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.

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.

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.

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.

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.

Methylation of AcGST1 Is Associated with Anthocyanin Accumulation in the Kiwifruit Outer Pericarp.

Most red-fleshed kiwifruit cultivars, such as Hongyang, only accumulate anthocyanins in the inner pericarp; the trait of full red flesh becomes the goal pursued by breeders. In this study, we identified a mutant "H-16" showing a red color in both the inner and outer pericarps, and the underlying mechanism was explored. Through transcriptome analysis, a key differentially expressed gene AcGST1 was screened out, which was positively correlated with anthocyanin accumulation in the outer pericarp. The result of McrBC-PCR and bisulfite sequencing revealed that the SG3 region (-292 to -597 bp) of AcGST1 promoter in "H-16" had a significantly lower CHH cytosine methylation level than that in Hongyang, accompanied by low expression of methyltransferase genes (MET1 and CMT2) and high expression of demethylase genes (ROS1 and DML1). Transient calli transformation confirmed that demethylase gene DML1 can activate transcription of AcGST1 to enhance its expression. Overexpression of AcGST1 enhanced the anthocyanin accumulation in the fruit flesh and leaves of the transgenic lines. These results suggested that a decrease in the methylation level of the AcGST1 promoter may contribute to accumulation of anthocyanin in the outer pericarp of "H-16".

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.

Multifunctional hemostatic polysaccharide-based sponge enhanced by tunicate cellulose: A promising approach for photothermal antibacterial activity and accelerated wound healing.

Fast and effective hemostasis and protection against wound infection play a crucial role in trauma care. In this study, a sponge scaffold with a self-expanding interpenetrating macropore structure was designed via two-step cross-linking method for hemostasis and photothermal antimicrobial activity. Oxidized Konjac glucomannan (OKGM) and chitosan (CS) were crosslinked once to form a dynamic covalent bonding network, and a basic three-dimensional fiber porous network framework was constructed by uniformly dispersing Tunicate nanocellulose (TCNCs). Secondary crosslinking introduced Polydopamine (PDA NPs) into the sponge, while dynamic hydrogen bonds were interleaved to stabilize the frame. PDA NPs enhanced the sponge's antibacterial and antioxidant properties due to its good photothermal conversion efficiency and oxygen radical scavenging ability. Compared to cotton gauze and gelatin sponges, the composite sponges showed superior blood cell adhesion and platelet activation. In tests on rat liver trauma models, composite sponges showed shorter hemostasis time (12 ± 2.17 s) and less blood loss (0.1 ± 0.052 g). Sponges can protect wound tissue through their adhesion properties. In the full-thickness wound model infected with S. aureus, the composite sponge accelerated wound healing. Overall, this composite sponge has great potential for clinical use as a wound dressing.

In-situ producing CsPbBr3 nanocrystals on (001)-faceted TiO2 nanosheets as S­scheme heterostructure for bifunctional photocatalysis.

Fabricating a cost-effective yet highly active photocatalyst to reduce CO2 to CO and oxidize benzyl alcohol to benzaldehyde simultaneously, is challenging. Herein, we construct an S-scheme 0D/2D CsPbBr3/TiO2 heterostructure for bifunctional photocatalysis. An in-situ synthetic route is used, which enables the precise integration between CsPbBr3 nanocrystals and ultrathin TiO2 nanosheets exposed with (001) facets (termed as TiO2-001), resulting in a tightly coupled heterointerface and desirable band offsets. The as-prepared CsPbBr3/TiO2-001heterojunctions exhibit boosted charge carrier kinetics, particularly, quick carrier separation/transfer and efficient utilization. Experimental results and theoretical calculations validate the S-scheme route in CsPbBr3/TiO2-001, which allows the enrichment of strongly conserved electrons-holes at conduction and valence bands of CsPbBr3 and TiO2-001, respectively. Consequently, compared to its counterparts, an excellent bifunctional activity (with 24 h reusability) is realized over CsPbBr3/TiO2-001, where the production rate of CO and benzaldehyde reach up to 78.06 µmol g-1h-1 and 1.77 mmol g-1h-1 respectively, without employing any sacrificial agents. This work highlights the development of perovskite-based heterostructures and describes the efficient harnessing of redox potentials and charge carriers towards combined photocatalytic systems.

Cardiac-specific BACH1 ablation attenuates pathological cardiac hypertrophy by inhibiting the Ang II type 1 receptor expression and the Ca2+/CaMKII pathway.

