Spatially Reprogramed Receptor Organization to Switch Cell Behavior Using a DNA Origami-Templated Aptamer Nanoarray.

Receptor oligomerization is a highly complex molecular process that modulates divergent cell signaling. However, there is a lack of molecular tools for systematically interrogating how receptor oligomerization governs the signaling response. Here, we developed a DNA origami-templated aptamer nanoarray (DOTA) that enables precise programming of the oligomerization of receptor tyrosine kinases (RTK) with defined valency, distribution, and stoichiometry at the ligand-receptor interface. The DOTA allows for advanced receptor manipulations by arraying either monomeric aptamer ligands (mALs) that oligamerize receptor monomers to elicit artificial signaling or dimeric aptamer ligands (dALs) that preorganize the receptor dimer to recapitulate natural activation. We demonstrated that the multivalency and nanoscale spacing of receptor oligomerization coordinately influence the activation level of receptor tyrosine kinase signaling. Furthermore, we illustrated that DOTA-modulated receptor oligomerization could function as a signaling switch to promote the transition from epithelia to mesenchymal-like cells, demonstrating robust control over cellular behaviors. Together, we present a versatile all-in-one DNA nanoplatform for the systematical investigation and regulation of receptor-mediated cellular response.

Hepatokine levels during the first or early second trimester of pregnancy and the subsequent risk of gestational diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: The relationship between hepatokine levels during the first or early second trimester of pregnancy and the subsequent risk of gestational diabetes mellitus (GDM) have been studied extensively. However, conclusions remain debateable whether hepatokines are potential markers of GDM. We conducted a meta-analysis of published articles to understand the association between circulating levels of selected hepatokines (including FGF21, fetuin-A, afamin, adropin, ficolin-3, selenoprotein P, ANGPTL4 and AGF) and the risk of GDM. MATERIALS AND METHODS: We searched the PubMed, Embase, Cochrane Library and Web of Science databases for studies published before January 2021 that examined the association between hepatokines and GDM (Prospero Registration# CRD42020191408). The quality was assessed by the Newcastle-Ottawa Scale (NOS). Pooled standard mean differences (SMDs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were used to compare the levels of hepatokines in different groups using fixed effects or random effects models. Meta-regression analysis and publication bias were conducted in accordance with standard methods. The trim-fill adjustment method was used to further assess the possible effect of publication bias. Sensitivity analysis was performed by omitting each study one at a time. RESULTS: The meta-analysis included 31 observational studies relating hepatokine levels to GDM in 4729 participants (1908 GDM, 2821 non-GDM). Serum FGF21 levels in patients with GDM were higher than those in healthy pregnant women during the second trimester and after delivery (SMD 0.89, [95% CI] 0.01-1.78 for the second trimester; SMD 1.42, [95% CI] 0.86-1.98 for after delivery). The serum levels of afamin in patients with GDM were significantly higher than those in healthy pregnant women during the first trimester and before pregnancy (SMD 0.51, [95% CI] 0.15-0.86 for first trimester; SMD 0.97, [95% CI] 0.45-1.50 for before pregnancy). Serum adropin levels in patients with GDM were higher than those in healthy pregnant women during the first and third trimesters of pregnancy (SMD 4.26, [95% CI] 3.30-5.23 for the first trimester; SMD 4.02, [95% CI] 3.09-4.94 for the third trimester). The serum levels of ficolin-3 in GDM patients were higher than those in healthy pregnant women during the second and third trimesters of pregnancy (WMD 1.43, [95% CI] 0.91-1.96 for the second trimester; SMD 1.28, [95% CI] 0.72-1.84 for the third trimester). The serum AGF level of patients with GDM was higher than that of healthy pregnant women in the control group in the third trimester (WMD 61 [95% CI] 37.04-81.96). The serum levels of selenoprotein P in patients with GDM were higher than those in healthy pregnant women in the control group during the first trimester (WMD 7.09 [95% CI] 4.6-9.57). CONCLUSIONS: Measurement of circulating hepatokines in the first or second trimester of pregnancy may improve the identification of women at risk of developing GDM later. Prospective evaluation of the combination of hepatokines and maternal characteristics for early identification of those who do and do not require OGTT is warranted. Additional well-designed prospective studies with longitudinal assessment of hepatokines during pregnancy are needed to understand the trajectories and dynamic associations of hepatokines with GDM risk.

