Dynamics, interactions and delays of the 2019 Ridgecrest rupture sequence.

The observational difficulties and the complexity of earthquake physics have rendered seismic hazard assessment largely empirical. Despite increasingly high-quality geodetic, seismic and field observations, data-driven earthquake imaging yields stark differences and physics-based models explaining all observed dynamic complexities are elusive. Here we present data-assimilated three-dimensional dynamic rupture models of California's biggest earthquakes in more than 20 years: the moment magnitude (Mw) 6.4 Searles Valley and Mw 7.1 Ridgecrest sequence, which ruptured multiple segments of a non-vertical quasi-orthogonal conjugate fault system1. Our models use supercomputing to find the link between the two earthquakes. We explain strong-motion, teleseismic, field mapping, high-rate global positioning system and space geodetic datasets with earthquake physics. We find that regional structure, ambient long- and short-term stress, and dynamic and static fault system interactions driven by overpressurized fluids and low dynamic friction are conjointly crucial to understand the dynamics and delays of the sequence. We demonstrate that a joint physics-based and data-driven approach can be used to determine the mechanics of complex fault systems and earthquake sequences when reconciling dense earthquake recordings, three-dimensional regional structure and stress models. We foresee that physics-based interpretation of big observational datasets will have a transformative impact on future geohazard mitigation.

A near-resonant excitation strategy to achieve ultra-low threshold GaN polariton lasing.

A near-resonant excitation strategy is proposed and implemented in a 4-µm-thick GaN microcavity to realize an exciton-polariton condensate/lasing with low threshold. Strong exciton-photon coupling is demonstrated, and polariton lasing is realized with an ultra-low threshold excitation power density of about 13.3 W/cm2 at room temperature. Such an ultra-low threshold is ascribed to the implementation of the near-resonant optical excitation strategy, which enables acceleration of the exciton and polariton relaxation and suppression of the heat generation in the cavity, thereby reducing the energy loss and enhance the cavity excitation efficiency.

Hemoadsorption in acute respiratory distress syndrome patients requiring venovenous extracorporeal membrane oxygenation: a systematic review.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) has been widely used for severe acute respiratory distress syndrome (ARDS) in recent years. However, the role of hemoadsorption in ARDS patients requiring VV ECMO is unclear. METHODS: Therefore, we conducted a systematic review to describe the effect of hemoadsorption on outcomes of ARDS patients requiring VV ECMO and elucidate the risk factors for adverse outcomes. We conducted and reported a systematic literature review based on the principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The systematic review searched Embase, CINHAL, and Pubmed databases for studies on ARDS patients receiving hemoadsorption and VV ECMO. The demographic data, clinical data and biological data of the patients were collected. RESULTS: We ultimately included a total of 8 articles including 189 patients. We characterized the population both clinically and biologically. Our review showed most studies described reductions in inflammatory markers and fluid resuscitation drug dosage in ARDS patients with Coronavirus disease 2019 (COVID-19) or sepsis after hemoadsorption. CONCLUSION: Because most of the studies have the characteristics of high heterogeneity, we could only draw very cautious conclusions that hemoadsorption therapy may enhance hemodynamic stability in ARDS patients with COVID-19 or sepsis receiving VV ECMO support. However, our results do not allow us to draw conclusions that hemoadsorption could reduce inflammation and mortality. Prospective randomized controlled studies with a larger sample size are needed in the future to verify the role of hemoadsorption in ARDS patients requiring VV ECMO.

Hypoxia stress alters gene expression in the gills and spleen of greater amberjack (Serioladumerili).