AIMS: BACH1 is up-regulated in hypertrophic hearts, but its function in cardiac hypertrophy remains largely unknown. This research investigates the function and mechanisms of BACH1 in the regulation of cardiac hypertrophy. METHODS AND RESULTS: Male cardiac-specific BACH1 knockout mice or cardiac-specific BACH1 transgenic (BACH1-Tg) mice and their respective wild-type littermates developed cardiac hypertrophy induced by angiotensin II (Ang II) or transverse aortic constriction (TAC). Cardiac-specific BACH1 knockout in mice protected the hearts against Ang II- and TAC-induced cardiac hypertrophy and fibrosis, and preserved cardiac function. Conversely, cardiac-specific BACH1 overexpression markedly exaggerated cardiac hypertrophy and fibrosis and reduced cardiac function in mice with Ang II- and TAC-induced hypertrophy. Mechanistically, BACH1 silencing attenuated Ang II- and norepinephrine-stimulated calcium/calmodulin-dependent protein kinase II (CaMKII) signalling, the expression of hypertrophic genes, and hypertrophic growth of cardiomyocytes. Ang II stimulation promoted the nuclear localization of BACH1, facilitated the recruitment of BACH1 to the Ang II type 1 receptor (AT1R) gene promoter, and then increased the expression of AT1R. Inhibition of BACH1 attenuated Ang II-stimulated AT1R expression, cytosolic Ca2+ levels, and CaMKII activation in cardiomyocytes, whereas overexpression of BACH1 led to the opposite effects. The increased expression of hypertrophic genes induced by BACH1 overexpression upon Ang II stimulation was suppressed by CaMKII inhibitor KN93. The AT1R antagonist, losartan, significantly attenuated BACH1-mediated CaMKII activation and cardiomyocyte hypertrophy under Ang II stimulation in vitro. Similarly, Ang II-induced myocardial pathological hypertrophy, cardiac fibrosis, and dysfunction in BACH1-Tg mice were blunted by treatment with losartan. CONCLUSION: This study elucidates a novel important role of BACH1 in pathological cardiac hypertrophy by regulating the AT1R expression and the Ca2+/CaMKII pathway, and highlights potential therapeutic target in pathological cardiac hypertrophy.

The association between triglyceride-glucose index and hyperferritinemia in patients with type 2 diabetes mellitus.

PURPOSE: To investigate the relationship between the triglyceride-glucose (TyG) index and serum ferritin (SF) levels in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 881 T2DM patients were divided into T1(TyG index < 1.66), T2 (1.66 ≤ TyG index < 2.21), and T3 (TyG index ≥ 2.21) groups according to the tertiles of the TyG index. The differences in SF levels and the prevalence of hyperferritinemia (SF ≥ 300 ng/mL for male or SF ≥ 150 ng/mL for female) were compared. The independent correlations between the TyG index and SF, and between hyperferritinemia and TyG in T2DM patients were analyzed, respectively. RESULTS: SF levels in male T2DM patients were higher in the T3 group (250.12 ng/mL) than in the T1 and T2 groups (180.45 and 196.56 ng/mL, both p < 0.01),while in female patients with T2DM,SF levels were higher in the T3 group (157.25 ng/mL) than in the T1 group (111.06 ng/mL, p < 0.05).The prevalence of hyperferritinemia in male T2DM patients was higher in the T3 group (31.3%) than those in the T1 and T2 groups (10.4% and 17.3%, both p < 0.05).The TyG index was positively correlated with SF levels in T2DM patients (R = 0.178, p < 0.001).TyG index was independently and positively correlated with SF levels after adjusting for confounders (ß = 0.097, 95%CI [2.870,38.148], p = 0.023).The TyG index was positively independently correlated with hyperferritinemia in male T2DM patients (OR = 1.651, 95%CI [1.120,2.432], p = 0.011). CONCLUSIONS: In parallel with increasing TyG index SF levels gradually increased. The TyG index was positively correlated with SF levels in patients with T2DM and was positively correlated with hyperferritinemia in male T2DM patients.

Ferroptosis: roles and molecular mechanisms in diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a serious complication of type 1 and type 2 diabetes, which leads to the aggravation of myocardial fibrosis, disorders involving systolic and diastolic functions, and increased mortality of patients with diabetes through mechanisms such as glycolipid toxicity, inflammatory response, and oxidative stress. Ferroptosis is a form of iron-dependent regulatory cell death that is attributed to the accumulation of lipid peroxides and an imbalance in redox regulation. Increased production of lipid reactive oxygen species (ROS) during ferroptosis promotes oxidative stress and damages myocardial cells, leading to myocardial systolic and diastolic dysfunction. Overproduction of ROS is an important bridge between ferroptosis and DCM, and ferroptosis inhibitors may provide new targets for the treatment of patients with DCM.

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.

Investigation on Preparation and Performance of High Ga CIGS Absorbers and Their Solar Cells.