The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus.

BACKGROUND: The effects of vitamin and mineral supplementation on women with gestational diabetes mellitus (GDM) have not been well established. We conduct a meta-analysis to evaluate the effects of vitamin and mineral supplementation on glycemic control, inflammation and oxidative stress for women with GDM. METHODS: A systematic search of randomized controlled trials (RCTs) was conducted from PubMed, Embase, Web of Science and Cochrane Library up to July, 2020. Various results were pooled by using Review manager 5.3 and Stata 12.0. Mean difference (MD) with 95% confidence interval (CI) was estimated. Heterogeneity between studies was assessed by I-squared (I2) tests. RESULTS: Six hundred ninety-eight patients from 12 trials were included in our meta-analysis. Magnesium, zinc, selenium, calcium, vitamin D and E (alone or in combination) were found to significantly improve glycemic control in women with GDM compared to those receiving placebos: fasting plasma glucose (FPG) (MD = - 9.02; 95% CI: - 12.09, - 5.96; P < 0.00001), serum insulin (MD = - 4.33; 95% CI: - 5.35, - 3.32; P < 0.00001), homeostasis model assessment-insulin resistance (HOMA-IR) (MD = - 1.34; 95% CI: - 1.60, - 1.07; P < 0.00001), and homeostasis model of assessment for ß cell function (HOMA-B) (MD = - 15.58; 95% CI: - 23.70, - 7.46; P = 0.0002). Vitamin and mineral supplementation was found to attenuated inflammation and oxidative stress through decreasing high-sensitivity C-reactive protein (hs-CRP) (MD = - 1.29; 95% CI: - 1.82, - 0.76; P < 0.00001), malondialdehyde (MDA) (MD = - 0.71; 95% CI: - 0.97, - 0.45; P < 0.00001), and increasing total antioxidant capacity (TAC) (MD = 45.55; 95% CI: 22.02, 69.08; P = 0.0001). CONCLUSIONS: This meta-analysis shows that vitamin and mineral supplementation significantly improved glycemic control, attenuated inflammation and oxidative stress in women with GDM.

Obesity is associated with severe disease and mortality in patients with coronavirus disease 2019 (COVID-19): a meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to global research to predict those who are at greatest risk of developing severe disease and mortality. The aim of this meta-analysis was to determine the associations between obesity and the severity of and mortality due to COVID-19. METHODS: We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases for studies evaluating the associations of obesity with COVID-19. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Meta-regression analyses were conducted to estimate regression coefficients. RESULTS: Forty-six studies involving 625,153 patients were included. Compared with nonobese patients, obese patients had a significantly increased risk of infection. (OR 2.73, 95% CI 1.53-4.87; I2 = 96.8%), hospitalization (OR 1.72, 95% CI 1.55-1.92; I2 = 47.4%), clinically severe disease (OR 3.81, 95% CI 1.97-7.35; I2 = 57.4%), mechanical ventilation (OR 1.66, 95% CI 1.42-1.94; I2 = 41.3%), intensive care unit (ICU) admission (OR 2.25, 95% CI 1.55-3.27; I2 = 71.5%), and mortality (OR 1.61, 95% CI 1.29-2.01; I2 = 83.1%). CONCLUSION: Patients with obesity may have a greater risk of infection, hospitalization, clinically severe disease, mechanical ventilation, ICU admission, and mortality due to COVID-19. Therefore, it is important to increase awareness of these associations with obesity in COVID-19 patients.

Full-color light-field microscopy via single-pixel imaging.

Light-field microscopy is a scanless volumetric imaging technique. Conventional color light microscope employs a micro-lens array at the image plane and samples the spatial, angular, and color information by a pixelated two-dimensional (2D) sensor (such as CCD). However, the space bandwidth product of the pixelated 2D sensor is a fixed value determined by its parameters, leading to the trade-offs between the spatial, angular, and color resolutions. In addition, the inherent chromatic aberration of the micro-lens array also reduces the viewing quality. Here we propose full-color light-field microscopy via single-pixel imaging that can distribute the sampling tasks of the spatial, angular, and color information to both illumination and detection sides, rather than condense on the detection side. Therefore, the space bandwidth product of the light-field microscope is increased and the spatial resolution of the reconstructed light-field can be improved. In addition, the proposed method can reconstruct full-color light-field without using a micro-lens array, thereby the chromatic aberration induced by the micro-lens array is avoided. Because distributing the three sampling tasks to both the illumination and detection sides has different possible sampling schemes, we present two sampling schemes and compare their advantages and disadvantages via several experiments. Our work provides insight for developing a high-resolution full-color light-field microscope. It may find potential applications in the biomedical and material sciences.