Greater amberjack (Seriola dumerili) is a fish species that has significant economic and cultural value. It has a large size and grows rapidly. However, the intolerance to hypoxia poses a major obstacle to the growth of its aquaculture industry. This study focuses on the gills and spleen, two organs closely associated with the response to acute hypoxic stress. By simulating the acute hypoxic environment and using Illumina RNA-Seq technology, we explored the gills and spleen transcriptome changes in the acute hypoxia intolerant and tolerant groups of greater amberjack. It was discovered that gill tissues in the tolerant group may maintain a stable intracellular energy supply by promoting glycolysis and ß-oxidation compared to the intolerant group. Additionally, it promotes angiogenesis, enhances the ability to absorb dissolved oxygen, and accelerates oxygen transport to the mitochondria, adapting to the hypoxic environment. Anti-apoptotic genes were up-regulated in gill tissues in the tolerant group compared to the intolerant group, thereby minimizing the damage of acute hypoxia. On the other hand, the spleen inhibited the TCA and energy-consuming lipid synthesis pathways to supply energy under acute hypoxic stress. Pro-angiogenic genes were down-regulated in the spleen of individuals in the tolerant group compared to the intolerant group, which may be related to organ function. The suppressed reactive oxygen species (ROS) production and the impaired immune response function of the spleen were also found. The study explored the acute hypoxic stress response in greater amberjack and the molecular mechanisms underlying its tolerance to acute hypoxia.

Myocd regulates airway smooth muscle cell remodeling in response to chronic asthmatic injury.

Abnormal growth of airway smooth muscle cells is one of the key features in asthmatic airway remodeling, which is associated with asthma severity. The mechanisms underlying inappropriate airway smooth muscle cell growth in asthma remain largely unknown. Myocd has been reported to act as a key transcriptional coactivator in promoting airway-specific smooth muscle development in fetal lungs. Whether Myocd controls airway smooth muscle remodeling in asthma has not been investigated. Mice with lung mesenchyme-specific deletion of Myocd after lung development were generated, and a chronic asthma model was established by sensitizing and challenging the mice with ovalbumin for a prolonged period. Comparison of the asthmatic pathology between the Myocd knockout mice and the wild-type controls revealed that abrogation of Myocd mitigated airway smooth muscle cell hypertrophy and hyperplasia, accompanied by reduced peri-airway inflammation, decreased fibrillar collagen deposition on airway walls, and attenuation of abnormal mucin production in airway epithelial cells. Our study indicates that Myocd is a key transcriptional coactivator involved in asthma airway remodeling. Inhibition of Myocd in asthmatic airways may be an effective approach to breaking the vicious cycle of asthmatic progression, providing a novel strategy in treating severe and persistent asthma. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Impact of Frailty on Short-Term Outcomes of Hepatic Lobectomy in Patients with Intrahepatic Cholangiocarcinoma: Evidence from the US Nationwide Inpatient Sample 2005-2018.

INTRODUCTION: This study aimed to evaluate associations between frailty and outcomes in patients with intrahepatic cholangiocarcinoma (ICC) undergoing hepatic lobectomy using a large, nationally representative sample. METHODS: This population-based, retrospective observational study extracted the data of adults ≥20 years old with ICC undergoing hepatic lobectomy from the US Nationwide Inpatient Sample database between 2005 and 2018. Frailty was assessed by the validated Hospital Frailty Risk Score (HFRS). Associations between frailty and surgical outcomes were analyzed using logistic regression analyses. RESULTS: After exclusions, 777 patients were enrolled, including 427 frail and 350 non-frail. Patients' mean age was 64.5 (±0.4) years and the majority were males (51.1%) and whites (76.5%). Frailty was significantly associated with increased odds of in-hospital mortality (aOR: 18.51, 95% CI: 6.70, 51.18), non-home discharge (aOR: 3.58, 95% CI: 2.26, 5.66), prolonged LOS (aOR: 5.56, 95% CI: 3.87, 7.99), perioperative cardiac arrest/stroke (aOR: 5.44, 95% CI: 1.62, 18.24), acute respiratory distress syndrome (ARDS)/respiratory failure (aOR: 3.88, 95% CI: 2.40, 6.28), tracheostomy/ventilation (aOR: 3.83, 95% CI: 2.23, 6.58), bleeding/transfusion (aOR: 1.67, 95% CI: 1.24, 2.26), acute kidney injury (AKI) (aOR: 14.37, 95% CI: 7.13, 28.99), postoperative shock (aOR: 4.44, 95% CI: 2.54, 7.74), and sepsis (aOR: 11.94, 95% CI: 6.90, 20.67). DISCUSSION/CONCLUSION: Among patients with ICC undergoing hepatic lobectomy, HFRS-defined frailty is a strong predictor of worse in-patient outcomes, including in-hospital death, prolonged LOS, unfavorable discharge, and complications (perioperative cardiac arrest/stroke, ARDS/respiratory failure, tracheostomy/ventilation, bleeding/transfusion, AKI, postoperative shock, and sepsis). Study results may help stratify risk in frail patients undergoing hepatic resection for ICC.

