Metabolomic profiling reveals decreased serum cysteine levels during gestational diabetes mellitus progression.

Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic disorder associated with short-term and long-term adverse health outcomes, but its pathogenesis has not been clearly elucidated. Investigations of the dynamic changes in metabolomic markers in different trimesters may reveal the underlying pathophysiology of GDM progression. Therefore, in the present study, we analyzed the metabolic profiles of 75 women with GDM and 75 women with normal glucose tolerance (NGT) throughout the three trimesters. We found that the variation trends of 38 metabolites were significantly different during GDM development. Specifically, longitudinal analyses revealed that cysteine (Cys) levels significantly decreased over the course of GDM progression. Further study showed that Cys alleviated GDM in female mice at gestational day 14.5 possibly by inhibiting phosphoenolpyruvate carboxykinase to suppress hepatic gluconeogenesis. Taken together, these findings suggest that the Cys metabolic pathway might play a crucial role in GDM and that Cys supplementation represents a potential new treatment strategy for GDM patients.

Effect of weight loss on proteinuria in adults with type 2 diabetes: A real-world study.

AIMS: To assess the impact of weight loss on proteinuria in patients with type 2 diabetes (T2DM) in real-world settings. METHODS: A total of 1054 participants were categorized based on weight change from baseline to one-year follow-up: weight gain (≥3%), stable weight, or weight loss (≥3%). Proteinuria outcomes were defined as urinary albumin/creatinine ratio (UACR) progression (≥30 % increase), UACR regression (≥30 % reduction), or UACR stable. Ordered logistic regression analysis evaluated the relationship between weight loss and UACR regression. RESULTS: Of the 1054 participants, 44.5 % were overweight, and 24.1 % were obese. Patients with obesity were at higher risk of developing proteinuria (OR, 1.783; 95 %CI, 1.195 to 2.659). Weight loss was associated with an 83.3 % increase in UACR regression compared to weight gain (OR, 1.833; 95 % CI, 1.262 to 2.663; P = 0.001). This association remained consistent across most subgroups and stronger in males (P for interaction = 0.023), with a 6 % UACR regression for every 1 kg weight loss (OR, 1.06; 95 % CI, 1.02 to 1.10; P = 0.003). CONCLUSIONS: Our real-world study reveals that weight reduction is associated with UACR regression in patients with T2DM, regardless of the approach used for weight management, and the association was much stronger in males.

Photoluminescent and Scintillating Performance of Eu3+-Doped Boroaluminosilicate Glass Scintillators.

In comparison with single crystal scintillators, glass scintillators are more promising materials for their benefits of easy preparation, low cost, controllable size, and large-scale manufacture. The emission of Eu3+ ion at 612 nm matches well with the photoelectric detector, making it suitable for the activator in glass scintillators. Therefore, the research on Eu3+ doped glass scintillators attract our attention. The photoluminescent and scintillating properties of Eu3+-activated boroaluminosilicate glass scintillators prepared by the conventional melt-quenching method were investigated in this work. The glass samples present good internal quantum yield. Under X-ray radiation, the optimal sample reveals high X-ray excited luminesce (XEL), and its integrated intensity of XEL is 22.7% of that of commercial crystal scintillator Bi4Ge3O12. Furthermore, the optimal specimen possesses a spatial resolution of 14 lp/mm in X-ray imaging. These results suggest that Eu3+-doped boroaluminosilicate glass is expected to be applied in X-ray imaging.

Effect of continuous glucose monitoring compared with self-monitoring of blood glucose in gestational diabetes patients with HbA1c<6%: a randomized controlled trial.

Objective: This study evaluated the effect of continuous glucose monitoring (CGM) versus self-monitored blood glucose (SMGB) in gestational diabetes mellitus (GDM) with hemoglobin A1c (HbA1c) <6%. Methods: From January 2019 to February 2021, 154 GDM patients with HbA1c<6% at 24-28 gestational weeks were recruited and assigned randomly to either SMBG only or CGM in addition to SMBG, with 77 participants in each group. CGM was used in combination with fingertip blood glucose monitoring every four weeks until antepartum in the CGM group, while in the SMBG group, fingertip blood glucose monitoring was applied. The CGM metrics were evaluated after 8 weeks, HbA1c levels before delivery, gestational weight gain (GWG), adverse pregnancy outcomes and CGM medical costs were compared between the two groups. Results: Compared with patients in the SMBG group, the CGM group patients had similar times in range (TIRs) after 8 weeks (100.00% (93.75-100.00%) versus 99.14% (90.97-100.00%), p=0.183) and HbA1c levels before delivery (5.31 ± 0.06% versus 5.35 ± 0.06%, p=0.599). The proportion with GWG within recommendations was higher in the CGM group (59.7% versus 40.3%, p=0.046), and the newborn birth weight was lower (3123.79 ± 369.58 g versus 3291.56 ± 386.59 g, p=0.015). There were no significant differences in prenatal or obstetric outcomes, e.g., cesarean delivery rate, hypertensive disorders, preterm births, macrosomia, hyperbilirubinemia, neonatal hypoglycemia, respiratory distress, and neonatal intensive care unit admission >24 h, between the two groups. Considering glucose monitoring, SMBG group patients showed a lower cost than CGM group patients. Conclusions: For GDM patients with HbA1c<6%, regular SMBG is a more economical blood glucose monitoring method and can achieve a similar performance in glycemic control as CGM, while CGM is beneficial for ideal GWG.

