The physiology of drought stress in two grapevine cultivars: Photosynthesis, antioxidant system, and osmotic regulation responses.

Drought stress impedes viticultural plant growth and development by modifying various metabolic pathways. However, the regulatory network response underlying drought stress is not yet clear. In this study, the leaves and roots of "Shine Muscat" ("SM," Vitis labruscana × Vitis vinifera) and "Thompson Seedless" ("TS," V. vinifera L. cv.) were subjected to drought stress to study the regulatory network used by drought stress. Morphophysiological results showed that the malondialdehyde content after 28 days of drought stress increased more significantly in "TS" than "SM." Furthermore, the multiomics analysis studies showed that a total of 3036-6714 differentially expressed genes and 379-385 differentially abundant metabolites were identified in "SM" and "TS" grapevine cultivars under drought stress. Furthermore, the retained intron was the major form of differential alternative splicing event under drought stress. The photosynthesis pathway, antioxidant system, plant hormone signal transduction, and osmotic adjustment were the primary response systems in the two grapevine cultivars under drought stress. We have identified GRIK1, RFS2, and LKR/SDH as the hub genes in the coexpression network of drought stress. In addition, the difference in the accumulation of pheophorbide-a reveals different drought resistance mechanisms in the two grapevine cultivars. Our study explained the difference in drought response between cultivars and tissues and identified drought stress-responsive genes, which provides reference data for further understanding the regulatory network of drought tolerance in grapevine.

High power density output and durability of microbial fuel cells enabled by dispersed cobalt nanoparticles on nitrogen-doped carbon as the cathode electrocatalyst.

To endow microbial fuel cells (MFCs) with low cost, long-term stability and high-power output, a novel cobalt-based cathode electrocatalyst (Nano-Co@NC) is synthesized from a polygonal metal-organic framework ZIF-67. After calcining the resultant ZIF-67, the as-synthesized Nano-Co@NC is characteristic of cobalt nanoparticles (Nano-Co) embedded in nitrogen-doped carbon (NC) that inherits the morphology of ZIF-67 with a large surface area. The Nano-Co particles that are highly dispersed and firmly fixed on NC not only ensure electrocatalytic activity of Nano-Co@NC toward the oxygen reduction reaction on the cathode, but also inhibit the growth of non-electrogenic bacteria on the anode. Consequently, the MFC using Nano-Co@NC as the cathode electrocatalyst demonstrates excellent performance, delivering a comparable initial power density and exhibiting far better durability than that using Pt/C (20 wt%) as the cathode electrocatalyst. The low cost and the excellent performance of Nano-Co@NC make it promising for MFCs to be used in practice.

A novel immune-related prognostic signature based on Chemoradiotherapy sensitivity predicts long-term survival in patients with esophageal squamous cell carcinoma.

Background: There is a heterogenous clinical response following chemoradiotherapy (CRT) in esophageal squamous cell carcinoma (ESCC). Therefore, we aimed to study signaling pathway genes that affect CRT sensitivity and prognosis. Methods: Gene expression analyses were performed in the GEO and TCGA datasets. A immunohistochemistry (IHC) analysis was performed in pretreatment biopsies. Results: MMP13 was found to be highly expressed in the "Pathologic Complete Response (pCR)" and "Complete Remission (CR)" and "Alive" groups. Th17 cells and MMP9/13 showed a negative correlation in immune infiltration analysis. In GSEA analysis, IL-4 and IL-13 signaling pathways were highly enriched in patients exhibiting high MMP expression in pCR and CR groups. IHC results suggested higher MMP13 & IL-4 and lower IL-17A & RORC expression in the CR group compared to the 0.70, and the model could well distinguish high-risk and low-risk subgroups. Conclusion: The above results may provide guidance for developing novel treatment and prognostic strategies in ESCC patients.

A facile synthesis of FeS/Fe3C nanoparticles highly dispersed on in situ grown N-doped CNTs as cathode electrocatalysts for microbial fuel cells.

