Heat-Localized and Salt-Resistant 3D Hierarchical Porous Ceramic Platform for Efficient Solar-Driven Interfacial Evaporation.

Solar-driven interfacial evaporation (SDIE) is a highly promising approach to achieve sustainable desalination and tackle the global freshwater crisis. Despite advancements in this field, achieving balanced thermal localization and salt resistance remains a challenge. Herein, the study presents a 3D hierarchical porous ceramic platform for SDIE applications. The utilized alumina foam ceramics (AFCs) exhibit remarkable corrosion resistance and chemical stability, ensuring a prolonged operational lifespan in seawater or brines. The millimeter-scale air-filled pores in AFCs prevent thermal losses through conduction with bulk water, resulting in heat-localized interfaces. The hydrophilic nature of macroporous AFC skeletons facilitates rapid water replenishment on the evaporating surface for effective salt-resistant desalination. Benefiting from its self-radiation adsorption and side-assisted evaporation capabilities, the AFC-based evaporators exhibit high indoor evaporation rates of 2.99 and 3.54 kg m-2 h-1 under one-sided and three-sided illumination under 1.0 sun, respectively. The AFC-based evaporator maintains a high evaporation rate of ≈2.77 kg m-2 h-1 throughout the 21-day long-term test. Furthermore, it achieves a daily water productivity of ≈10.44 kg m-2 in outdoor operations. This work demonstrates the potential of 3D hierarchical porous ceramics in addressing the trade-off between heat localization and salt resistance, and contributes to the development of durable solar steam generators.

AdipoRon Ameliorates Synaptic Dysfunction and Inhibits tau Hyperphosphorylation through the AdipoR/AMPK/mTOR Pathway in T2DM Mice.

There is growing evidence showing that adiponectin (APN) can improve Alzheimer's disease(AD)-like pathological changes by improving insulin resistance. However, the role of AdipoRon (an Adiponectin receptor agonist) on synaptic plasticity and cognitive dysfunction in the early stages of type 2 diabetes mellitus(T2DM) remains unknown. In this study, we investigated the neuroprotective effect and the molecular mechanism underlying the effect of AdipoRon in T2DM mice. We found that AdipoRon significantly restored the cognitive deficits in T2DM mice, including shorter escape latency, more crossing times, increased distances, and percentage of time in the target quadrant. In addition, AdipoRon treatment up-regulated synaptic proteins (PSD95, SYN, GAP43, and SYP), increased the number of hippocampal synapses and attenuated synaptic damage, including the length, the number and the density of dendritic spines in CA1 and DG regions. Furthermore, AdipoRon attenuated Tau phosphorylation at multiple AD-related sites (p-tau 205, p-tau 396, p-tau 404) by promoting AdipoR expression and activating the AMPK/mTOR pathway. Our data suggests that AdipoRon exerts neuroprotective effects on the T2DM mice, which may be mediated by the activation of the AdipoR/AMPK/mTOR signaling pathway.

Predictors of mortality and poor outcome for patients with severe infectious encephalitis in the intensive care unit: a cross-sectional study.

BACKGROUND: There are few thorough studies assessing predictors of severe encephalitis, despite the poor prognosis and high mortality associated with severe encephalitis. The study aims to evaluate the clinical predictors of mortality and poor outcomes at hospital discharge in patients with severe infectious encephalitis in intensive care units. METHOD: In two Chinese hospitals, a retrospective cohort study comprising 209 patients in intensive care units suffering from severe infectious encephalitis was carried out. Univariate and multivariate logistic regression analyses were used to identify the factors predicting mortality in all patients and poor outcomes in all survivors with severe infectious encephalitis. RESULTS: In our cohort of 209 patients with severe encephalitis, 22 patients died, yielding a mortality rate of 10.5%. Cerebrospinal fluid pressure ≥ 400mmH2O (OR = 7.43), abnormal imaging (OR = 3.51), abnormal electroencephalogram (OR = 7.14), and number of rescues (OR = 1.12) were significantly associated with an increased risk of mortality in severe infectious encephalitis patients. Among the 187 survivors, 122 (65.2%) had favorable outcomes, defined as the modified Rankine Scale (mRS) score (0 ~ 3), and 65(34.8%) had poor outcomes (mRS scores 4 ~ 5). Age (OR = 1.02), number of rescues (OR = 1.43), and tubercular infection (OR = 10.77) were independent factors associated with poor outcomes at discharge in all survivors with severe infectious encephalitis. CONCLUSIONS: Multiple clinical, radiologic, and electrophysiological variables are independent predictive indicators for mortality and poor outcomes in patients with severe encephalitis in intensive care units. Identifying these outcome predictors early in patients with severe encephalitis may enable the implementation of appropriate medical treatment and help reduce mortality rates.

