Natural Compound-Rhein and PROTACs Unleash Potent VEGFR-2 Degraders.

VEGFR-2 is a prominent therapeutic target in antitumor drug research to block tumor angiogenesis. This study focused on the synthesis and optimization of PROTACs based on the natural product rhein, resulting in the successful synthesis of 15 distinct molecules. In A549 cells, D9 exhibited remarkable antitumor efficacy with an IC50 of 5.88±0.50 µM, which was 15-fold higher compared to rhein (IC50=88.45±2.77 µM). An in-depth study of the effect of D9 on the degradation of VEGFR-2 revealed that D9 was able to induce the degradation of VEGFR-2 in A549 cells in a time-dependent manner. The observed effect was reversible, contingent upon the proteasome and ubiquitination system, and demonstrably linked to CRBN. Further experiments revealed that D9 induced apoptosis in A549 cells and led to cell cycle arrest in the G1 phase. Molecular docking simulations validated the binding mode of D9 to VEGFR, establishing the potential of D9 to bind to VEGFR-2 in its natural state. In summary, this study confirms the feasibility of natural product-bound PROTAC technology for the development of a new generation of VEGFR-2 degraders, offering a novel trajectory for the future development of pharmacological agents targeting VEGFR-2.

Regulatory T cells: A suppressor arm in post-stroke immune homeostasis.

The activation of the immune system and the onset of pro- and anti-inflammatory responses play crucial roles in the pathophysiological processes of ischaemic stroke (IS). CD4+ regulatory T (Treg) cells is the main immunosuppressive cell population that is studied in the context of peripheral tolerance, autoimmunity, and the development of chronic inflammatory diseases. In recent years, more studies have focused on immune modulation after IS, and Treg cells have been demonstrated to be essential in the remission of inflammation, nerve regeneration, and behavioural recovery. However, the exact effects of Treg cells in the context of IS remain controversial, with some studies suggesting a negative correlation with stroke outcomes. In this review, we aim to provide a comprehensive overview of the current understanding of Treg cell involvement in post-stroke homeostasis. We summarized the literature focusing on the temporal changes in Treg cell populations after IS, the mechanisms of Treg cell-mediated immunomodulation in the brain, and the potential of Treg cell-based therapies for treatment. The purposes of the current article are to address the importance of Treg cells and inspire more studies to help physicians, as well as scientists, understand the whole map of immune responses during IS.

Beyond traditional methods: Unveiling the skin whitening properties of Rhein-Embedded PROTACs.

Proteolysis Targeting Chimeras (PROTAC) technology has emerged as a promising approach for targeted protein degradation. In this study, we focused on tyrosinase (TYR), a key enzyme involved in melanin synthesis and pigmentation. For this target, we designed and synthesized a series of PROTACs (D3-D9), employing Rhein as the target protein-ligand. Through some experimental tests, we made a significant discovery. Preliminary experimental results show that the most promising compound (D6) demonstrated the ability to degrade MITF and inhibit the expression and TYR in B16-F10 cells, effectively suppressing melanogenesis in zebrafish. Notably, at equivalent concentrations, the whitening effect of D6 surpassed that of its precursor Rhein and was even comparable to that of the well-established whitening agent, ß-arbutin. Validating experiments further revealed that the action of D6 was reliant on the E3 ligand, indicating its capacity to degrade TYR and MITF through the ubiquitination pathway. Whether D6 acts directly on TYR or MITF needs to be further explored. These compelling results underscore the tremendous whitening potential of D6, suggesting its suitability as a valuable lead for whitening agents and its potential to expand the range of whitening cosmetic products.

Perspective of People With Type 2 Diabetes Toward Self-management: Qualitative Study Based on Web Crawler Data.