A novel composite of iron sulfide, iron carbide and nitrogen carbides (Nano-FeS/Fe3C@NCNTs) as a cathode electrocatalyst for microbial fuel cells (MFCs) is synthesized by a one-pot solid state reaction, which yields a unique configuration of FeS/Fe3C nanoparticles highly dispersed on in situ grown nitrogen-doped carbon nanotubes (NCNTs). The highly dispersed FeS/Fe3C nanoparticles possess large active sites, while the NCNTs provide an electronically conductive network. Consequently, the resultant Nano-FeS/Fe3C@NCNTs exhibit excellent electrocatalytic activity towards the oxygen reduction reaction (ORR), with a half-wave potential close to that of Pt/C (about 0.88 V vs. RHE), and enable MFCs to deliver a power density of 1.28 W m-2 after two weeks' operation, which is higher than that of MFCs with Pt/C as the cathode electrocatalyst (1.02 W m-2). Theoretical calculations and experimental data demonstrate that there is a synergistic effect between Fe3C and FeS in Nano-FeS/Fe3C@NCNTs. Fe3C presents a strong attraction and electron-donating tendency to oxygen molecules, serving as the main active component, while FeS reduces charge transfer resistance by transferring electrons to Fe3C, synergistically improving the kinetics of the ORR and power density of MFCs.

Differences in the Proportion of CYP2C19 Loss-of-Function Between Cerebral Infarction and Coronary Artery Disease Patients.

Background: Cytochrome P450 2C19 (CYP2C19) genotypes and metabolic phenotypes (extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM)) are related to the metabolism of therapeutic drugs for cardiovascular and cerebrovascular diseases. This study aimed to investigate the differences of CYP2C19 gene polymorphism distribution between coronary artery disease (CAD) patients and cerebral infarction (CI) patients. Methods: We identified 413 CI patients, 509 CAD patients, and 241 CI+CAD patients from 2016 to 2020 and studied genotypes of CYP2C19 rs4986893 (636G>A) and rs4244285 (681G>A) polymorphisms using PCR-gene chip detection method. Differences in CYP2C19 genotypes and metabolic phenotypes between the groups were compared. To analyze the efficacy of CYP2C19 metabolic phenotypes in discriminating between cerebral infarction and coronary artery disease, multiple logistic regression analysis was conducted after adjusting for gender, age, smoking history, drinking history, hypertension, and diabetes. Results: There were significant differences in the distribution of CYP2C19 genotypes and metabolic phenotypes between CI and CAD patients. The results of multivariate logistic regression (adjusted for sex, age, smoking, drinking, hypertension, and diabetes) indicated that CYP2C19 IM phenotype (IM vs EM: OR 1.443, 95% CI: 1.086-1.918, P=0.011) and CYP2C19 IM+PM phenotype (IM or PM vs EM: OR 1.440, 95% CI: 1.100-1.885, P=0.008) may be indicators of CI from CAD. Conclusion: CYP2C19 EM metabolic phenotype was dominant in CAD patients, and CYP2C19 IM metabolic phenotype was dominant in CI patients. After adjusting for other confounding factors, patients with the CYP2C19 IM metabolic phenotype were more likely to develop CI than CAD.

A Surrogate Endpoint for Overall Survival in Locally Advanced and Resectable Esophageal Squamous Cell Carcinoma: A Reanalysis of Data From the NEOCRTEC5010 Trial.

PURPOSE: This study aimed to investigate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) in patients with locally advanced and resectable esophageal squamous cell carcinoma. METHODS AND MATERIALS: We re-analyzed patient data from the NEOCRTEC5010 randomized controlled trial (N = 451 patients) to compare their OS with that of an age- and sex-matched cohort from the general population of China. We used expected survival and the standardized mortality ratio, respectively, in our analysis of data collected from a neoadjuvant chemoradiation therapy (NCRT) plus surgery group and a surgery-only group. Published data from 6 randomized controlled trials and 20 retrospective studies were used to examine the correlation between DFS and OS at the trial level. RESULTS: The annual hazard rate of disease progression decreased to 4.9% and 8.1% within 3 years in the NCRT and surgery groups, respectively. Patients who were disease-free at 36 months had a 5-year OS of 93.9% (95% CI, 89.7%-98.4%) in the NCRT group with a standardized mortality ratio of 1.1 (95% CI, 0.7-1.8; P = .5639). In contrast, the 5-year OS was only 12.9% (95% CI, 7.3%-22.6%) for patients in the NCRT group who exhibited disease progression within 36 months. At the trial level, DFS and OS were correlated with treatment effect (R2 = 0.605). CONCLUSIONS: Disease-free status at 36 months is a valid surrogate endpoint for 5-year OS in patients with locally advanced and resectable esophageal squamous cell carcinoma. Patients who were disease-free at 36 months showed a favorable OS, which was indistinguishable from that of the age- and sex-matched comparison group from the general population; otherwise, their 5-year OS was extremely poor.

