (50-70 W) and Group B (70-85 W). Efficacy was determined by three independent dermatologists using digital photographs and Echelle d'Evaluation Clinique des Cicatrices d'Acné (ECCA) scores, and patient-reported outcomes gauged satisfaction levels. Results: Eighty-six patients completed the study. Significant improvements were observed, with a reduction in ECCA scores from 107.21 to 42.27 (P<0.05), demonstrating notable scar amelioration across both groups, albeit with a superior outcome in Group B. All patients experienced transient side effects such as pain, erythema, and edema, deemed tolerable with no long-term adverse effects reported. The treatment was well-received, with high satisfaction rates, underscoring its efficacy and acceptable safety profile. Conclusion: Fractional microplasma RF therapy, particularly at higher power settings, is an effective and safe option for treating atrophic acne scars, offering significant aesthetic improvement with manageable discomfort. This modality presents a valuable addition to acne scar management strategies, especially for patients with darker skin tones seeking minimal downtime and reduced risk of hyperpigmentation.

A novel AVPR2 gene mutation in a Chinese pedigree with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin 2 (AQP2) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2, and leads to reduced tubular reabsorption of water.

Association between serum ferritin and bone turnover marker levels in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease.

OBJECTIVE: To investigate the correlation between serum ferritin (SF) and bone turnover markers in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Seven hundred and forty-two people with T2DM were selected. Serum bone turnover markers: osteocalcin (OC), type I procollagen N-terminal peptide (PINP), ß-I type collagen carboxy-terminal peptide (ß-CTx), and 25-hydroxyvitamin D3 (25-[OH]-D) levels were detected. High SF (HF) was defined as the indicated SF levels above 400 ng/mL in males and more than 150 ng/mL in females. Patients were divided into four groups: T2DM+normal SF (non-HF); T2DM+high SF (HF); T2DM+NAFLD+non-HF; andT2DM+NAFLD+HF. Relationships between SF and bone turnover markers were analyzed. RESULTS: Compared with the T2DM+non-HF group, ß-CTx levels were higher in the T2DM+HFgroup. Compared with the T2DM+NAFLD+non-HF group, ß-CTx levels were increased and 25-(OH)-D levels decreased in the T2DM+NAFLD+HF group (all p < 0.05). SF was positively correlated with ß-CTx [ß = 0.074; 95% CI (0.003, 0.205)] and negatively correlated with 25-(OH)-D [ß=-0.108; 95%CI (-0.006, -0.001)]. Compared with the T2DM+non-HF group, an independent positive correlation was found between ß-CTx and SF in the T2DM+NAFLD+HF group [OR = 1.002; 95% CI (1.001, 1.004)]. Among males, SF was positively correlatedwith ß-CTx [ß = 0.114; 95% CI (0.031, 0.266)]. SF was negatively correlated with 25-(OH)-D levels in both male and female patients [ß=-0.124; 95% CI (0.007,0.001) and ß=-0.168; 95% CI (-0.012, -0.002)]. Among those >50 years of age and postmenopausal females, SF was negatively correlated with 25-(OH)-D levels [ß=-0.117; 95% CI (-0.007, -0.001) and ß=-0.003; 95% CI (-0.013, -0.003)]. CONCLUSION: SF level was positively correlated with ß-CTx in T2DM patients with NAFLD, which may promote bone resorption and increase the risk of bone loss.

The Effect of Tirzepatide on Weight, Lipid Metabolism and Blood Pressure in Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Aim: To explore the effects of Tirzepatide (TZP), a new hypoglycemic drug, on weight, blood lipids and blood pressure in overweight/obese patients with type 2 diabetes mellitus (T2DM). Methods: Relevant studies investigating the influence of TZP therapy on weight, lipid profiles and blood pressure in overweight/obese T2DM patients were selected from the PubMed, Embase, Web of Science and Cochrane databases from establishment until November 2022. A systematic review and meta-analysis were conducted to evaluate the effect of TZP on weight, blood lipids and blood pressure in overweight/obese patients with T2DM. Results: Eight randomized controlled trials (RCTs), comprising 7491 patients with T2DM, were included in the meta-analysis. Results showed that compared with the glucagon-like peptide-1 receptor agonist (GLP-1RA), insulin, and placebo groups, body weight, triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) levels were significantly decreased in the TZP-treated groups, while high-density lipoprotein cholesterol (HDL-C) levels increased. With the gradual increase of TZP doses, the proportions of T2DM patients with weight loss >5% gradually increased. The 10 mg and 15 mg TZP doses had a stronger effect on the levels of TG, VLDL-C, and HDL-C. Moreover, the reduction in SBP levels in the 15 mg TZP-treated group was more pronounced than those in the 10 mg and 5 mg TZP-treated groups [MD=-2.07, 95% CI (-2.52, -1.63) and MD=-3.14, 95% CI (-4.42, -1.87)]. Compared with GLP-1RA, insulin, and placebo groups, the proportions of patients with HbA1c<7% in 10mg and 15mg TZP-treated groups were significantly higher than in the 5mg TZP-treated group [OR=1.53, 95% CI (1.25, 1.8)], OR=1.7, 95% CI (1.15, 2.50)].There was no significant difference regarding the risk of adverse reactions.

Didymin protects pancreatic beta cells by enhancing mitochondrial function in high-fat diet-induced impaired glucose tolerance.