Continuous voriconazole lavage in managing moderate and severe fungal keratitis: a randomized controlled trial.

PURPOSE: To assess the effectiveness and safety of continuous lavage with 1% voriconazole (CL) for moderate and severe fungal keratitis. METHODS: Thirty-one patients were randomized to receive topical eye drops either alone (T) or combined with continuous 1% voriconazole lavage (CL-T). The primary outcome was the cure rate at 3 months. The secondary outcomes were the 6-day efficacy, 3-day infiltration size and depth, hypopyon height, central corneal thickness (CCT), epithelial defect size, and subject feelings and clinical signs assessment scores. RESULTS: At 3 months, the cure rate was comparable between the groups in patients with moderate fungal keratitis (66.7% vs. 62.5%, P = 0.60). However, among severe cases, 4 cases (44.4%) in the CL-T group healed successfully, while none in the T group; this difference was not significant (P = 0.08), although it was very close to 0.05. This may be related to the small sample size. After 6 days, the percentage of patients with "worsened" ulcers in the CL-T group was lower than that in the T group (0% vs. 31%, P = 0.043). The infiltration size, infiltration depth, and hypopyon height in the CL-T group were smaller than those in the T group after 3 days (all P < 0.05). There was no difference in CCT, epithelial defect size, subject feelings scores, or clinical signs scores between groups. CONCLUSION: These outcomes suggest that CL is an effective and safe adjuvant method for controlling the progression of moderate and severe fungal keratitis. TRIAL REGISTRATION NUMBER: ChiCTR2100050565.

Combined Phacovitrectomy with Metallic Intraocular Foreign Body Removal through Corneal Incision Using A Novel "Magnetic Conduction" Technique.

PURPOSE: To describe a "magnetic conduction" technique for the removal of metallic intraocular foreign bodies (IOFBs) in the posterior segment combined with cataract extraction and pars plana vitrectomy and to report its outcomes. METHODS: We retrospectively analyzed the data of 42 eyes of 42 patients with posterior metallic IOFBs between April 2020 and February 2022. In all patients, cataract extraction was combined with pars plana vitrectomy. With an external magnet, the IOFBs were captured by a magnetized vitrectomy cutter, delivered to the anterior chamber, and then extracted through a corneal phacoemulsification incision. RESULTS: All patients were men, with a mean age of 45.6 ± 10.7 years. The mean size of the IOFBs was 3.5 ± 1.7 mm (range, 1.5-8.9 mm) in their longest dimension. A final best-corrected visual acuity of 20/200 or better was noted in 24 of 42 patients (57.1%). Postoperatively, recurrent retinal detachment was seen in three eyes. There were no other intraoperative or postoperative complications. CONCLUSION: The "magnetic conduction" technique combined with phacovitrectomy is a safe and feasible approach to removing IOFBs in the posterior segment.

The Experimental Study of Periodontal Ligament Stem Cells Derived Exosomes with Hydrogel Accelerating Bone Regeneration on Alveolar Bone Defect.