Drought stress in 'Shine Muscat' grapevine: Consequences and a novel mitigation strategy-5-aminolevulinic acid.

Drought is a common and serious abiotic stress in viticulture, and it is urgent to select effective measures to alleviate it. The new plant growth regulator 5-aminolevulinic acid (ALA) has been utilized to alleviate abiotic stresses in agriculture in recent years, which provided a novel idea to mitigate drought stress in viticulture. The leaves of 'Shine Muscat' grapevine (Vitis vinifera L.) seedlings were treated with drought (Dro), drought plus 5-aminolevulinic acid (ALA, 50 mg/L) (Dro_ALA) and normal watering (Control) to clarify the regulatory network used by ALA to alleviate drought stress in grapevine. Physiological indicators showed that ALA could effectively reduce the accumulation of malondialdehyde (MDA) and increase the activities of peroxidase (POD) and superoxide dismutase (SOD) in grapevine leaves under drought stress. At the end of treatment (day 16), the MDA content in Dro_ALA was reduced by 27.63% compared with that in Dro, while the activities of POD and SOD reached 2.97- and 5.09-fold of those in Dro, respectively. Furthermore, ALA reduces abscisic acid by upregulating CYP707A1, thus, relieving the closure of stomata under drought. The chlorophyll metabolic pathway and photosynthetic system are the major pathways affected by ALA to alleviate drought. Changes in the genes of chlorophyll synthesis, including CHLH, CHLD, POR, and DVR; genes related to degradation, such as CLH, SGR, PPH and PAO; the RCA gene that is related to Rubisco; and the genes AGT1 and GDCSP related to photorespiration form the basis of these pathways. In addition, the antioxidant system and osmotic regulation play important roles that enable ALA to maintain cell homeostasis under drought. The reduction of glutathione, ascorbic acid and betaine after the application of ALA confirmed the alleviation of drought. In summary, this study revealed the mechanism of effects of drought stress on grapevine, and the alleviating effect of ALA, which provides a new concept to alleviate drought stress in grapevine and other plants.

Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma-an exploration of surrogate endpoint.

BACKGROUND: Overall survival (OS) is the gold standard to assess novel therapeutics to treat cancer. However, to identify early efficacy and speed up drug approval, trials have used progression-free survival (PFS) as a surrogate endpoint (SE). Herein, we aimed to examine if PFS could function as an OS surrogate in advanced Esophageal Squamous Cell Carcinoma (ESCC) treated with first-line immunochemotherapy. METHODS: Two hundred ninety-two advanced ESCC patients treated using inhibitors of PD-1/PD-L1 + chemotherapy or chemotherapy alone were collected. In addition, six phase III randomized clinical trials were eligible for inclusion. Bayesian normal-induced-copula-estimation model in retrospective patient data and regression analysis in the published trial data were used to determine the PFS-OS correlation. RESULTS: PFS correlated moderately with OS in the retrospective cohort (Kendall's Tau = 0.684, τ = 0.436). In trial-level, treatments effects for PFS correlated weakly with those for OS in intention-to-treat population (R2 = 0.436, adj.R2 = 0.249, P > 0.05) and in PD-L1-enriched population (R2 = 0.072). In arm-level, median PFS also correlated weakly with median OS. Moreover, analysis of the retrospective cohort demonstrated that the annual death risk after progression in the continued immunotherapy group was considerably lower than that in the discontinued group. CONCLUSION: In trials of anti-PD-1 agents to treat advanced ESCC, the current results provide only weak support for PFS as an OS surrogate; OS cannot be substituted completely by PFS in these cases. The results also suggest that qualified patients with advanced ESCC might benefit from continuous immunotherapy beyond progression to achieve a decreased risk of death.

Trafficking protein TMED3 promotes esophageal squamous cell carcinoma.