PURPOSE: Prolonged exposure to plasma free fatty acids (FFAs) leads to impaired glucose tolerance (IGT) which can progress to type 2 diabetes (T2D) in the absence of timely and effective interventions. High-fat diet (HFD) leads to chronic inflammation and oxidative stress, impairing pancreatic beta cell (PBC) function. While Didymin, a flavonoid glycoside derived from citrus fruits, has beneficial effects on inflammation dysfunction, its specific role in HFD-induced IGT remains yet to be elucidated. Hence, this study aims to investigate the protective effects of Didymin on PBCs. METHODS: HFD-induced IGT mice and INS-1 cells were used to explore the effect and mechanism of Didymin in alleviating IGT. Serum glucose and insulin levels were measured during the glucose tolerance and insulin tolerance tests to evaluate PBC function and insulin resistance. Next, RNA-seq analysis was performed to identify the pathways potentially influenced by Didymin in PBCs. Furthermore, we validated the effects of Didymin both in vitro and in vivo. Mitochondrial electron transport inhibitor (Rotenone) was used to further confirm that Didymin exerts its ameliorative effect by enhancing mitochondria function. RESULTS: Didymin reduces postprandial glycemia and enhances 30-minute postprandial insulin levels in IGT mice. Moreover, Didymin was found to enhance mitochondria biogenesis and function, regulate insulin secretion, and alleviate inflammation and apoptosis. However, these effects were abrogated with the treatment of Rotenone, indicating that Didymin exerts its ameliorative effect by enhancing mitochondria function. CONCLUSIONS: Didymin exhibits therapeutic potential in the treatment of HFD-induced IGT. This beneficial effect is attributed to the amelioration of PBC dysfunction through improved mitochondrial function.

Clinical and functional characterization of a novel KCNJ11 (c.101G > A, p.R34H) mutation associated with maturity-onset diabetes mellitus of the young type 13.

PURPOSE: This study aimed to describe the clinical features, diagnostic and therapeutic course of a patient with MODY13 caused by KCNJ11 (c.101G > A, p.R34H) and how it contributes to the pathogenesis of MODY13, and to explore new therapeutic targets. METHODS: Whole-exome sequencing was used to screen prediagnosed individuals and family members with clinically suspected KCNJ11 mutations. Real-time fluorescence quantitative PCR, western blotting, thallium flux of potassium channels, glucose-stimulated insulin secretion (GSIS), and immunofluorescence assays were used to analyze the regulation of insulin secretion by the KCNJ11 mutant in MIN6 cells. Daily blood glucose levels were continuously monitored for 14 days in the proband using the ambulatory blood glucose meter (SIBIONICS). RESULTS: Mutation screening of the entire exon of the gene identified a heterozygous KCNJ11 (c.101G > A, p.R34H) mutation in the proband and his mother. Cell-based GSIS assays after transfection of MIN6 using wild-type and mutant plasmids revealed that this mutation impaired insulin secretory function. Furthermore, we found that this impaired secretory function is associated with reduced functional activity of the mutant KCNJ11 protein and reduced expression of the insulin secretion-associated exocytosis proteins STXBP1 and SNAP25. CONCLUSION: For the first time, we revealed the pathogenic mechanism of KCNJ11 (c.101G > A, p.R34H) associated with MODY13. This mutant can cause alterations in KATP channel activity, reduce sensitivity to glucose stimulation, and impair pancreatic ß-cell secretory function by downregulating insulin secretion-associated exocytosis proteins. Therefore, oral sulfonylurea drugs can lower blood glucose levels through pro-insulinotropic effects and are more favorable for patients with this mutation.

Variational relevance evaluation of individual fMRI data enables deconstruction of task-dependent neural dynamics.

In neuroimaging research, univariate analysis has always been used to localize "representations" at the microscale, whereas network approaches have been applied to characterize transregional "operations". How are representations and operations linked through dynamic interactions? We developed the variational relevance evaluation (VRE) method to analyze individual task fMRI data, which selects informative voxels during model training to localize the "representation", and quantifies the dynamic contributions of single voxels across the whole-brain to different cognitive functions to characterize the "operation". Using 15 individual fMRI data files for higher visual area localizers, we evaluated the characterization of selected voxel positions of VRE and revealed different object-selective regions functioning in similar dynamics. Using another 15 individual fMRI data files for memory retrieval after offline learning, we found similar task-related regions working in different neural dynamics for tasks with diverse familiarities. VRE demonstrates a promising horizon in individual fMRI research.

Controllable synthesis of FeMn bimetallic ferrocene-based metal-organic frameworks to boost the catalytic efficiency for removal of organic pollutants.

A series of FeMn bimetallic ferrocene-based metal-organic frameworks (FeMn-Fc-MOFs) with various molar ratios of Fe and Mn (1:9, 2:8, 4:6, 6:4) were successfully synthesized using a simple hydrothermal synthesis method and employed as an efficient activator on persulfate (PS) activation for water decontamination. Characterizations demonstrated that Fe and Mn were smoothly introduced into ferrocene-based MOFs and various molar ratios of Fe:Mn had some influence on crystallinity and surface structure of FeMn-Fc-MOFs. Within 120 min, Fe4Mn6-Fc-MOFs demonstrated the best catalytic activity among the different molar ratios, and acid orange 7(AO7) degradation rate was up to 92.0%. In addition, electrochemical experiments revealed that Fe4Mn6-Fc-MOFs possessed superior electron transfer capability than other FeMn-Fc-MOFs, leading to better catalytic performance. Moreover, quenching tests and electron paramagnetic resonance (EPR) detection indicated that hydroxyl radicals and sulfate radicals were both responsible for AO7 decomposition. Notably, the redox cycle of Fe(II)/Fe(III) and Mn(II)/Mn(IV) was discovered in the Fe4Mn6-Fc-MOFs/PS system, which was considered as the limiting process for the cleavage of the O-O bond in PS to generate active radicals. Ultimately, the Fe4Mn6-Fc-MOFs exhibits an excellent universality and good cycling stability for 5 continuous runs. This paper broadens the application of ferrocene-based MOFs on heterogeneous PS activation in environmental catalysis.