Tandem solar cells usually use a wide band gap absorber for top cell. The band gap of CuIn(1-x)GaxSe2 can be changed from 1.04 eV to 1.68 eV with the ratio of Ga/(In+Ga) from 0 to 1. When the ratio of Ga/(In+Ga) is over 0.7, the band gap of CIGS absorber is over 1.48 eV. CIGS absorber with a high Ga content is a possible candidate one for the top cell. In this work, CuInGa precursors were prepared by magnetron sputtering with CuIn and CuGa targets, and CIGS absorbers were prepared by selenization annealing. The Ga/(In+Ga) is changed by changing the thickness of CuIn and CuGa layers. Additionally, CIGS solar cells were prepared using CdS buffer layer. The effects of Ga content on CIGS thin film and CIGS solar cell were studied. The band gap was measured by PL and EQE. The results show that using structure of CuIn/CuGa precursors can make the band gap of CIGS present a gradient band gap, which can obtain a high open circuit voltage and high short circuit current of the device. With the decrease in Ga content, the efficiency of the solar cell increases gradually. Additionally, the highest efficiency of the CIGS solar cells is 11.58% when the ratio of Ga/(In+Ga) is 0.72. The value of Voc is 702 mV. CIGS with high Ga content shows a great potential for the top cell of the tandem solar cell.

All-inside versus complete tibial tunnel techniques in anterior cruciate ligament reconstruction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: All-inside anterior cruciate ligament reconstruction (ACLR) is a novel technique that has gained attention due to its minimally invasive. However, evidence surrounding the efficacy and safety between all-inside and complete tibial tunnel ACLR are lacking. Present work was aimed to compare clinical outcome for ACLR performed with an all-inside versus a complete tibial tunnel technique. METHODS: Systematic searches were conducted of published literature on PubMed, Embase, and Cochrane for studies according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines up to May 10, 2022. The outcomes included KT-1000 arthrometer ligament laxity test, International Knee Documentation Committee (IKDC) subjective score, Lysholm score, Tegner activity scale, and Knee Society Score (KSS) Scale, and tibial tunnel widening. Complications of interest extracted were graft re-ruptures and evaluated the graft re-rupture rate. Data from published RCTs meeting inclusion criteria were extracted and analyzed, and all the extracted data are pooled and analyzed by RevMan 5.3. RESULTS: A total of 8 randomized controlled trials involving 544 patients (consisting of 272 all-inside and 272 complete tibial tunnel patients) were included in the meta-analysis. We found clinical outcomes (International Knee Documentation Committee [IKDC] subjective score: mean difference [MD], 2.22; 95% CI, 0.23-4.22; p = 0.03; Lysholm score: MD, 1.09; 95% CI, 0.25-1.93; p = 0.01; Tegner activity scale: MD, 0.41; 95% CI, 0.11-0.71; p < 0.01; Tibial Tunnel Widening: MD = - 1.92; 95% CI, - 3.58 to - 0.25; p = 0.02; knee laxity: MD = 0.66; 95% CI, 0.12-1.20; p = 0.02; and graft re-rupture rate: RR, 1.97;95% CI, 0.50-7.74; P = 0.33) in the all-inside and complete tibial tunnel group. The findings also indicated that all-inside may be more advantageous in tibial tunnel healing. CONCLUSION: Our meta-analysis indicated that the all-inside ACLR was superior to complete tibial tunnel ACLR in functional outcomes and tibial tunnel widening. However, the all-inside ACLR was not entirely superior to complete tibial tunnel ACLR in knee laxity measured, and graft re-rupture rate.

HWJMSC-derived extracellular vesicles ameliorate IL-1ß-induced chondrocyte injury through regulation of the BMP2/RUNX2 axis via up-regulation TFRC.