BACKGROUND: The molecular mechanisms of esophageal squamous cell carcinoma (ESCC) remain poorly understood. Transmembrane emp24 trafficking protein 3 (TMED3) acts as an oncogene or tumor suppressor gene in different cancers. Our study was to explore the clinicopathological significance and functional roles of TMED3 in ESCC. METHODS: Immunohistochemistry, qPCR, and western blotting were used to analyze the expression of TMED3 in ESCC tissues and cells. Statistical analysis was performed to analyze the relationship between TMED3 expression and tumor characteristics in patients with ESCC. The role of TMED3 in vitro and in vivo was investigated by performing functional verification experiments and using a xenograft mouse model. Proteins that are functionally related to TMED3 were recognized by Affymetrix microarray and Ingenuity Pathway Analysis (IPA). Functional verification experiments were performed to analyze the role of FAM60A (a protein functionally related to TMED3) in vitro. RESULTS: We confirmed the overexpression of TMED3 was correlated with poor prognosis in ESCC patients. When TMED3 was knocked down, ESCC cell proliferation, migration, and invasion were inhibited whereas cell apoptosis was promoted in vitro, and tumorigenicity was inhibited in vivo. We further revealed significant changes in gene expression profile in TMED3 knockdown cells. Among these differentially expressed genes, FAM60A was overexpressed in ESCC tissues. Furthermore, knocking down FAM60A significantly weakened the proliferation ability of ESCC cells and reversed TMED3's tumorigenicity of ESCC cells. CONCLUSION: Our study revealed an oncogenic role of TMED3 in ESCC.

Comparative efficacy and safety of immunotherapy for patients with advanced or metastatic esophageal squamous cell carcinoma: a systematic review and network Meta-analysis.

BACKGROUND: The study aimed to compare efficacy and safety of various immune checkpoint inhibitors for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). METHODS: We searched Medline, Web of Science, Cochrane Central Register of Controlled Trials, Embase, Clinical Trials.gov and several international conference databases from January 1, 2000 to December 19, 2021. We conducted Bayesian network meta-analysis to assess the relative effects among treatments. Outcomes included overall survival (OS), progression-free survival (PFS), overall response rate and adverse events. RESULTS: Ten eligible trials with 5250 patients were included. Toripalimab and Camrelizumab plus chemotherapy were preferred to rank first on OS (probability, 61%) and PFS (probability, 37%) in the first-line setting, respectively. In refractory patients, Sintilimab and Camrlizumab were most likely to be ranked first on OS (probability, 37%) and PFS (probability, 94%). The toxicity related to immunotherapy was manageable in clinical trials. Camrelizumab and Nivolumab had the less adverse events of grade 3 or higher in the first and refractory setting, respectively. CONCLUSIONS: This study found that Toripalimab and Camrelizumab plus chemotherapy were likely to be the best option in terms of OS and PFS in the first-line setting for patients with advanced or metastatic ESCC respectively. Sintilimab and Camrelizumab were the preferred options for OS and PFS in refractory patients respectively. The toxicity of immunotherapy was different from conventional chemotherapy, but manageable in patients with ESCC. TRIAL REGISTRATION: PROSPERO registration number: (CRD 42021261554).

The perirenal fat thickness was independently associated with serum uric acid level in patients with type 2 diabetes mellitus.

BACKGROUND: Obesity is an important risk factor for hyperuricemia. We aimed to explore the relationship between perirenal fat thickness (PrFT) and paranephric fat thickness (PnFT) and serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study involving 257 patients with T2DM recruited from Beijing Luhe Hospital from September 2019 to May 2020. The basic and clinical information such as age, gender, duration of diabetes was collected through the medical records. All patients underwent a physical examination including height, weight, waist circumference, hip circumference, systolic blood pressures and diastolic blood pressure. The venous blood and urine samples were collected to measure SUA, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum creatinine, blood urea nitrogen and glycosylated hemoglobin. PrFT and PnFT were measured via ultrasonography. Pearson correlation test and linear regression analysis were used to analyze the association between PrFT and PnFT and SUA. RESULTS: We found that PrFT and PnFT increased according to the tertiles of SUA level (P = 0.001 and P = 0.009, respectively). In addition, the PrFT and PnFT were positively associated with SUA level (r = 0.25, P < 0.001, r = 0.23, P < 0.001, respectively). Moreover, this association was stronger in males, non-obesity patients and patients with normal renal function. In the multivariate analysis, the PrFT was independently associated with SUA level after adjusting confounding factors. CONCLUSIONS: The PrFT was independently associated with SUA level in patients with T2DM.

Assessment of serum dipeptidyl peptidase-IV levels in autoimmune thyroid disease.