Factors associated with SARS-CoV-2 vaccine hesitancy after stroke: a cross-sectional study.

BACKGROUND: The vaccination status of post-stroke patients, who are at high risk of severe outcomes from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is a significant concern, yet it remains unclear. We aimed to explore the vaccination status, factors associated with vaccine hesitancy, and adverse effects after vaccination among post-stroke patients. METHODS: This multi-center observational study enrolled hospitalized post-stroke patients from six Chinese hospitals (Oct 1, 2020 - Mar 31, 2021), examining vaccine uptake and self-reported reasons for vaccine hesitancy, utilizing logistic regression to investigate risk factors for vaccine hesitancy, and recording any adverse reactions post-vaccination. RESULTS: Of the total 710 post-stroke patients included in the study, 430 (60.6%) had completed the recommended full-3 dose SARS-CoV-2 vaccination, with 176 (24.8%) remaining unvaccinated. The most common reasons for vaccine hesitancy were concerns about vaccine side effects (41.5%) and impaired mobility (33.9%). Logistic regression identified advanced age (aOR = 1.97, 95%CI: 1.36-2.85, P = 0.001), lower Barthel Index score (aOR = 0.88, 95%CI: 0.82-0.93, P = 0.018), higher Modified Rankin Scale score (aOR = 1.85, 95%CI: 1.32-2.56, P = 0.004), and poorer usual activity level of EuroQol 5-Dimension (aOR = 2.82, 95%CI: 1.51-5.28, P = 0.001) as independent risk factors for vaccine hesitancy. Approximately 14.8% reported minor adverse reactions, mainly pain at the injection site. CONCLUSION: We found that post-stroke patients have insufficient SARS-CoV-2 vaccination rates, with key risk factors for vaccine hesitancy including concerns about side effects, advanced age, and functional impairments. No severe adverse reactions were observed among the vaccinated population.

Sulfur-manganese carbonate composite autotrophic denitrification: nitrogen removal performance and biochemistry mechanism.

A novel composite sulfur-manganese carbonate autotrophic denitrification (SMAD) system was developed to reduce sulfate production and provide pH buffer function while improving denitrification efficiency without external organics. The average removal efficiency of total nitrogen (TN) was 98.09% and 96.29%, and that of NO3--N was 99.53% and 97.77%, respectively, in the SMAD system with a hydraulic retention time (HRT) of 6 h and 3 h. They were significantly higher than that in the controls (quartz sand, manganese carbonate ore, and sulfur systems). The H+ produced by the sulfur autotrophic denitrification (SAD) process promoted the release of Mn2+ in the SMAD system. And this system had a stable pH with no accumulation of NO2--N. The decrease of sulfate and formation of Mn oxides through Mn2+ electron donation confirmed the presence of the manganese autotrophic denitrification (MAD) process in the SMAD system. Dominant functional bacteria in the SMAD system were Thiobacillus, Chlorobium, and Sulfurimonas, which were linked to nitrogen, sulfur, and manganese conversion and promoted denitrification. Meanwhile, Flavobacterium participating in Mn2+ oxidation was found only in the SMAD system. The SMAD system provided a new strategy for advanced tailwater treatment.

