Threshold of hyperglycaemia associated with mortality in critically ill patients: a multicentre, prospective, observational study using continuous glucose monitoring.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.

Resurgence and advancement of photochemical hydrogen atom transfer processes in selective alkane functionalizations.

The selective functionalization of alkanes has long been recognized as a prominent challenge and an arduous task in organic synthesis. Hydrogen atom transfer (HAT) processes enable the direct generation of reactive alkyl radicals from feedstock alkanes and have been successfully employed in industrial applications such as the methane chlorination process, etc. Nevertheless, challenges in the regulation of radical generation and reaction pathways have created substantial obstacles in the development of diversified alkane functionalizations. In recent years, the application of photoredox catalysis has provided exciting opportunities for alkane C-H functionalization under extremely mild conditions to trigger HAT processes and achieve radical-mediated functionalizations in a more selective manner. Considerable efforts have been devoted to building more efficient and cost-effective photocatalytic systems for sustainable transformations. In this perspective, we highlight the recent development of photocatalytic systems and provide our views on current challenges and future opportunities in this field.

RNA-sequencing approach for exploring the protective mechanisms of dexmedetomidine on pancreatic injury in severe acute pancreatitis.

Background: Severe acute pancreatitis (SAP) is a severe form of acute pancreatitis with the potential to cause life-threatening complications. Patients with acute SAP require surgical intervention and are admitted to the intensive care unit for non-invasive ventilation. Dexmedetomidine (Dex) is currently used by intensive care clinicians and anaesthesiologists as an adjunctive sedative. Therefore, the clinical availability of Dex makes it easier to implement in SAP treatment than developing new drugs. Methods: Randomly dividing thirty rats into sham-operated (Sham), SAP, and Dex groups. The severity of pancreatic tissue injury in each rat was assessed by Hematoxylin and eosin (HE) staining. Serum amylase activity and inflammatory factor levels were measured using commercially available kits. The expressions of necroptosis-related proteins, myeloperoxidase (MPO), CD68, and 4-hydroxy-trans-2-nonenal (HNE) were detected using immunohistochemistry (IHC). Transferase-mediated dUTP nick-end labeling (TUNEL) staining was utilized to identify pancreatic acinar cell apoptosis. The subcellular organelle structure of pancreatic acinar cells was observed using transmission electron microscopy. The regulatory effect of Dex on the gene expression profile of SAP rat pancreas tissue was investigated using RNA sequencing. We screened for differentially expressed genes (DEGs). Quantitative real-time PCR (qRT-PCR) measured critical DEG mRNA expression in rat pancreatic tissues. Results: Dex attenuated SAP-induced pancreatic injury, infiltration of neutrophils and macrophages, and oxidative stress. Dex inhibited the expression of necroptosis-associated proteins RIPK1, RIPK3, and MLKL and alleviated apoptosis in acinar cells. Dex also mitigated the structural damage caused by SAP to mitochondria and endoplasmic reticulum. Dex inhibited SAP-induced 473 DEGs, as determined by RNA sequencing. Dex may regulate SAP-induced inflammatory response and tissue damage by inhibiting the toll-like receptor/nuclear factor κB (TLR/NF-κB) signaling pathway and neutrophil extracellular trap formation. Conclusion: This study elucidated the remarkable effect of Dex against SAP and investigated the potential mechanism of action, providing an experimental base for the future clinical application of Dex in the treatment of SAP.

Cadmium Absorption in Various Genotypes of Rice under Cadmium Stress.