OBJECTIVE: Decreased serum dipeptidyl peptidase-IV (sDPPIV) levels have been reported in patients with autoimmune diseases. However, few studies have analyzed the association between sDPPIV levels and autoimmune thyroid disease (AITD). This study aimed to evaluate the association between sDPPIV levels and three types of AITD: Graves' disease (GD), Graves' ophthalmopathy (GO), and Hashimoto's thyroiditis (HT). METHODS: Patients newly diagnosed with GD (n = 65), GO (n = 22), and HT (n = 27) and healthy individuals (n = 30) were recruited. Clinical characteristics and thyroid function data were collected. sDPPIV was measured using enzyme-linked immunosorbent assays. RESULTS: Compared with controls (786.3 ± 46.95), patients with GD and GO had significantly lower sDPPIV levels (662.2 ± 38.81 and 438.4 ± 31.78). Additionally, sDPPIV levels were negatively associated with antithyroid peroxidase antibody (r = -0.20) and antithyroglobulin antibody (r = -0.19), but there was no significant relationship between thyroid hormone and sDPPIV levels. GO cases were divided by proptosis with and without muscle thickening; sDPPIV levels were lower in the muscle thickening group than those in the without muscle thickening group. Logistic regression analysis showed that sDPPIV was negatively correlated with GO and GD. CONCLUSIONS: sDPPIV concentrations were abnormal in patients with GD and GO, and reduced sDPPIV expression may be involved in the progression of GO and GD.

Copper stress in grapevine: Consequences, responses, and a novel mitigation strategy using 5-aminolevulinic acid.

Improper application of copper-based fungicides has made copper stress critical in viticulture, necessitating the need to identify substances that can mitigate it. In this study, leaves of 'Shine Muscat' ('SM') grapevine seedlings were treated with CuSO4 solution (10 mM/L), CuSO4 + 5-aminolevulinic acid (ALA) (50 mg/L), and distilled water to explore the mitigation effect of ALA. Physiological assays demonstrated that ALA effectively reduced malondialdehyde accumulation and increased peroxidase and superoxide dismutase activities in grapevine leaves under copper stress. Copper ion absorption, transport pathways, chlorophyll metabolism pathways, photosynthetic system, and antioxidant pathways play key roles in ALA alleviated-copper stress. Moreover, expression changes in genes, such as CHLH, ALAD, RCA, and DHAR, play vital roles in these processes. Furthermore, abscisic acid reduction caused by NCED down-regulation and decreased naringenin, leucopelargonidin, and betaine contents confirmed the alleviating effect of ALA. Taken together, these results reveal how grapevine responds to copper stress and the alleviating effects of ALA, thus providing a novel means of alleviating copper stress in viticulture.

The Perirenal Fat Thickness Was Associated with Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.

Purpose: Obesity is an important risk factor for nonalcoholic fatty liver disease (NAFLD). Perirenal fat and paranephric fat were seldom studied in NAFLD. We aimed to explore the relationship between perirenal fat thickness (PrFT) and paranephric fat thickness (PnFT) and NAFLD in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A total of 493 diabetic patients including 231 NAFLD patients were enrolled in our study from September 2019 to December 2020. Patients with NAFLD were categorized into three subgroups according to the severity and fibrosis risk of NAFLD. Anthropometric indices and clinical characteristics were collected from clinical records. PrFT and PnFT were measured via ultrasound. Multivariate logistic regression analysis was used to assess the association between PrFT, PnFT and presence, severity and advanced fibrosis risk of NAFLD. Results: Compared with non-NAFLD patients, those with NAFLD had significantly higher PrFT and PnFT. The PrFT and PnFT were independently associated with presence of NAFLD and the PrFT was independently associated with the advanced fibrosis risk of NAFLD after adjusting confounding factors. Conclusion: The PrFT was independently associated with the presence and advanced fibrosis risk of NAFLD in patients with T2DM.