Unveiling renal pathology's potential: exploring a rare subtype of amyloid - apolipoprotein CII amyloidosis in the youngest patient: a case report and literature review.

In this clinical case report, we present a rare subtype of amyloidosis, apolipoprotein CII (apo CII), which was diagnosed through a renal biopsy and subsequently confirmed by identifying the p.K41T mutation via germline DNA sequencing. Upon reviewing the literature, five patients exhibiting identical mutation were identified via renal biopsy, while an additional patient was diagnosed through biopsies of the fat pad and bone marrow. Notably, our patient is the youngest recorded case. We pioneered the application of immunofluorescence and immunogold electron microscopy techniques for apo CII evaluation. Our report provides a detailed description of this case, supplemented by an extensive review encompassing apo CII, documented instances of apo CII amyloidosis with renal or systemic involvement, and potential underlying mechanisms.

Effects of coffee and tea on postprandial cardiometabolic risk factors in healthy individuals: a randomized crossover trial.

BACKGROUND AND OBJECTIVES: The effect of different coffee and tea consumption on postprandial glucose and lipid metabolism has never been reported previously. The aim of the present study was to investigate the effect of different coffee or tea consumption at breakfast on postprandial cardiometabolic risk factors in healthy individuals. METHODS AND STUDY DESIGN: Eighteen healthy young subjects completed the trial. After 8-hour overnight fast, volunteers either ingested water, freeze-dried coffee, spray-dried coffee, green tea, black tea or oolong tea together with a breakfast consisting of an egg and 180g deep-fried dough sticks. Blood was drawn at 0h, 0.5h, 1h, 2h, and 3h. RESULTS: The differences in triglyceride (TG) values relative to the baseline levels at 2h and 3h of green tea was significantly decreased compared with black tea and oolong tea (p<0.05). Compared with black tea, green tea and oolong tea significantly reduced postprandial total cholesterol (TC) levels (p<0.05, p<0.01), respectively. Furthermore, the serum concentrations of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were substantially decreased after oolong tea consumption compared with black tea (p<0.05, p<0.01). CONCLUSIONS: Green tea ingestion can lower the elevation of serum TG and TC levels after high-fat or high-cholesterol diets. Our findings have far-reaching implications given the widespread use of coffee and tea and the current concern over cardiometabolic risk factors.

Tooth intentional replantation from 1964 to 2023: A bibliometric analysis.

BACKGROUND/AIM: There is no thorough overview of intentional tooth replantation techniques. We performed a bibliometric analysis of the development of intentional tooth replantation. MATERIALS AND METHODS: A comprehensive search of the Web of Science and SCOPUS databases was conducted in February 2023. Original articles and reviews of human studies with "intentional replantation" or synonyms in the titles, abstracts, or keywords were included. A descriptive analysis of bibliographic data, co-occurrence analysis, and coupling of publications was performed. Multivariate analysis was used to explore the bibliometric parameters associated with the citation counts. RESULTS: The study included 171 papers, which were co-authored by 500 individuals affiliated with 217 institutions from 28 countries/regions. The USA contributed the greatest number of publications, followed by China, and Japan. The USA had 694 citations, followed by Japan (210), and Turkey (210). The Journal of Endodontics and Dental Traumatology contributed the most citations. Five directions for future research were identified based on the coupling relationships of publications, including "managing vertical root fractures with adhesive resin using the intentional replantation technique," "intentional replantation for periodontally hopeless or endodontically compromised teeth," "intentional replantation for treating abnormalities of morphological development," "outcomes and prognosis factors of intentional replantation," and "treating root replacement resorption by intentional replantation." Multivariate analysis showed that the publication year, Journal Citation Reports ranking of journals, study design, and disease type were predictors of citation counts. CONCLUSIONS: This bibliometric analysis provides a comprehensive description of the intentional replantation technique. The USA published the greatest volume of papers and generated the most citations. The Journal of Endodontics and Dental Traumatology are considered the most influential. The Journal Citation Reports journal ranking (Q1, Q2), study design (case reports, cohort studies), and disease type (crown root fractures) were associated with the citation counts.