BACKGROUND: The diabetes disease burden in China is heavy, and medical standards such as diabetes guidelines are the core reference guidelines for diabetes management for health care providers and patients. However, patients' guideline compliance is too low, which correlates with the gap between guidelines and patients' self-management needs. Incorporating patient needs into the guideline development would reduce this gap. OBJECTIVE: We sought to capture the needs of patients with diabetes for self-management in everyday situations and to clarify the contradictions and misalignments between medical standards, such as guidelines, and patient needs. METHODS: This study collected crawler-based data from 4 online health communities. We selected 1605 text records collected from Chinese patients with diabetes between March 2020 and July 2020 for analysis. The text analysis applied grounded theory to separate issues that concerned patients into 3 themes, 7 subthemes, and 25 entries. RESULTS: Altogether, 69.03% (1108/1605) of texts were related to issues concerning disease treatment (theme B) and mainly inquired about medication use (B2 and B3; 686/1108, 61.91%), including medication choice, change in medication administration, side effects, and postmedication effects. In addition, 222 (N=1605, 13.8%) texts (theme A) concerned the explanation of disease etiology and knowledge of diabetes, and 275 (N=1605, 17.1%) texts (theme C) discussed lifestyle changes and various restrictions on life brought about by the disease. CONCLUSIONS: Our findings suggest an urgent need to improve diabetes health education and guideline development strategies and to develop health management strategies from a patient perspective to bridge the misalignment between patient needs and current medical standards.

Operando Imaging of Chemical Activity on Gold Plates with Single-Molecule Electrochemiluminescence Microscopy.

Classical electrochemical characterization tools cannot avoid averaging between the active reaction sites and their support, thus obscuring their intrinsic roles. Single-molecule electrochemical techniques are thus in high demand. Here, we demonstrate super-resolution imaging of Ru(bpy)32+ based reactions on Au plates using single-molecule electrochemiluminescence microscopy. By converting electrochemical signals into optical signals, we manage to achieve the ultimate sensitivity of single-entity chemistry, that is directly resolving the single photons from individual electrochemical reactions. High spatial resolution, up to 37 nm, further enables mapping Au chemical activity and the reaction kinetics. The spatiotemporally resolved dynamic structure-activity relationship on Au plates shows that the restructuring of catalysts plays an important role in determining the reactivity. Our approach may lead to gaining new insights towards evaluating and designing electrocatalytic systems.

mir-21-5p inhibits the progression of human chondrosarcoma by regulating CCR7/STAT3/NF-κB pathway.

Purpose: MicroRNAs (miRNAs or miRs) play an important role in the initiation and development of chondrosarcoma (CS). However, the role of miR-21-5p in CS progression and its underlying molecular mechanisms remains unclear.Materials and Methods: miR-21-5p expression was measured by qRT-PCR. Cell proliferation, migration, and invasion were detected by CCK-8 and Transwell assay. Dual-luciferase reporter assay was used to validate the target of miR-21-5p. Western blot was applied to explore the expressions of CCR7 and EMT biomarkers. Then, the xenograft model was established to confirm the effects of miR-21-5p.Results: miR-21-5p was significantly downregulated in CS tissues and cells and negatively correlated with grade, recurrence, and 5-year overall survival. In vitro, miR-21-5p caused G0/G1 cell cycle arrest and induced apoptosis by decreasing cyclin D1 expression and Bcl-2/Bax ratio. miR-21-5p suppressed cell migration and invasion of CS cells by inhibiting epithelial-mesenchymal transition (EMT). In vivo, miR-21-5p inhibited xenograft tumor formation of SW1353 cells. Mechanistically, miR-21-5p targeted the 3'-UTR of C-C chemokine receptor 7 (CCR7) mRNA to inhibit its expression. Overexpression of CCR7 reversed the inhibitory effects of miR-21-5p on CS cell behaviors. However, the silencing of CCR7 enhanced the inhibitory effects of miR-21-5p on CS cells. Besides, the overexpression of miR-21-5p or silencing of CCR7 obviously reduced the expression levels of p-STAT3, p-p56, and p-IκBα.Conclusion: miR-21-5p targeted CCR7 expression to inhibit the STAT3 and NF-κB signaling, thereby suppressing cell proliferation, migration, invasion, and EMT in CS cells, which might be a novel mechanistic study for CS therapy.Abbreviations: 3'-UTR: 3'-untranslated region; CCR7: C-C chemokine receptor type 7; CS: chondrosarcoma; DMEM: dulbecco's modified eagle's medium; EMT: epithelial-mesenchymal transition; HEK-293T: human embryonic kidney-293T; miR-21-5p: microRNA-21-5p; miR-NC: negative control miRNA; SD: standard deviation; si-CCR7: CCR7 siRNAs.

Energy Platform for Directed Charge Transfer in the Cascade Z-Scheme Heterojunction: CO2 Photoreduction without a Cocatalyst.