Metformin, beyond an insulin sensitizer, targeting heart and pancreatic ß cells.

Metformin, a biguanide derivate, is known as the first-line antidiabetic agent for type 2 diabetes mellitus (T2DM) treatment. It reduces insulin resistance and decreases blood glucose concentration by inhibiting gluconeogenesis and suppressing hepatic glucose production with improved peripheral tissue insulin sensitivity. As an insulin sensitizer, metformin takes pleiotropic actions and exerts protective effects on multiple organs mainly in insulin-targeted tissues such as liver, muscle, and adipose tissues. Recent studies discover that metformin also plays essential roles in heart and pancreatic ß cells - two important organs in metabolic regulation. Metformin not only protects T2DM patients from cardiovascular diseases and heart failure, but also restores insulin secretion activities and protects pancreatic ß cells from lipotoxicity or glucotoxicity. Although accumulated evidence shed light on the metformin action, the precise mechanism of metformin is still under investigation. Further laboratory investigations and clinical trials are needed to pinpoint a map of metformin action. Based on recent findings, this review characterizes the beneficial role of metformin in cardiovascular diseases and pancreatic ß cells.

cGAS suppresses ß-cell proliferation by a STING-independent but CEBPß-dependent mechanism.

AIMS/HYPOTHESIS: cGAS (cyclic GMP-AMP synthase) has been implicated in various cellular processes, but its role in ß-cell proliferation and diabetes is not fully understood. This study investigates the impact of cGAS on ß-cell proliferation, particularly in the context of diabetes. METHODS: Utilizing mouse models, including cGAS and STING (stimulator of interferon genes) knockout mice, we explored the role of cGAS in ß-cell function. This involved ß-cell-specific cGAS knockout (cGASßKO) mice, created by breeding cGAS floxed mice with transgenic mice expressing Cre recombinase under the insulin II promoter. We analyzed cGAS expression in diabetic mouse models, evaluated the effects of cGAS deficiency on glucose tolerance, and investigated the molecular mechanisms underlying these effects through RNA sequencing. RESULTS: cGAS expression is upregulated in the islets of diabetic mice and by high glucose treatment in MIN6 cells. Both global cGAS deficiency and ß-cell-specific cGAS knockout mice lead to improved glucose tolerance by promoting ß-cell mass. Interestingly, STING knockout did not affect pancreatic ß-cell mass, suggesting a STING-independent mechanism for cGAS's role in ß-cells. Further analyses revealed that cGAS- but not STING-deficiency leads to reduced expression of CEBPß, a known suppressor of ß-cell proliferation, concurrently with increased ß-cell proliferation. Moreover, overexpression of CEBPß reverses the upregulation of Cyclin D1 and D2 induced by cGAS deficiency, thereby regulating ß-cell proliferation. These results confirm that cGAS regulation of ß-cell proliferation via a CEBPß-dependent but STING-independent mechanism. CONCLUSIONS/INTERPRETATION: Our findings highlight the pivotal role of cGAS in promoting ß-cell proliferation and maintaining glucose homeostasis, potentially by regulating CEBPß expression in a STING-independent manner. This study uncovers the significance of cGAS in controlling ß-cell mass and identifies a potential therapeutic target for enhancing ß-cell proliferation in the treatment of diabetes.

Unraveling the relationship between ACTH and cortisol levels in COVID-19 infections: A meta-analysis.