Progression-free survival at 3 years is a reliable surrogate for 5-year overall survival for patients suffering from locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Despite 3-year survival being used as a primary endpoint in some randomized controlled trials (RCTs), limited evidence supports the use of intermediate endpoints to evaluate the effect of new therapies in esophageal squamous cell cancer (ESCC). This study aimed to systematically evaluate progression-free survival at 3 years (3-year PFS) and overall survival (OS) among patients with ESCC. METHODS: We identified 528 patients newly diagnosed with locally advanced ESCC who received definitive radiotherapy. OS was compared with an age- and sex-matched general Chinese population using the standardized mortality ratio (SMR). Regression analysis was used to validate the correlation between PFS and OS using published data. RESULTS: The annual risk of progression decreased to 11.5% after 3 years. Patients who did not achieve 3-year PFS had a median postprogression survival (PPS) of 7.3 months, with a 5-year OS rate of 9.6% and a SMR of 15.0 (95% confidence interval [CI], 12.9-17.5). Conversely, the SMR for patients who achieved 3-year PFS was 0.9 (95% CI, 0.6-1.3). We observed a significant correlation between log hazard ratio (HR) (PFS) and log HR (OS) at the trial level (r = 0.89; 95% CI, 0.88-0.90). The strongest correlation was observed between 3-year PFS and 5-year OS in RCTs and retrospective studies. CONCLUSIONS: Patients exhibiting progression within 3 years experienced poor survival, whereas patients achieving 3-year PFS had excellent outcomes. Our study supports 3-year PFS as a reliable primary endpoint for study design and risk stratification in locally advanced ESCC.

Risk factors and prognosis for esophageal fistula in patients with esophageal squamous cell carcinoma during radiotherapy.

PURPOSE: To determine risk factors, treatment outcomes, and prognostic factors for esophageal fistula (EF) in patients with esophageal squamous cell carcinoma (ESCC) during radiotherapy. METHODS: Between 2010 and 2018, 109 patients with EF during radiotherapy were retrospectively collected. A controlled cohort including 416 patients who received definitive chemoradiotherapy without EF was used to compare risk factors and survival outcomes. Univariate and multivariate logistic regression analyses were performed to identify predictors of EF. Propensity score matching (PSM) was applied to adjust for potential confounding factors. RESULTS: Multivariate analysis demonstrated that sex, body mass index, alcohol history, esophageal ulceration, primary tumor length, T stage, and absolute lymphocyte count were independent risk factors for EF. After PSM, patients with EF showed remarkably worse prognosis than those without EF (median overall survival: 13.0 versus 20.5 months; P = 0.009). For patients with EF, serum albumin level (≥ 35 g/L), subsequent radiotherapy, and fistula closure were associated with significantly prolonged survival. In addition, esophageal-mediastinum fistula and subsequent radiotherapy were positive predictors for fistula closure. CONCLUSIONS: We identified risk factors for radiotherapy-related EF and its unfavorable prognosis in patients with ESCC. Of them, patients with serum albumin level of ≥ 35 g/L, subsequent radiotherapy after EF, and fistula closure had a more favorable survival.

Increased Arterial Stiffness as a Predictor for Onset and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus.

INTRODUCTION: Brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, has been demonstrated to be associated with type 2 diabetes mellitus (T2DM) and its vascular complications. This study was aimed at investigating the correlations of baPWV with both the presence and severity of diabetic retinopathy (DR) at baseline and at exploring the predictive role of baPWV in the new onset/progression of DR in the follow-up analysis. METHODS: The prospective cohort study recruited 2,473 Chinese patients with T2DM, of whom 663 participants were finally included in the follow-up analysis. The presence and grading of DR were performed by the modified Early Treatment Diabetic Retinopathy Study. Uni- or multivariate linear and logistic regression models and Cox proportional-hazards regression analysis were conducted. RESULTS: Of 2,473 patients with T2DM at baseline, 734 individuals were assessed to have DR and further categorized into 630 with non-sight-threatening DR (NSTDR) and 104 with STDR. In addition to the positive relationship between increased baPWV and the presence of DR, multinominal logistic regression analysis revealed that higher tertiles of baPWV were significantly related to the NSTDR (T2: OR = 1.62 (1.22, 2.15), p < 0.001, and T3: OR = 2.58 (1.86, 3.58), p < 0.001) and STDR group (T3: OR = 3.87 (1.87, 8.02), p < 0.001). During a follow-up (mean period of 16.4 months), 111 participants had new onset/progression of DR. The cox regressions showed that high baseline baPWV was correlated with increased risk of development/progression of DR (HR = 2.24, 95% CI (1.24, 4.03), p = 0.007, for T2 baPWV and HR = 2.90, 95% CI (1.49, 5.64), p = 0.002, for T3 baPWV) after adjustments for multiple factors. CONCLUSIONS: Our results demonstrated that baseline baPWV might be an independent predictor in new onset/worsening of DR, suggesting that increased arterial stiffness might be involved in the development of DR. Follow-up studies with a longer duration are needed.