A universal strategy is developed to construct a cascade Z-Scheme system, in which an effective energy platform is the core to direct charge transfer and separation, blocking the unexpected type-II charge transfer pathway. The dimension-matched (001)TiO2 -g-C3 N4 /BiVO4 nanosheet heterojunction (T-CN/BVNS) is the first such model. The optimized cascade Z-Scheme exhibits ≈19-fold photoactivity improvement for CO2 reduction to CO in the absence of cocatalysts and costly sacrificial agents under visible-light irradiation, compared with BVNS, which is also superior to other reported Z-Scheme systems even with noble metals as mediators. The experimental results and DFT calculations based on van der Waals structural models on the ultrafast timescale reveal that the introduced T as the platform prolongs the lifetimes of spatially separated electrons and holes and does not compromise their reduction and oxidation potentials.

Split-Thickness Nail Bed Flap Graft in the Management of Distal Partial Defect of the Nail Bed Combined With Soft Tissue.

PURPOSE: We report a surgical procedure for the management of nail bed injuries combined with soft tissue defects. METHODS: We reviewed the records of patients with a nail bed injury combined with a soft tissue defect, who were surgically treated at our hospital from 2015 through 2018. According to the Allen classification, 5 patients were characterized as type 2 and 3 were characterized as type 3. Two also had partial defects of the distal phalanx. In all cases, we created a split-thickness nail bed flap of the great toe to reconstruct the nail bed injury. All patients underwent supervised postoperative rehabilitation. We reviewed patients' medical records for the Michigan Hand Outcomes Questionnaire, 2-point discrimination, and postoperative healing in the donor area. RESULTS: Both the nails and flaps of all patients survived. No complications were observed after surgery. The nail was completely attached to the nail bed. In addition, there were no deformities, and the nail plate appearance was close to normal. A nail with an unsatisfactory appearance was noted in one patient. The shape, texture, and elasticity of the flaps of all patients were acceptable. All patients were capable of normal pinching, gripping, and grasping. Twelve months after the operation, 3 of 8 patients had 2-point discrimination of 6 mm or less. All patients were satisfied with the hand function according to the Michigan Hand Outcomes Questionnaire. The toenail of the donor site grew well, and no deformity or pain with walking was noted. CONCLUSIONS: We demonstrate that this approach is a safe means of repairing a nail bed injury combined with a soft tissue defect. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Forefoot Replantation in a 3-Year-Old Boy: Case Report.

Few reports about successful forefoot replantation in children have been published. In this article, we present a case of a 3-year-old boy with severe complete amputation of the left forefoot from a crushed and degloved injury in a motorcycle accident. The replantation was successfully performed, even though total ischemia time lasted 8 hours, of which 4 hours was cold ischemia time. The child was able to walk without significant difficulties from 4 months postoperatively and led a normal life in school at 2 years of follow-up. In this case, we present the replantation of a high-velocity traumatic partial foot amputation in a child with excellent function and cosmetic outcome.

Dimension-Matched Zinc Phthalocyanine/BiVO4 Ultrathin Nanocomposites for CO2 Reduction as Efficient Wide-Visible-Light-Driven Photocatalysts via a Cascade Charge Transfer.

Cascade charge transfer was realized by a H-bond linked zinc phthalocyanine/BiVO4 nanosheet (ZnPc/BVNS) composite, which subsequently works as an efficient wide-visible-light-driven photocatalyst for converting CO2 into CO and CH4 , as shown by product analysis and 13 C isotopic measurement. The optimized ZnPc/BVNS nanocomposite exhibits a ca. 16-fold enhancement in the quantum efficiency compared with the reported BiVO4 nanoparticles at the excitation of 520 nm with an assistance of 660 nm photons. Experimental and theoretical results show the exceptional activities are attributed to the rapid charge separation by a cascade Z-scheme charge transfer mechanism formed by the dimension-matched ultrathin (ca. 8 nm) heterojunction nanostructure. The central Zn2+ in ZnPc could accept the excited electrons from the ligand and then provide a catalytic function for CO2 reduction. This Z-scheme is also feasible for other MPc, such as FePc and CoPc, together with BVNS.

One-Step Controllable Synthesis of Mesoporous MgCo2 O4 Nanosheet Arrays with Ethanol on Nickel Foam as an Advanced Electrode Material for High-Performance Supercapacitors.