OBJECTIVE: In December 2019, a novel pneumonia associated with the 2019 coronavirus emerged unexpectedly. However, limited data exist on the effects of COVID-19 on ACTH and cortisol levels. To address this gap in knowledge, we conducted a meta-analysis of published studies on the relationship between COVID-19 patients and their ACTH and cortisol levels. METHODS: We conducted a thorough search of the PubMed, Embase, Cochrane Library, and Web of Science databases up until May 2023. We assessed the relevance of each study we found, specifically looking for studies that reported on ACTH and cortisol levels in COVID-19 patients. We calculated weighted mean differences (WMD) and 95% confidence intervals (CI) to investigate the relationship between ACTH and cortisol levels in COVID-19 patients. We evaluated the quality of each study using the Newcastle Ottawa scale (NOS), and we assessed publication bias using Begg's rank correlation test, Egger's test, and funnel plot. We conducted our meta-analysis using the Stata 12.0 (Stata Corporation, TX). RESULTS: Our search yielded nine studies that met our inclusion criteria, which included a total of 440 COVID-19 patients and 474 controls, with data up to May 2023. Seven of these studies reported on ACTH levels, and six studies reported on cortisol levels. Our findings revealed that COVID-19 patients had significantly higher levels of cortisol compared to controls (WMD 3.46 (95% CI 2.29 to 4.62)). However, there was no significant difference in ACTH levels between COVID-19 patients and controls (WMD 1.58 (95% CI -5.79 to 8.94)). CONCLUSIONS: This meta-analysis indicates a potential relationship between elevated cortisol levels and COVID-19 infection. However, more well-designed, adequately powered, randomized controlled trial will be needed to assess the use of cortisol in patients with COVID-19 infection.

Bariatric surgery and COVID-19 outcomes: a systematic review and meta-analysis.

BACKGROUND: Obesity and its associated complications have a negative impact on human health. Metabolic and bariatric surgery (MBS) ameliorates a series of clinical manifestations associated with obesity. However, the overall efficacy of MBS on COVID-19 outcomes remains unclear. OBJECTIVES: The objective of this article is to analyze the relationship between MBS and COVID-19 outcomes. SETTING: A meta-analysis. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched to retrieve the related articles from inception to December 2022. All original articles reporting MBS-confirmed SARS-CoV-2 infection were included. Outcomes including hospital admission, mortality, intensive care unit (ICU) admission, mechanical ventilation utilization, hemodialysis during admission, and hospital stay were selected. Meta-analysis with fixed or random-effect models was used and reported in terms of odds ratios (ORs) or weighted mean differences (WMDs) along with their 95% confidence intervals (CIs). Heterogeneity was assessed with the I2 test. Study quality was assessed using the Newcastle-Ottawa Scale. RESULTS: A total of 10 clinical trials involving the investigation of 150,848 patients undergoing MBS interventions were included. Patients who underwent MBS had a lower risk of hospital admission (OR: .47, 95% CI: .34-.66, I2 = 0%), mortality (OR: .43, 95% CI: .28-.65, I2 = 63.6%), ICU admission (OR: .41, 95% CI: .21-.77, I2 = 0%), and mechanical ventilation (OR: .51, 95% CI: .35-.75, I2 = 56.2%) than those who did not undergo surgery, but MBS did not affect hemodialysis risk or COVID-19 infection rate. In addition, the length of hospital stay for patients with COVID-19 after MBS was significantly reduced (WMD: -1.81, 95% CI: -3.11-.52, I2 = 82.7%). CONCLUSIONS: Our findings indicate that MBS is shown to improve COVID-19 outcomes, including hospital admission, mortality, ICU admission, mechanical ventilation, and hospital stay. Patients with obesity who have undergone MBS infected with COVID-19 will have better clinical outcomes than those without MBS.

The relationship between daytime napping and obesity: a systematic review and meta-analysis.