INTRODUCTION: this study was conducted to investigate the osteogenic ability of periodontal ligament stem cells (PDLSCs) derived exosomes (PDLSCs-Exos) and the effect of PDLSCs-Exos with hydrogel on alveolar bone defect repairment in the rat. METHODS: the PDLSCs were obtained through primary cell culture, and PDLSCs-Exos were purified by the ultracentrifugation method. The CCK-8 kit and ALP staining were used to explore the effect of PDLSCs-Exos on promoting the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In vivo, the alveolar bone defect models were made mesial to the bilateral maxillary first molars of rats. MicroCT, HE staining, and Masson staining were used to analyze the new bone at the bone defect of rats. RESULTS: the periodontal ligament stem cells and the periodontal ligament stem cells derived exosomes were successfully extracted. The results of the CCK-8 kit and ALP staining showed PDLSCs-Exos significantly promoted the proliferation osteogenic differentiation of BMSCs. In vivo experiment results revealed that compared with the control group and the hydrogel group, the rats in the hydrogel with exosomes group showed more new bone formation in alveolar bone defects. CONCLUSION: Periodontal ligament stem cells and exosomes derived from periodontal ligament stem cells were successfully extracted. The results demonstrated that the hydrogel successfully delivered periodontal ligament stem cells derived exosomes for repairing alveolar bone defects in rats in vivo at the initial stage.

Cognitive Dysfunction in Type 2 Diabetes Is Not a One-Way Process: Evidence From a Longitudinal Brain Connectivity Study.

Background: Cognitive dysfunction is an important comorbidity of diabetes characterized by brain functional hypo-connectivity. However, our recent study demonstrated an adaptive hyper-connectivity in young type 2 diabetes with cognitive decrements. This longitudinal study aimed to further explore the changes in functional connectivity and cognitive outcomes after regular glycemic control. Methods: At 18 months after recruitment, participants underwent a second cognitive assessment and magnetic resonance imaging. Three enhanced functional connectivities previously identified at baseline were followed up. Linear mixed-effects models were performed to compare the longitudinal changes of cognition and functional connectivity in patients with type 2 diabetes and non-diabetic controls. A linear regression model was used to investigate the association between changes in functional connectivity and changes in cognitive performance. Results: Improvements in multiple cognitive domains were observed in diabetes; however, the enhanced functional connectivity at baseline decreased significantly. Moreover, the decrease in hippocampal connectivity was correlated with an increase in the accuracy of Stroop task and the decrease in posterior cingulate cortex connectivity was correlated with an increase in Montreal Cognitive Assessment in diabetes. Conclusion: This study suggests diabetes-related cognitive dysfunction is not a one-way process and the early-stage enhancement of brain connectivity was a potential "window period" for cognitive reversal.

Consistently Low Levels of Osteocalcin From Late Pregnancy to Postpartum Are Related to Postpartum Abnormal Glucose Metabolism in GDM Patients.

Objective: Increasing evidence suggests that osteocalcin (OC), a marker of bone formation, plays an important role in glucose homoeostasis. Few studies have investigated the relationship between OC levels in gestational diabetes mellitus (GDM) patients and their postpartum glucose metabolism. This study evaluated the relationship between OC levels in late pregnancy, their longitudinal changes, and postpartum glucose metabolism among GDM patients. Measures: Serum OC was measured in late pregnancy and the postpartum period for 721 GDM patients. All patients underwent a 75-g oral glucose tolerance test (OGTT) at 6-8 weeks postpartum. According to postpartum OGTT outcomes, patients were categorized into abnormal glucose metabolism (AGM) (n=255) and normal glucose tolerance (NGT) groups (n=466). Glucose metabolism-related indices were measured and calculated. Logistic regression analysis and linear mixed-effects model were used to assess the association between OC and postpartum AGM. Results: In late pregnancy, OC levels were lower in the AGM group than in the NGT group (13.93 ± 6.90 vs 15.33 ± 7.63 ng/ml, P=0.015). After delivery, OC levels increased in both groups. However, OC levels remained lower in the AGM group than in the NGT group (23.48 ± 7.84 vs 25.65 ± 8.37 ng/ml, P=0.001). Higher OC levels in late pregnancy were associated with decreased risk of progressing to postpartum AGM (OR:0.96, 95%CI:0.94-0.99). Linear mixed-effects analysis showed that postpartum AGM patients exhibited consistently lower OC levels than NGT group from late pregnancy to the postpartum period after adjustment for cofactors (ß=-1.70, 95% CI: -2.78- -0.62). Conclusions: In GDM patients, consistently low levels of OC from late pregnancy to postpartum were associated with increased postpartum AGM risk. The increase in serum OC may act as a protective factor to curb the progression of AGM at postpartum for GDM patients.

First-principles Insights into Cu-Decorated GaN Monolayers for Sensing CO and HCHO in Dry-Type Transformers.