Low-carbohydrate diets, low-fat diets, and mortality in middle-aged and older people: A prospective cohort study.

BACKGROUND: Short-term clinical trials have shown the effectiveness of low-carbohydrate diets (LCDs) and low-fat diets (LFDs) for weight loss and cardiovascular benefits. We aimed to study the long-term associations among LCDs, LFDs, and mortality among middle-aged and older people. METHODS: This study included 371,159 eligible participants aged 50-71 years. Overall, healthy and unhealthy LCD and LFD scores, as indicators of adherence to each dietary pattern, were calculated based on the energy intake of carbohydrates, fat, and protein and their subtypes. RESULTS: During a median follow-up of 23.5 years, 165,698 deaths were recorded. Participants in the highest quintiles of overall LCD scores and unhealthy LCD scores had significantly higher risks of total and cause-specific mortality (hazard ratios [HRs]: 1.12-1.18). Conversely, a healthy LCD was associated with marginally lower total mortality (HR: 0.95; 95% confidence interval: 0.94, 0.97). Moreover, the highest quintile of a healthy LFD was associated with significantly lower total mortality by 18%, cardiovascular mortality by 16%, and cancer mortality by 18%, respectively, versus the lowest. Notably, isocaloric replacement of 3% energy from saturated fat with other macronutrient subtypes was associated with significantly lower total and cause-specific mortality. For low-quality carbohydrates, mortality was significantly reduced after replacement with plant protein and unsaturated fat. CONCLUSIONS: Higher mortality was observed for overall LCD and unhealthy LCD, but slightly lower risks for healthy LCD. Our results support the importance of maintaining a healthy LFD with less saturated fat in preventing all-cause and cause-specific mortality among middle-aged and older people.

Compensation of the tool influence function changes under neighborhood effect in atmospheric pressure plasma processing.

Nowadays, computer controlled optical surfacing (CCOS) is greatly developed in the fabrication of ultra-precision optical surfaces. As one of the deterministic CCOS techniques, atmospheric pressure plasma processing (APPP) can achieve the efficient removal based on the chemical reaction. In this process, the temperature rising issue caused by plasma heating is of great importance for accelerating the etching rate, but also increases the difficulty of deterministic removal control, because the tool influence function (TIF) in APPP is no longer time-invariant. In the existing research, the time-variant TIF model can describe the TIF changes to a certain degree, which is considered in the dwell time calculation. However, there inevitably exists the strong neighborhood effect, which indicates that the TIFs of different dwell points are thermally interacted. Thus, the existing time-variant TIF model is no longer accurate for predicting TIF changes, and not suitable for application to further compensation. To solve this, the compensation of TIF changes under neighborhood effect is proposed in this paper. First, the mechanism of TIF changes caused by neighborhood effect is explained in depth. Then, the theoretical analysis is implemented and the compensation method is systematically discussed, encompassing the tool path optimization, model of TIF changes and dwell time calculation. Further, the proposed method is demonstrated and verified by a series of simulations. Finally, the experimental validation is carried out, which proves the capability of achieving high-precision removal and high convergence rate.

Simulation and an experimental study on the optical performance of a Wolter-I focusing mirror based on a 3D ray tracing algorithm.

The nested Wolter-I type focusing mirror is widely used in the field of X-ray astronomy. The thin-shell mirrors produced by the electroforming replication method will introduce various shape errors during the fabricating and assembling process. This study introduces a non-analytical 3D geometrical ray tracing algorithm capable of predicting optical performance for large mirror deformations. The algorithm's implementation involves error reconstruction, light source and ray simulation, and optical performance calculation. Experimental and simulation validation underscores the algorithm's precision and effectiveness. The results also indicate that edge deformation can seriously affect imaging contrast which is generally considered to be determined only by surface scattering. Applying the 3D ray tracing algorithm, a range of low-frequency fabrication and assembly errors are simulated, such as absolute radius, taper, roundness, edge effects, mirror posture, and hoisting deformation errors, and their effects on imaging quality are analyzed and discussed.