Cadmium (Cd) is a kind of heavy metal. Cadmium pollution in paddy fields will accumulate a large amount of cadmium in rice, which will affect the growth and development of rice. In addition, long-term consumption of rice contaminated with Cd can harm human health. In this study, four rice varieties with high Cd accumulation (S4699, TLY619, JHY1586, QLY155) and four varieties with low Cd accumulation (YY4949, CYJ-7, G8YXSM, MXZ-2) were screened through field experiments for two consecutive years (2021 and 2022) and differences in antioxidant enzyme systems and expression of genes in their organs were analyzed. The total Cd content showed as follows: indica rice > japonica rice, high-Cd-accumulation variety > low-Cd-accumulation variety, and the total Cd content of each organ of rice showed root > stem > leaf > grain. The results of the antioxidant enzyme system showed that the contents of malondialdehyde (MAD), reduced glutathione (GSH), oxidized glutathione (GSSH), and peroxidase (POD) were positively correlated with the total Cd content in rice, and superoxide dismutase (SOD) showed the opposite performance in the leaves. There was no correlation between catalase (CAT) and Cd content, but CAT content decreased in leaves and grains and increased in roots and stems with increasing fertility. Based on this study, RT-qPCR was used to further validate the expression of Cd-uptake-related genes in different rice varieties. It was found that high expression of OsHMA3, OsCCX2, OsNRAMP5, and OsHMA9 genes promoted Cd uptake and translocation in rice, especially in rice varieties with high Cd accumulation. The high expression of OslRT1, OsPCR1, and OsMTP1 genes hindered Cd uptake by rice plants, which was especially evident in low-accumulating Cd rice varieties. These results provide an important theoretical reference and scientific basis for our in-depth study and understanding of the mechanism of cadmium stress tolerance in rice.

Knockdown of lncRNA-ASLNC12002 alleviates epithelial-mesenchymal transition of type II alveolar epithelial cells in sepsis-induced acute respiratory distress syndrome.

Patients with sepsis-induced acute respiratory distress syndrome (ARDS) have higher mortality and poor prognosis than pneumonia-induced ARDS. Pulmonary fibrosis is an irreversible accumulation of connective tissue in the interstitium of the lung and closely associated with the epithelial-mesenchymal transition (EMT) of type II alveolar epithelial cells (AECIIs). Therefore, it is undoubtedly worth studying whether the EMT of AECIIs in sepsis-induced ARDS patients is different from that in patients with pneumonia-induced ARDS in the regulatory mechanism. Here, we will report for the first time that an lncRNA-ASLNC12002 is highly expressed in AECIIs of patients with sepsis-induced pneumonia and promotes EMT in AECIIs. The research results showed that the expression of ASLNC12002 in AECIIs derived from patients with sepsis-induced ARDS is significantly higher than that in normal people and pneumonia-induced ARDS patients. Mechanism research showed that ASLNC12002 can cause the inactivation of the anti-EMT pathway NR2F2/miR128-3p/Snail1 by acting as the sponge of miR128-3p. Functional experiments showed that targeted silencing of ASLNC12002 could effectively inhibit EMT progression in AECIIs of patients with sepsis-induced pneumonia by restoring NR2F2/miR128-3p/Snail1 pathway. In a word, our study shows for the first time that the inactivation of NR2F2/miR128-3p/Snail1 pathway caused by the enhanced expression of ASLNC12002 is the direct reason why AECIIs in sepsis-induced ARDS patients are prone to get EMT progress. ASLNC12002 has the potential to become a biological target for the prevention and treatment of pulmonary fibrosis in patients with sepsis-induced ARDS. At the same time, the expectation that ASLNC12002 and its related products may be used as clinical markers for the evaluation of early pulmonary fibrosis in ARDS patients should not be ignored.

Focusing on the Role of Natural Products in Overcoming Cancer Drug Resistance: An Autophagy-Based Perspective.

Autophagy is a critical cellular adaptive response in tumor formation. Nutritional deficiency and hypoxia exacerbate autophagic flux in established malignancies, promoting tumor cell proliferation, migration, metastasis, and resistance to therapeutic interventions. Pro-survival autophagy inhibition may be a promising treatment option for advanced cancer. Furthermore, excessive or persistent autophagy is cytotoxic, resulting in tumor cell death. Targeted autophagy activation has also shown significant promise in the fight against tumor drug resistance. Several research groups have examined the ability of natural products (NPs) such as alkaloids, terpenoids, polyphenols, and anthraquinones to serve as autophagy inhibitors or activators. The data support the capacity of NPs that promote lethal autophagy or inhibit pro-survival autophagy from being employed against tumor drug resistance. This paper discusses the potential applications of NPs that regulate autophagy in the fight against tumor drug resistance, some limitations of the current studies, and future research needs and priorities.