Low serum levels of bone turnover markers are associated with perirenal fat thickness in patients with type 2 diabetes mellitus.

BACKGROUND: Obesity is known as a common risk factor for osteoporosis and type 2 diabetes mellitus (T2DM). Perirenal fat, surrounding the kidneys, has been reported to be unique in anatomy and biological functions. This study aimed to explore the relationship between perirenal fat and bone metabolism in patients with T2DM. METHODS: A total of 234 patients with T2DM were recruited from September 2019 to December 2019 in the cross-sectional study. The biochemical parameters and bone turnover markers (BTMs) were determined in all participants. Perirenal fat thickness (PrFT) was performed by ultrasounds via a duplex Doppler apparatus. Associations between PrFT and bone metabolism index were determined via correlation analysis and regression models. RESULTS: The PrFT was significantly correlated with ß-C-terminal telopeptides of type I collagen (ß-CTX) (r = -0.14, P < 0.036), parathyroid hormone (iPTH) (r = -0.18, P ≤ 0.006), and 25 hydroxyvitamin D (25-OH-D) (r = -0.14, P = 0.001). Multivariate analysis confirmed that the association of PrFT and ß-CTX (ß = -0.136, P = 0.042) was independent of other variables. CONCLUSION: This study showed a negative and independent association between PrFT and ß-CTX in subjects with T2DM, suggesting a possible role of PrFT in bone metabolism. Follow-up studies and further research are necessary to validate the associations and to elucidate the underlying mechanisms.

miR-181a, delivered by hypoxic PTC-secreted exosomes, inhibits DACT2 by downregulating MLL3, leading to YAP-VEGF-mediated angiogenesis.

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, and angiogenesis plays critical roles in its recurrence and metastasis. In this study, we investigated the effects of hypoxia-induced exosomal microRNA-181 (miR-181a) from PTC on tumor growth and angiogenesis. Thyroid-cancer-related differentially expressed miR-181a was identified by microarray-based analysis in the Gene Expression Omnibus (GEO) database. We validated that miR-181a was highly expressed in PTC cells and even more so in cells cultured under hypoxic conditions, which also augmented exosome secretion from PTC cells. Exosomes extracted from PTC cells with manipulated miR-181a and mixed-lineage leukemia 3 (MLL3) were subjected to normoxic or hypoxic conditions. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-181a inhibitor/mimic or small interfering RNA (siRNA)-MLL3 or treated with exosomes from hypoxic PTC cells. Hypoxic exosomal miR-181a delivery promoted proliferation and capillary-like network formation in HUVECs. Mechanistically, miR-181a targeted and inhibited MLL3. Furthermore, miR-181a downregulated DACT2 and upregulated YAP and vascular endothelial growth factor (VEGF). Further, hypoxic exosomal miR-181a induced angiogenesis and tumor growth in vivo, which was reversed by hypoxic exosomal miR-181a inhibitor. In conclusion, exosomal miR-181a from hypoxic PTC cells promotes tumor angiogenesis and growth through MLL3 and DACT2 downregulation, as well as VEGF upregulation.

Effect of Rhodococcus sp. pretreatment on cellulose hydrolysis of corn stalk.

Pretreatment can improve the hydrolysis efficiency of cellulose, in which biological pretreatment plays an important role. In the present study, we uncovered that Rhodococcus has the ability of lignin degradation, which can decompose lignin and serve as a carbon source to meet the needs of its own growth. We used Rhodococcus to pretreat the corn stalks and evaluate the effect on cellulose hydrolysis. The concentration of reducing sugar produced by the hydrolysis of corn stalk after pretreatment of Rhodococcus is 2.95 g/L. SEM imaging showed that Rhodococcus pretreatment resulted the surface of corn stalk to be no longer complete, some lamellar structures fall off, and leave obvious traces, and obvious delamination was found at the edge of the fault. AFM imaging showed that the pretreatment changed the lignin structure of the corn stalk material surface, resulting in a higher surface roughness of 9.37. These results indicated that Rhodococcus pretreatment can improve the saccharification efficiency of cellulose by removing lignin and increasing the surface roughness of the material.