High-frequency dynamics of CO2 emission flux and its influencing factors in a subtropical karst groundwater-fed reservoir, south China.

Revealing the magnitude, dynamics, and influencing factors of CO2 emissions across the water-air interface in karst water with high frequency is crucial for accurately assessing the carbon budget in a karst environment. Due to the limitations of observation methods, the current research is still very insufficient. To solve the above problems and clarify the main influencing factors of CO2 emission in karst water, this study selected Dalongdong (DLD) Reservoir, located in the typical karst peak and valley area in southwest China, to carry out a multi-parameter high-frequency monitoring study from January to December 2021, and used the thin boundary model method to estimate the CO2 flux across the water-air interface (CF). The average annual flux of DLD reservoir is 84.48 mmol·(m2·h)-1, which represents a CO2 source overall. However, during the stratification period in August, there is a transient carbon sink due to negative CO2 emission. The alteration of thermal stratification in water is crucial in regulating the seasonal variation of CF. Meanwhile, the diurnal variation is significantly influenced by changes in hydrochemical parameters during the thermal stratification stage. Compared to low wind speeds (<3 m/s), high wind speeds (≥3 m/s) have a greater impact on the CO2 flux. Furthermore, high-frequency continuous data revealed that the reservoir triggered a CO2 pulse emission during the turnover process, primarily at night, leading to unusually high CO2 flux values. It is of great significance to monitor and reveal the process, flux, and control factors of CO2 flux in land water at a high-frequency strategy. They will help improve the accuracy of regional or watershed carbon budgets and clarify the role of global land water in the global carbon budget.

Aquatic photosynthetic carbon pump driven by periodic temperature variations affects dissolved inorganic carbon and hydrochemical characteristics in a groundwater-fed reservoir.

Under the influence of periodic temperature variations, biogeochemical cycling in water bodies is markedly affected by the periodic thermal stratification processes in subtropical reservoirs or lakes. In current studies, there is insufficient research on the influence and mechanism of dissolved inorganic carbon (DIC) distribution in karst carbon-rich groundwater-fed reservoirs under the coupled effects of thermal structure stratification and the biological carbon pump (BCP) effect. To address this issue, the Dalongdong (DLD) reservoir in the subtropical region of southern China was chosen as the site for long-term monitoring and research on relevant physicochemical parameters of water, DIC, and its stable carbon isotope (δ13CDIC), CO2 emission flux, as well as the reservoir's thermal stratification index. The results show that: (1) the DLD reservoir is a typical warm monomictic reservoir, which exhibits regular variations of mixing period-stratification period-mixing period on a yearly scale due to thermal structure changes; (2) DIC was consumed by aquatic photosynthetic organisms in the epilimnion during the stratification period, leading to a decrease in DIC concentration, partial pressure of CO2 (pCO2) and CO2 emission flux, and an increase in stable carbon isotope (δ13CDIC). During the mixing period, the trend was reversed; (3) During the thermal stratification, aquatic photosynthesis and water temperature were the primary factors controlling DIC variations in both the epilimnion and thermocline. Regarding the hypolimnion, calcite dissolution, organic matter decomposition, and water temperature were the dominant controlling factors. These results indicate that although carbon-rich karst groundwater provides a plentiful supply of DIC in the DLD reservoir, its availability is still influenced by variations in the reservoir's thermal structure and the metabolic processes of aquatic photosynthetic organisms. Therefore, to better estimate the regional carbon budget in a reservoir or lake, future studies should especially consider the combined effects of BCP and thermal structure variations on carbon variations.

Direct Alkylation of Quinoxalinones with Boracene-Based Alkylborate under Visible Light Irradiation.