Accuracy of the intermittently scanned continuous glucose monitoring system in critically ill patients: a prospective, multicenter, observational study.

OBJECTIVE: Continuous glucose monitoring (CGM) has the potential to improve glucose control in the intensive care unit (ICU) setting. We sought to evaluate the accuracy of the intermittently scanned CGM (isCGM) system in critically ill patients. RESEARCH DESIGN AND METHODS: Adult patients were consecutively enrolled from three ICUs from August 2020 to January 2021. The performance of FreeStyle Libre Pro was evaluated against the venous blood glucose samples as a reference. Numerical accuracy was examined by the mean absolute relative difference (MARD), the Bland-Altman analysis, and the International Organization for Standardization criteria. Clinical accuracy was assessed by performing the Clarke and consensus error grid analysis. RESULTS: A total of 122 patients were included and 3416 matched glucose pairs were analyzed. The overall MARD was 18.0%, and the highest MARD (33.1%) was observed in the hypoglycemic range (<70 mg/dL). The Bland-Altman analysis revealed a mean bias of -11.7 mg/dL, with the 95% limits of agreement of -73.0 to 49.5 mg/dL. The percentages of isCGM glucose values within ±15%/15, ±20%/20, and ±30%/30 mg/dL were 49.8%, 64.7%, and 84.5%, respectively. The Clarke and consensus error grid analysis showed acceptable clinical accuracy with 98.5% and 98.8% of glucose values falling into zones A and B. CONCLUSIONS: Our study demonstrated suboptimal overall accuracy of isCGM for critically ill patients. Whether the adjunctive use of isCGM could improve glucose management and health outcomes in the critically ill needs further investigation. CLINICAL TRIAL REGISTRATION: ChiCTR2100042036, Chinese Clinical Trial Registry.

Mechanism of Fuel Gas Denitration on the KOH-Activated Biochar Surface.

Previous experimental studies have found that biochar after KOH activation can significantly improve the efficiency of NO removal, but its mechanism is still unclear. To investigate the reaction mechanism of this denitration reaction, in this study, the aromatic benzene ring structure was used to simulate the surface of biochar, and the reaction process was calculated by density functional theory (DFT). The reaction process on the pristine biochar was simulated for comparison. The results indicated that there were two potential mechanisms for NO removal and had the identical rate-determining step, with an activation energy of 161.5 kJ/mol. Second, the influence by K coadsorbates on the NO reduction mechanism was studied. The adsorption by K atoms does not alter the last reaction step, but it was found to reduce the activation energy of this rate-determining step (to 129.3 kJ/mol). A third type of reaction mechanism was theoretically studied for the situation with both K and OH coadsorbates on the biochar surface. The reaction mechanism changed with an increase in the overall reaction rate by increasing the pre-exponential factor. In summary, the rate-determining activation energy for the heterogeneous NO reduction was found to decrease in the following order: 161.5 kJ/mol (pristine biochar) → 129.3 kJ/mol (activation by K adsorbates) → 125.8 kJ/mol (activation by both K and OH adsorbates); the pre-exponential factor was found to change in the following order: 6.23 × 1014 s-1 (pristine biochar) → 4.86 × 1014 s-1 (activation by K adsorbates) → 8.89 × 1014 s-1 (activation by K and OH adsorbates). Hence, the role by K adsorbates is primarily to reduce the rate-determining activation energy, while the OH group adsorbate increases the number of active sites on the surface of biochar.

Alkoxy Radicals See the Light: New Paradigms of Photochemical Synthesis.