Daytime napping, a habit widely adopted globally, has an unclear association with obesity. In this study, we executed a meta-analysis to explore the relationship between daytime napping and obesity. We conducted a comprehensive search of the PubMed, Embase, Cochrane Library, Scopus, PsycINFO, and Web of Science databases for pertinent articles published up to April 2023. Random-effects models were utilized to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and we assessed the heterogeneity of the included studies using the I2 statistic. To explore potential sources of heterogeneity, subgroup analyses were performed. The methodological quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS), and funnel plots were employed to detect any publication bias. Sensitivity analyses were conducted by sequentially omitting each study. We conducted a meta-analysis of twelve studies that included one each from the UK and Spain, five from the USA, and five from China, totalling 170,134 participants, to probe the association between napping and obesity. The pooled analysis suggested a higher risk of obesity in individuals who nap (OR: 1.22 [1.10-1.35], p < 0.001, I2 = 87%) compared to non-nappers. The meta-analysis results revealed variations in the summary ORs for studies conducted in China, Spain, the USA, and the UK. The ORs for China, Spain, the USA, and the UK were 1.05 (95% CI 0.90-1.23), 9.36 (95% CI 4.74-18.45), 1.27 (95% CI 1.10-1.47), and 1.39 (95% CI 1.32-1.47), respectively. A subgroup analysis based on age within the American population disclosed that napping in both adults and children heightened obesity incidence. A subgroup analysis based on nap duration found a significant rise in obesity occurrence when nap duration exceeded one hour, but no clear relationship emerged when nap duration was less than 1 h. In a subgroup analysis based on the definition of obesity, napping did not demonstrate a significant relationship with obesity when diagnostic criteria set obesity at a BMI of 25 or above. However, when the criteria were set at a BMI of 28 or 30 or more, napping significantly increased obesity risk. Our meta-analysis indicates a positive association between daytime napping and the risk of obesity. However, given the limited number of included studies, potential confounding factors might not have been fully addressed. Future well-designed prospective studies are required to further investigate this relationship. Large-scale studies are necessary to confirm our findings and elucidate the underlying mechanisms that drive these associations and causation.

Bariatric surgery and secondary hyperparathyroidism: a meta-analysis.

BACKGROUND: Obesity increases the risk of obesity-related medical problems. Weight loss after metabolic and bariatric surgery (MBS) has been well studied. However, the effects of MBS on parathyroid function remain unclear. OBJECTIVE: The objective of this study was to perform a meta-analysis to examine the impact of MBS on the risk of secondary hyperparathyroidism (SHPT). SETTING: The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. METHODS: The PubMed, Embase, Web of Science, and the Cochrane Library databases were systematically reviewed from inception to May 2022 to identify studies reporting quantitative measurements of SHPT risk pre-MBS and post-MBS. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated and compared. Effects were pooled using a random-effects or fixed-effects model. Subgroup analyses were performed according to the follow-up time and surgical procedure. RESULTS: The final meta-analysis included 9 studies with a total of 5585 patients. The mean follow-up time was 3.5 years (range 0.25-5). Overall, MBS appears to does not affect SHPT risk (OR = 1.34, 95% CI 0.81-2.20, I2 = 95%). Follow-up data showed no evidence of SHPT within 2 years following gastric bypass (GB) and sleeve gastrectomy procedures (OR = 1.42, 95% CI 0.66-3.07 for GB, OR = 0.39, 95% CI 0.09-1.62 for sleeve gastrectomy ). At the 2-year and long-term follow-up intervals, a marked increase in SHPT was detected for GB (OR = 6.06, 95% CI 3.39-10.85 for GB). In addition, the surgical procedure for GB decreased the likelihood of SHPT compared with the surgical procedure for biliopancreatic diversion with duodenal switch (OR = 0.29, 95% CI 0.17-0.49). CONCLUSIONS: Our meta-analysis indicated that GB appears to increase SHPT risk. Patients undergoing MBS should be aware of the risk of SHPT. Larger studies are needed to evaluate the outcomes and side effects and may eventually provide a better and more comprehensive understanding of the risks.

A gonadal gap junction INX-14/Notch GLP-1 signaling axis suppresses gut defense through an intestinal lysosome pathway.

Gap junctions mediate intercellular communications across cellular networks in the nervous and immune systems. Yet their roles in intestinal innate immunity are poorly understood. Here, we show that the gap junction/innexin subunit inx-14 acts in the C. elegans gonad to attenuate intestinal defenses to Pseudomonas aeruginosa PA14 infection through the PMK-1/p38 pathway. RNA-Seq analyses revealed that germline-specific inx-14 RNAi downregulated Notch/GLP-1 signaling, while lysosome and PMK-1/p38 pathways were upregulated. Consistently, disruption of inx-14 or glp-1 in the germline enhanced resistance to PA14 infection and upregulated lysosome and PMK-1/p38 activity. We show that lysosome signaling functions downstream of the INX-14/GLP-1 signaling axis and upstream of PMK-1/p38 pathway to facilitate intestinal defense. Our findings expand the understanding of the links between the reproductive system and intestinal defense, which may be evolutionarily conserved in higher organism.