Smurf1: A possible therapeutic target in dry age-related macular degeneration.

Smad ubiquitylation regulatory factor-1 (Smurf1) is one of C2-WW-HECT domain E3 ubiquitin ligases, it can regulate BMP pathway by mediating ubiquitylation degradation of Smad1/Smad5. Many functions about Smurf1 also are still unknown, especially in retina. This research is about to explore the role of Smurf1 in retina degeneration. Tail vein injection of sodium iodate (NaIO3) in C57BL/6J mice was the animal model of retina degeneration. In NaIO3 model, Smurf1 had more expression than normal mice. Specific Smurf1 inhibitor, A01, was injected into vitreous cavity. Results showed that inhibiting Smurf1 could alleviate acute retina injury, such as keeping a better retina structure in living imaging and histologic sections, less cell death and inflammation activation. Tert-butyl hydroperoxide (TBH) was used to establish oxidative stress injury in human retinal pigments epithelial cell line (ARPE-19). Oxidative stress injury gradually caused co-upregulation of Smurf1, TGF-ß1 and phosphorylated NF-κB (pNF-κB). TGF-ß1 could directly induce Smurf1 expression. Inhibiting Smurf1 had an anti-epithelial mesenchymal transition (anti-EMT) function. Similarly, A01 also could inhibit the expression of pNF-κB, NLRP3 and IL-1ß. At last, after searching bioinformatics database, Smurf1 had a possible interaction with beta-transducin repeat containing E3 ubiquitin protein ligase (ß-TrCP), another E3 ubiquitin ligases. ß-TrCP can mediate ubiquitination degradation of p-IκBα. Lentivirus-SMURF1 was used to overexpress Smurf1, and GS143 was used to inhibit ß-TrCP. The results showed Smurf1 could directly induce NF-κB, pNF-κB, and NLRP3 expression, and keep a stable ß-TrCP expression. However, inhibiting ß-TrCP could cause more NF-κB activation and NLRP3 expression. Therefore, ß-TrCP may play a negative role in NF-κB pathway activation. In summary, Smurf1 plays a role in exacerbating oxidative stress injury and inflammation in retina and may become a potential therapeutic target in ROS injury of retina.

Clinical Significance of Persistent Hematuria Degrees in Primary IgA Nephropathy: A Propensity Score-Matched Analysis of a 10-Year Follow-Up Cohort.

INTRODUCTION: The clinical significance of persistent hematuria degrees has not been expounded in primary IgA nephropathy (IgAN) and requires further research. METHODS: From January 2003 to May 2022, a total of 684 IgAN patients with persistent hematuria were enrolled to conduct a retrospective single-center study. Patients whose hematuria degree at baseline was higher than the second tertiles of the whole were included in the high-degree hematuria cohort (Hh), and the low-degree hematuria cohort (Lh) was constructed with 1:1 matched cases from the rest according to age, gender, and estimated glomerular filtration rate (eGFR) at baseline and follow-up time. Survival was determined using the Kaplan-Meier method (K-M) and generalized linear mixed-effects model (GLMM). Risk factors for survival were determined according to the Cox proportional hazards model. RESULTS: Both the Hh and Lh consisted of 228 cases. While the demographic data and the renal function at baseline were matched, both the K-M (p = 0.02) and GLMM (p = 0.04) proved that the prognosis of the Hh was significantly worse than that of the Lh within 10 years of follow-up. The higher persistent hematuria degree was an independent risk factor (3.93; 95% confidence interval, 1.33-11.6) associated with reaching the endpoint (eGFR decreased from the baseline ≥30% continuously or reached end-stage renal disease [ESRD]). The Hh had a significantly higher proportion of crescent (p = 0.003). The prognosis of the Hh was significantly worse than that of the Lh when accompanied by the crescent and presented an indistinct difference if the crescent was absent. CONCLUSIONS: The clinicopathologic manifestation of IgAN patients with persistent high-degree hematuria was severer, and the prognosis was worse than those with persistent low-degree hematuria.