This work using first-principles theory studies the sensing properties of Cu-decorated GaN (Cu-GaN) monolayers as a promising candidate for the detection of CO and HCHO in dry-type transformers. The Cu dopant prefers to be trapped on the TN site of the GaN surface with an E b of -1.13 eV. Chemisorption is identified for the two gas adsorption systems, given the large adsorption energy (E ad) of -1.35 and -1.09 eV. Caused by the chemisorption, the electronic property of the Cu-GaN monolayer is significantly deformed, narrowing its band gap of 0.548 eV to 0.00 eV, exhibiting metallic property, in two gas systems. Combined with the desirable recovery property for CO and HCHO desorption from the Cu-GaN surface, it could be proposed that the Cu-GaN monolayer is a promising gas sensor for toxic gas detection in dry-type transformers, so as to evaluate the operation status of the power system and guarantee safe working conditions for the maintenances.

Decreased Microstructural Integrity of the Central Somatosensory Tracts in Diabetic Peripheral Neuropathy.

CONTEXT: Although diabetic peripheral neuropathy (DPN) is predominantly considered a disorder of the peripheral nerves, some evidence for central nervous system involvement has recently emerged. However, whether or to what extent the microstructure of central somatosensory tracts may be injured remains unknown. OBJECTIVE: This work aimed to detect the microstructure of central somatosensory tracts in type 2 diabetic patients and to correlate it with the severity of DPN. METHODS: A case-control study at a tertiary referral hospital took place with 57 individuals with type 2 diabetes (25 with DPN, 32 without DPN) and 33 nondiabetic controls. The fractional anisotropy (FA) values of 2 major somatosensory tracts (the spinothalamic tract and its thalamocortical [spino-thalamo-cortical, STC] pathway, the medial lemniscus and its thalamocortical [medial lemnisco-thalamo-cortical, MLTC] pathway) were assessed based on diffusion tensor tractography. Regression models were further applied to detect the association of FA values with the severity of DPN in diabetic patients. RESULTS: The mean FA values of left STC and left MLTC pathways were significantly lower in patients with DPN than those without DPN and controls. Moreover, FA values of left STC and left MLTC pathways were significantly associated with the severity of DPN (expressed as Toronto Clinical Scoring System values) in patients after adjusting for multiple confounders. CONCLUSION: Our findings demonstrated the axonal degeneration of central somatosensory tracts in type 2 diabetic patients with DPN. The parallel disease progression of the intracranial and extracranial somatosensory system merits further attention to the central nerves in diabetic patients with DPN.

Development of eco-friendly CO2-responsive cellulose nanofibril aerogels as "green" adsorbents for anionic dyes removal.

A novel CO2-responsive cellulose nanofibril aerogel as a "green" adsorbent derived from poly(methacrylic acid-co-2-(dimethylamino) ethyl methacrylate) and carboxylated cellulose nanofibrils was successfully prepared via stepwise cation-induced gelation and freeze drying method. This aerogel exhibited CO2-triggered adsorption behavior towards anionic dyes with a rapid adsorption rate and a high adsorption capacity, as well as satisfactory mechanical properties. Upon CO2 stimulation, the charged aerogel can selectively adsorb anionic dyes from aqueous solutions based on an electrostatic interaction. The maximum adsorption capacities of this aerogel towards methyl blue (MB), naphthol green B (NGB), and methyl orange (MO) were 598.8, 621.1 and 892.9 mg g-1, respectively, accompanied by fast adsorption equilibriums towards MB and NGB within 7 min, and MO within 12 min. Meanwhile, the adsorption isotherms and the kinetics of the CO2-responsive adsorbents followed the Freundlich isotherm and the pseudo-second-order model, respectively. Furthermore, the resulting CO2-responsive adsorbent exhibited outstanding recyclability, as its adsorption performance can still be maintained even after twenty cycles. Accordingly, the resultant CO2-responsive cellulose nanofibril aerogel could be a promising adsorbent material for the removal of anionic dyes in wastewater remediation.

Lower free thyroid hormone levels are associated with high blood glucose and insulin resistance; these normalize with metabolic improvement of type 2 diabetes.