An efficient synthesis of a variety of 3-alkyl quinoxalinones via C-H direct alkylation by photoredox catalysis between quinoxalinones and alkylborates is reported. A range of quinoxalinones was tolerated well. This visible-light photocatalysis reaction allows access to structurally diverse 3-alkyl quinoxalinones in good to excellent yields. The practicality of this protocol was demonstrated by the concise synthesis of a potential bioactive nonpeptide angiotensin II receptor antagonist.

Association between serum uric acid and homocysteine levels among adults in the United States: a cross-sectional study.

BACKGROUND: Many studies have shown that both elevated serum uric acid (SUA) levels and hyperhomocysteinemia are risk factors for atherosclerosis. However, the relationship between the two has not been thoroughly investigated. OBJECTIVE: This study aimed to explore the possible link between SUA levels and homocysteine (Hcy) levels. METHODS: In this cross-sectional study, 17,692 adults aged > 19 years in National Health and Nutrition Examination Survey from 1999 to 2006 were analyzed. Multivariable linear regression analysis was performed to assess the association between SUA and Hcy levels. In addition, smooth curve fitting (penalized spline method) and threshold effect analysis were performed. RESULTS: Multivariable linear analysis showed that Hcy levels increased by 0.48 µmol/L (ß = 0.48, 95%CI: 0.43-0.53) for every 1 mg/dL increase in SUA levels. We found a nonlinear relationship between SUA and Hcy levels. The results of threshold effect analysis showed that the inflection point for SUA levels was 7.1 mg/dL (ß = 0.29, 95% CI: 0.23-0.36 and ß = 1.05, 95% CI: 0.67-1.43 on the left and right sides of the inflection point, respectively). The p-values was less than 0.001 when using the log likelihood ratio test. This nonlinear relationship was also found in both sexes. The inflection point for SUA levels was 5.4 mg/dL in males and 7.3 mg/dL in females, respectively. CONCLUSIONS: This cross-sectional study showed that the SUA levels were positively correlated with Hcy levels. And we found a nonlinear relationship between SUA and Hcy levels.

MoS2 nanosheets embedded in α-FeOOH as an efficient cathode for enhanced MFC-electro-Fenton performance in wastewater treatment.

Microbial fuel cell-electro-Fenton system (MEF) has attracted attention due to refractory organic pollutants removal, where H2O2 is in-situ produced without external energy supply. Enhancement of H2O2 production and the activation of H2O2 to ·OH are the keys to improve degradation performance. Development of bifunctional catalytic cathode is a viable strategy. Herein, the α-FeOOH/MoS2 nanocomposites was fabricated by a novel facile hydrothermal method based on molybdenite-exfoliated MoS2 nanosheets suspension, which was used as modified cathode in a MEF system. The obtained α-FeOOH/1 wt%MoS2 cathode exhibited highest power density of 292.38 mW/m2, which was about 3.7 and 1.7 times higher than that of graphite plate and α-FeOOH, respectively. Doping of MoS2 nanosheets significantly enhanced electrocatalytic activity of the cathode and promoted in-situ H2O2 generation. Meanwhile, the exposed reductive Mo4+ on the surface of MoS2 could greatly facilitate the conversion cycle of Fe(III)/Fe(II), leading to the efficient activation of H2O2 into ·OH. The MEF with α-FeOOH/1 wt%MoS2 cathode exhibited excellent degradation and mineralization performance for MB, rhodamine B and tetracycline hydrochloride at optimized reaction condition. Furthermore, the MEF can simultaneously achieve MB oxidation and Cr(VI) reduction, and the corresponding removal ratio can reach up to 91.45% and 100%, respectively. Based on simple preparation method as well as recyclability and excellent catalytic property, the α-FeOOH/MoS2 composite catalyst is considered as a promising MEF cathode for efficient wastewater treatment.

A Multilevel Primary Care Intervention to Improve Follow-Up of Overdue Abnormal Cancer Screening Test Results: A Cluster Randomized Clinical Trial.