Concordance of bone culture and deep tissue culture during the operation of diabetic foot osteomyelitis and clinical characteristics of patients.

PURPOSE: To retrospectively analyze the concordance of bacterial culture between bone tissue and deep soft tissue in diabetic foot osteomyelitis (DFO) patients and clinical characteristics of patients. METHODS: This study collected samples from 155 patients with suspected DFO (who required amputation after clinical evaluation). Bacterial culture and drug susceptibility tests were performed on the patients' deep soft tissue and bone tissue, and the consistency between the two was compared. In addition, the differences among DFO patients with different degrees of infection were compared classified by the PEDIS classifications. RESULTS: Among the 155 patients diagnosed with DFO, the positive rate of bone culture was 78.7% (122/155). This study cultured 162 strains, including 73 Gram-positive bacteria, 83 Gram-negative bacteria, and 6 fungi. Staphylococcus aureus (33 strains) was the most common bacteria. The overall agreement between bone culture and tissue culture was 42.8%, with Staphylococcus aureus and Enterobacteria having the best (64.3%) and least agreements (27.3%), respectively. The drug sensitivity results in bone culture showed that Staphylococcus aureus was the main Gram-positive bacteria. The bacteria were sensitive to linezolid and vancomycin. Proteus mirabilis was the main Gram-negative bacteria. These were more sensitive than biapenem and piperacillin/tazobactam. Fungi were more sensitive to voriconazole and itraconazole. CONCLUSION: The culture results of deep soft tissues near the bone cannot accurately represent the true pathogen of DFO. For DFO patients, bone culture should be taken as much as possible, and appropriate antibiotics should be selected according to the drug susceptibility results.

Associations between COVID-19 infection and sex steroid hormones.

Aims: Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and within a few months of the first outbreak, it was declared a global pandemic by the WHO. The lethal virus SARS-CoV-2 is transmitted through respiratory droplets and enters host cells through angiotensin-converting enzyme 2 (ACE-2) receptors. ACE-2 receptors are highly expressed in many tissues, including testes. Therefore, the objective of this study was to summarize the available literature regarding the correlation between sex hormone levels and COVID-19. Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were reviewed systematically through August 2022 for studies comparing sex hormone levels between different patient groups: COVID-19 versus no COVID-19, more severe versus less severe COVID-19, and non-survivors versus survivors. Various types of clinical research reporting sex hormone levels, including free testosterone (FT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17ß-oestradiol (E2), the oestradiol-to-testosterone ratio (E2/T), prolactin (PRL), and sex hormone-binding globulin (SHBG), were included. Random- or fixed-effects models were used to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity among the studies was assessed by the I2 index, and data analyses were performed using meta-analysis with Stata version 12.0. Results: Twenty-two articles that included 3369 patients were ultimately included in the meta-analysis. According to analysis of the included studies, patients with COVID-19 had significantly low T/LH, FSH/LH, and SHBG levels and high levels of LH, and E2/T, but their levels of FT, FSH, PRL, E2, and progesterone were not affected. Publication bias was not found according to funnel plots and Egger's regression and Begg's rank correlation tests. Conclusion: Low T/LH, FSH/LH, and SHBG serum levels and high LH, and E2/T levels may increase the risk of COVID-19. Additionally, the greater is the clinical severity of COVID-19, the higher is the probability of increases in LH, and E2/T serum levels and decreases in T/LH, FSH/LH, and SHBG levels. COVID-19 may have unfavourable effects on gonadal functions, which should be taken seriously by clinicians. Routine monitoring of sex hormone levels might help clinicians to evaluate disease severity in patients with COVID-19.

Bariatric Surgery and the Risk of Cerebrovascular Events: a Meta-analysis of 17 Studies Including 3,124,063 Subjects.