Chlorocholine Perchlorate is an Organic Ferroelectric with Two-Step Ladder-like Dielectric, Second Harmonic Generation Effects, and Ferroelectricity.

The organic salt chlorocholine perchlorate [ClCH2 CH2 N(CH3 )3 ⋅ClO4 ] (CCP) is found to be a molecular ferroelectric with a high theoretical spontaneous polarization (Ps) value up to 17.09 µC cm-2 . CCP exhibits two successive order-disorder phase transition at 332 and 365 K with space groups changing from Cc to Cmc21 and then P63 /mmc, accompanied by unusual two-step ladder-like dielectric, SHG signal with obvious "on/off" contrasts. These findingings provides a further instance of exploring successive thermal-stimuli multi-responsive switching materials applied as switches and sensors.

Effects of whole grain intake on glycemic traits: A systematic review and meta-analysis of randomized controlled trials.

Whole grains (WGs) may have various health benefits, including lowering blood glucose and improving insulin sensitivity. To conduct a meta-analysis of the effects of WGs compared with non-WGs on changes in fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR). A systematic literature search was performed for all published randomized controlled trials on the effects of WG intake on fasting glucose, fasting insulin, HbA1c and HOMA-IR response up to February 2021. Weighted mean differences (WMD) were calculated. Pre-specified subgroup and univariate meta-regression analyses were explored to identify the sources of heterogeneity. Sensitivity analysis and bias analysis were conducted to appraise study quality. Among 12,435 articles screened for eligibility, data were extracted from 48 articles. Meta-analysis of 4,118 participants showed that WG consumption resulted in a significant reduction in fasting glucose by -0.15 mmol/L, fasting insulin by -2.71 pmol/L, HbA1c by -0.44%, and HOMA-IR by -0.28, respectively. Compared with mixed grains, brown rice, and wheat, oats were significantly lower on marker of glycemic. Besides, multiple interventions per day consolidated effectiveness of WGs. WG consumption decreased the levels of fasting glucose, fasting insulin, HbA1c, and HOMA-IR compared with non-WG consumption.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.2001429 .

Targeted VEGFA therapy in regulating early acute kidney injury and late fibrosis.

Damage to peritubular capillaries is a key process that contributes to acute kidney injury (AKI) progression. Vascular endothelial growth factor A (VEGFA) plays a critical role in maintaining the renal microvasculature. However, the physiological role of VEGFA in various AKI durations remains unclear. A severe unilateral ischemia‒reperfusion injury model was established to provide an overview of VEGFA expression and the peritubular microvascular density from acute to chronic injury in mouse kidneys. Therapeutic strategies involving early VEGFA supplementation protecting against acute injury and late anti-VEGFA treatment for fibrosis alleviation were analyzed. A proteomic analysis was conducted to determine the potential mechanism of renal fibrosis alleviation by anti-VEGFA. The results showed that two peaks of extraglomerular VEGFA expression were observed during AKI progression: one occurred at the early phase of AKI, and the other occurred during the transition to chronic kidney disease (CKD). Capillary rarefaction progressed despite the high expression of VEGFA at the CKD stage, and VEGFA was associated with interstitial fibrosis. Early VEGFA supplementation protected against renal injury by preserving microvessel structures and counteracting secondary tubular hypoxic insults, whereas late anti-VEGFA treatment attenuated renal fibrosis progression. The proteomic analysis highlighted an array of biological processes related to fibrosis alleviation by anti-VEGFA, which included regulation of supramolecular fiber organization, cell-matrix adhesion, fibroblast migration, and vasculogenesis. These findings establish the landscape of VEGFA expression and its dual roles during AKI progression, which provides the possibility for the orderly regulation of VEGFA to alleviate early acute injury and late fibrosis.