Importance: Realizing the benefits of cancer screening requires testing of eligible individuals and processes to ensure follow-up of abnormal results. Objective: To test interventions to improve timely follow-up of overdue abnormal breast, cervical, colorectal, and lung cancer screening results. Design, Setting, and Participants: Pragmatic, cluster randomized clinical trial conducted at 44 primary care practices within 3 health networks in the US enrolling patients with at least 1 abnormal cancer screening test result not yet followed up between August 24, 2020, and December 13, 2021. Intervention: Automated algorithms developed using data from electronic health records (EHRs) recommended follow-up actions and times for abnormal screening results. Primary care practices were randomized in a 1:1:1:1 ratio to (1) usual care, (2) EHR reminders, (3) EHR reminders and outreach (a patient letter was sent at week 2 and a phone call at week 4), or (4) EHR reminders, outreach, and navigation (a patient letter was sent at week 2 and a navigator outreach phone call at week 4). Patients, physicians, and practices were unblinded to treatment assignment. Main Outcomes and Measures: The primary outcome was completion of recommended follow-up within 120 days of study enrollment. The secondary outcomes included completion of recommended follow-up within 240 days of enrollment and completion of recommended follow-up within 120 days and 240 days for specific cancer types and levels of risk. Results: Among 11 980 patients (median age, 60 years [IQR, 52-69 years]; 64.8% were women; 83.3% were White; and 15.4% were insured through Medicaid) with an abnormal cancer screening test result for colorectal cancer (8245 patients [69%]), cervical cancer (2596 patients [22%]), breast cancer (1005 patients [8%]), or lung cancer (134 patients [1%]) and abnormal test results categorized as low risk (6082 patients [51%]), medium risk (3712 patients [31%]), or high risk (2186 patients [18%]), the adjusted proportion who completed recommended follow-up within 120 days was 31.4% in the EHR reminders, outreach, and navigation group (n = 3455), 31.0% in the EHR reminders and outreach group (n = 2569), 22.7% in the EHR reminders group (n = 3254), and 22.9% in the usual care group (n = 2702) (adjusted absolute difference for comparison of EHR reminders, outreach, and navigation group vs usual care, 8.5% [95% CI, 4.8%-12.0%], P < .001). The secondary outcomes showed similar results for completion of recommended follow-up within 240 days and by subgroups for cancer type and level of risk for the abnormal screening result. Conclusions and Relevance: A multilevel primary care intervention that included EHR reminders and patient outreach with or without patient navigation improved timely follow-up of overdue abnormal cancer screening test results for breast, cervical, colorectal, and lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03979495.

Effects of potential allelochemicals in a water extract of Abutilon theophrasti Medik. on germination and growth of Glycine max L., Triticum aestivum L., and Zea mays L.

BACKGROUND: Velvetleaf (Abutilon theophrasti Medik.), primarily a cropland weed, exerts adverse impacts on the productivity of various crops, including soybean (Glycine max L.), wheat (Triticum aestivum L.), and maize (Zea mays L.), by hindering their vegetative growth. However, the interference mechanism of velvetleaf on the three crops remains unclear. RESULTS: The inhibitory effect of velvetleaf water extract on the germination and growth of soybean, wheat, and maize was determined in pot experiments and field trials. Four phenolic acids were identified as allelochemicals: protocatechuic acid (PA), gallic acid (GA), chlorogenic acid (CHA), and vanillic acid (VA). These allelochemicals were detected in different parts (leaves, roots, and stems) of velvetleaf, and in the rhizosphere soil of tested crops over the range of 1.19-556.23 µm kg-1 . These allelochemicals were administered in approximate concentrations as in velvetleaf roots and rhizosphere soil, and their effects varied with crop species and velvetleaf parts. The allelochemicals generally had low-dose stimulation and high-dose inhibition effects on the growth of soybean, wheat, and maize. Furthermore, the biomass distribution of these crops was affected by allelochemicals in the soil. In field trials, the allelochemicals significantly (P < 0.05) inhibited the growth of all tested crops over the whole growth period, and PA showed a significant (P < 0.05) inhibitory effect on the yield of soybean, wheat, and maize. CONCLUSION: GA, PA, CHA, and VA in velvetleaf aqueous extracts were identified as allelochemicals that play an inhibitory role on three crops. © 2022 Society of Chemical Industry.

Association of low-level blood lead with plasma homocysteine in US children and adolescents.