PURPOSE: To perform a meta-analysis of the literature to evaluate the prevalence of cerebrovascular comorbidities between patients undergoing bariatric surgery and those not undergoing bariatric surgery. MATERIALS AND METHODS: Studies about the risk of cerebrovascular disease both before and after bariatric surgery were systematically explored in multiple electronic databases, including PubMed, Web of Science, Cochrane Library, and Embase, from the time of database construction to May 2022. RESULTS: Seventeen studies with 3,124,063 patients were finally included in the meta-analysis. There was a statistically significant reduction in cerebrovascular event risk following bariatric surgery (OR 0.68; 95% CI 0.58 to 0.78; I2 = 87.9%). The results of our meta-analysis showed that bariatric surgery was associated with decreased cerebrovascular event risk in the USA, Sweden, the UK, and Germany but not in China or Finland. There was no significant difference in the incidence of cerebrovascular events among bariatric surgery patients compared to non-surgical patients for greater than or equal to 5 years, but the incidence of cerebrovascular events less than 5 years after bariatric surgery was significantly lower in the surgical patients compared to non-surgical patients in the USA population. CONCLUSION: Our meta-analysis suggested that bariatric surgery for severe obesity was associated with a reduced risk of cerebrovascular events in the USA, Sweden, the UK, and Germany. Bariatric surgery significantly reduced the risk of cerebrovascular events within 5 years, but there was no significant difference in the risk of cerebrovascular events for 5 or more years after bariatric surgery in the USA.

GRB10 regulates ß-cell mass by inhibiting ß-cell proliferation and stimulating ß-cell dedifferentiation.

Decreased functional ß-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10 (GRB10), a negative regulator of insulin and mTORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. ß-cell-specific knockout of Grb10 in mice increased ß-cell mass and improved ß-cell function. Grb10-deficient ß-cells exhibit enhanced mTORC1 signaling and reduced ß-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced ß-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of ß-cell dedifferentiation and ß-cell mass, which exerts its effect by inhibiting mTORC1 signaling.

The adipocyte-enriched secretory protein tetranectin exacerbates type 2 diabetes by inhibiting insulin secretion from ß cells.

Pancreatic ß cell failure is a hallmark of diabetes. However, the causes of ß cell failure remain incomplete. Here, we report the identification of tetranectin (TN), an adipose tissue-enriched secretory molecule, as a negative regulator of insulin secretion in ß cells in diabetes. TN expression is stimulated by high glucose in adipocytes via the p38 MAPK/TXNIP/thioredoxin/OCT4 signaling pathway, and elevated serum TN levels are associated with diabetes. TN treatment greatly exacerbates hyperglycemia in mice and suppresses glucose-stimulated insulin secretion in islets. Conversely, knockout of TN or neutralization of TN function notably improves insulin secretion and glucose tolerance in high-fat diet-fed mice. Mechanistically, TN binds with high selectivity to ß cells and inhibits insulin secretion by blocking L-type Ca2+ channels. Our study uncovers an adipocyte-ß cell cross-talk that contributes to ß cell dysfunction in diabetes and suggests that neutralization of TN levels may provide a new treatment strategy for type 2 diabetes.

Hyperglycemia at admission is a strong predictor of mortality and severe/critical complications in COVID-19 patients: a meta-analysis.

BACKGROUND: Hyperglycemia at admission has been demonstrated to exacerbate the outcomes of coronavirus disease 2019 (COVID-19) but a meta-analysis is lacking to further confirm this hypothesis. The purpose of this meta-analysis was to summarize the evidence on the association between hyperglycemia at admission and the development of COVID-19. METHOD: Four databases namely, PubMed, Web of Science, Embase and Cochrane Library, were screened for eligible studies. STATA software was utilized to pool data for this meta-analysis. The primary outcomes included mortality and severity. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with random-effects models, and the quality of evidence was appraised by the Newcastle-Ottawa Scale (NOS). This meta-analysis was prospectively registered online on PROSPERO, CRD42020191763. RESULTS: Sixteen observational studies with 6386 COVID-19 patients relating hyperglycemia at admission to COVID-19 outcomes were included. The overall data demonstrated that, compared with the control, the hyperglycemia at admission group was more likely to have increased mortality (OR = 3.45, 95% CI, 2.26-5.26) and severe/critical complications (OR = 2.08, 95% CI, 1.45-2.99) of COVID-19. CONCLUSION: Hyperglycemia at admission in COVID-19 patients may be a strong predictor of mortality and complications.

A systematic review and meta-analysis of the serum lipid profile in prediction of diabetic neuropathy.