Articular osteochondral injury is a common and frequently occurring disease in orthopedics that is caused by aging, disease, and trauma. The cytokine interleukin-1ß (IL-1ß) is a crucial mediator of the inflammatory response, which exacerbates damage during chronic disease and acute tissue injury. Human Wharton's jelly mesenchymal stem cell (HWJMSC) extracellular vesicles (HWJMSC-EVs) have been shown to promote cartilage regeneration. The study aimed to investigate the influence and mechanisms of HWJMSC-EVs on the viability, apoptosis, and cell cycle of IL-1ß-induced chondrocytes. HWJMSC-EVs were isolated by Ribo™ Exosome Isolation Reagent kit. Nanoparticle tracking analysis was used to determine the size and concentration of HWJMSC-EVs. We characterized HWJMSC-EVs by western blot and transmission electron microscope. The differentiation, viability, and protein level of chondrocytes were measured by Alcian blue staining, Cell Counting Kit-8, and western blot, respectively. Flow cytometer was used to determine apoptosis and cell cycle of chondrocytes. The results showed that HWJMSCs relieved IL-1ß-induced chondrocyte injury by inhibiting apoptosis and elevating viability and cell cycle of chondrocyte, which was reversed with exosome inhibitor (GW4869). HWJMSC-EVs were successfully extracted and proven to be uptake by chondrocytes. HWJMSC-EVs ameliorate IL-1ß-induced chondrocyte injury by inhibiting cell apoptosis and elevating viability and cycle of cell, but these effects were effectively reversed by knockdown of transferrin receptor (TFRC). Notably, using bone morphogenetic protein 2 (BMP2) pathway agonist and inhibitor suggested that HWJMSC-EVs ameliorate IL-1ß-induced chondrocyte injury through activating the BMP2 pathway via up-regulation TFRC. Furthermore, over-expression of runt-related transcription factor 2 (RUNX2) reversed the effects of BMP2 pathway inhibitor promotion of IL-1ß-induced chondrocyte injury. These results suggested that HWJMSC-EVs ameliorate IL-1ß-induced chondrocyte injury by regulating the BMP2/RUNX2 axis via up-regulation TFRC. HWJMSC-EVs may play a new insight for early medical interventions in patients with articular osteochondral injury.

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.

Indexes of ferroptosis and iron metabolism were associated with the severity of diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional study.

Objective: To explore the correlations between diabetic nephropathy (DN) and serum levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), iron, transferrin (Tf), and ferritin in patients with type 2 diabetes mellitus (T2DM). Methods: According to the urinary albumin excretion rate(UAER) or estimated glomerular filtration rate (eGFR) levels, a total of 123 patients with T2DM were separately divided into normoalbuminuria (NO), microalbuminuria (MI), macroalbuminuria (MA) groups, and G1 (eGFR ≥ 90 mL/min), G2 (eGFR ≤ 60 mL/min to < 90 mL/min), and G3 groups (eGFR< 60 mL/min), with 33 healthy participants as the control (HC). The differences in serum GPX4, ACSL4, iron, Tf, and ferritin levels between groups were compared, and the relationships between these levels were analysed. The independent correlations between UAER or DN severity and serum GPX4, ACSL4, iron, Tf, and ferritin levels were analysed by multiple linear and multinomial logistic regression, respectively. Results: To the patients with T2DM, with the increase in UAER levels, GPX4, iron, and Tf levels gradually decreased, whereas ACSL4 levels increased, meanwhile with the decrease in eGFR levels, GPX4 and Tf levels gradually decreased, whereas ACSL4 levels increased. UAER were independently and positively correlated with ACSL4 [ß = 17.53, 95% confidence interval (CI; 11.94, 23.13)] and negatively correlated with GPX4 [ß = -1.633, 95% CI (-2.77, -0.496)] and Tf [ß = -52.94, 95% CI (-95.78, -10.11)].The NO and MI groups were considered as reference groups, respectively. The severity of DN was negatively correlated with serum GPX4 [odds ratio (OR) = 0.925 and 0.902, p =0.015 and 0.001], and Tf (OR = 0.109 and 0.119, p =0.043 and 0.034), and positively correlated with ACSL4 (OR = 1.952 and 1.865, both p <0.001) in the MA group. Conclusion: DN severity was negatively correlated with serum GPX4 and Tf levels and positively correlated with serum ACSL4 levels in patients with T2DM.

Preparation of biodegradable carboxymethyl cellulose/dopamine/Ag NPs cryogel for rapid hemostasis and bacteria-infected wound repair.

Massive hemorrhage caused by accident or surgery is a major factor in accidental death. In addition, bacterial infection is also an important threat after bleeding. Cryogels with interpenetrating macroporous structures pose great application prospects in rapid hemostasis and infected wound repair. In this study, cryogels with different pore size are prepared by carboxymethyl cellulose (CMC) and dopamine (DA). The CMC grafted with different DA amounts is crosslinked by free DA through oxidative polymerization at low temperatures to form cryogels with different pore sizes. And the CMC/DA-3 cryogel is chosen as the optimal group for its high porosity, suitable mechanical, and good hemostatic ability. CMC/DA-3 cryogel is loaded with silver nanoparticles (Ag NPs) to prepare hemostatic cryogel with antibacterial properties. Antibacterial tests and animal hemostasis experiments confirm that the CMC/DA-3/Ag cryogel has good antibacterial properties and can finish rapid hemostasis. In the S. aureus infection skin defect model, the wound healing is significantly improved compared with commercial gelatin sponge. In summary, the novel cryogel has great potential in rapid hemostasis and infected wound healing.