In recent years, ternary transition metal oxides (TTMOs), especially spinel type TTMOs have attracted widespread attention as promising candidates for electrode materials. Among all of the popular TTMOs, MgCo2 O4 is an outstanding one, owing to its superior theoretical capacitance. In this work, MgCo2 O4 nanosheet arrays (NSAs) grown directly on nickel foams were fabricated through a facile hydrothermal process at 120 °C for 4 h. With a series of structural and morphological characterization techniques, it was found that the ethanol played a key role in controlling the composition and morphology during the synthesis process. The MgCo2 O4 NSAs exhibited a superior specific capacitance of 853.06 C g-1 (at 1 mA cm-2 ) and enhanced cycling performance, with 94.65 % of initial capacitance retained after 3000 cycles when used as a binder-free integrated electrode for electrochemical supercapacitors; much higher than other reported data for MgCo2 O4 as well. The excellent electrochemical properties mainly came from the unique morphology of the MgCo2 O4 NSAs. This study will demonstrate the applications of MgCo2 O4 NSAs based large-scale supercapacitors grown on low-cost nickel foams.

Cyanobacterial Bloom Formation by Enhanced Ecological Adaptability and Competitive Advantage of Microcystis-Non-Negligible Role of Quorum Sensing.

Microcystis-dominated cyanobacterial blooms (MCBs) frequently occur in freshwaters worldwide due to massive Microcystis colony formation and severely threaten human and ecosystem health. Quorum sensing (QS) is a direct cause of Microcystis colony formation that drives MCBs outbreak by regulating Microcystis population characteristics and behaviors. Many novel findings regarding the fundamental knowledge of the Microcystis QS phenomenon and the signaling molecules have been documented. However, little effort has been devoted to comprehensively summarizing and discussing the research progress and exploration directions of QS signaling molecules-mediated QS system in Microcystis. This review summarizes the action process of N-acyl homoserine lactones (AHLs) as major signaling molecules in Microcystis and discusses the detailed roles of AHL-mediated QS system in cellular morphology, physiological adaptability, and cell aggregation for colony formation to strengthen ecological adaptability and competitive advantage of Microcystis. The research progress on QS mechanisms in Microcystis are also summarized. Compared to other QS systems, the LuxI/LuxR-type QS system is more likely to be found in Microcystis. Also, we introduce quorum quenching (QQ), a QS-blocking process in Microcystis, to emphasize its potential as QS inhibitors in MCBs control. Finally, in response to the research deficiencies and gaps in Microcystis QS, we propose several future research directions in this field. This review deepens the understanding on Microcystis QS knowledge and provide theoretical guidance in developing strategies to monitor, control, and harness MCBs.

Meta-analysis for systematic review of global micro/nano-plastics contamination versus various freshwater microalgae: Toxicological effect patterns, taxon-specific response, and potential eco-risks.

Micro/nano-plastics (MNPs), as emerging persistent pollutants, are threatening freshwater ecosystems worldwide. Microalgae are important primary producers at the base of trophic level and susceptible to MNPs contamination, possibly resulting in further contamination in higher trophic levels and water quality. This study conducted a systematic review of 1071 observations from 63 publications, utilizing meta-analysis and subgroup analysis to investigate the toxicological effect patterns of MNPs parameters (size, concentration, and type) on microalgae. We also explored the potential eco-risks of certain specific MNPs parameters and subtle variations in the response of various microalgae taxa to MNPs. Results suggested that microplastics significantly inhibited microalgal photosynthesis, while nano-plastics induced more severe cell membrane damage and promoted toxin-release. Within a certain range of concentrations (0∼50 mg/L), rising MNPs concentration progressively inhibited microalgal growth and chlorophyll-a content, and progressively enhanced toxin-release. Among MNPs types, polyamide caused higher growth inhibition and more severe lipid peroxidation, and polystyrene induced more toxin-release, whereas polyethylene terephthalate and polymethyl methacrylate posed minimal effects on microalgae. Moreover, Bacillariophyta growth was inhibited most significantly, while Chlorophyta displayed strong tolerance and Cyanophyta possessed strong adaptive and exceptional resilience. Particularly, Komvophoron, Microcystis, Nostoc, Scenedesmus, and Gomphonema were more tolerant and might dominate freshwater microalgal communities under MNPs contamination. These results are crucial for acquiring the fate of freshwater microalgae under various MNPs contamination, identifying dominant microalgae, and reasonably assessing and managing involved eco-risks.

Enriched environment ameliorates fear memory impairments induced by sleep deprivation via inhibiting PIEZO1/calpain/autophagy signaling pathway in the basal forebrain.