Whether the lipid profile in diabetic patients is associated with diabetic neuropathy (DN) development remains ambiguous, as does the predictive value of serum lipid levels in the risk of DN. Here, we performed the first meta-analysis designed to investigate the relationship between DN and the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Candidate studies were comprehensively identified by searching PubMed, Embase, Cochrane Library and Web of Science databases up to May 2020. Observational methodological meta-analysis was conducted to assess the relationships of TG, TC, HDL, and LDL levels with DN. Changes in blood lipids were used to estimate the effect size. The results were pooled using a random-effects or fixed-effects model. Potential sources of heterogeneity were explored by subgroup analysis. Various outcomes were included, and statistical analyses were performed using STATA (Version 12.0). Mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The Newcastle-Ottawa Scale (NOS) was applied to assess the methodological quality. I2 statistics were calculated to evaluate statistical heterogeneity. Funnel plots were utilized to test for publication bias. A sensitivity analysis was performed by omitting each study one by one. Thirty-nine clinical trials containing 32,668 patients were included in the meta-analysis. The results demonstrated that DN patients showed higher TG and lower HDL levels (MD = 0.34, 95% CI: 0.20-0.48 for TG; MD = -0.05, 95% CI: -0.08--0.02, I2 = 81.3% for HDL) than controls. Subgroup analysis showed that patients with type 1 diabetes mellitus (T1DM) neuropathy had elevated TG levels in their serum (MD = 0.25, 95% CI: 0.16-0.35,I2 = 64.4% for T1DM). However, only patients with T1DM neuropathy had reduced serum HDL levels, and there was no significant difference in serum HDL levels between patients with T2DM neuropathy and controls (MD = -0.07, 95% CI: -0.10--0.03, I2 = 12.4% for T1DM; MD = -0.02, 95% CI: -0.07-0.03, I2 = 80.2% for T2DM). TC and LDL levels were not significantly different between DN patients and controls (MD = -0.03, 95% CI: -0.14-0.09, I2 = 82.9% for TC; MD = -0.00, 95% CI: -0.08-0.08, I2 = 78.9% for LDL). In addition, compared with mild or painless DN patients, those with moderate or severe pain DN pain had significantly reduced serum TC and LDL levels (MD = -0.31, 95% CI: -0.49--0.13, I2 = 0% for TC; MD = -0.19, 95% CI: -0.32--0.08, I2 = 0% for LDL). TG levels and HDL levels did not vary considerably between patients with mild or painless DN and those with moderate or severe DN pain patients (MD = 0.12, 95% CI: -0.28-0.51, I2 = 83.2% for TG; MD = -0.07, 95% CI:-0.14-0.01, I2 = 58.8% for HDL). Furthermore, people with higher TG and LDL levels had higher risk of DN (OR = 1.36, 95% CI: 1.20-1.54, I2 = 86.1% for TG and OR = 1.10, 95% CI: 1.02-1.19, I2 = 17.8% for LDL). Conversely, high serum HDL levels reduced the risk of DN (OR = 0.85, 95% CI: 0.75-0.96, I2 = 72.6%), while TC levels made no significant difference with the risk of DN (OR = 1.02, 95% CI: 1.00-1.04, I2 = 84.7%). This meta-analysis indicated that serum lipid profile changes are among the biological characteristics of DN. Lipid levels should be explored as routine laboratory markers for predicting the risk of DN, as they will help clinicians choose appropriate therapies, and thus optimize the use of available resources.

Association between maternal folate status and gestational diabetes mellitus.

Studies on the association between maternal folate status and gestational diabetes mellitus (GDM) have yielded inconsistent results. This meta-analysis was performed to determine whether there may exist some association between maternal folate status and GDM. Unrestricted searches of PubMed, Web of Science, Cochrane, and Embase were conducted. All relevant studies on the association between maternal folat status and GDM risk were screened. The standardized mean difference (SMD) with 95% CIs was used to determine the association between maternal folate and GDM. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models to assess the impact of maternal folate status on GDM risk. 12 studies were included. The overall data revealed that compared with the non-GDM group, women with GDM had higher level of folate (SMD 0.41, 95% CI 0.07 to 0.21, I2  = 17.2%) in second or third trimester. We also found that maternal high folate status may be associated with increased risk of GDM (OR 2.16, 95% CI 1.70 to 2.74, I2  = 0.0%). Compared with non-GDM group, women with GDM are prone to higher folate level. Moreover, high maternal folate status may predict a higher risk of GDM. As the number of included studies was limited, further large population studies are needed in the future.