Although research in adults has revealed a positive relationship between blood lead levels (BLLs) and homocysteine (Hcy) levels in adults, few studies have investigated this relationship in children and adolescents. We evaluated the relationship between lowlevel blood lead and Hcy levels in US children and adolescents. A total of 8,313 children and adolescents aged 8-19 participated in this study via the National Health and Nutrition Examination Survey 1999-2006. Multivariable linear regression analyses were performed to examine the association between continuous BLLs and Hcy levels. The dose-dependent relationship between continuous BLLs and Hcy levels was analyzed using smooth curve fitting. The average age of participants was 14.1 ± 3.3 years (50.3% male). The mean values of BLLs and Hcy levels were 1.45 µg/dL and 5.77 µmol/L, respectively. In a multivariable adjusted model, an increase in 1.0 µg/dL of BLLs was associated with an elevation of 0.06 µmol/L in Hcy levels (ß = 0.06, 95%CI:0.02-0.10, P = 0.001). A linear relationship between BLLs and Hcy levels was discovered using smooth curve fitting (P non-linearity = 0.464). The relationship between low-level blood lead and Hcy levels was stronger on participants with lower serum folate levels (P for interaction = 0.002). Low BLLs were positively associated with plasma Hcy levels in children and adolescents, which varies depending on the levels of folate, vitamin B, and dietary supplements involved in Hcy metabolism.

Decision quality and regret with treatment decisions in women with breast cancer: Pre-operative breast MRI and breast density.

PURPOSE: We evaluated self-report of decision quality and regret with breast cancer surgical treatment by pre-operative breast MRI use in women recently diagnosed with breast cancer. METHODS: We conducted a survey with 957 women aged 18 + with stage 0-III breast cancer identified in the Breast Cancer Surveillance Consortium. Participants self-reported receipt of pre-operative breast MRI. Primary outcomes were process measures in the Breast Cancer Surgery Decision Quality Instrument (BCS-DQI) (continuous outcome) and Decision Regret Scale (dichotomized outcome as any/none). Generalized estimating equations with linear and logit link were used to estimate adjusted associations between breast MRI and primary outcomes. All analyses were also stratified by breast density. RESULTS: Survey participation rate was 27.9% (957/3430). Study population was primarily > 60 years, White, college educated, and diagnosed with early-stage breast cancer. Pre-operative breast MRI was reported in 46% of women. A higher proportion of women who were younger age (< 50 years), commercially insured, and self-detected their breast cancer reported pre-operative breast MRI use. In adjusted analysis, pre-operative breast MRI use compared with no use was associated with a small but statistically significantly higher decision quality scores (69.5 vs 64.7, p-value = 0.043). Decision regret did not significantly differ in women who reported pre-operative breast MRI use compared with no use (54.2% v. 48.7%, respectively, p-value = 0.11). Study results did not vary when stratified by breast density for either primary outcome. CONCLUSIONS AND RELEVANCE: Breast MRI use in the diagnostic work-up of breast cancer does not negatively alter women's perceptions of surgical treatment decisions in early survivorship. CLINICAL TRIALS REGISTRATION NUMBER: NCT03029286.

Circ_0058063 contributes to cisplatin-resistance of bladder cancer cells by upregulating B2M through acting as RNA sponges for miR-335-5p.

Bladder cancer (BC) is one of the most common malignant tumors of the urinary system, and cisplatin (CDDP) is a critical chemical drug for the treatment of BC. However, CDDP-resistance seriously limits the therapeutic efficacy of this drug for clinical utilization. Thus, identification of pivotal molecule targets that regulate CDDP-resistance in BC become urgent and necessary. In this study, we firstly identified a novel BC-associated circular RNA circ_0058063 that participates in the regulation of CDDP-resistance in BC. Specifically, circ_0058063 was significantly overexpressed in CDDP-resistant tissue and cells, in contrast with the corresponding CDDP-sensitive counterparts. Further loss-of-function experiments validated that downregulation of circ_0058063 suppressed cell proliferation and tumor growth, whereas induced cell apoptosis in the CDDP-resistant BC cells in vitro and in vivo. In addition, we disclosed that circ_0058063 acts as a sponge for miR-335-5p to positively regulate B2M expression, and further rescuing experiments verified that the enhancing effects of sh-circ_0058063 on CDDP-sensitivity in the CDDP-resistant BC cells were abrogated by silencing miR-335-5p. Taken together, our results demonstrated that circ_0058063 contributed to CDDP resistance of bladder cancer cells via sponging miR-335-5p, and B2M might be the downstream effector gene. This study firstly evidenced that targeting circ_0058063 might be an effective strategy to improve CDDP-sensitivity in BC.