AIMS: To verify the hypothesis that an enriched environment (EE) alleviates sleep deprivation-induced fear memory impairment by modulating the basal forebrain (BF) PIEZO1/calpain/autophagy pathway. METHODS: Eight-week-old male mice were housed in a closed, isolated environment (CE) or an EE, before 6-h total sleep deprivation. Changes in fear memory after sleep deprivation were observed using an inhibitory avoidance test. Alterations in BF PIEZO1/calpain/autophagy signaling were detected. The PIEZO1 agonist Yoda1 or inhibitor GsMTx4, the calpain inhibitor PD151746, and the autophagy inducer rapamycin or inhibitor 3-MA were injected into the bilateral BF to investigate the pathways involved in the memory-maintaining role of EE in sleep-deprived mice. RESULTS: Mice housed in EE performed better than CE mice in short- and long-term fear memory tests after sleep deprivation. Sleep deprivation resulted in increased PIEZO1 expression, full-length tropomyosin receptor kinase B (TrkB-FL) degradation, and autophagy, as reflected by increased LC3 II/I ratio, enhanced p62 degradation, increased TFEB expression and nuclear translocation, and decreased TFEB phosphorylation. These molecular changes were partially reversed by EE treatment. Microinjection of Yoda1 or rapamycin into the bilateral basal forebrain induced excessive autophagy and eliminated the cognition-protective effects of EE. Bilateral basal forebrain microinjection of GsMTx4, PD151746, or 3-MA mimicked the cognitive protective and autophagy inhibitory effects of EE in sleep-deprived mice. CONCLUSIONS: EE combats sleep deprivation-induced fear memory impairments by inhibiting the BF PIEZO1/calpain/autophagy pathway.

Visual Eosin Y-Based Photosensitization Sensing Systems for Ultrasensitive Detection of Diclofenac with Single-Atom Co─N2O2 Site-Immobilized g-C3N4 Nanosheets.

It is highly desired to develop a visual sensing system for ultrasensitive detection of colorless diclofenac (DCF), yet with a significant challenge. Herein, a novel dye-based photosensitization sensing system has been successfully developed for detecting DCF for the first time, in which the used dye eosin Y (DeY) can strongly absorb visible light and then be decolorized obviously by transferring photogenerated electrons to g-C3N4 nanosheets (CN), while the built single-atomic Co─N2O2 sites on CN by boron-oxygen connection can competitively adsorb DCF to impede the photosensitization decoloration of DeY. This system exhibits a broad detection range from 8 ng L-1 to 2 mg L-1 with 535 nm light, an exceptionally low detection limit (3.5 ng L-1), and remarkable selectivity. Through the time-resolved, in situ technologies, and theoretical calculations, the decolorization of DeY is attributed to the disruption of DeY's conjugated structure caused by the triplet excited state electron transfer from DeY to CN, meanwhile, the adsorbed oxygen facilitates the charge transfer process. The preferential adsorption of DCF mainly depends on the strong interactions between the as-constructed single-atom Co and Cl in DCF. This study opens an innovative light-driven sensing system by combining dye and single-atom metal/nanomaterial for visually intuitive detection of environmental pollutants.

Prediction of developmental toxic effects of fine particulate matter (PM2.5) water-soluble components via machine learning through observation of PM2.5 from diverse urban areas.

The global health implications of fine particulate matter (PM2.5) underscore the imperative need for research into its toxicity and chemical composition. In this study, zebrafish embryos exposed to the water-soluble components of PM2.5 from two cities (Harbin and Hangzhou) with differences in air quality, underwent microscopic examination to identify primary target organs. The Harbin PM2.5 induced dose-dependent organ malformation in zebrafish, indicating a higher level of toxicity than that of the Hangzhou sample. Harbin PM2.5 led to severe deformities such as pericardial edema and a high mortality rate, while the Hangzhou sample exhibited hepatotoxicity, causing delayed yolk sac absorption. The experimental determination of PM2.5 constituents was followed by the application of four algorithms for predictive toxicological assessment. The random forest algorithm correctly predicted each of the effect classes and showed the best performance, suggesting that zebrafish malformation rates were strongly correlated with water-soluble components of PM2.5. Feature selection identified the water-soluble ions F- and Cl- and metallic elements Al, K, Mn, and Be as potential key components affecting zebrafish development. This study provides new insights into the developmental toxicity of PM2.5 and offers a new approach for predicting and exploring the health effects of PM2.5.