OBJECTIVE: This study aimed to explore the relationship of thyroid function and glucose metabolism and to investigate the changes in thyroid function after National Metabolic Management Center (MMC) management in type 2 diabetic mellitus (T2DM). METHODS: A total of 2000 euthyroid participants from MMC in Shanghai General Hospital and a community physical examination were recruited. They were categorized into four groups: normal glucose tolerance (NGT, n = 132), prediabetes (N = 147), DM well-controlled (T2DM with glycosylated hemoglobin [HbA1c] ≤ 7%, n = 505), and DM uncontrolled (T2DM with HbA1c > 7%, n = 1216). The parameters were compared among the groups and their changes before and after MMC follow-up in DM uncontrolled group were observed. RESULTS: Free triiodothyronine (FT3) and free thyroxine (FT4) levels varied significantly among groups. FT3 and FT4 levels negatively correlated with HbA1c level (P < 0.05), and positively correlated with the estimated glucose disposal rate (eGDR) (P < 0.05). Following MMC management, blood glucose and insulin resistance in the DM uncontrolled group were dramatically improved (P < 0.001). Meanwhile, FT3 was elevated compared to the baseline (from 4.51 ± 0.78 pmol/L to 4.68 ± 0.87 pmol/L, P < 0.05), and reverse triiodothyronine (r-T3) decreased from 1.03 ± 0.24 nmol/L to 0.92 ± 0.25 nmol/L (P < 0.001). Thyroid-stimulating hormone significantly decreased as well (P < 0.001). CONCLUSIONS: Decreased free thyroid hormone levels in normal range were associated with high glucose and insulin resistance. After MMC management, improvement of blood glucose and insulin resistance were accompanied by the restoration of low-normal thyroid function.

Human menstrual blood-derived stem cells promote functional recovery in a rat spinal cord hemisection model.

Spinal cord injury (SCI) is associated with a dismal prognosis including severe voluntary motor and sensory deficits in the presence of the current therapies, thus new and efficient treatment strategies are desperately required. Along with several advantages, such as easy accessibility, high-yield, potential of enormous proliferation, menstrual blood-derived mesenchymal stem cells (MenSCs) have been proposed as a promising strategy in regeneration medicine. In this study, the MenSCs were transplanted into incomplete thoracic (T10) spinal cord injury (SCI) rats, all rats were sacrificed at 7, 14, and 28 days after surgery. Based on the results, we found that MenSCs transplantation improved the hind limb motor function. Besides, H&E staining showed that MenSCs treatment markedly reduced cavity formation in the lesion site. Furthermore, treatment by MenSCs showed more MAP2-positive mature neurons, as well as axonal regeneration manifested by NF-200 and less expression of chondroitin sulfate proteoglycans (CSPGs) than the non-treatment in the lesion site. Additionally, immunofluorescence, Western blot, and qRT-PCR methods showed that levels of brain-derived neurotrophic factor (BDNF) were significantly higher in the injured spinal cord after implantation of MenSCs. Results of qRT-PCR indicated that inflammatory factors, including TNF-α and IL-1ß were inhibited after MenSCs transplantation. The improved motor function of hind limb and the increased cell body area of motor neurons were suppressed by blocking of the BDNF-TrkB signaling. It was eventually revealed that MenSCs implantation had beneficial therapeutic effects on the rehabilitation of the rat spinal cord hemisection model, mainly by enhancing the expression of BDNF. MenSCs transplantation may provide a novel therapeutic strategy for patients with SCI in the future.

Bioinformatics method identifies potential biomarkers of dilated cardiomyopathy in a human induced pluripotent stem cell-derived cardiomyocyte model.

Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy that account for the majority of heart failure cases. The present study aimed to reveal the underlying molecular mechanisms of DCM and provide potential biomarkers for detection of this condition. The public dataset of GSE35108 was downloaded, and 4 normal induced pluripotent stem cell (iPSC)-derived cardiomyocytes (N samples) and 4 DCM iPSC-derived cardiomyocytes (DCM samples) were utilized. Raw data were preprocessed, followed by identification of differentially expressed genes (DEGs) between N and DCM samples. Crucial functions and pathway enrichment analysis of DEGs were investigated, and protein-protein interaction (PPI) network analysis was conducted. Furthermore, a module network was extracted from the PPI network, followed by enrichment analysis. A set of 363 DEGs were identified, including 253 upregulated and 110 downregulated genes. Several biological processes (BPs), such as blood vessel development and vasculature development (FLT1 and MMP2), cell adhesion (CDH1, ITGB6, COL6A3, COL6A1 and LAMC2) and extracellular matrix (ECM)-receptor interaction pathway (CDH1, ITGB6, COL6A3, COL6A1 and LAMC2), were significantly enriched by these DEGs. Among them, MMP2, CDH1 and FLT1 were hub nodes in the PPI network, while COL6A3, COL6A1, LAMC2 and ITGB6 were highlighted in module 3 network. In addition, PENK and APLNR were two crucial nodes in module 2, which were linked to each other. In conclusion, several potential biomarkers for DCM were identified, such as MMP2, FLT1, CDH1, ITGB6, COL6A3, COL6A1, LAMC2, PENK and APLNR. These genes may serve significant roles in DCM via involvement of various BPs, such as blood vessel and vasculature development and cell adhesion, and the ECM-receptor interaction pathway.