Synthesis of [1,2,3]Triazolo-[1,5-a]quinoxalin-4(5H)-ones through Photoredox-Catalyzed [3 + 2] Cyclization Reactions with Hypervalent Iodine(III) Reagents.

An efficient synthesis of a variety of [1,2,3]triazolo-[1,5-a]quinoxalin-4(5H)-ones via a [3 + 2] cyclization reaction by photoredox catalysis between quinoxalinones and hypervalent iodine(III) reagents is reported. A range of quinoxalinones and hypervalent iodine(III) reagents were tolerated well. This cyclization reaction allows access to structurally diverse [1,2,3]triazolo-[1,5-a]quinoxalin-4(5H)-ones in moderate to good yields.

Association between hyperhomocysteinaemia and the risk of all-cause and cause-specific mortality among adults in the USA.

Hyperhomocysteinaemia (HHcy) is associated with all-cause mortality in some disease states. However, the correlation between HHcy and the risk of mortality in the general population has rarely been researched. We aimed to evaluate the association between HHcy and all-cause and cause-specific mortality among adults in the USA. This study analysed data from the National Health and Nutrition Examination Survey database (1999-2002 survey cycle). A multivariable Cox regression model was built to evaluate the correlation between HHcy and all-cause and cause-specific mortality. Smooth curve fitting was used to analyse their dose-dependent relationship. A total of 8442 adults aged 18-70 years were included in this study. After a median follow-up period of 14·7 years, 1007 (11·9 %) deaths occurred including 197 CVD-related deaths, 255 cancer-related deaths and fifty-eight respiratory disease deaths. The participants with HHcy had a 93 % increased risk of all-cause mortality (hazard ratio (HR) 1·93; 95 % CI (1·48, 2·51)), 160 % increased risk of CVD mortality (HR 2·60; 95 % CI (1·52, 4·45)) and 82 % increased risk of cancer mortality (HR 1·82; 95 % CI (1·03, 3·21)) compared with those without HHcy. For unmeasured confounding, E-value analysis proved to be robust. In conclusion, HHcy was associated with high risk of all-cause and cause-specific (CVD, cancer) mortality among adults aged below 70 years.

Severe contralateral carotid stenosis or occlusion drive 30-day risk after carotid endarterectomy.

OBJECTIVES: The significant effects on the treatment of severe carotid stenosis by carotid endarterectomy have been widely recognized. However, it is controversial whether patients with severe contralateral carotid stenosis or occlusion (SCSO) can benefit from carotid endarterectomy surgery. This study aimed to estimate the SCSO effects on early outcomes after carotid endarterectomy with selective shunting. METHODS: Between August 2011 and October 2019, a total of 617 patients who underwent carotid endarterectomy with selective shunting were analyzed. SCSO was defined as >70% luminal narrowing of the contralateral extracranial carotid stenosis or occlusion. Of these patients, 116 were categorized into an SCSO group while the rest were assigned to the non-SCSO group. Primary study outcomes were the occurrence of major adverse events, defined as stroke, all-cause mortality, and myocardial infarction during the perioperative period after carotid endarterectomy. Traditional multivariable logistic regression model and logistic regression model adjusted for propensity scores were used to estimate the SCSO effects on primary outcomes. Interaction and stratified analyses were conducted according to age, sex, comorbidities (hypertension, diabetes), preoperative neurological deficit, preoperative symptoms, and shunt use. RESULTS: Mean age was 68.5 ± 9.2 years (86.1% men). Overall major adverse events rate within 30 days was 2.5%. Major adverse events rates in SCSO and non-SCSO groups were 9.5% and 1.6%, respectively. This difference was statistically significant (p < 0.001). In multivariable regression analysis, patients with SCSO had a higher risk of major adverse events (non-SCSO vs. SCSO: aOR 5.05 [95% CI, 1.78-14.55]). In 342 propensity score matched patients, results were consistent (propensity score: aOR, 3.78 [95% CI, 1.13-12.64]). CONCLUSIONS: SCSO is an independent predictor of 30-day major adverse events. Whether these patients with SCSO are suitable for carotid endarterectomy should be carefully considered.

[Mechanism of Euodiae Fructus stir-fried with water decoction of Coptidis Rhizoma in treatment of chronic colitis based on UPLC-Q-TOF-MS, network pharmacology and experimental verification].