1D Cu(I)-based chiral organic-inorganic hybrid material with second harmonic generation and circular polarized luminescence.

In recent years, organic-inorganic hybrid materials have demonstrated exceptional performance in nonlinear optics, attracting widespread attention. However, there are relatively few examples of coordination compounds synthesized with Cu as the metal center that exhibit excellent nonlinear optical properties. In this study, we successfully synthesized a pair of enantiomers named R/S-Cu2I2 by reacting chiral ligands with CuI. The crystal structure reveals a one-dimensional copper-iodide chain structure built by Cu2I2 clusters, and its ordered arrangement in space provides not only a strong second harmonic generation (SHG) signal (1.24 × KDP) but also a large birefringence (0.15@1064 nm). Under excitation at 395 nm, the crystals exhibit red fluorescence peaked at 675 nm. The CD spectra of R/S-Cu2I2 show a distinct mirror-symmetric Cotton effect, and their CPL signals are corresponding and opposite in the emission range, with a maximum glum of approximately ±2.5 × 10-3. Theoretical calculations using density functional theory were also carried out to enhance our understanding of the correlation between their structures and optical properties.

Effect of Postoperative Prolonged sedation with Dexmedetomidine after successful reperfusion with Endovascular Thrombectomy on long-term prognosis in patients with acute ischemic stroke (PPDET): study protocol for a randomized controlled trial.

BACKGROUND: Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. METHODS: This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b-3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 µg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. DISCUSSION: This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

Direct probing of single-molecule chemiluminescent reaction dynamics under catalytic conditions in solution.

Chemical reaction kinetics can be evaluated by probing dynamic changes of chemical substrates or physical phenomena accompanied during the reaction process. Chemiluminescence, a light emitting exoenergetic process, involves random reaction positions and kinetics in solution that are typically characterized by ensemble measurements with nonnegligible average effects. Chemiluminescent reaction dynamics at the single-molecule level remains elusive. Here we report direct imaging of single-molecule chemiluminescent reactions in solution and probing of their reaction dynamics under catalytic conditions. Double-substrate Michaelis-Menten type of catalytic kinetics is found to govern the single-molecule reaction dynamics in solution, and a heterogeneity is found among different catalyst particles and different catalytic sites on a single particle. We further show that single-molecule chemiluminescence imaging can be used to evaluate the thermodynamics of the catalytic system, resolving activation energy at the single-particle level. Our work provides fundamental insights into chemiluminescent reactions and offers an efficient approach for evaluating catalysts.

A Mixed Methods Assessment of Self- Management Needs and Preferences of People with Type 2 Diabetes Mellitus in China.

Background: Consistent and effective self-management is a major challenge for people with diabetes and long-term effects can be difficult to sustain despite the many interventions. Interventions often fail to take patients' perceptions of self-management into account from their perspective. Exploring the needs preferences and the influencing factors of self-management in patients can improve the effectiveness of self-management. Methods: This study used a mixed research approach, exploring patient needs and preferences through web crawl methods and using qualitative interviews to explore the logic of preferences. 1605 data were obtained from 4 online health communities through web crawlers. Data were coded using grounded theory to analyze self-management needs. The codes were also coded for frequency statistics and ranked to explain the self-management preferences. The second phase explained the logic of the ranked distribution of preferences through one-on-one interviews with 22 patients. Results: This study summarized six self-management needs of people with diabetes through web crawler data, among which medication management and conflict between disease and daily life were the most important concerns of patients. The reasons why patients are particularly concerned about these two needs were explored through qualitative interviews, and it was found that patients' concerns about medication were mainly due to the following three aspects: the effect of drugs is direct and obvious, medication use makes life less complicated, and progressive side effects. The patients' concerns about the conflict between disease and daily life are often caused by the following three aspects: diabetes impacts social roles, disease complicates life, and reducing the impact of the disease on life. Conclusion: The self-management needs of Chinese diabetics have six themes. Medication management, conflict between disease and daily life, diet, diabetes knowledge, blood glucose monitoring and exerciseIn order of frequency of mention and possible preference: medication management, conflict between disease and daily life were the most frequent needs, while diet, knowledge about diabetes, blood glucose monitoring and exercise were their least frequent needs.Understanding the individual's perception and understanding of diabetes self-management and the expression of the patient's daily life situations can guide the medical team to optimize collaboration on personalized care plans.