Alkoxy radicals are highly reactive species that have long been recognized as versatile intermediates in organic synthesis. However, their development has long been impeded due to a lack of convenient methods for their generation. Thanks to advances in photoredox catalysis, enabling facile access to alkoxy radicals from bench-stable precursors and free alcohols under mild conditions, research interest in this field has been renewed. This review comprehensively summarizes the recent progress in alkoxy radical-mediated transformations under visible light irradiation. Elementary steps for alkoxy radical generation from either radical precursors or free alcohols are central to reaction development; thus, each section is categorized and discussed accordingly. Throughout this review, we have focused on the different mechanisms of alkoxy radical generation as well as their impact on synthetic utilizations. Notably, the catalytic generation of alkoxy radicals from abundant alcohols is still in the early stage, providing intriguing opportunities to exploit alkoxy radicals for diverse synthetic paradigms.

Strategies for indica rice adapted to high-temperature stress in the middle and lower reaches of the Yangtze River.

High temperatures caused by climate warming severely affect the grain yield and quality of rice. In this study, the rice cultivars Longliangyou Huazhan (LLYHZ) and Quanliangyou 2118 (QLY2118) were selected as the experimental materials for investigation of an optimal cultivation system under high-temperature treatment. In addition, the heat-resistant cultivar Huanghuazhan (HHZ) and heat-sensitive cultivar Huiliangyou 858 (HLY858) were chosen as the experimental materials to study the effects of exogenous plant growth regulators on heat stress responses under high-temperature treatment. The results showed that mechanical transplanting of carpet seedlings and delayed sowing effectively increased the leaf area index and reduced the canopy temperature of LLYHZ and QLY2118. Furthermore, carpet seedling mechanical transplantation and delayed sowing improved grain yield and quality. Spray application of five plant growth regulators revealed that brassinolide and salicylic acid had the strongest effects on significantly improving antioxidant enzyme activities in the panicle, which would reduce the damage caused by the accumulation of reactive oxygen species and enhance plant tolerance of high-temperature stress. In addition, brassinolide and salicylic acid enhanced the percentage of anther dehiscence and percentage seed set. In this study, a set of simplified eco-friendly cultivation techniques for single-season indica rice adaptation to high-temperature stress was established. These results will be of great importance in alleviating the effects of high-temperature stress on rice production.

[Trend in the prevalence of prostate cancer in Shihezi, Xinjiang from 2009 to 2017].

OBJECTIVE: To analyze the trend in the prevalence and mortality of prostate cancer in Shihezi, Xinjiang from 2009 to 2017 and provide some evidence for the prevention and control of the malignance. METHODS: We collected the data on the cancer registries in the Shihezi area between 2009 and 2017, calculated the incidence and mortality rates of prostate cancer, and analyzed the annual percent change (APC) and prevalence trend of the disease. RESULTS: The crude incidence rate, age-standardized incidence rate by Chinese standard population (ASIRC), age-standardized incidence rate by world standard population (ASIRW) and cumulative incidence rate of prostate cancer (in 0－74-year-olds) in Shihezi between 2009 and 2017 were 16.94, 10.33, 8.98 and 2.29 per 100 000, respectively. The crude mortality rate, age-standardized mortality rate by Chinese standard population (ASMRC), age-standardized mortality rate by world standard population (ASMRW) and cumulative incidence rate (in 0－74-year-olds) were 9.03, 5.39 and 4.72 and 0.49 per 100 000, respectively. Both the incidence and mortality rates showed an increasing trend from 2009 to 2017, with an APC of 16.69% (P < 0.05) and 19.71% (P < 0.05), respectively. From 2011 to 2017, the increase rates of incidence and mortality of prostate cancer in the >60-year-olds were 86.20% and 89.30%, with the peak values shifted from the 70－74 to the 80－84 years old males. CONCLUSIONS: The incidence and mortality of prostate cancer in Shihezi showed an increasing trend from 2009 to 2017, chiefly in the males aged over 60 years, with the peak value moving towards an older age.