To elucidate the mechanism of Euodiae Fructus stir-fried with water decoction of Coptidis Rhizoma in the treatment of chronic colitis, this study employed ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, and experimental verification to predict the involved targets and signaling pathways. The chronic colitis mouse model was constructed to verify the core targets. A total of 48 compounds in the herbal medicine were identified by UPLC-Q-TOF-MS. SwissTargetPrediction was used to screen the potential active components and drug targets. GeneCards, OMIM, PharmGKB, and TDD were used to search for the disease targets. A total of 31 active ingredients, 453 targets of the herbal medicine, and 3 960 targets of chronic colitis were obtained. The common targets shared by the herbal medicine and chronic colitis were introduced into STRING to construct the protein-protein interaction(PPI) network, and CytoNCA plug-in was used to screen the key targets. A total of 90 key targets were obtained, and the key active components included isorhamnetin, quercetin, limonin, and oxyberberine. GO annotation and KEGG pathway enrichment for the key targets were carried out via DAVID. The targets were mainly involved in the positive regulation of protein phosphorylation, positive regulation of nitric oxide biosynthetic process, and negative regulation of apoptotic process. The medicine may treat chronic colitis through PI3 K-Akt, VEGF, HIF-1, and TNF signaling pathways. A mouse model of chronic colitis was established and then treated with Euodiae Fructus stir-fried with the water decoction of Coptidis Rhizoma. The experimental results demonstrated that the medicine can alleviate the pathological damage of colon, significantly reduce the levels of IL-1ß, IL-6, and TNF-α, inhibit the activation of PI3 K/Akt pathway, and down-regulate the expression of VEGFA in the treatment of chronic colitis.

LINC00242/miR-1-3p/G6PD axis regulates Warburg effect and affects gastric cancer proliferation and apoptosis.

BACKGROUND: Reprogrammed glucose metabolism of enhanced Warburg effect (or aerobic glycolysis) is considered as a hallmark of cancer. Long non-coding RNAs (lncRNAs) have been certified to play a crucial role in tumor progression. The current study aims to inquire into the potential regulatory mechanism of long intergenic non-protein coding RNA 242 (LINC00242) on aerobic glycolysis in gastric cancer. METHOD: LINC00242, miR-1-3p and G6PD expression levels in gastric cancer tissues and cells were determined by qRT-PCR. Cell apoptosis or viability were examined by Flow cytometry or MTT assay. Western blot was utilized to investigate G6PD protein expression levels. Immunohistochemical (IHC) and hematoxylin and eosin (H&E) staining were used for histopathological detection. The targeted relationship between LINC00242 or G6PD and miR-1-3p was verified by luciferase reporter gene assay. Nude mouse xenograft was utilized to detect tumor formation in vivo. RESULT: LINC00242 and G6PD was high-expressed in gastric cancer tissues and cells, and LINC00242 is positively correlated with G6PD. Silencing of LINC00242 or G6PD within gastric cancer cells prominently inhibited cell proliferation and aerobic glycolysis in vitro and relieved the tumorigenesis of gastric cancer in vivo. miR-1-3p was predicted to directly target both LINC00242 and G6PD. Overexpression of miR-1-3p suppressed gastric cancer cells proliferation and aerobic glycolysis. LINC00242 competitively combined miR-1-3p, therefore relieving miR-1-3p-mediated suppression on G6PD. CONCLUSION: LINC00242 plays a stimulative role in gastric cancer aerobic glycolysis via regulation of miR-1-3p/ G6PD axis, therefore affecting gastric cancer cell proliferation.

Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Pathogenic variants of the DPYD gene are strongly associated with grade ≥3 toxicity during fluoropyrimidine chemotherapy. We conducted a systematic review and meta-analysis to estimate the risk of treatment-related death associated with DPYD gene variants. MATERIALS AND METHODS: We searched for reports published prior to September 17, 2020, that described patients receiving standard-dose fluoropyrimidine chemotherapy (5-fluorouracil or capecitabine) who had baseline testing for at least one of four pathogenic DPYD variants (c.1129-5923C>G [HapB3], c.1679T>G [*13], c.1905+1G>A [*2A], and c.2846A>T) and were assessed for toxicity. Two reviewers assessed studies for inclusion and extracted study-level data. The primary outcome was the relative risk of treatment-related mortality for DPYD variant carriers versus noncarriers; we performed data synthesis using a Mantel-Haenszel fixed effects model. RESULTS: Of the 2,923 references screened, 35 studies involving 13,929 patients were included. DPYD variants (heterozygous or homozygous) were identified in 566 patients (4.1%). There were 14 treatment-related deaths in 13,363 patients without identified DPYD variants (treatment-related mortality, 0.1%; 95% confidence interval [CI], 0.1-0.2) and 13 treatment-related deaths in 566 patients with any of the four DPYD variants (treatment-related mortality, 2.3%; 95% CI, 1.3%-3.9%). Carriers of pathogenic DPYD gene variants had a 25.6 times increased risk of treatment-related death (95% CI, 12.1-53.9; p < .001). After excluding carriers of the more common but less deleterious c.1129-5923C>G variant, carriers of c.1679T>G, c.1905+1G>A, and/or c.2846A>T had treatment-related mortality of 3.7%. CONCLUSION: Patients with pathogenic DPYD gene variants who receive standard-dose fluoropyrimidine chemotherapy have greatly increased risk for treatment-related death. IMPLICATIONS FOR PRACTICE: The syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency is an uncommon but well-described cause of severe toxicity related to fluoropyrimidine chemotherapy agents (5-fluorouracil and capecitabine). Patients with latent DPD deficiency can be identified preemptively with genotyping of the DPYD gene, or with measurement of the plasma uracil concentration. In this systematic review and meta-analysis, the authors study the rare outcome of treatment-related death after fluoropyrimidine chemotherapy. DPYD gene variants associated with DPD deficiency were linked to a 25.6 times increased risk of fluoropyrimidine-related mortality. These findings support the clinical utility of DPYD genotyping as a screening test for DPD deficiency.

Poor Neurological Deficit Was an Independent 30-day Risk Factor in Symptomatic Carotid Stenosis after CEA with Selective Shunting.

BACKGROUND: Carotid endarterectomy (CEA) prevents the occurrence of stroke in the future, although its efficacy depends on the detection and control of high perioperative risk factors. We aimed to analyze the association between preoperative neurological deficit and the 30-day risk of major adverse cardiovascular events (MACEs) in CEA with selective shunting for symptomatic carotid stenosis. METHODS: We assessed 653 patients who underwent CEA with selective shunting for symptomatic carotid stenosis between August 2011 and August 2019. The primary outcomes of the study were the occurrence of MACEs, defined as stroke (ischemic stroke or cerebral hemorrhage), all-cause mortality, and myocardial infarction during the perioperative period after CEA. Baseline patient characteristics were analyzed to identify factors associated with perioperative (<30 days) MACEs. Multivariable logistic regression models were used to estimate the association between preoperative modified Rankin Scale (mRS) and the 30-day risk of MACEs. Interaction and stratified analyses were conducted according to age, drinking, history of hypertension and coronary artery disease, and surgical side. RESULTS: The mean age of patients was 68.7 ± 9.1 years, and 86.4% were men. The 30-day MACEs rate was 2.5%. In univariate logistic regression, histories of coronary artery disease (odds ratio (OR), 2.57 [95% confidence interval (CI), 1.04-6.34]), a severe contralateral carotid stenosis or occlusion (OR, 4.52 [95% CI, 1.84-11.11]), and a poor neurological deficit (mRS ≥ 3 versus mRS < 3: OR, 3.78 [95% CI, 1.21-11.82]) were associated with higher primary outcome rates. A history of hypertension did not increase the risk of MACEs (OR, 0.37 [95% CI, 0.15-0.89]). In the multivariable regression analysis, poor neurological deficit was associated with a higher risk of the MACEs within 30 days (mRS ≥ 3 versus mRS < 3: 11.1% vs. 2.0%, adjusted OR 5.70 [95% CI, 1.50-21.60]). The interaction analysis revealed no interactive role in the association between neurological deficit and 30-day risk of MACEs. CONCLUSIONS: Poor neurological deficit was an independent risk factor associated with the 30-day risk of MACEs in symptomatic patients who underwent CEA with selective shunting. Our findings may provide guidance to surgeons when treating patients with poor neurological deficit. The decision to perform surgery should be made after careful consideration.